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Biomedical subjects

A Fox

Publications and source records attributed to A Fox.

At least 91 records · Page 5Linked to original sources

Epidemiology of an outbreak due to glycopeptide-resistant Enterococcus faecium on a leukaemia unit.

The clinical and molecular epidemiology of two clusters of colonization and infection of patients by glycopeptide-resistant enterococci (GRE) on a leukaemia and bone marrow transplantation unit was studied over a two-and-a half-year period. Thirty-five patients became colonized, of whom six developed clinical infections. Of the 53 isolates of GRE, 49 were Enterococcus faecium, multiply-resistant to vancomycin and ampicillin. DNA fingerprinting of 48 E. faecium isolates by pulsed-field gel electrophoresis identified six DNA types. One strain of VanB phenotype E. faecium predominated during the initial outbreak, and an unrelated strain of the VanA phenotype was present in a second cluster. Environmental and patient isolates of E. faecium were indistinguishable by DNA typing. The VanA phenotype enterococci probably arose by transfer from the renal ward at a nearby hospital, and a patient with persistent diarrhoea may have contributed to contamination and cross-infection. GRE may cause significant infections in immunocompromised patients, and are readily transmitted between them. GRE were controlled, but not eradicated on the unit; infection control measures included improved environmental cleaning and modification of antibiotic use. In order to control GRE, it is necessary to educate healthcare workers and implement the traditional, effective values of good personal hygiene and environmental cleanliness.

Adult↗

Moexipril versus captopril in patients with mild to moderate hypertension.

Moexipril is a new, long-acting angiotensin-converting enzyme (ACE) inhibitor. In contrast to captopril, it is a prodrug of the pharmacologically active agent moexiprilat and will be administered once daily. The objective of this study was to compare the efficacy, safety, and tolerability of moexipril with that of captopril during a 12-week treatment of patients with mild to moderate hypertension. Patients with a sitting diastolic blood pressure (SDBP) of 95-114 mm Hg, inclusive, were randomized in a 2:1 ratio to receive moexipril, 7.5 mg, once daily or captopril, 25 mg, twice daily. After 6 weeks of treatment, the dose of moexipril and captopril was increased to 15 mg once daily and 50 mg twice daily, respectively, if the patient's SDBP remained > or = 90 mm Hg. Blood pressure was measured at biweekly visits. At study endpoint, adjusted mean reductions in SDBP were comparable between the moexipril and captopril groups (-9.8 vs. -8.7 mm Hg), and moexipril was more effective than captopril in reducing sitting systolic blood pressure. Adverse experiences (headache, dizziness, and upper respiratory infection) occurred at similar frequencies in the moexipril and in the captopril groups. The data indicate that moexipril at dosages of 7.5 and 15 mg once daily is as efficacious as twice daily captopril in reducing blood pressure in patients with mild to moderate hypertension.

Adult↗

Capsule phase variation in Neisseria meningitidis serogroup B by slipped-strand mispairing in the polysialyltransferase gene (siaD): correlation with bacterial invasion and the outbreak of meningococcal disease.

A mechanism of capsular polysaccharide phase variation in Neisseria meningitidis is described. Meningococcal cells of an encapsulated serogroup B strain were used in invasion assays. Only unencapsulated variants were found to enter epithelial cells. Analysis of one group of capsule-deficient variants indicated that the capsular polysaccharide was re-expressed at a frequency of 10(-3). Measurement of enzymatic activities involved in the biosynthesis of the alpha-2,8 polysialic acid capsule showed that polysialyltransferase (PST) activity was absent in these capsule-negative variants. Nucleotide sequence analysis of siaD revealed an insertion or a deletion of one cytidine residue within a run of (dC)7 residues at position 89, resulting in a frameshift and premature termination of translation. We analysed unencapsulated isolates from carriers and encapsulated case isolates collected during an outbreak of meningococcal disease. Further paired blood-culture isolates and unencapsulated nasopharyngeal isolates from patients with meningococcal meningitis were examined. In all unencapsulated strains analysed we found an insertion or deletion within the oligo-(dC) stretch within siaD, resulting in a frameshift and loss of capsule formation. All encapsulated isolates, however, had seven dC residues at this position, indicating a correlation between capsule phase variation and bacterial invasion and the outbreak of meningococcal disease.

Amino Acid Sequence↗

Characteristics of rural homebound older adults: a community-based study.

OBJECTIVE: To determine the frequency and characteristics of homebound older adults in a rural community. DESIGN: An epidemiological survey of an age-stratified random community sample. SETTING: The rural mid-Monongahela Valley in Southwestern Pennsylvania. PARTICIPANTS: A total of 878 noninstitutionalized persons aged 68 years and older, fluent in English, and with at least grade 6 education. MEASUREMENTS: The frequency with which subjects left their homes, the Mini-Mental State Examination (MMSE) score, and additional information on demographics, self-reported health problems, health services utilization, IADLs, depression, and social support were measured. RESULTS: 10.3% of the sample was classified as homebound. In univariate analyses, being homebound was found to be associated significantly (P < .001) with being older, female, and widowed and with MMSE and IADL impairment, with more depressive symptoms and worse social supports, fair to poor self-rated general health, weight loss, and histories of stroke, angina, arthritis of the spine, and falls. In a multiple regression model, variables associated independently with homebound status were gender (odds ratio = 9.4, 95% confidence interval = 3.6 - 24.9), weight loss (OR = 3.7, CI = 1.7 - 8.2), IADL impairment (OR = 2.6, CI = 2.1 - 3.1), and depressive symptoms (OR = 2.1, CI = 1.3 - 3.2). Being homebound was also associated with recent acute hospitalization and use of home health and social services. CONCLUSIONS: These data provide evidence that homebound older adults have a disproportionate share of morbidity and disability and suggest a sociodemographic and clinical profile to help identify those older people at risk of being or becoming homebound. They also point to the need for home-based health services for the older adults, particularly in medically underserved communities such as rural areas.

Activities of Daily Living↗

Absolute identification of muramic acid, at trace levels, in human septic synovial fluids in vivo and absence in aseptic fluids.

This is the first report of a study employing the state-of-the-art technique of gas chromatography-tandem mass spectrometry for absolute identification of muramic acid (a marker for peptidoglycan) at trace levels in a human or animal body fluid or tissue. Daughter mass spectra of synovial fluid muramic acid peaks (> or = 30 ng/ml) were identical to those of pure muramic acid. Absolute chemical identification at this level represents a 1,000-fold increase in sensitivity over previous gas chromatography-mass spectrometry identifications. Muramic acid was positively identified in synovial fluids during infection and was eliminated over time but was absent from aseptic fluids.

Arthritis, Infectious↗

Do intracarotid barbiturate injections offer a way to investigate hemispheric models of anosognosia?

In a sample of 83 patients counterbalanced for side of temporal-lobe seizure focus, we examined unawareness of hemiplegia upon clearing of the deficit after bilateral sodium amobarbital injections. Unawareness occurred commonly (66%) and with equal frequency following left and right injections. These findings were not moderated by speech dominance, handedness, sex, or side of seizure focus. Unawareness occurred more frequently after injections contralateral to than ipsilateral to the major seizure focus and was related to objective memory performance after contralateral, but not after ipsilateral, injections. Unawareness of drug-induced hemiplegia was related to the functional status of the temporal lobe independently of hemispheric laterality or degree of frontal lobe inactivation as measured by filling of the anterior cerebral arteries.

Adolescent↗

Antihypertensive effects of moexipril, a new ACE inhibitor, as add-on therapy to nifedipine in patients with essential hypertension.

Moexipril is a new nonpeptide angiotensin-converting enzyme (ACE) inhibitor with an intermediate duration of action. The antihypertensive efficacy and safety of moexipril as add-on therapy to nifedipine retard (20 mg b.i.d) was compared to placebo during 8 weeks in a double-blind trial with a parallel group design. A total of 203 patients with essential hypertension and a sitting diastolic blood pressure (DBP) > or = 95 mm Hg on nifedipine alone were randomly assigned to placebo or moexipril 3.75 mg o.d., 7.5 mg o.d., or 15 mg o.d.. At endpoint, the adjusted mean reductions in DBP from baseline were 6 mm Hg, 9 mm Hg (p < 0.01), and 9 mm Hg (p < 0.05) in the moexipril 3.75 mg, 7.5 mg, and 15 mg groups, respectively, compared to 5 mm Hg in the placebo group. All dosages of moexipril were well tolerated, and the overall percentages of patients who reported adverse experiences were smaller than in the placebo group. We concluded that moexipril as add-on therapy to nifedipine is well tolerated and gives additional antihypertensive effects.

Adolescent↗

Experimental infection of human nasal mucosal explants with Neisseria meningitidis.

The interaction of Neisseria meningitidis with rhinopharyngeal epithelium was studied by experimental infection of explants of human nasal turbinate mucosa with two wild strains: a fully capsulate case isolate, and an epidemiologically related non-capsulate nasopharyngeal isolate. After incubation for 4 h, epithelial cells of infected explants changed conformation from tall columnar morphology towards cuboidal, and there was increased discharge of mucus globules from goblet cells. By 24 h there was significant damage to infected epithelia, including projection of cells out of the surface, cytoplasmic blebbing and mitochondrial abnormalities. Meningococci were associated with surface non-ciliated cells by 4 h after infection. By 24 h after infection they were associated extensively with all cell types exhibiting damage. There was little association with secreted mucus. In areas of cell damage, penetration between surface cells was observed. Endocytosis into non-ciliated cells was observed in only a minority of explants studied and only in those infected for 24 h. From this intracellular site there was apparent migration to adjacent cells and to intercellular locations. No organisms were observed within or beneath basement membrane collagen in any explants but internalisation into mononuclear phagocytes was observed occasionally.

Cilia↗

Detection of human cytomegalovirus antigenaemia: a rapid diagnostic technique for predicting cytomegalovirus infection/pneumonitis in lung and heart transplant recipients.

BACKGROUND: New rapid diagnostic techniques offer the opportunity of early diagnosis of human cytomegalovirus (CMV) infection in immunocompromised patients at risk of developing CMV disease. The use of human CMV antigenaemia as a predictor of clinical CMV infection and disease in lung and heart transplant recipients was studied prospectively. METHODS: Twenty three heart and nine lung transplant recipients who survived 40 days were observed by standard CMV surveillance with serological testing, culture, and by sequential testing for CMV antigenaemia. CMV antigenaemia testing is a rapid and quantifiable technique in which a viral lower matrix protein is detected in cytospin preparations of peripheral blood polymorphonuclear leucocytes (PMNLs) by immunofluorescent staining. RESULTS: Eleven patients developed CMV infection and five developed CMV disease (four pneumonitis, one duodenitis). These clinical events occurred at a median of 65 days following transplantation. CMV antigenaemia occurred in 17 patients at a median of 35 days following transplantation. Detection of CMV antigenaemia had a sensitivity of 100%, a specificity of 93.7%, and a positive predictive value of 94.1% for CMV related illness. CMV antigenaemia was positive at a significant interval before the clinical event. High levels of CMV antigenaemia (> 50 CMV antigen positive cells/2 x 10(5) PMNLs) occurred in 11 patients and five of these developed disease. CMV antigenaemia of > 50 CMV antigen positive cells/2 x 10(5) PMNLs had a positive predictive value of 45.5% for disease but a negative predictive value of 100%. Patients with disease had higher levels of antigenaemia than those without disease. CONCLUSIONS: CMV antigenaemia is a rapid diagnostic technique which can identify patients likely to develop CMV disease, potentially allowing early treatment.

Antigens, Viral↗

Electrospray tandem mass spectrometry for analysis of native muramic acid in whole bacterial cell hydrolysates.

Muramic acid is an amino sugar found in eubacterial cell walls and not elsewhere in nature. This study explored the use of electrospray tandem mass spectrometry (ESI MS/MS) in analysis of underivatized muramic acid in bacterial hydrolysates. Fungal hydrolysates were used as negative controls. The only processing used was hydrolysis in sulfuric acid followed by extraction with an organic base (N,N-dioctylmethylamine) to remove the acid prior to ESI MS/MS analysis. Compared with pure muramic acid, bacterial hydrolysates produced more complex ESI mass spectra, such that the protonated molecular ion at m/z 252 was barely detectable. In contrast, product ion spectra of m/z 252 were identical among pure muramic acid, Gram positive bacteria, and Gram negative bacteria. However, no characteristic product ion spectrum was manifested from m/z 252 in fungal samples. This allowed ready, visual differentiation of bacteria and fungi. Multiple reaction monitoring (MRM) following muramic acid fragmentations (m/z 252-->144 and m/z 252-->126) increased sensitivity and allowed quantitative differentiation when compared with the MRM of the internal standard N-methyl-D-glucamine (m/z 196-->44). ESI MS/MS required minimal sample preparation and allowed rapid sample throughput for analysis of muramic acid in whole bacterial cell hydrolysates.

Cell Wall↗

Interest in natural family planning among female family practice patients.

OBJECTIVE: Although modern methods of natural family planning (NFP) are effective both to avoid and to achieve pregnancy, relatively few women use these methods. It is not known whether this is due primarily to lack of interest or to other factors. We therefore explored the level of interest in NFP among female family practice patients. METHODS: We mailed information about NFP to 400 female patients between ages 21 and 42 and conducted follow-up interviews by telephone. We excluded 162 women for whom we could not obtain accurate addresses or phone numbers, 68 women we could not reach by telephone, 67 women who were not currently at risk of pregnancy, and 15 women for other reasons. Twenty-eight women refused to participate in the study. Sixty women completed telephone interviews. RESULTS: Forty-three percent of respondents (n = 60) were interested in learning more about NFP, 24% said they were likely to use NFP to avoid pregnancy, and 32% were likely to use NFP to achieve pregnancy. Younger women and women who were Christian but not Catholic and not of a major Protestant denomination were more interested in NFP. CONCLUSION: Some female family practice patients are interested in learning and using NFP.

Adult↗

Interleukin-1-beta changes the expression of metalloproteinases in the vitreous humor and induces membrane formation in eyes containing preexisting retinal holes.

PURPOSE: Proliferative vitreoretinopathy occurs when cells migrate into the vitreous humor, where they proliferate and produce a membrane composed of extracellular matrix. Interleukin-1-beta (IL-1-beta) may be involved in these processes because it is chemotactic and mitogenic, and it stimulates metalloproteinase production. In the present study, the effects of intravitreally injected IL-1-beta on retinal membrane formation and the associated changes in metalloproteinase content of vitreous humor were examined. METHODS: Rabbit eyes were injected with IL-1-beta in a buffer, with or without the prior creation of retinal holes. Control eyes received the buffer alone or no injection, with or without retinal holes. Animals were examined by slit lamp biomicroscopy and indirect ophthalmoscopy for 1 month. Zymography was performed on a portion of vitreous humor to assess collagenase content, and the remaining tissue was subjected to histologic analysis. RESULTS: Intraocular IL-1-beta induced perilimbal vessel engorgement, keratic precipitates, synechiae, flare, lens deposits, optic disk hyperemia, and granulomatous formations that gradually subsided during the first week. Intravitreal injection of IL-1-beta in eyes with preexisting retinal holes additionally induced membrane formation. Zymographic analysis of vitreous humor from animals sacrificed 24 hours after IL-1-beta injection showed a 100-kd and a 65-kd gelatinase, whereas control vitreous humor contained predominantly a single gelatinase species of approximately 65 kd. Retinal holes did not affect IL-1-beta induction of the 100-kd gelatinase. CONCLUSIONS: IL-1-beta induces a 100-kd gelatinase in the vitreous humor and epiretinal membrane formation in eyes containing preexisting retinal holes. The presence of retinal holes and abnormal production of cytokines may lead to a cascade of events, including aberrant extracellular matrix remodeling, that result in proliferative diseases of the eye.

Animals↗

What constitutes general surgical training? Evidence from the log books of trainees in one district general hospital.

It is accepted wisdom that surgical expertise in the UK is achieved by virtue of long service, and perhaps not enough genuine training. The average age at appointment to consultant posts in general surgery has risen from 37.0 years in 1978 to 38.0 in 1992. This message has reached the politicians who run the Health Service: at the Association of Surgeons in Training Annual General Meeting in September 1991 Mrs Virginia Bottomley said 'A complaint often made to me is that trainees, particularly surgical trainees, in the UK are over-experienced but under-trained'. Training posts acquire a reputation (good or bad) based on word of mouth, pass rate in examinations, and success in placing trainees into higher grades. Little is known about the relationship between training and operative experience. Log books have been introduced as a compulsory requirement for the Clinical Surgery in General and Intercollegiate Specialty Examinations. This report aims to define the operative experience of trainees at a District General Hospital by analysis of data obtained from their log books. This information has been used to calculate trainee workload in terms of intermediate equivalents (IE) and service equivalent value (SEV).

Education, Medical, Graduate↗