Carbapenemase-producing Pseudomonas aeruginosa in UK.
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Amikacin↗
Biomedical subjects
J Bates
Publications and source records attributed to J Bates.
Immunopotentiation of humoral and cellular responses to inactivated influenza vaccines by two different adjuvants with potential for human use.
Two quite different adjuvants, currently under development for use in humans, have been examined for their effects on the magnitude and type of immunity elicited in response to inactivated influenza vaccine. Immunostimulating complexes (ISCOM adjuvant) contain the saponin ISCOPREP 703, and SPT is an oil-in-water emulsion of squalane, non-ionic block copolymer (L121) and Tween 80. Influenza virus vaccines formulated in either adjuvant were far superior to the non-adjuvanted aqueous vaccine in eliciting antibody and T-cell responses in mice, particularly at lower doses of antigen. In addition, the vaccines containing adjuvant were superior in eliciting protective immunity. One of the shortcomings of the unadjuvanted inactivated influenza vaccine was its inability to elicit a primary proliferative T-cell response. However, after one dose of either adjuvanted vaccine, strong proliferative responses were achieved. We also show that subcutaneous vaccination with inactivated vaccines is capable of modulating the isotype profile of antibody secreting cells generated in the lungs of mice in response to intranasal challenge with live virus. In this system, the isotype of antibody elicited after challenge of mice that had received ISCOM vaccine more closely mimicked that of animals vaccinated with live virus.
Adjuvants, Immunologic↗
Studies on experimental adjuvanted influenza vaccines: comparison of immune stimulating complexes (Iscoms) and oil-in-water vaccines.
Detergent-disrupted influenza virus vaccines, formulated as Iscoms, or oil-in-water (o/w) emulsions, were administered parenterally to mice and evaluated for immunogenicity and protective efficacy. Both formulations enhanced both primary and secondary serum antibody responses. The magnitude of these responses with o/w emulsions was further enhanced by the addition of the non-ionic block copolymer L121 in the emulsion. Four weeks after primary immunization, mice were challenged by exposure to an aerosol containing infectious virus. Resistance to challenge in terms of survival rate and weight change correlated well with serum antibody titre for all formulations. Two major differences were observed between the adjuvant formulations. Iscom vaccines, formulated with Quil-A or the less toxic Quillaia saponin preparation Iscoprep 703, induced specific cytotoxic T-lymphocyte responses, whereas the o/w-based vaccines did not. In addition, dose-site reactivity studies in sheep showed that Iscom vaccines were less reactive than o/w-based vaccines, the degree of reactivity of the latter increasing sharply with increasing L121 concentration. On the basis of these studies, Iscoms were chosen for development as a potential adjuvant for human influenza vaccines.
Adjuvants, Immunologic↗
Gyri of the human neocortex: an MRI-based analysis of volume and variance.
This magnetic resonance imaging (MRI)-based morphometric analysis of cortical topography in the human brain is based upon the segmentation and parcellation of volumetric T1-weighted MRI data for a set of 20 young adult brains including 10 males and 10 females. For the most part, each parcellation unit (PU) of the neocortex corresponds to a single or a portion of a single gyrus. The volumes of each PU were computed for each brain. Subsets of PUs were also grouped so as to represent the neocortex for the frontal, temporal, parietal and occipital lobes. The coefficient of variation of the mean volume of total neocortex and that of the neocortex assigned to individual lobes cluster around 10%, whereas that of neocortex assigned to the individual gyri (PU) is more than twice that value. Approximately 80% of the total variance in gyral volume arises from determinants interactive for individual and specific gyri, while only approximately 10% of the total variance appears to be a reflection of uniform scaling to total neocortical volume. Sexual dimorphism contributes a pervasive though relatively small component of this variance. These results have implications for the study of structure-function correlation, and the proper statistical methods of handling volumetric data in morphometric studies. In addition, the nature of the covariance structure of the data will lead to future hypotheses regarding the relationships between the various potential genetic and epigenetic gyral influencing factors.
Adult↗
Process not litigation: dealing with physician incompetence and impairment in a hospital.
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British Columbia↗
Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci.
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Animals↗
Pasteurella multocida infection of a total hip arthroplasty following cat scratch.
Pasteurella multocida is a well recognized cause of sepsis following animal contact particularly bites and scratches. Spread to prosthetic joints may occur particularly in immunocompromised patients. Immunocompromised patients with prosthetic joints should be warned that animals are potential sources of serious infection and urgent medical advice should be sought if bitten or scratched.
Animals↗
Epidemiology of vancomycin-resistant enterococci in the community and the relevance of farm animals to human infection.
Several reports have documented the presence of vancomycin-resistant enterococci (VRE) in the stools of asymptomatic individuals from the community who have neither recently been in hospital nor received antibiotics. Such findings were contrary to the then existing perception of VRE as a strictly hospital-acquired infection of debilitated and immunocompromised patients on specialized units. Community-acquired infections with VRE are extremely rare but those that do occur may be conspicuous because of their serious nature, for example, endocarditis. If asymptomatic faecal carriage of VRE is present in the community, individuals admitted to hospital and subjected to the selective pressures of antibiotics on the normal gut flora, may act as the source of hospital outbreaks. VRE have also been found in sewage, from stools of healthy farm animals and animal products. Avoparcin, a glycopeptide showing cross-resistance to medically important glycopeptides, has been used in the European Community as a growth promoter in animal feeds. A possible link between the use of avoparcin, the selection of VRE, and humans becoming colonized via the food chain exists. To prove such a link is beset with many difficulties: it is necessary to explain the presence of VRE in the United States where avoparcin is not used, and the predominance of the VanA gene over the VanB gene. It is also proving difficult to show that animal and human strains are identical by means of molecular typing. To date, molecular typing of strains is only suggestive of a link, but epidemiological studies of farms that use avoparcin have shown a significant association with the presence of VRE in animal stools. As long ago as 1969, the Swann report declared that an antibiotic of medical importance should not be used as a growth promoter in animal feeds. The vasy array of antibiotics now being used in animal husbandry and fish-farming, and the cross-resistance of some antibiotics to their medically important counterparts is a real cause for concern. The emergence of multi-resistant enterococci causing human infections and the possibility of the transfer of the VanA gene from VRE to methicillin-resistant Staphylococcus aureus (MRSA) emphasizes the importance of this problem.
Animal Feed↗
The use of Bacillus diarrhoeal enterotoxin (BDE) detection using an ELISA technique in the confirmation of the aetiology of Bacillus-mediated diarrhoea.
A commercially available ELISA kit was used for the detection of Bacillus diarrhoeal enterotoxin (BDE) in a variety of foods and faeces. The ability of isolates of Bacillus spp., including Bacillus cereus, to produce BDE in Brain Heart Infusion broth containing 0.1% glucose was also checked by use of the kit. Results show that 29 out of 31 B. cereus isolates were enterotoxigenic. Foods positive for performed BDE were always contaminated with > 10(5) B. cereus cfu g-1, but not all foods contaminated with large numbers of B. cereus were positive for BDE. Bacillus sp., other than one isolate which closely resembled B. subtilis, were negative for BDE production. Criteria for the confirmation of Bacillus-mediated diarrhoea should now include reports of symptoms and incubation periods consistent with the diarrhoeal form of food-poisoning by Bacillus spp., together with the results of tests for enterotoxigenicity of the Bacillus isolate, and detection of BDE in either the food and/or faeces.
Bacillus↗
Rapid differentiation of bovine and human tubercle bacilli based on a characteristic mutation in the bovine pyrazinamidase gene.
Bovine tuberculosis (TB) caused by Mycobacterium bovis is an important veterinary disease that can also afflict humans. Although M. bovis shares an almost identical genome with M. tuberculosis, subtle differences in host specificity and several biochemical parameters can be used to distinguish the two closely related species. The current method for distinguishing M. bovis from M. tuberculosis relies on tedious testing of biochemical parameters, including natural resistance to pyrazinamide and defective pyrazinamidase (PZase) activity of M. bovis strains. In this study, we report the development of a rapid PCR-single-strand conformation polymorphism (SSCP) assay to differentiate M. bovis from M. tuberculosis strains, based on the detection of a single characteristic point mutation in the PZase gene (pncA) of M. bovis. Eighty-seven of 89 M. bovis strains could be distinguished from M. tuberculosis strains. Surprisingly, two animal isolates which were initially identified as M. bovis were shown to be M. africanum because they had a wild-type pncA sequence with positive PZase. These two M. africanum strains contain multiple (three and six) copies of insertion sequence IS6110, a feature they have in common with M. tuberculosis. The implication of this finding for the taxonomy of M. tuberculosis complex is discussed in relation to host preference and epidemiology. The development of a rapid PCR-SSCP test for distinguishing M. bovis from M. tuberculosis will be useful for monitoring the spread of bovine TB to humans in areas where bovine TB is endemic and for directing the treatment of human TB caused by M. bovis.
Amidohydrolases↗
Clinical value of CYFRA 21.1, carcinoembryonic antigen, neurone-specific enolase, tissue polypeptide specific antigen and tissue polypeptide antigen in the diagnosis of lung cancer.
In this study we looked at what useful information cytokeratin fragment detected by antibodies BM 19-21 and KS 19-1 (CYFRA 21.1), carcinoembryonic antigen (CEA), neurone-specific enolase (NSE), tissue polypeptide specific antigen (TPS), and tissue polypeptide antigen (TPA) gave when measured prospectively. All patients who were suspected of having lung cancer and who underwent diagnostic bronchoscopy in this hospital between July 1994 and May 1995 were included in the study. Of 184 patients, 87 were subsequently found to have intrathoracic malignancy, 93 were found to have benign lung disease and four were lost to follow-up. CYFRA 21.1 was the most efficient marker in differentiating benign from malignant disease, with a sensitivity of 54% and a positive predictive value of 96%. Thirty seven patients who had a negative bronchoscopy subsequently turned out to have malignant disease. Either CYFRA 21.1 or CEA was elevated in 26 (70%) of such patients. Multivariate analysis showed that only CYFRA 21.1 and CEA contributed significantly to the discriminatory power of the data. We conclude that measurement of cytokeratin fragment detected by antibodies BM 19-21 and KS 19-1 and carcinoembryonic antigen at the time of bronchoscopy significantly increased the diagnostic yield in this population and was especially useful in those patients in whom tumour biopsy was not possible at bronchoscopy.
Antigens, Neoplasm↗
Transfection alters ion transport in MDCK cells.
In the course of an investigation into the effect of Tamm-Horsfall protein (THP) on ion transport, we performed stable transfection of THP into MDCK cells using the SV40 or the cytomegalovirus (CMV) promoter. As controls, we transfected MDCK cells with an "empty" plasmid containing SV40 or CMV promoter but without THP cDNA. In another set of controls, we subjected cells to transfection procedures without DNA (mock transfection). K influx was not altered in cells subjected to mock transfection procedures without DNA, but both ouabain sensitive (OS) and ouabain resistant (OR) components of K influx were diminished in cells transfected with THP cDNA using either SV40 or CMV promoter. However, K influx was also reduced in cells transfected with a control plasmid containing either the SV40 promoter alone, or the CMV promoter alone, without the THP cDNA. Thus, the transport alterations were caused by transfection and not by THP. The reduction in ouabain-sensitive K influx was accompanied by a proportional reduction in the abundance of Na-K pump units as assessed by [3H] ouabain binding. [3H] bumetanide binding, a measure of the number of functioning NaK2Cl cotransporter sites, was reduced pari passu with the reduction in bumetanide-sensitive K influx. These results highlight the possibility that alterations in properties of transfected cells may not be solely due to the presence of transfected protein, but the result of some process associated with transfection itself. Without appropriate controls to evaluate this possibility, results of transfection studies are subject to potentially faulty and misleading interpretation.
Cell Line↗
Serotypes and antibiotic susceptibilities of Streptococcus pneumoniae in Nairobi, Kenya.
Two hundred and sixteen clinically significant isolates of Streptococcus pneumoniae from 138 adult patients attending clinics in Nairobi, Kenya over a 2 year period were characterized by antibiotic sensitivity testing and serotyping. Overall antibiotic resistance rates were: penicillin, 25%; tetracycline, 34%; erythromycin, 0%; chloramphenicol, 0.4%. Minimum inhibitory concentrations (MIC's) of penicillin ranged from < 0.008-0.5 microgram/ml. Determination of penicillin resistance (MIC > or = 0.1 microgram/ml) by oxacillin 1 microgram disc diffusion zone diameter < or = 20 mm was 100% sensitive, 92% specific. Relative resistance to oxacillin (MIC range 0.25-1.0 microgram/ml) accounted for penicillin sensitive isolates determined falsely to be penicillin resistant by oxacillin disc testing. Penicillin resistance was more frequent in sputum isolates at 35% than in blood isolates at 18% (P = 0.013). Serotypes 6, 10, 14, 16, 19 and 23 were associated with penicillin resistance. This study provides information of value for planning management strategies for pneumococcal disease from an area where there are few existing data.
Adult↗
Aluminium activation of "immediate early" gene expression in Swiss 3T3 fibroblasts.
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3T3 Cells↗
The impact of face-to-face educational outreach on diarrhoea treatment in pharmacies.
Private pharmacies are an important source of health care in developing countries. A number of studies have documented deficiencies in treatment, but little has been done to improve practices. We conducted two controlled trials to determine the efficacy of face-to-face educational outreach in improving communication and product sales for cases of diarrhoea in children in 194 private pharmacies in two developing countries. A training guide was developed to enable a national diarrhoea control programme to identify problems and their causes in pharmacies, using quantitative and qualitative research methods. The guide also facilitates the design, implementation, and evaluation of an educational intervention, which includes brief one-on-one meetings between diarrhoea programme educators and pharmacists/owners, followed by one small group training session with all counter attendants working in the pharmacies. We evaluated the short-term impact of this intervention using a before-and-after comparison group design in Kenya, and a randomized controlled design in Indonesia, with the pharmacy as unit of analysis in both countries (n = 107 pharmacies in Kenya; n = 87 in Indonesia). Using trained surrogate patients posing as mothers of a child under five with diarrhoea, we measured sales of oral rehydration salts (ORS); sales of antidiarrhoeal agents; and history-taking and advice to continue fluids and food. We also measured knowledge about dehydration and drugs to treat diarrhoea among Kenyan pharmacy employees after training. Major discrepancies were found at baseline between reported and observed behaviour. For example, 66% of pharmacy attendants in Kenya, and 53% in Indonesia, reported selling ORS for the previous case of child diarrhoea, but in only 33% and 5% of surrogate patient visits was ORS actually sold for such cases. After training, there was a significant increase in knowledge about diarrhoea and its treatment among counter attendants in Kenya, where these changes were measured. Sales of ORS in intervention pharmacies increased by an average of 30% in Kenya (almost a two-fold increase) and 21% in Indonesia compared to controls (p < 0.05); antidiarrhoeal sales declined by an average of 15% in Kenya and 20% in Indonesia compared to controls (p < 0.05). There was a trend toward increased communication in both countries, and in Kenya we observed significant increases in discussion of dehydration during pharmacy visits (p < 0.05). We conclude that face-to-face training of pharmacy attendants which targets deficits in knowledge and specific problem behaviours can result in significant short-term improvements in product sales and communication with customers. The positive effects and cost-effectiveness of such programmes need to be tested over a longer period for other health problems and in other countries.
Adult↗
Physician-assessment and physician-enhancement programs in Canada.
Since the mid-1980s, the licensing authorities in Quebec, Ontario and Manitoba have introduced programs to conduct in-depth assessments of the clinical skills and abilities of physicians with suspected deficiencies. These assessments are intended to supplement the provincial licensing authorities' existing peer review or patient-complaint mechanisms by confirming the physicians' overall level of competence and identifying specific clinical strengths and weaknesses. An "educational prescription," based on the results of the assessment, focuses on aspects of clinical practice in which the physicians need or wish to enhance their skills. In some situations, licensure decisions are based on the assessment information. This article describes the programs in Quebec, Ontario and Manitoba. Each program comprises a different process of personal assessment and individualized continuing medical education to help physicians improve their clinical competence, and each is built on sound principles of clinical-competence assessment and educational planning.
Clinical Competence↗
Nucleotide sequence and peptide motifs of mouse uromodulin (Tamm-Horsfall protein)--the most abundant protein in mammalian urine.
The mouse uromodulin cDNA sequence was sequenced. The predicted peptide sequence is 642 amino acids long and contains several modular components including four epidermal growth factor like repeats, one betaglycan-like domain (ZP domain), and a consensus sequence for attachment of a glycosyl-phosphatidyl-inositol anchor. An arginine-glycine-aspartate tripeptide reported for rat and human sequence is absent in the mouse. There are several potential sites for post-translational modification.
Amino Acid Sequence↗
Characterization of Streptococcus pneumoniae from human immunodeficiency virus--seropositive patients with acute and recurrent pneumonia.
Thirty-two isolates of clinically significant Streptococcus pneumoniae from 11 human immunodeficiency virus (HIV)-seropositive patients with single or multiple episodes of pneumonia were characterized by antibiotic susceptibility testing, serotyping, ribotyping, and repetitive extragenic palindromic polymerase chain reaction (REP-PCR). The isolates comprised 10 serotypes, 12 ribotyping patterns, and 12 REP-PCR patterns. There was close but not absolute correlation between techniques. By combining these characterization methods, 14 strains were identified. Five strains were found in > 1 patient, suggesting their frequent occurrence in this population. Two isolates of different serotype from 1 patient were highly related by ribotyping and REP-PCR, suggesting possible in vivo serotype change. Acute infection was associated with single strains or coinfection by distinct strains. Recurrent pneumonia was identified as relapse with the same strain or reinfection with new strains. The molecular characterization of pneumonococci from HIV-seropositive persons refines our understanding of pneumonococcal infection in these patients.
Acute Disease↗