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Biomedical subjects

P Roger

Publications and source records attributed to P Roger.

At least 91 records · Page 5Linked to original sources
PubMed1996

C618R mutation in exon 10 of the RET proto-oncogene in a kindred with multiple endocrine neoplasia type 2A and Hirschsprung's disease.

The cosegregation of multiple endocrine neoplasia (MEN) type 2A with Hirschsprung's disease (HSCR), two diseases associated with mutation of the RET proto-oncogene, is infrequent. A 30-yr-old man was referred for screening of MEN 2A. Surgery for HSCR was performed at 4 yr of age. Basal and pentagastrin-stimulated calcitonin levels were abnormal. Histological examination of the thyroid confirmed bilateral medullary thyroid carcinoma. Screening of family members revealed six subjects with medullary thyroid carcinoma or abnormal pentagastrin-stimulated calcitonin test; one had an unilateral pheochromocytoma and two were affected with HSCR. DNA sequence analysis showed a heterozygote C618R mutation in exon 10 of the RET proto-oncogene in the proband and his mother, as well as in second-degree relatives with MEN 2A phenotype or HSCR. In this study, we report on a novel kindred with MEN 2A and HSCR phenotype associated with a point mutation (C618R) in one of the cysteine codons at the extracellular domain of the RET proto-oncogene.

Adult↗
PubMed1996

[Development of bone mineral density after cure of Cushing's syndrome].

Both endogenous and exogenous glucocorticoid excess are well establish as causes of osteoporosis, however the reversibility of bone mass following the restauration of normal steroid levels is not well documented. In this longitudinal study, we mesured bone mineral density (expressed as Z-score) by dual-photon and X-ray absorptiometry of the lumbar spine (L2-L4) in 9 patients cured of Cushing's syndrome who were followed for the next 48 months (16-76). Initial Z-scores ranged from -2 to -1 standard-deviation (SD) in 6 patients consistent with osteopenia, and were below -3 SD in 2 patients consistent with osteoporosis. One patient developed lumbar spine fractures. There is no relationship between the severity of the Cushing's syndrome (assessed by the urinary free cortisol) and initial bone reduction (inital Z-score), nor between length of Cushing's symptoms and initial bone reduction. Our data show a marked variation (+74 +/- 9%) in bone mass in patients successfully treated for Cushing's syndrome. Seven patients completely recovered from steroid-induced osteoporosis, one patient partially recovered but remained osteopenic. One post-menopausal women presented several lumbar spine fractures despite successfull treatment of Cushing's syndrome. This longitudinal study confirms that if steroid-induced bone loss may improve substantially by cure of steroid excess even without other treatment, osteoporosis may worsen particularly in post-menopausal women. These results are important to take into account to properly manage patients with steroid-induced osteoporosis.

Adolescent↗
PubMed1996

[Cutaneous manifestations of acromegaly: 4 cases].

INTRODUCTION: Some skin changes in acromegaly belong to the classical dysmorphic syndrome. Furthermore, other minor skin changes can be associated. OBSERVATIONS: We report 3 patients consulting in the department of Dermatology for various skin changes that have lead to the diagnosis of acromegaly. However these patients have also typical dysmorphic syndrome that they have failed to recognize. The fourth patient associated a cutaneous mastocytosis and acromegaly, as reported only once in literature. The evolution of the minor skin changes was parallel with the endocrinopathy. Moreover in one case, they have preceded the recurrence of the acromegaly. COMMENTS: Our observations demonstrate the importance of the minor skin changes that lead the patient to consult more than the dysmorphic syndrome. Moreover these changes that depend of growth hormone and other associated growth factors can be evolutive signs for endocrinopathy.

Acromegaly↗
PubMed1995

Pseudo-tumours of the thymus after correction of hypercortisolism in patients with ectopic ACTH syndrome: a report of five cases.

We report the cases of four patients with occult, and one patient with overt, ectopic ACTH syndrome. Cushing's syndrome was cured by removal of the ACTH secreting tumour, op'DDD, ketoconazole or bilateral adrenalectomy. Six to 14 months after remission of hypercortisolism, follow-up computed tomography or magnetic resonance imaging of the thorax revealed in all five patients an anterior mediastinal mass 3-5 cm in length that suggested a thymic carcinoma. Exploratory thoracotomy was performed in four cases and allowed the removal of an enlarged, but normal, thymus. Histological examination revealed no tumour but showed benign thymic hyperplasia with negative immunostaining for ACTH. Thymic enlargement spontaneously disappeared 11 months after its demonstration in the patient who did not undergo thoracotomy. The mechanism of this abnormality is thought to be thymic depletion resulting from high plasma cortisol concentrations followed by 'rebound' thymic hyperplasia when cortisol levels fall. Physicians involved in the management of patients with Cushing's syndrome must be aware of this entity in order to avert a diagnostic thoracotomy.

ACTH Syndrome, Ectopic↗
PubMed1995

[Long acting sandostatine (sandostatine LAR) in the treatment of acromegaly].

A long-acting depot formulation of octreotide (Sandostatin LAR, Sandoz LTD) has been recently developed. Preliminary studies indicated that, in acromegalic patients previously controlled by Sandostatin 300-600 micrograms/day in 2-3 sc injections, the intramuscular administration of 20-30 mg of Sandostatin LAR achieved, during one month a similar control of GH hypersecretion. In the present study, the variations of plasma levels of octreotide, GH and IGF1 were followed during 2 months in acromegalic patients receiving a unique injection of 20 mg (n = 4) or 30 mg (n = 4) of Sandostatin LAR. Following Sandostatin LAR 20 mg i.m, the baseline values of GH (8.1 +/- 2.5 micrograms/l) and IGF1 (684 +/- 92 micrograms/l) were normalized after 2 weeks and remained into the normal range during the 28 following days. Similar results were obtained, after a 30 mg i.m administration of Sandostatin LAR. In this later case, the maximal inhibition of GH and IGF1 (1.3 +/- 1.0 micrograms/l and 392 +/- 266 micrograms/l respectively) lasted 2 months. These data showed that a monthly injection of Sandostatin LAR (20-30 mg) allowed a correct control of GH hypersecretion in this series of acromegalic patients.

Acromegaly↗
PubMed1995

[Lp(a) and weight loss in obese patients].

High concentrations of lipoprotein (a) (Lp(a)) are associated with an increased risk of atherosclerotic vascular disease. Lp(a) synthesis is mainly under genetic control but many endocrine disturbances may modulate Lp(a) plasmatic concentrations. There is no agreement upon Lp(a) variations in patients under a hypocaloric diet. This study was undertaken to assess this point in obese females subjected to a 1100 kcal/d diet. Ninety-two obese patients (42.4 +/- 10.4 yr old, BMI 33.9 +/- 5.6 kg/m2) came once a week as out patients during 9 weeks. Lp(a) concentrations distribution was highly skewed. The threshold Lp(a) concentration for a significant cardiovascular risk is estimated at 0.3 g/l. Concentrations above 0.3 g/l were found in 29/92 patients (31%). If the patients were distributed in 2 groups according to their Lp(a) values (< or = ou > 0.3 g/l), the BMI, total cholesterol or triglycerides were not different. There were no significant correlation between Lp(a) and age, total cholesterol or triglycerides. After 9 weeks BMI and total cholesterol values decreased (-1.6 +/- 3.4 kg/m2 and -0.17 +/- 0.68 mmol/l, respectively). Lp(a) concentrations were unchanged (0.3 +/- 0.3 vs 0.3 +/- 0.3 g/l). There were no significant correlation between Lp(a) variations and age, BMI or initial Lp(a) concentrations. No significant decrease of Lp(a) could be detected even in the sub-group of patients with initial concentrations of Lp(a) > 0.3 g/l or even in a sub-group with Lp(a) > 0.7 g/l (n = 7). Under our conditions, weight loss is not associated with a decrease of Lp(a) concentrations suggesting that in a given obese a single determination is enough to assess his Lp(a)-related atherosclerotic risk.

Adult↗
PubMed1994

Cathepsin D immunostaining in paraffin-embedded breast cancer cells and macrophages: correlation with cytosolic assay.

High cathepsin D (cath-D) concentration in breast cancer cytosol is associated with increased risk of metastasis. To specify the relative contribution of the different cells types responsible for cath-D level in cytosol, we validated semiquantitative cath-D immunoperoxidase staining on formalin-fixed, paraffin-embedded sections, using the M1G8 monoclonal antibody, one of the two antibodies of the cytosolic assay. Using computer-aided image analysis, cath-D level in cancer cells was estimated by integrating both staining intensity in each cell and proportion of stained cells. We confirmed on 41 primary breast cancers a higher expression of cath-D in cancer cells compared with peritumoral mammary glands. Cancer cell staining was mostly in lysosomes and for some invasive ductal carcinomas in large vesicles corresponding to phagosomes. Lymphocytes and fibroblasts were not or were only weakly stained. Macrophages also were stained for cath-D, generally on the periphery of the tumor area. The cytosolic cath-D level was correlated with cath-D expression in cancer cells (r = .76; P = 1 x 10(-4)) rather than with the number of macrophages in the tumor (r = .29; P = .09), as determined by use of the specific anti-CD68 antibody. There was a significant increase in the tissue cath-D level in tumors containing large vesicles compared with tumors without large vesicles. This approach provides a means to separately estimate the prognostic significance of cath-D expression in cancer cells and macrophages when evaluating risk of metastasis.

Breast Neoplasms↗
PubMed1994

[Mental deterioration and hypertension: uncommon manifestation of corticotropin insufficiency and functional carboxymethyl oxidase block].

We report a new case of muscle contractures associated with adrenocortical deficiency. Outstanding features were the diffusion of the contractures, rhabdomyolysis and an encephalopathy which disappeared with hormonal therapy. Endocrinological investigations revealed a functional carboxymethyl oxidase type II defect which could, in part, explain our patient's neuromuscular symptoms.

Abdominal Muscles↗
PubMed1994

Pretibial myxedema and high-dose intravenous immunoglobulin treatment.

Seven patients affected by Graves' ophthalmopathy and pretibial myxedema (four patients with nodular form, two with diffuse, and one with elephanthiasic form) have been treated with high-dose intravenous immunoglobulins. We have observed (a) clinical improvement of pretibial myxedema and Graves' ophthalmopathy in all patients, (b) a reduction of pretibial skin thickness, by ultrasonography evaluation, in four patients, (c) a reduction of mucopolysaccharide skin content in three patients, (d) disappearance of lymphocytic skin infiltration and IgG deposition in two patients, and (e) a parallel reduction of the titer of circulating autoantibodies as antithyroglobulin, antimicrosomal, anti-TSH receptor, and of non-organ-specific antibodies as antinuclear, anti-smooth muscle cells, and anti-mitochondrial. In comparison two patients with Graves' ophthalmopathy and pretibial myxedema treated with systemic corticosteroids did not present any improvement of the cutaneous ailment. Therefore, this study suggests that intravenous immunoglobulins are effective in the treatment of pretibial myxedema and may have an immunomodulant action in patients with Graves' disease and related disorders.

Adult↗
PubMed1993

[Paraneoplastic Cushing's syndrome. Pseudotumors of the thymus occurring after correction of hypercorticism. 3 cases].

Ectopic ACTH-secreting tumours responsible for paraneoplastic Cushing's syndrome are invisible at radiography in about 50 percent of the cases. In this situation, the current attitude is to correct the hypercorticism and then embark on a regular morphological monitoring in search of the initial tumour with the purpose of removing it. We report the cases of 3 patients who had a paraneoplastic Cushing's syndrome of unknown origin in 1 case and consecutive, in 2 cases, to a bronchial carcinoid tumour initially occult and discovered 30 and 42 months respectively after the onset of the disease. Six to 10 months after hypercorticism was cured with ketoconazole and bilateral adrenalectomy, a thymic mass 2 to 5 cm in length was detected by computerized tomography or magnetic resonance imaging in all 3 patients. At resection of the thymus, performed in 2 cases, a benign hyperplasia of this organ with negative immunohistostaining for ACTH was discovered. This abnormality, seldom reported, seems to result from the abrupt cessation of hypercorticism. It must be known to avoid an unnecessary thymectomy during supervision of patients with paraneoplastic Cushing's syndrome related to a radiologically occult tumour.

Adrenalectomy↗
PubMed1993

Heterogeneity of neuropeptide Y immunoreactivity in patients with pheochromocytoma: influence on the diagnostic power of measuring plasma NPY using antisera with different specificities.

The nature of NPY-like immunoreactivity (NPY-LI) was investigated in plasma and tumour tissue of 17 pheochromocytoma patients by HPLC, gel filtration and isoelectric focusing using two radioimmunoassays (RIAs) directed against the C- and N-terminals of NPY respectively. The two RIAs gave similar results in pheochromocytomas: 86% of cases had higher NPY-LI concentrations than those found in normal adrenal glands and NPY-LI behaved like authentic human NPY during gel filtration and HPLC. Assessed by isoelectric focusing, NPY was found to be amidated in seven of nine tumours. Contrary to the findings obtained in tumours, the results of the two RIAs in plasma samples were not always concordant: compared to controls, elevated concentrations of NPY-LI were found in 86% of cases of pheochromocytomas using the C-terminally directed RIA and in 76% of cases using the N-terminally directed RIA. The results of HPLC and gel filtration of NPY-LI in plasma suggested that circulating C- and N-terminal NPY fragments account for the discrepancy between the results of the two RIAs. In conclusion, most pheochromocytomas contain large amounts of NPY-LI that behaved like authentic NPY by chromatographic analysis. On the contrary, circulating NPY-LI in some pheochromocytoma patients is heterogeneous with cleaved products which influence differently the power of the C- and N-terminally directed RIAs for the diagnosis of pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1993

[Localized osteoplastic bronchopathy with tumoral expression, including Al amyloidosis].

We report a case concerning a 65 year old man who suffered from a drug resistant asthma and radiographically visible mass in the right lower lobe of the lung. Pathological studies demonstrated it to be "Bronchopathia Osteoplastica", involving segmental bronchi, with completed hematopoietic metaplasia. This rare dystrophic lesion was associated with localized lambda light chain amyloidosis as was proved by the immunohistochemistry. This association suggests a possible relation between amyloidosis and abnormal osteogenesis.

Aged↗
PubMed1992

Plasma concentration of neuropeptide Y in patients with adrenal hypertension.

The mechanisms of hypertension during primary hyperaldosteronism and Cushing's syndrome are not completely understood. An enhanced vascular sensitivity to noradrenaline has been described in both situations. Neuropeptide Y (NPY) induces direct vasoconstriction and potentiates the action of noradrenaline. Sodium retention and dexamethasone have been shown to increase circulating NPY levels in animals and the expression of NPY in neuroendocrine cells. In order to determine if NPY could be involved in the enhanced vascular sensitivity to noradrenaline associated with adrenocortical hyperactivity, we measured plasma NPY in patients with Cushing's syndrome (n = 26) and primary hyperaldosteronism (n = 15) and compared it with that of hypertensive patients with pheochromocytomas (n = 13) or essential hypertension (n = 51) and with normotensive controls (n = 47). The concentration of NPY-Like immunoreactivity (NPY-Li) (mean +/- S.E.) in controls was 39.6 +/- 3.0 pg/ml. Elevated concentrations were found in 77% of the samples collected from pheochromocytoma patients (1180.4 +/- 394.0 pg/ml). NPY-Li levels in patients with essential hypertension (35.0 +/- 2.6 pg/ml), primary hyperaldosteronism (31.3 +/- 3.9 pg/ml) and Cushing's syndrome (33.1 +/- 4.8 pg/ml) were not different from that of controls. NPY-Li levels in hypertensive and normotensive patients with Cushing's syndrome were similar (38.5 +/- 7.5 vs 24.2 +/- 3.7 pg/ml). No correlation was found between the NPY-Li level and the mean blood pressure at the time of sampling. Our results suggest that NPY is unlikely to be involved in the pathogenesis of hypertension associated with primary hyperaldosteronism and Cushing's syndrome.

Adolescent↗