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Biomedical subjects

M Tuck

Publications and source records attributed to M Tuck.

At least 19 recordsLinked to original sources
PubMed1996

Iodine-131-anti-B1 radioimmunotherapy for B-cell lymphoma.

PURPOSE: The CD20 B-lymphocyte surface antigen expressed by B-cell lymphomas is an attractive target for radioimmunotherapy, treatment using radiolabeled antibodies. We conducted a phase I dose-escalation trial to assess the toxicity, tumor targeting, and efficacy of nonmyeloablative doses of an anti-CD20 monoclonal antibody (anti-B1) labeled with iodine-131 (131I) in 34 patients with B-cell lymphoma who had failed chemotherapy. PATIENTS AND METHODS: Patients were first given tracelabeled doses of 131I-labeled anti-B1 (15 to 20 mg, 5 mCi) to assess radiolabeled antibody biodistribution, and then a radioimmunotherapeutic dose (15 to 20 mg) labeled with a quantity of 131I that would deliver a specified centigray dose of whole-body radiation predicted by the tracer dose. Whole-body radiation doses were escalated from 25 to 85 cGy in sequential groups of patients in 10-cGy increments. To evaluate if radiolabeled antibody biodistribution could be optimized, initial patients were given one or two additional tracer doses on successive weeks, each dose preceded by an infusion of 135 mg of unlabeled anti-B1 one week and 685 mg the next. The unlabeled antibody dose resulting in the most optimal tracer biodistribution was also given before the radioimmunotherapeutic dose. Later patients were given a single tracer dose and radioimmunotherapeutic dose preceded by infusion of 685 mg of unlabeled anti-B1. RESULTS: Treatment was well tolerated. Hematologic toxicity was dose-limiting, and 75 cGy was established as the maximally tolerated whole-body radiation dose. Twenty-eight patients received radioimmunotherapeutic doses of 34 to 161 mCi, resulting in complete remission in 14 patients and a partial response in eight. All 13 patients with low-grade lymphoma responded, and 10 achieved a complete remission. Six of eight patients with transformed lymphoma responded. Thirteen of 19 patients whose disease was resistant to their last course of chemotherapy and all patients with chemotherapy-sensitive disease responded. The median duration of complete remission exceeds 16.5 months. Six patients remain in complete remission 16 to 31 months after treatment. CONCLUSION: Nonmyeloablative radioimmunotherapy with 131I-anti-B1 is associated with a high rate of durable remissions in patients with B-cell lymphoma refractory to chemotherapy.

Adult↗
PubMed1995

Recognition of parts of famous-face photographs by children: an experimental note.

Children aged between 5 and 10 years were shown photographs of familiar TV personalities, presenters, and celebrities for immediate recognition (naming). The pictures were of whole faces, outer features only (hair, chin, ears), or inner features (eyes, nose, mouth). Only the oldest group (9-10 years) resembled adults in recognising these familiar faces more efficiently from internal than external parts. In the youngest children (5-6 years) there were some indications that the outer face features were more salient, particularly when cartoon characters were included in the array.

Attention↗
PubMed1995

Hormonal mechanisms in blood pressure reduction during hemodialysis in patients with chronic renal failure.

To elucidate the hormonal mechanisms of blood pressure (BP) reduction during hemodialysis in patients with chronic renal failure (CRF), we performed this study using 7 normotensive (NT) and 17 hypertensive (HT) patients who were strictly matched in age, body weight, body weight gain from the last HD, and duration of HD. Blood pressure, pulse rate, plasma norepinephrine (NE), and plasma dopamine levels were used as indices of sympathetic nerve activity, before, at 50% of hemodialysis (HD) and at 100% of HD (at the end of HD) on the third day after the last HD. As hemodialytic BP reduction was defined as BP decline of more than 10% in pre-HD mean BP, in normotensive patients with CRF, hemodialytic BP reduction was recognized in 0/7 (0%) at 50% of HD and 4/7 (57%) at 100% of HD, and in hypertensive patients it was recognized in 3/17 (18%) at 50% of HD and 4/17 (24%) at 100% of HD. Percentile changes in plasma NE levels increased slightly following hemodialysis in normotensive patients with hemodialytic BP reduction and in hypertensives without BP reduction, while those in normotensives without BP reduction and in hypertensives with BP reduction did not change. However, percentage changes in plasma dopamine (DA) levels decreased significantly at the end of HD (NT; p < 0.05, HT; p < 0.01) following hemodialysis in both normotensive and hypertensive patients with hemodialytic BP reduction, while changes in patients without BP reduction, percentage changes in DA did not change (patients with BP reduction vs. patients without BP reduction). In conclusion, hemodialytic BP reduction may be predisposed by abnormal sympathetic nerve responsiveness.

Adult↗
PubMed1994

Treatment of non-insulin-dependent diabetes mellitus and its complications. A state of the art review.

Non-insulin-dependent diabetes mellitus (NIDDM) is a major health problem which occurs predominantly in the older population; 16.8% of persons over age 65 years have NIDDM. The total health costs of NIDDM are in excess of $US20 billion annually. The primary objective in the treatment of NIDDM is to achieve normoglycaemia, without aggravating coexisting abnormalities. Common abnormalities include obesity, hypertension, retinopathy, nephropathy and neuropathies. Diet, and consequent bodyweight reduction, is the cornerstone of therapy for NIDDM. Total calorie intake should be limited, while the percentage of calories from carbohydrates should be increased and that from fats and cholesterol should be decreased. Exercise may also help to reduce bodyweight. Sulphonylurea drugs stimulate insulin secretion from beta-cells, and may be a useful adjunct to nonpharmacological therapy. Failure to respond to sulphonylurea drugs may be primary (25 to 30% of initially treated patients) or secondary (5 to 10% per year). It is not clear which is the most effective pharmacological intervention in such cases. Options include switching to or combining therapy with insulin, a biguanide, or other insulin-sparing antihyperglycaemic agents, e.g. alpha-glucosidase inhibitors, thiazolidinediones, chloroquine or hydroxychloroquine, or fibric acid derivatives such as clofibrate. Other experimental agents include the fatty acid oxidation inhibitors and dichloroacetate. Specific agents, such as antihypertensives, lipid lowering agents and sorbitol inhibitors, may be needed to prevent the complications arising from the spectrum of clinical and metabolic abnormalities which arise from insulin resistance.

Aged↗
PubMed1993

Long-term effects of the angiotensin converting enzyme inhibitor captopril on metabolic control in non-insulin-dependent diabetes mellitus.

The role of angiotensin converting enzyme (ACE) inhibitors in improving insulin-mediated glucose uptake has been described. However, their effects on long-term glucose control in diabetes mellitus are less well established. This study examines the effect of 4 months of captopril treatment on blood pressure (BP) and glucose control in 130 subjects with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension. Therapy for glycemic control was adjusted during a 3 month period prior to entry into active BP treatment and was not changed during 4 months of captopril administration. Fasting blood glucose and sitting BP were measured before and at 1, 2, 3, and 4 months of captopril monotherapy. Hemoglobin (Hb) A1c, serum electrolytes, creatinine, total cholesterol, and triglycerides were measured before and at 4 months. There were significant reductions in fasting blood glucose from baseline at 1 month (P < .01) and further stepwise decreases in values at 2, 3, and 4 months. Differences in glucose from month to month were highly significant. HbA1c was stable over a 3-month pretrial period, then decreased (P < .001) from baseline at 4 months of active treatment. Mean serum potassium increased from 4.4 to 4.7 (P < .001) at month 4 and there was an inverse correlation (r = -0.2, P < .025) between changes in potassium and HbA1c. Total serum cholesterol fell (P < .01) at month 4 of treatment. Serum creatinine and blood urea were unchanged, but of 18 patients with mild proteinuria pretrial, 12 of 18 were negative for protein at 4 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Potential role of 12 hydroxyeicosatetraenoic acid in angiotensin II-induced calcium signal in rat glomerulosa cells.

Recent evidence suggests that 12 hydroxyeicosatetraenoic acid (12HETE), a product of the 12 lipoxygenase (LO) pathway of arachidonic acid metabolism, may have a role in mediating angiotensin II (AII)-induced aldosterone secretion. The present study examined the possible role of the 12 LO product 12HETE in AII-induced calcium ([Ca++]i) signals in rat glomerulosa cells. The addition of 12HETE to glomerulosa cells induced a dose-dependent (10(-6)-10(-8) M) rise in [Ca++]i levels that was sustained over 15 min. The effects of 12HETE on [Ca++]i were attenuated but not blocked by nifedipine (5 x 10(-6) M) and were preserved in a calcium-free medium, suggesting mobilization of intracellular calcium stores. Furthermore, the 12HETE-mediated rise in [Ca++]i was almost entirely abolished by dantrolene. In parallel, 12HETE reversed the inhibitory effect of nifedipine on AII-induced aldosterone secretion [AII (10(-9) M) - 36 +/- 7, AII + nifedipine (5 x 10(-6) M) - 13 +/- 2, AII + nifedipine + 12HETE (5 x 10(-8) M) - 27 +/- 4 ng/10(6) cells]. Dantrolene also inhibited AII-dependent aldosterone secretion (AII 10(-9) M - 75.8 +/- 5.6, AII + dantrolene 10(-6) M 45.5 +/- 8.8 ng/10(-6) cells), but this inhibition could not be reversed by 12HETE 10(-8) M (45.4 +/- 10.6 ng/10(6) cells). The LO blockers baicalein and BW755C inhibited the effect of AII on aldosterone production and on [Ca++]i in a parallel fashion. During LO blockade, the addition of 12HETE (10(-7) M) restored the AII-induced rise in [Ca++]i. Collectively, these observations suggest that activation of the LO pathway in the rat adrenal glomerulosa contributes to change in cytosolic calcium, which may be important for the steroidogenic effect of AII.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1992

In vitro effects of insulin on aldosterone production in rat zona glomerulosa cells.

Though long standing diabetes mellitus is frequently accompanied by hypoaldosteronism, the role of insulin in this setting has never been clearly established. In the present study we have examined the direct effects of insulin on aldosterone production in rat zona glomerulosa cells in vitro. Insulin is shown to directly stimulate aldosterone production in a dose dependent manner, and to attenuate angiotensin II mediated aldosterone production, without affecting angiotensin II receptor binding kinetics. Insulin had no effect on aldosterone production mediated by the other physiological stimuli (K+ and ACTH). These data suggest a possible interaction between insulin and angiotensin II in the regulation of aldosterone secretion.

Adrenocorticotropic Hormone↗
PubMed1991

Glucose, insulin, and insulin resistance as biochemical predictors of hypertension.

Obesity, essential hypertension, and diabetes mellitus share certain metabolic disturbances. The predictive value of disordered glucose metabolism and insulin action for hypertension are discussed. Several studies have examined the relationship between hypertension and glucose metabolism in diverse populations, and tend to indicate a predictive role for insulin and glucose metabolism disturbances in the development of hypertension.

Blood Glucose↗
PubMed1991

Parathyroid hormone, platelet calcium, and blood pressure in normotensive subjects.

Relations between platelet cytosolic calcium, parathyroid hormone, and blood pressure were investigated in 91 normotensive subjects: 47 men and 44 women ranging in age from 24 to 70 years. The men had higher mean arterial blood pressure, serum creatinine, and body mass index than the women. Serum total calcium, plasma ionized calcium, and parathyroid hormone (measured as both intact hormone and mid-molecule fragment) were not different between men and women; however, serum phosphate was higher in women than in men. Basal platelet cytosolic calcium was higher in men than in women (113.7 +/- 1.9 versus 105.9 +/- 1.7, respectively; p less than 0.01), but there was no difference in the peak platelet cytosolic calcium responses to thrombin between the two groups. In the combined group of male and female subjects, platelet cytosolic calcium correlated with diastolic blood pressure and mean arterial pressure (r = 0.37, p less than 0.001 and r = 0.32, p less than 0.01, respectively). Intact parathyroid hormone correlated with systolic and mean arterial blood pressure (r = 0.41, p less than 0.001 for both). Age correlated with both systolic blood pressure (r = 0.40, p less than 0.001) and intact parathyroid hormone (r = 0.51, p less than 0.001). When multiple regression analysis was performed using mean arterial pressure as the dependent variable, platelet cytosolic calcium and intact parathyroid hormone maintained significant correlations with mean arterial pressure. Platelet cytosolic calcium did not correlate with intact parathyroid hormone. These results suggest that both platelet cytosolic calcium and intact parathyroid hormone are associated with blood pressure regulation in normotensive subjects. However, the influences of these two factors on blood pressure are not interrelated.

Adult↗
PubMed1990

Salt-sensitive blood pressure and exaggerated vascular reactivity in the hypertension of diabetes mellitus.

PURPOSE: This study evaluates the effects of dietary salt restriction and loading on blood pressure in normotensive and hypertensive patients with non-insulin-dependent diabetes mellitus (NIDDM). Salt sensitivity of blood pressure responses is compared to vascular reactivity to infused angiotensin II on the two sodium diets. PATIENTS AND METHODS: We studied 19 patients with NIDDM (seven normotensive, 12 hypertensive) and seven nondiabetic control subjects under metabolic balance after 6 days on a constant low- (20 mEq) sodium diet and again after 6 days on a high- (250 mEq) sodium diet. Salt sensitivity of blood pressure was determined by the increment in integrated 24-hour blood pressure values on changing from the low- to the high-sodium diet. Blood pressure and plasma aldosterone responses to a graded-dose infusion of angiotensin II were also examined on both sodium diets. RESULTS: Eight of 12 hypertensive patients with NIDDM displayed salt-sensitive blood pressure responses, whereas none of the normotensive patients with NIDDM or control subjects were salt-sensitive. Patients with NIDDM also had augmented blood pressure responses to infused angiotensin II on both sodium diets when compared to control subjects. Whereas controls had reduced vascular responses to angiotensin II on the low-sodium diet, these responses were not decreased in patients with NIDDM. Patients with NIDDM also retained more sodium on the high-sodium diet than did the control subjects. CONCLUSION: Hypertension in patients with NIDDM is frequently salt-sensitive, which may be due to sodium retention and enhanced vascular reactivity to angiotensin II. Since sodium restriction does not normally reduce vascular reactivity to angiotensin II in NIDDM, salt-restricted diets may be less effective in blood pressure control in hypertensive NIDDM.

Adult↗
PubMed1990

Captopril improves hypertension and cardiomyopathy in rats with pheochromocytoma.

Hypertension and cardiomyopathy are prominent findings in humans and rats harboring pheochromocytomas, tumors that can secrete enormous quantities of catecholamines. We have previously found that alpha- and beta-adrenergic receptor antagonists may ameliorate the hypertension and cardiomyopathy found in New England Deaconess Hospital rats implanted with pheochromocytoma. The present studies were designed to determine the possible action of the angiotensin converting enzyme inhibitor captopril on these changes in rats harboring pheochromocytomas. Rats were implanted with transplantable pheochromocytomas and treated with captopril dissolved in the drinking water (1 mg/ml) for 4-6 weeks. Systolic blood pressure was monitored by using the tail-cuff technique. In the rats with pheochromocytoma, blood pressure progressively increased to 184 +/- 3 mm Hg after the tumor was implanted. However, in rats with pheochromocytoma treated with captopril in the drinking water before the development of hypertension, blood pressure did not increase (137 +/- 3 mm Hg). In rats with pheochromocytoma with established hypertension, captopril normalized the systolic blood pressure. Plasma norepinephrine was markedly elevated to a similar extent in both groups compared with unimplanted control rats. Plasma renin activities were slightly lower in rats with pheochromocytoma compared with unimplanted control rats. Treatment with captopril of rats with pheochromocytoma did not modify contraction of isolated rings of thoracic aorta exposed in vitro to either phenylephrine or angiotensin II. Treatment with captopril markedly attenuated the cardiomyopathy induced by pheochromocytoma. These results demonstrate that captopril prevents the development of hypertension despite markedly elevated concentrations of catecholamines. In addition, captopril attenuates catecholamine-induced cardiomyopathy in pheochromocytoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1990

The differential efficacy of antihypertensive agents in the elderly.

A number of controlled trials have shown that antihypertensive therapy is beneficial to the elderly (greater than or equal to 60 years of age). Even so, there may be deleterious age-related effects associated with such therapy. Because of physiological and pathophysiological problems peculiar to the elderly (many of which remain to be defined precisely), both benefits and untoward effects of antihypertensive drugs differ, sometimes within classes of agents themselves. None of the traditional agents is ideal for the management of hypertension in the elderly. Differential efficacy and tolerability of various antihypertensive agents has often been claimed but none of these claims appears established beyond dispute. Increasing evidence, however, suggests that the serotonin antagonist ketanserin may be more effective and better tolerated in elderly hypertensives. If the elderly are to derive maximum benefit from antihypertensive therapy, the question of age-related differential effects of agents used needs to be addressed in carefully designed studies to determine the nature and magnitude of such effects, where they exist and what clinical implications they may have.

Aged↗