J Chemother, 2003 Dec, 15(6), 551 - 4 Antimicrobial susceptibility and synergistic activity of meropenem against Gram-negative non-fermentative bacteria isolated from cystic fibrosis patients; Campana S et al.; The objective of the present study was to evaluate the activity of meropenem (a beta-lactam carbapenem with good bactericidal potency and a very wide spectrum of activity) and of ticarcillin, ceftazidime ciprofloxacin, tobramycin, cefepime, which are the most commonly used antimicrobial agents for treatment of pulmonary infections associated with CF . The effect of these antibiotics was tested on 27 multiresistant strains isolated from 24 CF patients during 2000 and 2001 . Furthermore, the in vitro synergistic effect of meropenem in association with the other antibiotics was evaluated . Ciprofloxacin, ticarcillin, meropenem and ceftazidime had the most activity and inhibited 66%, 37%, 36% and 33% of strains respectively . The addition of a second antibiotic to meropenem resulted in a synergistic effect on 5 (18.5%) isolates; on average 2.8 synergistic combinations where determined per strain . Of these 27 isolates, antagonism was observed in 3 (11%) strains (1 antagonistic combination per strain) . Our study suggests that selecting effective double antibiotic therapy cannot be made empirically for CF patients infected with Gram-negative multiresistant bacilli . Therefore in vitro methods for testing double antibiotic combinations are mandatory. J Infect Chemother, 2004 Feb, 10(1), 37 - 41 An Aeromonas veronii biovar sobria infection with disseminated intravascular gas production; Shiina Y et al.; We report a case of Aeromonas veronii biovar sobria infection with disseminated intravascular gas production . The patient was an afebrile 15-year-old girl who had been quite healthy until the onset of the illness . She came to the hospital because of a 6-h history of increasing pain and swelling in her left thigh . On admission, no infection was suspected, and a tentative diagnosis of a ruptured left gracilis muscle was made . Because the pain increased continuously, the treatment concentrated on pain control . Unexpectedly, abrupt death occurred 23 h after her admission . Postmortem computed tomographic (CT) scans showed an abundance of gas in the blood vessels of the entire body . Postmortem investigation revealed disseminated intravascular gas production, marked intravascular hemolysis, and numerous intravascular Gram-negative bacilli in all organs examined . The organisms were identified as A . veronii biovar sobria, and were highly susceptible to third-generation cephalosporins . Regarding therapeutic problems, the early administration of these antibiotics should reduce the fatality rate in such infections . It is critical to keep the possibility of such an infection in mind when a patient complains of severe muscle pain. Surg Neurol, 2004 Mar, 61(3), 283 - 7; discussion 287 Intramedullary neurosarcoidosis in the medulla oblongata: a case report; Mahadewa TG et al.; OBJECTIVE: We present a rare case of neurosarcoidosis mimicking an intramedullary tumor in the medulla oblongata . The features of the clinical presentation, magnetic resonance (MRI) appearances, and management strategy are discussed . CASE PRESENTATION: A 59-year-old man without evidence of systemic sarcoidosis was presented with a history of progressive numbness and deep sensation disturbance in bilateral lower extremities . MR imaging revealed an enhanced intra-axial mass lesion on the dorsal side of medulla . Under neurophysiological monitoring, tumor biopsy was performed . Pathologic evaluation revealed noncaseating granuloma composed of large epithelioid cells with multinucleated giant cells, suggesting sarcoidosis . Findings of comprehensive hematologic laboratory studies; cerebrospinal fluid examination; and examinations for bacteria, fungi, and acid fast bacilli were all negative . This mass lesion was diagnosed as medullary neurosarcoidosis, and then high-dose steroid therapy was tried . On follow-up, nearly complete resolution of the neurosarcoidosis on MRI was revealed . CONCLUSION: To our knowledge, this is the first reported case of neurosarcoidosis manifested in the medulla oblongata . A biopsy is sufficient for a diagnosis and high-dose steroid is recommended. Rinsho Biseibutshu Jinsoku Shindan Kenkyukai Shi, 2003, 14(1), 45 - 50 {Detection of drug-resistant Mycobacterium tuberculosis isolates using DNA microarray}; Yoshikawa Y et al.; Rapid identification of drug-resistant strains of Mycobacterium tuberculosis is an important problem to adequate patient treatment . However, current clinical assays for determining antibiotic susceptibility in M . tuberculosis require many weeks to complete due to the slow growth of the bacilli . We have developed simple and rapid drug susceptibility test using DNA microarray "Oligoarray TB," that allows the detection of rifampicin (RFP), isoniazide (INH), kanamycin (KM), streptomycin (SM), and ethambutol (EM)-resistant strains within 6 h with DNA extracted directly from sputum or cultured cells . The genes related to drug-resistance, results of detection using Oligoarray TB, comparative evaluation with media, and sequencing analysis of strains generating discrepant results in testing for INH-resistant will be discussed in this presentation. Rinsho Biseibutshu Jinsoku Shindan Kenkyukai Shi, 2003, 14(1), 1 - 8 {Laboratory-based evaluation of a fully automated microbiology system, RAISUS for species-identification and antimicrobial susceptibility tests}; Onaga S et al.; A fully automated microbiology system, RAISUS newly developed (Nissui Pharmaceuticals Co., Ltd., Tokyo) was evaluated for gram-positive and gram-negative clinical isolates . In the species-identification, the RAISUS comparably identified 200 of 202 isolates (99.0%) consisting of 10 species of gram-positive cocci and of 16 species of gram-negative bacilli . When compared to the MicroScan Walk/Away, which resulted in six misidentifications, the RAISUS showed higher accuracy in species-identification . In the evaluation of antimicrobial susceptibility test, the RAISUS gave comparable minimum inhibitory concentrations (MICs) and category interpretations . Of 693 testings for gram-positive and of 721 testings for gram-negative isolates, 655 (94.5%) and 688 (95.4%) testings gave comparable interpretations to the reference microdilution test, respectively . Most identification results were reported within 5-hour incubation by RAISUS, and susceptibility test results were 4 to 7 hour-incubations . With these results obtained through laboratory-based evaluation, it became apparent that the RAISUS has enough accuracy and rapidity to determine species-identification and antimicrobial susceptibility, and is applicable to the routine testing in clinical laboratories. Infect Immun, 2004 Mar, 72(3), 1700 - 5 Susceptibility to tuberculosis: clues from studies with inbred and outbred New Zealand White rabbits; Dorman SE et al.; The rabbit model of tuberculosis (TB) is important because rabbits develop a disease that is similar to TB in humans, namely, granulomas with caseous necrosis, liquefaction, and cavities . We describe here a comparison of inbred and outbred New Zealand White rabbits infected by aerosol with either Mycobacterium tuberculosis Erdman or H37Rv strain . Five weeks after infection with either bacillary strain, the inbred rabbits had significantly larger pulmonary tubercles than did outbred rabbits (2.7 versus 1.4 mm in diameter; P < 0.01) . After infection with H37Rv, the inbred rabbits had significantly more pulmonary tubercles than did the outbred rabbits (98 +/- 12 versus 33 +/- 13; P < 0.01), with more mycobacterial CFU per tubercle (809 +/- 210 versus 215 +/- 115; P = 0.027) (means +/- standard errors of the means) . Compared with histologic examination of lung granulomas from outbred rabbits, histologic examination of those from inbred rabbits showed more caseous necrosis, more visible bacilli, and fewer mature epithelioid cells . The delayed-type hypersensitivity (DTH) responses to intradermal tuberculin were significantly lower, and peritoneal macrophages from uninfected inbred rabbits produced significantly less tumor necrosis factor alpha after lipopolysaccharide (LPS) stimulation in vitro than those from the outbred rabbits (2,413 +/- 1,154 versus 8,879 +/- 966 pg/ml) . We conclude that these inbred rabbits were more susceptible to TB than their outbred counterparts and had an impaired ability to contain disease, resulting in more grossly visible tubercles that were larger than those observed in outbred rabbits . Preliminary evidence is presented for a cell-mediated immune defect with lower DTH responses and macrophages that have a decreased ability to respond to in vitro stimulation with LPS or M . tuberculosis infection. Front Biosci, 2004 May 01, 9, 1701 - 19 Immunotherapy with Mycobacterium vaccae in the treatment of tuberculosis; Stanford J et al.; All the trials of immunotherapy of tuberculosis with killed Mycobacterium vaccae, published or not, that are known to the authors are reviewed here . Following an introduction giving a brief account of some earlier immunotherapies for tuberculosis, the origins of the concept of immunotherapy with M.vaccae are considered . Progress is traced from the early work with irradiation-killed organisms in leprosy to the study in London of modulation of tuberculin skin-test responses, and the first comparative trials in The Gambia and Kuwait . In the last of these studies, dosages and different preparations were compared . As a result of this subsequent studies have used 109 heat-killed organisms, equivalent to 1mg wet-weight of bacilli, as a standard dose . A series of small trials in Argentina, India, Nigeria, Romania, South Africa and Vietnam have pioneered the way forward, disclosing geographic variability, with South Africa as the only country where almost no effects were recorded . Together the studies have shown that a single dose may not be sufficient . These studies have confirmed the mode of action of M.vaccae to be regulation of cell-mediated immunity with enhancement of Th1 and down-regulation of Th2, and they have shown benefits in faster bacteriological conversion, reduction in ESR, recovery of body weight and resolution of radiological opacities, leading to better recovery from the disease even when given to patients receiving directly observed therapy, short-course (DOTS) . Three major randomised, placebo-controlled and partly blinded trials have been carried out in Africa . The first, in South Africa showed no M.vaccae-related effects . The second trial, in Uganda, confirmed the observations made in the earlier studies of faster sputum conversion and better radiological clearance . The third trial, in Zambia and Malawi, showed a trend towards benefits in the treatment of HIV seronegative patients but failed to show beneficial effects in HIV seropositive patients . Studies in patients with multi-drug-resistant tuberculosis have shown that multiple doses of immunotherapy are required in most cases, and that these markedly improve cure-rates for these patients . This is especially so when they are also treated with chemotherapy tailored to the resistance pattern of their infecting organisms . A small study has just commenced in which repeated doses of M.vaccae are being administered to a group of patients who have failed treatment with DOTS-Plus (directly observed therapy with drugs selected on the basis of drug susceptibility profiles) . Late in the investigation came publications from China supporting and confirming the data in both drug-sensitive and drug-resistant disease, by the use of multiple injections of their own different preparation of M.vaccae . The trial that is now beginning in Vietnam of 3 doses of M.vaccae in the treatment of newly diagnosed pulmonary tuberculosis, is accompanied by a chemotherapeutic regimen with a shortened continuation phase . If this important study is successful, immunotherapy with killed M.vaccae should be introduced into the treatment regimens for tuberculosis worldwide. Front Biosci, 2004 May 01, 9, 1136 - 56 Persistent and dormant tubercle bacilli and latent tuberculosis; Zhang Y; Tubercle bacillus has remarkable ability to persist in the human host and has caused latent infection in one third of the world population . The current tuberculosis (TB) chemotherapy while effective in killing growing bacilli is largely ineffective in killing persistent or dormant bacilli, leading to prolonged therapy . There is considerable recent interest to study mechanisms of persistence and dormancy in mycobacteria . Meanwhile, there is also confusion about the use of terminology of dormant and persistent bacilli . Different models of mycobacterial persistence have been established . Various mycobacterial factors have recently been identified that may be involved in persistence or dormancy and resuscitation of dormant organisms . The phenotypic resistance to antituberculosis drugs in persistent and dormant bacilli presents a major challenge for effective control of the disease . The host immune system is critical in controlling latent TB infection from reactivation . A recent interesting observation is the reactivation of latent TB infection by anti-TNF-alpha antibody used as a treatment for rheumatoid arthritis and Crohn's disease . The role of psychoneuroendocrinological factors in TB, which is often ignored in the era of modern chemotherapy but could be important for controlling latent infection, is also briefly reviewed . There is recent interest to develop new TB drugs that target persistent and dormant bacilli and also immunotherapeutic agents that enhance chemotherapy and better control latent infection . The complex interaction between the bacteria, drugs, host and the environment underscores the need for a combined approach that incorporates chemotherapy, immunotherapeutic agents, improved socioeconomic, nutritional and even conducive psychological factors for more effective control of TB and latent TB. Front Biosci, 2004 May 01, 9, 1059 - 72 The search for new sterilizing anti-tuberculosis drugs; Mitchison DA; To be of use in the control of tuberculosis, any new drug must be capable of shortening the duration of treatment by accelerating sterilizing activity, that is the rate at which Mycobacterium tuberculosis is killed in the lesions . The most difficult to kill are the extra-cellular bacilli in cavities . Persistence during therapy arises because there is a proportion of slowly metabolising bacilli (persisters) in the cavitary bacterial population at the start of treatment . Bacterial growth is slowed by low oxygen tension, quorum sensing and old age, but probably not by cellular immunity, since there are few professional phagocytic cells in cavities . The degree of phenotypic resistance to the bactericidal action of drugs can go through several stages: (i) the non-replicating stages 1 and 2 of micro-aerophilic adaptation, described by Wayne; (ii) a "tolerant" population that survives exposure to high rifampicin concentrations and is capable of growth in liquid medium but not on solid medium; and (iii) a population found in the sterile state of Cornell model mice which cannot grow initially in either liquid or solid medium but will eventually cause re-activation of tuberculosis . In all of these stages the bacilli are phenotypically resistant; there is no selection for genomic drug resistance . Rifampicin and pyrazinamide are the two drugs largely responsible for sterilizing activity during current treatment . Pyrazinamide is unique amongst anti-tuberculosis drugs in having no genomic site of action and having greater bactericidal activity as bacillary metabolism slows down; it is remarkably effective in human disease . The development of a new drug with a similar mode of activity might be very fruitful, especially if there were no need for an acid environment . Current methods advocated for drug development pass through a number of complex stages: choice of a genomic target, development of an in vitro assay, high throughput screening and identification of lead compounds, often with scaling up of synthesis of the molecule and preliminary studies of toxicity and animal pharmacology before tests are done for sterilizing activity . If the drug is not good at sterilizing, all of this initial work will be largely wasted as it would only have a very limited role in the treatment of MDR disease . One of the most important steps necessary is the development of rapid and simple tests to screen for sterilizing activity . Of tests currently available, none of those employing mice seem adequate, though a screen using a streptomycin dependent Mycobacterium tuberculosis seems the most hopeful . A set of in vitro tests is described . There is an urgent need to develop these tests further since the factors slowing growth are closer to those in tuberculous cavities than in mouse models . They have the advantages of simplicity and require only small amounts of a new molecule. Postgrad Med J, 2004 Feb, 80(940), 97 - 100 Clinical and laboratory observations of tuberculosis at a Mumbai (India) clinic; Gothi D et al.; OBJECTIVES: To study the positivity of sputum acid fast bacilli (AFB) smears in patients with pulmonary tuberculosis using 24 hour sputum collection . To detect HIV seropositivity in patients suffering from tuberculosis, and to analyse the pattern of tuberculosis disease in this subgroup . To determine the outcome of patients treated with directly observed therapy . SETTING: The tuberculosis referral unit of a tertiary care hospital . DESIGN: A total of 893 consecutive patients with tuberculosis, diagnosed between 1 November 2000 and 30 September 2002, were included in the study . An HIV test was performed in all patients, with adequate counselling and informed consent . Treatment was prescribed as per World Health Organisation treatment categories . RESULTS: Out of 893 patients with tuberculosis, 695 had pulmonary tuberculosis and 198 had extrapulmonary tuberculosis . Out of the 695 pulmonary tuberculosis patients, 673 (96.8%) were sputum smear AFB positive . Overall, 71 patients (8.0%) were HIV positive . The pattern of tuberculosis was the same in HIV seropositive and seronegative patients . Treatment outcome could be analysed in 112 out of 150 patients: 78 patients (70%) were declared cured or completed treatment . CONCLUSIONS: Sputum smear AFB could be a very sensitive test when a large quantity of sputum is used . The presence of HIV coinfection does not alter the clinical presentation . Only 70% of patients treated were cured/completed treatment, in spite of a strict directly observed therapy. Kekkaku, 2004 Jan, 79(1), 11 - 5 {A case of pulmonary tuberculosis complicated with tuberculosis of bilateral cervical lymph nodes and exacerbated pericostal abscess}; Yamada N et al.; A 23-year-old man was admitted to our hospital because of cough and sputum in April 2001 . A chest roentgenogram revealed infiltrative shadow with cavity formation in the bilateral lung fields . He was treated with sensitive antituberculous drugs . After starting the antituberculous therapy with INH, RFP, EB and PZA, bilateral cervical lymphadenopathy developed . Three months later, pericostal abscess appeared in the left anterior chest wall . Microscopic examination of the specimen obtained by needle aspiration biopsy disclosed positive for acid-fast bacilli . Smears of the pus showed acidfast bacilli identified as Mycobacterium tuberculosis by DNA-DNA PCR method . He developed tuberculous bilateral cervical lymphadenopathy and pericostal abscess during the course of antituberculosis chemotherapy . Drug sensitivity test revealed that tubercle bacilli in this case were sensitive . One year after the administration of chemotherapy, cervical lymphadenopathy and pericostal abscess were improved . Both masses were discontinuous with pulmonary tuberculosis and the possibility of lymphogenous spread of organism was speculated as its etiology . We assumed that both masses were due to paradoxical response to the antituberculosis chemotherapy. Biomedica, 2003 Dec, 23(4), 373 - 87 {Generalized adenopathy as a manifestation of type 2 reactional leprosy}; Rodriguez G; Generalized adenopathy as a manifestation of type 2 reactional leprosy Leprosy patient's reactions are severe clinical manifestations of acute inflammation of chronic lesions, capable of producing irreversible and invalidating damage . We studied a 46 year-old man with a type 2 leprosy reaction, who presented fever, cutaneous nodules, nasal obstruction and generalized adenopathy . The hemogram showed leucocytosis with neutrophilia . None of the initial diagnoses included leprosy . A lymph node biopsy revealed extensive necrotic areas infiltrated with polymorphonuclear lymphocytes, and foamy macrophages . Eosinophylic necrosis and thrombosis of venules with lymphoid nodule depletion was also in evidence . Ziehl Neelsen stain was not done, but the Gomori stain clearly showed Hansen's bacilli . These were were not detected by the pathologist and therefore a final diagnosis was not provided . Twenty months later, the patient presented similar symptoms, but with more generalized lymphadenopathy and presence of cutaneous nodules . Nodule biopsy showed lepromatous leprosy with erythema nodusum leprosum or type 2 reaction . Polychemotherapy treatment and anti-reaction treatment with thalidomide cured the patient . No sequelae were noted in 3 years following the treatment . A literature review of the type 2 reaction in leprosy is provided, including discussion of risk factors, histopathology, differential diagnosis for leprosy adenopathy, pathogenesis, prognosis, and treatment . Type 2 leprosy must be treated immediately upon diagnosis as it can cause serious and permanent tissue damage . As had occurred in the above patient, the disease can proceed with generalized and symptomatic lymphadenopathy. Epidemiol Infect, 2003 Dec, 131(3), 1071 - 6 Tuberculosis is still a major cause of cervical lymphadenopathies in adults from developing countries; Hernandez-Solis A et al.; To establish the frequency of infectious aetiology in Mexican adult patients with cervical lymphadenopathies (CLAs), 87 consecutive patients with enlarged cervical lymphatic nodes, HIV negative and without anti-tuberculous treatment, were selected from a tertiary-level speciality concentration hospital . Histopathological studies, investigation of acid-fast bacilli, cultures in Lowenstein Jensen and Mycobacterium growth indicator tube (MGIT) media, and in-house polymerase chain reaction (PCR) with IS6110-based primers for Mycobacterium tuberculosis complex were performed in resected lymphatic nodes . Non-infectious aetiology corresponded to 45 cases (52 %) . Tuberculosis was suspected in 42 cases (48%) by histology and confirmed positive results were obtained by staining in 8 (19%), by culture in 23 (55%), and by PCR in 34 (81 %) patients . All were confirmed after therapeutic success . In addition to the epidemiological transition process occurring in Mexico, tuberculosis remains an important cause of CLA . Histopathology with confirmatory studies including PCR can detect tuberculous aetiology. Pediatr Dermatol, 2004 Jan-Feb, 21(1), 39 - 43 Cutaneous sarcoid-like granulomas in a patient with X-linked hyper-IgM syndrome; Gallerani I et al.; We describe a 5-year-old boy with red-pink, firm, nodular lesions, with central resolution and prominent borders, localized to the face, backs of the hands, extensor surfaces of the arms and legs, and the buttocks . He also had recurrent bacterial respiratory infections . Quantitative immunoglobulin levels revealed hypogammaglobulinemia and increased IgM levels . Histopathologic examination of a nodular lesion revealed perivascular and periadnexal granulomas composed of epithelioid cells surrounded by a mantle of lymphocytes; three cultures for fungi and acid-fast bacilli were negative . Clinical, histopathologic, and immunologic studies supported a diagnosis of hyper-IgM (HIM) syndrome . The boy was treated with pulsed-dose antibiotics and intravenous gamma globulin every 3 weeks, with improvement of clinical symptoms . Skin lesions were treated with topical corticosteroids, with immediate recurrence upon cessation of therapy . To the best of our knowledge, this is the first description of cutaneous granulomas in HIM syndrome. Indian J Med Res, 2003 Dec, 118, 229 - 35 Role of mechanical ventilation & development of multidrug resistant organisms in hospital acquired pneumonia; Mukhopadhyay C et al.; BACKGROUND & OBJECTIVES: Among hospital-acquired infections, pneumonia is considered to be the leading cause of death mainly in patients with mechanical ventilation in intensive care units (ICUs) . The present study was undertaken to estimate the occurrence of hospital-acquired pneumonia (HAP) as well as ventilator-associated pneumonia (VAP) along with the effect of different variables and to detect the presence of multi drug resistant (MDR) organisms in the intensive care unit (ICU) . METHODS: Of the 328 patients admitted in the ICU during 2001, 241 stayed for > 72 h and 148 were ventilated . The respiratory specimens collected from the cases and controls were sent for cytology, bacterial culture and antimicrobial sensitivity . RESULTS: The overall rate of HAP was 53.9 per cent, mortality rate was 47.3 per cent and attributable risk of mortality with ventilator was 72.3 per cent . Occurrence of VAP was 81.7 per cent . The rate of acquisition of HAP increased along with the duration of stay in the ICU . Of the total bacterial isolates, 96.2 per cent were obtained from patients on ventilator, an overall preponderance of Gram-negative bacteria, commonest being Pseudomonas spp along with 16.3 per cent polymicrobial infection was found in ICU . A significant number of ICU isolates were MDR in comparison to those from the non-ICU settings . INTERPRETATION & CONCLUSION: Mechanical ventilation and duration of ICU stay emerged as important risk factors for the development of HAP and VAP . MDR Gram-negative bacilli were the commonest respiratory pathogens responsible for increased mortality in patients with VAP. Indian J Med Res, 2003 Dec, 118, 224 - 8 Application of enzyme amplified mycobacterial DNA detection in the diagnosis of pulmonary & extra-pulmonary tuberculosis; Tiwari V et al.; BACKGROUND & OBJECTIVES: As isolation of Mycobacterium tuberculosis in culture requires a long time, there is a need for simple rapid method for direct detection of M . tuberculosis from clinical specimens . Amplified nucleic acid hybridization assays such as polymerase chain reaction (PCR) have shown promising results . In the present study, the sensitivity of PCR assay was assessed over smear microscopy for rapid diagnosis of tuberculosis in pulmonary and extra-pulmonary samples from patients suspected to have tuberculosis . METHODS: A total of 37 clinical samples from patients with pulmonary tuberculosis and 133 from patients with extra-pulmonary tuberculosis were subjected to Ziehl-Neelsen staining for smear preparation and PCR for detection of mycobacterial DNA . RESULTS: It was observed that 100 per cent of acid fast bacilli (AFB) positive and 35.7 per cent of AFB negative pulmonary samples and 82.76 per cent of AFB positive and 56.73 per cent of AFB negative extra-pulmonary samples were positive for mycobacterial DNA detection . Total positivity rates of DNA amplification method in pulmonary and extra-pulmonary samples were 75.67 per cent and 61.7 per cent respectively which were significantly higher in comparison with AFB positivity, which was 62.16 per cent in pulmonary and 21.8 per cent in extra-pulmonary samples (P < 0.05 and P < 0.001 respectively) . INTERPRETATION & CONCLUSION: Routine application of DNA amplification method in diagnosis of AFB negative patients with pulmonary or extra-pulmonary tuberculosis may be a useful tool for detection of M . tuberculosis. Eur J Intern Med, 2003 Oct, 14(6), 367 - 371 The usefulness of PCR amplification of the IS6110 insertion element of M . tuberculosis complex in ascitic fluid of patients with peritoneal tuberculosis; Tzoanopoulos D et al.; Background: The diagnosis of tuberculous peritonitis (TP) may be difficult and elusive . The present study was designed to demonstrate the diagnostic usefulness of a nested polymerase chain reaction (PCR) assay, specific for the IS6110 insertion element of M . tuberculosis complex, in patients with ascites who were suspected of having TP in order to achieve a more timely diagnosis and treatment . Methods: Three HIV-negative patients suffering from fever and ascites were evaluated for suspected TP . Specimens were obtained from ascitic fluid, bone marrow, and peripheral blood and analyzed by both conventional methods and nested PCR for the presence of bacilli . Response to antituberculous treatment was considered as the final criterion for diagnosis of peritoneal tuberculosis . Results: All three patients had an excellent response to antituberculous therapy . Our PCR-based protocol detected M . tuberculosis complex DNA in the ascitic fluid of all patients, whereas conventional methods failed to establish the disease . Furthermore, in one patient, M . tuberculosis was also detected in both bone marrow and peripheral blood . Conclusions: PCR amplification of the IS6110 sequence of M . tuberculosis complex in ascitic fluid is a useful tool when peritoneal tuberculosis is suspected . However, its validity still needs to be established. J Clin Microbiol, 2004 Feb, 42(2), 906 - 8 Novel method using a laser scanning cytometer for detection of mycobacteria in clinical samples; Pina-Vaz C et al.; In order to evaluate the capacity of laser scanning cytometry (LSC) to detect acid-fast bacilli directly on clinical samples, a comparison between Kinyoun-stained smears analyzed under light microscopy and propidium iodide-auramine-stained smears analyzed by LSC was performed . The results were compared with those for culture on BACTEC MGIT 960 . LSC is a new, reliable methodology to detect MYCOBACTERIA: J Clin Microbiol, 2004 Feb, 42(2), 741 - 5 Genotyping of Mycobacterium leprae on the basis of the polymorphism of TTC repeats for analysis of leprosy transmission; Matsuoka M et al.; The polymorphism of TTC repeats in Mycobacterium leprae was examined using the bacilli obtained from residents in villages at North Maluku where M . leprae infections are highly endemic (as well as from patients at North Sulawesi of Indonesia) to elucidate the possible mode of leprosy transmission . TTC genotypes are stable for several generations of passages in nude mice footpads and, hence, are feasible for the genotyping of isolates and epidemiological analysis of leprosy transmission . It was found that bacilli with different TTC genotypes were distributed among residents at the same dwelling in villages in which leprosy is endemic and that some household contacts harbored bacilli with a different genotype from that harbored by the patient . Investigations of a father-and-son pair of patients indicated that infections of bacilli with 10 and 18 copies, respectively, had occurred . Genotypes of TTC repeats were found to differ between a son under treatment and two brothers . These results reveal the possibility that in addition to exposure via the presence of a leprosy patient with a multibacillary infection who was living with family members, there might have been some infectious sources to which the residents had been commonly exposed outside the dwellings . A limited discriminative capacity of the TTC polymorphism in the epidemiological analysis implies the need of searching other useful polymorphic loci for detailed subdivision of clinical isolates. Front Biosci, 2004 Jan 01, 9, 975 - 94 Mechanisms of drug resistance in Mycobacterium tuberculosis; Wade MM et al.; Tuberculosis is a worldwide health problem posing increasing threat with the spread of HIV infection and drug resistant Mycobacterium tuberculosis strains . Consequently, control of this disease has become a significant challenge despite the availability of chemotherapy and BCG vaccine . Drug resistance for all first-line anti-tuberculosis agents and some second-line agents has been observed . Moreover, the occurrence of strains of M . tuberculosis resistant to multiple anti-tuberculosis drugs is increasing . Mechanisms of action and resistance of major anti-tuberculosis drugs are reviewed . In addition, the phenotypic drug resistance such as dormant or persistent tubercle bacilli and its importance are also emphasized . In order to combat the threat of drug resistant tuberculosis and to more effectively control the disease, an understanding of the mechanisms underlying drug resistance is necessary . This knowledge could be used for the development of molecular tests for rapid detection of drug resistant bacilli and future anti-tuberculosis drugs. Rev Med Chir Soc Med Nat Iasi, 2003 Jul-Sep, 107(3), 589 - 94 {In vitro antibacterial activity and beta-lactamase stability of meropenem}; Poiata A et al.; The comparative activity of meropenem with that of imipenem, cefotaxime, ceftriaxone and ceftazidime against 856 gram-negative bacilli was studied studied by an agar dilution method . Meropenem and imipenem were high active against tested strains . Resistance to third generation cephalosporins was high for most microorganisms tested . For rapid detection of metallo-beta-lactamase (MBL)-producing gram-negative bacilli a simple disk diffusion test was used . EDTA, FeCl2 and CuCl2 were evaluated as IMP-1 inhibitors . The method is helpful for screening of IMP-1 producers in daily clinical activity. Diagn Cytopathol, 2004 Feb, 30(2), 82 - 7 Extrapulmonary tuberculosis as a mimicker of neoplasia; Hwang S et al.; Despite the efforts for control and eradication of tuberculosis, new cases of the disease are diagnosed daily . The diagnosis of tuberculosis is easily made when the classical features of pulmonary necrotizing granulomatous inflammation are seen . However, extrapulmonary lesions may clinically and radiographically mimic a neoplastic process, and this may lead to misdiagnosis and delay in treatment . We studied 6 patients by aspiration biopsy, all recent immigrants and immunocompetent, who presented with weight loss and fatigue . Of these, 5 patients had a mass . One patient presented with a lytic lesion of bone . In all cases the clinical diagnosis was neoplasia . In all aspirates, the smears showed necrotic debris with neutrophils . No neoplastic cells or granulomas were seen . All cases were signed out descriptively with no specific diagnosis . A search for acid-fast organisms leading to the correct diagnosis of tuberculosis was prompted by clinical investigations that revealed pulmonary lesions, or by repeat aspiration biopsy, which showed granulomatous inflammation . Tuberculosis when present in atypical forms is still a challenging diagnosis . The finding of necrotic debris in a needle biopsy without the clinical signs of an abscess should prompt a search for acid-fast bacilli, since the correct diagnosis will eliminate a needless surgical procedure and will lead to timely and appropriate therapy . Am J Infect Control, 2004 Feb, 32(1), 17 - 22 Polymerase chain reaction used for the detection of airborne Mycobacterium tuberculosis in health care settings; Wan GH et al.; BACKGROUND: Tuberculosis (TB) has re-emerged as a major infectious disease in several areas in the world . Airborne tubercle bacilli produced by individuals with pulmonary TB and droplet nuclei remain suspended in the air for a long time . This study attempts to use a sensitive polymerase chain reaction (PCR) analytic method coupled with a filter sampling method to detect the presence of airborne Mycobacterium tuberculosis (MTb) in health care settings . METHODS: Patients with TB history were recruited from a medical intensive care department and negative-pressure isolation rooms at Chang Gung Memorial Hospital in Taichung City, Taiwan, Republic of China . The exhaled gas from different patients with TB who were mechanically ventilated in the intensive care department was collected using a polycarbonate (PC) membrane or polytetrafluoroethylene (PTFE) filter . Airborne MTb concentrations in air exhausted through a bacterial filter attached to a mechanic ventilator were studied . Indoor air samples were taken through a 3-piece cassette with a filter (PC/PTFE) in patient rooms . MTb concentrations in these filters were analyzed using the PCR method . RESULTS: Overall, 75% (12/16) of the exhaled-gas samples in PTFE filters and 25% (4/16) of samples in PC filters were detected as having positive MTb-specific DNA products . Exhausted air from the bacterial filters in mechanic ventilators was found to have positive PCR results (57% in PC filters and 14% in PTFE filters) for MTb . Both negative-pressure isolation rooms and outpatient department areas in the TB center had positive samples (40%-60% in PC/PTFE filters) containing MTb by PCR amplification . CONCLUSIONS: Health care settings were sufficient for various risk factors, including physical, chemical, and biologic hazards . Infectious agents are produced by aerosolization that results in human respiratory-related diseases . The indoor air quality of the entire hospital environment should, therefore, be monitored by health care personnel and the public. Surg Neurol, 2004 Feb, 61(2), 136 - 9; discussion 139-41 Sacral tuberculosis: a case report and review of the literature; Wellons JC et al.; BACKGROUND: We present a patient with a heterogeneously enhancing lesion within the body of the sacrum and the sacral canal . Sacral tuberculosis (TB) was suspected because of a history of familial exposure . Few cases isolated to the sacrum have been reported in the literature . The characteristic histopathologic and magnetic resonance imaging (MRI) findings are also presented . CASE DESCRIPTION: A 31-year-old African-American male presented with an 8-month history of lower back pain radiating into his legs as well as numbness and weakness of the right foot . His history revealed PPD conversion following an exposure to active pulmonary TB 3 years prior for which he received 6 months of isoniazid prophylaxis . An MRI scan revealed a large heterogeneously enhancing lesion involving the sacrum with extension into the sacral canal . The patient underwent computed tomography (CT)- guided needle biopsy of the sacral lesion . Cytopathologic examination revealed caseating granulomas . Acid-fast bacilli cultures were positive for Mycobacterium tuberculosis . He was placed on a 6-month course of isoniazid, rifampin, pyrazinamide, and ethambutol . At 3-month follow-up, his examination and symptoms had improved . CONCLUSIONS: Sacral TB is an extremely rare cause of lower back pain with radiation into the lower extremities . TB should always be considered in the differential diagnosis of isolated sacral masses, especially in light of today's increasing multidrug resistance and immunosuppressed population. Clin Rheumatol, 2004 Feb, 23(1), 66 - 8 Epub 2003 Nov 12. Tuberculous fasciitis in scleroderma; Lee CH et al.; A 25-year old woman visited the hospital because of a painful swelling for 20 days in the midposterior portion of her right thigh . She had been diagnosed with systemic sclerosis and treated for 10 months . An MRI scan of the right thigh showed diffuse fascial thickening and involved the superficial portion of thigh muscles, which were hyperintense on the T(2)-weighted image . A biopsy of the involved muscles revealed chronic granulomatous inflammation with several acid-fast bacilli on a Ziehl-Neelsen stain . We here report a case of tuberculous fasciitis manifest with painful swelling of the midposterior muscles of the right thigh without pulmonary tuberculosis in a patient with scleroderma. J Trauma, 2004 Jan, 56(1), 105 - 10 Intestinal bacterial overgrowth induces the production of biologically active intestinal lymph; Deitch EA et al.; OBJECTIVE: We have previously documented that gut-derived lymph from rats subjected to trauma plus hemorrhagic shock (T/HS) is injurious to vascular endothelial cells and activates neutrophils (PMNs), two key events in postshock organ injury . Because T/HS leads to gut injury, intestinal bacterial overgrowth, and the loss of gut barrier function, the relative role of gut injury as opposed to intestinal bacterial overgrowth per se in the pathogenesis of biologically active intestinal lymph is unclear . We therefore studied whether mesenteric lymph can injure endothelial cells and/or active PMNs in an intestinal bacterial overgrowth model where there is no gut injury (monoassociation) . METHODS: Bacterial overgrowth was established in male rats by treating the animals with 4 days of oral antibiotics followed by administration of a nonpathogenic, streptomycin-resistant strain of Escherichia coli C25 . Mesenteric lymph was then collected from rats with normal flora and from E . coli C25 monoassociated rats . Its effects were tested on human umbilical vein endothelial cells (HUVECs) and human PMNs . As an additional control, lymph was collected from antibiotic-decontaminated rats that received antibiotics but were not colonized with E . coli C25 . RESULTS: As compared with medium, normal flora intestinal lymph, antibiotic-decontaminated lymph, or portal plasma from the monoassociated rats, mesenteric lymph from the monoassociated rats killed HUVECs and increased the permeability of a HUVEC monolayer . In contrast to the effects on HUVECs, lymph from the monoassociated rats did not increase PMN CD11b expression or prime PMNs for an augmented respiratory burst, as compared with lymph from the rats with normal flora or from antibiotic-decontaminated rats . The effects of lymph from the monoassociated rats was not caused by bacteria, because these lymph samples were sterile . CONCLUSION: These results indicate that disruption of the normal intestinal microflora resulting in bacterial overgrowth with enteric bacilli may participate in the production of mesenteric lymph that is injurious to endothelial cells in shock, but this mechanism does not appear to be significantly involved in the activation of PMNs. South Med J, 2004 Jan, 97(1), 74 - 6 Septic arthritis caused by Chryseobacterium meningosepticum in an elbow joint prosthesis; Kumar R et al.; Chryseobacterium meningosepticum is a Gram-negative bacillus historically associated with meningitis and sepsis in premature neonates . Clinicians should suspect this organism when Gram-negative bacilli are seen on Gram-stain and culture, particularly in immunocompromised patients, and in cases of disrupted host tissue integrity . We report the first case of septic arthritis due to this organism. Rev Inst Med Trop Sao Paulo, 2003 Sep-Oct, 45(5), 275 - 81 Pulmonary tuberculosis: relationship between sputum bacilloscopy and radiological lesions; Gomes M et al.; OBJECTIVES: To determine the frequency of radiological manifestations of chest tuberculosis among the tuberculosis outpatients at the Santa Casa de Misericordia de Sao Paulo Hospital, and to correlate these radiological findings with the sputum bacilloscopy . SAMPLE AND METHODS: A review was made of the medical record cards and chest X-rays of all patients attended between January 1996 and December 1998 . Patients with a diagnosis of tuberculosis who presented intrathoracic manifestations of the disease and negative anti-HIV serology were selected . RESULTS: The selection included 153 patients, with an average age of 37.5 years, who were predominantly male (60.8%) and white (56.9%) . Pulmonary lesions were present in 121 (79.9%) and extrapulmonary lesions in 32 (20.1%) . Parenchymal-infiltrate lesions appeared in 56 patients (36.6%), cavity lesions in 55 (36.0%), pleural effusion in 28 (18.3%), isolated nodules in 6 (3.9%), mediastinal enlargement in 4 (2.6%) and miliary pattern in 4 (2.6%) . Cavities were present in 45.5% of the patients with pulmonary lesions, generally in association with the parenchymal-infiltrate lesions . Parenchymal infiltrate was present in 86.8% of the patients with pulmonary lesions . There was significant presence of alcohol-acid resistant bacillus in the sputum of patients with cavities (76.4%), in comparison with those without cavities (50%) (p = 0.003) . CONCLUSIONS: Parenchymal-infiltrate lesions are the most frequent radiological manifestation of pulmonary tuberculosis, and they are generally associated with cavities . There is a relationship between the presence of acid fast bacilli in sputum and pulmonary cavity lesions. Infect Immun, 2004 Feb, 72(2), 958 - 65 Differential production of systemic and intralesional gamma interferon and interleukin-10 in nodular and ulcerative forms of Buruli disease; Prevot G et al.; Buruli disease, caused by Mycobacterium ulcerans, is the third most important mycobacterial disease in humans besides tuberculosis and leprosy . We have compared systemic and intralesional cytokine production in patients presenting with a nodular form and a necrotizing, ulcerative form of the disease . Gamma interferon (IFN-gamma) levels in response to whole M . ulcerans and Mycobacterium bovis BCG bacilli and in response to purified Ag85 protein from BCG were lower in peripheral blood mononuclear cells (PBMC) cultures from Buruli disease patients than in PBMC from healthy purified protein derivative-positive contacts . Interleukin-4 (IL-4) and IL-13 content was below the detection threshold in these PBMC cultures . IFN-gamma production after stimulation with M . ulcerans was significantly lower (P < 0.05) in PBMC cultures from patients with ulcers than in those from patients with nodules . On the other hand, PBMC from Buruli disease patients produced significant levels of IL-10 in response to M . ulcerans (but not to M . bovis BCG) and production was highest in patients with the ulcerative form . Third, semiquantitative reverse transcription-PCR analysis demonstrated a similar difference in the local, intralesional cytokine profile for the two forms of the disease: high IFN-gamma but low IL-10 mRNA levels in nodular lesions and high IL-10 but low IFN-gamma mRNA levels in ulcerative lesions . Intralesional IL-4 and IL-13 mRNA levels were low and only detected in patients with the ulcerative form . Our results indicate, although they do not formally prove, that production of IL-10 rather than production of IL-4 or IL-13 by Th2-type T cells may be involved in the low M . ulcerans-specific IFN-gamma response in Buruli disease patients. Antimicrob Agents Chemother, 2004 Feb, 48(2), 666 - 9 Class 1 integrons increase trimethoprim-sulfamethoxazole MICs against epidemiologically unrelated Stenotrophomonas maltophilia isolates; Barbolla R et al.; Twenty-five plasmid-specified antimicrobial resistance determinants common to gram-negative bacilli from nosocomial infection were investigated from 31 Stenotrophomonas maltophilia isolates . Twenty-four clones were identified by pulsed-field gel electrophoresis, and in three clones that exhibited an increased trimethoprim-sulfamethoxazole MIC, the sul1 determinant was found . These results support not only the higher spread of class 1 integrons compared to other mechanisms but also the potential limitation of using trimethoprim-sulfamethoxazole for therapy of severe S . maltophilia infections. J Parasitol, 2003 Dec, 89(6), 1258 - 60 Hepatitis associated with a Sarcocystis canis-like protozoan in a Hawaiian monk seal (Monachus schauinslandi); Yantis D et al.; A Hawaiian monk seal (Monachus schauinslandi) died in captivity at the National Marine Fisheries Service, Kewalo Basin Facility in Honolulu, Hawaii . The animal was icteric, and the liver was friable . Microscopic lesions were detected in the colon and liver . Colonic lesions included multifocal, necrohemorrhagic colitis associated with gram-negative bacilli . The liver lesions included random hepatic necrosis and cholestasis . Asexual stages of a Sarcocystis canis-like apicomplexan were detected in hepatocytes . The parasite divided by endopolygeny . Merozoites occasionally formed rosettes around a central residual body . Ultrastructurally, merozoites lacked rhoptries . This is the first report of S . canis infection in M . schauinslandi, which is an endangered pinniped in U.S . waters. Kekkaku, 2003 Dec, 78(12), 739 - 46 {Fluctuation in the ratio between drug-resistant and -susceptible M . tuberculosis bacilli which were isolated from patients with prolonged anti-tuberculosis treatment}; Ano H et al.; PURPOSE: In this study, we examined the fluctuation in the ratio between strains of tuberculosis bacilli resistant and susceptible to the anti-tuberculosis drugs . MATERIAL & METHOD: We selected the cases in which the bacilli acquired drug resistance during the therapy and the cases in which drug resistance was fluctuating during prolonged anti-tuberculosis treatment . We selected the isolates throughout the medication period, and the selected isolates were separated into respective single colonies . Then we measured the minimal inhibitory concentration (MIC) for each colony by microdilution test for M . tuberculosis complex, BrothMIC MTB-1 (Kyokuto Pharmaceutical Inc., Tokyo) . RESULTS: Five patients were eligible for analysis because their medical histories were clearly recorded and drug resistance changed during the course . The MIC of 19 isolates, 202 colonies were measured . Isolates with coexisting drug-resistant and -susceptible colonies were detected in 2 patients . From these results, we considered that the fluctuation in the ratio between drug-resistant and -susceptible bacilli changes with the progression of anti-tuberculosis medication . CONCLUSION: We showed in this article that the drug-resistant bacilli increased rapidly when the strains acquired the drug resistance during medication, and when the administration of particular anti-tuberculosis drug was stopped, the susceptible bacilli seemed to increase gradually . However, the strain immediately became fully drug-resistant when the particular antibacterial drug was readministered. Int J Antimicrob Agents, 2004 Jan, 23(1), 84 - 7 The effects of rifampicin and fluoroquinolones on tubercle bacilli within human macrophages; Duman N et al.; The objective of this study was to determine the activities of rifampicin, ciprofloxacin and sparfloxacin against M . tuberculosis H37Rv in human macrophages . The minimal inhibitory concentrations (MIC) were determined by agar macrodilution and broth microdilution methods and were 0.5, 1 and 0.125 mg/l, respectively . Concentrations of rifampicin at 0.5 and 2.5 microg (P<0.001), ciprofloxacin at 4 and 8 microg (P<0.001) and sparfloxacin at 0.125 microg (P<0.05), 0.625 microg (P<0.001) and 1.25 microg (P<0.001) were found to be effective against intracellular bacteria . Ciprofloxacin and especially sparfloxacin were effective in macrophages and may be useful in the treatment of tuberculosis particularly infections caused by multiply drug resistant strains. J Am Geriatr Soc, 2004 Feb, 52(2), 224 - 9 Radiographic resolution of community-acquired bacterial pneumonia in the elderly; El Solh AA et al.; OBJECTIVES: To investigate the radiographic clearance of proven community-acquired nontuberculous bacterial pneumonia in nonimmunocompromised older patients to provide working estimates of the rate of radiographic resolution as a function of the patient cumulative comorbidities, extent of initial radiographic involvement, functional status, and causative pathogens . DESIGN: A prospective study . PARTICIPANTS: Seventy-four patients aged 70 and older, consecutively admitted to a hospital for community-acquired bacterial pneumonia . SETTING: A university-affiliated teaching hospital . MEASUREMENTS: Chest radiographs were performed every 3 weeks from the date of admission for a total period of 12 weeks or until all radiographic abnormalities had resolved or returned to baseline . RESULTS: Sixty-four patients (86%) completed the study . The rate of radiographic clearance was estimated at 35.1% within 3 weeks, 60.2% within 6 weeks, and 84.2% within 12 weeks . Radiographic resolution was significantly slower for those with high comorbidity index, bacteremia, multilobar involvement, and enteric gram-negative bacilli pneumonias . Multivariate regression analysis demonstrated that the comorbidity index (relative risk for clearance=0.67 per class index, P<.001) and multilobar disease (relative risk for clearance=0.24 for more than one lobe, P<.001) had independent predictive value (Cox proportional hazards regression model) on the rate of resolution . CONCLUSION: The radiographic resolution of nontuberculous bacterial pneumonia in the elderly should take into account the extent of lobar disease and the burden of underlying illnesses . A waiting period of 12 to 14 weeks is recommended for slowly resolving pneumonia to be considered nonresolving. Comp Med, 2003 Dec, 53(6), 602 - 6 Detection of early secretory antigenic target-6 antibody for diagnosis of tuberculosis in non-human primates; Kanaujia GV et al.; Tuberculosis is one of the most economically devastating, zoonotic infections of captive non-human primates . The limitations of the tuberculin skin test, which is currently used to diagnose tuberculosis in living non-human primates, make it necessary to find new, simple, and economical diagnostic methods . We describe use of an enzyme-linked immunoassay to detect IgG antibodies against early secretory antigenic target (ESAT)-6, a small protein secreted by virulent tubercle bacilli, in paired (pre- and post-outbreak) sera from 57 non-human primates involved in an outbreak of Mycobacterium bovis infection in a research colony . Of 25 animals with tuberculosis lesions at necropsy, 22 (88%) had high serum levels of the ESAT-6 antibody . The ESAT-6 antibody was found in 16% (5/32) of post-outbreak sera from animals in which tuberculosis could not be confirmed at necropsy . The strong association between the ESAT-6 antibody and tuberculosis in non-human primates documented in this study, together with the robustness of the serologic assay, make the ESAT-6 ELISA a valuable tool for diagnosis of tuberculosis in captive non-human primates. Otolaryngol Head Neck Surg, 2004 Jan, 130(1), 125 - 30 Nasopharyngeal granulomatous inflammation and tuberculosis complicating undifferentiated carcinoma; Chan AB et al.; OBJECTIVE: Four cases of nasopharyngeal granulomatous inflammation after radiotherapy for undifferentiated carcinoma were analyzed for tuberculosis, and the histologic features were compared . STUDY DESIGN AND SETTING: We conducted a retrospective study with analysis of tuberculosis by Ziehl Neelsen staining and polymerase chain reaction analysis for Mycobacterium tuberculosis DNA on histologic materials . RESULTS: Three patients had previous nasopharyngeal undifferentiated carcinoma, one had previous metastatic undifferentiated carcinoma to cervical lymph nodes, and all patients received similar radiotherapy regimen . The light microscopic features were similar with epithelioid histiocytes and granulomas with Langhan's giant cells . In 3 cases, acid-fast bacilli were identified by Ziehl Neelsen stain, and 1 was negative . The results of 2 cases were confirmed by polymerase chain reaction analysis for Myocbacterium tuberculosis DNA . CONCLUSION: Granulomatous reaction after radiotherapy of nasopharyngeal undifferentiated carcinoma can be caused by tuberculosis . SIGNIFICANCE: Diligent search for organisms in postirradiation granulomatous inflammation is warranted to avoid missing an occult tuberculosis infection. Pharmacol Res, 2004 Mar, 49(3), 287 - 92 Effect of water extract of Turkish propolis on tuberculosis infection in guinea-pigs; Yildirim Z et al.; Mycobacterium tuberculosis (H(37)R(v))-infected guinea-pig model was used to investigate the effect of water extract of propolis (WEP) . After subcutaneous inoculation of tubercle bacilli, each animal received oral WEP (n=9), isoniazid (n=5) or saline (n=6) as placebo and were sacrificed 30 days later . Formation of necrosis was less prominent in the group treated with WEP, but was not statistically significant (P>0.05) . The granuloma formation in the same group was more prominent than the placebo and isoniazid groups; however, this finding failed to reach statistical significance by the Kruskal-Wallis test (P>0.05) . These findings suggest that Turkish WEP may have a limited effect on the development of tuberculosis infection in this guinea-pig model. Zhonghua Er Ke Za Zhi, 2003 Dec, 41(12), 940 - 4 {Protective effect and mechanism of pretreatment with curcumin on infectious brain edema in rats}; Luo F et al.; Curcumin is a natural compound extracted from the spice tumeric, possessing both anti-inflammatory antioxidant, and anti-carcinogenic effect, is a potent stimulator of the stress-induced expression of heat shock protein 70 kd (HSP70) . OBJECTIVES: To study the protective effect of pretreatment with curcumin against infectious brain edema in rats, and investigate its mechanism by assessing the free radical, cytokine and HSP70 expression of the brain . METHODS: An animal model of infectious brain edema induced by injecting pertussis bacilli (PB) through carotid artery was used . SD rats were randomly divided into five groups: (1) Normal control group (NS group, n = 9); (2) Infectious brain edema group (PB group, n = 12); (3) DMSO control group (DMSO group, n = 9); (4) HS pretreatment group (HS group, n = 9); (5) Curcumin pretreatment group (CUR group, n = 13) . The water content (WC), Na(+) and K(+) content in brain tissue were measured . The content of malondialdehyde (MDA) and super oxide dismitase (SOD) were assessed by chemical colorimetry . The levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were detected by ELISA . The HSP70 expression was examined by Western blot analysis . RESULTS: (1) The WC and Na(+), MDA, TNF-alpha and IL-1beta were increased in PB group compared with NS group (P < 0.01); they were decreased in HS and CUR groups compared with PB group (P < 0.01 or P < 0.05) . (2) The content of SOD was decreased in PB group than in NS group (P < 0.05), and was increased in HS and CUR group Compared with PB group, (P < 0.05) . (3) Western blot analysis showed that the band density areas of HS, CUR and PB groups were higher than those in NS and DMSO groups, especially in CUR group (P < 0.01) . CONCLUSION: Pretreatment with curcumin showed a protective effect against infectious brain edema in rats . The effect might be associated with antioxidant, inhibition of the activity of cytokines and inducing expression of HSP70 by curcumin. Antibiot Khimioter, 2003, 48(8), 7 - 10 {Efficacy of ofloxacin (zanocin) in the treatment of multidrug resistant pulmonary tuberculosis}; Mishin VIu et al.; Data concerning chemotherapy of patients with multiresistant tuberculosis of the lungs by reserve antituberculous agents in combination with ofloxacin are presented . It was shown that the ofloxacin-including chemotherapy regimen applied to patients with multiresistant destructive tuberculosis of the lungs provided by the end of the 6-month treatment course elimination of multidrug resistant tubercle bacilli isolation at least in 80% of the patients and closure of the lung caverns after artificial pneumothorax and routine surgical interventions in more than half of the patients . For all this, side effects that could not be eliminated were stated merely in 8.5% of the patients. Intensive Care Med, 2004 Apr, 30(4), 633 - 8 Epub 2004 Jan 13. Evaluation of a triple-lumen central venous heparin-coated catheter versus a catheter coated with chlorhexidine and silver sulfadiazine in critically ill patients; Carrasco MN et al.; OBJECTIVE: To compare the incidence of catheter colonization and catheter-related bloodstream infections between heparin-coated catheters and those coated with a synergistic combination of chlorhexidine and silver sulfadiazine . DESIGN: Randomized, controlled clinical trial . SETTING: A 20-bed medical-surgical intensive care unit . PATIENTS: A total of 180 patients requiring the insertion of a trilumen central venous catheter . INTERVENTIONS . Patients were randomized to receive either a trilumen heparin or chlorhexidine and silver sulfadiazine-coated catheter . MEASUREMENTS: Catheter colonization was defined by a semiquantitative catheter tip culture yielding 15 or more colony-forming units or quantitative culture of 1,000 or more colony-forming units/ml . Catheter-related bloodstream infection as the isolation of the same microorganism from a peripheral blood culture and catheter tip . RESULTS: A total of 260 catheters were cultured . Out of 132 heparin-coated catheters, 29 were colonized and out of 128 chlorhexidine and silver sulfadiazine-coated catheters, 13 were colonized ( p=0.03), relative risk RR=2.16 (1.18-3.97) . This represents an incidence of 23.5 and 11.5 episodes of catheter colonization per 1,000 catheter-days, respectively ( p=0.0059), RR=2.04 (1.05-3.84) . Microorganisms isolated in catheter colonization from heparin-coated catheters were gram-positive cocci 23, gram-negative bacilli 7, and Candida spp 4 . In chlorhexidine and silver sulfadiazine-coated catheters were gram-positive cocci 6 and gram-negative bacilli 11 ( p=0.009) . The incidence of catheter-related bloodstream infections per 1,000 catheter-days was 3.24 in heparin-coated catheters and 2.6 in chlorhexidine and silver sulfadiazine-coated catheters ( p=0.79), RR=1.22 (0.27-5.43) . CONCLUSIONS: In critically ill patients the use of trilumen central venous catheters coated with chlorhexidine and silver sulfadiazine reduced the risk of catheter colonization due to prevention of gram-positive cocci and Candida spp. Rheumatology (Oxford), 2004 Apr, 43(4), 518 - 21 Epub 2004 Jan 13. Gout complicated with necrotizing fasciitis--report of 15 cases; Yu KH et al.; OBJECTIVE: To analyse the clinical features and outcomes of gout complicated with necrotizing fasciitis . METHODS: From the database of our hospital, we identified 15 hospitalized cases of gout complicated with necrotizing fasciitis from 1987 to 2001 . The medical records of the patients were analysed in detail . RESULTS: Mean patient age was 54.7 +/- 12.8 yr . Fever was found in only 10 (66.7%) patients, while the remaining five patients were afebrile on presentation . The peripheral blood white count was raised in only nine (60%) patients . The median time from the onset of symptoms to hospital visit was 4 days (range 2 to 25) . Formation of bullae occurred in 60% of patients . Six patients had previous wound infection, two patients had concomitant septic arthritis and the remaining seven patients had no obvious source of infection . Diabetes mellitus and iatrogenic Cushing syndrome were each found in three patients . The identified causative microorganisms were Gram-positive cocci (eight cases) and Gram-negative bacilli (four cases); but in three patients the causative organisms were unknown . Thirteen patients received surgery, including amputation in four cases . Finally, six patients suffered septic shock, three of whom died as a result . CONCLUSIONS: Necrotizing fasciitis in gout patients represents a surgical and medical emergency, and is associated with a high mortality rate . Prompt diagnosis and treatment is imperative and may be lifesaving . Early diagnosis requires a high level of suspicion, even in patients without fever or leucocytosis. Indian J Pediatr, 2003 Dec, 70(12), 993 - 4 Thrombocytopenic purpura as a presenting manifestation of tubercular lymphadenitis; Bakhshi S et al.; A 11-year-old girl presented with thrombocytopenic purpura along with cervical lymphadenopathy . There was no hepatosplenomegaly; no evidence of microangiopathy; bone marrow examination was normal . Acid fast bacilli were seen in fine needle aspiration cytology of the lymph node . A diagnosis of tubercular lymphadenitis in association with immune thrombocytopenia was made, and the platelet count recovered with antitubercular therapy . This report illustrates immune thrombocytopenia as a rare manifestation of childhood tuberculosis; the authors also discuss other causes of thrombocytopenia in childhood tuberculosis. J Clin Microbiol, 2004 Jan, 42(1), 390 - 2 Mutations including IS6110 insertion in the gene encoding the MPB64 protein of Capilia TB-negative Mycobacterium tuberculosis isolates; Hirano K et al.; A simple immunochromatographic assay, Capilia TB, using anti-MPB64 monoclonal antibodies, is a kit for discriminating between the Mycobacterium tuberculosis complex and mycobacteria other than tubercle bacilli . The sensitivity of the kit was estimated to be 99.2% (381 of 384 samples) . The sequencing analysis revealed that all of the Capilia TB-negative isolates had mutations within the mpb64 gene, leading to the production of an incomplete protein as a result of a deletion of the C-terminal region of the protein. J Clin Microbiol, 2004 Jan, 42(1), 378 - 9 Improving the bacteriological diagnosis of tuberculous meningitis; Thwaites GE et al.; We made a bacteriological diagnosis of tuberculous meningitis in 107 of 132 (81%) adults with clinical tuberculous meningitis: acid-fast bacilli were seen in 77 of 132 (58%) and cultured from 94 of 132 (71%) . Volume of cerebrospinal fluid, duration of symptoms, cerebrospinal fluid neutrophils, lactate, and glucose were all independently associated with bacteriological confirmation. Expert Rev Vaccines, 2003 Dec, 2(6), 791 - 804 Under-explored experimental topics related to integral mycobacterial vaccines for leprosy; Gormus BJ et al.; Many leprosy vaccine studies have utilized live or killed whole mycobacteria, such as Bacille Calmette-Guerin, Indian Cancer Research Center (ICRC) bacilli and Mycobacterium w either alone or in combination with killed Mycobacterium leprae . For Bacille Calmette-Guerin, the vaccine dose is generally that which gives the largest delayed-type hypersensitivity response with minimal side effects . The doses of other integral mycobacterial vaccines appear to be arbitrarily chosen . Hypotheses governing immunologic responses to complex antigens predict that the doses used may be too high, resulting in protection of some individuals and increasing the susceptibility of other individuals to leprosy . The natural history of an individual's prior exposure to environmental mycobacteria will affect the outcome of protective vaccination using a given dose of mycobacterial vaccine in the individual. Anal Chem, 2003 Oct 15, 75(20), 5608 - 17 MALDI analysis of Bacilli in spore mixtures by applying a quadrupole ion trap time-of-flight tandem mass spectrometer; Warscheid B et al.; A novel ion trap time-of-flight hybrid mass spectrometer (qIT-TOF MS) has been applied for peptide sequencing in proteolytic digests generated from spore mixtures of Bacilli . The method of on-probe solubilization and in situ proteolytic digestion of small, acid-soluble spore proteins has been recently developed in our laboratory, and microorganism identification in less than 20 min was accomplished . In this study, tryptic peptides were generated in situ from complex spore mixtures of B . subtilis 168, B . globigii, B . thuringiensis subs . Kurstaki, and B . cereus T, respectively . MALDI analysis of bacterial peptides generated was performed with an average mass resolving power of 6200 and a mass accuracy of up to 10 ppm using a trap-TOF tandem configuration . Precursor ions of interest were usually selected and stored in the quadrupole ion trap with their complete isotope distribution by choosing a window of +/- 2 Da . Sequence-specific information on isolated protonated peptides was gained via tandem MS experiments with an average mass resolving power of 4450 for product ion analysis, and protein and bacterial sources were identified by database searching. Rev Neurol (Paris), 2003 Nov, 159(11), 979 - 95 {Neurological manifestations of leprosy}; Grimaud J et al.; Leprosy, also known as Hansen's disease, is a chronic, infectious disease caused by Mycobacterium leprae . Bacilli localize preferentially in the skin and peripheral nerves and have a propensity to cause nerve damage . The resulting disability has caused great suffering for victims in many countries . Despite recent advances in the immunopathogenesis, epidemiology and prognostic factors of leprosy nerve damage, many aspects of the disease have remained enigmatic . The spectrum of clinical and pathological manifestations of the disease ranges from lepromatous to tuberculoid, depending on the host's T-cell-mediated immune response . Diagnosis is based on three criteria: characteristic skin lesions in association with thickened nerves, demonstration of acid fast bacilli in slit skin smears, and histopathology of skin biopsies . Nerve biopsy is necessary to establish the diagnosis of pure "neural leprosy" . In developed countries, the diagnosis is suspected when a patient who has stayed in an endemic area suffers from a peripheral neuropathy of unknown etiology . To facilitate determination of the appropriate antibiotic regimen, patients are classified as either paucibacillary or multibacillary . Some patients may have multibacillary leprosy in nerves and paucibacillary leprosy in skin, which emphasizes the usefulness of nerve biopsy . The course of the disease is often complicated by immune mediated "reactions", which can rapidly lead to further nerve damage, namely reversal reaction and erythema nodosum leprosy . However, nerves are often functionally impaired before developing obvious symptoms such as skin reactions or nevralgia (silent neuropathy) . Early recognition and prompt treatment with corticosteroids of leprous reactions and "silent neuropathies" is very important to prevent disability with all its attendant problems . Research progress from clinical trials may improve current methods of prevention and treatment of nerve damage in leprosy. Retina, 2003 Dec, 23(6), 796 - 9 Subretinal fluid analysis in the diagnosis of choroidal tuberculosis; Salman A et al.; BACKGROUND: Diagnosis of intraocular tuberculosis is often difficult . A choroidal granulomalike lesion suspected to be the result of tuberculosis could be of other inflammatory, infective, or neoplastic causes . We report two cases in which a choroidal granuloma with exudative retinal detachment was diagnosed as tuberculosis by the detection of acid-fast bacilli in subretinal fluid . METHODS: Interventional case series . RESULTS: Two female patients had choroidal granulomas with surrounding exudative retinal detachment . Detailed laboratory investigations were unhelpful in diagnosis, and the patients' conditions worsened with systemic steroid therapy . Subretinal fluid was tapped and revealed acid-fast bacilli and grew Mycobacterium tuberculosis on culture . CONCLUSION: Subretinal fluid analysis can help in the detection of tuberculous granuloma and facilitate successful management. Int J Eat Disord, 2004 Jan, 35(1), 115 - 9 A young female patient with anorexia nervosa complicated by Mycobacterium szulgai pulmonary infection; Hotta M et al.; OBJECTIVE: Pulmonary infection with a rare atypical mycobacterium, Mycobacterium szulgai, was discovered during the treatment of anorexia nervosa in a 21-year-old Japanese woman without preexisting pulmonary disease . She had a long history of low body weight below 35 kg . METHODS: On admission, she was examined . She weighed 23 kg and presented with hypoproteinemia, decreased levels of rapid turnover proteins, liver dysfunction, and decreased serum level of insulin-like growth factor-I . RESULTS: Although she had had neither clinical symptom specific for mycobacterium pulmonary infection nor inflammatory data, a chest roentgenogram showed an infiltrative shadow with cavity formation in the right upper lung field . Isolated bacteria from sputum was acid-fast bacilli and identified as M . szulgai using the DNA-DNA hybridization method . DISCUSSION: In anorexia nervosa patients with a long history of severe malnutrition, special attention must be paid to the possibility of opportunistic infections, even in the absence of symptoms or inflammatory data . J Med Assoc Thai, 2003 Aug, 86 Suppl 3, S689 - 95 Congenital tuberculosis; Chotpitayasunondh T et al.; This is a retrospective study of congenital tuberculosis in Queen Sirikit National Institute of Child Health from 1979 to 1998 . There were 9 patients with a mean birth weight of 2,500 grams (range 1,800-3,300) . The onset of symptoms and age of diagnosis ranged from 7 to 42 (mean, 21) days and 14 to 75 (mean, 54) days after birth, respectively . The presenting signs and symptoms were fever (100%), poor feeding (100%), irritability (100%), failure to gain weight (100%), hepatomegaly (100%), splenomegaly (77.8%), cough (88.9%), respiratory distress (66.7%) and abdominal distension (77.8%) . The tuberculin skin test reaction with > or = 10 mm induration was found in 2 of 8 patients . Their abnormal chest radiographs revealed bronchopneumonia 66.7 per cent, miliary pattern 33.3 per cent and multiple cystic lesion 11.1 per cent . The bacteriological study from gastric aspirate content for acid-fast bacilli (AFB) staining and culture were positive in 62.5 and 71.4 per cent respectively . Fatality rate was 33.3 per cent with no sequele found in the survivors . Congenital tuberculosis is a rare entity and difficult to give an early diagnosis . There should be a high index of suspicion for tuberculosis in those who had pneumonia and were unresponsive to aggressive antibiotics or had unexplained etiology. Eur J Ophthalmol, 2003 Nov-Dec, 13(9-10), 800 - 2 Endophthalmitis caused by Mycobacterium abscessus; Marin-Casanova P et al.; PURPOSE: To describe the clinical and laboratory features of a case of endophthalmitis caused by Mycobacterium abscessus in a patient immunocompetent . METHODS: case report . A 65-year-old woman with bilateral cataracts was treated by surgery with phacoemulsification and posterior chamber lens implantation . RESULTS: The funduscopic examination showed vitreous cells over the optic nerve head, chorioretinal infiltrates, and focal vasculitis . Vitreous humor aspirate disclosed acid-fast bacilli . In the culture on Lowenstein-Jensen medium grew colonies identified as M . abscessus . CONCLUSIONS: M . abscessus is cause of endophthalmitis and crystalline keratopathy . Risk factor include surgical intervention or exogenous contamination . Our patient has no systemic pathology predisposing to the development of endophthalmitis. Am J Trop Med Hyg, 2003 Nov, 69(5), 461 - 5 Diagnosis of tuberculosis lymphadenitis using a polymerase chain reaction on peripheral blood mononuclear cells; Mirza S et al.; Providing prompt and precise laboratory confirmation of a clinical diagnosis of tuberculous lymphadenitis is difficult given the paucibacillary nature of lymph node specimens . In this study carried out in Karachi, Pakistan, a polymerase chain reaction (PCR) assay aimed at detecting Mycobacterium tuberculosis DNA in peripheral blood mononuclear cells (PBMC-PCR) was standardized and compared with standard M . tuberculosis diagnostic techniques or a lymph node PCR (LN-PCR) for the diagnosis of tuberculosis lymphadenitis . Thirty-seven (77%) specimens from 48 patients with clinical or diagnosis of tuberculosis lymphadenitis were positive by cytology {17/48 (35%) with no acid fast bacilli (AFB) (suggestive), and 20/48 (42%) with AFB (positive) in direct smears}, 30 (63%) by PBMC-PCR, 16 (33%) by LN-PCR, and 13 (27%) by culture . All controls were negative, with the exception of one false-positive LN-PCR . These data suggest the PBMC-PCR may be helpful in the diagnosis of tuberculous lymphadenitis. Antimicrob Agents Chemother, 2004 Jan, 48(1), 242 - 9 In vitro inhibition of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein reductase MabA by isoniazid; Ducasse-Cabanot S et al.; The first-line specific antituberculous drug isoniazid inhibits the fatty acid elongation system (FAS) FAS-II involved in the biosynthesis of mycolic acids, which are major lipids of the mycobacterial envelope . The MabA protein that catalyzes the second step of the FAS-II elongation cycle is structurally and functionally related to the in vivo target of isoniazid, InhA, an NADH-dependent enoyl-acyl carrier protein reductase . The present work shows that the NADPH-dependent beta-ketoacyl reduction activity of MabA is efficiently inhibited by isoniazid in vitro by a mechanism similar to that by which isoniazid inhibits InhA activity . It involves the formation of a covalent adduct between Mn(III)-activated isoniazid and the MabA cofactor . Liquid chromatography-mass spectrometry analyses revealed that the isonicotinoyl-NADP adduct has multiple chemical forms in dynamic equilibrium . Both kinetic experiments with isolated forms and purification of the enzyme-ligand complex strongly suggested that the molecules active against MabA activity are the oxidized derivative and a major cyclic form . Spectrofluorimetry showed that the adduct binds to the MabA active site . Modeling of the MabA-adduct complex predicted an interaction between the isonicotinoyl moiety of the inhibitor and Tyr185 . This hypothesis was supported by the fact that a higher 50% inhibitory concentration of the adduct was measured for MabA Y185L than for the wild-type enzyme, while both proteins presented similar affinities for NADP(+) . The crystal structure of MabA Y185L that was solved showed that the substitution of Tyr185 induced no significant conformational change . The description of the first inhibitor of the beta-ketoacyl reduction step of fatty acid biosynthesis should help in the design of new antituberculous drugs efficient against multidrug-resistant tubercle bacilli. J Infect Chemother, 2003 Dec, 9(4), 328 - 32 Usefulness of bronchial lavage for the diagnosis of pulmonary disease caused by Mycobacterium avium-intracellulare complex (MAC) infection; Sugihara E et al.; To evaluate the usefulness of bronchial lavage for the diagnosis of pulmonary disease due to Mycobacterium avium-intracellulare complex (MAC) infection, we examined the clinical records and bacteriologic findings of patients admitted to our hospital between 1999 and 2002 who fulfilled the 1997 American Thoracic Society (ATS) criteria for MAC pulmonary infection . Bronchoscopic examinations were performed in those patients with MAC pulmonary disease who showed negative sputum smears for mycobacteria on 3 consecutive days ( n = 14) or who could not expectorate sputum ( n = 2) . The bronchial lavage sample was smear-positive for acid-fast bacilli in 8 of the 16 patients (50.0%), polymerase chain reaction (PCR)-positive for MAC in 10 of 15 (66.7%), and culture-positive for MAC in 15 of 16 (93.7%) . The brushing sample was positive for MAC in 5 of 14 patients (35.7%), and transbronchial lung biopsy (TBLB)-positive for MAC in 2 of 5 (40.0%) . MAC was isolated by culture of bronchial lavage samples in a higher percentage of patients than that in whom MAC was isolated by sputum culture, and we could make an early diagnosis of MAC pulmonary disease based on the smear and PCR results for bronchial lavage samples . Bronchial lavage is useful to screen sputum smear-negative patients suspected of having MAC pulmonary disease. Zhonghua Xue Ye Xue Za Zhi, 2003 Oct, 24(10), 530 - 3 {The clinical features of severe aplastic anemia patients with complication of infection}; Wu YH et al.; OBJECTIVE: To study the clinical features of severe aplastic anemia (SAA) patients with complication of infection . METHODS: A retrospective analysis of prevalence of infection occurring in 229 SAA patients, their bacterial spectrum, and the effect of GM-CSF or G-CSF on the infection were done . RESULT: The prevalence of infection in SAA patients was 86.0%, among which 54.2% was infected with gram-positive organisms, 40.0% with gram-negative bacilli and 5.8% with fungal infections . Septicemia occurred mostly with E . coli and Pseudomonas infection . Patient's neutropenia was significantly related to the infection . The patients with neutrophil count less than 0.2 x 10(9)/L had more frequent and severe infection . Age, hemoglobin level, subtype of T lymphocytes and antithymocyte globulin therapy were not related to infection . Prophylaxis usage of floxacin could not reduce patient' gastrointestinal infection . The total mortality of SAA patients with infection was 23.1% . Pulmonary infection and septicemia increased mortality, and GM-CSF/G-CSF therapy reduce mortality . CONCLUSION: SAA patients were at high risk of infection which was significantly associated with severe neutropenia . GM-CSF or G-CSF therapy exerts an assistant role to antibiotics in controlling the infections. Pneumologie, 2003 Dec, 57(12), 741 - 5 {Benign fibrous histiocytomas as a differential diagnosis in cavitary lung disease}; Lienert T et al.; Benign fibrous histiocytomas (BFH) are uncommon pulmonary tumours . These lesions usually present as slow-growing, solid masses . We report the rare case of a young man with cavitary BFH . The 20-year-old patient, a non-invasive drug abuser, had suffered from hemoptysis for two months . The chest X-ray showed a solitary pulmonary nodule with a diameter of 2 cm in the left lower lobe with central cavitation . Fiberoptic bronchoscopy showed a normal bronchial system, biopsies were not diagnostic and no acid fast bacilli were found . Considering the patient's history and the cavitary process, a non-specific abscess was suspected and an antimicrobial treatment was started . Since no treatment effect was observed, biopsies from a second bronchoscopy were suspicious of a malignant mesenchymal tumour . Lower lobe resection with lymphadenectomy revealed a benign fibrous histiocytoma . This is--to our knowledge--the first reported case of a BFH presenting with cavitation. Asian Cardiovasc Thorac Ann, 2003 Dec, 11(4), 346 - 8 Repair of tuberculous aneurysm of distal aortic arch; Suresh K et al.; A 65 year old female patient presented with one episode of massive haemoptysis requiring transfusion and subsequently cough with streaky haemoptysis . Computerized tomographic scan and angiogram revealed aneurysm of the distal aortic arch . She underwent elective repair of the pseudoaneurysm through median sternotomy and the bronchial communication was closed through left thoracotomy . Tubercle bacilli were identified in the contents and excised wall of aortic tissue. Int J Tuberc Lung Dis, 2003 Dec, 7(12 Suppl 3), S363 - 8 Evaluation of tuberculosis contact investigations in California; Sprinson JE et al.; OBJECTIVE: To estimate the burden of tuberculosis (TB) contact investigations in California, assess outcomes and effectiveness, and identify performance gaps . METHODS: Aggregate program management reports were used to examine contact investigations conducted for pulmonary TB cases reported between 1 July 1999 and 30 June 2000 in California . Findings were compared to national objectives, and performance gaps were identified . Costs were estimated, and effectiveness of TB case detection and prevention was assessed . RESULTS: A total of 2032 acid-fast bacilli sputum smear-positive and sputum smear-negative/culture-positive cases was reported; 17774 contacts were elicited, and 15582 (88%) contacts were evaluated . TB disease and latent tuberculosis infection (LTBI) were diagnosed in 111 (<1%) and 4609 (30%) contacts, respectively; 1958 (43%) contacts with LTBI completed treatment . Costs of contact investigations were estimated at dollars 4.8 million; 81% of expected TB cases were detected, but only 35% of cases expected to occur within 2 years following the investigation were prevented . CONCLUSIONS: California's performance did not meet national objectives for contact evaluation or treatment completion; improved effectiveness of contact investigations in California is needed . Although analysis of existing contact investigation surveillance data provided a macro-level view of performance gaps, expanded surveillance data are required to inform interventions. Int J Tuberc Lung Dis, 2003 Dec, 7(12 Suppl 3), S349 - 52 Tuberculosis contact investigations in rural Alaska: a unique challenge; Funk EA; Alaska Natives suffered extraordinary rates of disease and death from tuberculosis (TB) during the first half of the 20th century . Although the epidemic was largely controlled in the 1960s, rates of TB among Alaska Natives remain higher than for other Alaskans, and village outbreaks of TB continue to pose major threats . In 2000, a contact investigation around a case patient with infectious TB involved eight villages in south-western Alaska and found 26 additional persons with TB disease and 48 people with newly positive TB skin tests . Rural Alaska brings unique challenges to TB contact investigations not seen elsewhere in the United States because many villages are accessible only by small aircraft or boat . To conduct an investigation, a public health nurse must fly into the village, bring food and water, and sleep at the village clinic or school . In spite of these obstacles, over the past 4 years contact investigations have been initiated for all TB cases with acid-fast bacilli smear-positive sputum, and the proportion of adequately examined contacts has increased from 51% to 75% . The Alaska TB Program plans to improve contact investigations through ongoing reports to regional public health centers and through a statewide training workshop. Kekkaku, 2003 Nov, 78(11), 717 - 22 {Tuberculosis in compromised hosts} {Agranulocytosis due to anti-tuberculosis drugs including isoniazid (INH) and rifampicin (RFP)--a report of four cases and review of the literature} Shishido Y, Nagayama N, Masuda K, Baba M, Tamura A, Nagai H, Akagawa S, Kawabe Y, Machida K, Kurashima A, Komatsu H, Yotsumoto H. Department of Respiratory Medicine, Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo 204-8585, JapanWe experienced 4 cases of agranulocytosis due to anti-tuberculosis drugs (rifampicin {RFP}, isoniazid {INH}, ethambutol {EB}, streptomycin {SM} or pyrazinamide {PZA}) among some 6,400 tuberculosis patients who underwent chemotherapy over the past 20 years from 1981 to 2002 in our hospital, and the incidence rate of agranulocytosis was estimated at 0.06% . The 4 cases of agranulocytosis were as follows . CASE 1: A 51-year-old woman with right chest pain and fever was admitted to our hospital on Jan 4, 2001 . The white blood cell (WBC) count was 5,200/microliter . The tubercle bacilli were cultured in her sputum . The treatment with INH 0.3, RFP 0.45, EB 0.75, PZA 1.2 g/day, allopurinol and teprenone was started on Jan 13 . Pyrazinamide and allopurinol were stopped because of hyper-uric acidemia on Feb 7 . Agranulocytosis and eosinophilia (WBC 1,300 {Neut 1%, Ly 57%, Eos 35%}) developed on Feb 13 . All drugs were withdrawn and G-CSF drug nartograstim 100 micrograms was injected subcutaneously for 3 days . The WBC recovered to normal level and she was thereafter treated with INH, EB and Levofloxacin (LVFX) without any further trouble . Agranulocytosis in this case was supposed to be due to RFP . CASE 2: A 66-year-old man who had had nephrotic syndrome and hypothyroidism and has been treated with prednisolone 10 mg/day was admitted to our hospital on Aug 9, 2000 because of miliary tuberculosis . The tubercle bacilli were cultured in his sputum and the treatment with INH 0.3, RFP 0.45, and EB 0.75 g/day were started on Aug 10, but it was withdrawn on Aug 17 because of general skin eruption . After re-starting treatment with EB and INH on Aug 24, RFP was added in small dosage (0.05 g) on Oct 12, but agranulomatosis (WBC 2,300/microliter {Neut 2%}) developed on Nov 21, and all drugs were withdrawn again . The G-CSF drug filgrastim was used once subcutaneously, and WBC recovered immediately . He was thereafter treated with INH, EB, LVFX successfully . Agranulocytosis was supposed to be due to RFP . CASE 3: A 60-year-old woman without symptoms had abnormal chest roentgenograph, and consulted with our hospital on Aug 26, 2002 . The broncho-alveolar lavage fluid was smear and culture-negative, but PCR-TB positive, and the case was diagnosed as pulmonary tuberculosis . Treatment with INH 0.3, RFP 0.45, EB 0.75, PZA 1.2 g/day, alloprinol 300 mg and rebamipide 300 mg/day was started on Sept . 5, 2002 . Late in September, she complained of appetite loss . The laboratory data on Oct 3 revealed WBC 900/microliter (Neut 1%, Ly 94%), aspartate aminotransferase (AST) 199 IU/l, and alanine aminotransferase (ALT) 253 IU/l, showing agranulocytosis and drug-induced hepatitis . The chemotherapy was immediately withdrawn and she was admitted to our hospital on the next day . Glycyrrhizin derivative (SNMC) 40 ml was injected for 5 days, and WBC recovered, and AST and ALT also became normal . CASE 4: A 60-year-old man was admitted to our hospital on March 11, 1981 because pulmonary tuberculosis had recurred . He had been treated with SM, PAS and INH in 1973 for pulmonary tuberculosis . On admission examination of blood count and blood chemistry were normal . Treatment with RFP, INH and SM was started on March 11 . He stopped out from the hospital on April 17, but in a few days he returned back with sore throat, lower lip swelling and gingival bleeding . Blood cell count on April 24 showed pancytopenia with RBC 226, Hb 7.5, WBC 800 (Ly 96%, Eos 4%) and Plt 10,000/microliter . The bone-marrow showed NCC (nuceated cell count) of 5,500, and megakaryocyte 0 . Thereafter ground glass appearance shadows were seen on the whole lung field, and he died May 26 . Autopsy showed generalized aspergillosis . It was strongly suspected that either of RFP, INH or SM was responsible for his pancytopenia . We collected another 10 cases of agranulocytosis due to anti-tuberculosis drugs in the world wide literature, and found men/women ratio 5/8 (in one case gender was not known), the duration of chemotherapy before appearance of agranulocytosis 1-3 months, no change in the lymphocyte count of the peripheral blood, and the accompanying of another allergic signs such as skin eruption, blood eosinophilia or drug-induced hepatitis in some cases, and these findings suggest that the mechanism of agranulocytosis due to anti-tuberculosis drugs was allergic in nature. Tuberculosis (Edinb), 2004, 84(1-2), 82 - 92 Molecular mechanisms of MHC linked susceptibility in leprosy: towards the development of synthetic vaccines; Gorodezky C et al.; Tuberculoid (TT) and lepromatous leprosy (LL) develop in the human host depending on his ability to trigger a specific cellular immune response(CIR) . Different genes have been demonstrated in susceptibility/protection and may explain the forms of leprosy . The major histocompatibility complex (MHC) play an important role . The aim of the study was to explore the contribution of human leukocyte antigen (HLA) DRB1, DQA1, DQB1 and DQ promoter genes in LL Mexican patients . Six families (26 LL, three TT patients and 27 controls) were analyzed; 114 unrelated patients were compared with 204 controls . Class I typing was done by the standard microlymphocytotoxicity and class II typing using PCR-SSOP . Haplotype segregation correlated with specific CIR in vivo and in vitro using lepromin . Haplotype sharing was significantly deviated in the affected sibs (p=0.01) . Six healthy sibs were non-responders to lepromin and four of them were DQ1 homozgotes . DQ1 was significantly associated with LL and with non-responders . We set up macrophage activation experiments after infecting these cells with 5x10(6) bacilli to demonstrate if elimination occurred in the context or DQ1 . When DQ1 was present on macrophages and on T cells, bacteria were poorly eliminated from the cell (32%) while when absent, 76% of the individuals were able to eliminate the bacilli (p=0.03) . DRB1*1501 DQA1*0102-DQB1*0602 (DQ1 subtype) was significantly increased in the patients, indicating its participation in susceptibility . QBP 5.11/5.12 promoter present in the mentioned haplotype, and QAP 1.4, linked to DRB1*1301/02 haplotypes were also associated . Two mechanisms are suggested: the promoter polymorphisms may influence allele expression and thus the amount of peptides presented to the T-cell receptor, leading to a deficient CIR: HLA restriction is important for vaccine design; the way peptides anchor the DRB1*1501 groove may be relevant to the activation of TH1 cells, which contribute to an efficient presentation of peptides inducing a protective T-cell response. Int J Antimicrob Agents, 2003 Dec, 22(6), 562 - 6 Susceptibility of Mycobacterium ulcerans to a combination of amikacin/rifampicin; Marsollier L et al.; The effectiveness of rifampicin (RIF), amikacin (AMK) and their combination were estimated in the treatment of mice experimentally infected by Mycobacterium ulcerans and the risk of relapse after the treatment was evaluated . After 7 weeks of treatment with RIF or with the combination of AMK/RIF and 8 weeks with AMK alone, no viable bacilli were found in the infected tissues and these remained uninfected during the following 6 months . Among the mice treated with AMK alone, three mice relapsed, but the minimal inhibitory concentration of AMK for these isolates remained unchanged . With RIF alone, two mice relapsed and the minimal inhibitory concentration of these isolated strains was higher . However, with all the mice treated with both RIF and AMK, no relapse was observed. Indian J Gastroenterol, 2003 Sep-Oct, 22(5), 190 - 1 Abdominal wall abscess secondary to subcapsular tubercular liver abscess; Desai N et al.; We report a 22-year-old woman who presented with an abdominal wall lump in the right upper quadrant 15 days after starting antitubercular treatment for right pleural effusion . CT scan revealed a right liver lobe subcapsular abscess communicating vith subcutaneous tissue . Aspiration of pus revealed acid-fast bacilli . She responded to 9 months of antitubercular treatment. Rev Med Interne, 2003 Dec, 24(12), 815 - 8 {Association of a pulmonary, breast and cerebral tuberculosis}; Ben Ghorbel I et al.; INTRODUCTION: The concomitant unexpected arrival of a breast tuberculosis and cerebral tuberculomas to a same immunocompetent patient has not been ever described in the literature . EXEGESIS: We report the case of an non-HIV-infected woman who presented a pulmonary, breast tuberculosis and intracranial tuberculomas . Investigation for acid-fast bacilli in sputum and cerebrospinal fluid was negative . The patient received an antituberculous therapy for 15 months, which led to the disappearance of the cerebral lesions . CONCLUSION: Our case was particular by the affected organs, the absence of immunodeficiency and the favorable outcome. Hist Cienc Saude Manguinhos, 2003, 10(Suppl 1), 277 - 90 {Hansen's disease in the laboratory}; Nunes Sarno E; A physical doctor with a PhD in Pathology, Euzenir Nunes Sarno studies the immunology factors of Hansen's disease, one of the oldest chronic infections and that is an exclusively human disease . Staff member of an ambulatory that has become a reference on the disease in Brazil with 220 to 250 new patients per year, Euzenir emphasizes that the fact one cannot cultivate Mycobacterium leprae brings about some everlasting questions in relation to the transmission of and the sensitivity to the disease . There are also many epidemiology questions that remain unanswered . Estimates show that, among those who have contact with multi-bacilli patients, 90% are infected but only about 8% get sick . The high infection rate of those who live with multi-bacilli patients but never fall sick shows that just a small number of individuals are sensitive to Mycobacterium leprae . This is one of the questions immunology has not been able to answer . Why do some people resist to it and some don't? The figures are even lower when compared to those who are in contact with patients that are paucibacillus-infected, i.e . a manifestation of the disease with few bacilli . Hansen's disease is known as a skin malady . But, according to the specialist, its first damage is to the nerve, when the area becomes insensitive . Besides damaging the sensitive skin nerves, the disease can lead to motor disability and irreversible deformities, which sometimes lead to the amputation of limbs and protruded parts of the body . Mycobacterium leprae was one of the first pathogenic bacteria whose genome sequence has been entirely mapped . Only now we have the capacity to have more precise assessments . The disease is not inherited, and only in 1986 health services in Brazil began to take the responsibility for both the disease and its patients . During the twenty-year military dictatorship the country underwent, the health system was dismantled . In 1991, the one-year treatment with three drugs - Dapsone, Rifanpicine and Clofazimine- was introduced in our country . Just 30% of the cases get to negative results after the treatment . according to the interviewee, whereas tuberculosis is a highly virulent multi-bacilli disease, leprosy bacillus is not virulent, is a 'lazy' germ at the end of its evolutional process . One third of its genome does not work. Hist Cienc Saude Manguinhos, 2003, 10(Suppl 1), 49 - 93 Adolpho Lutz and controversies over the transmission of leprosy by mosquitoes; Benchimol JL et al.; During his years of study in Switzerland and Germany, Adolpho Lutz published his first articles on zoology, clinical practice, and therapeutics . In Limeira, Sao Paulo, he began studies on animal and human diseases caused by germs and parasites . In 1885-86, Lutz traveled to Hamburg to study the morphology of germs related to skin diseases, in conjunction with Paul Gerson Unna, one of Germany's foremost dermatologists . He proposed the inclusion of Hansen's and Koch's bacilli in a new genus . In 1889, Unna nominated his student as physician-in-chief of the Leper Settlement on Molokai Island, Hawaii . From then on, Lutz sustained the theory that the disease was transmitted by mosquitos . He conducted research to prove this theory when he was head of the Instituto Bacteriologico de Sao Paulo (1893-1908) and, later, after he moved to the Instituto Oswaldo Cruz (1908-1940) . Although this research was not successful, on commissions and at congresses in which he participated until his death in October 1940, he still held to his conviction that leprosy was transmitted by mosquitoes. Infect Control Hosp Epidemiol, 2003 Nov, 24(11), 825 - 30 Potential nosocomial exposure to Mycobacterium tuberculosis from a bronchoscope; Larson JL et al.; OBJECTIVE: To investigate a possible nosocomial outbreak of tuberculosis (TB) . DESIGN: Retrospective cohort study . SETTING: Community hospital . METHODS: We reviewed medical records, hospital infection control measures, and potential locations of nosocomial exposure . We examined the results of acid-fast bacilli (AFB) smears, cultures, and drug susceptibility testing, and performed a DNA fingerprint analysis . We observed laboratory specimen processing procedures and bronchoscope disinfection procedures . We also reviewed bronchoscopy records . RESULTS: In October 2000, three patients had bronchoscopy specimen cultures that were positive for Mycobacterium tuberculosis . Of the three, only one had clinical signs and symptoms consistent with TB and positive AFB sputum smears . The other two did not have signs and symptoms consistent with TB and had no known exposure to individuals with infectious TB . The three M . tuberculosis isolates had matching DNA fingerprints . No evidence of laboratory cross-contamination was identified . The three culture-positive specimens of M . tuberculosis were collected with the same bronchoscope within 9 days . This bronchoscope was inadequately cleaned and disinfected between patients, and the automated reprocessor used was not approved for use with the hospital bronchoscope . CONCLUSIONS: One of the bronchoscopes at this hospital was contaminated with M . tuberculosis during bronchoscopy of an AFB-smear-positive patient . Subsequent specimen contamination likely occurred because the bronchoscope had been inadequately cleaned and disinfected . Patients who subsequently underwent bronchoscopy were also potentially exposed to M . tuberculosis from this bronchoscope. J Clin Pathol, 2003 Dec, 56(12), 966 - 9 Chronic granulomatous pleuritis caused by nocardia: PCR based diagnosis by nocardial 16S rDNA in pathological specimens; Wada R et al.; Nocardiosis is an uncommon infection caused by the aerobic actinomycete nocardia . Identification of the pathogen is essential for the definitive diagnosis and for an effective treatment . This report describes a case of chronic granulomatous pleuritis caused by nocardia . A 59 year old Japanese man had a history of repeated pyothorax . Right pleural decortication and thoracic drainage were performed . Microbiological examinations of the drained fluid failed to identify a pathogen . Pathological examinations revealed Gram positive filamentous and branching bacilli in the granulomatous lesion of the pleura . Sequencing of the 971 bp 16S ribosomal DNA extracted and amplified from paraffin wax embedded sections identified the microorganism as Nocardia sp . IFM 0860 . The patient received sulfamethoxazol/trimethoprim and minocycline . Although the presence of a brain abscess was disclosed by systemic examination, the clinical course has been favourable . In this patient, polymerase chain reaction analysis of 16S ribosomal DNA in pathological specimens was useful in making an accurate diagnosis of nocardiosis and in determining the appropriate treatment. Infect Immun, 2003 Dec, 71(12), 7099 - 108 Mycobacterium tuberculosis growth at the cavity surface: a microenvironment with failed immunity; Kaplan G et al.; Protective immunity against pulmonary tuberculosis (TB) is characterized by the formation in the lungs of granulomas consisting of macrophages and activated T cells producing tumor necrosis factor alpha and gamma interferon, both required for the activation of the phagocytes . In 90% of immunocompetent humans, this response controls the infection . To understand why immunity fails in the other 10%, we studied the lungs of six patients who underwent surgery for incurable TB . Histologic examination of different lung lesions revealed heterogeneous morphology and distribution of acid-fast bacilli; only at the surface of cavities, i.e., in granulomas with a patent connection to the airways, were there numerous bacilli . The mutation profile of the isolates suggested that a single founder strain of Mycobacterium tuberculosis may undergo genetic changes during treatment, leading to acquisition of additional drug resistance independently in discrete physical locales . Additional drug resistance was preferentially observed at the cavity surface . Cytokine gene expression revealed that failure to control the bacilli was not associated with a generalized suppression of cellular immunity, since cytokine mRNA was up regulated in all lesions tested . Rather, a selective absence of CD4(+) and CD8(+) T cells was noted at the luminal surface of the cavity, preventing direct T-cell-macrophage interactions at this site, probably allowing luminal phagocytes to remain permissive for bacillary growth . In contrast, in the perinecrotic zone of the granulomas, the two cell types colocalized and bacillary numbers were substantially lower, suggesting that in this microenvironment an efficient bacteriostatic or bactericidal phagocyte population was generated. Infect Immun, 2003 Dec, 71(12), 6871 - 83 The Mycobacterium tuberculosis complex-restricted gene cfp32 encodes an expressed protein that is detectable in tuberculosis patients and is positively correlated with pulmonary interleukin-10; Huard RC et al.; Human tuberculosis (TB) is caused by the bacillus Mycobacterium tuberculosis, a subspecies of the M . tuberculosis complex (MTC) of mycobacteria . Postgenomic dissection of the M . tuberculosis proteome is ongoing and critical to furthering our understanding of factors mediating M . tuberculosis pathobiology . Towards this end, a 32-kDa putative glyoxalase in the culture filtrate (CF) of growing M . tuberculosis (originally annotated as Rv0577 and hereafter designated CFP32) was identified, cloned, and characterized . The cfp32 gene is MTC restricted, and the gene product is expressed ex vivo as determined by the respective Southern and Western blot testing of an assortment of mycobacteria . Moreover, the cfp32 gene sequence is conserved within the MTC, as no polymorphisms were found in the tested cfp32 PCR products upon sequence analysis . Western blotting of M . tuberculosis subcellular fractions localized CFP32 predominantly to the CF and cytosolic compartments . Data to support the in vivo expression of CFP32 were provided by the serum recognition of recombinant CFP32 in 32% of TB patients by enzyme-linked immunosorbent assay (ELISA) as well as the direct detection of CFP32 by ELISA in the induced sputum samples from 56% of pulmonary TB patients . Of greatest interest was the observation that, per sample, sputum CFP32 levels (a potential indicator of increasing bacterial burden) correlated with levels of expression in sputum of interleukin-10 (an immunosuppressive cytokine and a putative contributing factor to disease progression) but not levels of gamma interferon (a key cytokine in the protective immune response in TB), as measured by ELISA . Combined, these data suggest that CFP32 serves a necessary biological function(s) in tubercle bacilli and may contribute to the M . tuberculosis pathogenic mechanism . Overall, CFP32 is an attractive target for drug and vaccine design as well as new diagnostic strategies. Int J Dermatol, 2003 Nov, 42(11), 893 - 4 Lepromatous leprosy and reversal reaction in a Micronesian immigrant; Ross RR et al.; A 25-year-old Micronesian man from the island of Otia developed erythematous plaques on his legs . He was diagnosed with erythema nodosum and treated with systemic prednisone . Two months later, he presented with erythematous nodules on his forehead, cheeks, and chin (Fig . 1) . Examination revealed scattered violaceous papules on his chest, arms, forearms, hands, and feet, and deep purple macules on his palms and soles . Laboratory evaluation included negative serologies for human immunodeficiency virus, rapid plasma reagin, and hepatitis A, B, and C . Routine histopathology revealed nodular aggregates of histiocytes, plasma cells, and lymphocytes . Histiocytes showed basophilic clusters of organisms within vacuoles, suggesting globi . Acid-fast stain revealed numerous acid-fast-positive rod-shaped organisms . The bacterial index on the Fite stain was four (bacterial index/Ridley's logarithmic scale, indicating 10-100 bacteria/high power field) (Fig . 2) . An acid-fast stain obtained from a smear of tissue was positive for acid-fast bacilli, but no acid-fast bacilli were cultured . After the first day of treatment with dapsone 100 mg, rifampin 600 mg, and clofazimine 50 mg, the patient complained of burning and pain in his ankles and wrists . There was intense erythema within the lesions . Edema developed in his hands and feet . Consultation with the Gillis W . Long Hansen's Disease Center in Carville, Louisiana, recommended prompt treatment with corticosteroids . The edema of the hands and wrists was treated as a type I reversal reaction with prednisone 1 mg/kg/day . Subsequently, the edema and neuralgia quickly resolved in his distal extremities. Eur J Immunol, 2003 Dec, 33(12), 3293 - 302 CD8+ T cell-mediated suppression of intracellular Mycobacterium tuberculosis growth in activated human macrophages; Brookes RH et al.; Animal models of tuberculosis point to a protective role for MHC class I-restricted CD8(+) T cells, yet it is unclear how these cells protect or whether such findings extend to humans . Here we report that macrophages infected with Mycobacterium tuberculosis, rapidly process and present an early secreted antigenic target (ESAT-6)-specific HLA class I-restricted CD8(+) T cell epitope . When cocultured with CD8(+) T cells restricted through classical HLA class I molecules the growth of bacilli within macrophages is significantly impaired after 7 days . This slow antimycobacterial activity did not correlate with macrophage lysis but required cell contact . We also found that inhibitors of apoptosis either had no effect or augmented the CD8-mediated suppressive activity, suggesting that an activation signal might be involved . Indeed we show that CD8(+) T cells were able to activate macrophages through receptors that include CD95 (Fas) . Consistent with these findings the CD8-mediated suppression of mycobacterial growth was partially reversed by Fas blockade . These data identify a previously unrecognized CD8(+) T cell-mediated mechanism used to control an intracellular infection of macrophages. Arch Pathol Lab Med, 2003 Dec, 127(12), 1619 - 22 Systemic Tropheryma whippleii infection associated with monoclonal B-cell proliferation: a Helicobacter pylori-type pathogenesis? Wang S, Ernst LM, Smith BR, Tallini G, Howe JG, Crouch J, Cooper DL. We report a case of Whipple disease in a 55-year-old woman who presented with arthralgia, weight loss, and lymphadenopathy . Tropheryma whippleii bacilli were identified in the mesenteric lymph nodes by diastase-resistant periodic acid-Schiff stain and confirmed by electron microscopy . Retrospectively, previous biopsy specimens from the duodenum and right axillary lymph node of this patient, which were initially considered to demonstrate reactive changes, also showed features consistent with involvement by Whipple disease . At the time of presentation, a large kappa-restricted monoclonal B-cell population with the phenotype CD20+CD19+CD5-CD10- was identified in the patient's peripheral blood, lymph nodes, and bone marrow by flow cytometry study . The monoclonality of the mesenteric lymph node B cells was confirmed by immunohistochemical stain for kappa chain after antigen retrieval and also by polymerase chain reaction with the primer set targeting FR2-V(H) . Routine cytogenetic study failed to reveal any chromosomal abnormalities, and polymerase chain reaction for Bcl-2 major and minor breakpoint cluster of t(14:18) was not detected . The monoclonal B cells have persisted in blood for the entire follow-up period (10 months) . The possibility of reactive monoclonal B-cell proliferation versus Whipple disease-related B-cell lymphoma is discussed. J Hosp Infect, 2003 Dec, 55(4), 276 - 82 Gastroscope processing in washer-disinfectors at three different temperatures; Zuhlsdorf B et al.; Endoscopes are processed chemo-thermally at approximately 56 degrees C in washer-disinfectors in Germany . In this study we investigated the processing of gastroscopes by an endoscope washer-disinfector at different temperatures . A total of 87 gastroscopes were tested hygienically and microbiologically before manual cleaning (after patient use), as well as after manual cleaning and after endoscope washer-disinfector processing at running temperatures of 43, 51 and 56 degrees C . In all tests the suction/biopsy channels of the gastroscopes were flushed with 50 mL sterile solution throughout their full length, from the proximal to the distal ends . The rinse solutions were plated on to various culture media . Also, in order to detect low bacterial counts, 3x10 mL rinse solution was membrane filtrated . The German guideline level for total bacterial counts, applicable since 2002, was exceeded at all temperatures tested (159 cfu/mL at 43 degrees C, <60 cfu/mL at 51 degrees C, and 8 cfu/mL at 56 degrees C) . A temperature increase from 43 to 51 degrees C resulted in a highly significant reduction of the residual contamination by aerobic bacteria (P<0.001, Mann-Whitney U Test), Gram-negative bacilli (P<0.001), and pseudomonads (P=0.002) . A further temperature increase from 51 to 56 degrees C resulted in a further highly significant drop in residual contamination by aerobic bacteria (P=0.021) and pseudomonads (P=0.036) . The aim of the user-minimizing material damage to endoscopes or prolonging their product life-cannot be achieved through lowering the processing temper