Search PubMed⌕ Search

Biomedical subjects

C R Lake

Publications and source records attributed to C R Lake.

At least 37 records · Page 2Linked to original sources
PubMed1988

Plasma and urinary catecholamines in salt-sensitive idiopathic hypertension.

Nineteen patients with normal renin idiopathic hypertension were arbitrarily classified as salt-sensitive or salt-resistant depending on whether their mean arterial pressure did or did not increase by 8% or more when sodium intake was increased. The responses of the two subsets and of five normal subjects to sodium intakes of 9, 109, and 249 mEq/day given for 7 days were as follows: The salt-sensitive subjects retained more sodium than normal and plasma or urinary norepinephrine did not decrease when they were given a high sodium intake; urinary dopamine was normal but did not increase normally when sodium intake was increased. The salt-resistant subjects excreted sodium normally and plasma and urinary norepinephrine was decreased by 30 and 37%, respectively, when they were given a high sodium intake; urinary dopamine was supernormal and did not increase further when sodium intake was increased. Cumulative sodium retention during the high sodium intake was directly related to the percentage of change in plasma norepinephrine in the hypertensive subjects, suggesting that renal adrenergic activity was a factor in the impaired sodium excretion in the salt-sensitive patients. Cumulative sodium retention and the percentage of change in plasma norepinephrine were inversely related to urinary dopamine in the hypertensive subjects, suggesting that increased formation of dopamine in renal and neural tissue in the salt-resistant subjects may have been responsible for the differences between the subsets in renal and adrenergic responses to a high sodium intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Hemodynamic and neural mechanisms of action of thyrotropin-releasing hormone in the rat.

The mechanisms mediating the effects of thyrotropin-releasing hormone (TRH) on the cardiovascular system were studied in the conscious rat. Intracerebroventricular (i.c.v.) injection of TRH (8 pmol-80 nmol/kg) induced dose-dependent increases in mean arterial pressure, heart rate, and cardiac index. Hindquarter blood flow increased due to vasodilation, while an increase in renal and mesenteric vascular resistance caused a decrease in blood flow in the respective organs. The plasma levels of norepinephrine and epinephrine were increased by TRH, while there was no change in plasma renin activity or vasopressin. The cardiovascular actions of i.c.v. TRH were not influenced by blockade of the renin-angiotensin system or vasopressin receptors. The ganglion blocker chlorisondamine and the alpha 1- and alpha 2-adrenoreceptor antagonist phentolamine (2 mg/kg i.v.) abolished the increase in blood pressure and mesenteric vasoconstriction after i.c.v. TRH. Propranolol (2 mg/kg i.v.) blocked the TRH-induced increase in cardiac index, heart rate, and hindquarter blood flow. The hindquarter vasodilation induced by TRH was also blocked by the selective beta 2-adrenoceptor antagonist ICI 188,551 (1 or 2 mg/kg i.v.), while the beta 1-adrenoceptor blocker practolol (10 mg/kg i.v.) had no effect on the hindquarter vasodilation produced by TRH but totally blocked the increase in cardiac index. In adrenal demedullated rats, the systemic hemodynamic effects of i.c.v. TRH were diminished along with the decrease in renal blood flow and increase in renal vascular resistance; however, the increase in hindquarter blood flow was attenuated only in adrenal demedullated rats pretreated with the sympathetic blocker bretylium. The renal vasoconstriction induced by i.c.v. TRH was not abolished by renal denervation. In sinoaortic debuffered rats, the pressor, tachycardic, and mesenteric vasoconstrictor responses to centrally administered TRH were significantly potentiated. Taken together, these data suggest that the putative neurotransmitter TRH may play a role in central regulation of cardiac functions and organ blood flow distribution through both the sympathetic nerves and the adrenal medulla. A pivotal role for beta 2-adrenoceptors in mediation of hindquarter vasodilation is also demonstrated.

Adrenalectomy↗
PubMed1988

Disulfiram-induced fulminating hepatitis: guidelines for liver-panel monitoring.

Although psychiatrists have medical responsibility for many alcoholic patients, the psychiatric literature, in contrast with the general medical literature, contains few reports of disulfiram-induced hepatotoxicity. For that reason, the authors review the literature on disulfiram hepatitis and report a case of severe fulminating hepatitis associated with disulfiram use, despite careful and currently accepted standard-of-care clinical and biochemical monitoring. All but two of the 17 disulfiram-associated hepatotoxic cases reviewed developed symptoms after 2 weeks to 2 months of use. Six patients died. This article discusses strategies for avoiding that rare but life-threatening side effect. The strategies include more frequent initial measurements of liver enzymes than is now accepted. Currently, only two reports recommend liver-function studies on a regular schedule for patients taking disulfiram. The authors believe that liver-function tests should be administered before treatment, at 2-week intervals for 2 months, and at 3- to 6-month intervals thereafter. The authors emphasize that the hepatotoxicity reaction is rare and do not discourage the use of disulfiram in appropriate patients; rather, they wish to heighten the index of suspicion to disulfiram-induced hepatotoxicity.

Adult↗
PubMed1987

Biochemical changes during clomipramine treatment of childhood obsessive-compulsive disorder.

Peripheral measures of serotonergic and noradrenergic function were obtained in 29 obsessive-compulsive adolescents and 31 age- and sex-matched controls, as well as in a subsample of 22 patients after five weeks of treatment with clomipramine hydrochloride (134 +/- 33 mg/d) (mean +/- SD) given in a double-blind placebo-controlled trial. Drug-free obsessive-compulsive subjects did not differ from controls on measures of platelet serotonin and monoamine oxidase (MAO) activity, nor on plasma epinephrine or norepinephrine concentrations at rest and after a standard orthostatic challenge procedure. Compared with placebo, treatment with clomipramine was clinically effective and produced a marked decrease in platelet serotonin concentration, a trend toward a reduction in platelet MAO activity, and a rise in standing plasma norepinephrine. Clinical improvement during drug therapy was closely correlated with pretreatment platelet serotonin concentration and MAO activity, as well as with the decrease in both measures during clomipramine administration. This suggests that the effects of clomipramine on serotonin uptake may be essential to the antiobsessional action observed.

Adolescent↗
PubMed1987

Radioenzymatic determination of phenylpropanolamine in plasma.

We modified a norepinephrine radioenzymatic method (C. R. Lake, M. G. Ziegler, and I. J. Kopin, 1976, Life Sci. 18, 1315-1326) for determination of plasma phenylpropanolamine (PPA) concentrations. PPA is converted to N[methyl-3H]ephedrine ([3H]EPD) by the enzyme phenylethanolamine N-methyltransferase (PNMT) and S-[methyl-3H]adenosyl-L-methionine ([3H]AdoMet). The product, [3H]EPD, is isolated from unreacted [3H]AdoMet and labeled side products by an organic extraction and a TLC procedure. In addition, a preincubation organic extraction procedure is included to remove inhibitors of PNMT from plasma and to concentrate the sample for enhanced enzymatic conversion. In order to accurately quantitate PPA across the wide range of possible concentrations, the assay is conducted at two plasma volumes. PPA concentrations between 0.3 and 50 micrograms/liter can be detected with 1 ml of plasma, while concentrations between 4 and 1500 micrograms/liter can be detected with 0.1 ml of plasma. The intra-assay coefficients of variation (CVs) are 9.3 and 5.7% at 0.5 and 1500 micrograms/liter, respectively, while the mean interassay CV is 13.8%.

Humans↗
PubMed1987

Cyclothymic disorder and bromocriptine: predisposing factors for postpartum mania?

Women are most susceptible to psychotic reactions during the postpartum period, a time of intense psychological and physiological stress. Mania and depression are particularly common at this time, especially in women with past or family histories of major or minor affective disorders, specifically cyclothymia and dysthymia. Close attention after childbirth is warranted to alleviate and prevent these episodes in such women. Sympathomimetic drugs such as bromocriptine and the over-the-counter diet aids, which are linked to the induction of manic episodes, are frequently used in the puerperal period and may act as catalysts. This case report documents a postpartum manic episode in a cyclothymic woman who was prescribed bromocriptine, a dopamine agonist, for prevention of lactation.

Adult↗
PubMed1987

Hormonal changes during decompression sickness.

Changes in plasma hormone levels were studied in anesthetized dogs during decompression sickness. Hormone levels were measured in 4 groups: control (no dive, n = 9); air group (air dive, ventilated with air postdive, n = 6); helium-oxygen (He-O2) group (air dive, ventilation changed to He-O2 at 30 min postdive, n = 9); nonsurvivor group (air dive, died within 30 min postdive, n = 9). Dived animals were subjected to repetitive dives until pulmonary artery pressure doubled. Plasma epinephrine (Epi) and norepinephrine (NE) concentrations rapidly increased postdive in all animals. Serum angiotensin-converting enzyme (ACE) activity increased postdive in the He-O2 group only, and these increases were small. Diving did not alter serum concentrations of cortisol, thyroxine (T4), or triiodothyronine (T3); however, T4 and T3 fell in all animals, probably as a consequence of anesthesia. He-O2 breathing did not affect concentrations of Epi, NE, cortisol, T4, T3, or serum ACE activity.

Animals↗
PubMed1987

Prevalence and recognition of depression among primary care outpatients.

Studies indicate that more individuals suffering from depressive symptoms will present to the primary care outpatient clinic than to any other medical care setting. Unfortunately, most of these patients complain of somatic problems, not mood disturbances. Consequently, less than one half of all depressed patients in the primary care clinic are initially identified and treated for their depression. As depression causes considerable morbidity and some mortality and is treatable, methods of improving recognition should be sought. Some of these include maintaining a high index of suspicion, conducting a brief but thorough screening interview for depression, and using a depression rating scale. Benefits derived from early recognition include saving time, effort, and money spent on unnecessary tests and inappropriate treatment, and avoiding substantial suffering. The threshold for many somatic complaints can be substantially raised with resolution of depression.

Depression↗
PubMed1987

Initial severity and diagnosis influence the relationship of tricyclic plasma levels to response: a statistical review.

There is considerable controversy about the clinical value of monitoring tricyclic antidepressant plasma levels. To investigate this issue the authors pooled data from 17 published plasma level studies of imipramine, amitriptyline, or nortriptyline, involving over 400 patients. The findings suggest that tricyclic antidepressant plasma level monitoring is important primarily for patients who are severely depressed or who have endogenous features. Monitoring is especially important for such patients who are treated with amitriptyline or nortriptyline, since failure to respond may be associated with very low or very high plasma levels. These data have implications for tricyclic antidepressant plasma level monitoring and future research.

Antidepressive Agents, Tricyclic↗
PubMed1987

Anticholinergic prophylaxis of acute haloperidol-induced acute dystonic reactions.

Young adults treated with a high potency neuroleptic such as haloperidol are at high risk of developing dystonic reactions. In this retrospective study, 15 of 16 young adult patients treated only with haloperidol had such reactions within 60 hours of beginning the drug, while none of the seven patients treated with haloperidol plus prophylactic benztropine mesylate developed dystonia. Although methodologic considerations limit the generalization of these results, they are consistent with other reports and suggest that initial anticholinergic prophylaxis is warranted in young patients treated with high potency antipsychotics. All dystonic reactions in these patients occurred within 2 1/2 days, justifying the consideration of discontinuing prophylaxis (which also causes side effects) after 1 week.

Acute Disease↗
PubMed1987

Hormonal responses to graded surgical stress.

We tested the hypothesis that selected hormonal responses to surgery reflect the degree of surgical stress. Plasma norepinephrine, epinephrine, thromboxane B2, cortisol, serum angiotensin converting enzyme, thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine levels were measured preoperatively, and then one hour, 24 hours, and five days postoperatively in three groups of patients. The groups were as follows: group 1, "minimal" stress, eg, inguinal hernia repair (n = 10); group 2, "moderate" stress, eg, cholecystectomy (n = 12); and group 3, "severe" stress, eg, subtotal colectomy (n = 9). Patients in group 1 showed no significant surgery-induced changes in hormonal values. The stress-induced changes in patients in groups 2 and 3 were seen at one and occasionally 24 hours; however, by five days postoperatively, circulating hormone values had returned to preoperative levels. Increases in plasma cortisol, norepinephrine, and epinephrine, and decreases in serum angiotensin converting enzyme levels characterized the surgery-induced hormonal changes. Conclusions are as follows: hormonal responses do reflect the degree of surgical stress; the hormonal changes are transient, lasting no longer than 24 hours in patients after uncomplicated surgery; hormonal responses to minimal surgical stress are negligible.

Adult↗
PubMed1986

Indices of noradrenergic output in depression.

Concentrations of plasma norepinephrine (NE) and plasma-3-methoxy-4-hydroxyphenylglycol (MHPG), blood pressure, and heart rate were measured on 2 days in 25 depressed patients and 25 controls. Comparisons were made between patients and controls, and also between days for both groups, to determine the short-term stability of these measures. The means of the plasma and urinary noradrenergic metabolite measures were not significantly different between groups. The variance of plasma MHPG, plasma NE, and mean blood pressure was greater in the depressed patients than in controls. Blood pressure, plasma MHPG, and plasma NE were relatively stable as suggested by the significant correlations between the 2 days for each of these variables. Plasma NE, plasma MHPG, and the sum of the deaminated urinary metabolites (MHPG and vanillylmandelic acid) were significantly intercorrelated. These results support other data in suggesting that plasma concentrations of NE and MHPG may be useful measures of noradrenergic activity, but may not consistently distinguish depressed patients from controls.

Adult↗
PubMed1986

Sympathetic nervous withdrawal in the vasodepressor (vasovagal) reaction.

When 40 subjects had 134 ml of blood drawn, 8 of them developed hypotension. These 8 subjects were younger, and when they stood they decreased their systemic arterial pressure, pulse rate and plasma norepinephrine. In contrast, normal subjects increased all these parameters after standing. The fall in plasma norepinephrine suggests a generalized withdrawal of sympathetic nervous tone during vasodepressor reactions. Three subjects maintained a heart rate above 60, but still developed hypotension. Withdrawal of sympathetic tone to the vasculature appears more important than increased vagal tone to the heart in causing hypotension in this reaction.

Adrenergic Fibers↗
PubMed1986

The effect of propranolol on catecholamine clearance.

Normal subjects given propranolol increased their plasma t1/2 for infused isoproterenol from 2.68 to 6.25 minutes. Propranolol increased plasma norepinephrine (NE) levels only slightly. Propranolol increased the t1/2 of isoproterenol but not that of NE in men with autonomic nervous system degeneration. This suggests that propranolol acts on nonneuronal uptake-2 processes, rather than on uptake-1 mechanisms. alpha-Blockers slow uptake-1 and beta-blockers slow uptake-2 processes. When 27 subjects exercised, those who attained the highest plasma levels of the alpha- and beta-receptor agonist NE also had the briefest apparent t1/2 for NE. Adrenergic receptor blocking drugs slow catecholamine clearance. NE may stimulate its own clearance.

Blood Pressure↗
PubMed1986

Hemorrhagic hypotension increases plasma beta-endorphin concentrations in the nonhuman primate.

The role which beta-endorphin plays in the pathogenesis of hemorrhagic hypotension is controversial. In the present experiment, 20 ml/kg of blood was bled from ten healthy male baboons (Papio anubis) over 60 min and then retransfused over the next 30 min. We found that the mean plasma beta-endorphin level increased 109% above baseline (p less than .05) within 15 min after starting hemorrhage, and rapidly returned to a baseline concentration with retransfusion. We conclude that in a primate species, circulating endogenous opioid peptide concentrations increase rapidly in response to sublethal hemorrhagic hypotension and normalize with restoration of the baseline intravascular volume. These findings support the concept that endogenous opioid peptides may mediate the hypotension of shock states.

Animals↗
PubMed1986

Positive end-expiratory pressure increases plasma catecholamine levels in non-volume loaded dogs.

UNLABELLED: Positive end-expiratory pressure (PEEP) is commonly used in the treatment of critically ill patients whose sympathetic nervous system is stressed; however, PEEP's actions on sympathetic nervous system activity are unknown. We therefore measured the plasma noradrenaline response (an index of sympathetic nervous system activity) to graded doses of PEEP in nine mongrel dogs. After 30 minutes at each level of PEEP, plasma noradrenaline concentrations increased from baseline mean values of 300 (SD 108) pg/ml to 388 (SD 225) pg/ml (P less than 0.05) at 5 cm, 433 (SD 255) pg/ml (P less than 0.01) at 10 cm and 1194 (SD 882) pg/ml (P less than 0.01) at 20 cm water pressure of PEEP. The increases in plasma noradrenaline concentrations correlated inversely (r = -0.43, P less than 0.01) with PEEP-induced changes in cardiac output. Plasma adrenaline levels did not change significantly in response to 5 or 10 cm of PEEP; however, plasma adrenaline increased, while heart rate and mean arterial blood pressure fell, at 20 cm water pressure of PEEP (P less than 0.05). Within 15 minutes after discontinuation of PEEP, the plasma catecholamine concentrations returned to baseline levels. CONCLUSIONS: 1. PEEP significantly increases sympathetic nervous system activity in a rapid, dose-dependent, reversible manner; 2. the PEEP-induced increases in sympathetic activity may explain the reductions in organ blood flow which others have observed following the initiation of PEEP; 3. PEEP-related changes in sympathetic nervous system activity are a consequence of PEEP-induced reductions in cardiac output.

Animals↗
PubMed1986

Glucagon: endocrine effects and calcium involvement in cardiovascular actions in dogs.

Although the cardiovascular effects of glucagon are understood, its mechanism(s) of action remains unclear. We studied the effects of increasing doses of glucagon (0.001, 0.01, 0.1 mg/kg) on cardiovascular responses in dogs relative to concurrent measurements of circulating glucagon, cyclic AMP, glucose, norepinephrine, epinephrine, triiodothyronine, thyroxine, and cortisol levels. Glucagon-induced increases in plasma cyclic AMP, glucose, and catecholamine concentrations paralleled the heart rate response to glucagon administration. Further studies were conducted to evaluate the role of beta-adrenergic function as well as calcium in mediating glucagon's actions. The tachycardic effects of glucagon (0.01 mg/kg) were unaltered by prior beta-adrenergic receptor blockade with propranolol (3.5 mg/kg total dose). The calcium antagonist verapamil (0.2 mg/kg bolus then 7.5 micrograms/kg/min/infusion) prevented glucagon-induced increases in heart rate. However, the coadministration of glucagon (0.01 mg/kg) with calcium (1.0, 5.0, 10.0, or 50.0 mg/kg) did not alter glucagon's cardiovascular effects. These data indicate that glucagon is a potent tachycardiac agent that also elevates circulating endocrine-related substances. The antagonism of glucagon's tachycardiac effects by verapamil suggests that glucagon's action may be via glucagon-induced calcium movement through calcium channels, although extracellular calcium changes do not alter glucagon's effect. Furthermore, the persistence of glucagon's cardiovascular actions following beta-adrenergic blockade indicates the potential clinical utility of glucagon in reversing the adverse effects of beta-blocker overdoses, and its potential usefulness in treating circulatory shock in "beta-blocked" patients.

Animals↗