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Biomedical subjects

E Grossman

Publications and source records attributed to E Grossman.

At least 109 records · Page 6Linked to original sources

On the existence of functional angiotensin II receptors on vascular sympathetic nerve terminals in the human forearm.

OBJECTIVE: The existence of presynaptic angiotensin II receptors, modulating the release of the sympathetic neurotransmitter norepinephrine, was examined in the perfused human forearm model. DESIGN AND METHODS: In three groups out of a total of 20 healthy volunteers, intra-arterial infusions of tracer amounts of tritiated norepinephrine were given to measure forearm spillover and total plasma appearance rate of norepinephrine during intra-arterial infusions of angiotensin II (0.02, 0.2 and 2 ng/kg per min), methoxamine (0.08, 0.4 and 2 micrograms/kg per min) to produce vasoconstriction by stimulating alpha 1-adrenoceptors and saralasin (0.5 ng/kg per min) to block angiotensin II receptors. Postganglionic sympathoneural activity was stimulated by intravenous infusion of sodium nitroprusside (about 1.3 ng/kg per min) or attenuated by intravenous infusion of trimethaphan (about 1 mg/min). RESULTS: Angiotensin II failed to increase the spillover and total plasma appearance rate of norepinephrine, when given without additional treatment or during sodium nitroprusside or trimethaphan administration. In contrast, the spillover of norepinephrine even decreased during angiotensin II administration, both before and during intravenous sodium nitroprusside administration, probably because of angiotensin II-induced forearm vasoconstriction. Similar vasoconstrictor doses of angiotensin II and methoxamine produced similar changes in spillover and total plasma appearance rate of norepinephrine. The highest dose of angiotensin II increased diastolic blood pressure by 9% and decreased the pulse rate by 6%. Saralasin affected the spillover and total plasma appearance rate of norepinephrine neither before nor during intravenous sodium nitroprusside infusion. CONCLUSION: The present results fail to support the view that angiotensin II receptors exert stimulatory modulatory effects on norepinephrine release from sympathetic nerves in the human forearm, at rest or during changes in sympathoneural outflow.

Adult↗

Enalapril improves glucose tolerance in two rat models: a new hypertensive diabetic strain and a fructose-induced hyperinsulinaemic rat.

1. The present study was undertaken to examine the effect of the angiotensin converting enzyme (ACE) inhibitor, enalapril, on blood pressure and spontaneous blood glucose levels in two rat models: our new diabetic hypertensive rat in which genetic hypertension and diabetes develop following cross-breeding of Cohen diabetic rat (CDR) and spontaneous hypertensive rats (SHR); and a rat in which hypertension, hyperinsulinaemia and hyperlipidaemia were induced by fructose diet. 2. The new strain of animal was fed the usual copper-poor sucrose diet, and for 4 weeks received enalapril. The fructose-induced hyperinsulinaemic animals were fed a fructose-enriched diet for 3 weeks, and enalapril 20 mg per kg per day was added to the drinking water for 2 more weeks. 3. The new strain of diabetic-hypertensive rats that received enalapril showed a significant decrease in blood pressure level. The fructose-fed animals showed a fall in insulin and blood pressure following the introduction of enalapril to their diet. 4. The present study confirms the advantage of the ACE inhibitor enalapril in improving the metabolic parameters of hypertensive diabetic rats, including insulin sensitivity.

Angiotensin-Converting Enzyme Inhibitors↗

Generalized pustular eruption associated with converting enzyme inhibitor therapy.

A 67-year-old man presented with a high fever and a generalized rash. His extended hospital stay was characterized by fever with repeated staphylococcal bacteremia and the appearance of axillary lymphadenopathy and splenomegaly. Skin lesions became hyperpigmented, dry, and atrophic with areas of exfoliation and uclers. Examination of skin and lymph node biopsy specimens showed findings consistent with mycosis fungoides. The patient unexpectedly recovered on discontinuation of captopril. A positive macrophage inhibiting factor response for both captopril and enalapril indicated that the non-sulfhydryl moiety was the antigenic stimulant for the lesion resembling mycosis fungoides.

Aged↗

Reduction of calculus and Peridex stain with Tartar-Control Crest.

Regular use of an effective oral rinse (0.12% chlorhexidine [CHX]) may be accompanied by tooth staining and slightly increased calculus formation. Since dentifrices containing soluble pyrophosphates are known to significantly reduce calculus formation, this study was designed to investigate whether CHX-induced staining and increased calculus may be reduced by the use of such dentifrices. The study compared stain and calculus formation in 163 subjects using a CHX oral rinse (Peridex, Procter & Gamble) according to label directions and either a pyrophosphate-containing anticalculus toothpaste (Tartar-Control Crest, 3.3% pyrophosphate) or an otherwise similar toothpaste without pyrophosphate (Regular Crest). Subjects were instructed to brush and floss ad lib and were examined after three and six months. Whole-mouth calculus occurrence was significantly reduced in the anticalculus toothpaste group at three and six months. Also, staining on the cosmetically important facial-anterior surfaces was significantly reduced at the 3-month examination. After six months the difference in facial anterior staining was still directionally favorable to the anticalculus toothpaste group but no longer statistically significant. These results indicate that routine brushing with an anticalculus toothpaste such as Tartar-Control Crest significantly reduces both facial-anterior staining and calculus occurrence in subjects using a CHX oral rinse. Whether more frequent or more thorough brushing would lead to still greater reductions remains to be investigated.

Adolescent↗

A comparative clinical investigation of the safety and efficacy of an oscillating/rotating electric toothbrush and a sonic toothbrush.

This clinical study compared the ability of a sonic toothbrush to remove plaque and control gingivitis with that of an oscillating/rotating electric toothbrush. One-hundred and sixteen subjects from a general population were randomly allocated to either a sonic toothbrush group (Sonicare) or an electric toothbrush group (Braun Oral-B Plaque Remover). After 8 weeks use, there was found to be no statistically significant difference in either plaque removal or gingival index between the two groups. Both devices were found to be safe, but whereas 100% of volunteers in the Braun Oral-B Plaque Remover group expressed a wish to continue using the toothbrush, approximately 25% of the Sonicare group did not like the device and said that they would not continue to use it. The Sonicare device was found to offer no advantages in clinical terms over an established oscillating/rotating electric toothbrush (Braun Oral-B Plaque Remover) with respect to removal of supragingival plaque or improvement in gingival health.

Adult↗

Urinary excretion rate of endothelin-1 in patients with essential hypertension and salt sensitivity.

To assess the possible role of ET-1 in the pathogenesis of hypertension and salt sensitivity levels of immunoreactive endothelin-1 (irET-1) were measured in plasma and urine of 17 patients with essential hypertension and in 19 normotensive control subjects. Effects of alterations in dietary sodium content on urinary irET-1 levels also were assessed. Plasma levels of irET-1 did not differ between the hypertensives and normotensive groups (1.1 +/- 0.3 and 1.3 +/- 0.1 pg/ml). Urine samples of both groups contained high concentrations of irET-1. However, the mean daily urinary excretion of irET-1 in the hypertensives was less than one-third that in controls (29 +/- 3 vs. 109 +/- 21 ng/day, respectively, P < 0.01). Changing dietary sodium content in the hypertensives had no effect on mean irET-1 excretion. However, on either low, intermediate, or high salt diet, "salt sensitive" hypertensives had lower levels of the peptide than "salt resistant" patients (23 +/- 3 vs. 36 +/- 5 ng/day, respectively, P < 0.05). The data demonstrate a marked reduction in irET-1 excretion in patients with essential hypertension, despite normal plasma levels of the peptide. Since ET-1 has diuretic and natriuretic properties, the decreased renal excretion of ET-1 may be of relevance to the pathophysiology of hypertension and salt sensitivity.

Adult↗

Quantitative effects of pelleting on performance, gastrointestinal tract and behaviour of meat-type chickens.

1. In an attempt to quantify the effects of "degree" of pelleting, two experiments were conducted. Diets were prepared by mixing together a mash composed mainly of maize (experiment 1) or sorghum (experiment 2) with soft pellets, or soft pellets mixed with hard pellets. 2. The pelleting degrees (PDs) were as follows: 0 mash; 0.5 mixture of soft pellets and mash 1 to 1; 1 soft pellets pelleted once; 1.5 mixture of soft and hard pellets 1 to 1; 2 hard pellets pelleted twice. 3. In experiment 2, the weight and length of the digestive organs were determined as well as digestive enzyme activities. In both experiments, the behaviour recorded was eating, standing, sitting and drinking. 4. Food intake and body weight gain were related to the degree of pelleting in a curvilinear manner. PD had a positive effect up to a peak (1 to 1.5 PD), after which its effect decreased. Food efficiency was not related to PD. In experiment 1, food efficiency of PDs 1 to 2 were superior to PDs 0 to 0.5 and in experiment 2, PDs 1.5 to 2 were superior to PD 0. 5. The relative weight of the gizzard was reduced by pelleting, whereas pelleting increased the relative weight of abdominal fat. The content of the crop was not affected by PD, whereas that of the proventriculus was lowest in the PD 2 group. Gizzard content was inversely related to PD. Pelleting reduced the length of the jejunum and ileum: which were shortened by about 15% with PDs 1 to 2, as compared to PD 0. The weight/length ratio of the jejunum and ileum tended to increase with increasing PD to a peak at PD 1.5, and to decrease thereafter. 6. Trypsin activity in the pancreas and amylase activity in the intestinal content were reduced by pelleting. 7. Chicks fed pelleted diets were less active: they 'sat' more and spent less time eating than their mash-fed counterparts.

Adipose Tissue↗

Hemodynamic and humoral effects of the angiotensin II antagonist losartan in essential hypertension.

Losartan (DuP 753) is a novel orally active angiotensin II antagonist that lowers blood pressure. The present study evaluates the hemodynamic and humoral effects of losartan in essential hypertension. Fifteen patients (12 men, 3 women; mean age, 46 +/- 2 years; range, 33 to 64 years) with a diastolic blood pressure (DBP) between 95 and 115 mm Hg after 2 weeks of placebo participated in the study. Initially the patients were treated with losartan (50 mg) once daily for 1 month. Then, if the trough DBP was > or = 93 mm Hg, hydrochlorothiazide (HCTZ), 6.25 to 12.5 mg daily, and nifedipine, 30 to 60 mg daily, were added as needed. Ten patients completed 12 months of treatment. Trough blood pressure, heart rate, plasma creatinine, potassium, uric acid, cholesterol, renin activity (PRA), aldosterone, and norepinephrine were measured at baseline and after 1 and 12 months of treatment. Losartan lowered mean arterial pressure significantly from 119 +/- 2 mm Hg at baseline to 113 +/- 2 mm Hg (P < .05) after 1 month of treatment. Coadministration of HCTZ and nifedipine further decreased the mean arterial pressure to 103 +/- 2 mm Hg after 12 months of treatment. Plasma levels of creatinine, potassium, uric acid, cholesterol, and norepinephrine remained unchanged. PRA increased and plasma aldosterone decreased significantly (P < .05). The decrease in mean arterial pressure was related to baseline PRA (r = 0.53, P < .05). and to the change in PRA (r = 0.52, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Left ventricular mass in hypertension: correlation with casual, exercise and ambulatory blood pressure.

The purpose of this work was to assess the best haemodynamic determinant of left ventricular hypertrophy (LVH) in patients with essential hypertension. We studied the relationships between left ventricular mass (LVM) and casual, exercise and 24h ambulatory blood pressure monitoring (ABPM) in 60 newly discovered patients with mild to moderate essential hypertension. LVM was only weakly related to both casual and exercise blood pressure, while it was significantly related to average ABPM values. Diastolic hypertensive load, calculated as the percentage of diastolic measurements > 90 mmHg, was the best predictor of the development of LVH (r = 0.51, P < 0.001). Six of six patients with a diastolic load > 50% had LVH, whereas only two of 18 patients (11%) with a diastolic load < 10% had LVH (P < 0.001). In conclusion, in patients with mild to moderate essential hypertension, LVM is poorly related to both casual and exercise blood pressure, but is related to ABPM. Blood pressure load is the best determinant of LVH. These findings suggest that blood pressure load should be considered when analysing ABPM.

Adolescent↗

On the existence of functional beta-adrenoceptors on vascular sympathetic nerve endings in the human forearm.

OBJECTIVE: To examine the existence of presynaptic beta-adrenoceptors modulating forearm norepinephrine release in 31 healthy volunteers. METHODS: The spillover rate of norepinephrine in forearm venous plasma and the total plasma appearance rate of norepinephrine in the forearm were estimated using intra-arterial infusion of [3H]-norepinephrine. Isoprenaline was infused intra-arterially to stimulate beta-adrenoceptors, terbutaline to stimulate beta 2-adrenoceptors, propranolol to block beta-adrenoceptors, metoprolol to block beta 1-adrenoceptors, isoprenaline combined with metoprolol to stimulate beta 2-adrenoceptors, epinephrine to stimulate alpha- and beta-adrenoceptors, yohimbine to block alpha 2-adrenoceptors and sodium nitroprusside to increase forearm blood flow directly. RESULTS: No systemic hemodynamic effects or changes in arterial plasma norepinephrine level were noted during the intra-arterial infusions. Metoprolol and propranolol decreased norepinephrine spillover and its rate of appearance in the forearm without affecting forearm blood flow. Isoprenaline and sodium nitroprusside increased and epinephrine decreased forearm norepinephrine spillover. Terbutaline increased forearm norepinephrine spillover and its rate of appearance in the forearm. Terbutaline increased the forearm rate of appearance and spillover of norepinephrine more than did sodium nitroprusside or isoprenaline at the same level of forearm blood flow. Infusion of isoprenaline failed to increase norepinephrine spillover or its forearm appearance rate more than would be expected from the increase in forearm blood flow. Administration of epinephrine increased spillover and forearm appearance rate of norepinephrine during intra-arterial infusion of yohimbine. CONCLUSIONS: The terbutaline, propranolol, metoprolol and yohimbine plus epinephrine results suggest that beta-adrenoceptors enhance release of norepinephrine from vascular sympathetic nerve endings in humans.

Adult↗

Two long-term clinical studies comparing the plaque removal and gingivitis reduction efficacy of the Oral-B Advantage Plaque Remover to five manual toothbrushes.

Two long-term studies were conducted to evaluate the therapeutic efficacy of five manual toothbrushes compared to the Oral-B Advantage Plaque Remover measuring plaque removal and gingivitis/bleeding reduction. Both studies were carried out under the same protocol and utilized the same examiners. In Study 1, the Oral-B Advantage Plaque Remover was compared to the Crest Complete and Colgate Precision toothbrushes. In Study 2, the Oral-B Advantage Plaque Remover was compared to the Reach Advanced Design, Colgate Plus and Jordan Exact toothbrushes. A total of 109 and 121 male and female subjects who met the inclusion and exclusion criteria completed Study 1 and Study 2, respectively. Subjects were initially screened for dental plaque eligibility having abstained from oral hygiene for a prior 24-hour period. Subjects were randomly assigned to one of the balanced groups and received a professional prophylaxis to reduce plaque scores. Subjects were then scheduled to return 4 weeks and 8 weeks later, having again abstained from all oral hygiene procedures for a prior period of 24 hours. At each visit, each subject was evaluated for plaque, gingivitis and bleeding. Upon completion of the study, the data were subjected to statistical analysis. The results of both studies are summarized as follows: The Oral-B Advantage Plaque Remover was significantly more effective than the Crest Complete, Colgate Precision, Colgate Plus and Jordan Exact toothbrushes in whole mouth plaque removal (p < 0.05), and vs. all brushes tested in gingivitis reduction (p < 0.01) and in reducing gingival bleeding (p < 0.001).

Adult↗

Left ventricular mass and cardiac function in patients with essential hypertension.

Two-dimensional guided M-mode echocardiography was used to estimate left ventricular mass and left ventricular performance in 140 untreated hypertensive patients, 38 (27%) of whom had left ventricular hypertrophy. Left ventricular contractility as reflected by ratio of end-systolic wall stress to end-systolic volume index and normalised early left ventricular peak filling rate were decreased in the patients with left ventricular hypertrophy compared with those without hypertrophy and correlated inversely with the left ventricular mass (r = -0.44; P < 0.0001 and r = -0.31; P = 0.0004, respectively). Positive correlations were found between the peak filling rate and either the ejection fraction or the contractility index (r = 0.44; P < 0.0001 and r = 0.24; P = 0.004, respectively). Left ventricular mass also correlated with mean arterial pressure in the whole study population (r = 0.43; P < 0.0001). The data suggest that with the development of left ventricular hypertrophy both contractility and filling of the left ventricle become progressively impaired in hypertensive patients. The decline in cardiac function with progressive left ventricular hypertrophy may represent a pathophysiological correlate of the epidemiological observation identifying left ventricular hypertrophy as one of the most powerful risk factors for future cardiovascular morbidity and mortality. The present study shows that with development of left ventricular hypertrophy in essential hypertension both contractility and filling of the left ventricle become progressively impaired.

Adolescent↗

Disparate cardiovascular response to stress tests during isradipine and fosinopril therapy.

Optimal antihypertensive therapy should control blood pressure at rest and during stress while preserving the physiologic hemodynamic response. In patients with mild to moderate hypertension, the hemodynamic profile and catecholamine response at rest, during isometric, mental, and orthostatic stresses were compared before and 12 weeks after angiotensin-converting enzyme inhibition or calcium channel blockade. Antihypertensive therapy was titrated either with the angiotensin-converting enzyme inhibitor fosinopril (10 to 40 mg; n = 9) or with the calcium antagonist isradipine (5 to 20 mg; n = 10) until diastolic blood pressure < 90 mm Hg was achieved. Groups were comparable in race, sex, body mass index, pretreatment mean arterial pressure and response to isometric stress (25% increase in mean arterial pressure) before treatment. At rest, total peripheral resistance was reduced to the same extent (18%) in both groups. After fosinopril, the percent increase in stroke volume was higher and heart rate lower than with isradipine. During isometric stress, the percent increase in mean arterial pressure and cardiac output was higher, with isradipine (p < 0.05) reaching pretreatment levels. Plasma catecholamines were also higher with isradipine (p < 0.05), increasing by 100% with plasma norepinephrine compared with 16% before treatment. During orthostatic stress significant reductions in mean arterial pressure and stroke volume were observed after isradipine but not after fosinopril. Neither medication significantly modified the response to mental stress. Our data suggest that despite a comparable reduction in total peripheral resistance at rest, fosinopril preserves a more physiologic hemodynamic response to isometric and orthostatic stress than isradipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular System↗

Positron emission tomographic imaging of cardiac sympathetic innervation using 6-[18F]fluorodopamine: initial findings in humans.

OBJECTIVES: This study evaluated the safety, efficacy and validity of 6-[18F]fluorodopamine positron emission tomographic scanning of cardiac sympathetic innervation and function in humans. METHODS: Positron emission tomography (PET) scans, arterial blood and urine were obtained after a 3-min intravenous infusion of 6-[18F]fluorodopamine (1 to 4 mCi, 188 to 809 mCi/mmol) in healthy volunteers, with or without pretreatment with oral desipramine to inhibit neuronal uptake of catecholamines. RESULTS: 6-[18F]Fluorodopamine PET scanning visualized the left ventricular myocardium. Blood pressure increased slightly and transiently. The estimated absorbed radiation dose to the main target organ, the wall of the urinary bladder, was 0.8 to 1.0 rad/mCi of injected 6-[18F]fluorodopamine. By 24 h after the injection, the main 6F-compound in urine was 6F-vanillymandelic acid, a metabolite of 6F-norepinephrine. Desipramine attenuated accumulation of myocardial 6-[18F]fluorodopamine-derived radioactivity and plasma 6F-dihydroxyphenylacetic acid. CONCLUSIONS: 6-[18F]Fluorodopamine produces negligible hemodynamic effects and acceptable radiation exposure at doses that visualize the left ventricular myocardium. Sympathetic nerves take up 6-[18F]fluorodopamine, which is translocated from the axoplasm into storage vesicles, where is it beta-hydroxylated to the fluorinated analogue of the sympathetic neurotransmitter norepinephrine. Therefore, the basis for visualization of myocardium after 6-[18F]fluorodopamine injection in humans is radiolabeling by 6-[18F]fluorodopamine and 6-[18F]fluoronorepinephrine of vesicles in sympathetic terminals. 6-[18F]Fluorodopamine PET scanning provides a novel means for assessing sympathetic innervation and function noninvasively in the human heart.

Adult↗

Derivation of urinary dopamine from plasma dihydroxyphenylalanine in humans.

1. Dihydroxyphenylalanine is the precursor of all endogenous catecholamines. In laboratory animals, renal uptake and decarboxylation of circulating dihydroxyphenylalanine accounts for most of dopamine in urine. Dopamine is natriuretic, and in rats, dietary salt loading increases renal dihydroxyphenylalanine uptake by increasing the rate of entry (spill-over) of dihydroxyphenylalanine into arterial plasma. In experimental animals and in humans, dietary salt loading increases urinary excretion of dihydroxyphenylalanine and dopamine. The present study examined in humans the extent to which circulating dihydroxyphenylalanine is the source of urinary dopamine and of the dopamine metabolite dihydroxyphenylacetic acid, and whether, as in animals, dietary salt loading affects dihydroxyphenylalanine spillover. 2. L-Dihydroxyphenylalanine (0.33 micrograms min-1 kg-1) was infused intravenously for 300 min after 7 days of a low-salt (mean 41 mmol/day) or a high-salt (mean 341 mmol/day) diet in 12 healthy subjects. Concentrations of dihydroxyphenylalanine, dopamine and dihydroxyphenylacetic acid were measured in urine and in antecubital venous plasma. Infusion of L-dihydroxyphenylalanine produced a steady-state mean dihydroxyphenylalanine level about 10 times the endogenous level. About 30% of infused dihydroxyphenylalanine estimated to be delivered to the kidneys via the arterial plasma was excreted as dopamine, and about 30% was excreted as dihydroxyphenyl-acetic acid. 3. Dietary salt loading increased urinary excretion rates of dihydroxyphenylalanine [from 0.08 +/- (SEM) 0.01 to 0.14 +/- 0.03 nmol/min, t = 2.80, P < 0.02] and dopamine (from 1.03 +/- 0.19 to 1.30 +/- 0.28 nmol/min, t = 2.35, P < 0.05), whereas dihydroxyphenylalanine spillover appeared to be unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗