CTX-M extended-spectrum beta-lactamase arrives in the UK.
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Biomedical subjects
Publications and source records attributed to N Todd.
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In this article the results are reported of an experiment to provide direct evidence for a perceptual and behavioral significance of human saccular acoustic sensitivity. Ten human subjects were stimulated monaurally with 100-ms trains of 10-ms tone pulses with pulse repetition rate of 40 Hz, and were required to rate the pleasantness of the stimuli on a nine-point scale. The design included three within-subject factors: carrier frequency (two levels, 200 and 4,000 Hz), intensity [13 levels from 55 to 115 dB(A) in 5-dB steps] and ear (left and right). For intensities above 90 dB myogenic vestibular evoked potentials (MVEP) were also obtained from the ipsilateral sternocleidomastoid muscle from which it was possible to obtain thresholds by linear regression of MVEP amplitudes against intensity. A further between-subjects factor was added which assessed subjects' attitude to vestibular sensations. The results indicate that across subjects there is a general trend of decreasing pleasantness with increasing intensity, but for the 200-Hz condition there is a significant positive departure from monotonicity in pleasantness (p<0.05) above the mean saccular threshold. However, when split by the between-subjects factor, the positive departure was only evident for those subjects who have a positive attitude to vestibular sensations (p < 0.01). Implications of these results for human responses to loud sound and the possible evolutionary significance of saccular acoustic sensitivity are discussed.
An 8 year old girl with cystic fibrosis had severe respiratory disease associated with chronic Pseudomonas aeruginosa bronchopulmonary infection. Despite regular courses of intravenous antipseudomonal antibiotics, she continued to deteriorate over 18 months with persistent productive cough, worsening respiratory function, and increasing oxygen dependence. During her 11th admission Streptococcus milleri was isolated from sputum cultures in addition to P aeruginosa. She failed to respond to antipseudomonal antibiotics but improved dramatically with the addition of intravenous benzylpenicillin. Although S milleri is considered a normal mouth commensal and its isolation from sputum of cystic fibrosis patients is of uncertain significance, it was associated with clinically significant infection in this child. S milleri was eradicated with antibiotic treatment and clinical improvement has been maintained.
A new selective differential medium for the isolation of Stenotrophomonas (formerly Xanthomonas) maltophilia was developed. The medium, VIA agar, contained vancomycin, imipenem, and amphotericin B as selective agents and incorporated a mannitol/bromothymol blue indicator system. Compared with Xanthomonas maltophilia Selective Medium (XMSM), VIA agar was less inhibitory to Stenotrophomonas maltophilia and was more selective than XMSM in preventing the growth of unwanted bacteria from contaminated specimens. Although vancomycin-resistant strains of Enterococcus faecium may grow on VIA agar, these can be easily distinguished from Stenotrophomonas maltophilia because of mannitol fermentation.
Auditory stream segregation is considered from the point of view of a theory of the central auditory system in which temporal information is spatially coded on three dimensions roughly corresponding to the level of the cochlea, the inferior colliculus and the auditory cortex, respectively. This theory is embodied in the form of a computational model which simulates peripheral and central processing including a cortical cross-channel correlation mechanism.
The records of 38 patients under 25 years of age presenting with pineal tumours between 1968 and 1993, identified from the Northern Region Children's and Young Adults' Malignant Disease Registry, were analysed retrospectively with regards to clinical presentation, diagnostic approach, treatment strategy, and outcome. The overall five year survival was 45%. Fifteen patients had a histological diagnosis: six with germinomas, three with teratomas, three with astrocytomas, and three with pinealoblastomas. One patient had a definitive diagnosis of teratoma made on the basis of raised tumour markers (alpha fetoprotein). Treatment consisted of surgery (87%) (ventriculoperitoneal or atrial shunt and/or biopsy), and/or radiotherapy (82%), and/or chemotherapy (26%). Those patients with a tissue diagnosis appeared to have a more favourable outcome, especially after 1976 when treatment was determined by tumour type (five year survival for those with a tissue diagnosis was 91% v 51% for those without, 95% confidence intervals 74 to 100% and 26 to 75%). This study suggests that tissue diagnosis allows more appropriate treatment to be delivered for children with pineal tumours resulting in improved survival. Referral to a centre with neurosurgery, radiotherapy, neuropathology, and paediatric oncology collaboration is essential.
Between the autumn of 1989 and January 1990, 21 of the 44 children on the paediatric oncology ward of St. James's University Hospital, Leeds, UK were infected or colonised with Enterobacteriaceae producing extended-spectrum beta-lactamases. This represents 48% of the patients on the ward. Only six patients (14%) had microbiologically proven septicaemia caused by such bacteria during this period. Eighty-one isolates of Enterobacteriaceae producing extended-spectrum beta-lactamases derived from blood culture (7 isolates from 6 patients) or faecal samples (74 isolates) were available for examination. These comprised 28 Escherichia coli, 28 Klebsiella oxytoca, 11 Klebsiella pneumoniae, 10 Citrobacter freundii, 3 Enterobacter spp. and 1 Serratia marcescens. Clinical isolates were resistant to penicillins and to ceftazidime. Strains isolated in this study also showed multiple resistance to a range of antimicrobial agents. Transfer to a nalidixic acid resistant laboratory strain of E. coli UB5201 was attempted, but transfer of the ceftazidime resistance determinant was only successful in 25 isolates (31%). Examination of plasmid DNA revealed sequences in each isolate that hybridised with the TEM beta-lactamase gene probe used on a variety of plasmids ranging in size from 2.5- > 150 kb, sometimes found on several replicons in a single isolate. The TEM gene probe also hybridised with chromosomal DNA in a large number of isolates. Nucleotide sequence analysis demonstrated the presence of three extended-spectrum beta-lactamases: TEM-10B produced by two isolates, TEM-12B produced by 37 isolates and TEM-26B produced by 40 isolates. In two cases, isolates produced two beta-lactamases, and it proved impossible to identify these enzymes unequivocally. The genes encoding TEM-10B and TEM-26B both differ from TEM-12B by single nucleotide substitutions. Analysis of the ribotype patterns derived from the clinical isolates provided evidence for cross-colonisation between patients, and this was confirmed by analysis of the plasmid profiles. Four years after discontinuing ceftazidime and other extended-spectrum cephalosporins on this ward, patients were still colonised with bacteria that produced extended-spectrum beta-lactamases.
TEM-26, an extended-spectrum beta-lactamase has been characterized in clinical isolates of Klebsiella pneumoniae and Escherichia coli derived from patients on the Paediatric Oncology Unit of St James's University Hospital, Leeds. The nucleotide sequence of this beta-lactamase gene (blaTEM26b) was determined, and compared with the nucleotide sequences of other TEM-type beta-lactamases. The blaTEM26b gene was found to differ from blaTEM12b by a single nucleotide. This difference causes the substitution of glutamic acid in blaTEM12b for lysine in blaTEM26b at position 102 in the predicted amino acid sequence. The blaTEM12b gene was first described in an isolate of Klebsiella oxytoca from a patient nursed on the same unit that yielded the strains that carry blaTEM26b. However, the blaTEM26b gene differs at no less than six nucleotides from the nucleotide sequence encoding the TEM-26 beta-lactamase that was first described in isolates from cancer patients nursed in the Children's Hospital, Stanford, California, USA. This indicates that the genes encoding TEM-26 have evolved from different progenitors.
We developed a continuous, volumetrically controlled veno-venous renal replacement system that can be operated in filtration or dialysis modes. We compared the clearances of substances with a range of molecular weights (MW) in each mode. Ten patients with acute renal failure underwent serial postdilutional hemofiltration and hemodialysis, for 30 min each, in sequence and in randomized order. All were receiving vancomycin for concurrent sepsis. The system incorporated a Filtral 10 AN69 artificial kidney; blood flow rate was 200 ml/min, and dialysate/filtrate flow rate was 25 ml/min. Sieving (SC) and diffusion (DC) co-efficients, for hemofiltration and hemodialysis, respectively, were identical for urea (MW 60; 1.01 +/- 0.05 vs 1.01 +/- 0.07) and creatinine (MW 113; 1.00 +/- 0.09 vs 1.01 +/- 0.06), and clearance equated with dialysate/filtrate flow. There was a modest difference in uric acid clearance (MW 168; SC 1.01 +/- 0.04 vs DC 0.97 +/- 0.04; p < 0.05). Vancomycin (MW 1,800) removal was 19% greater during filtration compared with dialysis (SC 0.87 +/- 0.10 vs DC 0.74 +/- 0.06; p < 0.01). For small solutes, the two modalities were equivalent. Vancomycin clearance was appreciably greater with hemofiltration, which is consistent with a greater potential for convection-based therapy in the removal of uremic and other middle molecules.
An isolate of Klebsiella oxytoca from the blood culture of a child with leukemia was found to produce two beta-lactamases, at least one of which conferred resistance to ceftazidime. Genes encoding both enzymes were located on a single self-transmissible 100-kb plasmid, pOZ201. This plasmid was introduced into Escherichia coli UB5201 (pACYC184), and the gene encoding one beta-lactamase was transposed onto plasmid pACYC184 by exploiting a gene dosage effect. The transposable gene was found to encode a TEM-12 enzyme as determined by nucleotide sequencing. This gene was subsequently transposed onto plasmid pUB307. The transposable element encoding the TEM-12 enzyme has been designated Tn841. Both plasmids pACYC184::Tn841 and pUB307::Tn841 were shown to encode a beta-lactamase with the same isoelectric point and substrate profile as the TEM-12 beta-lactamase. Transposon Tn841, at approximately 7 kb, is larger than TnA (4.8 kb) and transposes at a lower frequency. Although it produced a resolvase which can complement the resolvase of Tn3, its transposase function was not able to complement the transposition of a TnA element which lacked transposase. The occurrence of a gene encoding an extended-spectrum beta-lactamase on a transposable element in a clinically significant bacterium is potentially a cause for concern for the spread of resistance to the extended-spectrum cephalosporins.
Environmental contamination has been shown to be an important aspect of the epidemiology of salmonellosis in calves. Markets and transport vehicles are important links in the calf marketing chain and these were investigated to determine the level of salmonella contamination. Salmonellas were isolated from 7 of the 14 markets surveyed, with 31 of 838 samples (3.7%) being positive. Nine different salmonella serotypes, of which the commonest was Salmonella typhimurium, were isolated. Four different phage types of S. typhimurium were detected, the commonest being DT204C. Salmonellas were isolated from 22 of the 107 vehicles (20.6%) examined before washing and from 4 of the 62 vehicles (6.5%) examined after cleaning. Twelve different salmonella serotypes were isolated, of which the most frequent was S. typhimurium. The commonest of the six different S. typhimurium phage types was DT204C. These results indicate that improved cleaning and disinfection routines both for vehicles and markets are necessary to control salmonellosis in calves.
Epilepsy is a common condition which is often resistant to therapy and may cause neurological damage. It is postulated that changes in blood-brain barrier function may be involved in the pathophysiology of both problems.
Salmonellas were detected in the environment of 10 of the 12 calf dealers' premises studied. The cleaning and disinfection routines were often ineffective and salmonellas were isolated from 7.6% and 5.3% of the wall and floor samples before disinfection and 6.8% and 7.6% afterwards. Eight different salmonella serotypes were detected, of which the commonest were Salmonella typhimurium, predominantly phage type DT204C, and S. dublin. Plasmid profiles were used to fingerprint S. typhimurium DT204C and the results indicated that with the exception of one of the premises, prolonged salmonella-persistence in the environment was not occurring. Three separate epidemics of salmonellosis in calves were studied by use of plasmid profile analysis. The results illustrated the role of delers, and their subcontractors, in the dissemination of salmonellas. The study concludes with suggestions for methods to reduce the spread of salmonellas in the calf marketing chain.
Sixty-one patients with acute schizophrenia received either remoxipride (75-375 mg daily) or thioridazine (150-750 mg daily) for 6 weeks. There was no statistically significant between-drug difference in improvement in mental state, as measured by the Brief Psychiatric Rating Scale, although the trend favoured thioridazine; global assessment of illness severity at the last rating also favoured thioridazine. Sedation, anticholinergic effects, autonomic dysfunction, and weight gain were significantly more common in patients receiving thioridazine. Both drugs produced few extrapyramidal effects, but both were associated with cardiovascular changes in two patients; neither drug produced significant abnormalities in laboratory tests.
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Coagulase-negative staphylococci (CNS) were isolated by direct inoculation of anticoagulated whole blood onto agar from 14 (41.2%) of 34 episodes (30 neonates) of suspected bacterial infection, associated with isolation of CNS from the same blood sample by broth-dilution blood cultures. The equivalent of more than 1,000 cfu ml-1 were isolated from four samples (four neonates); the range of counts was 1-103 cfu 25 microliters-1. There was a statistically significant association between isolation of CNS by direct agar inoculation and a raised C-reactive protein level and/or a positive nitroblue tetrazolium test and with the use of an intravascular catheter when compared to those episodes where CNS were isolated from broth blood cultures only. This simple procedure provides an estimate of the number of CNS in the blood of a neonate with suspected bacteraemia and may help to corroborate a diagnosis of CNS bacteraemia.
The likelihood of airborne spread and infection by Salmonella typhimurium was studied in calves and mice. S typhimurium survived in air sufficiently long to present a significant hazard of airborne spread. In a dry climate (32 per cent relative humidity) its predicted viability five minutes after aerosolization was 4 per cent relative to its initial value. This increased to 24.8 per cent in a humid atmosphere (72 per cent relative humidity). Inhalation of S typhimurium by mice caused disease and death at times dependent upon the dose. Even the lowest dose of about 150 colony forming units (cfu) produced disease. Inoculation of approximately 10(4) to 10(6) cfu S typhimurium by either 'mouth and nose only' or 'whole body' aerosol exposure caused infection in calves. The consequences for the control of salmonellosis in intensive calf husbandry are discussed in the light of this demonstration that airborne transmission can be a primary mode of infection of S typhimurium.
This is the first comparative double blind study of remoxipride. Sixty-one patients with acute schizophrenia received either remoxipride (75-375 mg daily) or thioridazine (150-750 mg daily) for 6 weeks. There was no statistically significant between-drug difference in improvement in mental state, as measured by the Brief Psychiatric Rating Scale, although the trend favoured thioridazine; global assessment of illness severity at the last rating also favoured thioridazine. Sedation, anticholinergic effects, autonomic dysfunction and weight gain were significantly more common in patients receiving thioridazine. Both drugs produced few extrapyramidal effects, but both produced cardiovascular changes in two patients; neither drug produced significant abnormalities in laboratory tests.