Search PubMed⌕ Search

Biomedical subjects

P Jacob

Publications and source records attributed to P Jacob.

At least 127 records · Page 7Linked to original sources
PubMed1995

[Endoscopic ligation of esophageal varices: prevention of hemorrhagic recurrences caused by rupture of esophageal varices. Results in 45 patients].

OBJECTIVES: The aim of this study was to assess the morbidity and efficacy of endoscopic variceal ligation for the prophylaxis of rebleeding from oesophageal varices. METHODS: Forty-five patients with cirrhosis (Child's class: A: 18, B: 16, C: 11) and recent (< 48 h) variceal bleeding were included. Eleven of the patients were included after failure of sclerotherapy. All patients were treated by endoscopic ligation until the complete eradication of oesophageal varices. The mean follow-up was 8.7 +/- 6.8 months. RESULTS: Oesophageal varices were eradicated in 40 patients (89%) after an average of 2 sessions (range: 1-5). In a subset of 11 patients treated after failure of sclerotherapy, 8 (73%) had complete eradication of oesophageal varices. Six of the 45 patients (13%) had recurrence of haemorrhage, due to post-ligation ulcerations in 5 cases and to rupture of oesophageal varices in one case. The rate of complications was 7%. Of the 40 patients whose oesophageal varices were eradicated, 7 (17%) were lost for follow up, and another treatment was performed in 4 (10%): liver transplantation in 2, and transjugular intrahepatic portosystemic shunt in 2. Recurrence of oesophageal varices after eradication was observed in 3 (10%) of the remaining 29 patients after a follow-up of 8.9 +/- 12.9 months. Of these 3 patients, only one (3%) presented with recurrence of haemorrhage due to ruptured oesophageal varices. Three patients (7%) died before eradication of oesophageal varices from causes unrelated to the technique. CONCLUSION: This study confirms that endoscopic ligation is effective for eradication of oesophageal varices, with a low morbidity. This technique appears to be a method of choice in the prophylaxis of rebleeding from oesophageal varices, especially when sclerotherapy is ineffective.

Adult↗
PubMed1995

[Scaphoid fracture associated with displaced fracture of the distal end of the radius in children. Apropos of a case].

A child of 13 years, victim of a fall on his wrist at dorsal flexion position; he presented a scaphoid fracture associated with a displaced fracture of the distal end of the radius. The radius fracture was reduced under general anesthesia, by external manoeuvre; the consolidation was obtained after 10 weeks of plaster cast immobilization. The follow-up was of two years, with a good clinical and radiological result in spite of a non union of the Ulnar-styloid. It is important to remember this exceptionnel association in children not to forget the scaphoid fracture.

Adolescent↗
PubMed1995

Molecular characterization of Charcot-Marie-Tooth patients in 15 pedigrees from France.

Molecular characterization of Charcot-Marie-Tooth patients in 15 pedigree from France: We collected 15 Charcot-Marie-Tooth (CMT) pedigrees from France. DNA polymorphisms analysis by Southern blotting with probes at the D17S122 locus demonstrated 17p duplication in three CMT1a families and in one sporadic case. Two families affected by CMT2 showed no evidence of the duplication.

Blotting, Southern↗
PubMed1994

Attenuation effects on the kerma rates in air after cesium depositions on grasslands.

Since the reactor accident of Chernobyl, cesium depth profiles and nuclide-specific kerma rates in air have been determined for various grassland sites in south Bavaria and in Ukraine. The sites are described by soil characteristics, annual precipitation, distance from release point, mode of deposition, and activity per unit area. The effects of surface roughness and migration of cesium into the soil on the kerma rate in air over grasslands was determined by two methods. The kerma rates in air obtained by the evaluations of in situ gamma-ray spectrometry results and of measured activity distributions in the soil showed only negligible differences for the observation period of 6 years after deposition. For the sites in Ukraine the kerma rate in air per activity per unit area was found to be systematically 40% higher than in Bavaria. The results from Bavaria on the attenuation of the kerma rate and a data set, including experiences from the weapons test fallout, are analytically approximated as a function of time up to 25 years after deposition.

Air Pollutants, Radioactive↗
PubMed1994

Divergent tolerance to metabolic and cardiovascular effects of nicotine in smokers with low and high levels of cigarette consumption.

Cigarette smokers on average weigh less than nonsmokers. However, among smokers, those who smoke the most weigh the most. To better understand the effects of nicotine on body weight, we investigated the pharmacodynamics of intravenous nicotine and cigarette smoking in low-level smokers (10 or fewer cigarettes per day) and high-level smokers (15 to 30 cigarettes per day). Cigarette smoking and intravenous nicotine increased heart rate and energy expenditure in most smokers. The effects of intravenous nicotine and smoking were of similar magnitude, confirming that the effects of smoking are mediated by nicotine. Nicotine produced a slightly greater increase in heart rate in low-level versus high-level smokers, but energy expenditure increased to a much greater extent in low-level versus high-level smokers. The plots of plasma nicotine concentration versus responses suggest development of acute tolerance to both heart rate acceleration and increased energy expenditure in low-level smokers; high-level smokers show a similar pattern of tolerance for heart rate but show only a brief increase in energy expenditure and a hysteresis curve consistent with either rapid development of tolerance or no effect. Thus there is evidence of differential development or rate of loss of tolerance to cardiovascular versus metabolic effects of nicotine in low-level versus high-level smokers. Pharmacodynamic differences between low-level and high-level smokers may explain, at least in part, the unusual relationship between cigarette consumption and body weight.

Adult↗
PubMed1994

Metabolism of nicotine to cotinine studied by a dual stable isotope method.

OBJECTIVES: (1) To determine the disposition kinetics of nicotine and cotinine, including the fractional conversion of nicotine to cotinine, (2) to compare the disposition kinetics of deuterium-labeled and unlabeled cotinine, and (3) to develop a pharmacokinetically based method for estimating daily intake of nicotine from cigarette smoking. STUDY DESIGN: Twenty cigarette smokers received a combined infusion of deuterium-labeled nicotine (d2) and cotinine (d4). Six nonsmokers received a combined infusion of unlabeled cotinine, cotinine-d2 and cotinine-d4. Daily intake of nicotine was estimated with use of the plasma cotinine concentration during ad libitum smoking, clearance of labeled cotinine, and fractional conversion of nicotine to cotinine. RESULTS: The kinetics of labeled versus unlabeled cotinine and of cotinine in smokers versus nonsmokers were similar. On average, 72% of nicotine was converted to cotinine, with a range from 55% to 92%. Subjects with lower clearances of nicotine had lower fractional conversion of nicotine to cotinine, indicating that this is the most rapid of the proximate metabolic pathways for nicotine. The equation for estimating daily intake of nicotine from smoking was: Dnic (mg/24 hr) = K x (Plasma Cot) (ng/ml), where K averaged 0.08, with a range from 0.047 to 0.102. Individual variability in the clearance of cotinine (coefficient of variation, 27.5%) accounts for more of the variability in K than does variability in the fractional conversion of nicotine to cotinine (coefficient of variation, 12.3%). CONCLUSIONS: Our study provides quantitative data on individual variability in the extent of C-oxidation of nicotine to cotinine and a quantitative perspective on the use of plasma cotinine as an indicator of daily intake of nicotine from tobacco.

Adult↗
PubMed1994

Incidence of Guillain-Barré syndrome in Ontario and Quebec, 1983-1989, using hospital service databases.

To determine the incidence of Guillain-Barré syndrome (GBS) in the Canadian provinces of Ontario and Quebec during 1983-1989 and to demonstrate the feasibility of measuring the incidence of GBS through internal record linkage of Canadian hospital service data, we conducted a record linkage study. This study used the databases of the Hospital Medical Records Institute and the Ministère de la santé et des services sociaux du Québec. We extracted records containing the International Classification of Diseases, 9th revision, code for GBS or a diagnosis likely to harbor misclassified GBS cases from each database and linked them internally using computerized algorithms. We identified a total of 1,302 and 1,031 incident cases of GBS admitted to Ontario and Quebec hospitals, respectively. The calculated mean annual GBS incidence rate in each province, after age and sex standardization to the 1986 Canadian census population, was 2.02 per 100,000 person-years in Ontario and 2.30 per 100,000 person-years in Quebec. Chart reviews revealed that the false-positive diagnosis rate might be as high as 0.26 per 100,000 person-years in Ontario and 0.21 per 100,000 person-years in Quebec. With adjustment for these false-positive rates, the incidence rate of GBS becomes 1.51 per 100,000 person-years and 1.78 per 100,000 person-years in Ontario and Quebec, respectively. In both provinces, the incidence rate was higher in older age strata (70-80 years) and in males. We saw no seasonal or geographic pattern.

Adolescent↗
PubMed1994

Effects of cigarette smoking and its cessation on lipid metabolism and energy expenditure in heavy smokers.

The relationship between thermogenic and potentially atherogenic effects of cigarette smoking (CS) and its cessation was investigated. Heavy smokers (n = 7, serum cotinine > 200 ng/ml, > 20 cigarettes/d) were maintained on isoenergetic, constant diets for 2 wk, 1 wk with and 1 wk without CS. Stable isotope infusions with indirect calorimetry were performed on day 7 of each phase, after an overnight fast. CS after overnight abstention increased resting energy expenditure by 5% (not significant vs. non-CS phase; P = 0.18). CS increased the flux of FFA by 77%, flux of glycerol by 82%, and serum FFA concentrations by 73% (P < 0.02 for each), but did not significantly affect fat oxidation. Hepatic reesterification of FFA increased more than threefold (P < 0.03) and adipocyte recycling increased nonsignificantly (P = 0.10). CS-induced lipid substrate cycles represented only 15% (estimated 11 kcal/d) of observed changes in energy expenditure. De novo hepatic lipogenesis was low (< 1-2 g/d) and unaffected by either acute CS or its chronic cessation. Hepatic glucose production was not affected by CS, despite increased serum glycerol and FFA fluxes. Cessation of CS caused no rebound effects on basal metabolic fluxes. In conclusion, a metabolic mechanism for the atherogenic effects of CS on serum lipids (increased hepatic reesterification of FFA) has been documented. Increased entry of FFA accounts for CS-induced increases in serum FFA concentrations. The thermogenic effect of CS is small or absent in heavy smokers while the potentially atherogenic effect is maintained, and cessation of CS does not induce a rebound lipogenic milieu that specifically favors accrual of body fat in the absence of increased food intake.

Adipocytes↗
PubMed1994

Genetic heterogeneity in spinal muscular atrophy: a linkage analysis-based assessment.

The spinal muscular atrophies (SMAs) are among the most common autosomal recessive disorders. The mapping of the gene responsible for SMA to chromosome 5 has allowed the assessment of genetic heterogeneity in kindreds with a putative diagnosis of SMA. We report linkage analysis of 71 Canadian SMA families (types 1, 2, and 3) using polymorphisms that both flank and are linked to SMA. Data demonstrating nonlinkage to 5q markers were initially obtained in five kindreds; reexamination of the clinical status of these families showed that one fulfilled all the SMA diagnostic criteria, two showed patterns for which a diagnosis of SMA was possible but not conclusive, and two showed patterns for which the diagnosis of SMA appeared unlikely. This results in a degree of genetic heterogeneity between 1.5% and 4.5%. The three kindreds for which SMA appeared either possible or likely were simplex (ie, contained only one affected individual), and therefore the possibility that they represented new mutations could not be discounted. Thus, the significant majority of classic SMA cases are caused by a mutation in the 5q13.1 locus. Low genetic heterogeneity has implications for both genetic counseling and the applicability of conventional and genetic therapies following cloning of the SMA gene.

Adult↗
PubMed1994

[Major pancytopenia in Biermer disease. 5 cases].

Five cases of Biermer's disease presenting as pancytopenia were observed over a 17-year period. In all cases, haemorrhagic and/or infectious complications occurred. The myelogram revealed qualitative medullary deficiency and laboratory data led to diagnosis. The importance of prompt substitutive therapy is underlined.

Aged↗
PubMed1994

Nicotine metabolic profile in man: comparison of cigarette smoking and transdermal nicotine.

The objectives of this study were to 1) quantitatively assess human exposure to various metabolites of nicotine, 2) examine the influence of inhalation vs. transdermal administration on the patterns of nicotine metabolism, and 3) assess the extent of recovery of nicotine as various metabolites in people whose systemic intake of nicotine has been measured. Twelve smokers were studied while smoking cigarettes and while receiving transdermal nicotine. Urinary excretion of nicotine and eight of its metabolites was measured under steady state conditions. The systemic intake of nicotine in these subjects was determined using plasma concentrations and intravenous clearance data, so the percentage of their daily dose of nicotine excreted as various metabolites could be computed. The major findings of the study are as follows: 1) a high percentage (averaging 88%) of a systemic dose of nicotine can be accounted for by measurement of nicotine and its metabolites; 2) the pattern of metabolism is generally similar when nicotine is inhaled or absorbed transdermally; 3) while there is considerable interindividual variability in the pattern of metabolism, the pattern is consistent for an individual; and 4) within individuals, the extent of conjugation of nicotine and cotinine is highly correlated, but neither is correlated with the extent of conjugation of 3'-hydroxycotinine. This suggests that similar enzymes are involved in the conjugation of nicotine and cotinine, and that a different enzyme may be involved in the conjugation of 3'-hydroxycotinine.

Administration, Cutaneous↗
PubMed1993

Gas chromatographic-mass spectrometric method for determination of anabasine, anatabine and other tobacco alkaloids in urine of smokers and smokeless tobacco users.

A selected ion monitoring method for determination of the tobacco alkaloids anabasine, anatabine, nornicotine, metanicotine, dihydrometanicotine, and 2,3'-bipyridyl in urine of smokers and smokeless tobacco users is described. The method involves conversion of the secondary amine alkaloids to tertiary amine derivatives by reductive alkylation using an aldehyde and sodium borohydride, and chromatography on a 5% phenylmethylsilicone capillary column. These derivatives have good chromatographic properties, allowing determination of concentrations as low as 1 ng/ml. The alkaloid 2,3'-bipyridyl is unaffected by the derivatization procedure and may be determined simultaneously with the other alkaloids. The structural analogues 2-(3-pyridyl)hexahydroazepine, 5-methyldihydrometanicotine, and 6-methyl-2,3'-bipyridyl were synthesized for use as internal standards. Using the method, concentrations and 24 h excretion of anabasine, anatabine, and nornicotine in urine of twenty-two smokers, eight chewing tobacco users, and six oral snuff users were determined and compared with concentrations and excretion of nicotine and its metabolite cotinine. Excretion of nicotine and cotinine was similar in all tobacco users, but excretion of anabasine, anatabine and nornicotine was substantially greater in urine of smokeless tobacco users, presumably due to absence of pyrolysis of these alkaloids in smokeless tobacco products.

Alkaloids↗
PubMed1993

Decrease in the size of the myotonic dystrophy CTG repeat during transmission from parent to child: implications for genetic counselling and genetic anticipation.

Recently an unstable trinucleotide CTG repeat, located within the 3' untranslated region of a gene on 19q13.3 was discovered in kindreds with myotonic dystrophy (DM). The age-of-onset/severity of DM shows a good correlation with CTG repeat size, and pedigrees and data reported to date have shown a striking trend toward amplification of the size of the CTG repeat during transmission from parent to child. The amplification has been accepted as the biological explanation for anticipation in the clinical severity observed in many families with DM. In this paper we report on 3 families where CTG amplification decreased during transmission from parent to child. In one case there was a gene conversion event, while in the remaining 2 there was a simpler reduction in the size of the repeat length. The changes appear to have been accompanied by a reduction in clinical severity in the child when compared to the parent. These observations are discussed in terms of their clinical implications and the biases that may exist in much of the reported data.

Adolescent↗
PubMed1993

Miller-Dieker syndrome. Detection of a cryptic chromosome translocation using in situ hybridization in a family with multiple affected offspring.

OBJECTIVE: To describe a family in whom fluorescence in situ hybridization allowed for accurate diagnosis of Miller-Dieker syndrome in an at-risk pregnancy and determination of parental carrier status. DESIGN: Retrospective case analysis and application of a new molecular tool to evaluate the family. SETTING: Health maintenance organization. The family was followed up by the Departments of Medical Genetics, Pediatrics, and Obstetrics and Gynecology, Kaiser Permanente Medical Center, Panorama City, Calif. PARTICIPANTS: Members of a single family. INTERVENTIONS: Clinical evaluation and neuroimaging studies of the proband. Prenatal diagnosis via ultrasonography and amniocentesis. Chromosomal evaluation of the couple and their offspring. In situ hybridization studies in both parents and an affected fetus. MEASUREMENTS/MAIN RESULTS: We describe a family in whom fluorescence in situ hybridization detected a submicroscopic deletion of the Miller-Dieker syndrome critical region 17p13.3 arising from a cryptic translocation in one of the parents. The proband was determined at birth owing to the presence of multiple congenital anomalies, including low birth weight, microcephaly, agenesis of the corpus callosum, lissencephaly, cerebral atrophy, unilateral ptosis, polydactyly, and omphalocele. High-resolution chromosome-banding analysis findings were normal in the parents and proband, who died at age 4 years. There were four subsequent pregnancies: two ended in first-trimester spontaneous abortion, and in the other two, large omphaloceles were detected in fetuses at 15 and 13 weeks' gestation. Both pregnancies were terminated. Fluorescence in situ hybridization probes for 17p13.3 had become available before the most recent pregnancy and were used to study parental and fetal cells. As a result, a balanced cryptic translocation between chromosome 17 and chromosome 19 was identified in the father: 46,XY,t(17;19)(p13.3q13.33). An unbalanced form of the translocation, involving a deletion of 17p13.3, was detected with fluorescence in situ hybridization in the fetus. This finding was in accordance with a clinical diagnosis of Miller-Dieker syndrome. CONCLUSIONS: Molecular cytogenetic technology should be used in cases of suspected Miller-Dieker syndrome when high-resolution cytogenetic analysis fails to detect del(17) (p13.3). Positive findings should be followed up with parental studies. In addition, omphalocele should be included among the list of malformations that make up the Miller-Dieker syndrome.

Adult↗
PubMed1993

Genetic linkage analysis of Canadian spinal muscular atrophy kindreds using flanking microsatellite 5q13 polymorphisms.

The spinal muscular atrophies (SMA) are among the most common autosomal recessive disorders. We have performed linkage analysis using both standard restriction fragment length polymorphisms (RFLPs) as well as microsatellite polymorphisms [Ca(n)] on 49 Canadian SMA families (types 1, 2, and 3) that both flank and are linked to SMA. The closest SMA linkage was observed with the MAP1B locus (zmax = 8.04, theta max = 0.0). Multipoint linkage analysis gave a high probability of SMA mapping between D5S6 and D5S39. Only one family (type 3) that fulfilled our diagnostic criteria for SMA showed nonlinkage with 5q13 markers. This study shows the feasibility of accurate molecular diagnosis of SMA utilizing 5q13 satellite polymorphisms.

Canada↗
PubMed1993

A clinical pharmacological study of subcutaneous nicotine.

The stable isotope-labeled compound 3',-3'-dideuteronicotine (nicotine-d2) was used to investigate the disposition kinetics and effects of nicotine administered subcutaneously to 6 smokers. Plasma nicotine-d2 concentrations were measured for 8 h after subcutaneous injection of 4 doses (0.4, 0.8, 1.2, and 2.4 mg). Peak plasma nicotine concentration correlated well with the dose, averaging 2.8 to 14.8 ng/ml, 19 to 25 min after injection of the 0.4 mg and 2.4 mg doses, respectively. The plasma clearance over bioavailability ratio (CL/f) averaged 12 to 13 ml.min-1.kg-1, similar to the clearance reported previously for intravenously administered nicotine. Thus, bioavailability appears to be approximately 100%. The heart rate response was more sensitive to the nicotine dose than the blood pressure response. Subjective effects showed large interindividual variability. The results reported herein may be useful in planning future studies. Administration of nicotine by the subcutaneous route appears to be a practical and safe method for studying the human pharmacology of nicotine.

Adult↗
PubMed1993

Environmental behaviour of radionuclides deposited after the reactor accident of Chernobyl and related exposures.

Several radioecological experiences with isotopes of ruthenium, iodine, caesium and barium, obtained after the reactor accident of Chernobyl, are reported. It was found that for a wet deposition barium was the element with the highest retention on grass. The retention of caesium was lower by a factor of 1.6, retention of iodine by a factor of 2.4 and retention of ruthenium by a factor of 3.5. Former data on the caesium transport in cereals from leaves to grain were confirmed. Depending on the conditions the iodine transfer factor for milk varied between 0.002 and 0.007 d.kg-1. The caesium transfer factor for milk was (0.003 +/- 0.0006) d.kg-1 and was found to be relatively constant in the years 1986-1988. In 1991, the values were higher by a factor of 2-5. Radioecological model results of whole-body burdens in Southern Bavaria showed a reduction of the caesium ingestion doses due to countermeasures and spontaneous changes of consumption habits in the first 2 months by a factor of 5 and till the end of 1987 by a factor of 1.5. The model results agree well with the range of measured whole-body burdens. One month after the deposition, the external exposures in urban environments due to ruthenium, caesium and barium isotopes were found to be reduced by a factor of 2, compared with open lawns, in the case of iodine the reduction was even a factor of 2.5. External exposures of a population group from the Munich area were determined by thermoluminescence dosimetry. The results are in accordance with the spectral measurements of external dose rates in urban environments.

Accidents↗