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Biomedical subjects

P Roger

Publications and source records attributed to P Roger.

At least 73 records · Page 4Linked to original sources

Overnight urinary free cortisol determination: a screening test for the diagnosis of Cushing's syndrome.

OBJECTIVE: The collection of urine over 24 h to measure free cortisol (UFC) is used to diagnose Cushing's syndrome. However, a complete collection of urine is not easy to achieve and the sampling is frequently inaccurate, so a 24 h collection for the determination of UFC excretion is used as a confirmatory rather than a screening test for Cushing's syndrome. Our objective was to evaluate a more convenient urine collection for screening patients suspected of Cushing's syndrome. DESIGN: We have studied the possibility of using night-time (from 2000 h to 0800 h) UFC excretion as a screening test for Cushing's syndrome ('overnight UFC'). PATIENTS: Thirty patients with proven Cushing's syndrome were studied before treatment (21 cases of Cushing's disease, two cases of ectopic ACTH secretion, seven of adrenal adenoma). The results were compared to those from 150 control obese subjects. MEASUREMENTS: Overnight UFC, and creatininuria (UC), were evaluated at least once in the patients and in all subjects. The 24 h-UFC and UC were determined at least once in the patients and in 56 control subjects. RESULTS: The overnight UFC/UC ratio clearly separated all but one patient of the two groups: 194 +/- 386 vs 5.7 +/- 3.4 nmol/mumol (P < 0.0005) (ranges 16.2-2024 vs 0.6-17.4, Cushing's syndrome vs controls, respectively). The only patient with Cushing's syndrome who had an overnight UFC/UC ratio that overlapped with that of controls suffered from renal failure. The 24 h UFC/UC ratio of the patients differed from the ratio of controls: 184 +/- 365 vs 8.4 +/- 4.1 nmol/mumol (P < 0.0005) (ranges 14-1639 vs 1.5-21.2, respectively). Four patients with Cushing's syndrome had 24 h UFC/UC ratios lower than the upper control ratio. CONCLUSION: The overnight urinary sampling is a simple procedure compared to the 24 h urine collection performed in out-patients. For a sensitivity set at 100%, the specificities were 97% for the overnight UFC/UC ratio and 87% for the 24 h-UFC/UC ratio. This therefore appears to provide a good screening method for Cushing's syndrome.

Adult↗

Comparative evaluation of conventional and dynamic magnetic resonance imaging of the pituitary gland for the diagnosis of Cushing's disease.

OBJECTIVES: The ability of MRI to detect pituitary ACTH-secreting adenomas in patients with Cushing's disease is limited. Owing to different dynamics of contrast enhancement between adenomas and normal pituitary tissue, it has been suggested that obtaining images within seconds after gadolinium (Gad) injection using dynamic procedures increases the sensitivity of MRI in the detection of pituitary microadenomas. The objective of this study was to compare the ability of conventional magnetic resonance imaging (CMRI) and dynamic MRI (DMRI) to detect ACTH-secreting pituitary adenomas. DESIGN: Twenty-six consecutive patients with ACTH-dependent Cushing's syndrome and 10 normal subjects were investigated. According to the results of inferior petrosal sinus sampling, 21 patients had Cushing's disease and five had ectopic ACTH syndrome. Patients with Cushing's disease were operated regardless of the results of imaging studies. All underwent identical MRI and DMRI procedures using a 1.0 T magnet. Image sampling time during DMRI was 19 sec. Scans were randomly mixed and analysed blind, retrospectively and independently by two experienced radiologists. The clarity of the images was assessed by the analysis of agreement among radiologists. MRI findings were compared to surgical and histopathological findings. RESULTS: Surgical exploration identified three macrodenomas and 14 microadenomas. One microadenoma was found at pathological examination after subtotal hypophysectomy and no tumour was found in three cases. According to the combined opinion of radiologists, the three macroadenomas were identified equally well with CMRI and DMRI. Eight ACTH-secreting microadenomas were detected with CMRI and 11 with DMRI. The three microadenomas detected with DMRI only were visualized within 60 sec following Gad injection. No false positives occurred with CMRI. Three false positives were obtained with DMRI: one in a patient with ectopic ACTH syndrome while a silent microprolactinoma and normal tissue were found at the site of the radiological abnormality in two patients with Cushing's disease. In our study, the sensitivity of DMRI is greater than that of CMRI (0.67 vs. 0.52) but is associated with a loss in specificity (0.80 vs. 1.00). False positives may result from the increased sensitivity of DMRI which detects incidental pituitary lesions, technical artefacts or lowest clarity of images, as suggested by a lower observer agreement of DMRI (Kappa statistic 0.66 vs. 0.83). Overall, the two MR procedures had equivalent diagnostic power (0.72). CONCLUSIONS: In our hands, dynamic procedures did not improve the usefulness of MRI in Cushing's syndrome.

ACTH Syndrome, Ectopic↗

Experience with the Biostator for diagnosis and assisted surgery of 21 insulinomas.

Surgical removal is the treatment of choice for insulinomas. Definitive biochemical diagnosis of organic hyperinsulinism has to be established before surgery. These tumors are sometimes undetected by preoperative imaging investigations and, in addition, surgical management may also be complicated by the absence of palpable tumors or the presence of multiple tumors. We report the value of the euglycemic clamp technique for diagnosis and surgical treatment in 21 patients with confirmed insulinomas. Data were compared with 12 controls, and nine patients were retested after surgery. During the euglycemic hyperinsulinic clamp, the mean C-peptide value was 3.6+/-2.2 ng/ml and it remained high (3.8+/-2.5 ng/ml), despite exogenous hyperinsulinemia (1762.7+/-233.2 microU/ml for the highest plateau). In contrast, the C-peptide concentration declined in 12 control patients (0.3+/-0.1 ng/ml, P < 0.001) and after successful surgery in nine retested patients (0.3+/-0.2 ng/ml, P < 0.01). During continuous glucose monitoring, successful removal of the insulin-secreting tumor was accompanied by an increase in plasma glucose concentrations and a loss of requirement for endogenous glucose within 36 min (range 28-43 min). The continuing requirement for glucose after the ablation of the tumor revealed the existence of additional and initially undetected tumors in four patients, among whom two had the multiple endocrine neoplasia type I (MEN I) syndrome. We conclude that the euglycemic hyperinsulinic clamp is a reliable and convenient diagnostic test for insulinoma, as it is both safe (no hypoglycemia) and relatively brief (3 x 90 min). Glucose monitoring and glucose clamping provide a reliable indicator of complete removal of insulin-hypersecreting tissue, especially in patients with occult or multiple tumors.

Adult↗

[Vaginal metastases of breast cancer].

Metastases to the vagina from breast carcinoma are uncommon, and are most often detected during autopsies of patients who have died from a breast cancer or from metastases to the genital tract. A case of symptomatic vaginal metastasis secondary to bilateral breast carcinoma is reported. The potential routes of dissemination include lymphatic and vascular spread. Their respective frequencies vary in the literature. Lymphatic spread in this case is suggested by demonstrable ovarian, myometrial, and lymph node involvement associated with massive submucosal vaginal involvement. This observation of concomitant visceral and lymphatic spread improves our knowledge of metastatic spread from breast cancer to the female genital tract by the lymphatic route.

Breast Neoplasms↗

[Diagnosis of Conn's adenoma. Comparative study of x-ray computed tomography and scintigraphy using 19-noriodocholesterol].

OBJECTIVE: In order to differentiate an aldosterone producing adenoma (APA) and a bilateral adrenal hyperplasia (BAH) in case of primary hyperaldosteronism, an adrenal CT-scan is usually used as first line exploration. The contribution of adrenal 19-noriodocholesterol (NP59)-scintigraphy is controversial. PATIENTS AND METHODS: We describe 17 cases of primary hyperaldosteronism referred to surgery for suspected APA. The value of abdominal CT-scan and of adrenal scintigraphy was studied. RESULTS: After unilateral adrenalectomy, 15 cases with confirmed APA were cured and 2 cases with an unilateral hyperplastic macro nodule showed persistence of the disease. The pathologic findings were concordant with CT-scan in 76% (13/17) and with scintigraphy in 88% (15/17). Similar sensitivity was found for CT-scan and scintigraphy (86% and 88%) with 2 false negative results with both techniques. False positive results were observed only with CT-scan (2 cases) suggesting that scintigraphy has a better specificity. No case was misdiagnosed by both techniques. CONCLUSION: These results suggest that NP59-scintigraphy is complementary to adrenal CT-scan for the recognition of APA and is particularly useful in case of a unilateral hyperplastic macro nodule mimicking an APA.

19-Iodocholesterol↗

Isolated corticotroph insufficiency associated to myasthenia gravis.

Myasthenia gravis, a neuromuscular junction autoimmune disease, may be associated to glandular autoimmune diseases such as adrenalitis. We report here the association of myasthenia gravis with a rare cause of adrenocortical deficiency, i.e. isolated corticotroph deficiency. The patient suffered from myasthenia gravis for 5 yr when she reported increased asthenia. Basal cortisol and ACTH levels were low. Metyrapone failed to increase ACTH and 11-desoxycortisol. Corticotropin-releasing hormone or tetracosactide failed to increase normally the cortisol levels. No other endocrine dysfunction or autoimmune disease could be detected. This observation enlarges the spectrum of endocrine diseases associated to myasthenia gravis and strengthens the need for careful endocrine examination.

Adrenocorticotropic Hormone↗

Ocular naevus and melanoma in acromegaly.

Acromegaly favours the development of extrapituitary neoplasms presumably promoted through increased GH and IGF-I levels. We describe here two patients which acromegaly and benign and malignant melanocytic tumours of the eye choroid. The first patient had a 15 year history of progressive acromegaly despite trans-sphenoidal surgery, radiation and bromocriptine therapy when she presented with melanoma of the eye and a contralateral benign melanocytic tumour. The second patient was referred with typical acromegaly. The initial fundal examination revealed a right sided benign melanocytic tumour of the choroid. Subsequent follow up of the naevi has not shown any change in the tumours after one and three years respectively. The occurrence of melanoma has not been reported in acromegaly. Increased growth of benign naevi might be expected as GH and IGF-I receptors have been described on melanocytes. As naevi may degenerate into melanomas in normal subjects and radiation therapy could trigger their transformation, we suggest that prior to irradiation, acromegalic subjects should undergo a careful ocular examination in order to assess the presence of ocular naevi.

Acromegaly↗

[A study of biological and histological criteria of thyroid autoimmunity in diffuse goiters with hyperthyroidism].

Hyperthyroidism is usually classified as follows: with diffuse or with toxic plurinodular goiter, respectively considered as autoimmune and non-autoimmune thyroid disorders. This classification seems partially inadequate as signs of thyroid immunity may be found in some plurinodular toxic goiter and alternatively may by lacking in some cases of Graves' disease. These observations led us to study the intensity of intrathyroidal autoimmune process (IAP) and the levels of TBIAb, TPO- and Thyroglobulin-antibodies in 105 cases with diffuse goiter, hyperthyroidism and elevated RAIU (92 women and 13 men, age 34 +/- 11, mean +/- SD). The intensity of intrathyroidal autoimmune process (IAP) was determined by one pathologist (HT) by semi quantitative method applicable to routine clinical use. Subtotal thyroidectomy was performed because of a large goiter (n = 29), a concomitant cold nodule (n = 20), a recurrent disease (n = 18), intolerance to antithyroid drugs (n = 5) or because patients chose surgical treatment (n = 33). All cases were rendered euthyroid at the time of surgery using antithyroid drugs or iodine. The results show a lack of IAP and undetectable levels of TBIAb, TPO- and Thyroglobulin-antibodies in 10%, 11%, 25% and 47% respectively. The intensity of IAP was not different in case of first episode or recurrence of hyperthyroidism and was not related to type or duration of medical treatment. Comparison of patients with or without IAP show higher levels of TPO- and thyroglobulin-antibodies but not of TBIAb in the former group (P < 0.005). TBIAb were higher when ophthalmopathy and/or dermopathy were present vs absent (p < 0.05) and were correlated with FT4 levels (p < 0.05). The negative predictive value of TBIAb, TPO- and thyroglobulin-antibodies to predict the lack of significant IAP was 42%, 65% and 64%. The total absence of clinical, biological and histological signs of thyroid autoimmunity was found in only one case (female aged 35 with first episode of hyperthyroidism and no family history of thyroid disease) (0.9%). These results suggest that routine available criteria of thyroid immunity (including IAP) have a low specificity. It follows that they are probably inadequate to screen cases of hereditary toxic familial hyperplasia, a rare entity of still unknown prevalence.

Adult↗

[Cushing's disease: role of feeding].

We report a clinical case of a patient with corticotropin dependent Cushing disease. In this patient ingestion of mixed meals is followed by an increase of ACTH and cortisol. This effects seems secondary to ingestion of proteins, and it can be reproduced by intravenous injection of aminoacids. The pattern observed is similar to what is observed in normal subjects. Neurotransmitter substrate from protein meals or after intravenous injection of aminoacids may influence the factors controlling ACTH secretion in the studied patient.

Adrenocorticotropic Hormone↗

Estrogens increase the expression of fibulin-1, an extracellular matrix protein secreted by human ovarian cancer cells.

Ovarian cancers have a high ability to invade the peritoneal cavity and some are stimulated by estrogens. In an attempt to understand the mode of action of estrogens on these cancer cells and to develop new markers, we have characterized estrogen-regulated proteins. This study was aimed at identifying a protein secreted by ovarian cancer cells whose level was increased by estradiol [Galtier-Dereure, F., Capony, F., Maudelonde, T. & Rochefort, H. (1992) J. Clin. Endocrinol. Metab. 75, 1497-1502]. By using microprotein sequencing, the 110-kDa protein was identified as fibulin-1, a protein of the extracellular matrix that binds to fibronectin, laminin, and nidogen. The amount of immunoprecipitated fibulin-1 secreted into the medium and present in the cell extract was increased up to 10-fold by estradiol in three estrogen-responsive ovarian cancer cell lines. By immunohistochemistry fibulin-1 was located in the stroma of several ovarian cancers and cysts. The findings highlight a potential role for fibulin-1 in the spread of ovarian cancer in the peritoneal cavity and/or in distal metastases.

Adenocarcinoma↗

Functional and histologic effects of a free nonvascularised muscle graft implanted into a reinnervated muscle after prolonged denervation.

Striated muscle atrophy and degeneration, which increase with the delay of denervation, represent two of the main causes for poor recovery following delayed nerve repair. The present study, using a rat model, tests the hypothesis that an adjunction of small, free, nonvascularised muscle grafts of contralateral healthy triceps into a chronically denervated triceps improves muscle regeneration and recovery following sciatic nerve repair delayed for 3 months. Our experiments seem to show a relative increase in mechanical properties in animals in which free muscle graft into the triceps was performed 3 weeks following nerve repair. The improvement of the regenerative process of muscles which have suffered a long period of denervation should be considered as an additional therapeutic procedure in the case of late nerve repair.

Animals↗

Primary hyperparathyroidism in multiple endocrine neoplasia type IIa: retrospective French multicentric study. Groupe d'Etude des Tumeurs á Calcitonine (GETC, French Calcitonin Tumors Study Group), French Association of Endocrine Surgeons.

Primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia (MEN) type IIa is rare, occurring in 20% to 30% of the patients. The aim of this study was to evaluate clinical findings, surgical therapy, and outcome for 56 patients affected by PHPT among 249 MEN-IIa patients collected from 84 families assembled by the Groupe d'Etude des Tumeurs á Calcitonine (GETC, French Calcitonin Tumors Study Group). This retrospective study was based on cases registered by the GETC (20 participating centers) from 1969 to 1994. Characteristics of PHPT in 56 patients (31 women, 25 men) with MEN-IIa were reviewed. All but two underwent cervicotomy. The median age at diagnosis was 37.6 years. PHPT was found concomitantly with medullary thyroid carcinoma (MTC) or pheochromocytoma in 43 patients (77%). PHPT was asymptomatic in 68% of the patients. Serum calcium levels ranged from 2.20 to 3.70 mmol/L (median 2.82 mmol/L; normal 2. 10-2.60 mmol/L). The number of parathyroid glands removed at surgery was 0 (n = 2), 1 (n = 24), 2 (n = 5), > 2 (n = 12), 4 (n = 11). Pathology (initial surgery) consisted of 24 adenomas, 4 double adenomas, and 25 hyperplasia. Cure after initial surgery was obtained in 89%, including a 22% incidence of hypoparathyroidism. There were 6 cases (11%) with persistent PHPT. With a mean follow-up of 6.4 years, five patients (9%) had recurrent PHPT. The results indicate that MEN-IIa-related PHPT is generally associated with mild, often asymptomatic hypercalcemia. Despite recurrences encountered 5 to 15 years after the first cervicotomy, resection of only macroscopically enlarged glands generally appears sufficient. Subtotal or total parathyroidectomy with autotransplantation is associated with a high rate of hypoparathyroidism.

Adenoma↗

Molecular weight distribution of amylose fractions obtained by aqueous leaching of corn starch.

Ultracentrifugation was used to clarify seven amylose fractions obtained by aqueous leaching of corn starch by 5 degrees C steps over a temperature range of 65-95 degrees C. Each fraction was characterized by its hydrodynamic radius R-(H), as determined by dynamic light scattering--and by the macromolecular features (M-(W), the weight-average molecular weight; R-(G), the z-average gyration radius, MWD, the molecular weight distribution) determined by size-exclusion chromatography coupled on line with multi-angle laser light scattering using 0.1 M KOH as solvent. This procedure provided new insights into the leaching process. In particular, a key temperature (85 degrees C) was noted, after which amylose M-(W) increased markedly from 8 x 10(4) - 1.4 x 10(5) to 3 x 10(5) - 3.5 x 10(5) g.mol(-1). Molecular weight dependences of macromolecular sizes were consistent with the behaviour of an expanded chain in good solvent with in particular a hydrodynamic coefficient v within the 0.6-0.7 range for the R(G) approximately M(v) relation. Finally, a method was developed to fit corresponding experimental molecular weight distributions with mathematical distributions of two populations. This enable us to determine that the molecular weight distribution for each leached amylose fraction was at least bimodal and to calculate the corresponding M(W) to each component.

Amylose↗

Asialo GM1 is a receptor for Pseudomonas aeruginosa adherence to regenerating respiratory epithelial cells.

We investigated the implication of asialo GM1 as an epithelial receptor in the increased Pseudomonas aeruginosa affinity for regenerating respiratory epithelial cells from cystic fibrosis (CF) and non-CF patients. Human respiratory epithelial cells were obtained from nasal polyps of non-CF subjects and of CF patients homozygous for the delta F 508 transmembrane conductance regulator protein (CFTR) mutation and cultured according to the explant-outgrowth model. At the periphery of the outgrowth, regenerating respiratory epithelial cells spreading over the collagen I matrix with lamellipodia were observed, characteristic of respiratory epithelial wound repair after injury. P aeruginosa adherence to regenerating respiratory epithelial cells was found to be significantly greater in the delta F 508 homozygous CF group than in the non-CF group (P < 0.001). In vitro competitive binding inhibition assays performed with rabbit polyclonal antibody against asialo GM1 demonstrated that blocking asialo GM1 reduces P. aeruginosa adherence to regenerating respiratory epithelial cells in delta F 508 homozygous cultures (P < 0.001) as well as in non-CF cultures (P < 0.001). Blocking of asialo GM1 was significantly more efficient in CF patients than in non-CF subjects (P < 0.05). Distribution of asialo GM1 as determined by preembedding labelling and immunoelectron microscopy clearly demonstrated the specific apical membrane expression of asialo GM1 by regenerating respiratory epithelial cells, whereas other cell phenotypes did not apically express asialo GM1. These results demonstrate that (i) asialo GM1 is an apical membrane receptor for P. aeruginosa expressed at the surface of CF and non-CF regenerating respiratory epithelial cells and (ii) asialo GM1 is specifically recovered in regenerating respiratory epithelium. These results suggest that in CF, epithelial repair represents the major event which exposes asialo GM1 for P. aeruginosa adherence.

Adolescent↗

Pseudomonas aeruginosa adherence to remodelling respiratory epithelium.

Pseudomonas aeruginosa is an opportunistic organism, which frequently colonizes the respiratory tract of patients with impaired host defence. In cystic fibrosis (CF) patients, this pathogen causes a progressive destructive bronchitis and bronchiolitis and is responsible for high mortality. Normal respiratory epithelium is protected against bacteria via mucus and mucociliary clearance. Alteration of mucociliary clearance and of glycosylation of mucins in CF facilitates the access of bacteria to the underlying airway epithelial cells. Intact respiratory epithelium does not bind P. aeruginosa, whereas injured respiratory epithelium is highly susceptible to P. aeruginosa adherence. We found that the high affinity of respiratory epithelium, from CF and non-CF sources, for P. aeruginosa, during the wound repair process is related to the apical expression of asialo ganglioside M1 (aGM1). The affinity of repairing respiratory epithelium for P. aeruginosa is time-dependent, and is related to transient apical expression of aGM1 at the surface of repairing respiratory epithelial cells. CF respiratory epithelial cells apically express more aGM1 residues with relation to an increased affinity for P. aeruginosa than non CF cells. High epithelial damage followed by repair represents a major cause of P. aeruginosa adherence to airway epithelium in cystic fibrosis. However, P. aerurignosa adherence and colonization are not restricted to cystic fibrosis disease and P. aeruginosa pneumonia may also occur in severely immunocompromised patients, suggesting that epithelial injury and decreased host-response favour the colonization of the airways by P. aeruginosa.

Bacterial Adhesion↗