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Biomedical subjects

M Whitehead

Publications and source records attributed to M Whitehead.

At least 73 records · Page 4Linked to original sources
PubMed1995

Cloning and characterization of a novel polygalacturonase-encoding gene from Aspergillus parasiticus.

Pectinases produced by Aspergillus flavus and A. parasiticus are believed to play a significant role in the ability of these fungi to spread in cotton bolls and other crops. Utilizing a DNA probe, generated by PCR, of the Aspergillus niger pgaII gene, we have isolated a novel, constitutively expressed polygalacturonase (PG)-encoding gene (pecA) from an A. parasiticus cDNA library. DNA sequence analysis and the deduced amino acid (aa) sequence of pecA demonstrated significant identity at the nucleotide and aa levels with other PG of fungal origin. Northern blot analysis of RNA isolated from A. parasiticus grown on either glucose or pectin as the sole carbon source showed that pecA was expressed during growth in both media.

Amino Acid Sequence↗
PubMed1995

Menopause: refining benefits and risks of hormone replacement therapy.

In terms of our understanding of menopause and hormone replacement therapy, 1993-1994 did not see any seminal or definitive publications. However, the data that were published have helped refine our understanding of the benefits and risks of hormone replacement therapy. This article presents further evidence for the protective effects of hormone replacement therapy in preventing osteoporosis and arterial disease, including direct gonadal hormone effects upon the vessel wall; discusses changes in attitudes to progestogen additions, withdrawal bleeding and endometrial status; reviews controversies over the relationship between hormone replacement therapy and breast cancer risk, and briefly mentions a new device for delivery of non-oral oestradiol.

Breast Neoplasms↗
PubMed1995

Hormonal manipulation and gynaecological cancer: the tamoxifen dilemma.

Tamoxifen has a well established place in the adjuvant therapy of primary carcinoma of the breast. Its effects on breast cancer cells are both anti-oestrogenic and non-oestrogen-receptor mediated. Tamoxifen has oestrogenic effects on non-breast tissues such as liver, bone, the cardiovascular system and the urogenital tract. The effect on the endometrium is to increase the incidence of polyps, hyperplasia and carcinoma. Again, non-oestrogen receptor-mediated actions may be involved. With more widespread use of tamoxifen now being advocated, for instance in the primary prevention of breast cancer, careful assessment of benefit and risk is required.

Breast Neoplasms↗
PubMed1995

Mortality in regions and local authority districts in the 1990s: exploring the relationship with deprivation.

Regional and local authority patterns of mortality in England and Wales for both males and females are presented for the latest available years (1989-93). The familiar geographic pattern of higher mortality in the north and west and lower mortality to the south and east of the country has continued into the 1990s and there has been no significant widening or narrowing in the mortality gap between the worst and the best regions during the 1980s. The local authorities with higher mortality are still predominantly in urban areas. Using a modified form of the Department of Environment's 1991 deprivation index, mortality in more than 350 English local authorities in 1989-93 was analysed to study the interaction between socio-economic and geographic variables. There is a very strong relationship between mortality and deprivation at the local authority level measured by this new index, with a tendency for higher mortality to be associated with greater deprivation. This relationship is most marked for males, but is still strong for females.

Adolescent↗
PubMed1994

Who cares about equity in the NHS?

The concept of equity in relation to the National Health Service in Britain encompasses not one but at least eight distinct principles. Until the 1980s the NHS had a good record of incorporating these principles into practice. Throughout the 1980s, however, there has been a pronounced change, with the gradual introduction of business values into the service, culminating in the market based reforms of the 1990s. Several recent policies seem to be taking the NHS away from the goal of an equitable system--for example, the new arrangements for community care and the incentives within contracting to select patients on financial grounds. To restore equity as a value demands priority for ethical values, monitoring of policies for their effects on equity, some national planning, and a new debate about the entitlement to services such as continuing care.

Cost Sharing↗
PubMed1994

Hormonal regulation of HSP27 expression in human endometrial epithelial and stromal cells.

HSP27 has been analysed immunohistochemically in epithelium and stroma of premenopausal endometria obtained at different stages of the menstrual cycle and in endometria from postmenopausal women receiving oestrogens either alone or in combination with a progestin. The data indicate that HSP27 is increased by oestrogen and inhibited by progestins in glandular epithelium but not stroma. Oestrogen does not increase HSP27 in stromal cells and HSP27 is only present in stromal decidual cells seen in the late secretory phase where it continues to be detectable until the tenth week of gestation. Hormonal regulation of HSP27 is clearly different in endometrial epithelium and stroma and additional regulatory factors may be important as oestrogen alone does not increase postmenopausal epithelial HSP27 to the levels seen in the proliferative phase of premenopausal samples.

Antibodies, Monoclonal↗
PubMed1994

Cochlear endoscopy with preservation of hearing in guinea pigs.

Advances in fiberoptic technology have revolutionized the way many disorders are treated by otolaryngologists. We have previously described our experiences with cochlear endoscopy during cochlear implantation. However, endoscopy of the functioning cochlea has not previously been reported. To test the hypothesis that endoscopy of the guinea pig cochlea is possible without catastrophic loss of auditory function, we subjected 20 ears of 10 Hartley-strain albino guinea pigs to limited endoscopy of the cochlea through the round window with evaluation of distortion product otoacoustic emissions and auditory brain stem responses. Insertion of the endoscope caused measurable changes in auditory brain stem response latency and amplitude. Distortion product otoacoustic emission amplitudes were reduced an average of 6 dB with greater loss close to the round window. Frequencies above 18 kHz, corresponding to the region of endoscopy, were not evaluated in this preliminary study and are suspected to have sustained more damage. Results demonstrate that endoscopy of the guinea pig cochlea is possible without major loss of the above physiologic measures in the regions tested. If endoscopy of the cochlea is to become a tool with clinical and basic science applications, refinements in techniques to avoid damage are necessary.

Animals↗
PubMed1994

Progestins and androgens.

OBJECTIVE: To consider whether the addition of a progestin or an androgen to estrogen replacement therapy (ERT) will modify the effects of the estrogen upon arterial disease risk. DESIGN: Review of selected literature. SETTING: Population studies, clinical trials, and laboratory investigations. PATIENTS: Postmenopausal women. INTERVENTIONS: Exogenous progestin or androgen in hormone replacement regimens. MAIN OUTCOME MEASURES: Lipids and lipoproteins, carbohydrate metabolism, prostaglandin and thromboxane metabolism, fibrinolysis and coagulation, fat distribution, and arterial tone. RESULTS: The favorable lipid and lipoprotein changes induced by estrogens are modified by progestin and androgen addition. Some of these modifications are potentially adverse (progestin lowering of high-density lipoprotein-2 cholesterol) but some are potentially beneficial (progestin lowering of triglycerides). Recent studies suggest that progestins may not reverse the estrogen-induced reduction in low-density lipoprotein cholesterol. The scant data upon the effects of androgens on lipid and lipoproteins suggest that the addition of T to the estrogen may block the rise in high-density lipoprotein cholesterol seen in women receiving estrogen alone. Because of a lack of appropriate data, it is this author's opinion that the clinical effects of progestin or T addition to ERT cannot be predicted at this time. Further studies are urgently needed to clarify how progestin or T addition modify estrogen effects upon carbohydrate, prostaglandin and thromboxane metabolism, upon fibrinolysis and coagulation, and upon arterial tone.

Androgens↗
PubMed1993

Tackling inequalities in health: the Australian experience.

Federal and state governments in Australia have embarked on a series of national initiatives which show a firm commitment to tackling social inequalities in health. The development of national goals and targets for health, for example, covers social and environmental conditions and sets differential targets for specific social groups with very poor health status. In a complementary initiative, a wide ranging analysis of the health care system--the National Health Strategy--has as one of its main objectives to improve the equitable impact of the health system. Where problems of access to and quality of services have been exposed, policies have been devised to deal with them. The exceptionally poor health of the Aboriginal community has elicited cross party support for action. Resources have been allocated to implement the National Aboriginal Health Strategy: to improve living and working conditions, education, and employment opportunities. Britain can glean much from the Australian experience.

Australia↗
PubMed1993

Does low-dose, transdermal, norethisterone acetate reliably cause endometrial transformation in postmenopausal oestrogen-users?

In a prospective study, the symptomatic, psychological and endometrial effects of a combined oestradiol/progestogen transdermal therapeutic system which delivers a low daily dose of norethisterone acetate have been investigated in 18 postmenopausal women. Treatment was given in 28 day cycles. Patients received transdermal oestradiol 50 micrograms/day continuously and transdermal norethisterone acetate, 0.1-0.15 mg/day, was added for 14 days. Treatment was given for between 5 and 7 cycles. One patient discontinued therapy because of a skin reaction. Low dose, transdermal norethisterone acetate caused few adverse symptomatic or psychological side-effects and appeared well tolerated. Fourteen endometrial samples were obtained during the combined (norethisterone acetate/oestradiol) phase of the 5th, 6th or 7th treatment cycle. None showed hyperplastic or malignant change but proliferative endometrium, indicative of an inadequate progestational stimulus, was observed in 4 biopsy samples. Three of these patients had reported breakthrough bleeding during therapy. For these reasons, we regard this dose of transdermal norethisterone acetate as inadequate in combination with transdermal oestradiol 50 micrograms/day for routine use in postmenopausal oestrogen users.

Administration, Cutaneous↗
PubMed1992

Danazol induces resistance to both insulin and glucagon in young women.

1. Danazol elevates plasma insulin, plasma glucagon and serum low-density lipoprotein concentrations and reduces the serum high-density lipoprotein concentration. 2. Associations between these disturbances were studied in 17 women receiving danazol therapy for endometriosis. Eleven women underwent intravenous glucose tolerance tests with measurement of plasma glucose, insulin, C-peptide and glucagon concentrations and modelling analysis of intravenous glucose tolerance test concentration profiles. Six women underwent glucagon sensitivity tests. Serum concentrations of lipids and lipoproteins were measured in all cases. 3. Danazol reduced the fasting plasma glucose and insulin concentrations, but markedly raised the fasting plasma glucagon concentration. The insulin and C-peptide responses to the intravenous glucose tolerance test were increased twofold and the net decrement in glucagon concentration was increased tenfold. The glucose response to the intravenous glucose tolerance test was unaffected. Insulin sensitivity was reduced by 55%. Both first-phase plasma insulin responsiveness and net first-phase pancreatic insulin secretion were increased; insulin half-life was prolonged. The glucose response to the glucagon sensitivity test was reduced on treatment. The calculated low-density lipoprotein cholesterol level rose by 20%, whereas high-density lipoprotein cholesterol level fell by 47%. None of these changes in serum lipoprotein levels correlated with changes in insulin metabolism. In general, metabolic changes normalized after 3 months. 4. Danazol increases the sensitivity of pancreatic insulin and glucagon secretion to glucose. Danazol-induced insulin and glucagon resistance could be due to receptor down-regulation resulting from hypersecretion of insulin and glucagon.

Adult↗
PubMed1992

The concepts and principles of equity and health.

In 1984, the 32 member states of the World Health Organization European Region took a remarkable step forward in agreeing unanimously on 38 targets for a common health policy for the Region. Not only was equity the subject of the first of these targets, but it was also seen as a fundamental theme running right through the policy as a whole. However, equity can mean different things to different people. This article looks at the concepts and principles of equity as understood in the context of the World Health Organization's Health for All policy. After considering the possible causes of the differences in health observed in populations--some of them inevitable and some unnecessary and unfair--the author discusses equity in relation to health care, concentrating on issues of access to care, utilization, and quality. Lastly, seven principles for action are outlined, stemming from these concepts, to be borne in mind when designing or implementing policies, so that greater equity in health and health care can be promoted.

Europe↗
PubMed1991

Pulsatility index in internal carotid artery in relation to transdermal oestradiol and time since menopause.

The protection afforded by postmenopausal oestrogen replacement against cardiovascular disease is not fully explained by changes in plasma lipoproteins. To investigate the effect of oestrogen on arterial tone, Doppler ultrasound was used to assess blood flow characteristics in the internal carotid arteries of 12 postmenopausal women. Patients were studied pretreatment and at weeks 4, 6, 9, and 22 of therapy with transdermal oestradiol 50 micrograms/day. The pulsatility index (PI), which is thought to represent impedance to blood flow distal to the point of sampling, was measured from the flow velocity waveform. 11 of the 12 patients were within 5 years of menopause; 1 was 8 years postmenopausal but had experienced bleeding 4 years after menopause. In the 11 women there was a highly significant correlation (r = 0.77) between time since menopause and baseline PI. A similar correlation (r = 0.74) was observed when the episode of postmenopausal bleeding was redefined as time of menopause in the twelfth patient. For all 12 patients, there was a significant negative correlation (r = -0.70) between change in PI during transdermal oestradiol therapy and mean of baseline plus week 22 PI value. For all correlations between changes in PI and time since menopause, the longer the time the greater the fall in PI. These results, and previous observations of a reduction in uterine artery PI with oestradiol treatment, suggest that oestrogen has a generalised effect on the arterial system.

Administration, Cutaneous↗