Arch Neurol, 1995 Nov, 52(11), 1081 - 6 Plasma and red blood cell thiamine deficiency in patients with dementia of the Alzheimer's type; Gold M et al.; OBJECTIVES: To determine the prevalence of plasma thiamine deficiency in patients referred to a memory disorder clinic and to compare plasma thiamine levels with red blood cell (RBC) thiamine levels . To determine if patients with senile dementia of the Alzheimer's type (SDAT) differ from those without SDAT in either plasma or RBC thiamine levels . DESIGN: Case-control study . SETTING: Ambulatory care referral center . PATIENTS: Consecutive sample of 34 patients; 17 patients who met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer's disease and 17 patients with other forms of dementia . METHODS: Plasma and RBC thiamine levels were determined in all patients with the use of a microbiologic assay known for its specificity to biological forms of thiamine . Vitamin supplementation was determined by chart review . OUTCOME MEASURES: Plasma and RBC thiamine levels . RESULTS: Patients with SDAT were found to have significantly lower plasma thiamine levels than patients without SDAT . Low plasma thiamine levels were detected in a significantly larger proportion of patients with SDAT than in patients without SDAT . Red blood cell thiamine levels did not correlate with the clinical diagnosis of SDAT . Vitamin supplementation did not correlate with diagnosis and plasma or RBC thiamine levels . CONCLUSIONS: A significant proportion of patients with SDAT may have a thiamine deficiency, which may have an impact on cognitive function . Currently used assays may not be adequate to assess thiamine status. Acta Cytol, 1995 Nov-Dec, 39(6), 1089 - 93 Diagnosis of Pneumocystis carinii pneumonia by bronchoalveolar lavage in AIDS patients . Comparison of Diff-Quik, fungifluor stain, direct immunofluorescence test and polymerase chain reaction; Armbruster C et al.; OBJECTIVE: To assess the sensitivity, specificity and accuracy of Diff-Quik, fungifluor stain, the direct immunofluorescence test (DIFT) and the polymerase chain reaction (PCR) in the diagnosis of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients . STUDY DESIGN: From December 1992 through November 1993, 112 bronchoalveolar lavage fluid (BALF) samples were obtained from 80 HIV-infected patients . BALF samples were processed for cytologic and microbiologic analysis and for PCR . Cytologic examination was carried out on Diff-Quik-stained cytocentrifuge preparations and with May-Grunwald-Giemsa staining and fungifluor staining . For diagnosis of PC infection, DIFT and PCR were used . RESULTS: Thirty-two of 112 acute episodes were caused by P carinii . Diff-Quik had the highest sensitivity (84.8%) as compared to fungifluor stain (60.0%), DIFT (59.4%) and PCR (65.6%) . The specificity was 98.7% with Diff-Quik, 100% with fungifluor stain, and 98.6% and 97.3% with DIFT and PCR, respectively . Accuracy was high with every method (94.4% with Diff-Quik, 88.3% with fungifluor stain, 86.7% with DIFT and 87.6% with PCR) . CONCLUSION: Diff-Quik is a good diagnostic tool in the diagnosis of PCP . The combination of Diff-Quik and fungifluor stain is recommended because of its cost-effectiveness and because of its rapid diagnosis of severe PCP . PCR and DIFT should be used only on patients judged clinically to have PCP with discrepant results in Diff-Quik and fungifluor stain in BALF samples. Tidsskr Nor Laegeforen, 1995 Oct 20, 115(25), 3141 - 4 {Indications for testing for sexually transmitted Chlamydia trachomatis infections}; Aavitsland P et al.; Laboratory testing for sexually transmitted Chlamydia trachomatis infection is widely used in Norwegian general practice . The yield of this testing is declining, since the prevalence of infection in the community has decreased . Thus, the cost-effectiveness of testing is reduced, and the risk of false positive results using non-culture methods has increased . In cooperation with a panel of medical microbiologists, gynaecologists, venerologists, general practitioners and public health specialists, we have reviewed the literature and drawn up a set of recommendations for the use of laboratory testing for genital C . trachomatis infection . We emphasize clinical testing of men and women, notification of partners in order to reach males, and screening of women under the age of 25 after each change of sexual partner. MLO Med Lab Obs, 1995 Nov, 27(11), 48 - 53 Molecular infectious disease testing: the hype, the hope, and the hoopla; Wiedbrauk DL; To remain competitive in the next century, microbiologists and virologists must acquire molecular diagnostic skills or they will relinquish molecular infectious disease testing to labs with little experience in handling infectious agents. Cytopathology, 1995 Oct, 6(5), 331 - 8 The cytologic diagnosis of Mycobacterium kansasi tuberculosis by fluorescence microscopy of Papanicolaou-stained specimens; Kupper T et al.; The sensitivities of (i) Papanicolaou fluorescence, (ii) auramine rhodamine fluorescence, and (iii) Ziehl-Neelsen staining were compared for their ability to detect the atypical mycobacterium Myco . kansasi in cytological samples . Ninety-two cases were investigated, and the sensitivities of the three methods of detection were found to be 36.9%, 12.0%, and 20.7% respectively . The control groups consisted of 30 specimens from cases of bronchial carcinoma and 30 of pneumonia . All cases were proved by microbiology . No false-positive results were recorded using Papanicolaou fluorescence . An important but coincidental finding arising from this study was that infection by the atypical mycobacterium Myco . kansasi causes cytological patterns corresponding to those normally associated with acute pneumonia and not to tuberculosis. FEMS Immunol Med Microbiol, 1995 Oct, 12(2), 121 - 6 Peritoneal macrophages from C57BL/6 mice orally immunized with Toxoplasma gondii antigens in association with cholera toxin possess an enhanced ability to inhibit parasite multiplication; Bourguin I et al.; Gamma-interferon (IFN-gamma) has been reported to be a major mediator of resistance to toxoplasma infection, mainly through macrophage activation . Cholera toxin used as oral adjuvant induces enhanced protection . Following oral immunization of C57BL/6 mice with a Toxoplasma gondii sonicate (TSo), in association with either cholera toxin (CT) or its B subunit (CTB), the ability of primed sensitized peritoneal macrophages (PM phi) to prevent T . gondii intracellular proliferation in vitro was examined both with and without rIFN-gamma activation . Under these conditions, the inhibition of T . gondii multiplication was greatly enhanced in PM phi from mice immunized with a TSo and CT as an oral adjuvant . In contrast, PM phi from mice immunized with a TSo in association with CTB showed a decrease in their microbiostatic activity towards T . gondii . This negative effect on IFN-gamma-treated PM phi was cancelled out by the addition of a small amount of CT in association with TSo and CTB in the immunization regimen . These data suggest that CT could act as an oral adjuvant in vaccination against toxoplasmosis by increasing the microbiostatic activity of M phi activated with IFN-gamma . Further studies, using intestinal effector cells such as enterocytes, are needed to confirm the value of CT for enhancing this major mechanism of protection against T . gondii infection. Clin Biochem, 1995 Oct, 28(5), 481 - 97 Postdoctoral training in clinical chemistry: laboratory training aspects; Allen LC et al.; OBJECTIVE: To provide a general outline for a 2-year postdoctoral training program in clinical chemistry, and a detailed outline of the first year laboratory training program . METHODS & RESULTS: Essential elements of the 2-year Postdoctoral Training Program in Clinical Chemistry at the University of Toronto are its didactic courses and a comprehensive, structured laboratory rotation in the first year . Residents rotate in hospital laboratories in both years of the Program . The hospital laboratory rotation in first year includes a 36-week laboratory rotation based on the Laboratory Training Program Manual . In the second year, they consolidate the basic knowledge acquired in first year and gain experience in pediatric testing and other specialty areas . In both years, residents attend teaching and ward rounds on a regular basis, investigate unusual test requests and patient results, and make regular presentations at case presentation and journal club sessions . They undertake research and development projects which lead to presentations at scientific meetings and to publication . Residents attend departmental management meetings, arrange discussions on management topics, and attend a short course on key management topics . Approaches for strengthening the knowledge and skills of residents in the areas of hematology, microbiology and pathology are being developed . CONCLUSION: The program outline described should provide a useful framework for other such programs both nationally and internationally. Infect Control Hosp Epidemiol, 1995 Oct, 16(10), 600 - 6 Hospital epidemiology in smaller hospitals; Boyce JM; In hospitals with 200 to 300 beds, hospital epidemiologists serve primarily as medical and epidemiology consultants to the infection control practitioners, as advocates for the infection control programs, and as chairpersons of the infection control committees . Because smaller hospitals often have limited resources for infection control, surveillance and control activities must focus on issues that have caused problems for the facility and on compliance with mandates and recommendations made by healthcare agencies . The clinical microbiology laboratory plays an important role in ongoing surveillance activities and often is responsible for performing cultures obtained during point prevalence culture surveys or outbreak investigations . Because laboratory support often is limited, the indications for obtaining a culture from patients, personnel, or the inanimate environment for infection control purposes must be reviewed and discussed carefully with the clinical laboratory in advance. J Protein Chem, 1995 Oct, 14(7), 521 - 6 An improved method for large-scale purification of recombinant human glucagon; Okamoto H et al.; Glucagon was expressed in Escherichia coli as a fusion protein including the glucagon sequence {Ishizaki et al . (1992), Appl . Microbiol . Biotechnol . 36, 483-486} . The high-level expression of a protein in E . coli often results in an insoluble aggregate called an inclusion body containing a fusion protein . In our previous report {Yoshikawa et al . (1992), J . Protein Chem . 11, 517-525}, we solubilized this inclusion body by using guanidinium chloride . However, the existence of denaturant caused problems such as a low proteolytic activity for transforming the fusion protein into glucagon and complicated purification methods . We tried to improve the method to enable large-scale purification . At alkaline pH, the inclusion body could be solubilized to a high concentration and cleaved by amino acid-specific endopeptidases . By utilizing isoelectric precipitations as a new economical purification method for glucagon from intermediates, the glucagon obtained was shown to be over 99.5% pure by analytical RP-HPLC . The yield was almost equal that of our previous method, and the glucagon produced was chemically and biochemically equivalent to natural glucagon. Curr Opin Pediatr, 1995 Oct, 7(5), 547 - 52 Inflammatory bowel disease in children; von Allmen D et al.; Inflammatory bowel disease remains a serious chronic illness in children . Recent developments in the care of these patients involves both basic science research into the pathophysiology of ulcerative colitis and Crohn's disease and the development of refinements in the surgical techniques and medical therapies available as treatment options . In Crohn's disease, a new steroid analogue (budesonide) shows some promise as a possible medical treatment that would limit the devastating side effects of steroids in children . In addition, the bowel-sparing technique of strictureplasty has now been reported in children with good results . In ulcerative colitis, the surgical technique of endorectal pull-through continues to evolve with reports of the efficacy of specific pouch designs and surgical techniques . An understanding of pouchitis, the most common complication of endorectal pull-through, has focused on documenting specific alterations in the microbiology and physiology of the pouch, as well as investigating a possible link between autoantibodies and susceptibility to this complication. J Clin Pathol, 1995 Oct, 48(10), 915 - 8 Perceptions of a medical microbiology service: a survey of laboratory users; Morgan MS; AIM--To ascertain the perception of laboratory users regarding the quality of the medical microbiology services in a district general hospital . METHODS--Detailed questionnaires were circulated to all clinicians in the locality, with headings covering the quality of medical advice provided, the availability of information on specimen collection, format of request forms, specimen transport arrangements, turnaround times, the quality and need for interpretative advice, and the overall impression of the quality of the services provided . RESULTS--Two hundred and thirty five replies were received, giving a response rate of 69% . Transportation of specimens and communication of reports were identified as priority areas for improvement . The overall quality of the service was perceived as satisfactory, although areas were identified where substantial improvements could be made, some at little or no cost to the laboratory . CONCLUSIONS--The survey focused clinicians' attention on the service, raised the profile of the laboratory, and resulted in improved communications and a better understanding of customer needs . Overall, the exercise was felt to be extremely useful, and worthwhile repeating to gauge the effect of the changes instituted as a result. Tuber Lung Dis, 1995 Oct, 76(5), 387 - 93 The epidemiology of tuberculosis in Gran Canaria, Canary Islands, 1988-92: effectiveness of control measures; Caminero JA et al.; SETTING: Since there is no national programme for tuberculosis control in Spain and the epidemiological situation in this country is unknown, a programme against tuberculosis in Gran Canaria (Canary Islands) was started in 1987 . OBJECTIVE: To analyze the impact of this control programme, particularly the trend of new cases of tuberculosis by age groups and risk factors for 1988-92 . DESIGN: A detailed search of all new cases of tuberculosis was carried out by examining the files of all public and private hospitals and outpatient clinics of the island, the records of the Services of Clinical Microbiology and Pathology of the public hospitals, and the registers of patients with AIDS . RESULTS: The annual rates of new cases of tuberculosis per 100,000 were 32.2 in 1988 (214 cases), 26.2 in 1990 (174 cases), and 29.4 in 1992 (196 cases), and the rates of sputum-positive cases 13.3 (89 cases), 12 (80 cases) and 15 (100 cases), respectively . The distribution of tuberculosis cases by age peaked in the age groups 40-49 and 30-39 years . Between 1988 and 1992, statistically significant differences were found in the percentage of cured patients (21% {45/214} vs 85.7% {168/196}), patients with a delay in diagnosis > 3 months (40.2% {86/214} vs 21.9% {43/196}), and contacts evaluated (45.3% {97/214} vs 90.3% {177/196}) . However, an upward trend in the incidence of tuberculosis for 1990-92 was found in association with an increase of new cases among the homeless, immigrants, and HIV-infected people . When these three population groups were excluded from the analysis, the annual rate for the total population showed a progressive decline from 1988-92 . CONCLUSIONS: The data studied here show that successful priority control measures (cure rate, early diagnosis, study of contacts) have been achieved in this island . It is necessary, however, to develop strategies for combating the tuberculosis problem in specific high risk populations. Genitourin Med, 1995 Oct, 71(5), 295 - 8 Prevalence of Chlamydia trachomatis in women attending a family planning clinic in Papua New Guinea; Theunissen JJ et al.; OBJECTIVE--To determine the prevalence of Chlamydia trachomatis infection in women attending a family planning clinic in Papua New Guinea, in the period between April and June 1991 . SETTING--The outpatient department of Obstetrics and Gynaecology of Port Moresby General Hospital, Port Moresby, Papua New Guinea, the departments of Dermato-Venereology and Clinical Microbiology of the Erasmus University, Rotterdam, The Netherlands and the National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands . PATIENTS--A total of 254 consecutive women who attended the family planning clinic at Port Moresby General Hospital, Papua New Guinea were enrolled into this study . METHODS--Cervical infections with C trachomatis were diagnosed using the direct immunofluorescent assay (DFA) and the polymerase chain reaction (PCR) . Serum IgM and IgG antibodies directed against C trachomatis were detected using the enzyme-linked fluorescent assay (ELFA) . RESULTS--The prevalence of C trachomatis was 14.6% using the PCR, 9.1% using the DFA and 17.3% when the results of the PCR and the DFA were combined . An elevated IgM titre was observed in 14.2% of the women, whereas 44.1% had an elevated IgG titre . The titres of IgM or IgG were significantly higher in women who were positive using the PCR or the DFA than in those who were negative in both the PCR and the DFA (p = 0.032 and p = 0.0046, respectively) . CONCLUSION--Cervical infection by C trachomatis can be considered a major health problem in at least the studied population in Papua New Guinea . The prevalence of C trachomatis infection is at least comparable with that in groups with a high prevalence in industrialized countries . Effective screening and treatment programmes are imperative to combat this problem. Appl Environ Microbiol, 1995 Oct, 61(10), 3741 - 4 Substrate-dependent differential splicing of introns in the regions encoding the cellulose binding domains of two exocellobiohydrolase I-like genes in Phanerochaete chrysosporium; Birch PR et al.; Recently, we have shown differential splicing of an intron in the cbhI.2 gene of Phanerochaete chrysosporium ME446; this intron lies within the region of the gene encoding the cellulose binding domain (P.F.G . Sims, M . S . Soares-Felipe, Q . Wang, M.E . Gent, C . Tempelaars, and P . Broda, Mol . Microbiol . 12:209-216, 1994) . Here, we show that such differential splicing occurs in the cbhI.1 gene of this fungus as well as in the cbhI.2 gene and that this phenomenon is substrate dependent . Avicel elicits the synthesis of both classes of mRNA transcripts from both of these genes . In contrast, carboxymethyl cellulose predominantly elicits the synthesis of fully spliced transcripts from both genes . Such differential splicing might allow this fungus to regulate the specificities of substrate binding for these cellulases. Presse Med, 1995 Sep 16, 24(26), 1193 - 7 {Preimplantation diagnosis of delta F508 mutation of mucoviscidosis in transgenic mice}; Ji YZ et al.; OBJECTIVE: The aim of our study was to master preimplantation diagnosis in transgenic mice . METHODS: Stage 4 or 8 cells preembryos were collected from C57BL6xCBAF1 mice, three days after mating with transgenic C57BL6xSJLF1 mice homozygous for the human gene delta F508 mutation of cystic fibrosis . A single blastomere was sampled by microbiopsy and the preembryos transferred in Swiss mice foster mothers . Molecular biology for delta F508 mutation on a single blastomere was performed with a double PCR technique on a Perkin Elmer Cetus 9600 . RESULTS: The success rate of biopsy on the 122 preembryos with 4 cells was 90.2%, and 93.8% on the 128 prembryos with 8 cells . The rate of in vitro hatching was 84.6% after biopsy on 52 preembryos with 4 cells (92.2% for controls without biopsy, p > 0.05), and 90.0% for 50 preembryos with 8 cells (94.4% for controls without biopsy, p > 0.05) . The rate of birth after biopsy and transfer of 42 preembryos with 4 cells was 66.7% (72.5% for controls transferred without biopsy, p > 0.05) and 70.3% for 37 preembryos with 8 cells (71.9% for controls, p > 0.05) . No difference was evidenced for births weight or organ weight at 3 weeks between mice born from biopsied embryos and controls . Thirty-two double PCR were performed for the diagnosis of the cystic fibrosis delta F508 mutation, 20 on a single blastomere obtained by microbiopsy and 12 for various negative controls, with 100% specificity and 100% sensitivity . CONCLUSIONS: Microbiopsy of preembryos with 4 cells or 8 cells does not alter their viability or further development . The double PCR technique on a single blastomere for the cystic fibrosis delta F508 mutation is reliable with our current methods of investigation. Lik Sprava, 1995 Sep-Dec, (9-12), 49 - 51 {The pathogenetic role of dysbacteriosis of the large intestine in the recurrence of peptic ulcer}; Andrusiak OV et al.; Microbiologic investigations were carried out of excrements as were measurements of blood levels of malonic dialdegyde, reduced glutathione and activity of glutathione-dependent enzymes in 36 patients with peptic ulcer when they experienced exacerbation . Gastric and duodenal ulcer in exacerbation was accompanied by dysbacteriosis of the large intestine, uncontrolled augmentation of the processes of free-radical lipid oxidation against the background of impairment of functional systems of antiradical defence, which fact plays its part in relapsing of gastroduodenal ulcer. Baillieres Clin Obstet Gynaecol, 1995 Sep, 9(3), 529 - 43 Infectious diseases; Gilbert GL; Routine antenatal screening can detect some potentially serious infectious diseases or susceptibility to infection and allow intervention to prevent adverse outcomes . However, screening programmes can only be justified if appropriate criteria are met for the quality of laboratory tests and interventions . For many infections that are associated with adverse maternal or fetal effects, there are no suitable, cost-effective methods of screening or prevention . However, early diagnosis of infection in high-risk women or those with symptoms can allow preventive intervention . Acute febrile illness or other symptoms consistent with infection during pregnancy should be investigated more diligently than in a non-pregnant woman . Early diagnosis of an apparently trivial maternal infection may prevent serious fetal disease . When the diagnosis of maternal infection is made, appropriate action depends on the nature of infection and the stage of pregnancy at which it occurs . The results of serological test should be confirmed, preferably by a reference laboratory, by retesting the original specimen(s) and/or testing further specimens, as appropriate . Management decisions generally should be made in consultation with an infectious disease physician or clinical microbiologist with experience of infectious diseases in pregnancy. Diagn Microbiol Infect Dis, 1995 Sep-Oct, 23(1-2), 53 - 60 Evaluation of new technology in the clinical microbiology laboratory; Jenkins SG; Technology capable of significantly influencing the practice of clinical microbiology is evolving at an ever-accelerating rate . During their early developmental years, it is difficult to predict which evolving technologies will prove amenable for use in hospital laboratory settings . With the considerable and increasing cost constraints placed on our medical institutions and the resulting budgetary pressures exerted on clinical laboratories, evaluation of developing technology is essential . The Clinical Laboratory Improvement Act of 1988 mandates correlation studies by clinical laboratories as part of the evaluation of all new assays to compare their sensitivities and specificities with those obtained using established methodologies . With shrinking numbers of technologists available for such evaluations, however, the mechanism with which this will be accomplished promises to pose a significant challenge . Factors that demand consideration in any such evaluation include (but are not restricted to) utility, accuracy, prospective time savings, cost of related instrumentation and reagents, and potential for diverse applications . Specific current examples that exemplify the need for such evaluations include the emergence of gene-based techniques such as the polymerase chain reaction as clinical tools, availability of new blood culture systems based on divergent sensor systems, and varying techniques for the the detection of antibodies and antigens for the serodiagnosis of infectious diseases . We as clinical microbiologists have the opportunity to approach the challenges confronting us regarding evaluation of developing technologies with responsible innovation and insight . Only by embracing these responsibilities can we hope to influence the impact of health care reform in the hospital laboratory setting. Diagn Microbiol Infect Dis, 1995 Sep-Oct, 23(1-2), 45 - 51 The changing role of the clinical microbiology laboratory director: results of a survey; Thomson RB Jr; Health care reform has provided clinical microbiology laboratory directors with new responsibilities and challenges that should highlight and enhance their importance within the health care system . Results of a survey sent to directors suggest that management tasks have increased since 1990, and activities that move the director into the hospital and patient care environment underscore their value to the health care team . These activities include participation on clinical practice guidelines pathway committees and use of consultative and interpretative reports . Survey results also summarize the directors' qualifications, laboratory size, typical daily schedule, job responsibilities, hours worked, time away from the laboratory for professional purposes, and comments about one's most important functions . In summary, failure to recognize new responsibilities could result in the disappearance of the position of director as we know it . Capitalizing on this challenge will secure the microbiology director's role for decades to come. Diagn Microbiol Infect Dis, 1995 Sep-Oct, 23(1-2), 35 - 43 Impact of CLIA 88 on the clinical microbiology laboratory; Chapin K et al.; The Clinical Laboratory Improvement Amendments (CLIA 88) to the Clinical Laboratory Improvement Act of 1967 continues to undergo transformation since its implementation more than 2 years ago . The law and its subsequent regulatory modifications were intended to promote high quality in and accurate results from laboratory testing procedures, regardless of the site at which testing occurred . A number of federal regulatory agencies and committees such as the Healthcare Financing Administration, the Clinical Improved Amendments Committee, and the Commission on Laboratory Accreditation, as well as numerous new or modified regulations and requirements have gained importance since CLIA 88 was enacted . In this discussion, components of CLIA 88 that have the greatest impact on clinical microbiology laboratories are presented . In addition, the potential future significance of CLIA 88 are outlined. Diagn Microbiol Infect Dis, 1995 Sep-Oct, 23(1-2), 23 - 34 Quality management and the clinical microbiology laboratory; Baron EJ; Quality management in today's health care environment requires a fresh approach . Laboratories that have traditionally directed their efforts toward meeting the needs of physicians must now also satisfy the needs of society, the greater public health, and the agency's administrators . Technical advances must today be considered in the context of patient care cost-effectiveness or final outcomes . Examples of strategies for improving quality in the laboratory, such as seeking input from all individuals involved in interpreting or using laboratory test results, forming multidisciplinary committees for development of critical pathways, issuing surveys for assessing the level of satisfaction of the laboratory's customers, and providing visual feedback of the results of activities, are described. Diagn Microbiol Infect Dis, 1995 Sep-Oct, 23(1-2), 17 - 21 Influence of managed care and health maintenance organizations on the clinical microbiology laboratory; Scott DR; This article outlines the main source of the relentless cost squeeze facing health care and clinical microbiology in the 1990s, the explosive growth in services available, services done, and services demanded . The author also explained why he believes some type of rationing is inevitable . Health care professionals must enter the debate on how to ration or face unpleasant consequences . The approach outlined here is one proven way to create testing and treatment guidelines based on health outcomes as well as consumer satisfaction and cost . The long-term best interests of all patients deserve nothing less. Cancer, 1995 Sep 1, 76(5), 840 - 52 Improved long term survival after intracavitary interleukin-2 and lymphokine-activated killer cells for adults with recurrent malignant glioma; Hayes RL et al.; BACKGROUND . The median survival for adults with glioblastoma multiforme (GBM) is 12 months, despite surgery, radiation, and chemotherapy . Regimens using interleukin-2 (IL-2) plus lymphokine-activated killer (LAK) cells have been beneficial against systemic cancers, albeit with significant toxicity . METHODS . Nineteen adults with recurrent malignant glioma (5 GBMs, and 4 anaplastic astrocytomas (AA)), Karnofsky performance status 60 or greater, were treated with intracavitary autologous LAK cells plus IL-2 after reoperation . Lymphokine-activated killer cells and IL-2 were given on day 1, and IL-2 alone was given 5 times during a 2-week cycle . This cycle was repeated at 2 weeks to constitute one 6-week course of therapy . Each two-cycle course of treatment was repeated at 3-month intervals for patients with stable disease or response to therapy . At the conclusion of immunotherapy, all patients were offered chemotherapy, generally carmustine or procarbazine, including responders . Corticosteroids were strictly limited during immunotherapy . Sequential reservoir aspirates were obtained for microbiologic and cytologic analyses . RESULTS . The maximal tolerated dose for a 12-dose course of therapy was 1.2 million international units (MIU) per dose . Dose-limiting, cumulative IL-2-related central nervous system (CNS) toxicity was observed at 2.4 MIU per dose . Three responses were confirmed by computed tomography scan during therapy: one complete response (CR) (1 AA), and two partial responses (PR) (2 GBM); as well as a significant increase in GBM survival . One additional CR (GBM) was observed at 17 months . The median survival for immunotherapy patients with GBM was 53 weeks after reoperation (N = 15) (mean, 87.9 +/- 21.4 weeks, standard error for the mean), with 8 of 15 surviving more than 1 year (53%) . The median survival for 18 contemporary patients with GBM reoperated and treated with chemotherapy was 25.5 weeks (mean, 27.4 +/- 3.7 weeks), with 1/18 alive at 1 year (> 6%) . Six of the 15 patients with GBM had additional surgery or biopsy, and chemotherapy after immunotherapy . The contribution of subsequent chemotherapy to survival cannot be discounted . CONCLUSIONS . Lymphokine-activated killer cells and IL-2 can be administered safely within the CNS resulting in improved long term survival in patients with recurrent glioblastoma . Increased survival was associated with significant biologic changes characterized by a regional eosinophilia, and extensive lymphocytic infiltration . A prospective randomized clinical trial is warranted. Mycoses, 1995 Sep-Oct, 38(9-10), 411 - 4 Dermatophytes in northern Finland in 1982-90; Lehenkari E et al.; The epidemiology of human dermatophytes was studied in northern Finland in 1982-90 . The samples were analysed at the Department of Medical Microbiology, University of Oulu . The total number of samples was 17,822, of which 3185 (18%) were positive . The annual number of samples and positive cultures remained relatively constant . Trichophyton rubrum was the most common species being isolated from 2101 samples (66% of all positive cultures), while Trichophyton mentagrophytes was isolated from 815 samples (26%) and Epidermophyton floccosum from 193 samples (6%) . T . verrucosum caused an epidemic among cattle keepers in 1987-90, causing 47 infections . Microsporum canis, T . terrestre and T . violaceum were rare . The same species affected both children and adults . There was a tendency towards a decrease in tinea in the groin and a slight increase in tinea pedis . T . rubrum and T . mentagrophytes occurred most frequently in patients aged 41-45 years and as foot infections . E . floccosum usually affected the toe web and the groin in patients aged 21-25 years, more often infecting men . Fifty-four per cent of all positive samples came from men and 46% from women. Med Clin North Am, 1995 Sep, 79(5), 1205 - 40 Infective endocarditis; Bansal RC; IE is a fascinating disease that continues to challenge the clinicians . Over the last several decades, there have been marked changes in its presentation . The morbidity and mortality have markedly improved by early diagnosis and prompt treatment using highly effective antibiotic regimens and early valve replacement surgery whenever necessary . Early diagnosis is possible by improvement in blood culture techniques and advances in transthoracic and transesophageal echocardiographic approaches . This article has reviewed the pathogenesis, microbiology, clinical presentation, diagnostic methodology, treatment, and prevention of IE. J Clin Oncol, 1995 Sep, 13(9), 2394 - 400 Survival of patients with resistant Hodgkin's disease after polyclonal yttrium 90-labeled antiferritin treatment; Herpst JM et al.; PURPOSE: A follow-up study was initiated of patients with Hodgkin's disease who were treated with yttrium 90-labeled antiferritin . Prescription method, pharmacokinetics, acute and late side effects, and survival were evaluated . METHODS: Patients had measurable disease and failed > or = two multiagent chemotherapy regimens previously (N = 44) . All patients received 5-mCi indium 111-labeled antiferritin 2 mg intravenously and were scanned repeatedly by gamma camera . In five patients, polyclonal antiferritin (rabbit, pig, or baboon) failed to target the tumor . Thirty-nine patients were injected intravenously with 10-, 20-, 30-, 40-, or 50-mCi yttrium 90-labeled antiferritin 2 to 5 mg . Patients received between one and five cycles . Some patients were supported with 5 x 10(7) autologous bone marrow cells per kilogram . RESULTS: Yttrium 90-labeled polyclonal antiferritin does not produce immunologic, pharmacologic, or microbiologic complications in vivo . Bone marrow toxicity is the only side effect observed . Overall response rate is 20 of 39, or 51% . Two patients had stable disease . A significant positive correlation is found between blood radioactivity level 1 hour after radioimmunoconjugate administration and subsequent response of Hodgkin's disease . A dosage in millicuries per kilogram provides a higher positive correlation with blood radioactivity levels 1 hour after administration than a dosage in millicuries per square meter of body-surface area or in total millicuries . Fifty percent of patients survive for > or = 6 months . CONCLUSION: The low-dose protein used (2 to 5 mg) indicates that the high response rate is due to radiation and not to immunologic effects of the antibody . High-activity administrations followed by bone marrow transplantation are not required for tumor response . The therapeutic ratio of radiolabeled antiferritin is higher than the therapeutic ratio observed in most phase I studies of chemotherapeutic agents . This analysis does not identify a superior mode of treatment for patients with end-stage Hodgkin's disease . However, in a heavily pretreated patient population, prolonged survival is observed after relatively inexpensive treatment . Preclinical research with yttrium 90-labeled antiferritin indicates that significant increases in tumor dose can be obtained in the future without an increase in normal tissue toxicity. J Bacteriol, 1995 Sep, 177(17), 4872 - 80 A consensus sequence for binding of Lrp to DNA; Cui Y et al.; Lrp (leucine-responsive regulatory protein) is a major regulatory protein involved in the expression of numerous operons in Escherichia coli . For ilvIH, one of the operons positively regulated by Lrp, Lrp binds to multiple sites upstream of the transcriptional start site and activates transcription . An alignment of 12 Lrp binding sites within ilvIH DNA from two different organisms revealed a tentative consensus sequence AGAAT TTTATTCT (Q . Wang, M . Sacco, E . Ricca, C.T . Lago, M . DeFelice, and J.M . Calvo, Mol . Microbiol . 7:883-891, 1993) . To further characterize the binding specificity of Lrp, we used a variation of the Selex procedure of C . Tuerk and L . Gold (Science 249:505-510, 1990) to identify sequences that bound Lrp out of a pool of 10(12) different DNA molecules . We identified 63 related DNA sequences that bound Lrp and estimated their relative binding affinities for Lrp . A consensus sequence derived from analysis of these sequences, YAGHAWATTWT DCTR, where Y = C or T, H = not G, W = A or T, D = not C, and R = A or G, contains clear dyad symmetry and is very similar to the one defined earlier . To test the idea that Lrp in the presence of leucine might bind to a different subset of DNA sequences, we carried out a second selection experiment with leucine present during the binding reactions . DNA sequences selected in the presence or absence of leucine were similar, and leucine did not stimulate binding to any of the sequences that were selected in the presence of leucine . Therefore, it is unlikely that leucine changes the specificity of Lrp binding. Invest Ophthalmol Vis Sci, 1995 Sep, 36(10), 1976 - 87 Murine model of ocular infection by a human biovar of Chlamydia trachomatis; Whittum-Hudson JA et al.; PURPOSE . A human biovar of Chlamydia trachomatis was used to develop a murine model of ocular chlamydial infection . The inbred mouse model will allow detailed immunologic studies during ocular infection, and use of a human biovar for infection may aid in identification of appropriate vaccine strategies against chlamydial infections . METHODS . BALB/c, C3H/HeN, and C57B1/6J mice (n = 5 to 10 mice/group) were topically infected in the conjunctiva with C serovar of C . trachomatis . The effects were tested of single and repeated infection with 5000 inclusion-forming units (IFU) in 5 microliters and different inoculum doses . Conjunctival surfaces of both eyes were swabbed for microbiologic signs (isolation culture or direct fluorescent antibody staining) of infection over 4 to 6 weeks . Conjunctivae were removed for histopathologic study, and lymphocytes from draining cervical lymph nodes and spleens were tested for chlamydia-specific proliferative responses . Serum was obtained from all mice and tested for anti-chlamydial antibodies . RESULTS . BALB/c and C3H/HeN mice developed dose-dependent microbiologic, histopathologic, and immunologic evidence of ocular infection . Eyes of mice were culture-positive from day 7 through at least day 21, with the peak of infection at days 10 to 14 after infection . Histopathologically, the development of conjunctival subepithelial mononuclear infiltration, exudate, and loss of goblet cells occurred within 1 week . Dose-dependent lymphoproliferative responses to whole chlamydial elementary bodies were observed; anti-chlamydial antibody was detected by immunoblotting only in infected mice . CONCLUSIONS . Several strains of inbred mice are susceptible to human chlamydial biovars and may provide a useful alternative disease model in which to study the immunopathogenesis of ocular chlamydial infection and test of vaccine candidates derived from clinically relevant human biovars. J Acquir Immune Defic Syndr Hum Retrovirol, 1995 Sep 1, 10(1), 48 - 53 Treatment with letrazuril of refractory cryptosporidial diarrhea complicating AIDS; Loeb M et al.; Thirty-five AIDS patients (mean CD4 count 44 x 10(6)/L) with chronic cryptosporidiosis were treated with letrazuril at an initial oral daily dose of 50 mg in an open-label Phase I prospective trial . Treatment was continued for > or = 10 days and for as long as there was a response . The majority of subjects (91%), had previously failed paromomycin treatment . At baseline, 74% of patients had moderate (five to nine bowel movements per day) to severe (> 10 bowel movements per day) diarrhea . Twenty-three subjects (66%) had a clinical response within a mean of 1.7 weeks of treatment initiation . Twenty-two patients had a partial response (> 50% reduction in bowel movements per day for > or = 1 week), one patient had a complete response (two or fewer bowel movements per day) . Of the responders, 15 (65%) had a clinical relapse with worsening diarrhea at an average of 1.2 months following initiation of letrazuril . The other eight (35%) had had symptom control for an average of 2.9 months from initiation of letrazuril to the latest follow-up . Microbiologic eradication was demonstrated in 10 (40%) of 25 patients with follow-up stool examinations . Seven patients (20%) experienced a rash, all within 1 week of starting the drug, and resolved in all patients when the drug was discontinued . In conclusion, severely immunocompromised AIDS patients with refractory cryptosporidiosis may show a modest, short-lived response to letrazuril . Microbiologic response is variable and relapse high . Rash is a major limiting side effect of the drug. Microbiology, 1995 Sep, 141 ( Pt 9), 2111 - 21 Restriction site polymorphism of the genes encoding the major 25 kDa and 36 kDa outer-membrane proteins of Brucella; Cloeckaert A et al.; Seventy-seven Brucella reference and field strains from different geographic origins and hosts representing the six recognized species and their different biovars were analysed for diversity of their genes encoding the major 25 and 36 kDa outer-membrane proteins (OMPs) by PCR-RFLP . The 25 kDa OMP is encoded by a single gene (omp25) whereas two closely related genes (omp2a and omp2b) encode and potentially express the 36 kDa OMP . Analysis of PCR products of the omp25 gene digested with nine restriction enzymes revealed two species-specific markers, i.e . the absence of the EcoRV site in all Brucella melitensis strains and an approximately 50 bp deletion at the 3' terminal end of the gene in all Brucella ovis strains . Analysis of PCR products of the omp2a and omp2b genes digested with 13 restriction enzymes indicated a greater diversity than the omp25 gene among the six Brucella species and within the Brucella abortus, Brucella suis, B . melitensis and B . ovis species . Greater polymorphism was also detected for the omp2b than for the omp2a gene, especially in B . ovis which seemed to carry two similar (but not identical) copies of omp2a instead of one copy each of omp2a and omp2b for the other Brucella species as was previously suggested by Ficht et al . (1990; Mol Microbiol 4, 1135-1142) . Results of PCR-RFLP indicated that distinction can be made between Brucellia species and some of their biovars, except between B . canis and B . suis bv . 3 and 4, on the basis of the size and diversity of their major OMP genes, and that it could be of importance for diagnostic, epidemiological and evolutionary study purposes. J Clin Microbiol, 1995 Sep, 33(9), 2415 - 20 Outer surface protein C gene sequence analysis of Borrelia burgdorferi sensu lato isolates from Japan; Fukunaga M et al.; The nucleotide sequences of the outer surface protein C gene (ospC) from Borrelia burgdorferi sensu lato isolates representing six different restriction fragment length polymorphism (RFLP) ribotype groups were determined, and the deduced amino acid sequences were aligned in comparison with the previously published OspC protein sequences . The sequence similarity analysis revealed the high sequence variability of OspC protein, and the degree of amino acid similarity ranged from 53.8 to 100% among 25 isolates . It has been reported that the representatives belonging to the three species of B . burgdorferi sensu lato showed a species-specific amino acid sequence motif at positions 23 to 35 (B . Wilske, S . Jauris-Heipke, R . Lobentanzer, I . Pradel, V . Preac-Mursic, D . Rossler, E . Soutschek, and R.C . Johnson, J . Clin . Microbiol . 33:103-109, 1995) . Alignment with the OspC sequences of RFLP ribotype group IV, V, and VI isolates revealed that a sequence motif of all the isolates was quite similar to that of Borrelia garinii . A phylogenetic analysis based on OspC protein sequences also showed that most of the Japanese isolates were closely related to the species B . garinii . THe RFLP ribotype group IV species is predominant among clinical isolates of Lyme disease patients, reservoir rodents, and adult ticks in Japan . Although the isolates differed from type strains of the three delineated genospecies in genetic and immunological characteristics, it is likely that the spirochetes diverged within the species level . Therefore, the representatives of ribotype groups IV, V, and VI appear to have evolved within B . garinii and to have adapted to an Asiatic habitat, and there appeared to be a sufficient ecological pressure to allow bacterial species level development. J Clin Microbiol, 1995 Sep, 33(9), 2304 - 15 Genotypic and phenotypic characterization of Borrelia burgdorferi isolated from ticks and small animals in Illinois; Picken RN et al.; We have characterized 33 isolates of Borrelia burgdorferi from northern Illinois (32 isolates) and Wisconsin (1 isolate) representing the largest series of midwestern isolates investigated to date . The techniques used for molecular analysis of strains included (i) genospecies typing with species-specific PCR primers, (ii) plasmid profiling by pulsed-field gel electrophoresis of total genomic DNA, (iii) large-restriction-fragment pattern (LRFP) analysis by pulsed-field gel electrophoresis of MluI-digested genomic DNA (J . Belfaiza, D . Postic, E . Bellenger, G . Baranton, and I . Saint Girons, J . Clin . Microbiol . 31:2873-2877, 1993), (iv) sodium dodecyl sulfate-polyacrylamide gel electrophoresis of total proteins, (v) microsequencing of high-performance liquid chromatography-purified peptides derived from proteins showing high levels of expression, (vi) amino acid composition analysis of proteins, and (vii) immunological analysis of proteins with a polyclonal antiserum of human origin . Five reference strains as well as two atypical tick isolates from California (DN127) and New York (25015) were included for comparison . All of the Illinois and Wisconsin isolates were typed as B . burgdorferi sensu stricto with genospecies-specific PCR primers . The isolates were found to be heterogeneous with regard to their plasmid and protein profiles . One isolate from Illinois possessed two large-molecular-size plasmids instead of the usual 49-kb plasmid . Fragment patterns resulting from MluI digestion of genomic DNA from the 33 isolates and strains DN127 and 25015 were separable into six distinct LRFPs, five of which have not previously been described . Strain 25015 and an isolate from Illinois (CT39) shared an unusual LRFP that is not typical of other B . burgdorferi sensu stricto strains, suggesting that they may represent a fifth species of B . burgdorferi sensu lato . Five of the 33 isolates and strains DN127 and 25015 showed high-level expression of proteins with molecular masses of approximately 22 kDa . Investigation of these proteins by microsequencing of individual peptides and total amino acid composition analysis indicated that the 22-kDa proteins expressed by the seven strains were polymorphic OspC proteins . By using a polyclonal serum of human origin, expression of OspC could be detected in all 33 Illinois and Wisconsin isolates. J Clin Pathol, 1995 Sep, 48(9), 810 - 4 Routine application of the polymerase chain reaction for detection of Mycobacterium tuberculosis in clinical samples; Noordhoek GT et al.; AIM--To investigate the use of the polymerase chain reaction (PCR) in the routine laboratory for the detection of Mycobacterium tuberculosis in clinical samples . METHODS--Samples were divided and processed separately for the detection of M tuberculosis by microscopy, culture and PCR . After DNA extraction, PCR was performed with primers specific for the insertion element IS6110 and the product was analysed by agarose gel electrophoresis, Southern blotting or dot blotting and hybridisation with a digoxigenin labelled internal probe . Each sample was tested for inhibitors of Taq polymerase with the aid of an internal control . Multiple negative and positive controls were used to monitor each step of the procedure . RESULTS--The data from two laboratories, using the same operating procedures, were combined . Of 1957 specimens, 79 (4%) were culture and PCR positive, while 1839 (93.9%) were negative in both tests . Thirty specimens (1.5%) were PCR positive only and nine (0.5%) were culture positive but PCR negative . CONCLUSION--Using culture and clinical history as the gold standard, sensitivity and specificity for PCR were 92.1% and 99.8%, respectively . With elaborate precautions, PCR is a suitable and reliable method for the detection of M tuberculosis in clinical samples in a routine microbiology laboratory. Ultrasound Obstet Gynecol, 1995 Aug, 6(2), 121 - 5 Sonographic features of tuberculous peritonitis with female genital tract tuberculosis; Yapar EG et al.; Our aim was to illustrate the sonographic features of tuberculous peritonitis with female genital tract tuberculosis in an attempt to facilitate the recognition of the disorder preoperatively . Transabdominal and transvaginal sonographic features and the findings from laparotomy/laparoscopy, endometrial biopsy and microbiology were reviewed and compared in 15 patients with tuberculous peritonitis with female genital tract tuberculosis . Of the 15 patients, 12 had wet tuberculosis and three had dry (adhesive) tuberculosis . Sonographic features of wet tuberculosis were categorized as follows: septated ascites (ten patients), particulate ascites (two patients), loculated fluid (two patients), thickened peritoneum (eight patients), thickened omentum (eight patients), adnexal mass (11 patients), adhesions (seven patients) and endometrial involvement (five patients) . Adnexal masses, adhesions and loculated fluid were found to be present in the dry type . When sonographic findings were compared with those of laparotomy and/or laparoscopy and/or endometrial biopsy, ultrasound was able to identify aspects of tuberculosis infection as follows: ascites/loculated fluid, 13/13 (100%); adnexal mass, 12/13 (93%); peritoneal thickening, 9/13 (69%); omental thickening, 8/13 (61%); and endometrial involvement, 5/6 (83%) . We conclude that awareness of the sonographic changes associated with tuberculosis infection may improve diagnostic accuracy, and avoid clinical mismanagement and surgical explorations in the wet type of tuberculosis. Med Hypotheses, 1995 Aug, 45(2), 164 - 8 Leukocyte adhesion molecules as a cofactor in AIDS: basic science and pilot study; Allen AD et al.; It is well known that the AIDS pandemic is a consequence of pandemic HIV infection . However, Koch's postulates are not satisfied for two reasons: 1) AIDS cannot be experimentally produced in animals susceptible to HIV infection and 2) some people have AIDS (idiopathic CD4+ T lymphocytopenia) in the absence of HIV infection . It follows that there is a human immunologic cofactor (HIC) that causes AIDS when certain other conditions are satisfied, and the most common of these other conditions (but not the only one) is HIV infection . Results from microbiology make leukocyte adhesion molecules a good candidate for the HIC . We have tested this hypothesis with a pilot study in which a small number of patients with HIV disease were infused with a monoclonal mouse antibody (MmAb) directed against an LFA-1 adhesion epitope, and then with F(ab) and F(ab)2' fragments that bind to the same epitope but are nonimmunogenic . Both agents reduced peripheral viral burden significantly but fragments were more effective in this respect than the MmAb due to the mitogenic properties of the latter . For the same reason, only the MmAb were highly effective in raising circulating levels of single and double-marked CD4+ T lymphocytes, with a correlated resolution of cutaneous anergy. J Trauma, 1995 Aug, 39(2), 309 - 19 Cultured epithelial autograft: five years of clinical experience with twenty-eight patients; Williamson JS et al.; Cultured epithelial autograft (CEA) has been used as an adjunct in burn wound coverage at the Vancouver Hospital and Health Sciences Centre since 1988, and has been available to all patients admitted with significant burn injuries . During the 5-year period from 1988 to 1992 inclusive, 28 patients treated with CEA survived long enough for assessment . The mean age was 35.3 years with a mean total body surface area burn of 52.2% and a mean total full thickness injury of 42.4% . CEA was applied to wounds covering between 2% and 35% body surface area (BSA; mean 10.4%) after excision to fat or fascia . Most wounds had interim homograft coverage . Preservation of homograft dermis was attempted in three patients at the time of removal without effect . The mean CEA "take" was 26.9% of the grafted area . Eight patients had 50% or greater take and were discharged with between 1 and 19% BSA covered with CEA . Thirteen patients had no take on wounds between 2 and 16% BSA . Overall mortality in burn patients treated at the Vancouver Hospital and Health Sciences Centre from 1988 to 1992 was not significantly different from 1983 to 1987 with the populations being similar in terms of total BSA burns, age, inhalation injury, and homograft availability . When compared to a matched control population from the preceding 5 years, when CEA was not available, there was no significant difference in duration of hospital stay or number of autograft harvests . However, approximately one more debridement without autograft harvest per CEA patient occurred . Timing and depth of wound excision, interim coverage, type of dressing, and wound microbiology were not found to influence good versus poor take . The anterior trunk and thighs were the best recipient sites . Subjective differences between CEA and meshed autograft were noted . The results show that after 5 years of use, CEA engraftment continues to be unpredictable and inconsistent, and hence, it should be used as only a biologic dressing and experimental adjunct to conventional burn wound coverage with split thickness autograft. Arch Pathol Lab Med, 1995 Aug, 119(8), 706 - 12 User interface reengineering . Innovative applications of bar coding in a clinical microbiology laboratory; Willard KE et al.; Some clinical laboratory departments (such as microbiology) provide extensive reporting of text and other data not generated by instruments that can be interfaced to a laboratory information system . These data are usually entered into the laboratory information system manually by keyboard data entry, which can be cumbersome and time consuming . Bar codes, which are already used in laboratories to facilitate rapid entry of sample-identifying information, have the potential to be used much more broadly as a generalizable data entry technique . We developed a comprehensive system that takes advantage of several applications of bar coding to facilitate the work of our Clinical Microbiology Laboratory . Central to our system is the use of bar code "scripts" to meet many of our complex data entry requirements . Use of these scripts is transparent to the laboratory information system (ie, no special "drivers" are needed) because data are received as if they had been generated by typing the characters on the keyboard . The scripts consist of bar codes that encode the series of keystrokes needed to give the appropriate response at the series of prompts offered by the laboratory information system . Both alphanumeric and other keys, including carriage returns and special characters, can be converted into bar codes and incorporated into scripts . By creating and printing these scripts in the laboratory using standard wordprocessing software and bar code fonts for personal computers, laboratorians without specialized computer training have the tools to substantially improve the data entry efficiency of existing data entry terminals for a variety of laboratory information systems. J Bacteriol, 1995 Aug, 177(16), 4696 - 702 Modulation of flagellar expression in Escherichia coli by acetyl phosphate and the osmoregulator OmpR; Shin S et al.; During the search for unknown factors involved in motility, we have found that expression of the flagellar master operon flhDC is affected by mutations of the pta and ackA genes, encoding phosphotransacetylase and acetate kinase, respectively (S . Shin, J . Sheen, and C . Park, Korean J . Microbiol . 31:504-511, 1993) . Here we describe results showing that this effect is modulated by externally added acetate, except when both pta and ackA are mutated, suggesting the role of acetyl phosphate, an intermediate of acetate metabolism, as a regulatory effector . Furthermore, the following evidence indicates that the phosphorylation of OmpR, a trans factor for osmoregulation, regulates flagellar expression . First, in a strain lacking ompR, the expression of flhDC is no longer responsive to a change in the level of acetyl phosphate . Second, an increase in medium osmolarity does not decrease flhDC expression in an ompR mutant . It is known that such an increase normally enhances OmpR phosphorylation . Third, OmpR protein binds to the DNA fragment containing the flhDC promoter, and its affinity is increased with phosphorylation by acetyl phosphate . DNase I footprinting revealed the regions of the flhDC promoter protected by OmpR in the presence or absence of phosphorylation . Therefore, we propose that the phosphorylated OmpR, generated by either osmolarity change or the internal level of acetyl phosphate, negatively regulates the expression of flagella. Am J Med, 1995 Aug, 99(2), 164 - 72 Diagnosis and therapeutic monitoring of invasive candidiasis by rapid enzymatic detection of serum D-arabinitol; Walsh TJ et al.; BACKGROUND: Using a rapid automated enzymatic assay, we prospectively investigated serum D-arabinitol (DA), a biochemical marker of invasive candidiasis, in a large population of high-risk patients to determine its potential diagnostic, therapeutic, and prognostic significance in invasive candidiasis . PATIENTS AND METHODS: A total of 3,223 serum samples were collected from 274 patients with cancer . Serum DA concentrations were determined in coded serum samples analyzed by rapid enzymatic assay . Creatinine also was analyzed in the same system to determine a serum DA and creatinine ratio (DA/Cr) . The sensitivity, specificity, correlation with therapeutic response, and prognostic significance were analyzed for all patient study groups . RESULTS: A DA/Cr of > or = 4.0 mumol/L per mg/dL was detected in 31 (74%) of all 42 cases of fungemia and 25 (83%) of the 30 cases of the subset of persistent fungemia . Elevated DA/Cr was detected in 4 (40%) of 10 patients with tissue-proven, deeply invasive candidiasis and negative blood cultures (eg, hepatosplenic candidiasis or localized abscess) and 7 (44%) of 16 cases of deep mucosal candidiasis (eg, esophageal candidiasis) . Elevated serial DA/Cr levels also were detected in persistently febrile and granulocytopenic patients requiring empirical amphotericin B . Among 26 assessable cases of fungemia, abnormally elevated DA/Cr values were detected in 14 (54%) before, 10 (38%) after, and 2 (8%) simultaneously with the first microbiologic report of fungemia . The trends of serial DA/Cr values correlated with therapeutic response in 29 (85%) of 34 patients with assessable cases of fungemia, decreasing in 8 (89%) of 9 patients with clearance of fungemia and increasing in 21 (84%) of 25 patients with persistence of fungemia . Among the 34 assessable patients with fungemia, mortality was directly related to the trend of serial DA/Cr determinations over time: 71% among fungemic patients who had persistently elevated or increasing DA/Cr, and 18% among the fungemic patients who had resolving DA/Cr or never had elevated DA/Cr (P < 0.01) . CONCLUSIONS: Rapid enzymatic detection of DA in serially collected serum samples from high-risk cancer patients permitted detection of invasive candidiasis, early recognition of fungemia, and therapeutic monitoring in DA-positive cases . Serially collected serum DA determinations complement blood cultures for improving detection and monitoring therapeutic response in patients at risk for invasive candidiasis. Chirurg, 1995 Aug, 66(8), 818 - 22 {Thoracic actinomycosis}; Mohr VD et al.; Thoracic actinomycosis is a rare disease without characteristic clinical signs . Approximately 90% of patients suffering from thoracic actinomycosis have undergone diagnostic and therapeutic procedures based on a wrong diagnostic hypothesis (malignancies 35-44%, other pulmonary disorders 33-35%) . The opportunities for a timely and adequate diagnosis by the use of clinical examination, laboratory studies, microbiology studies, radiologic imaging or invasive measures are limited . In 85%, thoracic actinomycosis has not been identified prior to thoracotomy, open biopsy and histological examination . Based on a wrong diagnostic hypothesis, resective thoracic surgery according to the principles of oncologic surgery can hardly be avoided . We report on a 43-year-old male suffering from actinomycosis of the left hemithorax . Clinical signs, differential diagnosis, treatment and clinical course are described . The role of surgery in the treatment protocol of thoracic actinomycosis is discussed . In pulmonary and pleural disorders of unknown origin, differential diagnosis should include thoracic actinomycosis as early as possible . Due to the considerably high mortality rate of untreated disease, the outcome of thoracic actinomycosis can only be improved by a timely and combined employment of surgical and antibiotic therapy. Arzneimittelforschung, 1995 Aug, 45(8), 934 - 9 Intent and coincidence in pharmaceutical discovery . The impact of biotechnology; Drews J; Drug research developed around a purpose: the cure of diseases . This intent to cure, however, offered no clue to the understanding of diseases and to their treatment . Instead such guidance had to come from scientific disciplines which laid the foundations for drug research and offered specific opportunities for the solution of therapeutic problems . In the sequence of their appearance, these scientific disciplines were: chemistry, pharmacology/physiology, microbiology, biochemistry and molecular biology . It can be shown that new therapeutic classes of drugs like muscle relaxants, diuretics, L-dopa, antibiotics, recombinant proteins, monoclonal antibodies and others were generated on the basis of scientific opportunities rather than therapeutic need . All of these drugs were created within the confines of a chemical paradigm of medicine and drug therapy . We are now witnessing the entry of a new informational paradigm into medicine which is most prominently represented by genomic sciences . This paradigm will bring two important changes to the therapy of diseases . First, molecular biology has matured to such a degree that it can now study complex genomes and their functionality in complex organisms such as humans . Therefore, results from these studies no longer have to be translated into the context of medicine: they are already within this context . Secondly, drug therapy which used to be largely symptomatic, will now aim at targets which are closer to the causes of diseases than previously . Therapeutic progress, which used to be indirect, conjectural and coincidental, is about to become more directed, definitive and intentional . At least from the limited and utilitarian perspective of medicine, drug discovery will be more often based on intent rather than coincidence . But industry and, for that matter, society as a whole should not forget that this situation has come about through the evolution of science which was not, and can never be, predictable. Rev Clin Esp, 1995 Aug, 195(8), 546 - 9 {Extrapulmonary tuberculosis . Experience at a general hospital (1980-1993)}; Ramos JM et al.; In order to know extrapulmonary tuberculosis in our environment the results of all samples submitted for culture of mycobacteria to the Microbiology Department, Fundacion Jimenez Diaz, from 1980 to 1993 were analyzed . During this period 290 cases of extrapulmonary cases were diagnosed, 101 from 1980 to 1985 and 189 from 1986 to 1993 . The most common site of infection before 1985 was in genitourinary tract (42.6%); in contrast, from 1986 onwards the more common sites of infection were pleural (22.8%), genitourinary tract and lymphatic glands (22.2% in both sites) . When EPT was compared in the two periods of time the observations made were a relative decrease of genitourinary infections (p = 0.00004) and increase in disseminated (p = 0.015) and pleural tuberculosis (p = 0.011) from 1986 compared with previous years . From 1986 a greater proportion of disseminated form was observed (p < 0.0001) in positive-HIV patients and of genitourinary (p = 0.011) and pleural (p = 0.076) forms in negative HIV-patients . In conclusion, extrapulmonary tuberculosis has increased in our environment during the period 1980-1993, and this increase is not attributable only to positive-HIV patients . The distribution of clinical forms of this disease was different in the two studied periods and among positive and negative HIV patients. J Clin Microbiol, 1995 Aug, 33(8), 2048 - 53 Investigation of sheep-associated malignant catarrhal fever virus infection in ruminants by PCR and competitive inhibition enzyme-linked immunosorbent assay; Li H et al.; Development of control measures for the gammaherpesviral disease of cattle known as sheep-associated malignant catarrhal fever (SA-MCF) has been hampered by a lack of accurate diagnostic tests either for the causative virus or for antibody against that virus . A recently developed competitive-inhibition enzyme-linked immunosorbent assay (CI-ELISA) for the detection of antibody to malignant catarrhal fever (MCF) virus (MCFV) in ruminants based on a monoclonal antibody to a widely conserved epitope of MCFV (H . Li, D . T . Shen, D . P . Knowles, J . R . Gorham, and T . B . Crawford, J . Clin . Microbiol . 32:1674-1679, 1994) and a PCR assay based on previously reported primers (S . I . F . Baxter, I . Pow, A . Bridgen, and H . W . Reid, Arch . Virol . 132:145-159, 1993) were used to detect anti-MCFV antibody and SA-MCFV DNA in sheep and other ruminants . The PCR amplified a specific 238-bp SA-MCFV genomic DNA fragment from peripheral blood lymphocytes of adult sheep and other ruminants with clinical MCF . Of 144 samples from randomly selected healthy adult sheep, 143 (99%) were positive by PCR and 136 (94%) were positive by CI-ELISA . The agreement between the two assays exceeded 95% . Of nine samples collected from cattle and deer with clinical MCF of apparent sheep origin, seven were CI-ELISA positive and all 9 were PCR positive . Among 59 serum samples from presuckling lambs, none contained antibody detectable by CI-ELISA . After suckling, maternal anti-MCFV antibody was detectable for about 10 +/- 3 weeks . Although all colostrum and milk samples from infected ewes were strongly PCR positive, the appearance of detectable SA-MCFV DNA in lambs was correlated generally with antibody patterns, which suggests that the natural infection event in sheep may not occur during the perinatal period but occurs sometime later in life. Med Microbiol Immunol (Berl), 1995 Aug, 184(2), 73 - 80 Sequence analysis of ospA genes shows homogeneity within Borrelia burgdorferi sensu stricto and Borrelia afzelii strains but reveals major subgroups within the Borrelia garinii species; Will G et al.; The genes coding for the outer surface protein A (OspA) of 19 different Borrelia burgdorferi strains belonging to the seven OspA-serotypes 1-7, previously described {Wilske et al . (1993) J Clin Microbiol, 31: 340-350}, have been investigated . B . burgdorferi sensu lato strains were chosen from various biological sources (ticks, human skin and cerebrospinal fluid) as well as different geographical origins (Germany, Slovenia, Austria, United States) . The open reading frames of all ospA genes consist of 819-825 nucleotides corresponding to proteins of approximately 30 kDa . The ospA sequences obtained in this study and previous published studies were compared with the results from OspA serotyping with monoclonal antibodies . The classification into the seven OspA serotypes could be confirmed on a genetic basis (ospA genotypes 1-7) for all strains analyzed so far (n = 29) . In addition, one strain without OspA expression could be assigned to ospA genotype 2 . Genetic stability could be proven for the ospA gene of B . burgdorferi strain PWudI after inocculation and reisolation from a gerbil . However, we found evidence for intragenic recombination by cluster analysis of ospA sequence data . Accordance of ospA genotype 1 strains with B . burgdorferi sensu stricto and ospA genotype 2 strains with B . afzelii, as well as the ospA genotype strains 3-7 with B . garinii was confirmed by pulsed-field gel electrophoresis of MluI-digested genomic DNA . B . garinii is not only more heterogeneous in respect to the OspA-encoding genes, but shows moreover major subgroups formed by genotypes 4, 5 and 6 and genotypes 3 and 7, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) Appl Environ Microbiol, 1995 Aug, 61(8), 3014 - 8 Detection of Norwalk virus and hepatitis A virus in shellfish tissues with the PCR; Atmar RL et al.; A method for the detection of Norwalk virus and hepatitis A virus from shellfish tissues by PCR was developed . Virus was added to the stomach and hepatopancreatic tissues of oysters or hard-shell clams, and viral nucleic acids were purified by a modification of a previously described method (R.L . Atmar, T.G . Metcalf, F.H . Neill, and M.K . Estes, Appl . Environ . Microbiol . 59:631-635, 1993) . The new method had the following advantages compared with the previously described method: (i) more rapid sample processing; (ii) increased test sensitivity; (iii) decreased sample-associated interference with reverse transcription-PCR; and (iv) use of chloroform-butanol in place of the chlorofluorocarbon trichlorotrifluoroethane . In addition, internal standards for both Norwalk virus and hepatitis A virus were made which demonstrated when inhibitors to reverse transcription-PCR were present and allowed quantitation of the viral nucleic acids present in samples . This assay can be used to investigate shellfish-associated gastroenteritis outbreaks and to study factors involved in virus persistence in shellfish. FEMS Microbiol Lett, 1995 Jul 15, 130(1), 75 - 80 Phylogenetic analysis of polycyclic aromatic hydrocarbon degrading mycobacteria by 16S rRNA sequencing; Wang RF et al.; Mycobacterium sp . PYR-1 was previously isolated in our laboratory and was shown to be able to mineralize high molecular mass polycyclic aromatic hydrocarbons (PAHs) {Heitkamp and Cerniglia, (1988) Appl . Environ . Microbiol . 54, 1612-1614} . In this research, the 16S rRNA gene (rDNA) of this strain was amplified by polymerase chain reaction (PCR) and directly sequenced by cycle sequencing method . We compared this sequence with all known mycobacterial 16S rDNA sequences available from GenBank and found that Mycobacterium sp . PYR-1 16S rDNA differs from the other mycobacteria, especially in the region of nucleotides 168-200 (in the Escherichia coli numbering system) . Using the 16S rDNA sequences of the mycobacteria, a phylogenetic tree was constructed . The data from the phylogenetic tree and similarity values suggest that Mycobacterium sp . PYR-1 is closer to M . aurum and M . vaccae . Using the same approach, we also determined the 16S rDNA from an another PAH-degrading Mycobacterium sp . PAH135, isolated by Grosser and colleagues (1991) (Appl . Environ . Microbiol . 57, 3462-3469) . Mycobacterium sp . PAH135 was found to be closer to M . aichiense, and different from our Mycobacterium sp . PYR-1. Int J Syst Bacteriol, 1995 Jul, 45(3), 549 - 53 Mycobacterium branderi sp . nov., a new potential human pathogen; Koukila-Kahkola P et al.; A number of mycobacterial strains with similar growth characteristics, metabolic properties, and lipid compositions, which were previously placed in the Helsinki group (E . Brander, E . Jantzen, R . Huttunen, A . Juntunen, and M.-L . Katila, J . Clin . Microbiol . 30:1972-1975, 1992), were characterized by performing 16S rRNA gene sequencing . Of the 14 strains studied, 9 had a unique, previously undescribed sequence in the variable region of 16S rRNA . These nine strains, all of which were isolated from respiratory tract specimens, were nonpigmented and grew at 25 degrees C to 45 degrees C, reaching full colony size after 2 to 3 weeks . They produced arylsulfatase, nicotinamidase, and pyrazinamidase and were negative for Tween 80 hydrolysis, catalase, urease, and nitrate reductase activities, and niacin . Their glycolipid patterns were identical . A mycolic acid analysis performed by using thin-layer chromatography showed that these organisms contained alpha-mycolates, ketomycolates, and carboxy mycolates . Gas-liquid chromatography revealed that 2-eicosanol was the major alcohol and hexacosanoic acid was the major mycolic acid cleavage product . On the basis of their growth, biochemical, and lipid characteristics and their unique 16S rRNA sequence, we propose that these organisms should be assigned to a new species, Mycobacterium branderi . Comparative 16S rRNA sequencing revealed that this new species is closely related to Mycobacterium celatum, Mycobacterium cookii, and Mycobacterium xenopi . Strains 52157T (T = type strain) and 43548 have been deposited in the American Type Culture Collection as strains ATCC 51789 and ATCC 51788, respectively. Pathology, 1995 Jul, 27(3), 260 - 7 Selection and implementation of a laboratory computer system; Moritz VA et al.; The process of selection of a pathology computer system has become increasingly complex as there are an increasing number of facilities that must be provided and stringent performance requirements under heavy computing loads from both human users and machine inputs . Furthermore, the continuing advances in software and hardware technology provide more options and innovative new ways of tackling problems . These factors taken together pose a difficult and complex set of decisions and choices for the system analyst and designer . The selection process followed by the Microbiology Department at Heidelberg Repatriation Hospital included examination of existing systems, development of a functional specification followed by a formal tender process . The successful tenderer was then selected using predefined evaluation criteria . The successful tenderer was a software development company that developed and supplied a system based on a distributed network using a SUN computer as the main processor . The software was written using Informix running on the UNIX operating system . This represents one of the first microbiology systems developed using a commercial relational database and fourth generation language . The advantages of this approach are discussed. J Clin Microbiol, 1995 Jul, 33(7), 1860 - 6 Molecular analysis of genes encoding outer surface protein C (OspC) of Borrelia burgdorferi sensu lato: relationship to ospA genotype and evidence of lateral gene exchange of ospC; Jauris-Heipke S et al.; It has been shown by analysis with monoclonal and polyclonal antibodies that outer surface protein C (OspC) of Borrelia burgdorferi sensu lato is highly heterogeneous . To determine if the heterogeneity has a genetic basis, the genes of 18 different B . burgdorferi sensu lato strains have been amplified by PCR, cloned, and sequenced . The ospC genes could be amplified from all strains tested, even from two strains which did not express OspC in detectable amounts . Among the 18 strains, 16 significantly different types of ospC sequences have been found . The sequence identities of the deduced amino acid sequences of different ospC genotypes range between 62 and 80% (determined without the leader peptide) . The sequences range between 62 and 80% (determined without the leader peptide) . The sequences correspond to one of the 13 OspC types distinguishable by analysis with monoclonal antibodies (B . Wilske, S . Jauris-Heipke, R . Lobentanzer, I . Pradel, V . Preac-Mursic, D . Roessler, E . Soutschek, and R . C . Johnson, J . Clin . Microbiol . 33:103-109, 1995) or represent additional types . Two completely new types were found, and OspC type 8 (which was found in Borrelia afzelii and Borrelia garinii) could be divided into two groups with different sequences but the same antibody pattern . Thus, strains belonging to different species or OspA serotypes were always significantly different in their ospC sequences . This was also confirmed by ospA sequence analysis . Interestingly, some strains of the same OspA serotype or genotype were very heterogeneous with respect to OspC, while others had nearly identical OspC proteins . Such groups of strains were found among B . burgdorferi sensu stricto, B . afzelii, and B . garinii strains . Cluster analysis of 5'-terminal and 3'-terminal stretches of ospC suggested recent intragenic recombination events in the ospC gene at least one B . afzelii strain . In addition, other recombination events between ancestors of strains belonging to the same or different species were evidenced by this type of analysis. J Clin Microbiol, 1995 Jul, 33(7), 1716 - 9 Use of amplified fragment length polymorphism in molecular typing of Legionella pneumophila and application to epidemiological studies; Valsangiacomo C et al.; A novel method for molecular typing of organisms, amplified fragment length polymorphism analysis, was tested for its suitability in epidemiological studies in medical microbiology . Amplified fragment length polymorphism analysis, originally developed for typing crop plants, consists of a simple restriction-ligation reaction and a subsequent PCR amplification . In a single-step reaction, the genomic DNA is digested and the restriction fragments are ligated to specially constructed adapters . PCR amplification of such tagged restriction fragments with primers complementary to the adapters allows the detection of restriction fragment length polymorphisms upon resolution on agarose gels . The method is fast, efficient, and reproducible for typing strains of Legionella pneumophila isolated from both humans and the environment . The accuracy of the method was tested by comparison with standard restriction fragment length polymorphism typing performed with both a ribosomal and a genomic probe. Br J Gen Pract, 1995 Jul, 45(396), 349 - 51 Diagnosis and management of cases of suspected dermatomycosis in The Netherlands: influence of general practice based potassium hydroxide testing; De Kock CA et al.; BACKGROUND . Microscopy of a potassium hydroxide preparation of skin scrapings or nail clippings, although widely advocated as a test for dermatomycosis, is used in only a small proportion of cases . AIM . This study set out to investigate the effect of potassium hydroxide testing on the subjectively assessed probability that a dermatomycosis was present . METHOD . The study was undertaken in 1992 in Limburg, a province in the south of the Netherlands . Ten general practitioners and eight trainees completed a questionnaire and performed a potassium hydroxide preparation for each patient presenting with a skin condition that they thought might be caused by dermatomycosis . Skin or nail material was also sent to a microbiology laboratory where another potassium hydroxide preparation as well as a culture were performed, these two tests serving as a gold standard against which to judge the potassium hydroxide preparation by the general practitioners . Data from a total of 164 cases were analysed . RESULTS . The results of the potassium hydroxide test carried out in the practice had a considerable influence on the subjectively assessed probability that a dermatomycosis was present, especially if the outcome was positive . The indication for antifungal treatment was altered as a result of the test in a quarter of all cases, mostly from negative to positive . Use of the practice potassium hydroxide test could increase the proportion of correct therapeutic decisions from 54% to 69%, with 20% of cases being undertreated . Of cases that gave a positive test result in the practice 83% also had a positive laboratory test result, while of cases that gave a negative practice result 43% were positive in the laboratory . CONCLUSION . The potassium hydroxide test improves the diagnostic process in cases of possible dermatomycosis and may result in a change in management . The test can provide a confirmation of the diagnosis of dermatomycosis but is not useful in the exclusion of this diagnosis. J Bacteriol, 1995 Jul, 177(13), 3647 - 55 Nitrate repression of the Escherichia coli pfl operon is mediated by the dual sensors NarQ and NarX and the dual regulators NarL and NarP; Kaiser M et al.; The pfl operon is expressed at high levels anaerobically . Growth of Escherichia coli in the presence of nitrate or nitrite led to a 45% decrease in expression when cells were cultivated in rich medium . Nitrate repression, however, was significantly enhanced (sevenfold) when the cells were cultured in minimal medium . Regulation of pfl expression by nitrate was dependent on the NarL, NarP, NarQ, and NarX proteins but independent of FNR, ArcA, and integration host factor, which are additional regulators of pfl expression . Strains unable to synthesize any one of the NarL, NarP, NarQ, or NarX proteins, but retaining the capacity to synthesize the remaining three, exhibited essentially normal nitrate regulation . In contrast, narL narP and narX narQ double null mutants were devoid of nitrate regulation when cultured in rich medium but they retained some nitrate repression (1.3-fold) when grown in minimal medium . By using lacZ fusions, it was possible to localize the DNA sequences required to mediate nitrate repression to the pfl promoter-regulatory region . DNase I footprinting studies identified five potential binding sites for the wild-type NarL protein in the pfl promoter-regulatory region . Specific footprints were obtained only when NarL was phosphorylated with acetyl phosphate before the binding reaction was performed . Each of the protected regions contained at least one heptamer sequence which has been deduced from mutagenesis studies to be essential for NarL binding (K . Tyson, A . Bell, J . Cole, and S . Busby, Mol . Microbiol . 7:151-157, 1993). Invest Ophthalmol Vis Sci, 1995 Jul, 36(8), 1477 - 91 A chlamydial major outer membrane protein extract as a trachoma vaccine candidate; Campos M et al.; PURPOSE . As shown in infected humans and in animal models of chlamydial infection, the major outer membrane protein (MOMP) of Chlamydia trachomatis is immunogenically potent . The purpose of this investigation was to test in the cynomolgus monkey model of trachoma a new extract of MOMP as a candidate vaccine against ocular chlamydial infection . METHOD . The nonionic detergent octyl-beta-D glucopyranoside (OGP) was used to extract MOMP from purified C . trachomatis (serovar C) elementary bodies . Protective immunization with OGP-MOMP by mucosal and systemic routes was compared in the cynomolgus monkey model of trachoma . All control and immunized monkeys were challenged by topical application of infectious C . trachomatis to the conjunctivae 35 days after the initiation of immunization . RESULTS . Immunization with OGP-extracted MOMP successfully induced chlamydia-specific local and systemic immunity to MOMP and to whole organism before challenge and early clearance of infection by systemically immunized monkeys . Although ocular disease was not significantly reduced in either immunized group compared to control animals, the lowest clinical and microbiologic disease scores developed in two animals in the mucosal group with the highest immunoglobulin A tear antibody titers at day 0 to 14, whereas higher tear and serum immunoglobulin G correlated with reduced disease in the systemically immunized group . CONCLUSIONS . These data demonstrate that despite evidence of vigorous MOMP-specific and other chlamydia-specific serologic and cell-mediated immunity, as well as anamnestic serologic responses to chlamydia, vaccination with OGP-MOMP was only partially protective against chlamydial ocular disease . The partial protection correlated best with tear immunoglobulin A responses after mucosal immunization and with local and systemic immunoglobulin G responses after peripheral immunization, suggesting that alternative chlamydial antigens may have to be considered in future vaccine development to induce more effective protective immunity and that evaluation of efficacy must be appropriate to route of immunization. J Child Neurol, 1995 Jul, 10(4), 271 - 82 The diagnosis of congenital infections: contemporary strategies; Souza IE et al.; Congenital infections remain an important source of neurologic, ophthalmologic, and audiologic disability for thousands of children throughout the world . This review summarizes the clinical features and describes contemporary approaches to the microbiologic diagnosis of congenital infections . In particular, this review emphasizes the important roles that molecular methods, especially the polymerase chain reaction, have in detecting the many infectious agents capable of damaging the developing nervous system. Int J Food Microbiol, 1995 Jul, 26(2), 199 - 218 Mathematics of predictive food microbiology; Baranyi J et al.; Commonly encountered problems related to modelling bacterial growth in food are analysed from a mathematical point of view . Modelling techniques and terms, some misused, are discussed and an attempt is made to clarify how, and under what conditions, they may be used . A theoretical framework is given to provide a basis in which mathematical models having been used in predictive microbiology can be embedded . By using several simplifying idealizations as a compromise between the complexity of the biological system and the available data, a practically usable model becomes available. J Clin Pathol, 1995 Jul, 48(7), 667 - 9 Documentation of blood culture results; Howe RA et al.; AIMS--To evaluate the adequacy of documentation of blood culture results in patients' medical notes . METHODS--A pro-forma was completed following review of medical notes at 24 and 48 hours after a blood culture had been reported as positive . The study was performed on blood cultures received at the Department of Microbiology, Royal Hallamshire Hospital, Sheffield, from two local hospitals . Two periods were studied: (A) May to June 1993 and (B) September to October 1993 . RESULTS--There were 43 results studied in period A and 79 in period B, giving a total of 122 results studied . Overall, 72 (59%) of 122 results were recorded in the medical notes at 24 hours . Of those results deemed highly significant, 40 (63%) of 63 were recorded . There was no significant difference in the documentation of results if the result was given personally or via the telephone . Nor was there any difference in documentation between different medical grades . Throughout the study there were six inaccurate records . The cumulative documentation over 48 hours of positive results was 54 (86%) of 63 of highly significant, 27 (69%) of 39 of uncertain significance, and 11 (55%) of 20 probable contaminant results . CONCLUSIONS--Documentation of blood culture results is currently suboptimal. Gesundheitswesen, 1995 Jul, 57(7), 411 - 5 {Blind alleys and misconceptions in public health}; Muller HE; The concept of hygiene was created in the 19th century although Hippocrates had already conceived an influence of atmosphere, soil and water on human health . The concept of a public health organisation, however, is a fairly recent one . Environmental and social hygiene were the two poles of the new discipline that focussed on public health . However, the ideologies of capitalism, communism and socialism as well as of social darwinism and "survival of the elite" discredited social hygiene . The decline of totalitarianism was associated with a "loss of face" of state-controlled medicine, including social hygiene . Both the post-World War II German constitution and the previous German statutory health insurance ordinance had blocked it, and hence, no Federal bill on public health was carried . The consequences of this disregard of public health are poor protection by vaccination, a gap in compulsory notification and in epidemics control and high rates of nosocomial infections . Absolutely no development of the science of epidemiology was possible whereas that of medical microbiology is choked by the system now in existence . There is a great misconception within individual hygiene by identifying it merely with cleanliness . Hygiene became a synonym for cleanliness, although that had evolved during a long cultural sociological process centuries before hygiene was established . The modern evolution of the science of hygiene shows the danger that emphasis on healthy lifestyles or on environmental protection may result in regulations and finally in a tyranny that may threaten the liberty of human rights . The so-called "principle of concern" is an example of such irrationality because there is no sensible proportion between risk and expense. Curr Opin Rheumatol, 1995 Jul, 7(4), 290 - 8 Etiopathogenesis of reactive arthritis and ankylosing spondylitis; Careless DJ et al.; Advances in molecular biology have brought more refined techniques to the study of the structure and function of HLA molecules and the biology of arthritogenic bacteria . Site-directed mutations in HLA and bacterial genes have focused attention on amino acids that are playing a critical role in the dynamic interaction of host and pathogen . The role of HLA-B27 in conferring disease susceptibility is being evaluated in both human disease and in B27 transgenic animal models . The continued interchange between clinical research in the spondyloarthropathies and the in vitro systems analyzing the immunology and microbiology of these diseases has maintained a high level of interest in this field of arthritis research. Adv Dent Res, 1995 Jul, 9(2), 125 - 6 Saliva stimulants and the oral health of geriatric patients; Makinen KK et al.; Root-surface caries (RSC) has been recognized as a specific and important dental disease . Significant advances have been made in the pathology and microbiology of RSC, and the need to standardize the guidelines for recording RSC data has been recognized . Researchers have emphasized the increasing impact RSC will have on the geriatric population, especially since the methods to treat and prevent this disease are limited . The purpose of this study was to investigate the possibility of limiting RSC in a Veterans Administration (VA) patient population, using polyol-containing saliva stimulants that were voluntarily consumed by residents of a VA Medical Center (VAMC) over a period of from six to 30 months . Another aim was to study the effect of this program on the gingival health of periodontal patients. Vaccine, 1995 Jul, 13(10), 953 - 60 Isotype profiles induced in Balb/c mice during foot and mouth disease (FMD) virus infection or immunization with different FMD vaccine formulations; Perez Filgueira DM et al.; The IgG isotype response in Balb/c mice infected with FMDV or immunized with different vaccine formulations using inactivated virus particles as antigen was analyzed at various times post-inoculation . For this purpose an ELISA based on polyclonal antibodies for detection and quantification of mouse IgG isotypes with FMD virus (FMDV) specificity was developed . Three immunomodulators, which have been shown to be very effective in inducing strong and long-lasting antibody responses (Bahnemann, Arch . Virol . 1975, 47, 47-56; Polatnik and Bachrach, Appl . Microbiol . 1964, 12, 368-376), were employed to formulate different vaccines using aqueous and oil vehicles: a water-soluble fraction of the cell wall of Mycobacterium sp., a purified extract of lipopolysacharide from Brucella ovis and a synthetic lipoamide, Avridine . Infected animals between 14 and 60 days post-inoculation (d.p.i.) showed responses dominated by IgG2b, followed by IgG1, IgG2a and IgG3, respectively . The IgG3 isotype was the first, together with IgG1, to be elicited during the first 7 days after infection, whereas no IgG3 activity was detected in vaccinated animals at any time . With formulations including immunomodulators, persisting high levels of IgG2b (similar to those of infected animals) were detected until 180 d.p.i., while with conventional vaccines IgG2b responses were detected up to 60 d.p.i . Animals vaccinated with formulations including these immunomodulators presented an augmented resistance to viral challenge at 210 d.p.i . in relation with those immunized with conventional vaccines . The possible relationship of these differences in the isotype response and protection is discussed. Rev Med Brux, 1995 Jul-Aug, 16(4), 216 - 7 {Fine-needle cytopuncture and/or microbiopsies}; Dagnelie J; When lesions cannot be clearly identified by sonography or mammography and if their images are clinically occult, their cytology or histology confirmation is required . Stereotactic biopsy allows an accurate locating of non palpable lesions, that are also invisible at sonography . The choice between a fine needle aspiration biopsy and core needle micro-biopsy depends upon local and technical possibilities but above all upon mammographic aspect of the lesion . When microcalcifications have to be identified both methods should be used. Rev Med Brux, 1995 Jul-Aug, 16(4), 214 - 5 {Difficult diagnosis in breast cancer}; Baeyens L; A detailed senologic evaluation with complete clinical examination, (color Doppler) echography, comparative mammography and cytology or microbiopsy can avoid surgery in case of a post-traumatic fat necrosis, a Mondor Syndrome, an infectious mastitis or a ductal ecstasy with nipple discharge . Actually we have still difficulties to interpret non palpable breast lesions and to supervise operated and radiated breasts. Presse Med, 1995 Jun 17, 24(22), 1021 - 4 {Prognosis of acute tuberculous respiratory distress syndrome . 4 cases}; Roger PM et al.; OBJECTIVES: We examined the characteristics of 4 cases of adult respiratory distress syndrome in patients with tuberculosis in an attempt to improve prognosis . METHODS: Four new cases of adult respiratory distress syndrome were described together with a review of the cases reported in the literature . Inclusion criteria were the presence of the syndrome as defined according to the American-European consensus conference and the criteria described by Murray et al . and identification of the mycobacteria causing tuberculosis . RESULTS: A total of 52 cases were included in the study . The sex ratio was 0.71 and mean age 46 +/- 15 years . Eight patients had a past history of pulmonary tuberculosis . Alcoholism was the primary immunodepression factor observed (35%) followed by human immunodeficiency virus infection (13%) . For 74% of the patients, the disease course lasted 7 days . The initial chest X-ray was suggestive of tuberculosis in 11 . Intradermoreaction to tuberculin was positive in 2 out of 17 patients . Direct examination of non-invasive respiratory samples was positive in 44% for mycobacteria . Disseminated tuberculosis was seen in 64% . Anti-tuberculosis antibiotherapy was started on the first day of intensive care in 68% of the patients; rapid treatment was associated with better prognosis: 1.5 +/- 1.2 days versus 3 +/- 2.7 in fatal cases (p = 0.02) . Adjuvant corticosteroid therapy was used in 46% of the cases and was apparently associated with unfavourable outcome: 74% mortality versus 58% without corticosteroids . Ventilatory assistance was required in 88% and associated with poor prognosis (13% survival versus 100% without assistance) (p < 10(-3)) . Outcome was fatal in 36 cases (70%) with a mean delay of 9.7 +/- 10.8 days . CONCLUSION: The conditions required for improving the prognosis of adult respiratory distress syndrome in tuberculosis patients included suspecting tuberculosis in all cases of acute respiratory failure of unknown origin, particularly in the immunodepressed patient, and to avoid missing this diagnosis in case of a non-suggestive chest X-ray and a negative though exhaustive microbiology search . Adjuvant corticotherapy is uneffective and may be dangerous. Schweiz Med Wochenschr, 1995 Jun 3, 125(22), 1082 - 8 {Comparative study of preliminary and definitive anatomo-pathological diagnoses in 375 autopsies in adults}; Perren F et al.; For the past 5 years the institute of pathology of the University of Lausanne has been delivering both provisional and final autopsy reports . The provisional reports are based mainly upon macroscopic findings, whereas the final reports include the information provided by supplementary investigations such as microscopy, histochemistry, more rarely electron microscopy, immunohistochemistry and/or microbiology . The reliability and usefulness of the provisional reports were analyzed by systematic comparison between the provisional and final reports of 375 adult post-mortems as well as through an inquiry among requesting physicians . No significant difference was found between the two reports in 77.1% of the cases . In 22.1% the supplementary investigations provided information which had a bearing on the final diagnosis and made it possible to complete or correct the macroscopic diagnosis . In 0.8% the significant difference was due to the omission, in the provisional report, of an obvious macroscopic diagnosis . Finally, 95% of the consulted physicians found the provisional reports useful because of the precise written and particularly rapid information they provided . These results not only demonstrated that the establishment of such provisional reports is fully justified, but further emphasize the fundamental and complementary role played by the final autopsy reports. Malays J Pathol, 1995 Jun, 17(1), 11 - 5 Comparative study of a non-radiometric BACTEC system and a conventional blood culture system in a clinical microbiology laboratory; Yew OF et al.; The BACTEC NR730 blood culture system is a commercially available system which utilizes infrared spectrophotometry to detect bacterial growth in broth media inoculated with the blood specimen . The objective of this study is to compare this system with the conventional system used in our laboratory . A total of 479 blood samples were collected from adult patients in the Klang TAR Hospital and inoculated simultaneously into the two systems . Clinically significant isolates were recovered from 59 (12.3%) specimens by one or both systems yielding a total of 65 isolates of which 41 isolates were recovered in both systems, 18 in BACTEC only and 6 in the conventional system (P < 0.01) . Of the 40 (8.3%) blood cultures that were judged as contaminated, 2 were found in both systems, 12 in the BACTEC only and 26 in the conventional system . After 48 hours (day 2) the BACTEC system had recovered 93.2% of the total significant isolates while the conventional system recovered 61.7% only . Our results showed that the BACTEC system yielded more significant isolates in a shorter time and with a lower incidence of contamination as compared to the conventional system. Braz J Med Biol Res, 1995 Jun, 28(6), 693 - 8 The diameter of water pores formed by colicin Ia in planar lipid bilayers; Krasilnikov OV et al.; The effective size of colicin Ia channel was tested by a recently described method (FEMS, Microbiology and Immunology (1992) . 105: 93-100) in which the nonelectrolyte molecules with different hydrodynamic diameters (0.52 to 5.0 nm) were used as molecular tools . We have shown that despite low conductance (55-105 pS at 1.5 M KCl, pH 7.0) the ion channels formed by colicin Ia have a fairly large water pore diameter equal to 1.66-1.88 nm . The results are discussed in terms of an energetic barrier for ions passing into the channel lumen. Chest, 1995 Jun, 107(6), 1689 - 97 Intravenacaval membrane oxygenation and carbon dioxide removal in severe acute respiratory failure; Conrad SA et al.; STUDY OBJECTIVE: To characterize the physiologic response to, and safety of, intravenacaval membrane oxygenation and carbon dioxide removal . DESIGN: Interventional before-after study . SETTING: University teaching hospital ICU . PATIENTS: Twenty-two patients with severe acute respiratory distress syndrome (ARDS) . INTERVENTIONS: Implantation of a hollow-fiber membrane oxygenator (IVOX; CardioPulmonics; Salt Lake City, Utah) into the superior and inferior venae cavae by venotomy of the right femoral or right internal jugular vein for a duration of up to 20 days . MEASUREMENTS: Hemodynamic measurements using pulmonary artery and systemic artery catheters, ventilator settings (FIO2, minute ventilation, peak inspiratory pressure, and positive end-expiratory pressure), arterial and mixed venous blood gases (pH, PCO2, PO2, and measured saturation), and clinical laboratory determinations (CBC, fibrinogen, plasma hemoglobin, complement C3 and C5) were obtained . Calculations of PaO2/FIO2 ratio and PaCO2-VE product were used to assess gas exchange efficacy . Microbiologic cultures were obtained from the device and wound following explantation . Survival to ICU discharge and hospital discharge were recorded . RESULTS: Implantation was successful in 20 of 22 patients . Gas exchange rates averaged 50.4 +/- 15.8 mL.min-1 for carbon dioxide and 71.1 +/- 20.2 mL.min-1 for oxygen . A reduction in FIO2 from 0.78 +/- 0.16 to 0.63 +/- 0.21 and in VE from 177 +/- 94 mL.kg-1.min-1 to 127 +/- 58 mL.kg-1.min-1 was possible within 4 h post-implantation . By 12 h, FIO2 was reduced to 0.57 +/- 0.18 . Indices of gas exchange improved significantly after implantation, with PaO2/FIO2 ratio increasing from 79 +/- 20 to 112 +/- 47 and PaCO2-VE product decreasing from 7.6 +/- 4.2 to 4.9 +/- 2.5 within 4 h . A significant reduction in peak inspiratory pressure was achieved (45 +/- 10 to 38 +/- 9 cm H2O) . Major complications were blood loss during implantation requiring transfusion in 11 patients, a retroperitoneal bleed in 1 patient, and femoral deep venous thrombosis in 4 patients, but there were no long-term sequelae or IVOX-related deaths . The ICU and hospital survival were 10/20 (50%) and 8/20 (40%), respectively . CONCLUSIONS: Intravenacaval membrane oxygen and carbon dioxide removal can provide partial respiratory support during severe respiratory failure and permit reductions in the level of mechanical ventilator support, with an acceptable safety profile. J Bacteriol, 1995 Jun, 177(12), 3370 - 8 The proline-rich P65 protein of Mycoplasma pneumoniae is a component of the Triton X-100-insoluble fraction and exhibits size polymorphism in the strains M129 and FH; Proft T et al.; Previously, we described the identification of a novel Mycoplasma pneumoniae M129 protein, named P65 because of its apparent molecular mass of 65 kDa estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (T . Proft and R . Herrmann, Mol . Microbiol . 13:337-348, 1994) . DNA sequence analysis of the P65 open reading frame (orfp65), however, revealed an ORF encoding a protein with a molecular weight of 47,034 . This discrepancy can be explained by the unusual amino acid composition of this protein . According to the deduced amino acid sequence, the N-terminal half of P65 contains several penta- and hexapeptides (DPNAY and DPNQAY) forming a proline-rich acidic domain . Secondary-structure predictions indicated beta-sheets and turns within that region, suggesting an extended and rigid conformation . Near the C terminus of P65 the tripeptide Arg-Gly-Asp (RGD) was found . This motif is known to play an important role in binding of extracellular matrix proteins to integrins . P65 could be located exclusively to the Triton X-100-insoluble cell fraction . The results of immunofluorescence microscopy and of immunoadsorption experiments indicated that P65 carries surface-exposed regions . Mild treatment of whole cells with proteases resulted in cleavage of a limited amount of P65 molecules, suggesting either that only a small percentage of P65 molecules are exposed on the surface or that protease cleavage is hampered by a compact protein conformation or by binding of an unknown component to P65 . P65 exhibits size polymorphism in M . pneumoniae M129 and FH . This is caused by an intragenetic duplication of a 54-bp sequence within the FH orfp65 . As a consequence, the number of DPNAY pentapeptides increased from 9 to 12 repeats in the FH strain. Am J Respir Crit Care Med, 1995 Jun, 151(6), 1878 - 88 Diagnostic tests for pneumonia in ventilated patients: prospective evaluation of diagnostic accuracy using histology as a diagnostic gold standard; Marquette CH et al.; The diagnostic accuracy of protected-specimen brush (PSB), bronchoalveolar lavage (BAL), and endotracheal aspirates (EA) was prospectively evaluated in a series of 28 mechanically ventilated patients (MV patients) who died within 3 d of the bronchoscopic procedure, using postmortem lung examination as the gold standard for establishing the diagnosis of pneumonia . The entire fixed lungs were carefully dissected along the bronchovascular axes and each segment was cut into 5- to 10-mm thick sections, enabling gross examination of the lung parenchyma . Two tissue blocks were taken from each segment, including grossly abnormal areas whenever present . In several cases, two peripheral (subpleural) lung-tissue blocks were also taken from each lobe prior to systematic dissection of the lungs . Quantitative cultures (QC) and direct cytologic and microbiologic examination (DE) was performed on respiratory samples obtained within 72 h before death . Values of 10(3) cfu/ml of Ringer's solution, 10(4) cfu/ml of retrieved fluid, and 10(6) cfu/ml of respiratory secretions were used as cutoff points for quantitative PSB, BAL, and EA cultures, respectively . The main findings in this study were that: (1) Pneumonia was present in 67% of the patients . (2) Histologic lesions of pneumonia were mainly bilateral and predominated in the dependent lung segments . (3) Coexistence of a variety of noninfectious processes was a common finding in patients with pneumonia . (4) In several cases pneumonia was absent from peripheral lung samples while more central areas of the same segment displayed typical foci of pneumonia . (5) The sensitivity of quantitative cultures was 55%, 57%, and 47% for EA, PSB, and BAL, respectively, and the specificity was 85%, 88%, and 100%, respectively . Reducing the diagnostic threshold of EA to 10(5) cfu/ml of respiratory secretions instead of 10(6) cfu/ml resulted in a sensitivity of 63.1% and a specificity of 75% for EA . The sensitivity of direct examination (DE) was 50%, 47%, and 47%, respectively, and the specificity was 75%, 88%, and 87% . (6) The presence of intracellular organisms (ICO) in BAL had a 36.8% sensitivity and 100% specificity in establishing the diagnosis of pneumonia regardless of their percentage . (7) Although 15 patients (53%) were not on antibiotics or were off antibiotics for more than 48 h before testing, no relationship could be established between the patients' antibiotic status and the result of any diagnostic test . By using a recommended methodology for respiratory sampling techniques together with complete postmortem lung examination as a diagnostic "gold standard," this study provides a realistic insight into the diagnostic values of EA, PSB, and BAL in MV patients with suspected pneumonia. Clin Lab Med, 1995 Jun, 15(2), 437 - 46 Strategies for quality management in clinical microbiology; Schifman RB; Quality assessment and performance improvement are important management functions that add value to information and services produced by the clinical microbiology laboratory . Analytical quality control procedures are well standardized, and in many cases regulated . Whereas preanalytical and postanalytical factors have considerable impact on quality, performance assessment and improvement in this area have received less consideration . This article describes an approach to quality management of the total testing process in clinical microbiology, including interdisciplinary participation, specimen quality, test use, result use, turnaround time, information quality, user perceptions, and benchmarking. Clin Lab Med, 1995 Jun, 15(2), 407 - 31 The use of molecular techniques in the epidemiology and control of infectious diseases; Sader HS et al.; The ability to identify specific strains within a given species of pathogen is an important aid in the rational development of effective measures to prevent and control nosocomial infections . The efforts of both microbiologist and hospital epidemiologic are facilitated greatly by the availability of the newer molecular epidemiologic typing techniques . Although these methods clearly have limitations, they generally are a significant improvement over the more conventional typing methods, many of which are too cumbersome, insensitive, and time-consuming to be of practical value for epidemiologic evaluations . Based on current experience, the molecular typing methods that appear to be the most practical and useful for both large and small scale epidemiologic studies are the DNA-based methods of REAP and PFGE . Many questions remain concerning the appropriate role of molecular typing methods in the clinical microbiology laboratory . Often, molecular typing may be performed more efficiently in a reference laboratory . In contrast, selected methods such as plasmid analysis are well within the scope of clinical microbiology laboratories and may be an important adjunct to the hospital infection control effort . Given the limitations of the available methods and the complex nature of patients at risk for nosocomial infections, it is imperative that these methods be employed with clear epidemiologic objectives in mind . Typing should always include unrelated as well as epidemiologically related isolates and, whenever possible, all organisms should be typed under identical conditions, preferably within the same test run . In addition, results are most effectively used to supplement rather than to replace hypotheses and questions thoughtfully developed by the clinician or epidemiologist . Ideally, typing is performed independently by the laboratory to avoid bias, but the results are applied collaboratively to ensure that both the potential insights and the unavoidable ambiguities presented by the results are clearly appreciated . Additional studies based upon sound epidemiologic principles will help clarify the role of the various molecular typing methods as epidemiologic markers and advance our understanding of the epidemiology of nosocomial infections. Clin Lab Med, 1995 Jun, 15(2), 365 - 87 New aspects of emerging fungal pathogens . A multifaceted challenge; Schell WA; This article describes adventitious morphologic forms for species of Fusarium, Paecilomyces, Acremonium, and Scedosporium that can be easily mistaken on histologic, cytologic, and microbiologic examination for Candida species . These forms appear to be correlated with, and may provide explanation for, positive blood cultures in disseminated infections with these species . Adventitious histologic forms also are illustrated for Blastoschizomyces capitatus . Data from culture-proven mycoses for a 15-month period at one medical center are reviewed, and species are listed for which an increase is anticipated . These and other aspects of emerging fungal pathogens are related to the need for strengthened support of mycology training and for federal funding of a mycoses reporting program. Clin Lab Med, 1995 Jun, 15(2), 251 - 78 Fine-needle aspiration and surgical pathology of infectious lesions . Morphologic features and the role of the clinical microbiology laboratory for rapid diagnosis; Silverman JF et al.; There has been a renewed interest in the use of imprint smears at the time of frozen section in surgical pathology and FNA biopsy for the diagnosis of infectious disease because of the increasing need for rapid diagnosis of opportunistic infections in immunocompromised patients . Moreover, the use of FNA biopsy for the evaluation of superficial and deep masses has become more widespread . The critical step in the FNA biopsy and in evaluation of imprint smears from surgical specimens is immediate interpretation of the slides that have been stained by rapid methods as the Diff-Quik technique . This quick interpretation can identify as infectious case that may need ancillary studies such as a separate pass or more tissue for microbiologic examination and special stains on the aspirated smears, sections, or cell block . An infectious case may be suspected when the basic cytologic inflammatory patterns are identified including acute inflammation, chronic inflammation, granulomatous inflammation, or necrosis . There have been numerous reports describing the cytomorphologic features of several organisms seen in FNA and tissue specimens . The pathologist also needs to be aware of the potential for a false-negative diagnosis of neoplasms in those lesions having a prominent inflammatory component as well as the potential for false-positive diagnosis of malignancy when inflammatory atypia and a repair reaction is present . The interaction of anatomic pathologists and clinical microbiologists is essential for appropriate workup of specimens with an infectious disease etiology . Thus, pathologists need to be well versed in both the anatomic and clinical pathology features of infectious diseases . Finally, those involved with FNA biopsy and handling of surgical pathology specimens should use universal precautions, since all patients are potentially infectious with the HIV virus and other communicable agents. J Clin Pathol, 1995 Jun, 48(6), 560 - 3 Internal audit in a microbiology laboratory; Mifsud AJ et al.; AIM--To set up a programme of internal laboratory audit in a medical microbiology laboratory . METHODS--A model of laboratory based process audit is described . Laboratory activities were examined in turn by specimen type . Standards were set using laboratory s