Genome scan for susceptibility loci for schizophrenia and bipolar disorder.

BACKGROUND: Despite the widely accepted view that schizophrenia and bipolar disorder represent independent illnesses and modes of inheritance, some data in the literature suggest that the diseases may share some genetic susceptibility. The objective of our analyses was to search for vulnerability loci for the two disorders. METHODS: A genomewide map of 388 microsatellite DNA markers was genotyped in five schizophrenia and three bipolar disorder Austrian families. Linkage analyses was used to compute the usual parametric logarithm of the likelihood of linkage (LOD) scores and nonparametric linkage analysis (NPL scores Z(all)) was used to assess the pattern of allele sharing at each marker locus relative to the presence of the disease (GENEHUNTER). Affected status was defined as severe affective disorder or schizophrenia. RESULTS: Across the genome, p values associated with NPL scores resulted in evidence (i.e., p <.0007) for linkage at marker D3S1265 on chromosome 3q (NPL score Z (all) = 3.74, p =.0003). Two other markers (on 3q and 6q) showed p values of <.01. CONCLUSIONS: We detected a potential susceptibility locus for bipolar disorder and schizophrenia on chromosome 3q, which has not been reported previously. The possibility of a false positive result has to be taken into account. Our data suggest shared loci for schizophrenia and bipolar affective disorders and are consistent with the continuum model of psychosis.     

18F-fluorodeoxythymidine PET for evaluating the response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcomas.

Locally advanced soft-tissue sarcomas of an extremity can be treated either by amputation of the limb or by hyperthermic isolated limb perfusion (HILP) followed by resection of the tumor. In this study, the response to HILP was measured by PET with (18)F-fluorodeoxythymidine ((18)F-FLT). METHODS: Ten patients with primary nonresectable soft-tissue sarcomas of an extremity underwent HILP with tumor necrosis factor-alpha and melphalan. Before and after HILP, all patients underwent PET with (18)F-FLT for response evaluation. RESULTS: Before HILP, all tumors were clearly visible on (18)F-FLT PET; for the maximum standardized uptake value (SUV(max)), the mean was 3.5 (range, 1.0-6.7), and for the mean standardized uptake value (SUV(mean)), the mean was 1.9 (range, 0.7-2.7). After HILP, all but 1 tumor showed necrosis ranging from 10% to 95%. (18)F-FLT PET after HILP revealed significantly decreased uptake of the tracer. The mean SUV(max) decreased to 1.7 (P = 0.008), and the mean SUV(mean) decreased to 0.8 (P = 0.002). One small axillary lymph node metastasis was not visible on (18)F-FLT PET. CONCLUSION: (18)F-FLT PET revealed high uptake in soft-tissue sarcomas. (18)F-FLT uptake was correlated with the mitotic index of the tumors (r = 0.82 and P = 0.004 for SUV(max); r = 0.87 and P = 0.001 for SUV(mean)). After HILP, the uptake of (18)F-FLT decreased significantly (P = 0.008 and P = 0.002 for SUV(max) and SUV(mean), respectively). Tumors with initially high (18)F-FLT uptake showed a better response to HILP (r = 0.64, P < 0.05). Software fusion of PET images with images from conventional imaging modalities revealed the heterogeneity of the tumors before and after HILP. Such data can help a surgeon in planning the resection of a tumor.     

Acute chemotherapy-induced cardiovascular changes in patients with testicular cancer.

PURPOSE: After cisplatin- and bleomycin-containing chemotherapy for testicular cancer, part of the patient population will develop acute or long-term cardiovascular toxicity. It is largely unknown whether standard tests can be used to assess chemotherapy-induced cardiovascular changes. PATIENTS AND METHODS: In 65 testicular cancer patients (median age, 27 years; range, 18 to 48 years), we measured the following cardiovascular parameters before and within 10 weeks after completion of cisplatin-based chemotherapy: platelet numbers, plasma levels of hemostatic and fibrinolytic factors, 24-hour ambulatory blood pressure, baroreflex sensitivity, intima-media thickness of the common carotid artery, and flow-mediated vasodilation of the brachial artery. RESULTS: Compared with prechemotherapy values, the intima-media thickness of the carotid artery and plasma von Willebrand factor levels increased significantly after treatment. Platelet numbers and plasma levels of other hemostatic and fibrinolytic factors did not appear to change significantly. Blood pressure decreased significantly, but flow-mediated vasodilation and baroreflex sensitivity did not change. CONCLUSION: In testicular cancer patients treated with cisplatin-based chemotherapy, we found an increase in plasma von Willebrand factor levels and in the intima-media thickness of the carotid artery. These changes may indicate chemotherapy-induced vascular damage and be of prognostic significance for the development of cardiovascular complications in the long term.     

Dynamic MR imaging of human brain oxygenation during rest and photic stimulation.

Dynamic FLASH (fast low-angle shot) magnetic resonance (MR) imaging was used to monitor changes in brain oxygenation in the human visual cortex during photic stimulation. The approach exploits the sensitivity of the gradient-echo signal to susceptibility changes induced by varying concentrations of paramagnetic deoxyhemoglobin in the cerebral blood pool. After the onset of binocular photic stimulation (10 Hz, red light, checker-board), there was a distinct increase in the MR signal in the calcarine cortex within 6-9 seconds, indicating a decrease in the total deoxyhemoglobin concentration. After the stimulation was switched off, the MR signal returned to a basal value within a similar period of time. Assuming enhanced blood flow and only a minor increase in oxygen consumption (production of deoxyhemoglobin) during physiologic activation, the results reflect an enhanced supply of diamagnetic oxyhemoglobin and an increase in the partial oxygen pressure in the capillary and venous blood pools. In addition, a decrease in the basal MR signal in the calcarine cortex was observed during the first 60-90 seconds of persistent activation, which may be understood as an autoregulatory adaptation to increased overall brain activity associated with information processing due to continuous perception of visual stimuli.     

Distribution patterns of muscle fibre types in major muscles of the bull (Bos taurus).

Summary The study describes the variations in distribution and cross-sectional area (fibre size) of three muscle fibre types (I, IIA, IIB) in 34 of the largest muscles of the bull (Bos taurus). The animals had been kept strictly unexercised for one year before slaughter. Representative sampling was done at 15 positions within each muscle, and from 2700 to 4500 fibres were analysed in each muscle. Different intermuscular patterns are described. The overall volume fraction (%) of type I fibres was about 10% higher in the forepart muscles than in the hindpart muscles (41% and 31%, respectively), while the mean content of type IIB fibres was similar. Type I fibres were particularly abundant in antigravity muscles. Of these, the hindlimb muscles contained 50% more type I fibres (by weight) than those of the forelimb. Typical antigravity antagonists contained very few type I fibres. In the thigh cross-section the proportion of type I fibres was highest in the anterior and medial parts, while the IIB fibres tended to be concentrated in the superficial and posterior parts. Intramuscular patterns were revealed, with type I fibres becoming gradually more abundant from superficial to deep regions, while IIB fibres had an opposite distribution. This was particularly evident in the thigh proper and in the scapular region. Within each fasciculus of all the muscles, the I fibres in the muscles of the forepart were on average about 15% larger than those of the muscles in the hindpart. The IIB fibres were on average about 10% larger in the hindpart than in the forepart muscles. A covariation between the proportion of type I and IIB fibres and their cross-sectional area was indicated.