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Biomedical subjects

G Zaloga

Publications and source records attributed to G Zaloga.

14 recordsLinked to original sources
PubMed1999

Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure.

BACKGROUND: Patients with acute renal failure (ARF) have high morbidity and mortality rates, particularly if they have serious comorbid conditions. Several studies indicate that in rats with ARF caused by ischemia or certain nephrotoxins, insulin-like growth factor-I (IGF-I) enhances the recovery of renal function and suppresses protein catabolism. METHODS: Our objective was to determine whether injections of recombinant human IGF-I (rhIGF-I) would enhance the recovery of renal function and is safe in patients with ARF. The study was designed as a randomized, double-blind, placebo-controlled trial in intensive care units in 20 teaching hospitals. Seventy-two patients with ARF were randomized to receive rhIGF-I (35 patients) or placebo (37 patients). The most common causes of ARF in the rhIGF-I and placebo groups were, respectively, sepsis (37 and 35% of patients) and hypotension or hemodynamic shock (42 and 27% of patients). At baseline, the mean (+/- SD) APACHE II scores in the rhIGF-I and placebo-treated groups were 24 +/- 5 and 25 +/- 8, respectively. In the rhIGF-I and placebo groups, the mean (median) urine volume and urinary iothalamate clearances (glomerular filtration rate) were 1116 +/- 1037 (887) and 1402 +/- 1183 (1430) ml/24 hr and 6.4 +/- 5.9 (4.3) and 8.7 +/- 7.2 (4.4) ml/min and did not differ between the two groups. Patients were injected subcutaneously every 12 hours with rhIGF-I, 100 microgram/kg desirable body weight, or placebo for up to 14 days. Injections were started within six days of the onset of ARF. The primary end-point was a change in glomerular filtration rate from baseline. Other end points included changes from baseline in urine volume, creatinine clearance and serum urea, creatinine, albumin and transferrin, frequency of hemodialysis or ultrafiltration, and mortality rate. RESULTS: During the treatment period, which averaged 10.7 +/- 4.1 and 10.6 +/- 4.5 days in the rhIGF-I and placebo groups, there were no differences in the changes from baseline values of the glomerular filtration rate, creatinine clearance, daily urine volume, or serum urea nitrogen, creatinine, albumin or transferrin. In patients who did not receive renal replacement therapy, there was also no significant difference in serum creatinine and urea between the two groups. Twenty patients in the rhIGF-I group and 17 placebo-treated patients underwent dialysis or ultrafiltration. Twelve rhIGF-I-treated patients and 12 placebo-treated patients died during the 28 days after the onset of treatment. CONCLUSIONS: rhIGF-I does not accelerate the recovery of renal function in ARF patients with substantial comorbidity.

Acute Kidney Injury↗
PubMed1994

A review of disease-specific formulas.

Critical illness frequently leads to organ dysfunction. Nutritional support of individual organ function is an evolving area of nutritional support. Within the past several years, there was an increase in the number of nutritional products reported to improve organ function. In this article, the authors review disease/organ-specific nutritional support, including the theory behind therapy and the empiric data supporting or refuting these theories. It is hoped that this article will aid practitioners in their nutritional management of patients with organ dysfunction.

Enteral Nutrition↗
PubMed1991

Dose-dependent response to phenylpropanolamine: inhibition of orthostasis.

Phenylpropanolamine, a widely consumed over-the-counter drug, is known to elevate blood pressure, but the mechanism is unknown; it may be both a direct and indirect sympathomimetic. This study investigated the effects of 75-mg sustained-release phenylpropanolamine, 75-mg phenylpropanolamine plus 400-mg caffeine, and 150-mg phenylpropanolamine on blood pressure, plasma norepinephrine, and epinephrine levels in 16 normotensive subjects in a double-blind, placebo-controlled crossover design. Mean peak phenylpropanolamine levels of 317 +/- 26, 152 +/- 17, and 157 +/- 17 ng/mL for 150-mg phenylpropanolamine, 75-mg phenylpropanolamine, and 75-mg phenylpropanolamine plus 400-mg caffeine, respectively, were reached at about 3.6 hours after dosing. The maximal increases in supine diastolic blood pressures after all three phenylpropanolamine-containing drugs were almost three times that after placebo (P less than .05), but peak blood pressures occurred at about 2.3 hours earlier than peak phenylpropanolamine levels. Blood pressure increases correlated with phenylpropanolamine plasma levels (r = .49 for systolic blood pressure and r = .34 for diastolic blood pressure; P less than .0001 for both). Norepinephrine levels increased after the administration of 150-mg phenylpropanolamine and 75-mg phenylpropanolamine plus 400-mg caffeine; norepinephrine increases correlated with phenylpropanolamine levels (r = .34, P less than .0001). The expected increment in norepinephrine induced by standing was significantly decreased by phenylpropanolamine in a dose-dependent mode. The study supports the idea that phenylpropanolamine as both a direct (at alpha -1 and alpha-2 receptors) and an indirect sympathomimetic agent.

Blood Pressure↗
PubMed1990

Phenylpropanolamine increases plasma caffeine levels.

The effects of the widely consumed drugs caffeine and phenylpropanolamine are mediated through activation of the central and sympathetic nervous systems. Severe, life-threatening, and occasionally fatal hypertensive reactions have been reported after their combined use. This study examined the possible pharmacokinetic interaction of phenylpropanolamine and caffeine. Sixteen normal subjects received combinations of caffeine, phenylpropanolamine, and placebo. In subjects receiving 400 mg caffeine plus 75 mg phenylpropanolamine, the mean (+/- SEM) peak plasma caffeine concentration of 8.0 +/- 2.2 micrograms/ml was significantly greater than after 400 mg caffeine alone (2.1 +/- 0.3 micrograms/ml; t[24] = 2.4; p less than 0.01). Physical side effects were more frequent after the phenylpropanolamine-caffeine combination than after either drug alone or after placebo. Greater increases in both systolic and diastolic blood pressures occurred after the combination than after either drug alone. Because caffeine levels can be increased greatly when certain other drugs are coconsumed, these data indicate that phenylpropanolamine may enhance absorption or inhibit elimination of caffeine and may explain increased side effects reported after their combined use.

Adult↗
PubMed1989

Transient hypertension after two phenylpropanolamine diet aids and the effects of caffeine: a placebo-controlled follow-up study.

PURPOSE AND PATIENTS AND METHODS: Reports of severe adverse reactions following the ingestion of single (75 mg) or double doses of the sympathomimetic drug phenylpropanolamine (PPA), with and without caffeine, prompted us to undertake a study of the effects of five drug preparations (75 mg PPA, 150 mg PPA, 75 mg PPA plus 400 mg caffeine, 400 mg caffeine, and placebo) in 16 resting, normotensive subjects. The study was of a double-blind, randomized, crossover design. Each subject consented to take the five drug preparations on different study days, which were separated by at least 48 hours. RESULTS: Compared with blood pressure (BP) values obtained after placebo ingestion, significant BP increases occurred over several hours following 150 mg PPA and after 75 mg PPA plus 400 mg caffeine. Significant BP increases after ingestion of 75 mg PPA and after 400 mg caffeine were less frequent. The mean peak BP following 150 mg PPA was 173 +/- 9/103 +/- 4 mm Hg, compared with 148 +/- 4/97 +/- 3 mm Hg after the other three active preparations; after placebo, peak BP reached 137 +/- 8/85 +/- 5 mm Hg. CONCLUSION: These results indicate that 150 mg PPA (the amount in two diet aids) substantially elevates BP. Our findings may explain some of the recent case reports of nontraumatic intracranial hemorrhage in young, healthy persons ingesting PPA at recommended or minimally greater dosages. We suggest physicians inform patients who are likely consumers of PPA (i.e., those with allergies, those with eating disorders, overweight persons, women during the postpartum period) and patients at risk for stroke (i.e., the elderly and hypertensive patients) of the risks of taking more than the recommended amounts of PPA and of combining caffeine with PPA.

Adult↗
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↗
PubMed1986

Glucagon is an antagonist of morphine bradycardia and antinociception.

Glucagon and its receptors have been identified within the mammalian brain, and their anatomical distribution correlates well with the distribution of opioid peptides and their receptors. To evaluate possible physiological interactions between these two peptidergic systems, we examined the effects of glucagon on two opioid responses - bradycardia and antinociception. Glucagon administered either intravenously (iv) (100-1000 micrograms/kg) or intracerebroventricularly (icv) (5 micrograms) significantly attenuated morphine-induced (200 micrograms/kg, iv) bradycardia without producing any alterations in cardiovascular parameters when given alone. Furthermore, glucagon did not antagonize the bradycardia produced by phenyldiguanide (10 micrograms/kg, iv), a non-opioid substance. Peripheral (1 mg/kg, iv) and central (5 micrograms, icv) glucagon pretreatment antagonized morphine-induced (7.5 mg/kg, intraperitoneal) antinociception by 67% and 86%, respectively, at 30 minutes (as determined by the hot plate test). Glucagon treatment alone at these doses did not alter baseline response latencies. In both cases, central injections of glucagon were more effective than iv injections in antagonizing morphine's effects. These findings demonstrate a central action for glucagon and provide the first evidence that this neuropeptide may function as an endogenous antagonist of opioid actions.

Analgesia↗
PubMed1982

Hypocalcemia in critically ill patients.

Hypocalcemia is an important metabolic problem in critical care medicine. To determine the frequency of this problem and the patient subsets at risk, a retrospective study of a large series of ICU patients was performed. During the study period, 259 patients were admitted to the ICU, of whom 210 (81%) had a serum calcium (Ca++) measured. Of these 210 patients, 135 (64%) were hypocalcemic (serum Ca++ less than 8.5 mg/dl) and 75 (36%) were normocalcemic. Serum albumin concentration was less than 3.5 g/dl in 70% of the hypocalcemic patients who hd albumin measured, suggesting that the ionized Ca++ concentration may have been normal in many of these patients. On the other hand, 32% of the hypocalcemic patients were alkalotic (pH greater than or equal to 7.45) which indicates that ionized Ca++ levels may have been low because Ca++ binding to protein increases with alkalosis. Gastrointestinal bleeders and postabdominal surgery patients were more likely to have low total serum Ca++ whereas cardiac and neurosurgical patients were more likely to have a normal total serum Ca++ (p less than 0.05). Ionized Ca++ was calculated in 36 of the normocalcemic and 80 of the hypocalcemic patients. The hypocalcemic group had significantly lower ionized Ca++ levels when compared to those of the normocalcemic group (p less than 0.001). Patients with low serum Ca++ values spent a longer time in the ICU (p less than 0.01), had an increased incidence of renal failure and sepsis (p less than 0.01), had an increased mortality rate (p less than 0.001), and received a greater number of blood transfusions (p less than 0.001) than patients in the normocalcemic group. It is concluded that: (1) hypocalcemia is a frequent finding in critically ill patients; (2) determining ionized Ca++ levels is useful because many ICU patients have alterations in both arterial pH and serum albumin levels; (3) hypoalbuminemia, sepsis, red cell transfusions, and renal failure are predisposing factors for hypocalcemia; and (4) hypocalcemic patients do less well clinically than normocalcepatientsmic patients.

Calcium↗