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Biomedical subjects

P Hamel

Publications and source records attributed to P Hamel.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Fetal supraventricular tachycardia with anasarca complicating benign extrasystole: treatment with flecainide. Apropos of a case].

We report a case of fetal supraventricular tachycardia with intra-uterine cardiac failure, who complicate benign premature beats. It was treated with oral administration of flecainide acetate (Flecaine) to the mother. This treatment was rapidly effective. The fetus converted to sinus rhythm in 5 days and the ascites had completely resolved in 10 days. We conclude, that fetus with premature beats must be observed every 15 days, and we believe that flecainide acetate can be used as the "first line agent" to the fetal supraventricular tachycardias with cardiac failure.

Anti-Arrhythmia Agents↗
PubMed1997

[Feasibility of bilateral sacrospinous ligament vaginal suspension with a stapler. Prospective studies with the 34 first cases].

OBJECTIVE: Evaluation of the feasibility of bilateral sacropinous ligament suspension with a stapler. Morbidity study and short term results. STUDY DESIGN: Prospective study from July 1994 to August 1996. RESULTS: Bilateral sacrospinous ligament suspension with a stapler was possible in 100% of cases and surgical technique is described. Our indications are stage III Bp and stage IV genital prolapses (according to the American Urogynecologic Society classification, 1996), with or without uterus, and when a Bologna's procedure is performed, in order to prevent enterocele. In 24 patients, the uterus was present. 20 vaginal hysterectomies and 4 conservative bilateral uterine suspensions were performed. The sacrospinous ligament suspension was associated to anterior colporrhaphy (in 74% of patients), repair of rectocele (82%), repair of enterocele (26%), posterior colpoperineorrhaphy (79%), bladder neck suspension (71%). No vascular injury nor post operative constipation was noted. In 2 patients, a small rectal laceration occurred, and in one patient one branch of the staple transfixed the rectal mucosa. Removal of the staple was easily performed without any post-operative complication. First results after an average 19 months follow-up (range 9 to 32) shows a perfect anatomic result in 77% of cases. We noted one recurrence of a vaginal vault prolapse; the patient underwent a second sacrospinous ligament fixation with good result. One patient had a stage II Aa cystocele post-operatively and three patients had a short vagina (< 6 cm). Patients who were continent before the sacrocolpopexy did not develop further urinary stress-incontinence. CONCLUSION: Bilateral transvaginal sacrospinous ligament suspension with a stapler facilitates the procedure. No post-operative constipation was noted with this method. Our first results are good. The cost of the stappler may limit its extensive use.

Adult↗
PubMed1996

Dioxabicyclooctanyl naphthalenenitriles as nonredox 5-lipoxygenase inhibitors: structure-activity relationship study directed toward the improvement of metabolic stability.

Naphthalenic lignan lactone 3a (L-702,539), a potent and selective 5-lipoxygenase (5-LO) inhibitor, is extensively metabolized at two different sites: the tetrahydropyran and the lactone rings. Early knowledge of the metabolic pathways triggered and directed a structure-activity relationship study aimed toward the improvement of metabolic stability in this series. The best modifications discovered, i.e., replacement of the lactone ring by a nitrile group, replacement of the tetrahydropyran ring by a 6,8-dioxabicyclo[3.2.1]octanyl moiety, and replacement of the pendant phenyl ring by a 3-furyl ring, were incorporated in a single molecule to produce inhibitor 9ac (L-708,780). Compound 9ac inhibits the oxidation of arachidonic acid to 5-hydroperoxy-eicosatetraenoic acid by 5-LO (IC50 = 190 nM) and the formation of leukotriene B4 in human polymorphonuclear leukocytes (IC50 = 3 nM) as well as in human whole blood (IC50 = 150 nM). The good inhibitory profile shown by naphthalenenitrile 9ac is accompanied by an improved resistance to oxidative metabolism. In addition, 9ac is orally active in the functional model of antigen-induced bronchoconstriction in allergic squirrel monkeys (95% inhibition at 0.1 mg/kg).

Animals↗
PubMed1994

OXA1, a Saccharomyces cerevisiae nuclear gene whose sequence is conserved from prokaryotes to eukaryotes controls cytochrome oxidase biogenesis.

Yeast cells carrying a mutation in the OXA1 nuclear gene are respiratory deficient and lack cytochrome oxidase activity. We successively examined the different steps in the expression of the mitochondrial genes encoding the cytochrome oxidase subunits and apocytochrome b in strains carrying the oxa1-79 mutation. The ox1-79 strains exhibit a total absence of cytochrome aa3 and a decrease in cytochrome b, even in a strain devoid of mitochondrial introns, in which cox1 and cytb mRNAs normally accumulate. The three mitochondrial-encoded subunits of cytochrome oxidase are still detectable although their amount is reduced, and apocytochrome b is synthesized normally. These results suggest that the OXA1 gene is primary required at a post-translational step in cytochrome oxidase biogenesis, probably at the level of assembly, although the oxa1-79 mutation leads to some pleiotropic secondary defects in earlier steps of mitochondrial gene expression. The OXA1 gene has been cloned, sequenced, and disrupted. The phenotypes of the oxa1::LEU2 and oxa1-79 alleles are similar. Interestingly, the OXA1 gene, located on the yeast chromosome VIII, is adjacent to the gene PET 122, which controls the initiation of cox3 mRNA translation. In addition, the predicted OXA1 protein is homologous to several putative prokaryotic and eukaryotic proteins, suggesting that the function of the OXA1 protein is important for respiration in all living cells.

Amino Acid Sequence↗
PubMed1994

[The estimation of fetal weight by measurement of the adipose tissue of the extremities. Use in the diagnosis of hypotrophy].

OBJECTIVE: To investigate the accuracy of small for age fetuses diagnosis by a new method of fetal weight estimation, in comparison with some others models. A retrospective study. SUBJECTS AND METHODS: From a 232 fetuses population, whom age is known, ultrasound measurement have been performed (BPD, TBD, FL, AC and thigh circumference). Three physicians collaborated to data collection. All measurement have been done within a 3 days duration between measuring and birth in order to compare actual and calculated weight. There are 39 small fetuses coming from 10th percentile (17.5%), between then 24 from 5th percentile. RESULTS: Positive predictive value (PPV) of small for age diagnosis (from 10th P) by our model is 74% with a 74% sensibility and a 94% specificity. With Warsof estimation model, the PPV is only 47% with a 71% sensibility and a 83% specificity (p = 0.001). COMMENTS: Limbs subcutaneous fat ultrasound measurement improve considerably fetal weight estimation quality (mean error = 6% vs 10% for most of the classical models) and, as an extension, small for age fetuses diagnosis. The cutaneous and subcutaneous circumferences, between which is situated fat tissue have a better individual correlation to actual weight than abdominal circumference, usually considered as the best trophicity parameter. CONCLUSION: High positive predictive value show long term predictive detection possibility. It appears that this diagnosis could be done earlier with a better accuracy that the classical ultrasound biometry.

Abdomen↗
PubMed1993

Substituted thiopyrano[2,3,4-c,d]indoles as potent, selective, and orally active inhibitors of 5-lipoxygenase. Synthesis and biological evaluation of L-691,816.

Thiopyrano[2,3,4-c,d]indoles are a new class of 5-lipoxygenase (5-LO) inhibitors. SAR studies have demonstrated that the thiopyran ring, the 5-phenylpyridine substituent, and an acidic functional group on a four-carbon C-2 side chain are all required for optimal inhibitor potency. In contrast, the indolic nitrogen may be substituted with a variety of lipophilic groups. As a result of the SAR investigation, 44 (L-691,816; 5-[3-[1-(4-chlorobenzyl)-4-methyl-6-[(5-phenylpyridin-2-yl)methoxy ]- 4,5-dihydro-1H-thiopyrano[2,3,4-c,d]indol-2-yl]-2,2-dimethylpro pyl]-1H- tetrazole) has been identified as a potent inhibitor of the 5-LO reaction both in vitro and in a range of in vivo models. Compound 44 inhibits 5-HPETE production by both rat and human 5-LO and LTB4 synthesis in human PMN leukocytes (IC50s 16, 75, and 10 nM, respectively). The mechanism of inhibition of 5-LO activity by compound 44 appears to involve the formation of a reversible deadend complex with the enzyme and does not involve reduction of the nonheme iron of 5-LO. Compound 44 is highly selective for 5-LO when compared to the inhibition of human FLAP, porcine 12-LO, and also ram seminal vesicle cyclooxygenase. In addition, 44 is orally active in a rat pleurisy model (inhibition of LTB4, ED50 = 1.9 mg/kg; 8 h pretreatment) as well as in the hyperreactive rat model of antigen-induced dyspnea (ED50 = 0.1 mg/kg; 2-h pretreatment). Excellent functional activity was also observed in both the conscious allergic monkey and sheep models of asthma. In the latter case, the functional activity observed correlated with the inhibition of urinary LTE4 excretion.

Administration, Oral↗
PubMed1989

The pharmacology of L-670,596, a potent and selective thromboxane/prostaglandin endoperoxide receptor antagonist.

L-670,596 ((-)6,8-difluoro-9-rho-methylsulfonyl benzyl-1,2,3,4- tetrahydrocarbazol-1-yl-acetic acid) has been shown to be a potent receptor antagonist as evidenced by the inhibition of the binding of 125I-labeled PTA-OH to human platelets (IC50, 5.5 x 10(-9) M), inhibition of U-44069 induced aggregation of human platelet rich plasma (IC50, 1.1 x 10(-7) M), and competitive inhibition of contractions of the guinea pig tracheal chain induced by U-44069 (pA2,9.0). The compound was also active in vivo as shown by inhibition of arachidonic acid and U-44069 induced bronchoconstriction in the guinea pig (ED50 values, 0.04 and 0.03 mg/kg i.v., respectively), U44069 induced renal vasoconstriction in the pig (ED50, 0.02 mg/kg i.v.), and inhibition of ex vivo aggregation of rhesus monkey platelets to U-44069 (active 1-5 mg/kg p.o.). The selectivity of the compound was indicated by the failure to inhibit, first, ADP-induced human or primate platelet aggregation and, second, bronchoconstriction in the guinea pig in vivo and contraction of the guinea pig tracheal chain in vitro to a variety of agonists. It is concluded that L-670,596 is a potent, selective, orally active thromboxane A2/prostaglandin endoperoxide receptor antagonist.

Anesthesia↗
PubMed1987

L-641,953 (R-8-fluoro-dibenzo[b, f]thiepin-3-carboxylic acid-5-oxide): a novel thromboxane-prostaglandin endoperoxide antagonist.

The effects of L-641,953 (R-8-fluoro-dibenzo[b, f]thiepin-3-carboxylic acid-5-oxide) have been studied on pulmonary and other smooth muscle preparations in vitro and in vivo. When studied in vitro on guinea-pig tracheal chains, L-641,933 produced significant shifts in the dose-response curves to the prostaglandin endoperoxide analogues, U-44069 (pA2 7.06) and U-46619 (pA2 7.14), and prostaglandin (PG) F2 alpha (pA2 6.33) had minimal activity against contractions induced by histamine (pA2 4.38), 5-hydroxytryptamine (pA2 4.63), and acetylcholine (pA2 4.56) and slightly enhanced relaxation induced by PGE2. When tested on the guinea-pig gall bladder strip in vitro, L-641,953 antagonized contractions induced by U-44069 (pA2 7.03) but was less active against those induced by PGF2 alpha (pA2 6.03), PGE1 (pA2 5.62), and histamine (pA2 4.84). When tested in vitro on the guinea-pig pulmonary artery, L-651-953 significantly antagonized contractions induced by U-44069 (pA2 7.04), U-46619 (pA2 7.14), and PGF2 alpha (pA2 7.16) but was less effective against contractions induced by histamine (pA2 4.19). Schild analysis indicated that L-641,953 was fully competitive against contractions of either the guinea-pig tracheal chain induced by U-46619 or the guinea-pig pulmonary artery induced by U-44069 and U-46619. When tested on human platelets in vitro L-641,953 inhibited aggregation induced by U-44069 (IC50 1.3 X 10(-6) M) but not ADP.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1986

Neutrophil LTA4 hydrolases and leukotriene B4 receptors: effects of leukotriene epoxides and their enzymatic products.

A selection of inhibitors of rat and human neutrophil LTA4 hydrolases have been studied in vitro using partially purified enzymes. 5(S)trans 5,6 oxido-7,9-trans-11-cis-eicosatrienoic acid (LTA3) and 5(S)trans 5,6 oxido, 7,9-trans, 11,14,17-cis-eicosapentaenoic acid (LTA5) have been shown to inhibit neutrophil LTA4 hydrolases in a time-dependent manner. The products of hydrolysis of LTA3, LTA4 and LTA5 by human and rat neutrophil LTA4 hydrolase have been shown to displace [3H] LTB4 binding to human and rat neutrophil membranes. The order of displacement of [3H] LTB4 is LTB4 = LTB3 greater than LTB5 and this correlated well with their biological potencies for enhancement of neutrophil aggregation and chemokinesis.

Animals↗
PubMed1986

Aerobic performance in brothers, dizygotic and monozygotic twins.

Forty-two brothers, 66 dizygotic twins of both sexes and 106 monozygotic twins of both sexes, 16 to 34 yr of age, took part in this study that was designed to investigate the effect of heredity in aerobic performance. Maximal oxygen uptake (VO2 max), maximal heart rate (HR max), maximal ventilation, and maximal oxygen pulse were obtained from a progressive ergocycle test to exhaustion. Total work output in a 90-min maximal ergocycle test was also determined in the twins. Fat-free weight was estimated from body density measurements obtained through underwater weighing. Aerobic performance scores were adjusted for age (brothers), and age and sex (dizygotic and monozygotic twins) by regression procedures. Dizygotic twins and brothers of same sibship exhibited about the same level of resemblance for all variables or were only slightly different, with the exception of HR max. Monozygotic pairs were generally more alike than the other sibs, as suggested by the intra-class coefficients. Twin data were used to compute the genetic effects. The within-pair estimate of genetic variance revealed that it was significant (P less than or equal to 0.05) for all variables except VO2 max X kg-1 fat-free weight X min-1. In the case of HR max, the among-pairs component estimate had to be used, and it also proved significant (P less than or equal to 0.01). The size of the genetic effect was computed from three different methods, and it reached about 40% for VO2 max X kg-1 X min-1, 50% for HR max, 60% for maximal oxygen pulse and maximal ventilation, and 70% for 90-min work output X kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Heredity and muscle adaptation to endurance training.

To determine whether sensitivity of muscle characteristics and aerobic performances to endurance training was genotype-dependent, 6 pairs of monozygotic (MZ) twins, 21 +/- 4 yr of age (mean +/- SD), took part in a 15-wk ergocycle endurance training program. Tests were performed before and after 7 and 15 weeks of training. A biopsy of the vastus lateralis muscle was obtained for the determination of fiber type composition and activities of creatine kinase, hexokinase, phosphofructokinase, lactate dehydrogenase, malate dehydrogenase, 3-hydroxyacyl CoA dehydrogenase, and oxoglutarate dehydrogenase. Maximal oxygen uptake was measured with a progressive maximal ergocycle test, while endurance performance was determined as the total work output during a 90-min maximal ergocycle test. Results indicated that maximal oxygen uptake X kg-1 and endurance performance X kg-1 increased significantly (14 and 31%, respectively) with training, and intra-pair resemblance (intra-class) in response to 15 wk of training ranged from 0.65 to 0.83. Hexokinase (31%), phosphofructokinase (37%), lactate dehydrogenase (21%), malate dehydrogenase (31%), and 3-hydroxyacyl CoA dehydrogenase (60%) were significantly increased with training whereas no mean change in fiber-type proportions, oxoglutarate dehydrogenase and creatine kinase activities and the phosphofructokinase/oxoglutarate dehydrogenase ratio was observed. Similarity within twin pairs in the response to enzyme activities was mainly detected in the second half of the training program. The present results confirm, therefore, that both maximal oxygen uptake and endurance performance responses to training are largely genotype-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1985

Relationships between skeletal muscle characteristics and aerobic performance in sedentary and active subjects.

Forty-eight sedentary and 39 quite active or well-trained men participated in this study. Muscle biopsy samples were taken from the vastus lateralis for the determination of fiber type composition (I, IIa, IIb), fiber type area, and assay of the following enzymes: malate dehydrogenase (MDH), 3-hydroxyacyl CoA dehydrogenase (HADH) and oxoglutarate dehydrogenase (OGDH). Maximal oxygen uptake (VO2max) was determined with a progressive cycle ergometer test, while endurance performance or maximal aerobic capacity (MAC) was defined as the total work output during a 90-min cycle ergometer test. Correlation analysis revealed no evidence of association between fiber type composition and VO2max kg-1 or MAC kg-1 in sedentary subjects, while active men exhibited significant correlation between % type I (r = 0.52), % type IIb (r = 0.31) and VO2max kg-1. Enzyme activities were not significantly correlated with MAC kg-1 and VO2max kg-1 in sedentary men while active men exhibited significant correlation for the three enzymes (0.37 less than or equal to r less than or equal to 0.51) with VO2max kg-1. These results show that the contribution of muscle fiber type and enzyme activities to aerobic performance may be inflated from a statistical point of view by the training status heterogeneity of subjects. They also suggest that variation in these muscle characteristics does not account for the individual differences in aerobic performance of subjects who have never trained before. Therefore, the assessment of muscle characteristics is not as useful as originally thought for the detection of individuals with a high potential for endurance performance among untrained subjects.

Adolescent↗
PubMed1985

Specificity of aerobic and anaerobic work capacities and powers.

Thirty-three untrained subjects of both sexes, 18-31 years of age, performed several tests on cycle ergometers. Maximal aerobic power (MAP) was obtained in a progressive work test. Maximal aerobic capacity (MAC) was measured in a 90-min maximal test and was computed as the total work output during that period. Two all-out cycle ergometer work tests lasting 10 s and 90 s were used to estimate the anaerobic alactic capacity (AAC) and lactic capacity (ALC). Anaerobic alactic power (AAP) was computed as the highest output in 1 s in the AAC test and anaerobic lactic power (ALP) was obtained as the mean output during the last 5 s in an all-out test of 30 s. Correlation coefficients were computed between all measurements of capacity and power expressed per kg of body weight as well as with scores adjusted for sex differences. Common variances (r2 X 100) between measurements of power were either low (MAP-AAP, 40%) or moderate (MAP-ALP, 61%; AAP-ALP, 62%) while common variances between measurements of capacity were sometimes low (MAC-AAC, 49%) or higher (MAC-ALC, 76%; AAC-ALC, 77%). The common variances between tests of power and capacity reached high values when calculated with metabolic criteria of the same class (MAP-MAC, 81%; AAP-AAC, 92%). These results provide quantitative evidence to support the notion of specificity between the aerobic and the anaerobic work performances and support the distinction between capacity and power of the three energy systems.

Adenosine Triphosphate↗
PubMed1984

Responses of maximal aerobic power and capacity to aerobic training.

The purpose of this experiment was to investigate the individual differences and the specificity in the response of maximal aerobic power (MAP) and capacity (MAC) to a 20-week aerobic training program. Twenty-four subjects (25 +/- 4 years), ascertained as sedentary, including 13 women and 11 men, participated in this study. MAP was determined with a progressive maximal ergocycle test, while MAC was computed as the total work output accomplished during a 90-min maximal ergocycle test. A modified bicycle ergometer allowed the exact measurement of the distance and the load for the computation of the work performed during MAC. The aerobic training program enhanced mean MAP/kg and MAC/kg by 33% and 51%, respectively. Although MAP/kg response to training was similar in both sexes, there was a sex difference in the response of MAC/kg, men improving 50% more than women. Individual differences in the response to the standardized training program were considerable with training gains ranging from 5% to 88% for MAP/kg and from 16% to 97% for MAC/kg. Correlations between training increments in MAP/kg with those in MAC/kg were rather low ranging from 0.28 to 0.44. These results indicate that there is a sex difference in the trainability of aerobic capacity, but not of maximal aerobic power, under the same 20-week aerobic training program. Moreover, large individual differences in the response to similar aerobic training are observed in sedentary persons, suggesting that certain genotypes are more sensitive to training than others. Finally, there is a high level of specificity in the response to training of the power and of the capacity of the aerobic energy metabolism.

Adult↗
PubMed1984

Studies on L-640,035: a novel antagonist of contractile prostanoids in the lung.

The effects of L-640,035 (3-hydroxymethyl-dibenzo [b,f] thiepin-5,5-dioxide) have been studied on pulmonary smooth muscle contraction in vitro and in vivo. When studied in vitro on guinea-pig tracheal chains, L-640,035 produced significant shifts in the dose-response curves to a prostaglandin (PG) endoperoxide analogue (U-44069) (pA2 7.0), PGF2 alpha (pA2 5.9) and PGD2 (pA2 6.5). L-640,035 produced no significant shift in the dose-response curves to leukotriene D4 or histamine and produced a small but statistically significant shift in the dose-response curve to 5-hydroxytryptamine (5-HT) (pA2 5.2). With the exception of PGF2 alpha, Schild analysis did not in general indicate competitive inhibition. The main metabolite of L-640,035, L-636,499, also produced significant parallel shifts in the dose-response curves to U-44069 (pA2 6.0) and PGF2 alpha (pA2 6.0), but with some reduction in the maximal contraction. When L-640,035 was administered intravenously to guinea-pigs, significant inhibition of increases in pulmonary resistance or insufflation pressure induced by U-44069 (ED50 0.16 mg kg-1), leukotriene D4 (ED50 0.25 mg kg-1) and 5-HT (ED50 3.4 mg kg-1) but not histamine (ED50 greater than 10 mg kg-1) was observed. When L-640,035 was administered intravenously to dogs a significant inhibition of increases in pulmonary resistance induced by U-44069 (ED50 0.85 mg kg-1) but not histamine (ED50 greater than 30 mg kg-1) was observed. 5 When L-640,035 was administered by the intraduodenal route to dogs at doses of 3 and 10 mg kg- significant inhibition of increases in pulmonary resistance induced by sodium arachidonate (3 mgkg1 i.v.) was observed with a duration of action of > 255 min. 6 It is concluded that L-640,035 is a novel, relatively selective, and orally active antagonist of the actions of contractile prostanoids on pulmonary smooth muscle.

Airway Resistance↗