Bacillus

Toxicon, 1999 Sep, 37(9), 1241 - 58
Doctor Albert Calmette 1863-1933: founder of antivenomous serotherapy and of antituberculous BCG vaccination; Hawgood BJ; In 1891 in Saigon (now Ho Chi Minh City), Dr . Albert Calmette established the first daughter Pasteur Institute for the protection of the local population against rabies and smallpox . Inspired by the discovery of diphtheria antitoxin by Behring, Calmette studied ways of raising serum against cobra venom . In 1895, now in Lille at the second daughter institute that he established, Calmette produced anticobra serum for therapeutic use that was to revolutionize the treatment of snakebite worldwide . The incidence of tuberculosis in the working class of the industrial north shocked Calmette . In response, firstly he organized an antituberculous dispensary to provide assistance to the sick and help limit the spread of the disease by improving social hygiene and secondly he devoted himself, with the assistance of Camille Guerin, to obtaining an attenuated live strain of tubercle bacilli with fixed biological characteristics for use as a vaccine . Such a strain developed during repeated passage of a culture of Mycobacterium bovis grown on a bile potato medium . In 1919, Dr . Albert Calmette took up the appointment of Sub-Director of the Pasteur Institute of Paris . Prolonged trials of BCG (Bacille Calmette-Guerin) vaccine showed it to be safe and vaccination of very young infants born of tuberculous mothers commenced in 1921 . The use of BCG vaccine as a prophylactic against tuberculosis spread world-wide and has remained important in combatting this scourge.

J Mal Vasc, 1999 May, 24(2), 135 - 8
{Infection and angiomatous cutaneous lesions}; Janier M; The occurrence of angiomatous cutaneous lesions in the presence of an infective process is not a frequent phenomenon . Most infectious diseases are associated with an exanthematous reaction . The combination of an infective illness and angiomatous lesions is seen essentially in the bartonelloses and in Kaposi's disease . Bartonelloses: group of infections due to alpha-proteobacteria such as Bartonella . Bartonella bacilliformis (BB), is the causal agent of Carrion's disease, the chronic cutaneous form of which (verruga peruana), in which the vector is an arthropod of the Lutzomyia species found in South America, presents superficial and deep angiomatous cutaneous nodules . Spontaneous regression occurs in a few months or years . Bartonella henselae (BH) and Bartonella quintana (BQ), are the causal agents of bacillary angiomatosis (BA), described in 1983, in which angiomatous papules or nodules with an appearance like botryomycomas, are associated with visceral lesions . The characteristic histological features (with the demonstration or the bacilli by Warthin-Starry stain) together with culture of the bacterium in various tissues (including the blood) are diagnostic . BA occurs most commonly, but not exclusively, in patients with HIV infection . Furthermore, BH is responsible for cat scratch disease while BQ causes trench fever . The reservoir of BH is the cat . The bartonella produce angiogenic factors responsible for the neovascularisation seen in angiomatous lesions . The differential diagnosis is between botryomycomas and Kaposi's disease . Numerous antibiotics are effective against botryomycomas, particularly chloramphenicol and penicillin for BB and macrolides, cyclins and fluoroquinolones for BH and BQ . Kaposi's disease (KD): whether classical, endemic or epidemic (due to HIV infection) is characterised by cutaneous and visceral angiomatous lesions: these are associated with multifocal tumorous proliferations (of endothelial and fusiform cells) affected by angiogenic growth factors (PDGF, FGF, IL6, alphaTGF, HIVtat, androgens) and strongly linked to the lymphocytic and endothelial tropism of a gamma herpes virus (HHV8, Chang and Moore 1994) . HHV8 infection, probably sexually transmitted, is also the cause of lymphomas occurring in cavities and of Castleman's disease . The course of KD is very variable: from the indolent form in elderly HIV-ve patients, to the explosive forms in the immunodepressed (particularly in HIV+ve patients.

Crit Care Med, 1999 Jun, 27(6), 1090 - 5
Colonization with broad-spectrum cephalosporin-resistant gram-negative bacilli in intensive care units during a nonoutbreak period: prevalence, risk factors, and rate of infection; D'Agata EM et al.; OBJECTIVE: To define the epidemiology of broad-spectrum cephalosporin-resistant gram-negative bacilli in intensive care units (ICUs) during a nonoutbreak period, including the prevalence, the risk factors for colonization, the frequency of acquisition, and the rate of infection . DESIGN: Prospective cohort study . SETTING: Tertiary care hospital . PATIENTS: Consecutive patients admitted to two surgical ICUs . MAIN OUTCOME MEASUREMENTS: Serial patient surveillance cultures screened for ceftazidime (CAZ) resistance, antibiotic and hospital exposure, and infections . RESULTS: Of the 333 patients enrolled, 60 (18%) were colonized with CAZ-resistant gram-negative bacilli (CAZ-RGN) at admission . Clinical cultures detected CAZ-RGN in only 5% (3/60) of these patients . By using logistic regression, CAZ-RGN colonization was associated with duration of exposure to cefazolin (odds ratio, 10.3; p < or = .006) and to broad-spectrum cephalosporins/penicillins (odds ratio, 2; p < or = .03), Acute Physiology and Chronic Health Evaluation III score (odds ratio, 1.2; p < or = .008), and previous hospitalization (odds ratio, 3.1; p < or = .006) . Of the 100 patients who remained in the surgical ICU for > or = 3 days, 26% acquired a CAZ-RGN . Of the 14 infections caused by CAZ-RGN, 11 (79%) were attributable to the same species present in surveillance cultures at admission to the surgical ICU . CONCLUSIONS: Colonization with CAZ-RGN was common and was usually not recognized by clinical cultures . Most patients colonized or infected with CAZ-RGN had positive surveillance cultures at the time of admission to the surgical ICU, suggesting that acquisition frequently occurred in other wards and institutions . Patients exposed to first-generation cephalosporins, as well as broad-spectrum cephalosporins/penicillins, were at high risk of colonization with CAZ-RGN . Empirical treatment of nosocomial gram-negative infections with broad-spectrum cephalosporins, especially in the critically ill patient, should be reconsidered.

Am J Clin Pathol, 1999 Jul, 112(1), 63 - 8
Granulomatous myositis . Clinicopathologic study of 12 cases; Prayson RA; Granulomatous inflammation is infrequently encountered in skeletal muscle biopsy material . Of 2,985 muscle biopsy specimens reviewed over 12 years, 12 (0.4%) with granulomatous inflammation were identified . The patients included 9 women who ranged in age from 24 to 76 years (mean 50.3 years) . The most common clinical findings included decreased strength or weakness in the extremities (n = 8), muscle pain (n = 5), and weight loss (n = 3) . All muscles exhibited nonnecrotizing granulomas; an associated vasculitic process was identified in 2 . Endomysial chronic inflammation consisting primarily of lymphocytes and plasma cells was present in 10 muscles, and perivascular chronic inflammation in 8 . Degenerating muscle fibers were noted in 10 cases, and regenerating fibers in 11 . Evidence of neurogenic atrophy was seen in 8 muscles . Increased endomysial fibrosis was observed in 5 muscles, and type II muscle fiber atrophy in 5 muscles . Stains for acid-fast bacilli and Gomori methenamine silver stain were performed in all but 2 cases and failed to demonstrate organisms . In 3 cases, concomitant sural nerve biopsies were performed, and granulomas were identified in 2 of those cases . Clinicopathologic diagnoses included sarcoidosis (n = 6), vasculitis (n = 2), and granulomatous myositis not otherwise specified (n = 2) . In 2 cases, there was insufficient clinical information or follow-up data to determine a cause . In conclusion, granulomatous myositis is infrequently found in muscle biopsy specimens (0.5% of all biopsies in this series); most muscles demonstrate evidence of chronic endomysial or perivascular inflammation accompanied by muscle fiber degeneration and regeneration; and the most common cause for granulomatous myositis was sarcoidosis in this series.

Infect Control Hosp Epidemiol, 1999 Jun, 20(6), 421 - 5
Nosocomial tuberculosis exposure in an outpatient setting: evaluation of patients exposed to healthcare providers with tuberculosis; Bock NN et al.; OBJECTIVE: To evaluate the risk of tuberculosis (TB) transmission to patients potentially exposed to two healthcare providers who worked in outpatient settings for several weeks prior to being diagnosed with acid-fast bacilli smear-positive pulmonary TB . DESIGN: Potentially exposed patients were notified by letter and television reports of the recommended evaluation for TB infection or disease and availability of free screening at the hospital . Prevalence of infection in the screened patients and the incidence rate of TB over the subsequent 2 years were compared to those of a control group of unexposed outpatients . SETTING: An urban inner-city hospital . PATIENTS: 1,905 patients with potential exposure to the ill healthcare workers; 487 (25%) presented for evaluation . Controls consisted of 951 unexposed patients . RESULTS: 361 potentially exposed patients had their tuberculin test read; 97 (27%) had a purified protein derivative > or = 10 mm . In the comparison group, 148 (25%) of 600 with test readings had a > or = 10-mm reaction (risk ratio, 1.18; 95% confidence interval, 0.86-1.60) . In multivariate analysis, male gender, non-white race, and older age were significantly associated with a positive tuberculin test; exposure was not . No TB cases were identified during screening . Two years after the exposure, 7 TB cases had been reported to the state registry among 1,905 potentially exposed patients (184 cases/100,000 person-years) versus 4 cases in the comparison group of 951 (210 cases/100,000 person-years) . CONCLUSIONS: Evaluation of patients exposed to healthcare workers with TB disease in ambulatory settings of an inner-city hospital revealed no evidence of transmission of Mycobacterium tuberculosis due to the exposure.

Pneumonol Alergol Pol, 1998, 66(11-12), 551 - 4
{Familial occurrence of tuberculosis--a report of vice cases in a seven-person family in a period of 14 years}; Zalc-Swierczewska E et al.; Tuberculosis in five persons among the seven family members is reported . The main reasons for occurrence of tuberculosis in the majority of the family members were alcoholism and non-compliance with doctor's recommendations, then resistance of tubercle bacilli to antituberculous drugs, due to the above mentioned reasons . Even chemoprophylaxis in two of the family members did not protect then from the disease.

Am J Respir Crit Care Med, 1999 Jul, 160(1), 203 - 10
Measurement of sputum Mycobacterium tuberculosis messenger RNA as a surrogate for response to chemotherapy; Desjardin LE et al.; Effective treatment regimens for pulmonary tuberculosis are difficult to assess because of the slow growth rate of Mycobacterium tuberculosis in culture and its protracted clearance from sputum . A rapid method that reflects effective antimicrobial activity would markedly advance evaluation of treatment and promote the assessment of new antituberculosis drugs . Conventional methods measure the progressive reduction of numbers of acid-fast bacilli in the sputum smear and the clearance of organisms in sputum culture . In this study, we measured levels of M . tuberculosis 85B (alpha antigen) messenger RNA (mRNA), 16S ribosomal RNA (rRNA), and IS6110 DNA in patients' sputa to ascertain whether they could serve as potential surrogate markers of response to chemotherapy . Sputum specimens were sequentially collected for up to a year from 19 smear-positive pulmonary tuberculosis patients receiving an optimal drug treatment regimen . Nucleic acids were isolated from these specimens, and two M . tuberculosis molecular targets (mRNA, DNA) were quantified, using the ABI Prism 7700 Sequence Detection System . The Mycobacterium genus-specific 16S rRNA was quantified with a limiting dilution RT-PCR assay . Results show that levels of 85B mRNA declined after initiation of therapy, as did viable M . tuberculosis colony counts, with 90% of patients becoming negative for both markers after 2 mo of treatment . The rapid disappearance of M . tuberculosis mRNA from sputum suggests that it is a good indicator of microbial viability and a useful marker for rapid assessment of response to chemotherapy.

Kekkaku, 1999 May, 74(5), 457 - 61
{The combination therapy of clarithromycin and sparfloxacin for pulmonary Mycobacterium gordonae infection}; Tomiyama Y et al.; Seventy years old woman had fever and hemosputum at May 1997 . She was diagnosed as mycobacteriosis because of the positive acid fast bacilli smear from sputum . Mycobacterium gordonae was isolated from sputum, gastric juice, and bronchial aspirate . The combination therapy of isoniazid, rifampicin, ethambutol, and clarithromycin was administrated; however, M . gordonae was not eradicated from sputum . Sparfloxacin was administered instead of isoniazid based on the result of drug susceptibility test . The smear became negative and M . gordonae was eradicated from sputum one month after the initiation of treatment with the combination of clarithromycin and sparfloxacin.

Kekkaku, 1999 May, 74(5), 453 - 6
{A case of middle ear tuberculosis; PCR of the otorrhea was useful for the diagnosis}; Inoue T et al.; A 26-year-old female was admitted to our hospital with complaints of fever, cough, otorrhea and otalgia and progressive hearing loss of her left ear . Smears of her sputum were positive for acid-fast bacilli . Smears of her otorrhea were negative for acid-fast bacilli but PCR of her otorrhea was positive . Chest X-ray showed infiltrative shadows with the cavity . She was diagnosed as middle ear tuberculosis associated with pulmonary tuberculosis . After anti-tuberculous chemotherapy, fever, cough, otorrhea and pain of her left ear were improved, but her hearing level was not improved . In the case of middle ear tuberculosis, it is necessary to make an early diagnosis and treatment . This is the first reported case in Japan in which PCR of the otorrhea is positive.

Kekkaku, 1999 May, 74(5), 433 - 9
{Evaluations of MTD and Amplicor Mycobacterium for direct detection of Mycobacteria from clinical specimens}; Sato A et al.; MTD (GEN-PROBE AMPLIFIED MYCOBACTERIUM TUBERCULOSIS DIRECT TEST) for Mycobacterium tuberculosis, and Amplicor Mycobacterium for Mycobacteria (AMP-M . tb for M . tuberculosis, AMP-M . av for M . avium and AMP-M . in for M . intracellulare) were used for the detection of relevant Mycobacterium . Their sensitivity and specificity were evaluated . Total 244 clinical specimens including 164 sputa were examined by the above two tests . The results were compared with those obtained by the conventional methods . Of 244 samples, number of the M . tuberculosis positive samples by microscopy, cultural test, MTD and AMP-M . tb were 32, 33, 38 and 35, respectively . Among 33 culture positive samples, 25 were MTD positive and 26 were AMP-M . tb positive . Therefore, sensitivity of MTD and AMP-M . tb were 75.8% and 78.8%, and their specificity were 93.8% and 95.7%, respectively . When only sputa were used for the tests as the clinical specimens, both sensitivity of MTD and AMP-M . tb were increased to 94.4% . For MAC, positive samples of M . avium complex by culture, M . avium by AMP-M . av and M . intracellulare by AMP-M . in were 13, 16, and 8, respectively . Sensitivity and specificity of AMP-M . av/M . in were 100% and 95.2%, respectively . Clinical findings of the patients whose MTD tests were positive but negative by culture were reexamined . Three of 9 specimens were also positive in AMP-M . tb . From the records of the isolations of tubercle bacilli or other important pathogens from the other kind of clinical specimens, smear tests and patients' response to tuberculosis chemotherapy, four of 9 specimens were confirmed as true positive, three were suspected as positive, and two other specimens were false positive which might be caused by contamination . From these observations, it could be concluded that MTD and AMP-M . tb are more sensitive than conventional culture method, and MTD is more sensitive than AMP-M . tb but needs more careful treatment to avoid the contamination.

Kekkaku, 1999 May, 74(5), 425 - 32
{The prevalence survey on chronic tuberculosis patients with bacilli discharge in Osaka prefecture}; Mui K et al.; This survey was made at the end of 1996 in Osaka prefecture including three ordinance designated cities of Osaka, Sakai and Higashiosaka . As of December 31 1996, 109 or 3.3% of active tuberculosis cases were found to be chronic tubercle bacilli excreters in Osaka city, and 128 or 3.6% in Osaka prefecture other than Osaka city, respectively . In the area called Airin at Nishinari-ward, Osaka, which has been an area with high prevalence of the disease, 33 or 5.8% were chronic tubercle bacilli excreters, and the rate was slightly higher than the other areas . Compared to the survey conducted 10 years ago, while the number of the chronic tubercle bacilli excreters decreased by half to 109 from 200 in Osaka city, to 128 from 211 in Osaka prefecture excluding Osaka city, the rate of chronic excreters to total active tuberculosis showed almost no change . Various factors such as difficult living conditions often attributed to defaulting of active tuberculosis patients from their treatment, thus resulting to development of chronic excretion . It is highly recommended to apply DOTS strategy for the completion of their treatment . Public health centers that have personal clinical records of each patient should be familiar with the results of their bacillus examinations . They should also be required to cooperate with medical institutions to cope with those who need retreatment.

Kansenshogaku Zasshi, 1999 May, 73(5), 482 - 5
{Pulmonary infection caused by Mycobacterium gordonae}; Yanagisawa N et al.; A 57-year-old woman who had been operated on for colon cancer and given chemotherapy, presented in September 1995 with worsening cough and abnormalities on her chest X-ray film . Acid-fast bacilli were isolated from the sputum . The organism was classified as M . gordonae by biochemical tests and DNA/DNA hybridization . The patient was treated with rifampicin and clarithromycin . Subsequently, sputum cultures became negative and the chest x-ray film showed a decrease infiltration . The findings in the present case suggest that M . gordonae may cause pulmonary infection and should be considered as an opportunistic pathogen.

J Immunol, 1999 Jul 1, 163(1), 312 - 21
Surfactant protein D binds to Mycobacterium tuberculosis bacilli and lipoarabinomannan via carbohydrate-lectin interactions resulting in reduced phagocytosis of the bacteria by macrophages; Ferguson JS et al.; Surfactant protein-D (SP-D) is a collectin produced in the distal lung airspaces that is believed to play an important role in innate pulmonary immunity . Naive immunologic responses to Mycobacterium tuberculosis (M.tb) are especially important in the lung, since entry of this inhaled pathogen into the alveolar macrophage is a pivotal event in disease pathogenesis . Here we investigated SP-D binding to M.tb and the effect of this binding on the adherence of M . tb to human macrophages . These studies demonstrate specific binding of SP-D to M.tb that is saturable, calcium dependent, and carbohydrate inhibitable . In addition to purified SP-D, SP-D in bronchoalveolar lavage fluids from healthy donors and patients with alveolar proteinosis also binds to M.tb . Incubation of M.tb with SP-D results in agglutination of the bacteria . In contrast to its binding to M.tb, SP-D binds minimally to the avirulent Mycobacterium smegmatis . SP-D binds predominantly to lipoarabinomannan from the virulent Erdman strain of M.tb, but not the lipoarabinomannan from M . smegmatis . The binding of SP-D to Erdman lipoarabinomannan is mediated by the terminal mannosyl oligosaccharides of this lipoglycan . Incubation of M.tb with subagglutinating concentrations of SP-D leads to reduced adherence of the bacteria to macrophages (62.7% of control adherence +/- 3.3% SEM, n = 8), whereas incubation of bacteria with surfactant protein A leads to significantly increased adherence to monocyte-derived macrophages . These data provide evidence for specific binding of SP-D to M . tuberculosis and indicate that SP-D and surfactant protein A serve different roles in the innate host response to this pathogen in the lung.

Int J Tuberc Lung Dis, 1999 Jun, 3(6), 521 - 7
The role of tissue studies in facilitating early initiation of antimycobacterial treatment in AIDS patients with disseminated mycobacterial disease; Hsieh SM et al.; SETTING: The question of whether aggressive investigations are useful in diagnosis and initiation of treatment in AIDS patients with disseminated mycobacterial disease (DMD) is still under debate . OBJECTIVE: To define the role of tissue studies in facilitating early initiation of antimycobacterial treatment and in establishing diagnosis in AIDS patients with DMD . DESIGN: From July 1994 through June 1997, 167 AIDS cases with fever were evaluated by stepwise investigation using a standardized protocol . Data of DMD cases were analyzed to define the role of tissue studies . RESULTS: A total of 40 cases of culture-proven DMD were identified . Antimycobacterial treatment was initiated due to positive acid-fast bacilli smears of sputum in only five cases . In the remaining cases, positive pathologic findings from tissue biopsies (lymph node, bone marrow or liver) facilitated early initiation of treatment in 60% (21/35) . In 50% of all cases (20/40), the diagnosis could not have been established if cultures of tissue biopsies had not been performed . Both the pathologic examinations and mycobacterial cultures from liver biopsies had positivity rates of more than 50% (53.8% and 69.2%, respectively) . CONCLUSIONS: Tissue studies were useful in facilitating early initiation of treatment and establishing diagnosis at least in half of the AIDS cases with DMD . Liver biopsy is worthwhile if the cause of fever is not discovered using less invasive investigations.

Int J Tuberc Lung Dis, 1999 Jun, 3(6), 515 - 20
Chemotherapy of tuberculosis in mice using single implants of isoniazid and pyrazinamide; Gangadharam PR et al.; OBJECTIVE: To establish the chemotherapeutic value of a depot drug preparation of isoniazid and pyrazinamide against experimental tuberculosis . DESIGN: To see whether sustained levels of pyrazinamide are available for prolonged periods after a single subcutaneous administration of a biodegradable polylactic-glycolic acid (PLGA) polymer containing the drug, studies were done to ascertain whether a single administration of isoniazid and pyrazinamide in separate PLGA polymers could offer chemotherapeutic protection against a heavy intravenous challenge of susceptible mice with a virulent strain of Mycobacterium tuberculosis similar to that rendered by daily administration of the two drugs for 8 weeks . RESULTS: Even with three times the daily dose of pyrazinamide contained in the single PLGA polymer implant, no abnormally high (burst) levels of the drug were evident after administration, but sustained levels of the drug were seen up to 54 days . The chemotherapeutic activity of the single PLGA polymer implants was similar to that obtained with standard oral treatment with the two drugs given daily for the entire 8 weeks, as judged by mortality and colony forming unit (CFU) counts of tubercle bacilli from lungs and spleen . CONCLUSION: Treatment with single implants of the PLGA polymer containing anti-mycobacterial drugs offers a strong possibility of circumventing the compliance problem.

J Antimicrob Chemother, 1999 May, 43(5), 659 - 66
Bismuth-mediated disruption of the glycocalyx-cell wall of Helicobacter pylori: ultrastructural evidence for a mechanism of action for bismuth salts; Stratton CW et al.; The mechanism of bismuth's bactericidal activity against Helicobacter pylori was investigated using transmission electron microscopy (TEM) and analytical electron microscopy (AEM); time-kill kinetic methods evaluated the effect of excess divalent cations . TEM analysis of untreated H . pylori revealed a normal morphology . In contrast, H . pylori exposed to bismuth salts had swollen, distorted cells with membrane-cell wall blebbing and a cytoplasm containing electron-dense, sometimes crystalline aggregates . By AEM, swollen cells contained bismuth at the cell periphery, whereas bacillary forms contained cytoplasmic bismuth localizations . Time-kill studies showed that the bactericidal activity of bismuth could be prevented by pretreatment with divalent cations . The effects of bismuth salts on the glycocalyces-cell walls of H . pylori with reversal of bactericidal activity by divalent cations are identical to those produced by other polycationic agents on various gram-negative bacilli . We conclude that disruption of the glycocalyces-cell walls of H . pylori is one mechanism of action for bismuth salts.

Chest, 1999 Jun, 115(6), 1570 - 5
Oropharyngeal Gram-negative bacillary carriage: a survey of 120 healthy individuals; Mobbs KJ et al.; BACKGROUND: The presence of aerobic Gram-negative bacilli (AGNB) in the oropharynx can be either temporary or persistent . Prolonged colonization (ie, carriage) is distinguished from transient presence (ie, acquisition), which often occurs in healthy individuals but less frequently in those with underlying disease . Prevalence rates of up to 61.1% quoted previously for healthy individuals were obtained by using single sample surveys, which fail to differentiate acquisition from carriage . STUDY OBJECTIVES: To illustrate the need to distinguish carriage from acquisition in a healthy population at risk of acquisition of AGNB, and to show that although differing groups of healthy individuals may acquire oropharyngeal AGNB at differing frequencies, carriage is rare in healthy individuals . PARTICIPANTS: Two oral rinses were obtained within a 2-day interval from 120 healthy individuals comprising 40 nurses, 40 students, and 40 laboratory-associated persons . DESIGN: Two hundred forty oral rinses were quantitatively (1:10 dilution series) cultured for AGNB by using broth enrichment . MEASUREMENTS AND RESULTS: The rate of AGNB carriage based on two consecutive samples positive for the same AGNB was 6.6%; the rate of AGNB acquisition based on one positive sample was 35.8% . The concentrations of all carried and acquired AGNB were < or = 103 cfu/mL . AGNB acquisition was significantly higher in students (52.5%) compared to nurses (32.5%) and laboratory-associated persons (22.5%; p < 0.05) . CONCLUSION: Healthy individuals rarely carry oropharyngeal AGNB, suggesting effective oropharyngeal clearance in a healthy population predisposed to acquisition . Apparently, the oropharyngeal mucosa in healthy individuals is not receptive to adhesins of AGNB, resulting in rapid elimination of these bacteria.

Eur Radiol, 1999, 9(5), 886 - 9
Acute hepatobiliary tuberculosis: a report of two cases and a review of the literature; Hickey N et al.; Two cases of hepatobiliary tuberculosis are described . Case one, the macronodular type of hepatic tuberculosis, presented as pyrexia of unknown origin and was eventually diagnosed by sectional imaging when a mass lesion developed in the liver and aspiration revealed acid-fast bacilli . Case two presented with jaundice due to a hilar bile duct stricture . The patient was successfully treated by repeated bile duct stenting and later chemotherapy for tuberculosis . In both cases previous positive histology or culture would have expedited diagnosis and treatment . Acute hepatobiliary tuberculosis remains a rare disease . Suspicion of the disease and adequate biopsy are important to allow prompt appropriate treatment.

Surg Neurol, 1999 Jun, 51(6), 602 - 7
Atypical forms of spinal tuberculosis: case report and review of the literature; Naim-Ur-Rahman et al.; OBJECTIVE: The object of this report is to highlight some of the less known atypical features of spinal tuberculosis (TB) in the hope of facilitating early diagnosis . Pure neural arch and sacral TB is rare and the co-existence of these two as widely separated skip lesions in the same patient is even rarer . CLINICAL PRESENTATION: An unusual case of tuberculous process affecting the sacrum as well as the neural arches of upper cervical vertebrae is presented . Neither the clinical features nor the imaging techniques, including radiography, bone scintigraphy, computed tomography, and magnetic resonance imaging, were helpful in establishing the diagnosis . The destructive lesion of the sacrum with a rectally palpable presacral mass was thought to be a chordoma or chondrosarcoma until the patient developed upper cervical cord compression with an extradural myelographic block . Development of this second destructive lesion involving the posterior spinal elements (the neural arch) led to a diagnosis of malignant spinal metastasis . The true diagnosis was only revealed by the histology of the solid tumor-like extradural mass in the upper cervical region and demonstration of acid-fast bacilli (AFB) in the lesion . Anti-TB chemotherapy resulted in complete resolution of sacral and cervical lesions as well as the neurologic deficits . CONCLUSION: Differential diagnosis of the obscure spinal lesion should include tuberculosis, specifically the atypical forms; especially because complete cure is possible with early treatment and neurologic morbidity is high in neglected cases.

Am J Surg Pathol, 1999 Jun, 23(6), 656 - 61
Spindle cell tumors associated with mycobacteria in lymph nodes of HIV-positive patients: 'Kaposi sarcoma with mycobacteria' and 'mycobacterial pseudotumor'; Logani S et al.; Patients infected with HIV often have unusual manifestations of common infections and neoplasms . One such example is "mycobacterial pseudotumor," an exuberant spindle cell lesion induced in lymph nodes by mycobacteria . Kaposi sarcoma also produces a spindle cell proliferation in lymph nodes of HIV-positive patients . These two entities must be differentiated from one another because of differences in treatment and prognosis . We report here, however, three cases of intranodal Kaposi sarcoma with simultaneous mycobacterial infection, the occurrence of which has not been clearly documented . For comparison, we also studied three cases of mycobacterial pseudotumor, of which 14 cases have been described to date . There was considerable histologic overlap between these two lesions . Acid-fast bacilli were present in all cases, predominantly in the more epithelioid histiocytes in the cases of Kaposi sarcoma, and in spindle and epithelioid cells in the cases of mycobacterial pseudotumor . The morphologic features that favored Kaposi sarcoma over mycobacterial pseudotumor were the prominent fascicular arrangement of spindle cells and slitlike spaces, the lack of granular, acidophilic cytoplasm, and the presence of mitoses . Immunohistochemistry was a reliable adjunct study in the differential diagnosis, as the spindle cells in mycobacterial pseudotumor were positive for S-100 protein and CD68 whereas those of Kaposi sarcoma were CD31- and CD34-positive but negative for S-100 protein and CD68 . Awareness that Kaposi sarcoma may coexist with mycobacterial infection in the same biopsy specimen is important because these lesions may be misdiagnosed as mycobacterial pseudotumor . The clinical impact of distinguishing between Kaposi sarcoma with mycobacteria and mycobacterial pseudotumor is significant because the presence of Kaposi sarcoma alters treatment and prognosis.

Am J Pathol, 1999 Jun, 154(6), 1793 - 804
Immunohistological analysis of in situ expression of mycobacterial antigens in skin lesions of leprosy patients across the histopathological spectrum . Association of Mycobacterial lipoarabinomannan (LAM) and Mycobacterium leprae phenolic glycolipid-I (PGL-I) with leprosy reactions; Verhagen C et al.; The presence of mycobacterial antigens in leprosy skin lesions was studied by immunohistological methods using monoclonal antibodies (MAbs) to Mycobacterium leprae-specific phenolic glycolipid I (PGL-I) and to cross-reactive mycobacterial antigens of 36 kd, 65 kd, and lipoarabinomannan (LAM) . The staining patterns with MAb to 36 kd and 65 kd were heterogeneous and were also seen in the lesions of other skin diseases . The in situ staining of PGL-I and LAM was seen only in leprosy . Both antigens were abundantly present in infiltrating macrophages in the lesions of untreated multibacillary (MB) patients, whereas only PGL-I was occasionally seen in scattered macrophages in untreated paucibacillary lesions . During treatment, clearance of PGL-I from granulomas in MB lesions occurred before that of LAM, although the former persisted in scattered macrophages in some treated patients . This persistence of PGL-I in the lesions paralleled high serum anti-PGL-I antibody titers but was not indicative for the presence of viable bacilli in the lesions . Interestingly, we also observed a differential expression pattern of PGL-I and LAM in the lesions of MB patients with reactions during the course of the disease as compared with those without reactions . In conclusion, the in situ expression pattern of PGL-I and LAM in MB patients may assist in early diagnosis of reactions versus relapse.

Singapore Med J, 1999 Jan, 40(1), 44 - 5
Cutaneous tuberculosis mimicking cellulitis in an immunosuppressed patient; Chin PW et al.; A 28-year-old lady suffering from systemic lupus erythomatosus (SLE) with diffuse proliferative glomerulonephritis (DPGN) and who was on oral cyclophosphamide and prednisolone presented with left lower limb 'cellulitis' . The 'cellulitis' of the left lower limb failed to respond to usual antibiotics which prompted evaluation of the clinical diagnosis . The diagnosis is made based on the presence of granulomas, multinucleated giant cells and acid fast bacilli on the skin biopsy.

Cell Immunol, 1999 May 25, 194(1), 12 - 20
Differential regulation of IFN-gamma, TNF-alpha, and IL-10 production by CD4(+) alphabetaTCR+ T cells and vdelta2(+) gammadelta T cells in response to monocytes infected with Mycobacterium tuberculosis-H37Ra; Tsukaguchi K et al.; Mycobacterium tuberculosis bacilli readily activate CD4(+) and gammadelta T cells . CD4(+) and gammadelta T cells were compared for their ability to regulate IFN-gamma, TNF-alpha, and IL-10 production, cytokines with significant roles in the immune response to M . tuberculosis . PBMC from healthy tuberculin positive donors were stimulated with live M . tuberculosis-H37Ra . CD4(+) and gammadelta T cells were purified by negative selection and tested in response to autologous monocytes infected with M . tuberculosis . Both subsets produced equal amounts of secreted IFN-gamma . However, the precursor frequency of IFN-gamma secreting gammadelta T cells was half that of CD4(+) T cells, indicating that gammadelta T cells were more efficient producers of IFN-gamma than CD4(+) T cells . TNF-alpha production was markedly enhanced by addition of CD4(+) and gammadelta T cells to M . tuberculosis infected monocytes, and TNF-alpha was produced by both T cells and monocytes . No differences in TNF-alpha enhancement were noted between CD4(+) and gammadelta T cells . IL-10 production by M . tuberculosis infected monocytes was not modulated by CD4(+) or gammadelta T cells . Thus CD4(+) and gammadelta T cells had similar roles in differential regulation of IFN-gamma, TNF-alpha, and IL-10 secretion in response to M . tuberculosis infected monocytes . However, the interaction between T cells and infected monocytes differed for each cytokine . IFN-gamma production was dependent on antigen presentation and costimulators provided by monocytes . TNF-alpha levels were increased by addition of TNF-alpha produced by T cells and IL-10 production by monocytes was not modulated by CD4(+) or gammadelta T cells .

Kekkaku, 1999 Apr, 74(4), 377 - 84
{Nontuberculous mycobacteriosis; the present status of epidemiology and clinical studies}; Sakatani M; In Japan, The Mycobacteriosis Research Group at the Japanese National Chest Hospitals has continuously made the clinico-epidemiological study of nontuberculous mycobacteriosis (NTM) since early 1970s . The prevalence rate was determined as 0.82, 0.91, 1.22, 1.74 and 2.43 per 100,000 population per year in 1971, 1975, 1980, 1985 and in 1990 respectively . The newest datum in 1997 was 3.52 . These data indicates the prevalence rate has continuously increased and became 3.8 times than 25 years ago . While on the other hand, the prevalence rate of lung tuberculosis has decreased from 133.1 to 15.2, becoming one nines in the same period . The numbers of newly detected patients of lung mycobacteriosis in 1996 were also studied at 12 hospitals in Kinki district . The rate of NTM was 16.6% in 4 sanatorium hospitals, being about the same to the datum of The Mycobacteriosis Research Group . The rate of NTM in 8 general hospitals was surprisingly high, 40.0% . The 70% of NTM patients were infected with Mycobacterium avium complex (MAC) . The 24% were with M . kansasii, and the only 6% were with other miscellaneous species . That is, the about one thirds or more of total NTM patients were female MAC desease patients, another one thirds or less were male MAC patients, and the more than 90% of M . kansasii patients (about one fourth of total patients) were male . These 3 groups took the most part of NTM patients . The rate of female MAC patients with small non-cavitary lesion without underlying diseases showed a tendency to increase, and the rate of male MAC patients with cavitary lesions with underlying lung or systemic diseases decreased . In 1997, American Thoracic Society (ATS) published the official statement about the diagnosis and treatment of NTM disease . The table-1 in that statement showed the new criteria for diagnosis of NTM pulmonary disease . It is useful for precise diagnosis of lung NTM disease, and the old criteria made by The Mycobacteriosis Research Group of the Japanese National Chest Hospitals is also useful for rough diagnosis . In the ATS statement, for adult HIV-negative MAC patients, minimum three drug regimen of clarithromycin (or azithromycin), rifabutin (or rifampin) and ethambutol, with intermittent streptomycin which is option for extensive disease, is recommended . This regimen is the same that most of the Japanese specialists for NTM disease recommended . The follow-up study of 47 Japanese MAC patients treated by the regimen contained clarithromycin with other anti-tuberculous drugs revealed that 80% of cases converted into bacilli negative and that the regimen had durable effect for at least 24 months . The resectional surgery may be considered for localized disease, and supportive nutritional treatment must also be considered for the MAC patients to whom the drug therapy was not effective, as if for the tuberculosis patients of multi-drug resistant.

Kekkaku, 1999 Apr, 74(4), 361 - 4
{A case of pulmonary tuberculosis case with pancytopenia accompanied to bone marrow gelatinous transformation}; Sasaki Y et al.; A 45-year-old man did not visit a doctor in spite of his complains, cough and sputum lasting, for six months, and he finally could not eat without beer, and as a result, he lost his body weight and currently 52 kg . He became unconsciousness, was carried to a hospital, and was referred to our hospital . His sputum examination for acid fast bacilli was smear positive, Gaffky 6, for M . tuberculosis . His chest roentogenogram revealed large cavitary lesions in bilateral lung fields . On blood examination, WBC was 1100/microL, RBC was 256 x 10(4)/microL, and PLT was 13.4 x 10(4)/microL . Total protein was 4.7 g/dl, albumin was 1.9 mg/dl, and total cholesterol was 65 mg/dl . We tried to aspirate bone marrow from his sternum, but it was impossible . Hence we did biopsy of his ilium . The pathology of his bone marrow revealed gelatinous transformation . It was thought that the marked delay in visiting a doctor caused general consumption and loss of apetite, thus led to gelatinous transformation and finally pancytopenia.

Kekkaku, 1999 Apr, 74(4), 353 - 60
{Six-months chemotherapy (2HRZS or E/4HRE) of new cases of pulmonary tuberculosis--six year experiences on its effectiveness, toxicity, and acceptability}; Wada M et al.; The incidence of tuberculosis in Japan, 33.7 per 100,000 in 1997, is very high compared with USA or Western European countries . The decrease in the incidence has slowed down from the early 1980s, and the average annual rate of decrease has been 3.8% in the last 5 years . About 9 percent of tuberculosis patients defaulted from the nine-month regimen (6HRS or E/3HR) in urban areas . Regimens shorter than nine-month are needed to achieve high effectiveness of tuberculous chemotherapy . Out of 1128 new pulmonary tuberculosis patients, six-hundred twenty started treatment with six-month (2HRZS or E/4HRE) in Fukujuji Hospital, JATA, in Tokyo from January 1991 to December 1996 . Out of 620, four-hundred twenty eight were both smear and culture positive, 136 were smear negative and culture positive and 56 were bacilli negative . Out of 564 bacilli positive cases, 530 were susceptible to INH and RFP . Out of 530 drug susceptible cases three hundred ninety-three patients completed the regimen . Ninety-three percent of these patients had converted to negative at two months of chemotherapy and all of them at five months . Out of 450, two-hundred ninety five completed 6-month regimen, one-hundred fifty-five were changed their regimen or prolonged duration of chemotherapy . Out of 295, nine patients (3.1%) relapsed after the completion of 6-month chemotherapy . Mean follow-up period was 17.2 months and the median was 15.5 months . The relapse rate was 2.2 per 100 person-years . Six of the relapsed cases were complicated with Diabetes Mellitus . Relapse rate was higher in patients with Diabetes Mellitus than in patients without (6/54, 7.9 per 100 person-years vs 3/237, 0.8 per 100 person-years) (p < 0.001) . Drug-induced hepatotoxicity was defined as elevated serum transaminase level with clinical symptoms of hepatitis or elevated serum transaminase level more than 5 times of upper limit of normal range with or without symptoms . Drug-induced hepatotoxicity developed in 43 (8.0%) of 535 with initial normal liver function test results, this rate was similar to that in patients treated with nine-month regimen (34/420, 8.1%) . But the frequency of hepatotoxicity of more than 400 IU/ml of serum transaminase level was higher in patients treated with PZA-containing regimen than with nine-month regimen (16/536, 3.0% vs 4/420, 1.0%), but this deference was not statistically significant . Hepatotoxicity developed in 13/85 (15.3%) of patients treated with PZA-containing regimen with abnormal liver function tests at the beginning of chemotherapy, and this frequency was similar to 7/65 (10.8%) in patients with nine-month regimen . The relapse rate in patients with Diabetes Mellitus was statistically higher than in without Diabetes Mellitus (7.9 vs 0.8 per 100 person-years) . We concluded that the six-month regimen was highly effective, but the frequency of severe hepatotoxicity was relatively higher than in nine-month regimen and the duration of chemotherapy was not enough for patients complicated with Diabetes Mellitus . Further study is needed for sufficient chemotherapy in patients with Diabetes Mellitus.

Pneumonol Alergol Pol, 1998, 66(7-8), 404 - 11
{Analysis of tuberculosis mortality in the Toruń province in the years 1990-1993}; Sipak M et al.; There were 75 deaths from tuberculosis in Torun Vojevodship province in 1990-1993 . In 26 of them the diagnosis was made only after death during the autopsy examination and/or by positive culture for tubercle bacilli . In 27 patients diagnosis of tuberculosis was made very late, 15 days before death in 12, and 30 days in other 15 patients . In 19 patients the diagnosis was made 30 days or more before death . In majority of them, however, the treatment was interrupted or taken irregularly . We conclude that the main cause of death from tuberculosis in Torun province in the years 1990-1993 was the late diagnosis . The late diagnosis of tuberculosis was established mainly in those who died at home and also in those who were admitted to hospital in critical state and died during the first two weeks of hospitalization.

Neurogastroenterol Motil, 1999 Jun, 11(3), 141 - 61
The patterns of small bowel motility: physiology and implications in organic disease and functional disorders; Husebye E; The physiology and pathophysiology of small bowel motility are reviewed with particular focus on the motility patterns and periods that are detected by intraluminal manometry . Motility patterns are groups of phasic pressure waves resulting from contractions of the circular muscle layer of the small bowel that are organized by the enteric nervous system . Phase III of the migrating motor complex, the hallmark of the fasting motility period, thus reflects enteric neuromuscular function . Response to meal challenge also involves the CNS, reflexes beyond the gut and endocrine responses . Although specific disease diagnosis cannot be made by motility studies of the small bowel, the functional integrity is revealed . The normal occurrence of the essential patterns and periods of motility and the absence of distinctly abnormal patterns evidence preserved function, whereas the opposite indicates clinically significant dysmotility . Certain motility patterns are occasionally seen both in health and disease, and increased prevalence indicates a moderate dysfunction of yet unclear significance . Bacterial overgrowth with Gram-negative bacilli is the consequence of severe small bowel dysmotility, and a diagnosis that can be predicted by a motility study . Testing can be useful in the clinical management of paediatric and adult patients also by predicting the prognosis and response to enteral nutrition and medical therapy . Further studies are, however, needed to take full advantage of motility testing in clinical practise.

J Vet Diagn Invest, 1999 May, 11(3), 252 - 8
Isolation of cilia-associated respiratory (CAR) bacillus from pigs and calves and experimental infection of gnotobiotic pigs and rodents; Nietfeld JC et al.; Filamentous, gram-negative bacteria morphologically similar to cilia-associated respiratory (CAR) bacillus of rodents and rabbits were isolated from the tracheas of 5 pigs and 4 calves . All pigs but none of the calves had histologic lesions of chronic tracheitis . In silver-stained histologic sections, CAR bacilli were adhered to the tracheal epithelium of each pig but were not found in the calves . Like CAR bacillus of rats, the bacteria displayed gliding motility and grew only in cell culture or cell culture medium supplemented with fetal serum . Initially, all isolates were contaminated by Mycoplasma spp . This contamination was eliminated from 4 pig isolates by limiting dilutions, and mycoplasma-free isolates were used to intranasally inoculate gnotobiotic pigs and CAR bacillus-free mice and rats and to immunize guinea pigs . The gnotobiotic pigs remained healthy, and when they were necropsied 4 and 7 weeks after infection no macroscopic or microscopic lesions were found in the respiratory tract . However, CAR bacillus was isolated at both times from the nasal cavities and tracheas of inoculated pigs, and the ciliated tracheal epithelium of infected pigs necropsied 7 weeks after infection was colonized by low numbers of CAR bacillus-like bacteria . The rats and mice remained healthy through week 12 postinoculation, and evidence of short- or long-term colonization was not detected by histologic examination or culture . When used as primary antibody for immunohistochemical staining, sera from guinea pigs immunized with pig CAR bacillus specifically stained CAR bacilli colonizing the respiratory epithelium of naturally infected pigs, whereas sera collected prior to immunization failed to react with the bacteria . These results indicate that CAR bacilli are unlikely to be primary pathogens of pigs or cattle and that rodents do not act as reservoirs.

Infect Control Hosp Epidemiol, 1999 May, 20(5), 337 - 40
Trends in compliance with the guidelines for preventing the transmission of Mycobacterium tuberculosis among New Jersey hospitals, 1989 to 1996; Manangan LP et al.; OBJECTIVE: To determine trends in compliance with the guidelines for preventing the transmission of Mycobacterium tuberculosis in healthcare facilities among New Jersey hospitals from 1989 through 1996 . DESIGN: A voluntary questionnaire was sent to all 96 New Jersey hospitals in 1992 . The 53 that responded were resurveyed in 1996 . RESULTS: Of the 96 hospitals surveyed in 1992, 53 (55%) returned a completed questionnaire; 33 (64%) were community, nonteaching hospitals . In 1991, patients with tuberculosis (TB) were admitted at 38 (72%) of 53 hospitals, and from 1989 through 1991, patients with multidrug-resistant (MDR) TB were admitted at 15 (29%) of 52 hospitals . Twenty-nine (57%) of 51 reported having rooms meeting the Centers for Disease Control and Prevention (CDC) criteria for acid-fast bacilli (AFB) isolation . A nonfitted surgical mask was used as a respiratory protective device by healthcare workers (HCWs) at 28 (55%) of 51 hospitals . Attending physicians were included in tuberculin skin-testing (TST) programs at 5 (11%) of 45 hospitals . In the 1996 resurvey, 48 (94%) of 53 surveyed hospitals returned a completed questionnaire; 34 (81%) of 42 had TB patient admissions, and 4 (9%) of 43 had MDR TB patient admissions in 1996 . Forty-five (96%) of 47 reported having rooms that met CDC criteria for AFB isolation . N95 respiratory devices were used by HCWs at 45 (94%) of 48 hospitals . Attending physicians were included in the TST programs at 22 (54%) of 41 hospitals . CONCLUSION: New Jersey hospitals have made improvements in availability of AFB isolation rooms, use of proper respiratory protective devices, and expansion of TST programs for HCWs from 1989 through 1996.

Int J Lepr Other Mycobact Dis, 1998 Dec, 66(4), 464 - 74
Susceptibility to Mycobacterium leprae of ALY (alymphoplasia) mice and IFN-gamma induction in the culture supernatant of spleen cells; Yogi Y et al.; The aly/aly (alymphoplasia) mice from a mutation of a colony of the C57BL/6J mouse strain, which has a systemic absence of lymph nodes and Peyer's patches, are deficient in both T- and B-cell-mediated immune functions . We have undertaken a comparison of susceptibility to Mycobacterium leprae of ALY (aly/aly, aly/+) mice with C57BL/6J mice . The aly/aly mouse was found to have an excellent high susceptibility to M . leprae with no distinction between female and male . The aly/+ mouse also was more susceptible to M . leprae at an earlier stage than the C57BL/6J mouse . Therefore, we examined and compared the cytokine gene expression and gamma interferon (IFN-gamma) induction in the splenocytes of ALY mice . The expression of interleukin 4 (IL-4), IL-10 and IL-12 mRNA was weakly stimulated with ML-lysate in inoculated aly/aly mice but IL-2, IL-6, IGIF/IL-18 and IFN-gamma mRNA were not observed . None of the cytokine genes used appeared, except the mRNA for IL-1-alpha, when uninfected cultured spleen cells were stimulated with ML-lysate . Also, IFN-gamma production was not induced . However, the appearance of these cytokine genes was observed when stimulated with concanavalin A (ConA), and IFN-gamma production was also induced in the culture supernatant by aly/+ and even aly/aly mice stimulated with ConA . To examine the reason why IFN-gamma cannot be produced by splenocytes of ALY mice inoculated with M . leprae, we detected cytokine gene expression and IFN-gamma induction in the presence of recombinant murine IL-12 or IGIF/IL-18 . IL-2 mRNA expression was detected in all of the mice tested in the presence of IL-12 but not in aly/aly mice under IGIF/IL-18, and iNOS mRNA expression was not observed in aly/aly mice under IL-12 or IGIF/IL-18 . IL-4 and IL-10 mRNA were detected by aly/aly mice only by exposure to IGIF/IL-18 . In culture, the supernatant with ML antigens of the aly/aly mice did not produce IFN-gamma in spite of the presence of IL-12 and IGIF/IL-18, while IFN-gamma was weakly induced in aly/+ mice stimulated with ML-lysate and in the presence of IGIF/IL-18 . Nevertheless, IFN-gamma production was observed in splenocytes of the aly/aly mice stimulated with ConA and also with IGIF/IL-18 plus anti-CD3 antibody . Our results suggest that ALY mice might be showing a high susceptibility to M . leprae because of deficient priming for activation of T cells with the leprosy bacilli infection . Moreover, it is possible that the phagocytic activities of the macrophages of ALY mice are also impaired.

Int J Clin Pract, 1999 Jan-Feb, 53(1), 77 - 9
An unusual case of ileocaecal tuberculosis in an 80-year-old Caucasian male; Kelly J et al.; An 80-year-old Caucasian male presented with a seven-week history of diarrhoea and weight loss . Distal duodenal biopsies showed partial villous atrophy but he failed to respond to a gluten-free diet . Subsequently he developed a right iliac fossa mass associated with radiological evidence of ileocaecal ulceration . Colonoscopic biopsies from the caecum showed non-caseating granulomata and Ziehl-Neelsen (ZN) staining and culture for acid-fast bacilli (AFB) were negative . Crohn's disease was diagnosed and he was started on steroids . Although he showed an initial response, his condition then deteriorated and he died after six weeks . ZN staining of tissue at postmortem showed AFBs . Although a rare diagnosis in the UK, a high index of suspicion should be maintained for ileocaecal TB in patients with appropriate clinical features, even if classical risk factors for TB are absent.

Diagn Microbiol Infect Dis, 1999 May, 34(1), 45 - 50
Blood and charcoal added to acidified agar media promote the growth of Mycobacterium genavense; Realini L et al.; Ten different agar media were tested for the in vitro growth of Mycobacterium genavense in primary cultures and in subcultures from BACTEC vials . These agar media were based on Middlebrook 7H9, 7H10 and 7H11, and supplemented with additives: mycobactin J, yeast extract, charcoal, or defibrinated sheep blood . Some media were acidified with phosphoric acid to a final pH of 6.2 +/- 0.2 . Fourteen M . genavense strains from nude mouse organs as well as one decontaminated clinical specimen (from a bird) were tested . The optimal medium for primary cultures of M . genavense was Middlebrook 7H11 acidified to pH 6.2 +/- 0.2 and supplemented with charcoal and sheep blood: on this medium, all strains produced colonies within 6-12 weeks of incubation in numbers approaching the number of bacilli inoculated . It was also the only medium to support the growth of the decontaminated clinical specimen . Added blood and charcoal appeared not as essential for subcultures as for primary cultures . Three media supported the growth of all strains within 1 month incubation: they were acidified, and were supplemented with yeast extract or pancreatic digest of casein, and with either blood or charcoal.

Am J Respir Cell Mol Biol, 1999 Jun, 20(6), 1260 - 7
Ovalbumin (OVA) and Mycobacterium tuberculosis bacilli cooperatively polarize anti-OVA T-helper (Th) cells toward a Th1-dominant phenotype and ameliorate murine tracheal eosinophilia; Sano K et al.; A recent increase in allergic disorders has coincided with a decrease in infections, including tuberculosis . Although an inverse association between tuberculin responses and atopic disorders was reported, it was not known how T-helper (Th)1-biased immune responses to Mycobacterium tuberculosis influenced Th2-dominant responses to allergens . We examined whether M . tuberculosis could modulate ovalbumin (OVA)-induced eosinophilic inflammation in the murine trachea in a manner that transcended the barrier of antigen specificity . We found that CD4(+) T cells primed with OVA in complete Freund's adjuvant (CFA) inhibited OVA-induced tracheal eosinophilia through interferon (IFN)-gamma secretion . Immunization with an irrelevant antigen in CFA or with OVA in incomplete Freund's adjuvant failed to induce suppressor cells . In vitro experiments confirmed that both M . tuberculosis and OVA (as opposed to either one alone) were necessary to evoke polarized development toward a Th1-like phenotype through interleukin-12 secretion . These results indicate that exposure to an allergen along with M . tuberculosis switches development of allergen-specific T cells toward a Th1 phenotype, which, in turn, downregulates allergic manifestations in an antigen-specific manner . The possible implications of these results are discussed in the context of the causal relationship between a decrease in tuberculosis and an increase in allergic disorders.

J Fr Ophtalmol, 1999 Apr, 22(3), 371 - 6
{Bacillary endophthalmitis . Four case reports}; Maucour MF et al.; PURPOSE: Bacillary endophthalmitis occurring after penetrating ocular trauma with an intraocular foreign body is always associated with poor visual outcome . Bacilli cause fulminant infection associated with tissue damage in the intraocular structures . CASE REPORTS: Our series consisted of four patients with penetrating ocular trauma and endophthalmitis caused by B . cereus or B . licheniformis . Three eyes ultimately developed phtisis . Only on eye recovered good vision (2.5/10 P4) . DISCUSSION: Recommended early treatment includes topical, subconjunctival, parenteral antibiotics . A review of the literature indicates that intravitreal antibiotic infusion is crucial for sufficient concentration to control infection . Early vitrectomy is recommended in the management of endophthalmitis . Vitreous and intraocular foreign bodies should be cultured to identify pathogens and ascertain antibiotic susceptibilities.

J Allergy Clin Immunol, 1999 May, 103(5 Pt 1), 789 - 95
Diagnostic criteria for sarcoidosis of the sinuses; deShazo RD et al.; BACKGROUND: Although newer technologies facilitate its diagnosis and treatment, little is known about sarcoidosis of the paranasal sinuses . OBJECTIVES: We sought to better characterize sarcoidosis of the sinuses and establish criteria for diagnosis . METHODS: Case-finding criteria were established, and over 50 reports of sarcoidosis of the sinuses in the medical literature were reviewed . Nine case reports of patients fulfilling the case-finding criteria were identified, as were 6 additional patients from our clinics . RESULTS: Nasal obstruction and chronic sinusitis were the usual initial complaints from patients and were associated with mucosal crusting, studding, plaque-like changes, or polyps in the nose in 5 of 6 of our patients . The most consistent finding in nose and sinuses was an erythematous, edematous, friable, hypertrophied mucosa . Like 5 of 6 of our patients, most patients had extra-pulmonary sarcoidosis involving multiple organs, but some had isolated upper respiratory disease . Radiologic studies showed extensive and often complete opacification of the sinuses and nose similar to that seen in diffuse polyposis associated with chronic bacterial and fungal sinusitis . No specific histopathologic findings distinguished sinus disease from those reported with pulmonary involvement . Pharyngeal involvement was present in 2 case reports and caused the apparent asphyxiation of 1 of our patients . CONCLUSION: Sarcoidosis of the sinuses should be considered in the differential diagnosis of sinusitis, especially in association with nasal polyposis, even when the sarcoidosis has not been otherwise diagnosed . On the basis of this experience, we propose diagnostic criteria for sarcoidosis of the sinuses . These include (1) radiologic evidence of sinusitis, (2) histopathologic confirmation of noncaseating granuloma in the sinus tissue supported by negative stains for fungus and acid-fast bacilli, (3) negative serologic test results for syphilis and antineutrophil cytoplasmic antibodies, and (4) no clinical evidence of other disease processes associated with granulomatous nasal and sinus inflammation . These criteria will provide the basis for further studies to assess both the natural history and the effectiveness of treatment in sarcoidosis of the sinuses.

Am J Pathol, 1999 May, 154(5), 1611 - 20
Localization of Mycobacterium leprae to endothelial cells of epineurial and perineurial blood vessels and lymphatics; Scollard DM et al.; Infection of peripheral nerve by Mycobacterium leprae, the histopathological hallmark of leprosy, is a major factor in this disease, but the route and mechanisms by which bacilli localize to peripheral nerve are unknown . Experimentally infected armadillos have recently been recognized as a model of lepromatous neuritis; the major site of early accumulation of M . leprae is epineurial . To determine the epineurial cells involved, 1-cm segments of 44 nerves from armadillos were screened for acid-fast bacilli and thin sections were examined ultrastructurally . Of 596 blocks containing nerve, 36% contained acid-fast bacilli . Overall, M . leprae were found in endothelial cells in 40% of epineurial blood vessels and 75% of lymphatics, and in 25% of vessels intraneurally . Comparison of epineurial and endoneurial findings suggested that colonization of epineurial vessels preceded endoneurial infection . Such colonization of epineurial nutrient vessels may greatly increase the risk of endoneurial M . leprae bacteremia, and also enhance the risk of ischemia following even mild increases in inflammation or mechanical stress . These findings also raise the possibility that early, specific mechanisms in the localization of M . leprae to peripheral nerve may involve adhesion events between M . leprae (or M . leprae-parasitized macrophages) and the endothelial cells of the vasa nervorum.

J Clin Microbiol, 1999 Jun, 37(6), 2016 - 9
Species-specific identification of Mycobacterium leprae by PCR-restriction fragment length polymorphism analysis of the hsp65 gene; Rastogi N et al.; PCR-restriction fragment length polymorphism analysis (PRA) of the hsp65 gene present in all mycobacteria was used in the present investigation to characterize Mycobacterium leprae . Bacilli were extracted and purified from different organs from experimentally infected armadillos and nude mice (Swiss mice of nu/nu origin) . A total of 15 samples were assayed in duplicate, and the results were compared with those obtained for a total of 147 cultivable mycobacteria representing 34 species . Irrespective of its origin or viability, M . leprae strains from all the samples were uniformly characterized by two fragments of 315 and 135 bp upon BstEII digestion and two fragments of 265 and 130 bp upon HaeIII digestion . PRA is a relatively simple method and permits the conclusive identification of M . leprae to the species level.

J Am Geriatr Soc, 1999 May, 47(5), 539 - 46
Community-acquired pneumonia in the intensive care unit: epidemiological and prognosis data in older people; Leroy O et al.; OBJECTIVES: To compare epidemiological data, etiology, and prognosis of severe community-acquired pneumonia (CAP) in the intensive care unit (ICU) according to age (< or > or = 65 years) and to determine prognostic factors of CAP in older people . DESIGN: A retrospective (1987-1992) and prospective (1993-95) multicenter study . SETTING: Six ICUs in the north of France . PATIENTS: Five hundred five patients admitted to an ICU for severe CAP . MEASUREMENTS: Patient characteristics were compared with regard to age . Prognosis of CAP in older patients was studied by stepwise discriminant analysis . RESULTS: Two hundred seventy-eight patients (55%) were aged 65 years or older . Comparison of epidemiological data between older and younger patients revealed a higher prevalence of women (38% vs 29%), more severe underlying comorbidities (anticipated death within 5 years: 59% vs 26%), and more frequent chronic respiratory insufficiency (48% vs 33%) in the older patients . In this study group, 224 organisms were isolated from 172 patients (62%); those identified most frequently were Gram-negative bacilli (34%), S . pneumoniae (32%), and Staphylococcus sp . (19%) . Compared with younger patients, no significant differences in bacteriological data were observed . However, crude and attributable mortality rates were significantly higher in the older patients (33% vs 21% and 30% vs 19%, respectively) . Prognosis analysis identified four independent predictors of mortality in the older patients: initial septic shock (relative risk (RR) = 3), sepsis-related complications (RR = 4.3), hospital-acquired lower respiratory tract superinfections (RR = 2), and nonspecific pneumonia-related complications (RR = 2.8) . CONCLUSION: The bacterial etiology provides some approaches to empirical therapy for older patients with severe community-acquired pneumonia . In addition, the inappropriateness of withholding intensive care for reasons of age alone is emphasized.

Mol Microbiol, 1999 May, 32(3), 643 - 55
Identification of variable regions in the genomes of tubercle bacilli using bacterial artificial chromosome arrays; Gordon SV et al.; Whole-genome comparisons of the tubercle bacilli were undertaken using ordered bacterial artificial chromosome (BAC) libraries of Mycobacterium tuberculosis and the vaccine strain, Mycobacterium bovis BCG-Pasteur, together with the complete genome sequence of M . tuberculosis H37Rv . Restriction-digested BAC arrays of M . tuberculosis H37Rv were used in hybridization experiments with radiolabelled M . bovis BCG genomic DNA to reveal the presence of 10 deletions (RD1-RD10) relative to M . tuberculosis . Seven of these regions, RD4-RD10, were also found to be deleted from M . bovis, with the three M . bovis BCG-specific deletions being identical to the RD1-RD3 loci described previously . The distribution of RD4-RD10 in Mycobacterium africanum resembles that of M . tuberculosis more closely than that of M . bovis, whereas an intermediate arrangement was found in Mycobacterium microti, suggesting that the corresponding genes may affect host range and virulence of the various tubercle bacilli . Among the known products encoded by these loci are a copy of the proposed mycobacterial invasin Mce, three phospholipases, several PE, PPE and ESAT-6 proteins, epoxide hydrolase and an insertion sequence . In a complementary approach, direct comparison of BACs uncovered a third class of deletions consisting of two M . tuberculosis H37Rv loci, RvD1 and RvD2, deleted from the genome relative to M . bovis BCG and M . bovis . These deletions affect a further seven genes, including a fourth phospholipase, plcD . In summary, the insertions and deletions described here have important implications for our understanding of the evolution of the tubercle complex.

Proc Natl Acad Sci U S A, 1999 May 11, 96(10), 5657 - 62
Tumor necrosis factor alpha is a determinant of pathogenesis and disease progression in mycobacterial infection in the central nervous system; Tsenova L et al.; The pathogenesis of tuberculous meningitis, a devastating complication of tuberculosis in man, is poorly understood . We previously reported that rabbits with experimental tuberculous meningitis were protected from death by a combination of antibiotics and thalidomide therapy . Survival was associated with inhibition of tumor necrosis factor alpha (TNF-alpha) production by thalidomide . To test whether cerebrospinal fluid (CSF) levels of TNF-alpha correlated with pathogenesis, the response of rabbits infected in the central nervous system (CNS) with various mycobacterial strains was studied . CNS infection with Mycobacterium bovis Ravenel, M . bovis bacillus Calmette-Guerin (BCG) Pasteur, and M . bovis BCG Montreal were compared . M . bovis Ravenel induced the highest levels of TNF-alpha in the CSF in association with high leukocytosis, protein accumulation, and severe meningeal inflammation . BCG Pasteur had intermediate effects, and BCG Montreal was the least virulent . In addition, M . bovis Ravenel numbers were highest in the brain and CSF and the bacilli also disseminated more efficiently to distant organs, compared with BCG Pasteur and BCG Montreal . In subsequent experiments, rabbits were infected with either recombinant M . bovis BCG Montreal (vector), or BCG Montreal expressing the murine gene for TNF-alpha (BCG mTNF-alpha) . BCG Montreal was rendered virulent by the expression of murine TNF-alpha, as demonstrated by high CSF leukocytosis, high protein accumulation, severe meningeal inflammation, persistent bacillary load, and progressive clinical deterioration . Taken together, these results demonstrate that the level of TNF-alpha produced during mycobacterial CNS infection determines, at least in part, the extent of pathogenesis.

Nurs Clin North Am, 1999 Jun, 34(2), 427 - 42
Emerging infectious diseases and pathogens; Chou T; Emerging infectious diseases are caused by old, new, and mutant microorganisms . Emergence of these pathogens can be attributed to changes in the characteristics and risk factors of patients, the widespread use of antibiotics, changes in the environment, the role of xenotransplantation, and international travel . In the United States, the incidences of C . difficile, cyclosporiasis, enterohemorrhagic E . coli gastroenteritis, Hantavirus, hepatitis C virus infection, and Lyme disease have increased significantly over the past two decades . Malassezia pachydermatis, extended spectrum beta lactamase (ESBL), Gram negative bacilli, and antibiotic resistant Enterococci, S . aureus, S . pneumoniae, and M . tuberculosis have also emerged prominently . Although not yet seen in the United States, variant Creutzfeldt-Jakob disease has made a great emotional impact on this country . Identifying, treating, and controlling emerging infectious disease and pathogens have created enormous challenges.

Mikrobiologiia, 1998 Nov-Dec, 67(6), 788 - 91
{Defective pages as an antagonistic factor in closely-related bacilli}; Lotareva OV et al.; The antagonistic effect produced by the detective phage PBSX during cocultivation of the mutant strain B . subtilis 168, in which this phage is heat-inducible, and strain B . subtilis NRS231, which also bears a defective phage, was investigated . As soon as in the first hours of cocultivation under conditions of PBSX induction, the number of viable cells of strain NRS231 decreased by two orders of magnitude . However, the effect was not observed if the temperature of cocultivation was noninducing . The results confirm the supposition that defective phages may play a role in the competition between closely related bacilli.

Arch Histol Cytol, 1999 Mar, 62(1), 83 - 95
Roles of a macrophage receptor with collagenous structure (MARCO) in host defense and heterogeneity of splenic marginal zone macrophages; Ito S et al.; Class A type I and type II macrophage scavenger receptors (MSR-A) and a macrophage receptor with collagenous structure (MARCO) are trimeric membrane glycoproteins mediating the uptake of chemically modified low density lipoproteins . MSR-A is expressed constitutively in several tissue macrophages and in liver sinusoidal endothelial cells, whereas MARCO is expressed constitutively in splenic marginal zone macrophages and in macrophages and endothelial cells in the lymphatic medullary sinuses of lymph nodes . The administration of LPS, zymosan, BCG, or L . monocytogenes to mice resulted in marked and transient MARCO expression and in the upregulation of MSR-A expression in the liver and spleen . In osteopetrotic (op) mutant mice defective in the production on M-CSF, ER-TR9-positive marginal zone macrophages and MOMA-1-positive marginal metallophilic macrophages were absent, whereas MARCO-expressing marginal zone macrophages were present, indicating the heterogeneity of marginal zone macrophages . Intravenous administration of BCG resulted in marked accumulation of BCG bacilli in the both marginal zone macrophages and marginal metallophilic macrophages in littermate control mice . In contrast, BCG bacilli were incorporated almost exclusively by MARCO-expressing marginal zone macrophages in op/op mice . These results indicate that MARCO is not only expressed constitutively in specific macrophage subpopulations but is also induced by various bacterial antigens and plays a role in host defense against bacteria.

Postgrad Med, 1999 Apr, 105(4), 117 - 24
Severe pneumonia . When and why to hospitalize; Kohler RB; Relatively simple objective criteria are now available to predict which patients are at risk for bad outcomes from community-acquired pneumonia . In general, these include older patients and those with certain coexisting illnesses (especially neoplastic disease) or findings of altered mental status, hypotension, severe tachycardia, tachypnea, fever, acidemia, azotemia, hypoxemia, hyperglycemia, anemia, or hyponatremia . The major causes of severe pneumonia are S pneumoniae, H influenzae, and L pneumophila . Less common causes include mixed aerobic and anaerobic mouth flora, as well as M pneumoniae, C pneumoniae, gram-negative bacilli, and S aureus . Specific diagnosis is hampered by a lack of reliable diagnostic tests, but Gram's stain of expectorated sputum and cultures of sputum and blood may occasionally be helpful . Many empirical treatment regimens have been recommended, including those of the American Thoracic Society and the Infectious Diseases Society of America, which are reviewed here . It is hoped that better diagnostic tools will permit future targeting of microbes with narrow-spectrum therapy to diminish the risk of selection of resistant strains with empirical regimens.

Monaldi Arch Chest Dis, 1999 Feb, 54(1), 49 - 54
The Italian AIPO study on tuberculosis treatment results, report 1995 . National AIPO "Tuberculosis" Study Group; Ambrosetti M et al.; In Italy, no national data on tuberculosis (TB) treatment results were available . In 1995, the AIPO (Italian Association of Hospital Pneumologists) TB Study Group, in collaboration with the Istituto Superiore di Sanita (technical branch of the Ministry of Health), started a prospective monitoring activity based on World Health Organization (WHO) and International Union against Tuberculosis and Lung Disease (IUATLD) recommendations . Data were collected from a nationwide network of 41 TB units, managing a significant proportion of all TB cases notified in Italy each year . The aim of this study was to analyse the case findings and treatment results for the year 1995 . Seven hundred and seventy eight TB cases were reported (59% males; 21% immigrants), 640 (82%) being new cases . Of these cases, 517 (66%) were pulmonary, 239 (31%) extrapulmonary and 22 (3%) both pulmonary and extrapulmonary . The main risk factors for TB were a history of recent contact and alcohol abuse among native Italians and human immunodeficiency virus-seropositive status among immigrants . The majority of immigrants were from Africa and South America, and had been in Italy > 24 months before diagnosis of TB . Thirty-seven per cent of patients had a positive direct sputum smear examination for alcohol acid-fast bacilli; 20% were resistant to any drug (monoresistance to isoniazid 3.5%; multidrug resistance 5.2%) . In 95% of cases, the duration of treatment was < 12 months . The overall success rate (cured plus treatment completed) was 81.1% . A significantly higher percentage of deaths was found in native Italians (being age-related), whereas immigrants had a higher default rate.

Kansenshogaku Zasshi, 1999 Feb, 73(2), 130 - 7
{Computed tomography with normal chest radiography in childhood tuberculosis}; Katakura S et al.; During the recent 2 years we experienced 5 children (2 months-5 years old) with lung tuberculosis, all of whom had positive tuberculin skin-tests, and were in close contact with their family members who had active tuberculosis . However, no abnormal findings on chest X-ray films were pointed out by 2 independent roentogenologists, and no increased levels of inflammatory markers including WBC numbers, CRP, and ESR were detected in all but one child . Moreover, mycobacterial examination of sputa and/or gastric aspirates by microscope, culture technique, and PCR amplification revealed no causative bacilli in 4 children . To clarify whether these children were affected by Mycobacterium tuberculosis, chest CT scan was applied . Surprisingly, all 5 children were revealed to have abnormal changes including primary complexes in the lung field . Taken together, it is important to pursuit the apparent lung tuberculosis in children with a positive family history and positive tuberculin skin-test.

Mol Cell Probes, 1999 Apr, 13(2), 115 - 26
PCR-restriction endonuclease analysis for identification and strain typing of Mycobacterium avium subsp . paratuberculosis and Mycobacterium avium subsp . avium based on polymorphisms in IS1311; Marsh I et al.; Point mutations in the IS 1311 sequences from sheep and cattle strains of Mycobacterium avium subsp . paratuberculosis (M . paratuberculosis) and M . avium subsp . avium (M . avium) were targeted to develop a polymerase chain reaction (PCR) that would be useful in the diagnosis and control of Johne's disease . Candidate PCR tests were evaluated for sensitivity, specificity and ease of interpretation of the restriction endonuclease analysis (REA) products . One IS 1311 PCR, amplifying a 608 base pair product, was shown to be suitable when the amplified product was digested with Hinf I and Mse I . The PCR detected 50 fg of template DNA from M . paratuberculosis strain 316 V, the equivalent of 10 organisms . The test was evaluated further using purified DNA from M . paratuberculosis and M . avium isolates and diagnostic samples including primary radiometric cultures . All 89 M . paratuberculosis samples were correctly identified and typed according to host species or IS 900 restriction fragment length polymorphism (RFLP) type . All 28 isolates of M . avium were also correctly identified . A second PCR/REA strategy based on a shorter fragment of IS 1311 was developed for formalin-fixed paraffin-embedded tissue samples . It correctly differentiated sheep and cattle strains of M . paratuberculosis in 27 tissue samples in which acid fast bacilli had been observed in Ziehl Neelsen stains and in which sufficient amplified product was present for REA with Hinf I . Both tests were specific for M . paratuberculosis when tested against 24 other mycobacterial species . These simple and rapid tests can be used on a range of diagnostic samples for the confirmation of Johne's disease and will be of benefit in control and eradication programmes for this disease .

Int J Tuberc Lung Dis, 1999 Apr, 3(4), 330 - 6
Risk factors for negative sputum acid-fast bacilli smears in pulmonary tuberculosis: results from Dakar, Senegal, a city with low HIV seroprevalence; Samb B et al.; SETTING: Two teaching hospitals in Dakar, Senegal, a West African country with a low prevalence of human immunodeficiency virus (HIV) infection . OBJECTIVE: To determine whether patients with HIV-associated pulmonary tuberculosis have fewer acid-fast bacilli (AFB) in their sputum as assessed by routine microscopy, and to correlate the findings with systematically obtained clinical, radiographic and laboratory variables . DESIGN: Prospective study from November 1995 to October 1996 of 450 consecutive patients diagnosed with pulmonary tuberculosis . RESULTS: Tuberculosis was diagnosed in 380 patients (84.4%) by positive bacteriology, in 61 (13.6%) by a favorable response to anti-tuberculosis chemotherapy, and in nine (2.0%) by the presence of a miliary radiographic pattern . Forty (8.9%) patients were HIV-seropositive . AFB-negative smears were found in 14/40 (35.0%) of the HIV-seropositive patients with pulmonary tuberculosis compared with 71/410 (17.3%) of the seronegative patients (risk ratio {RR} = 2.02, 95% confidence interval {CI} 1.26-3.24, P = 0.01) . Multivariate analysis revealed that AFB smear negativity was associated with absence of cavitation (P = 0.002), lack of cough (P = 0.005), the presence of HIV seropositivity (P = 0.02), a CD4+ cell count above 200/mm3 (P = 0.02), and age over 40 years (P = 0.03) . CONCLUSIONS: Compared with HIV-seronegative patients with pulmonary tuberculosis, seropositive patients in Dakar, Senegal, are more likely to have negative sputum-AFB smears . This phenomenon has now been observed in seven of eight sub-Saharan African countries with varying HIV seroprevalence from which reports are available.

J Clin Microbiol, 1999 May, 37(5), 1419 - 25
Clinical evaluation of the enhanced Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test for rapid diagnosis of tuberculosis in prison inmates; Bergmann JS et al.; The reliability of the enhanced Amplified Mycobacterium Tuberculosis Direct Test (E-MTD; Gen-Probe, Inc., San Diego, Calif.) for rapid diagnosis of pulmonary tuberculosis (TB) was evaluated by testing 1, 004 respiratory specimens from 489 Texas prison inmates . Results were compared to those of mycobacterial culture (BACTEC TB 460 and Middlebrook 7H11 biplates), smear for acid-fast bacilli (AFB; auramine O), and clinical course . After chart review, three patients (nine specimens) who were on antituberculosis therapy before the study began were excluded from final analysis . Of the remaining 995 specimens, 21 were AFB smear positive: 13 grew Mycobacterium tuberculosis complex (MTBC), 6 grew nontuberculous mycobacteria, and 2 (from two patients diagnosed with TB and started on therapy after the study began) were culture negative . Twenty-eight specimens (20 patients) were positive for MTBC by culture and E-MTD . Seven specimens (seven patients) were positive by culture alone; three were from patients who had other E-MTD-positive specimens, two were false-positive cultures, and two were false-negative E-MTD results . Eight specimens were positive by E-MTD only; four specimens (four patients) were false-positive E-MTD results, and four specimens were from two patients with earlier E-MTD-positive specimens that grew MTBC . Thus, there were 22 patients with TB (10 smear positive and 12 smear negative) . The sensitivity and specificity of the AFB smear for diagnosis of TB, by patient, were 45.5 and 98.9%, respectively . After resolving discrepancies, these same values for E-MTD were 90.9 and 99.1% overall, 100 and 100% for the smear-positive patients, and 83.3 and 99.1% for the smear-negative patients . Excluding the one smear-negative patient whose E-MTD-negative, MTBC culture-positive specimen contained inhibitory substances, the sensitivity of E-MTD was 95.2% overall and 90.9% in smear-negative patients . The specificity and positive predictive value of E-MTD can be improved, without altering other performance characteristics, by modifying the equivocal zone recommended by the manufacturer . These data suggest that E-MTD is a reliable method for rapid diagnosis of pulmonary TB, irrespective of the AFB smear result . Guidelines for the most appropriate use of E-MTD with smear-negative patients are needed.

Surg Neurol, 1999 Apr, 51(4), 443 - 6; discussion 446-7
Role of stereotactic aspiration in the management of tuberculous brain abscess; Mohanty A et al.; BACKGROUND: Intracranial tuberculous abscesses are uncommon clinical entities, even in countries where tuberculosis is endemic . Surgical excision and antituberculous treatment is the treatment of choice . The role of stereotactic aspiration in the management of these lesions is highlighted in this communication . METHODS: Three patients, all receiving treatment for pulmonary tuberculosis, presented with symptoms of raised intracranial pressure and neurological deficits . Computed tomography (CT) scans revealed cystic lesions with enhancing rim in the thalamus in two patients and multiple coalescing cystic lesions in the deep temporal region in another . RESULTS: Stereotactic aspiration of the cyst and biopsy of the cyst wall were performed in all . In two, the pus revealed acid fast bacilli (AFB) . In another, though the pus did not reveal any AFB, the wall showed tuberculous granuloma . Antituberculous treatment was continued in all the patients . Follow-up CT revealed resolution of the lesions in all patients . CONCLUSION: Stereotactic aspiration is an useful alternative modality of management of tuberculous abscesses in a selected group of patients.

J Gastroenterol Hepatol, 1999 Mar, 14(3), 258 - 61
Isolated gastric tuberculosis of the cardia; Lin OS et al.; BACKGROUND: Isolated gastric tuberculosis is extremely rare, especially in the subcardiac region, where the low pH, high motility and absence of lymphoid tissue result in an unfavourable environment for the development of tuberculous lesions . METHODS AND RESULTS: Here we present a case of isolated gastric tuberculosis in the gastric cardia with no evidence of pulmonary involvement . Our patient was a young man with vague gastrointestinal symptoms and no previous history of tuberculosis . His condition was first detected on upper endoscopy as a raised subcardiac ulcer similar in appearance to a submucosal tumour . An endoscopic forceps biopsy showed the presence of caseating granulomata and acid-fast bacilli . The lesion resolved completely with 12 months of oral anti-tuberculosis therapy . CONCLUSIONS: This case illustrates the need for a high index of suspicion in order to diagnose this rare condition, as it can present in patients with no particular risk factors or symptoms . Once diagnosed, a complete cure can often be achieved with a course of oral anti-tuberculosis medication, with surgery being reserved for severely symptomatic or refractory lesions.

Semin Respir Infect, 1999 Mar, 14(1), 82 - 7
Tuberculous empyema; Sahn SA et al.; Tuberculous empyema represents a chronic, active infection of the pleural space that contains a large number of tubercle bacilli . It is rare compared with tuberculous pleural effusions that result from an exaggerated inflammatory response to a localized paucibacillary pleural infection with tuberculosis . The inflammatory process may be present for years with a paucity of clinical symptoms . Patients often come to clinical attention at the time of a routine chest radiograph or after the development of bronchopleural fistula or empyema necessitatis . The diagnosis of tuberculous empyema is suspected on computed tomography imaging by finding a thick, calcific pleural rind and rib thickening surrounding loculated pleural fluid . The pleural fluid is grossly purulent and smear positive for acid-fast bacilli . Treatment consists of pleural space drainage and antituberculous chemotherapy . Problematic treatment issues include the inability to re-expand the trapped lung and difficulty in achieving therapeutic drug levels in pleural fluid, which can lead to drug resistance . Surgery, which is often challenging, should be undertaken by experienced thoracic surgeons.

J Clin Invest, 1999 Apr, 103(7), 1023 - 9
Macrophages are a significant source of type 1 cytokines during mycobacterial infection; Wang J et al.; T-helper 1 (Th1) cells are believed to be the major producer of the type 1 cytokine interferon-gamma (IFN-gamma) in cell-mediated immunity against intracellular infection . We have investigated the ability of macrophages to release type 1 cytokines and their regulatory mechanisms using both in vivo and in vitro models of pulmonary mycobacterial infection . During pulmonary infection by live Mycobacterium bovis bacilli Calmette-Guerin (BCG) in wild-type mice, lung macrophages released interleukin-12 (IL-12), IFN-gamma, and tumor necrosis factor-alpha (TNF-alpha), and expressed surface activation markers . However, macrophages in infected IL-12(-/-) mice released TNF-alpha but not IFN-gamma and lacked surface activation makers . In freshly isolated lung macrophages from naive IL-2(-/-) mice, mycobacteria alone released TNF-alpha but not IFN-gamma, whereas exogenously added IL-12 alone released a minimum of IFN-gamma . However, these macrophages released large quantities of IFN-gamma upon stimulation with both mycobacteria and IL-12 . In contrast, mycobacteria and exogenous IFN-gamma released only a minimum of endogenous IFN-gamma . Endogenous IL-18 (IFN-gamma-inducing factor) played little role in IFN-gamma responses by macrophages stimulated by mycobacteria and IL-12 . Our data reveal that macrophages are a significant source of type 1 cytokines during mycobacterial infection and that both IL-12 and intracellular pathogens are required for the release of IFN-gamma but not TNF-alpha . These findings suggest that macrophages regulate cell-mediated immunity by releasing not only IL-12 and TNF-alpha but also IFN-gamma and that full activation of IFN-gamma response in macrophages is tightly regulated.

Int J Dermatol, 1999 Feb, 38(2), 122 - 7
Detection of Mycobacterium tuberculosis DNA using polymerase chain reaction in cutaneous tuberculosis and tuberculids; Tan SH et al.; BACKGROUND:The objective of this study was to explore the role of the polymerase chain reaction (PCR) fo the detection of Mycobacterium tuberculosis DNA as a diagnostic aid in cutaneous tuberculosis using routinely processed skin biopsy specimens . METHODS AND RESULTS: A wide range of clinical specimens representing different forms of cutaneous tuberculosis and so-called tuberculids were studied . A sensitive and specific PCR assay targeting the sequence IS6110 of Mycobacterium tuberculosis complex was used . The specimens were categorized as follows . 1 Acid-fast bacilli (AFB) positive on biopsy (nine specimens from seven patients who were immunocompromised) . PCR was positive in five specimens . Of these, one specimen was culture positive and three specimens were culture negative . 2 AFB negative on biopsy: (a) tuberculosis verrucosa cutis (23 specimens); (b) lupus vulgaris (three specimens); (c) cutaneous tuberculosis clinically suspected (six specimens) . PCR was negative in all specimens . 3 Tuberculids.' (a) erythema induratum/nodular vasculitis (20 specimens); (b) papulonecrotic tuberculid (two specimens); (c) erythema nodosum (20 specimens) . PCR was negative in all specimens . CONCLUSIONS: The role of PCR in clinical dermatologic practice, at this stage, may be in differentiating between cutaneous tuberculosis and atypical mycobacterial infections in the context of an immunocompromised patient where AFB can be demonstrated on biopsy and cultures may be negative . In this clinical situation, PCR allows the prompt diagnosis and early institution of appropriate therapy . We have not found PCR to be a useful complement to the clinical and histologic diagnosis of "paucibacillary" forms of cutaneous tuberculosis.

Wien Klin Wochenschr, 1999 Feb 26, 111(4), 157 - 60
Fulminant lethal tuberculous pneumonia (Sepsis tuberculosis gravissima) with ARDS in a non-immunocompromised western European middle-aged man; Peck-Radosavljevic M et al.; We report the case of a 42 years old, non-immunocompromised native Austrian living in Vienna . He presented at home with severe dyspnea and had to be intubated immediately . Shortly after hospital admission, he developed severe adult respiratory distress syndrome (ARDS) and septic shock with massive, bilobar patchy to confluent infiltrations and a need for norepinephrine . A CT-scan revealed severe loss of functional lung tissue with areas of consolidation and multiple communicating cystic spaces . Air leaking into the mediastinum through fistulas produced pneumomediastinum, pneumoperitoneum, and a massive soft tissue emphysema . Bronchoalveolar lavage performed within the first 24 hours of admission revealed + of acid-fast bacilli . Even though appropriate tuberculostatic medication was started immediately, the patient succumbed the next day to ARDS due to massive tuberculous pneumonia and miliary disease (Sepsis tuberculosis gravissima).

Kekkaku, 1999 Feb, 74(2), 151 - 6
{Management of mycobacteriosis in general hospital without isolation ward for tuberculosis patients . 5 . The management of the patients excreting tubercle bacilli in a university hospital without isolation ward for tuberculosis}; Kato H et al.; The Japanese low ruled that the patients excreting tubercle bacilli should be treated in the isolated ward for tuberculosis . However, it is often difficult to transfer a patient with serious illness to the isolated ward with insufficient medical facilities . We investigated retrospectively the manner of the management of patients excreting tubercle bacilli in the Aichi Medical University Hospital without the isolation ward for tuberculosis . Materials were 166 patients (0.17%) out of 97,275 in-patients during 11 years since 1986 to 1996 . Respiratory symptoms were observed in 114 patients (68.7% of 166 patients) on admission . The initial bacteriological examination was ordered by the attendant doctor within a week in 93 patients (81.6%) of 114 patients with respiratory symptoms . On the other hand, a half of the 52 patients without respiratory symptoms on admission were not examined for sputum bacteriology beyond a week . Anti-tuberculous treatment was started within a week after positive bacteriological results in 129 patients (77.7% of the whole 166 patients), while the treatment was not carried out or delayed in 21 patients (12.6%) because of the communication failure of the bacteriological report to the physicians . Some complications were observed in 101 patients: 21 diabetes mellitus, 20 cancers, 15 hematological disorders, 9 collagen diseases, 6 renal failures on dialysis . Serious illnesses were observed in 33 patients (20.6% of the 166 patients) . Twenty-four patients (73% of the seriously ill patients) were died of renal failure, pancytopenia, cancer or respiratory failure . We considered that an isolated room for infectious tuberculosis with independent air conditioning system in a general hospital or a educational hospital was very convenient not only to the treatment of the patients with serious complications, but also to the education and training on tuberculosis for the medical student or medical stuffs.

Kekkaku, 1999 Feb, 74(2), 145 - 50
{Management of mycobacteriosis in general hospital without isolation ward for tuberculosis patients . 4 . Actual status of the management of tuberculosis patients in a university hospital without isolation wards for infectious diseases}; Kako K et al.; We retrospectively evaluated clinical findings and the actual status of management of 69 tuberculosis patients admitted to the Fujita Health University Hospital, a hospital without isolation wards for infectious diseases, between 1991 and 1994 . Forty-nine patients were smear-positive and 22 patients were smear-negative and culture-positive . Twenty-five cases (36.2%) were classified as type II (cavitary) and 29 cases (42.0%) as type III (non-cavitary) according to the GAKKAI classification of findings on chest X-ray films for pulmonary tuberculosis . Physicians in charge did not diagnose twenty-four patients (34.8%) as tuberculosis on admission . Physicians in charge tended not to suspect smear-negative patients of tuberculosis . Most of the patients with cavities on their chest X-ray films were strongly suspected of tuberculosis on admission, but in some of them, tuberculosis was not considered at all . Smear-positive patients with strongly suspected tuberculosis were diagnosed with the disease within three hospital days, while it took about three weeks in patients who were not considered as tuberculosis on admission to be diagnosed as tuberculosis . In the case of smear-negative patients, it took about one month and two months respectively to diagnose the case as tuberculosis . About half (51.1%) of the smear-positive patients were admitted and treated in single-bed rooms while 44.7% were attended in multiple-bed rooms for 11 days before they were transferred to single-bed rooms . When acid-fast bacilli were detected, 57.4% of the smear-positive patients were transferred to hospitals with isolation wards for infectious diseases, while the remaining smear-positive patients were treated in single-bed rooms at the university hospital . About one-third (31.7%) of the smear-negative patients had already left the hospital when specimens were found to be culture positive for tubercle bacilli . In conclusion, it is utmost important for physicians to suspect to tuberculosis for the early diagnosis of the disease.

Kekkaku, 1999 Feb, 74(2), 133 - 7
{Management of mycobacteriosis in general hospital without isolation ward for tuberculosis patients . 2 . The problems of management of the patients diagnosed pulmonary tuberculosis after admission to the respiratory ward of university hospital having no an isolation ward for the tuberculous patients}; Hiraoka H et al.; The management of 28 patients, diagnosed pulmonary tuberculosis by bacteriological or pathologic findings after the administration to the Koshigaya Hospital of Dokkyo university school of Medicine from January 1994 through September 1997, which had no an isolation ward for tuberculosis patients was analyzed . The mean age of the patients was 50.6 +/- 16.7 (18-85), and the number of male and female patients was 22 and 6 respectively . The underlying diseases found in 10 patients were gastric cancer, breast cancer, osteochondrosarcoma, collagen disease, diabetes mellitus, liver cirrhosis, pneumoconiosis, and bronchial asthma . Two patients were complicated by a lung cancer . Six of 28 patients showed smear-positive and culture-positive specimens and 22 of 28 patients showed smear-negative and culture-positive specimens . The detection of mycobacterial DNA in the samples after amplification by the polymerase chain reaction (PCR) used in 15 patients and was positive for 7 of 15 patients . The pathological study of the specimens obtained by Transbronchial lung biopsy was performed for 14 patients . The pathological findings were compatible with tuberculosis in 7 of 14 patients . The chief complaints of the 11 patients admitted to the hospital with in 3 days after first visit, were fever in all patients and in 5 patients with pleural effusion . A few patients showed smear-negative and PCR positive specimens and complicated by lung cancer or other malignancy, were treated in non isolation ward in the particular case of emergency evacuation before admission, careful examination such as a tuberculin test, bacterial examination, and PCR of sputum should be performed in the patients suspected of having pulmonary tuberculosis . The patients isolating tubercule bacilli after administration should be transferred to the hospital with isolated ward for tuberculosis or isolated room in general hospital in the particular case of emergency evacuation with the greatest care.

Kekkaku, 1999 Feb, 74(2), 99 - 105
{Characteristics of the medical status and living conditions of the homeless registered as tuberculosis patients in Nagoya City}; Yamanaka K et al.; An Investigation by questionnaire was conducted in 1996 to know the tuberculosis (TB) status and living conditions of 50 homeless people registered as TB patients at one of Nagoya city's 16 health centers . 1 . All patients had one or more symptoms of TB, 64% of them showed positive TB bacilli on smear, and 35.3% of them had a previous history of TB treatment . However, only 15.2% suspected they had TB at the onset of symptoms . 2 . Main reasons of seeking medical treatment: 28.6% arrived by ambulance after falling down from exhaustion, 25.7% had consulted with welfare agencies after the onset of symptoms, and 20.0% had been diagnosed during the treatment of other diseases . 3 . When they were admitted to the hospital they had many concerns: 29.0% loss of income, 19.4% living expenses, 19.4% smoking prohibition, 12.9% admission fee, and 9.7% privacy . 4 . They lived in the following: 42.9% construction camps, 20.0% parks or streets, 17.1% single room occupancy hotels, 17.1% daily or monthly paid apartments, and 11.4% sauna baths . 5 . Past medical histories of the subjects included 40.6% injuries by labor accidents, and 25.0% stomach ulcers . Current diseases were 15.6% mental diseases, 15.6% liver diseases, 15.6% diabetes mellitus, and 9.4% alcoholic dependence . Seventy percent of them consumed alcohol daily (average pure ethanol 125 ml per day) . 6 . From the results outlined above, the following proposals relating to TB control of the homeless should be considered . 1) Educating the homeless as to the need for a health check when TB symptoms are present . 2) Opening a clinic for the homeless for easy access to consultation on TB . 3) Directly observed therapy short-course, for TB in the homeless . 4) Health examination of the employees of single-room occupancy hotels and sauna baths which are used frequently by the homeless . 5) A fundamental countermeasure to deal with alcoholic dependency among the homeless.

Kekkaku, 1999 Feb, 74(2), 83 - 90
{Global situation of TB and its control}; Shimao T; Tuberculosis occupies 4th place among major causes of death, and the number of new cases is estimated at 7.25 million in 1997, and 99% of TB deaths and 95% of new TB cases are seen in developing countries . TB had been brought under control in developed countries by applying modern TB control programme including chemotherapy, as basic health infrastructure was already well developed, and their economy can afford cost of control programme including TB drugs . The rapid decline of TB due to the success of TB control in developed countries had lowered the concern on TB, thus bought about the reduction in research grant for TB and difficulty in bringing up successors engaging in TB control . Similar trend was seen also in developing countries, where TB still remains one of most important health problems due to poor quality of the programme caused by poorly developed health infrastructure including man-power, budget and institutions . New obstacles which hinder the smooth implementation of TB control programme have appeared, and they are the rapid expansion of global population, the move of population, the impact of HIV epidemic on TB and the multi-drug-resistant TB (MDRTB) . The growth of population automatically increases the number of TB cases and gives heavier burden for TB control . TB has moved from developing to developed countries with the move of the population, and currently approximately half of new TB cases in developed countries is occupied by foreign born patients . Among several opportunistic infections seen in AIDS cases, TB comes out first as the virulence of tubercle bacilli is much higher than the other germs causing opportunistic infections . The pathogenesis of TB changes markedly among HIV positives, and the incidence becomes much higher, and the time interval from the primary infection to the disease, and that from the detection of the disease to death without any effective treatment are shortened, and the fatality rate becomes much higher . Because of the atypical clinical picture, attenuated tuberculin sensitivity and high incidence of side-effects of TB drugs, in particular thiacetazone, clinical management of HIV positive TB is much more difficult than ordinary TB . MDRTB is produce by the bad quality of TB control, and by improving treatment completion rate as well as the cure rate, decline in the prevalence of drug resistance, both primary and acquired, could be expected together with the decline of TB itself . WHO has made a great challenge with TB after the nomination of Dr Kochi to chief medical officer, TUB in 1989 . Currently, Global TB Programme (GTB) is promoting so-called DOTS strategy of TB control, consisting of the commitment of the government to give high priority to TB control, passive case-finding with sputum smear examination by microscopy, directly observed treatment by standardized short-course regimen of chemotherapy, well-organized logistics for TB drugs, and the provision of reporting and monitoring system of TB including the evaluation of treatment outcome by cohort analysis . Marked achievements have been obtained in several countries introduced DOTS strategy . Japan is asked to intensify its efforts in international cooperation in TB control.

Indian J Lepr, 1998 Oct-Dec, 70(4), 397 - 403
Identification of M.leprae in conjunctiva of leprosy patients using the superior tarsal conjunctiva scrape technique; Campos WR et al.; The technique of superior tarsal conjunctiva scrape was used for identifying M.leprae in the conjunctiva in 56 leprosy patients (all of them multibacillary, some untreated and others treated with multidrug therapy) . The technique of tarsal conjunctiva scrape was shown to be more suitable than conjunctival biopsy for identifying lepra bacilli . This technique is also easier to perform and has shown a statistical relation between bacilloscopical index of skin (BIsk) and bacilloscopical index of tarsal conjunctiva (BIconj) values . Thus, if the bacilli can be identified at tarsal conjunctiva we can assume greater systemic bacillary load in the patients.

Indian J Lepr, 1998 Oct-Dec, 70(4), 389 - 95
Quality control tests for vaccines in leprosy vaccine trial, Avadi; Sreevatsa et al.; All the vaccines supplied for the large scale comparative leprosy vaccine trial of ICRC bacilli, M.w, BCG plus killed M . leprae (candidate vaccines), BCG and normal saline (control arms) at CJIL Field Unit, Chennai were tested for quality control by the suppliers following the procedures laid down in the WHO protocol for killed M . leprae . Quality control for BCG was carried out at BCG vaccine laboratory as per protocol . Toxicity and sterility tests were done on all the vaccine batches/lots received . As part of the quality control, bacterial count, and protein estimation were also done . Studies showed that the bacterial content and protein concentration were comparable with the original preparations . Vaccines were free from micro-organisms, toxic materials and safe for human use . Thus the quality of all vaccine preparations was satisfactory.

Aviat Space Environ Med, 1999 Mar, 70(3 Pt 2), A137 - 40
Effects of low frequency noise upon the reaction of pleural milky spots to mycobacterial infection; Oliveira MJ et al.; INTRODUCTION: Milky Spots (m.s.), also known as Kampmeier's foci, are confined to the parietal leaflet and act as a barrier to mediastinum infections, having very important phagocytic functions . Previous studies have made clear that large pressure amplitude and low frequency (LPALF) noise (> or = 90 dB, < or = 500 Hz) induces morphofunctional changes on the pleural mesothelium . The purpose of this study was to investigate the dynamics of m.s., namely the response to infectious agents reaching the pleural space under noise stress . METHODS: Wistar rats (n = 20) were used; 5 as control and sham operated, 5 exposed to infection but not to noise, 5 exposed to 1696 cumulative hours of LPALF noise, and 5 exposed to 2184 cumulative hours . Following noise exposures, all rats except the 5 controls were injected with 0.2 ml of saline solution containing 2 x 10(8) viable mycobacterium avium bacilli (ATCC-25291 strain, sereotype 2) . The rats were sacrificed 21 d after infection and sections of the retrocardiac pleural leaflets were observed with a light microscope using the Ziehl-Neelsen staining method . RESULTS: There was an increase in the number and diameter of the m.s . due to hypercellularity, mainly caused by the increase of mononuclear cells, and there was formation of large granulomas containing many mycobacteria . Rats submitted to noise also presented alterations of the standard morphological changes, namely partial necrosis of the m.s . CONCLUSION: The data suggest that exposure to LPALF noise can interfere with the normal immune response to bacterial infection in rats . This can be an important contribution to the understanding of the disorders in the pleural space of vibroacoustic disease patients.

Pediatrics, 1999 Apr, 103(4 Pt 1), 719 - 23
Factors that predict preexisting colonization with antibiotic-resistant gram-negative bacilli in patients admitted to a pediatric intensive care unit; Toltzis P et al.; OBJECTIVE: To predict which patients hospitalized in a pediatric intensive care unit (ICU) are colonized with antibiotic-resistant gram-negative rods on admission . METHODS: Consecutive children admitted to a pediatric ICU over a 6-month period were entered into the study . A questionnaire soliciting information regarding the child's medical history and home environment was completed by the parent or guardian . Nasopharyngeal and rectal cultures were obtained on each of the first 3 days of ICU admission, and organisms resistant to ceftazidime or tobramycin were identified . Only clonally distinct organisms, as confirmed by pulsed field gel electrophoresis, were analyzed . The association between identification of colonization with an antibiotic-resistant gram-negative rod within 3 days of ICU admission and factors included in the questionnaire was tested by chi2 or t test . RESULTS . In 64 (8.8%) of 727 admissions, an antibiotic-resistant gram-negative bacillus was isolated within the first 3 ICU days . More than half were identified on the day of admission . Colonization was associated with two factors related to the patient's medical history, namely, number of past ICU admissions (1.98 vs.87) and administration of intravenous antibiotics within the past 12 months (67.9% vs 28.2%) . No association was found between colonization and exposure to oral antibiotics . In addition, factors related to the child's environment were also associated with presumed importation of an antibiotic-resistant gram-negative rod into the ICU . Specifically, residence in a chronic care facility was strongly associated with colonization (28.3% vs 2.6%); exposure to a household contact who had been hospitalized in the past 12 months also predicted colonization (41.7% vs 18.5%) . CONCLUSIONS: These data suggest that a profile can be established characterizing children colonized with resistant gram-negative bacilli before admission to a pediatric ICU . Infection control measures may help to contain these potentially dangerous bacteria once they have been introduced into the unit.

Acta Cytol, 1999 Mar-Apr, 43(2), 153 - 7
Fine needle aspiration diagnosis of mycobacterial lymphadenitis . Sensitivity and predictive value in the United States; Ellison E et al.; OBJECTIVE: Fine needle aspiration (FNA) has proven valuable in diagnosing tuberculous lymphadenitis in countries with endemic mycobacterial infection (MI) . Its role in developed countries, where sensitivity and positive predictive value are likely to be lower, has not been adequately explored . STUDY DESIGN: This retrospective, five-year study from a public hospital in the United States examined the predictiveness of 238 nodal FNAs in patients with MI; 59% of patients were also HIV+ . RESULTS: Diagnostic results (stainable acid-fast bacilli or positive culture) were present in nearly half the aspirates; sensitivity was 46%, specificity 100%, positive predictive value (PPV) 100% and negative predictive value (NPV) 94% . If granulomatous inflammation (GI) was also considered a positive result, sensitivity increased to 53%; false positive cases of GI reduced PPV to 80%, while specificity (98%) and NPV (95%) changed little . Considered alone, GI had the lowest sensitivity (25%) and PPV (65%) . CONCLUSION: FNA was useful in this U.S . population with MI, identifying almost half the affected patients . However, nondiagnostic results, such as granulomatous inflammation, should be interpreted with caution.

Int J Tuberc Lung Dis, 1999 Mar, 3(3), 231 - 8
Evaluation of the MycoDot test in patients with suspected tuberculosis in a field setting in Tanzania; Somi GR et al.; SETTING: Rapid, simple and inexpensive methods are needed to improve the diagnosis of tuberculosis in low-income countries . The MycoDot test has these characteristics . OBJECTIVE: To assess the utility of the MycoDot test in screening patients with suspected tuberculosis . DESIGN: Ambulatory patients presenting with symptoms of pulmonary tuberculosis were evaluated by physical examination and sputum acid-fast bacilli (AFB) microscopy . Separately, the MycoDot test was performed on whole blood . Patients with AFB-negative smears were treated with a 10-day course of erythromycin . Those remaining symptomatic had a chest radiograph . All sputum specimens were cultured for mycobacteria . Patients with culture-negative tuberculosis and those without a tuberculosis diagnosis were reassessed at 2 months . RESULTS: Among the 241 patients who were evaluated, the MycoDot test was positive in 26% of patients with AFB-positive/culture-positive tuberculosis, 7% with AFB-negative/culture-positive tuberculosis, 7% with culture-negative tuberculosis, 19% treated for tuberculosis who did not meet study case definitions, and 16% without tuberculosis . Twenty four patients did not complete the assessment . Test sensitivity was 16%, specificity 84% and positive predictive value 45% . Sensitivity was highest (41%) in AFB-positive/HIV-negative patients and lowest (3%) in AFB-negative/HIV-positive patients . CONCLUSION: The MycoDot test is not useful for the diagnosis of tuberculosis in sub-Saharan African countries, especially where HIV infection is prevalent.

Int J Tuberc Lung Dis, 1999 Jan, 3(1), 55 - 61
Quality control of smear microscopy for acid-fast bacilli: the case for blinded re-reading; Nguyen TN et al.; SETTING: Quality control of sputum smear microscopy, which is essential for ensuring correct tuberculosis (TB) diagnosis, is often performed through the unblinded rereading of all positive slides and a sample of negative slides . OBJECTIVE: To assess misclassification error introduced by knowledge of prior results . METHODS: The Southern Vietnam Regional TB Laboratory prepared three gold-standard sets of 750 slides: an unblinded set, an unblinded set in which 13% of negative slides were replaced by weakly positive slides purposefully mislabelled as negative, and a blinded set . Six provincial technicians who normally perform district quality control each reread 125 slides from each set . RESULTS: In the three sets only one negative slide was misread as positive . In the unblinded set (referent), 2.9% (9/311) positive slides were misread as negative, compared with 18.7% (57/305) in the blinded set (prevalence ratio {PR} = 6.5; 95% confidence interval {CI} 3.3-12.8; P < 0.001), and 11.3% (33/293) in the unblinded set with mislabelled slides (PR = 3.9; 95%CI 1.9-8.0; P < 0.001) . CONCLUSIONS: False-negative error was more common than false-positive error . Knowledge of prior reading influences re-reading . Blinded re-reading of systematically selected slides would appear preferable, although this method requires high levels of proficiency among quality control technicians.

Int J Tuberc Lung Dis, 1999 Jan, 3(1), 47 - 54
Prednisolone: a beneficial and safe adjunct to antituberculosis treatment? A randomized controlled trial; Bilaceroglu S et al.; SETTING: A referral centre for thoracic diseases in Izmir, Turkey, 1992-1995 . OBJECTIVE: To appraise the adjunctive role of prednisolone (PN) in pulmonary tuberculosis (PTB) with toxic reactions . DESIGN: After excluding other febrile causes, and 2 weeks of four/five-drug antituberculosis therapy insufficient to resolve toxic reactions, 178 human immunodeficiency virus (HIV) negative patients with advanced PTB causing persistent high-grade fever (> or =38 degrees C), weight loss (> or =2 kg/week) and/or low serum albumin levels (<3 g/dL) were randomly allocated to receive either a 12-month course of antituberculosis treatment using four first-line drugs and PN (20 mg b.i.d . IV/IM initially, decreasing over 40 days) (91 patients-PN group), or 12 months of antituberculosis treatment only (87 patients-CO group) . Twice-weekly sputum bacillary count, temperature recorded every 6 hours, weekly weight, serial albumin level and liver function measurements and chest roentgenograms were used to assess the effects of PN on PTB . RESULTS: Temperature decreased from 39.1+/-0.9 degrees C to 37.9+/-0.7 degrees C (P = 0.0030) within the first 72 (+/-9) hours in those patients on PN treatment, whereas a gradual decline occurred over 22 (+/-3) days in the CO group . In the PN group, patients' weight increased from 49.7+/-4.8 kg to 56.9+/-8.3 kg, compared to 47.1 +/- 6.4 kg to 51.31+/-5.9 kg in the CO group (P = 0.0022) . Increases in serum albumin levels in the PN and CO groups were from 2.26+/-0.8 g/dL to 3.32+/-0.6 g/dL and from 2.31+/-0.5 g/dL to 2.90+/-0.7 g/dL, respectively (P = 0.0035) . The radiographic regression and drop in bacillary count were more rapid, and the hospital stay shorter (53.4+/-3.1 days vs 71.3+/-5.6 days) in the PN group, although there were no differences in the acid-fast bacilli conversion rates . There were no detrimental side effects and relapses attributable to PN during the 1-3 year follow-up, even in 18 cases with drug resistance . CONCLUSION: Prednosolone is a beneficial and safe adjunct to 12-month antituberculosis treatment in advanced PTB causing toxic reactions, provided that close clinical, radiographic and bacillary monitoring is exercised.

Int J Tuberc Lung Dis, 1999 Feb, 3(2), 166 - 8
Innate resistance to tuberculosis: revisiting Max Lurie genetic experiments in rabbits; Werneck-Barroso E; Experimental inoculation of tubercle bacilli does not correspond to natural contagion . The classic and unique study published in the literature, performed by Max Lurie with inbred rabbit families to evaluate resistance and susceptibility to tuberculosis, closely simulated the natural mode of infection, reproducing the varying types of the disease as it occurs in man . Lurie observed that resistant families developed cavitary tuberculosis and susceptible families developed disseminated tuberculosis . The conclusions were based only on resistance to the progress of tuberculous infection due to cellular-mediated immunity . In this report we have made an additional analysis of this experiment, looking for the resistance to infection itself.

Infect Immun, 1999 Apr, 67(4), 2010 - 2
Vaccinated mice remain more susceptible to Mycobacterium tuberculosis infection initiated via the respiratory route than via the intravenous route; North RJ et al.; Mice given Mycobacterium tuberculosis bacilli via the respiratory route succumbed much sooner to infection than mice given 1,000 times more bacilli via the intravenous route . Vaccination provided increased protection to an M . tuberculosis challenge infection; however, mice infected via the respiratory route remained much more susceptible.

Chest, 1999 Mar, 115(3), 741 - 5
Mycobacterial infections in lung transplant recipients; Kesten S et al.; BACKGROUND: Immunosuppression and chronic lung disease are known risk factors for mycobacterial infection and might be expected to develop with an increased frequency in lung transplant recipients . We therefore sought to document the incidence and type of mycobacterial infections in a large lung transplant program . METHODS: A retrospective review of 219 transplant procedures (60 single lung transplants and 159 double lung transplants) in 210 patients was conducted . All patients had scheduled surveillance bronchoscopies at 3, 6, 9, 12, 18, and 24 months, and yearly thereafter . BAL samples were processed routinely for mycobacterium . RESULTS: Eight patients (3.8%) had evidence of infection (5 men, 3 women; age range, 26 to 63 years) . The reasons for transplant were obstructive lung disease (six), cystic fibrosis (one), and pulmonary fibrosis (one) . Five recipients had infection in their native lungs; two of five cultured mycobacterium from BAL following transplantation . At least four of five patients had nontuberculous mycobacterium (one showed acid fast bacilli and granuloma on a biopsy specimen that was not sent for culture) . None of the five developed disease (mean follow-up = 22 months; range, 3 to 30 months) . The organisms were Mycobacterium avium complex (three), Mycobacterium xenopi (one), and unidentified (one) . Of the three remaining patients who developed infection after transplantation, one grew Mycobacterium chelonae and the others grew Mycobacterium tuberculosis (both received double lung transplants and had no evidence of mycobacterium in their native lungs) . The only definite symptomatic disease occurred in the patients with M tuberculosis, one of whom had evidence of dissemination . The patients with M tuberculosis responded to standard treatment . There have been no deaths due to mycobacterium . CONCLUSION: Mycobacterial disease rarely occurs following lung transplantation . Cultures for mycobacterium in surveillance BALs in the absence of symptoms are likely unnecessary.

Mikrobiol Z, 1998 Sep-Oct, 60(5), 86 - 98
{Natural interferons: the methods of their isolation, the properties and characteristics of the preparations and their use in animal infections}; Kishko IaH; Data of studies carried out in the field of interferonology during the last 20 years which are based on the proposed new biotechnologies for production of natural alpha- and gamma-interferons (IFNs) have been analyzed . "Know-how" of these technologies consists in the usage of non-traditional source (spleen instead of blood) for preparing the suspension of immunocytes--producers of preparations, in introduction of the stage of "coinduction" when producing alpha-IFNs, use of bacterial lectins of apathogenic bacilli as inducers of gamma-IFN genesis . It was shown, that in vitro and in vivo the both types of preparations several times increased both absorbing and bactericidal activity of phagocytes of swine and cattle peripheral blood, 3-5 times increased antibody genesis in animals after their immunization by colibacteriosis vaccine . It was proved that immunomodulating ability of alpha-IFNs is significantly (3-5 times) higher than that for gamma-IFNs . In non-purified preparations of IFNs the fractions have been discovered which had antibacterial and antitoxic action of wide spectrum of specificity . Both preparations were effective for prophylaxis and therapy of not only viral, but also bacterial infections in animals: transmissive gastroenteritis of swine, parainfluenza of calves, colibacteriosis of pigs and calves, etc., and promoted the increase of animals productivity by 20-35% . If under hemoblastosis alpha-IFN caused remission, they could be effectively treated using homologous gamma-IFN.

J Clin Microbiol, 1999 Apr, 37(4), 971 - 5
Molecular markers demonstrate that the first described multidrug-resistant Mycobacterium bovis outbreak was due to Mycobacterium tuberculosis; Gutierrez MC et al.; We genetically characterized multidrug-resistant Mycobacterium tuberculosis complex strains which caused a nosocomial outbreak of tuberculosis affecting six human immunodeficiency virus (HIV)-positive patients and one HIV-negative staff member (E . Bouvet, E . Casalino, G . Mendoza-Sassi, S . Lariven, E . Vallee, M . Pernet, S . Gottot, and F . Vachon, AIDS 7:1453-1460, 1993) . The strains showed all the phenotypic characteristics of Mycobacterium bovis . They presented a high copy number of IS6110, the spacers 40 to 43 in the direct repeat locus, and the mtp40 fragment . They lacked the G-A mutation at position 285 in the oxyR gene and the C-G mutation at position 169 in the pncA gene . These genetic characteristics revealed that these were dysgonic, slow-growing M . tuberculosis strains mimicking the M . bovis phenotype, probably as a consequence of cellular alterations associated with the multidrug resistance . Spoligotyping and IS6110 restriction fragment length polymorphism (RFLP) analysis confirmed that the outbreak was due to a single strain . However, the IS6110 RFLP pattern of the strain isolated from the last patient, diagnosed three years after the index case, differed slightly from the patterns of the other six strains . A model of a possible genetic event is presented to explain this divergence . This study stresses the value of using several independent molecular markers to identify multidrug-resistant tubercle bacilli.

J Clin Microbiol, 1999 Apr, 37(4), 916 - 9
Extensive cross-contamination of specimens with Mycobacterium tuberculosis in a reference laboratory; de C Ramos M et al.; A striking increase in the numbers of cultures positive for Mycobacterium tuberculosis was noticed in a mycobacterial reference laboratory in Campinas, Sao Paulo State, Brazil, in May 1995 . A contaminated bronchoscope was the suspected cause of the increase . All 91 M . tuberculosis isolates grown from samples from patients between 8 May and 18 July 1995 were characterized by spoligotyping and IS6110 fingerprinting . Sixty-one of the 91 isolates had identical spoligotype patterns, and the pattern was arbitrarily designated S36 . The 61 specimens containing these isolates had been processed and cultured in a 21-day period ending on 1 June 1995, but only 1 sample was smear positive for acid-fast bacilli . The patient from whom this sample was obtained was considered to be the index case patient and had a 4+ smear-positive lymph node aspirate that had been sent to the laboratory on 10 May . Virtually all organisms with spoligotype S36 had the same IS6110 fingerprint pattern . Extensive review of the patients' charts and investigation of laboratory procedures revealed that cross-contamination of specimens had occurred . Because the same strain was grown from all types of specimens, the bronchoscope was ruled out as the outbreak source . The most likely source of contamination was a multiple-use reagent used for specimen processing . The organism was cultured from two of the solutions 3 weeks after mock contamination . This investigation strongly supports the idea that M . tuberculosis grown from smear-negative specimens should be analyzed by rapid and reliable strain differentiation techniques, such as spoligotyping, to help rule out laboratory contamination.

Hunan Yi Ke Da Xue Xue Bao, 1997, 22(5), 393 - 6
{Protective effects of nimodipine on brain edema induced by pertussis bacilli in rats}; Chen L et al.; The changes of brain water content and Evan blue(EB) were investigated on the model of infection brain edema induced by Pertussis Bacilli(PB) in 72 rats . Nimodipine was admenistred to show its effect on the PB induced brain edema . The experiment results showed that the water content and EB content in the PB group were significantly increased than those normal group and normal saline group at 30 min, 4 hours and 24 hours after the injection of PB (P < 0.05) . Nimodipine could significantly reduce brain water content and EB content, so that brain edema was attenuated . It indicates that nimodipine showed advantage to treatment of PB brain edema.

Zhongguo Yao Li Xue Bao, 1997 Mar, 18(2), 185 - 8
{Effects of 16 drugs on immunological liver injury induced by BCG + lipopolysaccharides in mice}; Yang TJ et al.; AIM: To evaluate anti-hepatitis drugs . METHODS: Mice were injected i.v . with viable BCG 5 x 10(7) (live) bacilli/mouse, after 10 d, i.v . lipopolysaccharides (LPS) 5-10 micrograms/mouse . Serum aminotransferase levels and liver tissue were examined 10 h after i.v . LPS . Sixteen drugs were evaluated in this model . RESULTS: The level of AlaAT and AspAT were increased markedly . Submassive necrosis and infiltrations of granulocytes and lymphocytes were seen, which were not recovered till 14 d after i.v . LPS . Administration of interferon alpha-2a, Ara-AMP, hepatocyte growth factor, biphenyl dimethyl dicarboxylate, bicyclol, prednisolone, and cyclophosphamide for 10 d prior to i.v . LPS suppressed the elevation of serum AlaAT and AspAT . CONCLUSION: The model of immunological liver injury reproduced by i.v . BCG + LPS in mice may be used for evaluating anti-hepatitis drugs.

Zhongguo Yao Li Xue Bao, 1997 Mar, 18(2), 173 - 6
Influences of Kupffer cell stimulation and suppression on immunological liver injury in mice; Wang GS et al.; AIM: To study the possible involvement of Kupffer cells (KC) in immunological liver injury in mice . METHODS: Liver injury was induced by i.v . injection of Bacillus Calmette-Guerin (BCG) 5 x 10(7) viable bacilli followed by i.v . injection of lipopolysaccharides (LPS) 7.5 micrograms to each mouse . Indian ink and silica were i.v . injected to suppress KC and retinol was given po to stimulate KC in these mice . Plasma alanine aminotransferase (AlaAT), aspatate aminotransferase (AspAT), nitric oxide (NO), and liver tissue were examined . RESULTS: Injection of LPS following BCG injection resulted in a remarkable elevation of plasma NO, AlaAT, and AspAT levels, and severe liver damage . The damages were enhanced by the activation of KC with retinol and reduced by suppression of KC with silica and Indian ink . CONCLUSION: The degree of liver injury induced by BCG + LPS is closely correlated with the status of KC, and NO from KC plays an important role in the pathogenesis of the liver damage in mice.

J Clin Pathol, 1998 Dec, 51(12), 925 - 7
Atypical mycobacterial lymphadenitis in childhood--a clinicopathological study of 17 cases; Evans MJ et al.; AIMS: To assess the clinical and pathological features of atypical mycobacterial lymphadenitis in childhood to define the salient clinical and histological features . METHODS: 17 cases were included on the basis of positive culture or demonstration of bacilli of appropriate morphology and staining characteristics . RESULTS: The mean age at diagnosis was 4.86 years . All children were systemically well, with clear chest x rays . Unilateral cervical lymphadenopathy was the commonest mode of presentation . Differential Mantoux testing played no part in diagnosis . Clinical diagnosis improved with awareness . Treatment varied with surgeons opting for excision and paediatricians adding six months antituberculous chemotherapy . Acid- and alcohol-fast bacilli were identified in nine cases . Bacterial cultures were conducted in 16 cases and were positive for atypical or nontuberculous mycobacteria in 14, the main organism being M avium-intracellulare complex (11 cases) . Histologically, 12 cases had bright eosinophilic serpiginous necrosis with nuclear debris scattered throughout the necrotic foci . Langhans type giant cells featured in the majority of cases but infiltration by plasma cells and neutrophils was not consistent . CONCLUSIONS: Atypical mycobacterial lymphadenitis of childhood represents a rare but significant disease with characteristic clinical and histological features.

Ann Intern Med, 1999 Mar 2, 130(5), 404 - 11
Delays in the suspicion and treatment of tuberculosis among hospitalized patients; Rao VK et al.; BACKGROUND: Despite increased awareness of tuberculosis, delays in management are common . OBJECTIVE: To investigate management delays among hospitalized patients with tuberculosis . DESIGN: Retrospective cohort study . SETTING: The Barnes-Jewish-Christian Health System, a network of eight community and tertiary-care facilities serving the St . Louis, Missouri, metropolitan area . PATIENTS: All 203 patients with tuberculosis hospitalized in the Barnes-Jewish-Christian Health System from 1988 to 1996 . MEASUREMENTS: Time from admission to first consideration of the diagnosis (suspicion interval), first consideration and treatment initiation (treatment interval), and admission and treatment initiation (overall management interval) were determined . Delays were defined as intervals longer than 24 hours . RESULTS: The overall management interval (median, 6 days {5th and 95th percentiles, 1 and 52 days}) exceeded 24 hours in 152 patients (74.9% {95% CI, 68.9% to 80.9%}) . The suspicion interval (median, 1 day {5th and 95th percentiles, 0 and 16 days}) exceeded 24 hours in 54 patients (26.6% {CI, 20.5% to 32.7%}), and the treatment interval (median, 3 days {5th and 95th percentiles, 0 and 51 days}) was prolonged in 130 patients (64.0% {CI, 57.4% to 70.6%}) . Overall management delays of more than 10 and 25 days occurred in 33.5% (CI, 27.0% to 40.0%) and 18.7% (CI, 13.3% to 24.1%) of patients, respectively . The 55 patients with smears that were positive for acid-fast bacilli had a median treatment interval of 3 days (5th and 95th percentiles, 0 and 33 days); in 58.2% of patients (CI, 45.2% to 71.2%), this interval exceeded 24 hours . CONCLUSIONS: Delays in initiation of treatment were more common than delays in the initial suspicion of tuberculosis . Both types of delays were common even in patients with disease that was confirmed by a positive smear . These data illustrate a need for improved education of physicians about the benefits of early initiation of therapy for tuberculosis.

Schweiz Rundsch Med Prax, 1999 Jan 21, 88(4), 105 - 12
{Diagnosis and therapy of lymph node tuberculosis}; Schneider K et al.; Due to an increase of lymph node tuberculosis and associated diagnostic problems the question for the easiest and most accurate diagnostic measures was asked . Furthermore, the success of surgical and pharmacologic treatment was evaluated . A total of 16 patients (nine females, seven males) treated at the medical outpatient clinic between 1977 and 1995 because of lymph node tuberculosis were evaluated retrospectively . Diagnosis had been established in all cases either by fine needle aspiration or surgical excision . The mean age was 31 years (range 17-68) . In 10 patients cervical lymphomas were found . Other localisations were supraclavicular, inguinal, axillary and mediastinal . In 94% of the patients a fine needle aspiration was performed to ascertain diagnosis . Acid-fast bacilli were found in 36% and mycobacteria were cultured in 92% . Five patients (31%) had a surgical excision with acid-fast bacilli in two and positive cultures from all specimens . All patients had chemotherapy, in most cases started by a combination of three and followed by a combination of two drugs . According to our results a fine needle aspiration is justified as a first diagnostic step if lymph node tuberculosis is suspected . A positive result can be regarded as conclusive and spares surgical intervention . Since negative results do not exclude tuberculosis they justify surgical excision for final diagnosis.

Kekkaku, 1999 Jan, 74(1), 53 - 61
{Current status and perspectives on the development of rifamycin derivative antibiotics}; Hidaka T; Rifampicin (RFP) was developed as one of the anti-tuberculosis drugs in 1966 and has been used for almost 30 years . Establishment of combination therapy using RFP has been contributing to the treatment/eradication of tuberculosis . A number of rifamycin derivatives, as post RFPs, have been synthesized/developed over the the years . Chemical modification of rifamycins has largely been concentrated on the moiety of naphthalene ring because modification of the ansa chain moiety reduces the activity . In 1992, rifabutin was approved as a preventive drug for MAC infection in AIDS patients in the United States and in European countries . It is noteworthy that rifapentine (RPT) was approved as an anti-tuberculosis drug in 1998 by FDA in the United States . A newly synthesized rifamycin derivative (KRM-1648, rifalazil) possesses a potent activity against both M . Tuberculosis and MAC, and it is now under clinical trial for the treatment of Tuberculosis in the United States . KRM-1648 is metabolized to 30-hydroxy KRM and 25-deacetyl KRM in the body, and its 30-hydroxylation is caused by liver cytochrome P450 3A . It is well known that RFP, RFB and RPT induce liver cytochrome P450 in animals and human, and these accelerate the metabolism of concomitant drugs such as HIV protease inhibitors resulting in lowering their blood levels . While KRM-1648 did not induce liver P450 in animals, but it is not examined yet in human . Clinical study of DOT with intermittent therapy of RPT in combination with INH resulted in the preferable therapeutic effect comparable to the RFP therapy . Since KRM-1648 has a potent activity, a high tissue distribution and a long half-life, it may be also suitable for intermittent therapy . For the future novel anti-tuberculosis drugs and therapy for tuberculosis, it is prerequisite to develop new drugs with a preferable antimicrobial activity, to shorten further the treatment period, and to be effective against multi-drug resistant bacilli . It is expected that more effective novel rifamycin derivatives can be developed with the above view points.

J Formos Med Assoc, 1999 Jan, 98(1), 62 - 5
Disseminated Mycobacterium genavense infection in a patient with acquired immunodeficiency syndrome: first case report in Taiwan; Yan JJ et al.; Mycobacterium genavense is a recently described fastidious mycobacterium identified as a pathogen causing disseminated infection in patients with advanced human immunodeficiency virus (HIV) disease . In this report, we describe the first reported case of disseminated M . genavense infection in a patient with acquired immunodeficiency syndrome (AIDS) in Taiwan . A 22-year-old Chinese man was found to be seropositive for HIV at age 18, in 1993 . In 1997, he presented with abdominal pain, weight loss, low CD4 lymphocyte count, hepatomegaly, and generalized lymphadenopathy . Microscopic examination of a biopsy specimen from an inguinal lymph node showed both ill- and well-formed noncaseating granulomas . Numerous acid-fast bacilli were present in the histiocyte cytoplasm . Although the organism did not grow on conventional solid media used in our laboratory, two molecular biology techniques, including polymerase chain reaction (PCR) followed by sequencing of 16S rRNA, and PCR together with restriction enzyme fragment polymorphism analysis, confirmed the M . genavense infection . The patient's abdominal symptoms responded well to a chemotherapy regimen that included ethambutol, ciprofloxacin, and clarithromycin, and he survived more than 6 months after diagnosis . However, the lymphadenopathy was still present at his final follow-up . Our report indicates that disseminated infection with M . genavense should be added to the list of differential diagnoses of secondary infections in advanced AIDS patients in Taiwan.

Arch Pathol Lab Med, 1999 Feb, 123(2), 170 - 2
Pulmonary artery fibrous bands: report of a case with extensive lung infarction and superinfection with Coccidioides immitis, Pseudomonas, and acid-fast bacilli; Perez MT et al.; A 46-year-old woman presented with shortness of breath and frequent lower respiratory tract infections . A ventilation-perfusion scan showed markedly reduced perfusion of the right lung, and pulmonary arteriogram showed stenosis of the right pulmonary artery . A right pneumonectomy revealed dense white fibrous bands partially occluding the pulmonary artery branches and two large abscess cavities filled with pus in the upper and lower lobes . Microscopic examination revealed extensive necrosis of lung parenchyma, suppurative granulomatous inflammation with Coccidioides immitis organisms and rare acid-fast bacilli . Pulmonary artery fibrous bands were originally believed to be congenital; however, they are now known to be sequelae of thromboembolic phenomena.

J Bacteriol, 1999 Mar, 181(5), 1380 - 7
Transcription of the stationary-phase-associated hspX gene of Mycobacterium tuberculosis is inversely related to synthesis of the 16-kilodalton protein; Hu Y et al.; The 16-kDa protein, an alpha-crystallin homologue, is one of the most abundant proteins in stationary-phase Mycobacterium tuberculosis . Here, transcription and translation of the hspX gene, which encodes the 16-kDa protein, have been investigated by Northern blotting analysis, primer extension, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a microaerophilic stationary-phase model . Two transcripts of about 2.5 and 1.1 kb were demonstrated by Northern blot analysis and hybridized to the hspX gene probe . Primer extension analysis revealed that the transcription start site is located 33 nucleotides upstream of the hspX gene start codon . The cellular level of the hspX mRNA was maximum in log-phase bacilli and was markedly reduced after 20 days in unagitated culture, when the organisms had entered the stationary phase . A third transcript of 0.5 kb was detected 0.6 kb downstream of the hspX gene; this transcript has a transcriptional pattern completely different from that of the 1.1- and 2.5-kb products, suggesting that there may be another gene in this region . In contrast to the high level of hspX mRNA in log-phase bacilli, 16-kDa protein synthesis was low in log-phase bacteria and rose to its maximum after 20 days . In both log-phase and stationary-phase bacteria the mRNA was unstable, with a half-life of 2 min, which indicated that the transcript stability was growth rate independent and not a general means for controlling the gene expression . However, the cellular content of 16-kDa protein, while low in log-phase bacteria, rose to a maximum at 10 days and remained at this high level for up to 50 days, which indicates that this protein is a stable molecule with a low turnover rate . These data suggest that the regulation of hspX expression during entry into and maintenance of stationary phase involves translation initiation efficiency and protein stability as potential mechanisms.

Am J Ophthalmol, 1999 Feb, 127(2), 209 - 10
Infectious crystalline keratopathy and endophthalmitis secondary to Mycobacterium abscessus in a monocular patient with Stevens-Johnson syndrome; Uy HS et al.; PURPOSE: To describe the clinical and laboratory features of infectious crystalline keratopathy and endophthalmitis secondary to Mycobacterium abscessus in a patient with Stevens-Johnson syndrome . METHOD: Case report . A 19-year-old man with a history of Stevens-Johnson syndrome and multiple corneal transplants developed white crystalline corneal infiltrates . RESULTS: Anterior chamber aspirate disclosed acid-fast bacilli . A repeat corneal transplant was performed and antibiotic therapy begun . Histopathology showed focal acute inflammation surrounding collections of acid-fast bacilli, which were speciated as M . abscessus . CONCLUSIONS: M . abscessus is a cause of infectious crystalline keratopathy and endophthalmitis . Risk factors include ocular surface disease, corneal transplantation, and immunosuppressive therapy.

Lett Appl Microbiol, 1999 Jan, 28(1), 57 - 60
Isolation of endospore-forming bacilli toxic to Culiseta longiareolata (Diptera: Culicidae) in Jordan; Khyami-Horani H et al.; Ten of 80 endospore-forming bacilli, isolated from various habitats of Jordan, were found to be highly toxic to the 4th instar larvae of Culiseta longiareolata (Macquart) . The bacilli were identified into the following species and strains: Bacillus sphaericus (H6), B . sphaericus (H9a, 9b), B . cereus Frankland and Frankland, B . brevis Migula and B . megaterium Bary . Bacillus cereus comprised 50% of the isolates . The toxic concentrations of these isolates against C . longiareolata ranged between 1.2 x 10(7) and 1.1 x 10(9) viable spores ml-1.

Nihon Hansenbyo Gakkai Zasshi, 1998 Nov, 67(3), 401 - 8
{Present situation of leprosy in highly endemic area of tropical Asia--a seroepidemiological study of Mycobacterium leprae infection in general inhabitants}; Izumi S et al.; One of the most important unsolved problems in epidemiology of leprosy is the heterogeneous geographic distribution of the disease . There are highly endemic area called "Pocket" in the endemic countries . Little is known why leprosy is so endemic in the area . We conducted, therefore, an epidemiological study on M . leprae infection and distribution of leprosy bacilli in the environment by using serological and molecular biological techniques . It was found that considerable number of general inhabitants in the pocket are infected with leprosy bacilli and more than 20% of the villagers are carrying M . leprae on the surface of the nasal cavity; suggesting that leprosy bacilli in the residential environment play an important role in high prevalence of leprosy in the endemic area . New preventive measures such as chemoprophylaxis, in addition to MDT, will be needed for global elimination of the disease.

Kekkaku, 1998 Dec, 73(12), 719 - 22
{A case of bronchiectasis with abundant expectoration of Mycobacterium gordonae}; Itou Y et al.; A 68 year old woman consulted our hospital because of 6 month history of dry cough . Her chest X-ray revealed bronchiectasis in the left lung . Three sputum specimens were culture positive for acid fast bacilli (AFB) 200 colonies . The bacilli were scotochromogenic, niacin test was negative and hydrolysis of tween 80 was positive, and they were identified as M . gordonae . M . gordonae is rarely implicated as a pathogen but a few reports suggest it may be pathogenic . Though our patient had clinical symptom and expected abundant M . gordonae, her chest X-ray revealed no progression . Thus, it was hardly possible to consider this case as a case caused by the infection with M . gordonae . In previous reports of M . gordonae pulmonary disease, chest X-ray findings showed cavity, infiltration and consolidation, however, no case with bronchiectasis was reported and chest X-ray findings of this case are interesting.

Kekkaku, 1998 Dec, 73(12), 713 - 8
{A tuberculosis epidemic among four relatives who live in the neighborhood of index case}; Sakamoto H et al.; A tuberculosis epidemic occurred among 4 relatives who live in the neighborhood of the index case . A thirty-three year old female was admitted to a hospital in July 1994 with high fever and cervical lymphoadenopathy . Culture examination of her sputum was positive for acid-fast bacilli and her chest X-ray showed diffuse small nodules . During the following sixteen months, five new patients with pulmonary tuberculosis were found among the relatives who lived in the neighborhood of the index case . The contact examination was first limited in her own family members, however, after detection of the second case, the examination was extended to other relatives living nearby, and another four patients were found . The results of PPD skin test of ten contact children showed strongly positive reaction, and chemoprophylaxis was indicated . Contacts examination is very important especially for patients with highly infectious tuberculosis.

QJM, 1998 Nov, 91(11), 743 - 7
Tuberculous meningitis in South African urban adults; Karstaedt AS et al.; We retrospectively reviewed 56 adults with culture-proven tuberculous meningitis (TBM), investigating clinical signs, cerebrospinal fluid (CSF) findings and outcome . There were 50 patients, aged 18-59 years, 39 with and 11 without human immunodeficiency virus (HIV) infection . Six were aged 60 years or older . Neurological signs of TBM in 18-59-year-olds were unaffected by HIV serostatus while, compared to those > or = 60 years of age, there were more patients with meningism (86.0% vs . 33.3%; p = 0.011) and fewer with seizures (12.0% vs . 50.0%; p = 0.046) . The HIV-infected 18-59-year-olds had significantly more extrameningeal tuberculosis compared to the non-HIV-infected (76.9% vs . 9.1%; p = 0.0001) and 23.1% had 'breakthrough' TBM . CSF analysis revealed 12 patients (21.4%) with acellular fluid (more common in those > or = 60 years of age, p = 0.016), of whom three had completely normal CSF . A neutrophil predominance was found in 22 patients (39.3%) . Only three patients (5.4%) had a positive CSF smear for acid-fast bacilli . In-hospital mortality occurred in 39 patients (69.1%), was similar in all study groups, and was not related to neurological stage . The diagnosis of TBM can be masked by lack of meningism in the elderly and by atypical CSF findings.

Abdom Imaging, 1999 Mar-Apr, 24(2), 200 - 1
Bilateral renal masses after local Bacillus Calmette-Guerin therapy for postcystectomy ureteral cancer; Squires FB et al.; Bacillus Calmette-Guerin was administered through the ileal conduit of a 63-year-old man with upper tract recurrence of transitional cell carcinoma . Subsequent computed tomography showed bilateral renal masses, which were granulomatous at pathologic examination . The bacilli likely reached the kidneys via proven ileoureteral reflux . Patients with reflux may benefit from antituberculous prophylaxis.

JAMA, 1999 Feb 10, 281(6), 517 - 23
Multiple antibiotic-resistant Klebsiella and Escherichia coli in nursing homes; Wiener J et al.; CONTEXT: Infections caused by ceftazidime sodium-resistant gram-negative bacteria that harbor extended-spectrum beta-lactamases (ESBLs) are increasing in frequency in hospitals in the United States . OBJECTIVES: To report a citywide nursing home-centered outbreak of infections caused by ESBL-producing gram-negative bacilli and to describe the clinical and molecular epidemiology of the outbreak . DESIGN: Hospital-based case-control study and a nursing home point-prevalence survey . Molecular epidemiological techniques were applied to resistant strains . SETTINGS: A 400-bed tertiary care hospital and a community nursing home . PATIENTS: Patients who were infected and/or colonized with ceftazidime-resistant Escherichia coli, Klebsiella pneumoniae, or both and controls who were admitted from nursing homes between November 1990 and July 1992 . MAIN OUTCOME MEASURES: Clinical and epidemiological factors associated with colonization or infection by ceftazidime-resistant E coli or K pneumoniae; molecular genetic characteristics of plasmid-mediated ceftazidime resistance . RESULTS: Between November 1990 and October 1992, 55 hospital patients infected or colonized with ceftazidime-resistant E coli, K pneumoniae, or both were identified . Of the 35 admitted from 8 nursing homes, 31 harbored the resistant strain on admission . All strains were resistant to ceftazidime, gentamicin, and tobramycin; 96% were resistant to trimethoprim-sulfamethoxazole and 41% to ciprofloxacin hydrochloride . In a case-control study, 24 nursing home patients colonized with resistant strains on hospital admission were compared with 16 nursing home patients who were not colonized on hospital admission; independent risk factors for colonization included poor functional level, presence of a gastrostomy tube or decubitus ulcers, and prior receipt of ciprofloxacin and/or trimethoprim-sulfamethoxazole . In a nursing home point-prevalence survey, 18 of 39 patients were colonized with ceftazidime-resistant E coli; prior receipt of ciprofloxacin or trimethoprim-sulfamethoxazole and presence of a gastrostomy tube were independent predictors of resistance . Plasmid studies on isolates from 20 hospital and nursing home patients revealed that 17 had a common 54-kilobase plasmid, which conferred ceftazidime resistance via the ESBL TEM-10, and mediated resistance to trimethoprim-sulfamethoxazole, gentamicin, and tobramycin; all 20 isolates harbored this ESBL . Molecular fingerprinting showed 7 different strain types of resistant K pneumoniae and E coli distributed among the nursing homes . CONCLUSIONS: Nursing home patients may be an important reservoir of ESBL-containing multiple antibiotic-resistant E coli and K pneumoniae . Widespread dissemination of a predominant antibiotic resistance plasmid has occurred . Use of broad-spectrum oral antibiotics and probably poor infection control practices may facilitate spread of this plasmid-mediated resistance . Nursing homes should monitor and control antibiotic use and regularly survey antibiotic resistance patterns among pathogens.

Rev Esp Quimioter, 1998 Dec, 11(4), 349 - 52
{Activity of trovafloxacin and ten other antimicrobials against gram negative anaerobic bacilli}; Chavez M et al.; As an increase in anaerobes resistant to a great variety of antimicrobials have been seen in the last few years, a search for new agents with activity against these microorganisms is needed . One of these agents is trovafloxacin . In our study, all strains were susceptible to imipenem, metronidazole, chloramphenicol and piperacillin/tazobactam . A total of 97% of the strains were inhibited with 2 mg/ml of trovafloxacin . The microorganisms Bacteroides fragilis and B . uniformis showed the least susceptibility against the antimicrobials studied, with a MIC90 for trovafloxacin of 1 and 2 mg/ml, respectively . Fusobacterium spp . were the most susceptible, with an MIC90 for trovafloxacin of 0.5 mg/ml . Trovafloxacin showed good activity against Gram-negative anaerobe rods, and could therefore be considered as an alternative in the treatment of the infections produced by these microorganisms.

Lancet, 1999 Feb 6, 353(9151), 444 - 9
Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli; Behr MA et al.; BACKGROUND: The microscopic examination of sputum for acid-fast bacilli, is a simple and rapid test that is used to provide a presumptive diagnosis of infectious tuberculosis . While patients with tuberculosis with sputum smears negative for acid-fast bacilli are less infectious than those with positive smears, both theoretical and empirical evidence suggest that they can still transmit Mycobacterium tuberculosis . We aimed to estimate the risk of transmission from smear-negative individuals . METHODS: As part of an ongoing study of the molecular epidemiology of tuberculosis in San Francisco, patients with tuberculosis with mycobacterial isolates with the same DNA fingerprint were assigned to clusters that were assumed to have involved recent transmission . Secondary cases with tuberculosis, whose mycobacterial isolates had the same DNA, were linked to their presumed source case to estimate transmission from smear-negative patients . Sensitivity analyses were done to assess potential bias due to misclassification of source cases, unidentified source cases, and HIV-1 co-infection . FINDINGS: 1574 patients with culture-positive tuberculosis were reported and DNA fingerprints were available for 1359 (86%) of these patients . Of the 71 clusters of patients infected with strains that had matching fingerprints, 28 (39% {95% CI 28-52}) had a smear-negative putative source . There were 183 secondary cases in these 71 clusters, of whom a minimum of 32 were attributed to infection by smear-negative patients (17% {12-24}) . The relative transmission rate of smear-negative compared with smear-positive patients was calculated as 0.22 (95% CI 0.16-0.32) . Sensitivity analyses and stratification for HIV-1 status had no impact on these estimates . INTERPRETATION: In San Francisco, the acid-fast-bacilli smear identifies the most infectious patients, but patients with smear-negative culture-positive tuberculosis appear responsible for about 17% of tuberculosis transmission.

Mol Microbiol, 1998 Dec, 30(5), 955 - 63
Identification of a co-repressor binding site in catabolite control protein CcpA; Kraus A et al.; The catabolite control protein CcpA is the central regulator of carbon catabolite repression in Bacilli and other Gram-positive bacteria . A comparison of 12 CcpA-like sequences with regulators from the LacI/GalR family defines a CcpA subfamily based on extensive similarities found among CcpAs and not in 32 other members of the family . These amino acids are clustered in three blocks in the CcpA sequence . Their interpretation, assuming a PurR-like fold, reveals that almost all of them are surface exposed and form a continuous patch on the N-terminal subdomain of the protein core extending into the DNA reading head . We introduced nine single amino acid exchanges in the subfamily specific residues of CcpA from Bacillus megaterium . Six mutants, namely CcpA47RS, 79AE, 89YE, 295YR, 299YE and 303RD, are inactive or severely impaired in catabolite repression, underlining their relevance for CcpA function . They are negatively transdominant over wild-type CcpA demonstrating their ability to correctly fold for dimerization . Five of them are unable or impaired in binding HPr-Ser-46-P in vitro, establishing a correlation between catabolite repression efficiency and HPr-Ser-46-P binding . These results support the hypothesis that the conserved region in CcpA is the HPr-Ser-46-P binding site.

J Clin Microbiol, 1999 Mar, 37(3), 832 - 4
Optimal detection and identification of Mycobacterium haemophilum in specimens from pediatric patients with cervical lymphadenopathy; Samra Z et al.; Acid-fast bacilli from pediatric patients with lymphadenopathy were detected in the BACTEC radiometric system and in MB Redox broth, but not on Lowenstein Jensen medium . PCR amplification identified the isolates as Mycobacterium haemophilum, which has special nutrition requirements (iron supplements) for growth . Suitable culture medium ensures optimal recovery of this microorganism, avoiding underdiagnosis.

Novartis Found Symp, 1998, 217, 99 - 106; discussion 106-11
Recombinant interleukin 2 adjunctive therapy in multidrug-resistant tuberculosis; Johnson B et al.; Multidrug-resistant tuberculosis patients respond poorly to antituberculosis therapy and therefore require new modalities of treatment to overcome the infection . Administration of low dose recombinant human interleukin 2 (rhuIL-2) in combination with chemotherapy to multidrug-resistant tuberculosis patients resulted in reduced or cleared sputum acid-fast bacilli in about 60% of the patients in association with enhanced activation of the immune system . Daily rhuIL-2 administration for 30 days induced increases in CD25+ and CD56+ cells in the blood . rhuIL-2 therapy also resulted in increased expression of gamma-interferon and IL-2 mRNA at the site of a delayed-type hypersensitivity (DTH) response to purified protein derivative of tuberculin . Differential display reverse transcriptase PCR revealed several genes expressed at the DTH skin test site that were up- or down-regulated during rhuIL-2 treatment . The differentially regulated genes included components of endocytic vacuoles, enzymes of the respiratory pathway and other regulators of cellular function . The physiological importance of the differential expression of these genes is under investigation to determine their roles in leukocyte activation and in the development of an antimycobacterial response.

Novartis Found Symp, 1998, 217, 57 - 69; discussion 69-72
Vaccines, genes and trials; Fine PE; This symposium takes place at the intersection of an acute success (the extraordinary recent developments in genetical research relevant to mycobacteria) and a chronic failure (the embarrassing failure of Bacillus Calmette-Guerin {BCG}, the world's most widely used vaccine, to control tuberculosis) . I will summarize the arguments that the variable efficacy of BCG is attributable, at least in part, to genetic differences in either the vaccine, the host populations or Mycobacterium tuberculosis . I will then address the problem of building upon our experience with BCG in order to develop and evaluate an improved vaccine against tuberculosis . The fact that the great burden of tuberculosis is associated with pulmonary disease in adults, much of which is associated either with reactivation of old infection or else with relatively recent reinfection, poses an immense problem for vaccine strategy and evaluation . One approach may be to vaccinate early in life, prior to initial infection with the tubercle bacillus, and then to follow up individuals for many decades . The alternative is to develop vaccines to boost appropriate protective immune mechanisms in individuals who have already been infected, and/or who have already been vaccinated (e.g . with BCG), and/or who may also have been sensitized to various environmental mycobacteria that influence the immune response to tubercle bacilli . The latter approach is novel, and may ultimately prove impossible, but its potential logistic and public health advantages are so great that it warrants serious attention by the research community before being abandoned.

Lepr Rev, 1998 Dec, 69(4), 358 - 66
Histological studies in primary neuritic leprosy: changes in the nasal mucosa; Suneetha S et al.; The nasal mucosae of 39 cases of primary neuritic leprosy (PNL) registered at Karigiri were studied histologically to determine nasal mucosal involvement in PNL and its relevance to the pathogenesis of the disease . Specific changes of leprosy were seen in 20 (51%) biopsies, ranging from macrophage granulomas with acid fast bacilli, to epithelioid granulomas and nerve inflammation . The remaining biopsies revealed chronic inflammatory changes of the mucosa or mild non-specific nerve changes . These findings show that there are widespread effects of the disease even in PNL patients in whom the disease is believed to be confined to the peripheral nerves . The findings also show that early leprosy involvement can be found in the nasal mucosa even before lesions become apparent in the skin or other parts of the body . The nasal mucosa could be one of the sites for the primary lesion in leprosy . Clinical and histological examination of the nasal mucosa may be useful and important in the early diagnosis of leprosy and especially in contacts.

Chest, 1999 Jan, 115(1), 19 - 25
The detection of airborne Mycobacterium tuberculosis using micropore membrane air sampling and polymerase chain reaction; Mastorides SM et al.; STUDY OBJECTIVES: Mycobacterium tuberculosis (MTb) bacilli are carried on airborne droplet nuclei produced by aerosolization that can occur from coughing, talking, or even singing . Because of their prolonged period of suspension, they can be filtered from the air onto a porous medium and readily detected using polymerase chain reaction (PCR) . DESIGN: Prospective cohort analysis . SETTING: Samples of circulating air were collected over a 12-month period from within the rooms of 10 hospitalized patients who were under respiratory isolation to rule out MTb infection . A small laboratory pump was used to draw ambient air at a rate of 2 L/min over a 6-h period through a 0.2-microm polycarbonate membrane filter placed near the patient's bed . Analysis of the membrane filters was conducted using PCR . Sputum cultures for MTb were performed simultaneously, and the results of smears stained for acid-fast bacilli (AFB) were noted . MEASUREMENTS AND RESULTS: MTb complex was successfully detected by PCR in six of seven patients in whom sputum MTb cultures were subsequently positive, and in zero of three with subsequently negative sputum cultures . Sampling in one patient with a positive culture, in whom PCR results were negative, was only carried out for 2 h due to pump malfunction . One of the six PCR-positive patients was AFB-smear negative at the time of air sampling . CONCLUSIONS: Our preliminary findings indicate that the technique of Micropore membrane air sampling with PCR analysis has important applications in the epidemiology and diagnosis of MTb.

Antimicrob Agents Chemother, 1999 Feb, 43(2), 403 - 5
Mycobacteriocidal action of exogenous nitric oxide; Long R et al.; We tested the hypothesis that exposure of extracellular Mycobacterium tuberculosis to low concentrations (< 100 ppm) of nitric oxide (NO) for short periods (24 h or less) will result in microbial killing . We observed that NO had both dose- and time-dependent cidal effects that were very significant by two-way analysis of variance (F ratios of 13.4 {P < 0.001} and 98.1 {P < 0.0001}, respectively) . Conceivably, extracellular bacilli in patients with pulmonary tuberculosis might be vulnerable to exogenous NO.

Can J Cardiol, 1998 Dec, 14(12), 1467 - 9
Rapidly evolving constrictive tuberculous pericarditis: case presentation and review of the literature; Gobeil F et al.; A 69-year-old male presented with a diagnosis of idiopathic pericarditis, first treated with prednisone for a few weeks with resolution of the symptoms . A few days after stopping the medication, he presented with malaise, cough and signs of pericardial constriction confirmed by echocardiography . He was diagnosed with pulmonary tuberculosis with pericardial involvement and treated accordingly . Pericardiectomy was performed after a few days of treatment because the symptoms related to constriction progressed . The procedure was successful, and the patient was completely asymptomatic after 10 months . The removed pericardium stained positive for acid-fast bacilli.

Am J Vet Res, 1999 Jan, 60(1), 123 - 7
Relation between pathologic findings and cellular immune responses in sheep with naturally acquired paratuberculosis; Perez V et al.; OBJECTIVE: To investigate the relation between lesions and cellular immune response-based tests in sheep with naturally acquired paratuberculosis and to evaluate efficacy of an interferon-gamma (IFN-gamma) assay and the intradermal skin test . ANIMALS: 110 and 88 adult sheep were used to evaluate the IFN-gamma assay and skin test, respectively . PROCEDURE: Before euthanasia, heparinized blood was collected and incubated with avian purified protein derivative (PPD) . Interferon-y production was assessed, using a commercial enzyme immunoassay . Skin testing in the caudal fold also was performed, using avian PPD . Sensitivity and specificity of these techniques were evaluated, using histopathologic findings as reference . RESULTS: Of the sheep examined, 61 (55.4%) had lesions that were classified in 5 categories, according to location, extension, cellular types, and presence of acid-fast bacilli . Regarding cellular immunity test results, 55.4% of sheep with and 6.1 % without pathologic changes had positive results of the IFN-gamma assay . Skin test sensitivity (55.6%) and specificity (100%) were slightly greater . CONCLUSION: Close association between pathologic findings and cellular immune response was apparent . Most sheep with focal (tuberculoid) and some with diffuse lesions (borderline tuberculoid), all with scant or no acid-fast bacilli in the intestine, had positive results of the IFN-gamma assay and skin test . Most sheep with diffuse lesions and high numbers of bacilli (borderline lepromatous) were test negative . CLINICAL RELEVANCE: Cellular immune response-based and serologic tests are useful tools for seeking evidence of paratuberculosis . Each technique detects different types of immune-reacting sheep, and their simultaneous use may detect most infected animals.

Ophthalmology, 1999 Jan, 106(1), 80 - 5
In vitro susceptibility of bacterial keratitis pathogens to ciprofloxacin . Emerging resistance; Kunimoto DY et al.; OBJECTIVE: To examine in vitro susceptibility of bacterial keratitis pathogens to ciprofloxacin . DESIGN: Retrospective review . PARTICIPANTS: The authors examined in vitro susceptibility of 1558 corneal isolates from 1303 patients with culture-proven bacterial keratitis seen at the LV Prasad Eye Institute in Hyderabad, India, during the 6-year period between March 1, 1991, and June 30, 1997 . RESULTS: Of 1558 corneal isolates, 478 (30.7%) were not sensitive to ciprofloxacin . Among the isolates, 355 (32.5%) of the 1091 gram-positive cocci were not sensitive to ciprofloxacin, and 2 (10%) of the 20 gram-positive bacilli, 22 (13.3%) of the 165 gram-negative organisms, and 99 (35.1%) of the 282 Actinomycetes and related organisms were not sensitive to ciprofloxacin . Results from chi-square for trends analysis showed a trend of significantly increasing ciprofloxacin insensitivity in bacteria between 1992 and 1997 (P = 0.011) . CONCLUSION: This is the first report of significantly increasing ciprofloxacin insensitivity among corneal pathogens . Although the lowered cost and convenience of dispensing a single, commercially available antibiotic such as ciprofloxacin in the initial treatment of bacterial keratitis is desirable, the emergence of ciprofloxacin resistance is a significant finding in this series, and the clinician should proceed with caution in the initial empiric treatment of bacterial keratitis with ciprofloxacin.

Pediatrics . 1999 Jan;103(1):E13.
Long-term remission for disseminated Mycobacterium avium-intracellulare complex associated with antibody deficiency; Grouhi M et al.; Mycobacterium avium-intracellulare (MAI) is a ubiquitous organism with limited virulence in the immunocompetent host . Disseminated disease is associated with a high mortality rate . Except for localized cervical adenitis, MAI disease is rare in immunocompetent children . We report a child with antibody deficiency (dysgammaglobulinemia) and disseminated MAI infection, in whom complete, long-term remission was attained with multiple antimycobacterial therapy . The patient presented with progressive cervical lymphadenopathy and hepatomegaly at 7 years of age . A lymph node biopsy showed acid-fast bacilli and granulomas . Despite a transient response to conventional antituberculous therapy, including isoniazid and rifampin, his symptoms progressed . Cultures from blood, bone marrow, spleen, and cervical lymph node tissues revealed an MAI organism . Subsequent treatment using a combination of clarithromycin, amikacin, and ethambutol for 16 months resolved clinical symptoms, and subsequent blood culture results became negative . By the time of this report, the patient has been disease-free for 4 years . Multiple-drug therapy is promising for the treatment of MAI in children with antibody deficiency; however, the selection of antiinfective drugs should include a member of the newer macrolide family . acquired immunodeficiency syndrome, clarithromycin, dysgammaglobulinemia, Mycobacterium avium-intracellulare, treatment.

Nihon Kokyuki Gakkai Zasshi, 1998 Nov, 36(11), 959 - 62
{Diagnosis of pulmonary tuberculosis by the amplicor test for Mycobacterium tuberculosis in induced sputum}; Kawada H et al.; The polymerase chain reaction (PCR) technique was compared with the conventional smear and culture method for the detection and identification of Mycobacterium tuberculosis in 25 induced sputa samples . Sputum induction was performed with an ultrasonic nebulizer using 3% hypertonic saline in 27 previously untreated patients suspected of active pulmonary tuberculosis clue to chest X-ray findings, but who were unable to spontaneously expectorate sputum . All patients received anti-tuberculosis drugs for at least 6 months after sputum induction . Two patients could not expectorate sputum after hypertonic saline inhalation . Microscopy failed to detect positive acid-fast bacilli in 25 induced sputa samples . Induced sputa were both PCR- and culture-positive for 10 patients, PCR-positive and culture-negative for 4 patients, and PCR-negative and culture-positive for 2 patients . These results suggest that the PCR method is useful in diagnosing tuberculosis in induced sputum, and that the results of PCR and culture Procedures can complement each other.

Nihon Kokyuki Gakkai Zasshi, 1998 Oct, 36(10), 908 - 12
{Miliary tuberculosis associated with subcutaneous tuberculous abscess}; Kondo H et al.; A 62-year-old woman was admitted because of a tumor on her right thigh, fever, generalized lymphadenopathy, and diffuse nodular shadows on chest X-ray films . She was given a diagnosis of miliary tuberculosis based on the findings of a cervical lymph-node biopsy and a broncho-alveolar lavage . Acute respiratory failure and disseminated intravascular coagulation developed, but resolved after the start of anti-tuberculous therapy . The tumor on the right thigh was diagnosed as a subcutaneous tuberculous abscess because tuberculous bacilli were detected in tumor tissue samples obtained by aspiration . The patient's fever disappeared and the abnormal shadows on her chest X-ray films receded significantly after drainage of the subcutaneous abscess . These findings suggested that miliary tuberculosis was associated with the subcutaneous tuberculous abscess in this case.

Adv Exp Med Biol, 1998, 452, 85 - 101
Cytotoxic T lymphocytes in resistance to tuberculosis; Mazzaccaro RJ et al.; Recent experimental evidence has suggested T cells recognizing antigens in the context of both classical MHC class I and nonclassical class I-like molecules contribute to protective responses against Mycobacterium tuberculosis (MTB) infection . Our aims were to characterize both types of T cells, and to explore the basis of communication between the tubercle bacilli and the MHC class I pathway of the host macrophage . A model system was developed using exogenously added ovalbumin as a surrogate antigen to study presentation by MTB-infected macrophages . Viable, virulent MTB and closely related mycobacterial species facilitated the presentation of ovalbumin on MHC class I molecules to CD8+ cytolytic T cells that was dependent upon the cytosolic transport of peptides, implying communication between the MTB phagosome and the host cell cytoplasm . MHC class I presentation of soluble antigens was mimicked by Listeria monocytogenes, which grows within the host cell cytoplasm, as well as its purified hemolysin . We have also characterized T cells that recognize nonpeptide MTB antigens presented by CD1 molecules . CD1-restricted T cells demonstrated to lyse macrophages infected with virulent MTB were divided into distinct subsets based on surface phenotype (CD4-CD8- versus CD8-) and cytotoxicity mechanism (Fas receptor-mediated versus granule exocytosis) . A functional consequence of these two mechanisms was observed that while both subsets lysed infected macrophages, only those T cells utilizing the granule exocytosis pathway were able to reduce viability of intracellular MTB.

J Immunol, 1999 Jan 1, 162(1), 372 - 9
Activation of human CD8+ alpha beta TCR+ cells by Mycobacterium tuberculosis via an alternate class I MHC antigen-processing pathway; Canaday DH et al.; Human immune responses to M . tuberculosis are characterized by activation of multiple T cell subsets including CD4+, CD8+, and gammadelta T cells, and the role of CD8+ alphabeta TCR+ T cells in this response is poorly understood . Stimulation of T cells from healthy tuberculin skin test-positive persons with live M . tuberculosis-H37Ra or soluble M . tuberculosis Ags readily up-regulated IL-2Ralpha (CD25) expression on CD8+ T cells . Purified resting and activated CD8+ T cells produced IFN-gamma and proliferated to both M . tuberculosis bacilli and soluble mycobacterial Ags with monocytes as APC . Precursor frequency of mycobacterial Ag-specific CD8+ T cells by IFN-gamma enzyme-linked immunospot was 5-10-fold lower than the precursor frequency of CD4+ T cells, and IFN-gamma secretion by CD8+ T cells was 50-100-fold lower . CD8+ T cells secreted approximately 10-fold less IFN-gamma per cell than CD4+ T cells in response to mycobacterial Ags . CD8+ T cell responses to M . tuberculosis bacilli were blocked by anti-MHC class I antibody and required Ag processing . Processing of M . tuberculosis bacilli by monocytes for presentation to MHC class I-restricted CD8+ T cells was insensitive to brefeldin A treatment, which blocks the conventional MHC class I Ag-processing pathway . These results represent the first demonstration that human cells can process pathogen Ags via an alternate Ag-processing pathway for MHC class I and suggest a mechanism for participation of IFN-gamma-secreting CD8+ T cells in the human immune responses to M . tuberculosis.

Diagn Microbiol Infect Dis, 1998 Nov, 32(3), 237 - 41
Kluyvera cryocrescens finger infection: case report and review of eighteen Kluyvera infections in human beings; West BC et al.; We report a case of soft tissue infection with Kluyvera cryocrescens and a critical review of Kluyvera infections . A 31-year-old diabetic man used a new chemical for stripping the floor with his bare hands . Two days later he developed a blister on a finger which progressed to tenosynovitis in spite of intravenous nafcillin therapy . After 11 days culture and sensitivity results dictated treatment with intravenous ticarcillin/clavulanic acid . The wound was debrided twice, and later a skin flap was done . Wound cultures became sterile after 7 days of treatment with ticarcillin/clavulanic acid, and he recovered . This case represents the fourth clinical infection with K . cryocrescens and the eighteenth of Kluyvera to be reported . Four others were K . ascorbata, and the remaining ten Kluyvera infections in humans were not identified beyond genus . Our case and review of the 17 previous cases emphasize that while Kluyvera rarely cause disease, these opportunistic Gram-negative bacilli may be virulent in a variety of sites under as yet poorly defined host conditions . Sites of infection varied, but the brain and meninges were not among them . Two patients had diabetes mellitus, none had AIDS, and four died . Once shown clinically to be the cause of an infection, Kluyvera deserve aggressive treatment which acknowledges their ampicillin resistance.

Kansenshogaku Zasshi, 1998 Nov, 72(11), 1236 - 41
{Pulmonary infection in the emphysematous bulla due to Mycobacterium szulgai diagnosed by percutaneus needle aspiration}; Inoue Y et al.; A 73-year-old male was admitted to our hospital because of productive cough and infiltrate on the chest roentogenogram . The underlying diseases was found to be multiple myeloma . He received a physical examination in June, 1996 . The chest X-ray and CT scan on admission showed an infiltrative shadow with multiple bulla in the left upper lung field . Internal use of antibiotics and drip infusion of IPM/CS were ineffective . The chest X-ray showed air-fluid level in left upper peripheral bullous lesion and a percutaneus needle aspiration of the lung was performed . The specimen was pus with blood and microscopical examination of smears revealed no acid-fast bacilli, but Mycobacterium szulgai was isolated and identified by DNA-DNA hybridization method . The patient was treated with isoniazid and rifampicin, and improved in a few months . There are a few case reports of pulmonary infection due to M . szulgai associated with emphysematous bulla of the lung in Japan . M . szulgai infection of the lung is similar to M . kansasii infection in respect to clinical features (improvement of chest abnormal shadow, efficacy of drug).

Nippon Rinsho, 1998 Dec, 56(12), 3195 - 8
{Clinical features and diagnosis of disease caused by nontuberculous mycobacteria}; Tanaka E; Number of patients infected with nontuberculous mycobacteria (NTM) is increasing world-wide in recent years . In Japan, M . avium complex, M . kansasii and rapidly growing mycobacteria account for most of the pathogens . They cause chronic and indolent pulmonary infection, lymphadenitis, disseminated diseases especially in patients with AIDS and localized skin, soft tissue, and skeletal infection . Because clinical features of NTM are not discernible from those of M . tuberculosis and NTM are ubiquitous in our environment, isolation and identification of the bacilli are mandatory for the diagnosis, and several diagnostic criteria are put forth.

Nippon Rinsho, 1998 Dec, 56(12), 3171 - 5
{Treatment of multi drug resistant tuberculosis}; Sumitomo S; Multi drug resistant pulmonary Tuberculosis (MDR-TB) are divided into two types . The one is primary drug resistance and the other is acquired drug resistance . Cases of acquired MDR-TB are more often . Chemotherapy of MDR-TB demands use in combination of three or more sensitive anti-tuberculosis drugs, but it is difficult to apply this combined treatment practically . In Japan, it is often effective to use in combination of sensitive anti-tuberculosis drugs added PZA, Newquinolon agents and Clarithromycin . When chemotherapy is not effective, surgical treatment should be performed . We experienced six operation cases of MDR-TB . Lobectomy were performed in five cases, and all cases were negative tuberculous bacilli after operation . One case of thoracic empyema with bronchial fistula was positive tuberculous bacilli after operation and died of MDR tuberculosis.

Nippon Rinsho, 1998 Dec, 56(12), 3144 - 7
{Tuberculosis of the skin}; Imamura S; Tuberculosis of the skin is now becoming one of the rare diseases . However, we can still see it in the patients with immunodeficiency or treated with immunosuppressants for a long time . Diagnosis of this disease is made by the characteristic clinical findings and the results of laboratory findings . This disease is divided into two types: true cutaneous tuberculosis and tuberculid . The former is produced by the proliferation of the tuberculous bacilli in the skin . Lupus vulgaris, tuberculosis verrucosa cutis, cutaneous primary tuberculosis, tuberculosis cutis orificialis and cutaneous miliary tuberculosis are included . The latter type is the skin manifestation of allergic reaction against tuberculous bacilli in the tuberculous lesions of other organs . Culture of tuberculous bacilli from the skin lesions shows usually negative . Erythema induratum Bazin, papulonecrotic tuberculid, penis tuberculid and lichen scrofulosorum are included.

Nippon Rinsho, 1998 Dec, 56(12), 3126 - 8
{Tuberculosis of the breast}; Ohgaki K et al.; Tuberculosis of the breast is a rare modern disease or a forgotten diagnosis . During the last 15 years (1982-1996), 28 cases of mammary tuberculosis were reported in Japan . The initial diagnosis of almost all were carcinoma . Physical sign, mammography and USG are not so usefull for the diagnosis . It is important for the early and certain diagnosis to detect acid-fast bacilli on smear or culture and to perform pathological examination on biopsied specimen.

Nippon Rinsho, 1998 Dec, 56(12), 3114 - 7
{Tuberculosis in circulation system}; Ashizawa N et al.; Tuberculous pericarditis develops either via hematogenous or lymphangeal spread, or directly from pulmonary lesions . Tuberculous pericarditis begins with fibrin deposits, granuloma formation, and the presence of live acid-fast bacilli . A pericardial effusion, which is serous but often contains some blood with a high level of protein . Recently, PCR technology has been employed to amplify M . Tuberculosis DNA from pericardial fluid . The elevation of ADA (> 45 U/l) is supportive of the diagnosis . Tuberculous pericarditis is detected clinically either in the effusive stage by nonspecific systemic syndrome or after the development of constrictive pericarditis . The short-course treatment of tuberculous pericarditis should consist of three-drug regimen, such as INH, RFP, PZA, SM, EB . The use of prednisolone is controversial . Tuberculous myocarditis is extremely rare because of low affinity between M . Tuberculosis and myocardium . Most cases of tuberculous pericarditis are clinically silent and diagnosed at autopsy.

Cell Immunol, 1998 Dec 15, 190(2), 112 - 20
Functional activity of alveolar and peripheral cells in patients with human acquired immunodeficiency syndrome and pulmonary tuberculosis; Bonecini-Almeida Mda G et al.; We compared the peripheral and pulmonary response to assess the phagocytic activity of monocytes/macrophages and neutrophils and the lymphoproliferative response (LPR) against Mycobacterium tuberculosis antigens from 21 AIDS patients, presenting at diagnosis with active pulmonary tuberculosis (TB), other non-TB pulmonary infection, or no pulmonary infection, as well as patients with active pulmonary TB and healthy control subjects . Alveolar lymphocyte analysis demonstrated that AIDS/TB patients had more markedly reduced percentages of CD4(+) lymphocytes than AIDS/TB patients and an increase in the percentage of CD8(+) lymphocytes, probably reflecting the impairment of CD4(+) T lymphocytes in peripheral blood at the lungs . Moreover, alveolar lymphocytes from AIDS/TB patients demonstrated a two- to fourfold decrease in LPR against M . tuberculosis antigens . Interestingly, it was observed an enhanced migration of natural killer cells to the lungs in all patients group . The phagocytic activity in alveolar macrophages and neutrophils showed that AIDS/TB patients had a twofold decreased capacity to ingest inert particles compared with AIDS patients . Comparing the alveolar and peripheral lymphocyte number and functional activity to M . tuberculosis-antigens it was possible to demonstrate that in both sites these cells had similar profile . However, the innate immune response in lungs showed a reduced activation in the presence of HIV infection, regarding the M . tuberculosis coinfection . These findings suggest that the advanced impairment of CD4(+) T lymphocyte in HIV-1 infection may lead to a deactivation of alveolar macrophages, enhancing bacilli burden and HIV replication in the lungs and furthering dissemination .

Br J Surg, 1998 Dec, 85(12), 1713 - 5
Ultrasonographically-guided fine-needle aspiration cytology in the diagnosis of colonic lesions; Heriot AG et al.; BACKGROUND: The use of fine-needle aspiration cytology (FNAC) in the diagnosis of colonic lesions was investigated . METHODS: Some 22 patients (median age 71 years) with a colonic lesion identified on abdominal ultrasonography underwent ultrasonographically-guided FNAC using a 21-G needle . The sample was checked immediately by a cytopathologist for adequacy . RESULTS: Eighteen patients had colonic carcinoma; aspiration cytology detected malignant epithelial cells consistent with colonic carcinoma in 17 patients and severely dysplastic cells in one patient . The sensitivity and specificity of ultrasonographically-guided FNAC in the diagnosis of colonic carcinoma was 94 and 100 per cent respectively . The remaining four patients had a diagnosis of ileocaecal tuberculosis, ileocaecal Crohn's disease, and metastatic adenocarcinoma in the liver with no identifiable primary (two patients) . One demonstrated granulomata, grew acid-fast bacilli and the patient was treated for tuberculosis . One had inflammatory cells and the patient was found to have Crohn's disease on histology . The remaining two patients had confirmed metastatic adenocarcinoma in the liver on aspiration cytology but suspected colonic lesions were found to be benign on cytological examination and no primary lesion was subsequently demonstrated . There were no complications of FNAC and patients complained of minimal discomfort . There has been no evidence of tumour recurrence with a median follow-up of 12 (range 1-25) months . CONCLUSION: Ultrasonographically-guided FNAC is a valid method for the diagnosis of colonic tumours.

J Am Board Fam Pract, 1998 Nov-Dec, 11(6), 459 - 64
Tuberculous cerebellar abscess; Oshinowo AG et al.; BACKGROUND: Tuberculosis is an important illness with an increasing occurrence . Although considered primarily a pulmonary disease, tuberculosis can affect any organ system . Central nervous system involvement is potentially devastating and occurs with escalating frequency in both immunocompetent and immunologically incompetent populations . METHODS: This case report involved a patient admitted to the authors' inpatient service . Data were obtained from the patient's medical record . MEDLINE and Index Medicus literature searches were conducted for the years 1977 to the present, with cross-references for earlier articles . RESULTS AND CONCLUSIONS: A 36-year-old previously healthy, immunocompetent woman with a diagnosis of extrapulmonary tuberculosis and no determined primary focus was found to have a cerebellar abscess . Treatment included surgical excision of the abscess combined with 6 months of antituberculosis therapy . Diagnostic tools included the tuberculosis skin test, smears and culture of specimens, computed tomographic scans, and rapid assays based on nucleic acid amplification, ie, polymerase chain reaction . The polymerase chain reaction has great potential for rapid diagnosis of Mycobacterium tuberculosis, particularly when there might be few bacilli, as in pleural, peritoneal, or cerebrospinal fluid . Appropriate therapy for tuberculous cerebellar abscess includes standard antituberculosis medications for 6 to 9 months and surgical excision of the abscess.

Scand J Immunol, 1998 Dec, 48(6), 577 - 84
Secreted proteins of Mycobacterium leprae; Harboe M et al.; In mycobacteria, secreted proteins represent a distinct group, probably of particular importance for development of immune responses following infection . Quantification of individual proteins in culture fluid and corresponding disrupted bacilli permits determination of a localization index for identification of secreted proteins . This procedure cannot be applied to Mycobacterium leprae because secreted proteins are lost during isolation of bacilli from tissues . The DNA sequences of secreted proteins of Mycobacterium tuberculosis were compared with sequences of M . leprae . Genes for homologues of the 85a, 85b, 85c, mpt32 (apa), mpt51, erp, mtc28, Rv2376c, Rv3354 and Rv0526 genes were identified . All of these contain signal sequences typical for secretion in M . leprae . In several instances the local distance between marker genes and occurrence on the same or the complementary DNA strand was similar in these two species . The genomic organisation of genes for secreted proteins is thus very similar in M . leprae and M . tuberculosis, the homology being higher for the mature polypeptide chains than for the corresponding signal peptides.

Pathol Biol (Paris), 1998 Oct, 46(8), 597 - 603
Diagnosis of extrapulmonary tuberculosis by a commercial polymerase chain reaction kit; Bemer-Melchior P et al.; The Roche Amplicor Mycobacterium tuberculosis PCR test was compared with mycobacterial culture for direct detection of M . tuberculosis in extrapulmonary specimens . From January 1995 to October 1996, 124 clinical specimens from 112 patients were assessed, including 47 body fluids, 61 tissue specimens and 16 abscesses . The sensitivity and specificity of Amplicor PCR compared to culture were 63.6% and 93.1% respectively . Analysis of 7 PCR-positive, culture-negative specimens confirmed that all were from patients with recently diagnosed tuberculosis under treatment . Eight specimens were PCR negative-culture positive, including a pleural fluid containing inhibitory substances . On acid-fast bacilli (AFB) smear-negative specimens, sensitivity and specificity were 53 and 100% respectively . The best results for Amplicor PCR were obtained with abscesses and biopsies . It is concluded that this test, highly specific for the diagnosis of tuberculosis, is at least as sensitive on extrapulmonary specimens as on smear-negative respiratory specimens.

Antimicrob Agents Chemother, 1999 Jan, 43(1), 85 - 9
Moxifloxacin (BAY12-8039), a new 8-methoxyquinolone, is active in a mouse model of tuberculosis; Miyazaki E et al.; Moxifloxacin (BAY12-8039) is a new 8-methoxyquinolone shown to be active against Mycobacterium tuberculosis in vitro . We tested moxifloxacin for activity in mice against M . tuberculosis CSU93, a highly virulent, recently isolated clinical strain . The MIC of moxifloxacin for the CSU93 strain was 0.25 microg/ml . The serum moxifloxacin concentration after oral administration in mice peaked within 0.25 h, reaching 7.8 microg/ml with doses of 100 mg/kg of body weight; the maximum concentration and the analysis of the area under the concentration-time curve revealed dose dependency . When mice were infected with a sublethal inoculum of mycobacteria and then treated with moxifloxacin at 100 mg/kg per day for 8 weeks, the log10 CFU counts in the organs of treated mice were significantly lower than those for the control group (0.6 +/- 0.2 versus 5.6 +/- 0 . 3 in the lungs and 1.5 +/- 0.7 versus 4.9 +/- 0.5 in the spleens, respectively; P < 0.001 in both organs) . The effectiveness of moxifloxacin monotherapy was comparable to that seen in mice receiving isoniazid alone . Combination therapy with moxifloxacin plus isoniazid was superior to that with moxifloxacin or with isoniazid alone in reducing bacillary counts in the organs studied . Using a sensitive broth-passage subculture method, we demonstrated that 8 weeks of treatment with moxifloxacin (100 mg/kg per day) or with moxifloxacin plus isoniazid (100 mg/kg and 25 mg/kg, respectively, per day) sterilized the lungs in seven of eight and in eight of eight mice, respectively . Among surviving bacilli isolated from animals infected with a high-titer inoculum and treated for 7 weeks with low-dose moxifloxacin (20 mg/kg per day), breakthrough resistance to moxifloxacin was not observed . These results indicate that moxifloxacin is highly effective in reducing M . tuberculosis infection in mice and has activity comparable to that of isoniazid . Combination therapy with moxifloxacin and isoniazid was highly effective, suggesting that moxifloxacin may be useful in multiple-drug regimens for human tuberculosis.

Sangre (Barc), 1998 Oct, 43(5), 436 - 8
{Drug-induced agranulocytosis: clinical study of 19 cases}; Marquez JA et al.; Agranulocytosis is one of the most serious side effects to drugs . From January 1991 to June 1996 were diagnosed 19 cases of agranulocytosis associated with drugs at our hospital (incidence rate: 9.4 over million hab . per year) . The average age was 62 and 11 cases were women . The drugs most commonly involved were metamizol and ticlopidine . In 15 of the patients fever blew up and 16 presented some infectious location . In 9 of the cases some positive microbiological culture was obtained, gram-negative bacilli being the commonest . G-CSF was used in 13 of the patients, observing a quicker haematological recovery (5.7 days vs 9.1, p = 0.07), though without any difference in mortality, which was of 0% . All this leads to the following conclusions: a high incidence of agranulocytosis in our environment and the important role of metamizol and ticlopidine in its origin.

Hunan Yi Ke Da Xue Xue Bao, 1997, 22(4), 301 - 3
{Delayed brain injury induced by Bordetella pertussis in rats}; Chen X et al.; To induced new model of delayed infection brain injury, we divided randomly 40 adult male Sprague-Dawley rats into four groups: bordetella pertussis (BP) groups, and normal sailine (NS) groups in 4 h (n = 10) and 24 h (n = 10), respectively, injected BP at 0.2 ml.kg-1 which contained the bacilli in 10.8 x 10(9).ml-1 into the rat left internal carotid artery of BP groups, and injected at the equal volume as control in the same way into NS groups . The water content (WC), Evans blue content (EB), cations of sodium, potassium, calcium in the brain tissues were measured and the morphologic changes in the hippocampal CA1 were detected by electron microscopy . These results were shown as follows: the left hemisphere of BP group in 4 h was characterized by the brain edema which predominated in swollen, necrotic astroglial cells, endothelial cells, and insignificant increase of contents of sodium, calcium and decrease of potassium; BP group in 24 h was characterized by dark cells, the brain edema also existed in astroglial cells . These results indicate that a delayed infection brain injury model is performed successfully by injection with BP into the left internal carotid artery of rats . The model is characterized by the features of delayed neuronal death and mixed type brain edema.

Kekkaku, 1998 Nov, 73(11), 679 - 85
{Multidrug-resistant tuberculosis . 5 . Human immunodeficiency virus infection and multidrug-resistant tuberculosis}; Fujita A; Outbreaks of multidrug-resistant tuberculosis (MDR-TB) among human immunodeficiency virus (HIV)-infected persons reported in the United States were very serious and the risks were increased by the delay of diagnosis, rapid progression from infection to active disease, inadequate therapy and poor tuberculosis (TB) control . Prevalence of drug-resistant TB among HIV-infected patients in Japan was studied . The results of drug susceptibility were collected through the nationwide working group for a survey of HIV-infected TB . Data of susceptibility for 39 cases were obtained . The isolates of two cases were resistant to isoniazid and rifampicin (including clinical failure of response), although no outbreak of MDR-TB was found in Japan . Case study of a patient who developed MDR-TB revealed that drug resistance might be selected by insufficient anti-TB therapy . The rate of resistance to any of the anti-TB drugs in HIV-infected patients seemed to be high, although strictly evaluation was difficult due to no standardization for drug susceptibility testing . Of 9 cases with resistance to any of the anti-TB drugs, 8 had extrapulmonary TB including 5 cases of disseminated TB . In contrast thirteen of 30 cases without drug resistance had extrapulmonary TB . Since it has been reported that HIV infection is related to increased rates of drug resistance of TB bacilli, treatment with four-drug regimen should be started and sufficient courses of therapy are needed in HIV-infected TB patients.

Kekkaku, 1998 Nov, 73(11), 665 - 72
{Multidrug-resistant tuberculosis . 3 . Epidemiology of drug-resistant tuberculosis in Japan}; Yoshiyama T; In Japan, the frequency of drug-resistant tuberculosis has been investigated every 5 years since 1950s and increase of initial and acquired drug resistance has not been observed . However, the mathematical model analyse of time trend of prevalence of drug-resistant tuberculosis and frequency of initial drug resistance in Korea shows that there is little difference of infectivity and/or proportion of clinical breakdown between susceptible bacilli and resistant ones . The prognosis of isoniazid (INH) and rifampicin (RFP) resistant tuberculosis cases in Fukujuji Hospital was investigated . 367 cases including 50 initial drug resistant cases were analyzed with life table analysis . 50% of all cases and 70% of initial drug resistant cases became negative, 13% of all cases and 4% of initial drug resistant cases remained as positive, 37% of all cases and 27% of new cases died . Among cases who did not convert negative within one year, 41% of all cases and 34% of initial drug resistant cases died . The prognosis of INH and RFP resistant tuberculosis cases were still not satisfactory.

Kekkaku, 1998 Nov, 73(11), 649 - 55
{Multidrug-resistant tuberculosis . 1 . Drug susceptibility testing and its standardization}; Abe C; Drug susceptibility testing is one of the most difficult procedures to standardize in mycobacteriology laboratories . International standardization of the test is needed for comparative evaluation of controlled chemotherapeutic trials, for epidemiological surveys on the prevalence of drug resistance, and for guidance in the treatment of tuberculosis patients . In 1996, a new procedure for drug susceptibility testing was proposed by an ad hoc committee of the Japanese Society for Tuberculosis . The proposal is for a test with the proportion method using an Ogawa egg medium similar to those recommended by the WHO . Resistance is expressed as the percentage of colonies that grow on critical concentrations of the drugs, i.e . 0.2 microgram/ml for isoniazid, 40 micrograms/ml for rifampicin, 10 micrograms/ml for streptomycin and 2.5 micrograms/ml for ethambutol . Strains of tubercle bacilli which are grown on drug-containing media represents more than 1% of the number of colonies that develop on drug-free media are considered to be clinically resistant to that agent . The results are recorded as susceptible (S) or resistant (R) on the laboratory forms . The proportion method using agar- and liquid-based media is used worldwide . In the near future a test with agar- or liquid-based media will be discussed for standardization of the test in Japan, as described by the National Committee for Clinical Laboratory Standards of the United States.

Kekkaku, 1998 Nov, 73(11), 625 - 31
{Investigations into the significance of routine health examinations for tuberculosis in teachers based on the analysis of results of extraordinary health examinations}; Yamamoto M; School teachers are regarded as one of the danger groups in contracting tuberculosis infection and are subjected to strict tuberculosis controls, since when they develop tuberculosis, many school children are exposed to infection to the disease . However, the recent decrease in the incidence of tuberculosis in Japan has led to disputes concerning the significance of routine mass health examinations for tuberculosis . In this study, the significance of routine health examinations for tuberculosis in teachers was investigated by the analysis of the results of extraordinary health examinations carried out for tuberculosis in teachers as the index cases . A total of 496 extraordinary health examinations were carried out by Nagoya City from 1975 to 1986 and by Aichi Prefecture from 1980 to 1995 . In 49 instances of these examinations, teachers were regarded as index cases, which included 25 teachers of public primary, middle or high schools and 14 teachers of private schools, including private instructors for piano, painting or calligraphy, and teachers for supplementary education . The results of these examinations in both groups were compared, regarding the routes of notification, the disease status of the index cases, and the frequency and the scale of the infections of tuberculosis observed among contacts with the index cases . "Group infections of tuberculosis" was defined as instances the infection in which 20 or more cases were infected by the index case, "small scale group infection" as 5-19 infected cases, and "cases with infection" as 1-4 infected cases . The result obtained were as follows . 1 . The response rates to routine health examinations were 99.9% in the teachers of public primary, middle or high schools, and about 20-30% in the teachers of private schools . 2 . The proportion of the cases notefied by routine examinations were 68.0% in the former group and 21.4% in the latter group . The cases notefied before the onset of the symptoms in the former group was significantly more frequent than in the latter group . 3 . In the former group, no far advanced cases were identified, whereas 2 (14.3%) far advanced cases were identified in the latter group . The cases with amount of tubercle bacilli in sputum exceed 3 on the Gaffky scale were 32.0% in the former group and 61.5% in the latter group . 4 . One (4.0%) case of the "group infections of tuberculosis" was observed in the former group, and 2 (14.3%) cases in the latter group . "Small scale group infection" was observed in 4.0% of the former group and in 21.4% of the latter group, and "cases with infection" in 8.0% of the former group and in 35.7% of the latter group . The frequency and the scale of the infections of tuberculosis observed among contacts with the index cases was significantly smaller in the former group than in the latter group . In conclusion, routine health examinations for tuberculosis for teachers seems valuable for the early diagnosis of tuberculosis cases and for the prevension of the infection of tuberculosis in schools.

No To Shinkei, 1998 Nov, 50(11), 1041 - 52
{A 61-year-old man with progressive gait disturbance, freezing, and vertical gaze paresis who developed esophagus cancer}; Miyashita N et al.; We report a 61-year-old Japanese man who died of complications of esophagus cancer surgery . He was well until his 55 years of the age, when he had an onset of speech disturbance and hand writing . He was seen by a neurologist who prescribed Menesit 600 mg/day . His symptoms improved with this medication . In 1993, three years after the onset, he started to show gait disturbance and easy to fall . In 1995, he noted difficulty in eye opening . He visited our clinic on October 26, 1996 . On examination, he showed vertical gaze paresis, masked face, nuchal rigidity, small step gait, freezing phenomena, and festination . His mental status was normal . He was treated with 800 mg/day of Menesit, 800 mg/day of L-dops, and 10 mg/day of bromocriptine with little improvement in his symptoms . Cranial CT scan revealed some dilatation of the third ventricle . Subsequent clinical course was one of the slow progression of his parkinsonism . In September of 1997, he noted difficulty in swallowing . He was admitted to the gastrointestinal service of our hospital on October 14, 1997 . On admission, neurologic status was essentially similar to the previous one, but he showed more advanced state of his parkinsonism . Upper gastrointestinal series revealed a mass lesion of about 11.5 cm in length protruding into the lower esophagus lumen . Subtotal esophagus resection including the mass was performed on December 2, 1997 . The stomach was elevated for anastomosis with the upper esophagus . No metastases were found in the mediastinum except for two lymph nodes in the para-esophageal region . The subsequent course was complicated by marked elevation of GOT, GPT, LDH, total bilirubin as well as direct bilirubin, alkaliphosphatase, and amylase starting in the evening of the surgery . On December 7, leukocytosis and pneumonic shadow were seen involving his right lung . On December 10, he developed cardiopulmonary arrest . He was once resuscitated; however, he developed cardiac arrest again seven hours later and pronounced dead . He was discussed in a neurologic CPC . The chief discussant arrived at the conclusion that the patient had PSP and the cause of the death was ascribed to circulatory disturbance to the liver . The discussant also thought that the terminal course was complicated by cholangitis or cholecystitis, sepsis, and pulmonary embolism . Surgical specimen of the esophagus tumor revealed carcinosarcoma . Postmortem examination revealed yellowish discoloration of the peritoneum and mesenterium, and accumulation of clouded ascites indicating the presence of peritonitis . Inflammatory change extended to the mediastinum . On microscopic examination, various kinds of bacilli and candida spores were seen . The liver was enlarged and a perforation was noted in the gallbladder causing biliary necrosis in the adjacent liver . An extensive infarct was seen in the left lobe of the liver; this was found to be due to obstruction of the hepatic artery at the site of the duodenohepatic mesenterium and obstruction of intrahepatic portal vein secondary to retrograde intrahepatic cholangitis in the left lobe . A piece of surgical threads was seen adjacent to the hepatic artery; foreign body granulomatous reaction was seen surrounding the surgical thread . The rupture of the gallbladder appeared to be due to the obstruction of the left branch of the hepatic artery . Neuropathologic examination revealed extensive degeneration of the pallidum, the substantia nigra, and the subthalamic nucleus and presence of neurofibrillary tangles in the remaining neurons . The neuropathologic findings were consistent with progressive supranuclear palsy, although the pathologic changes in the midbrain tegmentum was only mild gliosis.

Int J Mol Med, 1999 Jan, 3(1), 69 - 74
Opposite cellular accumulation and nitric oxide production in vivo after pleural immunization with M . leprae or M . bovis BCG; Moura AC et al.; Mycobacteria as intracellular pathogens have evolved mechanisms to survive within macrophages . Our previous data showed that M . leprae (ML), unlike M . bovis BCG, did not induce an inflammatory response in the mice subcutaneous tissue . Further, ML inhibited BCG-induced foot pad oedema and seemed to transform macrophages in epithelioid cells . Since these mycobacteria share common antigens, here we seeked to compare the acute and chronic cellular response evoked by ML and BCG in pleurisy of a mycobacteria-susceptible mice (BALB/c) . The total leukocytes, the cell type that migrated to the pleural cavity and macrophage activation assayed by nitric oxide release were determined . Live or dead BCG Moreau recruited the same extent of cells, essentially monocytes and neutrophils, dose-dependently, in both acute and chronic pleurisy . BCG-induced eosinophilia was observed only in the acute response (after 24 h of injection) . A significant nitric oxide release by pleural macrophages was triggered by BCG Moreau without previous activation . Nevertheless, ML failed to recruit leukocytes to the pleural space or to lead to nitric oxide production despite the number of bacilli used and the time studied (1, 7 or 14 days after injection) . Although these mycobacteria have common antigens that cross-react, these data show a distinct ability of ML or BCG to recruit cells to the pleural space and to activate pleural macrophage for nitric oxide production in vivo.

J Bacteriol, 1999 Jan, 181(1), 270 - 83
Adaptation of Mycobacterium smegmatis to stationary phase; Smeulders MJ et al.; Mycobacterium tuberculosis can persist for many years within host lung tissue without causing clinical disease . Little is known about the state in which the bacilli survive, although it is frequently referred to as dormancy . Some evidence suggests that cells survive in nutrient-deprived stationary phase . Therefore, we are studying stationary-phase survival of Mycobacterium smegmatis as a model for mycobacterial persistence . M . smegmatis cultures could survive 650 days of either carbon, nitrogen, or phosphorus starvation . In carbon-limited medium, cells entered stationary phase before the carbon source (glycerol) had been completely depleted and glycerol uptake from the medium continued during the early stages of stationary phase . These results suggest that the cells are able to sense when the glycerol is approaching limiting concentrations and initiate a shutdown into stationary phase, which involves the uptake of the remaining glycerol from the medium . During early stationary phase, cells underwent reductive cell division and became more resistant to osmotic and acid stress and pool mRNA stabilized . Stationary-phase cells were also more resistant to oxidative stress, but this resistance was induced during late exponential phase in a cell-density-dependent manner . Upon recovery in fresh medium, stationary-phase cultures showed an immediate increase in protein synthesis irrespective of culture age . Colony morphology variants accumulated in stationary-phase cultures . A flat colony variant was seen in 75% of all long-term-stationary-phase cultures and frequently took over the whole population . Cryo scanning electron microscopy showed that the colony organization was different in flat colony strains, flat colonies appearing less well organized than wild-type colonies . Competition experiments with an exponential-phase-adapted wild-type strain showed that the flat strain had a competitive advantage in stationary phase, as well a providing evidence that growth and cell division occur in stationary-phase cultures of M . smegmatis . These results argue against stationary-phase M . smegmatis cultures entering a quiescent state akin to dormancy but support the idea that they are a dynamic population of cells.

Infect Immun, 1999 Jan, 67(1), 74 - 9
Mycobacterium tuberculosis catalase and peroxidase activities and resistance to oxidative killing in human monocytes in vitro; Manca C et al.; Mycobacterium tuberculosis has a relatively high resistance to killing by hydrogen peroxide and organic peroxides . Resistance may be mediated by mycobacterial catalase-peroxidase (KatG) and possibly by alkyl hydroperoxide reductase (AhpC) . To determine the interrelationship between sensitivity to H2O2, catalase and peroxidase activities, and bacillary growth rates measured both intracellularly in human monocytes and in culture medium, we examined one laboratory strain, two clinical isolates, and three recombinant strains of M . tuberculosis with differing levels of KatG and AhpC . Five of the mycobacterial strains had intracellular doubling times of 27 to 32 h, while one KatG-deficient clinical isolate (ATCC 35825) doubled in approximately 76 h . Killing of mycobacteria by exogenously added H2O2 was more pronounced for intracellular bacilli than for those bacilli derived from disrupted monocytes . Strains with no detectable KatG expression or catalase activity were relatively sensitive to killing (43 to 67% killing) by exogenous H2O2 . However, once even minimal catalase activity was present, mycobacterial catalase activity over a 10-fold range (0.56 to 6.2 U/mg) was associated with survival of 85% of the bacilli . Peroxidase activity levels correlated significantly with resistance of the mycobacterial strains to H2O2-mediated killing . An endogenous oxidative burst induction by 4beta-phorbol 12beta-myristate 13alpha-acetate treatment of infected monocytes reduced the viability of the KatG null strain (H37Rv Inhr) but not the KatG-overexpressing strain {H37Rv(pMH59)} . These results suggest that mycobacterial resistance to oxidative metabolites (including H2O2 and other peroxides) may be an important mechanism of bacillary survival within the host phagocyte.

J Clin Microbiol, 1999 Jan, 37(1), 175 - 8
False-positive Gen-Probe direct Mycobacterium tuberculosis amplification test results for patients with pulmonary M . kansasii and M . avium infections; Jorgensen JH et al.; The Gen-Probe Amplified Mycobacterium Tuberculosis Direct (MTD) test has been approved for use in the United States for the rapid diagnosis of pulmonary tuberculosis in patients with acid-fast smear-positive sputum samples since 1996 . Four patients infected with human immunodeficiency virus and one chronic pulmonary-disease patient seen in our institutions with abnormal chest radiographs and fluorochrome stain-positive sputa were evaluated for tuberculosis, including performance of the MTD test on expectorated sputum samples . Three of these five patients' sputa were highly smear-positive (i.e . , more than 100 bacilli per high-power field), while two patient's sputa contained 1 to 10 bacilli per field . MTD results on sputum specimens from these patients ranged from 43,498 to 193,858 relative light units (RLU) . Gen-Probe has defined values of at least 30,000 RLU as indicative of a positive test, i.e., the presence of Mycobacterium tuberculosis RNA . Four of the patients' sputum cultures yielded growth of M . kansasii within 6 to 12 days, and the fifth produced growth of M . avium only . One patient's culture contained both M . kansasii and M . avium, but none of the initial or follow-up cultures from these five patients revealed M . tuberculosis . However, subsequent cultures from three of the patients again revealed M . kansasii . During the period of this study, in which MTD tests were performed on smear-positive sputum specimens from 82 patients, four of seven patients with culture-proven M . kansasii pulmonary infections yielded one or more false-positive MTD tests . The MTD sensitivity observed in this study was 93.8%, and the specificity was 85.3% . Five cultures of M . kansasii (including three of these patients' isolates and M . kansasii ATCC 12478), and cultures of several other species were examined at densities of 10(5) to 10(7) viable CFU/ml by the MTD test . All five isolates of M . kansasii and three of three isolates of M . simiae yielded false-positive test results, with readings of 75,191 to 335,591 RLU . These findings indicate that low-level false-positive MTD results can occur due to the presence of M . kansasii, M . avium, and possibly other Mycobacterium species other than M . tuberculosis in sputum . Low-level positive MTD results of 30,000 to 500,000 RLU should be interpreted in light of these findings . It remains to be determined if the enhanced MTD test (MTD 2) recently released by Gen-Probe will provide greater specificity than that observed in this report with its first-generation test.

Gerontology, 1999 Jan-Feb, 45(1), 49 - 52
Oral flora of elderly patients following acute medical admission; Preston AJ et al.; The human oral microflora is diverse and is usually predominately composed of Gram-positive bacteria . It is uncommon to find Gram-negative bacilli (GNB) in healthy mouths . The incidence of infection with GNB rises in institutionalised, frail elderly subjects . There is also evidence of an association between intra-oral GNB presence and denture wearing . There have been few studies which have investigated intra-oral GNB carriage in acutely ill elderly patients . The aim of this study was to evaluate the oral flora of a group of elderly patients during an acute medical admission and to investigate any associations between the oral microflora and existing medical or oral factors . A total of 28 patients (17 females and 11 males; age: 74-93 years) on a care for the elderly ward were studied . Epidemiological data, detailed medical histories and oral examinations were undertaken . In addition, oral swabs of the palate area were taken to determine their oral flora . Twelve (43%) of the patients had GNB in their oral cavities . These patients were suffering from a variety of medical conditions and were on various drug regimes . There was a correlation between oral GNB presence and denture use . There was no association between GNB presence and denture hygiene . As oropharyngeal GNB colonisation can be associated with infections such as aspiration pneumonia, it is important in patients at risk that intra-oral organisms are identified and managed.

Arq Neuropsiquiatr, 1998 Sep, 56(3B), 585 - 94
{Ulnar nerve palsy in leprosy without skin changes: biopsy of the superficial branch of the ulnar nerve in the hand}; de Freitas MR et al.; Leprosy is one of the most common diseases of peripheral nerves in the world . In Brazil it is particularly frequent, being a major health problem . In tuberculoid leprosy the ulnar nerve is the most common affected nerve . Sometimes there are no skin changes . In these cases in spite of nerve thickening only the nerve biopsy is capable to make a specific diagnosis . We performed a biopsy in the dorsal sensory branch of the ulnar nerve in the hand in 17 patients with ulnar palsy with thickening of the nerve in the elbow, without skin changes . The pathological findings consisted mainly of: loss of fibers (14 cases), inflammatory infiltration (13), fibrosis (12), demyelination and remyelination (9), presence of granuloma (6) and presence of bacilli (5 cases) . We conclude that in case of ulnar nerve palsy in leprosy without skin changes, the biopsy of the dorsal sensory branch of this nerve in the hand is a good procedure for the diagnosis of leprosy.

J S Afr Vet Assoc, 1998 Sep, 69(3), 98 - 101
Tuberculosis in Kafue lechwe (Kobus leche kafuensis) and in a bushbuck (Tragelaphus scriptus) on a game ranch in central province, Zambia; Zieger U et al.; Mycobacteriosis was diagnosed for the first time outside a national park in free-ranging wild animals on a game ranch in Zambia . A Kafue lechwe (Kobus leche kafuensis) was found dead with tuberculous lesions on a ranch near Lusaka . Acid-fast bacilli were found in the affected organs . Mycobacteria were isolated from these tissues . A bushbuck (Tragelaphus scriptus) was found dead on the same ranch with multiple superficial abscesses in the neck region, extensive granulomatous lesions in the lung, the bronchial and mediastinal lymph nodes and several nodular lesions in the spleen . Few acid-fast bacilli were found in the exudate from the abscesses and lesions in the affected organs . Histologically the lesions resembled those of tuberculosis, but mycobacteria could not be isolated . In addition, 1 Kafue lechwe among 37 wild ungulates of 13 species shot on the ranch showed typical tuberculous lesions in the lungs, but the diagnosis was not confirmed by bacterial isolation . The role of the Kafue lechwe as maintenance host for tuberculosis as well as in the possible spread of this disease to other wildlife are discussed.

Trans R Soc Trop Med Hyg, 1998 Jul-Aug, 92(4), 415 - 6
'Improved sensitivity of direct microscopy for detection of acid-fast bacilli in sputum in developing countries; Habeenzu C et al.; Diagnosis of pulmonary tuberculosis depends on the bacteriological examination of sputum . Sputum smear microscopy is efficient and can confirm the disease . However, direct microscopy of sputum, though rapid, has low sensitivity . There is, therefore, an urgent need to develop rapid, much more sensitive and specific methods . In a field study we collected sputum samples from 488 tuberculosis suspects and compared the results of examining smears prepared after treatment with sodium hypochlorite (NaOCl) and concentration of bacteria by centrifugation and direct staining with Ziehl-Neelsen stain . Direct smears stained with auramine-phenol were the reference standard . The use of NaOCl increased the sensitivity from 43.4% to 76.3%, with a specificity of 100% for both methods . The method is simple and cheap . As a potent disinfectant, NaOCl also reduces the risk of laboratory-acquired infection . Its application would increase the efficiency of tuberculosis control programmes.

Respir Med, 1998 Jun, 92(6), 815 - 9
Rapid diagnosis of smear-negative pulmonary tuberculosis via fibreoptic bronchoscopy: utility of polymerase chain reaction in bronchial aspirates as an adjunct to transbronchial biopsies; Wong CF et al.; Fibreoptic bronchoscopy was performed on 190 patients with chest radiographic lesions and negative sputum smears for acid-fast bacilli . Aside from obtaining transbronchial biopsies for histological examination, bronchial aspirate specimens were also tested for Mycobacterium tuberculosis complex DNA by a conventional polymerase chain reaction (PCR) technique . Of 177 transbronchial biopsies performed, a diagnosis was found in 64 cases {43 cases of tuberculosis (TB), 17 cases of lung carcinoma and four cases of other infective/inflammatory diseases} giving a diagnostic yield of 36.2% . PCR was positive in 105 of 108 finally diagnosed cases of TB and 22 of 82 non-TB cases . The sensitivity, specificity, positive predictive value and negative predictive value of PCR when applied to bronchial aspirate specimens for diagnosing smear-negative pulmonary TB were 97.2%, 73.2%, 82.7% and 95.2% respectively . Therefore, detection of M . tuberculosis complex DNA in bronchial aspirates by PCR might have an adjunctive place to transbronchial biopsies in the rapid diagnosis of smear-negative pulmonary tuberculosis.

Int J Tuberc Lung Dis, 1998 Nov, 2(11), 877 - 84
Outcome of chemotherapy in 107 patients with pulmonary tuberculosis resistant to isoniazid and rifampin; Park SK et al.; SETTING: National Masan Tuberculosis Hospital, Korea . OBJECTIVE: Treatment for multidrug-resistant tuberculosis (MDR-TB) is considered to be clinically important, but there are few reports on this topic . We therefore retrospectively evaluated the outcomes of chemotherapy only for pulmonary MDR-TB . DESIGN: We reviewed the clinical courses of 107 patients with pulmonary disease due to Mycobacterium tuberculosis resistant to rifampin and isoniazid who were under follow-up between March 1996 and June 1996 after hospitalization between January 1993 and January 1996 . We performed a retrospective cohort study for all the patients' records . Their regimens were selected individually and preferably included four medications that they had not been given previously and to which the strain was fully susceptible . RESULTS: The 107 patients (mean age 38.3 years) had previously received a mean of five drugs, and were shedding bacilli that were resistant to a mean of four drugs . Of 63 patients with sufficient follow-up data, 52 (82.5%) responded to chemotherapy (as indicated by negative sputum cultures for at least three consecutive months); 11 (17.5%) had no response, as shown by continually positive cultures . In a univariate analysis, an unfavorable response was significantly associated with resistance to a greater number of drugs before the current courses of treatment (relative risk 21.5; 95% confidence interval 1.2-3.0; P < 0.05) . The mean period of follow-up was 17 months . There was no subsequent relapse among the patients with responses, and there were no tuberculosis-related deaths . CONCLUSION: In this study, multidrug-resistant pulmonary tuberculosis responded relatively well to carefully selected regimens.

Am J Clin Pathol, 1998 Dec, 110(6), 806 - 9
Detecting disseminated Mycobacterium avium complex infections in HIV-positive patients . The usefulness of bone marrow trephine biopsy specimens, aspirate cultures, and blood cultures; Hussong J et al.; Disseminated Mycobacterium avium complex (MAC) infections are common in patients with acquired immunodeficiency syndrome (AIDS) . These patients frequently seek care with fever accompanied by generalized systemic symptoms and undergo bone marrow biopsy . It is our practice to stain all bone marrow trephine biopsy specimens from patients infected with HIV for acid-fast bacilli (AFB) . We evaluated this practice by comparing the sensitivity and turnaround time for detection of MAC by biopsy specimen staining, bone marrow aspirate culture, and blood culture . Bone marrow trephine biopsy specimens with corresponding bone marrow aspirate and blood cultures from 86 HIV-positive patients were reviewed . Of the 86 patients, 30 had positive results for disseminated MAC infection, and all 30 of those patients had positive blood cultures . Bone marrow aspirate cultures identified 17 MAC-positive cases, and AFB staining of the biopsy specimen identified 9 . The mean times to detection of MAC positivity were 1.1 days for AFB staining of the biopsy specimen, 19 days for bone marrow aspirate culture, and 16 days for blood culture . While AFB staining of biopsy specimens was the least sensitive of the detection methods, it was useful for the rapid diagnosis of disseminated MAC infection, allowing for prompt initiation of antimycobacterial therapy in one third of patients.

Kekkaku, 1998 Oct, 73(10), 591 - 7
{A case of miliary tuberculosis with brain tuberculoma, following intraocular tuberculosis}; Takakura S et al.; A 52-year-old woman with visual loss of her left eye consulted a ophthalmology clinic . She was conducted left vitrectomy and administered corticosteroid under the diagnosis of uveitis of unknown cause . But her visual acuity was not improved . Although re-surgery was planned, pus retention was found in her left eye . After her left eye was resected, fever and general malaise appeared suddenly . Her chest X-ray film revealed diffuse micronodular opacities . Acid-fast bacilli were detected from her sputum and identified to be Mycobacterium tuberculosis . She was diagnosed miliary tuberculosis, and then antituberculous chemotherapy consisting of 4 drugs was started . Granulomatous inflammation destructing retina and numerous acid-fact bacilli were found in histologic examination of the resected eye . This case was thought to be miliary tuberculosis disseminated from intraocular tuberculosis . After 2 months of therapy, neurologic symptoms which might be caused by brain tuberucloma appeared and deteriorated rapidly . But by adding corticosteroid to antituberculous therapy, symptoms were diminished gradually.

Kekkaku, 1998 Oct, 73(10), 585 - 90
{Significance of serum surfactant protein-D (SP-D) level in patients with pulmonary tuberculosis}; Kondo A et al.; Elevated levels of serum surfactant protein-D (SP-D) have been previously reported in patients with idiopathic pulmonary fibrosis (IPF) and pulmonary alveolar proteinosis . To determine whether the same change is seen in other pulmonary diseases, especially pulmonary tuberculosis (TB), we measured the serum SP-D levels in active pulmonary TB (smear and/or culture: positive), acute interstitial pneumonia (AIP), IPF, acute exacerbation of IPF, hypersensitivity pneumonitis (HP), pneumoconiosis, bronchiectasis, and bacterial pneumonia by an enzyme-linked immunosorbent assay using monoclonal antibodies to human lung SP-D, and compared them with those of healthy elderly subjects over 50 years of age . The SP-D level in the healthy elderly subjects was 57.6 +/- 38.4 ng/ml (mean +/- SD, n = 287) . The levels in patients with active pulmonary TB (140.6 +/- 18.2 ng/ml, n = 49), AIP (1,021 ng/ml, n = 1), IPF (307.0 +/- 180.7 ng/ml, n = 42), acute exacerbation of IPF (817.7 +/- 283.6 ng/ml, n = 3), and HP (716.6 +/- 548.8 ng/ml, n = 4) were significantly higher than those in the healthy elderly controls (p < 0.05), whereas those of pneumoconiosis, bronchiectasis, and bacterial pneumonia, 121.9 +/- 92.8 ng/ml (n = 8), 93.9 +/- 72.9 ng/ml (n = 11), and 72.7 +/- 3.4 ng/ml (n = 4), respectively, showed no significant difference with the controls . In active pulmonary TB, the percentage of patients whose serum SP-D levels were over 134.6 ng/ml (mean + 2SD of healthy elderly controls) was 34.7%, and therefore we considered the serum SP-D level was not useful for the diagnosis of pulmonary TB . However, it was significantly higher in the patients with cavity formation than in those without (p < 0.05), and there was a significant positive correlation between the serum SP-D level and the number of tubercle bacilli in the sputum (r = 0.416, p = 0.00165), erythrocyte sedimentation rate at 1 hr (r = 0.489, p < 0.01), and CRP level (r = 0.383, p = 0.003) . These findings suggest that the serum SP-D level is a useful indicator of the disease activity in pulmonary TB.

Intern Med, 1998 Oct, 37(10), 870 - 1
Rounded atelectasis that disappeared after bronchoscopy; Nakagawa Y et al.; We describe a 70-year-old man who presented with a round opacity that disappeared after bronchoscopy . Chest computed tomograms (CT) showed a round opacity in the left lower posterior lung field . Brushings and washings of the left B10 through bronchoscope yielded neither malignant cells nor acid fast bacilli . The patient was diagnosed as having a benign tumor and was not medicated . Chest CT 1.5 months after bronchoscopy showed that the round opacity had disappeared . Although this course was unusual, this radiopacity was quite typical of round atelectasis on the basis of CT appearance.

Rev Inst Med Trop Sao Paulo, 1998 May-Jun, 40(3), 177 - 81
Anti M . leprae IgM antibody determination by ultramicroimmunoenzymatic (UMELISA HANSEN) for the diagnosis and monitoring leprosy; Torrella A et al.; The relationship between the IgM antibody response, antigenic load as well as the clinical improvement after chemotherapy was studied in order to obtain useful data for the early diagnosis and monitoring leprosy . A level of 82% (94/115) agreement was obtained between IgM UMELISA HANSEN and slit-skin smear examination . Discrepant results were observed in 16 patients who showed positive IgM response despite negative by the skin smear examination . In these patients, the IgM response was seen to be associated to the early signal for bacilli recurrence in the skin . In one of these patients the presence of bacilli was demonstrated in the skin, two months after IgM antibodies being detected by UMELISA HANSEN . Also in one of the treated patients positive by both diagnostic techniques, a remarkable decrease in the IgM antibody levels was seen, correlating with a significant clinical improvement . Moreover it was found a direct relationship between the IgM antibody response and bacterial antigenic load, regardless the time elapsed in the disease's evolution.

Antibiot Khimioter, 1998, 43(10), 17 - 8
{Lomefloxacin in phthisiatric practice}; Grishin VK et al.; The efficacy and safety of lomefloxacin in the treatment of patients with hepatitis due to the use of routine antituberculosis agents were estimated . The trial group included 20 patients (10 with increased activity of enzymes such as alanine and asparagine transaminases, alkaline phosphatase and gamma-glutamate dehydrogenase) who were treated for various forms of tuberculosis with antitubeculosis drugs . The treatment course with lomefloxacin was 4 weeks (400 mg twice a day at 12-hour intervals) . The criteria of the enrolment to the trial group were a more than 2-3 times higher activity of the enzymes and the absence of the markers of the virus hepatitis A, B and C . The therapy efficacy before and after the use of lomefloxacin was estimated clinically and by the findings of the laboratory and instrumental investigations . As a result of the treatment with lomefloxacin normalization of the enzyme activity and a favourable time course of the main disease were observed in the patients with drug hepatitis due to the use of antituberculosis agents requiring continuation of the antituberculosis therapy . An important result of the complex treatment with lomefloxacin and antituberculosis agents was discontinuation of the tubercle bacilli isolation in 70 per cent of the patients . Lomefloxacin proved to be a safe and efficient up-to-date agent for the treatment of tuberculosis in patients with hepatitis due to the use of antituberculosis drugs.

Antibiot Khimioter, 1998, 43(10), 13 - 6
{Mechanism of action of lomefloxacin on Mycobacterium tuberculosis}; Mozhokina GN et al.; The peculiarities of the mechanism of the lomefloxacin bactericidal action on Mycobacterium tuberculosis were studied . The electron microscopy of ultrathin sections of the cells of M.tuberculosis H37Rv exposed to 10 micrograms/ml of lomefloxacin for 24 hours revealed severe changes in their ultrastructure: exfoliation of the cell wall from the cytoplasmic membrane, loosening and fragmentation of the cytoplasmic membrane, lowering of the cytoplasm thickness, vacuolization and twisting of the mesosomes . The exposure of the cells to lomefloxacin for 72 hours resulted in their complete destruction: the cells proved to be a mass of unidentifiable fragments . Some destructions such as exfoliation of the intracytoplasmic membrane and the cytoplasm loosening and vacuolization were observed in the tubercle bacilli localized inside the phagosomes of the murine lung macrophages exposed to lomefloxacin . Such destructions were evident of the antibiotic good penetration not only into the macrophages but also through the phagosome walls as well as of the lomefloxacin intracellular bactericidal activity . In the experiments with the culture of the lung tissue from the tuberculosis foci of mice the basic mechanism fo the lomefloxacin action on M.tuberculosis was demonstrated: the lomefloxacin bactericidal effect was realized through the pathway of mechanism A of the antimicrobial action of fluoroquinolones.

Antibiot Khimioter, 1998, 43(10), 10 - 2
{Lomefloxacin in complex treatment of acute progressive form of pulmonary tuberculosis}; Sokolova GB et al.; The effect of lomefloxacin in combination with isoniazid, pyrazinamide, streptomycin or ethambutol on the process of tuberculosis and concomitant nonspecific pathological processes in the lungs was investigated in the treatment of 69 patients with newly diagnosticated acute progressive destructive tuberculosis of the lungs and isolation of Mycobacterium tuberculosis . It was shown that lomefloxacin provided rapid disappearance of the disease clinical signs and bacillus isolation in the patients with tuberculosis due to the tubercle bacilli susceptible or resistant to the main antituberculosis drugs, acceleration of the resolution of the infiltrates and caseous lesions in the lungs and elimination of the pathological processes in the bronchi . The tolerance of lomefloxacin was satisfactory and it did not affect the tolerance of the other antituberculosis drugs.

Crit Care Med, 1998 Nov, 26(11), 1893 - 9
Antibiotic restriction does not alter endemic colonization with resistant gram-negative rods in a pediatric intensive care unit; Toltzis P et al.; OBJECTIVE: To test whether a ceftazidime restriction policy in a pediatric intensive care unit (ICU) could decrease the endemic rate of colonization with ceftazidime-resistant gram-negative bacilli . DESIGN: Prospective, pre- vs . postintervention study . SETTING: University hospital pediatric ICU . PATIENTS: Consecutive children admitted to the pediatric ICU over a 19-mo period . INTERVENTIONS: After an observation period in which antibiotic use was not controlled, ceftazidime was prohibited unless the patient's microbiological results indicated that the drug was necessary for cure . Aminoglycoside use was not regulated . The size of the endemic reservoir of ceftazidime- and tobramycin-resistant organisms was determined by daily nasopharyngeal and rectal swab specimens obtained on all admissions to the ICU . MEASUREMENTS AND MAIN RESULTS: Despite a 96% reduction in ceftazidime use, the incidence density (number of isolates/100 patient-days) of ceftazidime-resistant organisms increased through the course of the study, from 1.57 to 2.16 . The incidence density of tobramycin-resistant organisms was unchanged . Ceftazidime restriction resulted in a small but nonsignificant decrease in the proportion of ceftazidime-resistant organisms acquired late (beyond 72 hrs) in the patients' ICU course (56.5% vs . 45.9%) . However, there was a more substantial decrease in the proportion of ceftazidime-resistant organisms derived from species known to harbor derepressible amp C beta-lactamases (68.2% vs . 45.9%, p < .05) . CONCLUSIONS: These data indicate that antibiotic restriction policies in an ICU fail to diminish the size of the endemic reservoir of antibiotic-resistant gram-negative rods, and suggest that such policies in the absence of broader efforts to limit antibiotic use will have little impact.

Chest, 1998 Nov, 114(5), 1253 - 7
Anti-Kp 90 IgA antibodies in the diagnosis of active tuberculosis; Arikan S et al.; BACKGROUND: Accurate diagnosis of active tuberculosis (TB) has been difficult historically, yet a great demand persists for a rapid and reliable diagnostic method . Detection of Mycobacterium tuberculosis anti-Kp 90 IgA antibodies is one of the more novel techniques . STUDY OBJECTIVES: To evaluate the diagnostic value of a recently developed enzyme-linked immunosorbent assay (ELISA) test, which detects IgA antibodies against M tuberculosis Kp 90 antigen, and to compare the results with conventional diagnosis and the polymerase chain reaction (PCR) method . PARTICIPANTS: Serum, ethylenediaminetetraacetic acid (EDTA)-blood, and body fluid samples were obtained from 51 patients with active TB and 71 control subjects . The clinical diagnosis of TB was supported by a positive culture (n = 6), detection of acid-fast bacilli on smear (n = 35), or both (n = 10) . MEASUREMENTS AND RESULTS: IgA antibodies were detected in sera and/or body fluid samples from 82% of patients with TB and 10% of controls . M tuberculosis DNA was detected in body fluid sample of 96% and blood sample of 49% of patients with TB by PCR . None of the blood and 5.6% of the body fluid specimens from controls were PCR-positive . CONCLUSIONS: Anti-Kp 90 IgA antibodies were detected using ELISA in 78% of serum and 69% of body fluids from patients with TB, therefore, this test is promising for the diagnosis of active TB and appears to be more reliable, particularly for body fluid samples.

Am J Gastroenterol, 1998 Nov, 93(11), 2294 - 6
Tuberculous colitis mimicking Crohn's disease; Arnold C et al.; Intestinal tuberculosis is a rare disease in western countries and may mimic a variety of gastrointestinal disorders . Here, we report the case of a 63-yr-old patient who presented with profuse bleeding from a deep rectal ulcer . Similar lesions were found in different parts of the colon . Multilocular colorectal carcinoma was suspected based on the macroscopic appearance . Histology, however, suggested Crohn's disease . Intestinal tuberculosis was initially ruled out by negative staining for acid-fast bacilli, mycobacterial culture, and polymerase chain reaction analysis . A treatment for Crohn's disease was started . Endoscopic reexamination revealed progressive disease with extensive ulcerations of the terminal ileum . Histopathological examination then revealed acid-fast bacilli in the colonic mucosa typical for mycobacterium tuberculosis infection . This case emphasizes the need to include intestinal tuberculosis in the initial differential diagnosis of ulcerative colorectal lesions also in the western population.

J Infect, 1998 Mar, 36(2), 236 - 9
Massive hepatosplenomegaly, jaundice and pancytopenia in miliary tuberculosis; Evans RH et al.; A 29-year-old Caucasian woman presented to hospital with a 2-day history of diarrhoea, anorexia and rigors . Investigations showed abnormal liver function tests, hyponatremia, hypoalbuminaemia and lymphopenia . The initial chest radiograph was normal . A bone marrow trephine biopsy showed non-caseating granulomata and she subsequently developed miliary shadowing on the chest radiograph . A transjugular liver biopsy confirmed the presence of acid-alcohol fast bacilli . Despite starting triple therapy for miliary tuberculosis she remained febrile and developed massive hepatosplenomegaly, jaundice and pancytopenia . Standard triple therapy was substituted with ethambutol, streptomycin and oral prednisolone and the patient made a dramatic recovery . The clinical symptoms of miliary tuberculosis are frequently non-specific and the onset of the illness is often insidious . The liver is involved in almost all patients with miliary tuberculosis, but massive hepatosplenomegaly and jaundice are rare . Standard triple-therapy should be discontinued when there is significant liver dysfunction, and corticosteroids should be considered for patients with miliary tuberculosis who fail to respond to conventional therapy.

Microb Pathog, 1998 Oct, 25(4), 203 - 14
Change in colony morphology influences the virulence as well as the biochemical properties of the Mycobacterium avium complex; Kansal RG et al.; Factors that influence colony morphology are of crucial importance for drug development as well as for understanding the virulence of Mycobacterium avium complex (MAC) strains . The MAC 101 strain used in the present study grows as smooth transparent (SmT) colonies that tend to become opaque and pigmented when incubated for long periods of time . However, when MAC was passaged in animals, two types of colonies were recovered . The new rough transparent (RgT) colony morphology appeared more flat and transparent, having a central spot, irregular edges at times, and a dry, granular appearance like that of the rough mutants . In animal studies, the RgT bacilli multiplied at a much faster rate than that of the SmT bacilli, causing 60-80% mortality compared with the 10% mortality observed in mice infected with SmT . In vitro studies indicated that the SmT MAC did not grow and multiply as well in resident peritoneal macrophages as the RgT MAC did . The two morphotypes did not differ in their growth ratesin vitro but the RgT MAC failed to reduce dimethylthiazol-diphenyltetrazolium bromide (MTT), alamar blue and neutral red, suggesting that there might be significant changes in the cell wall or elsewhere causing changes in cellular permeability . These two morphotypes could serve as models for studying the biochemical markers or the identification of factors responsible for the virulence of the MAC .

Clin Nucl Med, 1998 Nov, 23(11), 739 - 42
F-18-FDG uptake in tuberculosis; Bakheet SM et al.; Two patients are described who showed abnormal fluorine-18 fluorodeoxyglucose (F-18 FDG) uptake that was due to benign disease, specifically tuberculous lymphadenitis and pneumonitis . The first patient had ulceration and oozing of the left nipple that was related to Paget's disease . An F-18 FDG PET, whole-body scan, which was performed for staging, showed no breast uptake . However, there was intense multifocal uptake in mediastinal, supraclavicular, and para-aortic areas that was confirmed radiologically to represent widespread lymphadenopathy . Pathologic examination of a mediastinal lymph node showed active tuberculosis . The second patient showed intense focal F-18 FDG uptake in mediastinal and supraclavicular areas and para-aortic lymphadenopathy due to non-Hodgkin's lymphoma . In addition, there was abnormal F-18 FDG lung uptake that revealed the presence of acid-fast bacilli on bronchial lavage . Intense focal F-18 FDG uptake in widespread lymphadenopathy or in the lung could be caused by infectious diseases such as tuberculosis . This possibility should be considered when whole-body scans of patients with cancer are interpreted, especially in those with a high incidence of infectious disease.

Indian J Med Res, 1998 Oct, 108, 115 - 9
Action of metronidazole in combination with isoniazid & rifampicin on persisting organisms in experimental murine tuberculosis; Paramasivan CN et al.; To study the activity of metronidazole on persisting tubercle bacilli, BALB/c mice were infected with Mycobacterium tuberculosis and, after 14 days, treated with isoniazid (H) or rifampicin (R) or isoniazid + rifampicin (HR) for 2 months . An untreated group and a group treated with metronidazole (M) alone served as controls . At the end of 2 months, M was added to the H, R, and HR regimen in half the mice, and the treatment was continued for 1 more month in all mice . At the end of treatment, no viable organisms were detected in the lung or spleen of mice treated with HR or HRM regimens . In contrast, compared to the mice treated with R alone, the log10 colony forming units (cfu) of mice treated with RM were lower by 1.84 and 0.52 in the lung and spleen, respectively . Similarly, compared to the H group, the log10 cfu were lower by 0.67 in the spleen of mice treated with HM, and no additional effect due to M was seen in the lung . Three months after stopping treatment, viable organisms were isolated from both the organs of all the groups . However, the log10 cfu in the lung and spleen for the groups with metronidazole were below the log10 cfu for the respective single or 2 drug groups, except the log10 cfu in the lung for the RM group . These findings suggest that metronidazole, given with bactericidal drugs such as rifampicin and isoniazid may be of value in eliminating persisting tubercle bacilli, but further studies are warranted.

Clin Diagn Lab Immunol, 1998 Nov, 5(6), 871 - 81
Pulmonary bovine-type tuberculosis in rabbits: bacillary virulence, inhaled dose effects, tuberculin sensitivity, and Mycobacterium vaccae immunotherapy; Converse PJ et al.; This report elucidates four aspects of the immunology of pulmonary tuberculosis produced in rabbits: (i) the virulence of bovine-type tubercle bacilli, strain Ravenel S, (ii) systemic factors influencing the generation of visible primary pulmonary tubercles, (iii) differences in tuberculin sensitivity of rabbits and humans, and (iv) the effect of Mycobacterium vaccae immunotherapy on cavitary tuberculosis . Laboratory strain Ravenel S (ATCC 35720) was not fully virulent . Fully virulent strains produce one visible primary pulmonary tubercle for each three bacillary units inhaled . Strain ATCC 35720 produced one such tubercle for each 18 to 107 bacillary units inhaled, indicating that its virulence was reduced by 6- to 36-fold . When a low dose of this Ravenel S strain was inhaled, the host resistance (measured by the number of inhaled bacilli needed to generate one visible primary pulmonary tubercle) was increased at least 3.5-fold compared to the host resistance when a high dose was inhaled . Rabbits and humans differ in the degree and in the maintenance of their dermal sensitivities to tuberculin . Compared to rabbits, humans are 100 times more sensitive to tuberculin . Also, at 33 weeks rabbits with well-controlled cavitary tuberculosis usually showed a decrease in their tuberculin reactions of about 50% from peak values, whereas humans with such well-controlled tuberculosis are thought to maintain strong reactions for many years . These species differences may be due to desensitization to group II mycobacterial antigens in the rabbits because they have a different diet and a different type of digestive tract . M . vaccae immunotherapy of rabbits with cavitary tuberculosis produced no statistically significant effects . Experiments with many more rabbits would be required to prove whether or not such immunotherapy is beneficial.

Infect Control Hosp Epidemiol, 1998 Oct, 19(10), 747 - 53
Medical-resource use for suspected tuberculosis in a New York City hospital; Griffiths RI et al.; OBJECTIVE: To compare resource use by diagnostic outcome among hospital admissions during which tuberculosis (TB) was suspected . DESIGN: Retrospective study based on chart review and microbiology laboratory data . SETTING: The department of medicine in a municipal hospital serving central Brooklyn, New York . PARTICIPANTS: We identified all adult admissions in 1993 during which TB was suspected . We assigned each admission to one of four mutually exclusive groups defined by the results of microbiological tests (acid-fast bacilli {AFB} smear and culture): culture-positive and smear-positive (C+S+); culture-positive and smear-negative (C+S-); culture-negative and smear-positive (C-S+); or culture-negative and smear-negative (C-S-) . Each admission was divided into two separate periods to which the utilization of medical resources was assigned: the diagnostic and the postdiagnostic periods, which were separated by the date of receipt of the first definitive culture report . RESULTS: Data on 519 admissions (93 C+S+; 57 C+S-; 30 C-S+; and 339 C-S-) were analyzed . Although C+S+ were more likely than other groups to have an admitting diagnosis of TB, approximately one quarter of the admissions without TB (C-S+, C-S-) were admitted with the principal diagnosis of TB . For the four groups, C+S+, C+S-, C-S+, and C-S-, the respective rates of TB isolation and anti-TB treatment, and median lengths of isolation were 98%, 87%, and 34 days; 74%, 74%, and 7 days; 83%, 83%, and 15 days; and 44%, 29%, and 0 days . During the diagnostic period, the rate and length of isolation were similar in the AFB-smear-positive groups (C+S+ and C-S+) . We estimated that admissions without culture-proven TB (C-S+ and C-S-) accounted for 3,174 (36%) of the 8,712 days of TB isolation expended and for 65% of the 16,671 days of anti-TB treatment . The vast majority of this resource consumption (2,737 {86%} of 3,174 days of isolation) occurred during the diagnostic period before a definitive culture result was known . CONCLUSIONS: Our results suggest that prolonged diagnostic uncertainty and misclassification of cases due to false-positive and false-negative smears are associated with substantial medical-resource consumption . New diagnostic modalities that reduce the period of diagnostic uncertainty could reduce the utilization of resources later found to be unnecessary.

Ann Thorac Surg, 1998 Oct, 66(4), 1174 - 8
Cold abscess of the chest wall: a surgical entity?
Faure E, Souilamas R, Riquet M, Chehab A, Le Pimpec-Barthes F, Manac'h D, Debesse B.
BACKGROUND: Cold abscesses of the chest wall are rare tuberculous locations . Because of the resurgence of tuberculosis, this diagnosis must be considered more frequently . METHODS: During a 15-year period (1980 to 1995), 18 patients with one or more cold abscesses of the chest wall were managed in our department . Epidemiologic characteristics, indications, methods and results of operation, and pathogenesis of the abscesses were considered in this retrospective study . RESULTS: Most of the patients were immigrant men . A previous history of tuberculosis was noted in 15 cases (83%) . Six patients had concomitant active pulmonary tuberculosis . There was mostly a solitary lesion in the chest wall, the most frequent location being the rib shaft (60%) . Before operation the diagnosis was confirmed only in 4 patients (by needle aspiration of the abscess) and presumed in 4 others: an antituberculous chemotherapy was therefore given preoperatively to 8 patients . One patient did not undergo operation after a favorable response to medical treatment . In the other patients, an operation was indicated because of lack of response in 5 patients and the absence of diagnosis in 12 patients . Adequate debridement and a postoperative antituberculous regimen were performed with recurrence prevention in mind . A follow-up was obtained in 11 of the 17 patients undergoing operation . The only patient who required a second operation because of a recurrence at the same location had refused the antituberculous therapy after the first surgical procedure . Locations of the abscesses, computed tomographic scan results, and histologic examinations are in favor of a lymph-borne dissemination of tubercle bacilli . CONCLUSIONS: Because fine-needle aspiration remains an inaccurate diagnostic tool and antituberculous medical treatment is not always efficient, chest wall tuberculous cold abscesses remain in most cases a surgical entity.

Pediatr Surg Int, 1998 Oct, 13(8), 572 - 5
Colonization of intestinal bacteria in ill neonates; Peng H et al.; Most previous studies have shown that the digestive tract of the neonate is rapidly and heavily colonized in the first few days of life, but all the studies so far used either feces or rectal swabs to isolate and identify bacterial colonization . The exact timing of intestinal colonization is not yet certain . From a retrospective analysis of 24 neonates with intestinal perforation and a prospective study of 30 ill neonates aged less than 10 days who recieved intestinal-tract operations, we found that the incidence of bacterial growth from small-and large-bowel specimens was significantly lower within 48 h after birth and the intestinal tract was almost completely sterile within 24 h after delivery . Most of the bacteria were aerobic gram-negative bacilli, and the most common species was Escherichia coli . Although our results may not represent conditions in the normal neonate, knowledge of bowel colonization in such patients will be helpful for further management.

Antimicrob Agents Chemother, 1998 Nov, 42(11), 3035 - 7
Bactericidal activities of the pyrrole derivative BM212 against multidrug-resistant and intramacrophagic Mycobacterium tuberculosis strains; Deidda D et al.; The pyrrole derivative BM212 {1, 5-diaryl-2-methyl-3-(4-methylpiperazin-1-yl)methyl-pyrrole} was shown to possess strong inhibitory activity against both Mycobacterium tuberculosis and some nontuberculosis mycobacteria . BM212 was inhibitory to drug-resistant mycobacteria and also exerted bactericidal activity against intracellular bacilli residing in the U937 human histiocytic lymphoma cell line.

Kekkaku, 1998 Sep, 73(9), 557 - 62
{A case of cutaneous tuberculosis associated with steroid therapy for mixed connective tissue disease}; Yagi T et al.; Patients receiving immunosuppressive therapy, such as adrenocorticosteroids, are high risk groups of tuberculosis . We report a case of cutaneous tuberculosis associated with steroid therapy for mixed connective tissue disease . A 63-year-old female was hospitalized after 6 months' treatment with prednisolone for connective tissue disease and bilateral abnormal shadows were revealed on her chest X-ray films . As her sputum smear was positive for acid-fast bacilli, the patient was transferred to our hospital for isolation and treatment . After three months' treatment with INH, RFP and EB, she complained the swelling of her left palm, left arm, and right leg, and skin puncture was performed . As smears of fluid aspirated from the swelling showed acid-fast bacilli, and fluid PCR tests showed positive for M . tuberculosis, she was diagnosed as cutaneous tuberculosis (scrofuloderma) . In spite of administration of antituberculous agents, the swelling showed little improvement . Therefore, the dose of prednisolone was reduced and cutaneous lesions were resected by surgery . High risk of tuberculosis should be considered when a patient administered immunosuppressive drugs, such as adrenocorticosteroids.

P N G Med J, 1996 Sep, 39(3), 181 - 2
Clinical manifestations of HIV infection in Melanesian adults; Seaton A et al.; PIP: By mid-1995, a total of 308 HIV cases had been reported in Papua New Guinea . The majority (74%) of these cases were diagnosed in Port Moresby . This article describes the clinical characteristics of HIV infection in 67 adults who presented to Port Moresby General Hospital in 1990-95 . The median age at presentation was 27 years in men and 28 years in women, with an equal distribution of cases by sex . The major presenting symptoms were wasting and weight loss exceeding 10% of body weight (94%), chronic diarrhea (47%), prolonged fever (77%), and oropharyngeal candidiasis (66%) . Pulmonary tuberculosis was diagnosed on the basis of chest X-ray and history in 37 patients (56%), but only 3 had sputum positive for acid-fast bacilli . Anemia was present in 75% . 65 patients (97%) fulfilled the World Health Organization criteria for AIDS . The inpatient mortality rate in this series was 43%, and 13 of these 29 patients died within a month of their first presentation .

Pediatrics . 1998 Nov;102(5):E49.
Central nervous system tuberculosis in children: a review of 214 cases; Yaramis A et al.; OBJECTIVE: To study the clinical, laboratory, and treatment features observed in pediatric patients with tuberculous meningitis in Turkey . Study Design . Retrospective case review study . METHODS: Review of medical records for demographic data, medical history, clinical manifestations, auxiliary test results, complications, and treatment of 214 children with central nervous system tuberculosis (TB) admitted to Dicle University's hospital between August 1988 and February 1996 . RESULTS: Of the 214 patients with tuberculous meningitis, 112 (52%) were male . The mean age at presentation was 4 . 1 years, with 165 patients (77%) younger than 5 years . Twenty-two patients (10%) were in the first stage of the disease, 120 (56%) in the second, and 72 (34%) in the third . Our epidemiologic data showed that 141 (66%) of the patients had a family history of TB, and 64 (30%) had a Mantoux skin test result of >10 mm of induration . Radiographic studies demonstrated abnormal chest findings in 187 patients (87%) (hilar adenopathy, 33%; infiltrates, 33%; miliary pattern, 20%; and pleural effusions, 1%, and 172 (80%) cases with hydrocephalus, 26% with parenchymal disease, 15% with basilar meningitis, and 2% with tuberculomas . Only 22 (13%) of 164 children had a positive acid-fast bacilli smear in cerebrospinal fluid, and Mycobacterium tuberculosis was isolated in 49 patients (30%) . All the patients were treated with Isoniazid, rifampin, and streptomycin or pyrazinamide for 2 months, followed by 10 months of Isoniazid and rifampin alone . Also, all the patients received adjuvant treatment with steroids early in the course of treatment, and 140 of 172 cases with hydrocephalus had surgical intervention . The overall mortality rate was 23% . CONCLUSION: One or more of these findings: a family history of TB, positive tuberculin skin test results, abnormal cranial computed tomography, and/or cerebrospinal fluid analysis compatible with TBM were found in all but 3 children in our study . central nervous system, tuberculous meningitis, diagnosis, hydrocephalus, children.

Rev Med Interne, 1998 Sep, 19(9), 661 - 5
{Infectious aneurysm due to Listeria monocytogenes: a new case and review of the literature}; Paccalin M et al.; INTRODUCTION: Infections due to Listeria monocytogenes usually occur in pregnant women, in the elderly and in immunocompromised patients . Arterial aneurysms due to this germ are rare . Only 16 cases have been previously described in the literature . EXEGESIS: We report the case of a patient who had been hospitalized for recurrent fever over the past 3 months . Aortic mycotic aneurysm was diagnosed; blood and aneurysm cultures revealed Gram-positive bacilli consistent with the presence of Listeria monocytogenes . We also review previous reports focusing on infections due to Listeria monocytogenes . Mycotic aneurysms due to this germ are mainly observed in elderly male patients and occur on large arteries . In the present study, only one patient was immunocompromised . Furthermore, all patients who were not operated on died . CONCLUSION: Arterial aneurysm due to Listeria moncytogenes is best managed via surgical resection in combination with antimicrobial therapy . Immunosuppression is not necessary for the development of arterial aneurysm due to Listeria . Bacteriological and histological examinations should be done systematically when surgical resection of an aneurysm is required.

Aust Vet J, 1998 Sep, 76(9), 604 - 7
Subcutaneous granuloma caused by Mycobacterium avium complex infection in a cat; Malik R et al.; A localised subcutaneous swelling developed on the nasal bridge of a cat receiving chemotherapy for alimentary tract lymphosarcoma . Cytological and histological examination of representative samples of the lesion demonstrated pyogranulomatous inflammation and abundant acid-fast bacilli . A Mycobacterium sp was cultured from tissue excised from the lesion . Extensive testing at three reference laboratories indicated the strain was a member of the Mycobacterium avium complex . The infection was treated successfully by cytoreductive surgery and a 6 weeks course of orally administered clofazimine.

J Med Microbiol, 1998 Oct, 47(10), 871 - 7
Induction of granulomas in interferon-gamma gene-disrupted mice by avirulent but not by virulent strains of Mycobacterium tuberculosis; Sugawara I et al.; To gain a better understanding of the pathological role of interferon-gamma (IFN-gamma) in specific granuloma formation, IFN-gamma gene-deficient mice (BALB/c and C57BL/6) were produced . The IFN-gamma gene in embryonic stem (ES) cells was disrupted by inserting the beta-galactosidase gene (lacZ) and the neomycin resistance gene (neo) at the translation initiation site in exon 1 by homologous recombination . Six-week-old IFN-gamma-deficient and wild-type mice were inoculated with 10(3)-10(7) bacilli of various strains of Mycobacterium tuberculosis (Kurono, H37Rv, H37Ra and BCG Pasteur) through their tail veins . The mice were examined 7 weeks later for granuloma formation . The avirulent BCG Pasteur and H37Ra strains (10(3)-10(4) bacilli/ml) induced granulomas in the spleen, liver and lungs of IFN-gamma-deficient mice . The granulomas consisted of epithelioid macrophages and Langhans multinucleate giant cells, but lacked caseous necrosis . The virulent Kurono and H37Rv strains induced disseminated abscesses but not granulomas in various organs of IFN-gamma-deficient mice and Mac-3-positive macrophages were not detected in the abscess lesions . These results suggest that IFN-gamma may be primarily responsible for macrophage activation and that other factor(s) may be involved in the granuloma formation mechanism.

Int J Tuberc Lung Dis, 1998 Oct, 2(10), 778 - 83
New tools for the diagnosis of tuberculosis: the perspective of developing countries; Foulds J et al.; New diagnostics for tuberculosis are urgently needed to replace or facilitate acid-fast bacilli (AFB) microscopy for the identification of smear-positive cases, and to improve the diagnosis of AFB smear-negative cases . These need to be appropriate for use in low income countries . Tests to replace or facilitate AFB microscopy must offer improvements to this test, including increased sensitivity, speed, ease of use, and safety . Products to improve the identification of smear-negative cases should focus on the diagnosis of patients with paucibacillary pulmonary disease, including children and human immunodeficiency virus (HIV) infected persons, and those with extrapulmonary forms of tuberculosis.

Pediatr Hematol Oncol, 1998 Sep-Oct, 15(5), 405 - 13
Fever and neutropenia in children with cancer in one pediatric hospital in Argentina; Paganini H et al.; The authors retrospectively analyzed 863 episodes of neutropenia and fever in 635 children with cancer or hematological disease hospitalized between October 1988 and November 1994 . The most frequent underlying diseases were solid tumors (45%) and acute lymphoblastic leukemia (29%) . Clinical site of infection could be determined in 454 (53%) episodes . Bacteremia was documented in 114 (13%) cases . Gram-positive cocci were the microorganisms most frequently isolated (47% of the cases) . Noninfectious complications could be determined in 140 (16%) episodes, and were mainly severe bleeding and metabolic impairment . The episodes were divided in two groups for comparative evaluation: group A, 404 episodes, study period 1988-1991, and group B, 459 episodes, 1992-1994 . According to the results, more patients in group A than group B were younger than 1 year old and had profound neutropenia; fewer patients in group A than group B had an endovascular catheter, a higher frequency of manifest clinical site of infection at admission, and a prevalence of isolation of gram-negative bacilli . A higher percentage of patients in group B had neutropenia of more than 14 days, gram-positive cocci in culture, and lower mortality . Multivariate analysis by logistic regression in 340 patients revealed that the presence of a severe noninfectious complication, severe neutropenia, and positive blood culture correlated with high mortality rate (p < or = 0.001).

Unfallchirurg, 1998 Aug, 101(8), 658 - 60
{Recurrent soft tissue infections after accidental inoculation with BCG vaccine}; Pinocy J et al.; Complications after BCG vaccine (bacilli Calmette-Guerin) occur rarely . They can reach from a local acute abscess to chronic ulceration's . Therapeutically concepts of these complications range from conservative to operative treatment . In the following case history recurrent soft tissue infections occurred after accidental inoculation with BCG vaccine . The time course of these recurrent infections with its therapeutic options is discussed and a treatment strategy is suggested . Currently, radical excision combined with antituberculotic treatment seems to be the most promising therapy of this specific soft tissue infection.

Kekkaku, 1998 Aug, 73(8), 513 - 7
{Tuberculosis of the central nervous system experienced at the International Medical Center of Japan}; Kobayashi N et al.; In spite of recent advances in diagnosis and chemotherapy of tuberculosis, prognosis of tuberculosis of the central nervous system (CNS) is still poor . We evaluated clinical characteristics of 14 patients with the CNS tuberculosis (10 male and 4 female, 21 to 71 years of age) who were hospitalized at IMCJ from 1988 to 1997 . Twelve patients had tuberculous meningitis (2 of them had also intracranial tuberculoma), 1 had intracranial tuberculoma and 1 had spinal cord tuberculosis . For the acid-fast bacilli, the smears of cerebrospinal fluids (CSF) were all negative but the cultures for M . tuberculosis were positive in 5 . Using PCR method, M . tuberculosis was identified from CSF specimens in 2 out of 9 culture negative patients, thus suggesting the usefulness of the PCR for the rapid diagnosis of CNS tuberculosis . The adenosine deaminase (ADA) levels in CSF may provide another diagnostic clue because they were elevated in 8 out of 10 cases . It is to be noted that there were three patients who developed clinical manifestations of CNS tuberculosis after the initiation of chemotherapy for pulmonary tuberculosis . In the last five cases, four-drug regimen which included PZA, was used with a good result . The success could be related to the addition of PZA which penetrates blood-brain barrier just as good as INH . Two patients died and one remains unconscious with severe neurological sequelae . The present study indicates that positive CSF culture, hydrocephalus and consciousness disturbance are important factors in determining poor prognosis of the CNS tuberculosis.

An Med Interna, 1998 Aug, 15(8), 436 - 8
{Psoas abscess secondary to lumbar spondylodiscitis caused by gram negative bacilli}; Ampudia-Blasco FJ et al.; The association between psoas abscess and lumbar spondylodiscitis by Gram negative bacilli represents a rare clinical entity . Sometimes the absence of demonstrative symptoms complicates the diagnostic schema . We report about a 72 year-old woman, without previous known diabetes mellitus, who was admitted because of fever of one week duration and a non-ketotic hyperosmolar coma . A left psoas abscess was identified by abdominal computed tomography (CT) . The abscess was in communication with the L1-L2 intervertebral space . Although Escherichia coli was identified as the causing agent and appropriate antibiotic therapy was administered, the resolution of the abscess occurred only after the implantation of a percutaneous catheter guided by CT without additional surgery . Percutaneous drainage as a diagnostic-therapeutic technique has rendered the surgery as the last resort in the treatment of psoas abscess.

Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi, 1998 Jul-Aug, 39(4), 257 - 9
Spontaneous resolution of an intratracheal mass: report of one case; Wong KS et al.; A 14 year-old boy was investigated for a slowly resolving right upper lobe consolidation persisting for 3 months after a pneumonic episode . A flexible bronchoscopy showed a polypoid mass in the carina with extension to the right proximal bronchus . The bronchial washings study for fungus, acid-fast bacilli and polymerase chain reaction for mycobacterium were negative . A reported bronchoscopic examination 8 months later revealed no tracheal mass or subsequent stenosis . A tracheal mass in an asymptomatic and non-progressive child may be managed alternatively by repeated bronchoscopic examinations at intervals instead of immediate bronchoscopic excision or thoracotomy.

Rev Med Interne, 1998 May, 19(5), 344 - 7
{Endobronchial tuberculosis presenting as an obstructive tumor in an HIV-1-positive patient . Apropos of a case and review of the literature}; Saadoun R et al.; INTRODUCTION: A rare case report of endobronchial tuberculosis is reported in an HIV-1 positive patient of black African origin . EXEGESIS: A 38-year-old woman of Guinean origin, HIV-1 positive, presented with persistent right upper lobe opacity at chest X-ray . Computerized tomography of the chest after injection confirmed this finding and revealed right laterotracheal and Barety space adenopathy . Investigations of acid-fast bacilli in the biological media were negative . Fiberoptic bronchoscopy showed endobronchial lesion on the wall of the ventral part of the right upper lobe, which had the appearance of bronchogenic carcinoma, and infiltrates in the dorsal mucosa . Biopsy of the lesion revealed granuloma formation, but no evidence of caseation necrosis . Identification of Mycobacterium tuberculosis in sputum culture helped arrive at a diagnosis of endobronchial tuberculosis similar to obstructive bronchial tumor . CONCLUSION: This case of endobronchial tuberculosis is the first described in an HIV-1 positive patient of black African origin . Mediastinal lymph node revealed by chest computerized tomography after injection could be the site of spreading of mycobacteria by fistulization of tuberculosis lymph node into the right main bronchus . Only the histology of lesions carried out during bronchial fibroscopy permitted the exclusion of endobronchial neoplasia . In addition, the sensitivity of direct microscopy for acid-fast bacilli is poor . Identification of Mycobacterium tuberculosis by sputum culture helped guide the diagnosis which was further confirmed by a good therapeutic response . This case of endobronchial tuberculosis in an immunodepressed patient underlines the difficulty in determining the etiology of pulmonary opacities.

Br J Radiol, 1998 Jul, 71(847), 723 - 7
Ultrasound guided fine needle aspiration cytology in abdominal tuberculosis; Suri R et al.; Although barium studies and CT are useful in assessing abdominal pathology in tuberculosis, imaging findings are not always specific and a histopathological or bacteriological confirmation is often required . The aim of the present study was to evaluate the role of ultrasound (US) guided fine needle aspiration cytology (FNAC) in the diagnosis of abdominal tuberculosis in patients with non-palpable lesions detected on US/CT . FNAC was performed on 31 sites in 30 patients . The sites included enlarged lymph nodes (n = 14), focal lesions in liver (n = 2) and spleen (n = 8), and thickened bowel in the ileocaecal region (n = 7) . The results were classified cytomorphologically into four groups: (1) definite evidence of tuberculosis; (2) presumptive evidence of tuberculosis; (3) suggestive of tuberculosis; and (4) negative for tuberculosis . 18 of the 31 FNACs (58%) revealed a positive diagnosis of tuberculosis (definite evidence in nine patients and presumptive evidence in nine patients) . 13 of the 31 FNACs (42%) showed either necrosis alone (n = 4) or negative results (n = 9) . Zeihl-Neelson staining for acid-fast bacilli on direct smear was positive in only nine patients (29%) . Splenic and lymph nodal FNAC had a high sensitivity (87.5% and 78.6%, respectively) in the diagnosis of tuberculosis . None of the bowel and liver FNACs was diagnostic . No complications were encountered . US guided FNAC offers a safe and accurate method of achieving a diagnosis in patients with suspected abdominal tuberculosis who present with radiologically demonstrable but non-palpable lesions, especially those involving lymph nodes and spleen.

Clin Infect Dis, 1998 Sep, 27(3), 474 - 7
Congenital tuberculosis in a neonatal intensive care unit: case report, epidemiological investigation, and management of exposures; Lee LH et al.; Disseminated tuberculosis was diagnosed at the autopsy of a 65-day-old premature infant who died in a 52-bed neonatal intensive care unit (NICU) . Both parents and one sibling had previously had positive tuberculin skin tests (TSTs); none had active pulmonary tuberculosis, but a second sibling had hilar adenopathy . Congenital transmission was confirmed by isolation of Mycobacterium tuberculosis from the mother's endometrium and the infant's lung tissue . Both strains were identical by DNA restriction fragment analysis . TSTs were performed on 14 neonates, 27 NICU visitors, 11 contacts of the family, and 260 health care workers . TST conversion occurred in two nurses (0.8%); both had normal chest radiographs and received isoniazid therapy . Exposed neonates had negative chest radiographs, had negative gastric aspirates for acid-fast bacilli, and received isoniazid preventive therapy . Diagnosis of congenital tuberculosis requires a high index of suspicion . Transmission of tuberculosis in the NICU setting is unusual but can occur.

Clin Infect Dis, 1998 Sep, 27(3), 463 - 70
Nosocomial sinusitis in patients in the medical intensive care unit: a prospective epidemiological study; George DL et al.; A prospective observational cohort study of nosocomial sinusitis was carried out in two medical intensive care units . Sinusitis was diagnosed by computed tomographic scanning and the culture of sinus fluid obtained by puncture of a maxillary sinus . Clinical and epidemiological data were collected at the time of admission to the unit and daily thereafter . Specimens from the nares, oropharynx, trachea, and stomach were cultured on admission and daily thereafter . The cumulative incidence of nosocomial sinusitis was 7.7%, and the incidence rates were 12 cases per 1,000 patient-days and 19.8 cases per 1,000 nasoenteric tube-days . Risk factors for nosocomial sinusitis, as determined by multiple logistic regression analysis, included nasal colonization with enteric gram-negative bacilli (odds ratio {OR}, 6.4; 95% confidence interval {95% CI}, 2.2-18.8; P = .007), feeding via nasoenteric tube (OR, 14.1; 95% CI, 1.7-117.6; P = .015), sedation (OR, 15.9; 95% CI, 1.9-133.5; P = .011), and a Glasgow coma score of < or = 7 (OR, 9.1; 95% CI, 3.0-27.3; P = .0001).

Am J Respir Crit Care Med, 1998 Oct, 158(4), 1173 - 7
Risk factors for pulmonary tuberculosis in bone marrow transplant recipients; Ip MS et al.; Little is known about the profile of infection with Mycobacterium tuberculosis in bone marrow transplant (BMT) recipients . Of five BMT series with a total of more than 5,000 patients, only 10 cases of M . tuberculosis infection were described, with an overall incidence of 0.19% . We have conducted a prospective evaluation of 183 consecutive BMT recipients, and 10 patients were found to develop pulmonary tuberculosis post-BMT, yielding an incidence of 5.5% . We described the clinical features of these 10 patients, and analyzed the risk factors for development of tuberculosis using age- and sex-matched case control subjects who did not develop the disease . The median age of the 10 patients who developed tuberculosis was 29 yr (range, 17 to 40 yr) . The median time for onset of symptoms was 150 d (range, 23 to 550 d), mainly presenting with fever and cough, with infiltrates on chest radiograph . Respiratory tract specimens, mostly sputum, yielded positive smears for acid-fast bacilli in three and positive M . tuberculosis culture in eight, whereas lung tissue histology was the first diagnostic test in two patients . Treatment with standard antituberculosis drugs for a longer duration was highly effective, with no excessive side effects . Risk factors identified for development of tuberculosis included allogeneic BMT (p < 0.05, relative risk {RR} = 23.7), total body irradiation (p < 0 . 05, RR = 4.9), and chronic graft-versus-host disease (GVHD) (p < 0 . 05, RR = 3.6) . It is postulated that chronic GVHD predisposed to development of tuberculosis mainly via disruption of host reconstitution of immune defenses against M . tuberculosis.

Am J Respir Crit Care Med, 1998 Oct, 158(4), 1150 - 5
Polymerase chain reaction to detect Mycobacterium tuberculosis in histologic specimens; Salian NV et al.; There is a need for rapid and sensitive detection of Mycobacterium tuberculosis in tissue specimens . A polymerase chain reaction (PCR)-based assay for the diagnosis of tuberculosis was evaluated in 60 formalin-fixed tissue specimens, the target for the amplification being a segment of IS6110 in the M . tuberculosis chromosome . Of the 60 formalin-fixed, paraffin-embedded tissue specimens studied, 57 showed granulomatous inflammation and 53 had been cultured for mycobacteria; 10 were positive for M . tuberculosis and three were positive for other mycobacteria . Of 60 samples, 15 showed acid-fast bacilli on special staining . When done comparatively on a positive culture for M . tuberculosis, PCR for M . tuberculosis DNA in 60 tissue samples was 100% sensitive and 93% specific, having a positive predictive value of 76.9% and negative predictive value of 100% . PCR for M . tuberculosis DNA done on tissue samples was positive for 14 of 19 patients who had a clinical diagnosis of tuberculosis, negative for all six patients with nontuberculous mycobacterial infections, and negative for all 33 patients who had a diagnosis of a disease other than mycobacterial infection . When compared with the clinical diagnosis of tuberculosis, PCR for M . tuberculosis DNA in these patients' tissues was 73.6% sensitive and 100% specific, having a positive predictive value of 100% and negative predictive value of 88.6% . These data indicate that PCR amplification is useful for detecting M . tuberculosis DNA in formalin-fixed tissue specimens, and that it can be used to increase diagnostic accuracy in patients who have perplexing diagnostic problems associated with a granulomatous tissue response.

Immunology, 1998 Sep, 95(1), 69 - 75
Analysis of T cells recruited during delayed-type hypersensitivity to purified protein derivative (PPD) versus challenge with tuberculosis infection; Pais TF et al.; The delayed-type hypersensitivity (DTH) to purified protein derivative (PPD) test has been used to infer about protective immunity to Mycobacterium tuberculosis and to diagnose tuberculosis . We showed that in memory tuberculosis-immune mice both DTH to PPD and resistance to M . tuberculosis could be effectively elicited in the footpad and both reactions led to the accumulation of reactive T cells in the regional lymph nodes with a CD4+ phenotype and characterized by the secretion of high levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and no IL-4 . By adoptive transfer into nude mice of highly purified CD4+ T cells harvested during the recall of protective immunity it was confirmed that this population mediated both manifestations . However, the specificity of the T cells recruited during these processes were found to differ markedly; T cells involved in protection to a challenge with live tuberculosis bacilli recognized predominantly low-mass culture filtrate antigens below 15 000 MW, while cells recruited during DTH to PPD were directed to molecular mass fractions between 15 000 and 31 000 . Using single purified antigens we showed that the latter cells recognized the secreted mycobacterial protein Ag85B and the heat-shock proteins, DnaK and GroEL . Protective T cells, in contrast, were characterized by a very high frequency of T cells directed to the ESAT-6 peptide 1-20.

J Hepatol, 1998 Sep, 29(3), 430 - 6
Norfloxacin primary prophylaxis of bacterial infections in cirrhotic patients with ascites: a double-blind randomized trial; Grange JD et al.; BACKGROUND/AIMS: Norfloxacin is useful to prevent infections in hospitalized cirrhotic patients with low ascitic fluid protein concentrations . It is also effective in preventing the recurrence of spontaneous bacterial peritonitis . The aim of our study was to determine the efficacy of norfloxacin in the primary prophylaxis of gram-negative bacilli infections in cirrhotic patients with low ascitic fluid protein levels (<15 g/l) . METHODS: One hundred and seven patients were randomized to receive norfloxacin (400 mg/day; n=53) or placebo (n=54) for 6 months . The patients had no history of infection since cirrhosis diagnosis and no active infection . RESULTS: The probability of gram-negative infection was significantly lower among patients treated with norfloxacin than among those treated with placebo . Six gram-negative bacilli infections occurred in the placebo group and none in the treatment group . Severe infections (spontaneous bacterial peritonitis, neutrocytic ascites and bacteremia) developed in nine patients in the placebo group (17%) and in one patient in the norfloxacin group (2%; p<0.03) . There was no between-group difference in the overall rate of infection or in survival . In ten patients from the norfloxacin group, gram-negative bacilli not present in baseline stool cultures were transiently isolated in follow-up cultures . CONCLUSIONS: These data show that primary prophylaxis with norfloxacin for 6 months is effective in the prevention of infections caused by gram-negative bacilli in cirrhotic patients with low ascitic fluid total protein levels.

Eur J Clin Microbiol Infect Dis, 1998 Jul, 17(7), 493 - 500
Use of microscopic morphology in smears prepared from radiometric cultures for presumptive identification of Mycobacterium tuberculosis complex, Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi; Gonzalez J et al.; The aim of this study was to assess the feasibility of a method for presumptive identification of mycobacteria, based on the morphology in smears prepared from radiometric Bactec-positive cultures (Becton Dickinson, USA) and to select the appropriate DNA probe (AccuProbe; Gen Probe, USA) . The smear morphology of acid-fast bacilli was evaluated in 468 positive cultures from clinical samples: 313 Mycobacterium tuberculosis complex, 67 Mycobacterium avium complex, 32 Mycobacterium kansasii, 49 Mycobacterium xenopi, and seven Mycobacterium gordonae . The sensitivity and specificity for various morphological patterns were as follows: cord formation for Mycobacterium tuberculosis complex 90% and 100%, respectively; striped bacilli for Mycobacterium kansasii, 66% and 99%; sea urchin for Mycobacterium xenopi, 96% and 99%; short bacilli for Mycobacterium avium complex, 61% and 99%; fine-striped bacilli associated with Mycobacterium avium complex from blood samples, 33% and 98% . This criterion was applied in the selection of a suitable DNA probe for the identification of 178 cultures . The correct probe was selected in 98%, 97%, and 72% of cultures, respectively, for Mycobacterium tuberculosis complex, Mycobacterium avium complex, and Mycobacterium kansasii . The observation of acid-fast bacilli morphology in radiometric cultures is a rapid and cost-efficient method for presumptive identification of common clinical isolates of mycobacteria.

Diagn Microbiol Infect Dis, 1998 Aug, 31(4), 537 - 41
Comparison of algorithms for selective use of nucleic-acid probes for identification of Mycobacterium tuberculosis from BACTEC 12B bottles; Nelson SM et al.; We retrospectively compared the sensitivity of two approaches, a time-to-detection algorithm and the presence of serpentine cords of acid-fast bacilli, for discriminating between BACTEC 12B cultures containing either Mycobacterium tuberculosis complex (MTB) or Mycobacterium avium complex (MAC) . From January 1996 through March 1997 a total of 217 of 2089 respiratory specimens received in our laboratory were positive in the BACTEC 12B radiometric culture system for either MTB (120 specimens) or MAC (97 specimens) . Use of a previously published time-to-positivity algorithm would have resulted in the correct use of the MTB probe on 109 of 120 cultures (91% sensitivity), and the MAC probe on 52 of 97 cultures (54% sensitivity) . The presence of serpentine cords was detected in 58 of 120 cultures containing MTB (48%), and in 3 of 97 (3%) cultures containing MAC . Using a combination of time to positivity and cord formation to determine initial probe selection would have resulted in first use of the MTB probe in 116 of 120 (97%) instances in which MTB was present in the culture . In only 49 of 97 (51%) cultures, however, from which MAC was recovered would the correct probe have been selected . These results indicate that limiting the initial use of the MTB probe to those cultures that are either identified by the time-to-detection algorithm or demonstrate serpentine cords on acid-fast smear would eliminate a considerable amount of unnecessary probe use without compromising the efficiency of identification of isolates of MTB.

Rinsho Byori, 1998 Aug, 46(8), 834 - 40
{Basic evaluation for new antimicrobial susceptibility testing of Mycobacterium tuberculosis by bioluminescence assay of mycobacterial ATP}; Yamazaki T et al.; It has been reported that the number of living bacteria is correlated to their ATP contents . Based on this, ATP measurement was applied to the susceptibility test for Mycobacterium tuberculosis to antimicrobial agents . ATP was extracted from the bacterial suspension prepared from M . tuberculosis H37Rv grown on 1% Ogawa medium and measured by bioluminescent assay . The highest relative light units (RLU) was obtained when ATP was extracted with the reagent supplied by Kikkoman Inc . (Chiba, Japan) at 100 degrees C for 3 minutes . The amounts of ATP recovered was constant at 100 degrees C for 8 minutes . The ATP contents correlated well with the number of bacteria expressed as CFU . The ATP contents of M . tuberculosis H37Rv inoculated into the Middlebrook 7H9 broth medium containing antituberculous agents were measured at days of 0, 3, 5 and 7 . The control culture showed the time-dependent increase in the RLU values, while cultures supplemented with antimicrobial agents reduced their ATP contents concomitant with the concentrations of drugs . The growth of tubercle bacilli was expressed as RLU ratio, the ratio of RLU in the drug-containing cultures to those in drug-free ones . RLU ratio of 0.5 or less was determined as sensitive and the ratio of more than 0.5 as resistant to drugs . The inoculum size of bacteria did not affect the days giving RLU ratio below 0.5 or 0.3 . Within 7 days, susceptibilities to drugs could be determined . In conclusion, this test is simple, rapid, sensitive and highly reproducible and useful for the assessment of susceptibility.

Int J Tuberc Lung Dis, 1998 Sep, 2(9), 756 - 65
Limitations and requirements for quality control of sputum smear microscopy for acid-fast bacilli; Van Deun A et al.; Sputum microscopy for acid-fast bacilli (AFB) is considered to be the most appropriate method for case-finding in a tuberculosis (TB) control programme . It is usually carried out by general technicians, often after minimal training . Quality control of their results therefore seems indispensable . The methods advocated for quality control are reviewed . Controls by culture leave too much uncertainty because of big differences in technical characteristics of the methods . Sets of smears sent out by a central laboratory can only be used to assess capability . Rechecking routine smears allows daily performance to be appraised and may be a strong motivation, but feasibility may be a problem . Based on our experience, we describe the technical requirements for cross-checking of routine smears . Counter-checking slides with discordant results is crucial for accurate assessments . A sample size should strike a balance between statistical accuracy and the man-power needed . Indicators for evaluation are proposed that allow discrimination of error gradings, to be used in a phased manner with priority at first being given to false negatives and false positives that pass the threshold for clinical decision-making . Estimates of critical values with suggestions about their interpretation are placed in the context of supervising TB laboratories.

Int J Tuberc Lung Dis, 1998 Sep, 2(9), 736 - 42
Metronidazole has no antibacterial effect in Cornell model murine tuberculosis; Dhillon J et al.; SETTING: Experiments in vitro on the bactericidal activity of metronidazole and in the Cornell model of murine tuberculosis . OBJECTIVE: To assess the sterilising activity of maximal metronidazole dosage and its activity against bacilli held dormant by immunity in the mouse . DESIGN: In vitro experiments showed that metronidazole was only bactericidal at attainable concentrations (50-100 microg/ml) under anaerobic conditions . In the Cornell model, isoniazid 25 mg/kg and high dosage pyrazinamide 1000 mg/kg was given in the diet with and without 1500 mg/kg metronidazole for the initial 14 weeks of sterilising chemotherapy . In the subsequent sterile state, metronidazole at 0, 100 and 250 mg/kg was given by daily gavage for 6 weeks . Finally, the mice were given 3 weeks of high dosage steroids and their organs were cultured in selective liquid medium . RESULTS: Metronidazole had no activity either in the initial sterilising phase or in the subsequent sterile state . CONCLUSION: The O2 tension in the cellular lesions of murine tuberculosis is unlikely to be sufficiently low to allow metronidazole to act . Its activity should be assessed in caseous lesions.

J Hand Surg {Br}, 1997 Oct, 22(5), 679 - 80
Upper limb Escherichia coli cellulitis in the immunocompromised; Brzozowski D et al.; The neutropenic state characteristic of acute lymphoblastic leukaemia (ALL) predisposes to infections involving Gram-negative bacilli . An Escherichia coli cellulitis originating in the first web space of the hand is described in a patient undergoing reinduction chemotherapy for ALL . Proximal extension of the infection progressed at a very rapid rate and required a forequarter amputation as a life saving measure . Due to the blunted inflammatory response in neutropenic patients, the need for close monitoring and quick intervention is stressed.

Wiad Lek, 1998, 51(7-8), 378 - 82
{Multi-organ tuberculosis in a child: diagnosis and therapeutic problems}; Kurylak D et al.; Diagnostic and therapeutic problems in the course of tuberculosis in a 4 year old boy were described . First symptoms of disease such as specific inflammation of lymph nodes were observed in THE third month of liFe . After typical antituberculous treatment the signs of disease regressed . In consequence of the contact with an individual expeCtorating tubercle bacilli superinfection and generalization of the disease took place what led to the boy's death.

Arch Ophthalmol, 1998 Sep, 116(9), 1232 - 4
Ocular manifestations of Whipple disease: an atypical presentation; Williams JG et al.; A 62-year-old man developed bilateral granulomatous iridocyclitis after uncomplicated cataract surgery . On ophthalmic examination, we found moderate inflammation in the anterior chamber and vitreous, with granular crystalline deposits on the iris, intraocular lens, and capsular bag . Biopsy of the lens capsule and vitreous revealed periodic acid-Schiff-positive, diastase-resistant bacilli consistent with Tropheryma whippelii . Electron microscopy and polymerase chain reaction confirmed the diagnosis of Whipple disease . A jejunal biopsy specimen also revealed T whippelii . Treatment with trimethoprim-sulfamethoxazole, cefixime, rifampin, and doxycycline resulted in improvement of systemic symptoms, but intraocular inflammation persisted . Intraocular inflammation was eventually reduced with the intravenous administration of ceftriaxone sodium.

Roum Arch Microbiol Immunol, 1998 Jan-Mar, 57(1), 5 - 10
Isolation and speciation of Prevotella strains from periodontal abscesses; Dumitriu S et al.; The aims of the study were to isolate and to identify at species level the Prevotella strains in pus samples collected by needle aspiration from 25 Romanian patients with periodontal abscesses . Gram-stained smears and cultures on selective and nonselective media were performed from each of the 25 pus samples . The isolates were identified on the basis of Gram staining, cultural characteristics and standard biochemical reactions . The Gram-negative anaerobic bacilli isolates were biochemically characterized and identified at species level using the Rapid ID 32 A system (Bio Merieux, France) . Fifteen Prevotella isolates belonging to one of the following species: P . melaninogenica, P . denticola, P . oralis, P . loescheii and P . bivia were recovered . All Prevotella isolates reacted similarly in 20 tests in the Rapid ID 32 A system . The P . melaninogenica strain showed approximately the same biochemical profile and only two sugar fermentation tests were not constantly positive . The study confirmed that Prevotella is often involved in periodontal abscesses (> 50% of the cases) in association with other anaerobic or/and aerobic bacteria . P . melaninogenica was the most frequently isolated Prevotella species from the investigated cases.

Bull World Health Organ, 1998, 76(3), 309 - 11
Brief communication: rapid culture of tubercle bacilli; Vasanthakumari R et al.; One of the biggest obstacles to the correct diagnosis and efficient treatment of tuberculosis is the absence of a rapid technique for culturing tubercle bacilli and for testing their susceptibility to antituberculosis drugs . Current procedures typically take 6-10 weeks to perform . This article describes a simple, rapid, reliable and cheap method of culturing tubercle bacilli using a liquid medium consisting of a mixture of coconut water, horse serum, glycerol and benzylpenicillin . Addition of specific concentrations of antituberculosis drugs to the medium, permits information on the drug susceptibility of tubercle bacilli to be obtained in only 6 days . The procedure requires no special instruments or technical skill and can therefore be carried out routinely in the average laboratory in developing countries.

Chest, 1998 Sep, 114(3), 681 - 4
Screening by specialists to reduce unnecessary test ordering in patients evaluated for tuberculosis; Divinagracia RM et al.; STUDY OBJECTIVE: To determine if screening by specialists could reduce unnecessary test ordering and reduce costs related to diagnostic workup in patients undergoing evaluation for tuberculosis . DESIGN: Prospective evaluation of expert opinion in consecutive patients suspected of having tuberculosis . SETTING: A large municipal hospital . PATIENTS: Patients for whom sputum acid-fast smears were ordered . INTERVENTION: For patients from whom sputum acid-fast bacilli smears and cultures were requested, the chest radiograph and a brief clinical history were presented separately to two pulmonologists with considerable experience in tuberculosis . Each expert reviewed each case independently (and was blinded to the opinion of the other) and indicated if he thought sputum smear examination and culture was, in fact, necessary . Final clinical diagnosis and microbiological information were correlated with the experts' opinion . MEASUREMENTS AND MAIN RESULTS: Ninety-seven patients had sputum smears ordered and had chest radiographs available for review . The two experts believed that sputum examination (smear and culture) was indicated in only 51.5% and 52.6% of cases, respectively . Interobserver agreement was 84.4% . Ultimately, six cases of active tuberculosis were diagnosed . Each expert detected all proven cases of tuberculosis, although one case occurred in a patient with a poor quality radiograph about which the experts offered no opinion . CONCLUSIONS: Screening by experienced clinicians may be effective in reducing unnecessary test ordering and reducing costs related to diagnostic workup in patients evaluated for tuberculosis.

Nihon Kokyuki Gakkai Zasshi, 1998 May, 36(5), 464 - 8
{A pulmonary tumorlet with caseous granuloma associated with atypical mycobacterium}; Nagai S et al.; We encountered a case of pulmonary tumorlet with caseous granuloma associated with atypical mycobacterium . A 73-year-old woman was admitted to the hospital because a chest x-ray film showed enlargement of an abnormal shadow in the middle lobe of the right lung . Primary lung cancer was suspected and right middle lobectomy was performed . Acid-fast bacilli (Gaffky 1) were found in a caseous lesion and examination of intraoperatively obtained frozen specimens showed caseous granulomas . The bacilli were later identified as Mycobacterium avium complex . The permanent specimen showed a minute lesion consisting of small clusters of epithelial cells resembling carcinoid tumor in contact with granulomatous tissue . Histopathological examination revealed argyrophilia on Grimelius stain and immunoreactivity to chromogranin-A in the clusters of epithelial cells . Although these results are consistent with small cell carcinoma or peripheral carcinoid tumor, pulmonary tumorlet was diagnosed because of the lesion's small and minimal cytologic atypia, and because of chronic pulmonary damage around the lesion . Pulmonary tumorlets are minute, usually microscopic, tumor-like lesions mostly found in damaged lung tissue obtained at autopsy or during surgery . Morphological diagnosis is sometimes very difficult, but recently these lesions have been regarded as hyperplastic lesions arising in pulmonary neuroendocrine cells (Kultschitzky cells) and caused by chronic pulmonary damage, such as hypoxia and inflammation . Pulmonary tumorlets must be considered in the differential diagnosis of minute lesions suspected to be small cell carcinoma or peripheral carcinoid tumor.

Ann Dermatol Venereol, 1997, 124(2), 139 - 43
{Cutaneous tuberculosis . A study of 4 cases}; Iborra C et al.; INTRODUCTION: The recent increase in the incidence of tuberculosis has led to the return of cutaneous forms of this disease . In addition, diagnosis can now be made rapidly using genoma amplification . CASE REPORT: Four cases of cutaneous tuberculosis are described in nonimmunosuppressed patients: two cases of lupus vulgaris, including one due to Mycobacterium africanum, and two others of gummas, including one associated with tuberculosis verrucosa . The diagnosis was suggested by epidemiological, clinical, histological and immunological findings and confirmed by culture of the bacilli in 3 cases and by genoma amplification in 1 . DISCUSSION: These observations illustrate the difficulties encountered in determining the tuberculosis nature of skin lesions . The clinical presentation, differential diagnosis, the pathophysiology of this disease and the new interest in genoma amplification are discussed.

APMIS, 1998 Jul, 106(7), 699 - 703
Diagnosis of pulmonary tuberculosis . Application of gen-probe amplified Mycobacterium tuberculosis direct test; Thomsen VO; The purpose of this investigation was to evaluate the Amplified Mycobacterium tuberculosis Direct Test (AMTDT) for the diagnosis of pulmonary tuberculosis (TB) . Six hundred and forty-six sputum samples were analysed by microscopy for acid-fast bacilli, by culture for mycobacterial growth, and by AMTDT for the presence of M . tuberculosis complex rRNA . If there were discrepant results, information as to whether the patient had a history of TB was obtained . The sensitivity was 85.7% (smear positive 100% and smear negative 71.4%, respectively) and the specificity was 96.8% compared with culture . By retesting, 12 of 13 false-positive samples could be divided into two major categories . The samples in one category were retest positive, had highly positive results, and the patients had previous culture-proven TB . The samples in the other category had less positive AMTDT results, were retest negative, and the patients were not notified as having TB . This investigation shows that AMTDT is a sensitive supplementary method for rapid detection of M . tuberculosis complex in respiratory specimens, that there is a risk of contamination which has to be monitored closely, and that positive samples should be retested.

Kekkaku, 1998 Jul, 73(7), 471 - 6
{Attributable factors to the emergence of multidrug-resistant Mycobacterium tuberculosis based on the observation of consecutive drug resistance test results}; Fujino T et al.; Thirty six cases with multidrug-resistant tuberculosis were retrospectively studied to define the causes attributable to the emergence of multidrug-resistant M . tuberculosis . All these tuberculosis cases were microbiologically confirmed and resistant to at least isoniazid and rifampicin . Data analysis using matched-pair sampling methods (1:3) demonstrated that the followings are the significant risk factors for the emergence of multidrug-resistant tuberculosis; incompliance to treatment (Odds ratio 21.0: 95% CI 4.10-107.63), alcohol abuse (Odds ratio 15.0: 95% CI 2.34-96.1) and the history of previous treatment (Odds ratio 5.0: 95% CI 2.04-12.21), while diabetes mellitus is not statistically significant . The incompliance to treatment which is primarily thought to be patient's responsibility results in non-optimal administration of antituberculous agents, leading to the multidrug-resistant tuberculosis . Other factors that may have contributed to the emergence of resistance included the unnecessary change of regimen before completion of chemotherapy . This is patient-unrelated situation where responsibility lies in the medical side . A clinical case presented here is an example . In this case RFP was replaced with ethambutol 3-months after the initiation of regimen including SM, INH and RFP because of abnormal elevation of GOT and GPT without any supporting evidence that RFP was causative . The readministration of RFP after 1-year cessation did not induce liver dysfunction, while the drug resistance was observed not only to RFP but also to INH . This case suggests unnecessary interruption of RFP could lead to the emergence of resistance to INH as well as RFP . One known mechanism of drug resistance is random mutation and the selection by drugs administered during the course of chemotherapy . The cases with advanced cavitary lesions would have a higher probability of the occurrence of mutation . The more the number of mutant bacilli, the higher the probability of emergence of multidrug resistance . Those cases in which longer period of time is needed for the negative conversion of M . tuberculosis should be treated with potent chemotherapy regimens under the intense supervision . Since both INH and RFP are the most potent among currently available antituberculous agents . It is crucial to preserve the potency of these essential agents before novel antituberculous are developed.

J Med Microbiol, 1998 Sep, 47(9), 821 - 7
Clinical evaluation of the Mycobacteria Growth Indicator Tube (MGIT) compared with radiometric (Bactec) and solid media for isolation of Mycobacterium species; Chew WK et al.; The aim of this study was to evaluate the clinical use of a new culture system for the isolation of mycobacteria . Routine clinical specimens were cultured in the Mycobacteria Growth Indicator Tube, the radiometric Bactec 460 TB system and on Lowenstein Jensen (LJ) medium to compare recovery rates and times for detection of mycobacteria and contamination rates . MGIT was tested for its ability to support the growth of a wide range of mycobacterial species . Acid-fast bacilli (AFB) were detected on direct smears of 76 of 603 clinical specimens and mycobacteria were isolated by at least one method from 109 specimens; 93% of these were detected in the MGIT, 95% in the Bactec 460 TB system and 87% on LJ medium . The MGIT, Bactec and LJ media detected 92%, 97% and 95%, respectively, of 61 M . tuberculosis isolates and 94%, 94% and 77% of the 48 isolates belonging to the M . avium complex (MAC) . The mean detection times in MGIT, Bactec and LJ media for M . tuberculosis were 22, 14 and 27 days respectively, and for MAC were 14, 12, and 29 days, respectively . Growth of M . tuberculosis was detected in Bactec, within 4 weeks, in 93% of the 61 culture-positive specimens, compared with only 61% in MGIT and 66% on LJ . The number of MAC detected within 4 weeks was similar in Bactec and MGIT, but less in LJ medium . Differences in sensitivity and time to detection of growth between media were greater for specimens in which AFB were not detected on direct smear than those on which AFB were seen . Contamination rates were similar in the three systems (3-4%) . MGIT supported the growth of all 28 Mycobacterium spp . inoculated . MGIT has significant safety advantages and is less labour intensive than other methods, but the time to detection of M . tuberculosis, especially in smear-negative specimens, was longer in MGIT than in Bactec.

J Mol Biol, 1998 Sep 18, 282(2), 241 - 54
In the absence of translation, RNase E can bypass 5' mRNA stabilizers in Escherichia coli; Joyce SA et al.; In Bacilli, ribosomes or 30 S ribosomal subunits that are stalled or bound on mRNAs can stabilize downstream regions, hence the view that the degradation machinery scans mRNAs from their 5' end . In E . coli, several mRNAs can also be stabilized by secondary structures involving their 5' end . To test whether a bound 30 S subunit can act as a 5' stabilizer in E . coli, we compare here the stabilities of two untranslated variants of the lacZ mRNA, the decay of which is controlled by RNase E . In the first variant, a 35 nt region including the Ribosome Binding Site (RBS) is deleted, whereas in the second it is replaced by an 11 nt-long Shine-Dalgarno (SD) sequence lacking an associated start codon . In the latter variant, an 80 nt fragment encompassing the SD and extending up to the mRNA 5' end was stable in vivo (t1/2>one hour), reflecting 30 S binding . Yet, the full-length message was not more stable than when the SD was absent, although two small decay intermediates retaining the 5' end appear somewhat stabilized . A third variant was constructed in which the RBS is replaced by an insert which can fold back onto the lac leader, creating a putative hairpin involving the mRNA 5' end . The fragment corresponding to this hairpin was stable but, again, the full-length message was not stabilized . Thus, the untranslated lacZ mRNA cannot be protected against RNase E by 5' stabilizers, suggesting that mRNA scanning is not an obligate feature of RNase E-controlled degradation . Altogether, these results suggest important differences in mRNA degradation between E . coli and B . subtilis . In addition, we show that mRNA regions involved in stable hairpins or Shine-Dalgarno pairings can be metabolically stable in E . coli .

Am J Gastroenterol, 1998 Sep, 93(9), 1579 - 82
PCR analysis of T . whippelii DNA in a case of Whipple's disease: effect of antibiotics and correlation with histology; Petrides PE et al.; A 58-yr-old man developed severe weight loss, arthralgias, and diarrhea . Endoscopic examination of the stomach and duodenum revealed thickened folds of duodenal mucosa . Biopsy of the gastric mucosa was negative, whereas duodenal biopsy revealed blunted epithelial villi and PAS-positive foamy macrophages within the lamina propria . Bacilli typical of those associated with Whipple's disease were found by electron microscopy . The diagnosis was confirmed by polymerase chain reaction (PCR) assay, which detected a portion of the 16S ribosomal RNA gene sequence corresponding to the Whipple bacillus (Tropheryma whippelii) in duodenum, stomach, and liver biopsies before therapy . T . whippelii DNA was eliminated from all tissues tested within 3 months of starting antibiotic treatment, but the histological improvement lagged behind the clinical and molecular evidence of improvement.

Am J Respir Crit Care Med, 1998 Sep, 158(3), 908 - 16
Effectiveness and cost of selective decontamination of the digestive tract in critically ill intubated patients . A randomized, double-blind, placebo-controlled, multicenter trial; Sanchez Garcia M et al.; We evaluated the effect of selective decontamination of the digestive tract (SDD) on the incidence of ventilator-associated pneumonia (VAP) and its associated morbidity and cost in a mixed population of intubated patients . Two hundred seventy-one consecutive patients admitted to the intensive care units (ICUs) of five teaching hospitals and who had an expected need for intubation exceeding 48 h were enrolled and received topical antibiotics or placebo . Uninfected patients additionally received ceftriaxone or placebo for 3 d . VAP occurred in 11.4% of SDD-treated and 29.3% of control-group patients (p < 0.001; 95% confidence interval {CI}: 7.8 to 27.9) . The incidence of nonrespiratory infections in the two groups was 19.1% and 30.7%, respectively (p = 0.04; 95% CI: 0.7 to 22.7) . Among survivors, the median length of ICU stay was 11 d (interquartile range: 7 to 21.5 d) for the SDD-treated group and 16 . 5 d (10 to 30 d) for the control group (p = 0.006) . Mean cost per survivor was $11,926 for treated and $16,296 for control-group patients . Mortality was 38.9% and 47.1%, respectively (p = 0.57) . In decontaminated patients, the prevalence of gram-negative bacilli fell within 7 d from 47.4% to 13.0% (p < 0.001), whereas colonization with resistant gram-positive strains was higher (p < 0 . 05) than in the placebo group . In a mixed population of intubated patients, SDD was associated with a significant reduction of morbidity at a reduced cost . Our findings support the use of SDD in this high-risk group.

Int J Lepr Other Mycobact Dis, 1998 Jun, 66(2), 190 - 200
Serial Mitsuda tests for identification of reactional tuberculoid and reactional borderline leprosy forms; Lastoria LC et al.; The authors studied the Mitsuda reaction in 37 leprosy patients (18 reactional tuberculoid, 19 reactional borderline cases) and compared the results with clinical findings, histopathology and bacilloscopy . Evaluation of the Mitsuda reaction was carried out on days 30, 60, 90 and 120 . Most of the reactional tuberculoid patients showed a Mitsuda reaction of +3 in opposition to the reactional borderline patients who showed only + . Bacilloscopic analysis revealed that in 75% of the reactional tuberculoid cases there were rare or no bacilli; bacilli were present in 95% of the reactional borderline cases . The authors conclude that reactional tuberculoid cases have a greater ability to clear bacilli than reactional borderline cases, and that the Mitsuda reaction is a useful tool for the differentiation between these two types of leprosy.

Int J Lepr Other Mycobact Dis, 1998 Jun, 66(2), 182 - 9
Why relapse occurs in PB leprosy patients after adequate MDT despite they are Mitsuda reactive: lessons form Convit's experiment on bacteria-clearing capacity of lepromin-induced granuloma; Chaudhuri S et al.; It is amazing how after years of scientific research and therapeutic progress many simple and basic questions about protective immunity against Mycobacterium leprae remain unanswered . Although the World Health Organization (WHO) has recommended short-term multidrug therapy (WHO/MDT) for the treatment of paucibacillary (PB) leprosy patients, from time to time several workers from different parts of the globe have reported inadequate clinical responses in a few tuberculoid and indeterminate leprosy patients following adequate WHO/MDT despite the fact that they are Mitsuda responsive . A few borderline tuberculoid patients harbor acid-fast bacilli (AFB) in their nerves for many years even though they become clinically inactive following MDT, a fact which has been ignored by many leprosy field workers . Keeping these patients in mind, we have attempted to investigate the cause of the persistence of AFB in PB cases and have looked into the question of why Mitsuda positivity in tuberculoid and indeterminate leprosy patients, as well as in healthy contacts, is not invariably a guarantee for protectivity against the leprosy bacilli . We have: a) analyzed the histological features of lepromin-induced granulomas, b) studied the bacteria-clearing capacity of the macrophages within such granulomas, and c) studied the in vitro leukocyte migration inhibition factor released by the blood leukocytes of these subjects when M . leprae sonicates have been used as an elicitor . The results of these three tests in the three groups of subjects have been compared and led us to conclude that the bacteria-clearing capacity of the macrophages within lepromin-induced granuloma (positive CCB test) may be taken as an indicator of the capability of elimination of leprosy bacilli and protective immunity against the disease . This important macrophage function is not invariably present in all tuberculoid and indeterminate leprosy patients or in all contacts even though they are Mitsuda responsive and are able to show a positive leukocyte migration inhibition (LMI) test . It is likely but not certain that this deficit of the macrophage is genetically predetermined and persists after completion of short-term WHO/MDT . Thus, after discontinuation of treatment slow-growing, persisting M . leprae multiply within macrophages leading to relapse.

Indian J Chest Dis Allied Sci, 1998 Jan-Mar, 40(1), 23 - 31
Pattern of secondary acquired drug resistance to antituberculosis drug in Mumbai, India--1991-1995; Chowgule RV et al.; A retrospective observational study was conducted to find out whether secondary acquired drug resistance to isoniazid and ethambutol is high and to rifamycin and pyrazinamide is low, as is commonly believed in India . There were 2033 patients, whose sputum samples (6099) were reviewed from a specimen registry of the microbiology laboratory for the years 1991 to 1995 . Of these, 521 (25.6%) patients {335 males and 186 females; age ranged from 11 to 75 years} had sputum positive culture and sensitivity for acid-fast bacilli (AFB) . The drug resistance patterns in our study were: isoniazid (H) 15%, rifamycin (R) 66.8%, pyrazinamide (Z) 72.2%, ethambutol (E) 8.4%, streptomycin (S) 53.6%, cycloserine (C) 39.2% kanamycin (K) 25.1% and ethionamide (Eth) 65.3% . The resistance to streptomycin showed a significant fall over a year while there was a rise in resistance to cycloserine and kanamycin which is significant . The rate of secondary acquired resistance of isoniazid and ethambutol was low, and the rate of secondary acquired resistance to rifamycin and pyrazinamide was high, which is contarary to the common belief regarding these drugs in India . This implies that isoniazid is still a valuable drug in the treatment of multidrug resistance in India.

Mol Cell Probes, 1998 Aug, 12(4), 207 - 11
Comparison of culture and acid-fast bacilli stain to PCR for detection of Mycobacterium tuberculosis in clinical samples; Aslanzadeh J et al.; The major drawback in effective use of polymerase chain reaction (PCR) for detecting Mycobacterium tuberculosis (MTB) in clinical samples is the presence of PCR inhibitors and unique cell components of the organism that complicate DNA extraction and subsequent PCR amplification . A PCR assay with a unique multistep DNA extraction method that minimizes these problems was compared in a prospective study to acid-fast bacilli stain (AFBS) and culture for detecting MTB in clinical samples . A total of 254 clinical specimens in two separate studies were processed for MTB by these techniques . While PCR and culture were 100% sensitive and specific, culture required up to 8 weeks of incubation and additional time to perform biochemical testing to identify the isolated micro-organism . Acid-fast bacilli stain had a specificity of about 87% and did not differentiate among Mycobacterial species . In contrast, the results from PCR were available within 48 h and did not require additional testing to attain a final result . Polymerase chain reaction was highly reliable for detection and confirmation and interpretation of positive AFBS results . The assay was easy to perform with a turn around time of about 2 days.

Ann Thorac Surg, 1998 Aug, 66(2), 325 - 30
Results of operation in Mycobacterium avium-intracellulare lung disease; Nelson KG et al.; BACKGROUND: Although operation remains part of the management of Mycobacterium avium-intracellulare lung disease, few series have assessed operation in the era of better therapeutic drugs (especially clarithromycin) . METHODS: From January 1, 1989, through June 30, 1997, 28 patients with M avirum-intracellulare lung disease underwent pulmonary resection . All were receiving multidrug therapy (17 of 28 were receiving clarithromycin) before and after operation . Eight patients underwent pneumonectomy (6 right, 2 left); 20 patients underwent partial resections including 18 with upper lobe lobectomies (14 right, 4 left) . The most common indications for operation were medical treatment failure (15) and as part of initial therapy (9) . RESULTS: Mean postoperative follow-up was 39 months . Complications occurred in 9 of 28 patients (32%), and included persistent air leak requiring surgical correction (5), early postoperative death (2), and late bronchopleural fistulae (1 patient) . Twenty-three of 26 patients were known to be acid fast bacilli culture negative within 1 month of operation . Only 1 of 26 patients who survived 2 years is known to have had a relapse . CONCLUSIONS: Operation continues to play an important role in treatment of M avium-intracellulare lung disease . More than 90% of patients become culture negative and remain so when they continue to receive drugs . Although morbidity is relatively high, it is manageable and the 12-month mortality in the current series was low (7%).

Lepr Rev, 1998 Jun, 69(2), 128 - 33
Choosing the decolourizer and its strength to stain Mycobacterium leprae . Does it actually matter?
de Soldenhoff R, Hatta M, Siro TW.
Leprosy bacilli are more easily decolourized during staining than tuberculosis bacilli, so a weaker concentration of decolourizer is usually recommended . In Indonesia, the same 'strong' decolourizer is used for identifying both organisms . In a study to compare the results using different concentrations of different decolourizers, no difference could be found in the bacterial index (BI) . It is suggested that the same staining technique can be used for tuberculosis and leprosy.

Int J Tuberc Lung Dis, 1998 Aug, 2(8), 690 - 3
Safety in laboratories carrying out sputum smear microscopy: a dilemma for resource-poor countries; Nyirenda TE et al.; Laboratory conditions and procedures for sputum smear microscopy (acid-fast bacilli) were assessed in 38 hospitals throughout Malawi . Of these, 17 (45%) had an area of less than 25 m2, eight (21%) had a separate room for tuberculosis work, and five (13%) had a safety cabinet . All laboratory personnel wore gloves, but in several hospitals there was no white coat, face mask, protective apron or soap for washing hands . Different disinfectants were used to clean work surfaces, only one laboratory decontaminated sputum specimens before disposal, and the laboratory cleaner was usually responsible for waste disposal . Laboratory conditions and safety procedures in Malawi are poor, indicating a need for education, training and supervision of staff.

Int J Tuberc Lung Dis, 1998 Aug, 2(8), 627 - 34
Pulmonary tuberculosis in Kweneng District, Botswana: delays in diagnosis in 212 smear-positive patients; Steen TW et al.; SETTING: Health facilities in Kweneng District, Botswana . OBJECTIVES: To describe and analyse causes of delays in the diagnosis of smear-positive pulmonary tuberculosis . DESIGN: Cross-sectional descriptive study based on data from patient records and interviews of 212 cases . RESULTS: Median total delay was 12 weeks (mean 17.3), median patient's delay was three weeks (mean 5.1), median health services' delay was five weeks (mean 12.2) . An inverse relationship was found between patient's delay and health services' delay . Treatment was started on the basis of positive acid-fast bacilli in 165 patients (78%), and chest X-ray findings in 47 (22%) . Delayed sputum examination despite prolonged productive cough was common, and 31 patients (15%) had one or more negative initial investigations . Significant risk factors for delay were: first visit to a health post, and visiting a traditional or faith healer before start of treatment (total delay and health services' delay); treatment of a sexually transmitted disease in the last three years (total delay); staying in a village without a hospital, self-rated health being held as poor or very poor, and being married (health services' delay); and self-rated health being fair or good (patient's delay) . CONCLUSIONS: Sputum must be examined in all patients with prolonged productive cough, and negative investigations should be repeated . Patients should be told to return if symptoms persist . Dialogue between modern health workers and traditional healers should be encouraged.

Mem Inst Oswaldo Cruz, 1998 Jul-Aug, 93(4), 487 - 90
Evaluation of three Mycobacterium leprae monoclonal antibodies in mucus and lymph samples from Ziehl-Neelsen stain negative leprosy patients and their household contacts in an Indian community; Cardona-Castro N et al.; Mucus and lymph smears collected from leprosy patients (9) and their household contacts (44) in the Cano Mochuelo Indian Reservation, Casanare, Colombia, were examined with monoclonal antibodies (MoAb) against Mycobacterium leprae . The individuals studied were: 5 borderline leprosy (BB) patients, 4 with a lepromatous leprosy (LL), all of whom were undergoing epidemiological surveillance after treatment and 44 household contacts: 21 of the LL and 23 contacts of the BB patients . The MoAb were reactive with the following M . leprae antigens: 65 kd heat shock protein, A6; soluble antigen G7 and complete antigen, E11 . All the samples were tested with each of the MoAb using the avidin-biotin-peroxidase technique and 3,3 diaminobenzidine as chromogen . The patients and household contacts studied were all recorded as Ziehl-Neelsen stain negative . The MoAb which showed optimal reaction was G7, this MoAb permitted good visualization of the bacilli . Five patients with BB diagnosis and one with LL were positive for G7; of the BB patients' household contacts, 9 were positive for G7; 7 of the LL patients' household contacts were positive for the same MoAb . MoAb G7 allowed the detection of bacillar Mycobacterium spp . compatible structures in both patients and household contacts . G7 permitted the visualization of the complete bacillus and could be used for early diagnosis and follow-up of the disease in patients.

AIDS, 1998 Jul 30, 12(11), 1301 - 7
Clinical features and outcome in disseminated mycobacterial diseases in AIDS patients in Taiwan; Hsieh SM et al.; OBJECTIVE: To describe and compare the clinical features and outcome of disseminated tuberculosis (TB) and Mycobacterium avium complex (MAC) disease in AIDS patients . DESIGN: Prospective cohort study . SETTING: A 1800-bed university teaching hospital, the largest centre for HIV/AIDS patients in Taiwan . METHODS: From July 1994 through June 1997, a standardized protocol was used to record the demographic and clinical features in all hospitalized HIV-infected patients, and to perform routine studies and invasive procedures for diagnosis of disseminated mycobacterial diseases . To compare the survival, control patients were selected from the HIV-infected patients hospitalized in the same hospital during the same study period, and had similar age, sex, CD4+ cell counts and antiretroviral therapy regimens . RESULTS: A total of 22 cases of disseminated TB and 15 cases of disseminated MAC were identified . Disseminated TB and MAC occurred in patients with similarly low CD4+ cell counts (median, 23 versus 5 x 10(6)/l; P = 0.08) . The clinical features favouring disseminated TB included night sweats, peripheral lymphadenopathy, acid-fast bacilli in sputum smears, chest radiographic findings of hilar enlargement, and lack of prior AIDS-defining illnesses . Hepatosplenomegaly, elevated serum alkaline phosphatase (more than twice the upper limit of normal), elevated serum gamma-glutamyl transpeptidase (more than three times the upper limit of normal), and leukopenia favoured disseminated MAC . The patients with disseminated TB survived much longer than patients with disseminated MAC (mean survival, 96 versus 22 weeks, P = 0.008) but had a similar outcome to control patients (P = 0.60) . CONCLUSION: Disseminated TB and MAC are distinguishable by clinical features in AIDS patients with similar immunocompromised states . Those features may facilitate diagnosis and selection of specific therapeutic regimens . Disseminated TB was not associated with a shortened survival period in AIDS patients when they completed anti-TB treatment . In contrast, disseminated DMAC was associated with shortened survival despite treatment with potent regimens . These results may emphasize the importance of prophylaxis for MAC in this population.

J Clin Microbiol, 1998 Sep, 36(9), 2791 - 2
Early detection of Mycobacterium tuberculosis in BACTEC cultures by ligase chain reaction; Tortoli E et al.; The LCx Mycobacterium tuberculosis ligase chain reaction system (Abbott Diagnostic Division, Abbott Park, Ill.) was used to detect M . tuberculosis in 150 consecutive BACTEC vials on the day on which a positive growth index (GI) was recorded . By LCx, M . tuberculosis DNA was detected in BACTEC vials on average 2.6 days before the presence of acid-fast bacilli could be confirmed by microscopic examination . A total of 106 of 108 M . tuberculosis isolates were detected without centrifugation from bottles presenting very low GIs (average, 70; median, 33) . No false-positive result was obtained from nontuberculous mycobacteria or from isolates with contaminants.

J Clin Microbiol, 1998 Sep, 36(9), 2565 - 70
Microaerophilic conditions promote growth of Mycobacterium genavense; Realini L et al.; Our studies show that microaerophilic conditions promote the growth of Mycobacterium genavense in semisolid medium . The growth of M . genavense at 2.5 or 5% oxygen was superior to that obtained at 21% oxygen in BACTEC primary cultures (Middlebrook 7H12, pH 6.0, without additives) . By using nondecontaminated specimens, it was possible to detect growth with very small inocula (25 bacilli/ml) of 12 different M . genavense strains (from nude mice) within 6 weeks of incubation under low oxygen tension; conversely, with 21% oxygen, no growth of 8 of 12 (66.7%) M . genavense strains was detected (growth index, <10) . The same beneficial effect of 2.5 or 5% oxygen was observed in primary cultures of a decontaminated clinical specimen . Low oxygen tension (2.5 or 5%) is recommended for the primary isolation of M . genavense . Microaerophilic cultivation of other atypical mycobacteria, especially slow-growing (e.g., Mycobacterium avium) and difficult-to-grow (e.g., Mycobacterium ulcerans) species, is discussed.

Haematologia (Budap), 1998, 29(1), 59 - 62
Incidence of tuberculosis after bone marrow transplantation in a single center from Turkey; Arslan O et al.; Tuberculosis (TB) is generally seen in immunodeficient states and its incidence would be expected to increase after hematopoietic stem cell transplantation (SCT), particularly in the allogeneic setting . However, recent reports from developed countries did not support this hypothesis . Turkey is one of the countries where the disease is endemic . Over a period of 10 years two cases of TB among 120 allogeneic and 65 autologous bone marrow or peripheral blood SCT were encountered . The first patient was a 42-year-old male with acute nonlymphoblastic leukemia (ANLL) who underwent allogenic SCT from his HLA-identical sister in first remission . His early post transplant period was unremarkable and showed no clinical acute or chronic graft versus host disease (GVHD) . His chest X-ray and CT scan revealed alveolar infiltrate of the left apical lobe one year after the procedure and sputum showed acid-fast bacilli, later identified as Mycobacterium tuberculosis . He was put on combination chemotherapy . He is now well and disease-free 30 months after transplant with no complaints of pulmonary TB . The second patient with chronic phase CML underwent allogeneic peripheral SCT from his HLA-identical sister . He suffered from grade II acute and extensive chronic GVHD partially treated with immunosuppressive therapy . He showed pulmonary TB 15 months after transplantation . He is still on combination chemotherapy . Although our numbers are small, the annual incidence of TB after SCT is 1.1% (2/185) which is nearly 30 to 40 times higher than the incidence of TB in the general Turkish population . In other words, an immunosuppressive state after allogenic SCT seems to increase the risk of TB in Turkey . In conclusion, TB should be considered in the differential diagnosis of unexplained infections after SCT, especially in countries, where the disease is endemic.

Diagn Cytopathol, 1998 Aug, 19(2), 94 - 7
Mycobacterium kansasii osteomyelitis presenting as a solitary lytic lesion of the ulna: fine-needle aspiration findings and morphologic comparison with other mycobacteria; Schnadig VJ et al.; A 35-yr-old woman, with acquired immunodeficiency syndrome, presented with right arm pain, erythema, and swelling . A lytic lesion of the ulna was found by radiograph . Ultrasonic and fluoroscopic guided fine-needle aspiration (FNA) yielded a neutrophilic and histiocytic exudate admixed with abundant long, bacillary forms that appeared as negative images on Papanicolaou stain and as very coarsely beaded acid-fast bacilli, resembling candy canes, on Kinyoun stain . These morphologic features permitted a preliminary diagnosis of mycobacteriosis, possibly of M . kansasii (MK) etiology . Appropriate therapy was initiated and resulted in not only marked symptomatic improvement of osteomyelitis and cellulitis, but resolution of chronic pulmonary infiltrates, presumed to be caused by fibrosis . Culture confirmed MK infection 3 wk after FNA . MK is one of the few mycobacteria that has a sufficiently characteristic morphology to permit presumptive diagnosis by smear . Culture, however, still remains the definitive method of speciation.

Infect Control Hosp Epidemiol, 1998 Jul, 19(7), 500 - 3
Cross-contamination with Mycobacterium tuberculosis: an epidemiological and laboratory investigation; Nivin B et al.; OBJECTIVE: To investigate possible cross-contamination of laboratory specimens, as suggested by an increased incidence of newly diagnosed patients with tuberculosis, many of whom had all negative smears for acid-fast bacilli and only one positive Mycobacterium tuberculosis culture referred to as "negative smears, one positive" or NSOP . METHODS: Medical-record reviews were performed for all patients with NSOP results diagnosed at this facility within a 9-month period . Laboratory logbooks were reviewed for all isolates processed; DNA fingerprinting was performed on available isolates . RESULTS: Of 80 patients with NSOP results, 45 (56%) were found to have false-positive cultures resulting from laboratory contamination with H37Ra, an avirulent stock strain of Mycobacterium tuberculosis . CONCLUSION: Laboratory cross-contamination resulted in the false diagnosis of tuberculosis in at least 45 individuals . Use of the Mycobacteria Growth Indicator Tube may have contributed to these contamination incidents by detecting small numbers of contaminating mycobacteria that may not have been detected with less sensitive media.

Neurosurgery, 1998 Aug, 43(2), 370 - 3
Intracranial tuberculous subdural empyema: case report; van Dellen A et al.; OBJECTIVE AND IMPORTANCE: Many types of neurotuberculosis have been described; the most common intracranial forms are tuberculous meningitis and tuberculomas . We report a unique and as yet unreported form of neurotuberculosis, which is an intracranial tuberculous subdural empyema . CLINICAL PRESENTATION: A 59-year-old man who had been previously treated for pulmonary tuberculosis (TB) presented at our institution with a long-standing history of headaches . General and neurological examinations revealed no abnormalities . Radiography of the chest confirmed fibrotic lung changes caused by healed pulmonary TB . A cranial computed tomographic scan revealed a hypodense extra-axial collection with mass effect as well as adjacent osteitis and scalp swelling . INTERVENTION: The patient underwent craniectomy of the osteitic bone and drainage of 50 ml of fluid pus located subdurally . Microscopic examination of the bone and pus revealed tuberculous granulation tissue with numerous acid-fast bacilli identified using Ziehl-Neelsen stain . Mycobacterium TB bacillus was cultured from the pus at 42 days . The patient required two further operative procedures as well as a protracted course of anti-TB therapy . CONCLUSION: The patient eventually achieved a good recovery . We recommend surgical drainage of tuberculous subdural empyema to relieve mass effect and to obtain microbiological confirmation . Furthermore, surgical treatment should be combined with an 18-month course of anti-TB chemotherapy, during which period patient compliance should be closely monitored.

Kekkaku, 1998 Jun, 73(6), 403 - 11
{A successfully treated case of miliary tuberculosis with adult respiratory distress syndrome and tuberculous aneurysm of abdominal aorta}; Ishibatake H et al.; A 52-year-old woman visited a physician on Oct . 17, 1995 because of dizziness, general fatigue and a slight fever . A Chest X-ray film showed micronodulous and infiltrative shadows in the bilateral upper lung fields . Liver dysfunction was also recognized . As dyspnea and hypoxemia progressed very rapidly, the patient was intubated and kept under mechanical ventilation . A diagnosis of miliary tuberculosis with adult respiratory distress syndrome (ARDS) was made based on the detection of acid-fast bacilli from sputum obtained from the endotracheal tube . She was admitted to our hospital on Oct . 24, 1995 receiving anti-tuberculous drugs combined with high-dose methylprednisolone . As disseminated intravascular coagulation (DIC) and acute pancreatitis also developed, gabexate mesilate was added to the preceding therapy . This combination therapy was effective and the patient gradually improved . Two months after the admission, aneurysms of the abdominal aorta and left renal artery were discovered . As the size of the aneurysms had been increasing along with abdominal and low back pain, the patient was transferred to an other hospital for surgical treatment . She underwent a successful operation for pseudoaneurysms, the etiology of which was tuberculosis according to pathological findings and detection of acid-fast bacilli from the resected specimens . This is the 10th case of tuberculous aneurysm of the aorta which was successfully operated on in Japan . ARDS, DIC and aneurysm occur rarely as complications of miliary tuberculosis, but they are life-threatening, and lead to a serious prognosis if untreated . Early diagnosis of miliary tuberculosis and tuberculous aneurysm is very important for a good outcome.

Respirology, 1998 Jun, 3(2), 125 - 9
Detection of Mycobacterium tuberculosis in bronchoalveolar lavage from patients with sputum smear-negative pulmonary tuberculosis using a polymerase chain reaction assay; Liam CK et al.; The objective of this study was to evaluate the utility of a polymerase chain reaction (PCR) assay in detecting Mycobacterium tuberculosis in bronchoalveolar lavage (BAL) specimens of patients suspected of having active pulmonary tuberculosis (TB) but who were sputum smear-negative . Patients undergoing investigation for suspected pulmonary TB at the University Hospital, Kuala Lumpur, and who were sputum smear-negative underwent fibreoptic bronchoscopy and BAL . One portion of each lavage specimen was submitted for smear examination for acid-fast bacilli and mycobacterial culture and the other portion assayed by PCR for the presence of a 562-base pair DNA segment belonging to the insertion sequence IS986, unique to the M . tuberculosis complex . As controls, lavage specimens from patients with other lung lesions were also similarly tested . The PCR assay gave a positivity rate of 80.9% (55 of 68) compared with 8.8% of smear examination and 7.4% of culture for detecting M . tuberculosis in BAL specimens . The assay was positive in two of 45 BAL specimens from 35 control subjects . The PCR assay was more sensitive than smear and culture in detecting M . tuberculosis in BAL specimens of patients with sputum smear-negative pulmonary TB.

Respirology, 1998 Jun, 3(2), 119 - 24
Nitric oxide expression in airway epithelial cells in response to tubercle bacilli stimulation; Kwon OJ et al.; In order to investigate the role of airway epithelial cells in pulmonary tuberculosis, inducible nitric oxide synthetase (iNOS) expression and nitric oxide (NO) production were studied in A549 cells . Peripheral blood mononuclear cells (PBMC) from normal volunteers were separated and cultured for 24 h with LPS or tubercle bacilli (H37Rv, H37Ra) . Thereafter, A549 cells were stimulated for another 24 h with culture supernatant fluids of PBMC . iNOS messenger RNA (mRNA) expression was measured with Northern blot analysis and NO production was measured with the Griess reaction, which can measure nitrite concentration . iNOS mRNA expression and NO production were minimal in the control cells . iNOS mRNA expression and NO production were significantly increased with LPS (P < 0.05) or tubercle bacilli (P < 0.01) stimulation . However, there was no difference in iNOS mRNA expression and NO production between H37Rv and H37Ra stimulations . Interestingly, iNOS mRNA expression and NO production were greater in A549 cells stimulated with tubercle bacilli-conditioned media than in the cells stimulated with LPS-conditioned media . IL-1beta, tumour necrosis factor-alpha and interferon gamma concentrations were increased in culture supernatant fluids of PBMC stimulated with tubercle bacilli . These findings suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis by producing NO . However, the role of airway epithelial cells, regarding the virulence of tubercle bacilli, was not clear in this study.

Nihon Kokyuki Gakkai Zasshi, 1998 Apr, 36(4), 353 - 7
{Reinfection tuberculosis at a day-laborers' facility equipped with a sauna}; Kawada H et al.; Restriction-fragment-length polymorphism (RFLP) analysis was used to study one outbreak of reinfection pulmonary tuberculosis at a day-laborers' facility equipped with a sauna . The results were interpreted in conjunction with clinical and epidemiologic data . The DNA prove was derived from the insertion sequence IS 6110 . A 63-year-old man who stayed at a day-laborers' facility for eight months was found to have advanced cavitary lung disease with sputum smears strongly positive for acid-fast bacilli . One year later a 46-year-old man staying at the same facility for 24 months was also found to have sputum-positive tuberculosis . The 46-year-old man had undergone treatment for tuberculosis 16 years previously and showed radiographic evidence of previous lung damage from tuberculosis . The second man had no tubercule bacilli in sputum when the 63-year-old man was found to have sputum-positive tuberculosis . The organisms isolated from these two men were both drug sensitive and had a similar RFLP pattern which suggests that 63-year-old man was the source of this outbreak and that pulmonary tuberculosis in the 46-year-old man was caused by exogenous reinfection . We conclude that exogenous reinfection may have been one pattern of tuberculosis transmission in this high-risk environment.

Proc Natl Acad Sci U S A, 1998 Aug 4, 95(16), 9578 - 83
The 16-kDa alpha-crystallin (Acr) protein of Mycobacterium tuberculosis is required for growth in macrophages; Yuan Y et al.; Although the 16-kDa alpha-crystallin homologue of Mycobacterium tuberculosis (MTB) is the dominant protein produced by stationary phase cultures in vitro, it is undetectable in logarithmically growing cultures . By growing bacilli at defined oxygen concentrations, acr transcription was shown to be strongly induced by mildly hypoxic conditions . Acr expression also was found to be induced during the course of in vitro infection of macrophages . The acr gene was replaced with a hygromycin resistance cassette by allelic exchange in MTB H37Rv . The resulting Deltaacr::hpt strain was shown to be equivalent to wild-type H37Rv in in vitro growth rate and infectivity but was significantly impaired for growth in both mouse bone marrow derived macrophages and THP-1 cells . In addition to its proposed role in maintenance of long-term viability during latent, asymptomatic infections, these results establish a role for the Acr protein in replication during initial MTB infection.

Eur J Epidemiol, 1998 Jun, 14(4), 339 - 42
Notification of tuberculosis in a university hospital; Denic L et al.; The aim of this study was to evaluate completeness of tuberculosis notification in Bichat Claude-Bernard University Hospital and to evaluate whether misclassification of atypical mycobacterial infection could have contributed to the inaccuracy of tuberculosis notification . Data from Microbiology Laboratory of the hospital and statutory notifications were compared . From 1 January 1994 to 31 December 1995, 299 tuberculosis cases were diagnosed in the Microbiology Laboratory and 316 cases were notified as tuberculosis . Notification rate for laboratory-documented tuberculosis was 57.5%, was significantly higher in cases with positive acid fast bacilli smear (75%) than without this feature (45%) and was similar in HIV-positive (59.4%) and HIV-negative (63.5%) patients . Among notified cases, diagnosis was established by laboratory proofs in only 54.4% and by clinical signs in 45.6% . Three cases with positive smear and culture growing atypical mycobacteria were wrongly notified . Notification of laboratory-documented tuberculosis was higher than that observed in a previous study in the same hospital, suggesting that the rise of tuberculosis incidence reported in our country could be partially artificial . Nevertheless, extent of notification remains insufficient and needs to be improved by combining microbiological data with current system of notification.

Acta Cytol, 1998 Jul-Aug, 42(4), 945 - 8
Cytologic findings in a neovagina created with Vecchietti's technique for treating vaginal aplasia; Belleannee G et al.; OBJECTIVE: To report long-term cytologic findings after treatment of congenital vaginal aplasia or Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) using progressive traction of the vulvar tissues, or Vecchietti's technique (VT) . STUDY DESIGN: In eight women with MRKH, neovaginal smears stained by the Harris-Schorr technique were collected 2-12 years after VT . RESULTS: Eosinophilic superficial cells observed in all cases indicate that the neovaginal epithelium responds to hormonal variations . The presence of Doderlein bacilli (seven cases) suggests that the regional environment of the neovagina is almost the same as that of the normal vagina . Gardnerella vaginalis (one case) and human papilloma virus infection (low grade squamous intraepithelial lesions) (one case) were also observed . CONCLUSION: Neovaginal smears taken after the cicatrization period following construction of a neovagina by VT show a remarkable resemblance to those from normal vaginal mucosa and suggest that these neovaginas are almost the same as normal vaginas.

Arch Ophthalmol, 1998 Jul, 116(7), 937 - 40
Use of retinal biopsy to diagnose Bartonella (formerly Rochalimaea) henselae retinitis in an HIV-infected patient; Warren K et al.; A patient with the acquired immunodeficiency syndrome developed bilateral retinitis due to a Bartonella (formerly Rochalimaea) henselae infection . A retinal biopsy was performed when severe and progressive retinal infection failed to respond to empirical treatment for cytomegalovirus and Toxoplasma gondii . The biopsy specimen was stained with routine histopathological stains and the Steiner silver stain . Ribosomal DNA was extracted from formalinfixed, paraffin-embedded retinal tissue and amplified with the polymerase chain reaction assay, using Bartonella-specific primers . The amplified DNA fragment was cloned and sequenced . Staining with hematoxylin-eosin revealed tufts of proliferating vascular endothelium with numerous fusiformappearing cells, consistent with a diagnosis of bacillary angiomatosis . A Steiner silver stain revealed numerous small bacilli in the biopsy specimen . Amplification of DNA extracted from the tissue produced a fragment of 16S ribosomal DNA of the expected size; sequencing of the DNA fragment revealed that the infection was caused by B henselae . The retinal infection was treated with minocycline, doxycycline, and ciprofloxacin with improvement in visual acuity in the ensuing 12 weeks . To our knowledge, this is the first human immunodeficiency virus-infected patient with retinitis due to B henselae who was diagnosed by the identification of silver-staining bacilli and amplification and sequencing of B henselae with a polymerase chain reaction assay using a biopsy specimen of retinal tissue . Retinal biopsy is indicated, despite its potential for serious complications, in patients with acquired immunodeficiency syndrome who have a progressive, sight-threatening retinitis that is undiagnosed and unresponsive to therapy.

Vaccine, 1998 Aug, 16(13), 1344 - 8
Leprosy vaccine: influence of dissolved oxygen levels on growth of a candidate strain (Mycobacterium w), and storage stability of the vaccine; Mukhopadhyay A et al.; The growth of Mycobacterium w, a candidate strain for leprosy vaccine in submerged culture, was inhibited by the presence of over 40% oxygen saturation in the medium . Intracellular levels of superoxide dismutase and catalase were very low in the beginning . However, under controlled oxygenation, these levels increased with time . The augmentations of these antioxidant enzymes were associated with the elevated oxygen consumption by the culture . By maintaining the oxygen level below 20% during 6-day culture, it was possible to grow Mycobacterium w in five production batches up to a cell density of 3.7 +/- 0.70 x 10(9) bacilli ml-1 . The shelf life of the vaccine produced in different batches was more than 2 years, both at 4 degrees C and at 26 degrees C . This provides a cost-effective, unit culture technology for the production of this candidate leprosy vaccine from a nonpathogenic organism, which will facilitate the widespread use of the vaccine.

J Photochem Photobiol B, 1998 May 15, 43(2), 152 - 7
Isolation and analysis of UV and radio-resistant bacteria from Chernobyl; Zavilgelsky GB et al.; The accident at the Chernobyl nuclear power station in 1986 led to the dispersal of large amounts of a variety of radioactive materials, most importantly uranium, plutonium, 137Cs, 131I and 90Sr, over very large distances estimated to reach as far as Sweden, Norway, Turkey and possibly the USA . As a consequence, the soil on which the radioactive materials fell was contaminated and the degree of contamination varied with distance from the station, the direction and strength of the wind and the amount of atmospheric scavenging by rainfall at that time . Some of the radioactive materials have left a significant impact on mankind in the form of chromosomal aberrations including trisomy, various forms of cancers and death, whilst others are still in the ground where they will remain for a prolonged period to continue to exert their effects . Likewise, microbes living in the soil and exposed to radioactive materials may have been affected in a number of ways; some perished, and others survived due to the acquisition of advantageous mutation . Six years after the accident, soil samples contaminated with different levels of radioactivity were obtained from five regions within a 30 km radius of the nuclear power plant . From these soil samples spore-forming bacilli were isolated, quantified, identified and tested for resistance to X-rays, UVC and 4-nitroquinoline 1-oxide (4NQO) . As a control, spore-forming bacilli were obtained from 'Zeleny mys' (an area 50 km south-east of the power station and emitting basal levels of radioactivity) . A mutant of Escherichia coli hyper-resistant to a variety of DNA-damaging agents and its parent strain were also included in the study . Analysis of results reveals that a proportion of isolates of the same species from near the power station and the E . coli mutant SA236 were more resistant to X-rays, UVC and 4NQO compared with isolates from the control site and the E . coli parent strain, KL14, respectively.

J Occup Environ Med, 1998 Jul, 40(7), 648 - 54
Assessing the relative importance of the components of an occupational tuberculosis control program; Nicas M; Hospital-based occupational tuberculosis (TB) control programs have four basic components: rapid detection of TB disease in presenting patients; use of environmental controls, including personal respiratory protection; periodic tuberculin skin testing; and administration of prophylactic antibiotic therapy to newly infected employees . This article assesses which component is the most important in reducing TB disease risk among health care workers . A quantitative framework for estimating disease risk is developed, and two important results are described . First, the rapid identification of TB disease in presenting patients is the most important element in the overall program . Second, once TB disease has been identified, the use of highly efficient environmental controls (which include respiratory protection) becomes the most important element; these controls are especially important for procedures such as bronchoscopy and autopsy, which can aerosolize large numbers of viable Mycobacterium tuberculosis bacilli.

Clin Infect Dis, 1998 Jul, 27(1), 205 - 8
Disseminated miliary tuberculosis of the skin in patients with AIDS: report of four cases; Daikos GL et al.; We present clinical, bacteriologic, and pathological findings for four patients with AIDS and cutaneous miliary tuberculosis . All patients had generalized tuberculosis with hematogenous dissemination to multiple organs including the skin . Microscopic examination of the skin lesions revealed ill-formed or no granulomata, extensive necrosis, and numerous acid-fast bacilli . Mycobacterium tuberculosis was detected in the skin lesions by cultures for three patients and by polymerase chain reaction for one . Three of the isolates were resistant to at least isoniazid and rifampin, and one was susceptible to these drugs . The outcome was rapidly fatal for the three patients with multidrug-resistant tuberculosis . This report draws attention to the reappearance of a once-rare manifestation of disseminated tuberculosis which, in the setting of advanced human immunodeficiency virus disease, may offer the first indication of infection with multidrug-resistant M . tuberculosis and a poor prognosis.

Clin Infect Dis, 1998 Jul, 27(1), 33 - 9
Pharmacodynamics of fluoroquinolones; Lode H et al.; Fluoroquinolone antimicrobial agents are highly active against aerobic or facultative gram-negative bacilli . The fluoroquinolones have been shown to be very concentration dependent in their rates of killing and also have a postantibiotic effect against most gram-negative pathogens . These properties resemble those of aminoglycosides more than those of the beta-lactam antibiotics . In animal studies, once daily administration of a dose that produced a high peak concentration/minimal inhibitory concentration (MIC) ratio of > 10-20:1 resulted in significantly better survival than did regimens in which the same daily dose was used on a more fractionated schedule . Studies in patients, most often with ciprofloxacin, demonstrated that the area under the concentration-time curve (AUC)/MIC ratio (AUIC) is the most important predictor of both clinical and microbiological cure . These findings, when combined with microbiological and pharmacokinetic data, provide the rationale and tools needed for targeting the dosage of fluoroquinolones to individual patients on the basis of pharmacokinetics and the susceptibilities of the bacterial pathogens.

Chest, 1998 Jul, 114(1), 317 - 23
Clinical application of the Mycobacterium tuberculosis direct test: case report, literature review, and proposed clinical algorithm; Gladwin MT et al.; The relatively new Mycobacterium tuberculosis direct test (MTDT) enzymatically amplifies M tuberculosis complex 16s ribosomal RNA . The sensitivity of the test ranges from 75 to 100%, with specificity of 95 to 100%, positive predictive value between 78% and 100%, and negative predictive value between 95% and 100% . Similar test characteristics have been documented in nonrespiratory specimens and in specimens that ultimately grow nontuberculous mycobacterium (NTM) . This test allows for rapid identification of M tuberculosis in the smear-positive patient and may greatly improve sensitivity over acid-fast bacilli smear alone . A negative test result with a positive smear suggests infection with NTM or Mycobacterium avium complex . We present a case that illustrates the value of MTDT for analysis of tissue specimens in immunocompromised patients with suspected mycobacterial disease and review the rapidly developing literature about this test . We propose an algorithm using MTDT, acid-fast smear, and mycobacterial culture for the diagnosis and treatment of the immunocompromised patient with suspected mycobacterial infection.

Aust Vet J, 1998 Jun, 76(6), 403 - 7, 398
Mycobacterial nodular granulomas affecting the subcutis and skin of dogs (canine leproid granuloma syndrome); Malik R et al.; OBJECTIVE: To obtain a better understanding of a disease affecting dogs in which nodular mycobacterial granulomas are present in the subcutis or skin . DESIGN: Retrospective survey PROCEDURE: A diagnosis of an unidentified mycobacterial infection was made in 45 dogs following detection of acid-fast bacilli surrounded by granulomatous or pyogranulomatous inflammation in tissue sections . Eight cases were identified from the records of our diagnostic laboratory . In all cases culture for mycobacteria was unsuccessful . Another 37 cases were identified by practitioners and veterinary pathologists in response to a survey mailed to veterinary clinics throughout Australia . Data from these 45 cases were entered into a data base . The data set was incomplete, as some respondents did not answer all questions . RESULTS: Over 90% of affected dogs had short coats and about half were Boxers or Boxer-cross dogs . A weak seasonal trend for the development of primary lesions in autumn and winter was identified . Cases were recorded from New South Wales (35 dogs), Western Australia (4), Queensland (4), Tasmania (1) and New Zealand (1) . The subcutis and skin of the ears and head (including the ears) were involved in 64% and 85% of cases, respectively, for which lesion site was recorded . Culture was attempted but was unsuccessful in 19 cases, including 11 cases where material was submitted to our laboratory and/or a Mycobacteria Reference Laboratory . Lymph node enlargement, internal organ involvement or constitutional signs were not a feature of the syndrome, and most lesions did not worry the dogs . Although many practitioners recorded a favourable response to therapy with doxycycline (response rate 57%) or amoxycillin-clavulanate (63%), spontaneous resolution of infection was thought to have occurred in six of seven dogs (86%) not given systemic antimicrobials, and three dogs where antimicrobials had failed previously . A minority of cases failed to respond to antimicrobial therapy and continued to have chronic lesions . There was no discernible trend for dogs of a particular age or sex to be affected . CONCLUSION: This syndrome is caused by saprophytic mycobacteria of limited pathogenicity that give rise to lesions restricted principally but not exclusively to the subcutis and skin of body extremities . Fastidious growth requirements have prevented their isolation on synthetic media used for culture of mycobacteria . Organisms presumably enter the subcutis following a breach in integrity of the epidermal barrier and produce self-limiting disease in immunocompetent dogs . Lesions tend to resolve spontaneously . The possibility of a public health threat from affected dogs is highly unlikely.

Infect Immun, 1998 Aug, 66(8), 3562 - 8
Altered cytokine production and impaired antimycobacterial immunity in protein-malnourished guinea pigs; Dai G et al.; Protein malnutrition leads to multiple detrimental alterations of host immune responses to mycobacterial infection . In this study, we demonstrated that splenocytes from low-protein (LP) guinea pigs vaccinated 6 weeks previously with attenuated Mycobacterium tuberculosis H37Ra failed to control the accumulation of virulent M . tuberculosis H37Rv in cocultured autologous peritoneal macrophages, despite the fact that they were able to control the accumulation of virulent tubercle bacilli in cocultured syngeneic peritoneal macrophages from normally nourished guinea pigs as successfully as did those from high-protein (HP) counterparts . Vaccine-induced growth control of virulent M . tuberculosis H37Rv in these cocultures appeared to be mediated by CD4 lymphocytes but not CD8 cells . Tuberculin (purified protein derivative {PPD})-induced lymphoproliferation was markedly impaired in vaccinated LP guinea pigs, and the depletion of CD4 lymphocytes significantly decreased lymphocyte proliferation whereas CD8 cell depletion did not . Protein malnutrition also impaired the abilities of cells from vaccinated LP guinea pigs to produce cytokines, including interferon, tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta), in response to PPD, despite the demonstration of higher serum levels of TNF-alpha and TGF-beta after an intravenous injection of PPD into LP guinea pigs . In contrast, peritoneal macrophages from protein-malnourished guinea pigs produced a higher level of TGF-beta 4 days after infection in vitro with M . tuberculosis H37Rv than did those from protein adequate controls . These results suggest that dietary protein malnutrition impairs vaccine-induced resistance to M . tuberculosis, in part, by altering the cytokine profile to favor macrophage deactivation.

Rays, 1998 Jan-Mar, 23(1), 239 - 46
Control strategies for tuberculosis and role of public health service; Ortona L et al.; The best strategy of prevention of tuberculosis is to control the contact with tubercle bacilli, implement the suggested therapeutic protocol and verify the patient's compliance with the therapy . To this purpose, it is important to plan outpatient controls, supply enough drugs to the patient to last until the first outpatient control and include the patient in directly observed therapy (DOT) programs . At the hospital level there should be three possibilities: isolation of potentially contagious patients, application of structural devices and of respiratory protection . The role of the Public Health Service in the control of tuberculosis at present is of the utmost importance to optimize prevention measures as well as to prepare protocols for health care and therapy . Particular controls are necessary in health facilities providing care for HIV-positive subjects where a program of control of tuberculous infection should be implemented according to the guidelines of the Ministry of Health.

FEMS Microbiol Lett, 1998 Jun 15, 163(2), 159 - 64
Oxygen depletion induced dormancy in Mycobacterium smegmatis; Dick T et al.; We report here that the physiological behaviour of the fast growing saprophytic Mycobacterium smegmatis under in vitro oxygen-depletion and reactivation conditions is strikingly similar to the characteristics shown by the slow growing pathogenic M . tuberculosis . M . smegmatis died rapidly when shifted abruptly from aerobic to anaerobic conditions . In contrast to the lethal shock of abrupt oxygen depletion, the slow depletion through a self generated oxygen gradient permitted an adaptation to a persistent state which showed increased resistance against the bactericidal effects of anaerobiosis . The anaerobic persistent culture did not synthesise DNA and showed synchronised division upon reactivation in oxygen rich medium, indicating that the persistent bacilli are uniformly arrested at a defined stage of the cell cycle . Upon reactivation the persistent culture started synthesising DNA only after the first cell division, suggesting that the persistent cells contain two chromosomes . Furthermore, the persistent culture developed sensitivity to metronidazole and resistance against ofloxacin . These results suggest that M . smegmatis might be useful as a fast growing non-pathogenic model for comparative molecular analyses of mycobacterial dormancy.

Aten Primaria, 1998 May 15, 21(8), 535 - 8
{Epidemiologic situation of tuberculosis under the influence of HIV in the health area of Ibiza and Formentera (1987-1993)}; Martinez M et al.; OBJECTIVES: To analyse the epidemiology of Tuberculosis and determine the characteristics of patients infected by HIV vs those not infected . DESIGN: A descriptive-retrospective study . SETTING: Ibiza and Formentera Health Area . PATIENTS: 268 patients over 16 diagnosed with TB between 7/1/1987 and 12/31/1993 . MEASUREMENTS AND MAIN RESULTS: The highest accumulated annual incidence was detected in 1989 (82.4/100,000 inhabitants), but had decreased considerably by 1993 (42.8/100,000) . The proportion of HIV+ cases increased to 37.0% of the total in 1993 . 75% of the total were male and 57.5% between 20 and 39 (x = 38.1; SD = 15.4) . 63.1% had pulmonary TB, 60.8% producing bacilli, 19.8% were HIV+, of which 47.2% were intravenous drug users and 20.8% homosexuals . There was a 75.4% cure rate, 4.9% who left treatment and 16.1% lost during follow-up . CONCLUSIONS: During the study period a progressive increase in the proportion of cases with HIV infection was observed . Control and follow-up of Tuberculosis was more difficult in these patients.

Scand J Infect Dis, 1998, 30(1), 59 - 68
A mouse model for latent tuberculosis; Phyu S et al.; The aim of the study was to establish a reproducible murine model for latent tuberculosis . We propose an operational definition of latent murine tuberculosis as a stable Mycobacterium-tuberculosis count in lungs and spleens without clinical signs or obvious histopathological changes in the lungs over a long period of time and without spontaneous reactivation of disease . B6D2F1Bom mice were inoculated with a wide range of Mycobacterium tuberculosis doses intraperitoneally or intravenously and followed for a long period to determine suitable conditions to produce latent infection . No anti-tuberculosis drug treatment was used . Microbiological and histopathological studies were carried out . Corticosterone challenge was used to reactivate the latent infection . Mice infected with 4 x 10(4) and 4 x 10(5) bacilli i.p . were followed up to 107 weeks without spontaneous reactivation . The present model is discussed in comparison with previous latent tuberculosis mouse models as well as the possible mechanisms of shift to stationary phase from multiplying bacilli.

Tuber Lung Dis, 1997, 78(1), 21 - 7
Serological diagnosis of childhood tuberculosis by estimation of mycobacterial antigen 60-specific immunoglobulins in the serum; Gupta S et al.; SETTING: An ELISA assay based on mycobacterial antigen 60 (A60) for the estimation of specific immunoglobulins in the serum has been used successfully for the rapid diagnosis of tuberculosis in studies done predominantly in Western countries . In a recent Indian study, encouraging results were reported in adult tuberculosis . OBJECTIVE: To evaluate the utility of this ELISA test for rapid diagnosis of different clinical forms of tuberculosis in Indian children . DESIGN: ELISA test based on mycobacterial A60 was used to estimate specific IgM, IgA and IgG antibodies in the sera obtained from 452 cases of tuberculosis and 161 controls in the paediatric population of Delhi, India . RESULTS: Of the 161 controls, only 7.4% were positive for IgM, 4.3% for IgG, 3.7% for IgA and 8% when a combination of IgM and IgA was considered . Of 58 cases of definite pulmonary tuberculosis, 55.2% were positive for IgM, 32.7% for IgG, 36.2% for IgA and a high positivity of 72.4% was seen when IgA and IgM estimations were combined . The corresponding figures in 150 cases of definite extrapulmonary tuberculosis were 57.3%, 36.6%, 38% and 76.6% . A relatively weak serology was observed in 244 cases of probable tuberculosis . A very high positivity (95%) was seen in acid-fast bacilli-positive cases of tuberculosis . CONCLUSIONS: Our findings point to a very good specificity (92%) and a reasonably good sensitivity (75.5%) of the test when combined IgM and IgA antibody titres are considered in the diagnosis of childhood tuberculosis.

Arch Intern Med, 1998 Jul 13, 158(13), 1440 - 4
Are US hospitals making progress in implementing guidelines for prevention of Mycobacterium tuberculosis transmission?
Manangan LP, Simonds DN, Pugliese G, Kroc K, Banerjee SN, Rudnick JR, Steingraber K, Jarvis WR.
BACKGROUND: Outbreaks of tuberculosis (TB) in hospitals have occurred when the Centers for Disease Control and Prevention (CDC) guideline recommendations for preventing the transmission of Mycobacterium tuberculosis were not fully implemented . OBJECTIVE: To determine whether US hospitals are making progress in implementing the CDC guidelines for preventing TB . METHODS: In 1992, we surveyed all public (city, county, Veterans Affairs, and primary medical school-affiliated) US hospitals (n = 632) and 444 (20%) random samples of all private hospitals with 100 beds or more . In 1996, we resurveyed 136 random samples (50%) of all 1992 respondent hospitals with 6 or more TB admissions in 1991 . RESULTS: Of the 1076 hospitals surveyed in 1992, 763 (71%) respondents returned a completed questionnaire . Among these, 536 (71%) of 755 reported having rooms that met CDC criteria for acid-fast bacilli isolation, ie, negative air pressure, 6 or more air exchanges per hour, and air directly vented to the outside . The predominant respiratory protective device for health care workers was nonfitted surgical mask and attending physicians were infrequently (50%) included in tuberculin skin-testing programs . In the 1996 resurvey, 103 (76%) of 136 respondents returned a completed questionnaire . Of these, 99 (96%) reported having rooms that met CDC criteria for acid-fast bacilli isolation . The N95 respiratory protective devices were predominantly used by health care workers, and attending physicians were increasingly (69%) included in the hospitals' tuberculin skin-testing programs . CONCLUSIONS: Most US hospitals are making progress in the implementation of CDC guidelines for preventing the transmission of M tuberculosis.

Pneumonol Alergol Pol, 1998, 66(1-2), 38 - 44
{Usefulness of redux properties in acid-resistant bacilli for rapid detection of their growth in culture}; Zwolska Z et al.; MB REDOX a new system for detection of Mycobacterium is described . It is a modified, serum supplemented Kirchner-medium containing a colourless tetrazolium salt reduced by the redox system used for self-indicating microbial growth . In this study we have tested sensitivity and time of isolation of Mycobacteria in MB REDOX and compared to the other different systems of cultivation.

Pneumonol Alergol Pol, 1998, 66(1-2), 24 - 30
{A new, automatic, non-radiometric system for culturing MB/BACT bacilli and its value in the microbiologic diagnosis of tuberculosis}; Zofia Z et al.; The MB/BacT is a fully automated, rapid, non-radiometric system, for the culture of Mycobacteria for clinical samples other than blood . CO2 production is measured and reported as reflective units from the MB/BacT Process Bottle colorimetric sensor . We are evaluating the MB/BacT system in comparison to our routine culture method--culture on egg media (glycerol and puruvate), in the Bactec 460-Tb radiometric machine and in MB Redox . A total of 286 clinical samples from respiratory tract were inoculated into three or four culture systems and incubated at 37 degrees C . There was only little difference in mean time to detection between the MB/BacT and Bactec system (for M.tuberculosis 11 days versus 9 days), but both systems were faster than egg media (16 days) . Contamination rates for MB/BacT system was 8.4%, and for Bactec 6.9% . The colorimetric technology used in the MB/BacT is a rapid and sensitive for the measurement of mycobacterial growth.

FEMS Immunol Med Microbiol, 1998 May, 21(1), 19 - 28
Protective efficacy of mycobacterial 71-kDa cell wall associated protein using poly (DL-lactide-co-glycolide) microparticles as carrier vehicles; Dhiman N et al.; Microparticles composed of poly (DL-lactide-co-glycolide) (DL-PLG) were used as delivery vehicles for evaluating the immunoreactive and immunoprotective properties of 71-kDa cell wall associated protein of Mycobacterium tuberculosis H37Ra . Mice immunized with 71-kDa microparticles entrapped in DL-PLG (PLG-MPs) exhibited significantly higher T-cell stimulation and cytokine release in comparison to 71-kDa emulsified in Freund's incomplete adjuvant (FIA) as well as a BCG vaccinated group throughout the post-immunization (p.im.) period . Further, the protective efficacy of 71-kDa was evaluated on the basis of survival rates and viable bacilli load in different organs at 30 days post challenge (p.c.), with the median lethal dose (LD50) of M . tuberculosis H37Rv at weeks 8 and 16 p.im . Both 71-kDa-PLG and 71-kDa-FIA immunized groups exhibited a comparable protection (90%) which was significantly higher (P < 0.5) than in the BCG group (70%) at week 8 p.im . and it was consistent with the decreased bacterial load in the target organs . However, on increasing the interval of challenge to 16 weeks p.im., the protective efficacy of 71-kDa-PLG was sustained (85%) while that of 71-kDa-FIA began to wane (70%) . Further . the 71-kDa-PLG immunized group exhibited a significantly higher (P < 0.001) clearance of bacterial load from the lungs and livers in comparison to the 71-kDa-FIA immunized group . The results suggest the long-term protective potential of a PLG-microparticle based antigen delivery system for tuberculosis.

Southeast Asian J Trop Med Public Health, 1997 Dec, 28(4), 801 - 2
Retrospective study of empyema cases in National Pediatric Hospital, Cambodia; Hong R et al.; Majority of empyema cases admitted into the National Pediatric Hospital (NPH), Cambodia were of bacterial origin (EB: 95%), the rest were caused by tuberculosis bacilli (ETB: 5%) . The morbidity of overall empyema, empyema of bacterial origin and empyema of TB origin between boys and girls was the same, even though boys were more likely to be exposed than girls . The mean age of patients with ETB was significantly greater than those of EB, 84.7 +/- 46 months versus 52.5 +/- 37 months . Since NPH is located in Phnom Penh, most of our cases were from Kandal, Phnom Penh, and provinces nearby . On average all of the patients stayed in the hospital for 23.26 +/- 14.9 days (rank 1-91 days), and the mean duration of hospitalization of the ETB patients was significantly longer than that of EB patients, 32 +/- 19 days versus 22 +/- 14 days respectirely . The yearly incidence of empyema cases in 1990-1993 had the trend of slightly increased frequency during March to May . The overall EB case fatality rate was 3%, contributed to by delayed referral of cases.

Southeast Asian J Trop Med Public Health, 1997, 28 Suppl 1, 37 - 45
Pulmonary paragonimiasis and tuberculosis in Sorsogon, Philippines; Belizario V et al.; The clinical epidemiology of pulmonary paragonimiasis and tuberculosis was investigated in a known endemic municipality of Sorsogon, Philippines . Records of diagnosed tuberculosis patients on treatment and follow up at the local Rural Health Unit over a two year period from 1993 to 1994 were reviewed to provide an overview of pulmonary tuberculosis in the area, specifically to describe the population at risk, the basis for diagnosis and the proportion of case notification who were sputum negative . Patients from the same group of individuals as well as undiagnosed tuberculosis patients with productive cough, fever with chest and/or back pain, or hemoptysis were examined to look into clinical manifestations, duration of symptoms, history of crab-eating and sputum examination results for acid-fast bacilli and Paragonimus . There was difficulty in determining the number of non-responders as the records did not have any provision for the recording of such . Annual tuberculosis case notification rates for the two years (374 and 401 per 100,000 population) were higher than the national figure in 1991 (325 per 100,000 population) indicating that tuberculosis is still a major health problem in the area and tuberculosis control efforts may have to be more aggressive to better contain the disease . Twenty-six out of 160 individuals surveyed were sputum smear positive for Paragonimus . Paragonimiasis rates were not significantly different in the two groups (15.6% vs 16.9%, respectively) indicating that there is a need for routine sputum examination for Paragonimus which is not available at present . Only six patients surveyed were sputum smear positive for acid-fast bacilli . A high index of suspicion is necessary to diagnose paragonimiasis and to be able to differentiate it from tuberculosis . The diagnosis may be suggested by a patient's place of origin being a known endemic area, a long period of chronic cough and the habit of eating raw or insufficiently cooked crabs or crayfish . Laboratories in endemic areas should have the capacity to differentiate between the two infections by being able to provide the routine laboratory procedures necessary for definitive diagnosis and treatment.

Microbiol Immunol, 1998, 42(5), 357 - 63
Cellular reaction to Mycobacterium avium complex (MAC) clinical isolates differing in hemolytic activity and virulence for C57BL/6 mice; Brzychcy M et al.; In this study we showed that Mycobacterium avium complex (MAC) clinical isolates differed by the expression of hemolytic activity . Two hemolytic MAC strains were less susceptible to the mycobactericidal effect of murine macrophages than two unhemolytic MAC isolates . In vivo, hemolytic MAC bacilli survived in the spleens of infected mice for a longer time than unhemolytic MAC strains . This suggested a role of hemolysins in the virulence of MAC strains . There was no difference in the cytotoxicity of T cells from mice immunized with M . bovis BCG towards macrophages infected in vitro with MAC strains expressing or not expressing hemolytic activity.

Scand J Immunol, 1998 Jun, 47(6), 548 - 53
Protective effect of beta-glucan against mycobacterium bovis, BCG infection in BALB/c mice; Hetland G et al.; Beta-1,3-glucan is a potent stimulator of macrophage functions and has a protective effect against a range of infections in rodent models . We examined whether the agent could also protect against the intracellular Mycobacterium bovis, bacillus Calmette-Guerin (BCG) infection in mice . BCG-susceptible BALB/c mice were injected intravenously (i.v.) with beta-glucan or vehicle 3 days before, or with beta-glucan 7 days after i.v . challenge with live BCG bacilli . The animals were killed 4 or 8 weeks later, their organs were homogenized and applied to object slides and stained with auramin for counting of bacilli, or seeded onto agar in Petri dishes . Mice treated with beta-glucan both pre- and postchallenge had significantly lower numbers of BCG bacilli and BCG colony-forming units in spleen homogenates compared with controls 4 weeks after challenge . A similar, but not statistically significant, tendency was observed in spleen homogenates from mice killed 8 weeks after challenge . In homogenates of liver and lungs there were similar findings, but less pronounced . There was a dose-dependent effect of beta-glucan injected before BCG challenge on the number of BCG bacilli found in spleen and liver homogenates . In addition, antibody cross-reactivity was demonstrated between M . tuberculosis cell wall and beta-glucan . The results suggest that beta-glucan has a protective effect against M . bovis, BCG infection in susceptible mice.

J Hosp Infect, 1998 Jun, 39(2), 111 - 7
An outbreak of multi-drug-resistant tuberculosis in a London teaching hospital; Breathnach AS et al.; We describe the epidemiology and control of a hospital outbreak of multi-drug-resistant tuberculosis (MDR-TB) . A human immunodeficiency virus (HIV)-negative patient with drug-sensitive tuberculosis developed MDR-TB during a period of unsupervised therapy . She was admitted to an isolation room in a ward with HIV-positive patients, but the room, unbeknown to hospital staff, was at positive-pressure relative to the main ward . Seven HIV-positive contacts developed MDR-TB . The diagnosis in the second patient was delayed, partly because acid-fast bacilli in his sputum were assumed to be Mycobacterium avium-intracellulare . All the available Mycobacterium tuberculosis isolates were indistinguishable by molecular typing . Nearly 1400 staff and patient contacts were offered screening, but the screening programme detected only one of the cases . Despite therapy, the index patient and two of the contacts died . HIV-positive patients are more likely than others to develop tuberculosis after exposure, and the disease may progress more rapidly . In these patients the possibility that acid-fast bacilli may represent M . tuberculosis must always be considered . Patients with tuberculosis (suspected or proven) should not be nursed in the same wards as immunosuppressed patients, and should be isolated . MDR-TB cases must be isolated in negative-pressure rooms . Hospital side-rooms may be positive-pressure as a fire safety measure; infection control teams must be aware of the airflows in all isolation rooms, and must be consulted during the design of hospital buildings . Good communication between infection control teams and clinicians is important, and all medical and nursing staff must be aware of the principles of management of patients with proven or suspected tuberculosis and MDR-TB.

J Clin Microbiol, 1998 Jul, 36(7), 1996 - 2003
Novel method for processing respiratory specimens for detection of mycobacteria by using C18-carboxypropylbetaine: blinded study; Thornton CG et al.; A novel method for processing respiratory specimens to improve culture and acid-fast staining of mycobacteria is introduced . This new method utilized N,N-dimethyl-N-(n-octadecyl)-N-(3-carboxypropyl)ammonium inner salt (Chemical Abstract Service no . 78195-27-4), also known as C18-carboxypropylbetaine (CB-18) . In a blinded, five-center study, CB-18-based processing was compared to the standard method combining NALC and NaOH (NALC/NaOH) . A total of 573 respiratory specimens were tested . Individual specimens were split approximately equally; the host institutions processed half of each specimen by the NALC/NaOH method, while the other half was processed with CB-18 at Quest Diagnostics--Baltimore . A total of 106 specimens were culture positive for acid-fast bacilli (AFB) . Replacement of the primary decontamination agent with CB-18 caused changes in all diagnostic parameters . Aggregate culture sensitivity improved by approximately 43% (P < 0.01), and smear sensitivity improved by approximately 58% (P < 0.01) . The sensitivity of smear relative to that of M . tuberculosis isolates exceeded 93% (P < 0.01) when specimens were processed with CB-18 . The average times to a positive result were reduced by 7.3 days in liquid culture (P < 0.01) and 5.3 days on solid media (P < 0.05); however, the CB-18 method had a 20.8% contamination rate in liquid culture versus a rate of approximately 7.5% with NALC/NaOH processing . There were also unusual reductions in liquid culture sensitivity and smear specificity among CB-18-processed specimens . The characteristics of the latter parameters suggested that refinement of the CB-18 processing method should allow further improvements in culture sensitivity . This study showed that the CB-18 method has the potential to improve both smear and culture detection for these important human pathogens.

J Clin Microbiol, 1998 Jul, 36(7), 2052 - 6
Direct susceptibility testing with positive BacT/Alert blood cultures by using MicroScan overnight and rapid panels; Waites KB et al.; Studies were conducted on a method of direct inoculation of MicroScan dried overnight and of rapid panels with positive aerobic blood cultures obtained from the BacT/Alert to determine antimicrobial susceptibilities . Inocula were limited to specimens that appeared unimicrobic on Gram stain . Results were compared to those obtained from panels inoculated following subculture . For 133 gram-negative bacilli, there were 94.7 and 93.5% categorical agreements between direct and standard methods for all drugs tested with overnight and rapid panels, respectively . For 104 gram-positive cocci, there were 93.2 and 93.1% categorical agreements for overnight and rapid panels, respectively . The major error (false resistance) rate for gram negatives was 1.4% for overnight versus 0.7% for rapid panels . The very major error (false susceptibility) rate was 2.7% for overnight versus 8.1% for rapid panels . The total error rates were 1.6% for overnight panels and 1.5% for rapid panels . The major error rates for gram-positive direct susceptibility tests were 2.6% for overnight and 2.5% for rapid panels . The very major error rates were 8.8 and 7.2% for overnight and rapid panels, respectively . Total error rates were 3.6% for overnight and rapid gram-positive panels . These findings suggest that susceptibility results obtained from directly inoculated gram-negative overnight panels have the greatest correlation to those obtained by standard methods . When discrepant results occur with direct-susceptibility testing, they are more likely to show false susceptibility than false resistance.

J Clin Microbiol, 1998 Jul, 36(7), 1964 - 8
Comparison of the ABI 7700 system (TaqMan) and competitive PCR for quantification of IS6110 DNA in sputum during treatment of tuberculosis; Desjardin LE et al.; Mycobacterium tuberculosis can persist in sputum for long periods of time after the initiation of antituberculosis chemotherapy . The purpose of this study was to determine whether quantitative estimates of M . tuberculosis DNA in sputum correlate with the numbers of viable bacilli and thus measure the therapeutic response of patients during treatment . Two methods of M . tuberculosis DNA quantification were examined by using DNA isolated from sputum specimens serially collected during the course of chemotherapy . A competitive PCR assay was compared to an automated system of real-time quantification with the ABI Prism 7700 Sequence Detection System (TaqMan) . The ABI 7700 system uses standard PCR in conjunction with a fluorogenic probe in which the intensity of fluorescence is proportional to the amount of target DNA present . The results showed that both PCR systems are reproducible and accurate . The amounts of M . tuberculosis DNA quantified in sputum corresponded well with the numbers of acid-fast bacilli (AFB) counted by microscopy . Before initiation of antituberculosis therapy, measures of AFB, M . tuberculosis DNA, and cultivable bacilli were similar, suggesting that quantification of DNA is a good method for measuring the initial bacillary load . However, the rate of disappearance of both AFB and M . tuberculosis DNA did not correlate with the decline in cultivable bacilli in the specimen; therefore, these tests are not appropriate for monitoring treatment efficacy.

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