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Biomedical subjects

G V Upton

Publications and source records attributed to G V Upton.

At least 19 recordsLinked to original sources

Lipids, cardiovascular disease, and oral contraceptives: a practical perspective.

Figure 9 is an attempt to summate the influences of life-style on lipid parameters. Based on the work of Nikkila, it shows the source of the production of HDL and LDL, the factors that can affect these lipoprotein levels, and where in the cascade of lipoprotein metabolism these factors exert influence. The source of HDL production is the liver and the intestine. At this stage, diet, exercise, hormones, genetics, drugs, and certain disease states can affect HDL levels. Lecithin-cholesterol acyl transferase (LCAT) esterifies HDL-free cholesterol in plasma, and HDL3 is formed that in turn is transformed to HDL2. At the same time, VLDL from the gut and the liver will be converted, under the influence of LPL, to HDL2 and LDL. Thus HDL2 is being formed by the breakdown of VLDL and from the transformation of HDL3 to HDL2. Insulin, exercise, alcohol, fats, drugs, and diet affect lipoprotein lipase and consequently influence levels of LDL and HDL2 indirectly. Progestogens increase and estrogens decrease hepatic endothelial lipase, thus affecting the HDL2 concentration. It is at this point that combination OCs influence HDL2. The balance between estrogen and progestogen in a given contraceptive determines the extent and direction of HDL2 concentration. A separate pathway in the liver also catabolizes HDL2 and HDL3. LDL is generated partly from catabolism of VLDL and is partly secreted from the liver. The removal of LDL is mediated by receptors in both the liver and peripheral tissues. It is here that the Brown-Goldstein theory plays a major role. If LDL receptors are present in an insufficient number or are defective, then the C will accumulate and atherosclerosis may follow. Thus two key enzymes, LCAT and LPL, control the production of HDL2 and LDL, whereas a third enzyme, hepatic endothelial lipase, catabolizes HDL2.

Cardiovascular Diseases

Contraception for the perimenopausal patient.

All the existing data show that combination estrogen/progestogen therapy is mandatory if any replacement therapy is to be given to the woman over age 40. Sufficient evidence has indicated that estrogen alone is inadequate; progestogen must be given to prevent endometrial hyperplasia, lower the risk of breast cancer, and prevent bone loss. In the premenopausal woman, such therapy should also provide contraception. Because of the lack of minimal dose products fulfilling such criteria, many physicians will allow women to continue with their contraceptive if they do not smoke and have no other contraindications. It will remain to be seen if a product close to ideal can be found to fulfill the contraceptive and therapeutic needs of women traversing the most physiologically hazardous period of their lives.

Adult

The contraceptive and hormonal requirements of the premenopausal woman: the years from forty to fifty.

There is a growing awareness that many women over 40 require both contraceptive protection and hormonal replacement for the symptoms of the climacteric. These women are still menstruating and the risk of pregnancy remains, overshadowed by the increased life-threatening risk due to childbirth in this age group. The risk of mortality due to the use of oral contraceptives is little increased for the nonsmoking woman in the over 40 years compared with the years under 40. In contrast, women over 40 who smoke are best advised not to use hormonal contraceptives. It is evident from all the existing data that combination therapy is strongly advised if any replacement therapy is to be given a woman. There is considerable evidence suggesting that estrogen alone may be insufficient therapy and progestogen should be added to prevent endometrial hyperplasia, decrease the risk of breast cancer and prevent bone loss. In the premenopausal woman, such therapy should also provide contraception. Many physicians allow women 35 to 45 who do not smoke to continue on an oral contraceptive if there is no contraindication. However, a minimum-dose product has yet to be found close to the ideal of fulfilling both the contraceptive and therapeutic needs of women traversing a physiologically very hazardous period.

Adult

Therapeutic considerations in the management of the climacteric. A critical analysis of prevalent treatments.

The natural aging process affects a woman greatly during the climacteric; hormonal patterns, metabolic parameters, reproductive target organs and bone are involved. In every instance one can compare these changes with the effects of hormone-replacement therapy (HRT) on these same parameters. Therapy should reverse the negative trends imposed by the aging process and preserve the status quo. The approach must be holistic, and consideration must be given to the effects of HRT on all the parameters and not just to the uterus as the sole end point. Ideally the smallest amount of hormone should be used that will effectively treat symptoms and favorably affect metabolic parameters, the reproductive target organs and bone. Since recent clinical evidence has emphasized the protective nature of estrogen-plus-progestagen therapy in the prevention of endometrial and breast cancer and of osteoporosis, combination therapy is an essential feature of treatment. The shortfalls in our knowledge of the ideal therapy are undeniable. However, it is crucial to provide hormonal support with the available therapy to the woman suffering from estrogen-deficiency symptoms, particularly in view of the high mortality rates associated with postmenopausal osteoporosis, a preventable disease.

Adult

The phasic approach to oral contraception: the triphasic concept and its clinical application.

The phasic approach to oral contraception is described with a historical review of the evolution of new administration regimens aimed at lowering total steroid content from monophasic to biphasic to the new triphasic approach. The phasic regimen designs which support the intended mechanism of action of each of the phasic approaches are discussed. Emphasis is placed on the discussion of the rationale for the new triphasic oral contraceptive and the clinical demonstration of the triphasic's inhibition of ovulation and maintenance of functional integrity of the pituitary-ovarian axis. A new theoretical formula and practical concept are presented that incorporate a progestogen potency factor, and consequently provide a common denominator enabling a comparison of the magnitude of the effects of various oral contraceptive products on pituitary responsiveness. Widespread clinical studies are described which reinforce the suggestion that the triphasic is the state of the art and represents an important contribution to contraceptive technology.

Contraceptives, Oral

Medullary thyroid carcinoma: ectopic production of peptides with ACTH-like, corticotrophin releasing factor-like and prolactin production-stimulating activities.

A 45-year-old women had medullary tyroid carcinoma associated with Cushing's syndrome and galactorrhoea. Elevated plasma immunoreactive ACTH and cortisol were partially suppressed by intravenous dexamethasone, appreciably raised by lysine vasopressin, and urinary excretion of 17-oxogenic steroids slightly elevated by metyrapone. A large arterio-venous increase in plasma corticotrophin releasing factor-like activity across the thyroid gland was observed and tumour tissue contained corticotrophin releasing factor-like activity. Biologically active ACTH was not detected in tumour extracts before incubation with trypsin, but after trypsinization a value of 3.2 mU per gram was obtained. Arterial plasma contained biologically active ACTH (1.5 mU/100 ml) prior to trypsinization. Venous effluent from the thyroid gland contained biologically active (9.6 mU/100 ml) and immunoreactive ACTH (970 pg/ml) before trypsinization. Tumour extracts also contained prolactin production-stimulating activity. These findings can explain the Cushing's syndrome and the galactorrhoea both of which disappeared completely after thyroidectomy.

Adrenocorticotropic Hormone