Biomedical subjects

Jean-Claude Souberbielle

Publications and source records attributed to Jean-Claude Souberbielle.

14 recordsLinked to original sources

PubMed2006

Factors involved in vascular calcification and atherosclerosis in maintenance haemodialysis patients.

BACKGROUND: Atherosclerosis and vascular calcifications are common causes of morbidity and mortality in maintenance haemodialysis patients. In addition to the well-known traditional risk factors, uraemia-specific factors appear to enhance dramatically the progression of the pathological processes involved. The aim of the present study was to evaluate the degree of atherosclerosis and vascular calcifications in chronic haemodialysis patients using non-invasive imaging methods, and to identify potentially involved factors. METHODS: The study included 73 patients (36 females, 37 males), aged 25-75 years, who were on haemodialysis treatment for 12-275 months (mean dialysis vintage 73.8 months). We assessed the following circulating parameters: calcium (Ca), phosphorus, 'intact' parathyroid hormone (iPTH), 25OH vitamin D, lipids, oxidized LDL (ox-LDL), Lp(a), homocysteine, leptin, IL-1-beta, IL-6, CRP, TGF-beta, TNF-alpha, (PDGF), advanced oxidation protein products (AOPP) and myeloperoxidase activity (MPO). Coronary artery calcification score (CACS) was assessed using multi-row spiral CT (MSCT). Intima-media thickness index of the common carotid artery (CCA-IMT) and presence of cervical artery atherosclerotic plaques were evaluated by ultrasonography. RESULTS: Coronary artery calcifications were observed in 79.5% of the patients, with CACS ranging from 0 to 4987. In univariate analysis, a positive correlation was observed between CACS and age, BMI, iPTH, CRP, IL-6 and CCA-IMT, whereas an inverse correlation existed with 25OH vitamin D, TGF-beta and PDGF. CCA-IMT ranged from 0.4 to 1.1 mm. It was positively correlated, in univariate analysis, with age, CACS, CRP and Il-6, and negatively with 25OH vitamin D, TGF-beta and PDGF. Only CACS remained as independent predictive factor of CCA-IMT in multivariate analysis. Atherosclerotic plaques were found in the carotid arteries of 53 patients (72%). The number of plaques was positively correlated with age, CACS, phosphorus, MPO, CRP and IL-6, and inversely with 25OH vitamin D in univariate analysis. In multivariate regression analysis, only age and CACS remained as independent variables. CONCLUSION: In addition to classic risk factors, the degree of atherosclerosis and vascular calcification in our dialysis patient population were associated with several factors that are frequently abnormal in advanced chronic renal failure, but except age, all of them were interdependent. Notably, as in the general population, CACS was an independent predictor of the degree of atherosclerosis in haemodialysis patients.

Adult↗

PubMed2006

Diencephalic syndrome due to hypothalamic tumor: a model of the relationship between weight and puberty onset.

CONTEXT: Changes in body weight, statural growth rate, and puberty may be the presenting symptoms of hypothalamic-pituitary tumors. OBJECTIVE: The objective of the study was to assess the relationship between the tumor and its treatment and the weight, growth rate, and onset of puberty, using the diencephalic syndrome of emaciation as model. PATIENTS: Eleven patients seen before 1 yr of age, except one aged 9 yr, for diencephalic syndrome of emaciation due to hypothalamic pilocytic astrocytoma, were treated by surgical resection (n = 9), cranial irradiation (n = 7), and/or chemotherapy (n = 10). RESULTS: At diagnosis, growth rate was normal, despite the emaciation, and there was no hypothalamic-pituitary deficiency, except in the oldest patient. After tumor treatment, all had GH and thyroid-stimulating hormone deficiencies, but only three, who underwent major surgical resection, also had ACTH deficiency and diabetes insipidus. Eight became obese, and all but the oldest had transient precocious puberty. Plasma leptin concentrations were very low at diagnosis, increased after tumor treatment, and decreased transiently in one boy when the testosterone increased. The plasma soluble leptin receptor concentrations changed in the opposite direction, leading to an increase in the free leptin index, including in the three patients whose tumor was reduced without surgery. The body mass index was correlated positively with plasma leptin (rho = 0.73, P = 0.0004) and free leptin index (rho = 0.63, P < 0.004) and negatively with ghrelin (rho = -0.49, P < 0.03) concentrations. CONCLUSIONS: The obesity that occurs after treatment of hypothalamic tumors is not due to dysregulation of leptin secretion because it and plasma soluble leptin receptor remain regulated by factors like testosterone. This study also shows the influence of weight, possibly via leptin secretion, on the transient hypothalamic-pituitary-gonadal activation that occurs during the first year of life.

Adrenocorticotropic Hormone↗

PubMed2006

Unexpected serum parathyroid hormone profiles in some patients with primary hyperparathyroidism.

BACKGROUND: Third-generation parathyroid hormone (PTH) assays have been reported to measure only intact PTH(1-84), in contrast to second-generation assays, which also detect PTH(7-84) fragments. Higher PTH measurements were observed with third- than with second-generation PTH assays in a few patients with either severe primary hyperparathyroidism or parathyroid carcinoma. METHODS: We analyzed biological data [second- and third-generation PTH assays, 25-hydroxyvitamin D (25-OHD), calcium, and phosphate concentrations] obtained before and after surgery for 2 groups of patients selected from a large series of consecutive patients with primary hyperparathyroidism (PHPT): 7 female patients with surgically and histologically confirmed PHPT (group 1) and a matched group (group 2). RESULTS: For group 1 but not group 2, PTH concentrations measured by third-generation PTH assays before surgery were higher than those measured by the second-generation assays. Circulating 25-OHD, calcium, and phosphate concentrations were similar in both groups. In addition, PTH values measured with the third-generation PTH assays in group 1 decreased after surgery. CONCLUSIONS: Our results confirm that third-generation PTH assays do not measure only PTH(1-84). The frequency of this unexpected finding of markedly lower PTH concentrations than previously reported was approximately 5% in patients with PHPT without malignancy. We do not know whether the presence of this unexpected profile is predictive of malignancy.

Adult↗

PubMed2006

Evaluating vitamin D status. Implications for preventing and managing osteoporosis and other chronic diseases.

Recent studies have added new dimensions to the fund of knowledge on vitamin D. In addition to the classic role of vitamin D in preventing rickets and osteomalacia, a preventive effect against osteoporotic fractures has been convincingly established, and abundant evidence suggests a role in preventing malignancies and autoimmune diseases. Serum 25-OH-vitamin D assay is a simple test for evaluating vitamin D status. However, recent review articles indicate that current reference ranges for serum 25-OH-vitamin D are too low. An appropriate lower normal limit may be between 50-100 nmol/l (20-40 ng/ml). Standard supplement dosages may fail to provide concentrations above this range.

Fractures, Bone↗

PubMed2006

Diagnosis of idiopathic growth hormone deficiency: contributions of data on the acid-labile subunit, insulin-like growth factor (IGF)-I and-II, and IGF binding protein-3.

UNLABELLED: The diagnosis of non-organic growth hormone (GH) deficiency (GHD) remains difficult. OBJECTIVE: To evaluate the value of measuring plasma insulin-like growth factor (IGF)-I and -II, IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS) as criteria for diagnosing GHD. PATIENTS: 120 prepubertal patients having at least one of the main auxological criteria defined by the GH Research Society for initiating GH exploration were classified as (1) certain GHD (n = 40), (2) transient GHD (n = 18), (3) idiopathic short stature (n = 27), or (4) extreme short stature (n = 35). RESULTS: All the patients with certain GHD had low (< or = -2 z-score) plasma concentrations of IGF-I and ALS, but only 35.1% had low IGF-II, and 48.6% had low IGFBP-3. All the patients but three (83.3%) with transient GHD had low IGF-I, but only 44.4% had low ALS, and only one had low IGF-II or IGFBP-3. The data for patients with idiopathic and extreme short stature and normal GH peak were similar to each other and to those for patients with transient GHD, except that IGF-I was less frequently low (49.2%, p <0.05). CONCLUSIONS: All the patients with certain GHD had both IGF-I and ALS z-scores < or = -2, unlike those with transient GHD, and idiopathic or extreme short stature. Almost all the patients with short stature and normal GH peak had normal serum IGF-II and IGFBP-3 concentrations.

Body Height↗

PubMed2005

Practical considerations in PTH testing.

New knowledge concerning PTH biology have accumulated during the past few years. The finding that the so-called "intact" PTH assays measure a "non-1-84" PTH fragment in addition to full-length PTH has led to the development of new assays. These new assays, which were initially thought to measure 1-84 PTH only, have been shown to recognize also another PTH species called "amino-PTH". As the various names given to the different assay methods are highly confusing, there is a need for a simplified nomenclature. A simple way would be to identify the older "intact" PTH assays as second-generation assays and the new assays (Whole, CAP, BioIntact) as third-generation assays. Although of considerable potential interest for the comprehension of PTH physiology, the third-generation PTH assays have not yet proved to be superior to the second-generation assays in clinical practice. There is thus currently no recommendation to switch from the second-generation to the third-generation assays in clinical practice, or to use a ratio derived from the concommitent measurement of PTH with both assay-generation. Because second- and third-generation PTH assays are usually highly correlated, significant differences in the clinical information provided by these methods are unlikely. However, our opinion is that more definitive bone biopsy studies in dialyzed patients selected according to their bone- and calcium-related treatment are still needed to reach a consensus. Finally, we have proposed that PTH reference values should be established in healthy subjects with a normal vitamin D status. This supposes that 25OHD is measured in the reference population beforehand, and that the subjects with vitamin D insufficiency are eliminated from the reference group. Although more complicated than the usual way to establish normative data, we have shown that it decreases the upper limit of normal by 25-35%, enhancing thus the diagnostic sensitivity for hyperparathyroidism without a decrease in specificity.

Chronic Kidney Disease-Mineral and Bone Disorder↗

PubMed2005

Third- or second-generation parathyroid hormone assays: a remaining debate in the diagnosis of primary hyperparathyroidism.

BACKGROUND: Since the demonstration that the second-generation PTH assays, also called intact PTH assays, recognize a non-1-84 PTH fragment in addition to the intact 1-84 PTH, new PTH assays defined as third-generation assays have been commercialized. Two previous studies aimed at evaluating whether these third-generation PTH assays improved the diagnostic sensitivity for primary hyperparathyroidism (PHPT), but they yielded opposite results. METHODS: In the present study we compared two second-generation PTH assays (the total intact PTH assay from Scantibodies Laboratory, Inc., and the intact PTH assay from Nichols Institute Diagnostics) with two third-generation assays (the cyclase-activating PTH assay also from Scantibodies Laboratory and the bio-intact PTH assay from Nichols Institute) in a series of 145 consecutive PHPT patients operated in our endocrine surgery department over a 10-month period. A group of 74 healthy subjects served as controls. RESULTS: The diagnostic sensitivities for PHPT of the total intact, the intact, the cyclase-activating, and the bio-intact assays were 93.8%, 97.3%, 84.2%, and 89.0%, respectively, with 95% confidence intervals in the control groups of 10-46, 11-60, 8.4-34, and 9-41 ng/liter, respectively. CONCLUSION: Our findings demonstrate that the diagnostic sensitivities of second- and third-generation PTH assays are similar. Third-generation PTH assays do not therefore improve the diagnosis of elevated serum PTH levels in PHPT, although there are numerical differences among the values.

Aged↗

PubMed2005

Influence of tumor location on the presentation and evolution of craniopharyngiomas.

OBJECT: This study was performed to optimize the management of craniopharyngiomas, particularly by identifying factors predicting weight changes to prevent obesity. METHODS: A series of 35 patients who had undergone surgery at a mean age of 7.4 +/- 3.7 years (standard deviation [SD]) and had been followed up until 14.9 +/- 5 years of age by the same endocrinologist were assigned to one of three groups according to their hypothalamic involvement: Group 1 (10 patients) had no involvement, Group 2 (eight patients) had compression without involvement, and Group 3 (17 patients) had severe involvement. Abnormal height and/or weight evolution indicated the craniopharyngioma in only 17% of the patients, although these elements were present at diagnosis in 85%. Before surgery, 85% of the patients lacked growth hormone, 24% lacked thyroid-stimulating hormone, 15% lacked adrenocorticotropin hormone, and 12% lacked antidiuretic hormone. All had complete hypothalamic-pituitary deficiencies after surgery. The body mass index (BMI) before surgery (mean SD 1.1 +/- 1.6) was positively correlated with BMI 1 year after surgery (mean SD 3.1 +/- 2), which correlated with the BMI at the last evaluation (mean SD 3.1 +/- 1.9; p < 0.0001 for both). Before surgery, patients in Group 3 had a greater BMI than did Group 1 (p < 0.02). The BMI of Group 1 patients did not change, but those of Groups 2 and 3 patients increased during the 1st year after surgery (p < 0.02 and p = 0.0003, respectively), with no further change. The changes occurred mainly during the first 3 months after surgery in Group 1, during the first 6 months in Group 2, and throughout the year in Group 3. CONCLUSIONS: The degree of hypothalamic involvement by the craniopharyngioma determines the presentation and predicts weight changes after surgery.

Body Height↗

PubMed2004

Assay-specific decision limits for two new automated parathyroid hormone and 25-hydroxyvitamin D assays.

BACKGROUND: The recent development of nonradioactive automated assays for serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD) has made measurement of these two hormones possible in many laboratories. In this study, we compared two new assays for PTH and 25OHD adapted on an automated analyzer, the LIAISON, with two manual immunoassays used worldwide. METHODS: We studied 228 osteoporotic patients, 927 healthy individuals, 38 patients with primary hyperparathyroidism, and 167 hemodialyzed patients. Serum PTH was measured with the Allegro and the LIAISON assays, and 25OHD was measured with DiaSorin RIA and the LIAISON assay. Regression analysis was used to calculate decision thresholds for the LIAISON assays that were equivalent to those of the Allegro PTH and DiaSorin 25OHD assays. RESULTS: The 25OHD concentrations obtained with the LIAISON assay and the RIA in osteoporotic patients were well correlated (r = 0.83; P <0.001). Regression and Bland-Altman analyses suggested that the LIAISON 25OHD assay reads lower than the DiaSorin RIA at low concentrations but higher at high concentrations. However, the cutoff (50 nmol/L) used in our laboratories to define vitamin D insufficiency with the DiaSorin RIA is applicable to the LIAISON 25OHD assay. In 927 healthy individuals, the 3rd-97th percentile intervals were 3-80 ng/L and 13-151 nmol/L for the LIAISON PTH and 25OHD concentrations, respectively. However, 506 individuals (54.6%) were vitamin D-insufficient; we therefore considered only the 421 individuals with a LIAISON 25OHD >50 nmol/L as eligible for the reference population for the LIAISON PTH assay. In this group, the 3rd-97th percentile interval for LIAISON PTH was 3-51 ng/L. Considering upper reference limits of 46 and 51 ng/L for the Allegro and LIAISON assays, respectively, the frequency of above-normal PTH concentrations in patients with primary hyperparathyroidism was similar in both assays. Regression analysis between serum PTH measured by the Allegro and LIAISON assays in 167 hemodialyzed patients and the corresponding Bland-Altman analysis of these data suggest that the LIAISON PTH assay tends to read higher than the Allegro assay at low concentrations but lower at high concentrations (>300 ng/L). CONCLUSIONS: Because clinical decision limits for both PTH and 25OHD should be assay specific, we propose equivalences between these assays and two manual assays used worldwide. These assay-specific decision limits should help potential users of the LIAISON PTH and 25OHD assays.

Autoanalysis↗

PubMed2004

Primary hyperparathyroidism and osteoporosis in 2004.

In patients with primary hyperparathyroidism, a definite diagnosis is the first step in the management strategy and relies on appropriately selected and carefully interpreted laboratory tests. Parathyroid hormone assays are being increasingly performed as part of the routine evaluation of osteoporosis. In this setting, laboratory tests are often consistent with primary hyperparathyroidism but should be interpreted with caution. Bone mineral density measurements are useful for assessing the impact of primary hyperparathyroidism. The recommended bone mineral density cutoffs for selecting patients requiring parathyroidectomy were lowered in 2003, and the number of surgically treated patients has increased as a result. Parathyroidectomy remains the treatment of choice given the low mortality associated with this procedure and the absence of pharmacological alternatives suitable for long-term use.

Bone Density↗

PubMed2003

Low-dose growth hormone in adult home parenteral nutrition-dependent short bowel syndrome patients: a positive study.

BACKGROUND & AIMS: Controversy surrounds a 3-week treatment with a high-dose (0.14 mg. kg(-1). day(-1)) growth hormone (GH), glutamine, and high carbohydrate diet in home parenteral nutrition (HPN)-dependent patients with short-bowel syndrome (SBS). This study assessed treatment with low-dose GH in these patients. METHODS: Twelve adult HPN-dependent (duration, 7 +/- 1 years; mean +/- SEM) patients with SBS (small-bowel remnant length, 48 +/- 11 cm) who were on an unrestricted hyperphagic diet were randomized in a double-blind, placebo-controlled, crossover study. Patients received daily low-dose GH (0.05 mg. kg(-1). day(-1)) and placebo for two 3-week periods separated by a 1-week washout period. Net intestinal absorption of macronutrients was assessed using a duplicate diet; nutritional assessment and blood tests were performed. Data from each group were compared using Wilcoxon rank sum test. RESULTS: Treatment with GH increased intestinal absorption of energy (15% +/- 5%, P < 0.002), nitrogen (14% +/- 6%, P < 0.04), carbohydrates (10% +/- 4%, P < 0.04), and fat (12% +/- 8%, NS). The increased food absorption represented 37% +/- 16% of total parenteral energy delivery. Body weight (P < 0.003), lean body mass (P < 0.006), D-xylose absorption (P < 0.02), insulin-like growth factor 1 (P < 0.002), and insulin-like growth factor binding protein 3 (P < 0.002) increased, whereas uptake of GH binding protein decreased (P < 0.01), without any major adverse effect. CONCLUSIONS: Three weeks of low-dose GH significantly improved intestinal absorption in HPN-dependent SBS patients who were on a hyperphagic western diet.

Adult↗

PubMed2003

Parathyroid function and growth in 22q11.2 deletion syndrome.

OBJECTIVE: To determine the frequency and expression of hypoparathyroidism and the factors of short stature in 22q11.2 deletion syndrome to optimize clinical care. STUDY DESIGN: Cross-sectional study of 39 patients 9.7 +/- 0.8 (2.5-20) years of age. RESULTS: The congenital abnormalities were cardiac defects in 33 of 39, thymus hypoplasia in 15 of 18 evaluated, and craniofacial dysmorphy in all; 15 patients (39%) had had one or more seizures. Before evaluation, 12 patients were hypocalcemic, with (n = 4) or without clinical manifestations, diagnosed before 1 month in 10 cases, at 3 months or 12 years in two others. At evaluation, 9 patients were hypocalcemic, 5 of 9 had been hypocalcemic, and 8 others had parathyroid hormone (PTH) concentrations low for their ionized calcium. One had high PTH without hypocalcemia and 2 were hypercalcemic. The values were below -2 SD at birth for weight and/or height in 26% of cases and at evaluation for height and body mass index in 23% and for insulin-like growth factor-I in 37%. CONCLUSIONS: Parathyroid function was abnormal in 27 of 39 (69%) patients. This was not diagnosed in the majority. Short stature was probably due to intrauterine growth restriction, underweight, and growth hormone deficiency, as suggested by low insulin-like growth factor I.

Abnormalities, Multiple↗

PubMed2003

The use in clinical practice of parathyroid hormone normative values established in vitamin D-sufficient subjects.

We have found recently that excluding subjects with low serum 25OHD has a significant impact on the PTH reference range (10-46 ng/liter instead of 10-65 ng/liter with the same assay). However, before being used routinely, this new range had to be clinically validated. We thus reviewed the chart of 708 consecutive osteopenic patients who were referred to our unit for a biological exploration in search of secondary causes for their low bone mass. They were classified into two groups. Group 1 (n = 360) included the patients for whom no reasons for high PTH were found after examination of their chart. Group 2 (n = 348) included patients with one of the following potential reasons for an increased PTH concentration: hyper- or hypocalcemia, normocalcemic primary hyperparathyroidism (PHPT), renal hypercalciuria, vitamin D insufficiency, chronic renal failure, use of bisphosphonates, and any chronic disease known to potentially alter calcium metabolism. Among the 360 group 1 patients, 15 (4.2%) had a serum PTH level more than 46 ng/liter, which is not different from the theoretical rate of 3% of normal subjects whose serum PTH may be above the 97th centile of the reference (chi(2) = 2.8; NS). Forty-two group 2 patients had a surgically proven PHPT. Among these, serum PTH was </=65 ng/liter in 17 (40.5%) and </=46 ng/liter in 5 (12%). In conclusion, our proposed PTH reference range allows to identify fewer patients with mild surgically proven PHPT who have a normal serum PTH concentration, without inducing an increase in the rate of falsely high PTH.

Adult↗

PubMed2002

Hoxa5 overexpression correlates with IGFBP1 upregulation and postnatal dwarfism: evidence for an interaction between Hoxa5 and Forkhead box transcription factors.

Transgenic mice expressing the homeobox gene Hoxa5 under the control of Hoxb2 regulatory elements present a growth arrest during weeks two and three of postnatal development, resulting in proportionate dwarfism. These mice present a liver phenotype illustrated by a 12-fold increase in liver insulin-like growth factor binding protein 1 (IGFBP1) mRNA and a 50% decrease in liver insulin-like growth factor 1 (IGF1) mRNA correlated with a 50% decrease in circulating IGF1. We show that the Hoxa5 transgene is expressed in the liver of these mice, leading to an overexpression of total (endogenous plus transgene) Hoxa5 mRNA in this tissue. We have used several cell lines to investigate a possible physiological interaction of Hoxa5 with the main regulator of IGFBP1 promoter activity, the Forkhead box transcription factor FKHR. In HepG2 cells, Hoxa5 has little effect by itself but inhibits the FKHR-dependent activation of the IGFBP1 promoter. In HuF cells, Hoxa5 cooperates with FKHR to dramatically enhance IGFBP1 promoter activity. This context-dependent physiological interaction probably corresponds to the existence of a direct interaction between Hoxa5 and FKHR and FoxA2/HNF3beta, as demonstrated by pull-down experiments achieved either in vitro or after cellular co-expression. In conclusion, we propose that the impaired growth observed in this transgenic line relates to a liver phenotype best explained by a direct interaction between Hoxa5 and liver-specific Forkhead box transcription factors, in particular FKHR but also Foxa2/HNF3beta. Because Hoxa5 and homeogenes of the same paralog group are normally expressed in the liver, the present results raise the possibility that homeoproteins, in addition to their established role during early development, regulate systemic physiological functions.

Animals↗