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Biomedical subjects

P Jacob

Publications and source records attributed to P Jacob.

At least 217 records · Page 12Linked to original sources
PubMed1985

Nicotine renal excretion rate influences nicotine intake during cigarette smoking.

We examined the hypothesis that rate of elimination of nicotine affects nicotine intake during cigarette smoking. Elimination rate was altered by administering ammonium chloride or sodium bicarbonate throughout the day. Nicotine intake during unrestricted cigarette smoking was measured using metabolic clearance data obtained after i.v. nicotine infusion together with blood and urinary nicotine concentrations measured during 24-hr periods of cigarette smoking. Compared with placebo treatment (urine pH 5.6), urinary acidification (pH 4.5) increased (208%) renal clearance and, to a lesser extent (41%), total clearance and increased (by 7.2 mg) daily urinary excretion of nicotine. Urinary alkalinization (pH 6.7) resulted in a decrease (78%) in renal clearance with a small decrease (3.7 mg) in daily nicotine excretion. Average blood nicotine concentrations were similar in placebo and bicarbonate treatment conditions, but were 15% lower during acid loading. Daily intake of nicotine was 18% greater during acid loading. The compensatory increase in nicotine consumption was only partial, replacing about half the excess urinary nicotine loss. This is the first direct demonstration that rate of elimination can influence self-determined drug consumption in humans.

Adult↗
PubMed1984

Determination of cocaine in plasma by automated gas chromatography.

A rapid and sensitive gas chromatographic method is described for the determination of cocaine in plasma. A close structural analogue of cocaine, m-toluylecgonine methyl ester, is used as an internal standard. The simplicity of the extraction scheme and the use of an automatic sampler makes the method convenient for large numbers of samples generated in pharmacokinetic studies.

Autoanalysis↗
PubMed1984

Trazodone-oral cocaine interactions.

Depression and dysphoria can follow the long-term use of cocaine. Little is known about the interaction of antidepressant drugs with cocaine and similar stimulants in humans. The physiologic and subjective effects of an oral 2-mg/kg dose of cocaine hydrochloride were measured in eight healthy cocaine-using men after pretreatment with a single, 100-mg oral dose of the triazolopyridine antidepressant trazodone hydrochloride or placebo in a double-blind study. The cocaine-induced effects of increased BP, increased pupil size, and decreased skin temperature were diminished by trazodone pretreatment. Trazodone alone did not alter plasma epinephrine or norepinephrine levels. An increase in plasma epinephrine levels after cocaine administration was not altered by trazodone pretreatment, but the increase in the norepinephrine level was larger. Trazodone alone produced mild sleepiness. Cocaine-induced euphoria was not altered by trazodone pretreatment, although feelings of tension and shakiness after cocaine administration were diminished.

Administration, Oral↗
PubMed1984

Sulfur analogues of psychotomimetic agents. 3. Ethyl homologues of mescaline and their monothio analogues.

All possible monothio analogues of the mono-, di-, and triethoxy homologues of mescaline have been synthesized and pharmacologically evaluated in man. Modifications at the ring position para to the ethylamine chain, either with a sulfur atom, a longer alkyl chain, or both, lead to compounds of high central nervous system activity. The 4-n-propoxy and 4-n-butoxy homologues and their corresponding 4-thio analogues were also synthesized and pharmacologically evaluated. The propyl homologues retain high potency, but a butyl group (either with or without a sulfur atom) leads to a decrease in activity. The m-ethyl or m-thio analogues retain some central action but the diethoxy and especially the triethoxy homologues are relatively inactive as psychotomimetic drugs.

Adult↗
PubMed1984

Blood cotinine levels as indicators of smoking treatment outcome.

Pretreatment blood cotinine levels, expired carbon monoxide levels, and self-reported cigarette consumption were evaluated as predictors of smoking treatment outcome in 114 patients. Of these indices of nicotine intake, blood cotinine level was the most useful predictor. High blood cotinine level was the best predictor of dropping out before completion of treatment and of smoking at the end of treatment and at follow-ups. The usefulness of cotinine as a marker of tobacco dependence is discussed.

Adult↗
PubMed1984

Influence of nicotine on cardiovascular and hormonal effects of cigarette smoking.

To elucidate the importance of nicotine in determining the effects of cigarette smoking, we studied 10 healthy subjects on a research ward who were either smoking their usual brand of cigarettes, smoking high- (HN, 2.5 mg) or low- (LN, 0.4 mg) nicotine research cigarettes, or abstaining. Blood nicotine concentrations were four times as high smoking HN than LN cigarettes. Values while smoking their own brands were intermediate. Cigarette smoking increased mean (24-hr) heart rate (HR), but HR effect did not differ as a function of nicotine exposure. Analysis of the hourly HR pattern showed that smoking increased HR more over the first few hours of the morning, but then followed a circadian pattern similar to that during abstention. HR remained elevated all night even though no cigarettes were smoked. Blood pressures tended to be higher while smoking, but plasma cortisol concentrations throughout the day did not differ while smoking or abstaining. Thus the amount of nicotine consumed when assessed over the whole day has little influence on magnitude of cardiovascular responses to cigarette smoking. Insofar as nicotine contributes to risk, changing nicotine content per se may not alter the risk of sudden adverse cardiac events associated with cigarette smoking.

Adult↗
PubMed1984

Nicotine and carbon monoxide intake from high- and low-yield cigarettes.

We measured daily nicotine intake in 11 habitual smokers who smoked their usual brand or commercial high-yield (Federal Trade Commission [FTC] yield 1.2 mg nicotine, 16 mg tar) or low-yield (0.4 mg nicotine, 5 mg tar) cigarettes. Daily nicotine intake was measured from metabolic clearance data in conjunction with blood and urinary concentrations of nicotine during 24-hr smoking periods. On the average, subjects consumed 35 mg nicotine while smoking their usual cigarettes and 26 mg while smoking either high- or low-yield commercial cigarettes different from their usual brand. This level of nicotine consumption from low-yield cigarettes was because smokers obtained 60% more nicotine per cigarette than predicted by FTC yield and they smoked 25% more cigarettes a day. Although there was considerable variability in nicotine intake between subjects, there was a correlation within subjects between intake while smoking their usual brand and experimental cigarettes. Nicotine intake between the two commercial high- or low-yield cigarettes also correlated (r = 0.86). These findings are consistent with a minimal level of acceptable daily intake of nicotine for individuals that is related to usual intake. We suggest that our protocol provides a better quantitative estimate of the yield of different cigarette brands and potential health hazards than those currently provided by the FTC.

Adult↗
PubMed1984

Daily intake of nicotine during cigarette smoking.

Daily intake of nicotine in 22 subjects was estimated from metabolic clearance data obtained after intravenous infusion of nicotine and from blood and urinary nicotine concentration data obtained over 24 hr when the subjects were smoking cigarettes. Daily intake of nicotine averaged 37.6 mg (+/- 17.7, SD) but varied widely among subjects (10.5 to 78.6 mg). Men metabolized nicotine faster than did women, but daily intake of nicotine did not differ. Intake correlated strongly with cigarettes smoked per day (r = 0.59) but not with machine-determined yield. Nicotine intake per cigarette averaged 1.04 mg (+/- 0.36) but did not correlate with machine-determined yield. Correlations between several commonly used biochemical markers of tobacco smoke and nicotine intake were examined; the afternoon (4:00 P.M.) blood level of nicotine was the best marker.

Adult↗
PubMed1984

[Therapeutic or palliative embolization aimed at analgesia for bone metastases of renal origin].

In addition to the chemotherapy, surgery and physical treatments usually employed in the treatment of bony secondaries from renal tumours, the authors propose embolization. They have performed this procedure in 4 patients, using a mixture of isobutyl-2-cyanoacrylate and lipiodol. Arteriography is performed before and after the embolization which is carried out under local anaesthesia. Disappearance or relief of pain was obtained in each case. This technique in no way changes the prognosis of the disease, but it can improve the quality of life of these patients. A review of the literature reveals that metastases other than renal have already been embolized, as have primary malignant bone tumours. The authors describe their method, the incidents associated with treatment, the contra-indications and the supposed mechanism of the analgesic action of embolization.

Aged↗
PubMed1983

Smokers of low-yield cigarettes do not consume less nicotine.

Advertisements suggest that smokers of cigarettes low in nicotine are exposed to less nicotine and tar. Nicotine yields are measured with smoking machines, but machines do not smoke cigarettes as people do. We therefore measured the actual nicotine content of commercial cigarettes with different nicotine and tar yields as determined with smoking machines, and also measured actual nicotine intake as indicated by blood concentrations of its metabolite, cotinine, in 272 subjects smoking various brands of cigarettes. We found that low-yield cigarette tobacco did not contain less nicotine; in fact, the nicotine concentration in tobacco inversely correlated (r = -0.53, P less than 0.05) with the concentration measured by smoking machines. Blood cotinine concentrations correlated with the number of cigarettes smoked per day but not with the nicotine yield measured by smoking machines. Only 3.8 to 5.0 per cent of total variance in blood cotinine was contributed by nicotine yield. We conclude that smokers of low-nicotine cigarettes do not consume less nicotine.

Adult↗
PubMed1983

[Yersinia enterocolitica and pseudotuberculosis reactive arthritis with antinuclear antibodies. 4 cases].

Antinuclear antibodies (ANA) were demonstrated in four patients (2 male, 2 female) with reactive arthritis (RA) due to Yersinia enterocolitica (YE) and Yersinia pseudotuberculosis (YPT). Changes in ANA titres and serologic tests were not correlated. The two patients are HLA B27 positive. Polysaccharides could be partly responsible for Yersinia antigenicity. The presence of ANA in chronic forms of RA due to Yersinia warrants discussion.

Antibodies, Antinuclear↗
PubMed1983

Sulfur analogues of psychotomimetic agents. 2. Analogues of (2,5-dimethoxy-4-methylphenyl)-and (2,5-dimethoxy-4-ethylphenyl)isopropylamine.

The two thio analogues of each of the well-known psychotomimetic drugs DOM [(2,5-dimethoxy-4-methylphenyl)isopropylamine] and DOET [(2,5-dimethoxy-4-ethylphenyl)isopropylamine] have been synthesized and pharmacologically evaluated in man. The 5-thio isomers are more potent as psychotomimetic agents than the 2-thio isomers but still represent a drop of an order of magnitude in potency from the sulfur-free counterparts. The dithio analogue of DOM was synthesized and found to be without central activity at a dosage of approximately 50 times the mean effective dose of DOM.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1983

Cotinine disposition and effects.

Cotinine is the major metabolite of nicotine in man. We studied cotinine disposition kinetics in 28 healthy habitual cigarette smokers. Eight subjects received cotinine fumarate, 4 micrograms base/kg/min IV for 60 min. Mean (+/- SD) metabolic clearance was 60 +/- 12 ml/min and mean renal clearance was 12 +/- 5 ml/min, averaging 17% of total clearance. Steady-state volume of distribution was slightly greater than body weight (mean 88 +/- 17 l). Terminal t 1/2 averaged 15.8 +/- 4.0 hr in these eight subjects and 19.7 +/- 6.5 hr in another 12 subjects who abstained from smoking for 3 days. The effect of urinary acidification and alkalinization on renal clearance of cotinine during cigarette smoking was studied in another group of eight subjects. Compared with baseline (mean urinary pH 5.8, renal clearance 12.3 +/- 5.9 ml/min), renal clearance was increased about 50% by urinary acidification (pH 4.4, clearance 18.6 +/- 10 ml/min), but it was not affected by alkalinization (pH 6.7, clearance 14.0 +/- 10.4 ml/min). Infusion of cotinine to blood concentrations seen in moderately heavy smokers had no effect on heart rate, blood pressure, or skin temperature, measures that are sensitive to effects of nicotine. No spontaneous subjective effects were reported. We conclude that, at levels to which cigarette smokers are generally exposed, cotinine exerts no cardiovascular activity and weak, if any, psychologic activity.

Adult↗