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Biomedical subjects

A Robert

Publications and source records attributed to A Robert.

At least 307 records · Page 17Linked to original sources

Implementation of the Louvain program for exercise ECG analysis on a microprocessor system.

Several years ago we developed a computer system for the processing of exercise ECGs: the Louvain program for exercise ECG analysis which runs on a minicomputer "Modcomp Classic" and processes XYZ data remotely collected on digital cartridge at the exercise room. This off-line batch procedure is time consuming for the technician (reading of cartridge), but theoretically could be fast. Our experience shows that the results of the exercise test are provided to the referring physician from one day to one week after the procedure because of delays at different levels. The implementation of the programs in a stand-alone unit can produce the results one minute after the end of the test. This solution obviously is more satisfactory for routine clinical testing.

Computers↗

Opposite effects of ecdysone and 20-hydroxyecdysone on in vitro uterus motility of a tsetse fly.

In order to examine the possible effects of ecdysteroids on parturition, we studied in vitro the influence of ecdysone and 20-hydroxyecdysone on the motility of isolated uterus from virgin and pregnant female tsetse fly (Glossina fuscipes). Ecdysone initiates phasic uterine contractions or enhances the frequency of preexisting contractile activity. In contrast, uterine contractions are decreased or abolished by 20-hydroxyecdysone. Pharmacological data indicate that tsetse fly uterus exhibits myogenic and nerve-evoked contractions. Ecdysteroids mainly act on nervous structures that control muscle contractions. Our results provide evidence for a specific action of ecdysteroids on a nerve-muscle target involved in female reproduction.

Animals↗

Effect of 16,16-dimethyl PGE2 on renal papillary necrosis and gastrointestinal ulcerations (gastric, duodenal, intestinal) produced in rats by mefenamic acid.

Mefenamic acid, given orally to rats at a single dose of 1200 mg/kg, produced renal papillary necrosis (RPN) in 63% of animals. The incidence was reduced to 27% by 16,16-dimethyl PGE2 (dmPGE2), given at an oral dose of 0.75 mg/kg t.i.d. RPN is likely to be caused by the renal prostaglandin depletion elicited by mefenamic acid, an inhibitor of prostaglandin cyclooxygenase. Substitution with dmPGE2 reduces RPN presumably by preventing the prostaglandin depletion. We conclude that the prostaglandin used is cytoprotective for the kidney. Mefenamic acid, like most nonsteroidal anti-inflammatory compounds (NOSAC), produced ulcerations of the small intestine (jejunum and ileum). These were prevented by dmPGE2 (intestinal cytoprotection). Unlike most other NOSAC, however, mefenamic acid produced duodenal ulcers in nearly all animals (80%). Of these ulcers, 88% were perforated. Twenty-five of the twenty-six animals that died had a perforated ulcer. These duodenal ulcers were also prevented by dmPGE2. Mefenamic acid-induced ulcers could be used as an experimental model for testing agents with a potential for preventing or healing duodenal ulcers.

16,16-Dimethylprostaglandin E2↗

The normal pediatric Frank orthogonal electrocardiogram: variations according to age and sex.

Quantitative computerized analysis of QRS and ST-T parameters of the Frank orthogonal electrocardiogram and vectorcardiogram was undertaken in a large series of 1317 normal infants, children and adolescents stratified according to age and sex. This study confirms the influence of these two constitutional variables, age and sex, over the normal VCG in the whole time span between birth and late adolescence. As children mature, the mid-portion of the spatial QRS loop shifts leftward and posteriorly with relatively little change in the initial and terminal vectors. The spatial T loop shifts anteriorly but at a different rate in males and in females. Unidirectional changes in many amplitude parameters are observed until age 19 in males whereas in females these changes stop earlier or even show a reverse trend around puberty, leading to more important differences between adolescent males and females. Sex-related differences are the most marked for parameters representing the repolarization process. Infants under six months of age form a distinct group with larger dispersions and more disparate variations in the values of vectorcardiographic parameters than in older children. In the newborn period larger sample size might be necessary in order to reduce the normal ranges of vectorcardiographic parameters.

Adolescent↗

The normal pediatric Frank orthogonal electrocardiogram: influence of weight, height and chest circumference.

The influence of body weight, height and chest circumference on the pediatric Frank vectorcardiogram (VCG) was investigated in a population of 1317 normal infants, children and adolescents. Simple linear regression analysis showed that 94, 96 and 57 VCG variables were significantly correlated with weight, height and chest circumference, respectively. These numbers were reduced to 10, 18 and 6 VCG variables after a stepwise multiple correlation analysis. The relationship between the VCG and the somatic variables was also studied in ten different age/sex subgroups. Simple regression analysis showed a residual significant correlation between the VCG and all three somatic variables in each group. The multiple correlation analysis allowed us to define a minimum set of VCG variables, from one to six, which could explain all the variation produced by the somatic variables. The coefficient of multiple correlation between VCG and weight was the highest in babies 0 to 6 months old (R = 0.73). For height, the strongest correlation was found in females two to five years old (R = 0.76). In subjects older than two years of age, the correlation between chest circumference and VCG (R = 0.30 to 0.69) was weaker than between VCG and pediatric VCG after stratification for age and sex, especially in the youngest groups.

Adolescent↗

Alteration of left ventricular diastolic filling in hypertensive patients: effects of nitrendipine and atenolol.

This study was undertaken to determine the chronic effects of a long-acting calcium-channel blocker (nitrendipine) on resting left ventricular filling abnormalities in ten patients with essential hypertension. Radionuclide left ventricular curves of these hypertensive patients were compared with the curves of twelve normal volunteers and of eight asymptomatic older patients. The curves were analyzed for ejection fraction, peak filling rate (normalized for end-diastolic counts and for stroke counts), time to peak filling rate and filling fraction in the first-third of diastole normalized for cycle length. Heart rate and ejection fraction were similar in both control groups and hypertensive patients before and after nitrendipine. Before nitrendipine, diastolic filling parameters were significantly different in the hypertensive patients as compared with the volunteers and with the asymptomatic aged patients: peak filling rate was lower, time to peak filling rate was longer and the first-third filling fraction was smaller. After six weeks of nitrendipine therapy, systolic and diastolic blood pressure decreased significantly. After nitrendipine, the time to peak filling rate decreased and the first-third filling fraction and the peak filling rate (normalized for stroke counts) increased significantly. The acute oral administration of 100 mg atenolol induced a further decrease in systolic blood pressure and a significant decrease in heart rate. The effect of combining nitrendipine and atenolol on diastolic indexes was a preserved effect on time to peak filling rate and on the first-third filling fraction. These results suggest that short-term therapy with nitrendipine improves early diastolic dysfunction in hypertensives: the addition of a beta-blocking agent further improved the early diastolic indexes.

Adult↗

Immunogenic properties of Klebsiella pneumoniae type 2 capsular polysaccharide.

The immunoprotective activity of Klebsiella pneumoniae K2 cell surface preparations and purified capsular polysaccharide was tested in mice. The 50% protective dose (PD50), expressed as capsular polysaccharide content, was 2 ng for cell surface preparations and 50 ng for purified capsular polysaccharide. Both preparations lost their immunoprotective activity after alkali treatment. Immune sera were raised in rabbits immunized with cell surface preparations. The precipitating and hemagglutinating capacity of these antisera was tested against either purified capsular polysaccharide or alkali-treated capsular polysaccharide. No difference was observed between the reactivity of the antisera against each antigen. The protective activity of these sera was tested on mice in passive transfer experiments, before and after absorption with either purified capsular polysaccharide or alkali-treated capsular polysaccharide. The sera lost their protective activity after absorption with purified capsular polysaccharide and after absorption with alkali-treated capsular polysaccharide. These experiments show that the difference in immunoprotective activity of cell surface preparations, purified capsular polysaccharide, and alkali-treated capsular polysaccharide is not due to a difference in their antigenic determinants. Cell surface preparations and purified capsular polysaccharide were fractionated by gel filtration on Sepharose 4B and by ultracentrifugation on cesium chloride density gradients. Three forms of capsular polysaccharide have been characterized. (i) A form of capsular polysaccharide with a very high protective activity (PD50 = 2 ng) that copurified with protein and lipopolysaccharide and was characterized by a low coefficient of distribution (Kd = 0.20) and a low density (1.5 to 1.6 g/cm3). (ii) A form of capsular polysaccharide with an intermediate protective activity (PD50 = 50 ng), contamined by less than 3% protein and 1% lipopolysaccharide, with a Kd of 0.35, and a density of 1.7 to 1.8 g/cm3. (iii) A nonimmunoprotective capsular polysaccharide obtained after alkali treatment of either cell surface preparations or purified capsular polysaccharide. The Kd of these fractions varied from 0.20 to 0.90 and their density from 1.7 to 1.8 g/cm3.

Animals↗

Improved survival rate in children with stage III and IV B cell non-Hodgkin's lymphoma and leukemia using multi-agent chemotherapy: results of a study of 114 children from the French Pediatric Oncology Society.

Children with B cell non-Hodgkin's lymphoma who have not relapsed 1 year after diagnosis and treatment are generally cured. We report here the results of treatment in 114 children who all had a minimum follow-up of 20 months. The protocol LMB 0281 from the French Pediatric Oncology Society was used. This nine-drug intensive-pulsed chemotherapy was based on high-dose cyclophosphamide, high-dose methotrexate (HD MTX), and cytosine arabinoside (ara-C) in continuous infusion. CNS prophylaxis was with chemotherapy only. No local irradiation was performed. No debulking surgery was recommended. There were 72 patients with stage III lymphoma and 42 patients with stage IV lymphoma or B cell acute lymphocytic leukemia (B-ALL). Among those 42 patients, seven had CNS involvement alone, 21 had bone marrow alone, and 14 had both; 26 had greater than 25% blast cells in bone marrow, 14 of whom had blast cells in blood. The primary site of involvement was the abdomen in 90 patients, the Waldeyer Ring in nine, and various sites in eight; seven patients presented without tumor. Seventy-seven patients are alive with a median follow-up of 2 years and 8 months. Seven patients died due to initial treatment failure, 11 died from toxicity, and 19 died after relapse. Among the 93 patients without initial CNS involvement, only one isolated relapse in CNS occurred. Survival and disease-free survival rates reached 67% and 64%, respectively, for all patients, 75% and 73% for stage III patients and 54% and 48% for stage IV and B-ALL patients. Bone marrow involvement was not an adverse prognostic factor. Contrary initial CNS involvement indicated a bad prognosis with a disease-free survival rate of 19% compared with 76% without CNS disease. This study showed that CNS prophylaxis and local control of the primary tumor can be achieved by intensive chemotherapy alone, without radiotherapy or debulking surgery.

Adolescent↗

Receptor-mediated endocytosis of polypeptide hormones is a regulated process: inhibition of [125I]iodoinsulin internalization in hypoinsulinemic diabetes of rat and man.

Much data suggest that receptor-mediated endocytosis is regulated in states of hormone excess. Thus, in hyperinsulinemic states there is an accelerated loss of cell surface insulin receptors. In the present experiments we addressed this question in hypoinsulinemic states, in which insulin binding to cell surface receptors is generally increased. In hepatocytes obtained from hypoinsulinemic streptozotocin-induced diabetic rats, [125I]iodoglucagon internalization was increased, while at the same time [125I]iodoinsulin internalization was decreased. The defect in [125I]iodoinsulin internalization was corrected by insulin treatment of the animal. In peripheral blood monocytes from patients with type I insulinopenic diabetes, internalization of [125I]iodoinsulin was impaired; this defect was not present in insulin-treated patients. These data in the hypoinsulinemic rat and human diabetes suggest that receptor-mediated endocytosis is regulated in states of insulin deficiency as well as insulin excess. Delayed or reduced internalization of the insulin-receptor complex could amplify the muted signal caused by deficient hormone secretion.

Adolescent↗

[Macrothrombocytosis and idiopathic thrombocytopenic purpura: effect of anticoagulant and prior fixation on the determination of platelet volume using the Coulter system].

This study was designed to evaluate the importance of anticoagulants and of prior fixation on the Coulter Counter platelet size determination in macrothrombocytosis occurring in patients affected with an idiopathic thrombocytopenic purpura (ITP). Native blood was sampled either in an iso-osmotic glutaraldehyde fixative solution at 37 degrees C or in standard citrated or EDTA vacutainers. Platelet size increased from the fixed whole blood sample to the unfixed standard citrate and EDTA samples. There was a good correlation between the three determinations. Of the 23 ITP cases 10 presented large sized platelets both in citrated and in fixed whole blood samples; however 4 of these patients presented a platelet size in the normal range in the EDTA samples. These results show that citrated blood samples are preferable to EDTA samples for detecting an increased platelet size in ITP and that ITP macrothrombocytosis does not result from an abnormal hypervolumetric shape change occurring in vitro after sampling.

Anticoagulants↗

[Sports and blood pressure: association in a population of wage-earners].

In a cross-sectional epidemiological survey, we examined the association between the practice of sports and blood pressure (BP). The study included 3,388 male employees (representing 90.1% of the target population) who were questioned about their habitual sports activity, in terms of average duration per week and intensity. The proportion of subjects who stated to engage in sports activity decreased with age, from 50.9% in the age class 20-29 years to 16.4% in the age class 50-59 years. We found a negative relationship between both systolic and diastolic BP and the weekly duration of sports activity. However this association increased with age and reached the statistical significance only in the age classes 40-49 years and 50-59 years (p less than 0.01 and p less than 0.001, respectively). Similar results were obtained when intensity of sports was used instead of duration. In order to test the independence of the observed association, the duration of sports activity (hours/week) was included as an independent variable in a multiple linear regression analysis, along with the following potential confounders: age, Quetelet index, alcohol consumption, cigarette smoking, heart rate, and level of education. In this analysis the sports-BP relationship was considerably attenuated or entirely disappeared. It remained statistically significant only in the age class 50-59 (p less than 0.01 for systolic BP an p less than 0.05 for diastolic BP). Our results support those of others showing a modest beneficial effect of leisure time physical exercise on BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cytoprotection and prostaglandins.

Among substances producing gastrointestinal cytoprotection, prostaglandins are the most potent. They protect the mucosa after either exogenous administration or stimulation of endogenous release by the stomach. The first type is called "direct" cytoprotection, and the second "adaptive" cytoprotection. Certain agents are cytoprotective by a mechanism other than endogenous formation of prostaglandins. Depletion of the gastrointestinal tract of prostaglandins by administration of nonsteroidal antiinflammatory compounds or corticosteroids can lead to ulcer formation. The mechanism of cytoprotection is unknown. It may involve stimulation of bicarbonate and mucus secretion, protection of the gastric mucosal barrier, and increase in mucosal phospholipid surfactants, and maintenance in mucosal blood flow, increase in sulfhydryl agents or increase in cellular resistance.

Animals↗

Ulcer formation and cytoprotection by acetazolamide.

Acetazolamide, a carbonic anhydrase inhibitor, was administered orally and subcutaneously to rats. Acetazolamide increased the gastric ulcerogenicity of indomethacin, but inhibited gastric ulcers produced by acidified aspirin. When administered alone to fasted rats, it did not produce gastric ulcers. Acetazolamide was also cytoprotective for the stomach (it reduced dose dependently the number of gastric necrotic lesions caused by absolute ethanol given orally) and for the small intestine (it prevented dose dependently intestinal lesions produced by administration of a high dose of indomethacin). Acetazolamide did not prevent the antiulcer effect of PGE2 (against aspirin-induced ulcers) nor the cytoprotective effect of 16,16-dimethyl PGE2 (against ethanol-induced gastric lesions). The degree of gastric cytoprotection increased with time after a single administration of acetazolamide; the optimal effect occurred 60 and 90 min after oral and subcutaneous administration, respectively. Pretreatment with indomethacin completely prevented the cytoprotective effect of acetazolamide; this suggests that the cytoprotective effect may be mediated by endogenous release of prostaglandins by the stomach. All the effects of acetazolamide reported here were observed after either oral or subcutaneous administration. The mechanism by which acetazolamide influences ulcer formation and is cytoprotective is unknown.

16,16-Dimethylprostaglandin E2↗

My years with Selye.

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History, 20th Century↗

Gastric mucosal blood flow in rats after administration of 16,16-dimethyl prostaglandin E2 at a cytoprotective dose.

The purpose of the present study was to determine whether the gastric cytoprotective effect of a prostaglandin such as 16,16-dimethyl prostaglandin (dmPGE2) is mediated by an increase in mucosal blood flow. Gastric mucosal blood flow was measured in urethane-anesthetized rats by the hydrogen gas clearance technique. In control rats given no ethanol, intragastric administration of dmPGE2 (10 micrograms/kg body wt) produced a significant reduction (15.3%) in gastric mucosal blood flow 30 min after treatment. This dose of dmPGE2 significantly reduced the formation of the gross gastric lesions produced by absolute ethanol in anesthetized rats. In vehicle-pretreated animals, blood flow was invariably absent in the ethanol-induced mucosal lesion areas. In the nonlesion areas, gastric mucosal blood flow was the same in prostaglandin-pretreated and vehicle-pretreated animals as in control (no ethanol) rats. Thus, although dmPGE2 pretreatment protected against ethanol-induced gastric mucosal injury and prevented the accompanying blood flow stasis, it did not do this by an increase in gastric mucosal blood flow. The protection also is not due to a decrease in flow because, in separate groups of anesthetized rats, a 15% reduction in gastric mucosal blood flow induced by either hemorrhage or intravenous vasopressin did not protect the gastric mucosa against absolute ethanol-induced injury. Whether the maintenance of gastric mucosal blood flow is a primary or secondary effect of prostaglandin cytoprotection remains to be determined.

16,16-Dimethylprostaglandin E2↗

Cytoprotective and antisecretory properties of a non-diarrheogenic and non-uterotonic prostacyclin analog: U-68,215.

U-68,215 [15-Cyclohexyl-9-deoxo-13,14-dihydro-2',9 alpha-methano-4,5,6,16,17,18,19,20-octanor-3-oxa-3,7-(1', 3'-interphenylene)-PGE1] is a stable prostacyclin analog. When given orally to rats, it is cytoprotective for the stomach (ED50: 0.8 micrograms/kg) and the intestine (ED50: 22 micrograms/kg), is gastric antisecretory (ED50: 35 micrograms/kg) and antiulcer (aspirin) (ED50: 5 micrograms/kg). The oral antisecretory ED50 in dogs is 50 micrograms/kg. It has a long duration of gastric cytoprotection: 8-10 hours compared to 3 hours for 16,16-dimethyl PGE2. Unlike most prostaglandins of the E type, it is not diarrheogenic (not enteropooling), it does not induce cellular proliferation of the gastrointestinal mucosa, when given twice a day for eight days, it is not uterotonic (in monkeys), and it does not prevent embryo implantation in hamsters. It inhibits ex vivo platelet aggregation (ED50: 300 micrograms/kg), but does not promote bleeding from cut vessels nor from gastric ulcers. U-68,215 lowers blood pressure at an oral dose corresponding to 1-5 times the antisecretory ED50 in rats and dogs, and to 150 times the cytoprotective ED50 in rats. It may be of therapeutic value in the treatment of conditions where inhibition of gastric acid secretion is desirable, e.g., gastric and duodenal ulcer, and in conditions responding to cytoprotection, e.g., stress ulcers, hemorrhagic gastritis and gastric erosions associated with nonsteroidal antiinflammatory drugs.

Alprostadil↗