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Biomedical subjects

B Chernow

Publications and source records attributed to B Chernow.

At least 73 records · Page 4Linked to original sources
PubMed1988

A double dose of phenylpropanolamine causes transient hypertension.

PURPOSE: Phenylpropanolamine is widely used and freely available without a doctor's prescription in drug and grocery stores; it is the active ingredient in most diet aids and many cold preparations. Several cases of multiple cerebral hemorrhages associated with transient hypertension have recently been attributed to phenylpropanolamine in dosages equal to or less than that contained in two diet aids (i.e., 150 mg). Some evidence also exists on the additive effects of the co-ingestion of phenylpropanolamine and caffeine. We therefore undertook a study to demonstrate that a significant health risk can be caused by a double dose of a typical over-the-counter (OTC) diet aid (i.e., 150 mg phenylpropanolamine) and also when 75 mg phenylpropanolamine is taken with caffeine. SUBJECTS AND METHODS: Five men and one woman, ranging in age from 20 to 30, participated in this study. The drug preparations were administered to each subject on different study days in a double-blind, randomized-crossover design. Identical capsules contained 75 mg sustained-release phenylpropanolamine, 400 mg of sustained-release caffeine, or placebo. Subjects ingested three capsules at the beginning of each study day. For 150 mg, two phenylpropanolamine-containing capsules and one placebo were taken; for 75 mg, one phenylpropanolamine capsule and two placebos; and for phenylpropanolamine plus caffeine, one 75 mg phenylpropanolamine capsule, one 400 mg caffeine capsule, and one placebo. Blood pressure and heart rate were monitored throughout the study. RESULTS: Although 75 mg of phenylpropanolamine did not cause clinically relevant hypertension in our subjects, 150 mg of phenylpropanolamine and 75 mg of phenylpropanolamine plus 400 mg caffeine did result in significant blood pressure increases into the hypertensive range. CONCLUSION: We believe that consumers often assume that double the recommended dosage of an OTC drug is safe and more effective. We suggest that requiring a physician's prescription or an additional, stronger warning label on phenylpropanolamine-containing products may prevent substantial mortality and morbidity.

Adult↗
PubMed1988

The effects of phenylpropanolamine on human sympathetic nervous system function.

Phenylpropanolamine (PPA) is a sympathomimetic agent, very similar in structure to amphetamine. In the United States, it is present in over 130 medications, primarily anorectic agents and cough and cold remedies, many available without a prescription. The effects of PPA on blood pressure (BP) remain controversial and its mechanisms of action unknown. We studied acute (1 and 2 hours) and 2-week effects of a daily dose of 75 mg of sustained release PPA administered to 14 normal volunteers. Measurements of heart rate, BP, and plasma catecholamines (CA) were made with the subject in the supine and standing positions, and upon gripping a hand dynamometer for 5 minutes. Although systolic BP across all postures and sampling times was significantly higher when subjects were taking PPA in comparison to placebo (F = 5.95, p = 0.03), in no subject did the increase in BP reach hypertensive or clinically significant levels and no substantial changes in CA levels were found. Our study population was relatively young and normotensive; even such a small BP increase may pose greater problems for hypertensive, obese subjects likely to be users of diet aids. Strenuous isometric exercise did not cause any greater increase in BP or CA after subjects took PPA versus placebo. PPA blood levels 24 hours after the last of 14 daily doses were similar to levels 1 and 2 hours after an initial dose. We conclude from these data that recommended doses of PPA have only minimal sympathetic nervous system (SNS) and cardiovascular effects in young, healthy, normotensive populations at the times and dose studied.

Adult↗
PubMed1988

Glucagon antagonism of calcium channel blocker-induced myocardial dysfunction.

Calcium channel blockers (CCBs) may produce profound myocardial depression. Glucagon antagonized verapamil-induced hypotension and bradycardia in rats; however, glucagon's ability to antagonize other CCBs is unexplored. This study determined: a) if glucagon reverses verapamil-induced depression by a direct cardiac effect, b) if myocardial depression induced by diltiazem and nifedipine (representing different classes of CCBs) is also reversed by glucagon, and c) the glucagon concentration needed to reverse myocardial depression. Isolated rat hearts were perfused at a constant flow rate in a Langendorff preparation. Developed pressure (dP), contractility (+dP/dtmax), relaxation (-dP/dtmax), heart rate, and coronary vascular resistance were recorded. A CCB (n = 6, each blocker) was infused until greater than 50% depression of contractility was achieved. Glucagon was then simultaneously infused (perfusion concentration of 0.6-1.1 x 10(-7) M), and repeat cardiac variables were recorded. In a separate group of 36 hearts, glucagon dose response was determined. After producing a greater than 50% depression in dP/dtmax with 3 mumol of diltiazem, a single concentration of glucagon was infused simultaneously into each heart (perfusion concentrations between 10(-6) and 10(-9) M) and percent recovery of baseline function was determined. Glucagon restored baseline contractility and dP with all three CCBs. Complete reversal of diltiazem-induced myocardial depression occurs at glucagon concentrations greater than or equal to 5 x 10(-7) M. We conclude that a) glucagon directly reverses myocardial depression from three classes of CCBs at concentrations achieved in vivo, and b) glucagon may be useful in the treatment of CCB-induced myocardial toxicity.

Animals↗
PubMed1988

The effects of acupuncture on operative pain and the hormonal responses to stress.

Variations in study results presented in this chapter may be attributed to a number of factors, including the population studied and type of hormonal assay used. Some researchers selected experimental groups from a population different from that used for the control group. It is unclear from the animal studies using nonacupunctured controls whether the controls received physical contacts with the experimenters comparable to those experienced by the experimental animals. The choice of acupuncture points used may also contribute to the inconsistency between experiments, since according to traditional acupuncture theory, points are not equivalent in their mediation of systemic effects. Duration of the acupuncture treatment, frequency of sampling, and time from treatment to last sample were not standardized. There is little consistency between studies even after adjustment for sampling time. Most of the statistically significant changes have been seen with electroacupuncture, and they appear to occur soon after onset of treatment, then disappear within 30 minutes of needle removal. However, the subjective changes in pain threshold have lasted several hours following needle removal. As an analgesic technique or adjuvant, acupuncture has been used most successfully in dental procedures and relatively superficial operations such as thyroidectomy; however, it has also been employed in more complex operations. The blood pressure and heart rate stability that have been observed with acupuncture analgesia have not been sufficiently explained and warrant further investigation, as does the possibility that acupuncture may be helpful in shock states characterized by increased stress hormone concentrations.

Acupuncture Therapy↗
PubMed1988

Endotoxin-induced hypocalcemia results in defective calcium mobilization in rats.

Hypocalcemia is common in critically ill patients with sepsis; however, its etiology remains unclear. We have previously reported that hypocalcemia occurs in approximately 20% of patients with gram-negative septicemia. Based upon this finding, we evaluated the effect of endotoxin on calcium homeostasis in laboratory animals. We report here that endotoxin produces a dose-related decrease in circulating ionized calcium levels and impairs calcium mobilization during ethylenebis (oxyethylenenitrilo)-tetraacetic acid infusion. We conclude that endotoxin or its products can cause ionized hypocalcemia during sepsis by impairing calcium mobilization.

Animals↗
PubMed1988

Hypercalcemia attenuates blood pressure response to epinephrine.

The potent alpha and beta adrenergic actions of epinephrine are probably mediated through an increase in free intracellular calcium concentration. Despite an absence of experimental evidence, many clinicians administer epinephrine with calcium to augment its cardiovascular effects. We evaluated the effects of calcium on epinephrine's pressor response in both normal and endotoxin-treated rats by administering epinephrine to animals made hypercalcemic with calcium chloride or hypocalcemic with the calcium chelator EGTA. EPI, given in incremental doses of 10, 20 and 50 micrograms/kg, produced incremental increases in mean arterial pressure. Calcium chloride infused i.v. at a rate of 50 mg/ml/hr significantly (P less than .05) blunted (50% decrease) the hypertensive response to 50 micrograms/kg epinephrine in normal animals. In endotoxin-treated rats, calcium chloride at 50 mg/ml/hr significantly blunted the hypertensive response to 10 micrograms/kg (73% decrease), 20 micrograms/kg (62% decrease) and 50 micrograms/kg (50% decrease) epinephrine. Endotoxemia plus calcium chloride at 25 mg/ml/hr also significantly blunted (30% decrease) the hypertensive response to 50 micrograms/kg EPI. By contrast, hypocalcemia produced by EGTA (30 mg/ml/hr) had no effect on epinephrine's hypertensive effects in normal or endotoxemic rats. Since calcium chloride significantly diminishes epinephrine's hypertensive effects in both normal and endotoxin-treated rats, the clinical use of calcium chloride along with epinephrine may not have a sound experimental basis.

Animals↗
PubMed1987

Pharmacotherapy of circulatory shock.

The rubric "shock" encompasses a wide spectrum of critical events, which if untreated, result in morbidity and mortality. Understanding of the various forms of shock has evolved rapidly in the past 20 years as new laboratory and clinical observations have been published. In this article, the authors discuss the physiology of the shock state, review the circumstances in which shock becomes likely, and review the etiologies and diagnostic characteristics of distributive (septic, spinal, anaphylactoid/anaphylactic), cardiogenic, hypovolemic, and obstructive shock. The rationale and applications of conventional and controversial therapies are discussed. The therapeutic potentials of current lines of shock research are also discussed.

Cardiotonic Agents↗
PubMed1987

Pharmacologic management of the critically ill patient in the perioperative period--emphasis on the sepsis syndrome.

The critically ill perioperative patient requires complex pharmacologic management. The ability to measure circulating drug concentrations has helped the clinician to properly modulate therapy, especially with potentially toxic agents. Postoperative sepsis remains a difficult therapeutic problem. Controversial therapies, such as the use of corticosteroids and the utility of newer pharmacologic approaches, are beginning to be properly tested in multicenter trials. Improvements in technology (e.g., development of monoclonal antibodies), biochemistry, and pharmacology have resulted in the development of exciting, new pharmacologic avenues for the management of the critically ill perioperative patient.

Bacterial Infections↗
PubMed1987

Verapamil reverses calcium cardiotoxicity.

High circulating concentrations of calcium are toxic to the heart and may cause cardiac arrhythmias and arrest. To investigate the therapeutic use of calcium antagonists in hypercalcemia, we evaluated the efficacy of verapamil hydrochloride and magnesium chloride in the treatment of experimental calcium-induced cardiac arrest in laboratory rats. Verapamil rapidly reversed the experimental calcium-induced arrest and improved survival (83% survival versus 0% in controls). Magnesium failed to reverse this toxic event. We conclude from these experimental studies that verapamil may be useful in the treatment of hypercalcemic cardiac toxicity.

Animals↗
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

Free fatty acids alter calcium binding: a cause for misinterpretation of serum calcium values and hypocalcemia in critical illness.

FFAs are bound with calcium on the albumin molecule. We hypothesized that changes in circulating FFA levels during critical illness altered calcium-albumin binding. We found that serum from both normal subjects and critically ill patients contained an ether-extractable factor which lowered ionized calcium concentrations and increased albumin-calcium binding. This factor was found in higher concentrations in serum from ill patients. Oleic acid and palmitic acid increased albumin-calcium binding from 2-28% in a dose-dependent manner when added in vitro to calcium-albumin solutions. Scatchard analysis demonstrated that 0.1 mM oleic acid increased the number of calcium-binding sites on the albumin molecule (from three to five sites per molecule) without altering binding affinity. A similar effect was found when we performed Scatchard analyses of ether extracts in serum from three critically ill patients (number of calcium-binding sites increased from three to six). We also found that lipid infusions (during parenteral nutrition) lowered mean serum ionized calcium values in six critically ill patients [4.6 +/- 0.2 (+/- SEM) to 4.1 +/- 0.2 mg/dL; P less than 0.05]. These data support the concept that FFAs increase calcium binding to the albumin molecule. Alterations in FFA concentrations during critical illness may contribute to the poor correlation between corrected total serum calcium and ionized calcium concentrations in critically ill patients. In addition, acute elevations in circulating FFA concentrations may contribute to hypocalcemia in patients with defects in bone calcium mobilization.

Acute Disease↗
PubMed1987

The multifactorial basis for hypocalcemia during sepsis. Studies of the parathyroid hormone-vitamin D axis.

To learn about the pathogenesis of sepsis-associated hypocalcemia, we measured serum ionized calcium concentrations in 60 critically ill patients with bacterial sepsis; 12 (20%) had hypocalcemia. The mortality rate in the hypocalcemic patients with sepsis (50%) was higher than that in the normocalcemic patients with sepsis (29%). Only patients with gram-negative sepsis became hypocalcemic, and hypocalcemia contributed to hypotension in 7 of the 12 hypocalcemic patients. Serum calcium concentrations returned to normal in each of those patients with sepsis who survived. Hypocalcemia during sepsis occurred in previously normocalcemic patients and was multifactorial in origin, resulting from acquired parathyroid gland insufficiency, renal 1 alpha-hydroxylase insufficiency, vitamin D deficiency, and acquired calcitriol resistance. We conclude that the hypocalcemia of sepsis is associated with a high mortality rate and usually occurs in previously normocalcemic patients who acquire a defect in the parathyroid-vitamin D axis.

Adolescent↗
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↗