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Biomedical subjects

P Jacob

Publications and source records attributed to P Jacob.

At least 181 records · Page 10Linked to original sources
PubMed1989

Upper esophageal sphincter opening and modulation during swallowing.

Studies were done on 8 normal subjects with synchronized videofluoroscopy and manometry to facilitate a biomechanical analysis of upper esophageal sphincter opening and volume-dependent modulation during swallowing. Movements of the hyoid and larynx, dimensions of sphincter opening, and intraluminal sphincter pressure were determined at 1/30th-s intervals during swallows of 1, 5, 10, and 20 ml of liquid barium. Our analysis subdivided upper esophageal sphincter activity during swallowing into five phases: (a) relaxation, (b) opening, (c) distention, (d) collapse, and (e) closure. Sphincter relaxation occurred during laryngeal elevation and preceded opening by a mean period of 0.1 s. Opening occurred as the sphincter was pulled apart via muscular attachments to the hyoid such that the hyoid coordinates at which sphincter opening and closing occurred were constant among bolus volumes. Sphincter distention after opening was modulated by intrabolus pressures rather than graded hyoid movement. The generation of intrabolus pressure coincided with the posterior thrust of the tongue that culminated in pharyngeal wall contact and the initiation of pharyngeal peristalsis. Larger volume swallows were associated with greater intrabolus pressure and increased bolus head velocity. The duration of sphincter opening increased in conjunction with a prolongation of the anterior-superior excursion of the hyoid and a delay in the onset of pharyngeal peristalsis (the event that determined the timing of sphincter closure). We conclude that transsphincteric transport of increasing swallow bolus volumes is accomplished by modulating sphincter diameter, opening interval, and flow rate (reflected by bolus head velocity). Furthermore, upper esophageal sphincter opening is an active mechanical event rather than simply a consequence of cricopharyngeal relaxation.

Adult↗
PubMed1989

Food and nicotine metabolism.

To examine the plausibility of the hypothesis that smoking a cigarette after a meal is motivated by accelerated metabolism of nicotine, we studied the influence of a high-protein meal on the disposition of nicotine in seven healthy smokers. Indocyanine green clearance, an estimate of hepatic blood flow, increased 31%, 50 minutes after the test meal. Consuming the meal during a steady state infusion of nicotine resulted in a small (18%) but consistent decrease in blood levels of nicotine. Our data demonstrate that food accelerates the metabolism of nicotine, but the time course and magnitude of the decline in levels of nicotine suggest that altered disposition of nicotine is not the primary motivation for smoking after meals.

Adult↗
PubMed1989

Nicotine gum and theophylline metabolism.

When cigarette smokers with chronic lung disease stop smoking, they may do so with the aid of chewing nicotine gum. Smoking is known to accelerate the metabolism of theophylline, but the effects of nicotine gum on theophylline metabolism have not been determined. We studied the effects of nicotine and placebo gum on theophylline metabolism in healthy volunteers. Clearance of theophylline decreased by 32% after cessation of smoking in comparison to while chewing placebo gum. Clearance while chewing nicotine gum was similar to that measured while chewing placebo gum. Nicotine gum appears to have no effect on theophylline metabolism. For smokers who are chronically taking theophylline, the dose of theophylline will need to be reduced by one-fourth to one-third after smoking cessation and initiation of nicotine gum use.

Adult↗
PubMed1989

A reordering of human chromosome 19 long-arm DNA markers and identification of markers flanking the myotonic dystrophy locus.

The gene for myotonic dystrophy (DM), the most common form of adult muscular dystrophy, has previously been mapped to the proximal long arm of chromosome 19. We have conducted linkage analysis on 53 DM families (comprising 421 individuals) using seven DM-linked DNA markers. This analysis, combined with our somatic cell hybrid mapping panel data, places the DM locus more distal on the chromosome 19 long arm than previously thought. Further, we have been able to unequivocally identify DNA markers that flank the disease locus. The definition of a 10-cM region of chromosome 19 that contains the DM locus should prove useful in both the search for the causative gene and the molecular diagnosis of DM.

Chromosome Mapping↗
PubMed1989

Flunarizine as a supplementary medication in refractory childhood epilepsy: a double-blind crossover study.

We report a double blinded cross-over study involving Flunarizine versus placebo in the treatment of refractory childhood epilepsy. The patients studied were between the ages of 2 and 18; and were having more than 4 seizures per month not responsive to regular anticonvulsant medications. Of the 34 patients treated, 8 had a 50% decrease in their seizures during the placebo phase, 5 had a 50% decrease during the Flunarizine phase, and 1 patient had a 50% increase in seizures while taking Flunarizine. The remaining 25 patients showed no change in seizure activity in either phase. Patients having partial seizures with secondary generalization tended to do better on Flunarizine than those with other seizure types. Monitoring serum Flunarizine levels showed no significant difference between patients having improved seizure control and those who were unimproved. No significant side effects were noted with this medication, nor were any significant drug interactions noted.

Adolescent↗
PubMed1989

[Spinal muscular atrophy: disappearance of RNA fluorescence of degenerating motor neurons. An acridine orange study].

The histochemical distribution of nucleic acids has been studied in degenerating motor neurons of 9 children who died with spinal muscular atrophy, using the fluorochrome acridine orange. Ribonucleic acid (RNA) fluorescence disappeared abruptly from involved motor neurons without chromatolysis, attenuation of intensity, or other intermediate transitions that follow axotomy or hypoxic insults. We found a nearly identical pattern in 3 adults with amyotrophic lateral sclerosis. The findings in older subjects are complicated, however, by the presence of cytoplasmic lipofuscin. The autofluorescence of this pigment is inhibited by acridine orange. Our results support the hypothesis that spinal muscular atrophy is a disturbance of the genetically coded mechanism that arrests the programmed physiological death of surplus motor neuroblasts after a certain time in embryonic life, so that the normal lethal developmental process becomes pathological by persisting postnatally. A failure of RNA transcription seems to be primary and results in a failure of synthesis of neurotransmitters, of enzymes, and of cytoplasmic proteins. Consequent inanition leads to cell death.

Acridine Orange↗
PubMed1989

Adequacy of "hot biopsy" for the treatment of diminutive polyps: a prospective randomized trial.

Patients with diminutive polyps in the rectum or sigmoid colon were randomized to "hot biopsy" treatment for either 1) electrocautery for 2 s (fixed duration cautery) or 2) cautery until visible necrosis of the polyp base was evident (variable duration cautery). Sigmoidoscopy was performed 4 wk after treatment to determine the adequacy of polyp eradication. In the fixed duration cautery group, 11 of 21 polyps (52%) were eradicated, compared with 12 of 14 polyps (86%) in the variable duration cautery group (p = 0.04). When analyzed according to whether or not visible necrosis was achieved (some of the polyps in the fixed duration cautery group showed necrosis with 2 s cautery), 19 of 23 polyps (83%) were eradicated when necrosis was evident, compared to 5 of 12 (42%) without necrosis (p = 0.004). We conclude that hot biopsy treatment for diminutive polyps is significantly more effective when visible necrosis is achieved during cautery. Furthermore, even with visible necrosis, there is a 17% failure rate of polyp eradication.

Adenoma↗
PubMed1988

Disposition kinetics of nicotine and cotinine enantiomers in rabbits and beagle dogs.

The disposition kinetics of nicotine and cotinine enantiomers was determined in rabbits. The clearance of (R)-nicotine was similar to that of (S)-nicotine, but clearance of (R)-cotinine was twice that of (S)-cotinine. Fractional conversions of both enantiomers of nicotine to cotinine were approximately 50%. These results suggest that in rabbits the biotransformation pathways of cotinine, but not nicotine, are influenced by stereochemistry. The disposition kinetics of nicotine enantiomers in beagle dogs was also studied. In dogs, the clearance of (R)-nicotine was slightly greater than the clearance of (S)-nicotine. Methods for the synthesis of (R)-nicotine and (R)-cotinine of high enantiomeric purity and a gas chromatographic method for determination of nicotine enantiomeric purity are described.

Animals↗
PubMed1988

Recent studies of nicotine metabolism in humans.

Recent studies of quantitative and qualitative aspects of nicotine metabolism, and the use of metabolic data for estimating nicotine intake in humans are discussed. Previously reported methodology for determining nicotine bioavailability has been improved by using stable isotope-labeled nicotine administered intravenously. Combined gas chromatography-mass spectrometry with selected ion monitoring has been used to simultaneously determine concentrations of isotopically-labeled nicotine and tobacco-derived nicotine in blood. Nicotine intake from cigarette smoking was estimated from clearance of labeled nicotine and blood concentrations of tobacco-derived nicotine. Progress in elucidating the metabolic profile of nicotine in humans, and the use of nicotine metabolites as markers of tobacco smoke consumption is summarized.

Adult↗
PubMed1988

Nicotine absorption and cardiovascular effects with smokeless tobacco use: comparison with cigarettes and nicotine gum.

Because of recent resurgence in its consumption, the effects and health consequences of smokeless tobacco are of considerable public health interest. We studied the extent and time course of absorption of nicotine and cardiovascular effects of smokeless tobacco (oral snuff and chewing tobacco) and compared it with smoking cigarettes and chewing nicotine gum in 10 healthy volunteers. Maximum levels of nicotine were similar but, because of prolonged absorption, overall nicotine exposure was twice as large after single exposures to smokeless tobacco compared with cigarette smoking. All tobacco use increased heart rate and blood pressure, with a tendency toward a greater overall cardiovascular effect despite evidence of development of some tolerance to effects of nicotine with use of smokeless tobacco. Relatively low levels of nicotine and lesser cardiovascular responses were observed with use of nicotine gum. Adverse health consequences of smoking that are nicotine related would be expected to present a similar hazard with the use of smokeless tobacco.

Adult↗
PubMed1988

Changes in rate and pattern of caffeine metabolism after cigarette abstinence.

Caffeine metabolism is known to be accelerated in cigarette smokers, but the effects of smoking on the kinetics and pattern of metabolism in a daily consumption pattern have not been described. We investigated the effects of tobacco abstinence on the rate and pattern of caffeine metabolism in nine habitual smokers who consumed six cups of coffee per day, each cup containing 2 mg/kg caffeine. Abstinence from smoking for 4 days resulted in a 46% increase in the 24-hour AUC. Thus, significant, although probably not complete, normalization of the enzyme-inducing effects of cigarette smoking can be seen after 4 days abstinence. During abstinence, 24-hour urine ratios of dimethylxanthines to caffeine and mono-dimethylxanthines to dimethylxanthines were reduced, suggesting that cigarette smoking accelerates both demethylation steps. Other metabolic pathways were unaffected.

Adult↗
PubMed1988

Organ doses from radionuclides on the ground. Part I. Simple time dependences.

Organ dose equivalents of mathematical, anthropomorphical phantoms ADAM and EVA for photon exposures from plane sources on the ground have been calculated by Monte Carlo photon transport codes and tabulated in this article. The calculation takes into account the air-ground interface and a typical surface roughness, the energy and angular dependence of the photon fluence impinging on the phantom and the time dependence of the contributions from daughter nuclides. Results are up to 35% higher than data reported in the literature for important radionuclides. This manuscript deals with radionuclides, for which the time dependence of dose equivalent rates and dose equivalents may be approximated by a simple exponential. A companion manuscript treats radionuclides with non-trivial time dependences.

Female↗
PubMed1988

Organ doses from radionuclides on the ground. Part II. Non-trivial time dependences.

Organ dose equivalent rates and cumulative organ dose equivalents for photon exposures from plane sources on the ground have been calculated for 159 radionuclides, which can be expected to be released in relevant quantities during accidents in nuclear reactors or reprocessing plants. For 45 of these radionuclides, the contributions of daughter nuclides induce a dependence of the dose equivalents on time, which is not approximated accurately enough by the method proposed for the other radionuclides in a companion article. Results are presented in tables which allow easy reference for radiological calculations.

Accidents↗
PubMed1988

Relaxation prophylaxis for childhood migraine: a randomized placebo-controlled trial.

A randomized controlled trial was used to evaluate the effectiveness of relaxation training in the treatment of paediatric migraine. Relaxation training was compared with-two control groups (psychological placebo and 'own best efforts') in a total of 99 children and adolescents with frequent migraine. Daily recording of the headaches following treatment, three months after treatment and at the one-year follow-up indicated that all three treatments were equally effective. The importance of the use of adequate control conditions which generate equivalent expectancies in pain treatment research was confirmed.

Adolescent↗
PubMed1988

Cotinine in the serum, saliva, and urine of nonsmokers, passive smokers, and active smokers.

Cotinine was measured in the serum, saliva, and urine of nonsmokers, passive smokers, and active smokers. Serum and saliva could not discriminate between nonsmokers and passive smokers. Mean urine cotinine was higher in passive smokers than nonsmokers but there was a great deal of intersubject overlap. Cotinine in all body fluids could separate active smokers from the other two groups. Among smokers, light smokers had lower levels than heavier smokers.

Adult↗
PubMed1988

Effects of the stereoisomers of nicotine and nornicotine on schedule-controlled responding and physiological parameters of dogs.

The behavioral and physiological effects of five tobacco alkaloids were assessed in two different test paradigms. One group of beagle dogs (N = 5) responded under a multiple fixed-interval (FI) 300 sec, fixed-ratio (FR) 30 response schedule of food presentation. With both l-nicotine (0.1-3.0 mumol/kg i.m.) and l-nornicotine (0.1-10.0 mumol/kg i.m.), FI response rates, when averaged across the entire session, were increased at low doses and decreased at high doses; FR response rates were only decreased. d-Nicotine (0.1-30.0 mumol/kg i.m.), and d- and dl-nornicotine (0.1-10.0 mumol/kg i.m.) produced a transient increase in FI response rates at low doses. The effects of the same five compounds on pupillary diameter, rectal temperature and heart rate were measured in a second group of beagle dogs (N = 6). Both pupillary diameter and rectal temperature were decreased initially by l-nicotine (0.6 mumol/kg i.v.), d-nicotine (6.0 mumol/kg i.v.) and d-, l- and dl-nornicotine (3.0 mumol/kg i.v.); base-line levels were recovered within 60 min. Aside from differences in potency, the time courses of action were similar for all five compounds. Increases in heart rate also were produced by all five compounds, but there were marked differences in the duration of action. l-Nicotine and d- and dl-nornicotine produced appreciable, sustained increases in heart rate, whereas d-nicotine and l-nornicotine produced moderate, brief increases. The combined results of the present experiments indicate the stereoisomers of nicotine and nornicotine are behaviorally and physiologically active, and may contribute in varying amounts to the pharmacologic actions of tobacco.

Animals↗