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Biomedical subjects

M Smith

Publications and source records attributed to M Smith.

At least 757 records · Page 42Linked to original sources

Modularisation--its versatility and value.

The issue of credit accumulation is topical and offers real prospects for nursing education to be considered as a part of an academic continuum in keeping with higher education. It cannot easily be considered without taking into account modularisation which offers a structure for the justification and award of credits. Modularisation of courses holds exciting prospects and offers a practical, logical approach to course development. Modules can be versatile and used in very cost-effective and efficient ways, both as an integral part of the course and as free-standing entities. This article considers the building of a curriculum using a modular approach. The terms module, credit and levels are examined to provide full background information. Also identified are some of the additional potential uses of modules. The work is written from the experience of developing modular courses and offers examples from an existing Diploma. There are, however, some notes of caution and these are raised to add balance to the otherwise enthusiastic discussion.

Curriculum↗

Effects of misoprostol on the pharmacokinetics of indomethacin in human volunteers.

The effects of misoprostol (200 micrograms as a single dose or q.i.d. as a multiple dose) on the pharmacokinetics of indomethacin (100 mg single-dose administration or 50 mg t.i.d. multiple-dose administration) were studied in 16 healthy human volunteers under single-dose and steady-state conditions in a randomized, double-blind, placebo-controlled, balanced three-period study design. The overall absorption as shown by the values for area under the concentration curve of indomethacin was unaffected by concurrent administration of misoprostol. However, misoprostol did significantly enhance the steady-state maximum concentration of indomethacin by 32%. Thus misoprostol does not interfere with the absorption of indomethacin despite the known inhibitory effects of this protaglandin analog on acid secretion.

Administration, Oral↗

Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder of unknown aetiology that affects numerous body systems including skin, brain and kidneys. Some TSC has been linked to chromosome 9, additional TSC genes on chromosomes 11 and 12 have been proposed, but the majority of TSC families remain unlinked. Using TSC families in which data had excluded linkage to chromosome 9, we failed to detect linkage with loci on chromosomes 11, 12 and others. One marker examined was D16S283, the closest locus on the proximal side of the polycystic kidney disease type 1 (PKD1) gene. Linkage between TSC and D16S283 demonstrated a lod score of 9.50 at theta = 0.02 with one family independently presenting a lod score of 4.44 at theta = 0.05. These data reveal an important TSC locus near the region of PKD1 on chromosome 16p13.

Alleles↗

Analysis of disulphide bridge function in recombinant bovine prolactin using site-specific mutagenesis and renaturation under mild alkaline conditions: a crucial role for the central disulphide bridge in the mitogenic activity of the hormone.

We have previously described a method for isolating Escherichia coli-produced methionyl bovine prolactin (Met-bPRL) and its renaturation using thioredoxin. This report describes an alternative renaturation procedure in which extracted Met-bPRL is incubated in air at pH 10 and 20 degrees C. Within 1 h of such treatment essentially all of the reduced Met-bPRL was converted to the oxidized form; this was accompanied by an increase to full mitogenic activity in the Nb2 cell bioassay. It was also found that, to minimize contamination by high mol. wt Met-bPRL derivatives, it is essential to have a reducing agent (dithiothreitol) present during disruption of the bacteria and to extract the protein at neutral pH. The contribution of each of the three disulphide bridges in bPRL to its bioactivity was studied with Met-bPRL variants, prepared via site-specific mutagenesis, in which cysteines were replaced by serines to prevent disulphide bond formation. Variants lacking the C4-C11 bridge, the C191-C199 bridge or both these terminal bridges were as mitogenic as authentic bPRL. (Variants lacking the C191-C199 bridge had markedly increased solubility in the presence of deoxycholate.) In contrast, variants lacking the C58-C174 bridge had greatly reduced bioactivity, indicating that integrity of the large disulphide loop is crucial to the hormone's mitogenic activity.

Animals↗

Potential precipitating factors of the onset of myocardial infarction.

Myocardial infarction (MI) usually results from thrombotic coronary artery occlusion at the site of a ruptured atherosclerotic plaque. The factors responsible for triggering MI are not known but conditions that increase serum catecholamines may be involved. Accordingly, the authors prospectively evaluated the presence of factors that may increase catecholamines immediately prior to MI in 186 patients. Myocardial infarction was documented by a rise in serum CK-MB. There were 149 men and 37 women, aged 57 +/- 12 (mean +/- SD) years. All patients were interviewed within 72 hours of admission concerning strenuous physical activity, emotional stress, and assumption of the upright posture immediately prior to the onset of symptoms. Seventy-five (40%) patients had one or more of these factors immediately prior to the onset of MI chest pain. Fourteen (8%) experienced acute emotional upset; 28 (15%) were involved in strenuous physical activity; and 39 (21%) had suddenly changed position. In the latter group, 18 changed from being supine for more than 1 hour to standing; three rose from supine to sitting; and 18 changed from prolonged sitting (greater than 60 minutes) to standing. The conclusion is that a potential triggering factor is present in many patients immediately prior to the onset of MI. A sudden change in position is the most frequent potential trigger, typically occurring the morning after awakening from sleep.

Circadian Rhythm↗

Diagnostic accuracy of three clinical case definitions for advanced HIV disease.

OBJECTIVE: To assess the accuracy of three clinical case definitions for advanced HIV disease: the World Health Organization (WHO) case definition, and the original and revised Caracas case definitions. DESIGN: Retrospective chart review. SETTING: A clinic for patients with all stages of HIV infection at the Johns Hopkins Hospital, Baltimore, [correction of Bethesda] Maryland, USA, a tertiary care university hospital. PATIENTS, PARTICIPANTS: Two hundred and twenty-four HIV-positive adults who underwent initial evaluation between 1 January 1990 and 31 December 1990. MAIN OUTCOME MEASURES: A score for each definition was assigned based on initial evaluation. The sensitivity, specificity, and predictive values were calculated using the Centers for Disease Control (CDC) staging criteria, and results were correlated with total CD4 cell counts. RESULTS: The sensitivities of the WHO, and the original and revised Caracas definitions were 40, 67, and 60%, respectively, using CDC disease stage IV as a positive standard. Specificities were between 99 and 100%, using CDC stage II-III disease as a negative standard. Mean CD4 cell counts for patients with positive scores were 184, 160, and 158 x 10(6)/l, respectively, compared to 191 x 10(6)/l for CDC stage IV patients. Sensitivity was lower when the positive standard was expanded to include all patients with CD4 cell counts less than 200 x 10(6)/l. CONCLUSIONS: In our study population, case definitions were specific, but only moderately sensitive for advanced HIV disease. Prospective studies should be conducted in diverse geographic regions, using lymphocyte or CD4 cell counts when possible.

Acquired Immunodeficiency Syndrome↗

Surveillance for CMV infection in orthotopic liver transplant recipients.

Infection with cytomegalovirus is a major cause of morbidity and mortality following orthotopic liver transplantation. In order that preventive strategies may be devised, a detailed assessment of risk factors for infection and disease is required. We have prospectively assessed 46 orthotopic liver transplant recipients for CMV excretion from multiple sites in order to determine incidence of, and risk factors for, CMV infection and disease. Risk factors for posttransplant CMV infection were donor CMV seropositivity, an increased volume of peritransplant whole-blood transfusion and an increased dose of extra steroid therapy to treat rejection episodes. These findings implicate, respectively, transfer of virus with donor organ, transfer of virus with blood transfusion, and stimulation of reactivation of latent virus in recipients through augmented immunosuppression. The possible ways of preventing or ameliorating these effects are discussed.

Adult↗

Identification of four VP4 serological types (P serotypes) of bovine rotavirus using viral reassortants.

A series of five reassortant viruses each containing the VP4 gene of a distinct bovine rotavirus and the VP7 gene of human rotavirus strain ST3 was prepared, and antisera to these were produced in rabbits. In neutralization tests, these antisera allowed the differentiation of the five original strains (from three different VP7 or G serotypes) into three or possibly four VP4 or P serotypes. All of a further seven bovine rotavirus strains adapted to cell culture were successfully typed by these antisera. There was a degree of cross-reaction between antiserum to the fourth bovine rotavirus P serotype and the predominant human rotavirus serotype. However, antisera raised in guinea-pigs to recombinant VP4 from this serotype showed the bovine serotype to be distinct. There was no significant serological relationship between these four bovine rotavirus P serotypes and previously described P serotypes from rotaviruses isolated from man and non-bovine animals. The predominant bovine rotavirus VP7 serotypes G6 and G10 tended to have distinct P serotypes also.

Animals↗

The community drug team.

The creation of a network of nearly 100 community drug teams (CDTs) across the UK stands as the most significant expansion to occur within drug services during the 1980s. Key characteristics include the narrowly defined geographical focus, the community emphasis, the multi-disciplinary composition and the promotion of generic contribution through 'consultancy'--as with Community Alcohol Teams. Subsequent adaptations have extended from the base of the CDT with outreach strategies and harm-minimization techniques. However, the extent of collaboration from generic colleagues (especially general practitioners) has been initially poor and is only slowly improving. An unplanned abandonment of the original consultancy role for the CDT is widely evident, as CDT workers have become more actively involved in the delivery of care--either directly or on a 'shared care' basis. It is proposed that separate consideration should be given to short- and long-term development strategies, including re-examination of the target populations, staffing composition, and methods of work through consultancy and/or direct provision of care.

Community Mental Health Centers↗

Ranitidine, cimetidine, famotidine have no effect on post-prandial absorption of ethanol 0.8 g/kg taken after an evening meal.

Forty-seven healthy male subjects were studied twice using a randomized, placebo-controlled design. Each subject took an 8-day course of two of the following four regimens; 300 mg ranitidine, 800 mg cimetidine, 40 mg famotidine or placebo (identical either to 300 mg ranitidine or 800 mg cimetidine). The systemic bioavailability of ethanol (integrated 6-h plasma ethanol concentration, peak plasma ethanol concentration, and the time to peak plasma ethanol concentration) was measured after the oral ingestion of 0.8 g of ethanol per kg body weight, given one hour after an evening meal on Day 8 of each regimen. There was no significant difference of integrated 6-h plasma ethanol concentration, peak ethanol concentration, or time to reach peak ethanol concentration after dosing with either ranitidine, cimetidine or famotidine or placebo.

Absorption↗

Oxygen saturation and cardiovascular changes during fibreoptic intubation under general anaesthesia.

Sixty patients who required fibreoptic nasotracheal intubation were studied. Arterial oxygen saturation, arterial blood pressure and heart rate were monitored continuously during fibreoptic intubation under deep halothane anaesthesia. There were significant decreases (p less than 0.001) in arterial blood pressure and heart rate despite administration of intravenous colloid and atropine. Almost one third of the patients (18 out of 60) suffered a decrease in arterial oxygen saturation below 90% during the intubation sequence and in five patients the saturation fell below 80%. The episodes of desaturation were not related to the induction-intubation time or to the grade of laryngeal visibility at direct laryngoscopy.

Adolescent↗

Reduced rate of uptake of zinc ions in a calf affected with the lethal syndrome A46 relative to clinically normal calves using whole body radio-isotope scanning of 62Zn.

Four clinically healthy control calves were scanned and blood clearance was determined from blood samples taken during the first hour after intravenous injection of 62Zn. Furthermore, one clinically healthy control calf and one calf suffering from the lethal hereditary syndrome A46 were scanned and blood samples taken from five min after intravenous and abomasal injection of 62Zn and onwards for a period of up to 26th. The results show a very fast liver uptake of 62Zn. The estimated rate of plasma/blood clearance and liver uptake for the control calves agrees with values derived from studies on other animals. In contrast, the A46 calf had a decreased rate of plasma/blood clearance and liver uptake relative to the control calves.

Animals↗

Regulation of delayed-early gene transcription by dual TATA boxes.

The 39K Autographa californica nuclear polyhedrosis virus (AcMNPV) gene is highly expressed throughout the virus life cycle and is controlled by tandem promoters that exhibit features of early and late baculovirus promoters. Late transcripts initiate at a conserved TAAG motif, while early transcripts are heterogeneous and initiate near a conserved CAGT motif. To define the nucleotide sequences that regulate early transcription of the 39K gene, a series of mutations was generated by substitution of 10-bp stretches in the 39K promoter with a BglII linker. The effects of these mutations on transcription from the early promoter were determined by transient expression and primer extension assays in the presence of the viral trans-activator IE1 gene. Mutations in the region from -15 to -44 revealed that early 39K transcription was controlled by dual TATA boxes. These TATA boxes are separated by 10 bp, which partially accounts for the heterogeneity in early 39K transcripts. Transcripts initiating at the CAGT motif (proximal transcripts) were abolished by deletion of the proximal TATA box located at -29 relative to CAGT. Proximal transcripts were not affected by alterations in the distal TATA motif located at -39 relative to the CAGT. Similarly, transcripts initiating upstream of CAGT (distal transcripts) were eliminated by mutations in the distal TATA but were unaffected by substitutions in the proximal TATA box. Proximal transcripts were not detected with a plasmid containing mutations in the CAGT motif, although the distal transcripts were unaffected by CAGT mutations. When the sequences surrounding the initiation site for the distal transcripts were altered, the start site was shifted one nucleotide, but transcription was not quantitatively affected. These results suggest that early 39K transcription is controlled by two distinct TATA elements, one that is dependent on an initiator and one in which the site of initiation is determined by the TATA element alone. Mutations in an upstream region from -45 to -68 relative to the CAGT motif had a quantitative effect but did not alter the heterogeneous pattern of early transcripts, suggesting these sequences function as an upstream regulatory region. Analysis of late transcription indicated that the TAAG element was essential, while transcription was unaffected by other mutations.

Animals↗

Changes in the plasma aminogram of parenterally fed infants treated with dexamethasone for bronchopulmonary dysplasia.

A substantial increase in the plasma concentration of most amino acids was observed in 59 preterm infants with chronic lung disease soon after the initiation of dexamethasone therapy. The size of increase appeared to be dose related. This phenomenon is likely to be the result of steroid induced protein catabolism. Interestingly, neither phenylalanine nor tyrosine concentrations were significantly increased.

Amino Acids↗