Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aminoglutethimide blocks several cytochrome P-450 mediated steroid hydroxylation steps, including those required for conversion of cholesterol to pregnenolone and for the aromatization of androgens to estrogens. Through these actions it blocks adrenal steroidogenesis and the production of estrogens in extraglandular tissues. Aminoglutethimide is indicated for treatment of certain patients with Cushing's syndrome and breast cancer. Other potential uses (prostate carcinoma, low renin hypertension, etc.) remain investigational. For treatment of Cushing's syndrome, aminoglutethimide is usually given alone or in combination with metyrapone. In women with breast carcinoma, replacement hydrocortisone must be administered with aminoglutethimide to prevent reflex ACTH hypersecretion from overcoming adrenal inhibition. Administration of aminoglutethimide to patients with Cushing's syndrome results in improvement in clinical status in 56% of cases. Results are most favorable in patients with adrenal tumors and patients with ectopic ACTH production. Aminoglutethimide and replacement glucocorticoid produce objective disease regression in 32% of unselected postmenopausal patients with metastatic breast carcinoma and in 52% of women whose tumors are estrogen receptor positive. Responses are similar in duration and frequency to those produced by surgical adrenalectomy and hypophysectomy and the antiestrogen, tamoxifen.
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PMID:Aminoglutethimide: review of pharmacology and clinical use. 676 87

Indications and complications of estrogen replacement therapy are discussed in this edited transcription of a conference held at the UCLA School of Medicine. Although many of the symptoms of loss of ovarian function can be corrected by estrogen replacement therapy, several potentially harmful side effects are associated with the administration of estrogen. Hot flashes, the most common menopausal symptom for which women seek treatment, may continue over extended periods of time and the loss of ovarian feedback signals. Several types of evidence indicate that hot flashes are centrally rather than peripherally mediated disturbances, and it now appears that the hypothalamic factors which stimulate pulsatile release of luteinizing hormone play an integral role in initiation of hot flashes. The fact that the extent of estrogen deficiency differs among postmenopausal women may explain why all women do not have hot flashes. The effects of body size on estrogen production and plasma protein binding appear to be significant variables modulating the extent of estrogen deficiency and hypothalamic function. Other studies suggest that calcitonin and gonadal steroids are linked in the pathogenesis and treatment of osteoporosis, but the mechanism of action of estrogen replacement therapy in the treatment of osteoporosis has not been elucidated. Most investigations have failed to show the presence of estrogen receptors in bone. It is likely that the term osteoporosis includes heterogeneous skeletal disorders and that both sex hormones and calcemic hormones are important in pathogenesis. Further research is required on the possible effect of estrogen replacement therapy in decreasing relative risk of arteriosclerotic heart disease. Vaginal atrophy is an accepted indication for estrogen replacement, but its use for skin indications should not be recommended until a beneficial cosmetic effect is shown. Complications of estrogen replacement include endometrial cancer, breast cancer, hypertension, hyperlipidemia, and gallbladder disease, the latter 3 apparently resulting from hepatic action of estrogen replacement therapy. Because of the enhanced hepatic action of orally administered estrogen, other routes of administration are being explored. Additional research is needed to define the risk-benefit ratio of estrogen replacement therapy.
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PMID:Estrogen replacement therapy: indications and complications. 682 55

In order to study the prognosis of Graves' disease, 236 patients, who had been diagnosed as having had Graves' disease more than 10 years before, were examined. Although one patient had died of leukemia and 2 patients had been operated on for breast cancer after 131I therapy, and another 6 patients had died between the ages of 20 and 50, the patients were doing quite well. Generally, the prognosis of Graves' disease is not considered to be serious if the thyroid function is controlled. Among the 72 patients who had been treated with 131I therapy, 15 patients (21%) showed low serum levels of both T3 and T4 and were considered to be suffering from late-onset hypothyroidism. About 67% of the 131I-treated patients were considered to be almost euthyroid, but serum TSH levels were high in half of them, suggesting latent hypothyroidism. The incidence of hypertension seemed to be significantly higher in the TSH-elevated euthyroid group compared with the TSH-nonelevated patients. An excessive reaction of the hypothalamus and/or pituitary gland might have an unfavorable effect not only on the apparent hypothyroidism, but also on the latent hypothyroidism after the therapy for Graves' disease.
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PMID:[Primary hypothyroidism as a possible cause of hypertension from long-term follow-up studies of patients with Graves' disease (author's transl)]. 689 8

In attempting to evaluate the usefulness of the screening physical examination, it is necessary to remember that these recommendations are for asymptomatic individuals. When specific symptoms are present they need to be evaluated using physical examination and laboratory techniques that are appropriate to diagnosis. Although some of the same examination techniques are applicable for diagnostic evaluation, the goals, techniques, and interpretation of results are frequently different. One must also be aware of the past history of the patient, which may suggest specific risk factors even in the absence of current symptoms. A past history of breast cancer, for instance, might increase the intensity and scope of the physical examination. A history of alcohol consumption might turn an optimal mouth and throat examination into a diligent search. Additional elements of the physical examination may be pertinent to special high-risk groups. For instance, a mental status examination might be part of the routine examination for the elderly. Finally, it is important to remember that the findings on routine physical examination may themselves alter what should be done during the rest of the examination. For example, the finding of high blood pressure requires a search for arterial narrowing, coarctation, and renal bruits. Positive findings on a screening physical examination must always be supplemented by physical examination techniques designed for specific diagnosis. The recommended elements for a screening physical examination are an attempt to assemble reasonable conclusions based on current clinical use. They do not deal with the question of how frequently routine screening should be done. These recommendations need to be adjusted to the needs and views of each individual physician. One cannot help but be impressed by the medical, social, economic, and technical advantages of the physical examination. Although not a perfect technology, it serves important clinical functions in diagnosis and screening for the 1980s. The physical examination, like the human memory, will not be displaced easily even in this era of the C.A.T. scan, the radioimmunoassay, or the nuclear angiogram.
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PMID:The dogged physical examination in the era of the C.A.T. 690 86

Ellipticine and some derivatives are highly cytotoxic substances which kill L1210 cells at concentrations ranging form 10(-8) to 10(-6)M. Some compounds in this series bind with high affinity to DNA (affinity constant between 10(7) M-1 and 10(5) M-1) by intercalation between base pairs. The antitumoral properties of these derivatives are thought to be related to their DNA-binding ability. Both 9-hydroxylation of ellipticine and quaternarization of 2-pyridinic nitrogen tend to increase DNA binding and antitumor activity. 2-Methyl-9-hydroxyellipticine (NSC 264-137) was selected for a phase I and later for a phase II trial in human cancer. This drug does not affect blood cell counts in animals or in man. It is not mutagenic in the Ames' test nor teratogenic in mice, but is endowed with anti-inflammatory properties and induces a marked decrease of motoricity in mice. Transient bradycardia and decrease of blood pressure are the most noticeable cardiovascular effects in dogs. This compound administered at 80-100 mg/m2/week in 1-h intravenous (IV) infusion induces objective remissions in about 25% of patients suffering from advanced breast cancer refractory to all other treatment. These remissions, which occurred after 3-4 weeks, lasted for 1-18 months. This drug seems particularly to improve the condition of patients suffering from oesteolytic breast cancer metastasis. Activity against anaplastic thyroid carcinoma and ovarian carcinoma has also been observed in some cases. Toxic side effects are nausea and vomiting (one-third of the patients), hypertension (less than 10% of the patients), muscular cramp (one-third of the patients), fatigue which can be very pronounced (in most patients after 3 months of treatment), mouth dryness, and mycosis of the tongue and esophagus (less than 20% of the patients).
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PMID:Antitumor activity, pharmacology, and toxicity of ellipticines, ellipticinium, and 9-hydroxy derivatives: preliminary clinical trials of 2-methyl-9-hydroxy ellipticinium (NSC 264-137). 700 58

The use of estrogen replacement therapy in postmenopausal women is under close scrutiny. The indications and side effects of replacement therapy are reviewed, and recommendations regarding its use are made. Hot flashes, atrophy of the vaginal epithelium, and prevention of osteoporosis have been established as indications for estrogen replacement therapy. Prevention of cardiovascular disease, aging changes of skin, and the occurrence of mental illness have also been suggested as indications, but beneficial effects of estrogen replacement therapy for these problems have not been clearly established. Studies have shown that side effects of estrogen replacement therapy include endometrial cancer, hypertension, gallbladder disease, and angina pectoris. Breast cancer may also be a risk factor, but a consensus of opinion has not been established. Pulmonary embolism, cerebral vascular accident, or myocardial infarction has not been associated with estrogen replacement therapy. The use of progesterone with estrogen replacement therapy has been shown to reduce the occurrence rate of endometrial carcinoma, but it does not prevent all the actions of estrogen. Oral administration of estrogen is the preferred route despite misgivings about portal absorption and liver metabolism. Further studies must examine this question. Various agents have been shown to be effective in treating some climacteric symptoms. These include progesterone for hot flashes and calcium for the prevention of osteoporosis. Other agents may also be effective but have not been tested critically.
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PMID:Estrogen replacement therapy. 702 79

Recent reports on the efficacy of pharmacological management in reducing mortality associated with mild hypertension have enhanced the importance of increasing our knowledge about drug toxicity. The Hypertension Detection and Follow-Up Program (HDFP) provides a convenient setting in which to examine the association reported between reserpine usage and breast cancer. In the intensively treated and followed group (Stepped Care [SC]), the relative breast cancer experience of those who did take reserpine and those who did not was examined. Of 2529 females in SC, 1036 received reserpine, with an average exposure of 1.97 years during 5 years of follow-up. Through extensive investigation, 21 cases of breast cancer were identified. using a life table regression method of analysis to adjust for actual time of reserpine exposure, race, sex, and medication status at entry, and comparing those who took reserpine with those who did not, the author's calculated a risk ratio of 1.28, with a confidence interval of 0.58 to 2.80. Adjustment for a number of other variables known to have relationships to breast cancer did not appreciably change the results. Thus, with certain precautions, the authors conclude that in this setting there is no indication of the recently postulated association of reserpine and the short-term enhancement of breast tumor growth.
Hypertension
PMID:Reserpine and breast cancer in the Hypertension Detection and Follow-Up Program. 704 Feb 29

With respect to steady increasing incidence of malignant tumors in Czechoslovakia the oncological program was established with the aim to achieve a gradual dispensarization of all population. The main part of the program is the secondary prevention through oncological examinations to find out early stages of tumors or precancerous lesions. The experimental examinations started in four districts and during two years 111,783 inhabitants from selected groups passed the screening. The examinations were also aimed on hypertension and diabetes. The first results revealed 0.2% new malignancies and 24% preneoplastic lesions. As far as hypertension and diabetes concerns there were 6,204 new cases of hypertension and 2,616 of diabetes. The examinations were supported by centers of clinical oncology created 3 years ago in all district and county hospitals. The task of the centers is not only the early diagnosis of all malignancies but also the application of a suitable therapy. For early diagnosis of some tumors there were established special committees which closely cooperate with the center. These are specially the committees for breast cancer and in some hospitals committees for malignant melanoma. The examinations will be gradually extended to other countries in CSR and in spite of many problems which remain to be solved we hope that all these arrangements will help in the fight against malignant tumors.
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PMID:Mass screening in cancer: efficacy, problems, principles. 722 5

An investigation was made of daytime plasma prolactin levels in three groups of women aged 50 to 64 years: (1) 139 women with a family history of breast cancer; (2) 50 women on Rauwolfia treatment for hypertension, and (3) 90 women of a control group. A significant difference in prolactin levels was found between groups 2 and 3 but not between 1 and 3. These findings are considered in relation to the results of a breast cancer screening programme in which the women took part. Here, it was the women with a family history of breast cancer who showed an increased breast cancer risk, whereas the risk in women on Rauwolfia was not significantly higher than expected on the basis of the experience among controls. It is concluded that the role of prolactin in the etiology of breast cancer is still not clear.
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PMID:Plasma prolactin levels in women at postmenopausal age with a family history of breast cancer or a prescription for antihypertensive Rauwolfia treatment. 735 May 53

To supplement several case-control studies questioning whether use of reserpine is associated with occurrence of breast cancer, we conducted a longitudinal study of nearly 2,000 hypertensive women residing in Rochester, Minn. Exposure to antihypertensive agents and subsequent incidence of breast cancer were ascertained. Expected numbers of cases, derived from local population data and from the Connecticut Tumor Registry, were compared with the numbers of cases observed in exposure groups of interest. No evidence was found of any association of reserpine use, thiazide use, or untreated hypertension with subsequent occurrence of breast cancer in these hypertensive women. In addition, several issues were investigated that warrant consideration in evaluating reports published to date, especially before conclusions are drawn as to the questionable contention that reserpine has caused breast cancer in women.
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PMID:Reserpine and breast cancer. A community-based longitudinal study of 2,000 hypertensive women. 737 97


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