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Biomedical subjects

P Jacob

Publications and source records attributed to P Jacob.

At least 199 records · Page 11Linked to original sources
PubMed1987

Determination of benzoylecgonine and cocaine in biologic fluids by automated gas chromatography.

A method is described for extraction of the cocaine metabolite benzoylecgonine, conversion to the butyl ester derivative and gas chromatographic analysis using packed or capillary columns. Using a capillary column, cocaine and benzoylecgonine may be determined simultaneously. The extraction scheme has been designed to facilitate processing of large numbers of samples generated in pharmacokinetic studies. Structural analogues, m-toluylecgonine and m-toluylecgonine methyl ester, are used as internal standards. Concentrations as low as 10 ng/ml in 1-ml samples of plasma or urine are readily determined. Between-run coefficients of variation were 1.01% for cocaine and 4.18% for benzoylecgonine for concentrations of 75 and 350 ng/ml, respectively.

Autoanalysis↗
PubMed1987

Determinants of nicotine intake while chewing nicotine polacrilex gum.

Nicotine polacrilex gum is widely used as substitution therapy during cigarette smoking cessation. We studied circadian blood nicotine concentrations, daily intake of nicotine, and extraction of nicotine from gum in smokers switched experimentally to 2 or 4 mg nicotine gum, 12 pieces per day. Nicotine levels and intake were much lower while chewing gum than during ad libitum smoking. Extraction of nicotine from gum by the chewer was incomplete, averaging 53% and 72% for 2 and 4 mg gum, and variable (more than twofold) among individuals. The systemic dose of nicotine was less than expected based on analysis of nicotine in the chewed gum. Disproportionately higher metabolite-to-nicotine ratios while chewing gum compared with smoking suggested that some nicotine was swallowed and underwent first-pass metabolism. Nicotine and metabolite data were used to estimate buccal vs. gastrointestinal absorption. Relative buccal absorption vs. swallowing of nicotine appears to be an important determinant of systemic nicotine intake.

Adult↗
PubMed1987

Influence of tobacco abstinence on the disposition kinetics and effects of nicotine.

Habitual tobacco smoking accelerates the metabolism of many drugs. With tobacco abstinence, it was expected that nicotine metabolism would be slower than when smoking. To test this hypothesis, the disposition kinetics of intravenous nicotine were studied in 20 healthy smokers while smoking, after abstaining from smoking for 1 week, and (in six subjects) when smoking again. Cardiovascular responses to nicotine were also measured. Unexpectedly, total and nonrenal clearance of nicotine increased by 36% and 39%, respectively, during abstinence. The increase in clearance after brief abstinence suggests that nicotine or its metabolites or another component of cigarette smoke inhibits nicotine metabolism in smokers. Cardiovascular responses to nicotine were greater after 1 week compared with overnight abstinence, consistent with loss of tolerance.

Adult↗
PubMed1987

Brain phenobarbital uptake during prolonged status epilepticus.

The brain uptake of phenobarbital during prolonged status epilepticus (3 h) was studied in paralyzed, ventilated sheep. The first 30 min of status epilepticus was characterized by systemic hypertension, increased CBF, increased peripheral vascular resistance, a fall in brain pH, and an elevation in brain lactate concentrations. Subsequently, hemodynamic factors normalized and brain acidosis persisted. Phenobarbital administered during the early phase of status epilepticus produced higher levels of brain phenobarbital concentration, which was greatest at the earliest sample time (5 min following infusion), compared to nonseizure controls. This elevation persisted for the first 3 h following the infusion. Phenobarbital administration during the established phase of status epilepticus, when systemic blood pressure, peripheral vascular resistance, and CBF had returned to preseizure values, resulted in attenuated brain phenobarbital uptake not different from controls for the first 30 min. These results are explained by disruption of the blood-brain barrier to phenobarbital during the early (hypertensive) phase of status epilepticus.

Animals↗
PubMed1987

Cigarette abstinence, nicotine gum, and theophylline disposition.

When cigarette smokers with chronic lung disease become acutely ill or require surgery, they are often forced to stop smoking and may use nicotine gum. Smoking is known to accelerate the metabolism of theophylline, but the effects of short-term abstinence or nicotine gum on theophylline metabolism have not been reported. We studied the effects of brief tobacco abstinence and nicotine gum on theophylline elimination in healthy volunteers. Abstinence from smoking for 1 week resulted in a 37.6% decrease in clearance and a 35.8% increase in half-life. Nicotine gum had no effect on theophylline clearance. Our data indicate that at least partial normalization of the enzyme-inducing effects of smoking can be seen after brief cigarette abstinence. For smokers who are taking theophylline chronically, their dose of theophylline will need to be reduced by one fourth to one third after brief tobacco abstinence. Plasma concentration monitoring may be necessary for optimal dosing of theophylline in such patients.

Adult↗
PubMed1986

Influence of smoking fewer cigarettes on exposure to tar, nicotine, and carbon monoxide.

In the hope of reducing the adverse health consequences of smoking, physicians frequently advise their patients who cannot quit to smoke fewer cigarettes. Habitual smokers may compensate for the reduced number of cigarettes, however, by taking in more smoke per cigarette. We measured the intake of tar (estimated as mutagenic activity of the urine), nicotine, and carbon monoxide during short-term cigarette restriction. With a reduction from an average of 37 cigarettes to an average of 5 cigarettes per day, the intake of tobacco toxins per cigarette increased roughly threefold and daily exposure to tar and carbon monoxide declined only 50 percent. We conclude that smoking fewer cigarettes may reduce exposure to toxins and related adverse health consequences. However, consistent with a tendency to maintain intake of nicotine, the magnitude of the benefit is much less than expected. Whether "oversmoking" persists during long-term restriction of cigarettes requires further investigation.

Adult↗
PubMed1986

Reduced tar, nicotine, and carbon monoxide exposure while smoking ultralow- but not low-yield cigarettes.

An unresolved public health issue is whether some modern cigarettes are less hazardous than others and whether patients who cannot stop smoking should be advised to switch to lower-yield cigarettes. We studied "tar" (estimated by urine mutagenicity), nicotine, and carbon monoxide exposure in habitual smokers switched from their usual brand to high- (15 mg of tar), low- (5 mg of tar), or ultralow-yield (1 mg of tar) cigarettes. There were no differences in exposure comparing high- or low-yield cigarettes, but tar and nicotine exposures were reduced by 49% and 56%, respectively, and carbon monoxide exposure by 36% while smoking ultralow-yield cigarettes. Similarly, in 248 subjects smoking their self-selected brand, nicotine intake, estimated by blood concentrations of its metabolite cotinine, was 40% lower in those who smoked ultralow but no different in those smoking higher yields of cigarettes. Our data indicate that ultralow-yield cigarettes do deliver substantial doses of tar, nicotine, and carbon monoxide, but that exposures are considerably less than for other cigarettes.

Adult↗
PubMed1986

[Metacarpal fractures. Use of an external cemented wire fixation device].

Osteosynthesis for fractures of the metacarpals using a simplified system of Kirschner wires introduced percutaneously and maintained by an acrylic cement bridge has been performed in 40 patients. Consolidation was obtained consistently, within one month on average, with almost no morbidity and virtually without sequelae. This procedure is extremely simple and can be used for all extra-articular fractures of the metacarpals with displacement.

Bone Wires↗
PubMed1986

Improving results from nerve and muscle biopsy in children: technical considerations in the harvesting of specimens.

The convergence of expertise in the neurological sciences, special interest in myoneuropathology, and improved surgical technique has resulted in a significantly improved yield from muscle and nerve biopsies in children with suspected neuromuscular disorders. We present a synthesis of all those factors that we have identified as contributing to optimal results, particularly site selection, sample size, a meticulous biopsy technique that avoids the introduction of artefacts, the use of the muscle biopsy clamp, prompt processing of the specimen, and participation of the neurologist in the biopsy procedure and the interpretation of the histologic sections.

Biopsy↗
PubMed1986

Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class.

The alpha-ethyl phenethylamine derivative 1-(1,3-benzodioxol-5-yl)-2-butanamine was prepared. An asymmetric synthesis was used to prepare the enantiomers of this compound and the related alpha-methyl homologue (MDA). The racemates and enantiomers of both compounds were evaluated in the two-lever drug discrimination assay in rats trained to discriminate saline from 0.08 mg/kg of LSD tartrate. Stimulus generalization occurred with the racemate and the R-(-) enantiomer of the alpha-methyl homologue and the S-(+) enantiomer of the alpha-ethyl primary amine. No generalization occurred with the other enantiomers or with the N-methyl derivatives of either series. Human psychopharmacology studies revealed that the N-methyl derivative of the title compound was nonhallucinogenic and that it had a new, novel psychoactive effect. It is suggested that this compound is the prototype of a new pharmacologic class that may have value in facilitating psychotherapy and that this class be designated as entactogens.

Adult↗
PubMed1986

Additive cardiovascular effects of nicotine and ethanol.

Ethanol and tobacco consumption are commonly associated. Both are risk factors for adverse cardiovascular events. To better understand the interactions, the influence of oral ethanol pretreatment (0.5 or 1.0 gm/kg over 60 minutes) on cardiovascular responses to and disposition kinetics of intravenous nicotine was studied in healthy volunteers. Ethanol increased heart rate, systolic blood pressure, and pressure-rate product in a dose-related manner. Nicotine had additive effects on heart rate and pressure-rate product. It also decreased skin temperature, reflecting cutaneous vasoconstriction, but this effect was antagonized by ethanol. Ethanol did not affect metabolic clearance but increased CLR of nicotine by 25%. Additive cardiovascular effects of ethanol and nicotine could contribute to arrhythmias and sudden death in patients with coronary heart disease. It is unlikely that an effect of ethanol on nicotine metabolism is responsible for increased cigarette smoking while drinking ethanol.

Administration, Oral↗
PubMed1986

A protocol for the evaluation of new psychoactive drugs in man.

A protocol is presented that has proven effective in the determination, in man, of the psychotomimetic potency and qualitative nature of action of a new drug. It involves a minimum of animal screening, but relies heavily upon the use of experienced human subjects. This procedure has been successful in the discovery of over 200 novel CNS-active agents.

Animals↗
PubMed1985

Hypophysectomy mitigates skeletal muscle fiber damage in hamster dystrophy.

Ablation of the pituitary gland by a radiofrequency lesion markedly retarded the musculoskeletal growth of young dystrophic hamsters. The prevalence of centronucleated muscle fibers, which is a reliable cumulative index of the microscopic pathological expression of dystrophy, was drastically reduced in quadriceps muscles of 35- and 45-day-old hypophysectomized dystrophic hamsters, compared with sham-operated controls. Mitigation of skeletal muscle fiber damage by musculoskeletal growth retardation may also occur in human dystrophy.

Animals↗
PubMed1985

Air-ground interface correction factors for gamma emitters in air.

For isotropic point photon sources above an air-ground interface, the spectral energy fluences at the ground have been calculated by the Monte Carlo method for source energies in the range 50 keV-10 MeV. The source heights and the horizontal source-detector distances varied from 0.05 to 5 mean free paths in air. Air-ground interface correction factors have been calculated and then analytically approximated. The greatest deviations from unity were found for 100-keV sources located on the ground. Near the source, kerma free in air is enhanced by 30%, and far from the source it is reduced by a factor of 3.

Air Pollution, Radioactive↗
PubMed1985

Ring-substituted beta-methoxyphenethylamines: a new class of psychotomimetic agents active in man.

Four members of a new class of psychotomimetic agents have been synthesized and evaluated in man. These compounds, which incorporate a beta-methoxy group onto a beta-phenethylamine sidechain, are the first reported psychotomimetics which are structural analogues of the neurotransmitter noradrenaline. These substances are more potent than the corresponding phenethylamines (lacking a beta-methoxy group) but less potent than the correspondingly substituted amphetamine derivatives.

Adult↗