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Biomedical subjects

A Stevenaert

Publications and source records attributed to A Stevenaert.

At least 37 records · Page 2Linked to original sources

Somatic MEN1 gene mutation does not contribute significantly to sporadic pituitary tumorigenesis.

Pituitary adenomas are a common manifestation of multiple endocrine neoplasia type 1 (MEN1) but most of them occur sporadically. There are only a few well defined genetic abnormalities known to occur in these sporadic tumours. The MEN1 gene located on 11q13 has recently been cloned and allelic deletion and mutation analysis studies have implicated the MEN1 gene in a significant fraction of the sporadic counterparts of typical MEN1 neoplasms (parathyroid tumours, insulinomas and gastrinomas). To determine if MEN1 gene inactivation is also involved in the development of sporadic pituitary adenomas, allelic deletions of chromosome 11q13 and MEN1 gene mutations and polymorphisms were assessed in 35 sporadic tumours of the anterior pituitary (9 prolactin-secreting, 8 GH-secreting, 3 TSH-secreting, 2 TSH/GH-secreting, 4 Cushing, 9 silent). Thirty-one tumours were found to be heterozygous for at least one MEN1 intragenic polymorphism (25 cases) or for a flanking gene polymorphism (6 cases). The remaining tumours were not informative. No mutations were found in any tumour except in one prolactinoma which was homozygous or hemizygous for a mutation (1-117 C-->T) in a region close to the promoter. Unfortunately, blood or normal tissue was not available in this case. Our data show that somatic MEN1 mutations do not contribute significantly to tumorigenesis of sporadic pituitary adenomas and suggest that mutation of other genes are likely to contribute to the pathogenesis of these tumours.

Adenoma↗

Posterior epidural migration of sequestered lumbar disc fragments. Report of two cases.

The posterior epidural migration of sequestered lumbar disc fragments is an uncommon event. The authors report two such cases in which patients presented with either intense radicular pain or cauda equina syndrome. The radiological characteristics were the posterior epidural location and the ring enhancement of the mass after injection of contrast material. The major diagnostic pitfalls are discussed.

Adult↗

[An immunologic etiology for hyperprolactinemia: macroprolactinemia].

Besides classical etiologies of hyperprolactinaemia (pregnancy, pharmacological treatments, pituitary or hypothalamic perturbations), another less known cause may explain a spectacular idiopathic elevation of plasma concentrations of prolactin hormone. Macroprolactinaemia is characterized by the presence of a circulating high molecular weight complex of prolactin with an immunoglobulin G. In this article, we report the cases of 3 female patients for whom size exclusion chromatography technique permitted to give a precise biological diagnosis and to avoid heavy, expensive, time consuming and unnecessary clinical investigations or therapeutic actions. Patients with macroprolactinaemia do not exhibit clinical features of classical hyperprolactinaemia, notably as regard to menstrual and fertility disturbances.

Adult↗

The burden of illness of hypopituitary adults with growth hormone deficiency.

OBJECTIVE: The negative metabolic and psychosocial consequences of growth hormone deficiency (GHD) in adults are now well established. In the present study, an attempt was made to quantify the burden of illness, in terms of lost productivity and increased medical consumption, associated with hypopituitarism and untreated GHD. DESIGN AND SETTING: The study population consisted of 129 Belgian adults with untreated GHD associated with hypopituitarism after pituitary surgery. The Short-Form 36 Health Survey (SF-36) was used to assess health status, and the Health and Labour Questionnaire was used to measure production losses and labour performance. Data on medical consumption were also collected. MAIN OUTCOME MEASURES AND RESULTS: Hypopituitary patients reported a lower health status than that of the general population in all but two dimensions of the SF-36 (pain and physical functioning). Nearly 11% of the patients reported being incapacitated for paid employment due to health problems, compared with 4.8% of the general Belgian population. Patients in paid employment reported a mean of 19.8 days of sickness leave per year, which is twice that in the general population. The annual number of visits to general practitioners and specialists was also higher in the patients (9.6 and 6.5 visits, respectively, for the patients compared with corresponding figures of 2.1 and 1.5 for the general Belgian population). The average annual number of days spent in hospital was 3.5 for the patients compared with 2.3 in the general population. The annual healthcare costs and costs due to production losses calculated for hypopituitary patients who had received pituitary surgery amounted to 135,024 Belgian francs (BeF) or $US4340 (1995 values). This compares with the mean annual cost per person for the Belgian population as a whole of BeF68,569 or $US2204. CONCLUSIONS: Hypopituitary patients with untreated GHD therefore have a higher cost to society in terms of lost production and medical consumption than the average Belgian population.

Adult↗

Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine.

UNLABELLED: This study evaluates the usefulness of PET for the preoperative evaluation of brain gliomas and methods of quantification of PET results. METHODS: Fifty-four patients with brain gliomas were studied by PET with 18F-fluorodeoxyglucose (FDG) (n = 45) and/or 11C-methionine (MET) (n = 41) before any treatment. Results of visual analysis, calculation of glucose consumption and five tumor-to-normal brain ratios for both tracers were correlated with two histologic grading systems and with follow-up. RESULTS: Visual analysis (for FDG) and tumor-to-mean cortical uptake (T/MCU) ratio proved to be the best tools for the evaluation of PET results. Methionine was proven to be better than FDG at delineating low-grade gliomas. Tumor-to-mean cortical uptake ratios for FDG and MET were clearly correlated (r = 0.78), leading to the equation T/MCU(FDG) = 0.4 x T/MCU(MET). We showed a good correlation between FDG PET and histologic grading. MET uptake could not differentiate between low-grade and anaplastic astrocytomas but was significantly increased in glioblastomas. Low-grade oligodendrogliomas exhibited high uptake of FDG and MET, probably depending more on oligodendroglial cellular differentiation than on proliferative potential. Uptake was decreased in anaplastic oligodendrogliomas, probably due to dedifferentiation. Care must be taken with peculiar histologic subgroups, i.e., juvenile pilocytic astrocytomas and oligodendrogliomas, because of a discrepancy between high PET metabolism and low proliferative potential (good prognosis). Both tracers proved useful for the prediction of survival prognosis. Methionine proved slightly superior to FDG for predicting the histologic grade and prognosis of gliomas, despite the impossibility of differentiation between Grades II and III astrocytomas with MET. This superiority of MET could be explained by patient sampling (low number of Grade III gliomas submitted to examination with both tracers). The combination of both tracers improved the overall results compared to each tracer alone. CONCLUSION: Both tracers are useful for the prediction of the histologic grade and prognosis. The apparent superiority of MET over FDG could be due to the small number of Grade III gliomas studied with both tracers.

Brain↗

Predegenerated nerve allografts versus fresh nerve allografts in nerve repair.

This study reevaluated the possibility of using predegenerated nerves as donor nerve allografts for nerve repair and compared the results of functional recovery to those obtained after standard, fresh nerve allograft repair. Twenty donor rats underwent a ligature/ section of the left sciatic nerve 4 weeks before nerve graft harvesting. Forty recipient rats underwent severing of the left sciatic nerve leaving a 15-mm gap between the nerve stumps. Graft repair was undertaken using either the predegenerated left sciatic nerve of the 20 donor rats (predegenerated group, 20 recipient rats) or the normal right sciatic nerve of the 20 donor rats (fresh group, 20 recipient rats). Recovery of function was assessed by gait analysis, electrophysiologic testing and histologic studies. Walking tracks measurements at 2 and 3 months, electromyography parameters at 2 and 3 months, peroperative nerve conduction velocity and nerve action potential amplitude measurements at 3 months, as well as assessments of myelinated nerve fiber density and surface of myelination showed that fresh and predegenerated nerve grafts induced a comparable return of function although there was some trend in higher electrophysiologic values in the predegenerated group. The only slight but significant difference was a larger mean nerve fiber diameter in the nerve segment distal to a predegenerated nerve graft compared to a fresh nerve graft. Although our study does not show a dramatic long-term advantage for predegenerated nerve grafts compared to fresh nerve grafts, their use as prosthetic material is encouraging.

Action Potentials↗

125I-Tyr0-hCRH labelling characteristics of corticotropin-releasing hormone receptors: differences between normal and adenomatous corticotrophs.

The presence of corticotropin-releasing hormone (CRH) receptors has been previously demonstrated in corticotrophs from normal pituitaries using a method combining immunocytochemistry and liquid emulsion autoradiography. The aim of this study was to compare the characteristics of the 125I-Tyr0-hCRH binding in corticotrophs from normal pituitaries (three obtained at autopsy and one obtained at surgery) with corticotrophs from pituitary adenomas (six corticotroph adenomas responsible for Cushing's disease and two silent corticotroph adenomas secreting a biologically inactive ACTH molecule). In normal corticotrophs, the larger part of the 125I-Tyr0-hCRH binding was localised in patchy conglomerates at the centre of the cell and, to a much lesser degree, in a diffuse pattern at the cell periphery. In adenomatous corticotrophs, CRH receptor expression is disturbed both quantitatively and qualitatively. Except for a minority of cells in one adenoma, all adenomatous corticotrophs showed only peripherally bound 125I-Tyr0-hCRH and no centrally localised binding. Furthermore, adenomatous corticotrophs revealed a statistically significant lower signal intensity when compared to normal corticotrophs and a strongly negative correlation was found between the labelling area in adenomatous corticotrophs and both the basal and CRH-stimulated plasma ACTH levels. These findings suggest defective processing of CRH receptors and could be relevant to the sustained ACTH secretion by adenomatous corticotrophs in Cushing's disease and, more generally, provide an explanation to its pathology. The silent corticotrophs secreting a biologically inactive ACTH molecule were characterised by a very faint signal intensity, although present on almost every cell.

Adenoma↗

Two years of replacement therapy in adults with growth hormone deficiency.

OBJECTIVES: Although several studies have shown beneficial short-term effects of recombinant human growth hormone (rhGH) therapy in adult GH deficient (GHD) patients, few data are available on large groups of patients treated for more than one year. In addition, the optimal dose of rhGH for each patient and the baseline parameters that predict which patients will benefit most from therapy or will have adverse events are not entirely elucidated. DESIGN: 148 adult GHD patients were enrolled in a multicentre 2-year rhGH replacement study which was placebo controlled for the first six months. rhGH (Genotropin/Genotonorm Pharmacia & Upjohn) was given in a dose of 0.25 IU/kg/week sc (1.5 IU/m2/day). MEASUREMENTS: Every 3-6 months body composition was measured using body impedance analysis and general well being was assessed using the Nottingham Health Profile (NHP) and social self-reporting questionnaire. At the same time patients had a full clinical examination and blood was sampled for glucose, HbA1c, IGF-1, creatinine, full blood count, thyroid hormones and liver function tests. RESULTS: With rhGH therapy IGF-1 levels increased from -2.00 +/- 2.60 SDS to 1.47 +/- 2.6 SDS after six months (P < 0.001), continued to rise despite no change in dose to 1.84 +/- 2.8 SDS after one year and remained constant thereafter (1.98 +/- 2.4 after 2 years). 56% of patients ultimately attained supranormal IGF-1 levels (+2 SD), 22% had levels below the mean, of which 9% were below -2 SD. Within 3 months lean body mass (LBM) increased by +5.09% (P < 0.001), total body water (TBW) by +5.40% (P < 0.001), while body fat (BF) dropped by -10.89% (P < 0.001) and waist circumference by -1.42% (P < 0.004). These effects were maintained during the first year of therapy, but the effect was attenuated after 24 months: LBM, +3.91% (P < 0.001); TBW, +3.28%, P < 0.001, BF, -6.42% (P < 0.001) and waist -2.22% (P < 0.009). Individual differences in response were large and could not be predicted by any of the baseline parameters, except for a better response in males. Treatment resulted in a large and progressive improvement on the NHP scale, especially energy, emotions and sleep, but a similar change was also found in patients during placebo treatment. With rhGH the number of full days of sick leave/6 months decreased from 12.17 +/- 3.90 days (SEM) to 7.15 +/- 3.50 days after six months (P = 0.009), 2.93 +/- 1.55 days after 12 months (P = 0.01), 0.39 +/- 0.17 days after 18 months (P < 0.001) and 3.3 +/- 2.51 days after 24 months (P = 0.026). Similarly, the hospitalization rate went down from 14.9 to 7% after 6 months and remained at this level thereafter (P = 0.12). About one third of patients on rhGH experienced fluid-related adverse events, most often within the first 3 months. They usually disappeared spontaneously or responded well to dose reduction. Cumulative dropout rates were 29% after 1 year and 38% after two years. Two thirds of these patients stopped treatment because of insufficient subjective improvement. Neither drop-outs nor fluid retention could not be predicted by any of the baseline parameters. CONCLUSIONS: We confirmed in a large group of patients the beneficial effects of rhGH therapy on body composition, metabolic parameters and general well-being and found a consistent drop in number of sick days and hospitalization rate. These effects were maintained during two years of therapy, except for an attenuation in body composition changes after 24 months. The high incidence of fluid-related adverse events suggests that it may be better to start with lower doses of rhGH and to increase the dose more slowly over a number of weeks. The finding of suboptimal high or low IGF-1 levels in many patients reinforces guidelines not to give rhGH in a weight-dependent dose but to titrate it individually for each patient.

Adult↗

Effects of Schwann cell transplantation in a contusion model of rat spinal cord injury.

Cultured Schwann cells were transplanted at various delays into a spinal cord contusion injury performed at low thoracic level in adult female rats. The Schwann cells were purified from the dorsal root ganglia of adult syngeneic animals. the transplants were well tolerated, and the transplanted Schwann cells invaded the injured spinal cord. As quantified using video image analysis, the survival and growth of the transplanted cells were poor when the grafting procedure was performed 3-4 days after injury and very good when performed immediately or 10 days after injury, in which cases post-traumatic micro- and macrocavitation were strongly reduced. In animals grafted immediately after injury but not in animals grafted after 10 days, post-traumatic astrogliosis was much reduced. The Schwann cells transplanted area was invaded by numerous regenerating axons, the vast majority of which were, based on the neurotransmitter (CGRP and SP) profile, originating from dorsal root ganglion. No regeneration of the corticospinal tract as assessed after anterograde tracing or of descending aminergic fibers could be demonstrated.

Animals↗

Presurgical Octreotide: treatment in acromegaly.

One hundred seventy-two acromegalics who were operated on using the trans-sphenoidal approach underwent long-term follow-up evaluation. Sixty-four received 100 micrograms octreotide subcutaneously three times daily: for 3 to 6 weeks before surgery in 14 patients (group 1); and for 3 to 9 months in 41 and for 13 to 39 months in nine (n = 50, group 2). In 18 group 2 patients, the dose was increased stepwise to 500 micrograms three times daily because of incomplete suppression of growth hormone (GH)/insulin-like growth factor-1 (IGF-1). Tumor shrinkage was seen in 60% within 3 weeks, being nearly maximal by 3 to 4 months. More group 2 patients had greater than 25% tumor shrinkage (14 of 48 v 1 of 14 in group 1). Clinical response was excellent or good in 89%. Decrease in soft-tissue swelling and weight loss, and improved vitality, performance, carbohydrate metabolism, and cardiovascular function, facilitated anesthetic and surgical management; tumor removal was easy in virtually all cases. In all 64 patients, GH levels decreased by > or = 50%, and to < 2 micrograms/L in three of 14 patients initially and 25 of 50 patients after more prolonged treatment. IGF-1 levels decreased to normal in seven of 14 group 1 and 31 of 50 group 2 patients. Light and electron microscopy showed that adenomatous tissue exposed to octreotide had lysosomal accumulation, amyloid deposition, mild to moderate perivascular fibrosis, and moderate size reduction in both cytoplasmic and nuclear areas, with virtually no cellular complications. Remission with enclosed adenomas was greater (p < .05) than for the 108 patients not treated with octreotide; there was no difference for invasive adenomas. Octreotide use for 3 to 4 months before surgery can be recommended.

Acromegaly↗

Recurrent ganglion cyst of the peroneal nerve: radiological and operative observations. Case report.

This 34-year-old man presented with right leg pain and foot drop of 1-month duration. The preoperative diagnosis of a 10-cm-long ganglion cyst of the peroneal nerve was achieved using ultrasonography (US), computerized tomography and, particularly magnetic resonance (MR) imaging. Surgical exploration disclosed a lobulated cystic mass filled with gelatinous material, which intermingled with the nerve substance of the deep peroneal nerve. The lesion was completely resected, with the sacrifice of some electrically nonfunctioning fascicles. No connection with the knee joint was found. A good postoperative recovery of motor function was obtained. However, routine postoperative MR imaging disclosed a recurrent ganglion cyst that was slightly less extensive than the original. A careful radiological examination of the knee joint was performed, including arthrography. A communication of the cyst with the tibiofibular joint was clearly demonstrated and was meticulously closed at reoperation. The patient's postoperative course was uneventful, and a third MR image, obtained 5 months after reoperation, showed no sign of cyst recurrence. The patient remained free of symptoms 11 months postoperatively. This case illustrates the value of US and MR in diagnostic imaging. The diagnostic efficacy of US and MR imaging in identifying and characterizing a ganglion cyst is described. Close contact between a ganglion cyst and the tibiofibular joint should raise the possibility of an existing cyst-joint communication and lead to an aggressive radiological workup and/or a surgical search for such a communication.

Adult↗

The prevalence of colonic polyps in acromegaly: a colonoscopic and pathological study in 103 patients.

Patients with acromegaly are reported to be at risk of developing adenomatous colonic polyps, which are considered to be preneoplastic lesions. This assumption is, however, usually drawn from results obtained in rather small series of patients or without a control group. We, therefore, undertook a prospective colonoscopic and pathological study comprising 103 acromegalic patients and 138 nonacromegalic control subjects referred for irritable bowel syndrome. The prevalence of adenomatous colonic polyps was significantly increased in acromegalic patients compared to that in control subjects (22.3% vs. 8.0%; P = 0.0024). The significance was similarly present in male acromegalic patients (28.6% vs. 5.5% in male control subjects; P = 0.0026), but was absent in female acromegalic patients. The prevalence of colonic polyps was also significantly increased in the group of acromegalic patients under 55 yr of age (20.0% vs. 3.0% in the control group of the same age; P = 0.0026). Other characteristics of adenomatous colonic polyps in acromegaly were the multiplicity and the presence proximal to the splenic flexure. No difference in the duration of acromegaly was found between patients with or without adenomatous polyps. The prevalence of hyperplastic colonic polyps was also significantly increased to 24.3% in acromegalic patients vs 4.4% in control subjects (P < 0.001). In conclusion, in view of the increased incidence of adenomatous colonic polyps, colonoscopy should be part of the follow-up examination in acromegaly.

Acromegaly↗

Radiation-induced gliosarcoma. Case report and review of the literature.

A 13-year-old boy presented with a cerebral gliosarcoma 12 years after having acute lymphoblastic leukemia treated by chemotherapy and central nervous system prophylaxis treated by radiation therapy (24 Gy) and intrathecal methotrexate. A review of the literature disclosed 129 possible radiation-induced gliomatous and/or sarcomatous brain tumors: namely, 89 gliomas, 36 sarcomas, and four gliosarcomas, including the present case. An analysis of these cases revealed several characteristics that differentiate them from similar spontaneous brain tumors, thus providing arguments for the carcinogenic effect of radiation therapy on intracranial tumors.

Brain Neoplasms↗

Radiation-induced myelopathy and vertebral necrosis.

Radiation-induced myelopathy is often a diagnosis of exclusion. In addition to the classic criteria needed to support the diagnosis, the presence of another radiation-induced lesion, such as aseptic vertebral necrosis, is useful to confirm the cause of the spinal cord lesion.

Aged↗

Dramatic improvement of severe dilated cardiomyopathy in an acromegalic patient after treatment with octreotide and trans-sphenoidal surgery.

Severe congestive heart failure developed in an acromegalic patient, and was successfully treated with octreotide followed by trans-sphenoidal surgery. Clinical, hormonal echocardiographic and haemodynamic findings as well as histological heart examination before and after treatment revealed that over-production of growth hormone may induce the myocardial cell degeneration responsible for mechanical heart dysfunction. In addition, this unique example demonstrates the reversibility of myocardial damage following octreotide and trans-sphenoidal surgery, leading to significant improvement in cardiac function with minimal diastolic dysfunction and moderate interstitial fibrosis.

Acromegaly↗