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Biomedical subjects

E Rey

Publications and source records attributed to E Rey.

At least 55 records · Page 3Linked to original sources
PubMed2000

Prophylaxis and treatment of thromboembolic diseases during pregnancy with dalteparin.

OBJECTIVES: To determine if a prophylactic dose of dalteparin, 5000 IU daily, and if the adjusted-weight dalteparin therapeutic dose of 100 IU/kg twice daily are appropriate in pregnancy. METHOD: Anti-Xa activity levels were used to assess prophylactic (33 women) and therapeutic (15 women) dalteparin dosage throughout pregnancy. Analysis of variance was used and P-values less than 0.05 were considered statistically significant. RESULTS: In the prophylactic group, anti-Xa activity levels did not vary significantly throughout pregnancy (P=0.15). The initial dalteparin dose was modified on the first anti-Xa activity measurement in eight women, whose weight was statistically different from those remaining on the initial dose (P<0.001). The adjusted-weight therapeutic dalteparin dose induced adequate anti-Xa activity levels. CONCLUSIONS: Dalteparin, 5000 IU daily, is suitable for most pregnant women and does not need to be modified in the third trimester. A therapeutic dalteparin dose adjusted according to pregnancy weight is appropriate.

Adult↗
PubMed2000

Phenytoin administration in the newborn and infant.

To evaluate the efficacy and safety of phenytoin (PHT) in the treatment of situation-related seizures and epilepsies in the newborn and infant; the clinical histories of 82 patients were retrospectively reviewed. Sixty patients received for status epilepticus (SE), intravenous PHT followed by long-term oral administration for 27 of them. The other 22 patients had oral treatment only. Intravenous administration made 55% of these patients seizure-free, whereas oral administration produced lasting seizure control in only 9.1%. During chronic oral treatment, it was most difficult to obtain adequate plasma concentrations in 69.1% of the patients, and 43.6% had side effects, most of which were related to very high plasma concentrations. In conclusion, in the first 2 years of life, intravenous administration of PHT is useful for SE, but oral treatment is poorly effective with difficulty to achieve appropriate and stable therapeutic plasma concentrations, and with frequent side effects.

Anticonvulsants↗
PubMed1999

Dose proportionality of reboxetine enantiomers in healthy male volunteers.

Reboxetine is a racemic mixture of FCE 22071 and FCE 21684 enantiomers. The pharmacokinetics of the enantiomers of reboxetine were observed to be linear in male healthy subjects (n = 6) after the administration of 1.5, 3, 4.5 mg dose of reboxetine as solutions. Kinetic analysis was based on chiral HPLC assay of the enantiomers in plasma collected up to 72 h after each administration. C(max) and AUC were more than double for FCE 22071 (C(max): 38.3+/-13.5, 76. 6+/-26.3, 99.8+/-24.1 ng/mL and AUC(infinity): 605.8+/-233.2, 1288. 3+/-796.4, 1780.7+/-669.3 ng. h/mL for 1.5, 3, 4.5 mg, respectively) than for FCE 21684 (C(max): 15.2+/-5.3, 34.6+/-14.0, 43.1+/-12.3 ng/mL and AUC(infinity): 247.0+/-103.9, 529.1+/-278.4, 773.0+/-355.3 ng. h/mL), whatever the administered dose. The half-lives of the enantiomers were similar (FCE 22071: 13.1, 11.0, 12.6 h and FCE 21684: 12.8, 11.2, 12.2 h after 1.5, 3, 4.5 mg, respectively) and not substantially affected by the dose level.

Administration, Oral↗
PubMed1999

Hypertension in pregnancy: new recommendations for management.

Hypertension in pregnancy is a frequent complication that has substantial adverse perinatal outcomes. Hypertension may be preexisting (chronic) essential or secondary hypertension; a second entity is pregnancy induced (gestational hypertension, preeclampsia). Recent advances have identified newer markers for pregnancy hypertension: several potential candidate genes may explain the apparent family inheritance of preeclampsia, and some thrombophilic markers have been associated with the condition. Management options for mild to moderate hypertension include a short hospital stay to exclude ongoing severe hypertension and to ascertain fetal well-being. Outpatient care with appropriate maternal and fetal surveillance, including umbilical artery doppler velocimetry, is recommended for better perinatal outcomes. Acute care for severe hypertension includes the use of magnesium sulfate to prevent eclampsia and antihypertensive medication. Expeditious delivery is recommended when the maternal or fetal states cannot be stabilized. Follow-up after delivery allows the uncovering of any other coexisting hypertensive or cardiovascular disorder.

Blood Pressure↗
PubMed1999

The effects of first-trimester diabetes control on the incidence of macrosomia.

OBJECTIVE: The aim of this study was to explore the association between glycosylated hemoglobin concentrations during pregnancy and macrosomia. STUDY DESIGN: One hundred thirty-six pregnancies in 120 women with type 1 or type 2 diabetes were studied longitudinally between January 1, 1991, and December 31, 1996. Glycosylated hemoglobin concentration and several maternal variables of mothers of neonates who were large for gestational age were compared with those of neonates who were appropriate for gestational age. Receiver-operator characteristic curves and regression analyses were used to determine a threshold related to macrosomia and to assess its predictive value. RESULTS: Glycosylated hemoglobin concentrations throughout pregnancy were higher in mothers of neonates who were large for gestational age (n = 65) than in mothers of neonates who were appropriate for gestational age (n = 71, P <. 001). A first-trimester glycosylated hemoglobin concentration of >/=5.5% (3 SD above the normal mean) was established by receiver-operator characteristic curves as the strongest predictor of macrosomia and yielded an odds ratio of 24 in multiple logistic regression analysis. CONCLUSION: Macrosomia is determined mainly by first-trimester diabetes control.

Adult↗
PubMed1999

Pharmacokinetics and tolerance of flunitrazepam in neonates and in infants.

OBJECTIVE: To study the pharmacokinetics of flunitrazepam (used for sedation in neonates and infants), to determine the influence of both gestational and postnatal age on the pharmacokinetic parameters, and to analyze the relationship between the hemodynamic parameters and flunitrazepam plasma concentration. METHODS: Flunitrazepam was infused for 20 minutes as a single dose (0.2 mg x kg(-1)) and as multiple doses (0.1 mg x kg(-1)). Six to eight 1-mL blood samples were collected per patient. Flunitrazepam plasma concentration was measured by gas chromatography-mass spectrometry. RESULTS: Thirty-one patients (25 neonates and six infants) were included in the study. Only three of them received multiple doses. After the single dose (n = 28), half-life was 22.6 +/- 7.3 hours, clearance was 0.15 +/- 0.14 L x kg x h(-1), and volume of distribution was 4.6 +/- 4.1 L x kg(-1) (mean +/- SD). Plasma clearance and volume of distribution significantly increased with postnatal age (P < .05), but no pharmacokinetic parameter varied significantly with gestational age. Diastolic blood pressure significantly decreased with increasing flunitrazepam plasma concentrations (P < .05). CONCLUSION: Postnatal age but not gestational age influenced flunitrazepam pharmacokinetic parameters in neonates and infants. Diastolic blood pressure was inversely correlated to flunitrazepam plasma concentration.

Age Factors↗
PubMed1999

Stiripentol: efficacy and tolerability in children with epilepsy.

PURPOSE: Stiripentol (STP) is a new antiepileptic drug (AED) that inhibits cytochrome P450, resulting in increased plasma concentrations of concomitant AEDs. The efficacy and tolerability of STP as an add-on therapy in children were assessed. METHODS: Two hundred twelve patients with refractory epilepsy, aged from 1 month to 20.5 years, received STP either in a single-blind, placebo-controlled trial (108 patients) or in a further open trial (104 other patients selected by epilepsy syndrome for possible efficacy based on the results of the previous trial). RESULTS: Among the 97 patients who could be analyzed for efficacy in the placebo-controlled study, the median seizure frequency was lower at 3 months with STP than with the placebo (p<0.0001); 49% responded to the drug, including 10% who became seizure free. Patients with partial epilepsy had the highest response rate (57%). Results were confirmed in the open study where 68% of the 91 patients receiving STP responded at 3 months. These patients were mainly those with partial epilepsy (73%) who were receiving carbamazepine (CBZ) (75%) as comedication (p<0.001). Ten of the 20 children with severe myoclonic epilepsy in infancy also responded with clobazam (CLB) as comedication. Efficacy was sustained long term in 74% of the 94 patients still receiving STP at a mean 30-month follow-up. Adverse events were reported in 48% of the 212 patients, mainly anorexia and loss of weight, but these events required STP discontinuation in only nine cases. Side effects were minimized in the open trial by optimizing the dose of comedication. CONCLUSIONS: STP seems to be a promising add-on drug, particularly when combined with CBZ in patients with partial childhood epilepsy refractory to vigabatrin (VGB) and with CLB in patients with severe myoclonic epilepsy in infancy.

Adolescent↗
PubMed1999

Does progesterone fluctuation across the menstrual cycle predispose to gastroesophageal reflux?

OBJECTIVE: Gastroesophageal reflux (GER) occurs in 30-50% of all pregnancies. The progressive rise in plasma progesterone has been suggested as a possible mediator of GER during pregnancy. It is not known whether progesterone, at physiological concentrations, has an effect on acid contact time. We sought to evaluate the relationship between progesterone concentrations, lower esophageal sphincter pressure (LESP), and acid contact time across the normal menstrual cycle. METHODS: LESP, 24-h ambulatory esophageal pH monitoring, and serum progesterone levels were determined in 19 healthy women known to have normal menstrual cycles. All tests were performed during the follicular phase (days 2-7) and the luteal phase (days 22-28) of one or two consecutive menstrual cycles. RESULTS: Despite marked oscillations in progesterone levels between the follicular phase (0.37 +/- 0.3 ng/ml) and luteal phase (4.64 +/- 2.92 ng/ml) we observed no significant differences in LESP (29.82 +/- 9.49 vs 30.45 +/- 8.56 mm Hg) or 24-h ambulatory pH levels (pH < 4) in total time (3.04 +/- 0.3% vs 3.18 +/- 2.51%), upright time (4.41 +/- 3.54% vs 4.18 +/- 3.36%), or supine time (0.77 +/- 1.32% vs 1.42 +/- 2.18%). CONCLUSIONS: The fluctuations in progesterone levels across the normal menstrual cycle have no significant impact on LESP and 24-h ambulatory pH parameters. Progesterone, at physiological concentrations, does not predispose to GER in healthy menstruating women.

Acids↗
PubMed1999

Pharmacokinetic optimization of benzodiazepine therapy for acute seizures. Focus on delivery routes.

All benzodiazepines enter cerebral tissue rapidly. However, the duration of action is short for diazepam (< 2 hours) and midazolam (3 to 4 hours) and longer for clonazepam (24 hours) and lorazepam (up to 72 hours), and is not correlated with the plasma concentration-time profiles of these drugs. Although a relationship between the plasma concentration of diazepam, lorazepam and midazolam and their pharmacodynamic effect has been demonstrated in healthy individuals, some caution is warranted as the clinical relevance of these data has not been clearly established. The physicochemical properties of benzodiazepines (lipid solubility and protein binding) regulate their rate and extent of entry into the brain and cerebrospinal fluid. However, the duration of the pharmacological activity of benzodiazepines may be in part related to the affinity of these compounds for the benzodiazepine receptors in the brain: midazolam, clonazepam and lorazepam have higher affinities than diazepam. In the emergency setting, the intravenous route is the most suitable, delivering adequate quantities of benzodiazepines as fast as possible. However, when intravenous administration is not available, rectal administration of a solution is a convenient method for diazepam, midazolam being the only one of these drugs that should be given intramuscularly. The assessment of the efficacy of benzodiazepines in the management of acute seizures and status epilepticus is mainly based on nonrandomized uncontrolled trials. According to the route of administration, the efficacy was 28.6 to 100% (intrarectal) and 54 to 100% (intravenous) for diazepam, 82 to 100% (intravenous) for lorazepam, and 79% (intranasal), 93 to 100% (intramuscular) and 100% (intravenous) for midazolam. Although diazepam was initially chosen for the management of refractory status epilepticus, the longer duration of action of lorazepam and clonazepam may favour the use of these 2 drugs. However, double-blind evaluations are necessary to determine which drug is best.

Benzodiazepines↗
PubMed1998

An approach for dose finding of drugs in infants: sedation by midazolam studied using the continual reassessment method.

AIMS: No drug has been demonstrated to provide simultaneously appropriate sedation, safety and lack of disturbance of the measured parameters during cardiac catheterization in infants. The objective of this study was to estimate the dose of midazolam, administered rectally, that would provide a 90% probability of adequate sedation in infants during cardiac catheterization. A sedation score > or =4 (six-point scale) 30 to 60 min after dosing was rated as a success. METHODS: A double-blind, continual reassessment method using a Bayesian approach has been used. Sixteen infants were administered a single midazolam dose, within a 0.1 to 0.6 mg kg(-1) dose range. RESULTS: Consecutive failures led to allocation of the highest dose to 15 out of 16 patients. The final estimated probability of failure of the 0.6 mg kg(-1) dose was 81% (95% CI: 78.5 to 84%). The time to reach a score > or =4 was longer than expected and the median duration-time at score > or =4 was shorter (15 min) than expected. CONCLUSIONS: Delayed absorption and low rectal bioavailability may explain these data. Higher doses or different routes of administration may lead to the expected sedation, but the safety of doses higher than 0.6 mg kg(-1) administered rectally has not been evaluated. The therapeutic strategy for sedation of this category of infants in the hospital has now been changed based on the present results in that rectal midazolam has been abandoned in this indication.

Administration, Rectal↗
PubMed1998

Vigabatrin: placental transfer in vivo and excretion into breast milk of the enantiomers.

AIMS: Vigabatrin is a new antiepileptic medication consisting of a racemic mixture of 50% active S enantiomer and 50% inactive R enantiomer. Since patients suffering from epilepsy may become pregnant, it is important to understand the extent of placental transfer of such medication. METHODS: During steady-state, vigabatrin enantiomer concentrations were measured in maternal and umbilical blood and in breast milk of two patients. RESULTS: The concentration ratios from the umbilical vein to maternal plasma were R:0.068, S:0.16; 4h25 min after drug administration (case 1) and R: 1.39, S: 0.91; 9h after drug administration (case 2). The milk: plasma concentration ratio was lower than 1 at pre dose sampling in both cases, as well as 3 and 6 h post dose in one case. An estimate of the maximum amount of R and S enantiomers of vigabatrin that a suckling infant would ingest in a day is 3.6% and 1% of the weight-adjusted daily dose respectively. CONCLUSIONS: These results would suggest a slow placental transfer of the vigabatrin enantiomers and that the quantity ingested through milk is small.

Adult↗
PubMed1998

Low-dose doxapram for treatment of apnoea following early weaning in very low birthweight infants: a randomized, double-blind study.

The effects of low-dose doxapram (0.5 mg kg(-1)h(-1)) in combination with caffeine were evaluated on apnoea frequency following weaning from mechanical ventilation, and on blood pressure, in very low birthweight (BW) premature infants. Twenty-nine infants with BW < or=1250 g, gestational age at birth (GA) <34 weeks and postnatal age <5 d, who required minimal respiratory support, were included. Following randomization, they received a loading dose of caffeine citrate and a continuous infusion of doxapram (doxapram, n=14) or placebo (n=15) was started. They were extubated 8 h after starting the infusion, which was continued for 5 d. During this period, weaning was well tolerated in both groups, apnoeas occurred less frequently and there was a greater increase in systolic blood pressure in infants treated with doxapram than in controls. Plasma doxapram levels were also higher than expected. It is therefore suggested that doxapram, even at low doses, should not be used during the first few days of life. Careful monitoring of blood pressure is required if doxapram is used later.

Apnea↗
PubMed1998

Isoniazid dose adjustment in a pediatric population.

This retrospective analysis was designed to evaluate the inactivation index (I3) method used to adjust the isoniazid dose during long-term administration in a pediatric population. Before starting on antituberculosis therapy, sixty-one children received one 10 mg.kg-1 isoniazid test-dose (D). The isoniazid and acetyl isoniazid concentrations were measured by high-performance liquid chromatography on a plasma sample collected 3 hours (C3h) after administration. The patients were separated into slow and fast acetylator groups according to the metabolic ratio. The dose adjustment method using the I3 is based on the assumption that there is a linear correlation between C3h and D [C3h = (I3 x D) - 0.6] in which the slope is I3 and the Y intercept is equal to -0.6 mg.l-1. I3 was determined from a single plasma concentration determination and used to calculate the dose recommended to obtain a desired C3h equal to 1.5 micrograms.ml-1: recommended dose (mg.kg-1) = (1.5 + 0.6)/I3.I3 was significantly higher in the slow acetylator group (0.55 +/- 0.16) than in the fast one (0.26 +/- 0.13), which leads us to recommend a significantly lower dose in the slow acetylator group (4.2 +/- 1.5 mg.kg-1) than in the fast one (10.3 +/- 4.6 mg.kg-1). The data obtained in a subgroup of 21 patients who had at least three consecutive determinations of C3h after different dosages allowed us to verify that there was a linear correlation between C3h and the dose. The mean slope of the correlation lines in that subgroup was 0.61 +/- 0.25 and the 95% confidence interval of the estimated Y-intercept include the theoretical value of -0.60, which shows that our data are consistent with those previously reported in adults. The percentage of patients with a C3h plasma concentration within the expected range (1.5 +/- 0.5 micrograms.ml-1) was significantly higher (69%) in those whose dose was derived from the calculation than in the others (25%). Within each acetylator group, the range of the recommended dose varied widely, and these results emphasize the usefulness of individual dose adjustment based on the inactivation index method.

Adolescent↗
PubMed1998

Drug disposition in cystic fibrosis.

There are many pathological changes in patients with cystic fibrosis (CF) which can lead to alterations in drug disposition. Although, in patients with CF, the extent of drug absorption varies widely and the rate of absorption is slower, bioavailability is not altered. Plasma protein binding for the majority of drugs studied did not differ in patients with CF compared with control groups. The difference in volume of distribution of most drugs between patients with CF and healthy individuals vanished when corrected for lean body mass. Despite hepatic dysfunction, patients with CF have enhanced clearance of many, but not all, drugs. Phase I mixed-function oxidases are selectively affected: cytochrome P450 (CYP) 1A2 and CYP2C8 have enhanced activity, while other CYP isoforms such as CYP2C9 and CYP3A4 are unaffected. Increased phase II activities are also demonstrated: glucuronyl transferase, acetyl transferase (NAT1) and sulfotransferase. The increased hepatic clearance of drugs in the presence of CF may be the consequence of disease-specific changes in both enzyme activity and/or drug transport within the liver. The renal clearance (CLR) of many drugs in patients with CF is enhanced although there has been no pathological abnormality identified which could explain this finding: glomerular filtration rate and tubular secretion appear normal in patients with CF. The precise mechanisms for enhanced drug clearance in patients with CF remain to be elucidated. The optimisation of antibiotic therapy in patients with CF includes increasing the dose of beta-lactams by 20 to 30% and monitoring plasma concentrations of aminoglycosides. The appropriate dosage of quinolones has not been definitively established.

Absorption↗
PubMed1998

Combination of behaviour therapy with fluvoxamine in comparison with behaviour therapy and placebo. Results of a multicentre study.

BACKGROUND: We investigated whether the combination of multi-modal behaviour therapy (BT) with fluvoxamine is superior to BT and placebo in the acute treatment of severely ill in-patients with obsessive-compulsive disorder (OCD). METHOD: In a randomised, double-blind design, 30 patients were treated for nine weeks with BT plus placebo and 30 patients with BT plus fluvoxamine (maximum dosage 300 mg, mean dose 288.1 mg). BT included exposure with response prevention, cognitive restructuring and development of alternative behaviours. RESULTS: Both groups showed a highly significant symptom reduction after treatment. There were no significant differences between the groups concerning compulsions. Obsessions were significantly more reduced in the fluvoxamine and BT group than in the placebo and BT group. Furthermore, the group BT plus fluvoxamine showed a significantly higher response rate (87.5 v. 60%) according to a previously defined response criterion. Severely depressed patients with OCD receiving BT plus placebo presented a significantly worse treatment outcome (Y-BOCS scores) than all other groups. CONCLUSIONS: The results suggest that BT should be combined with fluvoxamine when obsessions dominate the clinical picture and when a secondary depression is present.

Adult↗
PubMed1997

Report of the Canadian Hypertension Society Consensus Conference: 3. Pharmacologic treatment of hypertensive disorders in pregnancy.

OBJECTIVE: To provide Canadian physicians with evidence-based guidelines for the pharmacologic treatment of hypertensive disorders in pregnancy. OPTIONS: No medication, or treatment with antihypertensive or anticonvulsant drugs. OUTCOMES: Prevention of maternal complications, and prevention of perinatal complications and death. EVIDENCE: Pertinent articles published from 1962 to September 1996 retrieved from the Pregnancy and Childbirth Module of the Cochrane Database of Systematic Reviews and from MEDLINE; additional articles retrieved through a manual search of bibliographies; and expert opinion. Recommendations were graded according to levels of evidence. VALUES: Maternal and fetal well-being were equally valued, with the belief that treatment side effects should be minimized. BENEFITS, HARMS AND COSTS: Reduction in the rate of adverse perinatal outcomes, including death. Potential side effects of antihypertensive drugs include placental hypoperfusion, intrauterine growth retardation and long-term effects on the infant. RECOMMENDATIONS: A systolic blood pressure greater than 169 mm Hg or a diastolic pressure greater than 109 mm Hg in a pregnant woman should be considered an emergency and pharmacologic treatment with hydralazine, labetalol or nifedipine started. Otherwise, the thresholds at which to start antihypertensive treatment are a systolic pressure of 140 mm Hg or a diastolic pressure of 90 mm Hg in women with gestational hypertension without proteinuria or pre-existing hypertension before 28 weeks' gestation, those with gestational hypertension and proteinuria or symptoms at any time during the pregnancy, those with pre-existing hypertension and underlying conditions or target-organ damage, and those with pre-existing hypertension and superimposed gestational hypertension. The thresholds in other circumstances are a systolic pressure of 150 mm Hg or a diastolic pressure of 95 mm Hg. For nonsevere hypertension, methyldopa is the first-line drug; labetalol, pindolol, oxprenolol and nifedipine are second-line drugs. Fetal distress attributed to placental hypoperfusion is rare, and long-term effects on the infant are unknown. Magnesium sulfate is recommended for the prevention and treatment of seizures. VALIDATION: The guidelines are more precise but compatible with those from the US and Australia.

Antihypertensive Agents↗