The human GIMAP5 gene has a common polyadenylation polymorphism increasing risk to systemic lupus erythematosus

Background

Several members of the GIMAP gene family have been suggested as being involved in different aspects of the immune system in different species. Recently, a mutation in the GIMAP5 gene was shown to cause lymphopenia in a rat model of autoimmune insulin‐dependent diabetes. Thus it was hypothesised that genetic variation in GIMAP5 may be involved in susceptibility to other autoimmune disorders where lymphopenia is a key feature, such as systemic lupus erythematosus (SLE).

Material and methods

To investigate this, seven single nucleotide polymorphisms in GIMAP5 were analysed in five independent sets of family‐based SLE collections, containing more than 2000 samples.

Result

A significant increase in SLE risk associated with the most common GIMAP5 haplotype was found (OR 1.26, 95% CI 1.02 to 1.54, p = 0.0033). In families with probands diagnosed with trombocytopenia, the risk was increased (OR 2.11, 95% CI 1.09 to 4.09, p = 0.0153). The risk haplotype bears a polymorphic polyadenylation signal which alters the 3′ part of GIMAP5 mRNA by producing an inefficient polyadenylation signal. This results in higher proportion of non‐terminated mRNA for homozygous individuals (p<0.005), a mechanism shown to be causal in thalassaemias. To further assess the functional effect of the polymorphic polyadenylation signal in the risk haplotype, monocytes were treated with several cytokines affecting apoptosis. All the apoptotic cytokines induced GIMAP5 expression in two monocyte cell lines (1.5–6 times, p<0.0001 for all tests).

Conclusion

Taken together, the data suggest the role of GIMAP5 in the pathogenesis of SLE.     

Surgical treatment of selected tumors via the navigated minimally invasive presigmoidal suprabulbar infralabyrinthine approach without rerouting of the facial nerve

Neurosurgical Review - The feasibility of a novel skull base approach — the navigated minimally invasive presigmoidal suprabulbar infralabyrinthine approach (NaMIPSI-A) without rerouting of...     

Platelet function testing during 5-day storage of single and random donor plateletpheresis.

Platelet concentrates are routinely manufactured from whole blood by differential centrifugation (random donor platelets-RDP) or by plateletpheresis (single donor platelets-SDP). These platelet concentrates have a storage period of 5 days and many different approaches exist to measure the condition of platelets during their storage. In this study, platelet aggregation testing using adenosine diphosphate (ADP) and collagen and flow cytometric platelet activation analysis using CD41 FITC and CD62 PE before and after ADP was performed on days 1, 3 and 5 of storage of platelet preparations. Thirty three RDPs, stored in Baxter and Kansuk blood bags and 18 SDPs stored in Fresenius blood bags were evaluated. In RDPs and in SDPs; ADP and collagen induced PA responses were decreased significantly on the 3rd and 5th days compared to 1st day. CD62 positive platelet percentage after ADP were decreased significantly on the 3rd and 5th days compared to the 1st day in Kansuk((R)) bags. Flow cytometric analysis revealed minor changes in CD41 expression after ADP on the 3rd day compared to 1st day and on the 5th day compared to 3rd day. Differences in CD62 positive platelet percentage were not significant between the RDPs and SDPs. Our results suggest that: (1) ADP and collagen induced PA responses decrease both in RDPs and SDPs during storage. (2) Flow cytometric analysis does not show major significant changes in platelet activation after ADP during storage. (3) Continous shaking on the agitator does not cause a significant change in CD62 positive platelet percentage during storage. (4) Platelet aggregation responses in RDPs stored in Baxter((R)) and Kansuk((R)) blood bags do not differ during storage.     

Simulation of Three-Dimensional Free-Surface Flows Using Two-Dimensional Multilayer Shallow Water Equations

We present an efficient and conservative Eulerian-Lagrangian method for solving two-dimensional hydrostatic multilayer shallow water flows with mass exchange between the vertical layers. The method consists of a projection finite volume method for the Eulerian stage and a method of characteristics to approximate the numerical fluxes for the Lagrangian stage. The proposed method is simple to implement, satisfies the conservation property and it can be used for multilayer shallow water equations on non-flat bathymetry including eddy viscosity and Coriolis forces. It offers a novel method of calculating stratified vertical velocities without the use of the Navier-Stokes equations. Numerical results are presented for several examples and the obtained results for a free-surface flow problem are in close agreement with the analytical solutions. We also test the performance of the proposed method for a test example of wind-driven flows with recirculation     

Deep anterior lamellar keratoplasty in eyes previously treated with collagen crosslinking for keratoconus: 3-year results

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate the 3-year results of deep anterior lamellar keratoplasty (DALK) using the big-bubble technique in keratoconus...     

Pancreatic Morphological Changes in Long-Term Follow-Up after Initial Episode of Acute Alcoholic Pancreatitis

Objective

The long-term morphological changes induced by a single episode of alcoholic pancreatitis are not known. Our aim was to study these morphological changes in secretin-stimulated magnetic resonance cholangiopancreatography (S-MRCP) after the first episode of alcohol-associated acute pancreatitis and to evaluate the risk factors and possible protective factors potentially associated with later chronic findings. We have previously reported 2-year follow-up results in pancreatic morphology. This study extends the follow-up to 9 years.

Patients and Methods

In this prospective follow-up study, S-MRCP imaging was performed for 44 (41 M, 3 F; mean age, 46 (25–68)?years) patients after their first episode of alcohol-associated pancreatitis. Pancreatic morphology was evaluated at 3 months and at 2, 7, and 9 years after hospitalization. Recurrent attacks of pancreatitis were studied and pancreatic function was monitored by laboratory tests. Patients’ alcohol consumption was evaluated with questionnaires, laboratory markers, and self-estimated alcohol consumption via interview. Smoking and body mass index were annually recorded.

Results

At 3 months, 32 % of the patients had normal findings in S-MRCP, 52 % had acute, and 16 % had chronic changes. At 7 years, S-MRCP was performed on 36 patients with normal findings in 53 %, the rest (47 %) having chronic findings. Pancreatic cyst was present in 36 %, parenchymal changes in 28 %, and atrophy in 28 % of the cases. There were no new changes in the pancreas in the attending patients between 7 and 9 years (18 patients). Of the patients with only acute findings at 3 months, 60 % resolved to normal in 7 years, but the rest (40 %) showed chronic changes later on. The initial attack was mild in 65 %, moderate in 25 %, and severe in 10 % of the patients. Patients with mild first attack had fewer chronic changes at 7 years compared to patients with moderate or moderate and severe together (p?=?0.03, p?=?0.01). Of the patients in the seventh year of S-MRCP, 22 % had suffered a recurrent episode of acute pancreatitis (mean, 22 (2–60)?months) and 11 % had a clinical diagnosis of chronic pancreatitis. At 7 years, 88 % of the patients with recurrences had chronic findings in S-MRCP versus 36 % with nonrecurrent pancreatitis (p?=?0.02). Six (17 %) patients abstained from alcohol throughout follow-up (mean, 8.7 (7–9.1)?years), but even one of these developed pancreatic atrophy. Out of the non-abstinent patients who did not suffer recurrences, 4/22 (18 %) had developed new findings during at follow-up S-MRCP (NS). In univariate analysis, heavy smoking showed no correlation with increased chronic changes compared to nonsmoking.

Conclusions

Morphological pancreatic changes increase with recurrent episodes of acute pancreatitis. Patients with mild first attack have fewer chronic changes in the pancreas in the long term. However, even a single episode of acute alcoholic pancreatitis may induce chronic morphological changes in long-term follow-up.     

Improvement of right ventricular function with transcatheter aortic valve implantation

Background and aim. It has been demonstrated that right ventricular systolic dysfunction develops soon after surgical aortic valve replacement (s-AVR). While the impact of s-AVR or TAVI on the function of the left ventricle has been studied with various imaging modalities, little is known about the impact on right ventricular function (RVF). In the current study, we evaluated the impact of TAVI on RVF using conventional echocardiography parameters. Methods and results. Echocardiography was performed prior to 24 h, 1 month and 6 months after TAVI. RVF was assessed using (1) tricuspid annular plane systolic excursion (TAPSE); (2) RV Tissue Doppler Imaging (S’); (3) right ventricular systolic pressure (RVSP); (4) Fractional area change (FAC); and (5) RV ejection fraction (RVEF). TAVI was performed through the subclavian artery in two patients and femoral artery in 48 patients with an Edwards Sapien XT valve. TAVI was performed on 50 patients between the dates of December 2012 and June 2013. After TAVI, a statistically significant improvement was observed for all parameters related to RVF (RVSP, RVEF, TAPSE, FAC, RVTDI S’). During the 1st and 6th months this statistically significant improvement continued in TAPSE and FAC, and there was no deterioration in RVSP, RVEF, and RVTDI S during the 1st month but a statistically significant improvement continued in the 6th month. Conclusion. RVF assessed by conventional echocardiography did not deteriorate after TAVI in early and midterm follow-up. Further, TAVI provides improvement of RVF and can safely and efficiently be performed in patients with impaired RVF.     

The Effect of Bisphosphonates on Bone Mineral Density in Metastatic Prostate Cancer Patients Who Are Treated with Anti-Androgen Drugs and Radiotherapy

Objective

To evaluate the potential effect of bisphosphonates on bone mineral density (BMD) in patients who are treated with anti-androgen drugs and radiotherapy for metastatic prostate cancer.

Materials and Methods

The data of 31 patients with metastatic prostate cancer who were treated with anti-androgen drugs and radiotherapy during a 1-year period were retrospectively reviewed. Patients were divided in 2 groups, in which 17 patients in group 1 were treated with zoledronic acid (4 mg/month, intravenous) and 14 patients in group 2 who did not receive zoledronic acid. BMD was measured before the treatment and at the end of the 1st year by dual energy X-ray absorptiometry. Statistical analyses were performed with the T test.

Results

Mean age of the patients was 71.42 ± 6.7(range 59-85) years. A significant increase was noted for pelvic bone, femoral neck, and lumbar vertebrae t scores when pretreatment and 1st year measurements were compared in group 1 (p < 0.05). In group 2 a significant decrease was noted for pelvic bone and femoral neck t scores at the end of the 1st year (p < 0.05). A significant increase was noted for pelvic bone and femoral neck follow-up in BMD values at the end of the 1st year compared to initial measurements in group 1. A significant decrease was noted for lumbar vertebrae follow-up in BMD values at the end of the 1st year when compared to initial values in group 2.

Conclusion

Zoledronic acid significantly increases BMD and delays unfavorable outcomes for bones in men who are treated with anti-androgen drugs and radiotherapy for metastatic prostate cancer.Key Words: Metastatic prostate cancer, Osteoporosis, Radiotherapy, Bisphosphonate therapy     

Fournier's gangrene after hemorrhoidectomy: Association with drug-induced agranulocytosis

An unusual case of Fournier's gangrene after hemorrhoidectomy and drug-induced agranulocytosis, as the predisposing condition, is described. The patient had severe granulocytopenia that was attributed to the recent use of dipyrone. Together with hemodynamic resuscitation, broad-spectrum antibiotic and recombinant human granulocyte colony-stimulating factor were started. Wide surgical excision of all the gangrenous tissues, in addition to laparoscopic formation of a defunctioning sigmoid loop colostomy, was performed. The white blood cell count rose steadily and the patient experienced a rapid recovery. We emphasize that radical surgery must be accompanied by pharmacologic interventions for a successful outcome in such cases.     

The effect of 4-week aerobic exercise program on postural balance in postmenopausal women with osteoporosis

The aim of this study is to evaluate the effect of submaximal aerobic exercise program on postural balance in postmenopausal women with osteoporosis. Twenty-five postmenopausal women without osteoporosis and 28 postmenopausal women with osteoporosis enrolled in this study. Balance ability of all subjects was measured by timed up and go test (TUG), four square step test (FSS), Berg balance scale (BBS) and Kinesthetic ability trainer 3000. After completion of initial measurements of balance, postmenopausal women with osteoporosis attended the submaximal aerobic exercise program on treadmill. At the end of the exercise program, balance tests were repeated. Balance tests of postmenopausal women without osteoporosis were repeated approximately 4-weeks after the initial measurement. There was statistically significant improvement in all balance scores in the postmenopausal women with osteoporosis after exercise training whereas there were no statistically significant differences in the scores of postmenopausal women without osteoporosis who did not exercise. This study showed that a 4-week submaximal aerobic exercise program provided significant improvements in static and dynamic balances in postmenopausal osteoporotic women.