Korrelation der Netzhautdicke mit dem Verlauf der Purtscher-Retinopathie

BACKGROUND: The course of Purtscher's retinopathy (PR) or Purtscher-like retinopathy (P-lR) is dependent on time, length, and expression of confluent cotton-wool spots. To correlate the course of the disease with findings of optical coherence tomography (OCT), we present two extreme courses of PR and P-lR. METHODS: Complete ophthalmological examination plus electroretinography (ERG) and OCT were performed. In the first case the follow-up was carried out until complete resorption of the edema and in the second case 8 years after the occurrence of P-lR. RESULTS: An increase of the central retinal thickness (308-430 microm was observed during the acute phase of PR. Normalization of visual acuity and central retinal thickness to 210-273 microm with an ERG within normal limits (35 ms) was achieved after 8 weeks. In the course of P-lR the marked edema was visible even after 6 months and a markedly reduced neuroretina (112-120 microm) was measured after 8 years. CONCLUSIONS: Retinal thickness analysis correlates well with organic functions in the cases of PR or P-lR. Fast reduction of the edema was associated with a good prognosis for visual acuity.     

Crystal structure of carnidazole form II from synchrotron X-ray powder diffraction: structural comparison with form I, the hydrated form and the low energy conformations in vacuo

The crystal structure of carnidazole form II, O-methyl [2-(2-methyl-5-nitro-1H-imidazole-1-yl)ethyl]thiocarbamate, has been determined using synchrotron X-ray powder diffraction in combination with simulated annealing and whole profile pattern matching, and refined by the Rietveld method. For structure solution, 12 degrees of freedom were defined: one motion group and six torsions. Form II crystallizes in space group P2(1)/n, Z=4, with unit cell parameters after Rietveld refinement: a=13.915(4), b=8.095(2), c=10.649(3) A, beta=110.83(1) degrees, and V=1121.1(5) A3. The two polymorphic forms, as well as the hydrate, crystallize in the monoclinic space group P2(1)/n having four molecules in the cell. In form II, the molecules are held together by forming two infinite zig-zag chains via hydrogen bonds of the type N--H...N, the same pattern as in form I. A conformational study of carnidazole, at semiempirical PM3 level, was performed using stochastic approaches based on modification of the flexible torsion angles. The values of the torsion angles for the molecules of the two polymorphic forms and the hydrate of carnidazole are compared to those obtained from the conformational search. Form I and form II are enantiotropic polymorphic pairs this agrees with the fact that the two forms are conformational polymorphs.     

Childhood acute myelogenous leukaemia: association between PRAME, apoptosis- and MDR-related gene expression

The gene PRAME (preferentially expressed antigen of melanoma) encodes an antigen recognised by autologous cytolytic T lymphocytes. The mRNA level of PRAME is used as a tumour marker due to its overexpression in various malignancies. Furthermore, it is known that the overexpression of genes encoding antiapoptotic proteins leads to the survival of leukaemic cells via exclusion of apoptosis. On the other hand, overexpression of genes encoding ABC transporters may lead to multi drug resistance (MDR). Therefore, we investigated whether there is a relationship between PRAME overexpression and the expression of apoptosis- and MDR-related genes in childhood de novo acute myelogenous leukaemia (AML) patient samples and, furthermore, whether this is a general or an AML-subtype specific event. Microarray analysis and real time quantitative PCR revealed that clinical samples showing PRAME upregulation are associated with a decreasing expression of genes coding for apoptotic proteins and an overexpression of genes encoding ABC transporters. Our results indicate that patients showing PRAME upregulation may have an increased risk of MDR induction.     

Effects of dietary carbohydrate restriction with high protein intake on protein metabolism and the somatotropic axis

CONTEXT: Alterations in dietary macronutrient intake can influence protein turnover. OBJECTIVE: The purpose of this study was to assess the influence of a low-carbohydrate/high-protein diet (LC/HP) on skeletal muscle protein synthesis and whole-body proteolysis, without the confounding influence of a negative energy balance. DESIGN: Nine-day dietary intervention was applied. SETTING: Subjects remained in the General Clinical Research Center throughout the 9-d study. PARTICIPANTS: Eight young, healthy volunteers participated. INTERVENTION: Subjects ate a typical Western diet (60% carbohydrate, 30% fat, 10% protein) for 2 d, followed immediately by 7 d of an isocaloric LC/HP (5% carbohydrate, 60% fat, 35% protein). MAIN OUTCOME MEASURES: Skeletal muscle fractional synthetic rate and whole-body proteolysis [leucine rate of appearance in plasma (Ra)] were measured after an overnight fast before and after 2 and 7 d of LC/HP. We also measured plasma concentrations of insulin, GH, and IGF-I. RESULTS: Leucine Ra was increased (P = 0.03) after 2 and 7 d of LC/HP, and muscle fractional synthetic rate was approximately 2-fold higher (P < 0.01) after 7 d of LC/HP. Fat free mass was not altered by LC/HP. Average 24-h plasma insulin concentration was 50% lower (P < 0.001) after 2 and 7 d of LC/HP, whereas GH secretion and total plasma IGF-I concentrations were unchanged with LC/HP. However, plasma free IGF-I decreased by approximately 30% after 7 d of LC/HP (P = 0.002), whereas muscle IGF-I mRNA increased about 2-fold (P = 0.05). CONCLUSIONS: Increasing dietary protein content during a 7-d carbohydrate restricted diet stimulated muscle protein synthesis and whole-body proteolysis without a measurable change in fat free mass.     

Working status among Dutch patients with rheumatoid arthritis: work disability and working conditions

OBJECTIVES: To assess work disability and variables associated with work disability among Dutch patients with rheumatoid arthritis (RA). METHODS: A questionnaire on working status was filled out by 296 patients of working age. Employment and work disability rates adjusted for age and sex from the Dutch population were determined using indirect standardization. Cox proportional hazard analysis was used to assess baseline predictors of work disability in a subgroup of patients (n = 195). RESULTS: After a mean disease duration of 4.3 yr, patients had a 0.78 (95% CI 0.67-0.88) chance of being employed and a 2.14 (95% CI 1.75-2.54) risk of being work disabled when compared with the Dutch population. Functional disability and job type at the start of the disease were predictors of future work disability. In total, 48 (37%) currently employed patients had changed their working conditions, of which reduced working hours (46%), reduced pacing of work (42%) and help from colleagues (49%) were the most important alterations. Of the 60 work disabled patients without a paid job, only 11 patients (18%) would be willing to work again. CONCLUSION: This study shows that the adjusted employment rates were lower and that work disability rates were higher in patients with RA when compared with the general Dutch population. In addition, a substantial number of employed patients had to change their working conditions due to RA. Only a minority of work disabled RA patients was willing to return to the paid labour force.     

Bowel function in patients with urinary diversion: a gender-matched comparison of continent urinary diversion with the ileocecal pouch and ileal conduit

Purpose

To evaluate stool habits and associated quality of life (QoL) in a matched pair analysis of patients who underwent continent cutaneous diversion using the ileocecal segment [Mainz pouch I (MzPI)] with an intussuscepted ileal nipple as efferent segment with those receiving an ileal conduit (IC) after radical cystectomy.

Methods

We identified 250 patients who underwent radical cystectomy and urinary diversion (UD) with either MzPI with an ileal nipple or IC in our database. A detailed history of stool habits using the modified Wexner score was obtained, and questions addressing general lifestyle, comparison of symptom differences before and after surgery considering bowel function as well as bowel-associated QoL were assessed.

Results

Forty-five age- and sex-matched pairs could be compared. Overall, stool incontinence (p = 0.481) and the Wexner score (p = 0.464) revealed no differences between both groups. However, patients with MzPI as compared to those with IC had significant higher rates of stool frequency (53 vs 31 %), softer stool consistencies (60 vs 13 %), diarrhea (62 vs 20 %) and a lower rate of constipation (4 vs 22 %). Patients with MzPI had a trend toward lower bowel-associated QoL compared with patients with IC. Similarly, the MzPI group reported a significantly impaired overall postoperative QoL (51 %) compared to the IC group (29 %) (p = 0.024).

Conclusions

Patients following UD by MzPI have an increased stool frequency and softer stool consistency. However, there is no difference between both groups in terms of de novo stool incontinence. Change in bowel habits should be part of preoperative informed consent in any kind of UD. Careful patient selection is of paramount importance.

     

Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin

Huntington's disease (HD) is an inherited neurodegenerative disease caused by expansion of a polyglutamine repeat in the HD protein huntingtin. Huntingtin's localization within the cell includes an association with cytoskeletal elements and vesicles. We previously identified a protein (HAP1) which binds to huntingtin in a glutamine repeat length-dependent manner. We now report that HAP1 interacts with cytoskeletal proteins, namely the p150 Glued subunit of dynactin and the pericentriolar protein PCM-1. Structural predictions indicate that both HAP1 and the interacting proteins have a high probability of forming coiled coils. We examined the interaction of HAP1 with p150 Glued . Binding of HAP1 to p150 Glued (amino acids 879-1150) was confirmed in vitro by binding of p150 Glued to a HAP1-GST fusion protein immobilized on glutathione-Sepharose beads. Also, HAP1 co- immunoprecipitated with p150 Glued from brain extracts, indicating that the interaction occurs in vivo . Like HAP1, p150 Glued is highly expressed in neurons in brain and both proteins are enriched in a nerve terminal vesicle-rich fraction. Double label immunofluorescence experiments in NGF-treated PC12 cells using confocal microscopy revealed that HAP1 and p150 Glued partially co-localize. These results suggest that HAP1 might function as an adaptor protein using coiled coils to mediate interactions among cytoskeletal, vesicular and motor proteins. Thus, HAP1 and huntingtin may play a role in vesicle trafficking within the cell and disruption of this function could contribute to the neuronal dysfunction and death seen in HD.      

Dose-dependent effect of angiotensin II on human erythropoietin production

Current evidence suggests that angiotensin II may be involved in the regulation of renal erythropoietin (EPO) production. The present study assessed the role of angiotensin II (A II) in different doses in the control of EPO production in humans. In a parallel, randomized, placebo-controlled open design, 60 healthy male volunteers received a 6-h intravenous infusion of: placebo (placebo, electrolyte solution), a pressor dose of A II (1-3 microg/min; A II press), a combination of a pressor dose of A II and the selective AT1-receptor blocker losartan, 50 mg (A II press + L), a subpressor dose of A II (0.0375-0.15 microg/min; A II subpress) and a combination of a subpressor dose of A II and losartan (A II subpress + L). A II press treatment resulted in a significant increase of the maximum EPO concentration (CmaxEPO, 41% higher versus placebo) and the amount of EPO produced in 24 h (AUCEPO(0-24 h), 61% larger versus placebo), A II subpress treatment increased CmaxEPO (35% higher versus placebo) and AUC(EPO)(0-24 h) (34% larger versus placebo). A II press + L and A II subpress + L treatments did not significantly increase CmaxEPO and AUCEPO(0-24 h) compared to placebo. A II affects EPO production in a dose-dependent manner. The signal seems to be mediated via AT1-receptors. A II appears to be one modulator EPO production in humans.