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Biomedical subjects

A McMahon

Publications and source records attributed to A McMahon.

At least 91 records · Page 5Linked to original sources

Random X-chromosome inactivation in female primordial germ cells in the mouse.

The pattern of expression of the two X chromosomes was investigated in pre-meiotic germ cells from 12 1/2-day-old female embryos heterozygous for the variant electrophoretic forms of the X-linked enzyme phosphoglycerate kinase (PGK-1). If such germ cells carry the preferentially active Searle's translocated X chromosome (Lyon, Searle, Ford & Ohno, 1964), then only the Pgk-1 allele on this chromosome is expressed. This confirms Johnston's evidence (1979, 1981) that Pgk-1 expression reflects a single active X chromosome at this time. Extracts of 12 1/2-day germ cells from heterozygous females carrying two normal X chromosomes show both the A and the B forms of PGK; since only one X chromosome in each cell is active, different alleles must be expressed in different cells, suggesting that X-chromosome inactivation is normally random in the germ line. This result makes it unlikely that germ cells are derived from the yolk-sac endoderm where the paternally derived X chromosome is preferentially inactivated. In their pattern of X-chromosome inactivation, germ cells evidently resemble other tissues derived from the epiblast.

Animals↗

The hospital's perspective on cost containment.

Cost containment has long been a concern of hospitals and the American Hospital Association (AHA). In recent years, however, cost containment has assumed a special prominence in hospitals, becoming both a political and social necessity. The hospitals' and AHA's activities in cost containment fall into four major categories: first, the Voluntary Effort to Contain Health Care Costs, of which AHA is a founding partner; second, administrative effectiveness; third, capital effectiveness, and, finally, medical effectiveness. Some programs to promote administrative effectiveness are shared administrative services, energy conservation, careful attention to staffing patterns and management effectiveness review. Capital effectiveness involves technology assessment and other means of deciding how to make the most of the hospital's dollar. Medical effectiveness can be accomplished by such methods as medical audits, utilization reviews and shared clinical services.

American Hospital Association↗

Gearing up for primary care.

Although hospitals have long been involved in the provision of primary care services, a new opportunity now exists for hospitals to take the lead in better organizing these services.

Ambulatory Care↗

Subclinical changes in luteal function in cynomolgus monkeys with moderate blood lead levels.

The objective of the present study was to investigate luteal function in cynomolgus monkeys (n = 32), aged 15-20 years with blood lead levels (BLLs) in the range of < 3.0 micrograms dl-1 (control, n = 20), 10-15 micrograms dl-1 (low, n = 7) and 25-30 micrograms dl-1 (moderate, n = 5). Sampling was performed daily beginning with day 10 of the menstrual cycle and concluding on the first day of the subsequent menstrual cycle. Circulating levels of oestradiol (E2), progesterone (P4) and 20 alpha-hydroxyprogesterone (20-OHP) were normalized to the day of the ovulatory E2 surge. The area under the concentration curve (AUC) for P4 was significantly lower in monkeys with moderate BLLs compared to the control group (P = 0.04). The number of days for which circulating levels of P4 were greater than 1.0 ng ml-1 were also significantly fewer (P = 0.03) in monkeys with moderate BLLs compared to controls. There was no statistical evidence of a lead effect on circulating levels of E2, 20-OHP or menstrual cycle characteristics. These data suggest that chronic lead exposure suppresses corpora luteal production of P4 in the monkey at circulating BLLs lower than previously reported and relevant to humans with occupational exposure to lead.

Algestone↗

VAD chemotherapy--toxicity and efficacy--in patients with multiple myeloma and other lymphoid malignancies.

Thirty-three patients with multiple myeloma (11 untreated, 15 refractory and seven relapsed patients) have received vincristine and adriamycin infusion therapy with oral dexamethasone (VAD). The median number of course received was five. In addition 16 patients with lymphoid malignancy have received a median of four courses of VAD. Three patients who relapsed after VAD have received further VAD therapy making 52 patient treatments assessable for toxicity. Ten per cent had nausea, 4 per cent vomiting, 4 per cent total alopecia, 25 per cent constipation, 33 per cent paraesthesiae, 8 per cent proximal myopathy, 33 per cent dyspepsia, 23 per cent proven bacteraemia, and 19 per cent chest infections. Infections were not usually associated with neutropenia. Shingles was seen in four patients with myeloma, but none of the patients with lymphoid malignancy. The response rate in myeloma was 9/11, for previously untreated patients, 3/7 for relapsed, and 8/15 for refractory patients. Responses have been seen in other lymphoid malignancies-1/2 patients with relapsed acute lymphoblastic leukaemia had a complete remission. Two out of seven patients with chronic lymphocytic leukaemia achieved a partial remission, and a further three had a clinical improvement. Three out of six patients with non-Hodgkin lymphoma and one patient with macroglobulinaemia achieved a partial remission.

Adult↗

Experience with the Portacath.

Fifty Portacaths have been inserted in patients undergoing prolonged outpatient chemotherapy, most for haematological disease. Twenty-one are still working at a median duration of 12 months (range 1-27) and a further 15 were functioning normally at the time of the patients death (median survival 6 months). Four functioning Portacaths have been removed, three suspected of causing septicaemia and one believed erroneously to have occluded. Ten have ceased to function and nine of these have been removed. The causes of these failures are nearly all avoidable and are discussed in detail; many occurred early in our experience. With careful attention to detail and with management by trained and interested staff, the Portacath is a safe and reliable device for intermittent vascular access.

Antineoplastic Agents↗

Body distribution and endocrine toxicity of hexachlorobenzene (HCB) in the female rat.

Hexachlorobenzene (HCB) residue levels in dosed rats (50.0 mg kg-1 body wt.day-1, n = 9) were significantly (P < 0.05) greater in the periovarian fat compared to the thyroid gland. Hexachlorobenzene residue levels were significantly (P < 0.05) greater in the thyroid versus the adrenal and ovary. Ovarian HCB residue levels were greater than those found in the thymus, liver and lung. Serum thyroxin (T4) and the free T4 index (FTI) were significantly (P < 0.05) suppressed in HCB-treated rats compared to the control group (n = 8). In contrast, no significant differences in serum concentrations of oestradiol (E2), progesterone (P4) or percentage triiodothyronine uptake (%T3) were observed, thus suggesting an HCB-induced hypothyroid-like state. In a second experiment, adult female Sprague Dawley rats (n = 16) were dosed as above and superovulated with pregnant mare serum gonadotrophin (PMSG, 10 IU s.c.) and human chorionic gonadotrophin (hCG, 20 IU s.c.). Circulating levels of P4 were significantly (P < 0.05) elevated compared to the control group (n = 8). The %T3 uptake and serum T4 levels were significantly (P = 0.05) suppressed compared to controls. Hexachlorobenzene treatment had no effect on circulating levels of E2 or on the FTI. These results suggest that HCB-induced changes found in the spontaneously cycling rat are augmented by ovulation induction strategies. We also conclude that HCB concentrates in the endocrine tissues in addition to the fat.

Animals↗

Establishing an intracytoplasmic sperm injection (ICSI) programme for the treatment of male factor infertility in Ireland.

This paper chronicles the introduction and initial experiences of Intra Cytoplasmic Sperm Injection (ICSI) as a treatment for severe male factor infertility in Ireland. Following initial development of the technique using a bovine model, therapy was offered clinically from September 1995. Up to March 1996 a total of 60 couples underwent the procedure. Fertilisation and embryo transfers were achieved in 50 of these (83.3 percent). Fourteen (23 percent) became clinically pregnant per cycle commenced, 28 percent per embryo transfer. Despite a drop in the total number of oocytes available, fertilisation rates rose over the 6 months of the study from 22 percent to 54 percent. There were 2 miscarriages (14.2 percent) and the multiple pregnancy rate was 28.5 percent. Eight singletons, 2 twins and 2 triplet sets have been successfully delivered. Provided there is proper patient selection, ICSI should prove a valuable addition to treatment options available to infertile couples in Ireland.

Adult↗

Feasibility of a men's health promotion programme in Irish primary care.

BACKGROUND: To assess the feasibility of offering health promotion and preventive medicine initiatives in primary care. AIMS: A pilot study aimed at men in general practice to establish the uptake, acceptability and effectiveness of interventions in health initiatives. METHODS: One thousand men aged 18-65 were selected at random from five general practices in the Western Health Board area. Practices were randomly allocated to one of four brief interventions: cardiovascular screening, cancer screening, stress management or general lifestyle advice. RESULTS: Fifty-five per cent of men responded, with 35.7% actually attending. There were minor but significant short-term changes in health status and behaviours. Participants expressed high levels of satisfaction, but tended to prefer interventions with an explicit clinical component. CONCLUSION: It is at least as feasible to offer health promotion for men in primary care as it is for other demographic groups, but adequate training and resources are required.

Adult↗

Reproductive endocrine effects of chronic lead exposure in the male cynomolgus monkey.

The reproductive endocrine effects of chronic lead exposure were investigated in 9 year old male (n = 16) cynomolgus monkeys, orally dosed with lead acetate (1500 micrograms/kg/day) according to the following dosing regimens: continuous exposure from birth onward (lifetime, n = 4), beginning at postnatal day 300 (post-infancy, n = 5) and postnatal days 0 to 400 (infancy, n = 4), or vehicle only (control, n = 3). Altered Sertoli cell function was shown by a significant (P = 0.0286) decrease in the inhibin/follicle stimulating hormone (INH/FSH) ratio in both the lifetime and post-infancy groups compared to the control group. Gonadotropin releasing hormone (GnRH) stimulated levels of luteinizing hormone (LH) were significantly (P = 0.0370) lower in the lifetime group compared to the control group as determined by comparisons of the area under the curve. These data suggest that chronic lead exposure exerts a subtle effect on the pituitary as well as on Sertoli cell function.

Animals↗

Alterations in circulating ovarian steroids in hexachlorobenzene-exposed monkeys.

Hexachlorobenzene (HCB) is a global pollutant that has been identified in human serum and ovarian follicular fluid, and its effect on ovarian function has not been adequately defined. Thus, the effects of HCB on ovarian steroidogenesis and menstrual cycle characteristics were investigated in cynomolgus monkeys (n = 16) orally dosed by gelatin capsule (0.0, 0.1, 1.0, and 10.0 mg HCB/kg b.wt./d) for 90 d (approximately three menstrual cycles). Analysis of change in menstrual cycle length for each animal revealed a dose-dependent increase (P = 0.02) in cycle length. Ovulatory levels of estradiol (E2) were significantly reduced (P = 0.02) in the highest treatment group. During ovulation induction, the area under the E2 concentration curve (AUC) was significantly (P = 0.03) suppressed in the highest treatment group. Our data demonstrate that HCB treatment, under the conditions of the present study, alters both ovarian function and menstrual cycle characteristics with a no observable adverse effect level of 1.0 mg/kg.

Animals↗

Sperm chromatin structure is altered in cynomolgus monkeys with environmentally relevant blood lead levels.

Exposure to lead has been associated with a variety of adverse reproductive outcomes such as spontaneous abortion, impaired fecundity, and sterility. Although decreased sperm counts and serum testosterone levels have been found in men with occupational lead exposure, animal experiments suggest that fertility may be impaired at blood lead levels that have no apparent effect on reproductive hormone levels or sperm concentration. Consequently, this study investigated the effect of chronic lead treatment on semen quality in healthy cynomolgus monkeys aged 15-20 years with mean (+/-SD) blood lead levels of 10 +/- 3 micrograms/dL (range 6-20 micrograms/dL, n = 4) and 56 +/- 49 micrograms/dL (range 22-148 micrograms/dL, n = 7) compared to a reference group with blood lead levels < 1.0 microgram/dL (n = 8). Blood and semen samples were collected once from each monkey in five different months. Serum testosterone levels were determined by radioimmunoassay, and lead effects on chromatin structure were analyzed by flow cytometry. There were no effects of treatment on circulating levels of testosterone or parameters of semen quality such as sperm count, viability, motility, and morphology. However, significant (p < 0.03) treatment-related effects were seen on SD alpha t values in the treated vs control animals. Group comparisons also revealed that the effects of chronic lead exposure were significant (p < 0.05) for both lead-exposed groups compared to the reference group. We conclude that chronic lead exposure alters sperm chromatin structure at blood lead levels relevant to the human population and in the absence of effects on endocrine function and traditional measures of semen quality.

Animals↗

Evaluation in practice.

If the benefits of professional nursing are to be effectively articulated, the process of evaluation in practice must be fully exploited. Nurses in the Mid-Staffordshire General Hospitals have developed methods to help them evaluate their practice. In this article the principles underpinning these developments are described.

Humans↗