Objective-To assess the eVects of high frequency stimulation of the subthalamic nucleus (STN) on axial symptoms occurring in advanced stages of Parkinson's disease (PD). Methods-The eYcacy of STN stimulation on total motor disability score (unified Parkinson's disease rating scale (UPDRS) part III) were evaluated in 10 patients with severe Parkinson's disease. The subscores were then studied separately for limb akinesia, rigidity, and tremor, which are known to respond to levodopa, and axial signs, including speech, neck rigidity, rising from a chair, posture, gait, and postural stability, which are known to respond less well to levodopa. Patients were clinically assessed in the "oV" and "on" drug condition during a levodopa challenge test performed before surgical implantation of stimulation electrodes and repeated 6 months after surgery under continuous STN stimulation. A complementary score for axial symptoms from the "activities of daily living" (ADL)-that is, speech, swallowing, turning in bed, falling, walking, and freezing-was obtained from each patient's questionnaire (UPDRS, part II). Results-Improvements in total motor disability score (62%), limb signs (62%), and axial signs (72%) obtained with STN stimulation were statistically comparable with those obtained with levodopa during the preoperative challenge (68%, 69%, and 59%, respectively). When levodopa and STN stimulation were combined there was a further improvement in total motor disability (80%) compared with preoperative levodopa administration. This consisted largely of an additional improvement in axial signs (84%) mainly for posture and postural stability, no further improvement in levodopa responsive signs being found. Axial symptoms from the ADL showed similar additional improvement when levodopa and STN stimulation were combined. Conclusion-These findings suggest that bilateral STN stimulation improves most axial features of Parkinson's disease and that a synergistic eVect can be obtained when stimulation is used in conjunction with levodopa treatment. (J Neurol Neurosurg Psychiatry 2000;68:595-600)

E ssential hypertension is characterized by sustained elevations of blood pressure (BP) that can lead to target organ damage and an increased risk for cardiovascular disease. 1Potential life-threatening outcomes of hypertension, such as stroke, renal insufficiency, and cardiac hypertrophy, had been initially perceived as a result of macrovascular alterations. These macrovascular events, however, do not occur independently of microvascular derangement. [2][3][4] Studies have shown that alterations in microvascular structure (rarefaction), vasomotor tonus (enhanced vasoconstriction or blunted vasodilation), and endothelial dysfunction are principal processes in the pathogenesis of hypertension and are evident in several organs/tissue types. [5][6][7][8] In the skeletal muscle, microvascularization is important for oxygen and nutrient supply and for effective metabolite clearance. Studies in hypertension have shown structural or functional impairments in the microvasculature within skeletal muscles, 8 implying a reduced capacity for oxygen delivery and exchange. Furthermore, animal studies using experimental models of hypertension suggested that mitochondrial dysfunction (ie, decreased expression of mitochondrial components and defects in respiratory complexes) and increased oxidative stress result in impaired oxidative capacity and reduced mitochondrial ATP production.9,10 Importantly, in these animals, the mitochondrial dysfunction and the reduced oxidative capacity were present before the development of hypertension, suggesting a possible role of these processes to the pathogenesis of hypertension.11 However, information on skeletal muscle microvascular alterations and oxidative Abstract-This study examined in vivo (1) skeletal muscle oxygenation and microvascular function, at rest and during handgrip exercise, and (2) their association with macrovascular function and exercise blood pressure (BP), in newly diagnosed, never-treated patients with hypertension and normotensive individuals. Ninety-one individuals (51 hypertensives and 40 normotensives) underwent office and 24-hour ambulatory BP, arterial stiffness, and central aortic BP assessment, followed by a 5-minute arterial occlusion and a 3-minute submaximal handgrip exercise. Changes in muscle oxygenated and deoxygenated hemoglobin and tissue oxygen saturation were continuously monitored by nearinfrared spectroscopy and beat-by-beat BP by Finapres. Hypertensives had higher (P<0.001) central aortic BP and pulse wave velocity versus normotensives and exhibited (1) a blunted tissue oxygen saturation response during occlusion, with slower (P=0.006) deoxygenation rate, suggesting reduced muscle oxidative capacity, and (2) a slower reoxygenation rate and blunted hyperemic response (P<0.05), showing reduced microvascular reactivity. Muscle oxygenation responses were correlated with aortic systolic and pulse pressure and augmentation index (P<0.05; age and body mass index (BMI) adjusted). When exercising at the same submaximal intensity, hypertensives required a sig...

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Twenty males ran either on a level treadmill (nonmuscle-damaging condition) or on a downhill treadmill (muscle-damaging condition). Blood and urine samples were collected before and after exercise (immediately after, 1h, 4h, 24h, 48h, and 96h). The following assays were performed: F(2)-isoprostanes in urine, protein carbonyls in plasma, glutathione, superoxide dismutase, glutathione peroxidase, and catalase in erythrocytes. The main finding was that monophasic redox responses were detected after nonmuscle-damaging exercise compared to the biphasic responses detected after muscle-damaging exercise. Based on these findings, muscle-damaging exercise may be a more appropriate experimental model to induce physiological oxidative stress.

Background-Human chorionic gonadotropin (hCG) is normally produced and secreted by trophoblastic cells during pregnancy and from gestational trophoblastic neoplasms. It is also detected in ovarian, stomach, and colon adenocarcinomas, as well as in squamous cell carcinoma of the oesophagus. Recently, interest in its role in the pathogenesis of tumours has been enlivened after the presence of hCG in the cell membrane of several malignant cells was shown in vitro. Aims-To investigate the circulating concentrations of hCG in patients with exocrine pancreatic adenocarcinoma and to examine its potential prognostic value. Patients-Thirty six patients with exocrine pancreatic adenocarcinoma, 12 patients with chronic pancreatitis, and 21 healthy volunteers were studied. Methods-hCG serum concentrations were detected by the application of a radioimmunoassay technique. Results-Fifteen of 36 patients with pancreatic adenocarcinoma and only one patient with chronic pancreatitis had detectable plasma concentrations of hCG (p<0.01). The patients with circulating serum titres of hCG had a worse outcome compared with the group of hCG negative patients: the diVerence was statistically significant (p=0.01). Conclusion-More than 40% of pancreatic exocrine tumours produce hCG and its production is correlated with an adverse eVect on outcome. (Gut 1998;42:88-91)

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Multiple endocrine neoplasia type 2A (MEN2A) is a syndrome of familial neoplasias characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperplasia of the parathyroid glands. RET protooncogene mutations are responsible for MEN 2A. Mutations in exons 10 or 11 have been identified in more than 96% of patients with MEN 2A. We herein report for the first time a patient with MEN 2A harboring a mutation (Gly(533)Cys) in exon 8. A 66-year old male patient was referred to our department for bilateral adrenal nodules. The patient's family history was remarkable in that his mother had pheochromocytoma. Biochemical evaluation and findings of the magnetic resonance imaging of the adrenals were compatible with the diagnosis of bilateral pheochromocytomas. The patient underwent laparoscopic bilateral adrenalectomy and histological examination confirmed the preoperative diagnosis of pheochromocytoma. Absence of phenotypic characteristics of VHL or NF1 and elevated calcitonin levels both basal and post pentagastrin stimulation, raised the possibility of MEN 2A syndrome. Total thyroidectomy was performed and histological examination showed the presence of MTC. Direct sequencing of exon 8 from the patient's genomic DNA revealed the mutation c.1,597G-->T (Gly533Cys). Although this missense point mutation has been associated with familial MTC (FMTC), to the best of our knowledge mutations in exon 8 have not previously been identified in patients with MEN 2A. In conclusion, in patients with clinical suspicion of MEN 2A syndrome, analysis of RET exon 8 should be considered when the routine evaluation of MEN 2A-associated mutations is negative. Furthermore, patients with FMTC and exon 8 mutations should also be screened for pheochromocytoma.

Medical and sports medicine associations are reluctant to endorse isometric exercise to the same extent as dynamic resistance exercise (RE). The major concern is the fear of greater increases in blood pressure (BP) that might be associated with isometric exercise. This review comprehensively presents all human studies that directly compared the magnitude of hemodynamic responses between isometric and dynamic RE. We also discuss possible mechanisms controlling BP-response and cardiovascular adjustments during both types of RE. The most prominent finding was that isometric and dynamic RE using small-muscle mass evoke equal increases in BP; however, the circulatory adjustments contributing to this response are different in dynamic and isometric RE. In contrast, studies using large-muscle mass report inconsistent results for the magnitude of BP-response between the two types of RE. Thus, when the same muscles and workloads are used, the increase in BP during isometric and dynamic RE is more comparable to what is commonly believed. However, it should be noted that only a few studies equalized the workload in two types of RE, most used small sample sizes, and all studies employed healthy participants. More studies are needed to compare the cardiovascular risks associated with isometric and dynamic RE, especially in individuals with chronic disease.