Suggestive evidence of a locus on chromosome 10p using the NIMH genetics initiative bipolar affective disorder pedigrees

As part of a four-center NIMH Genetics Initiative on Bipolar Disorder, a genome screen using 365 markers was performed on 540 DNAs from 97 families, enriched for affected relative pairs. This is the largest uniformly ascertained and assessed linkage sample for this disease, and includes 232 subjects diagnosed with bipolar I (BPI), 32 with schizo-affective, bipolar type (SABP), 72 with bipolar II (BPII), and 88 with unipolar recurrent depression (UPR). A hierarchical set of definitions of affected status was examined. Under Model I, affected individuals were those with a diagnosis of BPI or SABP, Model II included as affected those fitting Model I plus BPII, and Model III included those fitting Model II plus UPR. This data set was previously analyzed using primarily affected sib pair methods. We report the results of nonparametric linkage analyses of the extended pedigree structure using the program Genehunter Plus. The strongest finding was a lod score of 2.5 obtained on chromosome 10 near the marker D10S1423 with diagnosis as defined under Model II. This region has been previously implicated in genome-wide studies of schizophrenia and bipolar disorder. Other chromosomal regions with lod scores over 1.50 for at least one Model Included chromosomes 8 (Model III), 16 (Model III), and 20 (Model I). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:18-23, 2000 Copyright 2000 Wiley-Liss, Inc.     

Apparent replication of suggestive linkage on chromosome 16 in the NIMH genetics initiative bipolar pedigrees

Analyses of a replication sample of families collected as part of the National Institute of Mental Health (NIMH) Genetics Initiative for bipolar disorder provide further evidence for linkage to a region of chromosome 16. Families who had a bipolar I (BPI) proband and at least one BPI or schizoaffective, bipolar type (SABP) first-degree relative were ascertained for the purpose of identifying genes involved in bipolar affective disorder. A series of hierarchical models of affected status was used in linkage analyses. Initial genetic analyses of chromosomes 3, 5, 15, 16, 17, and 22, completed at Indiana University in 540 subjects from 97 families, suggested evidence of linkage to chromosomes 5, 16, and 22 [Edenberg et al., 1997: Am J Med Genet 74:238-246]. Genotyping was subsequently performed on these chromosomes in a replication sample of 353 individuals from 56 families. Nonparametric linkage analyses were performed using both affected relative and sibling pair methods. Analyses in the new sample on chromosome 16, using the broadest model of affected status, corroborate previously reported suggestive linkage to the marker D16S2619. Combining the initial and replication samples further increased the evidence of linkage to this region, with a peak lod score of 2.8.     

Single motor unit analysis from spatially filtered surface electromyogram signals. Part 2: Conduction velocity estimation

The aim of the study was to compare experimentally conduction velocity (CV) estimates obtained with different estimation methods based on surface electromyogram (EMG) signals detected using five spatial filters. The filters investigated were the longitudinal single and double differential, transverse single and double differential, and normal double differential. The same surface EMG signals detected as described in Part 1 were used in this work. CV was estimated with four commonly used delay estimation techniques, i.e. from the distance between the peak values of two waveforms (with and without polynomial interpolation around the peak), and by the maximum likelihood estimate (MLE) based on two or more surface EMG channels. The average standard deviation of CV estimation (for all the MUs and the two muscles together) was 0.61 ms⁻¹ and 0.79 ms⁻¹ for the peak method, with and without interpolation, respectively, and 0.50ms⁻¹ and 0.31 ms⁻¹ for the MLE method, from two and more surface EMG channels, respectively. Moreover, the mean of CV estimates varied by as much as 1 ms⁻¹ depending on the spatial filter used and the method adopted for CV estimation. Considering the dependence on the spatial filter only, the average (over all estimation methods) CV estimates obtained with the five spatial filters were 4.32 ms⁻¹ (normal double differential), 4.23ms⁻¹ (longitudinal double differential), 4.61 ms⁻¹ (transverse double differential), 4.64ms⁻¹ (transverse single differential) and 4.03 ms⁻¹ (longitudinal single differential). It was concluded that the comparison of single MU CV values obtained in different studies is critical if different spatial filters and processing techniques are used for their estimation. Higher estimates of CV were attributed to a smaller reduction in non-travelling signal components and thus were assumed to be positively biased.     

Functional MRI correlates of the recall of unresolved life events in borderline personality disorder

BACKGROUND: Patients with borderline personality disorder (BPD) frequently report unresolved life events but it is still poorly understood, how these experiences are represented in the brain. Using functional magnetic resonance imaging (fMRI), the present study aimed at investigating the neural correlates of the recall of unresolved life events in patients with BPD and healthy controls. METHOD: Twenty female BPD patients and 21 healthy control subjects underwent fMRI. During measurement subjects recalled unresolved and resolved negative life events. Individual cue words were used to stimulate autobiographical memory. After scanning, subjects rated their emotional states during the recall of both types of memories. RESULTS: When contrasting unresolved and resolved life events, patients showed significant bilateral activation of frontotemporal areas including the insula, amygdala, and the anterior cingulate cortex, the left posterior cingulate cortex, right occipital cortex, the bilateral cerebellum and the midbrain. In healthy subjects, no differential brain activation was related to these conditions. The 2 x 2 factorial analysis (DeltaBPD - Deltacontrols) revealed similar results with bilateral activation of the frontal cortex including parts of the insula and of the orbitofrontal cortex, temporal activation including the amygdala, activation of the right occipital cortex, and parts of the cerebellum. Patients but not controls reported higher levels of anxiety and helplessness during the unresolved versus resolved memory condition. CONCLUSIONS: The activation of both, the amygdala and prefrontal areas, might reflect an increased effortful but insufficient attempt to control intensive emotions during the recall of unresolved life events in patients with BPD.     

A three year comparative study of auranofin and gold sodium thiomalate in rheumatoid arthritis

Summary One hundred twenty-one patients with active RA were randomly assigned to receive 6 mg auranofin (AF)/day (60 patients) or 50 mg gold sodium thiomamate (GST)/week (62 patients) in a double-blind fashion. There were no intergroup differences with respect to sex, age, duration (median 2 years), stage and activity of the disease. In the case of striking improvement after 24 weeks a dose reduction to 50 mg GST/month or 4 mg AF/day was allowed and carried out in all GST patients and no AF patient. The serum gold levels were 5 times higher with weekly GST, they approached those of the AF group with monthly GST injections. The clinical parameters — number of swollen joints, activity index, articular index, grip strength, ESR — improved significantly in both groups, but grip strength, articular index and ESR improved more pronounced in the GST group. The X-ray progression (hands and forefeet) was significantly greater in the AF group. Fourthy eight AF patients (80%) and 39 GST patients (36%) completed the first year. Thereafter the study was continued as an open study but the patients were allowed to switch from GST to AF. After the first and second year 14/7 GST patients switched to AF. The second/third year was completed by 37/22 AF pat. (62%/37%) and by 15/8 GST pat. (24%/13%). Skin reactions were more common with GST (41.9%/26.7%), diarrhoea was more common with AF (36.7%/19.4%), proteinuria occurred in 10% in both groups, leucopenia and thrombocytopenia were rare in both groups (1.7%). The withdrawal rate due to adverse events was 10%/26% in the AF/GST group during the first year (p<0.05) and 25%/32% over the three year period (n.s.).Conclusion Both AF and GST are effective in the long-term treatment of RA, but GST is more so in radiological progression and ESR.     

Context‐dependent coding and gain control in the auditory system of crickets

Sensory systems process stimuli that greatly vary in intensity and complexity. To maintain efficient information transmission, neural systems need to adjust their properties to these different sensory contexts, yielding adaptive or stimulus‐dependent codes. Here, we demonstrated adaptive spectrotemporal tuning in a small neural network, i.e. the peripheral auditory system of the cricket. We found that tuning of cricket auditory neurons was sharper for complex multi‐band than for simple single‐band stimuli. Information theoretical considerations revealed that this sharpening improved information transmission by separating the neural representations of individual stimulus components. A network model inspired by the structure of the cricket auditory system suggested two putative mechanisms underlying this adaptive tuning: a saturating peripheral nonlinearity could change the spectral tuning, whereas broad feed‐forward inhibition was able to reproduce the observed adaptive sharpening of temporal tuning. Our study revealed a surprisingly dynamic code usually found in more complex nervous systems and suggested that stimulus‐dependent codes could be implemented using common neural computations.     

Evaluation of renal transplant donors with 16-section multidetector CT angiography: comparison of contrast media with low and high iodine concentrations

PURPOSE: To compare the degree of contrast enhancement, image quality, and accuracy of renal computed tomographic (CT) angiography performed with a 16-detector row CT unit and equal iodine doses of low- and high-iodine-concentration contrast medium in the evaluation of renal transplant donors. MATERIALS AND METHODS: Eighty donors scheduled to undergo renal CT angiography with 16-detector row CT were administered nonionic contrast media with two iodine concentrations. The first group (group A, n=40) received a contrast medium with 300 mg of iodine per milliliter, and the second group (group B, n=40) received a contrast medium with 370 mg of iodine per milliliter. An equal iodine dose of 550 mg per kilogram body weight was given to both groups. Contrast enhancement was quantified by measuring attenuation in the abdominal aorta and in both renal arteries. Subjective assessment of contrast enhancement, quality of reformatted images, and visualization of branch order of renal arteries were rated with a 5-point scale. The number of renal arteries and veins seen at CT was correlated with the results at surgery. RESULTS: The mean enhancement values in group B were significantly greater (P<.001) than those in group A. The mean HU (+/-standard deviation) in groups A and B were 298+/-76 and 344+/-75, respectively, in the aorta, 284+/-74 and 331+/-71 in the right renal artery, and 285+/-72 and 329+/-73 in the left renal artery. The mean enhancement, image quality, and branch orders visualized were rated better in group B than in group A (P<.01). The accuracies for correctly identifying renal arteries and veins, respectively, were 91% and 95% for group A and 96% and 96% for group B. CONCLUSION: Renal donor CT angiography with a contrast medium of 370 mg of iodine per milliliter provides greater enhancement and image quality compared with a contrast medium of 300 mg of iodine per milliliter. The diagnostic accuracies were similar.     

On-line monitoring of multiple precordial leads in high risk patients with coronary artery disease--a pilot study

In a pilot study, a computerized precordial mapping system monitored ischaemia on-line in 50 patients (40 with acute myocardial infarction and 10 with unstable angina, class IV (Canadian Cardiovascular Society). All had ST-segment depression or elevation greater than or equal to 0.2 mV in one or more precordial leads when they were admitted to our coronary care unit. After preliminary precordial mapping with 48 electrodes to localize the area of ischemia, 5 to 8 electrodes were placed in and around the centre of the ST-segment changes. The patients were monitored between 24 and 48 h (mean 35.5 h). To minimize problems caused by artifacts, ECG signal quality was improved by the averaging technique. Thereafter, the ECG was evaluated with respect to Q and R wave amplitudes and ST-segment changes. At 3 min intervals, Q and R wave amplitudes and ST segment elevations or depressions, summed for all leads were plotted as a histogram. ECG signal quality was excellent and there were no problems with the attachment of the electrodes. All patients were treated with nitroglycerine intravenously and high doses of heparin and, in several cases, nifedipine as well. Some patients received thrombolytic therapy with streptokinase. Despite therapy, 21 ischaemic attacks were documented in five patients. Seventeen attacks were seen in patients with acute infarction but who were not treated with streptokinase. All attacks were accompanied by chest pain. The duration of ischaemia ranged from 18 to 87 min. Several attacks were stopped immediately by therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Incidence of ischemic stroke post-chemotherapy: a retrospective review of 10,963 patients

OBJECTIVE: Vascular occlusion is not an uncommon event in malignancy. However, the frequency of ischemic stroke after chemotherapy has been mentioned only occasionally in clinical studies. A large-scale study is lacking. METHODS: A retrospective study was conducted at Chang Gung Memorial Hospital, Kaohsiung, Taiwan, to analyze the incidence of ischemic stroke post-chemotherapy, further, to evaluate a possible causative relationship between the ischemic stroke and the chemotherapy regimen, the interval between the latest chemotherapy session and onset of ischemic stroke and the survival of patients with ischemic stroke post-chemotherapy. The data were retrieved from the Cancer Database from 1993 to 2004. RESULTS: During this period, a total of 10,963 patients, with malignancies were followed-up for 1 month after chemotherapy, underwent 45,294 chemotherapy sessions. Among this group, there were 15 patients experiencing 16 ischemic strokes within the first month after the latest chemotherapy. Among them, 14 patients were followed-up until death and one patient was lost in follow-up after discharge against medical advice. The incidence of post-chemotherapy ischemic stroke was 0.137% and the frequency of chemotherapy cycles complicated by ischemic stroke was 0.035%. Adenocarcinoma was the most common histological type not only in ischemic stroke (40%) but also in overall patients (36.7%). The hemispheric stroke with middle cerebral artery territory involvement was the most common image finding. Platinum compounds, especially cisplatin, were the most commonly used chemotherapeutic agents for ischemic stroke patients. Twelve (75%) of these 16 ischemic strokes occurred within 10 days of the latest chemotherapy session and 10 (62.5%) occurred after the first cycle of chemotherapy. The median survival after ischemic stroke was 4 weeks. CONCLUSION: Our results provide valuable data on the relationship between malignancy, treated with chemotherapy, and ischemic stroke. The risk of ischemic stroke after chemotherapy is predicted by the use of cisplatin-based chemotherapy not cancer histologic type. Infarction usually involves the territorial subtype, causes obvious neurological disabilities and carries a grave prognosis.