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Biomedical subjects

R Randall

Publications and source records attributed to R Randall.

At least 19 recordsLinked to original sources
PubMed2006

Selecting doctors for postgraduate training in paediatrics using a competency based assessment centre.

The design and implementation of an assessment centre in the South Yorkshire and South Humberside deanery for selecting doctors into postgraduate training in paediatric medicine is described. Eleven competency domains were identified in the job analysis. An assessment centre comprising of four exercises was implemented to assess candidates. There were modest relationships between candidates' performance on the various assessment centre exercises. Outcomes based on interview performance were related to, but not the same as, outcomes based on the combined results of the three other assessment centre exercises. Candidates perceived the assessment centre to be a fair selection method. It is concluded that an assessment centre approach to SHO recruitment is feasible and provides a greater breadth and depth of information about candidates than does a structured interview.

Chi-Square Distribution↗
PubMed2005

Comparison of the antibody in lymphocyte supernatant (ALS) and ELISPOT assays for detection of mucosal immune responses to antigens of enterotoxigenic Escherichia coli in challenged and vaccinated volunteers.

In the present study we compared the ELISPOT and antibody in lymphocyte supernatants (ALS) assays as surrogate measures of mucosal immunity. In separate studies, 20 inpatient volunteers received oral doses of 6 x 10(8) or 4 x 10(9)cfu of ETEC strain E24377A (LT+, ST+, CS1+, CS3+) and 20 subjects received 1 (n = 9) or 2 (n = 11) oral doses of the attenuated ETEC vaccine, PTL-003 expressing CFA/II (CS1+ and CS3+) (2 x 10(9)cfu/dose). Peripheral blood mononuclear cells (PBMCs) from all subjects were assayed for anti-colonization factor or toxin-specific IgA antibody responses using the ALS and ELISPOT procedures. ALS responses were measured using a standard ELISA, as well as by time-resolved fluorescence (TRF). Following challenge with E24377A, significant anti-CS3, CS1 and LT ALS responses were detected in the lymphocyte supernatants of 75-95% of the subjects. A similar proportion (75%) of subjects mounted an ALS response to CFA/II antigen after vaccination with the PTL-003 vaccine. Inter-assay comparisons between ALS and ELISPOT methods also revealed a high degree of correlation in both immunization groups. ALS sensitivity versus the ELISPOT assay for LT, CS3 and CS1-specific responses following challenge were 95%, 94% and 78%, respectively and 83% for the ALS response to CFA/II antigen after vaccination with PTL-003. Correlation coefficients for the LT and CS3 antigens were 0.94 (p<0.001) and 0.82 (p<0.001), respectively after challenge and 0.78 (p<0.001) after vaccination. The association between ALS and ELISPOT for the CS1 antigen was however, significant only when ALS supernatants were tested by TRF (r = 0.91, p<0.001). These results demonstrate the value and flexibility of the ALS assay as an alternative to ELISPOT for the measurement of mucosal immune responses to ETEC antigens, particularly when the complexities of ELISPOT may make it impractical to perform.

Adult↗
PubMed2001

Synthesis of N-alkyl substituted indolocarbazoles as potent inhibitors of human cytomegalovirus replication.

The synthesis and antiviral evaluation of unsymmetrical indolocarbazole derivatives of Arcyriaflavin A, substituted with a range of alkyl groups at the indole nitrogen, is described. Structure-activity relationships in this series against human cytomegalovirus (HCMV) replication in cell culture are reported. Compound 4b was identified as potent inhibitor of HCMV (IC(50)=19 nM), which retained activity against a range of HCMV strains including ganciclovir resistant isolates.

Antiviral Agents↗
PubMed1999

Strength of indication for cesarean delivery: comparison of private physician versus resident service labor management.

OBJECTIVE: Our purpose was to compare the strength of indication for cesarean delivery for 2 groups of patients who had undergone cesarean delivery-those treated by physicians in private or group practice and those treated by a clinic or resident service. STUDY DESIGN: From records of 119 cesarean deliveries performed in 1992, data concerning patient history, labor course and management, fetal monitor tracings, and indications for cesarean delivery were extracted, summarized, and presented to 3 reviewers. Each reviewer rated the strength of indication for cesarean delivery on a 10-point visual analog scale and specified how often they would have chosen an alternative management plan. Reviewers were blinded to the research hypothesis and to patient age, type of provider, and insurance status. RESULTS: Using a multivariate linear regression model to adjust for differences in age and indication for cesarean delivery, we found that strength of indication scores were higher among patients treated by a resident service than among those treated by private physicians (P <.0001) and that an alternative action plan was more often suggested for deliveries managed by private physicians (P <.0001). CONCLUSIONS: Among women who underwent cesarean delivery, the strength of indication judged by a panel of reviewers not involved with the patient's care was stronger among resident-treated patients than among cases treated by private physicians. Although there are several possible explanations, the findings may suggest that physicians in private practice use different criteria than do resident physicians for deciding to perform a cesarean.

Adult↗
PubMed1999

Indolocarbazoles: potent, selective inhibitors of human cytomegalovirus replication.

In our search for new, safer anti-HCMV agents, we discovered that the natural product Arcyriaflavin A (la) was a potent inhibitor of HCMV replication in cell culture. A series of analogues (symmetrical indolocarbazoles) was synthesised to investigate structure activity relationships in this series against a range of herpes viruses (HCMV, VZV, HSV1, and 2). This identified a number of novel, selective and potent inhibitors of HCMV, 12,13-dihydro-2,10-difluoro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazol e-5,7-(6H)-dione (1d) being the best example (IC50=40 nM, therapeutic index > 1450). Compounds described in this series were generally poor inhibitors of protein kinase C betaII, and no correlation was found between the ability to inhibit HCMV and the enzyme PKC.

Animals↗
PubMed1997

Audit of neonatal screening programme for phenylketonuria and congenital hypothyroidism.

The performance of the neonatal screening programme was audited against clinical standards in the Bath clinical area from 1 April 1994 to 31 March 1996. The standards and policy were agreed by local service provider representatives of the screening and were audited, using laboratory and child health computer systems and medical records. Two annual reports were produced with recommendations for improvement communicated to representatives of the service. Thus the first audit loop has been completed. The audit shows that the coverage of the service is excellent, with all eligible babies being offered screening; those with congenital hypothyroidism or phenylketonuria receive appropriate treatment by the 28 day standard. The process works extremely well, although areas for improvement have been identified, to increase the efficiency of the service. It is concluded that an effective and efficient audit cycle can be established, to monitor and improve the performance of the neonatal screening service.

Age Factors↗
PubMed1995

Biometry of the fetal cisterna magna: estimates of the ability to detect trisomy 18.

Measurements of the fetal cisterna magna were obtained from a prospective sample of patients undergoing diagnostic obstetric ultrasound examinations. These normal measurements were then compared to a retrospective sample of ultrasound scans from fetuses with the diagnosis of trisomy 18 by amniocentesis. The fetal cisterna magna increases in size throughout pregnancy. The sample from fetuses with trisomy 18 was different and had a higher rate of small and large cisterna magnas. After the two samples were mixed, it was determined that a cut-off of 2.5 standard deviations for the fetal cisterna magna would give a sensitivity of 26.3%, specificity of 99.1%, positive predictive value of 50.0% and negative predictive value of 97.6% for trisomy 18. The probability that a fetal cisterna magna of abnormal size will predict trisomy 18 in an early second-trimester ultrasound examination with the 2.5 standard deviation cut-off was estimated at 0.019. A fetal cisterna magna that is of abnormal size appears to be of diagnostic value in identifying the fetus with trisomy 18, but its sensitivity is low.

Adult↗
PubMed1994

The generation of monoclonal antibodies recognising novel epitopes by immunisation with solid matrix antigen-antibody complexes reveals a polymorphic determinant on feline CD4.

Monoclonal antibodies were generated against the feline homologue of CD4 (fCD4) by immunisation of mice with solid matrix antigen-antibody complexes of monoclonal antibody Fel7 (anti-fCD4) and formalin-fixed Staphylococcus A (SMAA-fCD4). The resulting fusion produced nine monoclonal antibodies each of which recognised a major population of feline lymphocytes and which immunoprecipitated a 55 kDa ligand from the feline T lymphosarcoma cell line 3201. Epitope mapping of the antibodies against soluble fCD4 by surface plasmon resonance indicated that the antibodies recognised five separate epitopes distinct from that defined by the Fel7 antibody used to prepare the SMAA-fCD4. These data demonstrate that SMAA complexes are an efficient means of generating monoclonal antibodies recognising novel epitopes on an antigen. One monoclonal antibody (vpg39) recognised an epitope that was expressed variably between cats, being either present or completely absent. Analysis of peripheral blood lymphocytes from specific pathogen free cats suggested that failure to react with the vpg39 antibody was an inherited trait.

Animals↗
PubMed1989

Modulation of hepatic glucose-6-phosphate dehydrogenase activity in male and female rats by estrogen.

The effect of estradiol-17 beta on the activity of glucose-6-phosphate dehydrogenase was studied in both male and female rats to further characterize the sex differences in the activity of this enzyme. Four groups of intact and castrated rats were implanted subcutaneously with graded doses (2.4, 4.8 and 7.2 micrograms/day) of pelleted estradiol in a physiologically relevant experimental system. After fourteen days the rats were sacrificed and their livers were assayed for G6PD activities. The result indicated that: (i) the enzyme activity was 3-fold higher in normal adult female than in male rats, (ii) low doses of E2 (2.4, 4.8 and 7.2 micrograms/day) increased the activity of G6PD 6-fold in castrated males and over 2-fold in female castrates as well as intact rats (iii) E2 stimulation of G6PD activity appears to be more effective in castrated males than in female rats (IV) sex difference in the activity of G6PD disappeared after treatment with E2 in castrated rats. It is concluded that the activity of G6PD in rats is markedly enhanced by low doses of E2, which appears to be largely responsible for the sex differences in the activity of this enzyme in rats.

Animals↗
PubMed1988

A novel type of pituitary adenoma: morphological features and clinical correlations.

Twenty patients with a novel, frequently aggressive type of pituitary adenoma, termed silent subtype 3 adenoma on the basis of fine structural criteria, are reported. The surgically removed tumors were studied by morphological techniques, and the findings were correlated with clinical and biochemical data. All tumors were macroadenomas, often with parasellar extension. The histologically diffuse tumors frequently exhibited focal immunopositivity for one or more adenohypophysial hormones, although the majority of adenoma cells were negative. The tumors had characteristic electron microscopic features, assuring specific diagnosis and delineating this tumor type as a distinct ultrastructural entity. The tumors were removed from 9 women and 11 men (median ages, 27 and 41 yr, respectively). In all women, mild to moderate hyperprolactinemia and its sequelae were present from the early phase of the disease, leading to the erroneous diagnosis of prolactinoma. Bromocriptine therapy (3 patients) reduced serum PRL levels to normal, but failed to halt tumor growth. In men, most adenomas were nonfunctioning; 4 men had mild to moderate hyperprolactinemia. Three men had elevated serum GH levels and acromegaly, suggestive of multidirectional differentiation. Although the putative cell type giving rise to silent subtype 3 adenomas is not known, the tumor should be recognized to avoid erroneous diagnosis and inappropriate treatment.

Adenoma↗
PubMed1985

Elevated beta-human chorionic gonadotropin and testosterone in cord serum of male infants of diabetic mothers.

Leydig cell hyperplasia is a common histological finding in male infants of diabetic mothers. The functional correlates of this histological finding were investigated by measuring beta hCG, testosterone, androstenedione, dihydrotestosterone, and progesterone in mixed cord serum of male and female infants of diabetic mothers (n = 40) and normal mothers (n = 40) at term. Male and female infants of diabetic mothers had significantly higher cord serum beta hCG levels than male and female controls. Male infants of diabetic mothers had significantly higher cord serum testosterone concentrations than male controls, female controls, and female infants of diabetic mothers. Cord serum testosterone concentrations were similar in female infants of diabetic mothers and female controls. In the male infants of diabetic mothers, there was a significant positive correlation between beta hCG and testosterone (r = 0.64; P less than 0.01). There was no significant correlation between beta hCG and testosterone in the male controls (r = -0.15; P = NS). There was no significant difference in cord serum dihydrotestosterone in any group tested. Cord serum progesterone was significantly higher in the males than in the females. Cord serum androstenedione was lower in the infants of diabetic mothers than in the controls. This study suggests that the Leydig cell hyperplasia found in male infants of diabetic mothers is due, in part, to elevated concentrations of hCG and is accompanied by elevated testosterone concentrations in the fetal compartment.

Androstenedione↗
PubMed1982

Petroleum refinery wastewater induction of the hepatic mixed-function oxidase system in Pacific staghorn sculpin.

Induction of hepatic microsomal cytochrome P450 and aldrin epoxidase was observed in the estuarine sculpin (Leptocottus armatus), following in vivo exposure to Class B petroleum refinery effluent from two West Coast refineries. The data demonstrate the presence and inducibility of the mixed-function oxidase system in Leptocottus armatus. Differences in the extent of mixed-function oxidase induction between the two effluents may be related to differences in wastewater chemistry.

Animals↗
PubMed1982

Effects of petroleum refinery wastewater exposure on gill ATPase and selected blood parameters in the Pacific staghorn sculpin (leptocottus armatus).

1. The effects of in vivo exposure to various concentrations of petroleum refinery wastewater on gill ATPase, plasma protein, plasma osmolarity, and hematocrit were measured in the euryhaline fish, Leptocottus armatus. 2. The extent of the reduction in Na,K-ATPase activity resulting from the exposure to the two refineries wastewaters may be related to wastewater chemical composition. 3. Changes in the blood chemistry parameters did not follow a consistent or easily explainable pattern.

Adenosine Triphosphatases↗