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Biomedical subjects

J J Wade

Publications and source records attributed to J J Wade.

At least 19 recordsLinked to original sources

Mycobacterium tuberculosis infection in pediatric liver transplant recipients.

OBJECTIVES: To study the incidence, clinical presentation, management, complications and outcome of tuberculosis in pediatric liver transplant recipients. METHODS: A retrospective review of the medical records of children who underwent liver transplantation between 1991 and 1998. RESULTS: Mycobacterium tuberculosis infection occurred in 6 of 254 (2.4%) children undergoing liver transplantation between 1991 and 1998. Cough, pyrexia and poor appetite were common presentations; one-half had normal chest radiographs. The median time to confirmation of diagnosis was 8 months (range, 1 to 17 months). Tests contributing to diagnosis included: Ziehl-Neelsen (ZN) stain (2 patients), M. tuberculosis polymerase chain reaction (1 patient), Mantoux test (1 patient) and histopathology (4 patients). Family health screening was productive for 4 patients. Duration of treatment varied from 9 to 18 months. Isoniazid-induced hepatitis was observed in 2 patients but resolved with dose reduction. Two patients died while receiving treatment, one of Klebsiella spp. septicemia and the other of pulmonary hemorrhage. CONCLUSIONS: Tuberculosis after liver transplantation has a significant morbidity and mortality. Pretransplantation a personal and family history of tuberculosis must be sought, and screening of patients and their families should be considered. Standard regimens incorporating isoniazid and rifampin are effective, but regular monitoring of liver function is essential to detect drug-induced hepatotoxicity.

Adolescent↗

Enterococcus faecium in hospitals.

Most of the characteristics that have ensured the success of enterococci as nosocomial pathogens were described early in this century. Enterococcus faecium and Enterococcus faecalis, the enterococci most frequently isolated from clinical material, differ fundamentally. The intrinsic antimicrobial resistance of Enterococcus faecium, supplemented by acquired resistance mechanisms, can generate a glycopeptide-multiply-resistant nosocomial pathogen that survives on hands and in the environment, and has the potential for intra-hospital and inter-hospital spread. The use of terms such as 'an enterococcus', 'faecal streptococci' and 'group D streptococci' have hindered, and still hinder, our understanding of a species rapidly emerging as the most problematic of nosocomial pathogens.

Anti-Bacterial Agents↗

Prospective study comparing the efficacy of prophylactic parenteral antimicrobials, with or without enteral decontamination, in patients with acute liver failure.

The efficacy of prophylactic parenteral antibacterials, with or without selective decontamination of the digestive tract, was compared in patients with acute liver failure (ALF) or severe acetaminophen hepatotoxicity. One hundred eight patients were randomized on admission to receive intravenous ceftazidime and flucloxacillin, plus either oral and enteral decontamination with colistin, tobramycin, and amphotericin B (group 1), or enteral amphotericin B alone (group 2). The two groups were comparable with respect to age, gender, etiology, coma grade on admission, international normalization ratio, presence of renal failure, Acute Physiology and Chronic Health Evaluation II score, and indicators of poor prognosis. Patients were monitored for clinical and microbiological evidence of infection. There were 15 episodes of infection in 10 of 47 patients (21%) in group 1 and 17 episodes in 12 of 61 patients (20%) in group 2. No differences in incidence, site, and causative organisms of infection were observed between the two groups. Overall, the incidence of infection was significantly higher in patients who developed encephalopathy than in those who did not. In patients who on arrival were not encephalopathic, the development of infection was associated with progression to coma. Duration of Liver Intensive Care Unit (LICU) stay was an independent risk factor for the development of infection. Parenteral antibiotics are effective at reducing the risk of infection in patients with ALF; enteral decontamination provided no additional benefit.

Adolescent↗

Bacterial and fungal infections after liver transplantation: an analysis of 284 patients.

A prospective study of bacterial and fungal infections after liver transplantation in 284 adults was undertaken. One hundred seventy-five (62%) became infected; bacterial or fungal infections occurred in 159 (56%) and 36 (13%) patients, respectively. Gram-positive cocci, in particular Staphylococcus aureus and Enterococcus faecium, were the commonest bacterial pathogens, and bacteremia and wound infection were the most frequent bacterial infections. Acute rejection and prolonged admission were independent risk factors for bacterial infection; pretransplantation antibacterials had a protective effect. Fungal infection most frequently involved the urinary tract and chest; Candida albicans was the most common pathogen. Four independent variables predicted fungal infection: low pretransplantation hemoglobin, high pretransplantation bilirubin, return to surgery, and prolonged therapy with ciprofloxacin. Patients with acute liver failure were more prone to bacterial, but not fungal, infection. No associations were found between infections and duration of surgery. Bacterial, and to a lesser extent, fungal infections are important complications of liver transplantation. However, liver transplantation surgery per se may not be the major determinant of infection.

Abscess↗

The emergence of Enterococcus faecium resistant to glycopeptides and other standard agents--a preliminary report.

We describe the emergence of vancomycin-resistant (VmR) Enterococcus faecium on a liver unit. Over a 22 month period, 110 patients acquired VmR E. faecium. Ribotyping identified 116 patient isolates. Five ribotypes accounted for 78% of patient isolates, the maximum number of patient isolates of a single ribotype was 37, and five clusters of four ribotypes were found. Seven patients acquired more than one ribotype. Environmental sampling yielded VmR E. faecium of the same ribotype as concurrent patient isolates. Clinical specimens from 38 liver transplant patients yielded VmR E. faecium and these were compared to 29 who acquired vancomycin-sensitive (VmS) E. faecium. Logistic regression analysis indicated that duration of admission was the only independent risk factor for acquisition of VmR E. faecium.

Anti-Bacterial Agents↗

Serious infections caused by multiply-resistant Enterococcus faecium.

Three liver transplant patients developed serious intraabdominal infections and recurrent bacteremias due to strains of Enterococcus faecium with high-level resistance to vancomycin. The enterococci were also resistant to all other antibacterials except pristinamycin, which, given orally, proved ineffective. One strain was sensitive to tetracycline. Increasingly, clinicians are likely to encounter infections caused by multiply-resistant enterococci, and these cases illustrate the seriousness of such infections in compromised patients.

Abdomen↗

Randomized comparison of oral fluconazole versus oral polyenes for the prevention of fungal infection in patients at risk of neutropenia. Multicentre Study Group.

An open, randomized study was performed at 18 European centres to compare the efficacy, safety and tolerance of oral fluconazole with oral polyenes for the prophylaxis of fungal colonization and infection in adults at high risk of developing neutropenia. Five hundred and thirty-six hospitalized patients with malignant disease, about to receive chemotherapy, radiotherapy, or bone marrow transplantation, and who were already neutropenic or were expected to develop neutropenia were included in the study. Before therapy or transplantation, patients commenced either oral fluconazole therapy (50 mg/day as a single dose) or oral polyenes therapy (amphotericin B 2 g/day and/or nystatin 4 x 10(6) units/day in four or more divided doses), for a mean of 29.3 days and 31.3 days, respectively. After baseline clinical and mycological testing, patients were re-evaluated at least weekly during prophylaxis, at the end of prophylaxis and two to six weeks later to identify proven or suspected fungal infection and to determine rates of colonization with fungi. Fungal infection was diagnosed in 41 of 511 evaluable patients, 10 (3.9%) of 256 in the fluconazole group and 31 (12.2%) of 255 in the polyene group (P = 0.001). This total included four patients (1.6%) in the fluconazole group who developed oropharyngeal candidiasis compared with 22 (8.6%) in the polyene group (P < 0.001). Systemic infections comprised 6 (2.3%) in the fluconazole group and 9 (3.5%) in the polyene group (P = not significant), and included three Candida krusei infections in each group. Parenteral amphotericin B therapy was given empirically for persistent fevers in an additional 62 (24.2%) patients receiving fluconazole and 59 (23.1%) receiving polyenes (P = not significant). Colonization with fungi was generally similar in each treatment group, although an increased proportion of patients receiving fluconazole developed colonization of the faeces (P < 0.01). Adverse reactions, possibly related to treatment, were recorded in 15 (5.6%) of 269 patients in the fluconazole group and 14 (5.2%) of 267 in the polyene group; these necessitated discontinuation of therapy in seven patients in each group. Once-a-day fluconazole was therefore more effective than oral polyenes for the prevention of oropharyngeal fungal infection and as effective for the prevention of infections at other sites in patients with neutropenia.

Administration, Oral↗

Colonial variation in vancomycin resistant Enterococcus faecium.

Vancomycin resistant enterococci are increasingly being isolated from inpatients. This report describes the colonial variation present in most isolates of vancomycin resistant Enterococcus faecium obtained at this hospital. Colonial variants within the same culture were indistinguishable by antimicrobial susceptibility, biochemical reactions, and ribotyping. Failure to appreciate this colonial variation will lead to pure cultures being regarded as contaminated or mixed.

Cross Infection↗

An open, comparative trial of aztreonam with vancomycin and gentamicin with piperacillin in patients with fulminant hepatic failure.

Fifty patients admitted with fulminant hepatic failure and clinically suspected infection were allocated to receive either aztreonam and vancomycin or piperacillin and gentamicin as first line treatment. Fourteen patients died within 48 h of admission and were excluded from the analysis. Of the remaining 36 patients, 16 received aztreonam/vancomycin and 20 piperacillin/gentamicin. There were 18 episodes of infection in the aztreonam/vancomycin group and 24 in the piperacillin/gentamicin group (P = not significant). The most frequent bacterial pathogen was Staphylococcus aureus. Fungal infection developed in 13 patients (nine in the aztreonam/vancomycin group and four in the piperacillin/gentamicin group; P = not significant). Death attributed to infection occurred in 4 (25%) of 16 patients receiving aztreonam/vancomycin and 4 (20%) of 20 receiving piperacillin/gentamicin (P = not significant). Thirteen patients (three in the aztreonam/vancomycin group and ten in the piperacillin/gentamicin group) had clinical and microbiological improvement without addition or substitution of other antibiotics. No side-effects attributed to the study drugs were recorded.

Adolescent↗

Hygienic hand disinfection for the removal of epidemic vancomycin-resistant Enterococcus faecium and gentamicin-resistant Enterobacter cloacae.

An outbreak strain of Enterococcus faecium, bearing plasmid-mediated vancomycin resistance, and an epidemic gentamicin-resistant, multiply-resistant strain of Enterobacter cloacae, both survived well on fingertips of three volunteers for up to 30 minutes after inoculation. Hand disinfection of inoculated fingers with 60% isopropyl alcohol, or with alcoholic chlorhexidine, reliably gave a 4 log10 reduction of both test organisms. Enterobacter cloacae could not be detected in any finger washings, even by enrichment culture. Chlorhexidine digluconate and povidone-iodine were also effective against E. faecium and Ent. cloacae, giving 4 log10 reductions, but finger washings taken after disinfection yielded low counts of the test strains, e.g. less than 45 recoverable colony forming units (cfu) per finger. Handwashing with soap and water was the least reliable method. The epidemicity, serious antimicrobial multiple resistance and survival on finger-tips of these two strains justifies the use of handwashing agents which have maximum effect. The rapid bactericidal (and residual) activity of alcoholic chlorhexidine suggests that, on the basis of present evidence, it is the preferred agent for hygienic hand disinfection against such strains.

Adult↗

The evaluation of residual antimicrobial activity on hands and its clinical relevance.

A model for evaluation of the residual activity of agents used for hygienic hand disinfection, which relates closely to the "in-use" setting, is described. We looked for residual activity following hand disinfection by a standard method with soap and water and four skin disinfectants in common use. Two test organisms known to have caused cross-infection and having clinically-significant antibiotic resistance were used: a strain of vancomycin-resistant Enterococcus faecium and one of gentamicin-multiply-resistant Enterobacter cloacae. Both organisms survived well on artificially inoculated hands. Residual activity on previously disinfected hands against both test organisms was most marked for alcoholic chlorhexidine ('Hibisol') which showed a 4 log10 reduction within 1 min of inoculation. Chlorhexidine digluconate skin cleanser ('Hibiscrub') and povidone-iodine surgical scrub ('Betadine') also had marked residual activity, but less than alcoholic chlorhexidine. 60% Isopropanol showed no residual activity and, except for marginal activity against E. cloacae, soap and water showed little residual activity. The residual activity of alcoholic chlorhexidine may be useful to control cross-infection with those multiply-resistant strains which survive well on fingers previously washed with soap and water.

1-Propanol↗

Randomized multicentre study of ciprofloxacin and azlocillin versus gentamicin and azlocillin in the treatment of febrile neutropenic patients.

In a randomized multicentre study ciprofloxacin combined with azlocillin was compared with gentamicin and azlocillin for the treatment of febrile episodes in neutropenic patients. In 147 evaluable episodes in 108 patients, 80 patients received ciprofloxacin/azlocillin and 67 received gentamicin/azlocillin. The two treatment groups were comparable in terms of age, underlying diagnosis, and duration of neutropenia. Microbiologically documented infections were the cause of fever in 34 (42.5%) and 29 (43.3%) episodes in the ciprofloxacin/azlocillin and gentamicin/azlocillin groups respectively. At the end of therapy, 46 patients (57.5%) receiving ciprofloxacin/azlocillin showed complete resolution compared with 30 (44.7%) for the gentamicin/azlocillin group (P = 0.14). The clinical response rate for microbiologically documented episodes was 58.8% and 48.3% respectively (P = 0.45). Among the microbiologically documented infections with follow-up cultures available, 24 (92.3%) of 26 isolates from patients receiving ciprofloxacin/azlocillin were eradicated, in comparison with 19 (86.4%) of 22 in the gentamicin/azlocillin group (P = 0.65). There were five superinfections, all in the gentamicin/azlocillin group. Significant resistance to the study drugs was not seen. Of all evaluable patients, including those subsequently withdrawn because of early modification of therapy, there were 12 deaths within the study period; six (6.8%) of these occurred in 88 patients randomized to the ciprofloxacin/azlocillin group, compared with two of 80 (2.5%) in the gentamicin/azlocillin group. Both treatments were generally well-tolerated; one patient in the ciprofloxacin/azlocillin group developed convulsions, probably related to ciprofloxacin. The combination of ciprofloxacin and azlocillin is as effective as gentamicin plus azlocillin and offers a useful alternative for the empirical treatment of febrile neutropenic patients.

Adolescent↗

Bronchodilator and other pharmacological activities of R-836 (2,5-diethyl-7-(4-thiomorpholino)-1,2,4-triazolo[1,5-c]pyrimidin e).

The bronchodilator activity of R-386 (2,5-diethyl-7-(4-thiomorpholino)-1,2,4-triazolo[1,5-c]pyrimidine) was demonstrated in isolated guinea-pig tracheal preparations and in vivo in dogs, guinea-pigs and rats. Guinea-pig tracheal preparations contracted by histamine, acetylcholine, BaCl2, leukotriene C4 or antigen were relaxed 50% by concentrations (IC-50 values) of R-836 of approximately 0.3 microgram/ml (10(-6) M) in all cases. In the conscious guinea-pig, oral or i.p. administration of R-836 prevented asphyxial collapse, death or dyspneic changes produced by histamine, antigen of LTC4. In anesthetized guinea-pigs, R-836 reduced bronchoconstriction produced by antigen or PAF (Konzett-Rössler preparation). In the dog, i.v. or intraduodenal administration of R-836 reduced bronchoconstriction produced by methacholine or histamine. In the rat, i.p. administration of R-836 reduced bronchoconstriction produced by 5-HT or antigenic challenge. In these in vivo models, when direct comparisons were made, R-836 was estimated to possess 2 to 3 times the potency of theophylline. R-836, at doses 80 times those necessary to produce bronchodilation, had no effect on blood pressure or heart rate of guinea-pigs. R-836 was not a CNS stimulant in mice, was not diuretic in rats, only marginally inhibited adenosine-induced responses in mice and guinea-pigs and was a weak inhibitor of phosphodiesterase in vitro.

Acetylcholine↗

Synthesis and antiallergic activity of some acidic derivatives of 4H-pyrimido[2,1-b]benzazol-4-ones.

Reactions of 2-aminobenzothiazole, 2-aminobenzoxazole, and 2-amino-1-methylbenzimidazole with dimethyl aminofumarate (DMAF) or diethyl ethoxymethylenemalonate (DEEM) led to 2- or 3-carboxy-4H-pyrimido[2,1-b]-benzazol-4-ones, respectively. Subsequent derivatization of these carboxylic acids gave the corresponding tetrazolylcarboxamides and tetrazoles. These acidic compounds were tested in the rat passive cutaneous anaphylaxis (PCA) assay as potential antiallergic agents. Many of the compounds displayed activity comparable to that shown by disodium cromoglycate (DSCG) when tested by the intraperitoneal route, and some, unlike DSCG, also showed activity when tested orally.

Animals↗

Some normal clinical chemistry values for cerebrospinal fluid of the rhesus monkey (Macaca mulatta).

The concentrations of many components of the cerebrospinal fluid are much lower than in serum. Values for sodium, potassium, calcium and magnesium are similar to those in other primates. Activities of alkaline phosphatase (18.7 U/1), creatine phosphokinase (9.9 U/1), glutamine oxaloacetate transaminase (13.7 U/1), glutamine pyruvate transaminase (9.2 U/1), gamma-glutamyl transpeptidase (3.1 U/1), alpha-hydroxybutyrate dehydrogenase (33.0 U/1, lactate dehydrogenase (47.2 U/1) and sorbitol dehydrogenase (3.9 U/1), and levels of zinc (1.0 mu g/dl), copper (2.6 mu g/dl), iron (35.9 mu g/dl) and triglycerides (33.2 mu g/dl) have not previously been reported for this species. Values for free amino acids, total protein, creatinine and urea nitrogen are compared with those of other primates. The use of gradient pore polyacrylamide gel electrophoresis for analysing proteins of CSF is described.

Amino Acids↗