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Biomedical subjects

J Guerin

Publications and source records attributed to J Guerin.

At least 55 records · Page 3Linked to original sources

Usefulness of the corticotropin-releasing hormone test during bilateral inferior petrosal sinus sampling for the diagnosis of Cushing's disease.

Inferior petrosal sinus blood sampling for ACTH measurement (IPSS) is used for the differential diagnosis of ACTH-dependent Cushing's syndrome and for the preoperative location of pituitary microadenomas. Intermittent ACTH secretion from pituitary adenomas may result in insignificant differences between petrosal and peripheral ACTH levels at the time of sampling. Thus, pituitary stimulation during IPSS may improve the procedure. The aim of the study was to evaluate the usefulness of CRH injection in combination with IPSS. Twenty-two patients with Cushing's disease (CD; 5 macroadenomas, 16 microadenomas, and 1 corticotroph hyperplasia) and 5 patients with ectopic ACTH syndrome were studied. Bilateral IPSS was successfully carried out on 25 patients. Patients with ectopic ACTH syndrome had, before and after CRH injection, central to peripheral ACTH gradients below 1.7. Four patients with CD had basal gradients below 1.4. After CRH administration all patients with CD had gradients above 3.2. Despite correct location of central catheters, the predicted location of pituitary microadenomas was erroneous in 41% of the cases. It was not improved after CRH injection. In conclusion, the combination of CRH injection with IPSS was useful for the differential diagnosis of ACTH-dependent Cushing's syndrome, as it increased the discrimination of the procedure. On the contrary, it was useless for the preoperative location of pituitary microadenomas, which was poorly predicted by IPSS.

ACTH Syndrome, Ectopic↗

[Adaptation to the Biomek 1000 workstation (Beckman) of the MHA-TP technique (Ames)].

The microhemagglutination-Treponema pallidum (MHA-TP) was automated with the Biomek 1000 workstation (Beckman). 3,000 serum specimens were studied with manual and automated procedures. Thirty nine serum specimens were found positive by both techniques, neither false positive nor false negative results were observed with the Biomek 1000 workstation. The statistical analyse showed no differences between the two procedures, variations were observed only with low titer sera. In conclusion, time saving and augmentation of productivity obtained by automation of this method could be interesting for a microbiology laboratory.

Diagnosis, Computer-Assisted↗

Effects of simultaneous active immunization against 17 beta-estradiol and testosterone on pituitary and ovarian activity in the rat.

Female rats were immunized with mixed 17 beta-estradiol-6-carboxymethyloxime-bovine serum albumin and testosterone-3-carboxymethyloxime-bovine serum albumin. All the animals produced antibodies against the 2 haptens and were better immunized against 17 beta-estradiol than against testosterone. Nevertheless the disappearance of cyclic ovarian function was only obtained in animals highly immunized against the two antigens. The 17 beta-estradiol serum concentration increased with the level of immunization whereas the progesterone concentration fell. Persistent vaginal cornification was observed and ovarian lesions (large fluid filled cysts, hemorrhagic follicles and absence of corpora lutea) coincided with increased serum levels of luteinizing hormone and prolactin.

Animals↗

The corticotropin-releasing factor test in the differential diagnosis of Cushing's syndrome: a comparison with the lysine-vasopressin test.

The diagnostic accuracy of the CRH test was compared with that of the LVP test in 28 consecutive patients with ACTH-dependent Cushing's syndrome. A false negative response to CRH was found in 3 of 21 patients with pituitary-dependent Cushing's disease and to LVP in 4. The 7 patients with ectopic ACTH secretion were unresponsive to CRH, whereas 2 did respond to LVP. CRH and high-dose dexamethasone tests combination led to concordant results in 79% of patients. In all cases the etiological diagnosis suggested was correct. LVP and high-dose dexamethasone tests combination led to concordant results in only 71% of patients and the etiological diagnosis suggested was erroneous in one. Individual tolerance to the CRH test was also clearly better than that to the LVP test. It is concluded that the CRH test, alone or in combination with the high-dose dexamethasone test must be preferentially used to the LVP test in the differential diagnosis of ACTH-dependent Cushing's disease.

Adolescent↗

[Efficacy and long-term tolerance of ketoconazole in the treatment of Cushing's disease].

Successful short term treatment of patients with Cushing's disease by Ketoconazole without adverse effects is now well established. Little data are available about prolonged treatment of this disease with ketoconazole. We report herein our experience of ketoconazole therapy in four patients with Cushing's disease treated for 9 to 38 months. One patient rapidly developed adrenal hypofunction and required transient steroid therapy adjunction. In the other patients, cortisol overproduction was reduced to normal levels within two months and their urinary free cortisol remained within the normal range throughout the study. In two patients ketoconazole dose could be decreased but had to be increased after ten months of therapy in one patient. None of the patients had clinical or biochemical signs of drug toxicity. Thus, ketoconazole seems to be a useful drug for the prolonged metabolic control of Cushing's disease. However, in this circumstance, ketoconazole daily dose adaptation can be necessary in order to maintain normal urinary cortisol levels and the ability of ketoconazole to cure Cushing's disease still remains to be determined.

Adrenocorticotropic Hormone↗

[Value of the CRF test in primary and secondary adrenal insufficiency].

The ACTH and cortisol responses after CRF administration were studied in 21 patients with adrenal failure and compared with those obtained in 15 control subjects. In patients with Addison's disease, cortisol and ACTH responses were respectively abolished or excessive. In patients with secondary adrenal failure, a unique bolus injection of CRF allows the differentiation between pituitary or hypothalamic secretory defect. With regard to previous reports, the usefulness of CRF test in primary and secondary adrenal failure is stressed.

Addison Disease↗

The electrophysiological effects of thyrotropin-releasing hormone are similar in human TSH- and prolactin-secreting pituitary cells.

We studied the electrophysiological properties of individually characterized TSH-secreting cells cultured from pituitary fragments surgically removed from three patients, two who had primary TSH-secreting adenomas and one who had chronic TSH hypersecretion (hyperplasia) secondary to primary hypothyroidism. The TSH-secreting cells were excitable and had calcium-dependent action potentials. More than 80% of the cells cultured from the two patients with TSH-secreting adenomas were spontaneously active, whereas fewer cells (20%) cultured from the hypothyroid patient were spontaneously active. TRH (50 nmol/L) induced a complex pattern of electrical changes. The initial response was transient hyperpolarization (activation of potassium conductance), followed by increased low amplitude voltage fluctuations occasionally leading to action potentials. These TRH-induced electrophysiological changes were similar to those reported in rat and human PRL-secreting adenoma cells. These results suggest that TRH may have an identical mode of action in tumoral PRL and TSH cells. In the cells from the hypothyroid patient, the initial response to TRH cells was similar, but the second phase response was greater. The findings that the cells cultured from these patients behaved differently with regard to their electrophysiological characteristics (action potentials) and responses to TRH may reflect the different clinical conditions from which they were derived.

Action Potentials↗

Electrical properties of cultured human adrenocorticotropin-secreting adenoma cells: effects of high K+, corticotropin-releasing factor, and angiotensin II.

ACTH-secreting pituitary adenoma cells were cultured from specimens obtained by transphenoidal hypophysectomy in five patients with Cushing's disease. The majority of adenoma cells (90%) stained specifically with antiserum against human ACTH. The electrophysiological properties and response to hormones of these cells were studied with intracellular recording techniques under current clamp and voltage clamp conditions. Most (80%) of the cells fired action potentials that were Ca2+-dependent inasmuch as they were blocked by Co2+ (5 mM) and by removal of Ca2+ from the medium, but were unaffected by tetrodotoxin (0.3 mM) and by Na+ removal. The cells responded to factors known to stimulate ACTH release, including high K+, CRF, and angiotensin II (AII). High K+ (50 mM) induced a membrane depolarization in association with an increase in conductance. CRF (100 nM) produced a depolarization, a decrease in conductance, an increase in spike firing, and an increase in spike duration. Although AII was inactive in ordinary recordings, in cells loaded with lithium (Li+) to promote the phospholipid-dependent second messenger system, the peptide produced an increase in spike firing and spike duration with no change in membrane potential. The combination of CRF and AII (CRF + AII; 100 nM each) in Li+-loaded cells caused a greater excitatory effect than either peptide alone. Under voltage clamp, the response either to CRF or to CRF + AII could be attributed, at least in part, to the inhibition of a slow, voltage-dependent K+ current that is persistently active at resting potential. These results indicate that modulation of action potential firing may be an early step in the regulation of ACTH release from pituitary cells by known secretagogues. Since action potentials in these cells are associated with Ca2+ entry, the resulting changes in intracellular Ca2+ levels could mediate the effects of the hormones on secretion.

Action Potentials↗

[Value of angioscanography in the morphologic exploration of hypophyseal adenomas].

Considerable progress has been made in the morphologic study of pituitary due to the availability of angioscan programs. An exceptional case is presented of a persistent intrasellar trigeminal artery associated with prolactinoma. Based on technological progress in CT scan imaging the place of angiographic explorations in the investigation of pituitary adenoma is reconsidered.

Adenoma↗

[Medulloblastoma of the posterior cranial fossa. A second tumor after Hodgkin's disease].

The case of a child presenting with Hodgkin's disease (stage I A, mixed cellular type) at the age of 23 months is reported. Chemotherapy (six treatments with MOPP) enabled a clinical remission, but an in situ relapse with the same histological pattern was observed at the age of 3 years and 9 months. After local irradiation, a second complete remission was observed. At the age of 6, a clinical picture of intraskull hypertension with ataxia, lead to the diagnosis of posterior cavity tumor. Complete excision was performed and the pathological examination showed a typical medulloblastoma. Adjuvant radiotherapy was carried out. Eight months later, a fatal plurifocal medullar relapse was observed. Second tumors in Hodgkin's disease are well known. However, this new case appeared to be the first report of a medulloblastoma after Hodgkin's disease.

Cerebellar Neoplasms↗

[Cerebral lesions in a case of Degos' disease].

The central nervous system may be involved in Degos disease, but neuropathologic observations are still few. We report a typical case with cerebral involvement. The diagnosis was suggested by the characteristic skin lesions and vascular damage. In the central nervous system, occlusive changes of small arteries were responsible for areas of ischaemic necrosis. These foci of infarction were of varying size, age and distribution. Intestinal lesions were discrete and death was due to several cerebral infarcts.

Adult↗

[Supratentorial malignant glioma in adults. Adjustment of the treatment of 3 groups according to a clinical classification].

Therapeutic goals cannot be the same for every patient with malignant glioma, as suggested by the study of 106 cases seen from 1975 to 1982. Seventy patients were uniformly treated by surgery, chemotherapy and radiotherapy. Two clinical parameters, i.e. age and postoperative neurological status (NS), were used to divide patients into three groups with a significantly different prognosis. Median survival was 59.5 months for group 1 (age 50 or less, good NS) and 11.5 months for group 2 (age 51 to 65 and good NS, or younger than 51 but poor NS). For group 3 (age 51 to 65 and poor NS, or older than 65), survival was six months. From 1978, two trials were carried out, with therapy being adjusted to each group. Whatever the group, surgical excision was done whenever it was consistent with preservation of the neurological status and followed by combination chemotherapy (Vincristine-VM 26-CCNU). For group 1, radiotherapy was not modified: 60 grays were delivered to the tumor and surrounding safety margin in 30 fractions over 6 weeks. Patients in group 2 received 69 grays in two daily fractions over 6 weeks (1.15 Gy each morning and evening five days a week). With this modified treatment, median survival was brought up to 20.5 months. Patients in group 3 were treated initially by surgery and chemotherapy; radiotherapy was restricted to recurrences. This policy significantly improved patients' comfort by enabling their prompt return to home. The median survival for 14 patients was 10.5 months. Our experience suggests that different therapeutic goals should be set for each group. In group 1, therapy should be aimed at obtaining prolonged survival. In group 3, survival remains short and the main concern is to improve patients' comfort. As patients in group 2 have an intermediate prognosis, they are the best candidates for therapeutic trials designed to improve the response to radiotherapy and chemotherapy.

Adolescent↗

[Tomodensitometric study of the course of supratentorial malignant glioma after treatment].

Computed tomography now is the primary method for the management of supratentorial malignant gliomas. In this study, analysis of CT scan controls done at 2 or 3 month intervals in 87 treated patients showed that: 1) in most instances, recurrence arose within the initial tumor site; 2) the tumor invades contiguous anatomical structures through intra-and inter-hemispheric association fibers; 3) multicentric gliomas are uncommon (less than 6% of patients). The purpose of this study was to reduce irradiated volumes and thus radiation toxicity. The finding that most patients experience recurrence within the original tumor site is evidence experience recurrence within the original tumor site is evidence that current radiation doses and total brain irradiation are inappropriate. Our results are consistent with those recently reported in the medical literature. Using computed tomography data, it should be possible to restrict the irradiated volume to the tumor site and to presumptive extension pathways. Higher doses may be delivered to this volume.

Adolescent↗

[Probable effect of cerebral irradiation on intellectual efficiency].

Thirty adult patients treated for brain tumors by radiation therapy were tested by the Weschler intelligence scale (WAIS). All patients were in complete clinical and scanographic remission. Intellectual quotient (IQ) and deterioration coefficient were evaluated. This coefficient was determined by separate study of intellectual faculties according to their relationship to external aggressions. During the first six months, IQ and deterioration coefficient are similar to those observed in the normal population. From 7 to 30 months, there is a significant diminution of the intellectual faculties (p = 0,01) noted on the deterioration coefficient but without global IQ alteration. After 30 months appears a decrease in the global IQ, testifying of further alteration of intellectual faculties. Radiation therapy seems to be the predominant factor in the induction of this deterioration and the importance of the irradiation volume appears to be essential. On the other hand, neurosurgery, chemotherapy and emotional status seem to be less important. Intellectual deterioration makes professional reinsertion difficult but not impossible. Further studies are necessary to define what place take other factors like age, vascular status, tumor site, type and number of chemotherapy cycles, acute radiation tolerance, in the induction of this deterioration.

Adolescent↗

[Management of advanced breast cancer in post-menopausal women. A comparative trial of hormonal therapy, chemotherapy, and a combination of both].

A randomized trial was done in 98 post-menopausal women with breast cancer. Hormonal receptors had not been assayed in any patient. Patients were given hormonal therapy with tamoxifen and drostanolone propionate (n = 34), or chemotherapy with the CMF protocol (n = 30), or a combination of both (n = 34). The results are in favour of hormonal therapy alone, which gave the best immediate objective responses, the least adverse side-effects, and possibly improved survival rates.

Androstanols↗

An electrophysiological study of cultured human pituitary cells.

The electrophysiological properties of tumoral pituitary cells were studied in 4 types of human adenomas including prolactinomas, growth-hormone-secreting tumors, adrenocorticotropin-hormone-secreting adenoma and 'non-functioning' tumors. Only 9% of the cells from prolactinomas and ACTH tumors were excitable but they never elicited spontaneous action potentials. These cells did not respond to substances known to act on the hormone-releasing process (thyreoliberin, dopamine). However, 37% of the cells cultured from growth-hormone-secreting adenomas and from 'non-functioning' tumors displayed action potentials. The action potential was calcium-dependent, i.e., it was blocked by cobalt, nickel and methoxyverapamil and could be recorded in a sodium-free medium. Thyreoliberin triggered action potentials, whereas dopamine and gamma-aminobutyric acid inhibited electrical activity. These results show that human tumoral pituitary cells in culture are able to generate Ca2+-dependent action potentials. The data from growth-hormone-secreting tumors are in good agreement with the stimulus-secretion coupling concept; however, differences in the response of cells cultured from other types of human pituitary tumors suggest that each type of adenoma has specialized membrane properties.

Action Potentials↗