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Biomedical subjects

F Robert

Publications and source records attributed to F Robert.

At least 145 records · Page 8Linked to original sources

Mixed growth hormone and prolactin-secreting human pituitary adenomas: a pathologic, immunocytochemical, ultrastructural, and immunoelectron microscopic study.

A study of 30 adenomas from patients with signs of growth hormone (GH) and prolactin (PRL) hypersecretion revealed the presence of mammosomatotroph cells (MSC) containing both hormones in all cases. Although the number of immunostained cells varied from case to case, in 14 of 25 tumors, all stained cells were MSC. Nine tumors had the ultrastructural appearance of densely granulated growth hormone adenomas, while 11 cases resembled sparsely granulated growth hormone adenomas with frequent fibrous bodies. Exocytosis was present in six of these 11 cases, a feature unusual for pure growth hormone adenomas. Nine tumors consisted of a mixture of cells with the morphology of GH and PRL cells. In the four cases examined, immunoelectron microscopy using double immunolabeling with protein A-gold particles revealed the presence of secretory granules containing both hormones in some tumor cells recognized as mammosomatotroph cells.

Adenoma↗

The neurohormonal thymic microenvironment: immunocytochemical evidence that thymic nurse cells are neuroendocrine cells.

Thymic neuroendocrine cells were identified by immunofluorescence in the murine thymus through the use of monoclonal antibody A2B5, and specific polyclonal antisera against neurophysin (NP), oxytocin (OT) and arginine vasopressin (AVP). Two reactive regions were clearly identified: the subcapsular cortex and the medulla. A close correspondence was observed between A2B5-reactive and NP-immunoreactive cells in the medulla. An important epithelial population of the subcapsular cortex, the thymic nurse cells (TNCs), were found to be A2B5-positive and to contain immunoreactive NP, OT and AVP. The neuroendocrine nature of TNCs was further substantiated by their high reactivity with an antiserum against neuron-specific enolase. These observations demonstrate the presence in the thymus gland of an original neuroendocrine microenvironment which could be of functional importance in the mediation of central influences upon T lymphocyte differentiation.

Animals↗

Neovascularization and tumor growth in the rabbit brain. A model for experimental studies of angiogenesis and the blood-brain barrier.

A model for the study of tumor angiogenesis within the rabbit brain is presented. Implantation of the VX2 carcinoma provides a reproducible tumor accompanied by angiogenesis. The authors report the sequential growth, histology, tumor neovascularization, and vascular permeability of this tumor following its intracerebral implantation. Tumor angiogenesis correlates with the rapid and logarithmic intracerebral tumor growth. The proliferation of blood vessels in the tumor and the organization of tumor cells around tumor vessels are described. Breakdown of the blood-brain barrier (detected by Evans blue leakage) starts in the early stages of tumor development and becomes prominent as the tumor vasculature and size increase. This model is useful for experimental studies of angiogenesis.

Animals↗

Trimetrexate combined with cisplatin or etoposide in the treatment of non-small cell lung cancer: a pilot study.

Trimetrexate glucuronate in combination therapy with cisplatin or etoposide was evaluated in non-small cell lung cancer patients in a pilot, dose escalation study. Trimetrexate was administered intravenously together with 20 mg/m2 cisplatin or 50 mg/m2 etoposide for 5 consecutive days at an initial dose of 4 mg/m2. Courses were repeated at 3 week intervals with the trimetrexate dosage escalated according to patient tolerance. In the 12 patients treated to date, reversible myelosuppression, consisting of leukopenia and thrombocytopenia, and nonhematologic grade 1 and 2 toxicities were observed. The study is ongoing. The maximum tolerated trimetrexate dosage levels in combination therapy will be established.

Adult↗

Trimetrexate as a single agent in patients with advanced head and neck cancer.

Trimetrexate is a nonclassical folate antagonist. It was evaluated in 43 patients, previously not exposed to chemotherapy, with incurable and/or demonstrated progression of squamous cell head and neck cancer following surgery and/or radiotherapy. Trimetrexate was initially administered at 8 mg/m2 intravenous (IV) daily for 5 days, repeated every 3 to 4 weeks with dose adjustments depending on patient tolerance. Thirty-eight of the 43 patients entered in this study were evaluable for response. The 28 males and 10 females had a median age of 60 years. Their median performance status on the Zubrod scale was 1. Thirty-seven patients (97%) had received prior radiotherapy. The disease had metastasized in 84% of the patients with dissemination primarily to the subcutaneous soft tissue (40%). Ten patients (26%; with a 95% confidence interval of 12% to 40%) achieved a partial response (PR) with a median duration of 12.2 weeks (median time to PR was 3.2 weeks). The median survival of the 43 patients was 17.3 weeks with 10 patients alive at last follow-up. Hematologic grade 3 to 4 toxicities included leukopenia (19%), thrombocytopenia (9%), and granulocytopenia (5%). Nonhematologic grade 3 to 4 toxicities possibly attributable to trimetrexate treatment included stomatitis (7%).

Adult↗

Hyperprolactinemia associated with clinically silent adenomas: endocrinologic and pathologic studies; a report of two cases.

Pituitary adenomas containing adrenocorticotropic hormone (ACTH) in one case, and ACTH, beta-lipotropin, and beta-endorphin in the other, were demonstrated in two patients who had amenorrhea-galactorrhea and hyperprolactinemia with no manifestation of Cushing's disease. Neither adenoma contained prolactin (PRL). Initial bromocriptine therapy resulted in cessation of amenorrhea-galactorrhea and normalization of PRL levels. However, there was radiologic evidence of tumor enlargement in both patients. After pituitary adenomectomy, the two patients resumed regular menses and normal PRL dynamics. These patients illustrate the need for bromocriptine therapy for possible enlargement of their pituitary adenomas. The diagnosis of silent corticotroph adenoma should be kept in mind.

Adenoma↗

Distinctive features of prolactin secretion in acromegalic patients with hyperprolactinaemia.

We have investigated the relationship between the plasma PRL concentrations of 98 untreated acromegalic patients and the GH levels during basal and dynamic conditions. Hyperprolactinaemia was present in 27 patients. In patients with marked hyperprolactinaemia (PRL greater than 80 ng/ml or greater than 1600 mU/l), basal plasma PRL and the TRH-induced response correlated with basal plasma GH (correlation coefficients of 0.9, P less than 0.001 and 0.74, P less than 0.02, respectively). The PRL response to TRH also correlated with GH response to TRH (r = 0.38, P less than 0.01). In contrast, in patients with moderately elevated PRL (20 to 80 ng/ml), and in those with normal plasma PRL (less than 20 ng/ml or less than 400 mU/l), no such correlations were found. Immunostaining for PRL was positive in 24 out of 25 adenomas of patients with hyperprolactinaemia, while no PRL was found in the tumour tissue of 10 normoprolactinaemic patients. In conclusion, our data suggest the existence of two populations of acromegalic patients with hyperprolactinaemia, one group with correlations between GH and PRL secretion, and the other without.

Acromegaly↗

Human corticotroph cell adenomas.

Sixty-one pituitary corticotroph adenomas from 47 patients with Cushing's disease, 10 with Nelson's syndrome, and four eucorticoid patients were studied by light microscopy, immunoperoxidase, and electron microscopy. Seventy nine percent of all tumors and 70% of Nelson's cases were microadenomas, sometimes minute. A contiguity between the posterior lobe and the adenoma was seen in ten cases. Spontaneous infarction of the tumor with remission of Cushing's syndrome occurred in one case. Light microscopy revealed that the adenoma cells were basophilic and contained PAS-positive granules also staining with Herlant tetrachrome and lead-hematoxylin. The granules stained positively with antiserum to adrenocorticotrophic hormone (ACTH), beta-lipotropic hormones (beta-LPH) and beta-endorphin. The most characteristic ultrastructural finding was the presence of perinuclear bundles of microfilaments found in all our cases. Oncocytic changes were seen in three tumors. Four silent corticotroph adenomas, two of them originally microadenomas that had enlarged to enclosed adenomas while being treated with bromocriptine for hyperprolactinemia and one a large diffuse invasive tumor, did not differ in their microscopic, immunocytological, or ultrastructural features.

Adenoma, Basophil↗

[Cardiac rhabdomyomas and aortic valve atresia: an unusual association].

Necroptic examination of a male newborn baby revealed multiple anomalies of the heart, including multiple cardiac rhabdomyomas, aortic valvular atresia, left cardiac hypoplasia, hypoplasia of proximal aorta and hypertrophy of the right heart. Tuberous sclerosis was not present. In are instances, the association of cardiac rhabdomyomas and other congenital cardiac malformations have been reported but the association documented here has not been, to our knowledge, previously described.

Aortic Valve↗

[Limulus test using a chromogenic method: application to the control of pyrogens in blood derivatives].

We report here the application of the LAL Test to a chromogenic substrate to detect endotoxins in Human Blood Products. In order to reduce the cost, we used a microplate procedure with the Multiskan Reader. Quantitative results in the range of 0,01 to 0,1 ng/ml allowed for a good correlation with the Rabbit Pyrogen test. For 20% albumins and 4% albumins, the mean endotoxins levels of non pyrogenic lots were 0,38 +/- 0,18 and 0,09 +/- 0,03 ng/ml. All the lots which passed the Rabbit Pyrogen test had endotoxins levels lower than 1 ng/ml and 0,2 ng/ml, respectively. We can use this test for other plasma derivatives; Gammaglobulines and PPSB are easily tested. Dried Concentrated Antihemophilic Factor and Dried plasma contain citrate which inhibits the reaction. Dilution and Addition of Calcium Chloride overcome this inhibition. For dried plasma, we should destroy plasma inhibitors by heating at 75 degrees C. This sensitive and reproductible in vitro assay improves the control of pyrogenecity in Human Blood Products.

Blood Transfusion↗

[Not Available].

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Ethics, Medical↗

Phase II trial of diaziquone in patients with colon cancer.

Seventeen patients with metastatic colon cancer received diaziquone iv daily for 5 days repeated every 28 days. Based on recommended starting doses for phase II trials (6-8 mg/m2 daily X 5), the first six patients received 7 mg/m2/day X 5. Two of these patients were heavily pretreated with chemotherapy, two had received prior 5-FU alone, and two had received no prior chemotherapy. There were no responses and three septic deaths (both of the heavily pretreated patients and one 5-FU-only patient who received concurrent radiotherapy). Eleven subsequent patients received 5.5 mg/m2/day X 5. Nine had no prior therapy; two had received prior 5-FU. No antitumor responses were observed. Myelosuppression was again the major toxic effect. No further septic deaths occurred. Diaziquone in this dose and schedule had no antitumor activity in this group of patients.

Adult↗

Isolation of thrombospondin released from thrombin-stimulated human platelets by fast protein liquid chromatography on an anion-exchange Mono-Q column.

Thrombospondin, a glycoprotein found in human platelet alpha granules, is thought to play a major role in platelet haemostatic functions. A rapid method to isolate thrombospondin for functional and structural studies was developed. Freshly prepared supernatants from thrombin-stimulated platelets were separated on an anion-exchange Mono-Q column on a fast protein liquid chromatography system. Detection of thrombospondin in the eluted peaks was performed using sodium dodecyl sulphate-polyacrylamide gel electrophoresis combined with silver staining and a solid-phase radioimmunoassay with monoclonal antibodies directed against thrombospondin and other platelet granule glycoproteins. Thrombospondin was isolated rapidly to a high degree of purity using the fast protein liquid chromatography Mono-Q system (20 min), compared with the time taken with other techniques.

Antibodies, Monoclonal↗

Randomized phase III comparison of three doxorubicin-based chemotherapy regimens in advanced non-small cell lung cancer: a Southeastern Cancer Study Group trial.

From 1978 to 1981, 537 patients with advanced non-small cell lung cancer were randomly assigned to three regimens containing cyclophosphamide and doxorubicin alone or in combination with methotrexate or cisplatin. Eligible patients had measurable disease and had no prior exposure to chemotherapy. Of the patients entered on the study, 505 were evaluable for toxicity and 488 were evaluable for response. The overall response rate (complete and partial responses) was only 9%. Response rates did not vary significantly with respect to treatment regimen, histologic subtypes, extent of disease, or performance status. There was no survival advantage for any regimen. The major toxicities were myelosuppression and nausea-vomiting. These doxorubicin-based chemotherapy regimens produced disappointing results in patients with advanced non-small cell lung cancer. A search for more active antitumor agents in lung cancer is necessary.

Adult↗