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Biomedical subjects

J Bringer

Publications and source records attributed to J Bringer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Obesity and pregnancy: complications and cost.

The prevalence of obesity is currently rising in developed countries, making pregravid overweight one of the most common high-risk obstetric situations. Although the designs and populations of published studies vary widely, most authors agree that pregravid overweight increases maternal and fetal morbidity. Even moderate overweight is a risk factor for gestational diabetes and hypertensive disorders of pregnancy, and the risk is higher in subjects with overt obesity. Compared with normal weight, maternal overweight is related to a higher risk of cesarean deliveries and a higher incidence of anesthetic and postoperative complications in these deliveries. Low Apgar scores, macrosomia, and neural tube defects are more frequent in infants of obese mothers than in infants of normal-weight mothers. The regional distribution of fat modulates the effects of weight on carbohydrate tolerance, hemodynamic adaptation, and fetal size. Maternal obesity increases perinatal mortality. Long-term complications include worsening of maternal obesity and development of obesity in the infant. The average cost of hospital prenatal and postnatal care is higher for overweight mothers than for normal-weight mothers, and infants of overweight mothers require admission to neonatal intensive care units more often than do infants of normal-weight mothers. Preconception counseling, careful prenatal management, tight monitoring of weight gain, and long-term follow-up could minimize the social and economic consequences of pregnancies in overweight women.

Female↗
PubMed2000

[Evaluation of the benefits brought by pregnancy planning in type 1 diabetes mellitus].

Fetal mortality and morbidity remain dramatically increased in diabetic women. To evaluate the benefit of a preconceptional education combined with a good metabolic control, we compared the outcome of pregnancy in 2 groups of type I diabetic women: group A (n = 21) planned before conception versus group B (n = 40) not planned. Both groups were similar related to the type and duration of diabetes, its complications, age, body mass index and different factors of risk. In group A, HbA1C levels were < or = 3 SD of the normal mean of non diabetic values before conception and during the pregnancy course and > or = 3 SD in group B. We observed a significant reduction (p < 0.05) of the main adverse events regarding fetus outcome (fetal, perinatal and neonatal mortality, malformations) and obstetrical complications in the planned group. These data lead to the need of an extensive policy of early planification of pregnancy in diabetic women.

Congenital Abnormalities↗
PubMed2000

[Non-genomic steroid effects: estrogen action revisited].

Estrogen receptors (ERs) are members of the nuclear receptor superfamily and act classically as transcription factors. However, it has been noted that estrogens could have early cell effects (within a few minutes) that cannot be explained by transcription activation and protein synthesis. There is now an emerging body of evidence that estrogens, like many other steroids, may cause rapid activation of signal transduction pathways. These non-genomic effects involve common second messengers, such as increased intracellular calcium levels phosphoinositide turnover or cAMP accumulation. Recent studies have also shown that estrogens can stimulate the MAP kinase signaling pathway through ERs. These effects have been observed in various estrogen target cells, including endothelial cells, osteoblasts, neurons and breast cancer cells. The ER membrane signaling pathway is thus a new component that could be taken into account to understand the complex modulation of estrogen effects in specific tissues. It could also be a new therapeutic target for the treatment of neurodegenerative, cardiovascular or breast cancer diseases.

Animals↗
PubMed1999

[Nutritional hypogonadism].

Functional hypothalamic amenorrhea are frequently observed. Body weight, body composition, eating attitudes, exercise are potent modulators of gonadotrop axis. Animal studies and clinical observations stress the fact of a major impact on ovary function of starvation or caloric restriction, weight loss and fat mass deficiency, eating disorders, stress or high intensive exercise training. From a pathophysiological point of view, insulin, IGF's system, leptine and central neuromediators are a link between nutrition and the gonadotropic axis. Initial clinical evaluation may strongly suggest the environmental origin of the amenorrhea. Basal hormonal evaluation (gonadotropins, prolactin, androgens ...) excludes other diseases and specialised evaluations [basal metabolic rate (BMR), Free T3 ...] could confirm the diagnosis. A low BMR, and a low Free T3, a normal FSH level with a low LH level suggest the nutritional origin of the amenorrhea. Improvement of nutritional intake and body composition with a psychological follow up may reverse the gonadotropin deficiency. If this deficiency persists hormonal replacement therapy is added in order to prevent the short or long term consequences (osteoporosis) of hypoestrogenism.

Amenorrhea↗
PubMed1999

Efficacy and acceptability of intranasal 17 beta-oestradiol for menopausal symptoms: randomised dose-response study. Aerodiol Study Group.

BACKGROUND: The benefit of oestrogen therapy for menopause symptoms is well recognised. However, the means of delivery currently available have disadvantages, including variable bioavailability, intestinal and hepatic first-pass effects, and dermatological reactions. An intranasal 17beta-oestradiol spray, S21400, which bypasses such drawbacks, has been developed. We studied the efficacy and tolerability of S21400 in the treatment of postmenopausal symptoms. METHODS: In this double-blind study, 420 postmenopausal women were randomly allocated to receive intranasal placebo or S21400 in doses of 100 microg, 200 microg, 300 microg, or 400 microg, or oral oestradiol valerate in doses of 1 mg or 2 mg, daily for 12 weeks. The primary outcomes were the Kupperman Index (KI) and the incidence of hot flushes. Tolerability assessments included rhinoscopy and ciliary function tests. FINDINGS: S21400 dose-dependently decreased KI (p<0.001), with a lowest effective dose of 300 microg/day at 4 weeks (p<0.05) and 200 microg/day at 12 weeks (p<0.01). The incidence of hot flushes decreased by a maximum of 75% (S21400 lowest effective dose 200 microg/day at 4 weeks and 100 microg/day at 12 weeks). S21400 increased serum oestradiol exposure dose-dependently, to concentrations similar to those achieved with oral oestradiol 1-2 mg, with lower intra-patient and inter-patient variability. There was no significant difference in ear, nose, and throat function or adverse events between the S21400 and the placebo or oral oestradiol groups, except for a greater incidence of sneezing and application site reaction (99% mild or moderate) in the S21400 groups. S21400 was thought to be effective and convenient by the patients, and compliance was high. INTERPRETATION: Intranasally administered 17beta-oestradiol is significantly better than placebo; its effectiveness at reducing menopausal symptoms is similar to that of oral oestradiol and is also well-tolerated. Intranasal administration avoids first-pass metabolism and provides a reproducible, easily adjustable dosing mechanism that represents a new option for hormone replacement therapy.

Administration, Intranasal↗
PubMed1999

Syndrome of body fat redistribution in HIV-1-infected patients: relationships to cortisol and catecholamines.

OBJECTIVE: Alterations of body fat distribution have been recently reported in HIV-infected patients. We aimed to investigate whether the hormones modulating adipose tissue metabolism could be implicated. SUBJECTS: We investigated twenty-eight HIV-infected patients who had developed abdominal fat, combined with peripheral lipodystrophy in 25 cases and 'buffalo hump' in 2 cases, but who had otherwise improved on antiretroviral therapies. Twelve patients with no change in body fat, matched for age, disease control and treatment, were studied as controls. MEASUREMENTS: Body composition was assessed by bioelectrical impedance analysis. Subcutaneous (SAT) and visceral (VAT) compartments of total abdominal adipose tissue (TAT) were measured by computed tomography. Resting metabolic rate (RMR) was assessed by indirect calorimetry. Endocrine investigations included plasma thyroid hormones, cortisol, testosterone, oestradiol and 24-hour urinary free cortisol (UFC) and catecholamines. RESULTS: Despite similar body mass index, the patients with body fat alterations showed significantly larger VAT and higher VAT:TAT ratio than controls (P = 0.002 and 0.0001, respectively). In these patients, RMR was significantly higher than estimated according to the Harris-Benedict formula (+ 19.7 +/- 11.6 %, P = 0.0001) and correlated with VAT (r = 0.58, P = 0.003) and 24-hour urinary output of catecholamines (r = 0.67, P = 0.002), that was significantly increased in comparison with controls (1737 +/- 1228 vs 476 +/- 292 nmol, P = 0.013). We also found a significant correlation between VAT and UFC (r = 0.41, P = 0.042) that was absent in controls, although levels of UFC were similar in the two groups. CONCLUSIONS: Our data suggest that body fat redistribution may involve cortisol and catecholamine actions. While high release of catecholamines may enhance RMR through increased lipolysis, cortisol may promote central fat storage. These effects might be related both to persistent hormonal responses to stress becoming inappropriate while disease control improved and to an increased sensitivity of visceral adipose tissue to cortisol in affected patients.

Adipose Tissue↗
PubMed1999

GH deficiency in adults: an epidemiological approach.

OBJECTIVE: The prevalence of adult onset GH deficiency (GH-D) is poorly documented. Epidemiological data are now required to estimate the financial cost of GH treatment in adults. The aim of the present study was to estimate the prevalence of GH-D, from a cohort of 1652 adult patients with hypothalamo-pituitary diseases. DESIGN: The hormonal status of all patients presenting with pituitary diseaseand observed during the year 1994 in 15 endocrine units was retrospectively analyzed, irrespective of the date of disease onset, of the nature and date of pituitary investigations, and whether or not they included specific testing of the GH axis. Of the whole population of 1652 patients, a selected group (RG2) was chosen after exclusion of patients with active acromegaly (n=1414). RESULTS: GH stimulation tests had been performed in 549 patients of the RG2 group and a documented GH-D was found in 301. A relationship between the value of the GH peak and the number of pituitary deficits was evaluated. For instance, it was shown that 93% of patients with three deficits had GH-D. These results constituted the basis for estimating the number of GH-D in the group of untested patients. The number of GH-D deduced from the number of established GH-D (n=301) and from the number of GH-D hypothesized from other pituitary deficits (n=406) was 707 cases. Prevalence and annual incidence were calculated from data recorded in a referral center with a well-defined catchment area, Marseilles (Bouches du Rhône department). We projected a prevalence of 2638 for France and an annual incidence of 12 GH-D per million of the adult population.

Adult↗
PubMed1999

Early hemorheologic aspects of overtraining in elite athletes.

A standardized questionnaire has been proposed by the French consensus group on overtraining of the Société Française de Médecine du Sport (SFMS) and allows the calculation of a 'score' that may help to quantify the early clinical symptoms of the overtraining syndrome in sportsmen submitted to a heavy training program. We investigated a possible relationship between this score and blood rheology in 36 male elite sportsmen (national level in football, volleyball and karate; age: 17-33 yr) who underwent a standardized check-up including biological measurements and an exercise-test. The overtraining score ranged between 0 and 21 items and was correlated with blood viscosity (r = 0.413, p < 0.02). This correlation was explained by a correlation of this score with plasma viscosity (r = 0.512, p < 0.01) and hematocrit (r = 0.387, p < 0.05). When subjects with a high score (>6) were compared to subjects with a lower score they appeared to have a higher blood viscosity at native (but not corrected) hematocrit (3.18 +/- 0.01 vs. 2.89 +/- 0.05 mPa.s, p < 0.02), explained by higher values in both plasma viscosity (1.39 +/- 0.02 vs. 1.31 +/- 0.02 mPa.s, p < 0.01) and hematocrit (42.8 +/- 0.45 vs. 41.1 +/- 0.44, p < 0.05). By contrast, there was no difference in RBC deformability and aggregation. Overtrained subjects have also lower levels of zinc (0.72 +/- 0.024 vs. 0.84 +/- 0.023 mg/l, p < 0.01), ferritin (55.1 +/- 7.3 vs. 92.3 +/- 9.4 ng/ml), and IGF-binding protein 3 (3.4 +/- 0.22 vs. 4.52 +/- 0.4 ng/ml). Neither zinc nor ferritin status were likely to explain the rheologic alterations since disturbances in zinc or iron are rather associated with abnormalities in erythrocyte deformability or aggregability. Therefore, the early signs of overtraining in elite sportsmen are associated with a hemorheologic pattern that suggests some degree of reversal of the 'autohemodilution' associated with fitness in athletes.

Adult↗
PubMed1999

Hemorheology of growth hormone-deficient adults.

Growth hormone deficiency (GHD) in adults results in alterations of body composition and metabolism associated with a lowered insulin sensitivity and an increased cardiovascular risk. Since hemorheologic disturbances (putative factors of vascular risk) are found in the insulin-resistance syndrome, we investigated blood rheology in 9 adults GHDs (5 men, 4 women; age 37.9+/-4.7 years; body mass index 30.23+/-3.2 kg/m2) compared with 23 lean controls and 37 controls matched for sex, age and body mass index. While this sample of GHDs exhibits the typical metabolic picture of this syndrome (upper body overweight with a waist-to-hip ratio at 0.91+/-0.07; low HDL cholesterol at 1.07+/-0.09 mmol x l(-1); low insulin sensitivity with the minimal model technique at 3.3+/-1.29 min(-1)/(microU/ml) x 10(-4)) they have similar values of blood viscosity at either native or corrected hematocrit, similar hematocrit, similar red cell rigidity viscometric index, similar red cell aggregation parameters than overweight matched controls. There is only a nonsignificant tendency for plasma viscosity to be higher in GHDs: this tendency becomes significant when women are considered alone (GHDs: 1.44+/-0.04 mPa.s; controls: 1.31+/-0.04 mPa.s, p<0.05) while it is no longer found in men. This study suggests that GHDs exhibit the classical hemorheological disturbances of non-GHD individuals with the same degree of obesity. There is no evidence for a further impairment of blood rheology associated with the specific metabolic and endocrine pattern of GHDs that may be involved in their increased vascular risk.

Adult↗
PubMed1999

[Insulin resistance: from clinical diagnosis to molecular genetics. Implications in diabetes mellitus].

Insulin resistance is observed in several diseases such as non insulin dependent diabetes mellitus (NIDDM) or polycystic ovarian syndrome (PCOS). To understand genetic determinism of this abnormality we have developed a multidisciplinary approach including selection of phenotypes with insulin resistance confirmed in vivo by minimal model of Bergman and characterization of cellular defects in insulin action on circulating erythrocytes and monocytes. Exploration of variability in candidate genes by direct sequencing in some genetic syndromes of severe insulin resistance and acanthosis nigricans (mainly the Type A syndrome) revealed mutations of the insulin receptor gene associated with major defects in insulin binding or kinase activity. In other rare genetic syndromes or patients affected by NIDDM or PCOS defects appear to be located at post-receptor level, where IRS (insulin receptor substrate) genes are the most attractive candidates. Prevalence of some allelic variants suggested a potential role of IRS genes in insulin resistance, although their involvement in the pathogenesis of NIDDM remains controversial. Genotype-phenotype correlations in first degree relatives of an index case caring the Type A syndrome, suggested that association of allelic variants of IRS-1 and IRS-2 with insulin receptor mutations contribute, by synergistic effects, to phenotypic expression of defects in signal transduction. These mechanisms through genetic epistasis, involving several genes in insulin action, fit better with the polygenic nature of current forms of NIDDM and represent a good model in the study of pathogenesis of insulin resistance.

Acanthosis Nigricans↗
PubMed1998

TSH suppression combined with carbimazole for Graves' disease: effect on remission and relapse rates.

OBJECTIVE: We studied the influence of TSH suppressive therapy combined with carbimazole (CBZ) on treatment outcome in Graves' disease. DESIGN: Open non-randomized prospective study. SETTING: University Hospital of Montpellier, France. SUBJECTS: Sixty-six consecutive patients without prior treatment were included. All the patients were treated initially with 30 mg of CBZ. After 1 month of treatment, one group continued CBZ alone (n = 23), another group received a combination of CBZ plus T3 (n = 19) and a third group received CBZ and 3,5,3'-triiodothyroacetic acid (Triac, n = 24). Therapy was stopped when remission was obtained based on clinical euthyroidism, normalization of FT4 and of early radioiodine uptake. Nine patients with medical treatment failure or major side effects requiring to stop antithyroid drugs underwent surgery or radioiodine therapy. Nine patients were lost to follow-up. The remaining 48 patients were available for analysis of both remission and relapse. RESULTS: The median duration of therapy was 18 months (range, 4-41 months). Based on clinical examination, goitre size at 4 months decreased more in the CBZ + T3 and CBZ + Triac groups than in the CBZ group (P = 0.02). The overall remission rate tended to be higher in the groups treated with CBZ + T3 and CBZ + Triac than in the group treated with CBZ alone, but the difference did not reach statistical significance (P = 0.17). No difference in the relapse rate was observed between the three groups. CONCLUSION: TSH suppression combined with CBZ has little or no effect on remission and relapse rates in Graves' disease patients.

Adolescent↗
PubMed1998

Vascular complications of diabetes mellitus: what role for phospholipid-binding antibodies?

Vascular complications are the main cause of morbidity in diabetes mellitus. However, the risk factors for vascular disease remain incompletely elucidated. It has been previously suggested that factors other than glycemia may contribute to the development of vasculopathy. In this study we determined the prevalence of phospholipid-binding antibodies in uncomplicated and complicated diabetes. We studied 53 uncomplicated diabetic patients, with type 1 (n = 32) or type 2 (n = 21) diabetes; 23 diabetic patients with proliferative retinopathy; 28 diabetic patients with an overt nephropathy; 37 diabetic patients with macroangiopathy and 22 non diabetic control patients. Both lupus anticoagulant and anticardiolipin antibodies were determined. Other risk factors for macroangiopathy were analysed. The prevalence of phospholipid-binding antibodies was similar in uncomplicated diabetic patients and in controls (type 1 diabetes: 9.4%; type 2 diabetes: 9.5%; control group: 4.6%; P= 0.76). In complicated diabetes, the frequency of these antibodies was increased only in patients with overt nephropathy (32.1%, P=0.01) or with macroangiopathy (32.4%, P=0.01) while patients with isolated retinopathy were comparable with uncomplicated diabetic patients (4.3%, P= 0.66). Uncomplicated diabetes was not associated with phospholipid-binding antibodies. We found a higher prevalence of these antibodies in diabetic patients with macroangiopathy or nephropathy. These results suggest a potential role of phospholipid-binding antibodies in the progression of vascular complications in diabetes mellitus.

Adult↗
PubMed1998

Improvement of HbA1c and blood glucose stability in IDDM patients treated with lispro insulin analog in external pumps.

OBJECTIVE: To compare the efficacy of the short-acting insulin analog lispro (LP) with that of regular insulin in IDDM patients treated with an external pump. RESEARCH DESIGN AND METHODS: Thirty-nine IDDM patients (age, 39.4 +/- 1.5 years; sex ratio, 22M/17W; BMI, 24.4 +/- 0.4 kg/m2; diabetes duration, 22.5 +/- 1.6 years) who were treated by external pump for 5.1 +/- 0.5 years were involved in an open-label, randomized, crossover multicenter study comparing two periods of 3 months of continuous subcutaneous insulin infusion with LP or with Actrapid HM, U-100 (ACT). Boluses were given 0-5 min (LP) or 20-30 min (ACT) before meals. Blood glucose (BG) was monitored before and after the three meals every day. RESULTS: The decrease in HbA1c was more pronounced with LP than with ACT (-0.62 +/- 0.13 vs. -0.09 +/- 0.15%, P = 0.01). BG levels were lower with LP (7.93 +/- 0.15 vs. 8.61 +/- 0.18 mmol/l, P < 0.0001), particularly postprandial BG levels (8.26 +/- 0.19 vs. 9.90 +/- 0.20 mmol/l, P < 0.0001). Standard deviations of all the BG values (3.44 +/- 0.10 vs. 3.80 +/- 0.10 mmol/l, P = 0.0001) and of postprandial BG values (3.58 +/- 0.10 vs. 3.84 +/- 0.10 mmol/l. P < 0.02) were lower with LP. The rate of hypoglycemic events defined by BG < 3.0 mmol/l did not significantly differ between LP and ACT (7.03 +/- 0.94 vs. 7.94 +/- 0.88 per month, respectively), but the rate of occurrences of very low BG, defined as BG < 2.0 mmol/l, were significantly reduced with LP (0.05 +/- 0.05 vs. 0.47 +/- 0.19 per month, P < 0.05). At the end of the study, all but two (95%) of the patients chose LP for the extension phase. CONCLUSIONS: When used in external pumps, LP provides better glycemic control and stability than regular insulin and does not increase the frequency of hypoglycemic episodes.

Adult↗
PubMed1998

Increased blood viscosity in iron-depleted elite athletes.

Since iron deficiency is associated with abnormal erythrocyte rheology, we investigated relationships between plasma ferritin and blood rheology in 36 male elite sportsmen (age: 22.38+/-0.9 years). On the whole, ferritin was negatively correlated with blood viscosity (r = -0.36, p < 0.05). When 23 subjects with low ferritin levels suggesting mild iron deficiency were compared with 13 matched sportsmen with normal ferritin levels, iron-deficient sportsmen were shown to have a higher blood viscosity at 1000 s(-l) (3.17+/-0.09 vs. 2.85+/-0.06 mPas, p < 0.05), explained by a higher plasma viscosity (1.38+/-0.02 vs. 1.31+/-0.02 mPa s, p < 0.05), while hematocrit and RBC rigidity index Tk were similar in the two groups. RBC aggregability index M (4.59+/-0.58 vs. 2.95+/-0.43 mPas, p < 0.05) and M1 (8.46+/-0.58 vs. 6.07+/-0.55, p < 0.01) were higher in iron-deficient subjects. Serum zinc was lower in iron-deficient sportsmen (0.73+/-0.02 vs. 0.83+/-0.02 mg/l, p < 0.01), but the score of early signs of overtraining was higher in this group (10.84+/-1.61 vs. 4.08+/-1.11, p < 0.01). These data suggest that mild iron deficiency as commonly seen in athletes, before anemia occurs, is associated with an increase in plasma viscosity and RBC aggregation, together with an increased subjective feeling of exercise overload.

Adult↗
PubMed1997

Identification of two novel insulin receptor mutations, Asp59Gly and Leu62Pro, in type A syndrome of extreme insulin resistance.

To elucidate genetic determinants of insulin resistance, we investigated insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) genes, in vitro IR function and in vivo insulin sensitivity in a family with Type A syndrome. Two missense IR mutations (Asp59Gly and Leu62Pro) found in the proband, resulted in reduction by 90% of insulin binding to erythrocytes, decreased receptor autophosphorylation and a dramatic reduction of insulin sensitivity. The proband and mother were heterozygote for Gly972Arg IRS-1 variant. Asp59Gly mutation, also carried by proband's brother with no consequence on insulin sensitivity, was inherited from the mother who is diabetic and insulin resistant and Leu62Pro was from the father. We conclude that severity of insulin resistance in the proband may be explained by the genetic condition of compound heterozygote for IR mutations while severe insulin resistance in the mother raises the possibility that other genetic factors, like IRS-1 polymorphisms, may contribute to the phenotypic expression of IR mutations.

Amino Acid Sequence↗