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Biomedical subjects

H M Perry

Publications and source records attributed to H M Perry.

At least 109 records · Page 6Linked to original sources
PubMed1983

Cardiac physiologic and tissue metabolic changes following chronic low-level cadmium and cadmium plus lead ingestion in the rat.

Female Long-Evans hooded rats received Schroeder's rye-based diet and 0 or 1 microgram/ml cadmium, or cadmium plus lead in mineral fortified drinking water from weaning to 18 months. The heavy metal-fed rats were normal with respect to control, including growth rates and final body weights. Rats receiving added cadmium and cadmium plus lead in the diet were characterized by a persistent hypertension which was evident after 2 months. Cardiac conduction system excitability was depressed preferentially in cadmium-(atrioventricular nodal region) and cadmium plus lead-(His-Purkinje system) fed rats. Although heart rates were comparable to control, myocardial contractile activity (peak active tension and dT/dt) was significantly decreased in intact perfused heart preparations from both heavy metal-treated groups. In conjunction with the observed physiologic changes, various tissue-specific metabolic alterations were detected in heart, kidney, and liver. Generally, prolonged heavy-metal ingestion at these levels resulted in impaired energy metabolism (e.g., decreased ATP, PCr; increased Pj, ADP concentrations) and altered essential mineral composition (e.g., calcium, magnesium, zinc, and to a lesser extent, sodium and potassium; copper levels were unaffected) that varied in severity according to the tissue. The addition of lead to the cadmium diet had little additive effect on the cardiovascular system; however, renal and hepatic tissues did exhibit apparent additive effects further suggesting that cadmium and lead actions and interactions may be tissue dependent. These experimental findings and the biologic inferences derived are consonant with the hypothesis that chronic, life-long cadmium exposure approximating environmental levels may have significant adverse effects on mammalian systems, that include effects on cardiovascular tissues.

Animals↗
PubMed1983

Monoclonal antibody with high affinity for 1,25-dihydroxycholecalciferol.

We have developed a monoclonal antibody capable of detecting 1 pg/ml of 1,25-dihydroxycholecalciferol. At a dilution of 1:80,000 of ascitic fluid this antibody has an apparent KD of 3.3 X 10(-11) ML-1. The immunogen used was a vitamin D analogue, calcitroic acid [1 alpha, 3 beta-dihydroxy-9, 10 seco-24-nor 5, 7, 10 (19) cholatriene-23-oic acid], conjugated to bovine serum albumin. Although this antibody is extremely sensitive, it also recognizes other important vitamin D3 metabolites.

Animals↗
PubMed1983

Some wrong-way chemical changes during antihypertensive treatment: comparison of indapamide and related agents.

Despite the beneficial therapeutic effects of antihypertensive drugs, some agents--particularly diuretics--seem to go in the "wrong direction" chemically. In fact, these changes could counteract some of the benefits resulting from lowering a patient's blood pressure. In the absence of hard evidence of the efficacy of long-term diuretic treatment of mild hypertension, we must be maximally sure that such therapy causes no harm. Thiazide and related diuretics have been associated with four distinct wrong-way chemical changes: increases in plasma concentrations of cholesterol, glucose, and uric acid, and a decrease in plasma potassium levels. The potential ramifications of such changes are well understood. The increase in circulating cholesterol, an established risk factor of myocardial infarction and stroke, is of particular concern--each year approximately one million hypertensive patients have myocardial infarctions. As a result, the search for safer and more effective diuretics must continue. Indapamide, a new antihypertensive drug, appears to meet these criteria. It is an effective diuretic with a considerable peripheral vasodilatory effect. Additionally, it does not appear to induce any significant change in circulating cholesterol, whereas chlorthalidone has been found to increase total cholesterol by 5%. Hydralazine is the only antihypertensive agent that seems to lower total cholesterol levels significantly. Neither indapamide nor hydralazine appears to affect plasma glucose levels; benzothiadiazines, however, have been found to induce an increase in circulating glucose.

Adult↗
PubMed1983

Does cadmium contribute to human hypertension.

In 1962 Schroeder reported marked hypertension in rats chronically fed a very low cadmium diet and 5 ppm cadmium in water, but subsequently he reported only moderate hypertension. Using Schroeder's food and water, but a slightly less cadmium-free environment, we repeatedly induced mild hypertension with 5 ppm cadmium, mild because control pressures were higher not because cadmium-fed animals had lower pressures. Seven laboratories have observed hypertension after feeding cadmium; six have not. Thus, chronically fed cadmium can induce hypertension in rats, but conditions are important. Additional observations on cadmium-induced hypertension indicate that: (1) concentrations from 0.1 to 5 ppm cadmium in water are pressor; (2) sex, strain, and age of animals are apparently not limiting factors; (3) there is associated sodium retention; (4) there is a concomitant decrease in the high energy phosphate content of tissues. Rats with cadmium-induced hypertension have renal cadmium concentrations which bracket those of the average environmentally exposed American or European. Finally, renal cadmium concentrations in man were significantly higher (p less than 0.05) for "hypertensives" than for normotensive "matches" in five of nine reported series, lower in one, and similar in three, with all series being small and suboptimal in subject selection.

Animals↗
PubMed1983

Calcitonin response in circulating human lymphocytes.

The concentration of cAMP increases in human mononuclear leukocytes after exposure to salmon calcitonin (SCT). This response is lost when the cells are separated into adherent (monocytic) and nonadherent (lymphocytic) cells, although the appropriate response to prostaglandin E2 remains in both groups. Adherent and nonadherent cells, each cultured alone for 16 h, do not regain the SCT response. Coculturing adherent and nonadherent cells together for 16 h restores the SCT response in the lymphocytes. The addition of a cyclooxygenase inhibitor to this culture system prevents development of the SCT response. The SCT response may be induced in nonadherent cells by culturing them for 16 h in medium previously conditioned by the growth of mixed mononuclear leukocytes.

Calcitonin↗
PubMed1983

Exogenous hyperthyroidism with osteoporosis.

Symptomatic osteopenia accompanied by subclinical hyperthyroidism developed in three women who were receiving excess thyroid hormone medication. Excessive thyroid replacement therapy resulted in mild hypercalcemia, hyperphosphatemia, and hyperphosphatasemia associated with diffuse skeletal demineralization and multiple fractures. Nondecalcified sections of double tetracycline-labeled iliac crest bone showed an accelerated rate of bone turnover with marked osteoclastosis and resorption of the cortical as well as the trabecular bone, typical of endogenous hyperthyroidism. Since thyroid hormones are among the most frequently prescribed medications, bone loss caused by exogenous hyperthyroidism may be more common than previously recognized.

Aged↗
PubMed1982

Cardiovascular actions of cadmium at environmental exposure levels.

A low intake of dietary cadmium induces specific dose-dependent functional and biochemical changes in the cardiovascular tissues of rats. Maximum changes occur when the cadmium intake is 10 to 20 micrograms per kilogram of body weight per day. The changes reflect the accumulation of "critical" concentrations of cadmium in the cardiovascular tissues. The biologic activity of cadmium is demonstrated for intakes that approach those of the average American adult exposed to the usual environmental concentrations of the element but not to industrial concentrations. The sensitivity of the cardiovascular system to low doses of cadmium could not be anticipated by extrapolation from data on exposure to high concentrations of cadmium. The data support the hypothesis that ingested or inhaled environmental cadmium may contribute to essential hypertension in humans.

Adenosine Triphosphatases↗
PubMed1982

Can dropout and other noncompliance be minimized in a clinical trial? Report from the Veterans Administrative National Heart, Lung and Blood Institute cooperative study on antihypertensive therapy: mild hypertension.

Long-term clinical trials must face the problem of participants who drop out before the study is closed or who in other ways do not comply with the protocol. In a joint Veterans Administration-National Heart, Lung and Blood Institute study of mild hypertension, 1,012 men and women, 21 to 50 years of age with diastolic pressure from 85 to 105 mm Hg, were randomized into two double-blind treatment groups and followed for up to 30 months. The data were analyzed for factors related to dropout and to medication and visit noncompliance. Large differences in dropout and compliance rates were found by clinic and age but not by treatment allocations (active vs. placebo) nor race-sex. In addition, noncompliance was 78%-118% higher in participants who subsequently chose to drop out of the study. Indications were that the attitude of a clinic towards participant complaints, willingness to temporarily reduce medication and vigorous pursuit of those who failed to keep appointments were important factors in reducing dropout. Strategies for minimizing dropout and noncompliance must be part of the study protocol, clinic personnel should be trained in using such strategies, and both clinic and participant compliance should be centrally monitored.

Adult↗
PubMed1982

Effect of diet on increases in systolic pressure induced in rats by chronic cadmium feeding.

Long-term exposure to cadmium in drinking water can induce hypertension in rats. We have consistently observed that from 0.1 to 5 ppm cadmium in deionized drinking water fortified with five essential metals induces a significant pressor effect in female Long-Evans rats on a noncommercial, low cadmium, rye-based diet. To test the effect of diet, a commercial stock diet (Purina Rodent Lab Chow), with either fortified or plain deionized water, was begun at weaning in rats that were receiving water containing 0.1 or 1 ppm cadmium. The overall effect of substituting the stock diet for the rye diet was initially to lessen, and later to prevent entirely, the cadmium-induced pressor effect. Whereas control rats on the rye diet have a constant systolic pressure of about 100 mm Hg throughout the experiment; control rats on the stock diet had an increase in systolic pressure of about 1 mm Hg/month, perhaps because of cadmium from food which contained 10 times as much of the metal as the rye diet. (There was also a somewhat lower pressure among the cadmium-fed rats on stock diet than among those on the rye diet). There were other (non-cadmium) differences between the stock and rye diets and between the remainder of our experimental conditions and those used by other investigators, presumably explaining the failure of some others to induce hypertension with cadmium.

Animals↗
PubMed1982

Clinical program for screening and treatment of hypertension in veterans.

Hypertension clinics, in which primary care is provided by specially trained nonphysician therapists under physician supervision, can provide very effective and relatively inexpensive control of hypertension for large numbers of patients. Since 1972, 32 VA Hypertension Screening and Treatment Clinics have screened about 500,000 veterans, 29 percent of whom have had diastolic pressures of 90 mmHg or more and 13 percent of whom have had diastolic pressures of 105 mmHg or more. Of subjects who returned for a second visit, 77 percent continued to have diastolic pressures of 90 mmHg or more. Blacks had a higher percentage of severe hypertension than whites.Since treatment became available in these clinics in 1974, 25,000 veterans have been treated. Computerized data are available for 10,777 of them who began treatment during 1974, 1975, or 1976. Of those with at least five treatment visits during that period, half had diastolic pressures below 90 mmHg at their most recent visit, and 80 percent had diastolic pressures below 100 mmHg. Moreover visit adherence was high, with two thirds of those who began treatment in these clinics during their first six months of operation continuing that treatment for two and a half years.

Adult↗
PubMed1981

Sodium retention in rats with cadmium-induced hypertension.

Chronic feeding of non-toxic doses of cadmium induces an average increase of 15 to 20 mm Hg in indirectly measured systolic pressure of lightly anaesthetized rats. The mechanism of this increase is not known, but cadmium has several potentially pressor effects, including increased sodium retention. This report describes both sodium balance and blood pressure in a pair of experiments where cadmium was fed and in a pair where it was injected. All four cadmium challenges induced sodium retention and also induced hypertension. Thus, rats with either low or moderate chronic exposure to fed cadmium (well below the exposures required to induce toxicity) retained more intraperitoneally injected radiosodium than controls and at the same time developed higher systolic pressures than controls. Immediately following intraperitoneally injected cadmium, rats lost a radiosodium more rapidly than controls; in both situations the blood pressure was higher than the controls. These data indicate that some of the pressor effect associated with cadmium exposure could result from its concomitant antinatriuretic effect.

Administration, Oral↗
PubMed1981

Skeletal sarcoidosis with osteopenia.

Diffuse osteopenia is not generally recognized as a radiological manifestation of skeletal sarcoidosis. Furthermore, the pathologic correlates of the skeletal abnormalities in sarcoidosis are poorly characterized. We quantitated the histomorphometric parameters of bone formation and resorption in a transiliac crest biopsy specimen from a patient with sarcoidosis, diffuse osteopenia, hypercalcemia, and hypercalciuria, who was treated only intermittently with corticosteroids and thiazides. Peritrabecular granulomas were associated with the histologic features of accelerated bone remodeling, namely: excess osteoid; increased numbers of osteoclasts and osteoblasts; increased osteoclastic resorbing surfaces; and increased bone formation rate. We conclude that the peritrabecular granulomas of skeletal sarcoidosis may result in rapid bone turnover with diffuse osteopenia which may contribute to the abnormalities of mineral metabolism.

Adult↗
PubMed1980

Serum lipoprotein levels during chlorthalidone therapy. A Veterans Administration-National Heart, Lung, and Blood Institute cooperative study on antihypertensive therapy: mild hypertension.

In a joint Veterans Administration-National Heart, Lung, and Blood Institute study of mild hypertension, 1,012 men and women, 21 to 50 years of age and with diastolic pressure from 85 to 105 mm Hg, were randomized into two double-blind treatment groups. Subjects in the active group received chlorthalidone or chlorthalidone plus reserpine, while the other subjects received matching placebo tablets. After one year of treatment, the chlorthalidone group had increases of 10.0 +/- 1.8 (SE) mg/dL in total cholesterol level, 9.8 +/- 5.2 mg/dL in triglyceride level, and 12.6 +/- 3.4 mg/dL in low-density lipoprotein-cholesterol level above the changes in the placebo group. There was no difference in high-density lipoprotein changes between the two groups (0.1 +/- 0.8 mg/dL). The possible net effect on risk of increasing lipid values while lowering pressure in the long-term treatment of mild hypertension with thiazides or related diuretics must be further evaluated.

Adult↗