Application of a new image analysis technique to study brain asymmetry in schizophrenia

The hypothesis that normal brain torque (i.e. rightward frontal and leftward occipital asymmetry) is anomalous in schizophrenia (Crow, 1997. Trends in Neuroscience, 20, 339-343) was tested by application of a novel image analysis technique on three-dimensional magnetic resonance images obtained in 26 adult patients with chronic schizophrenia (18 males, 8 females) and 24 controls (14 males, 10 females). Right and left cerebral hemisphere tissue was extracted via non-linear co-registration with a mask image, and maps were computed of inter-hemispheric differences in tissue volume in an array of columns of voxels orthogonal to the mid-plane (2D), and profiles of coronal slice volumes (1D). Furthermore, integration of two-dimensional column maps gave approximate lobar asymmetries, and occipital and frontal asymmetries were combined to give a volumetric measure of brain torque. Significant brain torque was revealed in male and female control and patient groups, and did not correlate with brain size. Frontal and occipital asymmetries were significantly correlated in all groups. Both frontal and occipital components of torque were significantly increased in males than females. Patients tended to have reduced torque, particularly the leftward occipital component. Furthermore, 3/26 patients (but no controls) had reversed torque (leftward frontal and rightward occipital asymmetry). Contrary to Crow's hypothesis, brain torque was not significantly reduced in patients with schizophrenia relative to controls, although reversal of torque was found in three cases. Future studies with larger sample sizes should consider sexual dimorphism and specific symptoms in relation to asymmetry.     

Prevalence of prostatitis-like symptoms in a community based cohort of older men

PURPOSE: We describe a community based study to estimate the prevalence of prostatitis-like symptoms using questions similar to the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). MATERIALS AND METHODS: Study subjects were a randomly selected sample of Olmsted County, Minnesota white men 40 to 79 years old in January 1990 who participated in a longitudinal study of lower urinary tract symptoms. Subjects were evaluated biennially using self-administered questionnaires. In 2000 questions similar to the NIH-CPSI were incorporated into the questionnaire and questionnaire responses were used to categorize men as having prostatitis-like symptoms. RESULTS: Of 1,541 men 182 (12%) had at least 1 urogenital pain symptom. Pubic (76 men, 4.9%) and testicular (73, 4.7%) pain were the most frequent pain symptoms. A total of 34 men with prostatitis-like symptoms (2.2%) had higher mean pain (6.7 versus 0.5), urinary symptom (3.5 versus 2.1) and quality of life impact (3.7 versus 1.9) scores compared to men who did not (all p <0.001). Pain frequency (OR 39.2, 95% CI 18.8, 81.9) and pain intensity (OR 21.5, 95% CI 8.7, 52.9) were more strongly associated with prostatitis-like symptoms than urinary symptom score (OR 2.8, 95% CI 1.4, 5.6) or quality of life impact score (OR 4.5, 95% CI 1.9, 10.7). CONCLUSIONS: Although urogenital pain is common among community dwelling men, prostatitis-like symptoms based on the modified questions from the NIH-CPSI are less common. While pain measures may be useful in distinguishing between men with and without prostatitis-like symptoms, the urinary symptom and quality of life impact scores could partly reflect benign prostatic hyperplasia.     

Ionizing radiation potentiates the antitumor efficacy of oncolytic herpes simplex virus G207 by upregulating ribonucleotide reductase

BACKGROUND: Replication-competent herpes simplex virus-1 (HSV-1) mutants have an oncolytic effect on human and animal cancers. The aim of this study was to determine whether G207, an HSV-1 mutant, can be combined with ionizing radiation (IR) to increase antitumor activity while decreasing treatment-associated toxicity. METHODS: This study was performed by using G207, a replication-competent HSV-1 mutant deficient in viral ribonucleotide reductase (RR) and the gamma(1)34.5 neurovirulence protein. The antitumor activity of G207 or IR was tested against HCT-8 human colorectal cancer cells in vitro and in an in vivo mouse subcutaneous tumor model. RESULTS: We demonstrated that G207 has significant oncolytic effect on HCT-8 cells in vitro in a cytotoxicity assay and in vivo in a mouse flank tumor model and that these effects are improved with low-dose IR. We further illustrated that the increased tumoricidal effect is dependent on the up-regulation of cellular RR by IR measured by a functional bioassay for RR activity. Chemical inhibition of RR by hydroxyurea abrogates the enhanced effect. In contrast to G207, R3616, the parent virus of G207 that expresses functional RR, does not exhibit enhanced oncolysis when combined with IR. CONCLUSIONS: These data encourage clinical investigation of combination radiation therapy and HSV oncolytic therapy.     

Elevated serum parathormone level after "concise parathyroidectomy" for primary sporadic hyperparathyroidism

BACKGROUND: Cure after parathyroid exploration is traditionally assessed by serum calcium concentration 6 months postoperatively. Postoperative normocalcemic elevation of serum parathormone (PTH) level has been described but is of unclear significance. METHODS: In a 6-year prospective study of outcomes in 380 patients undergoing initial parathyroidectomy for primary sporadic hyperparathyroidism, we measured intact serum PTH and calcium levels at more than 5 months. Those with normocalcemic high PTH levels were begun on oral calcium + vitamin supplements and monitored. RESULTS: At more than 5 months postoperatively, normocalcemic elevation in serum PTH level occurred in 28% of patients, was more common after resection of double adenomas (P =.01), and predated the onset of recurrent hypercalcemia in 3 of 3 patients with unrecognized multiglandular disease. Although delayed treatment with calcium and vitamin supplements produced no clear benefit, patients who took such supplements from the date of surgery were much less likely to have an elevated serum PTH level more than 5 months later (P =.0005). CONCLUSIONS: After successful parathyroid surgery, compensatory normocalcemic elevation in serum PTH level is frequent and may arise from dietary deficiency. Monitored supplemental intake of calcium and vitamin D appears to prevent or to normalize the condition in most patients. Patients with normocalcemic elevation in serum PTH level should receive evaluation for dietary deficiencies as well as follow-up for possible residual disease.     

Inhibition of chronic vascular rejection by donor-specific blood transfusion is associated with a reduction in transforming growth factor-beta1 expression

BACKGROUND: Concentric intimal thickening and the infiltration of inflammatory cells in cardiac allografts are the pathological hallmark characteristics of chronic vascular rejection (CVR), the leading cause of long-term graft failure. The precise mechanisms involved in the development and pathogenesis of CVR remain elusive. In the PVG-R23 to PVG-RT1u rat model of CVR, prior administration of a donor-specific transfusion (DST) was previously shown to prolong graft survival indefinitely and abolish the vascular lesions associated with CVR. The present study investigates in more depth the underlying mechanisms involved in the subsequent prolongation of allograft survival and inhibition of CVR by DST. METHODS: R23 heart grafts were monitored in nontransfused and transfused RT1u recipients injected 2 weeks before transplantation with 1.5 ml of R23 blood. Severity of arteriosclerosis, transplant infiltrate, transforming growth factor (TGF)-beta1 protein expression within the graft, plasma TGF-beta1 levels, class II MHC expression, tenascin protein expression, and serum alloantibody levels were measured. RESULTS: There was no significant difference in donor MHC class II, myocardial TGF-beta1, or tenascin expression between DST and non-DST-treated recipients. However, DST-pretreated recipients showed greatly reduced histological evidence of CVR and had lower titers of R23-specific IgG subclasses. Furthermore, DST-treated allograft recipients showed significant decreases in circulating TGF-beta1 levels and a reduction in TGF-beta1 and tenascin expression within coronary arteries of the allografts. CONCLUSION: The results suggested that DST inhibited CVR by altering and regulating the expression of TGF-beta1, thereby preventing the fibrogenic effects associated with TGF-beta1.