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G Ouaknine

Publications and source records attributed to G Ouaknine.

At least 19 recordsLinked to original sources
PubMed2005

Postoperative treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists decreases tumour remnant growth.

OBJECTIVE: There is no consensus as to the optimal postoperative treatment of patients with clinically nonfunctioning pituitary adenomas (NFPA) in whom total tumour removal has not been achieved. In this study we assessed whether dopamine agonist (DA) treatment can prevent postoperative remnant enlargement in NFPA. DESIGN AND METHODS: Thirty-three patients (25 men/8 women; mean age, 61.7 +/- 11.2 years; mean follow-up, 40.6 +/- 4.8 months) were treated with DA, and their outcome was compared to that of 47 untreated patients (33 men/14 women; mean age, 59 +/- 2 years; mean follow-up, 42.9 +/- 4.2 months). RESULTS: Tumour mass decreased or remained stable in 18/20 patients in whom DA treatment was initiated upon detection of residual tumour on postoperative MRI (group I). In 13 subjects (group II), DA therapy was started when tumour remnant growth became evident during the course of routine follow-up. Tumour growth stabilized or decreased in 8/13 (61.5%) of these patients. In contrast, tumour size remained stable in only 38.3% (18/47) of the untreated subjects (P < 0.0001 for comparisons among the three groups) and increased in the remaining 29 patients. Tumour enlargement free mean survival time was 103.7 +/- 8.8 months (CI 86.3-121) for group I, 43.9 +/- 9.6 months (CI 25.2-62.8) for group II and 36.7 +/- 3.8 (CI 29.2-44.2) for the control group (P = 0.0017). Treatment vs. control hazard ratio for tumour enlargement was 0.135 for group I (P = 0.007, 95% CI 0.032-0.577) and 0.892 for group II (P = 0.817; 95% CI 0.34-2.34). CONCLUSIONS: Dopamine agonist therapy is associated with a decreased prevalence of residual tumour enlargement in patients with nonfunctioning pituitary adenomas, particularly when treatment is instituted before tumour remnant growth is detected.

Adenoma↗
PubMed2003

Postoperative surveillance of clinically nonfunctioning pituitary macroadenomas: markers of tumour quiescence and regrowth.

BACKGROUND: Postoperative management of clinically nonfunctioning pituitary adenomas (NFPA) presents difficult challenges. There are no good serum markers for presence or growth of the tumour, medical treatment is not effective and radiotherapy carries the risk of significant side-effects. OBJECTIVE: The purpose of this study was to investigate the natural history and biological behaviour of surgically treated NFPA, with a special effort to identify characteristics indicative of a more aggressive course that could assist in the clinical decision-making process. STUDY DESIGN: Patients operated on at our institution for NFPA undergo uniform routine clinical follow-up at the endocrine clinic. Magnetic resonance imaging (MRI) studies are performed 3, 6 and 12 months after transsphenoidal surgery and yearly thereafter for the first 5 years. Subsequently, imaging is performed once every 2 years or as clinically indicated. From 1992 onwards, no patient received immediate postoperative radiation therapy. PATIENTS: One hundred and twenty-two patients (78M/45F) operated on at our institution since 1989 and with a minimal follow-up of 1 year comprised the study group. MEASUREMENTS: Tumour size and characteristics were determined by MRI using a modification of Hardy's and Wilson's classifications. Maximal tumour height was also recorded and the information was routinely stored in a computerized database. RESULTS: Mean (+/- SD) follow-up was 51 +/- 31 months. Fourteen patients received postoperative radiation therapy. Subsequent tumour growth was observed in five of them, reduction in tumour size in four and no size changes in five. One hundred and eight patients did not receive postoperative radiation. Tumour enlargement occurred in 41 of 78 and in six of 30 patients with and without residual tumour after operation (P = 0.0024). The presence of cavernous sinus invasion before surgery [P = 0.02, odds ratio (OR) 2.72; confidence interval (CI) 1.1-6.43] and the extent of suprasellar extension in the postoperative tumour remnant (P = 0.0054 for presence of stage A, OR 4.4; 95% CI 1.5-12.5; and P = 0.012 for presence of stages B or C, OR 16.2; CI 1.8-144) were strong independent predictors of tumour enlargement. CONCLUSION: Our data may ease the selection of patients in whom radiation therapy is likely to be necessary for tumour control, and confirms that close postoperative follow-up is an adequate primary approach in low-risk patients.

Adenoma↗
PubMed2001

Repeat endoscopic third ventriculostomy: is it worth trying?

OBJECT: The goal of this study was to evaluate the safety, efficacy, and indications for repeat endoscopic third ventriculostomies (ETV). METHODS AND RESULTS: We reviewed the records of 20 patients who had undergone repeat ETV from 1987 to 1999. Their ages ranged from 8 months to 53 years (mean 17 years). The primary etiologies of hydrocephalus were: primary aqueductal stenosis (9 cases), tumor (5), Chiari malformation (2), prior infection (2), prior intraventricular hemorrhage (1), and blocked foramen of Monro (1 patient). The interval between the first and second ETVs ranged from 8 days to almost 6 years (mean 12.8 months). The intraoperative findings at repeat surgery were: occlusion of the primary orifice by scar (10 cases), virginal floor of the third ventricle (5 cases), pinhole ventriculostomy (3 cases), incompletely penetrated membrane (1 case), and blood clot occluding the orifice (1 case). The follow-up period ranged from 3 to 47 months (median 20 months). Repeat ETV was successful in 13 patients (65%). These patients did not require further shunting or other procedures during follow-up. Seven patients (35%) required placement of a shunt after repeat ETV. Several complications were observed in 1 patient (5%), including seizures, elevated ICP, bilateral pulmonary edema, and cardiac arrhythmia. This patient ultimately recovered fully; the ETV was successful, and the patient did not require a shunt. CONCLUSIONS: Based on the experience of this group of patients, repeat ETV is as effective and as safe as a primary ETV procedure, and should be attempted in selected patients.

Adolescent↗
PubMed1998

The use of beta-subunits of gonadotrophin hormones in the follow-up of clinically non-functioning pituitary tumours.

OBJECTIVE: Clinically nonfunctioning pituitary adenomas (NFA) are mostly of gonadotroph origin. However, increased levels of circulating hormones or subunits in patients with NFA usually do not cause clinical symptoms, nor are they used as biological tumour markers. In this study we assessed the value of measuring beta subunits of gonadotrophin hormones in the post-operative follow-up of patients bearing these tumours. DESIGN: Patients harbouring NFA were studied before and three months after transphenoidal pituitary surgery. beta-LH and beta-FSH levels were measured before and following TRH administration on the two occasions. Hormone levels were analyzed in relation to imaging studies performed before and after surgery. PATIENTS: Twenty four patients operated at the Tel Aviv-Sourasky Medical Centre for NFA. RESULTS: Pathological beta-FSH and beta-LH levels were detected in 79% and 60% of patients respectively. beta-LH levels decreased after surgery but there were no significant changes in beta-FSH levels. There was a tendency for tumours with high basal beta-LH levels to be larger and to have a poor surgical outcome. Normalization of beta-LH levels post-operatively was usually associated with a decrease in tumour mass or complete removal of the tumour. Persistent pathological responses of beta-LH to TRH after surgery were common in patients with residual tumours on imaging. Nevertheless there were exceptions to this pattern, rendering post-operative beta-LH levels insufficiently reliable as a marker for the presence of residual tumour. CONCLUSION: Although there appears to be a relationship between beta-LH levels, tumour size and surgical outcome, this association is presently insufficient to allow the routine use of either basal or TRH induced beta-LH responses in the post-surgical follow-up of clinically nonfunctioning pituitary adenomas.

Adenoma↗
PubMed1997

Combined beta FSH and beta LH response to TRH in patients with clinically non-functioning pituitary adenomas.

OBJECTIVE: 'Paradoxical' responses of LH, FSH, alpha-subunits and beta LH to TRH have previously been reported in individuals with clinically non-functioning pituitary tumours (NFT). The present study was designed to assess the in vivo and in vitro responses of beta FSH to TRH in NFT. We further examined the possibility that a TRH challenge with combined measurement of beta FSH and beta LH will identify a common anomalous secretory pattern in patients with NFT. DESIGN, PATIENTS AND MEASUREMENTS: Forty patients with NFT underwent a standard TRH test (400 micrograms intravenously). Blood samples for the determination of beta FSH, beta LH, FSH and LH were collected prior to TRH as well as 15, 30, 45, 60 and 90 minutes following injection. Additionally, cultured adenomatous cells from eight to these patients were exposed to TRH in the absence and presence of octreotide and gonadotropin subunits were determined. RESULTS: TRH elicited a marked rise in circulating beta FSH in 29 of 40 individuals and in beta LH in 28 of 36 patients with NFT. In a subgroup of eight individuals whose tumours were harvested during surgery and cultured for 7-21 days, TRH increased beta FSH or beta LH and alpha-subunit release in cultured adenomatous cells in all cases, including tumours from subjects not responding to TRH in vivo. In this subgroup of patients octreotide inhibited basal beta FSH secretion but not basal beta LH secretion both in vivo and in primary cultures of NFT cells. Both the in vivo and in vitro beta FSH, beta LH and alpha-subunit responses to TRH were entirely inhibited by octreotide. In all, 38 of the 40 subjects could be identified by either elevated basal beta FSH or beta LH levels and/or an abnormal rise in either beta FSH or beta LH in response to TRH. CONCLUSION: The measurement of basal and TRH-stimulated beta-FSH and beta-LH levels identifies an abnormal hormonal secretory pattern in the vast majority (> 90%) of patients with clinically nonfunctioning pituitary tumours.

Adenoma↗
PubMed1995

Relative sparing of anterior pituitary function in patients with growth hormone-secreting macroadenomas: comparison with nonfunctioning macroadenomas.

Pre- and postoperative anterior pituitary function was assessed in 26 subjects with nonfunctioning macroadenoma (NFMA) and in 15 acromegalic subjects with macroadenomas. Preoperatively, NFMA patients had a higher prevalence of secondary hypogonadism (78% vs. 40%; P < 0.05), hypothyroidism (23% vs. 0%; P = 0.06), and hypoadrenalism (43% vs. 7%; P = 0.02) compared to individuals with GH-secreting macroadenoma (GHMA). Patients with NFMA also had a higher prevalence of more severe pituitary failure compared with acromegalic patients; 56% of the patients in this group had more than one pituitary hormone axis impaired compared to only 8% in the acromegalic group. These differences could not be accounted for by tumor grade and/or stage. Transsphenoidal pituitary surgery led to a significant improvement in anterior pituitary function in the NFMA group. Nevertheless, the prevalence of pituitary deficiency postoperatively was still significantly greater in NFMA patients than in the acromegalic group (68% vs. 17%, respectively; P < 0.04). The results suggest that anterior pituitary function is better preserved in GHMA than in NFMA and that this difference is independent of tumor size. The mechanism underlying the lower rate of hypopituitarism in acromegalics with macroadenomas remains to be elucidated.

Acromegaly↗
PubMed1993

Activating mutations of the Gs alpha-gene in nonfunctioning pituitary tumors.

The majority of pituitary tumors are of monoclonal origin; however, the molecular basis for their formation is poorly understood. Somatic mutations in the alpha-subunit of the GTP-binding protein, Gs alpha (gsp oncogene) have been found in about one third of GH-secreting tumors. Mutations in another alpha-subunit of a GTP-binding protein, Gi2 alpha (gip mutations) have been described in other endocrine tumors. In this study, we examined 21 nonfunctioning pituitary tumors and 4 macroprolactinomas for gsp mutations and 27 nonfunctioning tumors and 4 macroprolactinomas for gip mutations. Using the polymerase chain reaction and denaturing gradient gel electrophoresis, 2 nonfunctioning pituitary tumors displayed migration abnormalities when the Gs alpha-gene was analyzed. Sequence analysis of these abnormally migrating polymerase chain reaction products revealed two previously known gsp mutations: arginine at codon 201 altered to cysteine, and glutamine at codon 227 changed to leucine. No gip mutations could be demonstrated. These findings emphasize the monoclonal origin of nonfunctioning pituitary tumors and suggest that cAMP may play a role in tumorigenesis of nonfunctioning pituitary tumors.

Adrenocorticotropic Hormone↗
PubMed1986

A reproducible radionuclide procedure for measurement of cerebrospinal fluid shunt flow.

A radionuclide technique was developed to obtain reproducible measurements of cerebrospinal fluid flow in Rickham-Holter type shunt systems. In attempting to reproduce previously described radionuclide procedures, we found that different flow rate measurements can be obtained simply by changing the radiotracer injection technique or the method of analysis of the time activity curves which are generated. The importance of these technical pitfalls cannot be over-emphasized, since there is no gold standard to evaluate cerebrospinal fluid flow in vivo. An experimental model with a calibrated Harvard pump and a shunt system filled with normal saline was constructed. Aliquots of 500 microCi of pertechnetate in 0.05 ml of saline were injected serially into the center of Rickham reservoir using a size 28 needle. Time-activity curves were obtained after waiting five min to reach equilibrium, and standard curves of radiotracer clearance vs actual flow for each system used clinically in our institution were generated. In addition, a technique to quantify and thus correct for the small but significant leak of radiotracer which occurs at the site of injection in the reservoir is described. Excellent correlation was obtained between our results and the clinical and radiological findings in a preliminary clinical evaluation.

Cerebrospinal Fluid↗
PubMed1975

Electrocardiographic findings in brain death; description and presumed mechanism.

Electrocardiogram changes and pharmacologic responses were studied in 28 cases of brain death. Cardiac activity in this condition is possibly determined by the dynamic balance between the depressant action of hypothermia and the stimulating action of the sympathetic nervous system (without any vagal or central influence). The electrocardiographic alterations are the results of this dual influence, and are probably characteristic of this condition. In the initial stage of brain death the ECG shows J waves in the terminal part of the QRS, prolongation of the QT interval and the ST-T changes; in the advanced stages, progressive showing of the heart rate and the depolarization and repolarization processes are observed (manifested by gradual accentuation of the findings mentioned above); in the terminal stage dynamic electrocardiographic changes (among them, progressive depression of sinus activity, atrial fibrillation, atrioventricular and intraventricular conduction disturbances and severe ST-T changes) appear. It is possible that additional factors, like metabolic changes and possible myocardial damage in some instances, may have some influence on the electrocardiographic pattern. Final conclusions cannot be drawn from these preliminary observations. The atropine test was found to be an efficient and simple diagnostic aid in cases of brain death.

Adolescent↗
PubMed1975

Saphenous nerve entrapment simulating vascular disorder.

Saphenous nerve entrapment may cause a painful syndrome simulating vascular disorder of the leg. The anatomical relationship of the saphenous nerve is described to explain the pathogenesis of the syndrome. The clinical features, diagnosis, and results of treatment of 32 patients are reported. The differential diagnosis of the syndrome is discussed. It is concluded that entrapment of the saphenous nerve should be considered when other known syndromes are unable to explain the symptomatology.

Adolescent↗