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S Jennings

Publications and source records attributed to S Jennings.

17 recordsLinked to original sources

Species differences in 5 alpha-androstane-3 beta,17 beta-diol hydroxylation by rat, monkey, and human prostate microsomes.

The 6 alpha-, 7 alpha-, and 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by rat prostate microsomes appears to be catalyzed by a single, high-affinity cytochrome P450 enzyme. In the present study we have examined the hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by prostate microsomes from cynomolgus monkeys and from normal subjects and patients with benign prostatic hyperplasia. Our results suggest that although rat, monkey, and human prostate microsomes catalyze the 6 alpha-, 7 alpha-, and 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol, these pathways of oxidation in monkeys and humans are not catalyzed by a single cytochrome P450 enzyme. The ratio of the three metabolites was not uniform among prostate microsomal samples from individual humans or monkeys. The 6 alpha-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol varied independently of both the 7 alpha- and 7 beta-hydroxylation, which varied in unison. The 6 alpha-, 7 alpha-, and 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by monkey prostate microsomes appeared to be differentially affected by in vivo treatment of monkeys with beta-naphthoflavone or dexamethasone. Treatment of a monkey with dexamethasone appeared to cause a 2.5-fold increase in both the 7 alpha- and the 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol without increasing the 6 alpha-hydroxylation. The 7 alpha- and 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by human and monkey prostate microsomes, but not the 6 alpha-hydroxylation, was inhibited by antibody against rat liver NADPH-cytochrome P450 reductase. Similarly, the 7 alpha- and 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by human prostate microsomes, but not the 6 alpha-hydroxylation, was markedly inhibited (greater than 85%) by equimolar concentrations of the imidazole-containing antimycotic drugs ketoconazole, clotrimazole, and miconazole. These results suggest that the 7 alpha- and 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by monkey and human prostate microsomes is catalyzed by a cytochrome P450 enzyme, whereas the 6 alpha-hydroxylation is catalyzed by a different enzyme which may or may not be a cytochrome P450 monooxygenase. The hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by prostate microsomes from normal human subjects was quantitatively and qualitatively similar to its hydroxylation by prostate microsomes from patients with benign prostatic hyperplasia.(ABSTRACT TRUNCATED AT 400 WORDS)

Androstane-3,17-diol

The epidemiology of pertussis in the Republic of Ireland.

Epidemiological data on pertussis in the Republic of Ireland have been gathered annually since 1941. However, no detailed analysis of these data has, until now, been carried out. Fifteen epidemics occurred between 1941 and 1989, an average of one per 3.1 years, which is similar to epidemic intervals observed elsewhere. After the introduction of a vaccine in the 1950s, annual pertussis notifications declined, from 175 per 100,000 in 1956 to 7.6 per 100,000 in 1972. Following adverse publicity in 1973, uptake of the vaccine fell to 30% in 1976. Although uptake has increased again in recent years, it has levelled out at only 40-45% and large epidemics of pertussis occurred in 1985 and 1989. At the same time, mortality from pertussis has fallen to almost negligible levels. Most cases occur in children more than one year of age. Changes in the vaccination schedule could have a major impact on the incidence of the disease in the Republic of Ireland. However, if a further decline in the incidence of the disease is to be achieved, parents have to be persuaded of the benefits of pertussis vaccination.

Adolescent

Adjuvant radiotherapy in high stage transitional cell carcinoma of the renal pelvis and ureter.

This review was undertaken to assess the influence of adjuvant radiation therapy on failure patterns and survival in high stage transitional cell carcinoma of the renal pelvis or ureter. Ninety-four patients with transitional cell carcinoma of the renal pelvis or ureter were retrospectively reviewed. Twenty-six had American Joint Commission stage T3 or T4 N0/+, M0 disease and underwent curative resections (median follow-up 13.5 months, range 3-311). Local failure was defined as recurrence in the tumor bed, regional nodes, or ureteral stump. Time to recurrence and survival were calculated from the time of pathologic diagnosis. Variables associated with local failure, distant metastasis, and survival were analyzed using univariate and multivariate analysis. Seventeen received surgery only, nine received adjuvant radiation therapy (median dose 50 Gy). Local failure occurred in 9 of 17 without and 1 of 9 with adjuvant radiation therapy (p = 0.07). Actuarial 5-year local control was 34% without and 88% with adjuvant radiation therapy. Cox step-wise regression confirmed adjuvant radiation therapy (p = 0.006) and grade (p = 0.006) as significantly associated with local failure. No patients with low grade lesions suffered local failure either with or without adjuvant radiation therapy. High grade lesions had an local failure rate of 15% with and 71% without adjuvant radiation therapy. Metastatic disease occurred in 4 of 9 and 8 of 17 with and without radiation therapy. No significant factors influencing distant failure were identified. Five-year actuarial survival was 44% with and 24% without adjuvant radiation therapy. The survival differences were not statistically significant on univariate or multivariate analysis. High staged transitional cell carcinoma of the renal pelvis or ureter has a substantial local failure risk after surgery alone. Adjuvant radiation therapy markedly reduces this risk but has no impact on distant disease which occurs in approximately 50%. Effective adjuvant therapy will require effective systemic therapy in addition to adjuvant radiation therapy.

Aged

Neutrophil-derived oxidants promote leukocyte adherence in postcapillary venules.

The objective of this study was to determine whether hydrogen peroxide (H2O2), hypochlorous acid (HOCl), and monochloramine (NH2Cl), at concentrations produced by activated neutrophils, promote leukocyte adherence to microvascular endothelium in post-capillary venules. Cat mesenteric venules (30-45 microns diameter) were examined using intravital video microscopy. Red blood cell velocity (VRBC), venular diameter (DV), and the number of adherent leukocytes (NWBC) were measured in postcapillary venules. Venular blood flow and wall shear rate (tau) were calculated from the measured values of VRBC and DV. Different concentrations (0.01-1.0 mM) of H2O2, HOCl, or NH2Cl were superfused on the mesentery. In some experiments, the contributions of the leukocyte adhesive glycoprotein CD11/CD18 and platelet-activating factor (PAF) in the oxidant-induced leukocyte adherence were determined using a CD18-specific antibody (IB4) and a PAF-receptor antagonist (WEB 2086), respectively. The results of our in vivo experiments indicate that H2O2 and NH2Cl, but not HOCl, promote leukocyte adhesion to venular endothelium. Incubation of isolated cat neutrophils with either NH2Cl or H2O2 resulted in activation of CD11/CD18, as assessed by flow cytometry. Although the leukocyte adhesion induced by both H2O2 and NH2Cl was associated with a reduction in venular wall shear rate, corresponding decrements in shear rate induced by partial occlusion of the mesenteric artery did not lead to similar levels of leukocyte adherence. The leukocyte adherence induced by H2O2 and NH2Cl was largely prevented by monoclonal antibody IB4, indicating that both oxidants promote leukocyte adherence via activation of CD11/CD18. The H2O2-induced, CD18-mediated leukocyte adherence appears to be elicited by PAF and by a direct effect of the oxidant on CD11/CD18 expression. The mechanism underlying the NH2Cl-induced leukocyte adherence remain unclear.

Animals

Behavioural risk factors among young adults in small areas with high mortality versus those in low-mortality areas.

A community-based cross-sectional survey of behavioural risk factors for premature mortality was carried out on a group of 354 adults aged 25-44 from previously identified high-mortality 'black-spots' in Dublin who were compared with 333 others from low-mortality areas. In the black-spot areas, 50.9% of respondents were current smokers versus 28.5% in low-mortality areas and 14.6% took 'sufficient' exercise versus 31.4% in low-mortality areas. People living in black spots were also less likely to make 'healthy' dietary choices than those in low-mortality areas. There is a higher prevalence of behavioural risk factors for premature mortality among young adults living in electoral wards/district electoral divisions (DEDs) with high standardized mortality ratios (SMRs) from all causes than among those in areas with low SMRs. A health promotion programme aimed at increasing exercise levels, reducing smoking and encouraging healthy eating should be aimed at young adults in DEDs with high SMRs.

Adult

[Mortality in influenza epidemics in Switzerland 1969-1985].

In Switzerland from 1969-1985, 9 out of 11 influenza epidemics were associated with a statistically significant increase in mortality. A total of 12,202 excess deaths from all causes was identified. Expected deaths were forecast for each epidemic period separately for 4 age groups using Fourier and Arima modeling. 75.7% of all-cause excess deaths occurred in age group 70 to 89 and 5.1% in age group 1-59. In the 70-89 years old group the excess mortality risk during influenza epidemics was 271.6 per 100,000, whereas in age group 1-59 it was only 1.7 per 100,000. Only 40% of all excess deaths had been ascribed to acute respiratory conditions. Influenza viruses A H3N2 were the most frequently identified agents. In some instances mortality increased before the morbidity reports of the Swiss practitioners indicated the occurrence of an epidemic. Also, morbidity reporting decreased over successive years. A decrease in mortality following the epidemics was not observed. A more complete vaccination of high risk patients in Switzerland is desirable.

Adolescent

Student perceptions of the links between nursing and the liberal arts.

This article examines the extent to which nursing students are aware of the importance of liberal arts in their professional education. Based on a survey of nursing students and alumnae from a small, New York state college, the project further explored the channels through which they became aware of the significant links between these two aspects of their education. One finding is that nursing students give a relatively high weight to the importance of the liberal arts in their total learning process. The more important conclusion is that students, on the whole, believe that they have made the links between liberal arts and nursing themselves. To the extent that other agents help forge these links, the most important seem to be nursing labs and clinicals, other nursing students, and nursing texts and modules. Students perceive that nursing faculty help draw links more often than liberal arts faculty, but neither rank very high.

Adult

Community notification of child sexual abuse.

There has been a heightened awareness of sexual abuse of children in Ireland in the past four years. One-hundred and forty seven cases of alleged sexual abuse notified to the Director of Community Care in 1986-1987 were reviewed retrospectively from the medical and social work notes. In 81 (55%) cases, sexual abuse was either confirmed or strongly suspected and these were analysed further. Victims were twice as likely to come from an urban as from a rural background. Girls were more likely to be abused at all ages, and this was particularly marked in the teenage years. Abusers were either intra-familial or known to the family in most cases. A surprising number were under 16 years of age. The study highlights the time commitment needed to manage this problem in the community and the need to develop services directed towards the young perpetrator. It also raises concern at the sizable percentage of children who, following investigation, are found not to have been abused.

Adolescent

Enhancement of linear growth and weight gain by cyproheptadine in children with hypopituitarism receiving growth hormone therapy.

Cyproheptadine (Cp), an antihistamine serotonin antagonist drug with appetite-stimulating activity, was given to children with growth hormone (GH) deficiency to test the hypothesis that increased weight gain would enhance the effect of GH on linear growth. Six patients with idiopathic GH deficiency received GH 0.08 U/kg three times per week plus Cp 0.25 to 0.4 mg/kg/day for 4-month periods, alternating with 4-month periods of GH plus placebo, on average for 16 months. Overall, height velocity (HV) increased from 9.1 +/- 2.4 with GH alone to 12.1 +/- 2.1 cm/yr with GH-Cp (P = 0.01) and weight velocity (WV) increased substantially from 1.3 +/- 1.3 to 7.8 +/- 3.6 kg/yr (P = 0.01). For 10 of 11 8-month treatment intervals completed, HV was greater during GH-Cp treatment than during GH alone, and there was a good correlation between HV and WV for each 4-month observation period (r = 0.64, P less than 0.002). These findings should be considered preliminary because of the small number of patients, but suggest that weight gain induced by cyproheptadine results in improved linear growth in patients given GH and that this drug may be useful in optimizing the response to GH therapy.

Body Height

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Health Workforce

A multicase family study of rheumatoid arthritis in south west Ireland.

A study of 26 families with multiple cases of RA was conducted in South West Ireland. In 149 relatives examined, 67 cases of RA were identified. An analysis of affected sibling pairs and trios revealed significant linkage between HLA and RA (p less than 0.05). A high frequency of DR4 was observed in probands (80.7 per cent) and affected members (74.6 per cent) compared with controls (18 per cent). An elevated frequency of the haplotypes A2-B44-DR4 (19.2 per cent) and A2-Bw62-DR4 (5.7 per cent) was seen in the affected sample. HLA-Bw62 was at raised frequency in probands (19.2 per cent) compared with controls (9 per cent). The haplotype frequency of A2-B44-DR4 was raised in affected females and A2-Bw62-DR4 in affected males. A low haplotype frequency of A1-B8-DR3 was found in all RA subjects. Disease severity (clinical and radiological criteria) was associated with DR4, but this did not reach statistical significance. A high incidence of extra-articular features of RA was observed, with DR4 occurring in all cases of vasculitis (75 per cent of whom were DR4 homozygous).

Adult

Adolescents' theories about the development of their relationships with parents.

Using a retrospective method, we assessed late adolescents' developmental theories about their affective relationships with their parents. Subjects used drawings and questionnaire ratings to portray their relationships with parents at five points between infancy and the present. From infancy to their current age, adolescents portrayed their relationships in two major ways. They perceived themselves as gaining in responsibility, dominance, independence, and similarity from infancy to the present, whereas they portrayed their parents as experiencing a decline on these dimensions. For variables indicating closeness and love, however, there was a striking discontinuity in these linear trends: Although adolescents perceived linear trends from infancy to adolescence, they depicted their current relationships as involving a great deal more love and closeness. They also portrayed their relationships with mothers and fathers somewhat differently. More responsibility was felt towards the mothers and they were portrayed as especially friendly, but subjects felt more similar to their fathers, whom they perceived as dominant. We interpreted the results as indicating that late adolescents constructed theories of the affective components of their relationships with their parents to serve the needs of separation while maintaining a close affective tie to the parents.

Adolescent