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Mol Microbiol, 2003 May, 48(3), 833 - 43 Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis; Park HD et al.; Unlike many pathogens that are overtly harmful to their hosts, Mycobacterium tuberculosis can persist for years within humans in a clinically latent state . Latency is often linked to hypoxic conditions within the host . Among M . tuberculosis genes induced by hypoxia is a putative transcription factor, Rv3133c/DosR . We performed targeted disruption of this locus followed by transcriptome analysis of wild-type and mutant bacilli . Nearly all the genes powerfully regulated by hypoxia require Rv3133c/DosR for their induction . Computer analysis identified a consensus motif, a variant of which is located upstream of nearly all M . tuberculosis genes rapidly induced by hypoxia . Further, Rv3133c/DosR binds to the two copies of this motif upstream of the hypoxic response gene alpha-crystallin . Mutations within the binding sites abolish both Rv3133c/DosR binding as well as hypoxic induction of a downstream reporter gene . Also, mutation experiments with Rv3133c/DosR confirmed sequence-based predictions that the C-terminus is responsible for DNA binding and that the aspartate at position 54 is essential for function . Together, these results demonstrate that Rv3133c/DosR is a transcription factor of the two-component response regulator class, and that it is the primary mediator of a hypoxic signal within M . tuberculosis. Int J Dermatol, 2003 Apr, 42(4), 281 - 6 Polymerase chain reaction based detection of Mycobacterium tuberculosis in tissues showing granulomatous inflammation without demonstrable acid-fast bacilli; Hsiao PF et al.; BACKGROUND: Cutaneous tuberculosis is especially difficult to distinguish from other granulomatous dermatoses . We used polymerase chain reaction (PCR) to evaluate the incidence of cutaneous tuberculosis and atypical mycobacterial infection in formalin-fixed, paraffin-embedded tissues with unspecified granulomatous inflammation and negative results for acid-fast bacilli (AFB), and analyzed the pattern of cutaneous tuberculosis in this group of patients . METHODS: A total of 38 specimens which had been collected from 36 patients and fulfilled the criteria for tissues described above were used in this study . Two different primer pairs targeting the gene encoding for 16S ribosomal RNA (common to all mycobacteria) and the insertion sequence IS6110 (specific for M . tuberculosis complex) were used in the PCR assays . The clinical characteristics, histopathologic findings, and culture results of the patients were also analyzed . RESULTS: Four specimens were excluded from the analysis due to the lack of internal control testing . Of the remaining 34 specimens, 22 were PCR positive for the 16S rRNA gene . Among them, 18 specimens were PCR positive for both the 16S rRNA gene and IS6110 . Cutaneous tuberculosis could be diagnosed in these 18 cases (56.2%) . Out of the 18 cases, there were 8 women and 10 men . The age range was 15-77 years (mean: 44.2 years) . After reviewing their clinical presentation, 11 cases were considered as tuberculosis verrucosa cutis, 6 cases as lupus vulgaris, and 1 case as erythema induratum . The remaining 4 cases (12.5%) positive only for 16S rRNA gene were considered as possible atypical mycobacteria infection . CONCLUSIONS: These results show that in paucibacillary form of cutaneous tuberculosis with unclassical clinical and histological presentation, this PCR system provides rapid and sensitive detection of M . tuberculosis DNA in formalin-fixed, paraffin-embedded specimens . Cutaneous tuberculosis represents a significant proportion in specimens showing granulomatous inflammation . In areas like Taiwan, where prevalence of pulmonary tuberculosis is still high, tuberculosis verrucosa cutis and lupus vulgaris are common forms of cutaneous tuberculosis and are seen more frequently than atypical mycobacterial infection. J Assoc Physicians India, 2003 Jan, 51, 28 - 32 Current status of drug resistance among gram-negative bacilli isolated from admitted cases in a tertiary care centre; Chitnis SV et al.; AIMS: To study the prevalence of drug resistance among gram-negative bacilli and susceptibility to the Cefoperazone + Sulbactam and Piperacillin + Tazobactam combination among the hospital isolates resistant to all other antimicrobial agents . METHODS: A total of 367 gram-negative bacilli isolated from various pathological samples were tested for susceptibility to antimicrobial agent by the disc diffusion technique and 300 isolates of gram-negative bacilli which were resistant to all the other antibiotics were checked for sensitivity to piperacillin + tazobactam and cefoperazone + sulbactam combination . RESULTS: Resistance to ampicillin and amoxicillin + clavulanic acid ranged from (72.1-83.8%) which was highest . Resistance to cotrimoxazole, gentamicin, netilmycin, quinolones and all the generation of cephalsporins was often above 50% . piperacillin + tazobactam combination had the lowest incidence of resistance (14 to 20.5%) . CONCLUSION: Drug resistance for most of the antimicrobial agents was greater than 50% including the various generations of cephalosporins . Inefficiency of amoxicillin + clavulanic acid (resistance among 72-79.5% isolates) suggests the presence of extended spectrum beta-lactamases among the isolates . Addition of sulbactam to cefoperazone showed increased activity (resistance 27 to 34%) but piperacillin + tazobactam was the most effective combination in vitro. Nihon Kokyuki Gakkai Zasshi, 2003 Jan, 41(1), 14 - 8 {A Mycobacterium abscessus infection complicated with lipoid pneumonia}; Matsunaga S et al.; A 64-year-old man was admitted to our hospital because of productive cough and fever . Chest radiography on admission revealed air space consolidation in the right middle and lower lung fields and ground-glass opacity in the left middle lung field . He had been constipated for several years and had taken mineral oil for about a year . Sputum smears demonstrated acid bacilli, and cultures disclosed Mycobacterium abscessus . The transbronchial lung biopsy specimen showed granulomatous inflammation and numerous lipoid-laden macrophages in the alveolar spaces . Mycobacteria were present within the mineral oil and lipid-laden macrophages . It is likely that the mineral oil increased the pathogenicity of the mycobacteria. Crit Care Med, 2003 Apr, 31(4), 1088 - 93 Restriction of third-generation cephalosporin use decreases infection-related mortality; Du B et al.; OBJECTIVE: To determine the effect of restriction of third-generation cephalosporin use on antibiotic resistance and the outcome of patients with infection . DESIGN: A prospective, before-after comparative study . SETTING: A general intensive care unit with 14 beds at a university-affiliated teaching hospital . PATIENTS: All patients admitted to the intensive care unit within 2 yrs . INTERVENTIONS: A new antibiotic treatment strategy was implemented during phase II . All patients with confirmed or suspected Gram-negative bacterial infections were treated mainly with antibiotics other than third-generation cephalosporins . MEASUREMENTS AND MAIN RESULTS: Antibiotic resistance among common Gram-negative bacilli and infection-related hospital mortality during phase I were compared with phase II . A 26.6% reduction in third-generation cephalosporin use (from 168.2 +/- 48.0 to 123.5 +/- 39.3 g/month, p =.021), accompanied by a 277.7% increase in cefepime use (from 10.3 +/- 19.2 to 38.9 +/- 31.7 g/month, p =.014) occurred in phase II compared with phase I . This was accompanied by a significant decrease in reduced susceptibility of Gram-negative bacilli to third-generation cephalosporins (p <.05), mainly because of the improved susceptibility of Escherichia coli and Klebsiella species (p <.05) . Infection-related hospital mortality was significantly lower in phase II (19.3% vs . 36.3%, p =.014) . Multiple logistic regression analysis demonstrated lower respiratory tract infection, the status of immunocompromise, and continuous veno-venous hemofiltration as independent risk factors for infection-related hospital mortality (p <.05), whereas infection with E . coli or Klebsiella species (p =.039) and restriction of third-generation cephalosporin use (p =.025) were associated with a significantly lower mortality rate . CONCLUSIONS: Restriction of third-generation cephalosporin use may improve the antibiotic susceptibility and reduce infection-related hospital mortality in critically ill patients. Singapore Med J, 2002 Nov, 43(11), 570 - 5 Audit of transthoracic fine needle aspiration of the lung: cytological subclassification of bronchogenic carcinomas and diagnosis of tuberculosis; Tan KB et al.; INTRODUCTION: Transthoracic fine-needle aspiration cytology (FNAC) is a useful tool for evaluating neoplastic and inflammatory lung nodules . In view of the relative paucity of published audit studies regionally, such a study was undertaken to assess the use of the technique in our centre . METHODS: One hundred and fourteen FNACs were performed during 1997-1999 . Immediate assessment for specimen adequacy was done . Diagnoses were correlated with clinical-pathological information and selective blind review performed . RESULTS: Cytologically, 65.8% of cases were malignant, 1.8% were atypical, 25.4% were inflammatory/non-malignant and 7% were inadequate . Cytological-histological tumour diagnostic concordance was 94.4% . Diagnostic sensitivity for malignancy: 93.4%, specificity: 95.8%, accuracy: 94% . Eight inadequate/ benign cases (7%) proved to be malignant with clinical-pathological follow-up . Tuberculosis was confirmed (acid-fast bacilli detected) in six cases (5.3%) and suggested in a further 10 cases (8.8%) . The cytological review showed 96% concordance with the original benign/malignant diagnoses . Pneumothorax rate was 18% . CONCLUSION: FNAC is an accurate and safe method for the evaluation of lung nodules and it enables subclassification of bronchogenic carcinomas in the vast majority of cases . It is also useful for the diagnosis of tuberculous pulmonary nodules . Immediate assessment optimises specimen adequacy; inadequate/non-malignant smears in particular, need clinical correlation, close follow-up and re-biopsy, if necessary. Leuk Lymphoma, 2002 Sep, 43(9), 1755 - 62 Results of first salvage therapy for patients refractory to a fludarabine regimen in chronic lymphocytic leukemia; Keating MJ et al.; Resistance to purine analogs is emerging as a major problem in the management of patients with chronic lymphocytic leukemia (CLL) . Most of these patients have already been exposed to and have become refractory to alkylating agents . To define the natural history of fludarabine (Fludara) refractory patients with CLL, we reviewed the response to first salvage therapy of 147 patients who were refractory to Fludara or had a remission less than six months in duration after a Fludara-containing regimen . Thirty-three (22%) patients responded to their first salvage attempt . However, the median survival was only 10 months . Responders survived significantly longer than non-responders . The most effective salvage regimens were combinations of purine analogs and cyclophosphamide . Patients still possibly sensitive to alkylating agents had a superior response than alkylating agent resistant or naive patients . Subsequent salvage therapy was administered to 61 patients . The most promising results noted in the group were transplantation and the use of Campath-1H antibody . The major morbidity and cause of death were associated with infections . The probability of infection was most strongly associated with the response to salvage therapy . Gram-positive organisms were most commonly associated with infection . However, gram-negative bacilli or opportunistic infection such as fungi, Pneumocystis carinii, acid-fast bacilli and legionella were prominent causes of infection . Fludara-refractory patients are a poor prognosis group and need more effective therapeutic regimens and well-designed infection prophylactic regimens. Indian J Chest Dis Allied Sci, 2003 Jan-Mar, 45(1), 19 - 23 Role of gallium arsenide laser irradiation at 890 nm as an adjunctive to anti-tuberculosis drugs in the treatment of pulmonary tuberculosis; Puri MM et al.; BACKGROUND: Tuberculosis is a global emergency with about nine million people developing disease every year . The long duration of treatment has emerged as a major obstacle in the control of tuberculosis . There is a need for development of new drugs and or shortened therapy . METHODS: The present study was carried out to explore whether any benefit could be achieved by the addition of low level energy laser therapy (LLLT) to the conventional anti-tubercular chemotherapy . One-hundred-thirty new sputum smear positive patients of pulmonary tuberculosis were enrolled to evaluate the bio-stimulatory effects of Gallium Arsenide laser irradiation at 890 nm, as an adjuvant therapy . These patients were randomly divided into two groups to receive either LLLT or sham irradiation (control) concomitantly with anti-tuberculosis chemotherpy . RESULTS: The patients treated with semiconductor laser as an adjuvant therapy along with anti-tuberculosis drugs had a faster clearance of tubercle bacilli from the sputum as compared to the control group (P value at :45 days=0.1392, 60 days=0.0117, 75 days=0.00805, 90 days=0.00739) . CONCLUSIONS: These findings provide preliminary evidence that low level laser therapy with Gallium Arsenide laser may be a promising adjunctive therapy for patients with tuberculosis . Faster conversion of sputum should prevent the development of resistant mutants. Gerontology, 2003 May-Jun, 49(3), 173 - 6 Acute stroke predisposes to oral gram-negative bacilli -- a cause of aspiration pneumonia? Millns B, Gosney M, Jack CI, Martin MV, Wright AE. OBJECTIVES: To assess any change in the oral flora in the mouths of stroke patients during the acute and rehabilitation phases and to determine whether this is related to episodes of aspiration pneumonia and clinical outcome . MATERIALS AND METHODS: This observational study was carried out in hospital wards in a University teaching hospital . The subjects were patients immediately post-stroke and during the rehabilitation period, acute admissions and a group of healthy volunteers . An assessment of dentition and swallow in the presence or absence of oral aerobic gram-negative bacilli (AGNB) was correlated . RESULTS: Of the acute stroke patients 52% had an unsafe swallow . AGNB carriage was documented in 34% of the acute stroke group . Of the 11 patients who died 55% had AGNB, 73% had an unsafe swallow and 36% had a combination of both . CONCLUSION: AGNB is a common finding in acute stroke patients . It is not a consequence of age or acute hospitalisation and is associated with an unsafe swallow and a higher mortality . J Gastroenterol, 2003, 38(3), 222 - 8 Utility and limitations of a method for detecting Helicobacter pylori-specific antigens in the stool; Matsuda M et al.; BACKGROUND: Recently, a method for detecting Helicobacter pylori-specific antigens in the stool (HpSA) has been proposed to be useful clinically . The aim of this study was to determine the accuracy of HpSA for the diagnosis of H . pylori infection, including early assessment after eradication treatment, and the potential for quantitative evaluation of H . pylori in the stomach . METHODS: The subjects were 85 patients with gastroduodenal disorders who underwent endoscopic examination . Of these, 36 were treated for eradication of H . pylori infection and reassessed 4-8 weeks after treatment . HpSA was tested by enzyme immunoassay . For the definitive diagnosis of H . pylori infection, biopsy specimens were taken endoscopically and examined by quantitative culture, rapid urease test, and immunohistostaining . In addition, serum antibody against H . pylori was tested before the eradication treatment and a (13)C-urea breath test was conducted after treatment . The results of these reference tests were compared with those obtained by HpSA . RESULTS: The sensitivity and specificity of HpSA were 90.4% and 100% before eradication treatment and 57.1% and 100% after the treatment . There was a positive correlation between the optical density of HpSA and the number of H . pylori bacilli evaluated by quantitative culture . CONCLUSIONS: The HpSA test is considered to be an accurate method for the diagnosis of H . pylori infection, with high specificity . However, there may be problems of false negativity if HpSA is used for the early assessment of treatment efficacy . Furthermore, HpSA is suggested to have potential for the quantitative evaluation of H . pylori status in the stomach. Int J Pharm, 2003 Apr 14, 255(1-2), 43 - 8 Design and evaluation of an aerosol infection chamber for small animals; Bhaskar S et al.; In this report, we describe the design of an aerosol exposure chamber to reproducibly produce uniformly distributed clouds of droplet nuclei . The device can deliver desired number of bacilli (20-2000) in lungs of mice . All safety measures to handle infectious bacteria have been incorporated in the design and it is controlled remotely by a personal computer . It is an indispensable device to study the protective efficacy of vaccine candidates against Mycobacterium tuberculosis infection . This device would also be useful to study immunization and drug delivery by nasal route in experimental animals. Br J Cancer, 2003 Apr 7, 88(7), 1012 - 6 Oral mucositis and selective elimination of oral flora in head and neck cancer patients receiving radiotherapy: a double-blind randomised clinical trial; Stokman MA et al.; Mucositis is an acute inflammation of the oral mucosa because of radiotherapy and/or chemotherapy . All patients receiving radiotherapy in the head and neck region develop oral mucositis . The aim of this study was to analyse the effects of selective oral flora elimination on radiotherapy-induced oral mucositis, in a double-blind, randomised, placebo-controlled trial . Sixty-five patients with a malignant tumour in the head and neck regions to be treated with primary curative or postoperative radiotherapy participated in this study . The patients received either the active lozenges of 1 g containing polymyxin E 2 mg, tobramycin 1.8 mg and amphotericin B 10 mg (PTA) (33 patients) or the placebo lozenges (32 patients), four times daily during the full course of radiotherapy . Mucositis, changes in the oral flora, quality of feeding and changes of total body weight were assessed . Mucositis score did not differ between the groups during the first 5 weeks of radiotherapy . Nasogastric tube feeding was needed in six patients (19%) of the placebo group and two patients (6%) of the PTA group (P=0.08) . Mean weight loss after 5 weeks of radiation was less in the PTA group (1.3 kg) (s.d.: 3.0) than in the placebo group (2.8 kg) (s.d.: 2.9) (P=0.05) . Colonisation index of Candida species and Gram-negative bacilli was reduced in the PTA group and not in the placebo group (P<0.05) . No effect on other microorganisms was detected . In conclusion, selective oral flora elimination in head and neck irradiation patients does not prevent the development of severe mucositis. Ann Dermatol Venereol, 2003 Feb, 130(2 Pt 1), 184 - 6 {Evaluation of the clinical classification of new cases of leprosy . Study conducted at the Marchoux Institute in Bamako, Mali}; Keita S et al.; INTRODUCTION: The difficulties related to the bacilloscopic diagnosis of leprosy, providing a more reliable classification of cases, in 1995 led the WHO to recommend the use of a new classification, in endemic countries, based on clinical criteria alone, in order to simplify the poly-chemotherapeutic regimens . According to our experience in the Marchoux Institute, this classification may lead to errors in diagnosis through overzealous or mis-interpretation of the two forms of leprosy . The aim of our study was to evaluate the concordance between this clinical classification and that based on a bacilloscopic examination . PATIENTS AND METHODS: We conducted a descriptive study of new cases of leprosy seen at the Marchoux Institute, without distinction in gender or age, from January to December 2000 . All the patients included underwent clinical examination and a bacilloscopic exploration to provide a double classification . The concordance between the two classifications was assessed using the Kappa test.RESULTS: Two hundred new cases of leprosy were included . Out of 126 clinically multi-bacillary cases, 61 were confirmed bacteriologically, and 65 were false positives . Out of 74 clinical cases with few bacilli, 2 were bacteriologically multi-bacilli . The concordance between the two classifications was average (Kappa=0.40) . There was a significant difference between the percentages of multi-bacilli observed in both classifications (p<10(-8)) . DISCUSSION: The clinical classification may well overestimate the multi-bacillary form . In the absence of a reliable bacilloscopic apparatus, a more detailed clinical classification of leprosy forms must be developed. J Int Acad Periodontol, 2002 Jan, 4(1), 19 - 25 Connective tissue and bacterial deposits on rubber dam sheet and ePTFE barrier membranes in guided periodontal tissue regeneration; Apinhasmit W et al.; The aim of this study was to compare the connective tissue and bacterial deposits on rubber dam sheets and expanded polytetrafluoroethylene membranes used as barrier membranes in guided tissue regeneration for periodontal treatment . Twenty patients having intrabony defects and/or furcation defects were surgically treated by guided tissue regeneration employing either rubber dam sheets (10 patients) or expanded polytetrafluoroethylene membranes (10 patients) as barrier membranes . Four to six weeks after the first operation, membranes were retrieved from the lesion sites and processed for scanning electron microscopy . The lesion-facing surfaces of membranes were examined for the presence of connective tissue and bacterial deposits . The differences between the numbers of fields and the distributions of connective tissue and bacteria on both types of membranes were analysed by the Chi-square test at the level of 0.05 significance . The results showed a lot of fibroblasts with their secreted extracellular matrices, known as components of the connective tissue on rubber dam sheets and expanded polytetrafluoroethylene membranes . There was no significant difference in the total number of connective tissue on both types of membranes (P = 0.456) . Many bacterial forms including cocci, bacilli, filaments and spirochetes with the interbacterial matrices were identified . The total number of bacteria on rubber dam sheets was statistically less than that on expanded polytetrafluoroethylene membranes (P < 0.001) . The comparable number of connective tissue on both types of membranes suggests that the healing process under both types of membranes was also comparable . Therefore, the rubber dam sheet might be used as a barrier membrane in guided tissue regeneration. Curr Opin Investig Drugs, 2003 Feb, 4(2), 117 - 27 Antibacterial agents: patent highlights July to December 2002; Phillips OA; Forty-five patents dealing with disclosures on the different classes of antibacterial agents, reported between July and December 2002, are selected for review . Disclosures dealing with novel derivatives of known antibacterials (beta-lactam, oxazolidinone, macrolide, quinolone, tetracycline and peptide derivatives), development of new processes and formulations to improve cost, activity and stability are highlighted . In addition, patent disclosures on novel oxazolidinone derivatives with broad-spectrum activity extended against fastidious Gram-negative bacilli are highlighted in comparison to linezolid . Novel antibacterial agents (peptide-deformylase inhibitors) that could serve as potential lead compounds are also presented. Chin J Traumatol, 2003 Apr, 6(2), 118 - 23 Neuroprotective effects of nimodipine and MK-801 on acute infectious brain edema induced by injection of pertussis bacilli to neocortex of rats; Chen LH et al.; OBJECTIVE: To explore the mechanism and type of acute infectious brain edema induced by injection of pertussis bacilli (PB) in rat neocortex, to study the neuroprotective effect of non-competitive antagonist of N-methl-D-aspartate (NMDA) receptor (MK-801) and antagonist of Ca(2+) channels (nimodipine) on brain edema, and to investigate the relationship between percentage of water content and cytosolic free calcium concentration ({Ca(2+) }(i)) in synaptosomes or content of Evans Blue (EB) . METHODS: 95 SD rats were randomly divided into five groups, ie, normal control group, sham-operated control group, PB group, nimodipine treatment group and MK-801 pretreatment group . The acute infectious brain edema was induced by injection of PB into the rats . Quantitative measurements of water content and the concentration of EB were performed . {Ca(2+) }(i) was determined in calcium fluorescent indication Fura-2/AM loaded neuronal synaptosome with a spectrofluorophotometer . To observe the effect of MK-801 and nimodipine, we administered MK-801 48 hours and 24 hours before the injection of PB in MK-801 pretreatment group, and nimodipine after the injection of PB in nimodipine treatment group . The specific binding of NMDA receptor was measured with {(3)H}-MK-801 in the neuronal membrane of cerebral cortex . RESULTS: The levels of water content and EB content of brain tissues, and {Ca(2+) }(i) in the neuronal synaptosomes increased more significantly in the PB-injected cerebral hemisphere in the PB group than those of normal control group and sham-operated control group (P<0.05) . The water content and {Ca(2+) }(i) increased with the duration of infectious brain edema . Nimodipine administered after the injection of PB could significantly decrease the water content, EB and {Ca(2+) }(i) (P<0.05) . MK-801 could significantly decrease the water content, EB and {Ca(2+) }(i) in 4 h and 24 h groups (P<0.05) . The Kd values were 30.5 nmol/L+/-3.0 nmol/L and 42.1 nmol/L+/-4.2 nmol/L in PB group and NS group respectively (P<0.05), and Bmax were 0.606 pmol/mg.pro+/-0.087 pmol/mg.pro and 0.623 pmol/mg.pro+/-0.082 pmol/mg.pro respectively, without statistical significance (P>0.05) . CONCLUSIONS: The changes in the permeability of blood-brain barrier (BBB) and Ca(2+)-overload may participate in the pathogenesis of infectious brain edema . Treatment with nimodipine can dramatically reduce the damage of brain edema and demonstrate neuroprotective effect on brain edema by inhibiting the excess of Ca(2+) influx and reducing the permeability of BBB . MK-801 pretreatment may inhibit the delayed Ca(2+) influx into the neurons . The infectious brain edema is not only cytotoxic brain edema (intracellular edema) but also vasogenic brain edema (extracellular edema) followed by earlier BBB breakdown, so infectious brain edema is complicated with brain edema. Vet Clin Pathol, 1997, 26(2), 85 - 89 Disseminated Mycobacterium avium complex infection in a cat: presumptive diagnosis by blood smear examination; Latimer KS et al.; Disseminated mycobacteriosis was diagnosed in a 4-year-old, castrated male Domestic Shorthair cat following the observation of one to three retractile, non-staining bacilli in neutrophils and monocytes on a Wright-Leishman-stained blood smear Organisms were bright red following acid-fast staining by Kinyoun's technique . The cat had a history of progressive weight loss, anemia, fever, and sporadic vomiting after eating . In addition to blood smears, mycobacteria also were observed in bone marrow aspirates . During necropsy, multiple small white nodules were observed in the spleen and liver . An enlarged sternal lymph node and ascites also were present . In histologic sections, mycobacteria were observed in granulomas within the lungs, liver, spleen, colon, mesenteric and sternal lymph nodes, omentum, and kidney . Mycobacterium avium complex was isolated from cultures of liver, spleen, lung, and kidney . Occult feline leukemia virus infection, detected by immunofluorescent testing of bone marrow aspirates, may have predisposed this cat to bacterial infection . The serum ELISA test for group-specific feline leukemia virus antigen was negative. Kekkaku, 2003 Jan, 78(1), 27 - 31 {A case of pulmonary tuberculosis initially presented with syndrome of inappropriate secretion of antidiuretic hormone (SIADH)}; Nishizawa Y et al.; A 90-year old man was admitted to a hospital because of consciousness loss with hyponatremia . Although his symptom promptly improved with Na supply, his chest X-ray film showed pulmonary infiltration and direct microscopy of sputum smear was positive for acid-fast bacilli, then he was referred our hospital and was admitted . We made a clinical diagnosis of pulmonary tuberculosis with SIADH based on detailed examinations . But he should neither respiratory symptoms nor fever . He was medicated with the standard antituberculosis drugs with fluid restriction, and his tuberculosis and hyponatremia were improved gradually . We should be more careful about pulmonary tuberculosis irrespective of its severity as a cause of SIADH. Infect Immun, 2003 Apr, 71(4), 1953 - 60 Synthetic peptides identify promiscuous human Th1 cell epitopes of the secreted mycobacterial antigen MPB70; Al-Attiyah R et al.; MPB70 is a secreted protein of Mycobacterium bovis and Mycobacterium tuberculosis which stimulates both cellular and humoral immune responses during infection with bovine and human tubercle bacilli . In addition, vaccination with MPB70 has been shown to induce Th1 cell responses and protection in animal models of tuberculosis . The present study was carried out to map the dominant human Th1 cell epitopes of MPB70 in relation to major histocompatibility complex (MHC) class II restriction in healthy subjects showing strong T-cell responses to complex mycobacterial antigens . Peripheral blood mononuclear cells (PBMC) from HLA-DR-typed donors were tested with complex mycobacterial antigens (whole-cell M . tuberculosis and M . tuberculosis culture filtrates), with MPB70 purified from the culture filtrate of M . bovis BCG Tokyo, and with 13 synthetic peptides (25-mers overlapping by 10 residues) covering the sequence of MPB70 . The donors that responded to the complex antigens and MPB70 also responded to the cocktail of synthetic MPB70 peptides . Testing of PBMC with individual peptides showed that peptides p5 (amino acids {aa} 61 to 85), p6 (aa 76 to 100), p8 (aa 106 to 130), p12 (aa 166 to 190), and p13 (aa 181 to 193) were most frequently recognized in proliferation and gamma interferon (IFN-gamma) assays . Testing of antigen-specific CD4(+) T-cell lines with the individual peptides of MPB70 confirmed that peptides p8, p12, and p13 contain immunodominant Th1 cell epitopes of MPB70 . MHC restriction analysis with HLA-typed donors showed that MPB70 and its immunodominant peptides were presented to T cells promiscuously . The T-cell lines responding to MPB70 and peptides p8, p12, and p13 in IFN-gamma assays mediated antigen-peptide-specific cytotoxic activity against monocytes/macrophages pulsed with the whole-protein antigen or the peptides . In conclusion, the promiscuous recognition of MPB70 and its immunodominant peptide defined epitopes (aa 106 to 130 and 166 to 193) by IFN-gamma-producing Th1 cells supports possible application of this secreted antigen to subunit vaccine design. Infect Immun, 2003 Apr, 71(4), 1929 - 37 The Apa protein of Mycobacterium tuberculosis stimulates gamma interferon-secreting CD4+ and CD8+ T cells from purified protein derivative-positive individuals and affords protection in a guinea pig model; Kumar P et al.; The search to identify Mycobacterium tuberculosis antigens capable of conferring protective immunity against tuberculosis has received a boost owing to the resurgence of tuberculosis over the past two decades . It has long been recognized that lymphoid cells are required for protection against M . tuberculosis . While traditionally the CD4(+) populations of T cells were believed to predominantly serve this protective function, a pivotal role for CD8(+) T cells in this task has been increasingly appreciated . We show that the 50- to 55-kDa Apa protein, specified by the Rv1860 gene of M . tuberculosis, can elicit both lymphoproliferative response and gamma interferon (IFN-gamma) production from peripheral blood mononuclear cells (PBMC) of purified protein derivative (PPD)-positive individuals, with significant differences recorded in the levels of responsiveness between PPD-positive healthy controls and pulmonary tuberculosis patients . Flow cytometric analysis of whole blood stimulated with the recombinant Apa protein revealed a sizeable proportion of CD8(+) T cells in addition to CD4(+) T cells contributing to IFN-gamma secretion . PBMC responding to the Apa protein produced no interleukin-4, revealing a Th1 phenotype . A DNA vaccine and a poxvirus recombinant expressing the Apa protein were constructed and tested for their ability to protect immunized guinea pigs against a challenge dose of virulent M . tuberculosis . Although the DNA vaccine afforded little protection, the poxvirus recombinant boost after DNA vaccine priming conferred a significant level of protective immunity, bringing about a considerable reduction in mycobacterial counts from the challenge bacilli in spleens of immunized guinea pigs, a result comparable to that achieved by BCG vaccination. Antimicrob Agents Chemother, 2003 Apr, 47(4), 1228 - 32 Isolation of three Mycobacterium ulcerans strains resistant to rifampin after experimental chemotherapy of mice; Marsollier L et al.; By use of a murine model for Buruli ulcer, Mycobacterium ulcerans was found to be susceptible to rifampin, with the MIC being 0.5 to 1 micro g/ml . Three mutants were isolated after rifampin monotherapy . Two were resistant to rifampin at 8 micro g/ml, and one was resistant to rifampin at 32 micro g/ml . The mutants harbored Ser416Phe mutations and His420Tyr mutations in the rpoB gene, and these mutations have also been found to be responsible for rifampin resistance in the leprosy and tubercle bacilli . The results indicate that while rifampin may be active against M . ulcerans, it should never be used as monotherapy in humans. Arch Pathol Lab Med, 2003 Mar, 127(3), 326 - 30 Comparison of polymerase chain reaction with histopathologic features for diagnosis of tuberculosis in formalin-fixed, paraffin-embedded histologic specimens; Park do Y et al.; Objective.-To investigate the relationship between various histopathologic features and the results of the tuberculosis (TB)-polymerase chain reaction (PCR) method in routinely submitted histologic specimens for the histopathologic diagnosis of TB . Design.-We used 95 formalin-fixed, paraffin-embedded tissue blocks from 81 patients who were clinically suspected of having TB . We assessed the presence of histopathologic features including well-formed granuloma, poorly formed granuloma, caseous necrosis, and Langhans-type giant cells . We performed nested PCR for IS6110 and Ziehl-Neelsen staining for acid-fast bacilli (AFB) . Results.-Of the 81 patients studied, 53 patients had chronic granulomatous inflammation, whereas 28 patients had only chronic inflammation without definite granulomatous inflammation . Of the 53 cases with chronic granulomatous inflammation, 17 (32%) were AFB positive and 36 (68%) were TB-PCR positive . Among cases with chronic granulomatous inflammation, the percentage that were positive and negative by TB-PCR differed significantly with the presence of various histopathologic features . All of the 13 cases with well-formed granuloma, caseous necrosis, and Langhans-type giant cells were TB-PCR positive; however, 10 (36%) of the 28 cases with chronic inflammation without granulomatous lesions were also TB-PCR positive . Conclusions.-TB-PCR is a rapid, sensitive method for the diagnosis of TB in routinely processed formalin-fixed, paraffin-embedded histologic specimens and is readily available in histopathology laboratories . We recommend use of TB-PCR when TB is suspected clinically, especially in cases of chronic inflammation without definite evidence of granulomatous inflammation. Med Eng Phys, 2003 May, 25(4), 341 - 7 Development and evaluation of an automated stainer for acid-fast bacilli; Kim SC et al.; The current strategy for the control of tuberculosis (TB) relies on early diagnosis, and smear microscopy is an essential component of the laboratory diagnosis of TB in most countries with a high prevalence of the disease . However, even simple smear microscopy examination is far from satisfactory because staining results can vary among individual technicians . In an effort to minimize variations in manual staining procedures, we developed an automated stainer for AFB and evaluated its usefulness in comparison with manual staining . The key feature of our automated stainer is a heating apparatus required for fixation and carbol-fuchsin staining . After smear slides are placed into the machine, the entire staining process is fully automated, from fixation to final washing and drying . With the automated methods, five slides can be fixed and stained in 21 min at consistent high quality . Using sputum samples from 91 TB patients, the staining results of the automated stainer were compared blindly with those of manual staining . The concordance rate between the two methods was 94.5% . In addition, there was no significant difference in the rate of detection of AFB in the sputum samples . Although further optimization of the auto staining procedures is required, the results indicate that the automated AFB stainer developed in this study looks promising for use in clinical mycobacteriology laboratory in order to minimize personal variation during AFB staining. Postgrad Med, 2003 Mar, 113(3), 99 - 102, 105-6, 111-2 Aspiration pneumonia . Recognizing and managing a potentially growing disorder; Johnson JL et al.; Gross aspiration of liquid or particulate matter into the lung can result in severe hypoxemia, pulmonary infiltrates in dependent lung regions, fever, and leukocytosis . The initial lung injury is primarily due to inflammatory mediators rather than infection . The responsible bacterial pathogens differ between community-acquired and nosocomial aspiration pneumonia . Many aspiration pneumonias are mixed aerobic-anaerobic infections . Enteric gram-negative bacilli and S aureus are more common in nosocomial aspiration pneumonia . Current treatment guidelines support initial empirical antibiotic therapy in patients with severe aspiration pneumonia pending culture results . Appropriate initial treatment improves outcome . Antimicrobial therapy for aspiration pneumonia is often empirical and should be based on patient characteristics, the setting in which aspiration occurred, the severity of pneumonia, and available information regarding local pathogens and resistance patterns. Clin Nucl Med, 2003 Apr, 28(4), 286 - 9 Multifocal Pott's disease (tuberculous spondylitis) incidentally detected on Tc-99m MDP bone and Ga-67 citrate scintigraphy in a patient with diabetes; Kim SJ et al.; Pott's disease is an uncommon extrapulmonary form of tuberculosis . Delay in diagnosis and management may cause serious complications . The authors describe Pott's disease incidentally detected on Tc-99m MDP bone and Ga-67 imaging in a patient with diabetes . Tc-99m MDP bone scintigraphy showed intensely increased uptake in the lower cervical spine and lumbosacral regions . Ga-67 scintigraphy revealed intensely increased uptake corresponding to the areas noted on Tc-99m MDP bone scintigraphy . Magnetic resonance imaging showed destructive lesions in the C5-C6 and L5-S1 intervertebral discs with destruction of adjacent end plates . Biopsy of the lumbosacral area was guided by computed tomography, and histologic examination of the bone specimen showed caseation, giant cells, and acid-fast bacilli . Posterior decompression and posterolateral spinal fusion with bone grafts were performed . Antituberculous chemotherapy with isoniazid, rifampicin, pyrazinamide, and ethambutol was started . The patient showed remarkable relief of symptoms during a period of 9 months of therapy . Both Tc-99m MDP bone and Ga-67 imaging can offer the convenience of screening the entire body to detect multiple sites of Pott's disease. J Clin Invest, 2003 Mar, 111(5), 681 - 9 CD44 is a macrophage binding site for Mycobacterium tuberculosis that mediates macrophage recruitment and protective immunity against tuberculosis; Leemans JC et al.; Cell migration and phagocytosis are both important for controlling Mycobacterium tuberculosis infection and are critically dependent on the reorganization of the cytoskeleton . Since CD44 is an adhesion molecule involved in inflammatory responses and is connected to the actin cytoskeleton, we investigated the role of CD44 in both these processes . Macrophage (Mphi) recruitment into M . tuberculosis-infected lungs and delayed-type hypersensitivity sites was impaired in CD44-deficient (CD44(-/-)) mice . In addition, the number of T lymphocytes and the concentration of the protective key cytokine IFN-gamma were reduced in the lungs of infected CD44(-/-) mice . The production of IFN-gamma by splenocytes of CD44(-/-) mice was profoundly increased upon antigen-specific stimulation . Flow cytometry analysis revealed that soluble CD44 can directly bind to virulent M . tuberculosis . Mycobacteria also interacted with Mphi-associated CD44, as reflected by reduced binding and internalization of bacilli by CD44(-/-) Mphis . This suggests that CD44 is a receptor on Mphis for binding of M . tuberculosis . CD44(-/-) mice displayed a decreased survival and an enhanced mycobacterial outgrowth in lungs and liver during pulmonary tuberculosis . In summary, we have identified CD44 as a new Mphi binding site for M . tuberculosis that mediates mycobacterial phagocytosis, Mphi recruitment, and protective immunity against pulmonary tuberculosis. Am J Ophthalmol, 2003 Mar, 135(3), 393 - 5 Mycobacterium chelonae interface infection after endokeratoplasty; Busin M et al.; PURPOSE: To report a case of interface infection by Mycobacterium chelonae in a patient who underwent endokeratoplasty . DESIGN: Interventional case report . SETTING: Clinical practice . METHODS: Two weeks after endokeratoplasty, a 74-year-old woman developed multiple enlarging interface infiltrates in her right eye . Cultures performed on the preservation medium grew Mycobacterium chelonae . Penetrating keratoplasty (PK) surgery was performed after failure of conservative antibiotic therapy, including topical and systemic clarithromycin . RESULTS: Five months after PK surgery, the graft was clear and no signs of extraocular or intraocular inflammation were present . Cultures taken from the corneal interface at the time of PK surgery confirmed the presence of M . chelonae . Acid-fast bacilli were seen in the excised corneal button . CONCLUSIONS: M . chelonae should be ruled out as a possible etiologic agent when postoperative infection of the corneal interface occurs . Surgical intervention can lead to eradication of the infection when conservative treatment fails . J Microbiol Methods, 2003 Apr, 53(1), 107 - 12 Development of a new antigen detection dot-ELISA for diagnosis of tubercular lymphadenitis in fine needle aspirates; Jain A et al.; A sandwich dot enzyme-linked immunosorbent assay (ELISA) was standardized to detect mycobacterial antigen in fine needle aspirates of patients with tubercular lymphadenitis (TBLN) . The assay was performed on nitrocellulose paper by using antibodies raised in mice and rabbits against crude soluble protein (CSP) of Mycobacterium tuberculosis . The test was able to detect as low as 5 ng protein/ml . A total of 225 suspected cases of tubercular lymphadenopathy were screened, out of which 96 were cytomorphologically confirmed as cases of tubercular lymphadenitis (50 acid-fast bacilli (AFB)-positive and 46 AFB-negative) . These were considered as positive controls . Only 28 cases were proven to be of nontubercular etiology and were considered as negative controls . In the remaining 101 (39 scanty) aspirates, tubercular etiology could neither be ruled out nor confirmed . Out of 50 AFB-positive confirmed cases of tubercular lymphadenitis, 46 were ELISA-positive . Out of 46 AFB-negative but cytomorphologically confirmed aspirates, antigen could be demonstrated in only 42 aspirates . Four samples from patients with nontubercular etiology were also found to be ELISA-positive . Antigen was picked up in a total of 90.3% of aspirates with suspicion of tuberculosis and 79.5% of scanty aspirates . The assay was found to be 91.6% sensitive and 85.7% specific . The assay was found to be simple and rapid, and hence, could be performed in areas where health facilities are rudimentary. Kekkaku, 2002 Dec, 77(12), 805 - 13 {Treatment for multidrug-resistant tuberculosis in Japan}; Nakajima Y; INTRODUCTION: Multidrug-resistant (MDR) tuberculosis is now refractory against standard chemotherapy for tuberculosis . The curability of medical treatments for it has been up to 50-75% . In Japan several hundreds new MDR tuberculosis cases are supposed to occur every year . This review is the outline of Japanese preliminary guideline of treatment for MDR tuberculosis . DRUG SUSCEPTIBILITY TEST: One of the most important points to manage MDR tuberculosis is the drug usages according to drug susceptibility . Recently some susceptibility tests with liquid media were introduced in our country, but Japanese new standard test of Ogawa method (using absolute concentration with proportion method) is still important from point of true evaluation of susceptibility . MEDICAL CHEMOTHERAPY: In MDR tuberculosis one-half of two-third cases are cured by suitable resume of anti-tuberculosis chemotherapy . If patients would prove to be suffered from MDR tuberculosis, chemotherapy resume must be changed from standard resume to special one, that are made from effective and stronger four or five (at least three) anti-tuberculosis drugs including new quinolons . Those drugs should be changed at the same time, not one by one . Although CPM and Tb1 cannot be available in Japan, but sometimes we have to try administrations of those drugs, beta-lactam antibiotics, interferon . The duration of treatment will be 18-24 months usually . If decreasing of tuberculosis bacilli in sputa is failed under new effective resume through four months treatment, surgical treatment may be indicated . SURGICAL TREATMENT: (1) In Fukujuji Hospital, Japan Anti-Tuberculosis Association, surgical treatments for seventy four cases of MDR tuberculosis were undergone from 1983 to 2001 March . 85 surgical interventions for them were performed in 71 pulmonary resections (pneumonectomy in 20, lobectomy in 44, segmentectomy in 7) for 64 cases, 8 thoracoplasties alone for 8 cases, 5 cavernostomies for 5 cases, 1 phrenic nerve avulsion for 1 . The result of pulmonary resections was as follows; early negative conversion rate of tuberculosis expectorations was 97.2%, reexpectoration rate of sputa tuberculosis bacilli was 13.8%, final success rate of pulmonary resections was 91.7% . The factors significantly correlated to reexpectoration of tuberculosis bacilli were preoperative positive bacilli in sputa, few sensitive drugs, other cavitary lesions remained, postoperative prolonged bronchopleural fistula . The result of thoracoplasty alone revealed 75% success rate . In postoperative complications of 85 interventions, there was no operative death, prolonged bronchopleural fistula in 17.6%, respiratory failure in 8.7%, pyothorax in 5.9% . (2) Recently results of surgical treatment for MDR tuberculosis were reported in several literatures . Those success rates were almost same 85-95% as our result . They seemed to be very excellent for refractory cases against vigorous medical treatments . So any surgical treatment for MDR tuberculosis should be indicated more constructively in its earlier course . (3) Indication of surgical treatment is as follows; Main target lesions that should be removed are cavitary ones in pulmonary or pleural foci . And any capsulated localized tuberculosis foci more than 2 cm in diameter is better to be resected because of the possibility of later cavitation . Surgically it is the best that all tuberculosis foci are within a resected lobe, effective drugs remained as many as possible and no cardiopulmonary risks . But even if patient's state are over those criteria, resections of more extended pulmonary foci including in opposite sides can be tried within tolerable cardiopulmonary function . OTHER COMMENTS: Treatment for HIV-positive MDR tuberculosis and protection for nosocomial transmission of MDR tuberculosis are discussed briefly in this article . Preventive therapy for newly infected persons with MDR tuberculosis is controversial . At this time just in MDR tuberculosis cases no preventive therapy, careful following up, and drastic treatment with remained effective drugs after developping of disease will be recommended. Emerg Infect Dis, 2003 Feb, 9(2), 251 - 4 Photorhabdus species: bioluminescent bacteria as emerging human pathogens? Gerrard JG, McNevin S, Alfredson D, Forgan-Smith R, Fraser N. We report two Australian patients with soft tissue infections due to Photorhabdus species . Recognized as important insect pathogens, Photorhabdus spp . are bioluminescent gram-negative bacilli . Bacteria belonging to the genus are emerging as a cause of both localized soft tissue and disseminated infections in humans in the United States and Australia . The source of infection in humans remains unknown. Rev Prat, 2002 Dec 1, 52(19), 2121 - 6 {Thoracic tuberculosis}; Dautzenberg B; The diagnosis and treatment of thoracic tuberculosis follow common principles whatever the localisation . Tuberculosis is diagnosed on clinical signs: night sweats, fever, cough, weight loss, persisting after non-specific treatment, for more than 3 weeks . The demonstration of bacilli in sputum is the keystone of diagnosis, but in extrapulmonary localisations definitive proof is often drawn from a pleural, pericardial or even lymph node biopsy . After diagnosis, or when diagnosis is highly suspected, antituberculous treatment is started . Steroid could be useful in exsudative forms . The overall cure rate is 95% but side effects, poor compliance or bacteriological resistance can yield complex problems and lead to failures. Rev Prat, 2002 Dec 1, 52(19), 2115 - 20 {Biological diagnosis of tuberculosis}; Carbonnelle B et al.; Today, the diagnosis tests for tuberculosis are based on: the observation of acid-fast-bacilli after Ziehl-Neelsen staining or fluorescent microscopy, the growth of a culture, the study of drug sensibility, the observation of granulomatous tissue lesions and caseous necrosis . Use of radioactive liquid culture media (Bactec) or not, has shortened the time required for obtaining the result, but it remains too long and, so far, polymerase chain reaction has not answered the challenge . However molecular techniques have been applied with success to the identification of mycobacterial strains (DNA fingerprinting) and to rapid detection of antimicrobial resistance caused by mutation of the target genes . Progress of the molecular tests could lead to desoxyribonucleic microarrays, which would be able to revolutionize the microbiological diagnostic tests. Pneumologia, 2002 Jul-Sep, 51(3), 206 - 13 {Clinical and epidemiological changes in tuberculosis in children in the last 5 decades(1950-2000) }; Calciu M; This study analyses over a 48 years period (1953-2000) the incidence of various clinical forms of TB in children aged 0-8, admitted in several ftizio-pediatric institutions . Follow-up included: primary complex, pleuro-pulmonary involvement, bronchial adenogenic involvement, extra-respiratory forms and major sequelae of primary tuberculosis . The results show a marked decrease of incidence of all TB forms in children and disappearance of chronic extensive primary tuberculosis and major sequelae of primary tuberculosis . The incidence tappered in steps: a sudden decrease in 1964-65, another in 1974, followed by a gradual decline . On contrary, the incidence of multiple sequela calcifications seems to be increasing after 1980 . These clinical mutations, especially the one in 1974, may be attributed to strictly observed treatment, to reintroduction of national campaign of BCG vaccination and to the decrease of TB incidence in adults (diminished bacilli offer). Am J Respir Crit Care Med, 2003 Mar 1, 167(5), 723 - 5 Yield of sputum induction in the diagnosis of pleural tuberculosis; Conde MB et al.; We prospectively evaluated the diagnostic yield of acid-fast bacilli smear and culture for Mycobacterium tuberculosis using sputum induction (SI) in the workup of patients with suspected pleural tuberculosis (TB) who were unable to produce sputum spontaneously . Of the 113 patients studied, a final diagnosis of pleural TB was made in 84 patients (71 HIV seronegative) and a final diagnosis of another disease in 29 patients . Histopathologic examination of the pleural biopsy tissue had the highest diagnostic yield (78%; 66/84) . The bacteriologic yield was 62% (52/84) for the pleural tissue, 12% (10/84) for pleural fluid, and 52% (44/84) for sputum cultures obtained by SI . The yield of SI culture for M . tuberculosis was 55% (35/64) in patients with a normal radiograph (except for the pleural effusion) and 45% (9/20) in those with evidence of parenchymal disease suggestive of pulmonary TB (p = 0.6) . The yield of sputum cultures obtained by SI is high in patients suspected of having pleural TB even in those cases with no pulmonary parenchymal abnormalities on the chest radiograph. Intensive Care Med, 2003 Feb, 29(2), 179 - 88 Epub 2003 Jan 14. Outcome of postoperative pneumonia in the Eole study; Dupont H et al.; OBJECTIVES: Prognosis factors of ventilator-associated pneumonia (VAP) have been largely investigated, while the data concerning postoperative pneumonia (POP) are scarce . The aim of this multicenter, prospective study was to evaluate the predictive factors of mortality due to POP and the impact of initial antibiotic therapy on outcome . METHODS: Two hundred centers were included . Diagnosis of POP was assessed on clinical and laboratory criteria, chest X-ray changes and microbiological criteria, when possible . Outcomes of the patients were noted . An independent committee made a retrospective assessment of appropriateness of antimicrobial therapy . RESULTS: The overall mortality among the 556 cases of POP was 23% (126 patients) . Five parameters were independently associated with mortality: American Society of Anesthesiology (ASA) grade 3 or more ( p<0.001), age 64 years or more ( p<0.01), time to onset of pneumonia more than 3 days ( p<0.01), mottling ( p<0.05) and hypotension ( p<0.05) . Among the 322 microbiologically confirmed cases of pneumonia, 92 received inappropriate antibiotic (AB) therapy (29%) . No difference in mortality was observed between the patients receiving inappropriate and appropriate AB therapy (22.8 vs 16.9%) . In this subgroup, three parameters remained independently associated with mortality: ASA grade 3 or higher ( p<0.001), time to onset of pneumonia more than 3 days ( p<0.05) and hypotension ( p<0.05) . Inappropriate initial AB did not modify the model ( p=0.22) . CONCLUSIONS: Five independent predictive factors for mortality of POP were identified . Despite a trend toward decreased mortality with appropriate initial antimicrobial therapy, no difference was observed between the groups . Polymicrobial pneumonia or non-fermenting Gram-negative bacilli appeared to be a risk factor for inappropriate AB. Thyroid, 2002 Dec, 12(12), 1137 - 40 Primary tuberculosis of the thyroid gland: report of three cases; Pazaitou K et al.; We report on three cases with rapidly increasing thyroid masses who were referred with the provisional diagnosis of thyroid carcinoma . In the two cases, the diagnosis of tuberculosis was established after thyroidectomy, but in the third case diagnosis was made pre-operatively with acid fast bacilli (AFB) staining and culture from fine needle aspiration (FNA) material . Although rare, tuberculosis of the thyroid gland should be included in the differential diagnosis of thyroid masses . FNA, AFB staining and culture of the aspirate are important diagnostic tools in these cases. JAMA, 2003 Feb 19, 289(7), 885 - 8 Antibiotic resistance among gram-negative bacilli in US intensive care units: implications for fluoroquinolone use; Neuhauser MM et al.; CONTEXT: Previous surveillance studies have documented increasing rates of antimicrobial resistance in US intensive care units (ICUs) in the early 1990s . OBJECTIVES: To assess national rates of antimicrobial resistance among gram-negative aerobic isolates recovered from ICU patients and to compare these rates to antimicrobial use . DESIGN AND SETTING: Participating institutions, representing a total of 43 US states plus the District of Columbia, provided antibiotic susceptibility results for 35 790 nonduplicate gram-negative aerobic isolates recovered from ICU patients between 1994 and 2000 . MAIN OUTCOME MEASURES: Each institution tested approximately 100 consecutive gram-negative aerobic isolates recovered from ICU patients . Organisms were identified to the species level . Susceptibility tests were performed, and national fluoroquinolone consumption data were obtained . RESULTS: The activity of most antimicrobial agents against gram-negative aerobic isolates showed an absolute decrease of 6% or less over the study period . The overall susceptibility to ciprofloxacin decreased steadily from 86% in 1994 to 76% in 2000 and was significantly associated with increased national use of fluoroquinolones . CONCLUSIONS: This study documents the increasing incidence of ciprofloxacin resistance among gram-negative bacilli that has occurred coincident with increased use of fluoroquinolones . More judicious use of fluoroquinolones will be necessary to limit this downward trend. Int J Tuberc Lung Dis, 2003 Feb, 7(2), 159 - 64 Evaluation of undergraduate training on tuberculosis at Istanbul Medical School; Kilicaslan Z et al.; SETTING: Undergraduate training on tuberculosis at Istanbul Medical School . OBJECTIVE: To assess whether tuberculosis-related questions asked in chest medicine examinations comply with the World Health Organization's (WHO) learning objectives for tuberculosis training, and to investigate students' skills in interpreting radiology and smears with respect to tuberculosis . DESIGN: Tuberculosis questions set for 4th year medical students (n = 838) were compared with WHO objectives (n = 23): 122 students were each asked to interpret 10 chest X-rays which had been read by three experts as 'typical tuberculosis lesions', 'normal' or 'non-tuberculosis lesions'; 114 students were also each given five smears which had been interpreted by an expert as 'negative' or 'positive' with respect to acid-fast-bacilli (AFB), and were asked to interpret them . RESULTS: Questions covered only nine of the WHO objectives . Among 117 types of questions, 91 (77.8%) were about clinical-radiological findings, treatment and drugs; 334 (65.1%) of 513 X-rays with typical tuberculosis lesions, 77 (21.1%) of 364 normal X-rays and 87 (25.4%) of 343 X-rays with non-tuberculosis lesions were identified as tuberculosis (kappa 0.45) . Of 369 AFB-positive smears, 149 (40.4%) were evaluated as false negative, and of 185 AFB-negative smears, 48 (25.9%) were evaluated as false positive (kappa 0.49) . CONCLUSION: Examination questions set on tuberculosis at Istanbul Medical School do not adequately reflect WHO learning objectives . Students' skills in interpreting radiology and smears suggest that their practical training on tuberculosis is insufficient. Int J Tuberc Lung Dis, 2003 Feb, 7(2), 117 - 23 Causes of lower respiratory infection in HIV-infected Ugandan adults who are sputum AFB smear-negative; Worodria W et al.; SETTING: Mulago national referral and teaching hospital . OBJECTIVE: To assess the etiology of lower respiratory infections in HIV-infected Ugandan adults who are sputum acid-fast bacilli (AFB) smear-negative . DESIGN: A descriptive cross-sectional study . Participants included consecutive adult patients admitted to medical wards with respiratory symptoms of at least 3 weeks and infiltrates on chest radiograph . Those who were sputum AFB smear-negative and HIV-positive underwent bronchoscopy and bronchoalveolar lavage (BAL) . BAL fluid was obtained and stained for AFB and Pneumocystis carinii, and cultured for bacteria and fungi . RESULTS: Of 198 patients screened, 48 were sputum smear-positive for AFB . Sixty-seven were excluded for various reasons, leaving 83 patients who met the inclusion criteria and underwent bronchoscopy: 32 (38.6%) patients had P . carinii infection, 20 (24%) had pulmonary tuberculosis, nine (11%) had pulmonary Kaposi's sarcoma and pyogenic bacteria were identified in seven (8%) . No aetiological diagnosis was found in 24 (30%) patients . CONCLUSION: P . carinii and Mycobacterium tuberculosis were the commonest causes of disease among sputum AFB smear-negative, HIV-positive adults presenting to Mulago Hospital . Pulmonary Kaposi's sarcoma and pyogenic bacteria occurred with less frequency. Scand J Infect Dis, 2002, 34(12), 931 - 4 Multiple tuberculous brain abscesses; Wang KC et al.; Multiple tuberculous brain abscesses are rare . This report presents a female patient with a rapidly deteriorating clinical course . Computed tomographic scanning revealed multiple brain abscesses . Aspiration of one of the lesions yielded pus and positive acid-fast stained bacilli . The pathogenesis of multiple tuberculous brain abscesses is discussed. Pediatr Infect Dis J, 2003 Feb, 22(2), 109 - 14 Cefepime use in a pediatric intensive care unit reduces colonization with resistant bacilli; Toltzis P et al.; BACKGROUND: Cefepime has activity against many hospital-acquired Gram-negative pathogens resistant to earlier beta-lactam antibiotics . This study was designed to test whether preferential use of cefepime in a pediatric intensive care unit could reduce enteric colonization with antibiotic-resistant Gram-negative rods . METHODS: After a 6-month period of uncontrolled antibiotic use, cefepime was preferentially used during 2 years as treatment for nosocomial or serious community-acquired infection . Rectal swab specimens were obtained daily on every patient regardless of antibiotic exposure during the 6 months of uncontrolled antibiotic use and during the first and last 6 months of the 2 years of cefepime preference . The study outcome was rectal colonization with a facultative Gram-negative rod resistant to at least one of four antibiotics: cefepime; ceftazidime; gentamicin; or piperacillin-tazobactam . RESULTS: The incidence of colonization by a resistant organism decreased only slightly during the first 6 months of cefepime use . By contrast, the number of antibiotic-resistant bacilli isolated from rectal swab specimens diminished from 27.6/100 patients during the baseline period to 12.9/100 patients by the last 6 months of the 2 years of cefepime preference (P < 0.01) . The proportion of patients harboring at least one resistant organism decreased from 11.6% to 7.4% during the same time period (P < 0.01) . A decrease in colonization with resistant organisms occurred for all the tested resistance phenotypes, including cefepime . CONCLUSION: Cefepime may possess a low potential for promoting bacillary resistance in critically ill patients, suggesting that its preferential use might be a key element in limiting the presence of antibiotic resistance in the intensive care unit. Vet Immunol Immunopathol, 2003 Feb 10, 91(3-4), 169 - 82 Immunopathological studies on feline cutaneous and (muco)cutaneous mycobacteriosis; Kipar A et al.; Eight cases of feline (muco)cutaneous mycobacteriosis were studied to identify the causative agent and examine for phenotype and functional characteristics (expression of interleukin (IL)-1beta, IL-6, IL-12, tumour necrosis factor-alpha and inducible nitric oxide synthase) of the inflammatory cells . Polymerase chain reaction and sequencing identified the causative agents as Mycobacterium tuberculosis or M . avium complex in each four cases . Lesions were characterised by pyogranulomatous infiltration, with variability in the presence and size of necrotic areas, the presence of multinucleated giant cells and the degree of lymphocyte infiltration . Macrophages were positive for myeloid/histiocyte antigen (calprotectin), suggesting they represented freshly recruited monocytes; further differentiation to epithelioid cells and multinucleated giant cells was associated with loss of the myeloid/histiocyte antigen . Lymphocytes were found disseminated in the infiltrate (predominantly T cells) and as B cell-dominated accumulations mainly in the periphery of the lesions . Acid-fast bacilli were numerous . In M . tuberculosis complex infection, extracellular bacilli were most prominent, whereas in M . avium complex infection, bacilli were mainly located intracellularly . All cytokines examined as well as inducible nitric oxide synthase (iNOS) were variably expressed by macrophages, epithelioid cells and multinucleated giant cells . Expression was most intense in degenerating macrophages loaded with intracellular bacilli, but was also seen cell-free within necrotic areas . The intense induction of cytokine and iNOS expression especially in infected macrophages suggests a relatively low virulence for these infectious agents in cats . Furthermore, the confinement of the bacilli to lesions indicates a successful response to infection . Acta Cytol, 2003 Jan-Feb, 47(1), 51 - 5 Tuberculosis of the intercostal lymph nodes; Prasoon D; OBJECTIVE: To describe tuberculosis of the intercostal lymph nodes and discuss its clinical and cytologic profile and pathogenesis . STUDY DESIGN: Fifteen cases from March 1994 to March 2000 were retrieved from our cytology records . Only clinically and therapeutically proven cases were included in the study . RESULTS: The ages of the patients ranged from 4 to 63 years . The male:female ratio was 2:1 . The duration of disease at presentation ranged from one week to nine months . The lumps presented either in the parasternal region or between the midclavicular and posterior axillary lines . One case presented with an infrascapular lump . Most of the lumps were ill defined and cystic . Chest radiographs in all cases showed a soft tissue swelling without bony involvement . The aspirates were of two types, blood-mixed particles and necrotic material . Four cytologic pictures were seen: (1) epithelioid cell granulomas alone or (2) with necrosis or (3) with both necrosis and acid-fast bacilli (AFB), or (4) necrosis with AFB . AFB were detected in 53.3% of cases . CONCLUSION: If necrotic material is aspirated or if granulomatous inflammation is encountered in soft tissue swellings of the chest wall, particularly in the parasternal and axillary regions, the possibility of intercostal tuberculous lymphadenitis should be considered. Eur J Clin Microbiol Infect Dis, 2003 Jan, 22(1), 49 - 50 Epub 2003 Jan 18. A case of tuberculous sinusitis without concomitant pulmonary disease; Beltran S et al.; This case report highlights the difficulty of diagnosing tuberculous sinusitis in the absence of pulmonary foci . Although extrapulmonary localisations of tuberculosis are rare in immunocompetent patients, it is important to consider this diagnosis, since therapeutic delay usually results in an unfavourable outcome . Acid-fast bacilli are sometimes difficult to detect in pathological specimens . Consequently, the diagnosis is usually based on the following criteria: (i) the absence of clinical response to usual antibiotics, (ii) the presence of caseous granulomatous inflammatory lesion on histopathology, and (iii) identification of Mycobacterium tuberculosis by the polymerase chain reaction assay confirmed by bacteriological culture . The diagnosis of tuberculosis is finally confirmed by the efficacy of antituberculous treatment . The differential diagnosis is Wegener's disease. Eur J Biochem, 2003 Feb, 270(4), 625 - 34 Cytotoxic activity of nucleoside diphosphate kinase secreted from Mycobacterium tuberculosis; Chopra P et al.; Pathogenicity of Mycobacterium tuberculosis is closely related to its ability to survive and replicate in the hostile environment of macrophages . For some pathogenic bacteria, secretion of ATP-utilizing enzymes into the extracellular environment aids in pathogen survival via P2Z receptor-mediated, ATP-induced death of infected macrophages . A component of these enzymes is nucleoside diphosphate kinase (Ndk) . The ndk gene was cloned from M . tuberculosis H37Rv and expressed in Escherichia coli . Ndk was secreted into the culture medium by M . tuberculosis, as determined by enzymatic activity and Western blotting . Purified Ndk enhanced ATP-induced macrophage cell death, as assayed by the release of {14C}adenine . A catalytic mutant of Ndk failed to enhance ATP-induced macrophage cell death, and periodate-oxidized ATP (oATP), an irreversible inhibitor of P2Z receptor, blocked ATP/Ndk-induced cell death . Purified Ndk was also found to be autophosphorylated with broad specificity for all nucleotides . Conversion of His117-->Gln, which is part of the nucleotide-binding site, abolished autophosphorylation . Purified Ndk also showed GTPase activity . Collectively, these results indicate that secreted Ndk of M . tuberculosis acts as a cytotoxic factor for macrophages, which may help in dissemination of the bacilli and evasion of the immune system. Hunan Yi Ke Da Xue Xue Bao, 2002 Feb 28, 27(1), 88 - 90 {Determination of lipopolysaccharide by capillary zone electrophoresis}; Jing ZZ et al.; OBJECTIVE: To detect lipopolysaccharides (LPS) in frangibility bacilli, control the procedure of LPS preparation, examine the ally of the product by high performance capillary zone electrophoresis (CZE), and obtain rapidly high alloy of LPS for scientific research . METHODS: Theoptyline was added to the sample as an internal standard . The LPS was separated and detected by CZE in sodium tetraborate-borate buffer . The concentration of the buffer was 30 mmol.L-1 (pH 8.0); the diameter of the capillary column was 75 microns, and the length was 57 cm; the CZE operative voltage was 25 kV, the electric current was 112 microA, and the detecting wavelength was 230 nm . RESULTS: CZE was first internally used to separate and detecte LPS in bacillus . The LPS had a good linearity in the range of 2-30 mg.L-1 (r = 0.996) . The average recovery rate was 99%-101%, the in-day and day-to-day coefficients of variation (CV) were less than 5%, and the minimum detectable quantity was 1.0 mg.L-1 . CONCLUSION: Compared with the limulus test (LT) and gel electrophoresis, this method can resist heat source interference and is more simple, rapid and accurate . Moreover, it can control the preparative process of LPS immediately, and may be an advanced method to determine LPS. J Mol Evol, 2003 Feb, 56(2), 175 - 80 The p32K structural protein of the atadenovirus might have bacterial relatives; Elo P et al.; The primary structure of a novel adenoviral protein referred to as p32K and found exclusively in members of the proposed new genus Atadenovirus was analyzed . The p32K gene sequence was determined from two bovine and one snake adenovirus types . Altogether five different p32K sequences were examined, two of them were obtained from the Gene Bank . The C-terminal part of the protein is conserved and shares similarity with certain bacterial small acid soluble proteins (SASPs) . The sequence similarity seems coupled with functional relatedness, i.e . both protein groups are found in structures where the genome of the "dormant" organism is packaged in tight nucleoprotein complexes . In these complexes the DNA is protected against harmful environmental effects until the new reproductive cycle is started with specific protease cleavage of the packaging proteins . Although there is no experimental clue about the role of the p32K proteins, we hypothesize phylogenetic relationship between the two protein groups based on the sequence similarity and the supposed functional similarity . The alignments of these protein groups shows that the conserved part of the p32Ks probably is the result of the duplication of a shorter sequence similar to the SASPs of the Bacilli. Clin Nephrol, 2003 Jan, 59(1), 47 - 55 A preliminary survey of bacterial contamination of the dialysate circuit in continuous veno-venous hemodialysis; Kanagasundaram NS et al.; AIMS: The problem of dialysate bacterial contamination has not been defined in continuous renal replacement therapy . We assessed the bacterial integrity of source bicarbonate dialysate (study 1) and the continuous veno-venous HD (CVVHD) bicarbonate dialysate circuit (study 2) . METHODS: Study 1: 50 ml dialysate were collected from 41 bags randomly selected from 150 consecutively made dialysate bags, immediately after manufacture or after 24, 48 or 72 h . Study 2: 10 ml dialysate were drawn from 4 sample points ranged along the dialysate circuit in 18 therapies (mean duration 119.5 +/- 72.0 h) . All points were sampled at therapy start then daily, bar the proximal point which was sampled after each dialysate bag change . All dialysate samples underwent Gram stain and aerobic/anaerobic culture . Samples over 10 ml were cultured after centrifugation (15 min, 4,000 rpm) . A disseminated contamination (DC) involved > or = 1 sample point at a time and/or was sustained over time . RESULTS: Study 1: One bag was culture-positive (staphylococcal/diphtheroid growths; 48-h sample) . Study 2: Six DCs developed in 6 therapies (1 at therapy end, 5 sustained to therapy end (duration 57.25 +/- 45.95 h), 5 with Gram-negative bacilli, all involving reported growths of > or = 1,000 cfu) . Dialyzer-inclusive dialysate circuit changes were more frequent in non-DC therapies (change rate: DC, 0.08 +/- 0.12/day, non-DC, 0.34 +/- 0.23, p = 0.02, permutation tests with general scores) but did not entirely prevent DC or alter it once underway . CONCLUSIONS: Sustained bacterial contamination of bicarbonate-based CVVHD is common and could relate to the completeness of dialysate circuit change . The importance of technique and regular quality control is highlighted. Trop Doct, 2003 Jan, 33(1), 7 - 11 The diagnosis of extrapulmonary tuberculosis in Malawi; Harries AD et al.; There is little information on a country-wide basis in sub-Saharan Africa about how the diagnosis of extra-pulmonary tuberculosis (EPTB) is made . A country-wide cross-sectional study was carried out in 40 non-private hospitals in Malawi which register and treat (TB) patients in order to assess diagnostic practices in adults registered with EPTB . All patients aged 15 years and above in hospital on treatment for EPTB were reviewed usingTB registers, case note files and clinical assessment . There were 244 patients, 132 men and 112 women whose mean age was 36 years . In 138 (57%) patients, all appropriate procedures and investigations, commensurate with hospital resources, had been carried out . Of 171 EPTB patients with cough for 3 weeks or longer, 138 (81%) submitted sputum specimens for smear microscopy of acid-fast bacilli (AFB) . A confirmed diagnosis ofTB was made in 15 (6%) patients based on finding AFB or caseating granulomas in specimens . In 157 (64%) patients, the diagnosis of EPTB was considered to be correct . In 46 (19%) patients the diagnosis was considered to be TB, although different from the type of EPTB with which the patient was registered . In 39 (16%) patients an alternative non-TB diagnosis was made and in two (1%) patients it was not possible to make a decision . Diagnostic practices need to be improved, and ways of doing this are discussed. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi, 1999, 17(2), 113 - 4 {Preparation of DNA probe for Cryptosporidium parvum}; Guo B et al.; AIM: To prepare a probe with high specificity and sensitivity for the detection of Cryptosporidium parvum . METHODS: Using PCR method, a fragment from the DNA of C . parvum was amplified . The PCR product, 452 bp DNA, was labeled with hapten digoxigenin . RESULTS: Examination of sensitivity showed that the DNA probe could detect as low as 2 pg DNA from C . parvum . The dot-blot hybridizition assay showed that the probe hybridized with the DNA of C . parvum, but not hybridized with DNA of E . histolytica, G . lamblia, E . coli and D . bacilli . CONCLUSION: The probe was highly specific and sensitive for the detection of C . parvum. Clin Exp Immunol, 2003 Feb, 131(2), 292 - 8 Influence of Mycobacterium tuberculosis on differential activation of helper T-cells; Talreja J et al.; Host defence against tuberculosis infection involves T-lymphocyte mediated cellular immune responses . In this study we assessed T-cell activation by studying the early signal transduction events and production of cytokines by human CD4+ T-cells . The study constituted of five groups of subjects: (a) untreated acid fast bacilli (AFB)+ve TB patients who have not started anti-tuberculosis therapy (ATT) {New}; (b) patients who have taken ATT for two months {2T}; (c) patients who have taken ATT for six months {6T}; (d) mantoux positive healthy controls {T+ve}; (e) mantoux negative healthy controls {T-ve} . We found that mantoux positive healthy controls produced significantly higher levels of IP3, intracellular Ca2+ and presented increased PKC activity when CD4+ T-cells were stimulated with M . tuberculosis H37Rv cell lysate as compared to mantoux negative controls . Furthermore, decreased expression of CD54 (ICAM-1) and reduced {Ca2+}i were seen in TB patients as compared to T+ve healthy controls . TB patients showed significantly lower levels of IL-2 and IFNgamma and higher levels of IL-4 as compared to normal healthy controls, suggesting a diminished Th1 response . Thus, the reciprocal changes in cytokines, reduced {Ca2+}i levels, and CD54 expression in patients imply phenotype shifting of Th precursors to Th2 type in TB patients. J Commun Dis, 2001 Dec, 33(4), 241 - 4 Detection of tubercle bacilli in sputum: application of sodium hypochlorite concentration method; Saxena S et al.; Tuberculosis has emerged as the leading cause of death due to single infectious agent . Sputum microscopy forms mainstay of diagnosis as it is most reliable, specific and objective method available especially in developing countries . However, this method is hampered by lack of sensitivity . Liquefaction and concentration of sputum before Ziehl Neelsen staining improves yield and also makes examination of smears rapid and convenient . A total of 304 sputum samples were studied by direct staining and after sodium hypochlorite treatment and centrifugation . Direct smears stained with Auramine-Phenol were also examined . Use of sodium hypochlorite method increased the number of positive samples from 52 to 96 . No false positives were detected by either method . The method is simple as the only extra reagent required is sodium hypochlorite that is easily available . Additional advantage is that sodium hypochlorite, being a potent disinfectant, reduces the risk of laboratory acquired infections. Izv Akad Nauk Ser Biol, 2002 Nov-Dec, (6), 763 - 8 {Influence of different ecological groups of earthworms on the intensity of nitrogen fixation}; Tereshchenko NN et al.; The results of studying nitrogen fixation in organic substrates processed by different ecological groups of earthworms suggest that the earthworms Aporrectoidea caliginosa actively stimulate nonsymbiotic nitrogen fixation . In this respect, they exceed the manure worms Eizenia foetida tens of times due to the formation in the organic substrate of conditions favorable for the nitrogen fixing bacteria, and namely: low content of nitrogen easily accessible for microorganisms, changes in the structure of the microbial community of the substrate in favor of non-spore forms of bacteria, and suppression of the growth of saprophyte bacilli, the main competitors of nitrogen fixing bacteria for carbon nourishment sources. Enferm Infecc Microbiol Clin, 2003 Jan, 21(1), 42 - 55 {beta-Lactam antibiotics}; Marin M et al.; Betalactams, which act by inhibiting the last phase of bacterial cell wall synthesis, constitute the largest family of antimicrobial agents and the most extensively used in current clinical practice . These drug have a slow bactericidal action that is relatively independent of plasma concentrations, little toxicity and a broad therapeutic margin . Their spectrum has increased over the years with the incorporation of new molecules having greater activity against gram-negative bacilli . Nevertheless, the progressive emergence of acquired resistance has limited the empirical use of betalactams and their efficacy in certain situations . Despite this problem, penicillin is still the treatment of choice for a large number of classic infections, cephalosporins are widely used in surgical prophylaxis and severe community-acquired infections, carbapenems are the choice for mixed nosocomial and multiresistant bacterial infections and betalactamase inhibitors permit the effective use of amino- and ureido-penicillins in highly significant infections. J Feline Med Surg, 2003 Feb, 5(1), 37 - 41 Opportunistic mycobacterial granuloma in a cat associated with a member of the Mycobacterium terrae complex; Henderson SM et al.; An 18-month-old domestic short-haired neutered male cat presented with a nodular dermal thickening on a digit . Biopsy demonstrated pyogranulomatous inflammation with moderately frequent acid-fast bacilli . A member of theMycobacterium terrae complex was isolated . There was no evidence of systemic involvement . Treatment was initiated with enrofloxacin, rifampicin and clarithromycin . After 2 months there was no longer any clinically apparent dermal thickening . Treatment was continued for a further 3 months using enrofloxacin and rifampicin. Mil Med, 2003 Jan, 168(1), 24 - 7 Resistance patterns of Mycobacterium tuberculosis complex isolates in the Turkish Army from 1998 to 2000; Saracli MA et al.; The aim of this retrospective study was to investigate susceptibility rates of Mycobacterium tuberculosis complex (MTBC) isolates against streptomycin, rifampicin, isoniazid, and ethambutol between January 1998 and December 2000 in the Turkish Army . Specimens collected from patients were cultured both conventionally and radiometrically . Differentiation of MTBC bacteria from Mycobacteria other than tuberculosis bacilli was made by the BACTEC p-nitro-alpha-acetyl-amino-beta-hydroxypropiophenone test . Susceptibility testing of MTBC isolates was performed using the BACTEC radiometric susceptibility assay for mycobacteria . Most of the specimens originated from respiratory system . A total of 98 isolates in 1998, 123 isolates in 1999, and 84 isolates in 2000 were obtained and identified as MTBC using the radiometric BACTEC TB460 system . Initial resistance was most frequent to isoniazid followed by ethambutol, streptomycin , and rifampicin in this study period . The differences between resistance rates were not statistically significant on an annual basis . None of these isolates was resistant to all four antimycobacterial agents . Although resistance rates of our isolates were not as high as previously reported by some authors from Turkey and there was no significant difference between the annual susceptibility rates, routine screening of antituberculosis drug susceptibility should be continued to control the resistance development and its spread. Int J Tuberc Lung Dis, 2002 Dec, 6(12), 1098 - 101 Study of drug resistance in previously treated tuberculosis patients in Gujarat, India; Shah AR et al.; SETTING: Department of Tuberculosis and Chest Diseases and State Tuberculosis Diagnosis and Training Centre (STDTC), a DOTS centre in Ahmedabad, Gujarat State, India . The study was carried out by retrospectively reviewing patient data between January 2000 and August 2001 . OBJECTIVE: To evaluate the pattern of drug resistance among previously treated tuberculosis patients who remained symptomatic or smear-positive despite receiving anti-tuberculosis drugs under DOTS for a minimum of 5 months . DESIGN: A total of 1472 pulmonary tuberculosis patients who had taken anti-tuberculosis treatment were evaluated retrospectively with respect to their drug resistance pattern by sputum culture for acid-fast bacilli (AFB) and sensitivity testing with isoniazid, rifampicin, streptomycin and ethambutol (E) . RESULT: Of the 1472 patients evaluated, 804 (54.6%) were treatment failure cases and 668 (45.4%) were relapse cases; 822 patients (373 failure and 449 relapse) were culture-positive . Of these 822 patients, 482 (58.64%, 261 failure and 221 relapse) were resistant to one or more drugs . Resistance to one drug was observed in 86 patients (10.46%), to two drugs in 149 (18.13%), to three drugs in 122 (14.84%) and to four drugs in 125 (15.21%) . Single drug resistance was most commonly seen with isoniazid (62 patients, 7.5%), followed by streptomycin (12 patients, 1.4%), rifampicin (eight patients, 0.97%) and ethambutol (four patients, 0.4%) . Resistance to isoniazid plus rifampicin alone was seen in 76 patients (9.2%) . CONCLUSION: Drug resistance is a major problem in the treatment of pulmonary tuberculosis . Detection of drug resistance patterns and treatment with second-line anti-tuberculosis drugs in appropriate regimens are necessary in the treatment of failure and relapse cases in order to reduce the emergence of multidrug-resistant tuberculosis. Int J Tuberc Lung Dis, 2002 Dec, 6(12), 1058 - 66 Treatment results of DOTS in 1797 Sudanese tuberculosis patients with or without HIV co-infection; El-Sony AI et al.; SETTING: Consecutive new tuberculosis (TB) patients, from eight states in Sudan, who had never been previously treated for as much as 1 month between 1998 and 2000 . OBJECTIVE: To determine the impact of human immunodeficiency virus (HIV) co-infection on tuberculosis treatment outcome . DESIGN: All patients presenting with symptoms suggestive of tuberculosis underwent sputum microscopy for acid-fast bacilli (AFB) . Treatment is free of charge, and directly observed for all smear-positive patients . Treatment outcomes were those defined by the World Health Organization . All patients were tested anonymously for human immunodeficiency virus (HIV) using the Bionor test . RESULTS: Of 10 494 patients suspected of TB and referred for sputum microscopy, 1797 were TB cases; 983 had smear-positive pulmonary tuberculosis, 521 smear-negative pulmonary tuberculosis, and 293 extra-pulmonary tuberculosis . Smear-positive cases showed a cure rate of 77.2% and a failure rate of 1% . Smear-negative and extra-pulmonary patients had a completion rate of 79.4% . Cure rates for the smear-positive cases were 68.3% for HIV-positive and 77.6% for HIV-negative patients (P = 0.164) . Case fatality was significantly higher among HIV-positive (12%) than among HIV-negative cases (1.8%) (OR 7.7, 95% CI 3.51-16.8) . CONCLUSION: To date, a relatively low proportion of tuberculosis patients in Sudan also have HIV infection . These patients are substantially more likely to die while on treatment for their tuberculosis, a fact that underlines their need for more comprehensive care if their lives are to be prolonged . In addition, every effort is required to diminish the transmission of HIV infection to prevent the tragedy this infection represents to the community. Crit Care Med, 2003 Jan, 31(1 Suppl), S25 - 8 Restrictive antibiotic policies are appropriate in intensive care units; Paterson DL; Antibiotic use will always be an important part of medical practice in the intensive care unit . Antibiotic resistance increases the chance that empirical therapy will be inadequate to cover the organisms implicated in any particular infection . Therefore, strategies that can allow for optimal empirical antibiotic choice, while at the same time minimizing emergence of antibiotic resistance, are particularly important . In many situations, such strategies require some external stewardship of antibiotic use to be maximally effective . Antibiotic stewardship programs may take the form of management teams comprising infectious disease physicians and pharmacists . These clinicians work in concert with critical care specialists in choosing optimal empirical regimens and in streamlining therapy once culture results are available . Alternatively, computer-based clinical support systems have been developed that can guide physicians to utilize optimal antibiotic choices . External stewardship of antibiotic use may be particularly necessary in circumstances of increased antibiotic resistance, especially exhibited by Gram-negative bacilli . A number of examples exist in which antibiotic control programs can work when traditional infection control programs have failed . Mutation of organisms to produce antibiotic resistance is undoubtedly going to outstrip availability of new antibiotics in the near future . Antibiotic stewardship in concert with improved diagnostic methods may be our only hope in preventing endemic panresistant organisms. Auris Nasus Larynx, 2003 Feb, 30 Suppl, S131 - 4 A case report of difficult diagnosis in the patient with advanced laryngeal tuberculosis; Kenmochi M et al.; We report a patient with severe laryngeal tuberculosis (LTB) involving thyroid cartilage and combined with whole-bone metastasis . A 57-year-old male had presented only with hoarseness . Radiological findings were indicative of suspected metastasis from a malignant tumor . However, tuberculosis was considered by histopathological findings, and so sputum samples were tested for acid-fast bacilli and purified protein derivatives of tuberculin in order to detect the presence of LTB . A polymerase chain reaction confirmed the diagnosis . Anti-tuberculous medications were effective in resolving the hoarseness, and the removal of the mass in the right wing of thyroid cartilage was confirmed by computed tomography (CT). Chin J Traumatol, 2003 Feb 1, 6(1), 28 - 31 The risk factors of nosocomial infection in severe craniocerebral trauma; Yang ZM et al.; OBJECTIVE: To explore the risk factors of nosocomial infection in severe craniocerebral trauma and the way of prevention . METHODS: The clinical data of 387 patients with severe craniocerebral trauma were reviewed . RESULTS: The total nosocomial infection rate of this study was 22.99% . Pulmonary nosocomial infection presented most frequently . The G-bacilli were the most common infectious bacteria . The mortality rate of the infection group was 38.20% . CONCLUSIONS: Complications of nosocomial infection affect the prognosis of craniocerebral trauma patients . Nosocomial infection is related to the age of the patients, craniocerebral trauma severity, unreasonable utilization of antibiotics and invasive operations, such as tracheal cannula, mechanical ventilation, urethral catheterization and deep venous catheterization . Patients with severe craniocerebral trauma should be carefully treated and nursed to avoid nosocomial infection . In order to reduce the rate of nosocomial infection, intensive measurement should be adopted. J Pharm Pharmacol, 2002 Dec, 54(12), 1693 - 6 Continuous infusion versus intermittent administration of cefepime in patients with Gram-negative bacilli bacteraemia; Jaruratanasirikul S et al.; The objective of this study was to compare the pharmacokinetics of cefepime administered by continuous infusion and intermittent injection regimens . A prospective, randomized, cross-over study of ten patients with Gram-negative bacilli bacteraemia was conducted . All patients were randomized to receive cefepime either as a 4-g continuous infusion over 24 h for 48 h or a 2-g bolus administered intermittently intravenously every 12 h for 48 h . After 48 h the patients received the alternative dose regimen . Cefepime pharmacokinetic studies were carried out during hours 36-48 after the start of both regimens . All of the pathogens isolated from the blood in 7 patients had a minimum inhibitory concentration (MIC) < 1 microg mL(-1) . In both regimens, the serum cefepime concentrations at all time points were higher than the MIC for the pathogens isolated from this study . For the continuous infusion arm, the highest steady-state concentration was 49.80+/-18.40 microg mL(-1) and the lowest steady-state concentration was 41.42+/-16.48 microg mL(-1) . The steady-state concentrations were greater than 4 times the MIC of 8 microg mL(-1) . For the intermittent injection regimen, the mean trough concentration was 4.74+/-3.99 microg mL(-1) . The mean serum cefepime concentration was above 8 microg mL(-1) for 81.66% of the dosing interval . Therefore, we conclude that either continuous infusion or intermittent injection can be used as an effective mode of cefepime administration to achieve bactericidal activity. Infect Immun, 2003 Feb, 71(2), 864 - 71 Immunopathogenesis of pulmonary granulomas in the guinea pig after infection with Mycobacterium tuberculosis; Turner OC et al.; Pulmonary tuberculosis in guinea pigs is similar to the disease in humans and is accordingly widely used as a model to test tuberculosis vaccines . The primary site of expression of acquired immunity and the hallmark of tuberculosis is the granuloma . Granuloma morphology is well described, but there is limited information regarding T-cell subset influx . We monitored the course of pulmonary tuberculosis in guinea pigs and observed four distinct immunohistopathological stages . In all stages there were similar numbers and arrangement of CD4 and CD8 T cells . There were only small numbers of apoptotic lymphocytes, scattered around and within the necrotic core, and acid-fast bacilli were visible both within macrophages and free within airway debris . A key finding of the study was the observation that the development of the necrotic core was an early event and almost certainly preceded the emergence of the acquired immune response . This in turn suggests that innate mechanisms are the basis of the early lesions and that subsequent acquired responses are unable to moderate them . This hypothesis differs from the current dogma that excessive activity of T cells mediates delayed-type hypersensitivity and that cellular cytolysis is the root cause of the necrosis. Int Immunopharmacol, 2003 Jan, 3(1), 115 - 8 Freund adjuvant induces TLR2 but not TLR4 expression in the liver of mice; Lim SK; Freund adjuvants are used extensively to establish experimental animal models of autoimmune diseases and to produce antibodies . However, studies on their mechanisms of action have been largely neglected, particularly their effects on liver, the primary target organ for host-microbe interaction . Here we show that treatment with either complete (CFA) or incomplete (IFA) Freund adjuvant induced a 5-10-fold increase in toll-like receptor (TLR) 2 mRNA but not TLR4 mRNA in livers of mice . Since CFA is essentially made of killed Mycobacterium tuberculosis bacilli (Mtb) dissolved in IFA, it is the solvent in CFA that induced an increase in TLR2 expression . As TLR2 is the receptor activated by killed Mtb, this solvent-mediated increase in TLR2 expression will result in enhanced recognition of killed Mtb by hepatocytes during CFA administration . We propose that the potency of Freund adjuvant in eliciting an immune response lies in their ability to induce expression of the appropriate TLR, TLR2, for the active ingredient, killed Mtb, in CFA . Neurosurgery, 2003 Feb, 52(2), 331 - 8; discussion 338-9 Surgical management and outcome of tuberculous atlantoaxial dislocation: a 15-year experience; Sinha S et al.; OBJECTIVE: Tuberculous atlantoaxial dislocation is a rare disease entity . However, tuberculosis continues to be endemic in developing countries . Its earliest clinical presentation may be nonspecific, and delay in diagnosis may lead to irreversible neurological deficit . The management of tuberculous atlantoaxial dislocation includes ventral cervicomedullary decompression, occipitocervical arthrodesis, and administration of antituberculous medications . METHODS: Eighteen patients with tuberculous atlantoaxial dislocation who presented with neck pain and/or occipital headache, restriction of neck movement, difficulty swallowing, and signs of myelopathy were studied . Four patients had evidence of associated pulmonary tuberculosis . Plain x-rays of the cervical spine, computed tomographic scans, and magnetic resonance images were obtained in all patients for diagnosis and to assess the degree of dislocation and cervicomedullary compression . Simultaneous anterior neural decompression, via a transcervical retropharyngeal approach, and posterior arthrodesis were performed on all patients while they remained under anesthesia . Antituberculous chemotherapy was continued for 18 months . RESULTS: Histopathological analysis of excised tissue was consistent with tuberculosis in all patients . However, Ziehl-Neelsen staining for acid-fast bacilli was positive in two cases, and culture for Mycobacterium tuberculosis was negative in all patients . Patients with severe myelopathy experienced marked improvement . One patient died of fulminant resistant tuberculous meningitis . CONCLUSION: The transcervical retropharyngeal approach to the craniovertebral junction provides direct access to the lesion and avoids the potential bacterial contamination of the oral and pharyngeal cavity . It also prevents the development of persistent fistulae . Posterior stabilization should be performed directly after anterior neural decompression, while the patient remains under anesthesia, to prevent neurological deterioration before subsequent posterior fixation . This technique also is helpful for early mobilization of patients . The aim of surgical treatment should be to obtain biopsy tissue and to perform radical excision of epidural granulation tissue/abscess and infected bone using microsurgical technique . Antituberculous medication must be continued for 18 months with four drug regimens, and continuous monitoring of drug toxicity should be performed throughout the course of treatment. Rom J Gastroenterol, 2002 Dec, 11(4), 325 - 30 Whipple's disease . Case report; Andreica V et al.; The paper reports the clinical case of a 58 -year-old male patient admitted for diarrhea (6-7 stools/day, diffuse abdominal pain, borborygma, weight loss (20 kgs in two years), asthenia and fatigue . Physical examination evidenced a poor nutritional state (body mass index 19 kg/m2) . The abdomen was slightly distended . Biological tests evidenced moderate/severe anemia, hypoproteinemia and hypoalbuminemia . Endoscopic examination evidenced oedematous duodenal mucosa with white-yellowish deposits . Histology (HE stain) revealed the presence of foamy cells and the PAS-staining of the duodenal mucosa evidenced PAS-positive macrophages and numerous intracellular bacilli . Penicillin therapy 2 x 1 million U/day for 14 days, followed by tetracycline 4 x 250 mg/day improved the clinical picture, the patient had only one stool per day and gained weight . After 7 months of treatment the general condition was good and the patient had gained 17 kgs, the duodenal mucosa was normal . HE staining did not evidence foamy cells and no PAS-positive macrophages could be found. Paediatr Respir Rev, 2001 Jun, 2(2), 120 - 6 Diagnostic techniques in paediatric tuberculosis; de Charnace G et al.; Accurate diagnosis of tuberculosis (TB) in children is crucial to provide effective treatment and to identify the undiagnosed adult who probably infected the child . The diagnosis of tuberculosis in children is often based only on epidemiologic, clinical, and radiographic findings . Fibre-optic bronchoscopy may also be helpful but the recovery of tuberculous bacilli, which establishes the diagnosis, is difficult in children . Rapid diagnostic tests such as direct amplification and serological tests have been developed to improve early diagnosis . Their sensitivity is higher than that of conventional mycobacterial culture in most paediatric studies. Intensive Care Med, 2003 Jan, 29(1), 23 - 9 Epub 2002 Dec 04. Nosocomial pneumonia; Johanson WG et al.; Nosocomial pneumonia, or terminal pneumonia as it was formerly called, results from the repetitive microaspiration of contaminated oropharyngeal secretions into the lungs in the presence of impaired host defenses . This pathophysiologic sequence was suggested by the observations of Osler but clarified by the seminal work of Rouby and colleagues . The enormous impact of antimicrobial agents on the organisms responsible for nosocomial pneumonias was first identified by Kneeland and Price who found that organisms of the normal pharyngeal flora virtually disappeared in terminal pneumonias following administration of these drugs, being replaced by gram-negative bacilli . The remarkable susceptibility of seriously ill patients to becoming colonized by exogenous organisms, even in the absence of antimicrobial therapy, was shown by Johanson et al . These factors, antibiotics and the change in bacterial binding receptors in the airways associated with illness, lead to infections caused by exogenous organisms that are frequently resistant to antimicrobial agents . Clinical findings that usually identify patients with respiratory infections are unreliable for the diagnosis of nosocomial pneumonias as shown by Andrews et al . Invasive techniques, especially the protected specimen brush (PSB) technique, avoid contamination of the specimen by proximal secretions and accurately reflect the bacterial burden of the lung, as first shown by Chastre et al . Quantitation of such specimens serves as an excellent proxy for direct cultures of the lung and are the current gold standard for diagnosis. Rev Med Suisse Romande, 2002 Nov, 122(11), 531 - 3 {Traps of tuberculosis among the aged: an astonishing cyst of left foot}; Thievent B et al.; We report the case of a 75 years old man who insidiously developed a unusual presentation of tuberculosis . The story began with a tuberculous arthritis of the foot, later associated with pulmonary, endobronchial, mediastinal and cervical lymphadenitis tuberculosis . Because the microscopic examination was negative for acid-fast bacilli (AFB) in all involved sites, the diagnosis of sarcoidosis was suggested . We discuss the diagnosis difficulties of tuberculosis in the elderly, the extrapulmonary manifestations of tuberculosis and some aspects of its differential diagnosis with sarcoidosis. Afr J Med Med Sci, 2002 Mar, 31(1), 25 - 31 Pattern of active pulmonary tuberculosis in human immunodeficiency virus seropositive adult patients in University College Hospital, Ibadan, Nigeria; Awoyemi OB et al.; Fifty-eight confirmed HIV-seropositive adult patients were studied . All subjects were interviewed and examined . Subjects with positive respiratory symptoms and signs had their sputum examined and cultured for Mycobacterium tuberculosis (M . tuberculosis) . Their chest radiograph, full blood count (FBC) and erythrocyte sedimentation rate (ESR) were also estimated . Subjects with Pulmonary tuberculosis were treated using directly observed therapy short course (DOTS) regimen . Sixty-three percent of subjects were positive for Mycobacterium tuberculosis on direct smear and/or culture . Sputum acid fast bacilli (AFB) positive subjects who completed the intensive phase of antituberculous drugs were sputum converted at 2 months . The chest x-ray finding at diagnosis showed 2 subjects (11%) with normal chest x-ray; localised lesion in 7 (37%) subjects; diffuse lesion in 7 (37%); pulmonary cavities in 3 (16%); miliary pattern in 2 (11%); pleural effusion in 2 (11%); hilar adenopathy in 2 (11%) . Repeat chest-x-ray at 3 months showed complete clearance of pulmonary infiltrates in 29% whilst 71% had appreciable improvement in radiologic features . The study showed that although chest x-ray may be "normal" in sputum AFB positive HIV infected individuals, radiologic picture tends to be more diffuse and extensive . This study was therefore undertaken to determine the pattern of PTB in HIV seropositive adult patients in U.C.H., Ibadan. J Formos Med Assoc, 2002 Nov, 101(11), 741 - 8 Use of prophylactic antibiotics in surgery at a medical center in southern Taiwan; Chen YS et al.; BACKGROUND AND PURPOSE: Use of prophylactic antibiotics to prevent postoperative infection (POI) is a common practice in surgery . This study investigated the amount and cost of surgical prophylaxis in a representative general hospital in Taiwan in order to determine an appropriate course of action to control antibiotic use and decrease the burden of resistance . METHODS: The use of antibiotic prophylaxis for a wide variety of surgical procedures over a 6-month period was retrospectively evaluated in 3,104 patients at a medical center in southern Taiwan . RESULTS: Timing of perioperative parenteral antibiotics was inappropriate in 738 (23.8%) patients . The average duration of antibiotic use was 6.4 days (2.4 days intravenous + 4.0 days oral) . Only 4.9% of patients did not receive prophylactic antibiotics and only 9.2% received a single dose . Prophylaxis exceeded 1 day in 80% of patients and 3 days in 68.2% . The most common regimen was cefazolin plus gentamicin, used in 2,338 (75.3%) procedures . There were 146 POIs in 119 (3.8%) patients . The most common POI was at the surgical site . Aerobic gram-negative bacilli were most common among the 81 pathogens isolated (54.3%), followed by gram-positive cocci (34.6%), anaerobes (8.6%) and yeasts (2.4%) . The total cost for prophylactic antibiotics was New Taiwan (NT)$5,860,242 (approximately US$ 169,862) . Had a single dose of cefazolin been used for all patients, the cost would have been reduced by 92.1% . Had four doses of cefazolin been used, the cost would have been reduced by 68.5% . CONCLUSIONS: This study documented the excessive use and often inappropriate timing of administration of antibiotics for surgical prophylaxis in a representative medical center in Taiwan . Strategies are needed to improve the appropriate use of surgical antibiotic prophylaxis in Taiwan, not only to reduce costs but, more importantly, to delay the emergence of resistant microorganisms. J Assoc Physicians India, 2002 Sep, 50, 1110 - 4 Utility of bronchoalveolar lavage in the diagnosis of pulmonary infections in immunosuppressed patients; Menon LR et al.; AIM: To evaluate the utility of bronchoalveolar lavage (BAL) in immunocompromised patients . MATERIAL AND METHODS: We studied BAL cytology and microbiological culture in 16 kidney transplant recipients (Group A), 14 dialysis patients (Group B) and eight HIV positive patients (Group C) suspected of having pulmonary infections . A group of 21 individuals without pulmonary diseases were studied as controls . RESULTS: A comparison of the cytological profile in controls and study groups showed that percentages of lymphocytes and neutrophils were significantly increased in all three patient groups as compared to controls, BAL bacterial cultures were positive in 4, 3 and 4 cases of Group A, B and C, respectively . Direct examination of BAL cytosmears helped in detecting cytomegalovirus inclusions, acid fast bacilli and Pneumocystis carinii in 3, 2 and 5 cases of Group A, B and C, respectively though microbial cultures were negative . The sensitivity of BAL cytology was found to be 76.3%, whereas that of microbial culture was only 31.5% . The diagnostic yield of BAL was 68.75%, 71.42% and 100% in the Groups A, B and C, respectively, while it was 76% when all three groups were considered together . BAL cytology yielded the diagnosis in 47.36% of cases, a combination of BAL cytology and culture in 23.68% and culture alone in 5.3% of cases . CONCLUSIONS: BAL is useful relatively non-invasive investigative tool in the rapid diagnosis of infections in immunocompromised patients . BAL cytology was found to be more useful than microbial cultures. Hunan Yi Ke Da Xue Xue Bao, 2000 Dec 28, 25(6), 573 - 5 {Comparison of infectious brain edema models induced by different kinds of pertussis bacilli in rats}; Yin F et al.; OBJECTIVE: To understand the difference of infectious brain edema models induced by varied kinds of pertussis bacilli in rats and to look for a new infectious brain edema model . METHODS: Sprague-Dawley rats were randomly divided into 3 groups: normal saline group(NS); rude pertussis bacilli(PBR); purified pertussis bacilli(PBP) . After infectious brain edema model was induced by rude pertussis bacilli or purified pertussis bacilli, the water content(WC), Evan's blue content(EB), Na+ and K+ content in brain tissues were measured . RESULTS: The WC, EB and Na+ contents in brain tissues in PBR and PBP groups were significantly increased than those in NS group; K+ content was significantly decreased in PBR and PBP groups than that in NS group(P < 0.01) . Evan's blue discoloration was demonstrated in all rats of PBR group, but 6 rats of PBP group showed bluish discoloration . EB content in brain tissues was significantly increased in PBR group than that in PBP group . CONCLUSIONS: The infectious brain edema model can be induced by rude pertussis bacilli or purified pertussis bacilli in rats, the former gives priority to mixed brain edema, and the latter mainly avails cytotoxin brain edema. Hunan Yi Ke Da Xue Xue Bao, 2000 Dec 28, 25(6), 519 - 21 {Effect of baicalin and dexamethasone on cytokines in brain tissue of infectious brain edema}; Yu Y et al.; OBJECTIVE: To explore the effect of baicalin(BC) and dexamethasone(DXM) on interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha(TNF-alpha) in brain tissues of infectious brain edema . METHODS: The infectious brain edema model induced by pertussis bacilli(PB) was used . Brain water content(WC), content of Na+ and the levels of IL-1 beta, TNF-alpha were determined, and the morphological changes were observed under the light microscope . RESULTS: The results showed that the levels of WC, Na+, IL-1 beta and TNF-alpha in group PB were higher than those in group of normal saline(NS) (P < 0.01) . And they were lower in groups BC and DXM than those in group PB(P < 0.05) . In groups BC and DXM, there were no significant difference in the contents of water, Na+, IL-1 beta and TNF-alpha(P > 0.05) . The water contents were positive linar correlated with IL-1 beta or TNF-alpha(P > 0.05) . The water contents were positive linear correlated with IL-1 beta or TNF-alpha contents(r = 0.9381, 0.8349, P < 0.01) . The structure of brain tissues in group NS was normal . In group PB, there were severe edema in brain tissues . In groups BC and DXM, the edema of brain tissues was reduced . CONCLUSIONS: The results suggest that the protective effect of BC and DXM against infectious brain edema were similar, the mechanism may be associated with the reduction of TNF-alpha and IL-1 beta. J Vet Sci, 2002 Sep, 3(3), 163 - 6 Mycobacterium bovis infection in a farmed elk in Korea; Kim JH et al.; A case of tuberculosis is reported in an eight-year-old, male, elk (Cervus elaphus nelsoni) . The elk showed severe coughing, respiratory distress, abdominal breathing, anorexia, and severe progressive emaciation in the elk farm . At necropsy, the elk appeared in poor body condition . Mild enlargement of retropharyngeal and submandibular lymph node was observed in the head . Diffuse fibrinous pleuritis and purple red lobar pneumonia were found in the thorax . Well demarcated numerous dark yellow discrete or confluent nodules from 0.3 to 2 cm in diameter were scattered in the whole lung . Bronchial and mediastinal lymph nodes were also enlarged . Histopathologically, lungs had typical classical tuberculous granulomas, multiple abscesses, and numerous macrophages and Langhans giant cells infiltration in alveolar lumen . In the lymph nodes, there were small clusters of necrosis and infiltration of numerous macrophages, epithelioid cells, and Langhans giant cells . With the acid-fast staining, numerous mycobacteria were revealed in the lung and lymph nodes . According to this study, there are differences of the histopathologic lesions and the numbers of acid-fast bacilli in the lesions between this elk and cattle . Mycobacterium bovis was confirmed as a causative agent in this elk using bacterial isolation, biochemical characteristics, and PCR technique . The isolate was negative for niacin test, nitrate reductase, and pyrazinamidase . This is a first report for bovine tuberculosis of farmed elk in Asia. Proc Natl Acad Sci U S A, 2003 Jan 7, 100(1), 241 - 6 Epub 2002 Dec 27. Expression of Th1-mediated immunity in mouse lungs induces a Mycobacterium tuberculosis transcription pattern characteristic of nonreplicating persistence; Shi L et al.; The lung is the primary target of infection with Mycobacterium tuberculosis . It is well established that, in mouse lung, expression of adaptive, Th1-mediated host immunity inhibits further multiplication of M . tuberculosis . Here, real-time RT-PCR was used to define the pattern of expression against time of lung infection of key genes involved in Th1-mediated immunity and of selected genes of M . tuberculosis . Inhibition of bacterial multiplication was preceded by increased mRNA synthesis for IFN-gamma and inducible NO synthase (NOS2) and by NOS2 protein synthesis in infected macrophages . Concurrently, the pattern of transcription of bacterial genes underwent dramatic changes . mRNA synthesis increased for alpha-crystallin (acr), rv2626c, and rv2623 and decreased for superoxide dismutase C (sodC), sodA, and fibronectin-binding protein B (fbpB) . This pattern of M . tuberculosis transcription is characteristic of the nonreplicating persistence {Wayne, L . G . & Sohaskey, C . D . (2001) Annu . Rev . Microbiol . 55, 139-163} associated with adaptation of tubercle bacilli to hypoxia in vitro . Based on this similarity, we infer that host immunity induces bacterial growth arrest . In IFN-gamma gene-deleted mice, bacterial growth was not controlled; NOS2 protein was not detected in macrophages; sodC, sodA, and fbpB transcription showed no decrease; and acr, rv2626c, and rv2623 transcription increased only at the terminal stages of lung pathology . These findings define the transcription signature of M . tuberculosis as it transitions from growth to persistence in the mouse lung . The bacterial transcription changes measured at onset of Th1-mediated immunity are likely induced, directly or indirectly, by nitric oxide generated by infected macrophages. Indian J Pediatr, 2002 Nov, 69 Suppl 1, S39 - 43 Aspiration cytology for diagnosis of tuberculosis--perspectives in India; Verma K et al.; Tuberculosis (TB) a common cause of mortality can readily be diagnosed by fine needle aspiration . The technique is a simple, cost effective, out patient procedure with a high diagnostic accuracy both in adults and children . The diagnostic morphologic findings comprise of epithelioid cell granulomas and giant cells with or without necrosis . Often an acute inflammatory exudate is obtained . Stain for acid fast bacilli immensely augments diagnosis especially in cases where necrosis or an inflammatory exudate is obtained . Culture studies on aspirated material are time consuming though diagnosis is enhanced . PCR can be applied to detect mycobacterial DNA and has been applied on aspirated material and found to be more sensitive in the detection of tuberculosis . In children TB of lymph nodes is readily identified and so also from other sites such as bone and soft tissues . In children FNAC also plays a role in detection of BCG adenitis, infection with atypical mycobacteria and co-existing infections such as HIV and AIDS. Indian J Pediatr, 2002 Nov, 69 Suppl 1, S20 - 4 PCR diagnosis of tuberculosis--experience in India; Singh UB et al.; Rapid and accurate diagnosis of tuberculosis is the cornerstone of global tuberculosis control programmes . With increasing incidence of tuberculosis epidemics, the low sensitivity and the length of time taken by traditional diagnostic modalities have hampered the efforts to interrupt disease transmission . Introduction of Polymerase Chain Reaction has enhanced the diagnostic predictability of the disease especially in the extrapulmonary, paucibacillary samples . High specificity and sensitivity have been reported in different samples . The technique is capable of picking as few as ten to fifty tubercle bacilli . When PCR technique is performed under quality controlled conditions, false negatives (due to underfined polymerase inhibitors) and false positives (due to cross contamination during sample collection or in the laboratory) can easily by avoided . Samples from sites with a possible latent infection focus or DNA from dead bacilli may give a positive reaction . The use of PCR with traditional diagnostic tools along with clinical presentation can prove helpful in patients presenting with a diagnostic dilemma. J Mol Biol, 2003 Jan 17, 325(3), 411 - 20 Structures of phosphate and trivanadate complexes of Bacillus stearothermophilus phosphatase PhoE: structural and functional analysis in the cofactor-dependent phosphoglycerate mutase superfamily; Rigden DJ et al.; Bacillus stearothermophilus phosphatase PhoE is a member of the cofactor-dependent phosphoglycerate mutase superfamily possessing broad specificity phosphatase activity . Its previous structural determination in complex with glycerol revealed probable bases for its efficient hydrolysis of both large, hydrophobic, and smaller, hydrophilic substrates . Here we report two further structures of PhoE complexes, to higher resolution of diffraction, which yield a better and thorough understanding of its catalytic mechanism . The environment of the phosphate ion in the catalytic site of the first complex strongly suggests an acid-base catalytic function for Glu83 . It also reveals how the C-terminal tail ordering is linked to enzyme activation on phosphate binding by a different mechanism to that seen in Escherichia coli phosphoglycerate mutase . The second complex structure with an unusual doubly covalently bound trivanadate shows how covalent modification of the phosphorylable His10 is accompanied by small structural changes, presumably to catalytic advantage . When compared with structures of related proteins in the cofactor-dependent phosphoglycerate mutase superfamily, an additional phosphate ligand, Gln22, is observed in PhoE . Functional constraints lead to the corresponding residue being conserved as Gly in fructose-2,6-bisphosphatases and Thr/Ser/Cys in phosphoglycerate mutases . A number of sequence annotation errors in databases are highlighted by this analysis . B . stearothermophilus PhoE is evolutionarily related to a group of enzymes primarily present in Gram-positive bacilli . Even within this group substrate specificity is clearly variable highlighting the difficulties of computational functional annotation in the cofactor-dependent phosphoglycerate mutase superfamily . J Immunol, 2003 Jan 1, 170(1), 430 - 7 Survival of Mycobacterium tuberculosis in host macrophages involves resistance to apoptosis dependent upon induction of antiapoptotic Bcl-2 family member Mcl-1; Sly LM et al.; Mcl-1 protein expression was found to be up-regulated during infection with virulent Mycobacterium tuberculosis strain H37Rv . Mcl-1 induction in THP-1 cells was optimal at a multiplicity of infection of 0.8-1.2 bacilli per macrophage and was independent of opsonin coating of the bacteria . Mcl-1 expression was elevated as early as 4 h, peaked at 5.8-fold above control cells at 24 h, and remained elevated at 48 h after infection . In THP-1 cells, mMcl-1 mRNA was induced by infection with live H37Rv but not with attenuated M . tuberculosis strain H37Ra, heat-killed H37Rv, or latex beads . In THP-1 cells and monocyte-derived macrophages (MDMs), Mcl-1 protein was induced by infection with live H37Rv but not with attenuated M . tuberculosis strain H37Ra, heat-killed H37Rv, or latex beads . Treatment of uninfected, H37Ra-infected, and H37Rv-infected THP-1 cells and MDMs with antisense oligonucleotides to mcl-1 reduced Mcl-1 expression by >84% . This resulted in an increase in apoptosis of both MDMs and THP-1 cells that were infected with H37Rv, but not cells that were uninfected or infected with H37Ra . Increased apoptosis correlated with a decrease in M . tuberculosis CFUs recovered from antisense-treated, H37Rv-infected cells at 4 and 7 days after infection . In contrast, CFU recoveries from sense-treated, H37Rv-infected cells or from antisense- or sense-treated, H37Ra-infected cells were unchanged from controls . Thus, the antiapoptotic effect of the induction of Mcl-1 expression in H37Rv-infected macrophages promotes the survival of virulent M . tuberculosis. J Biol Chem, 2003 Feb 21, 278(8), 5513 - 6 Epub 2002 Dec 20. The cell surface receptor DC-SIGN discriminates between Mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan; Maeda N et al.; Interactions between dendritic cells (DCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, most likely play a key role in anti-mycobacterial immunity . We have recently shown that M . tuberculosis binds to and infects DCs through ligation of the DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and that M . tuberculosis mannose-capped lipoarabinomannan (ManLAM) inhibits binding of the bacilli to the lectin, suggesting that ManLAM might be a key DC-SIGN ligand . In the present study, we investigated the molecular basis of DC-SIGN ligation by LAM . Contrary to what was found for slow growing mycobacteria, such as M . tuberculosis and the vaccine strain Mycobacterium bovis bacillus Calmette-Guerin, our data demonstrate that the fast growing saprophytic species Mycobacterium smegmatis hardly binds to DC-SIGN . Consistent with the former finding, we show that M . smegmatis-derived lipoarabinomannan, which is capped by phosphoinositide residues (PILAM), exhibits a limited ability to inhibit M . tuberculosis binding to DC-SIGN . Moreover, using enzymatically demannosylated and chemically deacylated ManLAM molecules, we demonstrate that both the acyl chains on the ManLAM mannosylphosphatidylinositol anchor and the mannooligosaccharide caps play a critical role in DC-SIGN-ManLAM interaction . Finally, we report that DC-SIGN binds poorly to the PILAM and uncapped AraLAM-containing species Mycobacterium fortuitum and Mycobacterium chelonae, respectively . Interestingly, smooth colony-forming Mycobacterium avium, in which ManLAM is capped with single mannose residues, was also poorly recognized by the lectin . Altogether, our results provide molecular insight into the mechanisms of mycobacteria-DC-SIGN interaction, and suggest that DC-SIGN may act as a pattern recognition receptor and discriminate between Mycobacterium species through selective recognition of the mannose caps on LAM molecules. Infect Immun, 2003 Jan, 71(1), 254 - 9 THP-1 cell apoptosis in response to Mycobacterial infection; Riendeau CJ et al.; We previously reported that Mycobacterium tuberculosis infection primes human alveolar macrophages (HAM) for tumor necrosis factor alpha (TNF-alpha)-mediated apoptosis and that macrophage apoptosis is associated with killing internalized bacilli . Virulent mycobacterial strains elicit much less apoptosis than attenuated strains, implying that apoptosis is a defense against intracellular infection . The present study evaluated the potential for phorbol myristate acetate-differentiated THP-1 cells to mimic this response of primary macrophages . Consistent with the behavior of alveolar macrophages, attenuated M . tuberculosis H37Ra and Mycobacterium bovis BCG strongly induce THP-1 apoptosis, which requires endogenous TNF . THP-1 apoptosis is associated with reduced viability of infecting BCG . In contrast, virulent wild-type M . tuberculosis H37Rv and M . bovis do not increase THP-1 apoptosis over baseline . BCG induced early activation of caspase 10 and 9, followed by caspase 3 . In contrast, wild-type M . bovis infection failed to activate any caspases in THP-1 cells . BCG-induced THP-1 apoptosis is blocked by retroviral transduction with vectors expressing crmA but not bcl-2 . We conclude that differentiated THP-1 cells faithfully model the apoptosis response of HAM . Analysis of the THP-1 cell response to infection with virulent mycobacteria suggests that TNF death signals are blocked proximal to initiator caspase activation, at the level of TNF receptor 1 or its associated intracytoplasmic adaptor complex . Interference with TNF death signaling may be a virulence mechanism that allows M . tuberculosis to circumvent innate defenses leading to apoptosis of infected host cells. Biochemistry (Mosc), 2002 Nov, 67(11), 1207 - 16 Late stages of protein secretion in bacilli; Sharipova MR; This review highlights the later stages of protein secretion in bacilli, which include protein release from the membrane and their translocation through the cell wall . Mechanisms of release of secreted polypeptides into the medium differ in Gram-positive and Gram-negative bacteria due to different structure of their cell envelope . Exogenous factors including molecular chaperons that can influence polypeptide folding may be also involved in later stages of protein secretion in bacilli . In Gram-positive bacteria protein secretion also depends on structural components of the cell wall . Certain evidence exists that maintenance of the secretory function is important for normal development of the sporulation process in these bacteria. Avian Dis, 2002 Oct-Dec, 46(4), 1055 - 61 Outbreak of avian tuberculosis in 48-week-old commercial layer hen flock; Gonzalez M et al.; This report describes an outbreak of tuberculosis in a flock of 38,500 48-wk-old layer hens . Clinical characteristics of the process included a gradual drop in egg production and feed intake, as well as an increased mortality rate . Two well-defined clinical features were observed . On the one hand, a number of birds displayed good body condition and continued to lay but presented granulomatous nodular lesions, particularly in the infraorbital sinus, liver, and intestine . In contrast, other hens were emaciated and presented granulomatous lesions of various sizes throughout the internal organs . The lesions observed in the various organs of all the affected birds consisted of granulomas containing acid/alcohol-fast bacilli . The presence of Mycobacterium avium was confirmed through polymerase chain reaction techniques . This report describes the epidemiologic and histopathologic characteristics of the outbreak. Kekkaku, 2002 Nov, 77(11), 729 - 33 {A case of multidrug-resistant tuberculosis (MDR-TB) in young female complicated with acute respiratory distress syndrome and developing multiple giant cysts and pneumothorax in both lung}; Ito Y et al.; A 20-year-old woman was admitted to our hospital because of cough and dyspnea in April 2001 . On admission, laboratory data showed positive inflammatory signs . A chest roentogenogram revealed infiltrated shadow in the bilateral lung fields . Sputum smear examination showed acid-fast bacilli identified as Mycobacterium tuberculosis by DNA-DNA PCR method . Four days after admission, she had an acute respiratory distress syndrome (ARDS) and serious liver dysfunction . Moreover, drug sensitivity test revealed that this case was multidrug-resistant tuberculosis (MDR-TB), and she was treated with sensitive anti-tuberculous drugs (PZA, SM, LVFX) . Three months later, her sputa converted to negative for tubercle bacillis, however, a chest computed tomogram (CT) revealed multiple giant cysts in the bilateral lung fields, which developed during treatment . Pneumothorax of both sides was repeatedly observed, and it was difficult to treat . At present (1 year after admission), multiple giant cysts stopped its progression and treatment for tuberculosis is being continued. Kekkaku, 2002 Nov, 77(11), 725 - 8 {A case of Mycobacterium avium pulmonary disease accompanied with pleural effusion}; Kobayashi K et al.; Nontuberculous mycobacterial infection is seldom complicated with pleural involvement . We report a very rare case of M . avium pulmonary disease accompanied with pleural effusion . A 76-year-old man was admitted to our hospital because of cough and low-grade fever . A chest radiograph and computed tomograph showed centrilobular nodules in the right middle lobe and left lingula, and right pleural effusion . The patient had had a right spontaneous pneumothorax 50 days before his admission . The sputum smear was negative for acid fast bacilli . The smear of pleural effusion was positive for acid fast bacilli, the level of adenosine deaminase in the effusion was markedly elevated, and pleural effusion was positive for M . avium as assessed by polymerase chain reaction (PCR) . The pleural biopsy specimen showed fibrous change without granuloma, while the transbronchial biopsy specimen showed noncaseous epithelioid granulomas . We considered that the pneumothorax was caused by the spread of pulmonary M . avium infection to the visceral pleura with its perforation. Int J Dermatol, 2002 Dec, 41(12), 863 - 6 Polymerase chain reaction in cutaneous tuberculosis: is it a reliable diagnostic method in paraffin-embedded tissues? Senturk N, Sahin S, Kocagoz T. BACKGROUND: Most cutaneous tuberculosis lesions contain few bacilli, so identification of Mycobacterium tuberculosis in conventional laboratory tests is difficult . In vitro amplification of specific DNA sequences using polymerase chain reaction (PCR) has become a valuable tool in the rapid detection of slow-growing organisms like M . tuberculosis . AIM: To investigate the presence of M . tuberculosis DNA in cutaneous tuberculosis . METHODS: Twenty-two archival biopsy specimens diagnosed as cutaneous tuberculosis were investigated for the presence of M . tuberculosis DNA by PCR . Normal skin samples of 29 healthy patients were used as a control . RESULTS: Amplification of the M . tuberculosis DNA was observed in one of the cutaneous tuberculosis specimens and in a healthy control . CONCLUSION: Although PCR is a rapid diagnostic method, fixation procedures may decrease its sensitivity. Am J Transplant, 2003 Jan, 3(1), 88 - 93 Intracranial tuberculoma in a liver transplant patient: first reported case and review of the literature; Henderson C et al.; A 66-year-old female who had undergone an orthotopic liver transplant two years before admission was admitted with fever and neurological symptoms of several days' duration . Following an extensive work-up, which revealed positive intracranial lesions on computed typography and magnetic resonance imaging, the patient was begun on broad spectrum antimicrobials including corticosteroids . The patient responded though the etiology of infection remained unclear . After a stereotactic biopsy was performed revealing granulomas and acid-fast bacilli, the patient was started on antituberculous medications . A review of the literature reveals that the rare occurrence of intracranial tuberculoma should be considered in an orthotopic liver transplant (OLT) patient with central nervous system pathology. IUBMB Life, 2002 Sep, 54(3), 95 - 9 Nitric oxide and Mycobacterium leprae pathogenicity; Visca P et al.; Leprosy is an old, still dreaded infectious disease caused by the obligate intracellular bacterium Mycobacterium leprae . During the infectious process, M . leprae is faced with the host macrophagic environment, where the oxidative stress and NO release, combined with low pH, low pO2, and high pCO2, contribute to limit the growth of the bacilli . Comparative genomics has unraveled massive gene decay in M . leprae, linking the strictly parasitic lifestyle with the reductive genome evolution . Compared with Mycobacterium tuberculosis and Mycobacterium bovis, the leprosy bacillus has lost most of the genes involved in the detoxification of reactive oxygen and nitrogen species . The very low reactivity of the unique truncated hemoglobin retained by M . leprae could account for the susceptibility of this exceptionally slow-growing microbe to NO. Int J Lepr Other Mycobact Dis, 2002 Sep, 70(3), 191 - 200 The effect of exogenous peroxidase on the evolution of murine leprosy; Rojas-Espinosa O et al.; Mycobacterium lepraemurium (MLM) is a successful parasite of murine macrophages; in vitro, this microorganism infects macrophages without triggering these cells' ability to produce either the reactive oxygen intermediaries (ROI) or the reactive nitrogen intermediaries (RNI), and ends up lodging within these cells, that, in addition, do not contain myeloperoxidase (MPO) . In this study, we analyzed the effect of exogenous peroxidase on the evolution of murine leprosy . Bacilli were intraperitoneally injected, either alone (MLM) or precoated with horseradish peroxidase (MLM-PO), into two different groups of mice . At two-week intervals, the groups were blood-sampled to measure the levels of antibodies to protein- or lipid-MLM antigens . The extent of the disease was also assessed by looking at the histopathologic changes that occurred both in the liver and the spleen of the infected animals . We found that the animals injected with MLM-PO developed a disease that evolved at a slower pace than the disease that occurred in the animals injected with intact MLM . The difference between groups, both in terms of antibody levels and histological changes, was clearly evident at the intermediate stages of the disease (2 to 2.5 months), but was not so obvious at the more advanced stage of 3 months . Several possibilities to explain how the PO-coated bacilli might have regained their infectiousness are discussed . Lowering the infective dose of MLM and MLM-PO from 5 x 10(7) bacilli to 5 x 10(6) bacilli would, probably, have resulted in a different outcome of the disease: more extended in the MLM-group than in the MLM-PO group. Microbiology, 2002 Dec, 148(Pt 12), 3881 - 6 Expression of the mceA, esat-6 and hspX genes in Mycobacterium tuberculosis and their responses to aerobic conditions and to restricted oxygen supply; Haile Y et al.; The expression of six of the mammalian cell-entry (mce1a-mce1f) genes of the mce1 operon of Mycobacterium tuberculosis has been described previously . In this study, data are presented for the expression of other mammalian cell-entry homologues (mce-2a, mce-3a and mce-4a) at the RNA level, as determined by RT-PCR . The stress responses of these genes and of other immunologically important antigens are also characterized with respect to the introduction of oxygen depletion . Analysis of the expression of the mceA genes in relation to oxygen depletion revealed that they were expressed differentially . The RT-PCR results showed that mce-1a, mce-2a, hspX (encoding the alpha-crystallin antigen Acr) and esat-6 (encoding the early secretory antigenic target-6) were expressed throughout the cultivation period, whereas the expression of mce-3a and mce-4a was downregulated in the later stages of cultivation . This study gives new insights into the expression profiles of the different mce operons and the hspX and esat-6 genes in an in vitro model of dormant-like bacilli . Identification of the genes that are differentially expressed under aerobic conditions and under oxygen-limited conditions contributes to our understanding of the bacilli involved in latent tuberculosis. FEMS Microbiol Lett, 2002 Dec 17, 217(2), 199 - 205 Screening for biologically active metabolites with endosymbiotic bacilli isolated from arthropods; Gebhardt K et al.; Endosymbiotic bacteria from the genus Bacillus were isolated from different compartments of the gut of various members of insects (Hexapoda) and millipedes (Diplopoda) . They were grown in submerged culture and investigated by biological assays and HPLC-diode array analysis regarding their production of bioactive metabolites, which were isolated and determined in structure . Known compounds and yet unknown derivatives from the primary metabolism were detected, as well as antibacterially and antifungally acting peptide antibiotics . Respir Med, 2002 Dec, 96(12), 979 - 83 Impact of age and radiographic presentation on the presumptive diagnosis of pulmonary tuberculosis; Van den Brande P et al.; We compared delay in presumptive diagnosing pulmonary tuberculosis (PTB) in elderly and younger patents, yield of diagnosis and whether the yield is influenced by the radiographic presentation, even when PTB was suspected . Time from first complaints to first consideration of PTB was determined as suspicion interval (SI) and from first consideration to diagnosis as recognition interval (RI) . Presumptive diagnosis was defined as positive staining for acid-fast bacilli or presence of granulomatous lesions in pulmonary specimens . Inthe elderly and in the younger patients, the mean SI was 111.1 and 878 days respectively (P = NS), and the mean RI was 5.9 and 8.3 days, respectively (P = NS) . The mean RI was longer in uncharacteristic than in characteristic radiographic findings in both elderly (8.2 and 4.6 days; P = 0.007) and younger patients (10.6 and 3.9 days; P=0.0001) . A diagnosis was obtained in 89/113 elderly (79%) and in 109/138 younger (79%) patients (P=NS) and also in 59/80 (73%) patients with uncharacteristic findings and in 139/170 (82%) patients with characteristic findings (P = NS) . In the latter, sputum contributed for 66% ofdiagnosis, whereas it was only 31% in patients with uncharacteristic findings (P < 0.005) . In elderly patients with uncharacteristic radiographic findings, diagnosis was obtained from sputum in 41% and from other specimens in 35% (P = NS); in the younger group diagnosis was obtained from sputum in 23% and from other specimens in 48% (P < 0.05) . In conclusion, there was no difference in SI and RI in elderly patients in comparison with younger patients . Uncharacteristic radiographic findings increased RI in both age groups . Age or radiographic presentation did not influence diagnosing PTB . In patients with characteristic radiographic findings, diagnosis was especially made from examination of sputum, whereas in those with uncharacteristic findings, diagnosis was more often obtained from the complementary investigation of other specimens. Int J Tuberc Lung Dis, 2002 Nov, 6(11), 1029 - 32 Fixed-dose combination chemotherapy (Rifater/Rifinah) for active pulmonary tuberculosis in Taiwan: a two-year follow-up; Su WJ et al.; SETTING: Veterans General Hospital-Taipei, Taiwan . OBJECTIVE: To assess the efficacy and safety of a fixed-dose combination (FDC) of Rifater (RFT)/Rifinah (RFN) in the treatment of newly diagnosed smear-positive pulmonary tuberculosis . DESIGN: Patients were randomly assigned to two 6-month short-course chemotherapy regimens . One group of patients was treated with FDCs and another was given the four component drugs (INH, RMP, EMB and PZA) as separate formulations . RESULTS: The 105 patients enrolled in the study were divided into two treatment groups . Fifty-one patients who had completed treatment without interruption, 26 in the FDC group and 25 in the separate regimen, were eligible for analysis at the end of 2 years . Among the patients with a drug susceptibility test result available, four in the FDC group had bacilli resistant to pyrazinamide . In the separate regimen group, two patients had bacilli resistant to ethambutol and six had bacilli resistant to pyrazinamide . The two regimens were of similar effectiveness with regard to sputum conversion, compliance and radiological improvement . No patient with FDC treatment developed gastointestinal symptoms, visual disturbance or peripheral neuropathy (P < 0.05) . However, FDC treatment resulted in drug-induced fever in one patient . One patient (3.8%) in the FDC group relapsed 5 months after completing treatment . CONCLUSION: This study suggests that the two regimens had similar effectiveness in the treatment of smear-positive pulmonary tuberculosis . However, the fewer adverse drug events among those patients treated with the FDC regimen suggests that it has a better safety profile. Dis Colon Rectum, 2002 Dec, 45(12), 1685 - 8 Nested polymerase chain reaction in the diagnosis of negative Ziehl-Neelsen stained Mycobacterium tuberculosis fistula-in-ano: report of four cases; Shan YS et al.; PURPOSE: Mycobacterium is one of the causes of granulomatous diseases within the anorectal region . Early diagnosis of infection is important before the use of antituberculosis chemotherapy . Clinical diagnosis is usually dependent on microscopic detection using Ziehl-Neelsen stain and mycobacterial culture, but the sensitivity and specificity of these two methods are low . In this study nested polymerase chain reaction was used to detect mycobacterial infection in anal fistulas . METHODS: Paraffin-embedded specimens from three patients and discharge from one patient were used . DNA extraction was performed using phenol/chloroform techniques . IS6110-based nested polymerase chain reaction, yielding a 259-bp amplicon, for the diagnosis of infection was done to facilitate treatment . RESULTS: Four cases of suspected fistulas-in-ano presented with persistent fistula or unhealed wound . Histopathologic examination revealed granulomatous inflammation with failed microscopic detection of acid-fast bacilli using Ziehl-Neelsen stain . Nested polymerase chain reaction confirmed the presence of in all cases . The anal lesions healed rapidly following a course of antituberculosis therapy . CONCLUSION: Molecular diagnosis of fistula-in-ano by nested polymerase chain reaction is useful for clinically highly suspected infection despite a negative Ziehl-Neelsen stain. Arch Inst Pasteur Madagascar, 2001, 67(1-2), 37 - 40 {Diagnosis of tuberculosis by immunocapture of the tuberculous bacillus (using magnetic beads)}; Rabe O et al.; Tuberculosis is worldwide considered as a major health problem with high morbidity and mortality rates . Diagnosis of tuberculosis can be problematic . Microscopy, as the basic diagnostic method, stands inadequately alone due to a low sensitivity, and culture suffers from being time-consuming . A rapid, sensitive and simple diagnostic test, applicable in the field is therefore highly needed . A diagnostic method for the detection of M . tuberculosis by immunocapture technique has been developed using magnetic beads coated with polyclonal anti-M . tuberculosis . The detection of captured bacilli using biotinylated anti-APA monoclonal antibody (APA is a minor secreted antigen) was found more sensitive than microscopy . The results suggest that the development of a rapid strip test to detect major antigen could be a useful tool for the control of tuberculosis. Indian Pediatr, 2002 Nov, 39(11), 1034 - 9 Clinical and bacteriological profile of neonatal septicemia in a tertiary level pediatric hospital in Bangladesh; Ahmed AS et al.; The present article is a descriptive analysis of clinical and bacteriological profile of neonatal septicemia in a tertiary care hospital in Bangladesh . Eighty six neonates with suspected sepsis were enrolled, out of which 30 were culture positive . Clinical presentation was non-specific . Majority (70%) of the cultures isolated gram negative bacilli, most commonly E.coli and Klebsiella . These isolates were most often sensitive to gentamicin, ciprofloxacin, and third generation cephalosporins . Twelve out of 30 culture positive cases died. Ann Otolaryngol Chir Cervicofac, 2002 Nov, 119(5), 281 - 6 {Current aspects of laryngeal tuberculosis: a report of four cases}; Kossowski M et al.; OBJECTIVE: Laryngeal tuberculosis is a rare condition . This new clinical pattern of tuberculosis should be recognized by clinicians.METHODS: We report our experience with four cases of laryngeal tuberculosis.RESULTS: The principal differences in the disease pattern are an increase in the number of cases of primary laryngeal tuberculosis without any evident pulmonary involvement and the declining number of pseudotumor forms with an larger number of nonspecific laryngeal localizations.CONCLUSION: Tuberculosis should be entertained as a possible diagnosis in patients with nonspecific laryngeal disease . The diagnosis is confirmed by identification of granulomatous inflammation and acid-fast bacilli . New culture techniques and molecular biology methods such as polymerase chain reaction allow early identification of Mycobacterium tuberculosis. Arch Inst Pasteur Madagascar, 2000, 66(1-2), 18 - 22 {Laboratory network for the microscopic diagnosis of tuberculosis in Madagascar: quality control of slides}; Ramarokoto H et al.; As part of the National Tuberculosis Program (NTP), a quality control of the slides (search of acido-fast bacilli in the sputa) of the Treatment and Diagnosis Centers (TDC) forming the National Laboratory Network is carried out each year . In 1999, 76 TDC out of the 174 (44%) had been controlled using the method of double reading of the smears . The global concordance of the results in the 76 TDC is satisfactory (98%) . Reability was 91% for the positive smears and 92% for the negative smears . A good quality of smears was observed in 53% of the centers . The TDC reliable at 100% for both positive and negative smears were 51 (67%) of which 36 (47%) had also a good quality of smears . Those later were mainly found in Toamasina, Fianarantsoa, Antananarivo and Mahajanga. Arch Inst Pasteur Madagascar, 1996, 63(1-2), 4 - 7 {Microscopy laboratories for the diagnosis of tuberculosis in Madagascar: quality control}; Ramarokoto H et al.; As part of the National Tuberculosis Program (NTP), a quality control of the slides (search of acido-fast-bacilli in the sputa) of the Treatment and Diagnosis Centers (TDC) forming the National Laboratory Network was carried out in 1996 . 60 TDC of the 165 TDC (36%) had been controlled according to the system of double reading of the smears . The global concordance of the results in the 60 TDC is satisfactory since it was of 94% . Reliability of smears positive was of 83% . For the negative smears reliability, 14% of the TDC had a low or insufficient level . A good quality of smears was observed in 40% of the centers . The TDC that had both positive and negative reliability at 100% were 23 (38%) of which 13 had good quality of smears . Those were especially found in Antananarivo, Toliara, Fianarantsoa and Mahajanga. Lett Appl Microbiol, 2002, 35(6), 457 - 61 Novel cost-effective method of screening soils for the presence of mosquito-pathogenic bacilli; Dhindsa KS et al.; AIMS: The aim was to simplify the cumbersome conventional process of isolating virulent bacilli, which involves isolating all bacilli strains from a source followed by screening for strains that are effective for bio-control of mosquito vectors . METHODS: A new simplified technique involving eight steps was devised for screening soil samples for the presence of mosquito-pathogenic bacilli before isolating individual strains . RESULTS: Using the new technique, we obtained eight bacilli strains (KSD1-8) showing pathogenic activity against mosquito larvae from three out of 10 soil samples screened . These strains were characterized, identified and the main bioassay tests were performed with three most promising strains (KSD-4, KSD-7 and KSD-8), and their pathogenic activity against Anopheles stephensi Liston, Culex quinquefasciatus, Say and Aedes aegypti Linnaeus compared well with commercial reference strains of B . thuringiensis israelensis and B . sphaericus . SIGNIFICANCE AND IMPACT OF THE STUDY: The new technique of screening soil samples for the presence of virulent pathogenic strains of bacilli against mosquito larvae proved quick, efficient and cost effective. Diagn Microbiol Infect Dis, 2002 Oct, 44(2), 157 - 61 Evaluation of the BACTEC MGIT 960 in comparison with BACTEC 460 TB for detection and recovery of mycobacteria from clinical specimens; Scarparo C et al.; The BACTEC MGIT system (M960), a fully automated, non radiometric instrument, designed for rapid detection of acid fast bacilli (AFB) from clinical specimens, was compared with the radiometric BACTEC 460 system (B460) and Lowenstein-Jensen (L-J) solid medium . A total of 1,093 respiratory and extrapulmonary specimens were decontaminated by the NALC-NaOH standard method, and randomly inoculated into the media . A total of 122 mycobacteria were recovered, including 47 Mycobacterium tuberculosis complex (MTB) isolates and 75 nontuberculous mycobacteria (NTM) isolates . Overall recovery rates were 59% for M960 system (p < 0.0001), 58.2% for L-J . medium (p < 0.0001) and 82% for Bactec 460 system, whereas rates for MTB alone were 91.5, 76.6 (p = 0.007), and 95.7%, respectively . The combination of M960 or B460 systems with L-J medium showed the same recovery rates for MTB strains (97.9%), whereas NTM rates were 68% (p < 0.0001) and 93.3%, respectively . Mean time to detection of smear-positive MTB, smear-negative MTB, and NTM were 12.2, 13.4, and 23.3 days, respectively, with the M960, 11.7, 21.3, and 24.8 days with the B460 and 20.4, 28.7, and 28.4 days with L-J medium . The M960 system showed a contamination rate of 9.8%, while B460 and L-J medium showed contamination rates of 4.3 and 3.8% respectively . In conclusion, the M960 system appeared to be accurate and rapid for the recovery of MTB, but reduced recovery of NTM and a high number of contaminated cultures deserve further study in order to assess if this system can represent a valuable alternative to the radiometric system. Arch Immunol Ther Exp (Warsz), 2002, 50(5), 337 - 44 The lack of relationship between serum content of MBL, sCD14, anti-PPD and anti-Hsp65 IgG and ingestion of Mycobacterium bovis BCG bacilli by phagocytes; Paziak-Domanska B et al.; Prophylactic vaccination against tuberculosis (TB) with a live attenuated strain of Mycobacterium bovis bacille Calmette-Guerin (BCG) has been used worldwide . However, TB remains one of the most significant diseases of humans and animals . Better understanding of the mechanisms of human immunity to mycobacteria is essential for the development of new vaccines and the estimation of their efficacy . In this study we determined the levels of known humoral mediators of mycobacterial phagocytosis, i.e . mannose-binding lectin (MBL), soluble CD14 (sCD14), antibodies of the immunoglobulin G (IgG) class against mycobacterial purified protein derivative (PPD), and mycobacterial Hsp65 antigen, in the sera from healthy young volunteers vaccinated with BCG and presenting positive and negative Mantoux responses to PPD . Then we asked the question as to whether macrophages and polymorphonuclear leukocytes (PMNs) from the individuals with positive tuberculin test (TT(+)) and negative tuberculin test (TT(-)) differed in their ability to ingest mycobacteria . We also looked for a relationship between the intensity of mycobacterial ingestion by phagocytes in a medium of autologous sera containing different concentrations of MBL, sCD14 and anti-mycobacterial IgG . We found no significant differences between the investigated parameters for TT(+) and TT(-) volunteers . Our result suggest that the ability of macrophages and PMNs to ingest mycobacteria depends on an individual, intrinsic capacity of the phagocytes. J Nephrol, 2002 Sep-Oct, 15(5), 593 - 6 Fatal intestinal tubercolosis in a uremic patient with a renal transplant; Feriozzi S et al.; We report the case of a 52 year-old woman who was re-admitted to regular hemodialysis treatment because of chronic rejection of a renal transplant . She had received her mother's kidney 17 years before and had been treated for a long time with steroids, cyclosporin and azathioprine . In the last two months, fever had occurred, and persisted with the start of hemodialysis . She was admitted to our nephrology unit . Clinical, laboratory, radiological and endoscopic investigations did not lead to a precise diagnosis and broad-spectrum antimicrobial therapy failed . Some days later, a clear clinical picture of acute abdomen arose and at laparatomy a perforated jejunal ulcer was found . Histological investigation revealed caseous necrosis around the ulcer . Ziehl-Neelsen (ZN) stain showed a number of acid-fast resistant bacilli . Polymerase chain reaction (PCR) confirmed the presence of Mycobacterium tuberculosis . Specific therapy was started, but nevertheless the patient died a few days later, of septic shock . Our case shows that tuberculosis continues to be a significant, severe clinical problem in transplant recipients and is in fact still an important cause of death in these patients . The possibility of tuberculosis must be taken into account when a transplant patient shows fever and severe abdominal trouble with no clear evidence of another infection. Emerg Infect Dis, 2002 Nov, 8(11), 1197 - 209 Molecular epidemiology of tuberculosis in a sentinel surveillance population; Ellis BA et al.; We conducted a population-based study to assess demographic and risk-factor correlates for the most frequently occurring Mycobacterium tuberculosis genotypes from tuberculosis (TB) patients . The study included all incident, culture-positive TB patients from seven sentinel surveillance sites in the United States from 1996 to 2000 . M . tuberculosis isolates were genotyped by IS6110-based restriction fragment length polymorphism and spoligotyping . Genotyping was available for 90% of 11923 TB patients . Overall, 48% of cases had isolates that matched those from another patient, including 64% of U.S.-born and 35% of foreign-born patients . By logistic regression analysis, risk factors for clustering of genotypes were being male, U.S.-born, black, homeless, and infected with HIV; having pulmonary disease with cavitations on chest radiograph and a sputum smear with acid-fast bacilli; and excessive drug or alcohol use . Molecular characterization of TB isolates permitted risk correlates for clusters and specific genotypes to be described and provided information regarding cluster dynamics over time. Gastrointest Endosc, 2002 Dec, 56(6), 885 - 9 Microbiology of bile in patients with cholangitis or cholestasis with and without plastic biliary endoprosthesis; Rerknimitr R et al.; BACKGROUND: Cholangitis is a frequent complication of biliary stents . Empiric antibiotic selection is primarily based on bile cultures obtained from patients undergoing surgery and few data are available with respect to ERCP and biliary stents . This study analyzed the microbiology of bile and the antibiotic sensitivities of the organisms identified in patients presenting with clinical cholangitis or cholestasis . METHODS: All bile cultures collected during ERCP from January 1994 to January 2000 were identified by using an ERCP database . RESULTS: One hundred eighty cultures from 160 patients (mean age 55 years, range 6-94 years) were identified . Sixty-nine specimens were collected at ERCPs performed in patients with no biliary stent in place (group 1) . One hundred eleven specimens were obtained from patients with a biliary stent in situ (group 2) . The primary diagnoses for patients in groups 1 and 2 were as follows, respectively: malignant bile duct obstruction (25 and 85), choledocholithiasis (16 and 2), benign biliary strictures (6 and 18), acquired immunodeficiency syndrome (8 and 0), and miscellaneous (14 and 6) . There were 38 positive bile cultures in group 1 (55%) and 109 positive cultures in group 2 (98%; p < 0.05) . A higher frequency of polymicrobial infections (90%) was found in group 2 patients (vs . group 1, 45%; p < 0.001) . Escherichia coli was the most common organism found in group 1 (17%); Enterococcus the most common in group 2 (31%) . Among patients with positive bile cultures, bacteremia was more frequent in group 2 patients (46% vs . 21%; p < 0.05) . Ciprofloxacin and cefiriaxone were the most effective antibiotics against identified gram-negative bacilli, and vancomycin against Enterococci . CONCLUSION: In patients with cholangitis associated with biliary obstruction, the antibiotic selected initially should be active against gram-negative bacilli . Use of quinolones is recommended because these agents effectively penetrate an obstructed biliary tree and can be administered orally . Enterococci and polymicrobial infections are found more commonly in patients with a biliary stent than those without a stent . Pending definitive biliary decompression, patients with sepsis and those who do not quickly respond to treatment with a quinolone may benefit from the addition of antibiotic coverage against gram-positive organisms, targeted against Enterococci. J Bacteriol, 2002 Dec, 184(24), 6760 - 7 Mycobacterium bovis BCG response regulator essential for hypoxic dormancy; Boon C et al.; Obligately aerobic tubercle bacilli are capable of adapting to survive hypoxia by developing into a nonreplicating or dormant form . Dormant bacilli maintain viability for extended periods . Furthermore, they are resistant to antimycobacterials, and hence, dormancy might play a role in the persistence of tuberculosis infection despite prolonged chemotherapy . Previously, we have grown dormant Mycobacterium bovis BCG in an oxygen-limited Wayne culture system and subjected the bacilli to proteome analysis . This work revealed the upregulation of the response regulator Rv3133c and three other polypeptides (alpha-crystallin and two "conserved hypothetical" proteins) upon entry into dormancy . Here, we replaced the coding sequence of the response regulator with a kanamycin resistance cassette and demonstrated that the loss-of-function mutant died after oxygen starvation-induced termination of growth . Thus, the disruption of this dormancy-induced transcription factor resulted in loss of the ability of BCG to adapt to survival of hypoxia . Two-dimensional gel electrophoresis of protein extracts from the gene-disrupted strain showed that the genetic loss of the response regulator caused loss of the induction of the other three dormancy proteins . Thus, the upregulation of these dormancy proteins requires the response regulator . Based on these two functions, dormancy survival and regulation, we named the Rv3133c gene dosR for dormancy survival regulator . Our results provide conclusive evidence that DosR is a key regulator in the oxygen starvation-induced mycobacterial dormancy response. Br J Ophthalmol, 2002 Dec, 86(12), 1336 - 40 Ocular complications in newly diagnosed borderline lepromatous and lepromatous leprosy patients: baseline profile of the Indian cohort; Daniel E et al.; Aim: To describe ocular manifestations in newly diagnosed borderline lepromatous (BL) and lepromatous leprosy (LL) patients in India . METHODS: Ocular complications, at enrolment, occurring in all new borderline lepromatous and lepromatous leprosy patients detected by active case finding within the geographically defined leprosy endemic area of the Gudiyattam Taluk in India from 1991 to 1997 who consented to ocular examinations every 6 months, during and 5 years after treatment with multidrug therapy (MDT), were studied . RESULTS: Orbicularis oculi weakness (4.62%), lagophthalmos (4.20%), ectropion (0.42%), trichiasis (0.84%), blocked nasolacrimal ducts (1.68%), pterygium (11.34%), impaired corneal sensation (53%), corneal opacity (10.5%), corneal nerve beading (1.68%), punctate keratitis (1.26%), keratic precipitates (4.62%), iris atrophy (1.68%), and cataract (12.6%) were ocular complications seen in the 301 lepromatous patients at enrolment . 4.6% had blind eyes . Increasing age was associated with ocular complications . 80% of patients were skin smear acid fast bacilli (AFB) positive . The LL/BL ratio was 1:6.4 . 71% had some limb deformity . 44% had only leprosy related ocular complications (LROC), 28% had only general ocular complications (GOC) while 14% had both LROC and GOC . Ocular complications were significantly related to leg deformities . Corneal nerve beading was seen most in LL patients (100%) having high bacterial content . Lagophthalmos and muscle weakness were associated with reversal reactions . CONCLUSIONS: Corneal nerve beading occurs in LL patients with high bacillary count . Patients with reversal reaction are more likely to present with orbicularis oculi weakness and lagophthalmos . Leprosy related ocular complications and general ocular complications are significant problems in newly diagnosed lepromatous patients . Elderly, deformed, skin smear positive, lepromatous patients are associated with increased ocular morbidity and form a group that require acceptable and accessible eye care. Ann Dermatol Venereol, 2002 Oct, 129(10 Pt 1), 1156 - 8 {Digital purpura revealing septicaemical rat-bite fever}; Georgescu V et al.; INTRODUCTION: Infection with Streptobacillus moniliformis is an uncommon illness which can lead to death if untreated . We report the case in which initially cutaneous signs permitted diagnosis and further identification of the organism.CASE REPORT: A 42 year-old woman presented with a three-day history of acrally distributed purpuric macules on her fingers . Two days later, she was admitted for arthritis of the knees and wrists . There were two large pustules on the left elbow and the right knee . Laboratory studies showed inflammatory changes . The diagnosis of streptobacillary rat-bite fever was made after isolation of Gram-negative bacilli from a blood-culture and from cutaneous lesions . Finally identification of the organism was made by molecular biology analysis . The patient received intravenous ofloxacin and imipenem with complete resolution of arthritis and the cutaneous lesions.DISCUSSION: Streptobacillary rat-bite fever is a systemic infectious disease . It is caused by Streptobacillus moniliformis, organism found in the oropharyngeal flora of small rodents, especially rats . The illness is uncommon in urban settings . It starts by fever, followed by arthritis and rash . Septicaemical rat-bite fever may start only with cutaneous involvement such as acral purpura, like in our case . This clinical manifestation must be recognized by the dermatologist, because the illness can lead to death if untreated. Med J Malaysia, 2002 Sep, 57(3), 371 - 3 Isolated tuberculosis of talus without ankle and subtalar joint involvement; Anand A et al.; This case has been reported because of its rarity and atypical clinical presentation . An 8-year-old boy presented with a gradually increasing swelling localised on the antero-medial aspect of the foot haemogram, erythrocyte sedimentation rate (ESR), Mantoux and X-ray chest were normal . An irregular lytic lesion of the talus was seen on the x-ray of the affected part . Ziehl Nelson staining of the aspirated fluid revealed acid-fast bacilli . Material obtained after curettage and bone grafting was sent for histopathological examination which confirmed the diagnosis of tuberculosis . Post operatively a below knee cast was given for 12 weeks and anti tubercular treatment was given for 20 months . At the end of the treatment patient had full and painless motion at the ankle and subtalar joint . The lytic lesion had healed on X-ray. Kekkaku, 2002 Oct, 77(10), 679 - 86 {Tuberculosis control and strategy as an urban problem}; Takatorige T; Tuberculosis is always an urban problem . There are differences in the severity of pulmonary tuberculosis in relation to socio-economic groups . The percentages of cases shown to be positive by smear microscopy of acid-fast bacilli in their sputum specimens and of cases with cavitary lesions in the lungs were high for the lower socio-economic group . The percentage of cases having had chest X-ray examination within the preceding year was low for the lower socioeconomic group . The Osaka metropolitan area consists of many prefectures and cities . Osaka City is in the center of this great metropolis . Registered cases of each zone had statistically differences about social characteristics . This result was thought to reflect the population of each zone . Cooperative common political will against tuberculosis in this area is needed to promote tuberculosis control . We analyzed the incidence rate in Osaka City in five-year from 1978 to 1997 . Until the first half of 1980, the tuberculosis incidence rate in Osaka City had been dropping every year, but the rate of decline has been slowed substantially or even stopped since 1983 . The slowdown in the reduction of the tuberculosis incidence rate has occurred not in all wards, but in a few wards and it is a typical phenomenon of the middle-aged in those wards . Such tuberculosis among employees in an insecure position has a growing urban social problem . It is important to establish the cooperation between medical facilities and public health centers within the territory of tuberculosis hospitals in an urban area . The sources of tuberculosis infection in an urban area are quite diverse and complicated . We shall utilize a molecular epidemiologic analysis of Mycobacterium tuberculosis. J Formos Med Assoc, 2002 Aug, 101(8), 581 - 4 Mycobacterium kansasii infection presenting as cellulitis in a patient with systemic lupus erythematosus; Hsu PY et al.; The prevalence of mycobacterial infection has increased in recent years, especially in patients immunocompromised due to autoimmune disease, malignancy and AIDS . Mycobacterium kansasii infection most commonly presents as tuberculosis-like pulmonary disease . We report the case of a 38-year-old woman with systemic lupus erythematosus (SLE) who developed cellulitis over the left lower leg and had poor response to antibiotics . Two months before this admission, she had sustained a small wound over the right pretibial area and had noticed erythematous swelling after swimming at the beach . Pathologic examination of biopsied tissue showed acid-fast bacilli, and culture yielded M . kansasii . The cellulitis improved gradually during treatment with antimycobacterial agents for 1 year . This case emphasizes the possibility that cutaneous M . kansasii infection may occur in an immunocompromised patient and that exposure to contaminated water is a possible source . With early diagnosis, the response to an antimycobacterial multidrug regimen is usually satisfactory. Infect Immun, 2002 Dec, 70(12), 6672 - 9 Transgenic mice expressing human interleukin-10 in the antigen-presenting cell compartment show increased susceptibility to infection with Mycobacterium avium associated with decreased macrophage effector function and apoptosis; Feng CG et al.; Interleukin-10 (IL-10) is thought to play an important role in the regulation of microbial immunity . While T-cell-derived IL-10 has been shown to suppress cell-mediated immunity, there has been debate as to whether antigen presenting cell (APC)-derived cytokine can perform the same function in vivo . To assess the influence of APC-produced IL-10 on host resistance to mycobacterial infection, transgenic mice expressing human IL-10 under the control of the major histocompatibility complex class II promoter (hu10Tg) were infected with Mycobacterium avium, and bacterial burdens and immune responses were compared with those observed in wild-type (wt) animals . Hu10Tg mice harbored substantially higher numbers of M . avium and succumbed 16 to 18 weeks postinfection . The granulomas in infected hu10Tg mice showed marked increases in both acid-fast bacilli and host macrophages . In addition, these animals displayed a dramatic increase in hepatic fibrosis . The increased susceptibility of the hu10Tg mice to M . avium infection is independent of T-cell-produced endogenous murine IL-10, since bacterial burdens in mice derived by crossing hu10Tg mice with murine IL-10-deficient mice were not significantly different from those in hu10Tg mice . Importantly, gamma interferon (IFN-gamma) responses were not decreased in the infected transgenic animals from those in wt animals, suggesting the normal development of Th1 effector cells . In contrast, mycobacterium-induced macrophage apoptosis as well as production of TNF, nitric oxide, and IL-12p40 were strongly inhibited in hu10Tg mice . Together, these data indicate that APC-derived IL-10 can exert a major inhibitory effect on control of mycobacterial infection by a mechanism involving the suppression of macrophage effector function and apoptosis. Indian J Chest Dis Allied Sci, 2002 Oct-Dec, 44(4), 237 - 42 Prevalence of acquired MDR-TB and HIV co-infection; Deivanayagam CN et al.; BACKGROUND: Mounting prevalence of primary and acquired multidrug-resistant tuberculosis in India is a sorry reminder of all round failure in our fight against tuberculosis and also of the necessity for new effective strategies . OBJECTIVES: (1) To assess the prevalence and pattern of drug resistant pulmonary tuberculosis among treated patients or on those on treatment without adequate response and (2) to evaluate HIV seropositivity among MDR-TB patients . METHODS: Pulmonary TB patients, who had at least six months of unsuccessful anti-tuberculous treatment were selected for the study . Their sputum specimens were examined for M . tuberculosis culture and drug sensitivity pattern and serological examinations for HIV infection were carried out . RESULTS: Sputum specimens of 618 patients' (61.8%) of a total of 1000 examined had shown culturable M . tuberculosis . Four hundred ninty-five patients (49.5%) were found to expectorate tubercle bacilli resistant to one or more anti TB drugs . MDR-TB was detected in 339 patients (33.9%) . HIV seropositivity among MDR-TB was 4.42% . Significantly, 245 patients (24.5%) had tubercle bacilli resistant to one or more reserve drugs too (ethionamide, kanamycin and/or ofloxacin) . CONCLUSIONS: Prevalence of MDR-TB was high in the study population . It is essentially an acquired condition . Its association with HIV disease was at present on the lower side, an observation contrary to published western literature . Higher rates of resistance for reserve drugs (ethionamide, kanamycin and/or ofloxacin) in patients who never had these drugs in their earlier treatment schedules suggest the possibility of emerging spontaneous drug resistant mutants. Clin Chem Lab Med, 2002 Sep, 40(9), 893 - 902 Enhanced immune response in Mycobacterium bovis bacille calmette guerin (BCG)-infected IL-10-deficient mice; Jacobs M et al.; The role of the endogenous interleukin-10 (IL-10) in the control of Mycobacterium bovis Bacille Calmette Guerin (BCG) infection was assessed using IL-10-deficient (IL-10-/-) mice . Similar to wild-type (WT) mice, IL-10-/- mice were resistant to intravenous challenge with Mycobacterium bovis BCG . Significantly higher plasma concentrations of IL-12 and tumour necrosis factor (TNF) indicated an elevated protective immune response of IL-10-/- mice . Determination of bacilli burden in IL-10-/- mice showed accelerated clearance in the lungs, spleen and the liver in comparison to WT mice . Enhanced inflammation and a vigorous granulomatous response accompanied accelerated mycobacterial clearance . Immunohistochemical analysis of hepatic granulomas from IL-10-/- mice revealed augmented lymphocyte recruitment and macrophage activation, such as increased major histocompatibility complex (MHC) class II and inducible nitric oxide synthase (iNOS) expression . Further, it was found that enlarged granulomas persisted subsequent to mycobacterial clearance and failed to resolve in the absence of IL-10 . In conclusion, endogenous IL-10 dampens the cell-mediated immune response to mycobacterial infection. J Med Microbiol, 2002 Oct, 51(10), 895 - 8 An evaluation of the BD ProbeTec ET system for the direct detection of Mycobacterium tuberculosis in respiratory samples; Barrett A et al.; In controlling the spread of tuberculosis, early detection of disease caused by organisms of the Mycobacterium tuberculosis complex (MTBC) is vital . The BD ProbeTec ET system provides a method for the direct detection of MTBC by strand displacement amplification . Two hundred and five respiratory samples from patients with a high probability of tuberculosis were assessed by ProbeTec and by microscopy and culture for mycobacteria . ProbeTec positive results were obtained with 101 of 109 samples from which MTBC organisms were isolated . ProbeTec correctly signalled 78 of 81 samples that gave growths of mycobacteria other than tubercle bacilli (MOTT) as negative . Three samples gave false-positive results, corrected on repeat testing . Positive and negative predictive values (PPV, NPV) were 0.97 and 0.90 and the system showed a sensitivity and specificity of 92.7% and 96.0%, respectively . These values rose to PPV 0.97, NPV 0.96, sensitivity 97.1% and specificity 96.0% when data from the small number of gastric lavage samples tested were removed from the analysis . The BD ProbeTec ET system offers a robust and reliable molecular biological approach to the detection of MTBC organisms in respiratory samples in a semi-automated format. BMC Microbiol . 2002 Nov 13;2(1):33. Colony shape as a genetic trait in the pattern-forming Bacillus mycoides; Di Franco C et al.; BACKGROUND: Bacillus mycoides Flugge, a Gram-positive, non-motile soil bacterium assigned to Bacillus cereus group, grows on agar as chains of cells linked end to end, forming radial filaments curving clock- or counter-clockwise (SIN or DX morphotypes) . The molecular mechanism causing asymmetric curving is not known: our working hypothesis considers regulation of filamentous growth as the prerequisite for these morphotypes . RESULTS: SIN and DX strains isolated from the environment were classified as B . mycoides by biochemical and molecular biology tests . Growth on agar of different hardness and nutrient concentration did not abolish colony patterns, nor was conversion between SIN and DX morphotypes ever noticed . A number of morphotype mutants, all originating from one SIN strain, were obtained . Some lost turn direction becoming fluffy, others became round and compact . All mutants lost wild type tight aggregation in liquid culture . Growth on agar was followed by microscopy, exploring the process of colony formation and details of cell divisions . A region of the dcw (division cell wall) cluster, including ftsQ, ftsA, ftsZ and murC, was sequenced in DX and SIN strains as a basis for studying cell division . This confirmed the relatedness of DX and SIN strains to the B . cereus group . CONCLUSIONS: DX and SIN asymmetric morphotypes stem from a close but not identical genomic context . Asymmetry is established early during growth on agar . Wild type bacilli construct mostly uninterrupted filaments with cells dividing at the free ends: they "walk" longer distances compared to mutants, where enhanced frequency of cell separation produces new growing edges resulting in round compact colonies. Immunology, 2002 Nov, 107(3), 350 - 7 Reactivation of latent tuberculosis by an inhibitor of inducible nitric oxide synthase in an aerosol murine model; Botha T et al.; Exposure to Mycobacterium tuberculosis results in clinical tuberculosis only in a small percentage of healthy individuals . In most instances the bacilli are controlled by the immune system and survive in a latent state within granuloma . Immunosuppression, however, may result in reactivation of infection, resulting in clinical disease . Using a low-dose aerosol infection (30 colony-forming units) in mice, we describe a short-duration model for studying spontaneous and drug-induced reactivation of anti-tuberculous drug-treated, latent tuberculosis infection . Although a 4-week treatment with rifampicin and isoniazid reduced the number of bacilli to undetectable levels, the infection spontaneously reactivated following therapy . By contrast, an 8-week treatment period induced a state of latent infection, requiring immunosuppression to reactivate infection . Finally, a 12-week treatment period eliminated the bacilli completely and aminoguanidine did not induce reactivation of infection . In view of the fact that therapy in the selected protocol reduces the mycobacterial load to undetectable levels, the data suggest that an 8-week treatment period is necessary and sufficient to mount protective immunity in mice. Cytopathology, 2002 Oct, 13(5), 284 - 90 Fine needle aspiration cytology of suspected tuberculous lymphadenitis; Bezabih M et al.; Fine needle aspiration cytology of suspected tuberculous lymphadenitis The aims of this cross-sectional study were to describe the distributional patterns of tuberculous lymphadenitis and to assess the correlation between fine needle aspiration cytology (FNAC) and the Ziehl Neelsen staining technique in diagnosing tuberculous lymphadenitis . Romanowsky's method (Wright's stain) for cytological diagnosis and Ziehl Neelsen (hot method) for the identification of acid-fast bacilli were utilized . Out of one hundred and twenty-eight consecutive patients attending the cytological diagnostic service of the Department of Pathology within Jimma University, 89 (69.6%) of the patients were younger than 30 years of age . The male to female ratio was 1.3 : 1 . The cervical region was the most common site and involved 95 cases (74.2%), followed by the axillary and inguinal lymph node regions (20.3% and 4.3%, respectively) . The Wright's-stained cytology smears were grouped into three categories: epithelioid granulomas without necrosis, epithelioid granulomas with caseous necrosis and necrosis without epithelioid granulomas . The Ziehl Neelsen stains were undertaken on separate slides: 20.0% of the cases showing epithelioid granulomas without necrosis, 61.9% of those with epithelioid granulomas with necrosis/abscesses and 69.7% of those with necrosis without granulomas were found to be positive for acid-fast bacilli . The overall positivity for the ZiehlNeelsen stained cases was 59.4% . It can therefore be concluded that FNAC is a reliable diagnostic tool in helping to avert the more invasive surgical procedures undertaken in the diagnosis of tuberculous adenitis . The ZiehlNeelsen stain for identification of acid-fast bacilli should be incorporated as an adjunct to increase the diagnostic accuracy of tuberculous lymphadenitis. Bull Exp Biol Med, 2002 May, 133(5), 457 - 60 Pine resin and Biopin ointment: effects on repair processes in tissues; Simbirtsev AS et al.; The effects of Biopin (ointment containing pine resin) used in the treatment of burns, wounds, and pyoinflammatory processes on cell composition of the wound surface (smears) and granulation tissue were studied on rats . In vitro antibacterial activity of the drug was also evaluated . At the early stage of inflammation Biopin modulated the nonspecific and inhibited specific cell immune response, normalized hemodynamics in the inflammation focus, activated synthetic processes in the wound, and was effective towards anaerobes and bacilli. Rev Mal Respir, 2002 Sep, 19(4), 519 - 21 {Pulmonary tuberculosis presenting as tubercular lupus}; Fays S et al.; Pulmonary tuberculosis can be associated with skin manifestations . We report a case in which cutaneous tuberculous lesions were associated with asymptomatic pulmonary tuberculosis . A 15-year old woman had four cutaneous tumoral lesions on her face back, a few of which had evolved over a period of several years . They were asymptomatic nodular lesions, with rounded bumps, with, in places, cheloidal features . The biopsy specimen revealed non-caseating epithelioid granulomas with giant cells and the culture grew Mycobacterium tuberculosis . Cavitating pulmonary tuberculosis was then revealed by CT scan and acid-fast bacilli were isolated in her sputum . The skin lesions disappeared with anti-tuberculosis therapy . Cutaneous manifestations of tuberculosis are rare, polymorphous, and can be associated with an underlying visceral infection . Lupus vulgaris is the most common cutaneous manifestation of tuberculosis in industrialised countries, but nevertheless it remains rare and it is a very unusual presenting feature of underlying pulmonary tuberculosis. Clin Exp Immunol, 1989 Nov, 78(2), 214 - 8 Antibody response to phenolic glycolipid I and Mycobacterium w antigens and its relation to bacterial load in M . leprae-infected mice and leprosy patients; Moudgil KD et al.; Twenty-six inbred BALB/cBy mice were infected with live Mycobacterium leprae by injecting 6 x 10(3) bacilli in the hind footpad . Bleeds were collected at monthly intervals . After 6 months, acid-fast bacilli (AFB) were harvested monthly from the footpad of mice . The sera were analysed in enzyme immunoassay for antibodies against phenolic glycolipid I (PGL-I) of M . leprae and antigens of Mycobacterium w (M . w); 21 out of 26 (80.7%) mice demonstrated the presence of antibodies against PGL-I and M . w . Anti-M . w antibodies appeared slightly earlier than did anti-PGL-I antibodies . The titre of anti-M . w antibodies was higher than that of anti-PGL-I antibodies . The mice giving a positive antibody response had more than 7 x 10(5) AFB/footpad . The coefficient of correlation (r) between the number of AFB and antibody titres at the time of harvest was 0.566 for PGL-I and 0.628 for M . w . The value of r for bacterial index and antibody titres in 188 leprosy patients was 0.510 for PGL-I and 0.418 for M . w; these values were statistically significant (P < 0.001) . The decrease in bacterial index and antibody titres in treated lepromatous leprosy patients correlated with increase in the duration of chemotherapy . The measurement of anti-PGL-I antibodies of IgM class may serve as an adjunct to skin biopsy and skin-slit smear for serial monitoring of the bacterial load in the course of chemotherapy in leprosy control programmes. Mol Microbiol, 2002 Nov, 46(3), 709 - 17 Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti; Pym AS et al.; Although large human populations have been safely immunized against tuberculosis with two live vaccines, Mycobacterium bovis BCG or Mycobacterium microti, the vole bacillus, the molecular basis for the avirulence of these vaccine strains remains unknown . Comparative genomics has identified a series of chromosomal deletions common to both virulent and avirulent species but only a single locus, RD1, that has been deleted from M . bovis BCG and M . microti . Restoration of RD1, by gene knock-in, resulted in a marked change in colonial morphology towards that of virulent tubercle bacilli . Three RD1-encoded proteins were localized in the cell wall, and two of them, the immunodominant T-cell antigens ESAT-6 and CFP-10, were also found in culture supernatants . The BCG::RD1 and M . microti::RD1 knock-ins grew more vigorously than controls in immunodeficient mice, inducing extensive splenomegaly and granuloma formation . Increased persistence and partial reversal of attenuation were observed when immunocompetent mice were infected with the BCG::RD1 knock-in, whereas BCG controls were cleared . Knocking-in five other RD loci did not affect the virulence of BCG . This study describes a genetic lesion that contributes to safety and opens new avenues for vaccine development. Presse Med, 2002 Oct 5, 31(32), 1521 - 9 {Ocular infections of the elderly}; Labetoulle M et al.; A CLINICAL ASPECT DEPENDING ON THE PHYSIOPATHOGENESIS: Ocular infections are a frequent motive for ophthalmological consultations in geriatric settings because of the mechanical factors related to age (modifications in palpebral dynamics and lacrymal function) and in local and general immune factors leading to the rapid and/or more severe development of infections . The mechanism of microbial contamination of the eye also determines the clinical damage: predominantly local (dirty hands, traumas) with involvement of the surface tissues (conjunctive and cornea) or general, hematogenic or neurogenic, frequently at the origin of more internal infections (iris, choroid, retina, optical nerve) . CONJUNCTIVITIS AND KERATITIS: These provoke reddening of the eyes, tears and above all pain when the corneal epithelium is involved . Microbiological samples are useful in cases of severe, presumably infectious keratitis or conjunctivitis . Two emergency situations must be distinguished: any suspicion of herpes for which local corticosteroids are contraindicated and keratitis or conjunctivitis with the use of lenses, often due to Gram negative bacilli, amoeba or fungus, the treatment of which is intensive and the prognosis often severe . OPHTHALMOLOGICAL HERPES ZOSTER: The rapid diagnosis and introduction of efficient doses of antivirals reduces the initial pain, the ocular complications of herpes zoster and post-zoster pain . The latter, when it exists, requires specialized management . ACUTE UVEITIS: A context of intra-ocular inflammation in an elderly patient must always evoke a pseudo-uveitis syndrome, the principle cause of which is lymphoma . Conversely, an uveitis occurring in the days or weeks following ocular surgery, including cataract, must be considered as suggestive of a post-surgical infection and rapidly referred to a specialist . ACUTE DACRYOCYSTITIS: Is manifested by a hard and painful tumefaction below the internal angle of the eye . Following collection, it requires draining through an in incision in the skin, washing and packing of the sac, and systemic antibiotherapy . The preventive treatment of recurrences requires open dacryocystorhinostomy or via endonasal endoscopy. Adv Perit Dial, 2002, 18, 154 - 7 Rapid diagnosis of Mycobacterium tuberculous peritonitis in two continuous ambulatory peritoneal dialysis patients, using DNA amplification by polymerase chain reaction; Lye WC; Tuberculous peritonitis is not an uncommon cause of continuous ambulatory peritoneal dialysis (CAPD) peritonitis in endemic countries . The diagnosis is usually delayed because peritoneal fluid smears for acid-fast bacilli (AFB) are insensitive, and cultures for Mycobacterium tuberculosis require weeks . The present paper reports two cases of tuberculous CAPD peritonitis that were rapidly diagnosed using gene amplification for M . tuberculosis DNA complex by polymerase chain reaction with the commercial Amplicor M . tuberculosis nucleic acid amplification test (Roche Diagnostic Systems, Branchburg, NJ, U.S.A.) . A 18-year-old man and a 50-year-old man, both on CAPD, developed culture-negative peritonitis . Empirical therapy with intraperitoneal vancomycin and gentamicin failed . Peritoneal fluid AFB smears were negative . In both patients, M . tuberculosis DNA complex was detected by nucleic acid amplification using the Amplicor test . Anti-tuberculosis treatment was unsuccessful and their catheters were removed . Six weeks later, their peritoneal fluid cultures isolated M . tuberculosis . The use of molecular techniques to assist in the diagnosis of pulmonary tuberculosis is well accepted . Little information exists regarding the use of molecular techniques in the diagnosis of tuberculous CAPD peritonitis . The diagnosis of tuberculous peritonitis in CAPD patients is frequently delayed and may cause increased morbidity and mortality . Molecular diagnosis of tuberculous peritonitis using nucleic acid amplification tests may allow more rapid diagnosis . Further studies are required to determine the sensitivity and specificity of the technique in CAPD patients with tuberculous peritonitis. Pediatr Infect Dis J, 2002 Oct, 21(10), 982 - 4 Mycobacterium bohemicum cervical lymphadenitis; Palca A et al.; A lymph node excision was performed on a 2-year-old child with right submandibular swelling not responding to oral cefaclor therapy . Histology revealed granulomatous, partly necrotizing lymphadenitis and a large number of acid-fast bacilli subsequently identified by molecular techniques as Mycobacterium bohemicum. Kekkaku, 2002 Sep, 77(9), 621 - 5 {A study of case findings in pulmonary tuberculosis patients}; Sasaki Y; The incidence of tuberculosis patients increased again recently and many outbreaks of pulmonary tuberculosis (PTB) patients were reported . The purpose of this study is to investigate the present situation of the delay in case finding of PTB patients . 1) Of 236 PTB patients who were admitted to our hospital for treatment in 1997, 118 patients, who were detected by their symptomatic visits, were enrolled in to this study . 50 percentile patient's delay was 21.0 days, and 50 percentile doctor's delay was 7.2 days . 50 percentile total delay was 42.0 days, which was longer than about 28 days obtained by summing up the 50 percentile patient's delay and doctor's delay . The number of cases detected within 28 days was only 39 cases (33.1%) . Doctor's delay was mainly attributable to the performing the examination . Regarding the relationship between the period of total delay and sputum smear positive rate, the positive rate was less than 50% when total delay was less than 4 weeks, and came to more than 60% when the delay exceeded 4 weeks . 2) Of 236 PTB patients admitted to our hospital for treatment in 1997, 49 patients had been treated at medical institutions for other diseases . The majority of the cases were diagnosed as PTB in the routine examination, but early case findings was not made, with 9.5 weeks on an average and 50 percentile total delay was 5.5 weeks . The duration of doctor's delay in undergoing examination directly related to PTB diagnosis was accountable for doctor's delay . 3) The case finding of far-advanced cavitary PTB (bI3) patients was studied . Eighty-four patients were detected by symptomatic visits, 10 patients were detected during medical treatments of other disease, and 1 patients was detected by accident . The duration of patient's delay was 5.5 months on an average, while doctor's delay was 0.3 month on an average . The bI3 patients included many social and economical weak people . The body status on admission of bI3 patients were very severe . Twenty percentile of bI3 patients died of PTB, and 14 cases of 19 dead cases died within 1 month from admission . 4) The duration of case finding of tracheobronchial tuberculosis patients was studied . 50 percentile patient's delay was 14 days, while 50 percentile doctor's delay was 145 days . The delay in examination was considered accountable for doctor's delay, with 12 cases (57%) which were treated as bronchial asthma and 6 cases (29%) in which the sputum examination for tuberculosis bacilli was not performed after the detection of chest abnormal shadows on chest X-rays . 5) The present situation of case findings in Japan was studied . Patient's delay did not improve in recent years, while doctor's delay was improve in 2000, after Declaration of State of Emergency concerning tuberculosis . 6) As the countermeasures against patient's delay, it appears necessary to continue enlightenment on PTB, and selective detection by health examination for high risk groups is necessary . As the countermeasures against doctor's delay, it appears important to recommend to all doctors to pay attention to the patients with cough and sputum and undergo sputum examination. Kekkaku, 2002 Sep, 77(9), 609 - 14 {The present situation of daily life of tuberculosis patients treated in hospitals with beds for tuberculosis in Japan}; Yamagishi F et al.; We sent a questionnaire to hospitals with beds for tuberculosis in Japan to know current situation of daily life of tuberculosis patients treated in hospitals . It was evident that some services of daily life facilities was delayed; e.g . the difficulty in using stores in a hospital, no dining rooms and no installation of a personal television set . The use of personal computers was not allowed in many hospitals . Tuberculosis patients were subjected to a marked restriction in the hospital in spite of their isolation from the family and the society . Patients were prohibited to go out from the ward except when they undergo certain examinations in the hospitals, to take a walk in the hospital compound and to go out or stay overnight outside the hospital . In the majority of hospitals, patients were allowed to take a walk or to stay overnight outside the hospital only after the negative conversion of tubercle bacilli in sputum . Judging from the above findings, it appears that many tuberculosis patients under hospital treatment are not spending a pleasant daily hospital life. Ultrastruct Pathol, 2002 Sep-Oct, 26(5), 309 - 13 Quantitative transmission electron microscopic study of dental plaque--an in vivo study with different mouthrinses; Jentsch H et al.; Only a few studies of dental plaque in transmission electron microscopy (TEM) have been performed . The authors have applied TEM for morphometric analysis of dental plaque . Wearing acrylic splints with bovine enamel pieces on the buccal surface of teeth 36 and 46, 21 volunteers rinsed twice a day with a solution of chlorhexidine digluconate, amine/stannous fluoride, or sodium chloride . After 24, 48, and 72 h each a piece of enamel was taken and quantitatively analyzed by TEM for plaque thickness and composition . Similar results were obtained for plaque thickness after rinsing with chlorhexidine digluconate or amine/stannous fluoride . Numerical differences at the counts of cocci or bacilli after rinsing with chlorhexidine digluconate or amine/stannous fluoride did not always have statistical significance. Neurosurgery, 2002 Nov, 51(5), 1290 - 4; discussion 1294 Necrotizing neurosarcoidosis of the cranial base resembling an en plaque sphenoid wing meningioma: case report; Tobias S et al.; OBJECTIVE AND IMPORTANCE: Necrotizing sarcoid granuloma (NSG) has been recognized as a histological variant of sarcoidosis . Two cases of neurosarcoidosis (NS) with NSG with concomitant systemic disease have been described previously . We present an unusual case of primary NS-NSG that resembled an en plaque cranial base meningioma . CLINICAL PRESENTATION: A 51-year-old man presented with a 3-month history of progressive left visual deterioration and proptosis . Brain magnetic resonance imaging demonstrated a large cranial base lesion occupying the left anterior clinoid process and sphenoid wing, extending to the left frontotemporal convexity . A second dura-based lesion was observed in the right parietal convexity . Both lesions enhanced homogeneously after administration of intravenous contrast medium . Magnetic resonance imaging characteristics were consistent with a typical clinoidal meningioma with an en plaque extension laterally . INTERVENTION: A left frontotemporal craniotomy with extradural removal of the anterior clinoid process was performed . When the dura was opened, a red fibrous mass was identified . Intraoperative histological analysis revealed the presence of necrotizing and noncaseating granulomas . Postoperatively, cerebrospinal fluid, erythrocyte sedimentation rate, C-reactive protein, and serum and cerebrospinal fluid angiotensin-converting enzyme values were normal . The search for acid-fast bacilli or fungi was negative . A diagnosis of primary NS-NSG was made . The patient began long-term high-dose corticosteroid therapy . One and a half years after surgery, his vision had improved significantly and the lesions were stable as revealed by magnetic resonance imaging . CONCLUSION: The first case of primary NS-NSG in the absence of systemic sarcoidosis is reported . NS should be included in the differential diagnosis of dura-based lesions resembling meningioma. Extremophiles, 2002 Oct, 6(5), 391 - 5 Epub 2002 Jun 07. Revision of the taxonomic position of the xylanolytic Bacillus sp . MIR32 reidentified as Bacillus halodurans and plasmid-mediated transformation of B . halodurans; Martinez MA et al.; Bacillus sp . MIR32 has been isolated using xylan as the only carbon source, and one of its xylanolytic enzymes has been extensively studied . Biochemical analysis first related this strain to Bacillus amyloliquefaciens, but further studies based on a comparison of 16S rDNA sequences, G+C content, and DNA-DNA hybridization showed that strain MIR32 should be classified as a member of the species Bacillus halodurans . This change is also supported by the typical phenotype observed and by the results of PCR amplification directed toward spacers in rDNA and tDNA genes, which were assayed and compared with those of B . halodurans DSM 497(T) . Although among alkaliphilic bacilli competence development has not been experimentally demonstrated, in this work both B . halodurans MIR32 and DSM 497(T) were transformed according to a simple procedure developed in our laboratory, reaching 10(2)-10(3) stable transformants per microgram of plasmid DNA. East Afr Med J, 2002 Jan, 79(1), 11 - 5 Tuberculosis re-treatment outcomes within the public service in Nairobi, Kenya; Chakaya JM et al.; OBJECTIVES: This study was undertaken to describe treatment outcomes in patients started on a re-treatment drug regimen, assess the quality of follow up procedures and the adequacy of the currently advocated re-treatment drug regimen in Nairobi, Kenya . DESIGN: A retrospective study . SETTING: Mbagathi District Hospital (MDH), Nairobi, a public hospital that serves as the Tuberculosis (Tb) referral centre for Nairobi . MATERIALS AND METHODS: The Tb register at the MDH was used to identify patients who were on the re-treatment regimen for Tb . Case records for these patients were then retrieved . From these sources, information on age, sex, HIV status, previous and current tuberculosis disease and drug regimens, adherence to treatment and treatment outcomes, was obtained . Descriptive statistics was used to analyse the data . RESULTS: Of the total of 4702 patients registered at the MDH between 1996 and 1997, 593 (12.6%) were patients with either recurrent Tb, returning to treatment after default or had failed initial treatment . Of the 593 patients, case records were unavailable for 168 and 17 were children below the age of ten in whom the diagnosis of Tb was uncertain making a total of 185 patients who were excluded from the study . Of the remaining 408 patients, 77 (18.9%) were cured, 61 (15.0%) completed treatment without confirmation of cure, two (0.5%) defaulted, six (1.5%) died and 262 (64.2%) had no outcome information . There were no treatment failures . Treatment success defined as cure or treatment completion was achieved in 94.5% of the 146 patients in whom outcome data were available . HIV positive patients had a statistically significant poorer success rate (34/40, 85%) when compared with HIV negative patients (104/106, 94%), p=0.004 . Mycobacterium tuberculosis culture and drug susceptibility testing, was not done . CONCLUSION: The high number of patients with no treatment outcome information at the MDH is worrying, as these patients may harbour drug resistant bacilli and reflects an inadequate follow up service for Tb re-treatment in Nairobi . However, where treatment outcomes could be assessed, the currently advocated re-treatment regimen achieved a high success rate . These observations point to an urgent need to improve Tb documentation and follow up procedures within the public service in Nairobi in order to forestall the emergence and spread of drug resistant Tb. J Infect Chemother, 2002 Sep, 8(3), 242 - 6 A prospective study of hemodialysis access-related bacterial infections; Saeed Abdulrahman I et al.; The objective of this study was to describe hemodialysis vascular-access related infections that occurred in hemodialysis patients over an 18-month period . The study is a prospective descriptive analysis of incidence infection rates in a hemodialysis unit in a tertiary-care medical center . Prospective surveillance for hemodialysis vascular access-related infection was performed for all patients undergoing hemodialysis from November 1999 through April 2001 at King Fahd Hospital of King Faisal University, Al-Khobar, Saudi Arabia . The total number of dialysis sessions was calculated . The type of vascular access was noted . Cultures were obtained and all infections were recorded and infection rates were calculated . There were 9627 hemodialysis sessions (5437 via permanent fistulae or grafts, 2409 via temporary central catheters, and 1781 via permanent tunneled catheters) during the 18-month study period . We identified a total of 109 infections, for a rate of 11.32/1000 dialysis sessions (ds) . Of the 109, 23 involved permanent fistulae or grafts (4.23/1000 ds); 18 involved permanent-tunneled central catheter infections (10.1/1000 ds); and 68 involved temporary-catheter infections (28.23/1000 ds) . There were 38 bloodstream infections (3.95/1000 ds) and 34 episodes of clinical sepsis (3.53/1000 ds) . Seventy-one vascular access infections without bacteremia were identified (7.38/1000 ds), including 16 permanent-fistulae or graft infections (2.94/1000 ds), 7 permanent-tunneled central catheter infections (3.93/1000 ds), and 48 temporary-catheter infections (19.92/1000 ds) . Staphylococcal organisms were responsible for 77% of the infections, with Staphylococcus epidermidis being the strain most commonly implicated . Gram-negative organisms were responsible for 23% of the infections . In conclusion, infection rates were highest in hemodialysis patients with temporary vascular access, compared with rates in those with permanent arteriovenous fistulae and synthetic grafts . Most of the bacterial organisms isolated from the vascular access sites were gram-positive cocci, with S . epidermidis accounting for 50% of the organisms . The rate of infection with gram-negative bacilli was higher than in other reports . Our greater dependence on central venous catheters, due to local factors, coupled with the immune-compromising comorbid conditions of our patients, may be contributory to the pattern of infection reported . Delays in the creation of vascular grafts for hemodialysis access should be avoided. Microbiology, 2002 Oct, 148(Pt 10), 3161 - 71 Mycobacterium tuberculosis-infected human macrophages exhibit enhanced cellular adhesion with increased expression of LFA-1 and ICAM-1 and reduced expression and/or function of complement receptors, FcgammaRII and the mannose receptor; DesJardin LE et al.; The entry of Mycobacterium tuberculosis (Mtb) into the host macrophage and its survival in this environment are key components of tuberculosis pathogenesis . Following intracellular replication of the bacterium within alveolar macrophages, there is spread of bacilli to regional lymph nodes in the lungs and subsequent presentation of antigens to the host immune system . How this process occurs remains poorly understood, but one mechanism may involve the migration of macrophages containing Mtb across the alveoli to lymph nodes, where there is development of a protective host response with formation of granulomas composed in part of aggregated and fused, apoptotic, infected macrophages . Leukocyte integrins, including lymphocyte function-associated antigen-1 (LFA-1) and complement receptors CR3 and CR4, and their counter receptors play a major role in macrophage adhesion processes and phagocytosis . In this study, the appearance of Mtb-infected macrophages over time was examined, using inverted-phase microscopy and an in vitro culture model of human monocyte-derived macrophages (MDMs) . Prior to and immediately following infection of the MDMs with Mtb, the macrophages appeared as individual cells in monolayer culture; however, within 24 h of infection with Mtb, the MDMs began to migrate and adhere to each other . The kinetics of this response were dependent on both the m.o.i . and the length of infection . Quantitative transmission electron microscopy studies revealed that macrophage adhesion was accompanied by increases in levels of LFA-1 and its counter receptor (ICAM-1), decreases in surface levels of the phagocytic receptors CR3, CR4 and FcgammaRII, and an increase in major histocompatibility complex Class II (MHC-II) molecules at 72 h post-infection . Decreases in surface levels of CR3 and CR4 had a functional correlate, with macrophages containing live bacilli showing a diminished phagocytic capacity for complement-opsonized sheep erythrocytes; macrophages containing heat-killed bacilli did not show this diminished capacity . The modulation of macrophage adhesion and phagocytic proteins may influence the trafficking of Mtb-infected macrophages within the host, with increases in levels of LFA-1 and ICAM-1 enhancing the adhesive properties of the macrophage and decreases in phagocytic receptors diminishing the phagocytic capacity of an already-infected cell, potentially allowing for maintenance of the intracellular niche of Mtb. Microbiology, 2002 Oct, 148(Pt 10), 3139 - 44 Oxidative stress response genes in Mycobacterium tuberculosis: role of ahpC in resistance to peroxynitrite and stage-specific survival in macrophages; Master SS et al.; The Mycobacterium tuberculosis ahpC gene, encoding the mycobacterial orthologue of alkylhydroperoxide reductase, undergoes an unusual regulatory cycle . The levels of AhpC alternate between stages of expression silencing in virulent strains grown as aerated cultures, secondary to a natural loss of the regulatory oxyR function in all strains of the tubercle bacillus, and expression activation in static bacilli by a yet undefined mechanism . The reasons for this unorthodox regulatory cycle controlling expression of an antioxidant factor are currently not known . In this work, M . tuberculosis H37Rv and Mycobacterium smegmatis mc(2)155 ahpC knockout mutants were tested for sensitivity to reactive nitrogen intermediates, in particular peroxynitrite, a highly reactive combinatorial product of reactive nitrogen and oxygen species, and sensitivity to bactericidal mechanisms in resting and activated macrophages . Both M . tuberculosis ahpC::Km(r) and M . smegmatis ahpC::Km(r) showed increased susceptibility to peroxynitrite . In contrast, inactivation of ahpC in M . tuberculosis did not cause increased sensitivity to donors of NO alone . M . tuberculosis ahpC::Km(r) also showed decreased survival in unstimulated macrophages, but the effect was no longer detectable upon IFNgamma activation . These studies establish a specific role for ahpC in antioxidant defences involving peroxynitrite and most likely additional cidal mechanisms in macrophages, with the regulatory cycle likely contributing to survival upon coming out of the stationary phase during dormancy (latent infection) or upon transmission to a new host. Microbiology, 2002 Oct, 148(Pt 10), 3089 - 100 The impact of the absence of glycopeptidolipids on the ultrastructure, cell surface and cell wall properties, and phagocytosis of Mycobacterium smegmatis; Etienne G et al.; Glycopeptidolipids (GPLs) are a class of species- or type-specific mycobacterial lipids and major constituents of the cell envelopes of many non-tuberculous mycobacteria . To determine the function of GPLs in the physiology of these bacteria, a mutant of Mycobacterium smegmatis in which the gene encoding a mycobacterial nonribosomal peptide synthetase has been inactivated by transposon mutagenesis was analysed . Labelling experiments indicated that half of the bacterial GPLs were located on the cell surface and represented 85% of the surface-exposed lipids of the parent strain whereas the mutant was defective in the production of the GPLs . Compared to the parent smooth morphotype strain, the GPL-deficient mutant strain exhibited a rough colony morphology, an increase of the cell hydrophobicity and formed huge aggregates . As a consequence, the mutant cells were no longer able to bind ruthenium red, as observed by transmission electron microscopy . The altered surface properties of the mutant cells also affected the phagocytosis of individual bacilli by human monocyte-derived macrophages since mutant cells were internalized more rapidly than cells from the parent strain . Nevertheless, no specific release of surface constituents into the culture broth of the mutant was observed, indicating that the cell surface is composed of substances other than GPLs and that these are essential for maintaining the architecture of the outermost layer of the cell envelope . Importantly, the absence of these major extractable lipids of M . smegmatis from the mutant strain has a profound effect on the uptake of the hydrophobic chenodeoxycholate by cells, indicating that GPLs are involved in the cell wall permeability barrier of M . smegmatis . Altogether, these data showed that, in addition to being distinctive markers of numerous mycobacterial species, GPLs play a role in the bacterial phenotype, surface properties and cell wall permeability. Int J Tuberc Lung Dis, 2002 Oct, 6(10), 909 - 12 Bacteriological follow-up of tuberculosis treatment: a comparative study of smear microscopy and culture results at the second month of treatment; Ramarokoto H et al.; SETTING: Significance of a positive bacillary examination of sputum at 2 months of treatment in relation to the viability of the bacilli and the final treatment result . OBJECTIVE: To compare the results of smear microscopy and sputum culture at the second month of tuberculosis treatment and to follow the progress of the patients . METHODS: Follow-up of 297 patients with smear-positive pulmonary tuberculosis in Madagascar, 152 of whom were smear-positive at 2 months of treatment and 145 smear-negative . The number of bacilli was recorded, as were the culture results and the final outcome of treatment . RESULTS: Among the 152 patients who were smear-positive at the second month, 77 (51%) were culture-negative; there were 12 (8%) treatment failures and four relapses (4.6%) . Among the 145 smear-negative patients, 22 (15%) were culture-positive, of which one was a treatment failure (1%) . CONCLUSION: The majority of failures and relapses were observed in the group of smear-positive patients . It is important to reinforce the surveillance of these patients in order to reduce the number lost to follow-up . Furthermore, a positive smear microscopy at the end of the second month is not sufficiently specific for early identification of treatment failures . It is preferable to wait until the fifth month, as the great majority of patients who are positive at 2 months achieve cure . The treatment strategy currently recommended in Madagascar is satisfactory. Int J Tuberc Lung Dis, 2002 Oct, 6(10), 851 - 7 Prevalence and risk factors associated with tuberculin skin test positivity among household contacts of smear-positive pulnionary tuberculosis cases in Umerkot, Pakistan; Rathi SK et al.; STUDY POPULATION AND SETTING: Household contacts of acid-fast bacilli (AFB) sputum smear-positive tuberculosis patients in the Umerkot Taluka, Sindh, Pakistan . OBJECTIVE: To estimate the prevalence of and identify risk factors associated with tuberculin skin test (TST) positivity among household contacts of acid-fast bacilli (AFB) sputum smear-positive pulmonary tuberculosis cases . DESIGN: A cross-sectional study of household contacts of AFB sputum smear-positive tuberculosis cases, registered at the Umerkot Anti-Tuberculosis Association clinic from August 1999 to September 1999 . The contact's Mycobacterium tuberculosis infection status was assessed using TST . On the day of the TST, a pre-designed questionnaire was administered to collect data on putative risk factors for TST positivity among contacts . The data were analysed using a marginal logistic regression model by the method of generalised estimating equations (GEE) to determine risk factors independently associated with TST positivity . RESULTS: The prevalence of TST positivity among household contacts of AFB sputum smear-positive index patients was 49.4% . The final multivariate GEE model showed that contact's age and sleeping site relative to the index case, the intensity of the index case's AFB sputum-smear positivity and the contact's BCG scar status were independent predictors of TST positivity among household contacts of AFB sputum smear-positive index cases . CONCLUSIONS: The results suggest that the household contacts of AFB sputum smear-positive tuberculosis patients in a poor neighbourhood of rural Sindh had a high prevalence of M . tuberculosis infection as determined by TST . Poor housing conditions seem to contribute to the spread of M . tuberculosis infection . Early diagnosis of pulmonary TB through evaluation of TST-positive household contacts, followed by appropriate therapy, may prevent further spread of M . tuberculosis infection . We recommend an awareness programme to prevent household contacts from acquiring M . tuberculosis infection from smear-positive pulmonary TB cases. Int J Tuberc Lung Dis, 2002 Oct, 6(10), 843 - 50 Risk factors for transmission of Mycobacterium tuberculosis from HIV-infected tuberculosis patients, Botswana; Kenyon TA et al.; OBJECTIVE: To identify risk factors for transmission of Mycobacterium tuberculosis from patients with tuberculosis and human immunodeficiency virus (HIV) infection in Botswana . DESIGN: Transmission was studied in 210 children aged <10 years (contacts) of unknown HIV status exposed to 51 adults with tuberculosis (index cases), including 41/49 (83.7%) with HIV infection . METHODS: Data collected on index cases included demographics, clinical and social characteristics, sputum, HIV, and CD4 lymphocyte results . Tuberculin skin testing was performed on contacts, and their parent or guardian was interviewed . A positive test was defined as > or = 10 mm induration . Skin test results were compared with results obtained from a population survey of children of similar age from the same community . RESULTS: A positive skin test was found in 12.1% of exposed children compared with 6.2% in the community (P = 0.005) . Of the infected children, 22 (78.6%) were contacts of a close female relative . The risk of transmission increased with the degree of sputum smear positivity for acid-fast bacilli among female index cases (10.8% if smear 0+, 9.3% if smear 1+,29.4% if smear 2+, 44% if smear 3+, P < 0.001) . In multivariate analysis, severe immunodeficiency (CD4 lymphocyte count <200 cells/mm3) among HIV-infected index cases was protective against transmission (OR 0.08, 95%CI 0.01-0.5, P = 0.006) . CONCLUSION: The intensity of exposure to tuberculosis patients and the degree of sputum smear positivity for acid-fast bacilli remain important risk factors for transmission of M . tuberculosis during the era of HIV . However, tuberculosis patients with advanced AIDS may be less infectious than patients in earlier stages of AIDS. J Assoc Acad Minor Phys, 2002 Apr, 13(2), 53 - 6 Drug resistant tuberculosis; Kamholz SL; The emergence of multidrug resistant (MDR) strains of Mycobacterium tuberculosis (MDR-TB) represents a serious worldwide threat to the health of mankind . Approximately 2 billion persons are infected with Mycobacterium tuberculosis, and 8.8 million new cases of tuberculosis occur annually, with over 50,000 attributable deaths each week! Drug resistance is either acquired with the initial infection (from a host harboring resistant tubercle bacilli) or develops during treatment with antituberculous chemotherapeutic agents because of poor patient compliance or inadequate/inappropriate treatment regimens . The epidemiology of tuberculosis and drug resistance is reviewed; the likelihood of the development of resistance and the molecular mechanisms of resistance to each drug are also discussed . Principles of prevention of nosocomial transmission, use of involuntary detention, and drug treatment approaches for MDR-TB are discussed, and the potential roles of surgery and novel therapies (phenothiazines, suicide genes) are presented. Pediatrics, 2002 Oct, 110(4), 707 - 11 The effect of antibiotic rotation on colonization with antibiotic-resistant bacilli in a neonatal intensive care unit; Toltzis P et al.; OBJECTIVE: This study was designed to test whether rotation of antibiotics can reduce colonization with resistant Gram-negative bacilli in a neonatal intensive care unit (NICU) . METHODS: A monthly rotation of gentamicin, piperacillin-tazobactam, and ceftazidime was compared with unrestricted antibiotic use in side-by-side NICU populations (rotation team vs control team) . Pharyngeal and rectal samples were obtained 3 times a week and tested for Gram-negative bacilli resistant to each of the rotation antibiotics . Pulsed-field gel electrophoresis analysis determined the numbers of genetically discordant resistant organisms on each team . The association between colonization with a resistant bacillus (the primary outcome) and team assignment was tested . RESULTS: A total of 1062 infants were studied during a 1-year period . A total of 10.7% infants on the rotation team versus 7.7% on the control team were colonized with a resistant bacillus . No interteam differences were distinguishable when the numbers of genetically discordant resistant organisms were normalized to the total number of team admissions . The incidence of nosocomial infection and mortality also were similar across teams . CONCLUSION: These data indicate that rotation of parenteral antibiotics according to the applied protocol has no detectable effect in decreasing the reservoir of resistant Gram-negative bacilli in a tertiary-care NICU. Am J Respir Crit Care Med, 2002 Oct 1, 166(7), 994 - 7 Sensitivity of acid-fast staining for Mycobacterium tuberculosis in formalin-fixed tissue; Fukunaga H et al.; Microscopic examination of tissue sections of mycobacterial lesions frequently results in few or no bacilli seen, even if the lesions appear active histologically . This might be due to the effects of the fixative fluid and/or organic solvent, both of which are conventionally used to make tissue sections for histopathology, on the acid-fast staining of bacteria . The present study was performed to examine how formalin and xylene lower the sensitivity of acid-fast staining for Mycobacterium tuberculosis and to clarify the meaning of the staining result in tissue sections . Microscopic observation of mycobacteria smeared on glass slides revealed that both of these agents greatly reduced the sensitivity of acid-fast staining . Moreover, the number of bacilli was calculated in 30 samples of paraffin-embedded granulomatous lesions using acid-fast microscopy and real-time polymerase chain reaction . The numbers of bacilli present that were estimated by real-time polymerase chain reaction were considerably higher than those counted with a microscope . These results suggest that the bacilli are frequently missed or underestimated with acid-fast microscopy on formalin-fixed, paraffin-embedded tissue. Tuberculosis (Edinb), 2002, 82(2-3), 55 - 61 TNF-dependent BALB/c murine macrophage apoptosis following Mycobacterium tuberculosis infection inhibits bacillary growth in an IFN-gamma independent manner; Keane J et al.; SETTING: In vitro model of murine macrophage M . tuberculosis infection . OBJECTIVE: To evaluate the association and cytokine control of host cell apoptosis and bacillary killing in M . tuberculosis -infected murine peritoneal macrophage (PM) . DESIGN: Murine PM from different strains of mice were infected with H37Ra . Bacillary growth and macrophage apoptosis were evaluated under different cytokine conditions . RESULTS: Like human alveolar macrophages, PM from BALB/c mice were found to undergo apoptosis after infection with M . tuberculosis in a TNF-dependent manner . Neutralizing TNF with anti-TNF antibody inhibited PM apoptosis following infection, and resulted in increased bacillary growth . Pre-treatment of PM with interferon (IFN-gamma) resulted in significant killing of the infecting bacilli, which was not dependent on TNF or apoptosis of the cells . In contrast to BALB/c mice, PM from C3H/HeJ mice did not undergo apoptosis following infection and did not undergo TNF- and apoptosis-dependent inhibition of bacillary growth . CONCLUSION: These findings suggest that TNF contributes to macrophage inhibition of M . tuberculosis growth by a mechanism that is dependent on apoptosis and independent of IFN-gamma activity . This protective phenotype was not seen in all strains of mice and merits investigation as a marker of mycobacterial host susceptibility. Nippon Koshu Eisei Zasshi, 2002 Aug, 49(8), 790 - 4 {Detection of mycobacterium bovis BCG Tokyo in sputum from a tuberculosis patient and administrative action in public health}; Ohata R et al.; PURPOSE: We encountered a tuberculosis patient with the BCG strain in his sputum . Based on this experience, we investigated ideal surveillance and quality assurance for bacteriological examination as well as cooperation between medical organizations and public administrative organizations such as public health centers for prompt and appropriate measures against tuberculosis . METHODS: Acid-fast bacilli isolated in the laboratory of a hospital were analyzed by restriction fragment length polymorphism (RFLP) and molecular epidemiological data for pathogen were provided to the public health center in charge . RESULTS: DNA of acid-fast bacilli isolated from sputum of a tuberculosis patient showed a BCG like pattern on RFLP analysis using two IS6110 and PGRS (polymorphic GC-rich sequence) probes . Additional investigation revealed that the patient had been treated with BCG immuno-therapy against bladder cancer . Accordingly, it was suggested that this was the origin of the BCG strain in the sputum . Therefore, the patient was re-examined clinically, and further contact tracing by the public health center was stopped . CONCLUSIONS: This study indicates that adequate surveillance and quality assurance in bacteriological examination as well as effective exchange of information between medical organization and public health centers are very important for prompt and appropriate measures against tuberculosis . Further, it provided strong support for identification of pathogens of the molecular level by RFLP analysis. J Infect Dis, 2002 Oct 15, 186(8), 1155 - 60 Epub 2002 Sep 30. Killing of Mycobacterium avium and Mycobacterium tuberculosis by a mycobacteriophage delivered by a nonvirulent mycobacterium: a model for phage therapy of intracellular bacterial pathogens; Broxmeyer L et al.; Mycobacterium avium causes disseminated infection in patients with acquired immune deficiency syndrome . Mycobacterium tuberculosis is a pathogen associated with the deaths of millions of people worldwide annually . Effective therapeutic regimens exist that are limited by the emergence of drug resistance and the inability of antibiotics to kill dormant organisms . The present study describes a system using Mycobacterium smegmatis, an avirulent mycobacterium, to deliver the lytic phage TM4 where both M . avium and M . tuberculosis reside within macrophages . These results showed that treatment of M . avium-infected, as well as M . tuberculosis-infected, RAW 264.7 macrophages, with M . smegmatis transiently infected with TM4, resulted in a significant time- and titer-dependent reduction in the number of viable intracellular bacilli . In addition, the M . smegmatis vacuole harboring TM4 fuses with the M . avium vacuole in macrophages . These results suggest a potentially novel concept to kill intracellular pathogenic bacteria and warrant future development. J Clin Microbiol, 2002 Oct, 40(10), 3810 - 3 Detection of embB306 mutations in ethambutol-susceptible clinical isolates of Mycobacterium tuberculosis from Northwestern Russia: implications for genotypic resistance testing; Mokrousov I et al.; A total of 183 epidemiologically unlinked Mycobacterium tuberculosis isolates collected in the St . Petersburg area of Russia from 1996 to 2001 were screened for alterations in codon 306 of the embB gene; mutations in this codon are reported to confer resistance to ethambutol (EMB) . The embB306 mutations were detected in 14 (48.3%) of 29 EMB-resistant strains and, quite surprisingly, in 48 (31.2%) of 154 EMB-susceptible strains . A discrepancy between the results of phenotypic and genotypic EMB resistance tests was restricted to the strains already resistant to other antitubercular (anti-TB) drugs . In particular, 40 (60%) of the 69 EMB-susceptible strains resistant to rifampin, isoniazid, and streptomycin but none of the 43 pansusceptible strains harbored an embB306 mutation . We hypothesize that the phenomenon observed could reflect the presence of a target other than EmbB for the drug in tubercle bacilli; this unknown target could be sensitized and affected, sensu lato, by EMB during treatment with other first-line anti-TB drugs . Comparison with DNA fingerprinting data showed that, irrespectively of the phenotypic susceptibility profiles, 46 (50.6%) of 91 Beijing family strains and 16 (17.4%) of 92 strains of other genotypes had a mutation in embB306. Afr Health . 1997 Nov;20(1):18. New approach to laboratory diagnosis; Dhir VK; PIP: Mycobacterial infections are typically diagnosed in the laboratory through the direct microscopy of stained smears and culture of the organism upon egg-based media . While microscopy is rapid, inexpensive, and simple to perform, it is rather insensitive and does not allow speciation of the mycobacteria . The culture of mycobacteria from clinical samples is far more sensitive and allows the biochemical identification of mycobacterial species . However, the major disadvantage of this latter approach is the slow growth rate of M . tuberculosis upon all culture media and the resulting delay in detection by culture . New techniques to diagnose tuberculosis (TB) are being developed which either demonstrate specific host responses to M . tuberculosis infection or detect the bacilli or some of its constituents . However, since many of these new technologies require expensive equipment and specialist training, it is unlikely that they will become widely established as routine techniques in developing countries . Biotec Laboratories Ltd . is developing a system for the rapid detection and determination of drug susceptibility for M . tuberculosis from decontaminated sputum samples . The FAST-Plaque TB test uses bacteriophage to reflect the presence of target bacteria . This approach, scheduled for launch in early 1998, can provide rapid microbiology in laboratories in developing countries without expensive instrumentation . Child Trop, 1992, (196-197), 69 - 71 Chemoprophylaxis of tuberculosis in children; Baghriche M et al.; PIP: The situations when prophylactic antibiotics should be given to children in developing countries where BCG vaccination is common are explained . In most countries, 80-90% of children have been vaccinated with BCG by the age of 1 . Since BCG makes a tuberculin (PPD) test moot, because all BCG-vaccinated persons have positive PPD tests, the only children in developing countries who can be diagnoses with TB are those who are vaccinated and live in close contact with a TB infected person . The only prophylactic medication recommended for children is daily isoniazid, 5 mg/kg for 6 months . Preventive medication is never given to healthy BCG-vaccinated children . The multi-drug regimen is not appropriate because young children have relatively few Mycobacterium bacilli, and developing countries cannot even afford to treat infected adults with these regimens . The only situations for treating children prophylactically are: 1) healthy children, under 5, not BCG vaccinated, and tuberculin positive; 2) healthy children, age 5-14, tuberculin positive with documented negative PPD test within 2 years, and 3) age 1, not BCG vaccinated, recently diagnosed as tuberculin positive . In an infant living in close contact with an infected source, a PPD test is done after 3 months of treatment with isoniazid, and if positive, treatment is continued for another 3 months . If the PPD test is still negative, the BCG vaccination is given . J Obstet Gynaecol India, 1978 Dec, 28(6), 1106 - 9 Vaginal cytology and ferning of cervical mucus studies after intra-uterine instillation of solutions for medical termination of pregnancy; Nanda U et al.; PIP: The effectiveness of intrauterine instillation of solutions for midtrimester abortions is well established, but the mechanism for triggering the onset of labor is unclear and represents a challenging problem for obstetricians and physiologists . Vaginal cytology reflects the hormonal status . Of the total of 78 cases in this study, 20% sodium chloride solution was used in 55 cases, glucose 50% in 5 cases, and 0.1% unacredil with Foley's catheter in 18 cases . Vaginal smear was taken and stained with Papanicolaou's staining method . In the vaginal smear the following aspects were studied: presence of Doderlein bacilli; cytolysis; tendency of the cells to unfold and separate; degenerative changes in the cells, inducing perinuclear halo; fragmentation of nuclei; flatness and loss of haziness of cell border; Karyopyknotic index; and parabasal cells . Cervical mucus was taken, dried, and examined under the microscope for appearances of ferning . The cervical mucus and vaginal smear were taken before instillation and after instillation every 8 hours until abortion . In unacredil no significant changes in vaginal cytology were observed until abortion even when it was repeatedly instilled . The usual changes observed in vaginal cytology were observed until abortion even when it was repeatedly instilled . The usual changes observed in vaginal cytology in this series were within 8-24 hours in all saline instilled cases except the discreteness of cells which was not found in 11 cases until abortion . Karyopyknotic index rising above 10 from the baseline smear was observed in all cases but more than 30 Karyopyknotic index was noted in 26 cases . Parabasal cells appeared prior to abortion in 11 cases . Perinuclear halo was found in 1 case . In hypertonic glucose all identified changes were noted except the appearance of parabasal cells and perinuclear halo . With unacredil, the changes in vaginal cytology could not be appreciated until abortion . Ferning in pregnancy indicates placental insuffiency . In this study ferning was positive (atypical) in 2 cases before giving intraamniotic saline . After saline instillation ferning appeared in cervical mucus within 8-40 hours in all cases . In glucose instilled cases ferning appeared in all cases within 16-40 hours . Instillation of hypertonic saline probably is damaging the placenta and thus withdrawing progesterone blocks, which is reflected in vaginal cytology and cervical mucus ferning . In cases of hypertonic glucose this placental damage is not as extensive as revealed in vaginal cytology and cervical mucus fern test . In case of unacredil, it has no effect on hormonal function of placenta as is evident by no change in vaginal cytology and ferning . UN Chron . 1998;(2):73. Tuberculosis: an airborne disease; Mallozi J; PIP: This article focused on the complications for medical management of airborne diseases, such as tuberculosis . The bacilli that cause tuberculosis were first isolated in 1882, by Robert Koch . It took until 1944 for breakthrough treatment of tuberculosis . In 1998, the World Health Organization (WHO) is waging a new war against the spread of tuberculosis, which has made a comeback after years of quiescence . WHO predicts that 30 million people will die of tuberculosis and 300 million will be infected by 2008 . Tuberculosis is transmitted by air in coughing, sneezing, talking, or spitting . A tuberculosis infected person can easily infect an additional 10-20 people in the same year with the same strain . The re-emergence of tuberculosis infections is due to increased migration, international travel and tourism, AIDS, multi-drug resistance, and the weakening of public health care systems in both developed and developing countries . Multi-drug resistance occurs due to people's failure to take prescribed medications for the allotted time period . Treatment takes 6-8 months, but symptoms disappear after 2-3 months . People forget to take their drug regimens over such a long period . Some find costs too high for drugs or doctor visits . Tuberculosis bacilli can mutate and become resistant to new drugs if strains are not eradicated . WHO new management strategies offer a short course of treatment that must be followed up with support from medical staff . The Directly Observed Treatment Strategy (DOTS) eliminates the bacteria from the body and reduces the potential for contagion . DOTS has demonstrated high cure rates and low cost ($11-40/person) . Rev Gastroenterol Peru, 1997, 17 Suppl 1, 67 - 74 {GASTROINTESTINAL TUBERCULOSIS}; Celestino A DR; Tuberculosis is an ancient disease, still with highprevalence in developing countries . In Western countries there is anincreased incidence, perhaps by immigrants of the Third World, by peoplewith low socioeconomic status, and AIDS . Gastrointestinal tuberculosis, aspulmonary tuberculosis, is a common and serious problem . Symptoms and signsare nonspecific; general syndrome, fever with digestive syndrome, andabdominal pain is frequent . Digestive syndrome presents diarrhea, nausea andvomiting, abdominal pain and tenderness, abdominal mass, hepatomegaly, andassociated ascites . More than 80 percent of cases in our series have activepulmonary tuberculosis . Radiology with Barium in small bowel and colon areimportant diagnostic methods, but colonoscopy with biopsy and stained slides for acid-fast bacilli and caseose granuloma are of high yield in the colon, ileon, or ileocecal localization . If any doubt exists, therapeutic trial and exploratory laparotomy can be used . Important advances have been made in gastrointestinal tuberculosis serodiagnosis . Treatment is the same as for pulmonary tuberculosis, with short regimens; although, in certain cases, this regimen may last from 18 to 24 months . Surgical treatment is required for tuberculosls complications. Monday Dev, 1997 Nov 17, 15(22), 4 - 5 Drug-resistant TB poses global health threat, new report also finds TB control programs effective; AIDS gets the headlines et al.; PIP: Tuberculosis (TB) kills 2-3 million people each year . However, the World Health Organization estimates that only up to 6 million people have died of AIDS since the start of the epidemic in the late 1970s and early 1980s . Tuberculosis therefore kills many more people than AIDS, but AIDS gets more media attention and funding for research and prevention . One key reason why AIDS garners so much attention and funding is that it remains incurable, while TB can be cured . An aggressive anti-TB campaign is nonetheless needed in the Asia-Pacific region . One-third of the world's population is infected with the TB bacilli, with most TB cases reported in recent years being in China, India, the Philippines, Indonesia, and Bangladesh . It is also in these countries where careless or intermittent treatment of TB has allowed the disease to thrive and spread, giving rise to drug-resistant bacilli . TB kills an increasing number of HIV-positive people . The World Health Organization's Directly Observed Treatment, Short-course (DOTS) could save 10 million lives over the next decade . Child Health Dialogue, 1996 Apr-Jun, (Suppl), 8 - 9 Treatment of tuberculosis; Health care in-depth . Tuberculosis and HIV; PIP: Tuberculosis (TB) probably did not become a problem in sub-Saharan Africa (SSA) until around the 1850s . Poverty, inadequate TB control activities, and the HIV epidemic contribute to SSA having the world's highest TB case notification rate . HIV infection is responsible for a marked increase in TB in 15-45 year olds . In some parts of SSA, up to 70% of TB patients have HIV infection . A healthy immune system controls infection with Mycobacterium tuberculosis and prevents progression to TB but does not rid the body of dormant TB bacilli . HIV infection lowers immunity, therefore increasing susceptibility to TB . 25% of new TB cases each year in SSA are attributable to HIV infection . TB is the leading cause of death in HIV-infected individuals in SSA . The median CD4 count in HIV-infected adult TB patients is 200-250 . Many persons in late stage HIV infection with TB are sputum smear negative . HIV-infected persons are more likely to have disseminated and extrapulmonary TB than HIV-negative persons . HIV infection sometimes reduces the skin test response to tuberculin . It is best to avoid anti-TB treatment as a diagnostic test for TB . Clinicians should not treat HIV-infected TB patients with thiacetazone but rather ethambutol . Thiacetazone can induce a severe, and sometimes fatal, skin reaction in HIV-infected persons . Many National TB Programs recommend ethambutol in place of streptomycin due to the problems associated with inadequate sterilization of needles and syringes and the pain associated with streptomycin injections in wasted HIV-infected TB patients . HIV-infected TB patients are more likely to die within 12 months after anti-TB treatment has begun than HIV-negative patients . Active TB may boost HIV replication . The World Health Organization does not yet recommend widespread isoniazid preventive therapy for HIV-positive persons in high TB prevalence countries . AIDSlink . 1996 Mar-Apr;(38):1, 3. Tuberculosis and HIV - deadly co-infection; Broderick A; PIP: The World Health Organization estimates that 33% of the world's population is infected with the tuberculosis (TB) bacilli . Since a healthy immune system can effectively keep the bacilli in check, only about 5% of infected individuals will develop active TB in the first year or two after infection, while another 5% will develop the active disease later in their lives . TB nonetheless remains the world's single greatest infectious killer of youth and adults, claiming almost 3 million lives annually . HIV infection is the most significant known risk factor for the development of active TB . HIV is greatly facilitating the spread of TB, even though TB can be both prevented and cured even among persons with advanced HIV infection . TB accounts for 30% of AIDS deaths worldwide, 50% in Africa, and 70% in Asia . Since patients with contained TB infection are more likely to progress to active TB disease if they become infected with HIV, the HIV pandemic is a strong factor in the resurgence of TB . At the same time, TB infection may play an important role in accelerating the progression of HIV disease . The presence of a co-infection such as TB also appears to render a person's HIV infection more contagious . The author discusses the control of TB in the context of the HIV pandemic and the response of SidAlerte Internationale, an international network of NGOs in 13 African countries . Health Millions, 1995 Jan-Feb, 21(1), 34 - 5 TB and AIDS; Sehgal PN; PIP: The Indian National Tuberculosis Survey has indicated that 10 million persons above 5 years of age have pulmonary tuberculosis (TB), of whom 2.5 million are infectious . The annual infection rate amounts to 1.5% . In an average district with a population of 1.5 million, there are about 500 active, infectious TB cases and about 20,000 radiologically active cases . The World Health Organization has declared TB a global health emergency . The pandemic of AIDS had infected 13 million people worldwide by early 1993, and by the year 2000 over 40 million will be infected . In May 1986 only 1 AIDS case was reported, but by May 31, 1994, 728 cases of AIDS and 15,325 cases of HIV infections were reported . At the present rate of infection, there will be 5 million people infected with HIV by 2000 in India . HIV infection is the greatest risk factor for developing TB because of the multiplication of tubercle bacilli in quiescent foci, the progression of dormant infection to disease, and superinfection . The incidence of TB has doubled in the course of 5 years in some countries where HIV is epidemic . 30-70% of TB patients in these countries are estimated to be HIV-positive, imposing significant burden on national health services . On the other hand, efficient health services can still cure TB in HIV-positive patients and forestall the spread of the diseases . One-third of the world's population is infected with TB, and the lives of these people are shortened if they contract HIV . Worse still, for HIV-infected people exposure to TB means death, often within weeks . The only protection against the airborne TB germ is the complete cure of TB patients . At a 1993 conference in London several TB control measures were suggested: national TB control programs offering affordable treatment; faster diagnosis; education and incentives to increase patient compliance; proper drug supplies and quality control; education of influential people; and fight against poverty . Health Millions, 1995 Jan-Feb, 21(1), 27 - 8 Tuberculosis in children: some issues; Singh V; PIP: Tuberculosis (TB) causes 1-2 million deaths worldwide . In India almost 3.4 million children have TB; 40% of them contract TB by the age of 6 and 80% by the age of 16 . Active TB can be developed even via casual contact, especially with sputum-positive cases, according to a study carried out in British Columbia and Saskatchewan, Canada . If a child also has measles or whooping cough, the risk of infection is greater from an adult with TB . Even children vaccinated with BCG can develop TB after reinfection . About 10-15% of children infected with the bacilli develop TB, and the same percentage of TB cases is infectious . Approximately 4-10% of child mortality is related to TB . Often diagnosis is based on indirect evidence, because the child with TB frequently has general ill health and fails to develop properly . Symptoms like cough may also be related to respiratory infections, viral infections, and asthma . Lymph enlargement has also been misdiagnosed as tubercular . Clinicians have tended to treat children with strongly positive tuberculin reaction, although it is merely an index of infection . Short-course chemotherapy in children has shown shortcomings; for example, partial clearance of pulmonary lesion as indicated by radiology or the need for extended therapy in children with lymph node TB . The correct use of isoniazid is still controversial (5 mg/kg vs . 10 mg/kg), although recent studies have shown that the lower dose is effective with fewer side effects . Drug resistance is on the rise in child TB cases; thus, treatment modalities need to be developed . Parental attitudes are the major limiting factor in completion of therapy . The National Tuberculosis Program emphasizes the treatment of sputum-positive cases to reduce transmission . The control of TB requires: study of prevalence in vulnerable populations; emphasis of TB in the medical curriculum; training programs; and IEC to identify barriers in parental attitudes . Health Millions . 1995 Jan-Feb;21(1):17. Tuberculosis as a part of general health; Singh S; PIP: In the field practice areas of the Christian Medical College, Ludhiana, India, maternal and child health and family planning (FP) remain the major concerns of the urban FP center . Whenever symptoms of TB are detected patients are referred to private practitioners, the health center, or the Christian Medical College . The majority of patients are treated even if they cannot afford to pay . The district TB center treats them free of charge for 2 months, but then, if they cannot pay, treatment stops, they drop out, their TB becomes resistant to drugs because of incomplete treatment, and these bacilli pose a threat to the community . The issue is how to get such patients treated free of charge and how to provide the necessary supply of drugs until the patients complete the treatment . In the urban community in question there were 50 TB cases out of a population of 13,843; 18 were males and 32 were females; 4 were aged 0-1, 10 were aged 10-19, 20 were aged 20-29, 9 were aged 30-39, and 7 were aged 40 or over . Drugs were obtained from medical colleges in 9 cases, from private practitioners in 20 cases, from the district treatment center in 13 cases, and from outside the city in 4 cases according to a study carried out by medical interns in the field practice areas in late 1994 . J Anat Soc India, 1987 Aug, 36(2), 94 - 100 Vaginal cytology in women using oral contraceptives; Katira V et al.; The present study was undertaken to assess the effect of a known synthetic steroid on vaginal epithelium as a diagnostic and prognostic tool . Biweekly vaginal smears from 10 multiparous, normally menstruating Indian females ages 21-40 were studied for 3 consecutive cycles, during which time they received Voldy's 21 oral contraceptive which contained both estrogen and progesterone . 7 of these cases acted as controls for themselves since their daily smears had been studied prior to the medication . In general, all smears had present a large number of leukocytes and Doderlein bacilli . There was a loss of cyclic pattern normally seen by midzonal maturation index, low karyopyknotic index, and the appearance of navicular cells with marked curling and folding of cells . The appearance of occasional cells having larger than a 5 micron-sized nucleus during the 2nd and 3rd cycles of medication may be suggestive of some significant effect with regard to the prolonged use of this oral contraceptive. Pneumonol Alergol Pol, 2002, 70(3-4), 193 - 202 {Frequency of drug resistant tuberculosis in Poland in 2000 as compared to 1997}; Augustynowicz-Kopec E et al.; Prevalence of drug resistance to one drug and multidrug resistance--MDR in different categories of tuberculosis patients is an important information about the susceptibility pattern of Mycobacterium tuberculosis isolates against antimycobacterial drugs . Poland joined WHO/IUATLD global project on TB drug resistance surveillance, and carried out in 1996/1997 the first prospective survey, simultaneously on primary and acquired drug resistance . This study is repeated in 2000 according to the WHO/IUATLD protocol . The programme covered the whole country . A total of 16 regional centers participated in the co-operative study . 3705 questionnaires and cultures were obtained from patients who excreted TB bacilli during the 12-months from 1 st . January to 31st December 2000 . Drug resistance tests to INH, RMP, SM, EMB were performed on Lowenstein-Jensen medium according to the proportion method or/and Bactec 460 TB system . 3705 TB patients (3037 new and 668 treated cases) bacteriologically confirmed by culture were included in one-year study . Primary resistance to any drug was found in 6.12% (CI 5.27-6.56) of new cases . 35 patients (1.15%, CI 0.77-1.35) were infected with MDR strains . Acquired resistance to any drug was found in 16.6% (CI 5.27-6.56), 8.53% (CL 6.41-9.6) of the patients who excreted MDR strains . We have found increased resistance from 3.6% in 1997 to 6.12% (p < 0.001) in 2000 and MDR from 0.6% in 1997 to 1.15% (p < 0.001) in 2000 in untreated tuberculosis patients in Poland . The rate of resistance in the group of treated TB patients was very similar in 1997 (17.0%) and in 2000 (16.6%); except 20% increase of MDR cases--(7.0% in 1997, and 8.53% in 2000) . We observed an increase in drug resistant tuberculosis first time during 40 years long period of its monitoring . Regular monitoring of drug resistance in TB patients in Poland is recommended. Korean J Radiol, 2002 Jul-Sep, 3(3), 145 - 57 Nontuberculous mycobacterial pulmonary diseases in immunocompetent patients; Koh WJ et al.; Nontuberculous mycobacterial (NTM) infections are an increasingly recognized cause of chronic lung disease in immunocompetent adults, and the M . avium complex, M . kansasii, and a rapidly growing mycobacteria such as M . abscessus, M . fortuitum, and M . chelonae account for most of the pathogens involved . Because the clinical features of NTM disease are not distinguishable from those of tuberculosis, and NTM are ubiquitous in the environment, diagnosis requires that the bacilli are isolated and identified . NTM diseases have been difficult to treat, though since the introduction of new macrolides, the outcome for patients with some NTM diseases has improved significantly . For correct diagnosis and the successful treatment of NTM pulmonary disease, a knowledge of the full spectrum of clinical and radiological findings is important. Mikrobiologiia, 2002 Jul-Aug, 71(4), 491 - 3 {Endophytic bacilli--producers of type II restriction endonucleases}; Luk'ianchuk VV et al.; Two of thirteen bacillar strains isolated from the inner tissues of cotton plants were found to produce type II restriction endonucleases . The investigation of the site specificity of these enzymes showed that they are AsuI and Eco31I isoschizomers. Nervenarzt, 2002 Jun, 73(6), 489 - 99; quiz 500-1 {Neurologic complications in inflammatory bowel diseases}; Topper R et al.; Some inflammatory diseases of the gastrointestinal system are associated with neurological symptoms which, in rare cases, may precede the onset of the gastrointestinal manifestation of the disease . Celiac sprue is characterized by an intolerance to the wheat protein gluten . The typical neurological manifestation of celiac sprue is cerebellar ataxia . The ataxia as well as the gastrointestinal symptoms can be treated with a strictly gluten-free diet . The neurological symptoms of Whipple's disease, a disorder caused by gram-positive bacilli, are variable . Typical symptoms of cerebral Whipple's disease include dementia, ophthalmoplegia, movement disorders, and signs of hypothalamic dysfunction . Nowadays, the diagnosis of cerebral Whipple's disease is made by PCR detection of the bacilli in the CSF . Crohn's disease and ulcerative colitis are associated with neurological symptoms to a similar proportion . Various forms of polyneuropathies have been observed . The CNS manifestations of inflammatory bowel diseases include thromboembolic stroke, cerebral venous thrombosis, and cerebral vasculitis. J Assoc Physicians India, 2002 Jun, 50, 788 - 91 Needle aspiration as a diagnostic tool and therapeutic modality in suppurative lymphadenitis following Bacillus Calmette Guerin vaccination; Sataynarayana S et al.; OBJECTIVES: Outbreaks are known to occur after Bacillus Calmette Guerin (BCG) vaccination . An outbreak of suppurative lymphadenitis in 18 infants, following BCG vaccination is reported from Sikkim, with incidence of 8.6% . The outbreak occurred after a change of vaccine . METHODS: In a prospective study the cases of suppurative lymphadenitis were diagnosed by needle aspiration cytology and culture of the material aspirated and managed only with repeated needle aspiration and no antitubercular treatment was given . RESULTS: Cytomorphology revealed necrosis alone in 66.6% and necrotizing granulomas in 22.2% . Acid and alcohol fast bacilli were detected in 77.7% cases . Mycobacterium bovis was isolated in eight cases . One case of staphylococcal suppurative lymphadenitis was detected . Sixteen cases were managed with weekly aspiration with mean period of resolution in eight weeks . CONCLUSIONS: Needle aspiration is useful in the diagnosis and effective in the management of these cases . No antitubercular treatment is desired and required in the cases of suppurative lymphadenitis following BCG vaccination. Scand J Infect Dis, 2002, 34(8), 630 - 2 Persistent ulcers on the hand of an aquarium owner; Trampuz A et al.; We present a patient with skin ulcers that did not respond to a 3-week course of treatment with amoxicillin-clavulanic acid . As the patient maintained a fish aquarium, mycobacterial infection was suspected . Indeed, reassessment of histopathology revealed acid-fast bacilli, and mycobacterial cultures at 30 degrees C grew Mycobacterium marinum . Eventually, surgical reconstruction of the tendons was needed. Kekkaku, 2002 Aug, 77(8), 563 - 7 {A case of perforative peritonitis complicated with lung and intestinal severe tuberculosis}; Kuroda F et al.; A 27-year-old man was admitted to our hospital in September 18, 2000, complaining of fever, cough, appetite loss and body weight loss . He was diagnosed as advanced lung tuberculosis, because of chest X-ray findings and positive acid-fast bacilli in his sputum . He was administrated rifampicin (RFP), isoniazid (INH) and ethambutol (EB) . Two days after starting treatment he complained of abdominal pain and the signs of perforating peritonitis . Emergency laparotomy was performed and we observed multiple ulcers and a perforation of ileum . We resected a part of distal ileum and ascending colon and made ileostomy . Histopathologic examination of resected ileum and colon showed multiple ulcers and epithelioid cell granulomas with caseous necrosis . Many acid bacilli were identified from the lesion by specially stained tissue sections . He was administrated streptomycin and INH by injection post-operatively while oral administration was impossible . Six days after the first operation, we found the signs of perforation in another part of the ileum . So we were obliged to perform second laparotomy and resect the part involved . Five days after the second operation, he was able to take RFP, INH, and levofloxacin per oral route . On February 8, 2001 we performed ileocolonal reconstruction with side to side anastomosis and closed ileostomy at the third laparotomy . He had continued chemotherapy and went back to Korea in April 7, 2001 . Although intestinal tuberculosis has sharply declined in Japan thanks to development of effective antituberculous drugs, we should keep in mind that it could be a possible cause of the acute abdomen. Kekkaku, 2002 Aug, 77(8), 555 - 61 {Tuberculosis control in Kobe City--analyses of advisory contents and disqualified cases by integrated tuberculosis advisory committee}; Shirai C; The incidence of tuberculosis (TB) in Kobe City has been higher in comparison with that of Japan, thereby Kobe City ought to enforce anti-tuberculosis activities . Nine Wards public health departments of Kobe City used to convene their own tuberculosis advisory committees until April 1998, when a centralized committee was established to examine all TB patients . The new committee was authorized to issue clinical advice to registered physicians whenever necessary in order to improve treatment standard of TB . The author analyzed the contents of issued documents and observed any change in statistics before and after establishment of the committee . During the past 3 years, the new committee had sent 2,221 advisory documents to physicians, which occupied 35% of all 6,305 applied cases . Main suggestions included proper choice of anti-tuberculosis agents, adequate duration of treatment and reference to the results of laboratory examinations . In addition, 140 cases were rejected for medical expenses subsidy by TB Law to avoid unnecessary long-term treatment . Main reasons of rejection were long-term treatment despite negative bacilli too more than one year, continuous single INH administration following the completion of the standard treatment and unnecessary treatment for the cases with inactive findings on chest X-ray . Since the establishment of the integrated committee, the statistics of TB has demonstrated a significant decrease in the incidence and the prevalence of TB with its annual reduction of 5.6, and 11.5 per 100,000 respectively . The proportion of bacteriologically confirmed cases among newly registered patients has increased, and the diagnostic accuracy was improved due to the decrease in the unknown bacteriology case . The proportion of the case treated by INH alone fall down rapidly and it is lower than that of the whole country . These data demonstrate that the integrated tuberculosis advisory committee contributes to standardize anti-tubercular treatment through dissemination of proper guidance on TB diagnosis and treatment to all medical facilities in the city. Rinsho Shinkeigaku, 2001 Dec, 41(12), 1173 - 7 {Neuro-infections to be borne in mind}; Kamei S et al.; We presented atypical manifestations in tuberculous meningitis (TbM) and herpes simplex encephalitis (HSE), lymphocytic dominant cerebrospinal fluid pleocytosis in bacterial meningitis, and a hitherto easily overlooked critical illness polyneuropathy (CIP) associated with sepsis . 1) We presented 2 TbM patients with atypical manifestations . One patient was a 25-year-old man who exhibited polymorphonuclear (PMN) dominant pleocytosis in CSF throughout his clinical course . He died the next day after a CSF culture yielded the growth of tuberculous bacilli, before receiving appropriate anti-TBM therapy . This was a rare TbM example of persistent PMN dominant CSF pleocytosis . The other patient was a 39-year-old woman whose CSF pleocytosis changed from lymphocytic dominant to PMN dominant about 1 month after the initiation of antituberculous chemotherapy . This CSF change was followed by multiple cerebral infarcts due to vauculitis caused by TbM . Administration of prednisolone caused marked improvement of the patient's symptomatology . Tuberculomas appeared transiently during anti-TbM therapy, consistent with paradoxical progression of tuberculoma . 2) A few patients with HSE may show atypical CSF findings such as PMN dominant pleocytosis, absence of pleocytosis, and low sugar value . Our national survey of HSE patients showed following percentages of these atypical findings: PMN dominant pleocytosis observed in 10% of the patients in the early stage and at the time of exacerbation, no pleocytosis in 0.9% (1 patient), and low sugar value in 4% . 3) Bacterial meningitis typically causes PMN dominant CSF pleocytosis . However, Listeria meningitis (LM) may cause lymphocytic dominant pleocytosis in 30% of the patients, particularly in elderly ones . We showed one such 69-year-old patient with persistent lymphocytic dominant CSF pleocytosis throughout the clinical course . 4) CIP, septic encephalopathy and critical illness myopathy are 3 major complications associated with sepsis . CIP is a frequent cause of neuromuscular weakness due to axonal dysfunction, which occurs to critically ill patients with sepsis, particularly when multiple organ dysfunctions are present . We showed our CIP patient associated with acute bacterial endocarditis and multiple organ failure . We should bear in mind these atypical manifestations, and frequent and important complications associated with sepsis such as CIP, to provide appropriate management to patients with neuro-infection and sepsis. Nucleic Acids Res, 2002 Sep 15, 30(18), 3927 - 35 Genome sequence of Oceanobacillus iheyensis isolated from the Iheya Ridge and its unexpected adaptive capabilities to extreme environments; Takami H et al.; Oceanobacillus iheyensis HTE831 is an alkaliphilic and extremely halotolerant Bacillus-related species isolated from deep-sea sediment . We present here the complete genome sequence of HTE831 along with analyses of genes required for adaptation to highly alkaline and saline environments . The genome consists of 3.6 Mb, encoding many proteins potentially associated with roles in regulation of intracellular osmotic pressure and pH homeostasis . The candidate genes involved in alkaliphily were determined based on comparative analysis with three Bacillus species and two other Gram-positive species . Comparison with the genomes of other major Gram-positive bacterial species suggests that the backbone of the genus Bacillus is composed of approximately 350 genes . This second genome sequence of an alkaliphilic Bacillus-related species will be useful in understanding life in highly alkaline environments and microbial diversity within the ubiquitous bacilli. Scand J Immunol, 2002 Oct, 56(4), 383 - 91 Increased Bcl-2 and reduced Bax expression in infected macrophages in slowly progressive primary murine Mycobacterium tuberculosis infection; Mogga SJ et al.; Mycobacterium tuberculosis (MTB) persists in host macrophages (Mphis) because it has developed mechanisms to escape Mphi killing . In vitro studies have shown that MTB can induce and inhibit apoptosis by causing the expression of Bax and Bcl-2, respectively, suggesting that the infected cells' fate depends on pro- and antiapoptotic signals . In the present study, we investigated the role of Bcl-2 in MTB infection in situ . The aim was to study the pattern and distribution of Bcl-2 and Bax in cellular infiltrates of MTB-infected B6D2F1 hybrid mice and correlate the expression with the presence of MTB antigens (MAgs) . Using formalin-fixed lung tissues (n = 45), our results showed a significant difference in the percentage of Mphis stained for Bcl-2 or MAgs and Bax (P < 0.0001) . Bcl-2 expression was increased in a population of Mphis and corresponded in intensity, colocalization and percentage with that of MAgs on the same cells, while Bax expression was reduced . In lymphocyte aggregates, Bcl-2 and Bax did not show any differences . We conclude that overexpression of Bcl-2 in Mphis containing MTB may be associated with intracellular survival of the bacilli, thus demonstrating one way by which MTB can escape the host's cellular response and killing. Int J Tuberc Lung Dis, 2002 Sep, 6(9), 763 - 70 Efficacy of common antiseptics against multidrug-resistant Mycobacterium tuberculosis; Rikimaru T et al.; OBJECTIVES: The incidence of infections caused by multidrug-resistant strains of Mycobacterium tuberculosis (MDR-TB) has been increasing . Antiseptics are frequently used to prevent mycobacterial infection . The aim of this study was to determine those antiseptics that are useful against MDR-TB . DESIGN: We evaluated bactericidal activity against clinical isolates of MDR-TB in vitro . METHOD: Thirteen strains of MDR-TB were tested against povidone-iodine (PVP-I), cresol, akyldiaminoethyl glycine hydrocloride (AEG), and glutaraldehyde . After bacilli were exposed to the antiseptic solution with 2% human serum, the disinfectant was inactivated by addition of neutraliser . RESULTS: PVP-1 at a final concentration of 0.2% killed all of the strains within 120 seconds, and PVP-I at 0.1% killed 99.9% or more bacilli within 60 seconds . Most strains were killed after exposure to 0.5% cresol at 300 seconds and to 1.0% cresol at 60 seconds; 3.0% cresol killed all bacilli within 120 seconds, while 0.1%, 0.2%, and 0.5% AEG all required 60 minutes to kill 99.9% or more of the bacilli; 2.0% glutaraldehyde required 10 minutes to kill all bacilli . CONCLUSION: The bactericidal activities of antiseptics for MDR-TB were similar to those for drug-sensitive M . tuberculosis strains . PVP-I would be a useful antiseptic against MDR-TB . The bactericidal activities of glutaraldehyde are effective against MDR-TB as an antiseptic for medical equipment. Int J Tuberc Lung Dis, 2002 Sep, 6(9), 757 - 62 Anti-tuberculosis drug resistance in community and prison patients, Orel Oblast, Russian Federation; Spradling P et al.; SETTING: Orel Oblast, Russian Federation . OBJECTIVES: To determine baseline levels of anti-tuberculosis drug resistance in Orel Oblast . DESIGN: Drug susceptibility testing (DST) records from 1 July 1999 to 30 June 2000 for patients with sputum acid-fast bacilli smear-positive pulmonary tuberculosis were reviewed . Treatment and incarceration status were obtained from the tuberculosis register . Patients with 1 month or less of prior treatment were defined as new cases; those previously treated for more than 1 month were defined as retreatment cases . RESULTS: Of 246 smear-positive isolates, 212 (86%) had DST performed . Of these, 190 (90%) were from new and 22 (10%) from retreatment cases; 171 (81%) were from community and 41 (19%) were from prison patients . Any drug resistance was more common among prison than community patients (44% vs . 30%, P = 0.05) . MDR-TB was found in 14 (6.6%) of 212 isolates, and was more prevalent in prison compared with community patients (12% vs . 5%, P = 0.05) . Retreatment cases were more likely than new cases to have MDR-TB (prevalence ratio {PR} = 8.5, 95%CI = 3.3-22.3), although the PR was higher for prison than for community retreatment cases (10.0 vs . 5.8) . CONCLUSIONS: New cases with MDR-TB were less prevalent in Orel Oblast compared with other survey sites in Russia . Any drug resistance and MDR-TB were associated with prior treatment, especially in the prison population . Continued monitoring of trends in drug resistance following DOTS implementation is needed. Infect Immun, 2002 Oct, 70(10), 5628 - 34 Virulent Mycobacterium fortuitum restricts NO production by a gamma interferon-activated J774 cell line and phagosome-lysosome fusion; Da Silva TR et al.; The virulence of different isolates of Mycobacterium has been associated with two morphologically distinguishable colonial variants: opaque (SmOp) and transparent (SmTr) . In this report we used an in vitro assay to compare macrophage (Mphi) responses to SmOp and SmTr Mycobacterium fortuitum variants, taking advantage of the fact that these variants were derived from the same isolate . Cells preactivated or not with gamma interferon (IFN-gamma) were infected with SmOp or SmTr M . fortuitum . We showed that SmOp and SmTr induced different levels of nitric oxide (NO) production by IFN-gamma-stimulated Mphi . Indeed, the amount of IFN-gamma-induced NO production by J774 cells was 4.8 to 9.0 times higher by SmOp (23.1 to 37.7 micro M) compared to SmTr infection (3.9 to 4.8 micro M) (P = 0.0332), indicating that virulent SmTr bacilli restricted NO production . In addition, IFN-gamma-induced NO production by Mphi was higher when correlated with reduction of only avirulent SmOp bacillus viability . SNAP (S-nitroso-N-acetyl-DL-penicillamine)-induced NO production did not modify SmTr viability, indicating its resistance to nitrogen radicals . Electron microscopy studies were performed to evaluate the capacity of phagosomes to fuse with lysosomes labeled with bovine serum albumin-colloidal gold particles . By 24 h postinfection, 69% more phagosome-containing SmOp variant had fused with lysosomes compared to the SmTr-induced phagosomes . In conclusion, these data indicate that virulent SmTr bacilli may escape host defense by restricting IFN-gamma-induced NO production, resisting nitrogen toxic radicals, and limiting phagosome fusion with lysosomes. Infect Immun, 2002 Oct, 70(10), 5568 - 78 Bacterial artificial chromosome-based comparative genomic analysis identifies Mycobacterium microti as a natural ESAT-6 deletion mutant; Brodin P et al.; Mycobacterium microti is a member of the Mycobacterium tuberculosis complex that causes tuberculosis in voles . Most strains of M . microti are harmless for humans, and some have been successfully used as live tuberculosis vaccines . In an attempt to identify putative virulence factors of the tubercle bacilli, genes that are absent from the avirulent M . microti but present in human pathogen M . tuberculosis or Mycobacterium bovis were searched for . A minimal set of 50 bacterial artificial chromosome (BAC) clones that covers almost all of the genome of M . microti OV254 was constructed, and individual BACs were compared to the corresponding BACs from M . bovis AF2122/97 and M . tuberculosis H37Rv . Comparison of pulsed-field gel-separated DNA digests of BAC clones led to the identification of 10 regions of difference (RD) between M . microti OV254 and M . tuberculosis . A 14-kb chromosomal region (RD1(mic)) that partly overlaps the RD1 deletion in the BCG vaccine strain was missing from the genomes of all nine tested M . microti strains . This region covers 13 genes, Rv3864 to Rv3876, in M . tuberculosis, including those encoding the potent ESAT-6 and CFP-10 antigens . In contrast, RD5(mic), a region that contains three phospholipase C genes (plcA to -C), was missing from only the vole isolates and was present in M . microti strains isolated from humans . Apart from RD1(mic) and RD5(mic) other M . microti-specific deleted regions have been identified (MiD1 to MiD3) . Deletion of MiD1 has removed parts of the direct repeat region in M . microti and thus contributes to the characteristic spoligotype of M . microti strains. Curr Infect Dis Rep, 2002 Oct, 4(5), 426 - 432 The Role of Fluoroquinolones in the Treatment of Skin and Soft Tissue Infection; Alam MR et al.; Skin and soft tissue infections vary widely in their nature and severity, and their nomenclature is complex . Most are readily recognized and easily treated, but more severe infections may masquerade in forms similar to those of more innocent infections, causing delay in diagnosis and treatment that may result in loss of limb or life . Antimicrobial therapy is clearly beneficial for both recovery from these infections as well as preventing disease progression . The fluoroquinolones are potent broad-spectrum antimicrobial agents . The older fluoroquinolones mainly have excellent in vitro activity against gram-negative bacilli and borderline activity against clinically important gram-positive organisms, but newer fluoroquinolones were developed to have enhanced activity against both gram-positive and anaerobic organisms while retaining broad-spectrum anti-gram-negative activity . Several comparative trials using fluoroquinolones suggest that the efficacy of these agents is similar to that of b-lactam antimicrobial agents . Additional clinical trials are necessary to determine the overall role of newer fluoroquinolones as alternatives for skin and soft tissue infections. Indian J Chest Dis Allied Sci, 2002 Jul-Sep, 44(3), 159 - 63 Clinical profile of tuberculosis in patients with HIV Infection/AIDS; Kumar P et al.; Tuberculosis is said to be one of the commonest opportunistic infection in patients with HIV/ AIDS . A study was carried out to study the clinical, bacteriological and radiological features of HIV/TB patients . Over a period of two years, a total of 301 tuberculosis patients were suspected to have HIV/AIDS co-infection, and upon testing, 42 patients were found to be HIV seropositive . Most of the study patients were manual labourers followed by truck drivers . Sexual (heterosexual) route was found to be the major risk factor for HIV/AIDS . The most common symptom in these patients was cough and expectoration, followed by fever and weight loss . Acid-fast bacilli (AFB) smear positivity was found in 21.4% patients . On chest skiagram, infiltrative lesions were commonly seen in 61.9% patients . Extra-pulmonary tubercular manifestations were seen in 45.6% of HIV/TB cases. Mem Inst Oswaldo Cruz, 2002 Jul, 97(5), 725 - 9 Non-tuberculous mycobacteria I: one year clinical isolates identification in Tertiary Hospital Aids Reference Center, Rio de Janeiro, Brazil, in pre highly active antiretroviral therapy era; Ferreira RM et al.; The aim of this study was to determine the prevalence of non-tuberculous mycobacteria (NTM) isolates at University Hospital, Reference Center for Aids in Rio de Janeiro, Brazil, during one year . We used standard biochemical tests for species identification and IS1245 PCR amplification was applied as a Mycobacterium avium specific identification marker . Four hundred and four specimens from 233 patients yielded acid-fast bacilli growth . M . tuberculosis was identified in 85% of the patients and NTM in 15% . NTM disseminated infection was a common event correlated with human immunodeficiency virus (HIV) infected patients and only in HIV negative patients the source of NTM was non sterile site . M . avium complex (MAC) was biochemically identified in 57.8% (49/83) of NTM isolates, most of them from sterile sites (75.5%), and in 94% (46/49) the IS 1245 marker specific for M . avium was present . Twenty NTM strains showed a MAC biochemical pattern with the exception of a urease-positive (99% of MAC are urease-negative), however IS1245 was detected in 96% of the strains leading to their identification as M . avium . In this group differences in NTM source was not significant . The second most frequently isolated NTM was identified as M . scrofulaceum (7.2%), followed by M . terrae (3.6%), M . gordonae (2.4%), M . chelonae (1.2%), M . fortuitum (1.2%) and one strain which could not be identified . All were IS1245 negative except for one strain identified as M . scrofulaceum . It is interesting to note that non-sterile sites were the major source of these isolates (92.8%) . Our finding indicated that M . avium is still the major atypical species among in the MAC isolates recovered from Brazilian Aids patients without highty active antiretroviral therapy schema . Some discrepancies were seen between the identification methods and further investigations must be done to better characterize NTM isolates using other phenotypic and genotypic methods. Ann Dermatol Venereol, 2002 Jun-Jul, 129(6-7), 886 - 7 {Plantar pyoderma due to Stenotrophomonas maltophilia}; Pruvost C et al.; INTRODUCTION: Stenotrophomonas maltophilia is a Gram negative, opportunistic bacteria . We describe a case of community-acquired superficial pyoderma due to this bacteria in a immunocompetent host . CASE-REPORT: A 59-year-old man presented with an ulceration of the sole for two months . Several topical and systemic treatments had failed to cure the lesion, including oral ofloxacin for ten days . Microbiological study of the lesion showed numerous Gram negative bacilli with growth of S . maltophilia . This bacterium initially responded to ofloxacin, but became resistant after the oral use of this antibiotic . Finally, a topical treatment with polymyxin/tetracycline ointment resulted in complete healing within two weeks . DISCUSSION: S . maltophilia may be responsible for superficial pyoderma and serious opportunistic infections in immunocompetent persons . Topical antimicrobial therapy is efficient when oral quinolone therapy has failed to cure the lesion. J Immunol, 2002 Sep 15, 169(6), 3155 - 62 Toll-like receptor 4 expression is required to control chronic Mycobacterium tuberculosis infection in mice; Abel B et al.; Endotoxin from Gram-negative bacteria bound to CD14 signals through Toll-like receptor (TLR) 4, while components of Gram-positive bacteria, fungi, and Mycobacterium tuberculosis (M.tb.) preferentially use TLR2 signaling . We asked whether TLR4 plays any role in host resistance to M.tb . infection in vivo . Therefore, we infected the TLR4 mutant C3H/HeJ mice and their controls, C3H/HeN mice, with M.tb . by aerosol . TLR4 mutant mice had a reduced capacity to eliminate mycobacteria from the lungs, spread the infection to spleen and liver, with 10-100 times higher CFU organ levels than the wild-type mice and succumbed within 5-7 mo, whereas most of the wild-type mice controlled infection and survived the duration of the experiment . The lungs of TLR4 mutant mice showed chronic pneumonia with increased neutrophil infiltration, reduced macrophages recruitment, and abundant acid-fast bacilli . Furthermore, the pulmonary expression of TNF-alpha, IL-12p40, and monocyte chemoattractant protein 1 was significantly lower in C3H/HeJ mice when compared with the wild-type controls . C3H/HeJ-derived macrophages infected in vitro with M.tb . produced lower levels of TNF-alpha . Finally, the purified mycobacterial glycolipid, phosphatidylinositol mannosides, induced signaling in both a TLR2- and TLR4-dependent manner, thus suggesting that recognition of phosphatidylinositol mannosides in vivo may influence the development of protective immunity . In summary, macrophage recruitment and the proinflammatory response to M.tb . are impaired in TLR4 mutant mice, resulting in chronic infection with impaired elimination of mycobacteria . Therefore, TLR4 signaling is required to mount a protective response during chronic M.tb . infection. J Infect, 2002 Aug, 45(2), 112 - 4 BCG septicemia after radical cystectomy: a rare postoperative complication following BCG therapy; Del Prete R et al.; It is reported a case of life-threatening septic shock due to BCG septicemia after radical cystectomy in a patient with a previous treatment with BCG therapy . In the absence of response to standard antimicrobial therapy and a negative CT scan, a PCR-based technique detected the presence of BCG bacilli in bloodstream . Immediate antimycobacterial therapy resolved the sepsis, thus suggesting either the awareness of this infection or the prompt antimycobacterial therapy as the key for the appropriate management . Furthermore, isoniazid prophylaxis should be taken into consideration in patients with history of intravesical BCG therapy undergoing cystectomy. Clin Experiment Ophthalmol, 2002 Oct, 30(5), 375 - 7 Capnocytophaga canimorsus endophthalmitis following cataract surgery; Phipps SE et al.; An elderly man developed endophthalmitis 1 week after cataract extraction and lens implantation . Intraocular samples were collected and the patient received intravitreal vanco-mycin and ceftazidime, and topical tobramycin . A Gram stain of vitreous humour revealed spindle-shaped Gram-negative bacilli . He was then given systemic clindamycin and topical ofloxacin . Capnocytophaga canimorsus, a member of the oral flora of dogs and cats, was cultured after 3 days . The infection resolved leaving the patient with a visual acuity of 6/60 . An attempt was made to culture the organism from the mouth of the patient's pet dog . This was unsuccessful and the source of the infection remains unknown. Ren Fail, 2002 Jul, 24(4), 511 - 21 Extra-renal abscess in chronic hemodialysis patients; Chuang FR et al.; AIM: Infectious disease represents one of the major causes of morbidity and mortality in hemodialysis patients . Extra-renal abscess constitutes a specific form of infection . The aim of this study was to evaluate and analyze the clinical characteristics of extra-renal abscess in chronic hemodialysis patients . METHODS: We retrospectively studied the extra-renal abscess among chronic hemodialysis patients in Chang Gung Memorial Hospital at Kaohsiung, Taiwan . The records of 2,168 chronic hemodialysis patients from October 1986 to January 2000, were studied . The clinical features were reviewed and analyzed . RESULTS: Sixteen patients who were enrolled during the study period developed extra-renal abscess . Ten of them were male . The mean age was 59.2 +/- 11.8 years old . More than half of the patients had diabetes (53.6%, 9/16) . The locations of extra-renal abscess in these patients were liver (8/16), lung (5/16), spleen (1/16), perianal region (1/16), psoas muscle (1/16), and prostate (1/16) . One patient had concurrent liver and spleen abscesses . All patients presented with fever and chills . Laboratory studies revealed leukocytosis and thrombocytopenia in 2/3 of the patients . The patients were associated with malnutrition status with lower serum albumin level (2.94 +/- 0.55 gm/dL) and lower nPCR (normalized protein catabolism rate; 0.84 +/- 0.11 gm/Kg/day) comparing to the other hemodialysis patients (albumin: 4.05 +/- 0.47 gm/dL; nPCR: 1.14 +/- 0.31gm/kg/day) . There was no significant difference in kt/V between the patients with (1.28 +/- 0.34) or without abscess formation (1.47 +/- 0.36) . The major causative pathogen was Klebsiella pnewnoniae . Parenteral antibiotic treatment is sufficient to treat most of the diseases, except 2 patients who needed surgical intervention . Twelve patients recovered after 2-3 weeks of treatment . Conclusions: The study indicated that extra-renal abscess is rare in chronic hemodialysis patients . The abscesses occurred mostly in liver . Diabetes mellitus and poor nutrition status were the important predisposing factors . Gram-negative bacilli, K . pneumoniae, were the major pathogen . Most of the patients responded to parenteral antibiotics and surgical draining. Hua Xi Yi Ke Da Xue Xue Bao, 1999 Sep, 30(3), 321 - 3 {Light and electron microscope observations of heart and vascular tissues in animals acutely infected with tubercle bacilli}; Li G et al.; The objective of this study was to observe the heart and vascular pathological lesions of some animals acutely infected with H37Rv tubercle bacilli . C57 BL/6N mice and rabbits were used for the establishment of the models . Light sections were stained with HE, Z-N, MCT and BCGS-P . Ultrathin sections were stained with uranyl and lead citrate and examined by electron microscope . The results showed that tubercle bacilli were present in heart and vascular tissues . Myocardial fibre, pericardium and vascular tissues had various degrees of lesions . The lesions of myocardial fibre and pericardium were more serious than that of the vascular tissues . These findings suggest that the toxin of the tubercle bacilli can damage the tissues of the infected animals, and the excessive reproduction can be also a factor detrimental to the infected tissues. Hunan Yi Ke Da Xue Xue Bao, 2000 Apr 28, 25(2), 109 - 12 {Protective effects of baicalin, mannitol and dexamethasone on infective brain edema in rats}; Cao LZ et al.; OBJECTIVE: To compare the therapeutic effects of baicalin, mannitol and dexamethasone on infective brain edema(IBE) in rats . METHODS: Forty normal Sprague-Dawley(SD) rats (200 +/- 30) g by weight were divided into 5 groups randomly: (1) normal saline control group(NS, n = 8); (2) infective brain edema group (BE, n = 8); (3) mannitol treatment group(MAN, n = 8); (4) dexamethasone treatment group(DXM, n = 8); and (5) baicalin treatment group(BC, n = 8) . Pertussis bacilli(PB, contained bacilli in 10.8 x 10(9), 0.2 ml-1.kg-1) were injected into the left carotid arteries through the left common carotid arteries by puncture to obtain BE models . The contents of brain water, sodium ion, potassium ion and Evans blue in brain tissues were observed too . RESULTS: The contents of brain water, sodium ion, and EB in BE group were higher than those in BE group(P < 0.01), they decreased in MAN, DXM, BC groups and were lower than those in BE group(P < 0.01) . In MAN, DXM, BC groups, there were no significant difference in the contents of brain water and sodium ion(P > 0.05) . The EB content in BC group was higher than that in MAN and DXM groups(P < 0.01) . The content of potassium ion in BE group was higher than that in MAN and DXM groups, the content of potassium ion was similar to that in NS group, but lower than that in BC group . Light microscope inspection in MAN, DXM and BC groups showed lessened brain edema, slight increase of perivascular space, and occasional nerve cell pyknotic nucleus . We found on nerve cell vacuolar degeneration in DXM group . CONCLUSION: Baicalin, mannitol and dexamethasone all have similar protective effects on infective brain edema in rats. Int J Lepr Other Mycobact Dis, 2002 Jun, 70(2), 104 - 10 Study of HLA-DR expression on skin lesions of leprosy before and during multiple drug therapy; Abdel Latif AM et al.; Leprosy is a dynamic disease in which cell mediated immunity (CMI) plays an important role in host defense and control of the clinical spectrum . This study was carried out to detect immune activation in the granuloma of leprosy during multiple drug therapy (MDT) by studying the expression of human leukocytic antigen-DR (HLA-DR) in the granuloma before and during therapy . Skin punch biopsies were taken before and at least once 2-4 weeks after starting MDT in 20 newly diagnosed patients . Two biopsies, 2-4 weeks apart, were also taken from 10 new patients who did not yet receive any treatment, for comparison . Furthermore, biopsies were taken before and during corticosteroid therapy in five patients who developed reversal reaction during MDT . The biopsy specimens were studied for the expression of HLA-DR using the immunofluorescent staining which was found to be visibly increased in 17 out of 20 new cases (85%) within 2-4 weeks after starting MDT, while no change in the expression was noticed in those who did not receive any treatment (p < 0.001) . This might reflect the increased production of interferon gamma (IFN gamma) specially from granuloma lymphocytes after being stimulated with the excessive release of mycobacterial antigen from killed bacilli during therapy . The five patients who developed reversal reaction during MDT had strong HLA-DR expression in the first biopsies which declined subsequently 2-6 weeks after starting prednisolone therapy . Our results suggest that CMI was activated in skin lesions of leprosy during MDT . Such activation was not only restricted to those who developed reversal reaction across the therapeutic course, which indicates that the difference between patients who developed such reaction and those who did not, was likely to be quantitative rather than qualitative, with a more exaggerated CMI response in the former . Furthermore, it seems that the beneficial effect of MDT is accompanied by important changes in the immune cell profile which have a great role in overcoming such infection. Arch Microbiol, 2002 Oct, 178(4), 311 - 4 Epub 2002 Aug 07. The relationship of temperature to desiccation and starvation tolerance of the Mycobacterium avium complex; Archuleta RJ et al.; Mycobacterium avium grew in media at 14-37 degrees C, and persisted at 4 degrees C and 42 degrees C . The bacteria lost approximately 90% viability after 3 months in reverse-osmosis deionized water at 4-37 degrees C . Cooler temperatures lowered the death rate . Death rates also decreased after a 5- to 10-day starvation adaptation period . Alterations of the steady-state levels of different mycolic acid classes, presumably to facilitate thermoadaptation, were found . Following desiccation, M . avium lost viability at a constant rate (half-life of 2.3 days) . This implies that bacilli contaminating dry medical surfaces would persist for short periods of time . The remarkable stress survival exhibited by M . avium further suggests persistence in a range of environmental and clinical settings. Am J Ophthalmol, 2002 Sep, 134(3), 433 - 4 Bacillary angiomatosis of the anterior orbit, eyelid, and conjunctiva; Tsai PS et al.; PURPOSE: To report a case of bacillary angiomatosis of the lower eyelid, conjunctiva, and anterior orbit . DESIGN: Interventional case report . METHODS: A 76-year-old immunocompromised male patient developed a firm vascularized nodule in his left lower eyelid and anterior orbit . RESULTS: An excisional biopsy was performed . Histopathologic examination revealed an abnormal vascular proliferation and a mixed inflammatory infiltrate . A Warthin-Starry stain showed numerous bacilli . These findings are characteristic of bacillary angiomatosis . A serologic specimen was positive for antibodies to Bartonella Quintana . CONCLUSION: The lower lid and anterior orbit are rare locations for bacillary angiomatosis . Our case brings to attention the increasing importance of Bartonella infection as a causative agent of ophthalmic diseases. Mol Microbiol, 2002 Sep, 45(5), 1303 - 14 Nitric oxide scavenging and detoxification by the Mycobacterium tuberculosis haemoglobin, HbN in Escherichia coli; Pathania R et al.; Nitric oxide (NO), generated in large amounts within the macrophages, controls and restricts the growth of internalized human pathogen, Mycobacterium tuberculosis H37Rv . The molecular mechanism by which tubercle bacilli survive within macrophages is currently of intense interest . In this work, we have demonstrated that dimeric haemoglobin, HbN, from M . tuberculosis exhibits distinct nitric oxide dioxygenase (NOD) activity and protects growth and cellular respiration of heterologous hosts, Escherichia coli and Mycobacterium smegmatis, from the toxic effect of exogenous NO and the NO-releasing compounds . A flavohaemoglobin (HMP)-deficient mutant of E . coli, unable to metabolize NO, acquired an oxygen-dependent NO consumption activity in the presence of HbN . On the basis of cellular haem content, the specific NOD activity of HbN was nearly 35-fold higher than the single-domain Vitreoscilla haemoglobin (VHb) but was sevenfold lower than the two-domain flavohaemoglobin . HbN-dependent NO consumption was sustained with repeated addition of NO, demonstrating that HbN is catalytically reduced within E . coli . Aerobic growth and respiration of a flavohaemoglobin (HMP) mutant of E . coli was inhibited in the presence of exogenous NO but remained insensitive to NO inhibition when these cells produced HbN, VHb or flavohaemoglobin . M . smegmatis, carrying a native HbN very similar to M . tuberculosis HbN, exhibited a 7.5-fold increase in NO uptake when exposed to gaseous NO, suggesting NO-induced NOD activity in these cells . In addition, expression of plasmid-encoded HbN of M . tuberculosis in M . smegmatis resulted in 100-fold higher NO consumption activity than the isogenic control cells . These results provide strong experimental evidence in support of NO scavenging and detoxification function for the M . tuberculosis HbN . The catalytic NO scavenging by HbN may be highly advantageous for the survival of tubercle bacilli during infection and pathogenesis. Pediatr Pulmonol, 2002 Sep, 34(3), 159 - 63 Transmission of tuberculosis from adults to children in a Paris suburb; Madhi F et al.; Tuberculosis in children is often acquired by contact with a family or household member . The aim of our study was to evaluate risk factors for latent infection and active disease in exposed children in a suburb of Paris . We examined medical records for the period 1997-2000 at six departmental centers for medical prevention in Val de Marne . Thirty-nine patients aged 18 years or more with M . tuberculosis-positive sputum samples, and living with children or adolescents, were identified . Ninety-one children, aged 3 months-17 years, were exposed to these index cases . All the children initially underwent a tuberculin skin test and chest radiography, and children with no criteria for latent infection or active disease at time of initial evaluation were asked to attend a second evaluation 3 months later . Overall, 20 of the 91 (22%) children were infected, including 4 children identified only at the second evaluation . Eight (40%) of the 20 infected children had active disease, including 2 of the 4 children identified at the second evaluation . The risk of infection was not influenced by the children's age, but was significantly associated with three characteristics of the adult cases, i.e., age younger than 40 years, presence of cavitary lesions, and smears with more than 100 bacilli per microscopic field.In conclusion, our results call for early examination of all exposed children, in order to prevent infection and progression to active disease, and for a routine second evaluation after the adult contact has ended . Clin Infect Dis, 2002 Sep 15, 35(6), 659 - 64 Epub 2002 Aug 23. Aspergillosis: The most common community-acquired pneumonia with gram-negative Bacilli as copathogens in stem cell transplant recipients with graft-versus-host disease; Alangaden GJ et al.; We retrospectively reviewed all cases of pneumonia that required hospitalization among allogeneic hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) during the period of January 1996 through July 1999 . Twelve patients were identified among 88 allogeneic HSCT recipients . All had chronic GVHD and were receiving corticosteroid therapy . Ten of the 12 patients had pulmonary aspergillosis (PA) . For 6 of these 10 patients, a gram-negative bacterial pathogen was concurrently isolated from respiratory specimens . At least one-half of the patients with PA had an initial presentation suggestive of bacterial pneumonia; PA was only suspected on the basis of chest CT findings . Aspergillosis is the most common cause of community-acquired pneumonia among allogeneic HSCT recipients with GVHD . CT must be used to exclude an underlying fungal cause in patients who present with a gram-negative pneumonia. Tumori, 2002 May-Jun, 88(3), 251 - 4 Reactivation of pulmonary tuberculosis in malignancy; Karnak D et al.; AIMS AND BACKGROUND: Deterioration of immunity due to local or systemic effects of the tumor itself and/or administered chemotherapeutics or radiotherapy may play roles in the reactivation of tuberculosis, increasing the mortality in patients with various malignancies . In a country with a high prevalence of tuberculosis such as Turkey, most people have inactive tuberculous lesions and tuberculin test positivity . Therefore, a prospective study was carried out to investigate the frequency of tuberculosis reactivation in patients with a malignancy . METHODS: Seventy-three patients with a malignancy and undergoing diagnostic fiberoptic bronchoscopy were enrolled in the study during a 2-year period (1993-1995) . Bronchoscopic biopsies and cytologic materials were obtained . Bronchoalveolar lavage fluids, bronchial washings, and pre- and postbronchoscopic sputum specimens were also evaluated for acid-fast bacilli . A diagnosis of tuberculosis was based on smear and/or culture positivity for acid-fast bacilli . RESULTS: The mean age of the patients was 56.2 +/- 13.6 years, with a male/female ratio of 69/4 . The biopsy proven malignancies were as follows: primary lung carcinoma (n = 66, 90.4%), lymphoma (n = 5, 6.8%), metastatic breast adenocarcinoma (n = 1, 1.4%), and acute myelocytic leukemia (n = 1, 1.4%) . Thirty-one of all patients had findings compatible with tuberculosis on radiology . The sputa and bronchial washing specimens were smear negative in all patients . Acid-fast bacilli were grown on culture in 6 patients (8%) (primary lung cancer, n = 5; non-Hodgkin lymphoma, n = 1) . Four of these 6 patients had positive radiology for tuberculosis . These subjects were treated with a three- or four-drug anti-tuberculosis regimen . Two months later, smears remained acid-fast bacilli negative, or no bacilli were grown on culture . CONCLUSIONS: The possibility of coexisting tuberculosis should be kept in mind in patients with a malignancy, especially those with lung carcinoma in countries with a high prevalence of tuberculosis . Pulmonary infections encountered in such patients should raise the suspicion of tuberculosis reactivation, and in addition to direct microscopic evaluation, sputum specimens and materials obtained by fiberoptic bronchoscopy should be cultivated for tuberculosis . Three-four-drug anti-tuberculosis regimens should be given, especially in countries with high drug-resistance rates for eradicating tuberculosis. Respir Med, 2002 Jul, 96(7), 536 - 41 Adenosine deaminase activity in bronchoalveolar lavage in Turkish patients with smear negative pulmonary tuberculosis; Kayacan O et al.; The sputum smear-negative patients have been a diagnostic challenge for health professionals . Adenosine deaminase (ADA) activity has been shown to rise in various body fluids of patients with tuberculosis (Tb) . A prospective clinical trial was conducted to determine the diagnostic value of ADA activity in bronchoalveolar lavage (BAL) in sputum smear-negative subjects highly suggestive for pulmonary Tb . Nineteen (M/F: 15/4, mean age 46.8 +/- 16.5 years) sputum smear-negative patients highly suggestive for pulmonary Tb constituted Group I . Acid fast bacilli (AFB) grew on sputum and/or BAL culture of all subjects in this group . Twenty-nine patients (M/F: 19/10, mean age 55.7 +/- 8.0 years) with non-tuberculous pulmonary diseases constituted Group II . Ten of them had interstitial lung disease, nine lung cancer, five pneumonia and five COPD . Twelve subjects (M/F: 7/5, mean age 48.4 +/- 12.8 years) constituted the controls (Group III) undergoing fiberoptic bronchoscopy (FOB) for various indications and the lungs were found to be normal eventually . Albumin and ADA activity levels were measured in plasma and BAL in all the subjects . LocalADA was calculated . PlasmaADA and BALADA of Group I was significantly higher (P < 0.001) than that of the other groups . LocalADA was also the highest in Group I when compared with the others (P < 0.001) but that of Group II was also higher (P < 0.01) when compared with controls . With a cut-off value derived from the control subjects, sensitivity of BALADA was 100% and specificity 85.3% . Sputum PCR results are available in a couple of days whereas that of BALADA are available in a couple of hours and BALADA costs cheaper than PCR in our country . Therefore, we conclude that BALADA may be a useful, cheaper and faster diagnostic test in sputum smear-negative patients highly suggestive for pulmonary Tb . LocalADA need not be calculated as it is also significantly higher in Group II subjects and thus not as reliable as BALADA. Kekkaku, 2002 Jul, 77(7), 513 - 9 {The study on the duration of treatment in the standard short course chemotherapy containing pyrazinamide}; Yamazaki Y et al.; Based on the results of a questionnaire for the tuberculosis specialists in the whole country, we investigated whether the standard short course chemotherapy containing pyrazinamide (four drugs regimen: HRZE/S) were given for adequate duration . The results of a questionnaire revealed that the duration of treatment was prolonged in 60% of 848 cases due to several reasons . The reasons for the longer duration of treatment were (1) complication of other disease, (2) delay in the improvement on chest X-ray, (3) delay in negative conversion of bacilli, (4) drug resistance, (5) patient's request, and (6) others . According to our own experience in the National Dohoku Hospital for the past four years, the duration of therapy was prolonged in 86% of cases treated with the four drugs regimen, and in 64% of cases with the three drugs regimen (HRE/S) . Four drugs regimen was preferred for severer cases and the three drugs regimen for older patients . The reasons for the prolonged duration of treatment in our hospital were similar to those in the results of a questionnaire in the whole country . We recognized that the treatment was prolonged due to several meaningless reasons such as "no particular reason", "anxiety on relapse" and "patient's request" . In order to decide the adequate duration of treatment, it is needed to know the relapse rate in cases with the short course chemotherapy and its relationship with complications . It is hoped to establish the guideline for tuberculosis treatment including the duration of treatment based on the results of detailed clinical studies. Rinsho Byori, 2002 Jul, 50(7), 649 - 57 {Histopathological diagnosis of opportunistic infection}; Tsutsumi Y; The histopathological diagnosis of infectious diseases has definite and inevitable roles not only in identifying the appropriate treatment for the infected patient but also in protecting society from unnecessary risks of pathogen transmission and from exposure to biohazards . The potential for opportunistic infection has been increasing, in response to the gradual increase of aged and immunocompromised patients . Globalization of the world has promoted importation of non-domestic infectious diseases . This article reviews the following points . These include 1) the modes of defense mechanisms against pathogens (neutrophils vs . T-lymphocytes vs . antibodies), 2) epidemiologic aspects of opportunistic infection, including intrinsic, exogenous and imported routes of infection, 3) histopathological features of bacterial pneumonia, 4) immunohistochemical demonstration of pathogens on routine paraffin sections, using commercially available antibodies or patient sera, 5) opportunistic infection in immunosuppressive states, such as AIDS, hematopoietic stem cell transplantation and other special conditions, and 6) the pathologists' function in the prevention of nosocomial (hospital-acquired) infection with MRSA and tuberculous bacilli . Pathologists must realize the importance of correct and prompt histopathological diagnosis of a wide variety of infectious diseases in both immunocompetent and immunocompromised patients. J Med Microbiol, 2002 Aug, 51(8), 710 - 2 Early identification of Mycobacterium tuberculosis complex in BACTEC cultures by ligase chain reaction; Wang SX et al.; A total of 1431 acid-fast bacilli (AFB) in Bactec culture vials from 1427 patients was differentiated by the Bactec NAP method and tested by the LCx Mycobacterium tuberculosis ligase chain reaction system . In all, 1321 of 1325 M . tuberculosis complex (MTBC) isolates were correctly detected by the LCx assay . All the 106 non-tuberculous mycobacteria (NTM) isolates were negative by the LCx assay . No false MTBC-positive result was obtained from NTM isolates . However, the LCx assay failed to detect four MTBC isolates from one patient . Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 99.7, 100%, 100% and 96.4%, respectively . These data suggest that the LCx system can be used to identify MTBC in AFB-positive Bactec broth cultures when the growth index is > or = 100 . The method gives a 100% PPV and allows a faster turnaround time for MTBC than the NAP test. Ann Diagn Pathol, 2002 Aug, 6(4), 216 - 21 Necrotizing granulomas in B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma; Blanco M et al.; We present three cases of patients with B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia that were retrieved from our files during a period of 11 months and who suddenly developed lymphadenopathy . Clinically, this lymphadenopathy was thought to represent a manifestation of their background disease and, for this reason, no cultures were performed on fresh tissue . However, histologic studies in all cases showed necrotizing granulomas . When results of our special stains were negative, we submitted the specimens for molecular studies, which demonstrated the presence of tuberculous bacilli in two out of three cases . We believe that tuberculosis can present as a sudden lymphadenopathy in immunocompromised people and we would like to raise the awareness among the clinicians and nursing and pathology laboratory staff about the risks of handling these specimens without proper precautions . Also, we emphasize the fact that, in some cases, tuberculous bacilli cases may need molecular studies to be demonstrated . Respiration, 2002, 69(4), 362 - 5 Bronchoesophageal fistulae secondary to tuberculosis; Lado Lado FL et al.; An elderly patient with a bronchoesophageal fistula secondary to tuberculosis and a 3-month history of cough and dysphagia worsening with deglutition was admitted to hospital . Radiological examination and CT of the thorax revealed mediastinal adenopathy . Bronchoscopy, esophagoscopy and esophagraphy confirmed the presence of a bronchoesophageal fistula . Histological examination of the esophagus and bronchial biopsy specimens revealed nonnecrotic granulomas, and the acid-fast bacilli tested positive for Mycobacterium tuberculosis in respiratory secretions . Antituberculous treatment was started after diagnosis of intrathoracic lymph node tuberculosis with bronchoesophageal fistulization . A month and a half after initiating treatment, paroxistic coughing during deglutition persisted . An esophagoscopy was performed, and the orifice was closed with a fibrin tissue . After 9 months of treatment, the patient was asymptomatic and in good health . Respiration, 2002, 69(4), 335 - 8 Transbronchial needle aspiration in the diagnosis of intrathoracic lymphadenopathy; Cetinkaya E et al.; BACKGROUND: Transbronchial needle aspiration (TBNA) of intrathoracic lymph nodes has been shown to be useful in the diagnosis and staging of bronchogenic carcinoma . The usefulness of TBNA has not been widely investigated in benign disease other than sarcoidosis . OBJECTIVES: We investigated the diagnostic value of TBNA in consecutive patients who were referred to Yedikule Hospital of Chest Disease and Thoracic Surgery because of mediastinal and/or hilar adenopathy . METHODS: A total of 29 TBNA procedures were performed in 28 patients who had mediastinal or hilar adenopathy identified by computed tomography of the chest . TBNA of enlarged lymph nodes was performed using a flexible bronchoscope (BF 30T, Olympus) and a 19-gauge needle capable of obtaining core biopsy specimens (MW-319 Mill-Rose Laboratories, Mentor, Ohio, USA) from endobronchial or endotracheal locations . All patients had at least three examinations of sputum smears for acid-fast bacilli prior to bronchoscopy and the results of sputum smears were found to be negative . RESULTS: Adequate lymph node samplings were obtained by TBNA in 23 of 29 (79%) procedures . Diagnostic samples were obtained by TBNA in 20 of 29 (69%) procedures . We were able to make a diagnosis in 20 of 23 (87%) patients in whom adequate lymph node samples were obtained by TBNA . TBNA was the only means of diagnosis in 13 of 28 (46%) patients . The diagnoses provided using TBNA were tuberculosis in all of 10 patients (100%), sarcoidosis in 7 of 8 patients (87.5%), lymphoma in 1 of 2 patients (50%), small cell carcinoma in 1 patient and nonspecific lymphadenitis in 1 patient . No complication was observed and there was only minimal bleeding . CONCLUSIONS: We conclude that TBNA, using 19-gauge histologic needles through a flexible bronchoscope, is a valuable tool in the diagnosis of intrathroracic adenopathy, particularly in patients with tuberculosis and sarcoidosis . TBNA should be considered in the diagnosis of intrathoracic adenopathy before other invasive procedures . Malays J Pathol, 2001 Dec, 23(2), 89 - 92 Negative images in the fine needle aspiration cytologic diagnosis of mycobacterial infections; Iyengar KR et al.; Cytologic diagnosis of mycobacterial infection has conventionally depended on the recognition of granulomatous inflammation with caseous necrosis and the identification of acid-fast bacilli with special stains . Immunocompromised patients however may not mount the expected response . Mycobacteria can be seen as negative images in fine needle aspiration cytologic smears from patients with acquired immunodeficiency syndrome . We report the cytologic findings of lymphnode aspiration from four patients where the mycobacteria were seen in the routine May Grunwald Giemsa-stained smear as unstained rod-shaped structures in the background and within histiocytes . These were confirmed to be acid-fast bacilli with the Ziehl-Neelsen stain. Nihon Kokyuki Gakkai Zasshi, 2002 May, 40(5), 350 - 4 {Superior sensitivity of MGIT method in identification of specimens culture-positive for acid-fast bacilli (AFB) and individuals with positive AFB cultures}; Yonemaru M et al.; To investigate the superiority of the Mycobacteria Growth Indicator Tube (MGIT) over Ogawa medium in the detection of acid-fast bacilli (AFB), we surveyed all specimens for AFB culture using Ogawa medium in 1999 and MGIT in 2000 . The MGIT method increased the culture-positive rate from 23.1% (Ogawa medium) to 34.5% (p < 0.01) . The culture-positive rate in smear-negative specimens was greatly increased (from 9.5% to 16.9%) (p < 0.01) . The culture-negative rate in smear-positive specimens was decreased to 19.5% from 27.7% (p < 0.01) . More individuals with positive M . tuberculosis cultures were found by the MGIT method than with Ogawa medium . Many more individuals with nontuberculous mycobacteria (NTM), notably those with NTM other than M . avium complex, were detected by the MGIT method than with Ogawa medium . The use of the MGIT method in the clinical laboratory will improve sensitivity in the detection of AFB. Chin J Traumatol, 2002 Aug, 5(4), 224 - 7 Changes of neuronal calcium channel following brain damage induced by injection of pertussis bacilli in rats; Chen L et al.; OBJECTIVE: To explore changes of neuronal calcium channel following brain damage induced by injection of pertussis bacilli in rats, and to investigate the relationship between cytosolic free calcium concentration ({Ca(2+)}(i)) in the synaptosome and Ca(2+)-ATPase activities of mitochondria . METHODS: The level of {Ca(2+)}(i) in the synaptosome and Ca(2+)-ATPase activities of mitochondria in the acute brain damage induced by injection of pertussis bacilli (PB) in rat was determined and nimodipine was administrated to show its effects on {Ca(2+)}(i) in the synaptosome and on alteration of Ca(2+)-ATPase activity in the mitochondria . Seventy-three rats were randomly divided into four groups, ie, normal control group (Group A), sham-operation control group (Group B), PB group (Group C) and nimodipine treatment group (Group D) . RESULTS: The level of {Ca(2+)}(i) was significantly increased in the PB-injected cerebral hemisphere in the Group C as compared with that in the Group A and the Group B at 30 minutes after injection of PB . The level of {Ca(2+)}(i) was kept higher in the 4 hours and 24 hours subgroups after the injection in the Group C (P<0.05) . In contrast, the Ca(2+)-ATPase activities were decreased remarkably among all of the subgroups in the Group C . Nimodipine, which was administered after injection of PB, could significantly decrease the {Ca(2+)}(i) and increase the activity of Ca(2+)-ATPase (P<0.05) . CONCLUSIONS: The neuronal calcium channel is opened after injection of PB . There is a negative correlation between activities of Ca(2+)-ATPase and {Ca(2+)}(i) . Nimodipine can reduce brain damage through stimulating the activities of Ca(2+)-ATPase in the mitochondria, and decrease the level of {Ca(2+)}(i) in the synaptosome . Treatment with nimodipine dramatically reduces the effects of brain damage induced by injection of PB. J Vet Diagn Invest, 2002 Jul, 14(4), 326 - 8 Paratuberculosis in a mandrill (Papio sphinx); Zwick LS et al.; A 2.5-year-old captive female mandrill (Papio sphinx) died following a protracted course of intermittent abdominal bloat, diarrhea, and severe weight loss . Necropsy revealed emaciation and marked gastrointestinal distention with gas and ingesta . Histologic evaluation revealed severe diffuse granulomatous enterocolitis and mesenteric lymphadenitis with massive numbers of 1-2-microm acid-fast bacilli within macrophages . Additionally, there was moderate to severe multifocal myocardial and vascular amyloidosis, moderate multifocal pyogranulomatous interstitial pneumonia with no acid-fast bacteria, and moderate multifocal glossal candidiasis . Samples of feces, ileum, and colon were positive for Mycobacterium avium subsp . paratuberculosis by radiometric culture and a polymerase chain reaction-amplified DNA probe specific for the insertion sequence IS900 of this organism. Int J Tuberc Lung Dis, 2002 Aug, 6(8), 728 - 31 Evaluation of a two-reagent cold staining method for detection of acid-fast bacilli; Selvakumar N et al.; SETTING: Tuberculosis Research Centre, Chennai, India . OBJECTIVE: To evaluate a two-reagent cold staining method for detection of acid-fast bacilli in sputum smears . SPUTUM SAMPLES: Two hundred and forty-four samples from pulmonary tuberculosis patients attending Tuberculosis Research Centre were used . METHODS AND DESIGN: Two smears were prepared from each of the samples, of which one was allotted to the two-reagent cold staining method and the other to the Ziehl-Neelsen (Z-N) method . The smears were read blind by a single technician . To ensure correct grading, a senior technician checked all positives and 20% of the negative smears . All the samples were processed by modified Petroff's method for culture of Mycobacterium tuberculosis . RESULTS: The concordance (smear grade one above and one below) between the methods was 90% (kappa value, 0.7) . The performance of the cold method and the Z-N method was similar when their smear results were compared with culture results (cold method vs . culture, kappa = 0.61; ZN method vs . culture, kappa = 0.67) CONCLUSION: The two-reagent cold staining method was found to be as sensitive and specific as the Z-N method . However, large-scale multicentric studies in different climatic conditions need to be conducted to assess its efficacy in the diagnosis of pulmonary tuberculosis. Int J Tuberc Lung Dis, 2002 Aug, 6(8), 693 - 8 The early bactericidal activity of streptomycin; Donald PR et al.; SETTING: Patients with sputum smear-positive, newly diagnosed pulmonary tuberculosis studied at Tygerburg Hospital, Cape Town, for their early response to streptomycin (SM) . OBJECTIVE: To determine the standard early bactericidal activity (EBA), namely the fall in viable counts of tubercle bacilli in 16-hour sputum collections during the first 2 days of treatment with SM . DESIGN: Patients were randomised to logarithmically spaced daily doses of 7.5, 15 or 30 mg/kg SM . A comparison by standard biological assay methods was then made with previous estimations of the EBA of paromomycin in doses of 7.5 and 15 mg/kg . RESULTS: An EBA of 0.133 obtained with 30 mg/kg SM differed significantly from zero (P = 0.0009), while the EBAs of 0.043 with 15 mg/kg and -0.025 with 7.5 mg/kg did not so differ . A linear regression equation of EBA = -0.2587 + 0.2627 log10 dose was obtained with significant slope (P = 0.007) . Paromomycin was estimated to be 1.745 more potent than SM with wide 95% confidence limits (0.6-28.6), indicating that it cannot be considered more potent than SM . CONCLUSIONS: The low EBAs show that SM has low, dose-related, bactericidal activity in cavities, consistent with results from clinical trials . If streptomycin-resistant bacilli are present, paromomycin is probably the aminoglycoside of choice. Pediatr Infect Dis J, 2002 May, 21(5), 446 - 8 The natural course of nonsuppurative Calmette-Guérin bacillus lymphadenitis; Singla A et al.; In a tertiary level hospital in North India, we studied the outcome of infants with nonsuppurative Calmette-Guerin bacillus (BCG) lymphadenitis managed conservatively . Twenty-three infants with nonsuppurative BCG lymphadenitis diagnosed on the basis of clinical presentation, evidence of granulomatous inflammation and demonstration of acid fast bacilli in the aspirated material were followed prospectively without being offered specific antitubercular drug therapy . Twenty patients were available for final analysis; three were lost to follow-up . Seventeen (85%) had spontaneous regression of BCG lymphadenitis without progression and drainage . The mean time to resolution was 9.1 months . Three (15%) patients developed suppuration and drainage, but even these children had uneventful healing on conservative management only . Nonsuppurative BCG lymphadenitis follows a benign course in most individuals . Most of the cases regress spontaneously with conservative management. J Clin Microbiol, 2002 Aug, 40(8), 3041 - 3 Inefficiency of 0.3% carbol fuchsin in ziehl-neelsen staining for detecting acid-fast bacilli; Selvakumar N et al.; We compared the sensitivity and specificity of a modified Ziehl-Neelsen (modified-ZN) staining method for acid-fast bacilli (AFB) with that of the standard Ziehl-Neelsen (standard-ZN) staining method, using culture results with Mycobacterium tuberculosis as the "gold standard." The sensitivity (72%; 101 of 140) of the modified-ZN staining method, which uses 0.3% carbol fuchsin, was significantly lower than that of the standard-ZN staining method (84%; 117 of 140); the modified-ZN method missed 21% of cases detected by the standard-ZN method and 11% more of culture-positive samples than the standard-ZN method . The World Health Organization recommendation of 0.3% carbol fuchsin in the ZN method for staining AFB needs to be reconsidered. J Clin Microbiol, 2002 Aug, 40(8), 3017 - 20 Evaluation of the phenol ammonium sulfate sedimentation smear microscopy method for diagnosis of pulmonary tuberculosis; Selvakumar N et al.; We compared the sensitivity and specificity of the phenol ammonium sulfate (PhAS) sediment smear microscopy method for detection of acid-fast bacilli with those of direct smear microscopy, using culture results for Mycobacterium tuberculosis as the "gold standard." The sensitivities of the PhAS and direct smear methods were 85% (465 of 547) and 83% (454 of 547), respectively, and the specificity of each method was 97% . The PhAS method was better accepted by the laboratory technicians and safer but necessitates an overnight sedimentation, which delays reporting of results until 1 day after sputum collection. J Clin Microbiol, 2002 Aug, 40(8), 2791 - 4 Utility of gram staining for evaluation of the quality of cystic fibrosis sputum samples; Nair B et al.; The microscopic examination of Gram-stained sputum specimens is very helpful in the evaluation of patients with community-acquired pneumonia and has also been recommended for use in cystic fibrosis (CF) patients . This study was undertaken to evaluate that recommendation . One hundred one sputum samples from CF patients were cultured for gram-negative bacilli and examined by Gram staining for both sputum adequacy (using the quality {Q} score) and bacterial morphology . Subjective evaluation of adequacy was also performed and categorized . Based on Q score evaluation, 41% of the samples would have been rejected despite a subjective appearance of purulence . Only three of these rejected samples were culture negative for gram-negative CF pathogens . Correlation between culture results and quantitative Gram stain examination was also poor . These data suggest that subjective evaluation combined with comprehensive bacteriology is superior to Gram staining in identifying pathogens in CF sputum. J Cell Biol, 2002 Aug 5, 158(3), 421 - 6 Epub 2002 Jul 29. Mycobacterium and the coat of many lipids; Russell DG et al.; Pathogenic Mycobacterium reside inside vacuoles in their host macrophages . These vacuoles fail to fuse with lysosomes yet interact with early endosomes . Glycoconjugates released by the intracellular bacilli traffic through the host cell and are released through exocytosis . These molecules represent both antigens for immune recognition and modulators of immune function . The molecules play key roles in the induction and maintenance of the granuloma, a tissue response that limits bacterial spread yet ensures persistence of the infection. Conn Med, 2002 Jun, 66(6), 323 - 30 Emerging significance of Mycobacterium avium-complex infection in an inner-city hospital; Martin DS et al.; This study ascertains the incidence, trends, and clinical significance of acid-fast bacilli (AFB) isolates at Bridgeport Hospital from January 1, 1995 through September 30, 1999 . One hundred twenty-two isolates of nine different types of mycobacteria and nocardia were cultured from 117 patients . About 30% were HIV-positive, 34% were HIV-negative, and the HIV status of 36% was unknown . The predominant isolates were Mycobacterium avium-complex (MAC) (60%) and Mycobacterium tuberculosis (Mtb) (21.3%) . Pulmonary sources accounted for 74% of the isolates . The incidence of Mtb remained stable at 2.6-4.1 cases/100,000 total patient discharges/year . In contrast the incidence of MAC soared from a baseline rate of 1.6/100,000 total patient discharges/year in 1995/96 to 19.5/100,000 total patient discharges/year in 1999 . The increase was consistent across pulmonary and nonpulmonary sources, HIV status, and across disease likelihood . Seventy-three percent of MAC isolates were associated with definite or probable disease . Physicians need to consider the increased MAC incidence in the choice of empiric therapy for AFB-positive patients. Kekkaku, 2002 Jun, 77(6), 443 - 8 {A study on far-advanced cavitary pulmonary tuberculosis cases}; Sasaki Y et al.; In cases with far-advanced cavitary pulmonary tuberculosis, the most serious lesions according to the chest X-ray classification by the Japanese Society of Tuberculosis (b I 3), their prognosis is believed to be poor due to their emaciated general conditions, and a retrospective clinical study was made on these cases admitted to our hospital . The subjects consisted of 95 cases, and among them 87 were male and 8 were female, and their mean age was 49.5 +/- 13.0 years . Eighty four cases were detected by symptomatic visits to clinics, 10 cases during their treatment for other diseases, and 1 case was discovered accidentally . Sputum examination for acid fast bacilli was all smear positive . As to their social background, the majority were occupied by socially vulnerable groups; 31 cases (32.6%) were jobless on admission, 24 cases (25.3%) were day laborers, and 25 cases (26.3%) were receiving poor relief . Regarding their general condition on admission, 40 cases were very serious and they could not stand by themselves, and their nutritional conditions were poor, and 19 cases (20%) died during hospitalization . All of them were male, and they were found by symptomatic visit to clinics . The period from hospital admission to death was short, the average was 35.0 +/- 39.8 days, and the median was 11.0 days . Among 84 patients detected by symptomatic visit, the patient's delay was 5.5 +/- 5.0 months, while the doctor's delay was 0.3 +/- 0.9 months . Major cause of late detection at advanced stage of these cases was patient's delay which caused poor prognosis of these cases, and various measures to shorten the delay in case-detection must be taken. Pneumonol Alergol Pol, 2001, 69(11-12), 673 - 6 {Tuberculosis of the bone}; Panek B et al.; We describe a 75 year old patient treated because of arthrosis and recurrent pneumonia for a year . In hospital acid-fast bacilli were found in sputum . Chest x-ray revealed massive inflammatory and fibrous lesions . Pelvis x-ray revealed lesions estimated as tuberculosis . Tuberculosis of lungs and pelvis bones was recognised . After 3 months of antituberculous treatment patient was referred to outpatient department for further therapy. Pneumonol Alergol Pol, 2001, 69(11-12), 669 - 72 {Tuberculosis of ear and cutis}; Panek B et al.; We describe a 26 year old woman treated for near a year because of deafness, purulent otitis, cough and purulent skin lesions . She was treated by otolaryngologist . Sputum examination for acid fast bacilli and chest x-ray were not done a that time . In hospital chest x-ray revealed a cava in left lung and tuberculous bacilli were found in sputum and in content from ear . Tuberculin test was positive . Tuberculosis of lung, skin and cor was recognized . After 4 months of initial treatment patient was referred to outpatient department for further therapy. Vet Pathol, 2002 Jul, 39(4), 501 - 4 Bronchitis and bronchiolitis in a cat with cilia-associated respiratory bacillus-like organisms; Ramos-Vara JA et al.; A 10-year-old male domestic shorthair cat died during anesthesia . Grossly, the lungs had multiple nodules corresponding to inflamed airways (bronchitis and bronchiolitis) . Microscopically, cuffs and nodular aggregates of lymphocytes and plasma cells surrounded airways . Peribronchiolar fibrosis was also common . Globule leukocytes infiltrated the respiratory epithelium of noninflamed or mildly inflamed bronchi . Argyrophilic and filamentous organisms, consistent with cilia-associated respiratory bacillus-like organisms (CLO), were intermixed with cilia of respiratory epithelium . Ultrastructurally, CLO were longer and thinner than cilia and had a distinct trilaminar membrane, central electron-lucent areas, and no specialized external structures . Silver stained lung sections from 18 additional feline airways revealed similar bacilli in 2/9 normal lungs, 1/7 lungs with bronchitis and bronchiolitis, and 1/2 lungs with pneumonia . The significance of CLO in the pulmonary lesions was not determined. Antimicrob Agents Chemother, 2002 Aug, 46(8), 2533 - 9 Simple fibroblast-based assay for screening of new antimicrobial drugs against Mycobacterium tuberculosis; Takii T et al.; In this study, we propose a simple and reproducible host-cell-based assay for the screening of antimycobacterial drugs that is suitable for drug discovery . The method evaluates both antimycobacterial activity of the drugs and their cytotoxicity to host cells . The basis of this simple fibroblast-based assay (SFA) is that cells of human lung fibroblast cell line MRC-5, which are highly sensitive to mycobacterial cytotoxicity, are killed by virulent Mycobacterium tuberculosis strain H(37)Rv bacilli in response to the viability of bacilli . Clinically used antimycobacterial drugs inhibited the mycobacterial cytotoxicity to MRC-5 cells in a dose-dependent manner . MICs of isoniazid, streptomycin, rifampin, and ethambutol determined by this SFA (0.428, 1.816, 0.013, and 3.465 microg/ml, respectively) were within 1 log of MICs determined by the broth dilution test (BDT) using Middlebrook 7H9 medium . The MIC of pyrazinamide, which exhibits bactericidal activity only at a high dose by BDT (1,231 microg/ml at pH 6.6 and 492 microg/ml at pH 5.8), was 3.847 microg/ml in the modified method of SFA . On the other hand, sodium azide, a toxic agent for both mammalian cells and bacteria, exhibited cytotoxicity to fibroblasts at a dose lower than that required to inhibit mycobacterial growth . Thus, this fibroblast-based method enabled us to evaluate both antibacterial activity of drugs and their cytotoxicity to human cells within a short period of time. J Am Vet Med Assoc, 2002 Jul 15, 221(2), 258 - 62, 239-40 Acute necrotizing dermatitis and septicemia after application of a d-limonene-based insecticidal shampoo in a cat; Lee JA et al.; A 2-year-old female spayed domestic shorthair cat was examined because of lethargy, inappetance, vocalization, and abnormal aggressive behavior of 1 day's duration . The cat had been groomed the previous day with a d-limonene-based insecticidal shampoo . Skin lesions consisted of coalescing erythematous patches . Despite supportive care, the cat's condition deteriorated . Dermatohistopathologic changes included multifocal areas of acute coagulative epidermal necrosis . The dermis was infiltrated by a dense population of bacilli . d-Limonene toxicosis has been rarely described in dogs and cats . Toxic effects such as hypersalivation, ataxia, shivering, hypothermia, scrotal irritation, hypotension, and erythema multiforme major have been reported . Treatment for septicemia and disseminated intravascular coagulation, along with intensive supportive care, may be necessary. Southeast Asian J Trop Med Public Health, 2002 Mar, 33(1), 147 - 50 Clinical aspects of tonsillar tuberculosis; Srirompotong S et al.; A clinical analysis of 6 patients with pathologically confirmed tonsillar tuberculosis was carried out retrospectively . The subjects comprised three men and three women, ranging in age from 20 to 74 years . All of the patients presented with a sore throat and 5 had lymphadenopathy . Ulcerations, masses and white patches characterized the tonsillar lesions; the pathological findings included caseous granuloma with positive acid-fast bacilli (AFB) in 5 patients and chronic granulomatous inflammation with negative AFB in one patient . Four of the six patients had pulmonary tuberculosis . The three patients who received complete treatment responded well . The presenting symptoms and abnormal tonsillar findings associated with tonsillar tuberculosis are similar to those of malignant tumors and therefore it is difficult to differentiate the two pathologies; moreover, tonsillar tuberculosis often occurs with pulmonary tuberculosis and AIDS and therefore, a chest X-ray and HIV-screening are recommended for all patients with tonsillar tuberculosis. Infect Immun, 2002 Aug, 70(8), 4591 - 9 Tumor necrosis factor alpha stimulates killing of Mycobacterium tuberculosis by human neutrophils; Kisich KO et al.; The ability of human neutrophils to aid in defense against pulmonary infection with Mycobacterium tuberculosis is controversial . In this study, we have shown that neutrophils respond to and phagocytose M . tuberculosis in human lesions . Neutrophils from healthy individuals were able to kill significant fractions of an inoculum of M . tuberculosis within 1 h of phagocytosis, and this ability was enhanced by tumor necrosis factor alpha but not by gamma interferon . The mycobactericidal mechanism was nonoxidative, as inhibitors of reactive oxygen or reactive nitrogen intermediates did not interfere with killing . However, the mycobactericidal mechanism was associated with increased exposure of intracellular M . tuberculosis to neutrophil defensins . In vitro, human neutrophil peptides 1 to 3 were not able to kill the bacilli even at much higher levels . These studies support the concept that human neutrophils are directly involved in defense against infection with M . tuberculosis. FEMS Microbiol Lett, 2002 Jul 2, 212(2), 145 - 9 Demonstration of spread by Mycobacterium tuberculosis bacilli in A549 epithelial cell monolayers; Castro-Garza J et al.; We developed an in vitro tissue-culture model to analyze the process involved in mycobacterial spread through lung epithelial cell monolayers . A549 cells were infected with low numbers of viable Mycobacterium tuberculosis bacilli expressing the gfp gene . Subsequent addition of a soft agarose overlay prevented the dispersal of the bacilli from the initial points of attachment . By fluorescence microscopy the bacteria were observed to infect and grow within the primary target cells; this was followed by lysis of the infected cells and subsequent infection of adjacent cells . This process repeated itself until an area of clearing (plaque formation) was observed . The addition of amikacin after initial infection did not prevent intracellular growth; however, subsequent plaque formation was not observed . Plaque formation was also observed after infection with Mycobacterium bovis BCG bacilli, but the plaques were smaller than those formed after infection with M . tuberculosis . These observations reinforce the possibility that cell-to-cell spreading of M . tuberculosis bacilli, particularly early in the course of infection within lung macrophages, pneumocytes, and other cells, may be an important component in the infectious process. Intensive Care Med, 2002 Jun, 28(6), 763 - 7 Epub 2002 Apr 20. Ventilator-associated pneumonia and upper airway colonisation with Gram negative bacilli: the role of stress ulcer prophylaxis in children; Lopriore E et al.; OBJECTIVE: To assess the risk of ventilator-associated pneumonia (VAP) and the incidence of upper airway colonisation related to the use of stress ulcer prophylaxis in critically ill children . DESIGN: Retrospective study . SETTING: Paediatric intensive care unit (PICU) of a tertiary care centre . PATIENTS: All children who were mechanically ventilated for more than 48 h . INTERVENTIONS: None . RESULTS: A total of 54 patients were given ranitidine, 53 patients were given sucralfate and 48 patients were given no stress ulcer prophylaxis . Thirteen (8.4%) patients developed VAP: 6 (11.1%) patients in the ranitidine group, 4 (7.5%) in the sucralfate group and 3 (6.2%) in the group without prophylaxis . The rate of upper airway colonisation with Gram negative bacilli was 25.9% (14/54) in the ranitidine group, 22.6% (12/53) in the sucralfate group and 37.5% (18/48) in the group without prophylaxis . The differences among the groups were not significant . CONCLUSIONS: In contrast to findings in adults, we found that, in children, sucralfate does not decrease the incidence of VAP or the incidence of upper airway colonisation with Gram negative bacilli as compared to ranitidine or no stress ulcer prophylaxis . However, the small sample size and study design substantially limit our conclusions. Microbes Infect, 2002 Jul, 4(9), 945 - 53 Mycobacterial lipoarabinomannans: modulators of dendritic cell function and the apoptotic response; Nigou J et al.; The molecular bases of Mycobacterium tuberculosis pathogenicity remain unclear . We report here how M . tuberculosis mannosylated lipoarabinomannans contribute to the survival of bacilli in the human reservoir by (i) inhibiting IL-12 production by macrophages and dendritic cells and (ii) modulating M . tuberculosis-induced macrophage apoptosis. Int J Tuberc Lung Dis, 2002 Jul, 6(7), 592 - 8 Useful clues to the presence of smear-negative pulmonary tuberculosis in a West African city; Bah B et al.; OBJECTIVE: Tuberculosis suspects with negative sputum smears for acid-fast bacilli (AFB) may have either pulmonary tuberculosis (PTB) or some other pulmonary disease (non-PTB) . The aim of this study was to improve the differentiation between PTB and non-PTB . DESIGN: We enrolled 396 tuberculosis suspects 15 years of age or older who had cough of 21 days or longer and three negative AFB smears . Non-PTB was diagnosed by clinical and radiographic responses to amoxicillin; smear-negative PTB was diagnosed by positive culture for Mycobacterium tuberculosis or response to antituberculosis chemotherapy . RESULTS: Multivariate analysis, without X-ray variables, of 79 patients with a final diagnosis of non-PTB and 110 patients with smear-negative PTB indicated that age less than 37 years, family contact with TB, never having been married, loss of weight, lack of expectoration, human immunodeficiency virus (HIV) seropositivity, and tuberculin reactivity were significantly associated with PTB . When the initial X-ray findings were included, age younger than 37 years, lack of expectoration, HIV seropositivity, and tuberculin reactivity remained in the model, and cavitation and patchy densities were significantly associated . CONCLUSION: The response to 10 days of amoxicillin and certain demographic, clinical and radiographic characteristics are useful in separating non-PTB from PTB in tuberculosis suspects with negative AFB smears. Int J Tuberc Lung Dis, 2002 Jul, 6(7), 580 - 4 A rapid survey to determine the prevalence of smear-positive tuberculosis in Addis Ababa; Demissie M et al.; SETTING: Four kebeles (lowest administrative units) in a typical district of Addis Ababa, Ethiopia . OBJECTIVE: To determine the prevalence of smear-positive pulmonary tuberculosis (TB) in an adult population by using a screening questionnaire and sputum examination . DESIGN: A house-to-house visit was conducted . All those 14 years of age and above were screened for the presence of symptoms . Three sputum samples were collected from persons who had symptoms for acid-fast bacilli (AFB) examination . RESULTS: A total of 12,149 individuals were screened, of whom 173 had symptoms suggestive of TB . Twenty-three were positive for AFB (189/100,000, 95% CI 112-267) . No association was observed between smear positivity and socio-demographic factors . Only two of the 23 patients were on anti-tuberculosis treatment (8.7%, 95% CI 1.5-29.5) . CONCLUSION: This simple and cost-effective method provides a fairly realistic estimate of the prevalence of TB . Thus with further development of the method it can be used to monitor the progress of TB programmes in resource-poor settings. J Infect, 2002 May, 44(4), 244 - 51 Molecular analysis of clinical isolates of Mycobacterium tuberculosis collected from patients with persistent disease in the Khartoum region of Sudan; Sharaf-Eldin GS et al.; SETTING: Patients with positive smears for acid-fast bacilli were enrolled at tuberculosis (TB) clinics in the Khartoum region of Sudan . OBJECTIVE: To identify the presence of drug resistant genotypes in M . tuberculosis isolates which are difficult to treat.Methods: Genus specific PCR-SSCP was performed to confirm the presence of M . tuberculosis in clinical isolates . Genotypic drug resistance testing was performed by mutation analysis and spoligotyping was used to monitor transmission and to identify epidemic strains . RESULTS: Fifty (48%) of the original 105 samples were classified as M . tuberculosis . Four (4%) of the samples were typed as mycobacteria other than TB, while the remaining (n =50) samples were refractory to further molecular analysis . The fifty amplifiable M . tuberculosis samples were used for subsequent mutation analysis and typing . Mutations were identified in the genes conferring resistance to INH (kat G, 12%), RIF (rpoB, 8%), SM (r psL and rrs, 30%) and EMB (embB, 4%) . Two of the samples (4%) had mutations in genes associated to both INH and RIF and can be classified as MDR-TB . Thirty-three percent (13/39) of the persistant tuberculosis cases (5/18 treatment failure; 5/14 relapse; 3/7 defaulter) had mutations accounting for drug resistance . A total of 27 different spoligotypes were identified from 49/50 samples . Twenty-nine (59%) of the isolates were grouped into one of seven clusters, while 20 (41%) showed unique patterns . One patient was infected with M . bovis . CONCLUSION: This is the first molecular approach to characterize clinical isolates of M . tuberculosis from Sudan . The results show that drug resistance is indeed a serious problem and it may compliment the efforts of the National Tuberculosis Programme to improve strategies to control this disease . Hist Sci Med, 2002 Jan-Mar, 36(1), 75 - 81 {Armauer Hansen (1841-1912), portrait of a Nordic pioneer}; Hansen W et al.; Desending from a Danish family, Gerhard Henrik Armauer Hansen was born in Bergan, Norway, on 29 July, 1841 . Graduated in medicine in 1866 from the University at Christiana (the former name of Oslo), he started his medical career as an assistant physician at the National Hospital of Oslo for one year, working afterwards as a medical officer for a fishing company outside the Arctic Circle . Taking not well his routine job, he soon returned to Bergen where he began his work on a disease known as leprosy at the age of 26 and as an assistant of D.C . Danielssen at the Lungegaarden Hospital . There he engaged in research and investigations on the nature of the disease . Studying the various types of leprosy (skin, nerve and visceral lesions), he was awarded, one year after beginning his work, the gold metal of the University for his first publication on the disease . While Danielssen leaned toward heredity as a dominant factor in leprosy, Hansen's conviction was that the disease must have an infectious causal agent . In about 1871, Hansen began to observe tiny little rods in tissue specimens and considered they could be the ethiologic agent of leprosy, the more he found these rods in all the infiltrated nodular lesions in his patients . Finally, he proposed on February 28, 1873, that the rods were bacilli, responsible of leprosy . Promoted to the rank of Chief of the Leprosy Service in 1875, he held his job for 37 years; Hansen's entire adult life was spent at work in leprosy . He edited the journal <<Lepra>> . Hansen was also an eminent zoologist engaged in studies involving mollusks and worms; Since 1874, he was president of the Bergen Museum of Natural History . Armauer Hansen died on February 12, 1912, and the funeral ceremonies took place in the Museum of Bergen where his ashes are still kept. Ann Chir, 2002 May, 127(5), 385 - 7 {Tuberculosis of the thyroid . Diagnosis and treatment}; el Malki HO et al.; Thyroid tuberculosis is rare . We present the case of a 25 year-old woman with tuberculosis of the thyroid . Although seldom observed, tuberculosis should be considered in the differential diagnosis of nodular lesions of the thyroid . Diagnosis is made by histological examination and demonstration of the tubercle bacilli from biopsy or aspiration specimen . The efficacy of fine-needle aspiration cytology in diagnosis of tuberculosis of the thyroid is proved . Administration of antituberculous drugs is considered as the treatment of choice . Abscess drainage is sufficient . In rare cases surgery is necessary . The prognosis is good. Vet J, 2002 Mar, 163(2), 115 - 27 Mycobacterium bovis infection and tuberculosis in cattle; Pollock JM et al.; This review considers the possible events that can occur when cattle are exposed to Mycobacterium bovis and, where appropriate, draws on principles accepted for tuberculosis infection in humans and laboratory animal models . Consideration is given to the many complex factors which influence the outcome of challenge with tubercle bacilli . These include features inherent to the mycobacterium, the host and the environment . It is apparent that clinical disease probably occurs only in a relatively small, but undetermined, proportion of cattle that are exposed to Al . bovis . The majority of animals may clear infection or control the bacilli, possibly in a condition of latency . It is concluded that a better understanding of the dynamics of the events following M . bovis exposure and subsequent infection in cattle would be of significant benefit in developing new tools appropriate for disease control and to designing optimal approaches for their application. Clin Chest Med, 2002 Jun, 23(2), 513 - 9, xi-xii Whipple's disease: a granulomatous masquerader; James DG et al.; Whipple's disease is a multisystemic infection that affects middle-aged white men . It typically presents with fever, polyarthritis, diarrhea, steatorrhea, and weight loss . Many other systems can be involved, however, including the central nervous system, heart, lymphatics, lungs, bone marrow, and skin . Recent work has demonstrated the causative organism to be a complex bacteria, Tropheryma whipplei . The diagnosis is established most securely by periodic acid-Schiff staining of foamy monocyte-macrophages in biopsy tissue and body fluids, by electron microscopy, which reveals bacilli within membrane-bound vesicles, and by molecular amplification techniques using polymerase chain reaction of tissues and body fluids . The differential diagnosis includes chronic multisystemic infections and granulomatous disorders, because Whipple's disease is a fascinating blend of both . The condition can resemble sarcoidosis and mycobacterial disease and fungal, protozoal, and bacillary infections . Earlier diagnosis leads to earlier treatment and hopefully the prevention of chronic disabling complications and needless mortality from this once uniformly fatal condition. Am J Clin Pathol, 2002 May, 117(5), 771 - 5 Uterine granulomas: clinical and pathologic features; Almoujahed MO et al.; We retrospectively studied the clinical and pathologic features of uterine granulomas over a 10-year period . Granulomas were detected in 30 women, 22 to 81 years old, in the cervix (n = 12/1,090 cervical specimens; 1.1%) or uterine corpus (n = 18/12,000 uterine specimens; 0.15%) . They were discovered during evaluation of abnormal bleeding, cytologic specimens, or other gynecologic conditions . None of the patients had constitutional symptoms . These granulomas were often focal (n = 25 {83%}), exhibiting features of foreign body-type (n = 17 {68%}); or they were diffuse (n = 5 {17%}), all with negative acid-fast bacilli or fungal stains and sometimes necrotizing (2 {40%}) . Focal granulomas were highly associated with a preceding biopsy or surgery (22/25 vs 14/53 age-matched control subjects) . Follow-up of 28 patients (median, 16 months) showed that 27 remained healthy; only 1 patient developed generalized lesions consistent with sarcoidosis 16 months later Uterine granulomas are rare . They are eitherfocal, related to previous biopsy or surgery, or diffuse, usually representing local reaction without an obvious cause . Association with infection or systemic granulomatous disorders is uncommon. Rev Med Chir Soc Med Nat Iasi, 2000 Oct-Dec, 104(4), 117 - 22 {Bactericidal activity of Trovafloxacin and Moxifloxacin against Gram-negative anaerobic bacilli}; Bosnea D et al.; Anaerobes are often involved in human pathology, including oral infections . The therapy of anaerobic infection requires certain antibiotics such as: metronidazole, tetracycline or amoxicillin . But the incidence of resistant strains among anaerobes is continuously increasing and it is necessary to find some new agents effective against these bacteria . The aim of our study was to establish the bactericidal activity of two new quinolones against 14 strains of gram-negative anaerobic bacilli . The MIC of tested strains was first detected and then time-kill kinetics was determined by using Miles and Misra methodology . Ciprofloxacin was used as standard-quinolone . The results show that trovafloxacin and moxifloxacin have good activity against anaerobes, better than that of ciprofloxacin . Bactericidal curves suggest a rapid action of moxifloxacin (within the first 4 hours), but a prolonged cidal activity for trovafloxacin (24 hours) . For both agents, the antimicrobial effect is concentration-dependent . As previous studies suggest, the new quinolones have good activity against both aerobic and anaerobic bacteria so they are useful in the treatment of mixed infections (common feature of anaerobic infections). Diagn Microbiol Infect Dis, 2002 Jun, 43(2), 113 - 8 Diagnosis of pelvic actinomycosis by 16S ribosomal RNA gene sequencing and its clinical significance; Woo PC et al.; Traditional ways of identification of anaerobic Gram-positive non-sporulating bacilli by isolation of the organism and studying it phenotypically by elucidation of its morphologic and biochemical characteristics and metabolic end products are associated with a need for special equipment and expertise, and strains that are "unidentified" because of ambiguous biochemical profiles . In this study, an anaerobic Gram-positive non-sporulating bacterium was isolated from the intrauterine contraceptive device of a 36-year old woman with pyosalpinx . The Vitek system (ANI) showed that it was 99% Propionibacterium granulosum; whereas the API system (20A) showed that it was 78% Actinomyces meyeri/odontolyticus . The 16S ribosomal RNA gene of the strain was amplified and sequenced . There was 0 base difference between the isolate and A . odontolyticus (GenBank Accession no . AJ234047), indicating the isolate most closely resembled a strain of A . odontolyticus . Identification of the organism in this study was important because the duration of antibiotic therapy would be entirely different . In the present case, identification of the bacterium as A . odontolyticus inferred that the patient suffered from an intermediate form of pelvic actinomycosis . A prolonged course of antibiotics would be more desirable, as the relapse rate of actinomycosis after a short course of antibiotics is high. Nephrologie, 2002, 23(3), 135 - 40 {Tuberculosis in hemodialysis patients in Tunisia}; Hassine E et al.; BACKGROUND: Because of the immunity depression, patients with chronic renal failure undergoing haemodialysis are at increased risk for developing infections, Mycobacterium tuberculosis (MTb) in particular . OBJECTIVE: To evaluate, in a prospective longitudinal study over 36 months period, the frequency of Tb among these patients and underline the diagnostic difficulties . PATIENTS AND METHODS: Sixty dialysis patients were interested . The Tb assessment comprised: a questionnaire, a meticulous clinical examination, a chest X-ray, a tuberculin skin testing, as well as MT bacilli screening in biological fluids . RESULTS: Tb was seen in six among dialysis patients(10%), this rate represents 15 times the general population tuberculosis incidence in our country (23/100,000) . Tb has occurred early compared to the beginning of the haemodialysis . The Tb localizations were: 4 cases of extra-pulmonary tuberculosis (3 peritoneal and one ganglionic) and only 2 cases of pleuro-pulmonary localization . The positive diagnosis represents a real problem: no bacteriological confirmation in all patients and only in one, the histological diagnosis was obtained . CONCLUSION: There was a high rate of tuberculosis in our study . The prognosis appears to be closely related to therapeutic precocity, thus specific chemotherapy started sometimes without diagnostic confirmation. Microb Ecol, 2002 Aug, 44(2), 144 - 53 Epub 2002 Jun 28. Distribution and characterization of Bacillus thuringiensis on the phylloplane of species of piper (Piperaceae) in three altitudinal levels; Maduell P et al.; Bacillus thuringiensis is found naturally on the phylloplane . In this study 35 samples from 13 species of the genus Piper (Piperaceae) were collected from three altitudinal levels located between 1800 and 2900 m above sea level in the Colombian Andean forest of Central Cordillera . Two hundred and fifty-six isolates of B . thuringiensis were obtained from 74% of the samples studied . B . thuringiensis index (number of isolates of B . thuringiensis/number of isolates of sporulated bacilli) was 0.2 . The isolates were characterized by crystal morphology, the presence of cry genes by PCR, and toxicity against insects . Fifty-five percent of the isolates found presented bipyramidal-crystal morphology, and 42% had round-crystal morphology . Seventy percent of the isolates amplified cry1 {cry one} genes (generally toxic to lepidopterans); 41.4% amplified cry4 and/or cry11 {cry eleven} genes (generally toxic to dipterans), and none of the isolates amplified cry3 genes (generally toxic to coleopterans) . The most abundant genotype of cry genes (54.7% of the total) was cry1Aa, cry1Ab, cry1Ac, cry1Ad, and cry1B . From the total isolates found, 7.8% presented both cry1 and cry11 genes, and five isolates (2.0%) harbored cry1, cry4, and cry11 genes; all these isolates were toxic to Culex quinquefasciatus (Diptera) but not to Spodoptera frugiperda (Lepidoptera) . To our knowledge, these genotypes have not been previously reported . Overall, almost 60% of the isolates were toxic to S . frugiperda, and a little more than 40% of the isolates were toxic to C . quinquefasciatus . The populations of viable vegetative cells and spores per unit area were estimated and studied statistically . No significant differences in the number of B . thuringiensis isolates per cm2 of leaf among the three altitudinal levels were found, nor were they found among the different Piper species evaluated . This study increases the knowledge of the ecology of B . thuringiensis. Protein Eng, 2002 Jun, 15(6), 503 - 12 Proteomics analysis of carbon-starved Mycobacterium smegmatis: induction of Dps-like protein; Gupta S et al.; Mycobacterium tuberculosis is a globally successful pathogen, infecting more than one third of total world's population . These bacteria have the remarkable ability to persist in the host for long periods of time unrecognized by the immune system and then to re-emerge later in life causing the disease . The physiology of such persistent or dormant bacilli is not very well characterized . Some evidence suggests that the dormant bacilli survive in a nutrient-deprived state that is similar to the stationary phase of the bacteria with respect to gene expression and physiology . Under this assumption we have studied the survival of Mycobacterium smegmatis in carbon starvation conditions as a model for mycobacterial persistence . M.smegmatis, being a fast-growing strain, serves as a good model to study starvation responses . Using the two-dimensional electrophoresis-based proteomics approach, we identified a protein which was found to be expressed preferentially under starvation conditions . This protein is homologous to a family of proteins called Dps (DNA binding Protein from Starved cells) that are known to protect DNA under various kinds of environmental stresses and its existence has, so far, not been reported in mycobacteria . Upon expression and purification of this protein, we observed that it has non-specific DNA-binding ability . Formation of a cage-like dodecamer structure is a characteristic feature of Dps . Using comparative modelling we were able to show that Dps from M.smegmatis could form a dodecamer structure similar to the crystal structure of Dps from Escherichia coli. Hunan Yi Ke Da Xue Xue Bao, 1999, 24(6), 510 - 2 {Effect of pertussis bacilli on the release of excitatory amino acids in brain slice of rats}; Yin F et al.; OBJECTIVE: To investigate the effect of pertussis bacilli on the release of excitatory amino acids (EAAs) in rat-brain slice and to know whether MK-801(dizocipine) protects brain tissue from excitotoxicity . METHODS: SD rats were randomly divided into 3 groups: 1 . Normal slice cultured group(NC); 2 . 10% pertussis bacilli(PB) slice cultured group(PBC); 3 . 10% PB slice cultured group after pretreatment with MK-801 . The release of EAAs from brain slices was measured by high performance liquid chromatography . RESULTS: The concentrations of glutamate(Glu 29.53 +/- 8.00), aspartate(Asp 23.74 +/- 5.79) and LDH(38.03 +/- 8.45) were significantly higher in PBC group than those(Glu 16.46 +/- 4.00, Asp 15.27 +/- 5.31, LDH 23.10 +/- 5.11) in MPBC group and (Glu 16.09 +/- 3.74, Asp 11.47 +/- 2.51, LDH 25.82 +/- 4.50) NC group . CONCLUSION: Pertussis bacilli may elicit a large increase of extracellular EAAs and LDH in vitro, while MK-801 protects brain tissue from excitotoxicity. J Immunol, 2002 Jul 1, 169(1), 323 - 9 Contribution of IL-18 to Th1 response and host defense against infection by Mycobacterium tuberculosis: a comparative study with IL-12p40; Kinjo Y et al.; The present study was conducted to critically determine the protective role of IL-18 in host response to Mycobacterium tuberculosis infection . IL-18-deficient (knockout (KO)) mice were slightly more prone to this infection than wild-type (WT) mice . Sensitivity of IL-12p40KO mice was lower than that of IL-12p40/IL-18 double KO mice . IFN-gamma production caused by the infection was significantly attenuated in IL-18KO mice compared with WT mice, as indicated by reduction in the levels of this cytokine in sera, spleen, lung, and liver, and its synthesis by spleen cells restimulated with purified protein derivatives . Serum IL-12p40 level postinfection and its production by peritoneal exudate cells stimulated with live bacilli were also significantly lower in IL-18KO mice than WT mice, suggesting that attenuated production of IFN-gamma was secondary to reduction of IL-12 synthesis . However, this was not likely the case, because administration of excess IL-12 did not restore the reduced IFN-gamma production in IL-18KO mice . In further studies, IL-18 transgenic mice were more resistant to the infection than control littermate mice, and serum IFN-gamma level and its production by restimulated spleen cells were increased in the former mice . Taken together, our results indicate that IL-18 plays an important role in Th1 response and host defense against M . tuberculosis infection although the contribution was not as profound as that of IL-12p40. Nippon Ronen Igakkai Zasshi, 2002 May, 39(3), 314 - 7 {A rare case illustrating the difficulty of diagnosing and treating elderly patient with CAPD-related peritonitis caused by the perforation of sigmoid colon diverticulum}; Morimoto H et al.; A 67-year-old man was admitted with abdominal pain on April 23, 2000 . Continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis was diagnosed . Administration of antibiotics for five days obtained no improvement . Therefore the peritoneal catheter was removed on April 28th . Although his condition became settled, C-reactive protein remained positive . Moreover, two kinds of bacilli were detected from the CAPD fluid, just before the catheter was removed . As abnormalities in the colon were possible, an enema examination was performed on May 23rd . A constriction and several diverticula of the sigmoid colon were detected . High grade fever appeared on May 23rd, and the patient complained of abdominal pain the next day . As there was no improvement, we performed enhanced computed tomography and detected an abscess in the Douglas pouch on May 29th . The abscess was resected on the same day, and he was discharged . The number of patients with chronic renal failure has increased in recent years . Although hemodialysis has been the treatment of choice, peritoneal dialysis should be considered . More investigations into complications created by peritoneal dialysis are required, especially in elderly people who seldom show symptoms of CAPD-related peritonitis until they reach a critical condition . If peritoneal dialysis is being performed and inflammation reactions continue, it is necessary to examine the patient for perforated peritonitis and abscess formation. Surg Endosc . 2002 Sep;16(9):1362 . Epub 2002 Jun 20. Laparoscopic transgastric pancreatic necrosectomy for infected pancreatic necrosis; Ammori BJ; BACKGROUND: Secondary infection of pancreatic necrosis is an indication for surgical debridement, and has traditionally been treated by laparotomy, and more recently by laparoscopic transmesocolic or transgastrocolic and retroperitoneoscopic approaches . This report describes and evaluates the safety and feasibility of a laparoscopic transgastric approach to extensive necrosectomy for infected pancreatic necrosis . METHOD: A 66-year-old man developed severe acute pancreatitis with more than 50% necrosis of the body and some necrosis of the tail of the gland . Clinical deterioration with respiratory and renal impairment at 2 weeks prompted a computed tomogram (CT) guided fine-needle aspiration of the necrosis, which proved to be infected with Gram-negative bacilli . A favorable response to supportive therapy and systemic antibiotics enabled a cautious deferment of surgery to week 6 of the illness while the necrosis and its inflammatory wall matured . A laparoscopic transgastric pancreatic necrosectomy with drainage of an associated abscess was performed . RESULT: Intraoperative blood loss was minimal, and Operative time was 270 min . The debrided pancreas (30 g) was infected with anaerobes . The patient made an uneventful recovery and was discharged on postoperative day 14 . At this writing, he remains well after 2 months of follow-up evaluation . CONCLUSION: Laparoscopic transgastric pancreatic necrosectomy appears to be a safe and effective minimally invasive approach for the debridement and internal drainage of infected pancreatic necrosis in the selected patient . Further experience with this technique is needed to define the selection criteria and its limitations, advantages, and disadvantages. Crit Care Med, 2002 Jun, 30(6), 1204 - 9 Selective decontamination of the digestive tract to prevent postoperative infection: a randomized placebo-controlled trial in liver transplant patients; Zwaveling JH et al.; OBJECTIVE: To determine the efficacy of selective decontamination of the digestive tract (SDD) in patients undergoing elective transplantation of the liver . DESIGN: Randomized, double-blind, placebo-controlled study . SETTING: Two academic teaching hospitals . PATIENTS: Adult patients undergoing elective liver transplantation: 26 patients receiving SDD and 29 patients receiving a placebo . INTERVENTIONS: Patients undergoing SDD were administered 400 mg of norfloxacin once daily as soon as they were accepted for transplantation . Postoperative treatment for this group consisted of 2 mg of colistin, 1.8 mg of tobramycin, and 10 mg of amphotericin B, four times daily, combined with an oral paste containing a 2% solution of the same drugs until postoperative day 30 . Prophylactic intravenous administration of antibiotics was not part of the SDD regimen in this study . Control patients were given a similar regimen with placebo drugs . MEASUREMENTS: The mean number of postoperative bacterial and fungal infections in the first 30 days after transplantation was the primary efficacy end point . Days on a ventilator, days spent in the intensive care unit, and medical costs were registered as secondary outcome variables . MAIN RESULTS: Of the 26 patients undergoing SDD, 22 (84.5%) developed an infection in the postoperative study period; in the placebo group (n = 29), these numbers were not significantly different (25 patients, 86%) . The mean number of postoperative infectious episodes per patient was also not significantly different: 1.77 (SDD) vs . 1.93 (placebo) . Infections involving Gram-negative aerobic bacteria and Candida species were significantly less frequent in patients receiving SDD (p <.001 and p <.05) . Total costs were higher in the group receiving SDD . CONCLUSIONS: Selective decontamination of the digestive tract does not prevent infection in patients undergoing elective liver transplantation and increases the cost of their care . It does, however, affect the type of infection . Infections with Gram-negative bacilli and with Candida species are replaced by infections with Gram-positive cocci. Biochem J, 2002 Jul 1, 365(Pt 1), 89 - 97 Lipid-restricted recognition of mycobacterial lipoglycans by human pulmonary surfactant protein A: a surface-plasmon-resonance study; Sidobre S et al.; The human pulmonary surfactant protein A (hSP-A), a member of the mammalian collectin family, is thought to play a key defensive role against airborne invading pulmonary pathogens, among which is Mycobacterium tuberculosis, the aetiologic agent of tuberculosis . hSP-A has been shown to promote the uptake and the phagocytosis of pathogenic bacilli through the recognition and the binding of carbohydrate motifs on the invading pathogen surface . Recently we identified lipomannan and mannosylated lipoarabinomannan (ManLAM), two major mycobacterial cell-wall lipoglycans, as potential ligands for binding of hSP-A . We demonstrated that both the terminal mannose residues and the fatty acids are critical for binding, whereas the inner arabinosyl and mannosyl domains do not participate . In the present study we developed a surface-plasmon-resonance assay to analyse the molecular basis for the recognition of ManLAM by hSP-A and to try to define further the role of the lipidic aglycone moiety . Binding of ManLAM to immobilized hSP-A was consistent with the simplest one-to-one interaction model involving a single class of carbohydrate-binding site . This observation strongly suggests that the lipid moiety of ManLAM does not directly interact with hSP-A, but is rather responsible for the macromolecular organization of the lipoglycan, which may be necessary for efficient recognition of the terminal mannosyl epitopes . The indirect, structural role of the lipoglycan lipidic component is further supported by the complete lack of interaction with hSP-A in the presence of a low concentration of mild detergent. Saudi Med J, 2002 May, 23(5), 503 - 8 Extrapulmonary tuberculosis, epidemiology and patterns in Saudi Arabia; Alrajhi AA et al.; Annual incidence rates of extrapulmonary tuberculosis have been increasing over the last few years in the Kingdom of Saudi Arabia . True rates may even be higher due to incomplete reporting . Diagnosis of this condition requires high clinical suspicion, special diagnostic procedures, special staining, and culture media for acid fast bacilli . Delayed diagnosis results in increasing morbidity, mortality, and cost to the health care system . Particularly in areas of high endemicity of Mycobacterium tuberculosis, clinicians should be aware of the various forms of extrapulmonary tuberculosis . The available epidemiology and patterns of various forms of extrapulmonary tuberculosis in the Kingdom of Saudi Arabia are presented in this review. Am J Clin Dermatol, 2002, 3(5), 319 - 28 Cutaneous tuberculosis: diagnosis and treatment; Barbagallo J et al.; As we move into the 21st century, cutaneous tuberculosis has re-emerged in areas with a high incidence of HIV infection and multi-drug resistant pulmonary tuberculosis . Mycobacterium tuberculosis, Mycobacterium bovis, and the BCG vaccine cause tuberculosis involving the skin . True cutaneous tuberculosis lesions can be acquired either exogenously or endogenously, show a wide spectrum of morphology and M . tuberculosis can be diagnosed by acid-fast bacilli (AFB) stains, culture or polymerase chain reaction (PCR) . These lesions include tuberculous chancre, tuberculosis verrucosa cutis, lupus vulgaris, scrofuloderma, orificial tuberculosis, miliary tuberculosis, metastatic tuberculosis abscess and most cases of papulonecrotic tuberculid . The tuberculids, like cutaneous tuberculosis, show a wide spectrum of morphology but M . tuberculosis is not identified by AFB stains, culture or PCR . These lesions include lichen scrofulosorum, nodular tuberculid, most cases of nodular granulomatous phlebitis, most cases of erythema induratum of Bazin and some cases of papulonecrotic tuberculid . Diagnosis of cutaneous tuberculosis is challenging and requires the correlation of clinical findings with diagnostic testing; in addition to traditional AFB smears and cultures, there has been increased utilization of PCR because of its rapidity, sensitivity and specificity . Since most cases of cutaneous tuberculosis are a manifestation of systemic involvement, and the bacillary load in cutaneous tuberculosis is usually less than in pulmonary tuberculosis, treatment regimens are similar to that of tuberculosis in general . In the immunocompromised, such as an HIV infected patient with disseminated miliary tuberculosis, rapid diagnosis and prompt initiation of treatment are paramount . Unfortunately, despite even the most aggressive efforts, the prognosis in these individuals is poor when multi-drug resistant mycobacterium are present . An increased awareness of the re-emergence of cutaneous tuberculosis will allow for the proper diagnosis and management of this increasingly common skin disorder. Scand J Infect Dis, 2002, 34(5), 331 - 7 Evaluation of outpatients with suspected pulmonary tuberculosis in a high HIV prevalence setting in Ethiopia: clinical, diagnostic and epidemiological characteristics; Bruchfeld J et al.; In a setting with a high prevalence of HIV we studied (i) the prevalence of pulmonary tuberculosis (PTB) and HIV; (ii) clinical and epidemiological characteristics of PTB; and (iii) the usefulness of standard procedures for diagnosing PTB . Of 509 consecutive outpatients evaluated on clinical suspicion of PTB in Addis Ababa, 33.0% were culture-verified as having PTB . PTB patients, non-TB patients and controls were HIV-1-positive in 57.1%, 38.5% and 8.3% of cases, respectively . Predictors for culture-verified PTB were age < 25 y, male gender and the presence of HIV and fever, whereas profound weight loss indicated HIV infection . Diagnosis of PTB based on clinical symptoms, sputum microscopy for acid-fast bacilli and chest radiography was sensitive (86.7%) but unspecific (64.1%) . In HIV-positive patients both sensitivity and specificity were significantly lower (p < 0.05) . HIV-related pulmonary infections are often misinterpreted as smear-negative PTB . HIV screening is therefore warranted not only in cases of verified TB but also as part of the diagnostic work-up in patients with respiratory symptoms suggestive of PTB . Also, increased awareness of, and improved diagnostic tools for, HIV-related pulmonary infections other than PTB are required, together with algorithms for patients with suspected PTB. Int J Tuberc Lung Dis, 2002 Jun, 6(6), 510 - 5 Transforming growth factor-beta gene polymorphism in sarcoidosis and tuberculosis patients; Niimi T et al.; SETTING: Transforming growth factor-beta (TGF-beta) plays an important role in many diseases, influencing as it does such processes as immune responses, fibrosing processes, and angiogenesis . Recently, polymorphisms have been described for TGF-beta that are associated with the risk of several diseases . In this study, we investigated whether TGF-beta 1 polymorphism has an effect on sarcoidosis and tuberculosis . OBJECTIVE: TGF-beta 1 Codon 10 T869C polymorphism was investigated in 110 healthy control subjects, 104 sarcoidosis patients, and 101 tuberculosis patients . DESIGN: The TGF-beta genotype was determined using polymerase chain reaction restriction fragment length polymorphism . RESULTS: We found no significant differences in TGF-beta genotypes between sarcoidosis patients and healthy controls or tuberculosis patients and controls . The long axis of the tuberculin skin test was larger in the CC type compared with the CT type . However, there was no association between the TGF-beta genotype and the roentgenographic stage, the disappearance of shadows, or organ involvement in sarcoidosis, nor any association between genotype, the extent or type of roentgenographic shadow, or detected volume of tubercle bacilli in tuberculosis . CONCLUSION: From the results, we believe that TGF-beta polymorphisms on the whole do not have a strong influence on disease onset or clinical progression in sarcoidosis and tuberculosis, although this polymorphism might have an effect on the immune response in a tuberculosis host. Infect Immun, 2002 Jul, 70(7), 3318 - 23 DNA immunization in a mouse model of latent tuberculosis: effect of DNA vaccination on reactivation of disease and on reinfection with a secondary challenge; Repique CJ et al.; Individuals who are latently infected with Mycobacterium tuberculosis can develop active disease via either endogenous reactivation of the latent bacilli or exogenous reinfection with a second mycobacterial strain . In this study, we investigated whether immunization with a tuberculosis DNA vaccine cocktail that induces significant protective responses in mice could prevent reactivation of disease in a murine latent-tuberculosis model . In addition, we assessed whether DNA vaccination could retard the growth of a secondary aerogenic infection with M . tuberculosis (exogenous reinfection) in latently infected mice . In the reactivation studies, administration of the DNA vaccine combination did not prevent recrudescence of the latent infection after injection of dexamethasone . Moreover, for the reinfection experiments, only a modest decrease in the growth of a secondary M . tuberculosis challenge in DNA-vaccinated animals, compared to controls, was observed 14 and 28 days after the reinfection of previously exposed mice . Interestingly, although proliferation of the secondary challenge was reduced significantly in a nonvaccinated chronic-infection group relative to the naive controls, the number of bacilli still increased by 500-fold 1 month after the secondary challenge in mice with active tuberculosis . These results indicate that novel immunotherapeutic approaches will be required to prevent reactivation of infection or reinfection of individuals with latent tuberculosis. Avian Dis, 2002 Apr-Jun, 46(2), 509 - 14 Diagnosis by polymerase chain reaction of Erysipelas septicemia in a flock of ring-necked pheasants; Hennig GE et al.; A flock of 810 pheasants experienced 6.2% mortality over 6 days . Affected birds were weak and lethargic for up to 24 hr before death . Examined birds were thin, and gross lesions consisted of thick opaque crops and cecal cores . Histologically, there was capillariasis of the crop and multifocal ulcerative typhlitis with Heterakis spp . infection, and numerous systemic intravascular monocytes were filled with clusters of blue rod-shaped organisms . The organisms were gram-positive bacilli by Brown and Brenn staining and ultrastructural analysis . Liver bacterial cultures were negative for pathogenic bacteria . Erysipelas septicemia was diagnosed by an Erysipelothrix species-specific polymerase chain reaction method with the substrate DNA isolated from formalin-fixed, paraffin-embedded liver. Proc Natl Acad Sci U S A, 2002 Jun 11, 99(12), 8330 - 5 Reduced immunopathology and mortality despite tissue persistence in a Mycobacterium tuberculosis mutant lacking alternative sigma factor, SigH; Kaushal D et al.; The pathogenesis of tuberculosis involves multiple phases and is believed to involve both a carefully deployed series of adaptive bacterial virulence factors and inappropriate host immune responses that lead to tissue damage . A defined Mycobacterium tuberculosis mutant strain lacking the sigH-encoded transcription factor showed a distinctive infection phenotype . In resistant C57BL/6 mice, the mutant achieved high bacterial counts in lung and spleen that persisted in tissues in a pattern identical to those of wild-type bacteria . Despite a high bacterial burden, the mutant produced a blunted, delayed pulmonary inflammatory response, and recruited fewer CD4(+) and CD8(+) T cells to the lung in the early stages of infection . In susceptible C3H mice, the mutant again showed diminished immunopathology and was nonlethal at over 170 days after intravenous infection, in contrast to isogenic wild-type bacilli, which killed with a median time to death of 52 days . Complete genomic microarray analysis revealed that M . tuberculosis sigH may mediate the transcription of at least 31 genes directly and that it modulates the expression of about 150 others; the SigH regulon governs thioredoxin recycling and may be involved in the maintenance of intrabacterial reducing capacity . These data show that the M . tuberculosis sigH gene is dispensable for bacterial growth and survival within the host, but is required for the production of immunopathology and lethality . This phenotype demonstrates that beyond an ability to grow and persist within the host, M . tuberculosis has distinct virulence mechanisms that elicit deleterious host responses and progressive pulmonary disease. J Bacteriol, 2002 Jul, 184(13), 3485 - 91 Hypoxic response of Mycobacterium tuberculosis studied by metabolic labeling and proteome analysis of cellular and extracellular proteins; Rosenkrands I et al.; The events involved in the establishment of a latent infection with Mycobacterium tuberculosis are not fully understood, but hypoxic conditions are generally believed to be the environment encountered by the pathogen in the central part of the granuloma . The present study was undertaken to provide insight into M . tuberculosis protein expression in in vitro latency models where oxygen is depleted . The response of M . tuberculosis to low-oxygen conditions was investigated in both cellular and extracellular proteins by metabolic labeling, two-dimensional electrophoresis, and protein signature peptide analysis by liquid chromatography-mass spectrometry . By peptide mass fingerprinting and immunodetection, five proteins more abundant under low-oxygen conditions were identified from several lysates of M . tuberculosis: Rv0569, Rv2031c (HspX), Rv2623, Rv2626c, and Rv3841 (BfrB) . In M . tuberculosis culture filtrates, two additional proteins, Rv0363c (Fba) and Rv2780 (Ald), were found in increased amounts under oxygen limitation . These results extend our understanding of the hypoxic response in M . tuberculosis and potentially provide important insights into the physiology of the latent bacilli. Folia Histochem Cytobiol, 2002, 40(2), 129 - 30 Value of PCR technique in detection of Helicobacter pylori in paraffin-embedded material; Ciesielska U et al.; Methods which permit effective detection of Helicobacter prlori are based on endoscopic sampling of gastric mucosa followed by a direct or indirect demonstration of Helicobacter pylori bacilli, e.g . searching for specific proteins or gene fragments . PCR technique represents one of techniques employed for diagnosing the biopsies . The present study was aimed at examining how effective is the detection of Helicobacter pylori in paraffin-embedded material by PCR technique using primers for the Ure C gene fragment . The material for studies involved gastric biopsies, routinely fixed in formalin and embedded in paraffin . In order to perform PCR, DNA was isolated and purified, subjected to amplification with the use of starters for the Ure C gene fragment . The performed experiments have confirmed suitability of PCR technique for detection of Helicobacter pylori. FEMS Immunol Med Microbiol, 2002 Jun 3, 33(2), 125 - 32 Mycobacterium tuberculosis mammalian cell entry operon (mce) homologs in Mycobacterium other than tuberculosis (MOTT); Haile Y et al.; The cloned mammalian cell entry gene mce1a from Mycobacterium tuberculosis confers to non-pathogenic Escherichia coli the ability to invade and survive inside macrophages and HeLa cells . The aim of this work was to search for and characterize homologs of the four M . tuberculosis mammalian cell entry operons (mce1, mce2, mce3 and mce4) in mycobacteria other than tuberculosis (MOTT) . The dot-blot and polymerase chain reaction (PCR) experiments performed on 24 clinical isolates representing 20 different mycobacterial species indicated that the mce operons were widely distributed throughout the genus Mycobacterium . BLAST search results showed the presence of mce1, mce2 and mce4 homologs in Mycobacterium bovis, Mycobacterium avium and Mycobacterium smegmatis . A homologous region for the mce3 operon was also found in M . avium and M . smegmatis . DNA and protein alignments were done to compare the M . tuberculosis mce operons and the deduced M . bovis, M . avium, and M . smegmatis homologs . The deduced proteins of M . bovis mce1, mce2 and mce4 operons had 99.6-100% homology with the respective M . tuberculosis mce proteins (MTmce) . The similarity between M . avium mce proteins and the individual M . tuberculosis homologs ranged from 56.2 to 85.5% . The alignment results between M . smegmatis mce proteins and the respective MTmce proteins ranged from 58.5% to 68.5% . Primer sets were designed from the M . tuberculosis mce4a gene for amplification of 379-bp fragments . Amplification was successful in 14 strains representing 11 different mycobacterial species . The PCR fragments were sequenced from 10 strains representing eight species . Alignment of the sequenced PCR products showed that mce4a homologs are highly conserved in the genus Mycobacterium . In conclusions, the four mce operons in different mycobacterial species are generally organized in the same manner . The phylogenetic tree comparing the different mce operons showed that the mce1 operon was closely related to the mce2 operon and mce3 diverged from the other operons . The wide distribution of the mce operons in pathogenic and non-pathogenic mycobacteria implicates that the presence of these putative virulence genes is not an indicator for the pathogenicity of the bacilli . Instead, the pathogenicity of these factors might be determined by their expression.
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