Arch Pathol Lab Med, 1998 Apr, 122(4), 361 - 5 Primary T-cell lymphoma of the brain in a patient at advanced stage of acquired immunodeficiency syndrome; Aydin F et al.; OBJECTIVE: To present, to our knowledge, the first case of primary central nervous system T-cell lymphoma in the setting of acquired immunodeficiency syndrome . Design.Clinical, radiological, laboratory, and pathological data from a young patient at advanced stage of acquired immunodeficiency syndrome were studied . RESULTS: A 38-year-old white man with stage CIII human immunodeficiency virus infection presented with headaches . Cerebrospinal fluid culture was positive for mycobacterium . He had facial herpes simplex virus and disseminated cytomegalovirus infections . Magnetic resonance imaging of the brain showed multiple areas of patchy or ring-shaped contrast enhancement in the periventricular zone of the right frontoparietal region . Stereotactic brain biopsy showed perivascular CD3 (pan T-cell marker)-positive lymphocytic infiltrates with partial necrosis extending into the neuropil . Not a single cell was labeled with L26, a B-cell marker . Negative and positive controls were appropriate . Special stains for cytomegalovirus, herpes simplex virus, Epstein-Barr virus, acid-fast bacilli, and fungi were negative . Gene rearrangement studies showed rearranged Tgamma and Tbeta bands . Polymerase chain reaction with a primer specific for Epstein-Barr virus genome-encoding nuclear antigen 1 region was positive . Human T-cell leukemia/lymphoma virus I work-up was negative . The patient was treated for mycobacteria . Four months later, he presented with a paravertebral neck mass . Needle biopsy showed a T-cell lymphoma with morphology similar to that in the brain . CONCLUSIONS: To our knowledge, this case represents the first example of T-cell lymphoma of the brain in a patient with advanced stage of acquired immunodeficiency syndrome . Epstein-Barr virus may play a role in T-cell lymphomagenesis . The other unique finding is the complete absence of B cells in a central nervous system lesion . The underlying mechanism eradicating the B cells is unknown. Kansenshogaku Zasshi, 1998 May, 72(5), 504 - 11 Evaluation of two commercial diagnostic kits for Mycobacterium tuberculosis completely based on bacterial DNA and rRNA amplification for direct detection of tubercle bacilli in sputum specimens; Sato K et al.; The Roche Amplicor Mycobacterium Tuberculosis Kit (Amplicor PCR) and Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (MTD) were compared for efficiency in the direct detection of tubercle bacilli in sputum specimens . In total, 72 sputum specimens obtained from patients with active tuberculosis were examined with the Amplicor PCR and MTD kits . Of the 72 test specimens, 45 and 41 samples were positive by the Amplicor PCR and MTD methods, respectively . These values were larger than those obtained by the culture method (Septi-Chek) and acid-fast bacilli-smear test, yielding 37 and 20 positive results, respectively, and the sensitivities were as follows: smear, 39.2%; culture, 72.5%; Amplicor PCR, 88.2%; MTD, 80.4% . Amplicor PCR was similarly or somewhat more sensitive in direct detection of M . tuberculosis in sputum samples from patients with clinically active tuberculosis than was MTD. Am J Infect Control, 1998 Jun, 26(3), 270 - 6 Tuberculosis control in New York City hospitals; Stricof RL et al.; OBJECTIVES: To assess the implementation of tuberculosis (TB) control measures in New York City hospitals in 1992 and determine trends during the subsequent 2 years . METHODS: The 22 acute care facilities with the largest number of hospitalized TB patients in 1991 were selected for inclusion in the study . Medical and laboratory records of the 10 most recent acid fast bacilli (AFB) smear-positive patients in each of the selected facilities in 1992, 1993, and 1994 were reviewed by using a standardized questionnaire to determine risk factors for TB, previous history of TB, clinical signs and symptoms, AFB laboratory turnaround times, emergency department contact, timing of isolation, timing of treatment, case reporting, and status on discharge . The patients' rooms were evaluated for TB environmental control measures if the patient was still on respiratory isolation precautions . RESULTS: More than one third of patients were admitted with a previous history of TB, 31% were admitted with a cavitary lesion on chest x-ray examination, and 48% were known to have HIV infection . Eighty-five percent were admitted from the emergency department where they stayed for up to 116 hours (mean stay: 17 hours) . The proportion of patients placed in AFB isolation on admission to the floor increased from 75% in 1992 to 84% in 1994 . The proportion of patients given a minimum of four anti-TB drugs increased from 88% in 1992 to 94% in 1994 . Patients "on isolation" were sharing rooms with up to nine other patients in 1992, whereas no patients were sharing rooms in the 1994 survey . In 1992, 51% of the rooms were under negative air flow with respect to the corridor . During the 1994 survey, 80% of rooms were under negative air flow . Between 1992 and 1994, the proportion of AFB isolation rooms with dust/mist respirators increased from 28% to 76% (p < 0.00001) . Approximately 25% of discharged patients left against medical advice (no trend over time) . The proportion of medically discharged patients with three negative AFB smears before discharge increased from 26% to 48% (p = 0.03) and the proportion referred for directly observed therapy increased from 15% to 53% (p = 0.00001) . CONCLUSION: TB control efforts in New York City hospitals improved dramatically between 1992 and 1994 . The ultimate control of TB will continue to depend on the coordinated efforts within and between health care facilities, providers, and the community. Rinsho Ketsueki, 1998 May, 39(5), 392 - 7 {Hemophagocytic syndrome due to miliary tuberculosis in the course of aplastic anemia}; Yashima A et al.; We report a 63 year-old female with aplastic anemia (AA) who was complicated with hemophagocytic syndrome induced by systemic miliary tuberculosis . Two years before admission to our hospital, she was diagnosed as AA and had been treated with granulocyte colony-stimulating factor, erythropoietin and methenolone acetate . In May, 1996, She was transferred to our hospital because of high fever and exacervation of pancytopenia . She showed severe pancytopenia, and an increase in macrophages showing remarkable erythrophagocytosis and decrease in hemopoietic cells in the bone marrow . In initial examination, high titer of IgM antibody to herpes simplex virus type I was identified and methylprednisolone pulse therapy was started under the diagnosis of virus associated hemophagocytic syndrome . Ten days later, however, she died for intestinal hemorrhage followed by multiorgan failure . In autopsy, multiple epitheloid cell granulomas with acid-fast bacilli were found in bone marrow, lungs, liver, spleen and kidneys. Kekkaku, 1998 May, 73(5), 371 - 7 {The short-term effects of multidrug chemotherapy for pulmonary Mycobacterium avium-intracellulare complex (MAC) infection}; Kurashima A; In performing MAC chemotherapy, we are faced with the following two problems: first, unlike for Mycobacterium tuberculosis, we have neither any suitable bacteriocidal drugs nor bacteriocidal regimens for MAC treatment; secondly, in case of MAC, unlike in the case of Mycobacterium tuberculosis, in vitro sensitivity does not correlate with in vivo sensitivity . For these reasons, we find difficulty in planning a rational protocol for MAC treatment, and thus depend on previous experiences of other physicians in MAC chemotherapy . Here, we have tried to evaluate such previous experiences objectively, and studied retrospectively the effects of previous combination chemotherapy cases of pulmonary MAC infections at National Tokyo Hospital . We selected 170 cases which had received the same chemotherapy continuously over a period of six months . Concentration of bacilli cultured, 8 weeks in Ogawa solid egg containing medium was translated semi-quantitatively to colony forming units (CFU) according to the Japanese guideline for acid fast bacilli test . Having set a mean CFU of 3 times sputum culture before treatment as 100%, we calculated a six month sequential bacillary response to a regimen and plotted the bacillary response curves . The response curve of the total 170 MAC treatment cases exhibits a minimum point of 42.9% at 2 months, and subsequently rises to 71.1% after six months compared to the state before treatment . The response curves of various regimens of multidrug chemotherapy indicate that combinations of more than 3 drugs including aminoglycoside and clarithromycin are most effective . However, although some effectiveness is indicated, neither the present drugs nor regimens are capable to achieve a bacteriocidal effect in MAC treatment. Kekkaku, 1998 May, 73(5), 355 - 9 {A preventable case who died of miliary tuberculosis after receiving contact examination}; Sasaki Y et al.; A 30-year-old-man was admitted to our hospital because of headache and fever . His consciousness on admission was clouding . Sputum examination was positive for acid fast bacilli which later identified as Mycobacterium tuberculosis . Chest-X-ray and computed tomogram on admission showed multiple cavitary lesions on bilateral upper lung fields and bilateral diffuse nodular shadow . He was diagnosed as miliary tuberculosis with tuberculous meningitis . His mother admitted because of pulmonary tuberculosis four months ago, and her sputum examination was smear positive for acid fast bacilli, Gaffky 4, and she complained of cough for 6 months before admission . Because of this situation, he rapidly underwent the contact examination with chest X-ray, but not examined by tuberculin skin test because he was 30-year-old . As then chest X-ray was normal, he was not indicated of chemoprophylaxis, and he died of miliary tuberculosis and tuberculous meningitis 4 months after the contact examination. J Immunol, 1998 Jun 15, 160(12), 6101 - 11 Lack of both types 1 and 2 cytokines, tissue inflammatory responses, and immune protection during pulmonary infection by Mycobacterium bovis bacille Calmette-Guérin in IL-12-deficient mice; Wakeham J et al.; Understanding of key cytokines and the nature of protective immune responses in pulmonary mycobacterial diseases remains a task of paramount importance . In this study, both wild-type (wt) and IL-12-deficient (IL-12(-/-)) mice were infected by airways inoculation of live Mycobacterium bovis bacille Calmette-Guerin (BCG) . The type 1 cytokines IL-12, IFN-gamma, and TNF-alpha, but not the type 2 cytokines IL-4 and granulocyte macrophage (GM)-CSF, markedly increased in the lung and peripheral blood of wt mice postinfection, which resulted in the development of intense granulomatous responses and the effective control of mycobacterial infection in the lung . In contrast, IL-12(-/-) mice demonstrated a lack of both types 1 and 2 cytokines in the lung and blood and a severely impaired tissue immune-inflammatory response lacking not only macrophages and neutrophils but CD4 and CD8 T cells and NK cells in the lung throughout the entire course of study . Total lung mononuclear cells isolated from these mice, in contrast to wt mice, had an impaired recall immune response to Ag challenge in vitro . These impaired responses resulted in an uncontrolled local growth and systemic spread of bacilli . Our findings reveal that IL-12 plays an irreplaceable role in the initiation of Th1 responses, and the loss of its function cannot be compensated for by alternative mechanisms in the lung . This cytokine, together with IFN-gamma and TNF-alpha, and granulomatous inflammation are critically required for the effective control of pulmonary mycobacterial infection . Our results also indicate that the absence of type 1 cytokines does not necessarily favor a Th2 response. Diagn Microbiol Infect Dis, 1998 Jul, 31(3), 473 - 7 The role of fourth-generation cephalosporins in the treatment of serious infectious diseases in hospitalized patients; Wilson WR; For many years, the third-generation cephalosporins have been utilized in the treatment of a broad range of infections . The reduction in the efficacy of these antimicrobials in hospitals seen in recent years is a result of the development of resistance to these compounds . This resistance, caused in part by the production of beta-lactamases which can spread from species to species, has intensified the search for alternative agents . Compared with third-generation cephalosporins, fourth-generation cephalosporins possess enhanced activity against Gram-positive organisms, excellent penetration into Gram-negative bacilli, and are more stable against the activity of some beta-lactamases . Accordingly, fourth-generation cephalosporins are attractive candidates to replace third-generation cephalosporins for the treatment of many nosocomial infections. Nat Biotechnol, 1996 Mar, 14(3), 343 - 7 Efficient synthesis of mosquitocidal toxins in Asticcacaulis excentricus demonstrates potential of gram-negative bacteria in mosquito control; Liu JW et al.; The control of mosquitoes with chemical insecticides pollutes the environment and leads to resistance in mosquito populations . Bacterial control of mosquito larvae with Bacillus sphaericus and Bacillus thuringiensis subsp . israelensis, which produce protein toxins, has proved useful, safe, and nonpolluting . These bacteria do, however, suffer from disadvantages, including rapid setting, UV sensitivity, and lack of persistance of spores, proteolysis of toxins, narrow host range, and high production costs . Here we show that the Gram-negative bacterium Asticcacaulis excentricus is a promising host for delivering toxins to mosquito larvae . Plasmid-transformed A . excentricus cells expressing the binary toxin of B . sphaericus exhibited toxicity to Culex and Anopheles mosquito larvae similar to that of the high-toxicity strains of B . sphaericus which produce several toxins . A . excentricus has potential advantages as a larvicide compared with the bacilli, especially persistance in the larval feeding zone, resistance to UV light, lack of toxin-degrading proteases, and low production costs. Am J Surg Pathol, 1998 Jun, 22(6), 736 - 41 Xanthomatous hypophysitis; Folkerth RD et al.; Inflammatory lesions of the hypophysis include lymphocytic hypophysitis, pituitary abscess, and granulomatous inflammation, with or without specific infections (i.e., sarcoidosis, mycobacteria) . These lesions are known to mimic pituitary neoplasms . We report the clinical and pathologic findings in three patients who underwent transsphenoidal resection for presumed pituitary adenoma . Two were women aged 30 years (one with a 5-month history of headache, the other with a 1-year history of menstrual irregularity) and one was a 12-year-old girl with headache, nausea, and diabetes insipidus . Preoperative endocrinologic studies showed increased prolactin in one patient and normal serum thyroid stimulating hormone and prolactin levels in another . By magnetic resonance imaging (MRI), the first case had a 1.2-cm mass with increased signal on T1 and isointensity on T2, ring enhancement after gadolinium, and lateral deviation of the pituitary stalk . The second patient had a 1.1-cm "cystic" mass seen during magnetic resonance imaging with adjacent bony changes seen during computed tomography . In the third, computed tomography showed a hypodense pituitary mass that enlarged during 1-month observation . At surgery, abnormal soft tissue surrounded liquefied material in the anterior pituitary in all cases . Histologic studies showed fragments of intact normal anterior pituitary with preserved vascular and reticulin network and regions of anterior pituitary infiltrated by foamy histiocytes . Other fragments resembled granulation tissue, and some consisted of acellular debris . Histiocytes were immunoreactive for the macrophage marker CD68 and negative for S-100 and CD1a . Ultrastructurally, the normal adenohypophysis was permeated by lipid-laden macrophages . There were no well-formed granulomas or giant cells, hemosiderin, acid-fast bacilli, or fungi . Serial sections and keratin immunostains failed to identify an epithelial cyst lining or keratin among the debris . We propose the term "xanthomatous hypophysitis" for this lesion. Lepr Rev, 1998 Mar, 69(1), 24 - 39 Impaired responses to Mycobacterium leprae antigens in rhesus monkeys experimentally inoculated with simian immunodeficiency virus and M . leprae; Gormus BJ et al.; Seven of eight rhesus monkeys (RM) coinfected with simian immunodeficiency virus (SIV) and Mycobacterium leprae harboured acid-fast bacilli (AFB) at sites of dermal inoculation and/or at disseminated sites at times of humane sacrifice (up to 270 days post-M . leprae inoculation) due to SIV-induced debilitation or, in one long term survivor's case, to date over 3 years post-M . leprae inoculation . Detectable AFB were cleared in biopsies of inoculation sites of RM inoculated with M . leprae alone after 63 days postinoculation; these sites have, so far, remained AFB-negative, thereafter . Compared to animals infected with M . leprae alone, RM coinfected with SIV plus M . leprae showed: 1, completely suppressed serum antibody responses to M . leprae-specific PGL-I antigen, but strong anti-SIV Gp120 antibody responses; 2, impaired sensitization of blood mononuclear cells (MNC) to in vitro recognition of M . leprae-specific antigens in blastogenic stimulation assays; 3, impaired in vitro responses of blood MNC to nonspecific (ConA) blastogenic stimuli; and 4, early post-M . leprae inoculation, there was a significant incremental diminution of percentages of blood CD4+CD29+ T-cells in addition to the existing SIV-induced diminished percentages of CD4+CD29+ T-cells . The results indicate that humoral and cellular immune responses to M . leprae antigens are compromised in M . leprae-inoculated RM previously infected with SIV . These results provide an immunologic basis for the demonstration of enhanced M . leprae persistence or leprosy susceptibility in SIV-M . leprae coinfected RM. Ugeskr Laeger, 1998 May 18, 160(21), 3066 - 9 {Multiresistant tuberculosis in Denmark 1993-1996}; Viskum K et al.; Infections with multiresistant tubercle bacilli have also become a problem in the rich part of the world . The reasons are lack of compliance in patients with life style problems and ineffectiveness of the health system due to lack of fundings . During a four year period, 1993-1996 ten patients were seen in Denmark with tuberculosis due to multiresistant Mycobacterium tuberculosis . Nine were infected abroad, one developed MDR-TB during treatment in Denmark . It is possible to cure these patients, but it is expensive and takes a long time . In the future more cases created within Denmark are likely to be seen due to lack of funding for the tuberculosis programme and, depending on immigration, further cases created abroad are expected. Kansenshogaku Zasshi, 1998 Apr, 72(4), 410 - 3 {A case of solitary pulmonary nodule caused by Mycobacterium avium}; Yokomura K et al.; A 56-year-old male without respiratory symptoms, past history nor familial history, was admitted to our hospital because of pulmonary solitary nodule on the chest radiograph . Computed tomograph showed a smooth surface nodule in the left lower lobe (segment 8) . Bronchofiberscopy could not give any specific histological findings nor bacteriological findings, therefore the patient underwent partial pulmonary resection by videoassisted thoracoscopic surgery . Pathology of the resected specimen revealed epithelioid cell granuloma with giant cells but not any acid-fast bacilli . He was treated with rifampicin and isoniazid for "tuberculoma" . After three weeks, thirty colonies grew on an Ogawa's egg medium, which were identified as Mycobacterium avium by PCR . There are few reports about the solitary pulmonary nodule due to M . avium-intracellurale complex infection, however, it is supposed that there are many "tuberculoma's" without bacteriological differentiation between tuberculosis and nontuberculous mycobacterial infection . It is difficult to diagnose a solitary pulmonary nodule caused by nontuberculous mycobacterial infection with bronchofiberscopy, and the location of the lesion is usually subpleural, therefore it is thought that videoassisted thoracoscopic surgery is valied for the diagnosis of solitary pulmonary nodule due to nontuberculous mycobacterium. Hinyokika Kiyo, 1998 Apr, 44(4), 253 - 7 {Intravesical bacillus Calmette-Guerin instillation for patients over 80 years old}; Kanematsu A et al.; To study the efficacy and the safety of intravesical bacillus Calmette-Guerin (BCG) therapy for very elderly patients with superficial bladder cancer, we retrospectively compared patients over 80 years old who had received BCG therapy at our department between 1991 and 1996 (Group A; 10 patients 11 courses), with those below 80 years old (Group B, 17 patients 18 courses) . In these patients, skin test reactivity to purified protein derivative showed a significant negative correlation with age (p = 0.016) . No irreversible complications were observed in any patient . Persistence of acid-fast bacilli for more than one month after the termination of the course was observed in two patients in group A, and one in group B . A comparison of the cases undergoing eradicational BCG therapy in the two groups, grade 2 transitional cell carcinoma (TCC) was significantly more predominant than grade 3 TCC in group A (p = 0.004) . (None of the tumors in group A were of grade 3) The disease-free rate was significantly lower in group A (p < 0.05), but 5 of the 10 patients in this group were finally disease-free . From these results, we conclude that intravesical BCG instillation therapy can be performed in patients over 80 years old, although a relatively lower disease-free rate is expected and special attention should be taken with regard to persistent BCG infection . The lower disease-free rate could be attributable to either diminished cellular immunity or a difference in tumor grade, although a definite conclusion could not be obtained here. Infect Control Hosp Epidemiol, 1998 May, 19(5), 345 - 7 Pseudo-outbreak of tuberculosis in an acute-care general hospital: epidemiology and clinical implications; Cronin W et al.; A 10-fold increase in patients with Mycobacterium tuberculosis-positive specimens in one hospital laboratory prompted an investigation . Clinical and epidemiological data, along with M tuberculosis DNA fingerprinting results, indicated that laboratory contamination led to nine false-positive M tuberculosis cultures . Pseudo-infection should be considered in patients with unusual tuberculosis presentations, negative acid-fast bacilli smears, and only one positive culture with a low colony count. Int J Tuberc Lung Dis, 1998 May, 2(5), 397 - 404 Impact of human immunodeficiency virus type-1 infection on the initial bacteriologic and radiographic manifestations of pulmonary tuberculosis in Uganda . Makerere University-Case Western Reserve University Research Collaboration; Johnson JL et al.; SETTING: TB Treatment Centre, Kampala, Uganda . OBJECTIVE: To evaluate the impact of human immunodeficiency virus (HIV) co-infection on the bacteriologic and radiographic presentation of pulmonary tuberculosis (TB) in Uganda, a nation with high rates of Mycobacterium tuberculosis and HIV infection . DESIGN: To compare baseline characteristics among HIV-infected and non-HIV-infected adults with initial newly-diagnosed episodes of culture-confirmed pulmonary TB screened for participation in a randomized prospective TB treatment trial . RESULTS: Negative and paucibacillary (very scanty or scanty) sputum acid fast bacilli (AFB) smears were more frequent in HIV-infected patients presenting with pulmonary TB (P = 0.007) . More HIV-infected individuals also had sputum cultures that required 7-8 weeks incubation until positivity than non-HIV-infected patients (P < 0.01) . Lower lung field and diffuse pulmonary infiltrates were more frequent among HIV-infected patients . Rates of atypical X-ray presentations and cavitary disease were comparable between HIV-seropositive and -seronegative patients; however, atypical disease was more frequent in HIV-infected patients with small tuberculin reactions or tuberculin anergy (PPD = 0 mm) . CONCLUSION: HIV co-infection was associated with a higher frequency of negative and paucibacillary sputum AFB smears . The differences in the diagnostic yields of microscopy and culture between HIV-infected and non-HIV-infected individuals were small and do not, in our opinion, significantly affect the utility of these important diagnostic tests in developing countries . Examining more than one sputum specimen and monitoring cultured specimens for a full 8 weeks may assist in optimizing the diagnostic yield . Upper lobe infiltrates and cavitary disease are still the most frequent radiographic presentations of pulmonary TB in HIV-infected and non-HIV-infected adults in countries with a high prevalence of TB. Int J Tuberc Lung Dis, 1998 May, 2(5), 360 - 4 Two-year follow-up of directly-observed intermittent regimens for smear-positive pulmonary tuberculosis in China; Cao JP et al.; SETTING: The tuberculosis component of the Infectious and Endemic Disease Control Project in the People's Republic of China is the largest single tuberculosis control project in the world using directly-observed therapy and standardized intermittent regimens . OBJECTIVE: To determine the two-year relapse and mortality rates following completion of treatment . DESIGN: A prospective cohort study of 649 cases cured in this project . The 306 new and 343 retreatment cases were treated under field conditions with 2H3R3Z3S3/4H3R3 and 2H3R3Z3E3S3/6H3R3E3, respectively . Following treatment completion, two sputum samples were collected every six months for two years and examined for acid-fast bacilli . Causes of death were identified . RESULTS: The two-year relapse rates for new and retreatment cases were 3.3% and 5.6%, respectively . Retreatment cases with delayed sputum conversion had a greater risk for subsequent relapse . The two-year mortality rate for new and retreatment cases was 3.3% and 8.5%, respectively . The higher mortality rate in retreatment cases was not attributable to relapse of disease, but rather to non-infectious sequelae of tuberculosis . CONCLUSION: The use of directly-observed intermittent regimens is effective in permanently removing infectious tuberculosis cases from the community. Kekkaku, 1998 Apr, 73(4), 315 - 20 {A case of pulmonary tuberculosis complicated with intracranial tuberculous abscess}; Inoue T et al.; A 75-year-old male was admitted to our hospital with complaints of fever and cough . Chest X-ray showed infiltrative shadows with cavity, and sputum smears were positive for acid-fast bacilli . About 2 months after the initiation of anti-tuberculous chemotherapy, suddenly generalized convulsion occurred . CT of the brain showed the solitary mass with the ring enhancement in the left subcortical area . About 4 weeks later, brain aspiration drainage was performed and pus was aspirated . He was diagnosed as intracranial tuberculous abscess . After the drainage, neurological symptoms disappeared completely and there were no recurrence of abscess . Attention should be called to the complication of intracranial tuberculosis, especially in cases worsened during anti-tuberculous chemotherapy. Australas J Dermatol, 1998 May, 39(2), 92 - 5 Concurrent infection due to Shewanella putrefaciens and Mycobacterium marinum acquired at the beach; Papanaoum K et al.; Infection with marine bacteria is uncommon . A patient with systemic lupus erythematosus who developed concurrent infection with Shewanella putrefaciens and Mycobacterium marinum (M . marinum) is described . After bathing leg ulcers in sea water, severe cellulitis of the left leg with necrotic areas and extensive bullae developed . Infection due to S . putrefaciens was confirmed and a long course of hospitalization, oral ciprofloxacin and skin grafting was required . During hospitalization subcutaneous nodules developed on the other leg . Biopsy revealed acid-fast bacilli and culture grew M . marinum . These lesions responded to rifampicin and cotrimoxazole . Patients with leg ulcers, peripheral vascular disease, diabetes, or receiving immunosuppressive drugs may acquire unusual infections after salt water exposure. Appl Environ Microbiol, 1998 Jun, 64(6), 2256 - 61 Mycobacterium avium bacilli grow saprozoically in coculture with Acanthamoeba polyphaga and survive within cyst walls; Steinert M et al.; Protozoans are gaining recognition as environmental hosts for a variety of waterborne pathogens . We compared the growth of Mycobacterium avium, a human pathogen associated with domestic water supplies, in coculture with the free-living amoeba Acanthamoeba polyphaga with the growth of M . avium when it was separated from amoebae by a 0.1-micron-pore-size polycarbonate membrane (in a parachamber) . Although viable mycobacteria were observed within amoebal vacuoles, there was no significant difference between bacterial growth in coculture and bacterial growth in the parachamber . This suggests that M . avium is able to grow saprozoically on products secreted by the amoebae . In contrast, Legionella pneumophila, a well-studied intracellular parasite of amoebae, multiplied only in coculture . A comparison of amoebae infected with L . pneumophila and amoebae infected with M . avium by electron microscopy demonstrated that there were striking differences in the locations of the bacteria within amoebal cysts . While L . pneumophila resided within the cysts, M . avium was found within the outer walls of the double-walled cysts of A . polyphaga . These locations may provide a reservoir for the bacteria when environmental conditions become unfavorable. Can J Microbiol, 1998 Mar, 44(3), 259 - 69 Expression of a Bacillus thuringiensis delta-endotoxin gene by Bacillus pumilus; Selinger LB et al.; The delta-endotoxin genes from Bacillus thuringiensis were introduced into a rhizosphere-inhabiting Bacillus pumilus isolate to create a delta-endotoxin expression and delivery system for subterranean feeding insects such as the larvae of pale western cutworm (Agrotis orthogonia Morrison (Lepidoptera: Noctuidae)) . Preliminary experiments indicated that Bacillus thuringiensis subsp . kurstaki cultures were toxic to pale western cutworm larvae . Three different cry genes from Bacillus thuringiensis subsp . kurstaki were cloned into high and low copy number vectors and mated into Bacillus pumilus RB8 . When carried on high copy number vectors, cry genes appeared to inhibit sporulation and delta-endotoxin production in Bacillus pumilus RB8 cultures, since microscopic examination of these cultures revealed that < 0.1% of the cells of late stationary phase cultures had sporulated and produced parasporal inclusions . On low copy number vectors, the cry genes did not inhibit sporulation; however, production of delta-endotoxins was undetectable . Using a heat shock regime for enrichment of sporogenous crystalliferous variants, a Bacillus pumilus isolate, carrying cryIA(c) on a high copy number plasmid, was obtained in which high level delta-endotoxin production occurred concomitant with sporulation . Synthesis of functional delta-endotoxin by this strain was confirmed by Western blot analysis and bioassay with pale western cutworm larvae . These results show that rhizosphere-inhabiting bacilli are indeed a potential route for introduction of delta-endotoxins to the root environment for biocontrol purposes. J Immunol, 1998 Jun 1, 160(11), 5448 - 54 Fas ligand-induced apoptosis of infected human macrophages reduces the viability of intracellular Mycobacterium tuberculosis; Oddo M et al.; Mycobacterium tuberculosis-specific cytolytic activity is mediated mostly by CD4+CTL in humans . CD4+CTL kill infected target cells by inducing Fas (APO-1/CD95)-mediated apoptosis . We have examined the effect of Fas ligand (FasL)-induced apoptosis of human macrophages infected in vitro with M . tuberculosis on the viability of the intracellular bacilli . Human macrophages expressed Fas and underwent apoptosis after incubation with soluble recombinant FasL . In macrophages infected either with an attenuated (H37Ra) or with a virulent (H37Rv) strain of M . tuberculosis, the apoptotic death of macrophages was associated with a substantial reduction in bacillary viability . TNF-induced apoptosis of infected macrophages was coupled with a similar reduction in mycobacterial viability, while the induction of nonapoptotic complement-induced cell death had no effect on bacterial viable counts . Infected macrophages also showed a reduced susceptibility to FasL-induced apoptosis correlating with a reduced level of Fas expression . These data suggest that apoptosis of infected macrophages induced through receptors of the TNF family could be an immune effector mechanism not only depriving mycobacteria from their growth environment but also reducing viable bacterial counts by an unknown mechanism . On the other hand, interference by M . tuberculosis with the FasL system might represent an escape mechanism of the bacteria attempting to evade the effect of apoptosis. J Clin Microbiol, 1998 Apr, 36(4), 1046 - 9 Sensitivity of fluorochrome microscopy for detection of Mycobacterium tuberculosis versus nontuberculous mycobacteria; Wright PW et al.; The results for 6,532 consecutive mycobacterial respiratory specimens collected from 1,040 patients from 1993 to 1995 in a Texas hospital were studied to determine the sensitivity of fluorescence microscopy for detection of Mycobacterium tuberculosis and nontuberculous mycobacteria (NTM) . Smears were positive for acid-fast bacilli (AFB) in 63% (677 of 1,082) of specimens growing M . tuberculosis and 56% (638 of 1,148) of specimens growing the four most common species of NTM . Smear positivity by species was 58% (446 of 776) for M . avium complex, 51% (154 of 300) for rapidly growing mycobacteria (98% were M . abscessus), 78% (29 of 37) for M . kansasii, and 26% (9 of 35) for M . gordonae . Definite or probable disease by clinical criteria was present in 79% of patients with M . avium complex, 93% of patients with rapidly growing mycobacteria, 100% of patients with M . kansasii, and 0% of patients with M . gordonae . Patients with M . avium complex had a low incidence of AIDS (7%), and approximately 50% of non-AIDS patients had upper-lobe cavitary disease and 50% had nodular bronchiectasis . Only 23 of 6,532 (0.35%) of AFB smears were positive with a negative culture excluding patients on therapy for established mycobacterial disease . These studies suggest that NTM are as likely as M . tuberculosis to be detected by fluorescent microscopy in specimens from patients from areas endemic for NTM lung disease and at low risk for AIDS. Indian J Lepr, 1998 Jan-Mar, 70(1), 97 - 102 Presence of M . leprae in the conjunctiva, vitreous body and retina of a patient having lepromatous leprosy; Orefice F et al.; Histopathological study of the ocular globe of a lepromatous leprosy patient revealed the presence of lepra bacilli in the conjunctiva, sclera, episclera, cornea, iris, ciliary body, vitreous body and retina. Minerva Ginecol, 1998 Mar, 50(3), 93 - 6 {Postmenopausal endometrial tuberculosis . A clinical case}; Mantovani A et al.; Post-menopausal tuberculosis of the female genital tract is an uncommon condition that has received relatively little attention in the literature . The case described by the authors is about a sixty year old woman whose condition was brought to attention by leukorrhea and abnormal bleeding associated with a smear test suggesting CIN 1 . An endometrial aspiration biopsy revealed necrotic debris with focal granulomata and numerous acid-fast bacilli . Fungal stains were negative while mycobacterium tuberculosis was found . After three months of combination antimycobacterial treatment, she underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by six months of post-operative drug therapy. Trop Med Int Health, 1998 Mar, 3(3), 189 - 96 Mycobacterium ulcerans infection in a child from Angola: diagnosis by direct detection and culture; Bar W et al.; Buruli ulcer, caused by Mycobacterium ulcerans, is a chronic ulcerative skin disease, found predominantly in central and west Africa and Australia . A boy of 2.5 years of age from Angola was admitted to our hospital with severe kwashiokor and a large ulcer with undermined edges on the left side of the thorax . Further examination revealed anaemia, hypoproteinaemia, bacterial superinfection of the ulcer and intestinal parasites . Histological analysis showed acid-fast bacilli and histopathological changes typical of Buruli ulcer . M . ulcerans was detected by PCR and culture . The patient was treated by surgical excision of diseased skin, followed by split-skin grafting . He also received antibiotic therapy (ciprofloxacin, clarithromycin, rifabutin, and dapsone) . After six months, the child was discharged from hospital in good condition . This is the first published case of Buruli ulcer from Angola. Zhonghua Yan Ke Za Zhi, 1996 Sep, 32(5), 376 - 8 {Anterior chamber associated immune deviation inhibiting experimental autoimmune uveoretinitis}; Zheng M et al.; OBJECTIVE: To study the inhibition of occurrence and development of experimental autoimmune uveoretinitis (EAU) by the induction of anterior chamber associated immune deviation (ACAID) . METHODS: All animals (guinea pigs), except controls, were pretreated with anterior chamber injection of allogeneic retinal extract to induce ACAID, and thereafter, they received intradermal footpad immunization of the same antigen in complete Freund's adjuvant (CFA) for induction of EAU, and dead pertussis bacilli were also subcutaneously injected as a second adjuvant . The pathological changes were investigated by light and electron microscopy . RESULTS: The incidence of EAU in experimental group was 25.0%, whereas 85.7% in the positive controls . CONCLUSION: ACAID does, to a great extent, inhibit the incidence and development of EAU. Electrophoresis, 1998 Apr, 19(4), 573 - 6 Mycobacterial genome structure; Philipp WJ et al.; Genome maps have been constructed for the mycobacterial pathogens Mycobacterium leprae and Mycobacterium tuberculosis, as well as for the attenuated vaccine strain Mycobacterium bovis BCG Pasteur . While the chromosomes of M . tuberculosis and M . bovis BCG Pasteur show extensive conservation at the gross level, comparison with M . leprae revealed a high degree of diversification, with a mosaic-like pattern apparent . The ordered libraries of M . tuberculosis and M . leprae produced during the course of these studies played a central role in the genome sequencing projects of these two bacilli, showing the utility of this approach for systematic sequencing of bacterial genomes. Jpn J Ophthalmol, 1998 Mar-Apr, 42(2), 115 - 8 Clinicopathologic study of satellite lesions in nontuberculous mycobacterial keratitis; Hu FR et al.; Multifocal stromal infiltrates or "satellite lesions" have been considered a characteristic feature of fungal keratitis . We examined two patients with nontuberculous mycobacterial keratitis who clinically presented with satellite lesions . The keratitis consisted of multifocal stromal infiltrates with indistinct white and fluffy margins . Both patients received topical fortified amikacin therapy with poor response . Lamellar keratectomy or penetrating keratoplasty was performed, respectively, in the two patients because of progressive stromal thinning and enlarging satellite lesions . Histopathologically, the main lesions consisted of dense infiltration of inflammatory cells with numerous acid-fast bacilli, while the satellite lesions were composed chiefly of inflammatory cells with fewer mycobacteria . Besides fungal keratitis, nontuberculous mycobacterial keratitis should also be considered when satellite lesions are present. Am J Kidney Dis, 1998 Apr, 31(4), 701 - 5 Laryngeal tuberculosis in renal allograft patients; Tato AM et al.; Laryngeal tuberculosis, although the most common granulomatous disease of the larynx, is a rare form of extrapulmonary tuberculosis, never reported in immunosuppressed allograft recipients . We present two cases of laryngeal tuberculosis in renal transplant patients and a review of the literature . Two women, a 29-year-old and a 60-year-old, each more than 9 years after their cadaveric renal allograft, presented with a 2-week febrile illness with hoarseness and dysphagia, and both were found to have laryngeal tuberculosis by direct laryngoscopy . Although both radiographs were unremarkable, both patients had sputum positive for acid-fast bacilli that subsequently grew Mycobacterium tuberculosis . Clinical response promptly followed institution of isoniazid, rifampicin, and pyrazinamide in each case, although both required threefold increases in daily cyclosporin A dosage to maintain therapeutic levels. Am J Clin Pathol, 1998 May, 109(5), 642 - 6 Polymerase chain reaction assay for the detection and identification of Mycobacterium leprae in patients in the United States; Scollard DM et al.; The differentiation of leprosy from other cutaneous granulomatous diseases is routinely based on characteristic histopathologic features and the demonstration of Mycobacterium leprae by acid-fast staining . Increased ascertainment of other mycobacterial infections in the skin has made this task more difficult, but the distinction remains fundamental for the selection of appropriate treatment . Experience with formalin-fixed, paraffin-embedded tissues, frozen tissues, and tissue lysates referred for detection of M . leprae DNA by a polymerase chain reaction (PCR) assay during the past 4 years was reviewed . This assay was done by using primers and probes previously developed in our laboratory to amplify a 360-base-pair fragment of the gene for an 18-kD protein of M . leprae . Among biopsy samples obtained from 37 patients, PCR results were positive for 10 of 20 samples diagnosed as leprosy by histopathologic criteria and in 0 of 17 not diagnosed as leprosy . The specificity of the assay was 100% in this clinical referral material; sensitivity ranged from 50% to 83% . The PCR assay also identified M . leprae in one third of samples in which acid-fast organisms were seen and the histopathologic features were consistent with but not definitive of leprosy . In a nonendemic population, the sensitivity and specificity of PCR assay recommend its use primarily to identify M . leprae when acid-fast organisms are discernible but atypical clinical or histopathologic features obscure the diagnosis . The assay is not highly informative when acid-fast bacilli are not detectable by light microscopy. J Clin Microbiol, 1998 May, 36(5), 1352 - 6 Reverse transcription-PCR detection of Mycobacterium leprae in clinical specimens; Kurabachew M et al.; A reverse transcription (RT)-PCR assay targeting the 16S rRNA of Mycobacterium leprae was developed to detect the organism in clinical specimens . A 171-bp fragment was amplified when M . leprae RNA was used as a template but not when a panel of RNAs from 28 potentially cross-reacting mycobacterial species, seven genera related to Mycobacterium, and three organisms normally found among skin or nose flora were tested . As few as 10 organisms isolated from infected tissue could be detected, confirming the sensitivity of the assay . When the test was applied to clinical specimens, M . leprae was detected in 82% of skin biopsy specimens obtained from untreated leprosy patients, while skin biopsy specimens from healthy volunteers and patients with other dermatological disorders were negative . The sensitivity of the RT-PCR was higher than that of slit skin smear staining for acid-fast bacilli or acid-fast staining of fixed biopsy specimens since 53% of acid-fast bacillus-negative biopsy specimens were RT-PCR positive . Because 16S rRNA is rapidly degraded upon cell death, the assay may detect only viable organisms and may prove to be useful in assessing the efficacy of chemotherapy. J Immunol, 1998 May 1, 160(9), 4490 - 9 Induction of in vitro human macrophage anti-Mycobacterium tuberculosis activity: requirement for IFN-gamma and primed lymphocytes; Bonecini-Almeida MG et al.; Mycobacterium tuberculosis (Mtb) is the world's leading infectious cause of mortality . Despite the overwhelming data supporting the critical role of cellular immunity, little is known of the early microbial and immune cell interactions and whether human macrophages can be activated to express anti-Mtb activity . We report the reconstitution of an in vitro system whereby human macrophages express anti-Mtb activity only in coculture with PBL and with IFN-gamma . Omission of IFN-gamma in the cocultures or Mtb lysate/IFN-gamma-primed lymphocytes was associated with high growth of Mtb, high IL-10 and IL-12 p40, nearly undetectable IL-12 p70 levels, and the highest percentages of CD4 and CD8 T cells . In contrast, IFN-gamma treatment of cocultures containing Mtb lysate/IFN-gamma-primed PBL reduced bacilli count by approximately 2.5 log, decreased the production of IL-10 by 5.7-fold, increased IL-12 p70 by approximately 50-fold, and reduced the percentages of CD4 and CD8 T cells . Activation of anti-Mtb activity was time and dose dependent . At 2000 U/ml of IFN-gamma, bactericidal activity was achieved (10-fold reduction from initial inoculum) . Anti-Mtb activity against several strains of M . tuberculosis (H37Ra and H37Rv, and C, a clinical isolate) was observed and was associated with expression of inducible nitric oxide synthase . These data suggest that induction of human macrophage anti-Mtb activity required dual signaling from PBL and IFN-gamma . Thus, the development of an in vitro human system may greatly facilitate studies to delineate immune cells, cytokines, and effector functions/genes critical in controlling Mtb . Defining the mechanisms may also provide novel treatment strategies for tuberculosis. J Comp Pathol, 1998 Feb, 118(2), 109 - 21 Changes in lymphocyte subsets in the intestine and mesenteric lymph nodes in caprine paratuberculosis; Navarro JA et al.; Changes in the number and distribution of lymphocyte subsets were investigated in the intestinal mucosa and mesenteric lymph nodes of three goats with natural paratuberculosis, comparisons being made with a single uninfected control animal . Lesions in the naturally infected goats varied from small granulomata with scarce epithelioid or multinucleated giant cells, containing few or no bacilli, in the intestine (tuberculoid type) to an extensive, diffuse epithelioid cell infiltrate containing numerous bacilli in the gut and mesenteric lymph nodes (lepromatous type) . The number and distribution of lymphocyte subsets in the control were consistent with data reported from other non-infected goats . However, in the goats with paratuberculosis, significant changes were observed in the number and distribution of CD4+ and CD8+ T lymphocytes, the changes being related to the severity of the lesions . In the intestinal mucosa of the goat with tuberculoid lesions no significant changes were observed, but in the cortical area of mesenteric lymph nodes the number of CD4+ T lymphocytes decreased and the number of CD8+ T lymphocytes increased . In the two goats with lepromatous lesions, there was a decrease in the CD4+ T subpopulation and an increase of CD8+ T lymphocytes in the lamina propria of the intestine and particularly in the cortical area of the mesenteric lymph nodes, the CD4:CD8 ratio (< 1) being the opposite of that observed in healthy goats . Because of the small numbers of animals, further studies including additional animals are needed to confirm these preliminary results, which suggest that the progression of paratuberculous lesions may be due to an ineffective host immune response attributable to the CD8+ T lymphocyte subset that "downregulates" the activity of the CD4+ T lymphocytes required for macrophage activation. J Vet Dent, 1997 Dec, 14(4), 127 - 30 Dental plaque flora of the dog with reference to fastidious and anaerobic bacteria associated with bites; Allaker RP et al.; Animal bite wounds are amongst the most common types of traumatic injuries in humans . The organisms isolated from these wounds generally reflect the oral flora of the biting animal, and may be fastidious in nature and difficult to identify . This study was undertaken to determine the prevalence of Eikenella corrodens, Actinobacillus actinomycetemcomitans, Porphyromonas and Prevotella spp . in supragingival dental plaque collected from the right maxillary canine and carnassial teeth and the right mandibular canine tooth of dogs . In part one of the study, 30 dogs were used . E . corrodens was found in 62% of these dogs and 44% of individual plaque samples . A . actinomycetemcomitans was not detected in any of the dogs sampled . In part two, 34 dogs were used to determine the prevalence of the black pigmented anaerobic bacilli (Porphyromonas and Prevotella spp.) . Porphyromonas gingivalis was present in 68% of these dogs and 47% of individual plaque samples . Prevotella intermedia was present in 44% of the dogs and 23% of individual plaque samples . The recently described Porphyromonas canoris, Porphyromonas salivosa, Porphyromonas cangingivalis, Porphyromonas cansulci, Porphyromonas crevioricanis and Prevotella denticola species were isolated from only 9%, 6%, 3%, 3%, 3% and 3% of dogs respectively . Porphyromonas gingivicanis was not isolated from any of the animals sampled . In conclusion, black-pigmented anaerobic bacilli were isolated from 91% of the animals sampled and therefore constitute a significant risk with respect to bite wound infections . It is also suggested that the prevalence of E . corrodens in wound infections has been underestimated in previous reports because of use of inappropriate techniques for detecting this organism. J Immunol, 1998 Feb 1, 160(3), 1290 - 6 Cytokine activation leads to acidification and increases maturation of Mycobacterium avium-containing phagosomes in murine macrophages; Schaible UE et al.; Mycobacterium avium (MAC) organisms multiply in phagosomes that have restricted fusigenicity with lysosomes, do not acidify due to a paucity of vacuolar proton-ATPases, yet remain accessible to recycling endosomes . During the course of mycobacterial infections, IFN-gamma-mediated activation of host and bystander macrophages is a key mechanism in the regulation of bacterial growth . Here we demonstrate that in keeping with earlier studies, cytokine activation of host macrophages leads to a decrease in MAC viability, demonstrable by bacterial esterase staining with fluorescein diacetate as well as colony-forming unit counts from infected cells . Analysis of the pH of MAC phagosomes demonstrated that the vacuoles in activated macrophages equilibrate to pH 5.2, in contrast to pH 6.3 in resting phagocytes . Biochemical analysis of MAC phagosomes from both resting and activated macrophages confirmed that the lower intraphagosomal pH correlated with an increased accumulation of proton-ATPases . Furthermore, the lower pH is reflected in the transition of MAC phagosomes to a point no longer accessible to transferrin, a marker of the recycling endosomal system . These alterations parallel the coalescence of bacterial vacuoles from individual bacilli in single vacuoles to communal vacuoles with multiple bacilli . These data demonstrate that bacteriostatic and bactericidal activities of activated macrophages are concomitant with alterations in the physiology of the mycobacterial phagosome. Clin Exp Immunol, 1998 Apr, 112(1), 52 - 62 Gammadelta+ and CD4+ alphabeta+ human T cell subset responses upon stimulation with various Mycobacterium tuberculosis soluble extracts; Batoni G et al.; By using a flow cytometric technique which allows direct identification of proliferating cells within mixed cell populations, we have previously described that soluble extracts obtained from Mycobacterium tuberculosis or M . avium represent strong stimuli for human gammadelta+ T cells . In the present study, we demonstrate that the protocol used for the preparation of M . tuberculosis soluble extracts may have an impact on their gammadelta+ T cell stimulatory capacity . In agreement with our previous data, soluble extracts prepared from bacteria killed at 85 degrees C and directly disrupted by prolonged sonication (TBe), elicited a strong proliferation of gammadelta+ T cells after 6-7 days of stimulation . In contrast, when soluble extracts were obtained from bacteria autoclaved (121 degrees C, 25 min) and then washed by centrifugation, a predominant proportion of CD4+ alphabeta+ T cells was achieved in the responding population . The stimulatory activity for gammadelta+ T cells was recovered in the supernatant of the autoclaved bacteria, indicating that autoclaving of M . tuberculosis bacilli releases an antigen(s) into the supernatant which stimulates human gammadelta+ T cells . While protease digestion of TBe only partially reduced its stimulatory capacity on gammadelta+ T cells, the stimulatory component(s) released into the supernatant after autoclavation of bacilli was found to be sensitive to protease digestion . Interestingly, in contrast to the preponderant proportion of gammadelta+ T cells induced in the responding population by unfractionated TBe, when the extract was fractionated by fast performance liquid chromatography (FPLC), most of the fractions exhibited a strong stimulatory capacity on CD4+ alphabeta+ T cells only . The gammadelta+ T cell stimulatory activity was confined to the low molecular weight range FPLC fractions . Such results may suggest a possible regulatory role of gammadelta+ T cells on CD4+ alphabeta+ T cells. FEMS Immunol Med Microbiol, 1998 Mar, 20(3), 231 - 8 Mycobacterial crossreactivity of M . tuberculosis reactive T cell clones from naturally converted PPD positive healthy subjects; Oftung F et al.; Mycobacterium tuberculosis reactive CD4+, CD8- T cell clones were established from six naturally converted PPD positive healthy subjects by using whole bacilli as the primary stimulation antigen in vitro . Antigen specificity of the T cell clones was mapped by testing their proliferative response against a panel of pathogenic and environmental mycobacterial species . The crossreactivity patterns obtained showed that the T cell clones distributed along a spectrum from reactivity restricted to the M . tuberculosis complex to broadly crossreactive clones recognizing all mycobacterial species tested . Two of the T cell clones were able to discriminate between M . tuberculosis and M . bovis BCG, and importantly one of these clones was exclusively specific to M . tuberculosis . All of the CD4+ T cell clones tested, displayed MHC class II restricted cytotoxicity against macrophages pulsed with M . tuberculosis . In addition, some of these clones secreted GM-CSF upon antigen stimulation . The T cell clones described here represent relevant tools to identify and characterize target antigens of the immune response against M . tuberculosis with relevance to diagnosis and subunit vaccine design. Int J Tuberc Lung Dis, 1998 Feb, 2(2), 164 - 7 Computed tomography findings of tuberculous pleurisy; Yilmaz MU et al.; SETTING: Review of the records of 491 patients with tuberculous pleurisy hospitalized between 1993 and 1995 in Izmir, Turkey . Those cases with typical histopathology or demonstrated acid-fast bacilli on pleural needle biopsies and/or positive pleural fluid/tissue cultures and available computed tomography (CT) scans are included . OBJECTIVE: To determine the CT features of tuberculosis of the pleural space . DESIGN: The CT scans of 66 patients with proven tuberculous pleurisy were interpreted retrospectively by three observers . RESULTS: Of 66 patients, 65 (98.5%) had pleural effusions; 38 (57.5%) had pleural lesions; six (9%) had involvement of interlobar fissure; and one patient (1.5%) had involvement only of the mediastinal pleura . All but one of the pleural lesions involved regular thickening of greater than 1 cm . Fibrotic parenchymal changes were seen in 11 of 66 patients (17%), cavitary changes were seen in eight (12%), and heterogeneous nodular shadows were seen in four (6%) . Two cases (3%) had parenchymal consolidation and one (1.5%) had a calcified subpleural nodule . In 39% (26/66) of cases, hilar and mediastinal lymphadenopathy was identified . CONCLUSION: Tuberculous pleurisy in our series was characterized on CT by the presence of pleural effusion, often with smooth pleural thickening; rarely was there involvement of the mediastinal pleura . Underlying lung parenchymal abnormalities were seen in 39% of cases . Although these findings are non-specific, they may help to distinguish tuberculous pleurisy from other causes of pleural effusion, such as malignancy. Int J Tuberc Lung Dis, 1998 Feb, 2(2), 147 - 52 Adenosine deaminase activity and lysozyme levels in bronchoalveolar lavage fluid in patients with pulmonary tuberculosis; Orphanidou D et al.; SETTING: The estimations of adenosine deaminase (ADA) activity and lysozyme (LYS) levels in pleural fluid have been proved useful tools in the diagnosis of tuberculous pleural effusions . Little is known about their usefulness when estimated in bronchoalveolar lavage fluid (BALF) . OBJECTIVE: To evaluate whether both ADA activity and LYS levels in BALF could be employed in the diagnosis of pulmonary tuberculosis, and especially in active but acid fast bacilli (AFB) smear negative cases . DESIGN: ADA activity and LYS levels were determined in BALF and serum obtained on the same day in 28 patients with tuberculosis, 21 with interstitial lung diseases, 14 with lung cancer and 13 with infectious diseases . RESULTS: Patients with pulmonary tuberculosis had significantly higher ADA activity in BALF than patients with non-tuberculous lung diseases (P < 0.001) . High BALF ADA activity in pulmonary tuberculosis patients suggests increased local production . In contrast, in this group of patients BALF LYS levels were not significantly higher than in the other groups of patients, but were in the group with interstitial lung diseases . CONCLUSION: BALF ADA activity seems to be a useful tool in the differentiation of tuberculosis from other lung diseases . Its estimation can be restricted to the detection of cases with AFB negative smears. Infect Control Hosp Epidemiol, 1998 Mar, 19(3), 186 - 8 Risk factors associated with the acquisition of amikacin-resistant gram-negative bacilli in central New Jersey hospitals; Jessop AB et al.; A case-control study was performed in central New Jersey hospitals to evaluate the potential patient factors associated with the acquisition of amikacin-resistant gram-negative bacilli (ARGNB) . Univariate analysis revealed an association between numerous patient factors, and multivariate analysis revealed four factors to be associated independently with ARGNB: the number of hospital admissions during the prior year, previous aminoglycoside exposure, intubation, and intensive-care-unit admission. Zhonghua Yi Xue Za Zhi (Taipei), 1998 Mar, 61(3), 170 - 4 Genitourinary tuberculosis complicated with adrenal involvement and primary adrenocortical insufficiency: a case report; Lin SY et al.; Genitourinary tuberculosis (TB) rarely involves the adrenal gland . A 67-year-old man presented with progressively hyperpigmented skin and an enlarged mass over both testes . Early morning plasma cortisol concentration was low and adrenocorticotropic hormone (ACTH) concentration was high . A rapid ACTH stimulation test revealed the absence of plasma cortisol response and confirmed a diagnosis of primary adrenocortical insufficiency . An abdomen computed tomography (CT) scan disclosed enlargement of the right adrenal gland and punctuate calcification over the left one . This is compatible with tuberculous adrenalitis . Currettage biopsy of the prostate demonstrated chronic granulomatous inflammation with Langerhan's giant cells, but without TB bacilli . Anti-TB treatment, in addition to glucocorticoid and mineralocorticoid replacement, was administered . The testicular mass decreased progressively though the results of a subsequent ACTH stimulation test, six months later, disclosed no significant change . A follow-up CT scan, one and a half years later, showed a decrease in the size of the right adrenal mass. Int J Artif Organs, 1998 Jan, 21(1), 23 - 5 Fatal hepatic failure caused by miliary tuberculosis in a hemodialysis patient: case report; Kushihata S et al.; A 57 year-old male dialysis patient died soon after the onset of high fever, hypoglycemia, and disturbance of consciousness . Autopsy revealed granulomatous lesions associated with caseous necrosis mainly found in the liver, despite the absence of pulmonary changes on chest radiographs performed during the patients illness . It appears that tubercle bacilli were hematogenously disseminated mainly to the liver causing miliary tuberculosis without producing typical diffuse lesions in the lungs . Since tuberculosis is a common complication in hemodialysis patients, the potential development of atypical miliary tuberculosis should always be borne in mind. Antibiot Khimioter, 1998, 43(2), 20 - 3 {Effect of probiotics from bacilli on macrophage functional activity}; Sorokulova IB; The influence of new probiotics from bacilli i.e . biosporin and subalin on the functional activity of murine peritoneal macrophages was studied . After a single oral administration of the probiotics the maximum activation of the macrophages was observed in 4 hours . The activation level depended on both the dose and the probiotic . The highest value of the stimulation index was recorded with subalin . Analogous regularities were stated with parenteral administration of the probiotics . Some mechanisms of activation of peritoneal macrophages after oral administration of probiotics from live microbial cultures are discussed. Kekkaku, 1998 Feb, 73(2), 65 - 70 {Biochemical and immunological properties of the fractions of tubercle bacilli}; Azuma I; In 1954, Dr . Yuichi Yamamura and his coassociates, National Sanatorium Toneyama Hospital, has reported the formation of experimental tuberculous cavity in rabbits . This work was a milestone of the researches in the field of cellular immunology . In 1960, I have started my scientific carrier in Kyushu University Medical School as the post-graduate student under the guidance of Prof . Yamamura . Since then, I have worked on the field of biochemical and immunological properties of tubercle bacilli . The arabinose mycolate, polysaccharides, cell-wall skeleton (CWS) and trehalose dimycolate (TDM) were purified from tubercle bacilli and their Chemical structures and biological activities were investigated in detail in our laboratory . In 1971, we have reported that adjuvant active principle of tubercle bacilli was a CWS fraction, and the details of chemical structure and adjuvantity of mycobacterial CWS were investigated in our research group . The application of BCG-CWS to cancer immunotherapy was also studied . In 1974, Prof . E . Lederer and his coworkers, University of Paris, have reported that N-acetyl muramyl-L-alanyl-D-isoglutamine (MDP) was the minimum adjuvant-active structure of bacterial cell wall . We have synthesized several hundreds of MDP derivatives and selected, MDP-Lys(L18), romurtide, as the candidate of cytokine inducer for the clinical application . Romurtide is applied in cancer patients for the recovery of the number and functions of monocytes, neutrophils and platelets . These results suggest that the tubercle bacilli, especially, CWS and related synthetic MDP derivatives, are effective for the potentiation of host resistance against infectious diseases and cancer. J Leukoc Biol, 1998 Apr, 63(4), 440 - 50 Nonspecific and immune-specific up-regulation of cytokines in rabbit dermal tuberculous (BCG) lesions; Sugisaki K et al.; To our knowledge, this is the first sequential study of cytokines in tissue sections of developing and healing tuberculous (BCG) lesions . In situ hybridization, immunohistochemical, and RT-PCR techniques were used . Cytokine mRNAs showed a biphasic pattern . The percentage of mononuclear cells (MN) containing IL-1beta, TNF-alpha, MCP-1, and IL-8 mRNAs was highest in 1- to 3-day lesions, apparently because of the nonspecific inflammatory response caused by the tubercle bacilli in the BCG vaccine . At 5 days, this percentage was significantly reduced . With IFN-gamma, the peak and trough were delayed by 2 days . By 9 days, the percentage of MN containing the mRNAs of all five cytokines had again increased and the rabbits had become tuberculin-positive . In general, MCP-1 and TNF-alpha proteins and the vascular adhesion molecules, ICAM, VCAM, and perhaps ELAM, peaked at about 3 days . Many mononuclear cells surrounding the central areas of solid and liquefied caseous necrosis contained chemokine IL-8 mRNA . IL-8 is known to attract PMN, and PMN were present nearby . In contrast, MN containing chemokine MCP-1 mRNA were present more peripherally in areas rich in macrophages and lymphocytes . The early nonspecific cytokine response seems to be an adjuvant effect of the mycobacteria in BCG vaccine in that it causes a rapid entry of macrophages, lymphocytes, granulocytes, and probably dendritic cells into local sites of antigen deposition . This effect should be considered in developing improved vaccines for the prevention of tuberculosis, because BCG vaccines producing a strong early cytokine response should be more immunogenic than BCG vaccines with similar antigens producing a weak response. FEMS Immunol Med Microbiol, 1998 Feb, 20(2), 129 - 38 Characterization of antigens recognized by new monoclonal antibodies raised against culture filtrate proteins of Mycobacterium bovis bacillus Calmette-Guérin; Freer G et al.; Effective protection against Mycobacterium tuberculosis may be achieved in experimental animals by immunization with proteins secreted by tuberculous bacilli in the extracellular milieu during growth . In this study, monoclonal antibodies were raised against Mycobacterium bovis bacillus Calmette-Guerin (BCG) culture filtrate proteins or live BCG, in an attempt to identify novel mycobacterial secretion antigens: the localization of the antigens recognized by the monoclonal antibodies within the mycobacterial cell was studied and interspecies reactivity was also investigated . The monoclonal antibodies obtained recognized proteins of molecular mass ranging from 5 to 82 kDa, with a prevailing frequency in the 30 kDa region . Three of the monoclonal antibodies recognized proteins present only in culture filtrates, one reacted with a cytoplasmic antigen, while the remaining antibodies recognized components which were mainly associated with the cell wall and the cytoplasmic membrane . The chemical nature and possible identity of the antigens was checked . Three monoclonal antibodies are likely to react with novel mycobacterial antigens of 5, 42 and 82 kDa, respectively. J Trop Pediatr, 1998 Feb, 44(1), 40 - 2 Diagnosis of tuberculosis: PPD or BCG test; Sonmez E et al.; In recent years, several articles have been published about BCG tests in the diagnosis of tuberculosis, particularly in children . The test is reportedly more sensitive and more specific than tuberculin test (PPD) . We evaluated the results of simultaneous application of PPD and BCG test in order to assess its efficacy in adults and adolescents with tuberculosis (tbc) . We applied BCG test and PPD concurrently in 35 healthy controls and 41 tuberculosis cases presented to Research Hospital, Inonu University and Malatya Tuberculosis Dispensary with clinical and radiological findings . The subjects also had sputum examined for presence of acid-fast bacilli (AFB) by direct microscopy, culture on Lowenstein Jensen medium and by polymerase chain reaction (PCR) . We conclude that BCG test is more sensitive and more specific than PPD in diagnosis of tuberculosis in adults and adolescents. FEMS Immunol Med Microbiol, 1997 Dec, 19(4), 297 - 305 Stazyme, a mycobacteriolytic preparation from a Staphylococcus strain, is able to break the permeability barrier in multiple drug resistant Mycobacterium avium; Rastogi N et al.; As a strategy to augment the potential of existing drugs against Mycobacterium avium we investigated a mycobacteriolytic preparation (stazyme) from the Staphylococcus strain Clavelis, which results in significant mycobacterial growth inhibition . A total of 10 specific protein bands were characterized in the stazyme preparation: three bands within a major 40-60 kDa fraction, five bands within the range of 30-90 kDa, and two bands of about 12 and 14 kDa respectively . Tested at concentrations of 50 and 200 microg ml(-1) of total protein, stazyme was highly bactericidal against M . smegmatis, and bacteriostatic against M . tuberculosis and M . avium . Stazyme was able to break the permeability barrier of M . avium isolates, significantly enhancing the activity of other antituberculous drugs (ethambutol, rifampicin, and amikacin), used at sub-MIC level . Stazyme essentially possessed a lytic activity as evidenced by its ability to lyse purified M . smegmatis cell walls . This lytic activity was also confirmed on intact M . smegmatis and M . avium bacilli by transmission electron microscopy . Precise identification of this mycobacteriolytic determinant(s) in stazyme may be helpful to define novel drug targets in mycobacteria. Pathology, 1998 Feb, 30(1), 65 - 7 Actinomycosis of the cholecystic duct: case report and review; Ormsby AH et al.; Actinomycosis of the gall bladder, cholecystic duct or common bile duct is rare, with only 16 cases reported to our knowledge . We report a case of actinomycosis in the cholecystic duct remnant of an 80-year-old woman with a history of cholecystitis, choledocholithiasis and cholecystoduodenal fistula requiring cholecystectomy and fistula closure three years prior . Histologic sections of the cystic duct remnant showed several dense basophilic masses containing numerous, dark blue, Gram-positive branching bacilli compatible with actinomycotic granules . Fluorescent antibody staining was positive for Actinomyces naeslundii . Staining for acid-fast bacilli was negative . The pathogenesis, presentation, diagnosis and management of abdominal actinomycosis with specific reference to disease involving the gall bladder are discussed. Curr Microbiol, 1998 Apr, 36(4), 220 - 5 SASP (small, acid-soluble spore proteins) and spore properties in Bacillus thuringiensis israelensis and Bacillus sphaericus; Cucchi A et al.; Entomopathogenic bacilli B . thuringiensis israelensis (Bti) and B . sphaericus (Bf) exhibit low survival on field application . It was previously shown that their spores are very sensitive to different stress effectors (heat, UV light) and especially to osmotic variations . Since SASP (Small, Acid-Soluble Spore Proteins), alpha/beta and gamma type, are involved in spore tolerance to heat, UV light, peroxide, and salt, they were analyzed in Bti and Bf . The molecular weight, migration pattern and amino acid composition of different SASP were determined and compared with other bacilli, in particular to B . subtilis . A relation between spore osmotolerance, SASP content, and amino acid composition was shown . In addition, the absence of gamma SASP in Bti and Bf is discussed. Curr Biol, 1998 Jan 29, 8(3), R99 - R101 Microbial immunology: a new mechanism for immune subversion; Lachmann PJ; The number of mechanisms that have evolved in microbes to subvert the immune response seems limitless . Tubercle bacilli have found a novel way to coat themselves with the C3 complement protein and invade macrophages by interactions with complement receptors. Antimicrob Agents Chemother, 1998 Feb, 42(2), 419 - 24 In vitro activities of Y-688, a new 7-substituted fluoroquinolone, against anaerobic bacteria; MacGowan AP et al.; The in vitro activities of Y-688, a new 7-substituted fluoroquinolone derivative, against 317 nonduplicate anaerobic isolates were determined . Eighty-five percent of the Bacteroides fragilis group (n = 89) were inhibited by < or = 2 mg of Y-688 per liter, while 78, 100, 89, and 98% of gram-negative bacilli (n = 135), gram-positive cocci (n = 59), and non-spore-forming (n = 58) and spore-forming (n = 51) gram-positive bacilli, respectively, were inhibited by < or = 1 mg of Y-688 per liter. Electrophoresis, 1997 Dec, 18(14), 2558 - 65 The interaction between Mycobacterium and the macrophage analyzed by two-dimensional polyacrylamide gel electrophoresis; Sturgill-Koszycki S et al.; The intramacrophage pathogen Mycobacterium avium resides in a vacuole which displays unusual fusion characteristics, expressed as both a failure to mature into phagolysosomes and a continued access to the early recycling pathway . In contrast, compartments containing inert IgG-opsonized latex beads mature to phagolysosomes . Techniques were developed for the isolation of these particle-containing phagosomes from macrophages to facilitate analysis of phagosomal constituents by electrophoresis and autoradiography . Metabolic labeling of macrophages followed by phagosome isolation and two-dimensional polyacrylamide gel electrophoresis revealed only minor differences in the protein profiles between the M . avium and IgG-bead phagosomes despite the marked differences in the fusigenicity of the respective vacuoles . Pulse-chase labeling experiments revealed greater differences in the accessibility of Mycobacterium avium and IgG-bead phagosomes to newly synthesized proteins . These phagosome isolation techniques were extended to analyze the protein synthesis profile of intracellular M . avium for comparison with bacteria that were metabolically labeled in broth culture . Not surprisingly, the majority of polypeptides in the bacilli were common to both growth conditions . However, despite these similarities, intracellular M . avium express several unique proteins, most notably one abundant protein with a molecular weight of 51 kDa . In addition, the bacteria manifest a restricted set of proteins expressed while in stasis shortly after infection. Clin Infect Dis, 1998 Mar, 26(3), 576 - 83 Randomized comparison of sulbactam/cefoperazone with imipenem as empirical monotherapy for febrile granulocytopenic patients; Winston DJ et al.; In a prospective, randomized, controlled trial, we compared sulbactam/cefoperazone with imipenem as empirical monotherapy for febrile, granulocytopenic patients; 101 patients received sulbactam/cefoperazone (2 g/4 g every 12 hours) and 102 patients received imipenem (500 mg every 6 hours) . Documented infections were present in 40% of patients treated with sulbactam/cefoperazone (40 of 101) and in 39% of patients receiving imipenem (40 of 102) . The number of pretherapy gram-positive pathogens (52 isolates) was twice the number of pretherapy gram-negative pathogens (26 isolates) . The overall favorable clinical response rates for sulbactam/cefoperazone (91 of 103 patients, or 88%) and imipenem (84 of 104 patients, or 81%) were similar . Both drugs were generally well tolerated . However, diarrhea occurred more often in patients treated with sulbactam/cefoperazone (31 of 101 patients, or 31%, vs . 15 of 102 patients, or 15%; P = .007), while seizures developed only in patients receiving imipenem (0 of 101 patients vs . 3 of 102 patients, or 3%) . Superinfections developed in 16% of patients in both study groups but were infrequently caused by beta-lactam-resistant gram-negative bacilli (two cases with sulbactam/cefoperazone therapy and six cases with imipenem) . These results support the efficacy and safety of either sulbactam/cefoperazone or imipenem as empirical monotherapy for febrile granulocytopenic patients. J Zoo Wildl Med, 1997 Dec, 28(4), 494 - 7 Fatal Erysipelothrix rhusiopathiae septicemia in a captive Pacific white-sided dolphin (Lagenorhyncus obliquidens); Kinsel MJ et al.; One male of a group of seven Pacific white-sided dolphins (Lagenorhynchus obliquidens) died after a brief period of nonspecific clinical signs . Four beluga whales (Delphinapterus leucas) and four harbor seals (Phoca vitulina) were managed in the same water system . Gross examination of the dolphin revealed only moderately enlarged mesenteric lymph nodes . Histopathology revealed small to massive numbers of gram-positive bacilli, usually intravascular, in all tissues . Bacteria were both extracellular and present in macrophages, monocytes, and neutrophils . Aerobic bacterial culture of lung, liver, kidney, and spleen yielded pure cultures of Erysipelothrix rhusiopathiae . Based on clinical course, histopathology, and bacteriology, a diagnosis of acute erysipelas septicemia was made . None of the other cetaceans or pinnipeds exhibited clinical signs. Neurologia, 1998 Jan, 13(1), 41 - 4 {Patient with Hansen disease and lepromatous reaction with predominant neural involvement}; Galvez J et al.; We describe a patient with a diagnosis of Hansen's disease borderline type, presenting as cutaneous lesions and silent multineuritis . Samples of nasal mucus, earlobe and cutaneous lesions were positive for acid-fast bacilli . He was given treatment with rifampin, dapsone and clofazimine . Five years later, he developed fever, poliarthritis, orchitis and hepatic involvement . Searching for acid-fast bacilli in many cutaneous and mucosal locations was fruitfulness . Because of clinical suspicion of erythema nodosum leprosum, he was treated with steroids with improvement of his clinical picture, but subsequently he developed multineuritis with many sensitive symptoms . A high number of bacilli was seen in nerve biopsy . We comment on atypical features of clinical evolution and erythema nodosum leprosum, and emphasize the significance of large number of bacilli into peripheral nerve in contrast with their absence at other levels. Clin Diagn Lab Immunol, 1998 Mar, 5(2), 211 - 8 Involvement of antilipoarabinomannan antibodies in classical complement activation in tuberculosis; Hetland G et al.; We examined alternative and classical complement activation induced by whole bacilli of Mycobacterium bovis BCG and Mycobacterium tuberculosis products . After exposure to BCG, there were higher levels of the terminal complement complex in sera from Indian tuberculosis patients than in sera from healthy controls . The addition of BCG with or without EGTA to these sera indicated that approximately 70 to 85% of the total levels of the terminal complement complex was formed by classical activation . Sera from Indian tuberculosis patients contained more antibody to lipoarabinomannan (LAM) than sera from healthy Indians . Levels of anti-LAM immunoglobulin G2 (IgG2), but not anti-LAM IgM, correlated positively with classical activation induced by BCG in the sera . By flow cytometry, deposition of C3 and terminal complement complex on bacilli incubated with normal human serum was demonstrated . The anticomplement staining was significantly reduced in the presence of EGTA and EDTA . Flow cytometry also revealed the binding of complement to BCG incubated with rabbit anti-LAM and then with factor B-depleted serum . This indicates that classical activation plays a major role in complement activation induced by mycobacteria and that anti-LAM IgG on the bacilli can mediate this response . Classical complement activation may be important for the extent of phagocytosis of M . tuberculosis by mononuclear phagocytes, which may influence the course after infection. Acta Microbiol Pol, 1997, 46(4), 377 - 85 Haemolytic activity of Mycobacterium spp; Brzychcy M et al.; Haemolytic activity of clinical isolates of Mycobacterium bacilli (98) was determined by the method of King et al., 1993 . During 3-h incubation, all M . tuberculosis (MTB) isolates (28) and one out of 38 M . avium-intracellulare (MAI) strains, produced a strong contact-dependent haemolysin (CDH) . Six MAI strains expressed a weak CDH . One MAI isolate produced a strong and five other MAI strains a weak contact-independent haemolysin (CIH) . Two M . bovis BCG strains and 7 M . vaccae strains did not demonstrate haemolytic activity . The persistence of chosen Mycobacterium strains differing by haemolytic activity, in the spleens of infected C57BL/6 mice was examined . Mycobacteria producing a strong CDH (MTB H37Rv, MTB 101/92, MAI 83/93) or CIH (MAI 475/93) survived in the spleens of nonimmunized or M . bovis BCG-immunized mice for longer time than MAI strains expressing weak haemolytic activity or M . bovis BCG vaccine strain. Nihon Hansenbyo Gakkai Zasshi, 1997 Nov, 66(3), 223 - 6 A genomic study on the cultivable and nerve invading Mycobacterium HI-75 after the recovery 3 months of the inoculation to nude mice; Sakai T et al.; The sequence of the polymerase chain reaction (PCR) product of 16S ribosomal RNA (16S rRNA) of the leproma-derived and cultivable Mycobacterium HI-75 (M . HI-75) which was obtained from the infected regions of inoculated mice, was examined and compared with that of the cultured bacteria by the direct sequencing techniques . The sequence was completely consistent with the cultured bacilli in the comparable 837 bases of 16S rRNA . The mycobacterium examined in this study was originally isolated as M . leprae (ML) by Skinsnes, et al . in 1975 from leproma of a lepromatous type Hansen's disease patient and therefore named as Mycobacterium leprae HI-75 by them, and was maintained from 1984 using either Ogawa's or Sauton's media in the beginning and Ogawa's medium enriched with glucronic acid and N-acetyl-D-glucosamine recently . Sasaki and Hamit reported the nerve invasion and the growth of the inoculated bacilli either to the nude mice or the I131 treated immunocompromised Swiss mice . We previously reported that cultured HI-75 was most similar to M . scrofulaceum by the direct sequencing of the gene of 16S rRNA . The 16S rRNA obtained from the mouse tissue in the present study indicated that M . HI-75 would be a variant of M . scrofulaceum possessing an ability to invade into peripheral nerve . The results suggest that the HI-75 strain claims a nature as a pathogen to develop a leproma-like lesion. Nihon Hansenbyo Gakkai Zasshi, 1997 Nov, 66(3), 215 - 21 {On the lesions caused by a leproma-derived and cultivated Mycobacterium HI-75 produced in ddY mice . With special reference to a factor influencing the lesions and the differences from those by BCG}; Furuno Y; Not only in the experimental leprosy, primary aim to make every experimental model crucial for the medical research has been the simulation of the aspect of disease encountered in human case by the simplest possible way . The present study was conducted to do so making some variations in addition to the experimental lepromata, produced in nude mice by Sasaki et al . and by Hamit, utilizing a leproma-derived and cultivated Mycobacterium HI-75 (HI-75) . In this study HI-75, Mycobacterium bovip BCG (BCG) and female SPF ddY(ddY) were utilized to make experimental models . In addition to these combinations, the effect of the immunization of beta-glucuronidase binding protein (BGBP) to the lesion was also examined . The BGBP extracted from pisum sativum and utilized in this study shows cross-immunoreactivity with those of HI-75 and M . leprae . As the results, the lesions caused by HI-75 and BCG were somewhat resembling though HI-75 caused a little more extensive lesions especially in lymphocytic and monocytic infiltration . Also HI-75 caused distinct nerve lesions(NL) in which the bacilli were often encountered in the endoneurium but not in those by BCG . Contrarily in mice immunized with BGBP, the lesions were only a little milder and the affected tissue was a little fibrosed . However, in NL the solid form HI-75 were more often observed in the endoneurium . The results indicated that the effect of BGBP immunization on the HI-75 induced lesion was not very clear by the present study alone, however, the proposed models itself should be and will become very useful, for experimental leprology with only slight modifications. Eur J Clin Microbiol Infect Dis, 1998 Jan, 17(1), 53 - 5 Fatal Legionella longbeachae infection following heart transplantation; Korman TM et al.; A case of fatal Legionella longbeachae infection following heart transplantation is described . Gram stains of respiratory secretions on day 17 posttransplant revealed leucocytes and gram-negative bacilli, but there was no growth on routine bacterial culture . Legionella longbeachae serogroup 1 was isolated from respiratory specimens, blood, and postmortem lung tissue . Legionella longbeachae is a common cause of legionellosis in Australia, and infection has been associated with exposure to potting mixes . Specific culture for Legionella spp . should be performed for any patient who develops pneumonia following organ transplantation. J Natl Med Assoc, 1998 Feb, 90(2), 73 - 6 Tuberculosis in African Americans: clinical characteristics and outcome; Funnye AS et al.; This study examined the clinical characteristics and outcome of pulmonary tuberculosis in African Americans hospitalized in a teaching hospital in south-central Los Angeles from May 1992 through April 1994 . The charts of 41 African Americans with culture-positive Mycobacterium tuberculosis were reviewed . Predisposing factors for pulmonary tuberculosis were identified in nearly half of cases . Cough and fever were the most common symptoms . Seventy-six percent had positive acid-fast bacilli (AFB) smears . Nine patients were human immunodeficiency virus (HIV)-positive, and 6 of 9 HIV-positive patients had positive AFB smears whereas 17 of 19 HIV-negative patients had positive AFB smears . Radiographic changes were not significantly different between HIV-positive and HIV-negative patients . Drug resistance was identified in nine of 31 patients (29%) . Eight of 41 patients (19.5%) died, with 2 being drug resistant . Human immunodeficiency virus infection was a major predisposing factor for tuberculosis, and no statistical differences were found in radiographic features or AFB smear positivity between HIV-positive and HIV-negative patients . Drug resistance and mortality were disproportionately high . These results indicate that HIV infection and drug resistance are major problems that predispose for tuberculosis infection and make its treatment difficult. Gastroenterol Hepatol, 1997 Dec, 20(10), 490 - 3 {Isolated colonic tuberculosis}; Perez Fernandez T et al.; Two cases of colonic tuberculosis (TB) isolated in two elderly, not HIV seropositive women, presenting unspecific clinical manifestations (constitutional syndrome, fever, abdominal pain and diarrhea) and stenosis of the colon in diagnostic imaging techniques are presented . In the second case, endoscopy showed stenosis of the colonic lumen and inflammatory mucosa, the biopsy of which demonstrated granulation tissue with no signs of specificity (in the first case, technical problems did not allow the colonoscopy to reach the affected site) . In both cases, diagnosis was performed postoperatively by study of the surgical pieces . Biopsy showed granulomas with acid-alcohol resistant bacilli . Both patients responded favorably to tuberculostatic treatment. Trends Microbiol, 1998 Feb, 6(2), 47 - 9; discussion 49-50 Mycobacterium tuberculosis and the complement system; Schlesinger LS; Accumulated evidence to date confirms the importance of the C3-CR pathway in the phagocytosis of pathogenic mycobacteria . Detailed receptor-ligand studies for phagocytosis are creating the framework to test the hypothesis that the entry pathway for these bacteria influences the immediate host cell response and their intracellular fate . These types of study are particularly important for improving our understanding of the outcome of primary infection in humans, where the number of bacilli is presumed to be very low. Lepr Rev, 1997 Dec, 68(4), 301 - 15 Transmission and protection in leprosy: indications of the role of mucosal immunity; Ramaprasad P et al.; Recent advances in treatment have achieved a large drop in the prevalence of active leprosy cases, but the incidence is at best decreasing slowly . Most people within leprosy-endemic populations have been exposed to Mycobacterium leprae, but few develop disease and it seems likely that the majority of the population develops protective immunity . If the site of initial infection is in the nose, dissemination of bacilli around the body to skin and nerve implies that the initial infection is bacilliferous and it has been shown that nasal M . leprae are detectable by polymerase chain reaction (PCR) of nasal swabs . Since salivary anti-M . leprae IgA (sMLIgA) levels are correlated with protection, we have surveyed groups of leprosy patients, contacts and the general population for both their sMLIgA and nasal PCR positivity . A total of 304 subjects were enrolled in the study: PCR and mucosal challenge tests were performed in 204 of these individuals . sMLIgA was present in 66% of treated patients, 76% of leprosy workers and 72% of healthy contacts . However, only 33% of indigenous subjects were sMLIgA+, in contrast to the earlier studies showing 74% positivity . PCR for M . leprae was present in both household contacts (2%) and indigenous controls (5%) . In a subsequent follow-up study, nasal swabs were taken from 97 of those studied in the first series: three PCR+ individuals followed up after one year became negative, while of the remaining 94 PCR- individuals retested, 2 became positive . Of 112 subjects retested with the mucosal challenge test for sMLIgA: 22 converted from positive to negative and 12 from negative to positive . These results suggest that there is widespread subclinical transmission of M . leprae with transient infection of the nose resulting in the development of a mucosal immune response, despite the fact that few individuals will develop clinical disease . This may explain the current lack of effect of multidrug therapy (MDT) control programmes on incidence, although the reduction in general population immunity is consistent with some effect of MDT on transmission. Clin Infect Dis, 1998 Feb, 26(2), 389 - 92 Bordetella holmesii-like organisms associated with septicemia, endocarditis, and respiratory failure; Tang YW et al.; We recovered an unusual bacterial strain from blood or sputum of three patients with septicemia, endocarditis, and/or respiratory failure . The three isolates were thin, curved, gram-negative, light brown, pigment-producing bacilli with variable catalase activity . They were asaccharolytic, oxidase-negative, nonmotile, and fastidious . Identification was not possible on the basis of these characteristics alone or in combination with cellular fatty acid profiles . Nucleic acid amplification and sequence analysis of the 16S rRNA gene revealed that all three isolates were identical and most closely related to the emerging pathogen Bordetella holmesii, diverging from the published sequence at three nucleotide positions (99.8% similarity) . Isolation of a B . holmesii-like pathogen from sputum suggests that, in addition to producing septicemia, the organism may inhabit the respiratory tract like other Bordetella species. Br J Anaesth, 1998 Jan, 80(1), 41 - 5 Endogenous source of bacteria in tracheal tube and proximal ventilator breathing system in intensive care patients; Inglis TJ et al.; Although bacteria from both the ventilator breathing system and the gastrointestinal tract have been implicated in the pathogenesis of ventilator-associated pneumonia, an endogenous source of bacteria in the proximal respiratory breathing system has yet to be demonstrated conclusively . We investigated a potential route of bacterial colonization from the stomach contents to the efferent limb of the ventilator breathing system by bacterial culture of daily specimens from six sites in 20 surgical intensive care patients . Gram-negative bacilli were isolated in a progressively increasing proportion of samples at successive sampling points, consistent with an endogenous-to-external route of spread (patients, chi-square = 14.12, P < 0.02; samples, chi-square = 106.15, P < 0.001) . Identical strains of gram-negative bacilli, confirmed by REPS typing, were found at two or more sites in seven patients . In all seven, gram-negative bacilli were first isolated from a site in the patient . In none of the 20 patients was there evidence of a sequence of colonization from the ventilator tubing or Y-piece connector towards the patient . Probable colonization sequences plotted from the time of first isolation supported the proposed sequence in six patients, and in five began with the stomach contents . Isolation sequences contrary to the proposed direction of colonization involved four bacterial species and two patients, and did not extend beyond two sample sites . These findings imply that the retrograde route of bacterial colonization of the ventilated lung extends into the proximal respiratory breathing system and may help to identify additional targets for preventive intervention. Chest, 1998 Feb, 113(2), 542 - 8 Pulmonary Mycobacterium avium complex disease without dissemination in HIV-infected patients; Hocqueloux L et al.; Pulmonary disease due to Mycobacterium avium complex (MAC) without evidence of dissemination is uncommon in HIV-infected patients . Five cases were observed over a 2-year period . All patients had AIDS and the median CD4 cell count at the time of presentation was 90 x 10(6)/L . Radiographic patterns included unilobar alveolar infiltrates or diffuse alveolar densities . All patients had a favorable clinical response to antimycobacterial chemotherapy with a median follow-up period of 10 months . MAC should be considered in HIV-infected patients with positive respiratory samples for acid-fast bacilli and pulmonary infiltrates . Patients with such findings in whom presumptive therapy for tuberculosis has failed should receive broad-spectrum antimycobacterial chemotherapy until final identification is available. Immunology, 1997 Dec, 92(4), 429 - 36 Lipids from Mycobacterium leprae cell wall suppress T-cell activation in vivo and in vitro; Moura AC et al.; The influence of Mycobacterium leprae cell wall lipids on lymphocyte functions has been investigated in vivo (delayed-type hypersensitivity) and in vitro . The inflammatory response has been earlier evaluated by the mouse footpad oedema model and the delipidated mycobacteria evoked a mild but significant inflammatory response . Herein a higher level of hypersensitivity reaction was observed with delipidated bacilli than with the intact mycobacteria . The lipids obtained from the extract of M . leprae external cell wall were used to prepare liposomes, which have not been shown to be toxic to lymphocytes . The method of lipidic extraction and the sodium dodecyl sulphate-polyacrylamide gel electrophoresis of the lipid fraction did not reveal any trace of proteins . Thin-layer chromatography of this extract detected four different bands with an apolar character, suggestive of mycolic and fatty acids . These same M . leprae liposomes potently suppressed lymph node cells, as well CD4+ and CD8+ T-cell lines, and an antigen-specific T-cell clone (T 4-9) proliferation, even under potent stimulus . Cholesterol-choline liposomes, unrelated to M . leprae liposomes, used as a control in the biological assays showed no significant effect on lymphoblastic activity, which points to the specificity of M . leprae lipids . These data demonstrated that M . leprae cell wall lipids induce immune suppression in mice without causing any membrane alteration in T cells as assessed throughout kinetic studies in vitro . This fact is closely related to the down-regulating effect induced by M . leprae lipids which we have previously observed in macrophage functions in vivo and in vitro . Although this lipidic fraction showed a suppressive action on T lymphocytes in vitro (proliferation) and in vivo (delayed-type hypersensitivity), its possible significance in the establishment of a specific immune response to M . leprae must be further investigated. J Gastroenterol, 1998 Feb, 33(1), 14 - 7 Evaluation of combined antibiotic-omeprazole therapies in Helicobacter pylori-infected Mongolian gerbils; Kusuhara H et al.; Mongolian gerbils are a laboratory host for gastric colonization with Helicobacter pylori, showing gastritis followed by typical gastric ulcer after infection with H . pylori . In such gerbils, we evaluated combined therapies of amoxicillin (AMPC) and clarithromycin (CAM) as antibiotics, and omeprazole (OPZ) as a H+/K+ adenosine triphosphatase (ATPase) inhibitor . The gerbils were orally inoculated with 2 x 10(8) bacilli of H . pylori ATCC 43504 . Four weeks after inoculation, the infected gerbils were orally treated singly with OPZ, AMPC, and CAM, and their insufficient efficacy on bacterial clearance was confirmed by a polymerase chain reaction technique, and by a culture method . In contrast, combined therapy of OPZ plus either AMPC or CAM showed significant bacterial clearance, demonstrating the efficacy of this combined therapy in the gerbil model . Mongolian gerbils are suggested to be useful for the pharmacological evaluation of anti-H . pylori compounds. Rev Mal Respir, 1997 Dec, 14 Suppl 5, S124 - 9 {Prevention of tuberculosis}; Zellweger JP; Tuberculosis is transmitted by aerial route from an infected patient to a healthy subject and is facilitated when the receiver is immunologically sensitive . Even when the risk of transmission is low, measures should be taken to prevent emission of bacilli, their suspension in air and inhalation by sensitive subjects, especially immunodeficient subjects . Surveillance of hospital staff and preventive antituberculosis regimens are generally recommended, but often quite controversial. Rev Mal Respir, 1997 Dec, 14 Suppl 5, S105 - 20 {Surgery of thoracic and pulmonary tuberculosis and the sequelae of its treatment in adults}; Riquet M et al.; Surgery for tuberculosis was the starting point for thoracic and cardiovascular surgery in the modern day, but its place was more and more restricted to the treatment of the disease . Excisions (lobectomies, pneumonectomies, segmentestomies) currently represent the majority of operations, after this come operations on the pleura (decortication) and rarely those on the thoracic wall (thoracoplasty, parietectomy) . The indications for excision are principally encountered with disease of the parenchyma itself: progressive disease under treatment or with resistant tubercle bacilli, sequelae of parenchymal complications (infections, aspergilloma or haemoptysis) and certain forms of atypical mycobacteria, and also a small but significant group in which excisions are aimed at diagnosis . Sometimes excisions are associated by necessity with decortication for pleural disease which may or may not have originally been intended for the underlying parenchyma or the lesions may be the sequelae of previous complications of treatment such as collapse therapy . Occasionally surgery is indicated in the treatment of lymph node masses in the mediastinum which have not responded to antituberculous therapy and during the treatment bronchial complications have evolved or there have been other sequelae . As for the indications for surgery of the thoracic wall such as thoracoplasty, they appear more than ever obsolete and even if they are still used in certain complications of surgery, they have apart from a few exceptions, lost their original therapeutic role in tuberculosis . However, currently there is a recrudescence of tuberculosis favoured by certain socio-economic situations and strengthened by the appearance of TB cultures which are more and more resistant . The surgery of tuberculosis in its oldest forms (thoracoplasty and removal of cavities) can no longer be said to be the surgery of the past . They proved in the old days that they could cure . Surgery has once more its place in the therapeutic arsenal of new forms of the disease and indirectly in limiting the risk of spread it has a role to play in prevention. Rev Mal Respir, 1997 Dec, 14 Suppl 5, S49 - 59 {Tuberculous infection and pulmonary tuberculosis in adults}; Huchon G; A tuberculous infection is the result of inhalation of tubercle bacilli either in great numbers or in subjects with diminished immunity . Clinical tuberculosis will only occur in 10 per cent of subjects following a first infection (primary tuberculosis) or subsequently (secondary tuberculosis or by a reactivation of a tuberculous lesion) . All the intrathoracic structures may be involved in isolation or in the case of extra thoracic tuberculosis eventually disseminated . The clinical manifestations are most often non-specific . The persistence of respiratory symptoms are nevertheless suggestive, above all in a subject belonging to a group at elevated risk of tuberculosis . The radiological aspects may be very suggestive of tuberculosis . The diagnosis of an infection is based on a study of the skin responses to tuberculin and those on tuberculosis on the evidence of the tubercle bacillus. Rev Mal Respir, 1997 Dec, 14 Suppl 5, S27 - 32 {The natural history of tuberculosis infection and skin tuberculin reaction}; Flament-Saillour M et al.; Though most often asymptomatic, tuberculous infection induces a delayed hypersensitivity reaction in the host by activating cellular immunity thus rendering the host refractory, "a priori", to a new infection; at least provided that the infecting dose is not massive or that the immune system of the host is not compromised . Less that ten per cent of immuno-competent individuals infected by Mycobacterium tuberculosis will develop tuberculous disease during their life . The intradermal reaction (IDR to tuberculin) in revealing delayed hypersensitivity to Mycobacterial antigens is in the absence of obvious signs, the only means of diagnosing a tuberculous infection in an individual . It is performed in France by an intradermal injection of 0.1 mls (10 U) of Merieux tuberculin . The response is read at 72 hours . In those who have not had BCG vaccination, an area of induration with a diameter of greater than or equal to 10 mm gives a positive result and is evidence of a tuberculous infection . The test is negative if the diameter is less than 5 mm and indeterminate between 5 and 9 mm . These indeterminate reactions may be the consequence of previous BCG vaccination or of a contact with atypical Mycobacteria in the environment . An IDR of greater than or equal to 10 mm less than ten years after BCG vaccination would not permit any discrimination between a reaction to the vaccine or an authentic tuberculous infection . On the other hand, an IDR of greater than 10 mm ten years after BCG vaccination is evidence of renewed contact with wild tubercle bacilli in 88 per cent of cases . In individuals whose immune defence is altered in particular in patients infected with HIV the threshold of positivity for IDR is lowered to 5 mm. Rev Mal Respir, 1997 Dec, 14 Suppl 5, S19 - 26 {Pathophysiology and immunology of tuberculosis}; Marchal G; Only isolated bacilli are capable of reaching the pulmonary alveoli . Draining towards the lymphatic glanglia which corresponds to the infected pulmonary segment or transported by alveolar macrophages after being phagocytosed, these bacteria liberate molecules (antigens) presented to T lymphocytes . After clonal expansion, specific lymphocytes migrate out of the lymph nodes . From the initial area, other areas are infected and these specific lymphocytes lead to a local inflammatory reaction which is very rich in cells, in particular in activated monocytes and macrophages . The inflammatory granuloma or "tubercle" leads to control of the infection in the majority of cases . The inverse of this is that in five or ten per cent of cases a part of this granuloma is necrosed and caseus and leads to (or accompanies) an intense bacterial multiplication . At this stage with the formation of the cavity numerous bacilli may seed other regions of the lung or infect other people . The immune response in which T lymphocytes play a fundamental role thus permit at the same time the control of infection and the establishment of a lesion assuring the perpetuation of the species of Mycobacterium tuberculosis by contaminating new subjects . The respective roles of the different types of T lymphocyte and of liberated lymphokines remains to be determined . Also the principle antigens of the bacillus need to be characterised . The "dominant" antigens are probably liberated by bacteria during their growth phase. Am J Clin Pathol, 1998 Mar, 109(3), 331 - 4 Histologic parameters predictive of mycobacterial infection; Tang YW et al.; Tissue specimens from a wide variety of anatomic locations are frequently examined for mycobacteria using a combination of cultures and special stains . Auramine-rhodamine (AR) staining is a sensitive method for detecting acid-fast bacilli (AFB) in tissue sections . We reviewed 85 AR-positive and 275 randomly selected AR-negative biopsy specimens collected during the past 2 years at the Mayo Clinic, Rochester, Minn . Pathologic diagnoses and culture results were also reviewed . Biopsy specimens containing necrotizing granulomas yielded the highest positivity rate for AFB (61 {47.7%}), followed by nonnecrotizing granulomas (14 {17.7%}) . Poorly formed granulomas (5 {16.1%}) and acute inflammation (5 {15.6%}) were less frequently positive . Cases with fibrotic or hyalinized granulomas, nonspecific chronic inflammation, nonspecific reactive or reparative changes, no significant histologic abnormality, or malignancy failed to disclose AFB . These specimens, which were consistently negative for AFB, were responsible for 25% of the samples submitted . Of the 360 tissue specimens submitted, 166 had a corresponding mycobacterial culture . Mycobacteria were cultured only from the biopsy specimens that contained necrotizing granulomas (38.2%), nonnecrotizing granulomas (32.4%), poorly formed granulomas (30.0%), or acute inflammation (15.8%) . Tissues with fibrotic or hyalinized granulomas, nonspecific chronic inflammation, nonspecific reactive or reparative changes, no significant histologic abnormality, or malignancy failed to yield positive cultures . These data suggest that biopsy specimens with these latter diagnoses are inappropriate specimens for mycobacterial culture or AR staining. Eur Respir J, 1997 Dec, 10(12), 2722 - 4 Bronchoscopic diagnosis of sarcoidosis; Leonard C et al.; Transbronchial lung biopsy (TBLB), transbronchial needle aspiration (TBNA) of mediastinal lymph nodes and bronchoalveolar lavage (BAL) are routinely performed at fibreoptic bronchoscopy . Up to the present time, no data have been available on the efficacy of performing all three of these procedures simultaneously in the bronchoscopic work-up of sarcoidosis . A prospective study was undertaken to compare the diagnostic yield from TBLB, TBNA and BAL in patients presenting with clinical and radiological features typical of sarcoidosis . Thirteen consecutive patients with clinical and radiological features consistent with stage I and II sarcoidosis underwent bronchoscopy with TBLB, TBNA and BAL . Noncaseating granulomata (stain and culture negative for tuberculosis bacilli and fungi) were found in seven of the 13 patients by TBLB, and in six of the 13 patients by TBNA (of which four patients had negative TBLB) . Eight of the 13 patients had classical "sarcoid" BAL findings, i.e . >12% lymphocytes, and high CD4+:CD8+ lymphocyte ratio . Combining TBLB, TBNA and BAL gave a diagnostic sensitivity of 100% (12 out of 12 patients) for sarcoidosis . The remaining patient had nondiagnostic bronchoscopic studies and mediastinoscopy biopsy showed a non-Hodgkin's lymphoma . Our data suggest that performing simultaneous transbronchial lung biopsy, transbronchial needle aspiration and bronchoalveolar lavage produces optimal results in the diagnosis of sarcoidosis. Pneumonol Alergol Pol, 1997, 65(9-10), 643 - 8 {Non-sporeforming anaerobic bacteria in bronchoalveolar lavage fluid of patients with pneumonia during the course of lung cancer}; Jassem E et al.; The aim of this study was to assess the occurrence of non-sporeforming anaerobes in bronchoalveolar lavage in patients with pneumonia coexisting with lung cancer . Material consisted of 40 patients with lung cancer . Bronchoalveolar lavage was performed before administration of antimicrobial treatment and obtained material was cultivated in anaerobic and aerobic conditions . Quantitative assessment of anaerobic bacteria and their susceptibility to common antimicrobial agents were also performed . Peptostreptococcus, Prevotella, Fusobacterium and Bacteroides were the most common anaerobes . Among aerobic bacteria, the most frequent were G-negative bacilli . G-negative anaerobes were susceptible to most tested agents, whereas G-positive rods were resistant to metronidazole and tinidazole . This study demonstrates presence of non-sporeforming anaerobic bacteria in lower respiratory tract infections accompanying lung cancer. Int J Tuberc Lung Dis, 1997 Dec, 1(6), 509 - 17 A controlled clinical trial of oral short-course regimens in the treatment of sputum-positive pulmonary tuberculosis . Tuberculosis Research Centre; An outbreak involving extensive transmission of a virulent strain of Mycobacterium tuberculosis; Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USABACKGROUND AND METHODS: From 1994 to 1996, there was a large outbreak of tuberculosis in a small, rural community with a population at low risk for tuberculosis . Twenty-one patients with tuberculosis (15 with positive cultures) were identified; the DNA fingerprints of the 13 isolates available for testing were identical . To determine the extent of transmission, we investigated both the close and casual contacts of the patients . Using a mouse model, we also studied the virulence of the strain of Mycobacterium tuberculosis that caused the outbreak . RESULTS: The index patient, in whom tuberculosis was diagnosed in 1995; the source patient, in whom the disease was diagnosed in 1994; and a patient in whom the disease was diagnosed in 1996 infected the other 18 persons . In five, active disease developed after only brief, casual exposure . There was extensive transmission from the three patients to both close and casual contacts . Of the 429 contacts, 311 (72 percent) had positive skin tests, including 81 {corrected} with documented skin-test conversions . Mice infected with the virulent Erdman strain of M . tuberculosis had approximately 1000 bacilli per lung after 10 days and about 10,000 bacilli per lung after 20 days . In contrast, mice infected with the strain involved in the outbreak had about 10,000 bacilli per lung after 10 days and about 10 million bacilli per lung after 20 days . CONCLUSIONS: In this outbreak of tuberculosis, the growth characteristics of the