Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease

Unlike most other cell types, neurons preferentially metabolize glucose via the pentose phosphate pathway (PPP) to maintain their antioxidant status. Inhibiting the PPP in neuronal cell models causes cell death. In rodents, inhibition of this pathway causes selective dopaminergic cell death leading to motor deficits resembling parkinsonism. Using postmortem human brain tissue, we characterized glucose metabolism via the PPP in sporadic Parkinson's disease (PD), Alzheimer's disease (AD), and controls. AD brains showed increased nicotinamide adenine dinucleotide phosphate (NADPH) production in areas affected by disease. In PD however, increased NADPH production was only seen in the affected areas of late-stage cases. Quantifying PPP NADPH-producing enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by enzyme-linked immunosorbent assay, showed a reduction in the putamen of early-stage PD and interestingly in the cerebellum of early and late-stage PD. Importantly, there was no decrease in enzyme levels in the cortex, putamen, or cerebellum of AD. Our results suggest that down-regulation of PPP enzymes and a failure to increase antioxidant reserve is an early event in the pathogenesis of sporadic PD.     

Hepatitis E in hemodialysis and kidney transplant patients in south-east Italy

AIM:To investigate the serovirological prevalence and clinical features of hepatitis E virus(HEV) infection in end-stage renal failure patients and in the healthy population.METHODS:HEV infection is a viral disease that can cause sporadic and epidemic hepatitis.Previous studies unexpectedly showed a high prevalence of HEV antibodies in immunosuppressed subjects,including hemodialysis(HD)patients and patients who had undergone kidney transplant.A cohort/case-control study was carried out from January 2012 to August 2013 in two hospitals in southern Italy(Foggia and S.Giovanni Rotondo,Apulia).The seroprevalence of HEV was determined in 801 subjects;231 HD patients,120 renal transplant recipients,and450 health individuals.All HD patients and the recipients of renal transplants were attending the Departments of Nephrology and Dialysis at two hospitals located in Southern Italy,and were included progressively in this study.Serum samples were tested for HEV antibodies(Ig G/Ig M);in the case of positivity they were confirmed by a Western blot assay and were also tested for HEV-RNA,and the HEV genotypes were determined.RESULTS:A total of 30/801(3.7%)patients were positive for anti-HEV Ig(Ig G and/or Ig M)and by Western blot.The healthy population presented with a prevalence of 2.7%,HD patients had a prevalence of 6.0%,and transplant recipients had a prevalence of 3.3%.The overall combined HEV-positive prevalence in the two groups with chronic renal failure was 5.1%.The rates of exposure to HEV(positivity of HEV-Ig G/M in the early samples)were lower in the healthy controls,but the difference among the three groups was not statistically significant(P>0.05).Positivity for anti-HEV/Ig M was detected in 4/30(13.33%)anti-HEV Ig positive individuals,in 2/14 HD patients,in1/4 transplant individuals,and in 1/12 of the healthy population.The relative risk of being HEV-Ig M-positive was significantly higher among transplant recipients compared to the other two groups(OR=65.4,95%CI:7.2-592.7,P<0.001),but the subjects with HEV-Ig M positivity were numerically too few to calculate a significant difference.No patient presented with chronic hepatitis from HEV infection alone.CONCLUSION:This study indicated a higher,but not significant,circulation of HEV in hemodialysis patients vs the healthy population.Chronic hepatitis due to the HEV virus was not observed.     

7q32-q36 translocations in childhood T cell leukemia: cytogenetic evidence for involvement of the T cell receptor beta-chain gene

Blast cell chromosomal rearrangements involving the long arm of chromosome 7 were identified in eight of 197 cases of childhood acute lymphoblastic leukemia (ALL). Breakpoints were variable but tended to cluster in either the proximal or the terminal 7q region, depending on the immunophenotype of the cells. The 7q32-q36 region, the locus of the T cell receptor beta-chain gene, was the site of breakpoints in four of 31 cases of T cell ALL but was not involved in any of the 166 cases originating from B cell precursors (P less than .0004). In three of the four T cell cases it was possible to identify the chromosomal segment that had been translocated to the 7q32-q36 region: 1p32, 2p21, and 6p21. The 1p32 and 6p21 bands are particularly interesting, as they contain the sites of two known protooncogenes, c-L-myc and hpim, respectively. Our findings suggest that the locus of the beta-chain gene of the T cell receptor is a preferential site for certain chromosomal rearrangements in leukemic T lymphoblasts, analogous to the T cell receptor alpha-chain gene on human chromosome 14. Translocation of proto-oncogenes to a site near the beta-chain regulatory sequences provides a potential mechanism for oncogene activation.     

Prolonged survival of B-lineage acute lymphoblastic leukemia cells is accompanied by overexpression of bcl-2 protein

Overexpression of bcl-2 delays the onset of apoptosis in lymphohematopoietic cells. We measured levels of bcl-2 protein in normal and leukemic human B-cell progenitors with a specific monoclonal antibody and flow cytometry. Normal immature B cells had low levels of bcl-2 protein; the intensity of fluorescence, expressed as molecules of soluble fluorochrome per cell, within CD10+ cells was 3,460 +/- 1,050 (mean +/- SD; 5 samples). In 16 cases of B-lineage acute lymphoblastic leukemia (ALL), cells had levels of bcl-2 that were strikingly higher than those of their normal counterparts (33,560 +/- 14,570; P < .001 by t-test analysis). We next investigated whether the intensity of bcl-2 expression correlated with the resistance of immature B cells to in vitro culture. In 12 cases of B-lineage ALL, the cells recovered after 7 days of culture on allogeneic bone marrow stromal layers were 69% to 178% (median, 95.5%) of those originally seeded. Prolonged survival of leukemic cells in vitro was observed even in the absence of stromal layers in 6 of these 12 cases; the intensity of bcl-2 protein expression in these cases was 45,000 +/- 13,270, compared with 21,500 +/- 7,260 in the 6 cases in which greater than 99.5% of cells rapidly died by apoptosis under the same culture conditions (P = .003). Five immature B-cell lines, continuously growing in the absence of stroma, had the highest bcl-2 expression (79,400 +/- 20,330). By contrast, most normal CD19+, sIg-immature B cells died despite the presence of bone marrow stromal layers; 9.7% to 28.2% were recovered after 7 days of culture in three experiments. We conclude that abnormal bcl-2 gene expression influences the survival ability of B-cell progenitors. This may contribute to leukemogenesis and explain the aptitude of leukemic lymphoblasts to expand outside the bone marrow microenvironment.     

Improving the outcomes in gastric cancer surgery

Gastric cancer remains a significant health problem worldwide and surgery is currently the only potentially curative treatment option. Gastric cancer surgery is generally considered to be high risk surgery and five-year survival rates are poor, therefore a continuous strive to improve outcomes for these patients is warranted. Fortunately, in the last decades several potential advances have been introduced that intervene at various stages of the treatment process. This review provides an overview of methods implemented in pre-, intra- and postoperative stage of gastric cancer surgery to improve outcome. Better preoperative risk assessment using comorbidity index (e.g., Charlson comorbidity index), assessment of nutritional status (e.g., short nutritional assessment questionnaire, nutritional risk screening - 2002) and frailty assessment (Groningen frailty indicator, Edmonton frail scale, Hopkins frailty) was introduced. Also preoperative optimization of patients using prehabilitation has future potential. Implementation of fast-track or enhanced recovery after surgery programs is showing promising results, although future studies have to determine what the exact optimal strategy is. Introduction of laparoscopic surgery has shown improvement of results as well as optimization of lymph node dissection. Hyperthermic intraperitoneal chemotherapy has not shown to be beneficial in peritoneal metastatic disease thus far. Advances in postoperative care include optimal timing of oral diet, which has been shown to reduce hospital stay. In general, hospital volume, i.e., centralization, and clinical audits might further improve the outcome in gastric cancer surgery. In conclusion, progress has been made in improving the surgical treatment of gastric cancer. However, gastric cancer treatment is high risk surgery and many areas for future research remain.     

Einnahmen aus dem Liquidationsrecht eines Chefarztes für wahlärztliche Leistungen als Arbeitslohn oder als Einnahmen aus selbstständiger Tätigkeit

Abstrakt 1. Wird von den Patienten eines Krankenhauses neben dem Vertrag mit dem Krankenhaus für die Erbringung wahl?rztlicher Leistungen zus?tzlich ein Vertrag mit dem Chefarzt geschlossen, ergibt sich daraus ein unmittelbarer Anspruch des Patienten gegen den Chefarzt auf Erbringung der vereinbarten wahl?rztlichen Leistungen, den der Chefarzt grunds?tzlich „pers?nlich“ zu erfüllen hat, ist das von dem Chefarzt berechnete Honorar an diesen pers?nlich zu zahlen und zieht der Chefarzt oder seine Abrechnungsstelle die Honorare selbst ein, so spricht dies dafür, dass die Einnahmen aus dem Liquidationsrecht für wahl?rztliche Leistungen Einnahmen aus selbstst?ndiger T?tigkeit sind. 2. Auch wenn die wahl?rztlichen Leistungen zu den vertraglich gegenüber dem Krankenhaus geschuldeten Dienstaufgaben geh?ren, ist für die Frage, ob die wahl?rztlichen Leistungen selbstst?ndig oder unselbstst?ndig erbracht werden, eine Abw?gung aller Umst?nde des Einzelfalls vorzunehmen. (Leits?tze des Bearbeiters)     

Clinical significance of CD34 expression in childhood acute lymphoblastic leukemia

The CD34 antigen was detected on > or = 10% of the blast cells in 235 (70%) of 335 cases of newly diagnosed childhood acute lymphoblastic leukemia (ALL) treated in two consecutive chemotherapy trials. By immunophenotype, the distribution of positive cases favored early pre-B ALL (83%; n = 180) followed by pre-B ALL (61%; n = 89) and then T-cell ALL (46%; n = 61) (P < .001). Among the B-lineage cases, CD34 expression was significantly associated with favorable presenting features: age 1 to 10 years, white race, absence of central nervous system (CNS) leukemia, low serum lactate dehydrogenase level, CD10 expression, and leukemic cell hyperdiploidy (> 50 chromosomes or DNA index > or = 1.16). Event-free survival was clearly superior for patients with CD34+ leukemia (P = .01), with an estimated 83% +/- 6% (SE) of the cohort remaining free of adverse events at 5 years post diagnosis, as compared to 63% +/- 10% of the group without this feature. Multivariate analysis showed that the prognostic influence of the antigen was independent of age, leukocyte count, and other well- recognized factors, suggesting that it would add discriminatory power to current systems of risk assignment. Findings in T-cell ALL were the reverse: CD34 expression showed positive correlations with initial CNS leukemia and CD10 negativity but not with any good-risk presenting characteristics. Log-rank analysis indicated no adverse effect on treatment outcome by CD34 antigen expression, although additional patients with need to be studied to obtain a definitive answer. The opposed clinical associations of CD34 expression in B- and T-lineage ALL may reflect fundamental biologic differences between these leukemia species.