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Biomedical subjects

R A Wiseman

Publications and source records attributed to R A Wiseman.

At least 19 recordsLinked to original sources
PubMed2002

Combined oral estradiol valerate-norethisterone treatment over 3 years in postmenopausal women: effect on lipids, coagulation factors, haematology and biochemistry.

OBJECTIVE: To determine the effect of continuous estradiol valerate 2 mg and norethisterone 0.7 mg daily as hormone replacement on lipid profiles, coagulation factors, haematology and biochemistry over 3 years. METHODS: An open label trial with 107-133 postmenopausal women assessed pre-treatment and at annual visits with extensive lipid and coagulation profiles, and observation of circulatory adverse events. Standard haematology and biochemical profiles were also analysed. Results were compared at point of entry and at 36 months. RESULTS: Total cholesterol (TC) and HDL and LDL fractions fell significantly (P=0.0001) and there was a significant decline in favourable ratios as well as a rise in VLDL mass (P=0.0001). Lipoprotein (a) (Lp(a)) decreased significantly (P=0.0053). Fibrinogen, free protein, prothrombin time and thrombin increased (P=0.0001) while platelets and KPTT were unchanged. Protein C, antithrombin III and total protein S decreased (P=0.0001) and there was a rise in the frequency of lupus anticoagulant positivity. Significant but small changes were seen in haematology and biochemical parameters although this did not raise safety issues and their clinical significance was uncertain. CONCLUSION: The direction of lipid and coagulation factors move in competing ways, emphasising the complexity of metabolic change and making interpretation of outcome for venous and arterial thrombosis or atherosclerosis difficult to predict. Eight patients developed thromboembolic or ischaemic events over the 3 year period of this study but these patients had lipid changes normally considered beneficial to cardiovascular disease and coagulation changes not thought to be associated with thromboembolism. Decrease in lipoprotein 'a' levels might be an indicator of long-term decreases in atherosclerotic events.

Adult↗
PubMed2000

Types of intra-muscular opioids for maternal pain relief in labour.

BACKGROUND: Pethidine is the most widely used intra-muscular opioid for the relief of labour pain. However concerns have been raised about its effectiveness and the possibility of depressing respiration in newborns. OBJECTIVES: The objective of this review was to assess the effects of different opioids (and different doses of the same opioid) administered intra-muscularly in labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register (Cochrane Library, issue 4, 1997) and reference lists of articles. SELECTION CRITERIA: Randomised trials comparing the effects of different currently used opioids (and different doses of the same opioid) administered intramuscularly in labour for women who request systemic analgesia. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality and extracted data. Analysis was based on the groups as randomly allocated. MAIN RESULTS: Sixteen trials were included. There were problems with methodological quality of some of the trials, and lack of consistency in the way various outcomes were reported. There was no evidence of a difference between pethidine and tramadol in terms of pain relief, interval to delivery, or instrumental or operative delivery. There appeared to be more adverse effects such as nausea and vomiting and drowsiness with pethidine. Maternal pain relief seemed almost identical between the meptazinol and pethidine groups, whether assessed as maternal satisfaction with pain relief, visual analogue scales, or use of other pain relief, but meptazinol gave rise to slightly more side effects. Maternal satisfaction with pain relief appeared similar for pentazocine and pethidine, with more frequent nausea and vomiting with pethidine. REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate the comparative efficacy and safety of the various opioids used for analgesia in labour.

Analgesia, Obstetrical↗
PubMed2000

Combined oral oestradiol valerate-norethisterone treatment over three years in postmenopausal women: correlation between oestrogen levels and bone mineral density sites.

OBJECTIVE: To compare trabecular and compact bone response and relationship to oestrogen status using continuous oestradiol valerate 2 mg and norethisterone 0.7 mg daily as hormone replacement and to determine the therapeutic range of 17 beta-oestradiol. DESIGN: Open label trial. SETTING: Independent endocrine clinic SAMPLE: One hundred and thirty-one patients were compared at point of entry and at 36 months. METHODS: Postmenopausal women were assessed using a Lunar dual photon and single photon bone scanner, and bone mineral density of the lumbar spine, right hip and left forearm were annually correlated with 17 beta-oestradiol and oestrone levels over three years. Total alkaline phosphatase was compared between improvers and decliners of bone mineral density. RESULTS: Significant improvement in bone mineral density (P < 0.0001) occurred at all sites except the left forearm, where bone loss was prevented. There was no correlation between oestrogen levels and bone mineral density improvements at hip sites. However, in the lumbar spine larger improvements in bone mineral density occurred in women with 17 beta-oestradiol levels > 185 pmol/L compared with those below, which were statistically significant for those with 17 beta-oestradiol levels > 248 pmol/L. Bone turnover, as quanitifed by total alkaline phosphatase measurements, was suppressed in most patients, but there were no differences in the mean alkaline phosphatase levels between the best improvers and worst decliners for lumbar spine bone mineral density. Improvers had an age mean of 5.21 years greater than decliners (P = 0.01) and a mean duration difference since the menopause of 5 1 years compared with decliners (P = 0.007). CONCLUSION: This combined continuous preparation of hormone replacement therapy improves not only trabecular bone but prevents compact bone loss, and the data suggest that the therapeutic range of 17 beta-oestradiol is between 200 pmol/L and 350 pmol/L.

Administration, Oral↗
PubMed2000

Breast cancer hypothesis: a single cause for the majority of cases.

STUDY OBJECTIVE: The main cause of breast cancer remains unknown. Numerous causal factors or predisposing conditions have been proposed, but account for only a small percentage of the total disease. The current search for multiple causes is unavailing. This report explores whether any single aetiological agent may be responsible for the majority of cases, and attempts to define its properties. METHODS: Examination of all relevant epidemiological and biological evidence. MAIN RESULTS: Genetic inheritance is not the main cause of breast cancer because most cases are sporadic, there is a low prevalence of family history, and genetically similar women have differing rates after migration. Environmental exposure, such as pollution by industrialisation, is not a major cause, as deduced from a spectrum of epidemiological data. The possibility of infection as cause is not persuasive as there is no direct biological evidence and no epidemiological support. Oestrogen status is closely related to breast cancer risk, but there are numerous inconsistencies and paradoxes. It is suggested that oestrogens are not the proximate agent but are promoters acting in concert with the causal agent. Dietary factors, and especially fat, are associated with the aetiology of breast cancer as shown by intervention and ecological correlation studies, but the evidence from case-control and cohort studies is inconsistent and contradictory. CONCLUSIONS: The hypothesis that best fits the epidemiological data is that dietary fat is not itself the causal agent, but produces depletion of an essential factor that is normally protective against the development of breast cancer. Many of the observed inconsistencies in the epidemiology are explainable if deficiency of this agent is permissive for breast cancer to develop. Some properties of the putative agent are outlined, and research investigations proposed.

Adult↗
PubMed1998

Combined oral estradiol valerate-norethisterone treatment over three years in postmenopausal women. 1. Clinical aspects and endometrial histology.

The aim of this study was to determine the medium-term safety and efficacy of once-daily, oral estradiol valerate 2 mg with norethisterone 0.7 mg on menopausal symptoms, bleeding incidence, endometrial pathology, adverse events and other clinical parameters. A three-year, single-center, open study was performed. Women with menopausal symptoms and > or = 6 months since the last spontaneous menstrual period were recruited. Patients were assessed using questionnaires and daily records of bleeding incidence and severity. Adverse events were recorded at each visit and endometrial histopathology was determined at baseline and annually. There were 206 patients at entry and 133 completers at the end of year 3. Menopausal symptoms showed significant improvements within 4 months (p < 0.0001 compared with baseline). By the end of month 4, 79.9% of patients had stopped bleeding. The mean number of days bleeding per month declined from 2.8 (month 1) to 1.1 (month 12). Significantly less bleeding was observed in patients who were > or = 2 years postmenopausal. No abnormalities in endometrial histology were found. Bleeding and breast tenderness were the commonest adverse events. Twenty-four patients experienced serious adverse events although no definite relationship to drug therapy was considered likely. We therefore conclude that the oral combination of estradiol valerate 2 mg and norethisterone 0.7 mg given daily and continuously leads to amenorrhea and symptom alleviation in the majority of patients and is well tolerated.

Adult↗
PubMed1984

Cardiovascular birth defects and antenatal exposure to female sex hormones: a reevaluation of some base data.

A re-evaluation of the base data as reported by Heinonen et al. from the Drug Epidemiology Unit of the Boston Collaborative Perinatal Project (CPP) was undertaken in order to examine particularly three matters which were not fully considered in the publication. These were, first, the timing of administration of sex hormones during the index pregnancy, which is relevant to determining whether any statistical association reported between sex hormone exposure and malformations could be causal; second, the incidence of serious maternal vaginal bleeding in early pregnancy, which could be an indication of threatened abortion, which in turn is associated with an increased malformation rate, and in addition is an indication for sex hormone administration; and third, the incidence of malformations or other adverse outcome in previous pregnancies, which, if present, might play a material role in the risk of malformation in the index pregnancy. Examination of the records of the 19 cases described by Heinonen et al. as hormone-exposed/cardiac-malformed revealed that no preparation containing hormone was administered in two patients, that five cases were given hormones too late in the index pregnancy to have any effect on cardiac organogenesis (which by general consensus begins on day 19 and ends at the latest on day 50 of gestation), that two cases were given hormones too early and two cases had Down's Syndrome. Thus eight children were exposed to hormones during the critical period of cardiac organogenesis, out of 17 actual hormone takers (47%). The description of vaginal bleeding did not allow any conclusions regarding differential rates of threatened abortion. It was found that the incidence of major malformations was 17% in the index group and 4% in the non-malformed group. This suggests that the hormone-exposed patients who gave rise to children with cardiac malformations were a highly selected group. The re-evaluation therefore reveals that the incidence of exposure to sex hormones during the critical period of cardiac organogenesis was not significantly different statistically in those women whose children had cardiac lesions as compared to those without such lesions. It is suggested that the result of this re-evaluation should direct the attention of epidemiologists to the quality of their base data. Re-examination of the base data of the Boston CPP does not support their reported association between the exposure to female sex hormones during pregnancy and the occurrence of cardiac malformations.

Abnormalities, Drug-Induced↗
PubMed1984

Absence of correlation between oral contraceptive usage and cardiovascular mortality.

Oral contraceptive (OC) usage and cardiovascular mortality rates for all women (and men) of reproductive age, but specifically for those aged 35-44 years, were examined in the United Kingdom. These data show: OC-usage increased from 14.1 million packs in 1968, to 45.1 million in 1976, decreasing to 37.1 million in 1980. Ischaemic heart disease (IHD) mortality rates for the years 1968-1980 for women of reproductive age of 15-34 years were stable: for those aged 35-44 years the rates fell gradually by 19%. Mortality rates for all types of cerebrovascular disease (CVD) for 1969-1978 remained stable for women of 15-34 years, but for women of 35-44 years rates for subarachnoid haemorrhage and cerebral haemorrhage (the two largest groups) declined by 11% and 34% respectively. The absence of a positive correlation between OC usage and cardiovascular mortality rates is difficult to explain if OCs are the cause of fatalities, as claimed by some epidemiological studies. Possible counteracting variables--such as decreased ascertainment or decreased usage by women of 35-44 years, or decreased relative risk over the time period--which might account for this paradoxical result, were examined but discarded as being unlikely. Evidence from other data--e.g. the similarity of male and female mortality rates for each group, the increased mortality rates for women of 45-54 years (who do not take OCs), and the similarity of mortality rates in women in years when OC-usage was widely different--all suggest that a counteracting variable does not exist. The data on cardiovascular mortality rates in the UK, showing an absence of positive correlation with OC-usage, are thus opposed to the conclusions of epidemiological studies claiming an increased risk of cardiovascular mortality due to OCs, and specifically contradict the claim that such increased risk is found in 35-44 year-old OC-users.

Adolescent↗
PubMed1981

Oral contraceptives and the decline in mortality from circulatory disease.

Many publications have claimed that oral contraceptives (OCs) are associated with an increased risk of circulatory disease, yet between the years 1962 and 1976, when OCs became widely used in the United Kingdom, death rates from circulatory disease in women of reproductive age fell steadily. This decreased mortality was greater in young women than in men of comparable age, and did not occur in older women. These data tend strongly to refute the belief that OCs are causative of circulatory disease. The possibility that the decreased mortality rate is due to a protective effect of OCs was examined. It was concluded that they could not be completely responsible, although a partial effect could not be ruled out with certainty. It is suggested that, when mortality trends are opposed to the results of case-control or cohort studies, serious doubts are cast on the conclusions about causal relationships.

Adolescent↗
PubMed1978

A study of the comparative efficacy of diflucortolone valerate 0.3% ointment and clobetasol propionate 0.05% ointment.

Three hundred and fifty-four patients with symmetrical dermatoses took part in a multicentre, doubleblind, half-side study in order to compare the efficacy of a new topical steroid, diflucortolone valerate 0.3% (Nerisone Forte) against that of an established, potent topical steroid, clobetasol propionate 0.05% (Dermovate). The assessment of overall response, as judged by the physicians' preference for one side or another, showed no difference between the two compounds. However, when the results were examined by separate diagnostic category, the number of preferences was greater for diflucortolone valerate 0.3% in eczema, and for clobetasol propionate 0.05% in psoriasis, although neither of these differences reached levels of statistical significance. The graded assessments of response indicated that both compounds were highly effective, potent, topical steroids. Eighty-one percent of all patients showed marked improvement or healing with diflucortolone valerate 0.3%, and 84% showed marked improvement or healing with clobetasol propionate 0.05%. This difference was not statistically significant. Analysis of response, either by diagnosis or grade of severity, showed no statistically significant differences between the two compounds. No significant differences in the incidence of severity of side-effects were observed. It was concluded that the two compounds were of equal clinical efficacy.

Adrenal Cortex Hormones↗
PubMed1978

Plasma cortisol values after topical application of diflucortolone valerate (0.3%) or clobetasol propionate (0.05%) in psoriatic patients.

A double-blind randomized study to compare the plasma cortisol values at both 9.00 a.m. and 12 midnight following topical application fo 10 g daily for 7 days of either diflucortolone valerate 0.3% (Nerisone Forte) ointment or clobetasol propionate 0.05% (Dermovate) ointment in 20 hospital inpatients suffering from severe psoriasis, showed that clinically both compounds behaved as potent, highly active topical preparations and caused rapid clinical improvement. Diflucortolone valerate 0.3% caused only slight and non-significant depression of mean plasma cortisols. On the other hand, clobetasol caused an immediate, persistent and statistically significant depression of the 9.00 a.m. coritsol values, which appeared to recover towards normality only on the third day after therapy had been withdrawn. the difference between these 2 compounds was found to be statistically significant (P less than 0.05). From these observations, it is concluded that diflucortolone valerate 0.3% ointment suppresses adreno-cortical function to a significantly lesser extent than clobetasol propionate 0.05% ointment.

Adrenal Cortex Hormones↗