Biomedical subjects

Frédéric-Simon Hould

Publications and source records attributed to Frédéric-Simon Hould.

9 recordsLinked to original sources

PubMed2006

Omental and subcutaneous adipose tissue steroid levels in obese men.

We examined plasma and fat tissue sex steroid levels in a sample of 28 men aged 24.8-62.2 years (average BMI value of 46.3 +/- 12.7 kg/m(2)). Abdominal adipose tissue biopsies were obtained during general or obesity surgery. Omental and subcutaneous adipose tissue steroid levels were measured by gas chromatography and chemical ionization mass spectrometry after appropriate extraction procedures. BMI and waist circumference were negatively correlated with plasma testosterone (r = -0.49 and -0.50, respectively, p < 0.01) and dihydrotestosterone (r = -0.58 and -0.56, respectively, p < 0.01), and positively associated with estrone levels (r = 0.64 and 0.62, respectively, p < 0.001). Regional differences in adipose tissue steroid levels were observed for dihydrotestosterone (p < 0.005), androstenedione (p < 0.0001) and dehydroepiandrosterone levels (p < 0.05), which were all significantly more concentrated in omental versus subcutaneous fat. Positive significant associations were found between circulating level of a steroid and its concentration in omental and subcutaneous adipose tissue, for estrone (r = 0.72 and 0.57, respectively, p < 0.01), testosterone (r = 0.66 and 0.58, respectively, p < 0.01) and dihydrotestosterone (r = 0.58 and 0.45, respectively, p < 0.05). Positive correlations were observed between plasma dehydroepiandrosterone-sulfate and omental (r = 0.56, p < 0.01) as well as subcutaneous adipose tissue dehydroepiandrosterone level (r = 0.38, p = 0.05). Positive significant associations were found between omental adipocyte responsiveness to positive lipolytic stimuli (isoproterenol, dibutyryl cyclic AMP and forskolin) and plasma or omental fat tissue androgen levels. In conclusion, although plasma androgen or estrogen levels are strong correlates of adipose tissue steroid content both in the omental and subcutaneous fat depots, regional differences may be observed. Androgen concentration differences in omental versus subcutaneous adipose tissue suggest a depot-specific impact of these hormones on adipocyte function and metabolism.

Abdominal Fat↗

PubMed2006

Health-related quality of life in morbid obesity.

BACKGROUND: In order to evaluate the impact of severe obesity and its treatment on quality of life (QoL), it would be important to first identify the areas of QoL most likely to be affected by the disease. METHODS: We first constructed a list of 187 items potentially related to QoL of patients with morbid obesity. From this list, consecutive candidates for bariatric surgery were asked to identify what they felt were the most significant items and to grade their importance. The item impact was determined from the proportion of patients who identified it as important, and the mean importance score attributed to this item (impact score = frequency X importance). RESULTS: 100 patients (68 female; mean body mass index 51.5 kg/m(2); mean age 42) were interviewed. Overall, the impact of morbid obesity was more important in women than in men. The areas of impairment were very similar in both groups, with the important difference that women ranked their dissatisfaction with physical appearance higher than men. The items having the most important impact on QoL clustered into 7 domains: 1) activity/mobility; 2) symptoms; 3) personal hygiene/clothing; 4) emotions; 5) social interactions; 6) sexual life; and 7) eating behavior. CONCLUSION: The impact of morbid obesity on QoL is not limited to the activity/mobility domain. Morbid obesity contributes to the impairment of all domains of what is usually referred to as "health-related quality of life".

Adult↗

PubMed2006

Large maternal weight loss from obesity surgery prevents transmission of obesity to children who were followed for 2 to 18 years.

OBJECTIVE: Our aim was to compare the prevalence of obesity in 172 children who were aged 2 to 18 years and born to 113 obese mothers (BMI: 31 +/- 9 kg/m2) with substantial weight loss after biliopancreatic bypass surgery with 45 same-age siblings who were born before maternal surgery (mothers' BMI: 48 +/- 8 kg/m2) and with current population standards. METHODS: In this case series, with >88% follow-up in a tertiary referral center, cross sectional office chart and telephone data on childhood and adolescent weights were transformed to z scores. RESULTS: After maternal surgery, the prevalence of obesity in the offspring decreased by 52% and severe obesity by 45.1%, with no increase in the prevalence of underweight. The z score reduction in obesity was gender specific, with boys reducing from 1.4 +/- 1.3 before to 0.57 +/- 1.7 after maternal surgery, corrected for birth order. The difference was not significant in girls (0.8 +/- 1.3 vs 0.8 +/- 1.2). Among children of both genders who were aged 6 to 18 years of age and born after maternal surgery, the prevalence of overweight was reduced to population levels. CONCLUSIONS: Contrary to outcomes after intrauterine under- and overnutrition, the prevalence of overweight and obesity in children of mothers with large voluntary postsurgical weight loss was similar to that in the general population, with no increase in underweight. The results demonstrate the importance of potentially modifiable epigenetic factors in the cause of obesity.

Adolescent↗

PubMed2006

Androgen inactivation and steroid-converting enzyme expression in abdominal adipose tissue in men.

We examined 5alpha-dihydrotestosterone (5alpha-DHT) inactivation and the expression of several steroid-converting enzymes with a focus on aldoketoreductases 1C (AKR1C), especially AKR1C2, in abdominal adipose tissue in men. AKR1C2 is mainly involved in the conversion of the potent androgen 5alpha-DHT to its inactive forms 5alpha-androstane-3alpha/beta,17beta-diol (3alpha/beta-diol). Subcutaneous (s.c.) and omental (Om) adipose tissue biopsies were obtained from 21 morbidly obese men undergoing biliopancreatic derivation surgery and 11 lean to obese men undergoing general abdominal surgery. AKR1C2 mRNA and 5alpha-DHT inactivation were detected in both s.c. and Om adipose tissue. After incubation of preadipocytes with 5alpha-DHT, both 3alpha-diol and 3beta-diol were produced through 3alpha/beta-ketosteroid reductase (3alpha/beta-HSD) activity. In preadipocyte cultures, 3alpha-reductase activity was significantly predominant over 3beta-reductase activity in cells from both the s.c. and Om compartments. Expression levels of AKR1C1, AKR1C3 and of the androgen receptor were significantly higher in s.c. versus Om adipose tissue while mRNA levels of 17beta-HSD-2 (hydroxysteroid dehydrogenase type 2) and 3(alpha-->beta)-hydroxysteroid epimerase were significantly higher in Om fat. 3Alpha/beta-HSD activity was mainly detected in the cytosolic fraction, suggesting that AKR1C may be responsible for this reaction. Experiments with isoform-specific AKR1C inhibitors in preadipocytes showed that AKR1C2 inhibition significantly decreased 3alpha-HSD and 3beta-HSD activities (3alpha-HSD: 30 +/- 24% of control for s.c. and 32 +/- 9% of control for Om, 3beta-HSD: 44 +/- 12% of control for s.c.). When cells were incubated with both AKR1C2 and AKR1C3 inhibitors, no significant additional inhibition was observed. 5Alpha-DHT inactivation was significantly higher in mature adipocytes compared with preadipocyte cultures in s.c. adipose tissue, as expressed per microgram total protein (755 +/- 830 versus 245 +/- 151 fmol 3alpha/beta-diol per microg protein over 24 h, P < 0.05 n = 10 cultures). 5Alpha-DHT inactivation measured in tissue homogenates was significantly higher in the s.c. depot compared with Om fat (117 +/- 39 versus 79 +/- 38 fmol 3alpha/beta-diol per microg prot over 24 h, P < 0.0001). On the other hand, Om 3alpha/beta-HSD activity was significantly higher in obese men (body mass index (BMI) >or= 30 kg/m2) compared with lean and overweight men (84 +/- 37 versus 52 +/- 30 fmol 3alpha/beta-diol per microg protein over 24 h, P < 0.03). No difference was found in s.c. 3alpha/beta-HSD activity between these groups. Positive correlations were found between s.c. 5alpha-DHT inactivation rate and circulating levels of the androgen metabolites androsterone-glucuronide (r = 0.41, P < 0.02) and 3alpha-diol-glucuronide (r = 0.38, P < 0.03) and with the adrenal precursor androstenedione (r = 0.42, P < 0.02). In conclusion, androgen inactivation was detected in abdominal adipose tissue in men, with higher 3alpha/beta-HSD activity in the s.c. versus Om depot. Higher Om 5alpha-DHT inactivation rates were found in obese compared with lean men. Further studies are required to elucidate whether local androgen inactivation in abdominal adipose tissue is involved in the modulation of adipocyte metabolism and regional fat distribution in men.

17-Hydroxysteroid Dehydrogenases↗

PubMed2005

Accelerated satiation after duodenal switch.

BACKGROUND: This is to introduce a new test "negative alliesthesia" for measuring satiation after bariatric surgery. It is a test that is well known by physiologists but has never been used clinically. It is based on the observation that repeated pleasant gustatory stimuli turn into unpleasantness in the process of satiation. METHODS: We measured the time it took for a repeatedly ingested sweet stimulus to become first unpleasant (negative alliesthesia) and then intolerable (satiety). At the same time, we measured the degree of pleasure aroused by the sweet stimulus (hedonic rating). The test was given to 9 patients before and 3 and 6 months after the duodenal switch procedure and in 10 morbidly obese patients, three times, 3 months apart. RESULTS: The test showed that negative alliesthesia and satiety were three times faster after surgery. The negative alliesthesia time decreased from 16.0 +/- 3.9 minutes to 5.7 +/- 1.4 minutes (P < 0.0004). The satiety time decreased from 26.7 +/- 5.0 minutes to 10.7 +/- 1.3 minutes (P <0.001). Finally, the hedonic rating for the sweet stimulus decreased from 78.8% +/- 15.7% to 49.9% +/- 13.0% at 3 months and 39.3% +/- 20.6% at 6 months after surgery, without, however, reaching statistical significance. CONCLUSION: The duodenal switch modified negative alliesthesia. It is too soon to say what place this test may have in bariatric surgery, but its simplicity and ingenuity are attractive.

Adult↗

PubMed2004

Twenty years of biliopancreatic diversion: what is the goal of the surgery?

BACKGROUND: Comparative evaluation of weight loss after bariatric surgery is difficult without definition of success and without a norm for presenting results. We explored the pertinence of defining success: a residual BMI <40 or <35 kg/m(2), and the need for reporting results with stratification by initial obesity and length of follow-up. METHODS: Results of 1,271 consecutive biliopancreatic diversion (BPD) patients were compared when presented with or without stratification, and we searched for landmarks of success which would be shared by patients themselves. RESULTS: Presented globally, after a mean follow-up of 7.9 +/- 4.2 years, BMI decreased from 48.4 +/- 9.4 to 31.3 +/- 6.5, and only 10% and 26% of patients would have been considered failures with a residual BMI >or= 40 or >or= 35 respectively. Because heavier patients were losing less in terms of percentage ( P <0.0001) and regained weight faster ( P <0.0001), global and cumulative results failed to show a failure-rate doubling every 5 years and a very high failure-rate in heavier patients. The landmarks of BMI 40 and 35 were the same unconsciously used by patients to express their own perception of failure. For patients with an initial BMI <50, a residual BMI of 35 caused a significant drop in the degree of satisfaction from 90 to 40%. For super-obese, the same critical point was found at a BMI of 40 where satisfaction dropped from 91 to 57%. CONCLUSION: Landmarks of success at BMI 40 and 35 were realistic, reasonable and coincided with patients' own expectations. Since initial obesity and duration after surgery made so much difference in results, a comparison of different surgical approaches was useless without stratification for both factors together.

Adult↗

PubMed2004

Outcome of pregnancies after biliopancreatic diversion.

BACKGROUND: Severe obesity has deleterious effects on fertility and pregnancy outcomes. Although surgery is the best long-term treatment for severe obesity, there is a risk of gestational undernutrition in operated mothers because bariatric surgery reduces nutrient availability. This is a follow-up report of our initial findings regarding pregnancy and neonatal outcomes in biliopancreatic diversion (BPD) patients, with addition of a new cohort of children born to mothers after BPD. METHODS: All women (n = 916) who had successfully undergone BPD in our hospital were mailed a questionnaire containing multiple-choice and essay questions concerning gynecologic and obstetric history, and pregnancy and neonatal outcomes in both preoperative and postoperative pregnancies. Patients operated between 1984 and 1995 (n = 568) were mailed an additional questionnaire regarding children's weight and height progress, and school performance. Perinatal records from our patients' obstetric clinics were also reviewed. RESULTS: The questionnaire was completed by 783 women (85.5%). 251 postoperative pregnancies in 132 women resulted in 166 infants by 109 mothers. 47.0% of patients who were unable to become pregnant preoperatively were successful postoperatively. 90 out of 109 women (82.6%) reported an appropriate weight gain (9.1 +/- 5.9 kg) during postoperative pregnancies. The incidence of fetal macrosomia decreased from 34.8 to 7.7%, with a concomitant increase in normal-weight babies from 62.1 to 82.7%. The elevated miscarriage rate (26.0%) in these obese women persisted after surgery. CONCLUSION: Major weight loss following BPD improves the reproductive function of severely obese women. BPD provides major beneficial effects for both mother and child, including normalization of gestational weight changes, reduction of fetal macrosomia, and normalization of the infant's birth-weight. Our results speak in favor of delaying pregnancy in obese women until after the substantial surgical weight loss has occurred.

Adolescent↗

PubMed2003

[Abdominal complications associated with cardiac surgery. Review of a contemporary surgical experience and of a series done without extracorporeal circulation].

INTRODUCTION: To evaluate the prevalence, risk factors and morbidity associated with gastrointestinal (GI) complications after cardiac surgery, with and without cardiopulmonary bypass, we carried out a retrospective cohort study at a university teaching hospital. METHODS: We divided the 11,405 eligible adult patients into 2 groups: group A (operated on between January 1992 and June 1996) (4657 patients) and group B (operated on between July 1996 and December 2000) (6748 patients). RESULTS: We found 147 GI complications in 134 (1.2%) patients. The incidence of GI morbidity was similar for the 2 groups of patients (group A, n = 59/4657 [1.2%]; group B, n = 75/6748 [1.1%]. Patients from group B were older, obese, diabetic and presented with more peripheral and cerebrovascular disease. Bleeding, gastritis and ulcer with perforation, the most common of these GI events, were associated with the esophagus and stomach (67/147 [45.5%]). Other events that we documented included cholecystitis 10 (6.8%), pancreatitis 13 (8.8%), episodes of small and large bowel ischemia 17 (11.6%), pseudomembranous colitis 12 (8.3%) and diverticulitis 5 (3.4%). Mesenteric ischemia was responsible for 11 (37.9%) of the 29 deaths. Two hundred and ninety-three patients were revascularized without extracorporeal circulation during this study. In this group, we were able to pinpoint 5 (1.7%) GI complications with 3 cases of mesenteric ischemia. Multivariate analysis identified renal insufficiency, prolonged intubation and sepsis as significant, predictive variables of GI complications for the 2 groups of patients whereas the Parsonnet score and stroke were predictive for the second group. CONCLUSIONS: Although cardiac surgery is now being performed on older patients with significant comorbidity, we could not demonstrate a significant increase of GI complications after cardiac surgery. Off-pump coronary artery bypass does not seem to protect patients from these complications.

Aged↗

PubMedDate not supplied

Effects of the peroxisome proliferator-activated receptor-gamma co-activator-1 Gly482Ser variant on features of the metabolic syndrome.

Factors influencing the severity of the metabolic syndrome among obese subjects or the conversion to cardiovascular disease or type 2 diabetes (T2D) remain largely unknown, but there is strong evidence for genetic susceptibilities. Peroxisome proliferator-activated receptor-gamma co-activator-1 (PPARGC1) is a transcriptional co-activator of many nuclear receptors including PPAR-gamma, involved in the regulation of fatty acid oxidation, skeletal muscle fiber type specificity, and gluconeogenesis. Given the critical role of PPARGC1, it becomes a promising candidate gene for the metabolic syndrome and T2D. This study aimed to investigate whether genetic variations in human PPARGC1 gene are associated with metabolic syndrome-related phenotypes and T2D among obese subjects. Molecular screening of the PPARGC1 gene in 24 morbidly obese French-Canadians revealed 13 variants. Eight genetic variations were in introns: c.55-27T>A, c.234+52C>A, c.553-40A>G, c.553-11T>C, c.757+161T>C, c.1793+19C>G, c.2141+192G>A, and c.2293+146A>G, and five were in coding regions: Thr394Thr, Asp475Asp, Gly482Ser, Thr528Thr, and Thr612Met with a relative allele frequency of 18.5, 5.2, 37.0, 42.5, and 6.8%, respectively. Thr394Thr, Asp475Asp, and Thr528Thr were in linkage disequilibrium with the Gly482Ser variant, the only non-synonymous variant with a relative allele frequency of more than 10%. Association studies were performed with the Gly482Ser variant. In non-diabetics, we compared between genotype differences in metabolic syndrome-related traits (waist girth, SBP, DBP, triglycerides, HDL-cholesterol (C), and fasting glucose levels). There was a difference in mean plasma HDL-C concentrations, the Gly/Gly group had lower concentrations than the Gly/Ser group (P<0.05). These results suggest that the Gly482Ser polymorphism may explain some of the between-obese variance observed in metabolic syndrome-related traits.

Base Sequence↗