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Biomedical subjects

P Simon

Publications and source records attributed to P Simon.

At least 217 records · Page 12Linked to original sources

The atpB and rbcL promoters in plastid DNAs of a wide dicot range.

The plastid atpB-rbcL intergene has been analyzed within a wide range of plants covering the major dicot lineages. New sequences from 13 plant species were determined and aligned with three already-known sequences. The promoters of the rbcL and the atpB genes were localized and analyzed according to published observations in spinach and tobacco. The evolutionary conservation of two atpB promoters, separated by 113-262 nucleotides, is strong support that both are functionally active, and it also allows a discrimination between the previously reported atpB transcripts. Moreover, the radically distinct sequences of the two atpB promoters suggest that they interact with two distinct initiation complexes. The alignment also confirms the much higher conservation of the leader sequence in the rbcL mRNA than in the atpB mRNA among dicots, presuming a function at the posttranscriptional level.

Base Sequence↗

Dietary habits, a non-negligible source of 2-thiothiazolidine-4-carboxylic acid and possible overestimation of carbon disulfide exposure.

2-Thiothiazolidine-4-carboxylic acid (TTCA) is the accepted urinary indicator of occupational exposure to carbon disulfide. This compound was detected in blank urine of individuals unexposed to carbon disulfide during an experimental validation of a new method of determination. Diet was suspected to be the source of TTCA, and particularly the consumption of brassica vegetables. This assumption was confirmed by collection and analysis of urine samples after ingestion of crude cabbage. TTCA was detected at concentrations higher than 2 mg/l in urine, and 3 mg/kg in crude cabbage. The identity of TTCA was confirmed after extraction and separation by capillary electrophoresis, supercritical fluid chromatography, and mass spectrometry. The results show that the diet should be considered as a nonnegligible source of the overestimation of carbon disulfide exposure.

Biomarkers↗

The stimulant effect of modafinil on wakefulness is not associated with an increase in anxiety in mice. A comparison with dexamphetamine.

Modafinil is a new drug used in the treatment of narcolepsy. Its administration in mice induced a dose-dependent increase in locomotor activity. The effects of modafinil were compared with those of dexamphetamine on three tests that assessed the anxiety level (drugs were used at doses which induced a roughly similar stimulation of locomotor activity). Dexamphetamine increased the latency of exploration of a white compartment, increased thigmotaxis in an open-field and decreased the time spent in the open arms of an elevated plus-maze. None of these responses was significantly modified by modafinil. We conclude that modafinil does not share the anxiogenic effects of dexamphetamine.

Animals↗

Epidemiology of primary glomerular diseases in a French region. Variations according to period and age.

Between January 1, 1976 and December 31, 1990, histological diagnosis of primary glomerular diseases (PGD) was made in 480 patients born and living at the time of diagnosis in a region of France, comprising 410,664 inhabitants, of whom 390,574 were aged from 10 to 80 years. The prevalence of PGD during a 70 year exposure to risk (10 to 80 years of age) was evaluated to 5.7 in 1000 (7.6 in 1000 males and 3.8 in 1000 females). The most common PGD was IgA nephropathy with a prevalence of 1.9 in 1000 (3.3 in 1000 males, 1 in 1000 females). The annual incidence of the disease was evaluated separately for three consecutive five-year periods: period A (1976-80), period B (1981-85), and period C (1986-90). Within each of these three periods the number of patients with PGD was 179, 170 and 131, respectively, and annual incidence was 9.3, 8.8 and 6.7 in 100,000. The incidence of IgA nephropathy remained the same throughout the three periods: 2.6, 3.1 and 2.5 in 100,000. The incidence of membranoproliferative glomerulonephritis decreased from 1981 onward (0.9, 0.5 and 0.15 in 100,000), while that of membranous nephropathy increased slightly (1.2, 1.6 and 1.7 in 100,000). Acute streptococcal glomerulonephritis virtually disappeared during periods B and C. Lipoid nephrosis was less frequent in period C and idiopathic proliferative glomerulonephritis with crescents slightly increased (0.3, 0.4 and 0.6 in 100,000). There was no significant difference between the three periods regarding the incidence of other PGD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Sinus of Valsalva aneurysm: a late complication after repair of ascending aortic dissection.

Surgical advances and the introduction of new more rapid and accurate diagnostic techniques have led to significant improvement in the survival of patients with aortic aneurysms. However, considerable long-term morbidity and mortality remains a concern. In the present study we report on the occurrence of sinus of Valsalva (SV) aneurysm after repair of the ascending aorta for aortic dissection as a significant long-term complication. Since transesophageal echocardiography (TEE) became available it has been used for the follow-up of 33 hospital survivors after ascending aortic replacement for a mean of 27 +/- 20 months. Those patients who received a valved conduit were excluded from this analysis. The aortic valve was conserved in 22 patients: 17 had a dissecting aneurysm involving the ascending aorta and 4 patients non-dissecting aneurysms. A sinus of Valsalva diameter > 45 mm was considered an aneurysm and was found in a total of 7 patients (33%), 5 being patients with aortic dissection. The overall reoperation rate on account of SV aneurysms was 24%. We conclude that SV aneurysm is a significant long-term complication of patients after repair of the ascending aorta. In the light of these results we have changed our operative policy of repair to include resorcin glue as a reinforcing agent or to perform more extensive repair.

Aortic Dissection↗

Intramedullary pressure changes and fat intravasation during intramedullary nailing: an experimental study in sheep.

In this study, intramedullary reaming and nailing were performed following the insertion of pressure transducers in intact tibias and femora. The femur and tibia were instrumented in 12 sheep (group I) and both tibiae in four (group II). The eight procedures of group II were monitored additionally using echocardiography to detect emboli. Intravasation of fat globules was demonstrated in the blood by the Gurd test and correlated with intramedullary pressure and with echocardiographic monitoring in group II. Medullary nailing was found to be always associated with a severe increase in intramedullary pressure, reaching an average of 1126 mm Hg (304 to 1450 mm Hg) in the tibia and of 753 mm Hg (310 to 1126 mm Hg) in the femur during the first reaming procedures. Particle or fat intravasation was greatest during nail insertion. This phenomenon did not depend on the rise in intramedullary pressure. Our findings indicate that fat and bone marrow intravasation occurs during reaming and nailing in long bones. The maximum embolization of marrow contents demonstrated by echocardiography is seen during nail insertion independent of the changes in intramedullary pressure.

Animals↗

The effects of dobutamine therapy in critically ill patients measured by transoesophageal echocardiography and intracardiac monitoring.

Fourteen patients with severe hypotension and adult respiratory distress syndrome after trauma (n = 7), general surgery (n = 6) or burns (n = 1) were studied. After volume loading with 6 ml.kg-1 hydroxyethyl starch over 30 min (time I), dobutamine was infused intravenously at 5 micrograms.kg-1.min-1 (time II) and 10 micrograms.kg-1.min-1 (time III). A 5 MHz transoesophageal echocardiographic probe was used to image a standard transgastric short axis view of the left ventricle. Haemodynamic data were obtained from thermodilution studies using pulmonary flotation catheterisation. Echocardiographic measurements (off-line from videotape) and qualitative visual assessment of left ventricular function (visual assessment, on-line) were performed. All measurements were made after fluid replacement, and during infusion of the two dobutamine doses. An improvement in mean systemic arterial blood pressure and mean stroke volume occurred from time I to the end of dobutamine infusion (p < 0.05). All patients, after volume infusion, were normovolaemic according to transoesophageal echocardiography and there was a good correlation between end-diastolic area and stroke volume (r = 0.73). During dobutamine infusion, echocardiographic measurements showed no significant dose-related increase in mean (SD) percentage left ventricular short axis area change from baseline after hydroxyethyl starch (time I: 60 (2); time II: 63 (2); time III: 64 (2)). However, a significant increase in short axis area change was seen in nine of the 14 patients (67%). Analysis of the end-diastolic area/short axis area change relationship revealed a heterogeneous response to dobutamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Typing of Clostridium perfringens by in vitro amplification of toxin genes.

The strains of Clostridium perfringens are classified according to major toxins produced. Classically, this determination involves the seroneutralization of their lethal effect in mice. However, this method requires specific antisera and a large number of mice. In this work, a new typing method was developed based on the amplification of toxin genes by polymerase chain reaction (PCR). By combination of several pairs of primers, the toxinotype of a Cl. perfringens strain was determined by looking at the pattern of bands on an agarose gel electrophoresis. This mixture contained primers amplifying simultaneously a part of alpha-toxin, beta-toxin, epsilon-toxin and enterotoxin genes. In order to distinguish between toxinotype A and E, the l-toxin gene fragment must be amplified in a separate PCR reaction. Moreover, with the primers combination, in most cases, a PCR product corresponding to the alpha-toxin gene was obtained from direct enrichments of animal intestinal contents.

Animals↗

Thoracoabdominal aneurysm repair: spinal cord protection using profound hypothermia and circulatory arrest.

Between January 1991 and February 1993, 14 patients (11 male, 3 female) between 21 and 79 years of age (median 50 years) underwent reconstruction of the thoracic (n = 7) and thoracoabdominal aorta (n = 7). Four patients had previously undergone operation of the ascending aorta, and in three patients coronary artery bypass grafting had previously been performed. All patients were operated on a via a posterolateral thoracotomy using cardiopulmonary bypass with continuous blood cardioplegia and hypothermic circulatory arrest (11 degrees C nasopharyngeal temperature, flat-EEG). All patent lower intercostal and lumbar arteries (T3 to L5) were reimplanted. The 30-day mortality after repair of the thoracic aorta was 0%; after replacement of the thoracoabdominal aorta, mortality was 28.5% (n = 2). One patient died 70 days after replacement of the thoracic aorta as a consequence of a perioperative stroke. None of the surviving 11 patients developed a permanent neurological deficit or renal or cardiac dysfunction. The average intensive care stay was 6 days for patients after replacement of the thoracic aorta and 18 days for patients after replacement of the thoracoabdominal aorta. Our results suggest that use of elective hypothermia and circulatory arrest for spinal cord protection is highly effective. We, therefore, recommend this method for complex reconstructions of the thoracoabdominal aorta.

Adult↗

Drooping upper eyelids and polycystic kidney disease.

Over the last 26 yr, 33 cases and/or families of patients with autosomal dominant polycystic kidney disease (ADPKD) and a particular appearance of the eyes have been observed. ADPKD was unremarkable and in most cases had led to the usual slow development of end-stage renal failure. The facial feature concerned the upper eyelid, which drooped obliquely over the eyeball with a fold hiding the upper segment of the iris (blepharochalasis). The aspect was so typical that the diagnosis of ADPKD was suggested on first contact with new renal patients. All affected patients were white, of various origins, including French, Polish, Scandinavian, Italian, and Spanish. In retrospect, drooping eyelids had been present in the parents and/or grandparents who had died of renal failure, with or without an established diagnosis of ADPKD. In order to disclose the cosegregation of blepharochalasis with ADPKD, the screening of its prevalence in a well-circumscribed region with a catchment population of 410,000 was undertaken. The facial feature was found in 24 (32%) of 75 ADPKD families. Family transmission was confirmed in those kindreds, because at least two members suffered from ADPKD. Cosegregation was sought by analyzing family group photographs taken over several generations, the oldest member of which was born in 1973. All members with blepharochalasis had died of renal failure or are presently being followed up for ADPKD. A bibliographic search showed that the association of ocular and/or eyelid deformities and various inborn renal diseases is far from rare, suggesting a simultaneous event in the embryonic timetable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Aprotinin does not decrease early graft patency after coronary artery bypass grafting despite reducing postoperative bleeding and use of donated blood.

Forty-five male patients with planned coronary artery bypass operation were randomized in a double blind fashion to receive either 6 million kallikrein inactivator units of aprotinin (high-dose group), 2 million kallikrein inactivator units of aprotinin (low-dose group), or placebo (control group). Postoperative bleeding was significantly decreased in both aprotinin groups in comparison to that in the control group (590 ml [290 to 1800 ml] high-dose group and 650 ml [280 to 1900 ml] low-dose group versus 920 ml (350 to 2700 ml) control group, p < 0.001). There was no difference between the two aprotinin groups. The need for postoperative blood transfusion was significantly lower in the aprotinin groups (1.46 [0 to 4] blood units high-dose group and 1.65 [0 to 5] blood units low-dose group versus 2.43 [0 to 7] blood units control group, p < 0.05). All patients underwent coronary angiography between the seventh and twelfth postoperative day. No difference was found among the three groups in patency of vein grafts-93.8% in the high-dose group, 94.5% in the low-dose groups, and 93.3% in the control group. Therefore, aprotinin significantly reduced postoperative bleeding and transfusion requirement after coronary artery bypass grafting without influencing early graft patency.

Aprotinin↗

Evaluation in patients with Alport syndrome of knowledge of the disease and attitudes toward prenatal diagnosis.

Cloning of the COL4A5 gene has now made possible prenatal testing for Alport syndrome with X-linked dominant inheritance. We interviewed 27 females and 24 males with Alport syndrome to evaluate their knowledge of the disease and its transmission, and their attitudes to prenatal testing. Twenty-two males and 8 females were on renal replacement therapy. In all cases transmission was compatible with X-linked disease. Only 59% of the interviewees (74% of women, 42% of men) knew that gender was the major determinant in progression of the disease. Knowledge of the mode of inheritance was adequate in only 25%, in both sexes. Seventy percent of the participants (78% of women, 63% of men) would use prenatal testing. Of the women in favor of prenatal diagnosis, 67% and 39% would terminate pregnancy in the case of an affected male or female fetus, respectively. Of the men in favor of prenatal diagnosis, 53% would consider termination of an affected fetus. In summary, a majority would use prenatal testing, but only one or two thirds of them wished to use selective abortion. As in other inherited disorders, there is a discrepancy between the demand for prenatal diagnosis and the decision to terminate pregnancy. Most of the participants who would terminate a pregnancy had, however, little knowledge of the clinical and genetic aspects of Alport syndrome on which to base such a decision. An important aspect of genetic counselling is to assist consultants in reaching a decision regarding future reproductive behaviour which is appropriate to their situation. This study underlines the need to improve education and counselling to assure appropriate use of prenatal testing.

Abortion, Eugenic↗

Experience of a single team of operators in 891 diagnostic funipunctures.

OBJECTIVE: To assess the efficacy and safety of diagnostic funipuncture. METHODS: Between October 1985 and November 1993, fetal circulation was accessed 891 times in 828 pregnancies. The technique was similar to that described in earlier studies. We did not make more than two attempts at the procedure in any session. Each procedure was recorded prospectively in a computerized data base. Data included information about indications, laboratory indices, gestational age, number of successful and failed punctures, duration of fetal bradycardia, duration of bleeding, ultrasonographic findings, follow-up of pregnancies, and perinatal outcome. RESULTS: The most frequent indication was rapid karyotyping (48.9%), followed by risk of congenital infection (38.6%). The success rate of the method was high (98.6%). Most samples (97%) were pure fetal blood, undiluted by amniotic fluid. Transient bleeding was observed from the cord puncture site in 9.8% of the procedures. Sixty-three percent of prolonged bradycardia occurred in growth-retarded or congenitally malformed fetuses. Seven fetal and neonatal deaths (five pregnancies) occurred within 1 week after the funipuncture; the funipuncture indication was rapid karyotyping in four of these cases. CONCLUSION: Funipuncture performed by operators trained in ultrasonic needle guidance is a safe and reliable procedure.

Blood Specimen Collection↗

5-HT1A receptor blockade increases penile erections induced by indirect serotonin agonists.

Indirect serotonergic agonists, whether promoters of 5-HT release such as fenfluramine (5 mg kg-1) or inhibitors of 5-HT uptake such as fluoxetine (10 mg kg-1), elicited in rats penile erections at a modest but significant level. Their effects were markedly potentiated by the beta-blocker tertatolol, (0.6-5 mg kg-1) which displays 5-HT1A receptor blocking activity, but not by the beta-blocker labetalol (6.25 and 25 mg kg-1), which lacks such activity. In addition, tertatolol, but not labetalol, potentiated penile erections induced by meta-chloro-phenylpiperazine (1 mg kg-1). Thus, it appears that increasing serotonergic transmission increases only moderately penile erections because of the functional opposition exerted by 5-HT1A (inhibition) and 5-HT1C (activation) serotonin receptors on this response.

Adrenergic beta-Antagonists↗

The European Myocardial Infarct Amiodarone Trial (EMIAT). EMIAT Investigators.

The objective of the European Myocardial Infarct Amiodarone Trial (EMIAT) is to assess the efficacy of amiodarone on mortality of patients with depressed left ventricular (LV) function following myocardial infarction (MI). The rationale for the trial is as follows: patients with poor LV function after acute MI have a high sudden cardiac death (SCD) mortality; amiodarone is a successful prophylactic therapy against SCD in patients with ventricular arrhythmias; a number of small studies (Canadian Amiodarone Myocardial Infarction Arrhythmia Trial [CAMIAT] pilot study, Basel Antiarrhythmic Study & Infarct Survival [BASIS], and the Polish Amiodarone Trial [PAT]) of prophylactic amiodarone post AMI have shown a beneficial response attributable to amiodarone. Patients are enrolled between 5 and 21 days after acute MI if LV ejection fraction (assessed by multiple-gated image acquisition nuclear angiography) is < or = 40%. The study group is stratified according to ejection fraction (stratum 1, 31-40%; stratum 2, < 31%). Amiodarone or placebo treatment (blind, randomized) is initiated prior to the discharge of the patient from the hospital and each patient is followed up for the duration of the study, at least 1 year. Recruitment began on November 30, 1990, and will continue for 4 years; > 700 patients are enrolled from > 60 centers (13 countries). The total study mortality (10% at 500 days) and the differential mortality of both strata are as anticipated. Side effects have been infrequent and very few patients have been withdrawn from the study. Trial conclusion is forecast for October 1995.

Amiodarone↗

Automated column-switching high-performance liquid chromatography for the determination of 2-thiothiazolidine-4-carboxylic acid in urine.

2-Thiothiazolidine-4-carboxylic acid (TTCA) is the accepted urinary indicator of occupational exposure to carbon disulfide. An extractionless automated column-switching procedure for the determination of this compound in urine was developed. The biological fluid is directly injected into the chromatographic system after dilution. A clean-up procedure is performed in an anion-exchange pre-column, with aqueous formic acid as eluent, followed by a transfer to a cyan-amino or amino analytical column in order to carry out analysis of TTCA under isocratic elution conditions, with a mixture of acetonitrile, water and formic acid as eluent, combined with ultraviolet detection. The detection limit of the method in urine is estimated to be 0.1 mg/l.

Acetonitriles↗