Relapsed infection due to Listeria monocytogenes confirmed by random amplified polymorphic DNA (RAPD) analysis.
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Biomedical subjects
Publications and source records attributed to D Reeves.
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1 A questionnaire about undergraduate teaching on antimicrobial chemotherapy was sent to academic Departments of Clinical Pharmacology, Pharmacology and Medical Microbiology throughout the UK. 2 Questionnaires about postgraduate lectures and information circulated to doctors about antimicrobial chemotherapy were sent to Drug Information Centres and Postgraduate Tutors throughout the UK. Review articles and editorials in general medical journals were assessed. 3 The median amount of core undergraduate teaching on antimicrobial chemotherapy was 13.5 h but the range was from 9.0 h to 102.0 h. Content was predominantly oriented towards drugs rather than diseases and towards prescribing in hospital rather than in the community. Most teaching was by formal lecture as part of a core programme. On a scale from 0 to 5 the median emphasis given to individual topics ranged from 2.50 to 3.75 but the range of emphasis given by individual medical schools was wide, for example from 1.00 to 4.50 for teaching on pharmacokinetics. 4 Postgraduate tutors identified advice from local specialists and requests from local practitioners as the most important determinants of content of continuing medical education. Material from drug information centres was predominantly oriented towards discussion of individual drugs rather than management of specific diseases and even this limited survey found evidence of duplication. The UK general medical literature contained a total of 112 reviews or editorials on antimicrobial chemotherapy covering a wide range of topics but these were not, and should not be assumed to be comprehensive. 5 Almost all doctors regularly prescribe antimicrobials and require education about the subject. Wide variations in current medical practice should be addressed explicitly through more extensive use of problem solving. The literature suggests that knowledge is most effectively disseminated through local networks of practitioners. There should be more national co-ordination of the content of information to be disseminated through the existing drug information networks.
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We have recently described the production of large amounts (< or = 65 grams per litre) of enzymatically active human alpha 1 antitrypsin in the milk of transgenic sheep (Wright et al., 1991). Here, we describe in more detail the expression of the human protein in the milk of these animals throughout the lactation period. Human alpha 1 antitrypsin is also found at much lower levels in the plasma of transgenic ewes before, during and after lactation. It is also detected in male plasma at very low levels. We have previously shown human alpha 1 antitrypsin purified from transgenic sheep milk to be indistinguishable from commercially available human plasma derived alpha 1 antitrypsin in terms of gross sugar content and in vitro activity. Here we extend this comparison to more detailed analyses of glycosylation state, amino-terminal sequence, pI value, and molecular weight determination by mass spectrometry.
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We describe the generation of five sheep transgenic for a fusion of the ovine beta-lactoglobulin gene promotor to the human alpha 1-antitrypsin (h alpha 1AT) genomic sequences. Four of these animals are female and one male. Analysis of the expression of h alpha 1AT in the milk of three of these females shows that all express the human protein at levels greater than 1 gram per liter. In one case initial levels exceeded 60 grams per liter and stabilized at approximately 35 grams per liter as lactation progressed. Human alpha 1AT purified from the milk of these animals appears to be fully N-glycosylated and has a biological activity indistinguishable from human plasma-derived material.
The antimicrobial activity of temafloxacin for 328 anaerobic bacteria was determined and compared to that of cefotetan, cefoxitin, ciprofloxacin and metronidazole. The Wadsworth agar dilution technique using Brucella-lysed sheep blood agar was used throughout. At the recommended breakpoint concentration 4 mg/L, temafloxacin inhibited 60/62 (97%) of the isolates of Bacteroides fragilis and 82/87 (94%) of the isolates of other species of the B. fragilis group. Ninety-six percent of the 24 isolates of Peptostreptococcus, 97% of the 31 isolates of other Bacteroides species and 88% of 66 isolates of Fusobacterium species were also inhibited by 4 mg/L temafloxacin. Metronidazole (breakpoint 16 mg/L) had a broader spectrum of activity than temafloxacin (judged by the percentage of strains tested susceptible at the breakpoints employed) with the exception of non-sporing Gram-positive bacilli. The cephalosporins tested (breakpoint 32 mg/L) had a narrower spectrum of activity. Ciprofloxacin (breakpoint 2 mg/L) was the least effective agent against the majority of the anaerobes tested.
The Stenger test was employed to estimate the genuine hearing thresholds in normally hearing volunteer subjects simulating a total unilateral loss. The test was carried out in its standard form and in a modified form in which a phase shift was introduced between the signal delivered to the two ears, set to produce phase-induced lateralization towards the 'poor' ear. The standard test estimated the thresholds at a mean of 13.5 dB above the true thresholds at five frequencies from 250 Hz to 4 kHz. Thresholds at the different frequencies were compared, and although thresholds were lower for the higher frequencies, the apparent effect of frequency was not statistically significant. The modified test, using a 90 degrees phase shift, was found to enhance the test at 250 and 500 Hz (thresholds estimated at about 7 dB above true values), but not significantly at 1 kHz.
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Leukoplakia is associated with increased risk of oral cancer and is considered a premalignant lesion. Retinoids, particularly 13-cis retinoic acid, can frequently reverse leukoplakia. However, these drugs have considerable toxicity and are not suitable for large-scale use in the prevention of oral cancer. Beta-carotene is a naturally occurring, nontoxic carotenoid with biologic properties that suggest that it might be efficacious against oral leukoplakia. In 1986, we began a randomized study of 13-cis retinoic acid (1 mg/kg/d) versus beta-carotene (30 mg/d) in leukoplakia. However, owing to the marked differences in toxicity between the two compounds outlined in the consent form, 11 of the initial 16 eligible patients refused to participate unless they were "guaranteed" beta-carotene. Therefore, the study design was changed to a phase II trial of beta-carotene in which the compound was given daily for 3 months. Responding patients were continued for another 3 months of treatment. All lesions were examined histologically at entry. Responses were monitored by bidimensional measurements and photography done at entry, then monthly while on treatment and at study completion. Twenty-four evaluable patients were treated, and 17 had major responses (two complete, 15 partial), a response rate of 71% (95% confidence limits, 53% to 89%). There was no significant toxicity requiring drug discontinuation or dose reduction. These results indicate that beta-carotene has substantial activity in oral premalignancy. Because of its lack of toxicity, it is an excellent candidate for a preventive agent for oral cancer.
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Three currently used anaerobic susceptibility testing methods were compared: (1) the technique used at the Wadsworth Microbial Diseases Research Laboratory, (2) the technique listed as the reference standard by the National Committee on Clinical Laboratory Standards, and (3) the technique used at the Tufts New England Medical Center. Four-hundred-seventy anaerobic microorganisms, isolated from clinical specimens, were tested against cefoxitin, cefotetan, ceftizoxime, cefotaxime, ceftazidime, imipenem, and clindamycin. Significant differences were noted in mean inhibitory concentrations and percent susceptible at breakpoint among the three techniques used and varied with the antimicrobial agent and species tested.
One hundred and five mothers of British children aged 1-5 years completed the EASI-1 Temperament Survey and the age appropriate version of the Carey questionnaire (Toddler Temperament Scale or Behavioural Style Questionnaire). Detailed statistical analyses revealed psychometric weakness in all three instruments, most notably in the Carey questionnaires. Neither factor analysis nor item-to-scale correlations provided clear support for the nine NYLS dimensions incorporated within the TTS and BSQ. Mothers' opinions of their child's temperament constellation differed considerably from those resulting from the questionnaire analysis for the STWU and Difficult constellations. Issues of reliability and validity are discussed.
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To assess the suitability of latamoxef (moxalactam) as single agent chemoprophylaxis in elective colorectal surgery, 120 consecutive patients were randomized to receive latamoxef (L) 1 g or cephazolin 1 g and metronidazole 500 mg (CM) administered intravenously at induction of anaesthesia and 6 and 12 h postoperatively. The groups were well matched for age, sex, pathology and procedures. Serum and tissue levels of latamoxef were well above the MIC90 for most bowel organisms. Inpatient stay was similar for both groups. Pyrexia was seen in 44 patients (11 L, 23 CM) and eight developed a wound infection (3 L, 5 CM). Major intra-abdominal sepsis occurred in seven patients (2 L, 5 CM), secondary to anastomotic leakage in four (1 L, 3 CM). Twenty patients developed a chest infection (5 L, 15 CM) and eight urinary sepsis (2 L, 6 CM). No bleeding complication occurred, and there was no difference in clotting function between the two groups. Six patients died prior to follow-up at six weeks (1 L, 5 CM), two from anastomotic dehiscence. All but three wounds had healed (1 L, 2 CM) and one further patient had an incisional hernia (CM). These results suggest that latamoxef is an efficient chemoprophylactic agent in elective colorectal surgery, and is marginally better than cephazolin plus metronidazole.