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Biomedical subjects

B Kennedy

Publications and source records attributed to B Kennedy.

At least 91 records · Page 5Linked to original sources
PubMed1992

Chronic regurgitation among persons with mental retardation: a need for combined medical and interdisciplinary strategies.

A survey of institutionalized adults with severe mental retardation and chronic regurgitation was conducted. A high prevalence of dysphagia and gastroesophageal abnormalities was found. Many of these abnormalities require further evaluation and treatment prior to the diagnosis of rumination. More studies are needed to explore the causes and treatment approaches for chronic regurgitation in adults with developmental disabilities.

Adult↗
PubMed1991

Epinephrine synthesis by rat arteries.

Carotid artery and aorta homogenates synthesized epinephrine (E) from norepinephrine (NE) in the presence of S-adenosylmethionine. Aorta synthesized epinine by the N-methylation of dopamine (DA) about 3 times as well as it synthesized E from NE. In contrast, adrenal homogenates which contain phenylethanolamine N-methyltransferase (PNMT) methylated DA only 1% as well as NE. The PNMT inhibitor SKF 29661 had no significant effect on methylation of NE by aorta but inhibited adrenal PNMT by 88%. N-Methylating activity in arterial homogenates was increased by dexamethasone and following catecholamine depletion by 6-hydroxydopamine (6-OHDA) and reserpine. Nine days after adrenal demedullation blood E levels collected at decapitation were less than 7% of levels found in sham operated controls but artery homogenate E was unchanged. Demedullated rats given 6-OHDA followed by reserpine for 4 days also had unchanged arterial E levels despite arterial NE levels that were less than 15% of controls. We conclude that arteries synthesize E in vitro and appear to synthesize E in vivo using an extraneuronal N-methyltransferase. This enzyme differs from adrenal PNMT in substrate and inhibitor specificity and its activity is enhanced by catecholamine depletion and by glucocorticoid treatment.

Animals↗
PubMed1991

Ultradian variations of chromogranin A in humans.

Chromogranin A (CgA) is an acidic soluble protein exocytotically released from virtually all neuroendocrine secretory vesicles. Here we examined spontaneous variations in CgA and catecholamine concentrations in humans. In normal subjects, basal CgA showed no day-to-day, week-to-week, or diurnal variability. Plasma CgA had significant ultradian variation in normotensives and hypertensives, and in bilaterally adrenalectomized subjects. Gender, but not age or blood pressure, influenced CgA variations, males having fewer (P less than 0.05) peaks per 8 h. Plasma catecholamines had significant ultradian variations in both controls and bilaterally adrenalectomized subjects. Within individuals, neither basal nor peak plasma CgA correlated with catecholamines, nor was there concordance between plasma CgA and catecholamine peaks. Somatostatin, a widespread inhibitor of nonsympathoadrenal neuroendocrine secretion, diminished both the frequency and amplitude of plasma CgA peaks. Thus spontaneous variations in basal CgA are not directly linked to alterations in sympathoadrenal catecholamine secretion. Furthermore, neuroendocrine secretion at sites other than the sympathoadrenal system contributes to spontaneous variations in CgA concentration.

Activity Cycles↗
PubMed1991

Contribution of exercising legs to the slow component of oxygen uptake kinetics in humans.

Rates of performing work that engender a sustained lactic acidosis evidence a slow component of pulmonary O2 uptake (VO2) kinetics. This slow component delays or obviates the attainment of a stable VO2 and elevates VO2 above that predicted from considerations of work rate. The mechanistic basis for this slow component is obscure. Competing hypotheses depend on its origin within either the exercising limbs or the rest of the body. To resolve this question, six healthy males performed light nonfatiguing [approximately 50% maximal O2 uptake (VO2max)] and severe fatiguing cycle ergometry, and simultaneous measurements were made of pulmonary VO2 and leg blood flow by thermodilution. Blood was sampled 1) from the femoral vein for O2 and CO2 pressures and O2 content, lactate, pH, epinephrine, norepinephrine, and potassium concentrations, and temperature and 2) from the radial artery for O2 and CO2 pressures, O2 content, lactate concentration, and pH. Two-leg VO2 was thus calculated as the product of 2 X blood flow and arteriovenous O2 difference. Blood pressure was measured in the radial artery and femoral vein. During light exercise, both pulmonary and leg VO2 remained stable from minute 3 to the end of exercise (26 min). In contrast, during severe exercise [295 +/- 10 (SE) W], pulmonary VO2 increased 19.8 +/- 2.4% (P less than 0.05) from minute 3 to fatigue (occurring on average at 20.8 min). Over the same period, leg VO2 increased by 24.2 +/- 5.2% (P less than 0.05). Increases of leg and pulmonary VO2 were highly correlated (r = 0.911), and augmented leg VO2 could account for 86% of the rise in pulmonary VO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Cardiac epinephrine synthesis. Regulation by a glucocorticoid.

BACKGROUND: The heart can synthesize epinephrine. Homogenates of rat heart, which contain the enzymes phenylethanolamine N-methyltransferase (PNMT) and nonspecific N-methyltransferase (NMT), methylate norepinephrine to form epinephrine. The cardiac atrium contains primarily PNMT and the cardiac ventricle contains both PNMT and NMT. METHODS AND RESULTS: Rats were given the glucocorticoid dexamethasone at doses ranging from 0.2 to 20 mg/kg. Twenty-four hours later, cardiac atria, ventricle, skeletal muscle, and adrenal had increases in PNMT activity to as much as 230% of baseline. NMT activity was unchanged. Longer-term treatment with 1 mg/kg dexamethasone daily for 12 days increased cardiac PNMT activity about fivefold and also increased atrial epinephrine levels. Dexamethasone did not alter ventricular epinephrine levels but increased levels of both PNMT and catechol-O-methyltransferase, the major catabolic enzyme for epinephrine. After dexamethasone treatment, greater volumes of anti-PNMT antiserum were needed to decrease PNMT enzymatic activity, indicating that dexamethasone treatment resulted in greater amounts of PNMT and did not just activate existing PNMT molecules. Denervation of the masseter muscle of rats by unilateral superior cervical ganglionectomy markedly diminished tissue norepinephrine and epinephrine levels but had no effect on masseter PNMT or NMT levels. We have previously shown that chemical sympathectomy with 6-hydroxydopamine increases cardiac PNMT levels. These findings suggest that PNMT is an extraneuronal enzyme in both cardiac and skeletal muscle. CONCLUSIONS: Glucocorticoids have several cardiovascular effects, including increased cardiac output and blood pressure. Enhanced cardiac epinephrine synthesis may mediate some of these glucocorticoid effects.

Adrenal Medulla↗
PubMed1990

Epinephrine synthesis in rat skin by an N-methyltransferase.

Homogenates of rat skin N-methylated norepinephrine to form epinephrine. In the brain and adrenal medulla the enzyme phenylethanolamine-N-methyltransferase synthesizes epinephrine, but the skin epinephrine forming enzyme was an N-methyltransferase distinct from phenylethanolamine-N-methyltransferase. Skin N-methyltransferase was not inhibited by the phenylethanolamine-N-methyltransferase inhibitor SKF 29661. Unlike phenylethanolamine-N-methyltransferase, skin readily methylated dopamine to form epinine. Sympathetic denervation by superior cervical ganglionectomy had no effect on skin N-methyltransferase levels. Procedures that reduced skin norepinephrine levels to 2% of control left skin epinephrine levels at 38% of control even when plasma epinephrine levels were very low. Skin contains an extraneuronal enzyme that synthesizes epinephrine in vitro and appears to synthesize part of the epinephrine normally present in skin. The enzyme can synthesize epinephrine and epinine, both of which can regulate epidermal proliferation, skin blood flow, and atopic responses.

Animals↗
PubMed1990

Epinephrine synthesis by an N-methyltransferase in rat liver.

We investigated if liver can synthesize epinephrine in vitro and in vivo. Homogenates of rat liver readily synthesized [3H]epinephrine from [3H]S-adenosylmethionine and norepinephrine. Liver homogenates also N-methylated dopamine at more than twice the rate that they N-methylated norepinephrine. In contrast, adrenal homogenates, which N-methylate norepinephrine to form epinephrine using the enzyme phenylethanolamine-N-methyltransferase (PNMT), methylated dopamine only about 1% as well as norepinephrine. Synthesis of epinephrine by liver homogenates was not significantly inhibited by the PNMT inhibitor SKF 29661 at a concentration that inhibited adrenal homogenate epinephrine synthesis by nearly 90%. These findings indicate that liver can synthesize epinephrine in vitro using an enzyme other than PNMT. Adrenal demedullation of rats reduced plasma epinephrine levels to 7% of control values, but left liver epinephrine and epinephrine-forming enzyme levels unchanged. Treatment of demedullated rats with 6-hydroxydopamine plus reserpine also resulted in dramatically reduced plasma epinephrine levels but no change in hepatic epinephrine and N-methylating enzyme levels. We conclude that the liver synthesizes its own epinephrine.

Animals↗
PubMed1990

A more sensitive and specific radioenzymatic assay for catecholamines.

This modification of the catechol-O-methyltransferase (COMT) based radioenzymatic assay for norepinephrine (NE) and epinephrine (E) improves sensitivity, selectivity and eliminates many inhibitors of COMT. Prior to assay, samples are extracted into heptane with diphenylborate, then into dilute acetic acid. This extraction procedure has an efficiency of 78% for NE but less than 2% for S-adenosylmethionine (SAM). The extraction procedure also excludes calcium and other COMT inhibitors present in urine, plasma and every tissue tested. This eliminates the requirement for individual standardization of tissue and urine samples. Sensitivity of the assay for NE and E is 10 and 6 pg/ml respectively in 1 ml of plasma. The intraassay coefficients of variation for NE and E are 4 and 13% and the interassay coefficients of variation for NE and E are 10 and 16% in a human plasma sample containing low catecholamine levels. The assay permits quantitation of plasma E levels that were undetectable in prior assays.

Animals↗
PubMed1990

Decreased adrenergic sensitivity in patients with hypothyroidism.

Cardiovascular sensitivity to catecholamines was assessed in 15 patients with hypothyroidism (mean [+/- SEM] thyroxine [T4] index 2.7 +/- 0.5 micrograms/100 ml, thyroid stimulating hormone [TSH] 136.9 +/- 48.3 microU/ml), aged 45 +/- 4 years and in 8 healthy control subjects. The study was repeated in 10 patients with hypothyroidism 4.0 +/- 0.5 months after thyroid replacement therapy (T4 index 9.9 +/- 2.1 micrograms/100 ml, TSH 3.5 +/- 1.3 microU/ml). In addition, basal, average and maximal heart rates were measured using 24 h ambulatory electrocardiographic (ECG) monitoring, and plasma levels of epinephrine and norepinephrine were determined before and after thyroid replacement. Heart rate increased less after bolus injection of 0.8, 1.6 and 3.2 micrograms of isoproterenol in the hypothyroid (10 +/- 2, 15 +/- 2 and 21 +/- 4 beats/min, respectively) than in the euthyroid (16 +/- 3, 22 +/- 3 and 30 +/- 4 beats/min, respectively) state (p less than 0.05). Control subjects reacted similarly to patients receiving thyroid replacement. Basal heart rate (64 +/- 3 versus 68 +/- 3 beats/min, p less than 0.05) and maximal heart rate (116 +/- 5 versus 133 +/- 5 beats/min, p less than 0.05) were lower on 24 h ambulatory ECG monitoring in the hypothyroid than euthyroid state despite higher basal plasma norepinephrine levels (394 +/- 45 versus 315 +/- 45 pg/ml, p less than 0.05). Thus, patients with hypothyroidism display a decreased cardiac chronotropic response to beta-adrenergic stimulation. This may contribute in part to the decreased basal and maximal daily heart rates seen in patients with hypothyroidism, which occurs despite elevated plasma norepinephrine levels.

Adrenergic beta-Agonists↗
PubMed1990

Norepinephrine clearance, chromogranin A and dopamine beta hydroxylase in renal failure.

Plasma norepinephrine (NE) levels are normal or elevated in patients with renal failure even though uremia often damages the sympathetic nerves that release NE. We infused 3H-NE into subjects with normal, mildly depressed, or absent renal function. 3H-NE clearance was depressed 20% in mild renal failure and 40% in patients on hemodialysis. The calculated rate of NE release into plasma was low in uremics even though their plasma NE was normal. Dopamine beta hydroxylase (D beta H) and chromogranin A are released from sympathetic nerve endings along with NE. D beta H levels were low in uremia and D beta H levels doubled following hemodialysis. Chromogranin A levels were very high in uremics and increased slightly following hemodialysis. Plasma clearance of both NE and chromogranin A appears low in renal failure. The calculated rate of NE release is diminished in uremics, which is in accord with reports of autonomic neuropathy in these patients.

Adult↗
PubMed1990

Invasive fusariosis associated with an injury by a stingray barb.

A previously healthy adult male suffered a wound to the dorsal ulnar aspect of his right hand by a stingray barb while fishing off the East coast of Florida. Two weeks after the imbedded barb had been surgically removed, an erythematous lesion developed around the wound. Histopathologic and microbiological studies revealed infection caused by Fusarium solani. The patient was successfully treated with debridement and skin grafting in conjunction with ketoconazole therapy.

Adult↗
PubMed1990

Elevated insulin, norepinephrine, and neuropeptide Y in hypertension.

To investigate the relationship between insulin and sympathetic activity, plasma norepinephrine, neuropeptide Y, serum glucose and insulin concentrations were measured in ten age-, weight-, and sex-matched normotensive and untreated hypertensive subjects at fasting and 2 h following ingestion of a 75 g oral glucose dose. Hypertensives had higher fasting serum insulin (27 +/- 6 v 12 +/- 2 microU/mL; P = .02) and plasma norepinephrine (356 +/- 38 v 235 +/- 35 pg/mL; P = .03) concentrations than normotensives. Glucose load increased serum insulin (P less than .001) and plasma norepinephrine concentrations (P = .001) in both groups and hypertensives had still higher postglucose insulin (P = .003) and norepinephrine levels (P = .003) than normotensives. Fasting neuropeptide Y was higher in hypertensives than in normotensives (P = .03) and correlated with age in both groups (r = 0.7; r = 0.77). Postglucose serum insulin correlated positively with plasma norepinephrine (r = 0.75; P = .013) in normotensives, but these parameters correlated negatively in hypertensives (r = -0.7; P = .036). We hypothesize that elevated plasma norepinephrine and neuropeptide Y levels reflect an increased level of sympathetic nervous activity in hypertensives, which in turn may be responsible for the abnormal relationship between plasma NE and insulin levels.

Blood Glucose↗
PubMed1990

Sources of urinary catecholamines in renal denervated transplant recipients.

When a human kidney is transplanted, sympathetic nerves to that kidney are cut. We infused 3H-noradrenaline and then measured noradrenaline, dopamine and 3H-noradrenaline levels in the plasma and urine of renal transplant recipients and uninephrectomized control subjects. Less than 10% of 3H-noradrenaline cleared from the plasma appeared in the urine. Noradrenaline and dopamine appeared in the urine of transplant recipients at one-third the rate of control subjects, even though 3H-noradrenaline levels were slightly higher in the urine of transplant recipients. Transplant patients had a noradrenaline clearance of 128 +/- 50 ml/min, compatible with simple glomerular filtration, while controls had a higher calculated clearance of 229 +/- 41 ml/min. Plasma dopamine levels were very low compared with urinary dopamine. These results suggest that two-thirds of renal noradrenaline and dopamine depend on the presence of renal nerves. Almost all urinary dopamine comes from the kidney. For noradrenaline, urinary excretion is a very minor pathway for clearance from the plasma.

Adult↗
PubMed1990

Lung epinephrine synthesis.

We studied in vitro and in vivo epinephrine (E) synthesis by rat lung. Nine days after removal of the adrenal medullas, circulating E was reduced to 7% of levels found in sham-operated rats but 30% of lung E remained. Treatment of demedullated rats with 6 hydroxydopamine plus reserpine did not further reduce lung E. In the presence of S-[3H]adenosylmethionine lung homogenates readily N-methylated norepinephrine (NE) to form [3H]E. The rate of E synthesis by lung homogenates was progressively more rapid with increasing NE up to a concentration of 3 mM, above which it declined. The rate of E formation was optimal at an incubation pH of 8 and at temperatures of approximately 55 degrees C. We compared the E-forming enzyme(s) of lung homogenates with those of adrenal and cardiac ventricle. The adrenal contains mainly phenylethanolamine N-methyltransferase (PNMT), which is readily inhibited by SKF 29661 and methylates dopamine (DA) very poorly. Cardiac ventricles contain mainly nonspecific N-methyltransferase (NMT), which is poorly inhibited by SKF 29661 and readily methylates both DA and NE. Lung homogenates were inhibited by SKF 29661 about half as well as adrenal but more than ventricle. We used the rate of E formation from NE as an index of PNMT-like activity and deoxyepinephrine synthesis from DA as an index of NMT-like activity. PNMT and NMT activity in rat lung homogenates were not correlated with each other, displayed different responses to change in temperature, and were affected differently by glucocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1990

Plasma norepinephrine kinetics, dopamine-beta-hydroxylase, and chromogranin-A, in hypothyroid patients before and following replacement therapy.

Whether the increased plasma norepinephrine level reported in hypothyroidism is the result of impaired norepinephrine (NE) clearance or increased NE release by nerve terminals is unknown. We, therefore, measured plasma NE levels and clearance in 11 hypothyroid patients before [T4 index, 41.2 +/- 7.7 nmol/L (mean +/- SEM); TSH, 71.4 +/- 23.0 mU/L] and 4 +/- 0.5 months after thyroid replacement (T4 index, 136.4 +/- 24.4 nmol/L; TSH, 3.2 +/- 1.2 mU/L) and in 8 healthy volunteers. Plasma dopamine-beta-hydroxylase and chromogranin-A, which are coreleased with NE by sympathetic nerve endings, were also measured. Plasma NE was higher in the hypothyroid (2.37 +/- 0.24 nmol/L) than in the euthyroid state (1.86 +/- 0.24 nmol/L; P less than 0.02) or in the controls (1.87 +/- 0.27 nmol/L). Plasma clearance of NE, however, was not affected after thyroid replacement (hypothyroid, 2.08 +/- 0.31 L/min; euthyroid, 1.94 +/- 0.21 L/min; controls, 1.86 +/- 0.15 L/min). There was no significant change in plasma dopamine-beta-hydroxylase (hypothyroid, 720 +/- 139 nmol/mL.h; euthyroid, 553 +/- 97 nmol/mL.h) or plasma chromogranin-A (hypothyroid, 48.9 +/- 7.1 ng/mL; euthyroid, 42.9 +/- 5.3 ng/mL) after thyroid replacement. We conclude that the increased plasma NE in hypothyroid patients is not due to a change in plasma clearance, but is more likely secondary to increased NE release.

Adult↗
PubMed1990

Decreased sensitivity to alpha-adrenergic stimulation in hypothyroid patients.

Nine hypothyroid patients had blood pressure and pulse rate responses to the alpha-adrenergic agonist phenylephrine measured before [T4 index, 45.045 +/- 9.009 nmol/L (mean +/- SEM); TSH, 57.1 +/- 23.6 mU/L] and after 4 +/- 0.5 months of thyroid replacement therapy (T4 index, 141.570 +/- 29.601 nmol/L; TSH, 2.6 +/- 1.0 mU/L). Hypothyroid patients had a smaller blood pressure increment and heart rate decrement at both 66.7 and 100 micrograms/min infusion rates of phenylephrine. Furthermore, the slope of the dose-response curves for systolic (2.06 +/- 0.22 vs. 1.32 +/- 0.19; P less than 0.01) and diastolic (1.04 +/- 0.18 vs. 0.62 +/- 0.08; P less than 0.01) blood pressures were significantly greater after thyroid replacement therapy. Pulse rate changes remained proportional to blood pressure changes in hypothyroid patients, so there was no change in baroreflex sensitivity. Plasma norepinephrine levels were higher before than after thyroid replacement (2.41 +/- 0.28 vs. 1.82 +/- 0.29 nmol/L, respectively; P less than 0.01). Thus, hypothyroid patients have diminished pressor sensitivity to an alpha-adrenergic agonist and increased plasma levels of the alpha-adrenergic neutrotransmitter norepinephrine.

Adult↗