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Biomedical subjects

F Robert

Publications and source records attributed to F Robert.

At least 109 records · Page 6Linked to original sources

High prolactin levels in patients with Cushing's disease without pathological evidence of pituitary adenoma.

OBJECTIVE: This study was designed to compare the clinical and biochemical features of patients with Cushing's disease without pathological evidence of pituitary adenoma (n = 11) to those in whom a pituitary ACTH adenoma was documented (n = 11). DESIGN: The clinical and biochemical features of 11 patients with Cushing's disease without pathological evidence of pituitary adenomas were compared to 11 subjects with ACTH-secreting adenomas. The patients underwent transsphenoidal microsurgery between 1979 and 1989. During surgery, when an adenoma was not visualized, a partial hypophysectomy of the central mucoid wedge was performed. MEASUREMENTS: Cushing's disease was established by the clinical features of hypercortisolism and the high levels of 24-hour free urinary cortisol with no suppression in response to low, but with suppression in response to high, doses of dexamethasone. Basal and post TRH-GnRH plasma prolactin, FSH and LH levels were assessed in each patient before transsphenoidal microsurgery. RESULTS: Similar results were observed in patients with and without ACTH-secreting adenomas regarding cure rate, and free urinary cortisol levels both basal and after 2 days of dexamethasone, 8 mg daily. After surgery, plasma cortisol levels in cured patients were lower in subjects with ACTH-secreting adenomas than in those without pituitary tumours (P < 0.05). Areas under the curve of PRL (P < 0.002) and LH (P < 0.04) were significantly higher in patients without pituitary adenoma after TRH-GnRH administration. Compared to controls, the peak prolactin level after TRH-GnRH administration was higher in patients without pituitary adenoma (P < 0.005) and lower in those with ACTH adenoma (P < 0.005). Furthermore, a peak prolactin level equal to or greater than 1410 mU/l during the TRH-GnRH test was found in 11/11 patients without ACTH adenoma and 3/11 patients in the other group (P < 0.001), while the CT-scan findings were suggestive of pituitary adenoma in six patients of each group. CONCLUSION: This study suggests that patients with Cushing's disease without pituitary adenomas can be distinguished from those with ACTH-secreting adenomas by their high prolactin levels after TRH-GnRH administration.

Adenoma↗

In vivo microdialysis study of the extracellular 3,4-dihydroxyphenylacetic acid in the rat locus ceruleus: topographical and pharmacological aspects.

In vivo microdialysis coupled with HPLC and electrochemical detection was used to monitor extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC) of the locus ceruleus (LC) in halothane-anesthetized rats. The identity of DOPAC was confirmed by experiments showing that the chromatographic peak was totally suppressed after inhibition of monoamine oxidase by pargyline. Histological examinations allowed to relate the quantity of DOPAC measured in the dialysates with the localization of the probe implantation site. We found that the DOPAC concentration was inversely proportional to the distance between the probe and the lateral border of the LC. Regardless of the caudorostral level of the nucleus, concentrations were maximal when the axis of the probe was 100 microns from the lateral border of the LC and decreased by 53% when this distance reached 300 microns. Activation of LC noradrenergic neurons by systemic administration of the alpha 2-antagonist piperoxane increased by 100% DOPAC concentrations in LC dialysates. These results suggest that the DOPAC measured by microdialysis could be considered an indicator of the functional state of LC noradrenergic neurons.

3,4-Dihydroxyphenylacetic Acid↗

Microdialysis monitoring of 3,4-dihydroxyphenylalanine accumulation after decarboxylase inhibition: a means to estimate in vivo changes in tyrosine hydroxylase activity of the rat locus ceruleus.

An on-line microdialysis approach was developed to estimate changes in tyrosine hydroxylase activity in the locus ceruleus noradrenergic neurons of anesthetized rats by measuring the 3,4-dihydroxyphenylalanine (DOPA) accumulation in the extracellular fluid during perfusion of an aromatic amino acid decarboxylase inhibitor through a dialysis probe. The aromatic amino acid decarboxylase inhibitor used was difluoromethyl-DOPA, which was shown to be more stable than NSD 1015 or Ro 4-4602 in the perfusion fluid. A 1-h perfusion of a 10(-4) mol/L of difluoromethyl-DOPA solution induced a linear increase in DOPA concentration in the locus ceruleus dialysates that achieved a steady state within 1 h. The identity of DOPA accumulated in dialysates during aromatic amino acid decarboxylase inhibition was confirmed by the disappearance of the chromatographic peak when DOPA formation was blocked by the administration of alpha-methyl-p-tyrosine. Systemic administration of the alpha 2-antagonist piperoxane before difluoromethyl-DOPA perfusion markedly increased the DOPA concentration during both the accumulation and the steady-state periods, showing that the present technique is a suitable in vivo approach to monitor changes in tyrosine hydroxylase activity occurring in the locus ceruleus neurons.

3,4-Dihydroxyphenylacetic Acid↗

Dural arteriovenous malformations of the ethmoidal region: report of two cases.

Dural arteriovenous malformations of the ethmoidal region are extremely rare. They are usually supplied by the ipsilateral anterior ethmoidal artery with contralateral contribution in about half of the cases. They are characterized by a fistulous nidus within the dura, and their progression seems to involve a retrograde leptomeningeal vascular stasis with formation of varices and venous aneurysms. They have more propensity to rupture than dural malformations in other locations. Two patients who presented with an acute frontal hemorrhage are reported.

Cerebral Angiography↗

[Intrathoracic hydatid cyst. Contribution of tomodensitometry. Apropos of 25 cases].

Twenty-five cases of thoracic hydatic disease, studied by CT since 1982, are reviewed. Fifteen patients were Maghrebin, 10 were native. The lungs were interested 22 times, the mediastinum 3 times and the heart only once. Complications of hydatic disease were present 8 times. We compare contribution of CT to the other diagnosis criterious. Our results show the accuracy of CT for the diagnosis of non complicated cyst and the lack of specificity for complicated cysts.

Echinococcosis↗

Evidence that insulin-like growth factor 2 (IGF2) is the dominant thymic peptide of the insulin superfamily.

The central T-cell tolerance of neuroendocrine functions has been proposed to be primarily induced by the thymic repertoire of neuroendocrine self antigens. The present study aimed at characterizing the human thymic insulin-related autoantigen able to represent the pancreatic B-cell function in face of the developing T-cells. Immunofluorescence studies were performed on human and rat thymic sections, as well as on the rat IT-45R1 thymic epithelial cell line using several antibodies to epitopes of the insulin peptide superfamily. These studies identify beyond any doubt that insulin-like growth factor 2 (IGF2) is the dominant thymic peptide of the insulin family. The sequence of an insulin-derived autoantigen is proposed. This autoantigen is a nonamer and has a hydrophobic residue leucine (L) at position 9. In the human species, this autoantigen would primarily be tolerogenic for the pancreatic B-cell endocrine function during fetal development.

Amino Acid Sequence↗

Multicenter phase II trial of brequinar sodium in patients with advanced squamous-cell carcinoma of the head and neck.

A total of 19 patients with advanced squamous-cell carcinoma of the head and neck who had not previously been exposed to chemotherapy were treated with brequinar sodium as first-line chemotherapy. Brequinar was given intravenously at a median weekly dose of 1,200 mg/m2. The toxicity was moderate, with 7 patients (37%) experiencing grade 3 or 4 toxicity. In all, 16 patients who were evaluable for efficacy showed no objective response. We conclude that brequinar given at this dose and on this schedule has no significant activity in advanced squamous-cell carcinoma of the head and neck.

Adult↗

A phase II trial of CI-921 in advanced malignancies.

CI-921, (9-[[2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino]- N,5-dimethyl-4-acridinecarboxamide 2-hydroxyethanesulfonate (1:1)), an anilinoacridine derivative with activity in experimental solid tumors was studied in a multicenter phase II trial in patients with solid tumors. Eligible tumor types included cancers of the breast, stomach, pancreas, nonsmall cell lung, small cell lung, colon, head and neck area, and melanoma. Prestudy requirements included an ECOG performance status of < or = 2, no CNS metastases, and measurable disease. CI-921 was administered intravenously over 1-2 hours on days 1, 8, and 15 of a 35-day course at an initial dose of 270 mg/M2, with modification in subsequent courses based upon tolerance. Principal toxicities included leukopenia, marked phlebitis, and mild nausea and vomiting. One hundred fifty patients were entered of whom 132 were evaluable for response. There was one complete and one partial response among 19 patients with breast cancer, and two partial responses, one each among 14 head and neck and 36 nonsmall cell lung cancer patients.

Adult↗

Similarity of the infrared spectrum of an Orgueil organic polymer with interstellar organic compounds in the line of sight towards IRS 7.

We present a comparison between the IR spectrum of the galactic center source IRS 7 and the spectrum of a carbonaceous polymer from the Orgueil meteorite. We have obtained an almost perfect match between the two spectra in the region between 3020-2790 cm-1, which suggests that the chemical composition of the interstellar organic matter and that of the meteorite polymer are similar or that the meteoritic polymer could be a well preserved interstellar organic molecule. Assuming that the meteoritic polymer has the same C/H ratio as these interstellar molecules, we find that 45 % of the total abundance of carbon in the line of sight toward IRS 7 is trapped in such an interstellar organic grain material.

Carbon↗

Coronary reperfusion rates in acute myocardial infarction patients after thrombolytic treatment with anistreplase: correlation with the delay from onset of symptoms to treatment: a review of 424 case records of patients admitted to coronary reperfusion studies with anistreplase.

The individual data for 424 acute myocardial infarction patients from 15 reperfusion studies conducted with anistreplase were reviewed to assess the correlation between the delay onset of symptoms to treatment and reperfusion of the coronary artery. The patients had a mean age of 56 years and 85.4% were male. All patients had a baseline angiogram showing an occluded coronary artery. Anistreplase was given in doses ranging from 3.75 to 35 IU (60% of patients received 30 IU). The mean delay between onset of symptoms to treatment was 3 h 29 min and reperfusion was observed in a total of 61.1% of patients. There was a highly significant correlation between reperfusion and the delay from onset of symptoms to treatment (p less than 0.001). A multivariate logistic regression was performed adjusting for age, sex, location of infarct, dose, and concomitant treatment. The only remaining statistically significant prediction factor for reperfusion was the delay between onset of symptoms to treatment (p less than 0.001). In conclusion, the ability of anistreplase to cause the lysis of coronary thrombi appears to be increasingly important as the delay from onset of symptoms to treatment is decreased. This may contribute to the lower mortality rate observed with early fibrinolytic treatment.

Acute Disease↗

[How can the extension of lung cancer to the osteo-muscular wall of the diaphragm, the pleura and the apex be assessed radiologically?].

The merits of evaluating the parietal extension of lung cancers is emphasized by the new TNM classification. CT and MRI have added to the conventional radiological techniques. The authors successively analyze the contribution of these techniques to the assessment of extension of lung cancers to the wall, including the costal and phrenic compartments, to the pleura and to the apex. Lung radiographs show obvious lesions, such as extensive costal lysis and major pleural extensions. Computed tomography has better sensitivity and specificity than lung radiographs to establish pleuroparietal involvement; it is best performed in the inclined plane of the ribs and in the high-resolution mode. The presence of costal lysis means parietal involvement, while the integrity of the pleura can be established if the lesion remains at a distance from the wall. The persistence of an extrapleural fatty rim between the tumor and the wall allows ruling out parietal extension. MRI provides accurate details in case of doubtful CT findings for the extension to the costovertebral groove, to the intervertebral foramina, to the peridural space and to the diaphragm. Its major asset is to assess the vertebral, vascular and nervous extension of cancers of the apex pulmonis.

Carcinoma, Non-Small-Cell Lung↗

Immunomodulatory properties of cyclic hexapeptide oxytocin antagonists.

The thymic repertoire of neuroendocrine 'self' antigens has been previously described on the basis of the intrathymic expression of neurohypophysial (NHP)- and tachykinin-related peptide signals and receptors. According to that model, the cryptocrine signalling between thymic epithelial/nurse cells and thymocytes through NHP-related signals and receptors constitutes one accessory pathway in the process of T-cell differentiation and/or activation. A pharmacological manipulation of that novel type of cell-to-cell signalling was tested by the investigation of the immunomodulatory properties of novel cyclic hexapeptide oxytocin (OT) antagonists (MSD Research Laboratories). These compounds were found to significantly inhibit the productions of cytokines (mainly IL-1 beta and IL-6) elicited by anti-CD3 treatment of human whole blood cell cultures. Cytokine productions were more significantly reduced by OT antagonists in whole blood cell cultures derived from female volunteers than in those obtained from male donors, suggesting an influence of the gonadal steroid environment on the expression of NHP peptide receptors by immune cells. These observations support the concept of novel immunomodulating approaches through immune-specific neuropeptide antagonists, as well as the pharmacological value of such strategies in selective immunotherapy.

Adjuvants, Immunologic↗

Monoclonal antibodies to oxytocin: production and characterization.

To induce a good immune response to oxytocin (OT) we developed a two-step technique to conjugate OT to thyroglobulin (TG) using glutaraldehyde. We obtained 30 hybridomas recognizing OT-ovalbumin conjugates and 16 stable lines. Three monoclonal antibodies were selected for further characterization. One of them (O13) was found very specific for OT using three different techniques (enzyme-linked immunosorbent assay, radioimmunoassay and immunohistochemistry); it is directed to the C-terminal tripeptide. The other two probably recognize tyrosine containing epitope(s) also shared by vasopressin and other related nonapeptides.

Animals↗