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Biomedical subjects

J Blanchard

Publications and source records attributed to J Blanchard.

At least 127 records · Page 7Linked to original sources
PubMed1990

Effects of age and intake on vitamin C disposition in females.

The pharmacokinetics of vitamin C following a 500 mg oral tablet dose were compared in a group of fourteen healthy young women whose age was 26.0 +/- 2.8 years (mean +/- s.d.), and in a group of fourteen healthy elderly women aged 68.1 +/- 2.6 years. The body composition of each subject was assessed using several anthropometric measurements in order to help explain any observed differences in the pharmacokinetic behavior of vitamin C. The vitamin C doses were characterized with the subjects in two states of vitamin C nutriture: a 'depleted' state which was achieved by 4-5 weeks on a vitamin C-restricted diet of less than 10 mg/d and a 'supplemented' state in which the subjects were given daily doses of 500 mg of vitamin C for 3 weeks. Plasma and urine samples were collected for 72 h following the dose of vitamin C from subjects in a 'depleted' state and for 24 h from subjects in a 'supplemented' state and analysed for their vitamin C content. None of the pharmacokinetic parameters measured differed significantly between the two age groups. In contrast, the vast majority of these parameters were significantly different in depleted and supplemented subjects. The peak times (tmax) were greater in the depleted state in both young and elderly groups whereas the peak concentrations (Cmax) were greater in the supplemented state. The absorption rate constant (Ka) was significantly larger in the supplemented state compared to the depleted state in the young group and the absorption half-life (t 1/2, Ka) was significantly greater in the depleted state in the young group only. The absorption lag time (tlag) did not differ with respect to age or nutritional status. The elimination half-life (t 1/2, Ke) was significantly longer in supplemented subjects. Although the apparent high volume of distribution (Vd) was not significantly different within each age group the Vd was significantly greater in the depleted state when the two age groups were combined. The clearance (CL), and the nonrenal clearance (CLNR) were significantly greater in the depleted state. The renal clearance (CLR) and the amounts of vitamin C excreted in the 0- to 12- and 12- to 24-h intervals were significantly larger in the supplemented state. The urinary excretion data also indicate that, in supplemented subjects, an average of about 40 percent of the administered dose is excreted as unchanged vitamin C in the first 12 h after dosing, with very little being excreted thereafter.

Adult↗
PubMed1989

Calcium absorption in man: some dosing recommendations.

The absorption of calcium involves a saturable (active) and a nonsaturable (passive) component. The work of several investigators indicates that an inverse relationship exists between calcium intake and absorption efficiency. Human calcium absorption data from the literature were analyzed using a model which included both an active and a passive absorption component. Simulations were provided to illustrate the suitability of this model, and another previously reported model, to fit the data and to estimate the absorption efficiency of calcium when using different dosing regimens. Comparisons of the values predicted in this study with some literature values are provided and some assumptions and potential limitations associated with the use of this method are discussed. The division of the daily dose into equal increments taken at equally spaced intervals over the course of the day is recommended as a useful procedure for increasing the absorption efficiency and efficacy of calcium.

Absorption↗
PubMed1989

A multivariate study of determinants of vigorous exercise in a community sample.

The purpose of this study was to explore the associations between several social learning theory variables and self-reported vigorous exercise and to consider the implications for exercise promotion. A random sample of adults in San Diego, California, was surveyed by mail. The 2,053 respondents (response rate, 43.4%) overrepresented Caucasian, affluent, and well-educated groups. A model of 24 variables accounted for 0.27 of the variance in exercise, and results strongly supported social learning theory. The strongest correlates were self-efficacy (i.e., confidence in the ability to exercise in specific situations), perceived barriers to exercise, modeling, dietary habits, support from friends, and age. Smoking was inversely associated with exercise in men only. We encourage researchers to conduct intervention trials to test the hypotheses generated in this study.

Adult↗
PubMed1989

Management of apnea in infants.

The incidence and proposed mechanisms of apnea of infancy and apnea of prematurity are briefly reviewed, and the use of methylxanthines in managing these conditions is discussed. Apnea may result from incomplete neurological development of the infant. A sleep-related defect in respiratory control mechanisms has been proposed. Apnea may be secondary to physiologic abnormalities that cause airway obstruction or to cardiac disease or arrhythmia, seizure disorders, infection, or other disorders. Therapy often includes supportive management. The primary pharmacologic agents used to treat apnea of prematurity are caffeine and theophylline. The metabolism of these drugs differs greatly between newborns and adults and changes rapidly in the first nine months of life; in infants up to 4 1/2 months of age, the half-life of these compounds is prolonged. While only theophylline is approved in the United States for management of apnea, caffeine has several potential advantages. However, no suitable caffeine product is available. The accepted pharmacologic treatment for apnea of prematurity is the use of the methylxanthines theophylline and caffeine. Theophylline has also been used in treating apnea of infancy, although there are fewer data documenting its efficacy for this indication.

Apnea↗
PubMed1989

Incidence of venous air embolism during cesarean section is unchanged by the use of a 5 to 10 degree head-up tilt.

One hundred healthy parturients were divided at random into two demographically similar groups and were positioned for cesarean section either horizontally or flexed 5 to 10 degrees head up, with a 15 degrees lateral tilt. A Doppler ultrasound transducer was positioned over the fourth intercostal space parasternally. Initially, two patients received spinal, three general, and 95 epidural anesthesia. Two patients subsequently needed general for failed epidural anesthesia. Changes in Doppler heart tones (greater than 15 sec duration) indicative of venous air embolism (VAE) were identified 15 times in 11 patients--seven in supine and four in head-up patients (no statistically significant difference). Six awake patients (three horizontal, three head-up) developed chest tightness or pain during surgery, but only one episode correlated with VAE. No patient developed breathlessness. Moderate hypotension (greater than 10% decrease in systolic arterial pressure [SAP]) occurred in seven of 11 (63.6%) patients with, and in 26 (29.2%) of 89 patients without, VAE (P less than 0.001). More severe hypotension (SAP less than 90 mm Hg) due to bleeding occurred once. We conclude that a modest (5-10 degrees) head-up position does not influence the occurrence of VAE in patients having cesarean section. An 11% incidence of clinically insignificant VAE, although low, is still worrisome, as even small air bubbles in the circulation are potentially harmful, especially if the foramen ovale is patent. VAE during cesarean section should be anticipated and the anesthetic management planned accordingly.

Adult↗
PubMed1989

Comparison of plasma, mononuclear and polymorphonuclear leucocyte vitamin C levels in young and elderly women during depletion and supplementation.

The levels of vitamin C in plasma, mononuclear (MN) and polymorphonuclear (PMN) leucocytes were measured in healthy, free-living, young and elderly women on three occasions over an 8-10-week period: (a) at entry into the study, (b) following 5 weeks of dietary depletion of vitamin C, and (c) following 3 weeks of supplementation with 500 mg of vitamin C per day. The combined mean vitamin C levels (expressed as microgram/10(8) cells) in MN cells were higher than those found in PMN cells at all three times, although the difference was only statistically significant in the depleted state. There were no age-related differences in the levels of vitamin C in plasma, MN or PMN cells at any of the three times. Significant overall differences in vitamin C levels between the entry and depleted and the depleted and supplemented states were observed for plasma and PMN cells but not for MN cells, possibly indicating that plasma and PMN cells are more sensitive indicators of vitamin C status than MN cells. The mean levels of vitamin C found in plasma clearly do 'track' those found in MN and PMN cells. However, attempted correlations between plasma and MN, plasma and PMN, and MN and PMN vitamin C levels at each time proved to be non-significant. In addition, the changes in vitamin C levels from entry to depleted and from depleted to supplemented times were non-significant when comparing plasma to MN and plasma to PMN, whereas the MN vs PMN comparison indicated a significant change in vitamin C levels between the depleted and supplemented states.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Determination of the partition coefficients, acid dissociation constants, and intrinsic solubility of carbenoxolone.

The dissociation constants, partition coefficients, and solubility of carbenoxolone (1) were determined using tritium-labeled drug. The partition and solubility methods were used to assess the dissociation constants of carbenoxolone, while the pKa of the structurally related triterpenoid, enoxolone (2) was determined using a spectrophotometric method. The true partition coefficient (TPC) of carbenoxolone was found to be 643.8 in an n-octanol:aqueous buffer system, while its intrinsic solubility (So) was 1.63 x 10(-5) M. The apparent partition coefficient (APC) was independent of the concentration of carbenoxolone over the pH range of 3 to 7. The values of pk1 and pk2 for carbenoxolone, obtained by the partition and solubility methods, were in reasonably good agreement. The observed pKa value of enoxolone enabled the assignment of pk2 (the weaker acid grouping) to the carboxyl group at C-30.

Carbenoxolone↗
PubMed1988

Meta-analysis of clinical trials: summary of an international conference.

An international conference of clinicians, clinical investigators and biostatisticians discussed meta-analysis in relation to clinical trials, i.e. the combination of data from separate studies for the purpose of obtaining information that cannot be derived from the individual studies. Meta-analysis can be a helpful tool for generating hypotheses for future trials, for studying the consistency of trials of the same or similar goals, and for generating more precise estimates of effect. There are still a number of unresolved questions about the methodology and interpretation of meta-analysis. Better and more uniform reporting of primary studies would increase the usefulness of meta-analysis.

Clinical Trials as Topic↗
PubMed1988

Multicenter double-blind study of ticlopidine in the treatment of intermittent claudication and the prevention of its complications.

In this multicenter trial 169 patients with chronic intermittent claudication due to obstructive peripheral vascular disease were randomized in a double-blind fashion into two parallel groups receiving either 250 mg ticlopidine or placebo, twice daily. At entry, the two groups (83 ticlopidine, 86 placebo) were well matched for the major clinical features apart from an excess of women in the ticlopidine group. At six months, 167 patients were alive, 2 having died of malignant disease (1 from each group). At this stage, 39 patients from the ticlopidine group and 29 from the placebo group (p = 0.04) had increased their walking distance by more than 50% of baseline values. For the groups as a whole pain-free and total walking distance were greater in the ticlopidine group than in the placebo group (194 vs 124 meters, p = 0.03 and 236 vs 170 meters, p = 0.04, respectively). Two patients from the ticlopidine group vs 9 patients from the placebo group (p = 0.03) developed significant cardiovascular events during the study. These results indicate that ticlopidine has a beneficial effect both in the treatment of the symptoms and the prevention of vascular complications in patients with intermittent claudication.

Clinical Trials as Topic↗
PubMed1988

[Increase of the frequency of HLA DR4 antigens in recurrent arterial hypertension of pregnancy].

We studied the frequency of HLA DR antigens in 96 women whose 50 with preeclampsia (PE = proteinuria greater than 0.5 g/l + HTA) and 46 with gestational HTA (GHTA = pregnancy-induced HTA without proteinuria). Sixty had later pregnancies (28 PE and 32 GHTA) and were followed for from 3 to 23 years (m = 8.5 yrs) after the first pregnancy. HLA DR antigen distribution was determined by a search on B lymphocytes for the 10 antigens of locus DR. The normal population included 38 control couples (76 mothers and fathers) with normotensive pregnancies (A) and 200 healthy controls recruited from a local blood donor population (B). The frequency of alleles was compared to that of the different group of primiparous women and whole group of women with later pregnancies. Significant variations were evaluated by the chi 2 test, using Woolf's method: the p values obtained was multiplied by the number of antigens looked for (p corrected or pc). Only the DR4 antigen, present in 19.7% of control couples (A) and 26.5% of the blood donor population (B), was increased in proportions that depended on clinical classification: 54.3% (pc less than 0.005 with A, less than 0.007 with B) in all primiparous women with GHTA, 38% (NS) in all primiparous women with PE. However significant variation was also observed when the frequency of DR4 in PE women was compared to that in only women of A (38% vs 5.2%, pc less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1987

Growth hormone (GH) response to a single intravenous injection of synthetic GH-releasing hormone in prepubertal children with growth failure.

In this collaborative study involving 27 European medical centers, the plasma GH response to a single iv bolus dose of 2 micrograms/kg BW synthetic GHRH-(1-44)NH2 was determined in 574 children with growth failure of various etiologies. Analysis of the plasma GH response to GHRH was performed in 394 validated prepubertal children; these children were subdivided into 3 groups according to the degree of GH deficiency assessed within 6 months by conventional provocative tests (insulin, arginine, etc.): normal GH status (n = 210), partial GH deficiency (n = 73), or severe GH deficiency (n = 111). The mean peak GH values (+/- 2 SEM) after GHRH treatment in the three groups were 45.8 +/- 4.8, 29.2 +/- 6.3, and 16.8 +/- 3.1 microU/mL, respectively, and were greater than those after the conventional tests. The GH responses were consistent with the degree of GH deficiency based on the responses to the conventional tests. In addition, the areas under the GH response curves in the three groups were significantly different (P less than 0.0001). Among children with severe idiopathic GH deficiency 77% had a peak plasma GH level after GHRH above 10.0 microU/mL and 39% had a peak GH above 20.0 microU/mL. In these children, a single GHRH injection provides information on both their GH secretory capacity and the putative supresellar etiology of their GH deficiency, and may be of potential therapeutic value.

Adolescent↗
PubMed1987

Craniosynostosis in two African green monkeys.

Multiple craniosynostoses were found in two infant African green monkeys. The bones of the calvariums were overlapped and fused at all the cranial sutures with resulting pressure necrosis of the cerebral cortices. The cause of the craniosynostoses is unknown, but the two infants were born within 15 days of each other and had the same father, suggesting either exposure to a teratogen or a genetic etiology. The overlapping of the cranial bones is unlike craniosynostosis in humans.

Animals↗
PubMed1986

[Detection of drug-induced nephrotoxicity].

This is a report of a round table organized during the second meeting of Clinical Pharmacology held in Giens (France) in September 1985. At the beginning of the meeting, the clinical aspects of drug-induced nephrotoxicity were reviewed. Thus we tried to precise the real interest of the studies of proteinuria, urinary cytology, enzymuria and fractional clearances of lithium or magnesium. The most interesting part of our discussions was to know the point of view of men working in drugs companies when a renal abnormality is found during a clinical trial of a drug and when previous experimental studies did not find any renal adverse effects of the drug. It was suggested in a such situation to do particular studies. Methods generally used to study renal physiology as autoradiography micropuncture, microinjection had to be performed to localize the action of the drug along the nephron. It was also discussed of the use of isolated perfused kidney as a tool in drug disposition and the use of renal cells culture. A better understanding of the mechanisms of direct renal toxicity of drugs was obtained from the results of experimental models. It is not so easy, at the present time, to know the mechanisms of immunological drug-induced nephrotoxicity. It seems necessary to develop new experimental models. The results obtained in animals with Cl2Hg or D. Penicillamine or gold salts afford to suspect some mechanisms for these types of nephropathies. This aspect of drug induced nephropathy is more complex because there is a large interindividual variation in susceptibility to these drugs.

Animals↗