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Biomedical subjects

P Jacob

Publications and source records attributed to P Jacob.

At least 163 records · Page 9Linked to original sources
PubMed1991

Stable isotope studies of nicotine kinetics and bioavailability.

The stable isotope-labeled compound 3',3'-dideuteronicotine was used to investigate the disposition kinetics of nicotine in smokers, the systemic absorption of nicotine from cigarette smoke, and the bioavailability of nicotine ingested as oral capsules. Blood levels of labeled nicotine could be measured for 9 hours after a 30-minute intravenous infusion. Analysis of disposition kinetics in 10 healthy men revealed a multiexponential decline after the end of an infusion, with an elimination half-life averaging 203 minutes. This half-life was longer than that previously reported, indicating the presence of a shallow elimination phase. Plasma clearance averaged 14.6 ml/min/kg. The average intake of nicotine per cigarette was 2.29 mg. A cigarette smoke-monitoring system that directly measured particulate matter in smoke was evaluated in these subjects. Total particulate matter, number of puffs on the cigarette, total puff volume, and time of puffing correlated with the intake of nicotine from smoking. The oral bioavailability of nicotine averaged 44%. This bioavailability is higher than expected based on the systemic clearance of nicotine and suggests that there may be significant extrahepatic metabolism of nicotine.

Administration, Inhalation↗
PubMed1991

Elevated nicotine levels in cervical lavages from passive smokers.

One hundred forty-five nonsmokers found to have normal cytologic diagnoses on routine Pap smears were interviewed regarding environmental exposure to tobacco smoke, and a 3 ml saline lavage of the cervix was collected for measurement of cervical nicotine levels by gas chromatography-mass spectroscopy. Nicotine levels tended to be highest among women exposed to tobacco smoke in the home, intermediate in women exposed only outside the home, and lowest in women recalling no exposure (p = 0.001).

Adolescent↗
PubMed1990

Natural history and significance of esophageal squamous cell dysplasia.

Balloon-mesh cytologic screening for esophageal cancer done in 255 asymptomatic high-risk United States veterans (age greater than 40 years, ethanol abuse for greater than 20 years, and cigarette smoking greater than 20 pack years) identified 37 patients with squamous cell dysplasia. Of the 37 patients with dysplasia, 28 were re-evaluated prospectively at 6-month intervals for up to 36 months by balloon-mesh cytology, esophagoscopy with vital staining and biopsies, chest radiographs, oropharyngeal examination, and indirect laryngoscopy. During prospective follow-up evaluation, cytology specimens were repetitively normal in 16 patients (57%), showed inflammatory changes in eight patients (29%), persisted as dysplasia in two patients (7%) (both had endoscopic and histologic evidence of esophagitis), and progressed to carcinoma in two patients (7%) (one esophageal, one laryngeal). Although histologic findings concurred with the resolution of dysplasia, biopsy specimens were characterized by a similar difficulty in distinguishing dysplasia from inflammation. Erroneous histologic diagnoses of carcinoma in situ were made in two patients with reflux esophagitis evident endoscopically and confirmed during the course of a 24-36 month follow-up period. The authors conclude that squamous cell dysplasia detected by balloon-mesh cytology is seldom a precursor of esophageal cancer in the high-risk U.S. population but, rather, is often related to esophagitis. Thus, balloon-mesh cytology has limited use as a screening method for the early detection of esophageal cancer in the United States.

Adult↗
PubMed1990

Determination of nornicotine in smokers' urine by gas chromatography following reductive alkylation to N'-propylnornicotine.

A sensitive gas chromatographic assay has been developed to measure concentrations of nornicotine in human urine. A structural analogue, 5-methylnornicotine, is used as an internal standard. Both nornicotine and the internal standard were converted to the corresponding N'-propyl derivatives using a novel reductive alkylation procedure. The N'-propyl derivatives have good chromatographic properties, which allows quantitative measurement in the low nanograms per milliliter range. Concentrations of nornicotine in smokers' urine were quantitated and compared with the concentrations of nicotine and its metabolites, cotinine, nicotine-N-oxide and cotinine-N-oxide.

Alkylation↗
PubMed1990

Peristaltic dysfunction associated with nonobstructive dysphagia in reflux disease.

An evaluation was done of 325 consecutive patients who underwent esophageal manometry to investigate the relationship between solid food dysphagia and peristaltic dysfunction in gastroesophageal reflux disease. All patients with dysphagia were endoscoped to evaluate for mechanical obstruction. Manometry was done focusing on the incidence of peristaltic dysfunction (failed peristaltic sequences or sequences characterized by foci of hypotensive peristalsis). The major finding was that the severity of manometrically demonstrated peristaltic dysfunction in reflux patients correlated with the prevalence of dysphagia. After excluding patients with esophageal rings or strictures from the analysis, the overall prevalence of dysphagia was 39% among the 157 reflux patients. Within this group, 29% of patients with minimal peristaltic dysfunction experienced dysphagia compared to 78% of patients with severe peristaltic dysfunction. We conclude that peristaltic dysfunction should be considered along with mechanical obstruction as a potential cause of dysphagia in patients with gastroesophageal reflux disease.

Deglutition Disorders↗
PubMed1990

MR of uncommon congenital and vascular lesions of the intracranial visual pathways.

The MR findings of two patients with rare congenital abnormalities of the optic pathways are reported and illustrated, including one case of unilateral aplasia of the optic chiasm, tract, and visual radiations and another patient with anophthalmos. In three other patients with unusual vascular causes of visual disturbance, MR was important in early establishment of an accurate diagnosis and had consequent implications for decisions regarding further patient management.

Adult↗
PubMed1990

Synthesis of (3'R,5'S)-trans-3'-hydroxycotinine, a major metabolite of nicotine. Metabolic formation of 3'-hydroxycotinine in humans is highly stereoselective.

A method for the synthesis of (3'R,5'S-trans-3'-hydroxycotinine, a major metabolite of nicotine in humans, is described. The method involves deprotonation of (S)-cotinine with lithium diisopropylamide (LDA) followed by oxidation with the transition metal peroxide oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric triamide) (MoOPH) to give an 80:20 mixture of trans-/cis-3'-hydroxycotinine. The pure (greater than 98%) trans isomer is obtained by conversion to the solid hexanoate ester, recrystallization, and cleavage of the ester by heating with n-butylamine. GC-MS analysis of urine extracts from several smokers indicated that in humans metabolic 3'-hydroxycotinine is 95-98% trans.

Biotransformation↗
PubMed1990

Dose-dependency of caffeine metabolism with repeated dosing.

Some recent epidemiologic studies have reported a nonlinear dose-response in the relationship between coffee consumption and health risks, such that the risks increase disproportionately to the increase in dose. Assuming caffeine contributes to the adverse health effects of coffee, a possible explanation for the nonlinear dose-response relationship is dose-dependent metabolism of caffeine. We examined the hypothesis that under chronic dosing conditions the metabolism of caffeine is dose-dependent. Nine healthy subjects were given, in randomized 5-day treatment blocks, placebo, 4.2 (low) and 12 (high) mg/kg/day caffeine in decaffeinated coffee, in six divided doses spaced throughout the day. On the third day of each dosing period, 25 mg of stable-isotope labeled caffeine (2-13C, 1,3-15N2) was given intravenously. Clearance of labeled caffeine fell from 0.118 (placebo treatment) to 0.069 (low dose; p less than 0.005) and to 0.54 (high dose; p less than 0.001) L/hr/kg. The formation and metabolite clearances of paraxanthine, the major primary metabolite of caffeine, also decreased comparing the low and high doses (p less than 0.05). We conclude that caffeine metabolism is dose-dependent, resulting in nonlinear accumulation of methylxanthines in the body. Dose-dependent metabolism of caffeine may explain in part why people who drink large amounts of coffee are at greater risk for cardiovascular disease.

Adult↗
PubMed1990

Determinants of upper esophageal sphincter pressure in dogs.

Chronic experiments were done on six dogs fitted with EMG electrodes on pharyngeal and esophageal musculature. Electromyographic activity of the cricopharyngeus was recorded in awake and sedated animals with and without manometric recordings as well as during esophageal distension. Intraluminal upper esophageal sphincter (UES) pressure had two distinct components; active contraction accompanied by cricopharyngeal EMG activity and passive elasticity that persisted in the absence of EMG activity. Between swallows, the cricopharyngeal EMG activity patterns observed were of either tonic activity, no activity, or phasic activity with inspiratory bursts. The activity level was markedly affected by anesthesia, phonating, whining, panting, level of alertness, or changes in head posture. A brisk UES contraction was elicited in response to passage of the manometric assembly and to intraesophageal balloon distension. Persistent EMG augmentation after stationing of the manometric sensor suggested that intraluminal manometry tends to exaggerate resting sphincter pressure. We conclude that electrical activity of the cricopharyngeus, and by inference UES pressure, is markedly affected by many variables that are difficult to control during clinical or experimental determinations of UES pressure.

Anesthesia, General↗
PubMed1990

Intravenous nicotine replacement suppresses nicotine intake from cigarette smoking.

Insofar as smokers regulate body levels of nicotine, nicotine replacement is expected to suppress the desire to smoke a cigarette. Our study was designed to test the hypothesis that i.v. replacement of nicotine will suppress daily intake of nicotine from ad libitum cigarette smoking and to compare the physiological effects of prolonged exposure to nicotine infused i.v. to the effect of smoking cigarettes throughout the day. Eight subjects received a 14-hr infusion of deuterium-labeled nicotine dosed to achieve levels of nicotine similar to those while smoking cigarettes for each individual (average, 33.1 mg; range, 17.7-49.9 mg) or saline (placebo). Cigarette smoking was permitted as desired. Nicotine infusion did not significantly affect the number of cigarettes smoked or the amount of tobacco burned, but nicotine intake from cigarette smoking was suppressed in all but one subject by an average of 24.6% (range, 4.0-51.2%). Down-regulation of levels of nicotine while smoking in response to infusion of nicotine was imprecise, which may be a result of psychosocial factors influencing smoking behavior along with the development of tolerance to toxic effects of nicotine as a consequence of prolonged exposure to nicotine. Intravenous nicotine and cigarette smoking increased average heart rate and blood pressure throughout the day and 24-hr urinary epinephrine excretion to a similar extent. Despite higher levels of nicotine when subjects smoked during infusion of nicotine, there were no additional nicotine-related effects. No adverse effects were noted; most subjects could not distinguish nicotine from saline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Radiation-induced esophageal injury: a spectrum from esophagitis to cancer.

Radiation esophagitis is a common but frequently unrecognized complication of therapeutic radiation to the neck, chest, or mediastinum. The spectrum of injury ranges from acute self-limited esophagitis to life-threatening esophageal perforation. Complications such as stricture or primary esophageal cancer may occur many years after irradiation, and their linkage to radiation may not be considered. Five cases of radiation-induced injury are described, and the spectrum of radiation-induced esophageal injury is reviewed.

Aged↗
PubMed1989

Sulfonium salts as derivatizing agents. 2. Determination of theophylline in plasma by automated gas chromatography.

An automated gas chromatographic method for determination of theophylline in plasma is described. A novel feature of this assay is the use of triethylsulfonium hydroxide as an on-column alkylating agent. A simple extraction procedure together with automated sample injection and data processing has facilitated processing of large numbers of samples generated in pharmacokinetic studies. The between-run coefficient of variation was 2.2% at 5 micrograms/ml (n = 5) and 3.9% at 15 micrograms/ml (n = 6). Within-run coefficient of variation was 2.4% at 5 micrograms/ml (n = 9) and 3.3% at 15 micrograms/ml (n = 6). Accuracy was 105% at a concentration of 5 micrograms/ml and 102% at 15 micrograms/ml.

Alkylation↗
PubMed1989

Daily use of smokeless tobacco: systemic effects.

STUDY OBJECTIVE: To compare exposure to nicotine and related cardiovascular effects as well as urinary mutagenicity (a potential marker of systemic absorption of carcinogenic compounds) during use of oral snuff, chewing tobacco, and cigarettes, as desired. DESIGN: Crossover sequential treatments, balanced-order experimental study. SETTING: Clinical research center. PARTICIPANTS: Eight healthy men who regularly smoked cigarettes and had previous experience with the use of both oral snuff and chewing tobacco. INTERVENTIONS: Four 3- or 4-day blocks during which participants used oral snuff, chewing tobacco, and cigarettes as desired, or abstained from all tobacco. Concentrations of nicotine and cotinine (the primary metabolite of nicotine), cardiovascular effects, and urine sodium, catecholamine and mutagenicity were measured over 24 hours at the end of each treatment block. MEASUREMENTS AND MAIN RESULTS: Circadian exposure to nicotine and cardiovascular effects, including urinary catecholamine excretion, were similar for all forms of tobacco use. Urine sodium excretion was greater while using smokeless tobacco than while smoking, probably due to absorption of sodium from the smokeless tobacco. Urine mutagenicity was markedly increased while smoking cigarettes and tended to be increased (P less than 0.10) while chewing tobacco but not while using oral snuff. CONCLUSIONS: Systemic absorption of nicotine, sodium, and carcinogenic chemicals from smokeless tobacco may cause or aggravate human illness in addition to the known adverse effects on the oral cavity.

Adult↗
PubMed1989

Dapsone, trimethoprim, and sulfamethoxazole plasma levels during treatment of Pneumocystis pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Evidence of drug interactions.

STUDY OBJECTIVE: To examine the interaction between dapsone and trimethoprim in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Measurement of drug levels as part of an open study of dapsone alone and randomized, double-blind comparison of trimethoprim-dapsone with trimethoprim-sulfamethoxazole in treating Pneumocystis carinii pneumonia in patients with AIDS. SETTING: County hospital and AIDS clinic. PATIENTS: Eighteen patients treated with dapsone alone, 30 with trimethoprim-dapsone, and 30 with trimethoprim-sulfamethoxazole. INTERVENTION: Dapsone, 100 mg/d; trimethoprim, 20 mg/kg body weight per day, and sulfamethoxazole, 100 mg/kg.d; administered for 21 days. MEASUREMENTS AND MAIN RESULTS: Concentrations of dapsone were 40% higher in patients treated with trimethoprim-dapsone than in those treated with dapsone alone (2.1 compared with 1.5 micrograms/mL; P less than 0.05). Trimethoprimdapsone-treated patients had fewer treatment failures but more side effects and treatment terminations due to toxicity than those treated with dapsone alone. The concentration of trimethoprim was 48.4% higher in patients treated with trimethoprim-dapsone than in those treated with trimethoprim-sulfamethoxazole, (18.4 compared with 12.4 micrograms/mL; P less than 0.05). Discontinuation of therapy due to toxicity was commoner in the trimethoprim-sulfamethoxazole group (57% compared with 30%). CONCLUSIONS: A bidirectional drug interaction exists between dapsone and trimethoprim, resulting in higher concentrations of each in the presence of the other.

Acetylation↗
PubMed1989

Preliminary observations on the effects of age on oropharyngeal deglutition.

Swallows of 4 bolus volumes (1, 5, 10, 20 ml) were examined in three groups of subjects: 6 subjects 20-29 years of age, 12 subjects 30-59 years of age, and 6 subjects 60-79 years of age. A simultaneous manometric and videofluoroscopic data collection protocol permitted measurement of bolus transit, temporal aspects of the oropharyngeal swallow, and pharyngeal peristalsis. Statistically significant effects of increasing bolus volume were oral transit of the bolus head (decreased) and duration of cricopharyngeal opening (increased). Five measures were significantly changed with increasing age: duration of pharyngeal swallow delay (increased), duration of pharyngeal swallow response (decreased), duration of cricopharyngeal opening (decreased), peristaltic amplitude (decreased), and peristaltic velocity (decreased).

Adult↗