Surv Ophthalmol, 2002 May-Jun, 47(3), 275 - 87 The ophthalmic trials of G . H . A . Hansen; Marmor MF; G . H . A . Hansen (1841-1912) is widely known as the discoverer of the infectious cause of leprosy . It is less well known that his career was threatened by an episode involving experimentation on the eye . As a staff physician at the leprosy hospitals of Bergen, Norway, early in his career, Hansen learned about ocular involvement in leprosy and co-authored Leprous Diseases and the Eye . In 1873 he observed bacilli in leprous nodules, but proof of an infectious origin was difficult to obtain because the agent could not be cultured and no one had demonstrated direct transmission . Hansen tried several unsuccessful experiments, and in 1879 he passed a cataract knife that had incised an active leprous nodule into a woman's conjunctiva . No nodule developed, but the woman complained of pain and said she was never asked for permission . Hansen was brought to trial where eminent physicians testified on his behalf-but Hansen himself readily admitted that no permission had been sought for fear the woman would say no . He was convicted, and relieved of his post as staff physician, but he was allowed to retain an appointment as Chief Medical Officer of Health for Leprosy, in which capacity he worked for the rest of his life. J Am Vet Med Assoc, 2002 Jun 1, 220(11), 1661 - 3, 1650 Pulmonary mycobacteriosis caused by Mycobacterium haemophilum and M . marinum in a royal python; Hernandez-Divers SJ et al.; An adult female royal python was referred with an 18-month history of chronic respiratory tract disease . Anemia and moderate leukocytosis with heterophilia and monocytosis were detected and interpreted as evidence of a chronic inflammatory condition . Evaluation of lateral and dorsoventral radiographic views revealed multiple soft-tissue opacities within the cranial lung fields . Endoscopic evaluation revealed that the normal reticulated pattern on the surface of the lung had been largely replaced by diffuse, granulomatous tissue . Histologic examination of biopsy specimens revealed classic pyogranulomas . Ziehl-Neelsen stains revealed numerous acid-fast bacilli consistent with Mycobacterium spp . Molecular methods including polymerase chain reaction restriction assays and DNA sequencing confirmed the identification of M . haemophilum and M . marinum . The snake was euthanatized . Mycobacteriosis is an uncommon and sporadic pyogranulomatous disease of reptiles . In most cases of reptile mycobacteriosis, treatment is not advised because of the chronic nature and often advanced stage of the disease, long-term and expensive nature of potential treatment regimens, and the risk of spread to other animals, including humans. J Forensic Sci, 2002 May, 47(3), 640 - 4 Fatal meningitis and encephalitis due to Bartonella henselae bacteria; Gerber JE et al.; Bacterial infection due to Bartonella henselae commonly develops in children and young adults following cat/dog contacts and/or cat/dog scratches . Regional lymphadenopathy is its most common clinical expression . However, encephalitis and Parinaud's syndrome (oculoglandular syndrome) have also been reported as has systemic illness . A review of the international literature in all languages revealed no fatal complications in immunocompetent hosts . A four-year-old white child with no underlying illness began to have seizure-like activity . She was taken to a local hospital and subsequently transferred to a medical center . The child was treated aggressively for seizures and fever of unknown origin . However, her condition rapidly declined and she died without a specific diagnosis . At autopsy there was marked cerebral edema with no gross evidence of acute meningitis . Microscopic exams revealed multiple granulomatous lesions as well as a meningitis and encephalitis . A variety of cultures and stains were negative for acid fast and fungal organisms . Warthin-Starry stains of involved tissue including brain and liver revealed pleomorphic rod shaped bacilli consistent with Barronella henselae . Analysis of brain tissue with polymerase chain reaction (PCR) and Southern blot for the deoxyribonucleic acid (DNA) was definitive for DNA of Bartonella henselae bacteria. Acta Chir Belg, 2002 Apr, 102(2), 118 - 21 Tuberculous lymphadenopathy in adults: a review of 35 cases; Mert A et al.; We retrospectively reviewed clinical, diagnostic, therapeutic and prognostic features of 35 patients (25 female, 10 male, mean age: 33 years, range: 16-70) with tuberculous lymphadenopathy (TB LAP) which had been followed since 1980 . The diagnosis was established by tissue sampling in 32 cases (caseating granulomatous adenitis in 89%) or presence of acid-fast bacilli (AFB) in the aspirate in 2 cases and in the drainage in 1 case . Paraffin-embedded granulomatous tissues were stained by Ehrlich-Ziehl-Neelsen (EZN) and also Mycobacterium tuberculosis DNA was studied by polymerase chain reaction (PCR) (n = 21) . The patients were admitted with enlarging LAP (34%), draining LAP (9%), and both systemic complaints and enlarging LAP (57%) . Cervical lymph nodes were the most frequently involved site (77%) . Pathologic findings on chest X-ray were seen in 23% . Erythrocyte sedimentation rate (ESR) was higher than 100 mm/hour in 25% and associated with systemic complaints . Tuberculin skin test was positive in 91% . AFB could not be seen in any granulomatous tissue (n: 21), but PCR study was positive in 33% (7/21) . All patients were given anti-TB treatment (INH,RMP,EMB and/or PZA) . Surgical excision of draining LAP with surrounding inflammatory tissues in addition to the medical treatment was needed in 2 cases . Clinical improvement was obtained within 3 months of the treatment and ESR returned to normal within 5 months . After completion of the treatment, 22 patients were followed-up; mean duration was 3 years, and none relapsed . In conclusion, a patient with TB LAP generally presents with a few small, painless, cervical lymph nodes, which are slowly enlarging . For exact diagnosis, excisional biopsy for histologic and microbiologic studies is essential . Use of anti-TB drugs is the main therapeutic option. Orbit, 2000 Mar, 19(1), 41 - 44 Orbital cellulitis with gas; Cheema RA et al.; Orbital cellulitis due to presumed gas-producing organisms has been associated with poor visual prognosis . We report successful visual recovery in a 14-year-old boy with orbital cellulitis and gas in the orbit on CT scan . The patient was treated with intravenous antibiotics and prompt orbital decompression . Pus from the sinus aspirate and orbital drain grew H . influenzae and Gram-negative bacilli . Repeat orbital surgery with drainage of residual abscess was performed and the patient made a complete recovery . J Biotechnol, 2002 Jul 3, 96(3), 259 - 70 Cultivation of Mycobacterium bovis BCG in bioreactors; Dietrich G et al.; The Mycobacterium bovis BCG vaccine for commercial use is classically produced as surface pellicles by culture on synthetic medium . Under these conditions, reproducibility of the cultures and quality assessment are hampered by slow growth of the bacilli, the formation of bacterial aggregates and a high proportion of dead bacilli after processing and final formulation of the vaccine . Here, we established dispersed cultures of M . bovis BCG in synthetic media in small-scale bioreactors . These cultures allow recording and adjusting of culture parameters and give rise to single bacilli with a high degree of live bacteria . In the murine model, bioreactor-grown M . bovis BCG exhibited slightly stronger replication and persistence than the vaccine produced under the classical conditions . The protective efficacy against challenge with M . tuberculosis was identical for both vaccine preparations. Rev Med Chil, 2002 Mar, 130(3), 319 - 21 {Tuberculosis bursitis: report of case}; Perez C et al.; We report a previously healthy 51 years old woman with a one year history of pain in the left hip associated with a mass without fever or local inflammatory changes . Magnetic resonance imaging located the mass in the medial gluteal muscle . The pathological examination of the mass disclosed unspecific inflammatory changes . Due to worsening of pain, a left throchanteric bursitis was diagnosed two weeks later and a throchanteric bursectomy was performed, obtaining a second biopsy . Aerobic, anaerobic and fungal cultures were negative . Lowenstein-Jensen culture showed development of mycobacteria and a genetic probe confirmed the presence of Mycobacterium tuberculosis . The second biopsy also identified several granulomas with areas of caseation and the Ziehl-Nielsen stain was positive for acid fast bacilli . Osteoarticular tuberculosis, specially bursitis, should be suspected in the presence of chronic pain associated with swelling. Southeast Asian J Trop Med Public Health, 2001 Dec, 32(4), 835 - 43 Simple microplate hybridization assay for detection of amplified products of Mycobacterium tuberculosis; Tansuphasiri U et al.; We describe a simple microplate hybridization assay for the rapid detection of the IS6110 PCR products of Mycobacterium tuberculosis from clinical cultures and from sputum specimens . The assay is based on the specific detection with a fluorescein-labeled detection probe of biotinylated PCR products which are captured on avidin coated microplate . Hybridized products with fluorescein were identified by using anti-fluorescein antibody, horseradish peroxidase conjugate and colorimetric peroxidase substrate . The specificity of the assay was assessed by analysis of 56 bacterial strains: the assay discriminated perfectly between the positive and negative groups when an OD490 of 0.18 was used as the cut-off point . The assay was sensitive enough to detect as little as 1 pg of M . tuberculosis H37Rv DNA, which is equivalent to approximately three bacilli . To evaluate the assay performance clinically, 190 sputum samples from newly diagnosed TB patients were tested; 79 were classified as TB positive, and 111 were classified as TB negative by culture and acid-fast staining as the 'gold standard' . The sensitivity, specificity and accuracy of the PCR-microplate hybridization assay were 90, 100 and 96%, respectively . The total assay time of hybridization following the PCR was 4 hours . The PCR-microplate hybridization assay is fast, simple and accurate and is suitable for use in the microbiology laboratory or for the analysis of large numbers of samples. Rev Mal Respir, 2002 Apr, 19(2 Pt1), 161 - 5 {Tuberculosis of the lung bases}; Ben Miled-M'rad K et al.; Tuberculosis of the lung bases is a rare condition that can mimic pneumonia, bronchial carcinoma, lung abscess or bronchiectasis . Diagnostic delays, that can lead to serious complications not amenable to surgical resection, are often the result of repeatedly negative bacteriological examinations . We report a series of 10 cases of tuberculosis of the lung bases collected between 1993 and 1998 that were examined by computerised tomography . The chest x-ray most commonly showed a heterogeneous opacity . On the CT scan this corresponded with an area of alveolar consolidation which, when it was associated with centrilobular micronodules and cavitated nodules and masses, suggested the diagnosis of basal tuberculosis . Indeed the absence of apical lesions and the frequency of involvement of mediastinal and bronchial lymph nodes support the hypothesis of bronchial dissemination of the bacilli from tuberculous nodes . This explanation is supported by the high incidence of endobronchial lesions found at bronchoscopy in this form of tuberculosis. Appl Environ Microbiol, 2002 Jun, 68(6), 3159 - 61 Identification of nontuberculous mycobacteria existing in tap water by PCR-restriction fragment length polymorphism; Chang CT et al.; This paper presents the finding of the possible cause of the high false-positive rate in acid-fast staining in histological examinations . Using acid-fast staining, culture, and PCR, acid-fast bacilli were detected in 83.7% of 49 hospital tap water samples and nontuberculous mycobacteria (NTM) were detected in 20.4% of the same 49 samples . The 10 NTM isolates were also identified to the species level using PCR-restriction fragment length polymorphism . Our findings indicate that NTM in hospital tap water are the possible cause of false positives in acid-fast staining and of nosocomial infection in immunocompromised patients. Ann Med Interne (Paris), 2002 Mar, 153(2), 75 - 81 {Neuromeningeal tuberculosis in northeastern suburbs of Paris . Nineteen cases}; Grimaud-Ayina M et al.; SUBJECT: Analyze characteristics of neuromeningeal tuberculosis in the northeastern suburbs of Paris . MATERIAL AND METHOD: Retrospective study of 19 observations between 1988 and 1999 . RESULTS: Thirteen cases of meningitis, 3 cases of meningitis associated with a tuberculoma and 3 cases with isolated tuberculoma were described . Young subjects (average age 46.4), foreign born (73.7%) were preferentially affected . Three patients were infected by the human immunodeficiency virus . Weight-loss and weakness (84%), fever (79%), headache (63%) dominate the clinical manifestations . The diagnosis delay was 56.6 days, and the therapeutic time, 8.6 days . The search for acid fast bacilli was positive only in one case on direct examination of the cerebrospinal fluid, whereas the culture was positive in 68.7% of the cases . Cerebral imagery was abnormal in13 patients . Average duration of antituberculous treatment was 13,4 months (range: 9-24) . Corticosteroids were associated in 12 patients . Thirteen patients were cured, 3 died and 3 were lost to follow up . CONCLUSION: The characteristics of neuromeningeal tuberculosis are not modified, but the diagnosis delay of the neuromeningeal tuberculosis, which conditions the prognosis, remains significant . The optimal duration of the antituberculous treatment and the conditions of the steroid therapy have to be specified. Life Sci Space Res, 1965, 3, 142 - 8 Ultra-high vacuum and microorganisms; Imshenetsky AA et al.; Experimental study of the space environment effect on living organisms is one of the most important tasks of exobiology . However location of the living organisms under study outside space vehicles and sputniks is combined with technical difficulties . Therefore it is much more suitable to reproduce conditions found in space in laboratory and to study its effect on living cells . It was proved that low temperatures, even those approaching absolute zero do not kill microorganisms . The fact of microorganisms surviving radiation of some million roentgen suggests that they would not be killed by ionizing radiation in space . UV rays should be considered as the most active sterilizing agent . The ability of microorganisms to resist high vacuum is studied much worse . Under the action of high vacuum at 10(-8)-10(-9) mm Hg during 72 hours all studied seven species of spore-forming bacilli remained viable . As for nonsporeforming bacteria under conditions mentioned, cells of some species perished (correction of parished) completely while other species retained viable cells . Conidia of fungi and parts of mycelium of fungi which do not form conidia, sustained high vacuum well. Indian J Pathol Microbiol, 2001 Oct, 44(4), 435 - 8 Prevalence of gram negative anaerobic bacilli in routine clinical specimens; De A et al.; A total of 206 gram negative anaerobic bacilli were isolated from 2591 routine clinical specimens . Majority of them (78.2%) were part of a mixed flora . A high incidence of gram negative anaerobic bacilli was found in post-operative wound infections and diabetic foot infections (30.1%), followed by necrotizing fasciitis and crush injuries (18%), pus of empyema and lung abscesses (14.5%) and aspirates from other deep abscesses (10.7%) . Bacteroides fragilis was the most frequently recognized species (42.2%), followed by Fusobacterium sp . (17.4%), Prevotella sp . (15.1%) and Porphyromonas sp . (11.2%) . Neomycin blood agar plate yielded the maximum number (72.8%) of strains in pure culture . Gram negative anaerobic bacilli in infective processes are significantly on the rise and so suspected cultures should be processed for both aerobic and anaerobic organisms. Kekkaku, 2002 Apr, 77(4), 361 - 6 {A case of multiple bone and joint tuberculosis which had been misdiagnosed as the rheumatoid arthritis and treated with prednisolone for eleven months}; Tsuduki E et al.; A 34-year-old man had a multiple arthralgia for about eleven months . The swelling of his right wrist and foot had appeared in the dorsal side, and he had been misdiagnosed as the rheumatoid arthritis . He was treated with prednisolone in the dosages of 2.5 mg per day for one month, and 10 mg per day for ten months . When he admitted to our hospital, the bone X-ray examinations of the wrist and foot revealed the marked atrophy and destruction of the carpal and tarsal bones . The aspiration fluid from the swelling around his wrist and foot was positive for acid-fast bacilli on smear and Mycobacterium tuberculosis was found on culture . He was treated with isoniazid, rifampicin, ethambutol and pyrazinamide, however, these medication was not adequately effective to his complications of tuberculous arthritis . Curettage, irrigation and synovectomy of his right carpal and tarsal bone were performed in order to control his bone and joint infection . He recovered from his arthritis and tenosynovitis after these operations . The clinical practitioners should not omit tuberculosis from the differential diagnosis of persistent osteoarthralgia. Kekkaku, 2002 Apr, 77(4), 329 - 39 {Discussing the current situation of tuberculosis case-finding by mass miniature radiography in Japan}; Ohmori M et al.; The system of tuberculosis (TB) case-finding by mass miniature radiography (MMR) was established and expanded for almost all Japanese citizens in the 1950s . And, as stipulated by the TB Prevention Law, periodic mass screenings for schools, inhabitants, employees and institutions have been carried out . Among those aged over 25 years, the proportion of people screened by MMR was estimated to be 60.3% . This means that about 54 million people aged over 25 years are receiving medical service with MMR every year . However, the detection rates of TB cases by MMR have declined markedly compared with those in 1950s . As of 1998, the detection rate was 0.03 per 1,000 for school children and students, 0.06 per 1,000 for employees, and 0.16 per 1,000 for inhabitants . The proportion of cases detected by MMR among newly notified TB cases was 12.8% in 1998, and this ratio has been almost constant for the last 10 years . This ratio was greater among young adult TB cases . Approximately 20% of notified TB cases aged 20-39 years were detected by MMR for employees . Although the purpose of MMR is to find the cases before discharging TB bacilli, 35.1% of the cases were bacteriologically confirmed, and this proportion was greater among elderly TB cases . The Japan Anti-Tuberculosis Association (JATA) has been carrying out MMR for a long time . Eight selected branches of JATA that has been doing high quality case-finding reported 228 TB cases out of 965,440 inhabitants aged over 40 years examined by MMR in 1996 . Based on these results, the cost per TB case detected by MMR was calculated . The cost was 4.4 millions yen (yen) per case for all forms of TB, yen 2.3 millions for male, yen 8.4 millions for female, yen 7.3 millions for those aged 40-49 years and yen 1.8 millions for those aged over 80 years . TB detection rate by MMR for inhabitants was correlated with TB incidence rate in various areas, and based on this correlation, the cost was calculated for various incidence rates . For all forms of TB, the cost was yen 4.0 millions per case for an incidence rate of 30 per 100,000, and yen 6.7 millions for an incidence rate of 20 per 100,000 . MMR is not economically cost-effective even among elderly people and in areas with incidence rate less than 50 per 100,000, because the medical expense for a TB patient treated under hospitalization for 2 months and outpatient's clinic for 4 months is approximately yen 0.9 millions in 1996 . The decision making in continuation or abolition or limitation of MMR should be discussed from a wide range of cost-effectiveness analyses as well as from the view of public health service and willingness of people . For the purpose of decision making, this study provides the detection rates; the costs stratified by sex, age and incidence; and the proportion of cases detected by MMR among newly notified TB cases by age-group and bacteriological status. J Lab Clin Med, 2002 Apr, 139(4), 244 - 50 Adherence of Helicobacter pylori to gastric epithelial cells and mucosal inflammation; Kaji T et al.; Adherence of Helicobacter pylori to the gastric epithelium is believed to be an important step in the induction of active inflammation of the mucosal layer . However, structural evidence showing a quantitative relationship between the adherence of H . pylori and severity of gastric mucosal inflammation is lacking . We therefore investigated the correlations between severity of gastritis and adherence of morphologically different forms of H . pylori . Fifty-seven biopsy specimens from the gastric bodies of patients with H . pylori-induced gastritis were examined . The severity of gastritis and the adherence and structure of H . pylori were determined with the use of light and scanning electron microscopy . We also investigated the ability of H . pylori organisms with different structural features to induce interleukin-8 secretion by human gastric adenocarcinoma (AGS) cells in vitro because production of interleukin-8 is related to H . pylori-associated gastritis . Furthermore, serum pepsinogen concentrations and cytotoxin-associated protein status in relation to adherence of H . pylori to the epithelial surface were examined . The results indicated that H . pylori organisms, which adhered firmly to the epithelial surface, were consistently long, tightly coiled bacilli . Histologically, those gastric mucosa samples with H . pylori firmly attached showed severe gastritis . H . pylori bacilli of greater length induced higher levels of interleukin-8 secretion . The serum pepsinogen I/II ratio showed a significant negative correlation with the grade of H . pylori adhesion (r = -0.401, P <.01) . We also noted a significant correlation between cytotoxin-associated protein status and the adherence of H . pylori (r = 0.344, P <.05) . A quantitative correlation was found between adherence of H . pylori and gastric inflammation . Both adherence and the induction of inflammation were found to be related to the structure of H . pylori. BMC Gastroenterol . 2002 May 13;2(1):10. Colonic tuberculosis mimicking Crohn's disease: case report; Chatzicostas C et al.; BACKGROUND: Intestinal tuberculosis is a rare disease in western countries, affecting mainly immigrants and immunocompromised patients . Intestinal tuberculosis is a diagnostic challenge, especially when active pulmonary infection is absent . It may mimic many other abdominal diseases . CASE PRESENTATION: Here, we report a case of isolated colonic tuberculosis where the initial diagnostic workup was suggestive of Crohn's disease . Computed tomography findings however, raised the possibility of colonic tuberculosis and the detection of acid-fast bacilli in biopsy specimens confirmed the diagnosis . CONCLUSIONS: In conclusion, this case highlights the need for awareness of intestinal tuberculosis in the differential diagnosis of chronic intestinal disease Indian J Exp Biol, 2001 Dec, 39(12), 1227 - 34 Evaluation of immune responses directed against 30kDa secretory protein of Mycobacterium tuberculosis H37Ra complexed in different adjuvants; Yadav D et al.; Ability of different adjuvants to promote cell mediated immune responses towards 30 kDa secretory protein of Mycobacterium tuberculosis H37Ra was monitored by assessing the lymphocyte proliferation and IgG1/IgG2a subclass profile in mouse model . Six formulations, viz . poly lactide-co-glycolide (PLG) microspheres, dimethyldioctadecyl ammoniumbromide (DDA), liposomes, liposomes containing monophosphoryl lipid A and coated with alum (L-LIPA-AL) or without alum (L-LIPA) were evaluated in comparison to standard Freund's incomplete adjuvant (FIA) . Two adjuvant formulations of 30kDa-L-LIPA-AL and 30kDa-PLG showed maximum reactivity on VIIIth week post immunization (p.im) in terms of lymphoproliferation w.r.t . other adjuvant formulations . Both the vaccine formulations also exhibited a Th1 shift in terms of higher IgG2a response over IgGI . Flowcytometric analysis in the mesenteric lymph nodes (MLNs) of immunized animals revealed the capacity of 30kDa-PLG and 30kDa-L-LIPA-AL to activate T cell subsets like CD4 and CD8 T cells . The upregulation of B7 costimulatory molecules (B7-1 & B7-2) after immunization further proved the ability of the two vaccine formulations to activate antigen presenting cells . The immunostimulatory nature of the two formulations was also reflected in their capacity to reduce the bacilli load from the lungs of the experimentally infected mice . This study demonstrates PLG and L-LIPA-AL as potent adjuvants and their bioacceptibility and nontoxic nature make them suitable candidates for future subunit vaccine development against tuberculosis. Curr Infect Dis Rep, 2002 Jun, 4(3), 249 - 256 Aerobic Gram-negative Bacillary Pneumonia; Parodi S et al.; Gram-negative bacilli (GNB) are a common cause of severe hospital-acquired pneumonia . Due to changes in the health care environment and selective antimicrobial pressure, these bacteria also are becoming a more common cause of pneumonia in venues outside of the traditional hospital setting and are increasingly resistant to antimicrobial agents . Risk factors for acquisition of GNB allow the clinician to efficiently identify patients who are likely to have pneumonia due to these pathogens . Available diagnostic techniques have a limited capacity to accurately detect GNB pulmonary infection . Yet, a pathogen specific diagnosis and knowledge of local resistance patterns are quintessential elements in formulating an effective treatment plan . This article reviews the epidemiologic characteristics, pathogenesis, and current management issues of GNB pneumonia. New Microbiol, 2002 Apr, 25(2), 131 - 7 Diagnosis of paratuberculosis in naturally infected goats; Cerri D et al.; A survey was carried out to verify if an immunohistochemical method associated with agar gel immunodiffusion (AGID) will establish a firm diagnosis of caprine paratuberculosis . One hundred and thirty-six goats were tested by AGID for antibodies against Mycobacterium avium subsp . paratuberculosis at two different times: the first time 22 (19.1%) were positive and the second time 25 (18%) . One seronegative goat with severe diarrhea and 5 seropositive goats, two of which showing similar clinical signs, were sacrificed and necropsied . Samples were taken from small intestine, liver, spleen, mesenteric lymph nodes for bacteriological, histological and immunohistochemical examinations . M.a . paratuberculosis was isolated from intestine samples of 4 seropositive goats and from mesenteric lymph nodes of one seropositive goat; the microorganism was not isolated from samples of one seropositive and the seronegative animals . Ziehl Neelsen staining showed acid-fast bacilli in macrophages of the 5 seropositive animals and the immunohistochemical method for M . a . paratuberculosis detected bacterial antigen in the same samples. Quintessence Int, 2002 May, 33(5), 376 - 82 Risk and prevention of transmission of infectious diseases in dentistry; Araujo MW et al.; Health care providers are at risk for infection with bloodborne pathogens, including hepatitis B virus, human immunodeficiency virus, and hepatitis C virus . Recommended infection control practices are applicable to all settings in which dental treatment is provided . Dentists remain at low risk for occupationally acquired human immunodeficiency virus . Dental health care workers, through occupational exposure, may have a 10 times greater risk of becoming a chronic hepatitis B carrier than the average citizen . Tuberculosis is caused by Mycobacterium tuberculosis . In general, persons suspected of having pulmonary or laryngeal tuberculosis should be considered infectious if they are coughing, are undergoing cough-inducing or aerosol-generating procedures, or have sputum smears positive for acid-fast bacilli . Although the possibility of transmission of bloodborne infections from dental health care workers to patients is considered to be small, precise risks have not been quantified by carefully designed epidemiologic studies . Emphasis should be placed on consistent adherence to recommended infection control strategies, including the use of protective barriers and appropriate methods of sterilization or disinfection . Each dental facility should develop a written protocol for instrument reprocessing, operatory cleanup, and management of injuries . Such efforts may lead to the development of safer and more effective medical devices, work practices, and personal protective equipment. Dermatology, 2002, 204 Suppl 1, 15 - 20 Bactericidal activities of commonly used antiseptics against multidrug-resistant mycobacterium tuberculosis; Rikimaru T et al.; Seventeen clinical isolates of Mycobacterium tuberculosis were selected in order to study the bactericidal activities against drug-resistant M . tuberculosis . The effects of different antiseptics against multidrug-resistant M . tuberculosis (MDR-TB) were examined . Each of the test strains was cultured on the surface of an agar slant containing Lowenstein-Jensen medium . 0.05 ml of the bacillary suspension was poured into a test tube, and 0.45 ml of various antiseptics was added . After the bacilli had been exposed to the antiseptic solution with 2% human serum for various periods of incubation time, the antiseptic was inactivated by addition of 0.45 ml neutralizer, a mixture containing 10% Tween 80, 3% soybean lecithin and 0.5% sodium thiosulfate . As the results, povidone-iodine (PVP-I) at a concentration of 0.2% killed 99.9% or more of all strains tested within 30 s . All of the strains tested with PVP-I were killed almost completely within 60 s . There was no difference in bactericidal activities of PVP-I between standard strain H37Rv and MDR-TB . 99.9% or more of all strains tested were killed after exposure to 1.0% cresol for 60 s . In the case of cresol however, the exposure time of 30 s was not enough to get satisfactory effects . 2.0% glutaraldehyde needed 5 min to kill 99.99% or more of the bacilli tested, and 0.2% alkyldiaminoethylglycine hydrochloride required 60 min to do so . The results of bactericidal activities of common antiseptics against MDR-TB were similar to those against H37Rv . We conclude that the commercially available PVP-I product is a useful antiseptic against MDR-TB similar to other M . tuberculosis . Vet Pathol, 2002 Mar, 39(2), 234 - 9 Clinical, microscopic, and molecular aspects of canine leproid granuloma in the United States; Foley JE et al.; Leproid granulomas from seven dogs in the United States were evaluated . Gross characteristics included nodular and ulcerated dermal and subcutaneous lesions primarily on the caudal aspects of the pinnae and to a lesser extent on the muzzle, face, and forelimbs . In all except one dog, there was complete regression of the lesions within 6 months, either with no therapy or after surgical resection . Cytology or histopathology revealed pyogranulomatous inflammation with few to many acid-fast mycobacterial bacilli within macrophages . The organisms could not be cultivated in vitro . DNA sequencing of part of the 16S ribosomal RNA gene region revealed 99-100% homology among fragments from five of these dogs and fragments from dogs in the south Pacific . This syndrome occurs in dogs in North America and the prognosis is excellent, in contrast to the prognosis for rapid-growing or tuberculous mycobacteriosis. Int J Antimicrob Agents, 2002 May, 19(5), 361 - 70 New findings in beta-lactam and metronidazole resistant Bacteroides fragilis group; Fang H et al.; Beta-lactam antibiotics and 5-nitroimidazoles have been extensively used against anaerobic bacteria . However, antibiotic resistance is increasingly common among anaerobic Gram-negative bacilli . The classical mechanisms of resistance to beta-lactams are, (1) production of beta-lactamases; (2) alteration of penicillin-binding proteins (PBPs); and (3) changes in outer membrane permeability to beta-lactams . The 5-nitroimidazole molecule is a prodrug whose activation depends upon reduction of the nitro group in the absence of oxygen . Decreased uptake and altered reduction are believed to be responsible for metronidazole resistance . Five nim genes (A, B, C, D and E) have been identified in Bacteroides fragilis group spp . that confer resistance to 5-nitroimidazole antibiotics . Knowledge of the status and the mechanisms of resistance is critical for both the selection of antimicrobial therapy and the design of new antimicrobial agents . The purpose of this article is to review the mechanisms for and the prevalence of beta-lactam and metronidazole resistance in strains belonging to the B . fragilis group. Chest, 2002 May, 121(5), 1486 - 92 Applying sputum as a diagnostic tool in pneumonia: limited yield, minimal impact on treatment decisions; Ewig S et al.; STUDY OBJECTIVES: We evaluated the role of sputum examination in the management of patients with community-acquired pneumonia (CAP) in a primary-care hospital without microbiologic laboratory facilities . Design and interventions: A diagnostic strategy using regular collection of sputum samples, Gram staining in a local laboratory, and mailing of samples to a commercial laboratory for culture analysis . SETTING: A 200-bed primary-care hospital without subspeciality physicians . PATIENTS: One hundred sixteen consecutive patients with a diagnosis of CAP were prospectively evaluated during a 12-month period . RESULTS: Of 116 patients, 42 patients (36%) were capable of producing a sputum sample . Age > or = 75 years (odds ratio {OR}, 0.4; 95% confidence interval {CI}, 0.18 to 0.93) and prior ambulatory antimicrobial treatment (OR, 3.2; 95% CI, 1.2 to 8.4) were independent predictors of sputum production . A delay in collection and processing of sputum samples of > 24 h was present in 31% and 39%, respectively . A delay in collection yielded an increased number of Gram-negative enteric bacilli and nonfermenters (44% vs . 7%, p = 0.056) . A delay in processing was associated with an increased number of Candida spp isolates (33% vs . 9%, p = 0.16) . The overall diagnostic yield was low (10 of 116 patients, 9%) due to a limited number of valid samples (n = 23 of 42 patients, 55%) and a limited number of definitely or probably positive samples on Gram's stain and culture (n = 10 of 42 patients, 24%) . Prior ambulatory antimicrobial treatment was associated with a reduction in diagnostic yield (14% vs . 56%, p = 0.09) . The impact of diagnostic results on antimicrobial treatment decisions was minimal, with antimicrobial treatment directed to diagnostic results in only one patient . CONCLUSIONS: We conclude that in this setting representative of primary-care hospitals in Germany, sputum had a low diagnostic yield and did not contribute significantly to patient management. Curr Microbiol, 2002 Jun, 44(6), 450 - 9 Isolation and screening of brittlestar-associated bacteria for antibacterial activity; Strahl ED et al.; Many microbes associated with marine organisms have antimicrobial activity . We report the isolation of bacteria associated with Amphipholis gracillima that have broad-spectrum antibacterial activity against a number of common bacterial strains . Fifty-eight isolates of bacilli obtained from A . gracillima arm homogenates, from excised wound tissue, or from swabs of arm stumps exhibited 20-100% inhibition of one or more of 16 test bacteria at 35% salinity . Forty-one of the isolates were capable of 20-100% inhibition of one or more of 19 subject bacteria at 10% salinity at 37 degrees C . Three isolates, BE37, BE52, and BE53, exhibited the greatest range of antibacterial activity at both 10% and 35% salinity . Our results suggest that some of the bacteria associated with A . gracillima may provide the animal with chemical defenses against adverse bacterial infection . The water-soluble inhibitory chemicals produced by the bacteria could potentially function as antimicrobial compounds against human pathogenic bacteria. Pediatr Dermatol, 2002 Mar-Apr, 19(2), 122 - 6 Lichen scrofulosorum: a rare manifestation of a common disease; Thami GP et al.; Tuberculids develop as hypersensitive immunologic reactions in the skin to an occult internal focus of tuberculosis . These eruptive lesions are due to hematogenous dissemination of bacilli in a host with a high degree of immunity against Mycobacterium tuberculosis . Although rare, these specific lesions are important diagnostic markers of tuberculosis . Lichen scrofulosorum is one of the recognized tuberculids, usually seen in children and young adults . We report three children with lichen scrofulosorum; in two children it developed during treatment of tuberculosis . The appearance of lichen scrofulosorum after initiation of treatment due to a probable increase in cell-mediated immunity is emphasized. Poult Sci, 2002 Apr, 81(4), 585 - 9 Oral lavage with polyethylene glycol reduces microbial colonization in the gastrointestinal tract of broilers; Farhat A et al.; Oral lavage of 7-wk-old broiler chickens with polyethylene glycol (PEG) was conducted to induce rapid evacuation of the gastro-intestinal tract (GIT) before processing . Three groups of birds were fed ad libitum (FF), subjected to feed withdrawal 12 h before processing (FW), or received 115 mL of PEG by oral lavage 3 h before processing (PEG(L)) . The crop, a section of small intestine, and the right cecum were aseptically collected for determination of contents and Gram-negative bacilli (GNB) counts . The PEG(L) effectively cleansed the upper GIT and intestine of treated birds within 3 h before processing . However, the ceca were not completely empty for all the birds subjected to PEG(L) . The PEG(L) group had a significantly lower crop and cecal GNB concentrations than the FW group . Birds on FW and PEG(L) treatments had significantly lower GNB concentrations in the small intestine than FF birds . Polyethylene glycol resulted in complete evacuation of the upper GIT, as well as the intestine, within 3 h of use, and significantly reduced GNB concentrations. Am J Infect Control, 2002 May, 30(3), 158 - 64 Hospital-acquired meningitis in patients undergoing craniotomy: incidence, evolution, and risk factors; Reichert MC et al.; OBJECTIVES: To establish the incidence of postcraniotomy meningitis, identify etiologic agents, assess patients' medical progress in relation to both length of hospitalization and mortality, and analyze risk factors . MATERIAL AND METHODS: This study was developed at Hospital Sao Paulo, a tertiary university hospital, between August 1995 and January 1998 . We conducted a case-control trial, in which 50 pairs of patients were matched . RESULTS: An 8.9%-postcraniotomy meningitis incidence was found . Gram-negative bacilli were the most common etiologic agents isolated . Mortality among the patients was 30% . Mean hospital stay for the patients was 42.9 +/- 22.1 days; for the controls, mean hospital stay was 19.0 +/- 11.4 days (P =.00001) . Although several risk factors were identified by univariate analysis, including postoperative external ventricular shunt (OR = 2.92, CI 95% = 1.245-6.865, P =.014), remote site infection (OR = 2.85, CI 95% = 0.995-8.173, P =.051), and repeat operation (OR = 5.02, CI 95% = 1.569-16.066, P =.007), only repeat operation remained in the multivariate analysis model (OR = 3.68, CI 95% = 1.158-11.700, P =.027) . CONCLUSION: Postcraniotomy meningitis resulted in a high mortality rate and a longer hospital stay, with repeat operation identified among the risk factors. J Basic Microbiol, 2002, 42(2), 105 - 10 Toxicity of Bacillus thuringiensis and B . sphaericus to laboratory populations of Drosophila melanogaster (Diptera: Drosophilidae); Khyami-Horani H; A total of 65 samples, consisting of 8 sample types, collected from the Jordan Valley, were examined for the presence of Bacillus thuringiensis and B . sphaericus and for their toxicity against the larvae of the fruit fly Drosophila melanogaster . The frequency of samples containing toxic aerobic spore-forming bacilli was 12%; of which 21.7% belonged to B . thuringiensis and 17.4% to B . sphaericus . The B . thuringiensis populations consisted of 5 serogroups: thuringiensis (H1), entomocidus (H6), pakistani (H13), autoagglunated, in addition to a new serotype . The B . sphaericus population consisted of 3 serogroups, and belonged to serovars H5, H9, and H13.All B . thuringiensis and B . sphaericus local isolates, in addition to the reference strains B . thuringiensis kuristaki, and B . thuringiensis israelensis, showed high toxicity towards 3(rd) instar larvae of D . melanogaster . The toxic concentrations ranged between 2.0 x 10(6) and 4.4 x 10(7) viable spores ml(-1). Childs Nerv Syst, 2002 Apr, 18(3-4), 118 - 23 Epub 2002 Mar 22. Tuberculous brain abscess: clinical presentation, pathophysiology and treatment (in children); Kumar R et al.; BACKGROUND: Tubercular brain abscess (TBA) is a rare manifestation of CNS tuberculosis . It is characterised by an encapsulated collection of pus, containing viable tubercular bacilli without evidence of tubercular granuloma.PRESENTATION AND HISTORY: Patients may present with features of raised intracranial pressure and focal neurological deficit commensurate with the site of the abscess . A history of pulmonary tuberculosis may be present, as documented in one of our six cases; three of our six children developed TBA despite 3-weeks to 12-month courses of antitubercular chemotherapy prescribed for post-TBM hydrocephalus.DIAGNOSIS: Contrast CT head, MRI, MR spectroscopy is helpful in making the diagnosis and planning the treatment . TBA may be unilocular or multilocular on contrast CT scan . A relatively long clinical history and an enhancing capsule with thick wall are suggestive of TBA . Pyogenic abscess, however, has a thin rim on contrast CT . The capsule of TBA is formed of vascular granulation tissue containing acute and chronic inflammatory cells, particularly polymorphs . Proof of tubercular origin must be demonstrated either by presence of acid fast bacilli in culture or staining of pus or wall.TREATMENT: Treatment options include simple puncture, continuous drainage, fractional drainage, repeated aspiration through a burr hole, stereotactic aspiration and total excision of the abscess . Total excision usually becomes necessary in multilocular noncommunicating and thick-walled abscesses . Antitubercular therapy is the mainstay of management . The development of fulminant tubercular meningitis is sometimes problematic following surgical excision of TBA, as seen in one of our four operated cases . Mortality is reported to be high despite progress in treatment, while five of the six children treated by us responded well to the treatment. Ann Plast Surg, 2002 May, 48(5), 557 - 61 Nonhealing ulcerative mass of the elbow: do not forget tuberculosis; Ayhan S et al.; Skeletal tuberculosis is a rare condition and is seen in only 1 to 2% of all cases of tuberculosis . The authors present a 69-year-old white woman with tuberculosis of the left elbow joint whose disease was suspicious for synovial sarcoma . Skeletal tuberculosis usually conflicts with neoplastic or inflammatory diseases . One should remember the possibility of bone-joint tuberculosis and send biopsy specimens for culture to determine the presence of acid-fast bacilli . However, neither culture nor polymerase chain reaction nor histological examination may be capable of showing the bacilli . Only a suspicion may be enough . The treatment protocol is usually a combination of surgical debridement and multidrug antituberculous chemotherapy. Curr Opin Infect Dis, 2001 Dec, 14(6), 711 - 5 Evidence for antibiotic cycling in control of resistance; Pujol M et al.; There is growing concern about the increasing rates of resistance among human pathogens . These high rates of resistance, which are a consequence of antibiotic misuse, highlight the need for a thorough revision of strategies that deal with the proper use of antibiotics . The so-called 'optimal use of all antibiotics', restriction guidelines and use of a combination of antibiotics are well established strategies in most hospitals but new potential strategies, such as dosage optimization and antibiotic cycling, require further study and evaluation . Cycling antibiotic therapy consists of the scheduled replacement of one antibiotic for another, in order to avoid the development of bacterial resistance . Initial studies suggest that this strategy could be useful in reducing the rates of bacterial resistance as well as the incidence of nosocomial infections caused by Gram-negative bacilli in intensive care unit patients . This strategy, however, does not prevent antibiotic misuse and needs to be applied in a complete antibiotic policy program. Clin Orthop, 2002 May, (398), 107 - 13 Tuberculosis of the foot and ankle; Dhillon MS et al.; Tuberculosis of the foot and ankle is an uncommon presentation of skeletal tuberculosis . The uncommon site, lack of awareness, and ability to mimic other disorders clinically and on radiographs, leads to diagnostic and therapeutic delays . In the early stages and when the disease is limited to bone, medical treatment leads to excellent healing and limited residual disabilities . Joint involvement occurs because of spread from a periarticular bony focus, and in the midfoot, the disease may spread to involve all the interconnected joints, leading to a stiff foot and residual deformities . Of 74 cases reviewed, the calcaneus was involved most commonly, followed by infection of the midtarsal, Lisfranc joints, and ankle . The most common radiologic finding is that of osteoporosis, which may be intense: cancellous bone involvement may present as a cystic lesion with or without sequestrum . Computed tomography scans and magnetic resonance imaging are helpful examinations . Because the disease is paucibacillary, a positive acid fast bacilli culture is rare and the diagnosis usually is confirmed by obtaining granulomatous tissue on biopsy . The treatment basically is medical, with surgical intervention being reserved for patients with intractable disease or as a salvage procedure for patients with deformed hindfoot joints. Appl Microbiol Biotechnol, 2002 Mar, 58(4), 547 - 53 Bacillus naphthovorans sp . nov . from oil-contaminated tropical marine sediments and its role in naphthalene biodegradation; Zhuang WQ et al.; A Bacillus sp., designated as strain MN-003, was isolated as the dominant cultivatable naphthalene-degrading organism from oil-contaminated tropical marine sediments . Strain MN-003 is strictly aerobic, rod-shaped, Gram-positive, catalase positive, oxidase negative, and forms endospores . Strain MN-003 grew at salinities ranging from 0.28 to 7.00% and temperatures ranging from 15 to 41 degrees C . Phylogenetic analyses reveal that strain MN-003 is most similar to Bacillus sp . VAN14, with a 16S rRNA sequence identity of 97.9% . Based on taxonomic and 16S rRNA data, strain MN-003 was named Bacillus naphthovorans sp . nov . When grown with naphthalene as sole carbon source, strain MN-003 had a maximal specific growth rate (mu(max)) of 0.32 +/- 0.03 h(-1), and a half-saturation constant (K(S)) of 22.3 +/-4.2 microM . A batch study of the tropical marine sediments enriched with naphthalene showed that cells of the Bacillus genus grew to become dominant members of the microbial community . The bacilli comprised 39.5 +/- 6.5% of the microbial fraction after 20 days of enrichment. Infect Immun, 2002 May, 70(5), 2566 - 75 Glucan is a component of the Mycobacterium tuberculosis surface that is expressed in vitro and in vivo; Schwebach JR et al.; The outermost layer of Mycobacterium tuberculosis is composed primarily of two polysaccharides, glucan (GC) and arabinomannan . To analyze the surface polysaccharide composition of M . tuberculosis, we generated a monoclonal antibody (MAb) that binds M . tuberculosis GC and is known as MAb 24c5 . Immunofluorescence and whole-mount immunoelectron microscopy indicated that GC is on the outermost portion of the bacteria . M . tuberculosis strains Erdman and CDC 1551 were analyzed for their ability to bind MAb 24c5 after in vitro growth in media with and without the detergent Tween 80 . MAb 24c5 bound to Erdman and CDC 1551 at all culture times with only slightly greater apparent affinity after extended culture in the absence of Tween 80, indicating that a stable amount of GC polysaccharide antigen is associated with the cell surface of M . tuberculosis . An enzyme-linked immunosorbent assay indicated that GC is antigenically similar to glycogen, and the amount of GC antigen increased in the media of M . tuberculosis cultures grown either with or without the detergent Tween 80 . Other nontuberculosis mycobacteria have antigenically similar GCs on their surfaces after in vitro growth . Inoculation of mice with live bacilli but not inoculation with dead bacilli elicited a strong antibody response to GC consistent with production of this antigen in vivo . Our results provide a more comprehensive picture of the M . tuberculosis cell envelope and the conditions that allow expression of M . tuberculosis GC. Zhonghua Jie He He Hu Xi Za Zhi, 2002 Jan, 25(1), 21 - 4 {Experimental study on prevention of diabetes complicated with tuberculosis by Mycobacterium vaccae}; Chen H et al.; OBJECTIVE: To study if Mycobacterium vaccae has any effect in prevention of rats with diabetes from tuberculosis . METHODS: Wistar rats with diabetes which were produced by injection of streptozotocin one week before were divided into four groups . Mycobacterium vaccae was injected into Wistar rats with diabetes and one month later H(37)R(v) was injected intravenously . The rats were sacrificed six weeks later to observe pathomorphologic changes in lung tissues . Indexes for evaluation included quantitative culture of Mycobacterium tuberculosis of lung tissue, tubercular lesion, count of Mycobacterium tuberculosis in alveolar macrophages and histopathological changes . RESULTS: Pathological change index of tubercular lesion, quantitative culture of Mycobacterium tuberculosis in lung tissue, count of Mycobacterium tuberculosis in alveolar macrophages were 2.5 +/- 0.7, (4.1 +/- 0.6) x 10(4) cfu, 2.6 +/- 0.9 respectively in group injected with Mycobacterium vaccae, while 3.3 +/- 0.5, (9.9 +/- 1.0) x 10(4) cfu, 7.2 +/- 0.7 respectively in the control group . Statistically significant differences were found between the two groups (P < 0.05, < 0.01, < 0.01 respectively) . The histopathological changes of lung tissue in group of diabetes complicated with tuberculosis revealed that the lesions were predominant with necrosis, while in group injected with Mycobacterium vaccae, the lesions showed proliferation mainly . This indicated that Mycobacterium vaccae could decrease the damage to the lung tissue of the rat with diabetes by tubercle bacilli . CONCLUSION: Mycobacterium vaccae might play a role in prevention of rat with diabetes from tuberculosis. Mikrobiol Z, 2002 Jan-Feb, 64(1), 31 - 6 {Screening of collagenase and keratinase producers}; Ivanko OV et al.; The study of the capacity of 310 strains of microorganisms from different taxonomic groups (40 bacilli, 43 yeast, 105 streptomycetes, 12 micromycetes) to hydrolyze collagen and keratin allowed to establish that the highest level of collagenase (KA) and keratinase (KerA) activity is inherent in representatives of streptomycetes . Two strains of Streptomyces sp.--1349 and 1382 with the highest KA and KerA indices--1.9 and 1.85 un./mg of protein, respectively, have been chosen . It has been established that collagenase activity in the medium without adding the inducers decreases 4.76 times, while that of keratinase--5.71 times, i.e . the above enzymes are inducible . The investigation of the spectrum of activities has demonstrated that the both strains possess low level of the general proteolytic and elastase activities and high level of collagenase and keratinase activities . Partial purification of the enzyme complex of Streptomyces sp . 1349 by the successive precipitation by ammonium sulphate with 30, 60 and 80% saturation and a single precipitation by ammonium sulphate with 80% saturation helped to increase the level of KA 5.6-5.9 times, and that of KerA--4.2-4.5 times. Hunan Yi Ke Da Xue Xue Bao, 1999, 24(2), 150 - 2 {Intestinal bacterial translocation in patients with biliary tract diseases}; Yu M et al.; To determine whether intestinal bacterial translocation occurs in man, the authors cultured the tissues of mesenteric lymph nodes(MLNs), bile, portal and peripheral venous blood obtained prior to and during operation in 35 patients with biliary diseases . No positive peritoneal swab, portal blood and peripheral blood culture were shown . Thirteen of 20 patients with biliary obstruction (65%) had bacteria in their MLNs, while no positive MLN culture was found in 12 patients without biliary obstruction . The most common bacteria recovered from the MLNs were Gram-negative enteric bacilli . Thus, it is considered that extrahepatic biliary obstruction may induce intestinal bacterial translocation in man. Int J Tuberc Lung Dis, 2002 Mar, 6(3), 270 - 2 Washing of new microscopic glass slides in dichromate solution does not influence sputum AFB smear results; Selvakumar N et al.; SETTING: Microscopy centres in Tiruvallur District, Tamil Nadu, India, implementing DOTS . OBJECTIVE: To know whether washing new glass slides in dichromate solution is essential for effective sputum acid-fast bacilli microscopy . METHODS: Two direct smears were prepared from each of 1750 sputum samples . One was made on dichromate solution-cleaned new glass slides and the other was made on unwashed new glass slides . The smears were blinded and examined . RESULTS: Of the 1750 specimens, 13.5% and 13.08% were positive for AFB using washed and unwashed slides, respectively (P = 0.12) . The concordance between these two (including one grade above and one below) was 98.7% . CONCLUSION: Washing of new glass slides in dichromate solution is not essential for AFB microscopy. Int J Tuberc Lung Dis, 2002 Mar, 6(3), 222 - 30 Optimal tuberculosis case detection by direct sputum smear microscopy: how much better is more? Van Deun A, Salim AH, Cooreman E, Hossain MA, Rema A, Chambugonj N, Hye MA, Kawria A, Declercq E. SETTING: A tuberculosis control project in Bangladesh . OBJECTIVE: To define the efficiency of numbers of microscopic fields screened and the sputum collection scheme used for diagnostic smear examination . DESIGN: Quality controllers noted cumulative numbers of acid-fast bacilli per 100 fields screened . The incremental diagnostic yield of different sputum sampling strategies was determined . Doubtful series were re-checked and/or further samples examined . RESULTS: Acid-fast bacilli were found in 99.6% of 1412 positive and in 79.3% of 576 scanty slides in the first 100 fields . Examination of a third specimen yielded a maximum of 2.7% positives incrementally . The most efficient strategy, using three morning specimens, yielded 94.2% positives on the first and 1.0% on the third sputum; although 10% of suspects did not return, only 1.5% of the positives were among them and more cases were confirmed and treated . The positive predictive value of a single positive or scanty smear was very high (99.2%) . CONCLUSIONS: Reading more than 100 fields per smear or examining a third sputum has insufficient marginal returns to justify the workload . Examining morning samples only is more efficient, and their collection does not necessarily inconvenience patients . Treatment can be started on the basis of one positive smear . Provided that a well functioning system of smear-microscopy quality control is in place, we propose a strategy based on examination of two morning sputum samples for negative suspects, with the diagnosis based on a single positive result. Int J Tuberc Lung Dis, 2002 Feb, 6(2), 91 - 7 Relation of grading of sputum smears with clinical features of tuberculosis patients in routine practice in Sudan; El-Sony A et al.; SETTING: Health services in Khartoum, Red Sea, Gadarif, Kassala, Bahr el Jebel, Gezira and North Kordofan States of Sudan . OBJECTIVE: To investigate the association of presenting symptoms and clinical history with grade of sputum smear positivity in tuberculosis patients . METHODS: The 5338 tuberculosis suspects aged 15 to 49 years who consulted between March 1998 and March 1999 underwent sputum smear microscopy, with smears graded by a standardised method . Patients who gave consent had a structured interview concerning the nature and duration of their symptoms and whether they had a sick relative at home . Statistical analysis determined the association of symptoms and home characteristics with the results of smear examination . RESULTS: A total of 514 suspects (9.6%) demonstrated acid-fast bacilli: 45 (8.8%) grade +1, 167 (32.5%) grade +2 and 302 (58.8%) grade +3 . Most of the patients had a duration of symptoms of 6-9 weeks, while 100 had symptoms of more than one year's duration, many (n = 47) with other chronic respiratory diseases . Multiple chest symptoms were positively, and duration of symptoms negatively associated with grade of positivity (P = 0.018 and 0.028, respectively) . A high grade of smear positivity (+3) and the longest duration of symptoms, among those reporting symptoms of less than one year's duration, were significant predictors of the presence of a sick household member (OR = 1.99, 95%CI 1.12-3.55; OR = 1.004, 95%CI 1.000-1.008) . CONCLUSION: This study demonstrates a relation between the grade of smear positivity and the clinical features of tuberculosis patients. Int J Tuberc Lung Dis, 2002 Feb, 6(2), 150 - 4 Mycobacterium tuberculosis typing: usefulness of DRE-PCR to confirm cross-contamination in the mycobacteriology laboratory of a general reference hospital for AIDS; Filho LA et al.; In this study two molecular typing methods, a simple double repetitive element PCR-based assay and the standardized restriction fragment length polymorphism (RFLP), were used to confirm cross-contamination in the mycobacteriology laboratory . Clinical specimens from 12 patients, submitted for acid-fast bacilli stain smear and processed for culture in Lowenstein-Jensen on the same day, resulted in positive bacterioscopy (+++) and confluent growth only for one of the patients . The specimens from all the other patients but two were smear-negative and culture-positive, with one or two colonies . None of them had clinical symptoms and radiological findings for active tuberculosis (TB) . The suspicion of false-positive cultures arose when a health care worker who had had a PPD skin test conversion, claimed to be healthy and had no TB symptoms, was found to have a positive sputum culture . DRE-PCR demonstrated that all nine cultures typed belonged to one cluster, further confirmed by RFLP . Although DRE-PCR has been found to be poorly reproducible, it has enough discriminatory power to be useful for rapid epidemiological investigation in selected settings. Int J Tuberc Lung Dis, 2002 Feb, 6(2), 143 - 9 A retrospective study for the outcome of pulmonary resection in 49 patients with multidrug-resistant tuberculosis; Park SK et al.; BACKGROUND: Outcome of treatment using only chemotherapy for multidrug-resistant tuberculosis is usually considered not to be satisfactory . The combination of chemotherapy with surgical treatment has been producing higher acid-fast bacilli (AFB) negative sputum conversion and longer survival rates . This treatment strategy may be the solution for patients with multidrug-resistant tuberculosis . MATERIALS AND METHODS: A retrospective review was performed of the medical records and laboratory findings of 49 patients with multidrug-resistant tuberculosis among 130 patients who underwent pulmonary resection for pulmonary tuberculosis between January 1995 and December 1999 at National Masan Tuberculosis Hospital, Korea . RESULTS: The mean number of drugs to which the patients were resistant was 4.5 . Patients had a mean age of 35 years . Cavitary lesions on plain chest X-ray were shown in 43/49 patients (87.8%); 31 had positive sputum cultures preoperatively (63.3%) . The surgical techniques used were as follows: 12 pneumonectomies, 28 lobectomies, seven lobectomies with segmentectomies or wedge resections, one wedge resection and one cavernoplasty . The AFB negative sputum conversion rate was 93.5% with continuous postoperative chemotherapy . There were no deaths after surgery . Postoperative complications that developed were six cases of air leakage over a week, one of postoperative bleeding and one of wound infection . CONCLUSIONS: This study demonstrated the effectiveness of pulmonary resection with postoperative chemotherapy in cases of multidrug-resistant tuberculosis . Although there are different ideas about indications for surgery and the length and content of postoperative drug regimens, pulmonary resection should be considered an effective measure in combination with chemotherapy for treatment of multidrug-resistant pulmonary tuberculosis. Int J Tuberc Lung Dis, 2002 Jan, 6(1), 47 - 54 Quality assessment of sputum transportation, smear preparation and AFB microscopy in a rural district in Malawi; Mundy CJ et al.; SETTING: Ntcheu District, Central Region of Malawi . OBJECTIVES: To assess 1) the feasibility of introducing simple internal quality control procedures for acid-fast bacilli (AFB) microscopy, and 2) the quality of the district sputum smear microscopy service . DESIGN: A simple internal quality control system was piloted in which district laboratory staff assessed: 1) specimen suitability, 2) time between sputum submission and smear examination, 3) smear preparation and staining, and 4) microscopy . Actual times for processing specimens were compared with recommended times . External quality validation was carried out . RESULTS: Of 4805 sputum specimens: 1) documentation was complete in 95%, 2) 93% reached the laboratory within 7 days of collection, 3) 96% of smears were well prepared and stained, and 4) 97% concordance (96.4% smear-positive and 97.6% smear-negative) was demonstrated when 208 smears were re-examined by a second technician . The aggregate index of reliability was 86% . The mean time spent on microscopic examination was 3.8 minutes, compared with the recommended time of 10 minutes . When all smears from 164 patients were assessed externally, 98.2% concordance (98.1% smear-positive and 98.2% smear-negative) was demonstrated . False smear-negative and smear-positive rates were less than 2% each . CONCLUSION: District laboratory staff were able to incorporate simple quality control procedures for AFB microscopy into their routine practice, resulting in a reliable service . The lessons learnt are widely relevant and potentially useful for implementation of a national quality assurance scheme. Mol Microbiol, 2002 Feb, 43(3), 717 - 31 Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling; Betts JC et al.; The search for new TB drugs that rapidly and effectively sterilize the tissues and are thus able to shorten the duration of chemotherapy from the current 6 months has been hampered by a lack of understanding of the metabolism of the bacterium when in a 'persistent' or latent form . Little is known about the condition in which the bacilli survive, although laboratory models have shown that Mycobacterium tuberculosis can exist in a non-growing, drug-resistant state that may mimic persistence in vivo . Using nutrient starvation, we have established a model in which M . tuberculosis arrests growth, decreases its respiration rate and is resistant to isoniazid, rifampicin and metronidazole . We have used microarray and proteome analysis to investigate the response of M . tuberculosis to nutrient starvation . Proteome analysis of 6-week-starved cultures revealed the induction of several proteins . Microarray analysis enabled us to monitor gene expression during adaptation to nutrient starvation and confirmed the changes seen at the protein level . This has provided evidence for slowdown of the transcription apparatus, energy metabolism, lipid biosynthesis and cell division in addition to induction of the stringent response and several other genes that may play a role in maintaining long-term survival within the host . Thus, we have generated a model with which we can search for agents active against persistent M . tuberculosis and revealed a number of potential targets expressed under these conditions. Pneumonol Alergol Pol, 2001, 69(9-10), 564 - 7 {Tuberculous peritonitis as still probable cause of ascites}; Ucinska R et al.; A 38-year-old man was admitted to hospital because of ascites, fever, weakness, abdominal pain . Chest x-ray revealed old post-tuberculous opacities in the left subclavicular region and fluid in left pleural cave . Cirrhosis of the liver and malignant disease were suspected . Treatment with antibiotics and evacuation of pleural fluid caused short-lasting improvement . After 6 weeks of diagnostic procedures parenchymal infiltrations in left lung were confirmed . In sputum tuberculous bacilli were found . Tuberculous peritonitis was confirmed histopathologically . Antituberculous treatment was successful. Nihon Kokyuki Gakkai Zasshi, 2002 Jan, 40(1), 35 - 9 {A case of mixed pulmonary infection with Mycobacterium tuberculosis and M . intracellulare due to familial prevalence}; Kobashi Y et al.; A 76-year-old woman was admitted to our hospital because of an abnormal shadow on chest radiography and a suspected familial prevalence of pulmonary tuberculosis . Her son had previously been admitted to our hospital with pulmonary tuberculosis and tuberculous pleuritis . In the present case, a diagnosis of pulmonary tuberculosis and atypical pulmonary mycobacteriosis was made on the basis of detection of both Mycobacterium tuberculosis and M . intracellulare several times in a sputum culture of anti-fast bacilli . Restriction fragment length polymorphism (RFLP) analysis was then performed for both the woman and her son . The RFLP analysis revealed the same pattern in both mother and son, and confirmed that this was a case of mixed pulmonary infection passed from son to mother. Comp Med, 2001 Apr, 51(2), 171 - 5 Atypical piscine mycobacteriosis in Japanese medaka (Oryzias latipes); Sanders GE et al.; Japanese medaka, (Oryzias latipes), small, freshwater, tropical cyprinodonts, are principally used for toxicologic and carcinogenicity assays, but are finding more applications in developmental genetic and biological research . An increase in mortality began in brood stock of adult medaka that had been shipped and housed separately by sex . Initially, mortality averaged one fish daily and began in females two weeks after they were received . Cohabitation began eight weeks after arrival . After four to six weeks of cohabitation in different spawning aquaria, mortality was observed in males . Clinical signs of disease included loss of scale luster and color, with subsequent blanching of dorsal flank musculature, small raised nodules on various external surfaces, emaciation, fraying of fin tips, and equilibrium disturbances . Histologic examination of affected adults revealed multi-organ granulomatous inflammation with intracellular acid-fast bacilli . Specimens from 46 juvenile medaka that were spawned from affected adults, were submitted for culture and histologic evaluation . Of 18 fish, two had lesions similar to those of adults . The organism isolated from the remaining fish was identified as Mycobacterium fortuitum . Due to atypical rapid progression of disease, spread of M . fortuitum to progeny, and poor prognosis, the entire colony was euthanized. Niger Postgrad Med J, 2001 Dec, 8(4), 199 - 202 Tuberculosis myocarditis: a case report; Danbauchi SS et al.; A 35-year old man presented with fever, weight loss, drenching night sweats and symptoms of cardiac failure for three months . Examination revealed wasting, peripheral oedema, bilateral pleural effusion and constrictive pericarditis . A diagnosis of constrictive pericarditis with bilateral pleural effusion probably due to tuberculosis was made . Human immunodeficiency virus antibodies and six sputum for acidfast bacilli were negative . Electrocardiograph revealed low voltages globally and echocardiography showed global myocardial hypokinesia . He had pericardiectomy, pericardial and pleural histology was non-specific inflammatory reaction but myocardial histology showed granulomatous changes of tuberculous myocarditis . We suggest that in experienced hands myocardial biopsy could be useful in making the diagnosis. J Clin Microbiol, 2002 Apr, 40(4), 1219 - 24 Relatively alcohol-resistant mycobacteria are emerging pathogens in patients receiving acupuncture treatment; Woo PC et al.; Acupuncture has been gaining popularity as a form of alternative medicine . In the past, only blood-borne viruses and anecdotal reports of bacterial infections have been associated with acupuncture . We report on four patients with mycobacterial infections complicating acupuncture who were encountered in a 2-year period . All had clinical and/or radiological lesions at acupuncture point- and meridian-specific locations . There was no other history of trauma or other clinical foci of infections, and the chest radiographs were normal . Histological studies of biopsy specimens of all four patients showed changes compatible with chronic inflammation, with granulomatous inflammation present in three patients and acid-fast bacilli present in two . Conventional biochemical tests and whole-cell fatty acid analysis for identification were inconclusive for all four nonpigmented mycobacteria recovered from tissue biopsies . 16S rRNA gene sequencing showed that the strains from two patients were Mycobacterium chelonae and that those from the other two were Mycobacterium nonchromogenicum . Alcohol resistance assay using the quantitative suspension test revealed that all four strains showed prolonged survival in 75% alcohol compared to other skin flora . Mycobacterial infections transmitted by acupuncture are an emerging problem . A high index of suspicion is essential to recognize this clinical syndrome, and strict implementation of proper infection control guidelines for acupuncture is mandatory. Infect Control Hosp Epidemiol, 2002 Mar, 23(3), 141 - 4 Preventing nosocomial transmission of pulmonary tuberculosis: when may isolation be discontinued for patients with suspected tuberculosis? Siddiqui AH, Perl TM, Conlon M, Donegan N, Roghmann MC. OBJECTIVE: The Centers for Disease Control and Prevention and the American Thoracic Society recommend obtaining cultures of at least three sputum specimens for acid-fast bacilli (AFB) from patients in whom tuberculosis (TB) is suspected . On the basis of this, most hospitals isolate patients with suspected TB for 3 days or more until three smear (not culture) results are negative . Our objective was to evaluate the predictive value and sensitivity of these smears . DESIGN: Observational study . SETTING: Four urban medical centers . METHODS: The posttest probability of TB given sequential negative AFB smears from 274 patients isolated for suspected TB and the sensitivity of sequential AFB smears from 209 patients with positive results on culture for pulmonary TB were measured . RESULTS: The posttest probabilities of having TB given one, two, and three negative AFB smears were low: 1.1% (3 of 265; 95% confidence interval {CI95}, 0.23% to 3.27%), 0.4% (1 of 262; CI95 0% to 2.1%), and 0% (0 of 260; CI95, 0% to 1.4%), respectively . Among the 209 patients with positive results on culture for pulmonary TB, 169 (81%) had an expectorated sputum specimen sent, of which 91 (54%) were positive for AFB . Forty (24%) of the 169 patients had a second expectorated sputum specimen sent after the results of the first specimen were negative; only 6 (15%) of these had positive AFB smears . None of the 10 patients in whom the first two expectorated sputum samples yielded an AFB smear without an organism had a third AFB smear that was positive . CONCLUSION: Unless there is high clinical suspicion of pulmonary TB in a specific patient, the use of three AFB smears on expectorated sputa is a rational approach to discontinuing isolation for patients with suspected TB. Acta Cytol, 2002 Mar-Apr, 46(2), 386 - 8 Cytodiagnosis of erythema nodosum leprosum . A case report; Anshu et al.; BACKGROUND: The application of cytology in leprosy has been restricted to the evaluation of morphologic and bacterial indices by slit skin smears to facilitate diagnosis of cases according to the Ridley-Jopling scale . Isolated reports have now documented the use of fine needle aspiration cytology (FNAC) in the diagnosis of leprosy . CASE: A 45-year-old male presented with the abrupt onset of multiple nodular eruptions all over the body . The clinical diagnosis was Sweet's syndrome . FNAC showed numerous neutrophils in a background of foamy macrophages . Special stains revealed the presence of a large number of fragmented acid-fast bacilli in the smears . A diagnosis of erythema nodosum leprosum (ENL) was made on FNAC . CONCLUSION: The presence of neutrophils in a characteristic milieu of foamy macrophages is seen in lesions of ENL . Such a picture should prompt the cytologist to use a modified Ziehl-Neelsen stain to demonstrate acid-fast bacilli, as ENL can present as an acute episode in patients without a previous diagnosis of leprosy. Acta Crystallogr D Biol Crystallogr, 2002 Apr, 58(Pt 4), 615 - 21 Epub 2002 Mar 22. Specificity of TRAP-RNA interactions: crystal structures of two complexes with different RNA sequences; Hopcroft NH et al.; The trp RNA-binding attenuation protein (TRAP) regulates expression of the tryptophan biosynthetic genes in bacilli by binding to the leader region of the nascent trp operon mRNA . When activated by binding tryptophan, the 11-subunit circular TRAP molecule binds to a target sequence consisting of 11 (G/U)AG repeats, separated by two or three variable 'spacer' nucleotides . Reported here are two crystal structures of TRAP bound to RNAs containing 11 GAG repeats separated by UU and CC spacer nucleotides, determined at 1.75 and 2.50 A resolution, respectively . These show the spacer regions of the RNA molecules to be highly flexible, making no direct hydrogen-bonding contacts with the protein . Comparison of these structures with the previous structure of TRAP bound to (GAGAU)(10)GAG RNA, in which the spacer nucleotides stack with each other close to the protein surface, shows that the RNA can adopt different conformations depending on the sequence of the spacer regions . This gives insight into the structural basis of the specificity of TRAP and into the mechanism of binding. Tuberculosis (Edinb), 2002, 82(1), 31 - 6 Interaction of Mycobacterium tuberculosis with human respiratory epithelial cells (HEp-2); Reddy VM et al.; SETTING: Mycobacterium tuberculosis (MTB) is known to adhere to, invade, multiply inside, and modulate respiratory epithelial cell functions . However, the mode and the molecules involved in the interaction of MTB with respiratory cells are not known . OBJECTIVE: To study post-adherence morphological changes in human respiratory epithelial cells and identify MTB components involved in the binding to these cells . DESIGN: The mechanism of interaction of MTB human respiratory epithelial cells (HEp-2) was investigated by incubating MTB with HEp-2 cells, whereupon the morphological changes were examined under scanning electron microscopy . MTB components involved in the interaction with HEp-2 cells were identified by probing Western blots of mycobacterial sonicates with biotinylated HEp-2 extracts . RESULTS: MTB readily bound to the surface of HEp-2 cells . Adherence of tubercle bacilli on the surface caused membrane perturbation resulting in increased surface membrane projections, particularly towards the margins of the cells . Long thin epithelial membrane projections formed loops around the bacilli holding them on the surface . Membrane projections fused to form a web in which the bacilli were entrapped . Concomitant membrane cavitations seen beneath the site of attachment of the bacilli conceivably caused internalization of the organisms . At least five MTB proteins ( approximately 112, 35, 28, 21 and 15 kDa) specific for HEp-2 cells were identified . Of these, the 28 kDa protein was the predominant HEp-2-binding protein and was found to be heparin-binding hemagglutinin (HBHA) . While M . bovis BCG strain showed the same five HEp-2-binding proteins, M . smegmatis, displayed only one (31 kDa) HEp-2-specific protein . CONCLUSION: MTB binds to HEp-2 cells through multiple proteins, and the binding causes membrane perturbations that result in internalization of the organisms . Mikrobiologiia, 2002 Jan-Feb, 71(1), 37 - 48 {Comparative study of the elemental composition of vegetative and dormant microbial cells}; Muliukin AL et al.; X-ray microanalysis showed that vegetative cells, viable resting forms, and nonviable forms (micromummies) of the bacteria Bacillus cereus and Micrococcus luteus and the yeast Saccharomyces cerevisiae differ in the contents of bioelements S, P, Ca, and K and the Ca/K and P/S ratios . Viable resting forms (cystlike refractory cells and bacillar endospores) had more calcium and less phosphorus and potassium than vegetative cells, the difference being higher for bacilli than for micrococci and yeasts . The distinctive feature of all viable resting microbial forms was their low P/S ratios and high Ca/K ratios . The differences revealed in the cellular content and ratios of bioelements probably reflect changes in ionic homeostasis accompanying the transition of vegetative microbial cells to the dormant state . Relevant potassium parameters indicate that the membranes of viable resting forms retain their barrier function . At the same time, the nonviable forms, even morphologically intact, of B . cereus and S . cerevisiae exhibited an anomalously low content of potassium, while those of M . luteus had an anomalously high content of this element . This suggests that the cellular membranes of micromummies lose their barrier function, which results in a free diffusion of potassium ions across the membranes . The possibility of using the elemental composition parameters for quick analysis of the physiological state of microorganisms in natural environments is discussed. Tunis Med, 2001 Oct, 79(10), 491 - 7 {Basis and guidelines for empirical antibody therapy in the management of community-acquired pneumonia}; Louzir B et al.; The choice of the antibiotic should be based on clinical, chest X-ray radiography and essentially microbiologic criteria . Incurrent practice treatment is more often empiric based on epidemiologic characteristics of the microbiologic agents and the particularities of each patient . A satisfactory approach requires, in addition, a perfect knowledge of different available antibiotics and the resistance of certain etiologic pathogens to these latters . because S . Pneumoniae is the most frequently encountered pathogen, B lactams and especially Penicillin G . and amoxicillin remain the most useful drugs prescribed for adults with risk factors . However, in advanced age patients and those with comorbidity, the spectrum should be enlarged and should include, besides S . Pneumoniae, H . influenzae and other Gram negative bacilli . When the pneumonia is more severe and has required hospitalization, the antimicrobial therapy must be immediate, multiple and large . The causal agent must be searched for desperately, so that the antimicrobial therapy can be adapted secondary to the results of the antibiogram. Kekkaku, 2002 Feb, 77(2), 73 - 7 {A case of disseminated tuberculosis requiring extended period for the identification of Mycobacterium tuberculosis on culture}; Ashino J et al.; A 80-year-old male visited an outpatient department of a nearby hospital complaining of fever, cough, and poor appetite on June 2000 . The patient was diagnosed as bacterial pneumonia and was treated with antibiotics although specific cause could not be identified . After one month, he was hospitalized due to lack of improvement . After admission, acid-fast bacilli (AFB) was found from the bronchial washing . The patient was then transferred to our hospital . Upon admission, sputum smear examination was positive for AFB and MTB was confirmed by PCR . Therapy was initiated with INH 300 mg, RFP 450 mg, EB 1000 mg, and PZA 1000 mg, orally daily . However, on the day following the admission, he became unconscious . Brain MRI showed several small granulomas on the cortex of the bilateral anterior and temporal brain . Although AFB was not detected from the cerebrospinal fluid, tuberculous meningitis was suspected and steroid was given . Nine days after admission, the patient died due to tuberculous meningitis . The isolation of MTB had been attempted on Ogawa culture medium using patient's sputum and liquor, and it took 14 weeks to find colony growth both from sputum and liquor . In the autopsy, numerous granulomas were detected in his lung, liver, kidney, and pancreas . These findings indicate that disseminated growth of MTB occurred in vivo in spite of very slow growth of MTB in vitro. Kekkaku, 2002 Feb, 77(2), 51 - 9 {Tuberculosis in the patients undergoing haemodialysis in Japan, 1996}; Sasaki Y et al.; We conducted a questionnaire survey on patients undergoing haemodialysis about the present situation of tuberculous incidence . They are immunocompromised hosts and are said to be at high risk of developing tuberculosis in many reports . (1) DESIGN Of the 167,192 patients on haemodialysis registered on December 31, 1996 in Japan, 71,411 patients were available for the questionnaire survey . Of the 2,893 hospitals used as the study subjects, 1,108 hospitals gave satisfactory replies . Of them, 141 hospitals reported that they had patients with tuberculosis in 1996, and 79 cases were collected by the detailed survey on tuberculosis patients conducted later . They included 45 male cases, 34 female cases for tuberculosis of all forms, 28 male cases, 15 female cases for pulmonary tuberculosis (PTB), 13 male cases, 4 female cases for tuberculosis bacilli positive pulmonary tuberculosis (TB positive PTB), and 17 male cases, 19 female cases for extrapulmonary tuberculosis . (2) RESULTS: In tuberculosis of all forms, the number of observed patients (O) against the number of patients expected (E) was calculated, and the standardized patients ratio (O/E ratio) was computed . It was 1.55 for male, 2.79 for female and 1.99 for total . The incidence of tuberculosis haemodialysis patients was significantly higher compared with the general population (p < 0.01) . As to PTB, the O/E ratio was 1.01 for male, 1.40 for female and 1.16 for total; the incidence of PTB was not significantly higher compared with the general population . With TB positive PTB, the O/E ratio was 0.96 for male, 0.80 for female and 0.97 for total, and no significant difference was found . As for extrapulmonary tuberculosis, the O/E ratio was 13.45 for male, 13.07 for female and 12.97 for total; the incidence of extrapulmonary tuberculosis in haemodialysis patients was significantly higher (p < 0.01), but it was lower than these reported in the past literature . The seventy nine cases consisted of 52 primary treatment cases, 23 retreatment cases, and 4 unknown cases . Out of 79 cases, 36 cases developed tuberculosis almost at the same time or within 1 year after undergoing haemodialysis, and thereafter it decreased gradually . Underlying diseases for haemodialysis were mainly glomerulonephritis and diabetic nephropathy . There were many patients who failed to notify to the public health centers after the diagnosis of tuberculosis was made, and it is needed to improve such a situation in the future . The prognosis of tuberculosis undergoing haemodialysis was poor . Three out of 43 patients with PTB and 2 out of 13 tuberculosis pleurisy cases died . (3) CONCLUSION: The risk of developing PTB in patients undergoing haemodialysis was not high compared with the general population, however, the risk was much higher for extrapulmonary tuberculosis . Moreover, the treatment outcome was not satisfactory in patients with PTB and pleurisy . As patients undergoing haemodialysis have the factors which suppress the cell-mediated immunity, it is required to restudy the measures to prevent development of tuberculosis, management and treatment in the future. Res Microbiol, 2002 Mar, 153(2), 81 - 8 Spoligotyping and IS6110-RFLP typing of Mycobacterium tuberculosis from French Guiana: a comparison of results with international databases underlines interregional transmission from neighboring countries; Filliol I et al.; In this investigation, 94 clinical isolates of Mycobacterium tuberculosis obtained over a 3-year period (1996-1998) from French Guiana were characterized by spoligotyping and IS6110-RFLP and the patterns obtained were compared with genotypes representing the worldwide diversity in an international spoligotyping database (n = 4269) and a IS6110-RFLP database (n = 4189) . All the clustered isolates giving < or = 6 copies of IS6110 were further typed using the double-repetitive element (DRE)-PCR . The results obtained underlined the highly diverse nature of the M . tuberculosis population in French Guiana with potential links to neighboring countries within the Americas . It may be hypothesized that the genetic heterogeneity of tubercle bacilli in French Guiana is linked to the high number of imported cases of tuberculosis, that may account for as high as 68% of all tuberculosis cases . Although an epidemiological investigation based on direct interrogation of patients was not performed, available medical records suggested that the clustering of isolates was mostly linked to the following risk factors: pulmonary tuberculosis, smear-positive samples, foreign-born nationals and/or immigrants, and a high rate of HIV-TB coinfection . Thus the persisting foci of endemic disease and increased active transmission due to high population flux and HIV coinfection may be largely responsible for the relatively high incidence of tuberculosis in French Guiana. Acta Cient Venez, 2001, 52 Suppl 1, 50 - 1 {Transcription regulation in the ribosomal RNA operon of mycobacteria}; Gonzalez Rico S et al.; Tuberculosis is a extremely important infectious disease, caused by the bacilli Mycobacterium tuberculosis . One of the characteristic of this bacteria is its very slow rate of growth, that allows it to survive for long periods of time inside the host cells . Among the genetic elements involved in growth regulation the operon rrn is of extreme importance . This operon contains the genes that code the three rRNA molecules, essential components of the bacterial ribosome . The tuberculosis bacilli, differently from most of the microorganisms, has a single copy of the rrn operon per genome, meaning that it must be submitted to very strict control mechanisms . Another important conclusion is that the sequences of the rrn operon constitute ideal targets for anti-mycobacterial drugs . In this work we have studied some of the elements involved in transcription control in M . tuberculosis, particularly those present in the leader region of the operon . By using basic molecular biology techniques we have identified sequence elements in the leader region that seem to be involved in the control of transcription elongation, by a mechanism related to anti-termination. Acta Cient Venez, 2001, 52 Suppl 1, 36 - 9 Resistance to antimicrobial agents in Mycobacterium tuberculosis; Pfyffer GE; According to the World Health Organization (WHO) more people will currently die of tuberculosis (TB) than in any other year in history . Of equal concern are the emergence and nosocomial transmission of multidrug-resistant (MDR) strains of Mycobacterium tuberculosis . Only recently, with the advent of new molecular biological techniques, the mechanisms of drug resistance in TB bacilli are more and more understood . In M . tuberculosis, the primary mechanism of drug resistance seems to be exclusively confined to chromosomal DNA and not, as in other bacteria, to mobile genetic elements as well. Folia Microbiol (Praha), 2001, 46(5), 363 - 70 Nontraditional microbial bioactive metabolites; Behal V; Microorganisms produce low-molar-mass secondary metabolites exhibiting different biological activities, which are used . e.g., in medicine as antimicrobial and antifungal agents, alkaloids and toxins . Some of these substances have highly diverse biological activities and unusual structures . They are produced by streptomycetes, fungi, and bacilli, but interesting products have also been obtained from microorganisms growing in extreme conditions . Several thousands of microbial products have so far been discovered and many other, which can be potentially useful and/or prospective for human use, can still be in the offing. Am J Respir Crit Care Med, 2002 Mar 15, 165(6), 812 - 7 Limited transmission of multidrug-resistant tuberculosis despite a high proportion of infectious cases in Los Angeles County, California; Nitta AT et al.; Preventing transmission of multidrug-resistant tuberculosis is critical because of treatment toxicity, cost, and the lack of effective therapy for latent infection . We attempted to determine the extent of transmission in Los Angeles County by comparing relatedness of multidrug-resistant tuberculosis cases using restriction fragment length polymorphism and by cross-matching contact information to the Tuberculosis Registry . Strain typing was done on isolates of 102 pulmonary multidrug-resistant cases identified between August 1993 and 1998 . Seventy-one (70%) of the cases had cavitary lesions on chest radiograph, and 94 (92%) had sputa smear-positive for acid fast bacilli . Fifteen (15%) of the cases were known to be infected with human immunodeficiency virus . Four molecular clusters of two cases each and one closely related pair were identified among the 102 cases; contact investigation successfully identified all clusters but one . Among 946 contacts identified and cross-matched with the county's Tuberculosis Registry, one secondary case due to drug-resistant Mycobacterium bovis was found . To summarize, a very high proportion of pulmonary multidrug-resistant tuberculosis cases in Los Angeles County were infectious . Molecular strain typing indicated limited spread of disease, although it underestimated transmission compared with contact investigation . We believe aggressive surveillance and case management were critical to limiting the spread of multidrug- resistant tuberculosis. Proc Natl Acad Sci U S A, 2002 Mar 19, 99(6), 3684 - 9 Epub 2002 Mar 12. A new evolutionary scenario for the Mycobacterium tuberculosis complex; Brosch R et al.; The distribution of 20 variable regions resulting from insertion-deletion events in the genomes of the tubercle bacilli has been evaluated in a total of 100 strains of Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium canettii, Mycobacterium microti, and Mycobacterium bovis . This approach showed that the majority of these polymorphisms did not occur independently in the different strains of the M . tuberculosis complex but, rather, resulted from ancient, irreversible genetic events in common progenitor strains . Based on the presence or absence of an M . tuberculosis specific deletion (TbD1), M . tuberculosis strains can be divided into ancestral and "modern" strains, the latter comprising representatives of major epidemics like the Beijing, Haarlem, and African M . tuberculosis clusters . Furthermore, successive loss of DNA, reflected by region of difference 9 and other subsequent deletions, was identified for an evolutionary lineage represented by M . africanum, M . microti, and M . bovis that diverged from the progenitor of the present M . tuberculosis strains before TbD1 occurred . These findings contradict the often-presented hypothesis that M . tuberculosis, the etiological agent of human tuberculosis evolved from M . bovis, the agent of bovine disease . M . canettii and ancestral M . tuberculosis strains lack none of these deleted regions, and, therefore, seem to be direct descendants of tubercle bacilli that existed before the M . africanum-->M . bovis lineage separated from the M . tuberculosis lineage . This observation suggests that the common ancestor of the tubercle bacilli resembled M . tuberculosis or M . canettii and could well have been a human pathogen already. Ann Rheum Dis, 2001 Nov, 60 Suppl 3, iii6 - 12 Differential roles of Toll-like receptors in the elicitation of proinflammatory responses by macrophages; Jones BW et al.; BACKGROUND: Mammalian Toll-like receptor (TLR) proteins are pattern recognition receptors for a diverse array of bacterial and viral products . Gram negative bacterial lipopolysaccharide (LPS) activates cells through TLR4, whereas the mycobacterial cell wall glycolipids, lipoarabinomannan (LAM) and mannosylated phosphatidylinositol (PIM), activate cells through TLR2 . Furthermore, short term culture filtrates of M . tuberculosis bacilli contain a TLR2 agonist activity, termed soluble tuberculosis factor (STF), that appears to be PIM . It was recently shown that stimulation of RAW264.7 murine macrophages by LPS, LAM, STF, and PIM rapidly activated NF-kappaB, AP1, and MAP kinases . RESULTS: This study shows that signalling by TLR2 and TLR4 also activates the protein kinase Akt, a downstream target of phosphatidylinositol-3'-kinase (PI-3-K) . This finding suggests that activation of PI-3-K represents an additional signalling pathway induced by engagement of TLR2 and TLR4 . Subsequently, the functional responses induced by the different TLR agonists were compared . LPS, the mycobacterial glycolipids, and the OspC lipoprotein (a TLR2 agonist) all induced macrophages to secrete tumour necrosis factor alpha (TNFalpha), whereas only LPS could induce nitric oxide (NO) secretion . Human alveolar macrophages also exhibited a distinct pattern of cellular response after stimulation with TLR2 and TLR4 agonists . Specifically, LPS induced TNFalpha, MIP-1beta, and RANTES production in these cells, whereas the TLR2 agonists induced only MIP-1beta production . CONCLUSION: Together, these data show that different TLR proteins mediate the activation of distinct cellular responses, despite their shared ability to activate NF-kappaB, AP1, MAP kinases, and PI-3-K. Chest, 2002 Mar, 121(3), 774 - 81 Adequately washed bronchoscope does not induce false-positive amplification tests on bronchial aspirates in the diagnosis of pulmonary tuberculosis; Shim TS et al.; STUDY OBJECTIVES: To investigate the clinical usefulness of amplification (COBAS AMPLICOR; Roche Diagnostics Systems; Branchburg, NJ) on bronchoscopic aspirate specimens in the diagnosis of pulmonary tuberculosis, with particular regard to the possibility of false-positive results in subsequent specimens due to residual Mycobacterium tuberculosis DNA . DESIGN AND SETTING: A prospective clinical study at a tertiary referral medical center . PARTICIPANTS AND METHODS: Four hundred fiberoptic bronchoscopic procedures were performed, using seven bronchoscopes on 335 consecutive patients, for therapeutic or diagnostic purposes . Serial bronchial aspirates were collected and tested for M tuberculosis, using COBAS AMPLICOR (CA) . Bronchoscopes were cleaned and disinfected automatically, between patient use, by the same endoscope washer . The name of each bronchoscope and the sequence of its use were recorded, together with the sequence of washing . The CA results were compared with the bacteriologic and histologic results for M tuberculosis infection . When there was a suspicion of contamination, outward polymerase chain reaction analysis was performed . RESULTS: Of 392 specimens (332 subjects), excluding the 8 specimens (4 subjects) in which bacteriologic and histologic analyses were omitted, a smear-positive result for acid-fast bacilli (AFB), culture-positive or biopsy-positive results, and CA-positive results were obtained in 16, 49, and 32 specimens, respectively . In AFB smear-positive subjects, the sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) were 92%, 67%, 92%, and 67%, respectively . In AFB smear-negative subjects, the sensitivity, specificity, PPV, and NPV values were 38%, 99%, 74%, and 94%, respectively . The CA test was more sensitive than the AFB smears for the diagnosis of pulmonary tuberculosis (53% vs 27%, respectively; p < 0.05) . False-positive CA results were seen in only six specimens . Three of these six subjects received a diagnosis of pulmonary tuberculosis on clinical and radiologic grounds, and none of the six results seemed to be associated with bronchoscopic cross-contamination . CONCLUSIONS: Adequately cleaned and disinfected bronchoscopes did not cause false-positive amplification test results for M tuberculosis on bronchial aspirates by cross-contamination . Furthermore, sensitivity was greater with the CA tests . Therefore, CA tests on bronchial aspirates seem to be useful in the diagnosis of pulmonary tuberculosis. Med Sci Monit, 2002 Mar, 8(3), CS26 - 9 Cat-scratch disease in an immunocompromised host; Harsch IA et al.; BACKGROUND: The main causative agents of cat-scratch disease are Bartonella henselae, tiny, gram-negative bacilli . The disease usually has a benign course with the development of a papule at the inoculation site, followed by regional lymphadenopathy . In most cases, complete resolution occurs, but in immunocompromised hosts, the course of the disease can be aggravated . CASE REPORT: A patient received methotrexate and corticosteroids for 3 months due to rheumatoid arthritis . He developed fever, exanthema and leukopenia under methotrexate therapy . Dark red indurations with central ulcerations at his right thigh revealed a further problem apart from the methotrexate-induced leucopenia and immunosuppression . The ulcerations were the remainders of recurrent scratches from the patient's cat . The patient's antibody titers against Bartonella henselae remained low and inguinal lymph node swelling was only for a short time to be observed, this reaction obviously weakened as a result of the immunosuppression . However, the typical course, the exclusion of other reasons for the exanthema and the rapid improvement of the patient's condition after antibiotic treatment ascertained the diagnosis . CONCLUSIONS: In immunocompromised hosts, diseases with a typically benign course can become severe and life-threatening illnesses . Ownership of pets should be taken into consideration before onset of an immunosuppressive therapy. Bull World Health Organ, 2002, 80(1), 16 - 25 Etiology of child mortality in Goroka, Papua New Guinea: a prospective two-year study; Duke T et al.; OBJECTIVE: To collect accurate data on disease- and microbial-specific causes and avoidable factors in child deaths in a developing country . METHODS: A systematic prospective audit of deaths of children seen at Goroka Hospital in the highlands of Papua New Guinea was carried out . Over a 24-month period, we studied 353 consecutive deaths of children: 126 neonates, 186 children aged 1-59 months, and 41 children aged 5-12 years . FINDINGS: The most frequent age-specific clinical diagnoses were as follows: for neonates--very low birth weight, septicaemia, birth asphyxia and congenital syphilis; for children aged 1-59 months--pneumonia, septicaemia, marasmus and meningitis; and for children aged 5-12 years--malignancies and septicaemia . At least one microbial cause of death was identified for 179 (50.7%) children and two or more were identified for 37 (10.5%) . Nine microbial pathogens accounted for 41% of all childhood deaths and 76% of all deaths that had any infective component . Potentially avoidable factors were identified for 177 (50%) of deaths . The most frequently occurring factors were as follows: no antenatal care in high-risk pregnancies (8.8% of all deaths), very delayed presentation (7.9%), vaccine-preventable diseases (7.9%), informal adoption or child abandonment leading to severe malnutrition (5.7%), and lack of screening for maternal syphilis (5.4%) . Sepsis due to enteric Gram-negative bacilli occurred in 87 (24.6%) . The strongest associations with death from Gram- negative sepsis were adoption/abandonment leading to severe malnutrition, village births, and prolonged hospital stay . CONCLUSIONS: Reductions in child mortality will depend on addressing the commonest causes of death, which include disease states, microbial pathogens, adverse social circumstances and health service failures . Systematic mortality audits in selected regions where child mortality is high may be useful for setting priorities, estimating the potential benefit of specific and non-specific interventions, and providing continuous feedback on the quality of care provided and the outcome of health reforms. Clin Nutr, 2001 Dec, 20(6), 527 - 34 Colonization and bacteremia risk factors in parenteral nutrition catheterization; Llop J et al.; AIMS: 1) To establish the relationship between the kind of microorganism that colonizes parenteral nutrition catheters and several risk factors related to catheterization and patient characteristics . 2) To investigate the risk factors associated to bacteremia episodes originated in these colonized catheters . METHOD: An observational, non-controlled, retrospective and cohorts study of the parenteral nutrition catheters implanted between 1988 and 1994 in our hospital . Risk factors were studied in 6 multiple-logistic regression models . RESULTS: 3632 catheters were studied . Incidences of colonization and bacteremia per 1000 days of catheterization were 17.56 and 3.93, respectively . Coagulase-negative staphyloccoci (CNS) were the most frequently isolated microorganisms . The colonization risk factors were: insertion site for all the microorganisms except fungi, catheterization time for CNS and fungi, hospitalization area, sex and age for CNS model, the existence of other infectious foci for Gram negative bacilli (GNB), S . aureus and other microorganisms, hypoalbuminemia for GNB model, and neoplasm for other microorganisms . The bacteremia risk factors were jugular insertion site, catheterization time greater than 10 days, catheter's hub colonization, and catheter colonization by gram-negative bacilli, fungi and S . aureus . CONCLUSION: Risk factors for catheter colonization vary depending on the microorganism which colonizes the catheter . Indian J Exp Biol, 2001 Oct, 39(10), 984 - 8 A dot-immunobinding assay (dot-Iba) for rapid diagnosis of pulmonary tuberculosis; Sumi MG et al.; IgG antibody to Mycobacterium tuberculosis from the sera of patients with 'definite' pulmonary tuberculosis (PT) was isolated and coupled with Cyanogen bromide-Sepharose 4B . Using an immunoabsorbent affinity chromatography, 14 kDa antigen was recovered from the culture filtrates of M . tuberculosis . With this mycobacterial antigen, a dot immunobinding assay (Dot-Iba) was developed for the detection of specific antibody to M . tuberculosis in the sera of patients with PT and controls . The assay gave positive results in all the 12 sputum-smear positive {acid fast bacilli (AFB)} patients with PT and gave negative results in the 50 sera from control groups . The Dot-Iba as described in this study, is simple, rapid and specific for laboratory diagnosis of PT. Indian J Exp Biol, 2001 Oct, 39(10), 962 - 83 Leprosy bacillus--possibly the first chemoautotrophic human pathogen cultivated in vitro and characterised; Chakrabarty AN et al.; Leprosy bacillus (LB) and leprosy derived in vitro culture forms, the chemoautotrophic nocardioform (CAN) bacteria, showed an extremely close homology and identity with each other as regards a chemoautotrophic nutritional pattern, a nocardioform morphology, a weak acid-fastness coupled with Gram and Gomori's stain positivity, an exclusive mycolate and lipid profile, a phenolic glycolipid (PGL-I) and a highly sequestrated DNA characteristic, namely, a unique small size, a low G+C % mole, an exceptionally high gamma and UV radiation resistance, and a high thermal resistance . LB/CAN bacteria (CANb) gave positive signals for 36 kDa protein PCR, as well as, for 65 kDa epitope, and hybridisation with two or more probes and also by RFLP-analysis . Both LB/and CAN bacteria exhibited bacillary multiplication in the mouse footpads (MFP), nerve infiltration and evidences for local pathogenicity associated with pronounced systemic invasion . A highly reproducible mutilation model could be established which enabled a successful application of the postulates of Koch . The proof of their total identity was their anergic reactions in LL cases counterpoised against Mitsuda type strong nodular responses, mirroring the reactions of leprosy bacilli in TT cases, in accordance with the dictum of XIth International Leprosy Congress (1978) . Thus, the chemoautotrophic nutritional requirements of LB, entirely unsuspected for a medically important pathogenic bacterium, having dimorphic (both bacillary and mycelial) characters with spores, mycelia and granules and unique pathogenicity of multilation manifested through the virulence factor, the enzyme collagenase, made LB or M leprae the highly enigmatic bacterium for so long. Indian J Med Sci, 2001 Jul, 55(7), 382 - 92 Drug resistance among tubercle bacilli from pulmonary tuberculosis cases in central India; Hemvani N et al.; An estimate of drug resistance is extremely important in the epidemiology and control of tuberculosis . Data on drug resistance among mycobacterial isolates from sputum samples analysed at Microbiology dept . of Choithram Hospital and Research Centre, Indore, M.P . is presented here . Drug sensitivity testing was carried out on 1426 Mycobacterial isolates by the method of proportion using critical concentration in Lowenstein Jensen medium . Resistance for Isoniazid, streptomycin, and pyrazinamide was found to be high (54.2%, 41.5% and 50% respectively) and was followed by resistance to rifampin (25%) and ethambutol (22%) . Resistance for kanamycin, p-aminosalicylic acid, thiacetazone and ciprofloxacin was much lower (18%, 13%, 6.5% and 3.6% respectively) . Only 12% of the isolates were sensitive to all the anti-TB drugs while resistance to two, three, and four or more drugs was in the range of 20-25% . Pattern wise, simultaneous resistance to INF and Rifampin with or without resistance to other drugs was observed in 8.1% while resistance for Isoniazid + pyrazinamide and Isoniazid + streptomycin was 11.9 and 11.5% respectively . Resistance for Isoniazid + ethambutol was the lowest (5.1%) . Growing multiple drug resistance among tubercle bacilli warrant urgent attention in tuberculosis control programme. Pathol Int, 2001 Oct, 51(10), 807 - 11 Malignant lymphoma of bronchus-associated lymphoid tissue (BALT) coexistent with pulmonary tuberculosis; Inadome Y et al.; A case in which malignant lymphoma occurred in association with a tuberculosis focus in a 70-year-old man is reported . Surrounding the epithelioid cell granulomas with caseous necrosis was a dense and diffuse monotonous infiltration of atypical lymphoid cells . Acid-fast bacilli were found in the granulomas and pulmonary tuberculosis was diagnosed . The infiltrating atypical lymphoid cells occasionally invaded the respiratory epithelium producing lymphoepithelial lesions . Immunohistochemically, the lymphoid cells were positive for CD20, and clonal rearrangement of the immunoglobulin heavy chain gene was demonstrated by polymerase chain reaction (PCR) . We diagnosed the lesion as a pulmonary malignant lymphoma of bronchus-associated lymphoid tissue (BALT) occurring in the background of tuberculosis . This is the first reported case of pulmonary BALT lymphoma coexistent with pulmonary tuberculosis. Int J Lepr Other Mycobact Dis, 2001 Sep, 69(3), 177 - 86 Distinct histopathological patterns in single lesion leprosy patients treated with single dose therapy (ROM) in the Brazilian Multicentric Study; Costa MB et al.; This paper aims to describe the histomorphologic features of skin biopsies of single lesion leprosy patients recruited at outpatient clinics in four Brazilian states in the Northeast (Amazonas and Rondonia), Southeast (Rio de Janeiro) and Center-West (Goias) between October 1997 and December 1998 . Patients clinically diagnosed as single skin lesion paucibacillary (SSL-PB) leprosy had a standard 4-mm punch biopsy taken from the lesion before rifampin, ofloxacin, minocycline (ROM) therapy . The features of the cellular inflammatory infiltrates, the presence of nerve involvement and acid-fast bacilli (AFB) were used to categorize SSL-PB biopsies into different histopathological groups . Two-hundred-seventy-eight (93.0%) out of 299 patients had a skin biopsy available . Seven single lesion patients were diagnosed as BL or LL leprosy types (MB) by the histopathological exams and 12 cases were excluded due to other skin diseases . Therefore, 259 patients had skin lesions with histomorphological features compatible with PB leprosy categorized as follows: 33.6% (N = 87) of the biopsies represented well-circumscribed epithelioid cell granuloma (Group 1); 21.6% (N = 56) less-circumscribed epithelioid cell granuloma (Group 2); 12.0% (N = 31) were described as mononuclear inflammatory infiltrate permeated with epithelioid cells (Group 3), and 29.7% (N = 77) had perivascular/periadnexal mononuclear inflammatory infiltrate (Group 4) . Minimal/no morphological alteration in the skin was detected in only 8 (3.1%) SSL-PB patients categorized as Group 5, who were considered to have leprosy by clinical parameters . SSL-PB leprosy patients recruited in a multicentric study presented histomorphology readings comprising the whole PB leprosy spectrum but also a few MB cases . These results indicate heterogeneity among SSL-PB patients, with a predominance of well-circumscribed and less-circumscribed epithelioid cell granulomas (Groups 1 and 2) in the sites studied and the heterogeneity of local cellular immune response. Br J Cancer, 2002 Feb 1, 86(3), 336 - 41 Clinical and immunological assessment of Mycobacterium vaccae (SRL172) with chemotherapy in patients with malignant mesothelioma; Mendes R et al.; The objectives of this study were to determine the toxicity of intratumoural/intrapleural SRL172 in addition to intradermal SRL172 and standard chemotherapy (mitomycin-C, vinblastine and cisplatin) in patients with malignant mesothelioma . Patients received chemotherapy (mitomycin-C: 8 mg m(-2), vinblastine: 6 mg m(-2), cisplatin 50 mg m(-2)) on a 3-weekly basis for up to six courses . IP SRL172 injections were given 3-weekly prior to chemotherapy and escalated in groups of three patients from 1 microg to 1 mg bacilli in 10-fold increments . Patients were also given ID SRL172 at a dose of 1 mg bacilli 4-weekly . Patients were assessed for toxicity after each course of chemotherapy and for response by CT imaging . Immuno-haematological parameters were analyzed pre-treatment and 1 month after completion of treatment . There was no dose limiting toxicity with IP SRL172 although there was greater toxicity at the highest dose (n=13) . There were six out of 16 partial responses (37.5%) . Haemato-immunological parameters, measured in seven patients pre and post-therapy, revealed that response rate correlated with a decrease in platelet count and there was an increase in activation of natural killer cells and a decrease in the percentage of IL-4 producing T cells in all tested patients post-treatment . SRL172 can be given safely into tumour deposits and the pleural cavity in patients with malignant mesothelioma and we have establ