Modelling difficulties in abstract thinking in psychosis: the importance of socio-developmental background.

INTRODUCTION: Abstract thinking is important in modern understanding of neurocognitive abilities, and a symptom of thought disorder in psychosis. In patients with psychosis, we assessed if socio-developmental background influences abstract thinking, and the association with executive functioning and clinical psychosis symptoms. METHODS: Participants (n = 174) had a diagnosis of psychotic or bipolar disorder, were 17-65 years, intelligence quotient (IQ) > 70, fluent in a Scandinavian language, and their full primary education in Norway. Immigrants (N = 58) were matched (1:2) with participants without a history of migration (N = 116). All participants completed a neurocognitive and clinical assessment. Socio-developmental background was operationalised as human developmental index (HDI) of country of birth, at year of birth. Structural equation modelling was used to assess the model with best fit. RESULTS: The model with best fit, χ2 = 96.591, df = 33, p < .001, confirmed a significant indirect effect of HDI scores on abstract thinking through executive functioning, but not through clinical psychosis symptoms. CONCLUSIONS: This study found that socio-developmental background influences abstract thinking in psychosis by indirect effect through executive functioning. We should take into account socio-developmental background in the interpretation of neurocognitive performance in patients with psychosis, and prioritise cognitive remediation in treatment of immigrant patients.

Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci.

Converging evidence implicates immune abnormalities in schizophrenia (SCZ), and recent genome-wide association studies (GWAS) have identified immune-related single-nucleotide polymorphisms (SNPs) associated with SCZ. Using the conditional false discovery rate (FDR) approach, we evaluated pleiotropy in SNPs associated with SCZ (n=21,856) and multiple sclerosis (MS) (n=43,879), an inflammatory, demyelinating disease of the central nervous system. Because SCZ and bipolar disorder (BD) show substantial clinical and genetic overlap, we also investigated pleiotropy between BD (n=16,731) and MS. We found significant genetic overlap between SCZ and MS and identified 21 independent loci associated with SCZ, conditioned on association with MS. This enrichment was driven by the major histocompatibility complex (MHC). Importantly, we detected the involvement of the same human leukocyte antigen (HLA) alleles in both SCZ and MS, but with an opposite directionality of effect of associated HLA alleles (that is, MS risk alleles were associated with decreased SCZ risk). In contrast, we found no genetic overlap between BD and MS. Considered together, our findings demonstrate genetic pleiotropy between SCZ and MS and suggest that the MHC signals may differentiate SCZ from BD susceptibility.

Partial volume corrected 18F-FDG PET mean standardized uptake value correlates with prognostic factors in breast cancer.

AIM: The aim of this paper was to assess the prognostic role of pretherapy partial volume corrected (PVC) 18F-fluorodeoxyglucose mean standardized uptake value (SUV) in breast cancer (BC). METHODS: Forty oncological patients, BC diagnosed by biopsy, with breast tumor mass diameter >1 cm measured to the mammography, designed for surgical intervention, underwent a pretherapy semi-quantitative 18F-FDG positron emission tomography/computed tomography (18F-FDG PET/CT) whole-body study for tumor staging. Mean Body-Weight Standardized Uptake Value with Correction for Partial Volume effect (PVC- SUVBW-mean) was calculated in all mammary detected lesions. Excised tissues from primitive BC were sectioned and classified according to the WHO guidelines, evaluating biological features. Univariate (Mann-Withney/Kruskal-Wallis) and multivariate (linear regression, hierarchical clustering) statistical tests were performed between PVC-SUVBW-mean and biological indexes. ROC analysis was performed. PVC-SUVBW-mean thresholds were derived allowing to distinguish groups of BC patients with different biological characteristics. Specificity and Sensitivity were also calculated. RESULTS: Statistical and multiple correlations between pretherapy 18F-FDG PET PVC-SUVBW-mean and histological type, grade, ER/PgR hormone receptors and Mib-1 cellular proliferation index were found. In our samples, PVC-SUVBW-mean <≈4 g/cc was found correlated to BC patients with Invasive Lobular Carcinoma (ILC) or well differentiated Invasive Ductal Carcinoma (IDC), a positive expression of ER and PgR and a negative expression of MiB-1, while PVC-SUVBW-mean >≈7.00 is associated to BC patients with moderately and poorly differentiated IDC, negative expression of ER and PgR and a positive expression of MiB-1. CONCLUSION: Pretherapy PVC 18F-FDG PET PVC-SUVBW-mean measurement correlates with prognostic factors in BC and could be used to stratify patients before intervention.

Nonpalpable breast lesions: preoperative radiological guidance in radioguided occult lesion localisation (ROLL).

PURPOSE: This study evaluated the methods, technical aspects and impact of preoperative radiological guidance in radioguided occult lesion localisation (ROLL) for single nonpalpable breast lesions. MATERIALS AND METHODS: A total of 288 patients underwent ROLL before surgery. Human serum albumin macroaggregates labelled with 3.7-7.4 MBq of technetium(99) were injected into the lesion. In the case of ultrasonographic guidance (221/288 patients), inoculum positioning resulted in a change of echogenicity at the lesion site. In the case of mammographic guidance (67/288 patients), iodinated contrast medium was injected following the radiotracer for subsequent mammographic evaluation. Patients underwent surgery within 24 h from ROLL. A gamma-detecting probe was used to locate the lesion during surgery and guide its removal. After excision, the specimen was examined by either ultrasonography or mammography to verify complete lesion removal before histological evaluation. RESULTS: The lesion was correctly localised in 281/288 patients (97.5%). One ROLL procedure failed because surgery could not be performed within 24 h and the radioactivity decayed. Of the six incorrect localisations, 2 were due to the radiological guidance and 4 to technetium(99) dispersion. CONCLUSIONS: Radiological guidance in ROLL ensured the outcome of the procedure of localisation and removal of single, nonpalpable breast lesions in the majority of cases.

Impact of recipient and donor ages on patient and graft survival after kidney transplantation.

BACKGROUND: The purpose of the study was to evaluate the impact of donor and recipient ages on patient and graft survival after kidney transplant. METHODS: Patients in a hospital database undergoing kidney transplant for end-stage renal disease (ESRD) during the period 1985 to May 2006 (n = 410; mean age 42 +/- 10 years; 61% men and 39% women) were divided into two groups: group A, patients of 60 years or older (6%, n = 24), and group B, those younger than 60 years (94, n = 386). In 204 patients (49.8%) the pancreas was transplanted simultaneously with the kidney. RESULTS: Overall 1-, 3-, 5-year patient survivals were 92%, 90%, 88% in group A and 95%, 90%, 87% in group B (P = .6, NS). Overall 1-, 3-, 5-year kidney graft was 92%, 75%, 65% in group A and 92%, 84%, 79% in group B (P = .7, NS). Donors were divided into two groups: group 1, 55 years or older (15%, n = 62), versus group 2, those younger than 55 years (85%, n = 348). Overall 1-, 3-, 5-year patient survivals were 91%, 86%, 76% in group 1 and 97%, 94%, 90% in group 2 (P = .0009). Overall 1-, 3-, 5-year kidney graft survivals were 87%, 82%, 76% in group 1 and 94%, 86%, 82% in group 2 (P = .02). CONCLUSIONS: Renal transplantation is an effective option for the treatment of ESRD in elderly patients. The overall rates of patient and kidney graft survival are comparable to those of younger patients. Donor age > or =55 years had a negative effect on patient and kidney graft survival.

Triple arterial reconstruction improves vascularization of whole pancreas for transplantation.

We assessed the effect on duodenal stump vascular supply of reconstruction of the gastroduodenal artery performed before pancreas transplantation. The median pancreas graft and patient survival times were 144 and 72 months for cases with or without gastrointestinal bleeding. Transmural blood flow values were significantly different between the donor duodenal stump and the recipient anastomosed jejunum (P < .01). The rate of gastrointestinal bleeding was lower in patients who received a pancreatic graft with back-table reconstruction of the gastroduodenal artery (P = .005).

Cardiovascular benefits of simultaneous pancreas-kidney transplant versus kidney alone transplant in diabetic patients.

UNLABELLED: The aim of our study was to demonstrate the cardiovascular benefits of simultaneous pancreas-kidney transplantation when compared to kidney-alone transplants in diabetic recipients. PATIENTS AND METHODS: A total of 386 renal transplants were performed from 1985 to 2004, including 262 (68%) in diabetic recipients and 124 (32%) in nondiabetics. Among the former group, 200 kidneys were transplanted simultaneously to the pancreatic graft (KP group) and 62 were kidney-alone transplants (KA group). The mean time on dialysis was 31 +/- 20 months (range 0-126 months). The duration of diabetes was 24 +/- 7 years (range 5-51 years). Ninety-nine percent of the patients were on renal replacement therapy (79% on hemodialysis and 20% on peritoneal dialysis). RESULTS: Among 262 patients, 28 (11%) died due to a cardiovascular event, which was higher among KA patients compared with the KP group (P = .004). Overall patient survival was significantly higher in the KP group when compared with the KA group (log-rank: P = .0004). Patient survivals were 80% and 70% versus 70% and 40% at 5 and 10 years in the KP and KA groups, respectively. Kidney graft survivals were 81% and 60% versus 63% and 26% at 5 and 10 years in the KP and KA groups, respectively. Pancreas graft survival was 70% and 50% at 5 and 10 years, respectively. CONCLUSIONS: This clinical evaluation, even if retrospective, confirmed that simultaneous pancreas-kidney transplantation has a protective effect against cardiovascular mortality in diabetic recipients affected by end-stage renal disease.

Multivariate analysis of factors affecting patient and graft survival after renal transplant.

AIM: To evaluate factors affecting patient and kidney survival after renal transplant. PATIENT AND METHODS: Among 361 patients undergoing renal transplant: 52% (n = 189) were simultaneous with pancreas transplant (SPKT group) and 48% (n = 172), a kidney transplant alone (KT group). Out of 361 patients, 75% (n = 270) were diabetics. The patients were 220 (61%) men and 141 (39%) women of mean age 41 +/- 9 years. The mean time of dialysis was 42 +/- 21 months (range 0 to 126), and the mean duration of diabetes 24 +/- 7 years (range 5 to 51). A Cox regression analysis was done. RESULTS: The multivariate analysis revealed that in the final model diabetes and donor age were significant predictors of kidney graft survival; moreover, diabetes and recipient age were predictors of patient survival. Overall patient survival was significantly greater among nondiabetic patients (P = .002) or in diabetic patients who received SPKT, when compared with diabetics in whom only the kidney was transplanted (P = .001). CONCLUSIONS: Diabetes and donor age were independent prognostic factors affecting kidney graft survival after renal transplant, and recipient age and diabetes were prognostic factors affecting patient survival. Combined pancreas and kidney transplantation should be offered to patients with end-stage diabetic nephropathy.

Long-term survival after kidney and kidney-pancreas transplantation in diabetic patients.

PURPOSE: To investigate the influence of diabetes mellitus on patient and graft survival among renal versus renal-pancreatic recipients. METHODS: Among 270 renal transplants performed from 1985 to 2002, a total of 204 (75%) were in diabetic patients and 66 (25%) in nondiabetic patients. Among the 204 diabetic patients 161 (60%) kidneys were transplanted simultaneously with a pancreatic graft (SKPT group). The overall group of patient included 164 (61%) men and 106 (39%) women with mean time on dialysis of 31 +/- 21 months (range 0 to 126 months). The mean duration of diabetes was 24 +/- 7 years (range 5 to 51 years). Ninety-nine percent of the patients were on renal replacement therapy (79% hemodialysis and 20% peritoneal dialysis). RESULTS: The overall rejection rate was similar (NS). Both patient and kidney graft survival rates were worse in diabetics. Patient survival was 82% at 5 years among patients undergoing SKPT, 60% in diabetics receiving only a kidney, and 88% in nondiabetic transplanted patients. Kidney graft survival at 5 years was 77% in diabetics receiving SKPT, 68% in diabetics receiving a kidney alone, and 82% in nondiabetic patients. Overall patient survival was significantly greater among nondiabetics (P =.002) or in diabetics who received SKPT compared with diabetics who only had a kidney transplant (P =.001). CONCLUSIONS: This retrospective clinical evaluation confirms that combined pancreas and kidney transplantation should be the first choice to insulin-dependent diabetes mellitus (IDDM) patients with end-stage diabetic nephropathy.

Regulation of polyhomeotic transcription may involve local changes in chromatin activity in Drosophila.

The polyhomeotic (ph) gene of Drosophila is a member of the Polycomb group of genes and encodes a chromatin protein required for negative regulation of homeotic genes and other loci, in particular the ph locus itself. We have studied the genetic control of ph transcription during development. Early ph expression is under the control of bicoid and engrailed as activators and of oskar as an inhibitor. The negative autoregulation of ph starts at the blastoderm stage and is partly mediated by a transvection effect. As the number of functional copies of ph increases in the same genome, a concomitant reduction of the transcription of each copy is observed. This regulation is ensured, likely at the chromatin level, positively by the trithorax group and negatively by the Polycomb group gene products like a homeotic gene, but it occurs in the same cells. We propose that an equilibrium between these two states of chromatin activity ensures an accurate level of ph transcription.

[Effect of experimental allergic encephalomyelitis on the intensity of phospholipid metabolism in the brain and spinal cord]. / Vliianie éksperimental'noro allergicheskogo éntsefalomielita na intensivnost' obmena fosfolipidov golovnogo i spinnogo mozga.

Metabolism of separate phospholipid fractions was studied in rabbit brain hemispheres, truncus cerebri, cervical and lumbar parts of spinal cord in experimental allergic encephalomyelitis (EAE). Different alterations in metabolic activity of phospholipids in brain and spinal cord were noted in EAE. In brain incorporation of 14C into separate phospholipid fractions was inhibited similarly. In spinal cord the direction of metabolic changes was different: metabolism of phosphatidyl choline and phosphatidyl serine was maximally inhibited in lumbar part and intensity of metabolism of phosphatidyl ethanolamine and phosphatidic acid was increased in cervical part.

[Intensity of the metabolism of separate brain phospholipid fractions in hyperphenylalaninemia]. / Intensivnost' obmena otdel'nykh fraktsii fosfolipidov mozga pri giperfenilalaninemii.

Effect of acute and chronic forms of hyperphenylalaninemia on intensity of metabolism and content of some phospholipid fractions was studied in brain of growing rats. Acute form of hyperphenylalaninemia caused a decrease in metabolic activity of phospholipids but did not affect their content. In chronic hyperphenylalaninemia more distinct alterations in brain phospholipids metabolism were manifested as a decrease in their content and in their metabolic intensity. The data obtained suggest that brain demyelination developed in chronic hyperphenylalaninemia.