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Biomedical subjects

N Benowitz

Publications and source records attributed to N Benowitz.

At least 37 records · Page 2Linked to original sources
PubMed1989

Changes in food intake and activity after quitting smoking.

Quitting smoking often results in weight gain. The causes of the gain are not known. The present study evaluated changes in calories, total sugars, sucrose, fat, protein, and nonsugar carbohydrates as well as changes in activity levels after quitting smoking. Ninety-five subjects were randomly assigned to either early (Week 2) or late (Week 6) quit dates. Subjects were assessed on weight, food intake, activity levels, and smoking levels at baseline, at Weeks 4 and 8, and at Weeks 12 and 26 postquit. The results indicated significant increases in calories, sucrose, and fats 2 weeks after the quit date. Changes for total sugars were less consistent. Activity levels did not change significantly. Early caloric increases predicted weight gain at 26 weeks for abstinent women. No relation was found for abstinent men, but interpretation of this finding is weakened by a small subsample size. Abstinent subjects gained over 9 lb by 26 weeks postquit. Despite this gain, Week 26 results showed that caloric intake for abstinent women was approximately equal to that observed at baseline, whereas that for abstinent men had dropped significantly.

Adult↗
PubMed1986

Hyperthermia associated with drug intoxication.

Hyperthermia (temperature of at least 40.5 degrees C for at least one hour) associated with drug intoxication was identified in 12 patients over a 5-yr period. Intoxication was due to anticholinergic drugs (tricyclic antidepressants, antipsychotics, antihistamines), CNS stimulants (phencyclidine, cocaine, 3,4-methylene dioxyamphetamine, mescaline, lysergic acid diethylamide), salicylates, or combinations of these. Hyperthermia was present in four patients on admission, but its onset was delayed up to 12 h in the remainder. Outcome of hyperthermic patients was poor: five died and four had severe permanent neurologic sequelae. Clinical signs common to patients who developed hyperthermia were increased muscular activity and absence of sweating. Five patients suffered seizures, and four did not respond to anticonvulsant medication until body temperature was lowered. Cooling did not appear to favorably affect the outcome after body temperature had remained above 40.5 degrees C for a prolonged period. Prevention of death or neurologic sequelae from drug-induced hyperthermia depends upon the recognition of risk factors and the prompt treatment of hyperthermia.

Adolescent↗
PubMed1985

Influence of the blood-brain pH gradient on brain phenobarbital uptake during status epilepticus.

Brain uptake and blood concentrations of phenobarbital were determined in rats during pentylenetetrazol-induced status epilepticus and compared to nonconvulsing controls. Brain phenobarbital concentrations and the brain-to-blood phenobarbital ratio were increased 2-fold in freely convulsing animals as compared to controls. The degree of systemic acidosis during motor convulsions was greater than the degree of brain acidosis. Because phenobarbital is a weak acid, this pH gradient favors movement of phenobarbital into the brain during status epilepticus. Motor paralysis prevented the development of systemic acidosis and the brain-blood partition of phenobarbital was similar to that of nonconvulsing controls. Blood phenobarbital concentrations were slightly higher in animals paralyzed during status as compared to controls, presumably due to hemodynamic effects of convulsions. These studies, as well as our previous studies with lidocaine, support the idea that the brain-blood pH gradient is an important determinant of drug uptake by the brain during seizures.

Animals↗
PubMed1984

Antihypertensive therapy with diltiazem and comparison with hydrochlorothiazide.

Fourteen hypertensive patients with a mean sitting systolic and diastolic blood pressure (BP) of 153 +/- 16/100 +/- 4 mm Hg were treated successively with hydrochlorothiazide and diltiazem for 8 weeks each. The BP response and changes in heart rate, left ventricular size and function, and plasma catecholamine concentrations and renin activity were monitored. The 2 drugs had comparable antihypertensive effects, with mean decreases of 14, 9 and 11 mm Hg for the sitting, standing and supine diastolic BP, respectively, during hydrochlorothiazide treatment and mean decreases of 16, 18 and 12 mm Hg during diltiazem treatment. Heart rate was unchanged, although plasma norepinephrine concentrations increased significantly during diltiazem treatment. Plasma renin activity increased slightly, from 0.6 to 0.9 ng/ml/hour during diltiazem treatment, but the change was not significant (p less than 0.10). Left ventricular ejection fraction and end-diastolic volume were not affected by either agent. In conclusion, diltiazem is an effective antihypertensive agent, which because of its benign side effect profile, may be useful as a step 1 agent.

Aged↗
PubMed1984

Monotherapy in mild to moderate hypertension: comparison of hydrochlorothiazide, propranolol and prazosin.

There has been recent interest in using nondiuretic drugs as initial antihypertensive therapy. Therefore, a study was designed to compare the efficacy and the effects on left ventricular function of hydrochlorothiazide, propranolol and prazosin in 13 patients with mild to moderate hypertension. After a 4-week washout period, patients were treated serially with each drug in a randomized order for 2 months each. Dosages were titrated until the patient showed a sitting diastolic blood pressure less than or equal to 90 mm Hg or to a maximum dosage of 100 mg/day of hydrochlorothiazide, 320 mg of propranolol and 20 mg of prazosin. Blood pressure was measured, plasma catecholamine concentrations were assayed and radionuclide determinations of rest and exercise left ventricular function and volume were made at the end of each period as well as after a second 1-month washout period at the end. In the sitting and standing positions, systolic and diastolic blood pressure control was equivalent for all 3 drugs. Goal blood pressure was achieved in 10 of 13 patients receiving hydrochlorothiazide, in 8 of 12 receiving propranolol and in 9 of 13 on prazosin. Importantly, 3 of 4 patients not controlled with prazosin, 5 of 6 uncontrolled with propranolol and 2 of 3 whose blood pressure was not reduced by hydrochlorothiazide were controlled when receiving 1 of the other medications. None of the drugs changed rest or exercise ejection fraction or volume, and side effects were minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Efficacy and mechanism of action of sodium bicarbonate in the treatment of desipramine toxicity in rats.

Alkalinization of the blood by administration of sodium bicarbonate or hyperventilation is widely recommended for treatment of cardiac toxicity due to tricyclic antidepressant overdose, yet its efficacy and mechanism of action are poorly defined. We studied the effects and possible mechanism of action of 1 M NaHCO3 on desipramine (DMI) toxicity in anesthetized, paralyzed rats. Administration of DMI (45 mg/kg i.p.) produced a mean increase in QRS duration of 142% and a mean decrease in mean arterial pressure of 46%. Treatments were administered i.v. 35 min after DMI and their effects were assessed 10 min later. NaHCO3 (1 M) at doses of 3 and 6 mEq/kg decreased mean QRS duration 15 +/- 5 and 24 +/- 6%, respectively (mean +/- S.D.) and was superior to no treatment (P less than .01). NaCl (1 M) was as effective as NaHCO3 in decreasing QRS duration, as was 1 M NaHCO3 supplemented with 48 mM KCl. Respiratory alkalosis and 10% mannitol did not decrease QRS duration. NaHCO3, NaCl and NaHCO3/KCl all produced comparable increases in mean arterial blood pressure. Respiratory alkalosis and mannitol did not increase mean arterial pressure, but did prevent the decline seen in control animals. Acidosis produced by ventilation with 10% CO2 exacerbated QRS prolongation due to DMI. In acidotic animals, NaHCO3 and NaCl were equally effective in reversing QRS prolongation and hypotension. Correction of respiratory acidosis by discontinuation of inhaled CO2 did not improve QRS duration or mean arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Respiratory↗
PubMed1983

Relationship of duration of analgesia to opioid pharmacokinetic variables.

That physiological effects are directly related to concentration at the site of action has been validated for only a few classes of drugs. For opiates, a direct correlation is known to exist between concentration and magnitude of analgesia, but has not been shown for duration of analgesia. These experiments in rats, using opiates whose elimination half-lives differ by a factor of 2 1/2, in a range of doses that produce 10-90% of maximal analgesic effect, show that duration is not dependent on dose or rate of elimination of opiate analgesics. The data suggest that analgesic duration is not determined by the pharmacokinetics of opiates at the receptors where these drugs act to elicit analgesia.

Animals↗
PubMed1983

(--)-alpha-Acetylmethadol effects on alcohol and diazepam use, sexual function and cardiac function.

Selected behavioral and physiological effects of maintenance on (--)-alpha-acetylmethadol (LAAM) were examined for 67 men beginning LAAM maintenance. Thirty-four began LAAM maintenance after 1 month or more on methadone; 33 others were using street heroin immediately before beginning LAAM. Subjects were followed for 20 weeks on LAAM; assessment focused on changes in alcohol and diazepam use, sexual behavior and testicular function, and cardiovascular function. There was a trend toward increased alcoholism-related behaviors, but not consumption of alcohol, when on LAAM. Use of diazepam remained low. Subjects reported slightly enhanced sexual activity: reported number of ejaculations tended to increase, although interest in sexual activity remained constant. Semen volume values remained in the low normal range. In contrast to an earlier published report of reduced sperm motility in methadone and heroin users, normal motility was noted in this sample. The incidence of abnormal sperm morphology decreased from baseline to the end of the study. Cardiovascular function, as assessed by response to standard exercise, was unchanged during LAAM maintenance. Electrocardiograms revealed minor abnormalities prior to beginning LAAM maintenance; but these abnormalities did not consistently change during treatment. There is little evidence that the effects of LAAM maintenance differ from the effects of methadone maintenance on these behavioral and physiological functions.

Adult↗
PubMed1980

Resin hemoperfusion in ethychlorvynol overdose.

An 18-yr-old male with a severe ethchlorvynol (ECV) overdose was treated with Amberlite XAD-4 resin hemoperfusion. Plasma ECV concentration declined 33% during a 3.5-hr hemoperfusion, but rebounded substantially, peaking 6 hr later. It was estimated that 16% of ECV in the body was removed. Following hemoperfusion, plasma ECV concentrations declined linearly at a rate of 13 mg/1/day. Hemoperfusion clearance was estimated by both the traditional method, using extraction ratios across the column and column blood flow (Cl = 270 ml/min), and an alternative method, using blood concentrations during hemoperfusion and recovery of drug from the resin (Cl = 184 ml/min). The latter may provide a better estimate of hemoperfusion clearance because it is not subject to error (which can be substantial) in measurement of column blood flow. The resin completely extracted ECV from plasma, resulting in a rate of elimination 10 times that expected from endogenous processes. To aid in kinetic analysis, blood:plasma partition and protein binding of ECV in 3 normal subjects were also examined. Blood:plasma ratio averaged 0.88 +/- 0.04 and fraction free in plasma, 0.38 +/- 0.02; neither changed as a function of blood concentration between 27 and 108 mg/1. Our data indicate that removal of ECV from the overdosed patient by hemoperfusion is limited by extensive distribution in and slow redistribution from body tissues, but because of the extremely slow rate of removal by the body and the severe nature of the ECV overdose, Amberlite XAD-4 hemoperfusion may be clinically useful.

Adolescent↗
PubMed1976

Phytohemagglutinin-induced lymphocyte transformation in humans receiving delta9-tetrahydrocannabinol.

Eight otherwise healthy male chronic marijuana smokers were hospitalized for a period of 30 days. Initially they received placebo, then a sustained dose of 210 milligrams of delta9-tetrahydrocannabinol (delta9-THC) per day for 18 days, followed by placebo. Lymphocyte responses to phytohemagglutinin were examined during each of these periods. Neither the daily ingestion of marijuana extract containing 210 milligrams of delta9-THC for 18 days nor the history of chronic marijuana smoking had a depressive effect on the lymphocyte responses of these subjects to phytohemagglutinin.

Adult↗
PubMed1976

Gestational differences in lidocaine toxicity in the fetal lamb.

Effects of lidocaine on arterial pressure, heart rate and electrocortical activity were studied in nine fetal lambs at 0.77 to 0.92 gestation (116 to 138 days of gestation; term in sheep is 150 days). Lidocaine was administered into a fetal femoral vein either as a continuous infusion or as a bolus injection. Epileptiform activity was observed in all fetuses both after continuous infusion and after bolus injection of lidocaine. Fetal arterial concentrations of lidocaine at the time of the first epileptiform discharge during continuous infusion ranged from 6.9 to 40.0 mug/ml, and correlated negatively with gestational age (Y equals -1.727 x +242.7; r equals -0.94). The increases in fetal mean arterial pressure during epileptiform bursts correlated directly with the gestational age (Y equals 1.27 x -150.0; r equals 0.91). The convulsive doses of lidocaine injected as a bolus ranged from 8.0 to 34.1 mg/kg, and correlated negatively with gestational age (Y equals -0.991 x +144.9; r equals -0.88). The increased sensitivity to lidocaine of the fetal central nervous system with advancing gestation probably reflects differences in fetal brain development. The increase in cardiovascular responses to epileptiform activity with advancing gestation could be related to differences either in the strength of epileptiform discharges or in permeability of the blood-brain barrier to lidocaine, or to immaturity of the autonomic nervous supply to the cardiovascular system in young fetuses.

Animals↗