Decreased Brain Ventricular Volume in Psychiatric Inpatients with Serotonin Reuptake Inhibitor Treatment.

Background: Brain ventricles have been reported to be enlarged in several neuropsychiatric disorders and in aging. Whether human cerebral ventricular volume can decrease over time with psychiatric treatment is not well-studied. The aim of this study was to examine whether inpatients taking serotonin reuptake inhibitors (SRI) exhibited reductions in cerebral ventricular volume. Methods: Psychiatric inpatients, diagnosed mainly with depression, substance use, anxiety, and personality disorders, underwent two imaging sessions (Time 1 and Time 2, approximately 4 weeks apart). FreeSurfer was used to quantify volumetric features of the brain, and ANOVA was used to analyze ventricular volume differences between Time 1 and Time 2. Inpatients' brain ventricle volumes were normalized by dividing by estimated total intracranial volume (eTIV). Clinical features such as depression and anxiety levels were collected at Time 1, Time 1.5 (approximately 2 weeks apart), and Time 2. Results: Inpatients consistently taking SRIs (SRI + , n = 44) showed statistically significant reductions of brain ventricular volumes particularly for their left and right lateral ventricular volumes. Reductions in their third ventricular volume were close to significance (p = .068). The inpatients that did not take SRIs (SRI-, n = 25) showed no statistically significant changes in brain ventricular volumes. The SRI + group also exhibited similar brain structural features to the healthy control group based on the 90% confidence interval comparsions on brain ventricular volume parameters, whereas the SRI- group still exhibited relatively enlarged brain ventricular volumes after treatment. Conclusions: SRI treatment was associated with decreased brain ventricle volume over treatment.

Onset and progression of de novo donor-specific anti-human leukocyte antigen antibodies after BK polyomavirus and preemptive immunosuppression reduction.

BACKGROUND: BK polyomavirus (BKPyV) viremia/nephropathy and reduction in immunosuppression following viremia may increase the risk of alloimmune activation and allograft rejection. This study investigates the impact of BKPyV viremia on de novo donor anti-human leukocyte antigen (HLA)-specific antibodies (dnDSA). PATIENTS AND METHODS: All primary renal transplants at East Carolina University from March 1999 to December 2010, with at least 1 post-transplant BKPyV viral load testing, were analyzed. Patients were negative for anti-HLA antibodies to donor antigens (tested via single antigen beads) at transplantation and at first BKPyV testing. RESULTS: Nineteen of 174 patients (11%) tested positive for BKPyV viremia. Within 24 months of BKPyV viremia detection, 79% of BKPyV-viremic patients developed dnDSA. Only 20% of BKPyV viremia-persistent cases, compared to 86% of BKPyV viremia-resolved cases, developed dnDSA (P = 0.03). Poor allograft survival was evident in BKPyV viremia-persistent patients (60% failure by 2 years post BKPyV diagnosis) and in BKPyV viremia-resolved patients with dnDSA (5-year post BKPyV diagnosis allograft survival of 48%). CONCLUSIONS: Post-transplant BKPyV viremia and preemptive immunosuppression reduction is associated with high rates of dnDSA. When preemptively treating BKPyV viremia, dnDSA should be monitored to prevent allograft consequences.

Higher risk of kidney graft failure in the presence of anti-angiotensin II type-1 receptor antibodies.

Reports have associated non-HLA antibodies, specifically those against angiotensin II type-1 receptor (AT1R), with antibody-mediated kidney graft rejection. However, association of anti-AT1R with graft failure had not been demonstrated. We tested anti-AT1R and donor-specific HLA antibodies (DSA) in pre- and posttransplant sera from 351 consecutive kidney recipients: 134 with biopsy-proven rejection and/or lesions (abnormal biopsy group [ABG]) and 217 control group (CG) patients. The ABG's rate of anti-AT1R was significantly higher than the CG's (18% vs. 6%, p < 0.001). Moreover, 79% of ABG patients with anti-AT1R lost their grafts (vs. 0%, CG), anti-AT1R levels in 58% of those failed grafts increasing posttransplant. With anti-AT1R detectable before DSA, time to graft failure was 31 months-but 63 months with DSA detectable before anti-AT1R. Patients with both anti-AT1R and DSA had lower graft survival than those with DSA alone (log-rank p = 0.007). Multivariate analysis showed that de novo anti-AT1R was an independent predictor of graft failure in the ABG, alone (HR: 6.6), and in the entire population (HR: 5.4). In conclusion, this study found significant association of anti-AT1R with graft failure. Further study is needed to establish causality between anti-AT1R and graft failure and, thus, the importance of routine anti-AT1R monitoring and therapeutic targeting.

Impact on health-related quality of life in kidney transplant recipients with late posttransplant anemia administered darbepoetin alfa: results from the STRATA study.

Posttransplant anemia (PTA) is a common, multifactorial condition that has a substantial negative impact on patients' health-related quality of life (HRQOL). Erythropoietin-stimulating agents are an effective treatment for PTA, but there is little research on HRQOL in posttransplant patients. This multicenter, prospective study enrolled adults with PTA (hemoglobin [Hb] < 11.0 g/dL). Subjects (n = 66) received subcutaneous darbepoetin alfa every 2 weeks for 24 weeks. Hb and patient-reported outcomes using the Short Form (SF)-36 questionnaire were assessed. Mean (standard deviation) Hb concentration increased from 9.9 (1.2) g/dL at baseline to 11.7 (1.3) g/dL during the evaluation period (14 to 24 weeks). At baseline, SF-36 scores in all the eight domains were lower (worse) compared with the general population and patients with other chronic conditions. In subjects with baseline Hb < 10 g/dL, SF-36 subscales and component summary scores were lower than in subjects with Hb ≥ 10 g/dL. Following treatment with darbepoetin alfa, statistically significant improvements were observed for all subjects in physical component summary (0.5 points, P < .001), physical functioning (11.8 points, P = .001), limitations due to physical health (26.5 points, P < .001), bodily pain (7.7 points, P = .01), limitations due to emotional health (15.7 points, P = .01), and vitality (12.8 points, P < .001) from baseline to week 24. Clinically significant improvements (>5 points) were observed in six subscales: physical functioning, limitations due to physical health, limitations due to emotional health, bodily pain, social functioning, and vitality. Darbepoetin alfa in kidney transplant recipients with PTA significantly increased Hb concentrations and improved HRQOL scores.

Field efficacy of sweet corn hybrids expressing a Bacillus thuringiensis toxin for management of Ostrinia nubilalis (Lepidoptera: Crambidae) and Helicoverpa zea (Lepidoptera: Noctuidae).

Field studies were done in 1995-1996 to assess the efficacy of three sweet corn hybrids that express the Bacillus thuringiensis (Bt) toxin, CrylAb, against two lepidopteran pests, Ostrinia nubilalis (Hubner) and Helicoverpa zea (Boddie). The Bt hybrids tested were developed by Novartis Seeds, using the event BT-11, which expresses Bt toxin in green tissue as well as reproductive tissues including the tassel, silk, and kernel. Bt hybrids were compared with a standard non-Bt control or the non-Bt isoline for each hybrid; none of the hybrids were treated with insecticides during the study. Hybrid efficacy was based on larval control of each pest, as well as plant or ear damage associated with each pest. In both years, control of O. nubilalis larvae in primary ears of all Bt hybrids was 99-100% compared with the appropriate non-Bt check. Plant damage was also significantly reduced in all Bt hybrids. In 1996, control of H. zea in Bt hybrids ranged from 85 to 88% when compared with the appropriate non-Bt control. In 1996, a University of Minnesota experimental non-Bt hybrid (MN2 x MN3) performed as well as the Bt hybrids for control of O. nubilalis. Also, in 1996, two additional University of Minnesota experimental non-Bt hybrids (A684su X MN94 and MN2 X MN3) performed as well as Bt hybrids for percent marketable ears (ears with no damage or larvae). In addition, compared with the non-Bt hybrids, percent marketable ears were significantly higher for all Bt hybrids and in most cases ranged from 98 to 100%. By comparison, percent marketable ears for the non-Bt hybrids averaged 45.5 and 37.4% in 1995 and 1996, respectively. Results from the 2-yr study strongly suggest that Bt sweet corn hybrids will provide high levels of larval control for growers in both fresh and processing markets. Specifically, Bt sweet corn hybrids, in the absence of conventional insecticide use, provided excellent control of O. nubilalis, and very good control of H. zea. However, depending on location of specific production regions, and the associated insect pests of sweet corn in each area, some insecticide applications may still be necessary.

Cytomegalovirus-induced necrotizing and crescentic glomerulonephritis in a renal transplant patient.

A 35-year-old black man with end-stage renal disease from biopsy-proven focal segmental glomerulosclerosis developed worsening function of his renal allograft 160 days after living related donor renal transplantation. Renal biopsy showed necrotizing and crescentic glomerulonephritis (NCGN) and presence of intraglomerular viral inclusions confirmed by immunocytochemical stain and in situ hybridization techniques to be cytomegaloviral in origin. Electron microscopy showed no immune complexes, and workup for other causes of NCGN was negative. The patient was treated with ganciclovir without other changes in his immunosuppressive regimen. After 8 weeks of ganciclovir therapy, a second renal transplant biopsy showed resolution of the glomerular process and disappearance of the cytomegalovirus (CMV) inclusions. The resolution of the glomerular process with treatment for CMV infection, and without other change in therapy, strongly supports a causative link between CMV and NCGN in this patient. This case represents the first report of CMV-associated NCGN in a renal transplant patient.

Clinical response to prolonged corticosteroids in a patient with human immunodeficiency virus-associated nephropathy.

Human immunodeficiency virus-associated nephropathy (HIVAN) is characterized by massive proteinuria with rapidly progressive renal failure. We report an adult with HIV infection who developed nephrotic-range proteinuria and acute renal failure requiring hemodialysis. Renal biopsy findings were consistent with HIVAN, exhibiting focal and segmental glomerulosclerosis with dilated microcystic tubules filled with pale eosinophilic material. Institution of corticosteroid therapy was followed by significant improvement in renal function and proteinuria. Corticosteroids were tapered, and the patient experienced worsening of his renal failure and proteinuria. A second course of corticosteroids was again associated with improved renal function. This and other reports suggest that corticosteroids may improve the clinical course of HIVAN.

Cyclosporin-associated thrombotic microangiopathy: successful retreatment with cyclosporin.

This report describes a patient who developed cyclosporin-induced thrombotic microangiopathy in a renal allograft. Cyclosporin-induced thrombotic microangiopathy is considered by many as a contraindication to subsequent therapy with cyclosporin. This case is notable for successful treatment with cyclosporin following resolution of thrombotic microangiopathy in a renal allograft.

Acute and chronic responses of human renal kallikrein and kinins to dietary protein.

Glomerular filtration rate (GFR; creatinine clearance) and renal excretion rates of active kallikrein, prokallikrein, and kinins were measured in seven normal male subjects after a week on a constant low (40 g/day)-protein diet (LP) and during a subsequent week when only protein content was increased to 140 g/day (HP). Renal kinin excretion increased from 19.7 +/- 1.2 micrograms/day on day 7 of LP to 26.0 +/- 2.5 on day 1 of HP (P less than 0.002), and this higher rate persisted during HP. Active kallikrein excretion increased from 105 +/- 16 to 171 +/- 40 micrograms/day on day 2 of HP (P less than 0.006). Prokallikrein excretion did not increase significantly until day 4 of HP, 52 +/- 16 vs. 96 +/- 38 micrograms/day (P less than 0.03). The increases in active kallikrein and kinin excretion preceded an increase in GFR, which went from 117 +/- 6.8 ml/min on LP to 130 +/- 10 ml/min on day 5 of HP (P less than 0.003). At the end of the LP diet, acute ingestion of 40 g of a casein solution produced an increase in kinin excretion after 2 h (586 +/- 64 vs. 402 +/- 33 pg/min, P less than 0.001) and further to 640 +/- 74 pg/min at 3 h (P less than 0.001). This was accompanied by an increase in GFR at 3 h (154 +/- 18 vs. 132 +/- 10 ml/min, P less than 0.05). Kinin excretion rate correlated directly with GFR during both chronic (r = 0.87) and acute (r = 0.77) studies.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of isolation and aminooxyacetic acid (AOAA) on GABA in muricidal rats.

The influence of isolation was studied on the development of muricidal behavior and on brain GABA. GABA was significantly lower in several parts of the limbic system of brain taken from muricidal rats, when compared to their non-muricidal counterparts. Isolation potentiated the development of muricidal behavior and lowered GABA levels. Administration of aminooxyacetic acid (AOAA) resulted in a preferential elevation of GABA in the olfactory lobes. Muricidal behavior was inhibited during the AOAA-induced increase in GABA.