Biomedical subjects

F Borson-Chazot

Publications and source records attributed to F Borson-Chazot.

At least 19 recordsLinked to original sources

PubMed2006

[Metabolic radiotherapy for gastroenteropancreatic endocrine tumors using radiolabeled somatostatin].

Surgery is the only curative treatment of gastro-entero-pancreatic endocrine tumors. In inoperable or metastasized forms, therapeutic options are limited. The metabolic or systemic radiotherapy, using radiolabeled somatostatin analogs, constitutes a new therapeutic alternative, currently in development which requires the presence of high affinity somatostatin receptors on tumoral cells. Using (111)In-pentetreotide, the main result is a symptomatic effect. With new somatostatin analogs coupled to B- emitters, such as Octreother or (177)Lu-DOTA-Octreotate, 10 to 30% of objective tumoral responses are observed in progressive patients, unresponsive to conventional treatments. Such results are explained by the high affinity for somatostatin receptors and the large emission diameter of these radiolabeled compounds. Renal toxicity is limited by amino-acid infusion whereas changes in blood count are usually moderate and transient. Multicentric prospective studies are necessary to identify the predictive factors of tumoral response and toxicity. The prospects are related to the development of new radiopharmaceuticals, even more specific of somatostatin receptors sub-types and to the use of other peptide analogues whose applications will overflow the framework of endocrine tumours.

Hormone Antagonists↗

PubMed2006

Pituitary deficiency after brain radiation therapy.

Brain radiotherapy is a frequent and overlooked cause of pituitary deficiency in adults which may alter patients' health and quality of life. Hormonal consequences have been better studied in children. The onset of hormonal deficiencies depends on the dose delivered to the pituitary-hypothalamic region while their incidence and severity depends on dose fractionating and follow-up duration. Somatotrophic function is the first affected, 90% of patients being GH deficient 10 years after radiotherapy. Other anterior pituitary functions are affected later and less frequently. While initial damage occurs in the hypothalamus, accounting for mild hyperprolactinemia in 30-50% of cases, diabetes insipidus is never observed. Direct pituitary deficiency may occur later. Responses to ACTH or GHRH-arginine tests may be normal for several years though an ACTH and/or GH deficiency has been demonstrated by an insulin tolerance test, which is considered as the gold standard. When the cranio-spinal area--including the neck--has been irradiated, primary thyroid deficiency might occur. Repeated cervical ultrasonographic follow-up is mandatory to exclude radiation-induced thyroid cancer. The gonadotrophic function might be altered after small doses of irradiation causing precocious puberty, while at higher doses delayed puberty or true gonadotrophic deficiencies are more often observed. Combined radio- and chemotherapy might result in mixed central and peripheral deficiencies that might be difficult to diagnose. When radiotherapy is performed in adulthood, GH deficiency is less common, although the sequence of hormonal deficiencies is similar to that observed in children. Prospective longitudinal studies are required to determine the time course and sequence of onset of each deficiency, in order to tailor the monitoring of these patients to their specific needs.

Adrenocorticotropic Hormone↗

PubMed2006

[KIMS observational study of GH therapy in GH-deficient adults: 12-month follow-up analysis of the French cohort].

KIMS study is an international, observational study initiated in 1994 in which France has been involved since 2003. Its aim is to collect on a widespread basis long-term data from GH-deficient adults treated or not treated with growth hormone in daily practice. Among 330 patients already enrolled by 128 centers in France at the data lock point for this first interim analysis, 122 patients were followed up for at least 12 months and their results are presented herein. After one year of treatment, IGF-1 level adjusted for age and sex was normalized for 77% of patients naive of GH-treatment, 71% of semi-naive patients and 85% of non naive patients. Lean mass increase was 5.1% and fat mass decrease 5.7%. Quality of life assessed through QoL-AGHDA questionnaire was improved with a median score decrease from 10 to 6. These are the first results available from French patients and suggest that growth hormone is an appropriate indication for adults with severe GH deficiency.

Adult↗

PubMed2006

[Role of hospital claims databases from care units for estimating thyroid cancer incidence in the Rhône-Alpes region of France].

BACKGROUND: Incidence measures are essentially based on the data collected by cancer registries. Hospital claims databases from care units (PMSI) can be used as a source of information for registries because they contain standard records of most cancer patients. Regarding thyroid cancer, we have evaluated the PMSI as a source of information for the Rhône-Alpes thyroid cancer registry and usefulness of PMSI as a tool for surveillance of thyroid cancer incidence. METHODS: Patients with incident thyroid cancer in 2002 were identified in the claims data of the Rhône-Alpes region using an algorithm based on DRG codes of thyroidectomy and on diagnosis codes of thyroid cancer in a principal or secondary position. The patients identified were compared to those in thyroid cancer registry of the Rhône-Alpes region regarding sex, age, ZIP code of residence, month of discharge and length of stay versus the diagnosis date. When the percentage of cases of claims data identified in the cancer registry and the percentage of cases of the cancer registry identified in claims data were obtained, the capture-recapture method was applied to estimate the number of missing cases and the total number of incident thyroid cancers in the region. RESULTS: 667 patients were identified in claims data while the cancer registry included 677 patients. 95.2% of patients identified in claims data were in the cancer registry and 82.3% of patients in the cancer registry were identified in claims data. Cases lacking in claims data mostly corresponded to micro-cancers which represented 41% of cases in the cancer registry. Regarding cancer above 1 cm, 92% of the cancer registry cases were identified in claims data. Sensitivity of combining information from cancer registry and claims data was 99.2%. Cases lacking in cancer registry, present in claims data base and considered as true cases after obtaining pathological confirmation represented 2% of the whole thyroid cancer population. CONCLUSION: Claims data obtained from anonymous regional or national bases can be helpful for checking the completeness of thyroid cancer registries and to provide a small amount of unknown cases. They can be considered an acceptable tool for surveillance of thyroid cancer incidence. The significance of the variations in incidence that could be observed from claims data remains to be evaluated in comparison with comparable data obtained from registries.

Algorithms↗

PubMed2005

[Neuroendocrine tumours treated with mIBG and radiolabeled peptides].

Neuroendocrine tumours are a heterogeneous group, characterized by good prognosis, but important disparities of the evolutionary potential. In the aggressive forms, the therapeutic strategies are limited. The metabolic or systemic radiotherapy, using radiolabelled peptides, which can act at the same time on the primary tumour and its metastases, constitutes a tempting therapeutic alternative, currently in evolution. The preliminary results are encouraging; the prospects are related to the development of new radiopharmaceuticals, with the use of other peptide analogues whose applications will overflow the framework of the neuroendocrine tumours.

3-Iodobenzylguanidine↗

PubMed2004

Octreotide (long-acting release formulation) treatment in patients with graves' orbitopathy: clinical results of a four-month, randomized, placebo-controlled, double-blind study.

There are few effective, safe modalities for the management of Graves' ophthalmopathy (GO), a cell-mediated immune comorbidity of thyroid disease. Somatostatin analogs inhibit lymphocyte proliferation and activation, and accumulate in the orbital tissue of patients with GO. A double-blind, placebo-controlled study of a long-acting somatostatin analog [16 wk of long-acting release formulation of octreotide (octreotide-LAR)] was conducted in 51 patients with mild active GO with the aim of preventing deterioration and precluding the need for more aggressive therapeutic modalities, such as glucocorticoids or radiotherapy. No treatment effect was observed for the primary end point (a composite parameter defining the outcome as either success or failure on the basis of changes in class/grade of the severity index and Clinical Activity Scale of GO). The Clinical Activity Scale score was reduced for patients treated with octreotide-LAR, but without any significant difference with respect to patients receiving placebo. However, octreotide-LAR significantly reduced proptosis (as measured by exophthalmometry). This was associated with nonsignificant differences in favor of octreotide-LAR in a series of proptosis-related parameters: class III grade, opening of the upper eyelid, the difference in ocular pressure between primary position and upgaze, and extraocular muscle involvement. By magnetic resonance imaging evaluation the extraocular muscle volumes appeared reduced, but nonsignificantly. No significant correlation between the initial uptake of the somatostatin analog indium-labeled and the response to treatment was observed. One patient in the octreotide-LAR group developed gallstones. In this study, octreotide-LAR did not seem suitable to mitigate activity in mild GO. Surprisingly, it significantly reduced proptosis, one of the most debilitating symptoms of GO. Additional studies are warranted to define the benefit to risk ratio of the somatostatin analogs in this indication.

Delayed-Action Preparations↗

PubMed2004

Interest of Chromogranin A for diagnosis and follow-up of endocrine tumours.

OBJECTIVE: To determine the interest of Chromogranin A (CgA) determination for diagnosis and follow-up in patients with gastroenteropancreatic endocrine tumours (GEP-ET) and multiple endocrine neoplasia type 1 (MEN-1). PATIENTS AND METHODS: CgA levels were measured with an immunoradiometric assay in 124 sporadic GEP-ET, 34 MEN-1 and 127 controls. Serial determinations were performed in 56 patients (212 visits). Changes in CgA levels over 25% were considered as significant. RESULTS: Using a cut-off value of 130 micro g/l, established from a receiver-operating characteristic curve, the specificity of CgA was 98.4%, with a sensitivity of 62.9%, higher in secreting than in nonsecreting tumours (73%vs. 45%; P < 0.003) and related to the extent of metastatic spreading (P < 0.001). In nonsecreting tumours, the positive predictive value (PPV) of CgA for the presence of metastases was 100% but the negative predictive value (NPV) was only 50%. In MEN-1, high CgA levels indicated a pancreatic tumour with a 100% specificity but the sensitivity was 59%. During the follow-up, the concordance between CgA and tumour evolution was 80%, whatever the secretory status. In patients with carcinoid tumours, the concordance was higher for CgA than for serotonin (81%vs. 54%; P < 0.001). CONCLUSION: Due to its high specificity, CgA determination may help to discriminate the endocrine character of a GEP tumour and to indicate a pancreatic tumour in MEN-1. However, its low NPV in nonsecreting tumours limits its interest for diagnosis and staging. By contrast, serial evaluation of CgA seems of particular interest for the follow-up of GEP-ET tumours.

Adolescent↗

PubMed2004

Melatonin secretion is supersensitive to light in migraine.

The present study examined the sensitivity to light of melatonin (MLT) secretion in familial migraine during a headache-free interval. Twelve female patients and 12 healthy controls were included in the trial. All subjects were studied twice. In each session, light exposure (300 lx) or placebo was randomly administered for 30 min between 00.30 and 01.00 h. Blood was sampled hourly between 20.00 and 24.00 h, and 02.00 and 04.00 h and every 15 min between 00.30 and 01.30 h. Plasma MLT levels were determined by radioimmunoassay. MLT suppression was more marked in the migraine group than in the control group [difference of area under curve (DeltaAUC)=-53.8 +/- 16.2 vs. 18.5 +/- 12.7 pg/h/ml, P<0.005; maximum of MLT suppression (Delta)=-35.7 +/- 10.2 vs. - 6.7 +/- 5.8 pg/ml, P<0.05]. These findings show a clear hypersensitivity to light in young female migraineurs during the headache-free period.

Circadian Rhythm↗

PubMed2003

[Therapeutic strategies in somatotroph adenomas with extrasellar extension: role of the medical approach, a consensus study of the French Acromegaly Registry].

UNLABELLED: From the first 198 patient files included into the French Acromegaly Registry, we analyzed 68 patients harboring a somatotroph adenoma with extrasellar extension, after exclusion of those treated by stereotactic or conventional radiotherapy. In these patients (including 37 women), aged 21-77 yr. (45.7 +/- 13.3), GH concentrations ranged from 2-260 microg/L (38.6 +/- 44.3), and IGF I from 86-967% of age-matched upper limit of normal (303 +/- 164). Maximal diameter of the adenoma at MRI was 11-36.5 mm (20.4 +/- 6.5), with cavernous sinus involvement in 68% of cases. Three subgroups were defined: 20 patients treated by long-acting somatostatin analogs only (group M), for a mean duration of 3 yr. (extremes 1-7 yr.), 48 patients initially treated by transsphenoidal surgery (group C), of whom 21 were secondarily treated by long-acting somatostatin analogs (group CM) for a mean duration of 1.2 yr. (extremes 0.2-2 yr.). All 3 groups were not statistically different in terms of tumor mass and initial levels of GH and IGF-1. Patients from group M were significantly older than those of the other groups (p<0.05). RESULTS: 46% of patients from group C after surgery vs. 45% of patients from group M had a mean GH below 2.5 microg/L. Biochemical remission (GH<2.5 microg/L and normal IGF1 normal) was obtained in 31% of cases in group C, vs. 25% in group M. In this group, a decrease of the largest tumor diameter was observed in 10 patients (71.5%), ranging from 10-25% in 7 (50%) and exceeded 50% in 3 (21.5%). In group CM, the biochemical remission rate (42%) and final GH or IGF1 values were not significantly different from group M. In conclusion, these data suggest that surgery or long-acting somatostatin analogs have a comparable efficacy in terms of remission rates in somatotroph macroadenomas with extrasellar extensions.

Acromegaly↗

PubMed2002

[Hashimoto's encephalopathy: an anatomicoclinical observation].

Hashimoto's encephalopathy (HE) is a rare neurological complication of chronic lymphocytic thyroiditis. As its clinical presentation is aspecific, other etiologies of acute encephalopathy have to be ruled out. We report the case of a 29-year old woman with neuropsychiatric signs preceding coma, myoclonus and epileptic seizures. Clinical and electroencephalographic features were consistent with the diagnosis of new variant of Creutzfeldt-Jakob disease. However, high titres of antithyroid antibodies in serum directed towards the diagnosis of HE. Despite oral steroids, the patient died five months later. Neuropathological findings ruled out spongiform encephalopathy and disclosed aspecific activated microglia. Our observation suggests that this process could be involved in the pathogenesis of HE. Even in the absence of clinical dysthyroidism, HE diagnosis has to be suspected in the settings of acute encephalopathy associated with seric antithyroid antibodies.

Acute Disease↗

PubMed2002

[Necrosis of a hypophyseal adenoma and ischemic cerebral vascular accident ].

A 78-year old man developed an acute intracranial hypertension followed by central left facial palsy. CT Scan and MRI revealed an ischemia within the right lenticulostriate arteries territory and a hemorrhagic infarction of a pituitary adenoma without extrinsic carotid artery compression. Neuroophthalmologic examination and hormonal screening were normal. Though pituitary apoplexy and stroke might represent a fortuitous association, several mechanisms underlying such clinical picture are advanced.

Adenoma↗

PubMed2001

Expression of insulin target genes in skeletal muscle and adipose tissue in adult patients with growth hormone deficiency: effect of one year recombinant human growth hormone therapy.

Our aim was to investigate the effects of one year recombinant human growth hormone (rhGH) therapy on the regulation by insulin of gene expression in muscle and adipose tissue in adults with secondary GH deficiency (GHD). Six GHD subjects without upper-body obesity were submitted to a 3-h euglycemic hyperinsulinemic clamp before and after one year of rhGH therapy. Muscle and abdominal subcutaneous adipose tissue biopsies were taken before and at the end of each clamp. The mRNA levels of insulin receptor, p85 alpha-phosphatidylinositol-3 kinase (p85 alpha PI-3K), insulin dependent glucose transporter (Glut4), hexokinase II, glycogen synthase, lipoprotein lipase (LPL) in muscle and in adipose tissue, hormone sensitive lipase and peroxisome proliferator-activated receptor gamma (PPAR gamma) in adipose tissue were quantified by RT-competitive PCR. One year treatment with rhGH (1.25 IU/day) increased plasma IGF-I concentrations (54+/-7 vs 154+/-11 ng/ml, P<0.01) but did not affect insulin-stimulated glucose disposal rate measured during the hyperinsulinemic clamp (74+/-9 vs 85+/-5 micromol/kg free fat mass/min). Insulin significantly increased p85 alpha PI-3K, hexokinase II and Glut4 mRNA levels in muscle both before and after rhGH treatment. One year of GH therapy increased LPL mRNA levels in muscle (38+/-2 vs 70+/-7 amol/microg total RNA, P<0.05) and in adipose tissue (2490+/-260 vs 4860+/-880 amol/microg total RNA, P<0.05), but did not change the expression of the other mRNAs. We conclude from this study that GH therapy did not alter whole body insulin sensitivity and the response of gene expression to insulin in skeletal muscle of adult GHD patients, but it did increase LPL expression in muscle and adipose tissue. This result could be related to the documented beneficial effect of GH therapy on lipid metabolism.

Adenoma↗

PubMed2001

[Should silent corticotroph-cell adenoma be classified as a non-functional pituitary adenoma?].

A 45-year-old man underwent surgery for a silent corticotroph-cell pituitary adenoma which developed in 9 months. The tumor was termed silent because it exhibited increased corticotropic secretion without clinical signs of hypercorticism. This classes it as a non-functional adenoma. The non-functional group includes different types of adenomas such as gonadotroph and other silent thyreotroph and somatotroph adenomas with variable proliferative potential. Silent corticotroph-cell adenoma is considered as an aggressive tumor. In contrast, gonadotroph adenomas usually grow slowly and postoperative tumor remnants can remain stable for years. Because of this variability in tumor growth, the therapeutic decision is difficult if there is a postoperative remnant. No precise guidelines can be established. We suggest that non-functional pituitary adenomas should be considered separately, according to the histological type. This classification is essential for improving knowledge and specifying indications for radiotherapy.

Adenoma↗

PubMed2001

[Melatonin and circadian rhythm].

Melatonin is an indole hormone that is produced by the pineal gland, mainly at night, with a peak around 3.00 a.m. under normal environmental conditions. This endogenic secretion cycle is generated by the suprachiasmatic nuclei in response to the day/night alternation. Light either suppresses or entrains melatonin production according to the time of light exposure. Melatonin can be viewed as the "hand" of the internal clock and is regulated via the central nervous and sympathetic systems. Melatonin synchronizes biological cycles, particularly the temperature and sleep/wake cycles. Exogenous melatonin can influence the endogenous secretion of melatonin according to a phase response curve, an effect that provides a rationale for the use of melatonin to treat disorders of biological rhythms (rapid time-zone change syndrome, delayed sleep phase syndrome, desynchronization in blind subjects or shift workers, insomnia in the elderly).

Circadian Rhythm↗

PubMed1999

Occurrence of hyperhomocysteinemia 1 year after gastroplasty for severe obesity.

Severe obesity exposes one to an increased risk of cardiovascular mortality. Gastroplasty has been shown to induce substantial weight loss and to improve the atherogenic profile of severely obese subjects. However, vitamin deficiencies after gastroplasty have been reported. Because hyperhomocysteinemia, an independent risk factor for cardiovascular disease, is influenced by nutritional status (and especially by folate intake), we hypothesized that a marginal folate deficiency induced by gastroplasty could promote hyperhomocysteinemia. Thus, plasma homocysteine concentrations were measured by high-performance liquid chromatography in 53 severely obese patients (body mass index = 42 +/- 1), before and 1 yr after vertical gastroplasty. Plasma homocysteine concentrations increased, on an average, from 9.9 +/- 0.4 to 12.8 +/- 0.6 micromol/L (P < 0.0001). This increase in homocysteine levels was observed in two thirds of the subjects, leading to clear-cut hyperhomocysteinemia (>15 micromol/L) in 32%. The changes in homocysteine concentrations were correlated to weight loss (P < 0.001) and to decrease in plasma folate concentrations (P < 0.01). Whereas gastroplasty induced a mean 32-kg weight loss and a striking improvement in conventional risk factors, the occurrence of iatrogenic hyperhomocysteinemia might hamper the benefit of surgery on cardiovascular risk in most of the patients. Our results further support use of a systematic efficient folate supplementation after gastroplasty.

Adult↗

PubMed1999

Decrease in carotid intima-media thickness after one year growth hormone (GH) treatment in adults with GH deficiency.

An increased carotid arterial intima-media thickness (IMT) has been reported in hypopituitary adults untreated for GH deficiency. In the present study, the effect of GH replacement on IMT and cardiovascular risk factors was prospectively investigated, in GH deficiency patients treated at a mean dose of 1 UI/day during 1 yr (n = 22) and 2 yr (n = 11). The IMT measurements were performed by the same experienced physician, and the coefficient of variation (calculated in two control groups) was below 6.5%. IMT at baseline was related to conventional risk factors. After 1 yr GH treatment, IMT decreased from 0.78 +/- 0.03 mm to 0.70 +/- 0.03 mm (P < 0.001). The decrement was observed in 21 of 22 patients. After 2 yr GH treatment, IMT had stabilized at 0.70 +/- 0.04 mm and remained significantly different from baseline values (P < 0.003). GH treatment resulted in a moderate decrease in waist circumference and body fat mass and an increase in VO2 max. Conventional cardiovascular risk factors were unmodified except for a transient 10% decrease in low-density lipoprotein cholesterol at 6 months. The contrast between the limited metabolic effect of treatment and the importance and precocity of the changes in IMT suggests that the decrease in IMT was not exclusively attributable to a reversal in the atherosclerotic process. A direct parietal effect of GH replacement on the arterial wall might also be involved. The consequences, in terms of cardiovascular risk, should be established by randomized prospective trials.

Adult↗

PubMed1998

Effect of selenium and vitamin E supplementation on lipid abnormalities in plasma, aorta, and adipose tissue of Zucker rats.

Twenty-nine obese female Zucker rats (fa/fa) were fed with a laboratory chow supplemented or not with a selenium-rich yeast (Selenion), or Selenion + vitamin E, or vitamin E alone. Twelve lean female Zucker rats (Fa/Fa) of the same littermates fed with the same diet were used as control. After 32 wk of diet, obesity induced a large increase in plasma insulin and lipid levels. A significant decrease in the plasma vitamin E/triglycerides ratio (p<0.005) and an increase in plasma thiobarbituric reactive substances (TBARS) (p<0.005) were also observed. Plasma selenium and vitamin E increased in all supplemented rats. The plasma insulin level was decreased by selenion supplementation and the vitamin E/triglycerides ratio was completely corrected by double supplementation with Selenion + vitamin E. TBARS were also efficiently decreased in two obese groups receiving vitamin E. In plasma, adipose tissue and aorta, obesity induced an increase in palmitic acid (C16:0), a very large increase in monounsaturated fatty acids (palmitoleic acid C16:1, stearic acid C18:1) associated with a decrease in polyunsaturated n-6 fatty acids (linoleic acid C18:2 n-6, arachidonic C20:4 n-6). These alterations in fatty acid distribution were only partly modulated by Se and vitamin E supplements. However, in the aorta, antioxidant treatment in obese rats significantly reduced the increase in C16:0 and C16:1 (p<0.05 and p<0.01, respectively) and the decrease in arachidonic acid (p<0.05). These changes could be beneficial in the reduction of insulin resistance and help to protect the vascular endothelium.

Adipose Tissue↗

PubMed1998

Effect of selenium and vitamin E supplements on tissue lipids, peroxides, and fatty acid distribution in experimental diabetes.

The protective role of selenium (Se), given as a Se-rich yeast, selenomethionine or selenomethionine + vitamin E supplement, toward changes in lipid, peroxide, and fatty acid distribution in tissues of streptozotocin-induced diabetic rats, was investigated, after 24 wk of disease. Diabetes increased liver thiobarbituric acid-reactive substances and conjugated dienes; Se supplement completely corrected these changes. In kidney, as in heart, the peroxide levels were not significantly changed by diabetes. In diabetic rat liver, a significant drop in triglycerides and phospholipids (P < 0.05) was observed; this was modulated by Se + vitamin E supplementation. Se + vitamin E supplementation also inhibited the decrease in 18:2n-6 and the increase in 22:6n-3 observed in liver of diabetic rats, changes which reflect altered glycemic control. In kidney, heart, and aorta, diabetes produced some changes in lipid content and fatty acid distribution, especially an increase in heart triglycerides which was also corrected by the Se supplement. Se supplementation to diabetic rats also increased 18:0 ether-linked alcohol, 20:4 n-6, and 22:5 n-3 in cardiac lipids. In aorta, Se + vitamin E significantly increased 20:5 n-3. These polyunsaturated fatty acids are precursors, in situ, of prostaglandin I2 (PGI2) and PGI3 which may protect against cardiovascular dysfunction. In kidney, conversely, Se decreased 20:4 n-6, the precursor of thromboxane A2 implicated in diabetic glomerular injury. Thus Se, and more efficiently Se + Vitamin E supplementation, in experimental diabetes could play a role in controlling oxidative status and altered lipid metabolism in liver, thereby maintaining favorable fatty acid distribution in the major tissues affected by diabetic complications.

Animals↗