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Biomedical subjects

P Jacob

Publications and source records attributed to P Jacob.

At least 109 records · Page 6Linked to original sources
PubMed1997

Subnanogram-concentration measurement of buprenorphine in human plasma by electron-capture capillary gas chromatography: application to pharmacokinetics of sublingual buprenorphine.

We describe a sensitive and specific method for the measurement of buprenorphine in human plasma. The method involves a structural analog as an internal calibrator, careful control of pH during sample extraction to maximize drug recovery, and back-extraction into acid followed by reextraction to eliminate endogenous interferences. After evaporation, sample residues are derivatized with heptafluorobutyric anhydride and analyzed by separation on a fused-silica polymethylsiloxane capillary column and electron-capture detection. Calibration curves were linear in the ranges 0.1-2.0 micrograms/L and 2.0-20 micrograms/L, with within-run CVs of 9.7% at 0.1 microgram/L to 5.0% at 20 micrograms/L, and total CVs of 15.9% at 0.1 microgram/L to 6.5% at 10 micrograms/L. The limit of quantification was 0.1 microgram/L. The method was utilized in studies to determine the absolute bioavailability of sublingual doses of 2 mg of buprenorphine in 1 mL of 300 mL/L ethanol and the bioequivalence of sublingual 8-mg tablet and 300 mL/L ethanol solution formulations.

Administration, Sublingual↗
PubMed1997

Releasable suture technique for trabeculectomy.

A retrospective review of 154 trabeculectomies with releasable sutures was performed to assess the effect of suture release on intraocular pressure (IOP) at various postoperative periods. Release of the suture was necessary in 38% of cases. The immediate reduction in IOP was significant (p < 0.01) when the suture was released during the first three postoperative weeks. Seventy percent of eyes had a reduction in IOP more than 5 mmHg if released within the first week compared to 20% after the third week. With suture release after the third postoperative week, there was no clinically significant decrease in IOP. The decrease in IOP was similar in eyes undergoing trabeculectomy alone or when cataract extraction through a separate corneal incision was undertaken simultaneously. The period during which release of suture was effective was not prolonged by use of antimetabolites. Complications included a typical windshield-wiper keratopathy (18 eyes), failure to release the suture (13 eyes), epithelial abrasion (6 eyes) and a sub-conjunctival bleed (1 eye).

Cataract Extraction↗
PubMed1996

Fibrinogen binding and platelet retention: relationship with the thrombogenicity of catheters.

One of the major problems in the use of catheters is their thrombogenicity, since the embolization of clots near the central nervous system or the coronary arteries can cause permanent damage. In this work we have compared the in vivo thrombogenicity of four different angiography catheters and their in vitro activation of fibrinogen binding and platelet retention. The thrombogenicity of catheters has been evaluated in angiographic conditions by kinetic evaluation of the reduction of blood flow rate through the catheters. The binding of adhesive proteins (fibrinogen and von Willebrand factor [vWF] was studied in vitro using a direct-ELISA technique after circulation of anticoagulated whole blood through sections of catheters. The retention of platelets was studied in vitro using 111Indium-labelled platelets. Fibrinogen binding and platelet retention both seem to be good predictors of catheter thrombogenicity, fibrinogen being the better of the two. The most thrombogenic material has the highest fibrinogen and platelet retention rate. This study also confirms the inefficiency of albumin precoating for the prevention of fibrinogen deposition. The determination of fibrinogen deposition by direct-ELISA technique and platelet retention rate is very useful for preclinical testing of catheters.

Biocompatible Materials↗
PubMed1996

In situ gamma-spectrometry several years after deposition of radiocesium. Part I. Approximation of depth distributions by the Lorentz function.

Several years after the deposition of fallout-radiocesium, the maximal activity of this radionuclide will not remain at the soil surface but be found rather in deeper layers. In order to estimate the total radiocesium contamination of a large area and the resulting gamma-dose rate by in-situ spectrometry, it is necessary to approximate the vertical distribution of this radionuclide by an analytical function. Observations at ten undisturbed grassland soils and Bavaria, Germany, show that the resulting depth distributions can be approximated closely by a three-parameter Lorentz function. This function characterises the observed distributions in all three critical sections, i.e. the surface layer, the distribution around the maximal concentration, and the tail at greater depth. It is also shown that the observed total activity per unit area of the soil due to 137Cs agrees very well with the corresponding value obtained from the integrated Lorentz function. The two coefficients of the Lorentz function, which characterise the location (depth) and width of the maximum in the activity distribution, are shown to be correlated. In part II of this study, it will be shown how the parameters of the Lorentz function can also be obtained by in-situ gamma-ray spectrometry. As a result, it is possible to use in-situ gamma-ray spectrometry to obtain the total 137Cs activity per unit area also for sites where the vertical distribution of this radionuclide in the soil is no longer exponential.

Cesium Radioisotopes↗
PubMed1996

Pilot study of the Urals population by tooth electron paramagnetic resonance dosimetry.

During 1949-1956, about 76 x 10(6)m3 of radioactive liquid waste containing a total activity of 10(17) Bq was discharged into the Techa River by the first Russian industrial nuclear facility Mayak. As a consequence, the population living in the river valley received considerable internal and external radiation doses. The results of a first application of electron paramagnetic resonance (EPR) of tooth enamel for a retrospective individual dose evaluation of the residents of the Techa riverside are presented. Three main contributions to the dose absorbed in tooth enamel have been considered: external exposure mainly from the Techa River sediments, internal exposure mainly due to 90Sr; and background radiation including all other sources of exposure except the Techa River. The teeth of 86 inhabitants of the town Kamensk-Uralskii were analysed to determine the age-dependent contribution of the background radiation to the enamel dose. For 22 residents of the middle and lower Techa riverside, measurements of the 90Sr whole-body content and EPR measurements of the absorbed dose in enamel were used to establish a correlation between these two quantities. Finally, absorbed doses in the enamel of five residents of the upper Techa riverside were determined by EPR method. Contributions of the background radiation and the internal 90Sr contamination were subtracted to determine the external exposure of the residents.

Aged↗
PubMed1996

Depth-dose distribution in bricks determined by thermoluminescence and by Monte-Carlo calculation for external gamma-dose reconstruction.

The analysis of depth-dose distributions in bricks sampled from walls in areas with nuclear waste or accident contamination has the potential of providing information on the energy and source configuration of the gamma-radiation that had been incident on the brick. In this study, a brick from a mill facing a shallow water reservoir of the contaminated Techa river in the South Ural region is investigated. Thermoluminescence (TL) methods were used to measure the accumulated dose at several depths in the brick. The accidental external gamma-dose is obtained by subtracting the natural radiation background dose from the total accumulated dose. In the first segment of the brick, at a depth of about 1.5 cm, the accident dose was found to be roughly 3.5 Gy. Monte-Carlo simulations of the photon transport from the reservoir bed contaminated with 137Cs were calculated for different depths in the brick. The calculations were made assuming different attenuating water levels. It is found that the depth-dose distribution determined by measurements corresponds to a water level between 20 and 50 cm. The results indicate that TL measurements combined with Monte-Carlo modelling calculations are highly promising for external gamma-dose reconstruction applications.

Beta Particles↗
PubMed1996

Validation of urine caffeine metabolite ratios with use of stable isotope-labeled caffeine clearance.

OBJECTIVE: A number of caffeine metabolite ratios have been proposed to measure CYP1A2 activity in vivo. The data to validate these ratios are scanty. The objective of this study was to validate urine caffeine metabolite ratios versus stable isotope-labeled caffeine clearance under different caffeine dosing conditions. STUDY DESIGN: Two experiments, one with nine nonsmoking subjects and the other with 12 cigarette smokers, were performed. We explored the relationship between caffeine clearance, measured by means of intravenous infusions of stable isotope-labeled caffeine, and a number of caffeine metabolite ratios during administration of different single or multiple doses of caffeine to smokers and nonsmokers on three different occasions over a 2-week period, using different durations of urine collections, including spot urines. The stable isotope technique allowed simultaneous oral dosing of caffeine and measurement of caffeine metabolite ratios and caffeine clearance, the latter reflecting CYP1A2 activity. RESULTS: The caffeine metabolite ratio of AAMU + 1U +1X/17U (5-acetylamino-6-amino-3-methyluracil + 1-methyluric acid + 1 methylxanthine/1,7-dimethyluric acid) maintained a significant correlation with caffeine clearance for all the above conditions (gamma2 range, 0.4 to 0.9) except for dose. With high doses of caffeine (12 mg/kg), a significant relationship was not observed. AAMU + 1U + 1X/17U also correlated with the formation clearance of paraxanthine (gamma2 = 0.6, p = 0.002). Other reported caffeine metabolite ratios did not display the same robust correlation with caffeine clearance under all these different conditions. CONCLUSIONS: We conclude that AAMU+1U+1X/17U measured from a single spot urine collection is a valid measure of CYP1A2 activity except at very high levels of caffeine dosing. The validity of the other proposed caffeine metabolite ratios is questionable.

Adult↗
PubMed1996

The effect of liver disease on urine caffeine metabolite ratios.

OBJECTIVES: A number of caffeine metabolite ratios (CMRs) have been proposed to measure CYP1A2 activity in vivo. The effect of liver disease on these ratios is not clear. The objective of this study was to determine the influence of liver disease on caffeine metabolite ratios. STUDY DESIGN: Two studies were performed. First, in healthy control subjects and in subjects with cirrhosis, caffeine clearance was measured by intravenous infusion of stable isotope-labeled caffeine while subjects consumed oral caffeine. Second, spot urine samples were collected from control subjects and from subjects with either chronic hepatitis or cirrhosis while they consumed caffeine. RESULTS: In study 1, caffeine clearance was decreased in subjects with cirrhosis (control mean, 0.14 L/hr/kg; cirrhosis mean, 0.04 L/hr/kg; p = 0.003). CMRs were affected by liver disease (e.g., ratio characterizing paraxanthine demethylation [AAMU + 1X + 1U/17U], control median, 8.3; cirrhosis median, 6.2; p = 0.005). AAMU + 1X + 1U/17U correlated significantly with caffeine clearance in the control group (r2 = 0.68; p = 0.0001) and in subjects with cirrhosis (r2 = 0.41; p = 0.05). In study 2, there was a significant difference between control subjects and subjects with cirrhosis for AAMU + 1X + 1U/17U (median for control subjects, 6.2; median for subjects with cirrhosis, 4.3; p = 0.001) but not between control subjects and patients with chronic hepatitis. CONCLUSIONS: We conclude that AAMU + 1X + 1U/17U is affected by liver disease and reflects the decrease in CYP1A2 activity in subjects with cirrhosis. AAMU + 1X + 1U/17U measured from a spot urine sample reflects caffeine clearance in subjects with cirrhosis and may be useful as a hepatic function test. Despite the large interindividual variation observed, the test can be repeated easily in the same patient and an individual patient's decline in CYP1A2 activity, such as in patients with progressively deteriorating liver function, can be monitored.

Adult↗
PubMed1996

Effective doses due to external irradiation from the Chernobyl accident for different population groups of Ukraine.

A model for the external exposure of the Ukrainian population after the Chernobyl accident was developed. It is based on extensive measurements of external gamma-exposure rates (EGER) in air and of external effective doses of members of five population groups. Questionnaires were used to determine the occupancy times of members of the population groups at three types of locations; inside houses, outdoors, and outside of the home settlement. Behavior factors are defined as the ratio of individual external doses to a reference dose for a phantom standing permanently over an open field with the same average 137Cs activity per unit area as in the settlement. The behavior factors were derived for five population groups (children younger than seven years, the age group from eight to seventeen years, employees, agricultural workers, and pensioners) by two methods: first from direct measurements of individual doses by thermoluminescent dosimetry and an experimental determination of the average 137Cs activity per unit area in the settlement of interest; and second from external gamma-exposure rates in air at various types of locations and from the questionnaire data. The methods were found to be consistent and the results were used to calculate external exposures of the five population groups in the years 1987 through 1991.

Adult↗
PubMed1996

CYP2D6 phenotype and the metabolism of nicotine and cotinine.

That CYP2D6 activity is an important determinant of nicotine metabolism and that people who have abnormal CYP2D6 genes are poor metabolizers of nicotine has been reported in the medical literature. The aim of this study was to assess the role of CYP2D6 in nicotine metabolism. Specifically, we compared the clearance of stable isotope-labelled nicotine and cotinine in 11 poor and 33 extensive metabolizers of dextromethorphan, a probe for CYP2D6 activity. The groups were matched by gender, age and ethnicity. Nicotine and cotinine kinetics were quite similar for cases and controls. These data suggest that CYP2D6 is not a major isozyme for the metabolism of nicotine or cotinine.

Adult↗
PubMed1996

Estimation of 131I thyroid doses for the evacuees from Pripjat.

The thyroid doses of 49,360 inhabitants of Pripjat evacuated after the accident at Chernobyl were reconstructed. During their evacuation most of the evacuees passed through highly contaminated territories. The evaluation of a large-scale public survey showed that only about 50% of the evacuees had left the contaminated areas within 5 days and that 30% of them stayed there for more than 30 days. As a first step, the model of dose estimations was improved, and thyroid doses were assessed for the group of evacuees for whom the 131I activity in the thyroids was measured. The 131I incorporation during the first 5 days after the accident was described by a single-intake model (inhalation); later incorporations were assumed to be proportional to the radioiodine activity in milk. As a second step, the correlation between the calculated doses and individual parameters (place of residence in Pripjat, intake of stable iodine, and age at the time of the accident) was described by an empirical equation. This equation was applied to all evacuees who completed the questionnaires of the public survey. Previous dose assessments were found to overestimate the thyroid doses especially for the younger evacuees. On the basis of these estimations, collective doses and the resulting radiation risks for thyroid cancer were assessed for different age groups.

Adolescent↗
PubMed1995

Gas chromatographic determination of methamphetamine and its metabolite amphetamine in human plasma and urine following conversion to N-propyl derivatives.

A gas chromatographic method for the simultaneous determination of methamphetamine and its metabolite amphetamine in human plasma and urine is described. The method utilizes reductive alkylation with propionaldehyde and sodium borohydride to produce N-propyl derivatives, which have excellent chromatographic properties. Structural analogs of the analytes, p-methylmethamphetamine and p-methylamphetamine, are used as internal standards. The method has good precision and accuracy for concentrations ranging from less than 10 ng/ml to 5000 ng/ml and has been used to measure plasma concentrations as part of a pharmacokinetic/pharmacodynamic study of methamphetamine in humans.

Aldehydes↗
PubMed1995

Sympathomimetic effects of paraxanthine and caffeine in humans.

Caffeine is metabolized extensively (on average 80%) to paraxanthine. With regular caffeine consumption, average serum levels of paraxanthine are two thirds those of caffeine. Both caffeine and paraxanthine competitively and nonselectively inhibit adenosine receptors in vitro. To examine the contribution of paraxanthine to the pharmacologic activity of caffeine, we administered to 12 subjects in a crossover design oral caffeine (2 or 4 mg/kg) versus placebo or oral paraxanthine (same dose as caffeine) versus placebo, each after 3 days of methylxanthine abstinence. Both caffeine and paraxanthine significantly increased diastolic blood pressure, plasma epinephrine levels, and free fatty acids. Caffeine and paraxanthine produced a similar magnitude of response at 4 mg/kg; however, caffeine appeared to produce greater responses than paraxanthine at 2 mg/kg. Caffeine and paraxanthine have similar sympathomimetic actions. The activity of paraxanthine needs to be considered in understanding the clinical pharmacology of caffeine, particularly with chronic, repetitive caffeine consumption.

Adult↗
PubMed1995

Methamphetamine and ethanol interactions in humans.

OBJECTIVE: Methamphetamine and ethanol are commonly used together. We examined the effects of intravenous methamphetamine (30 mg), oral ethanol (1 gm/kg), and the combination of methamphetamine (30 mg) and ethanol (1 gm/kg). METHODS: Eight methamphetamine and ethanol users were studied in a double-blind, double-placebo, within-subject, balanced Latin-square design. Ethanol was administered in six drinks over 30 minutes. Methamphetamine was injected 60 minutes after the first drink was begun. Cardiovascular, subjective, and neuropsychologic effects of the drug combinations were measured for 6 hours. Methamphetamine and amphetamine in plasma and urine were measured by capillary gas chromatography for 48 hours. Data were analyzed by repeated-measures ANOVA. RESULTS: Compared with methamphetamine alone, the combination increased heart rate but decreased systolic blood pressure. The net cardiovascular effect was an increase in rate pressure product, an index of cardiac work and myocardial oxygen consumption. The combination diminished the subjective effects of ethanol while not affecting the subjective effects of methamphetamine. Methamphetamine pharmacokinetics were not altered by the concurrent administration of ethanol, with the exception of lowering the apparent volume of distribution at steady state for methamphetamine. CONCLUSIONS: As a potent sympathomimetic drug with alpha-agonist-like effects, methamphetamine increased systolic blood pressure, with minimal change in heart rate. The concurrent administration of methamphetamine and ethanol increased cardiac work, which could produce more adverse cardiovascular effects than either drug taken alone. The increased perceived global intoxication may explain the popularity of this drug combination.

Administration, Oral↗
PubMed1995

Deficient C-oxidation of nicotine.

In most people, nicotine is extensively (70% to 80%) metabolized to cotinine by C-oxidation. In a clinical trial, a 57-year-old woman was found to have the expected plasma levels of nicotine but unusually low plasma levels of cotinine both when smoking cigarettes and while receiving transdermal nicotine. To characterize her metabolism, simultaneous infusions of deuterium-labeled nicotine (d2) and cotinine (d4) were administered, with comparison to 20 other control smokers. The clearance of nicotine was unusually low (6.5 ml/min/kg versus 17.2 ml/min/kg), and the half-life of nicotine significantly longer (348 minutes versus 138 minutes) in the index case subject compared with the control subjects. The clearance of cotinine was normal. The index case subject converted only 9% of nicotine to cotinine, compared with 72% for the control subjects. As far as we know, this is the first person with deficient C-oxidation of nicotine to be characterized. Deficient C-oxidation of nicotine is associated with a long half-life of nicotine and deficient generation of cotinine, both of which could influence the risks and addictiveness of tobacco use in affected individuals.

Adult↗
PubMed1995

Calcium alginate swab versus Bard Parker blade in the diagnosis of microbial keratitis.

A prospective comparative evaluation of Bard Parker blade no. 15 and calcium alginate swab in the collection of corneal material was conducted. The study group included 30 consecutive cases of bacterial (n = 17), fungal (n = 11), and mixed (n = 2) cases of microbial keratitis. The samples collected by blade and swab were processed in an identical manner for viable colony counts. The yields from blade and swab were compared using the proportion test, taking into consideration the mean counts of each organism. The swab yielded significantly greater growth than blade (p = 0.003) in mycotic ulcers. However, the two patients (2/11) who showed no growth by blade but were positive by swab had smears positive and were diagnosed as mycotic ulcers. The difference between the two methods was not significant for bacterial and mixed ulcers. Replacement of blade with calcium alginate swab did not appear to be advantageous for the investigation of infectious keratitis.

Alginates↗