Greater Epoetin alfa Responsiveness Is Associated With Improved Survival in Hemodialysis Patients

Background and objectives: Among hemodialysis patients, achieved hemoglobin is associated with Epoetin alfa dose and erythropoietin responsiveness. A prospective erythropoietin responsiveness measure was developed and its association with mortality evaluated.Design, setting, participants, & measurements: Data from 321 participants were used and randomized to the hematocrit normalization arm of the Normal Hematocrit Cardiac Trial. Subjects were to receive a 50% Epoetin alfa dose increase at randomization. The prospective erythropoietin responsiveness measure was defined as the ratio of weekly hematocrit change (over the 3 wk after randomization) per Epoetin alfa dose increase (1000 IU/wk) corresponding to the mandated 50% dose increase at randomization. The distribution of responsiveness was divided into quartiles. Over a 1-yr follow-up, Cox proportional hazard modeling evaluated associations between this responsiveness measure and mortality.Results: Erythropoietin responsiveness values ranged from −2.1% to 2.4% per week per 1000 IU. Although subjects were similar across response quartiles, mortality ranged between 14% and 34% among subjects in the highest and lowest response quartiles (P = 0.0004), respectively. After adjusting for baseline prognostic indicators, highest versus lowest responsiveness was associated with a hazard ratio of 0.41 (95% confidence interval, 0.20 to 0.87).Conclusion: Lower erythropoietin responsiveness is a strong, independent predictor of mortality risk and should be considered when evaluating associations between clinical outcomes and potential prognostic indicators, such as Epoetin alfa dose and achieved hemoglobin values.More than 90% of end-stage renal disease patients require exogenous erythropoietin or transfusion to achieve and maintain target hemoglobin values (1,2) because of decreased endogenous erythropoietin production. The ability to achieve and maintain target hemoglobin levels is complicated by a variety of mediating factors that impact responsiveness to erythropoietin, including comorbidities, inflammation, and malnutrition. These factors are independently associated with poor clinical outcomes (3–9).The impact of erythropoietin responsiveness on mortality is not well understood. Although higher hemoglobin levels have been associated with reduction in mortality in observational studies (10,11), evidence from randomized clinical trials of hemodialysis patients does not suggest a mortality benefit (12). Paradoxically, in the Normal Hematocrit Cardiac Trial (13), the largest randomized trial conducted to date in hemodialysis patients, survival rates were higher among those achieving higher hematocrit values, but targeting a higher hematocrit was associated with a 1.3-fold increased risk of mortality or nonfatal myocardial infarction (95% confidence interval [CI], 0.9 to 1.9). This suggests that unknown/unmeasured patient characteristics associated with the ability to achieve greater hemoglobin values may confound analyses assessing mortality risks among dialysis patients.Achieved hemoglobin level is associated with both the Epoetin alfa doses administered and patient responsiveness to erythropoietin. Greater survival among patients with higher hemoglobin values may be partly due to greater erythropoietin responsiveness (14) in addition to a direct result of anemia correction. Likewise, lower survival among those with lower achieved hemoglobin values may be partly the result of lower relative erythropoietin responsiveness. Patients who require higher Epoetin alfa doses to achieve a given hemoglobin level, that is, who are less responsive to erythropoietin, may experience poorer outcomes at any achieved hemoglobin value (15).In this study, data from the hematocrit normalization arm of the Normal Hematocrit Cardiac Trial (13) were used to develop a prospective measure of erythropoietin responsiveness, which was then evaluated in relation to mortality.     

Nonlinear Optical Limiting and Radiation Shielding Characteristics of Sm2O3 Doped Cadmium Sodium Lithium Borate Glasses

Strong nonlinear absorption (NLA), reduced optical limiting (OL) thresholds, and high radiation shielding parameters are required for the effective use of glasses in the laser radiation and nuclear radiation protecting materials. In view of this, the efficacy of Sm₂O₃ on the nonlinear optical (NLO) and OL properties were ascertained (at 532 nm) along with radiation shielding characteristics. The open and closed aperture Z-scan profiles revealed the presence of positive NLA and nonlinear refraction (NLR) phenomena respectively. OL measurements showed the existence of limiting behavior in the studied glasses. The NLA and NLR coefficients were improved while the OL thresholds were decreased as the doping of Sm₂O₃ elevated to a higher doping level. These improvements in NLA, NLR coefficients and OL efficiencies were attributed to the non-bridging oxygens and high polarizable Sm³⁺ ions. The NLA and OL results clearly suggest the high (5 mol %) Sm₂O₃ doped glass (Sm5CNLB) glass is beneficial to protect the delicate devices and human eye by suppressing the high energy laser light. The theoretical linear attenuation coefficients (LAC) values of the presented SmxCNLB glasses were obtained with the help of Phy-X software between 0.284 and 1.333 MeV. At 0.284 MeV, the maximum values occur and take values between 0.302 (for Sm0CNLB) and 0.409 cm⁻¹ (for Sm5CNLB). We found that the LAC for the presented SmxCNLB glasses is a function of Sm₂O₃ content, where the LAC tends to increase, corresponding to the high probabilities of interaction, as the content of Sm₂O₃ changes from 0 to 5 mol %. The effective atomic number (Z_eff) for the presented SmxCNLB glasses was examined between 0.284 and 1.333 MeV. As the amount of Sm₂O₃ is added, the Z_eff increases, and this was observed at any energy.     

Apoptogenic activity of ethyl acetate extract of leaves of Memecylon edule on human gastric carcinoma cells via mitochondrial dependent pathway

ObjectiveTo evaluate the anti-proliferative and apoptogenic activity of ethyl acetate extract from the leaves of Memecylon edule (EtAc-LME) in MKN-74, NUGC gastric cancer cells and non cancerous gastric mucous cells (GES-1), and to explore the mechanism of EtAc-LME induced apoptosis.MethodsThe mechanism of EtAc-LME induced apoptosis was explored by analysing the activation of pro-caspases, PARP cleavage, expression of cytochrome-c (Cyt-c) was determined by western blotting, mRNA expression of Bcl-2, Bax by RT-PCR, loss of mitochondrial potential using DiOC6 dye, annexin binding assay and its influence on cell cycle arrest by flow cytometry.ResultsThe results indicated that EtAc-LME inhibited the gastric cancer cell growth in dose-dependent manner and cytotoxicity was more towards the gastric cancer cells (NUGC and MKN-74) compared to normal gastric cells (GES-1), suggesting more specific cytotoxicity to the malignant cells. Over expression of Cyt-c and subsequent activation of caspases-3 and down regulation of Bcl-2 and loss in mitochondrial potential in EtAc-LME treated MKN-74 and NUGC cells suggested that EtAc-LME induced apoptosis by mitochondrial dependent pathway.ConclusionsThe present findings suggest that ethyl acetate extract of Memecylon edule induces apoptosis selectively in gastric cancer cells emphasizing the importance of this traditional medicine for its potential in the treatment of gastric cancer.     

Abdominal wall abscess due to spilled gallstone presenting 11 years after laparoscopic cholecystectomy

Gallstone spillage during laparoscopic cholecystectomy may be a source of significant morbidity. In this report, we describe the clinical course of a patient who presented with a tender right subcostal swelling. She had had a laparoscopic cholecystectomy 11 years earlier. Imaging revealed a dumbbell-shaped abscess in the perihepatic area with communication into the subcutaneous tissue with a stone inside the cavity. The patient underwent abscess drainage and the stone was retrieved. During laparoscopic cholecystectomy, every effort should be made to remove spilled gallstones to prevent further complications but conversion is not mandatory.     

Live/Real Time Three‐Dimensional Transthoracic Echocardiographic Assessment of Inferior Vena Cava and Hepatic Vein Thrombosis in Sickle Cell Disease

We describe the value of live/real time three‐dimensional transthoracic echocardiography (3DTTE) over two‐dimensional transthoracic echocardiography (2DTTE) in the assessment of inferior vena cava (IVC) and hepatic vein (HV) obstruction in a patient with sickle cell disease. 3DTTE provided additional information when compared to 2DTTE by (1) identifying the obstructing lesion as a likely thrombus, (2) by providing assessment of anatomical severity of IVC lumen obstruction since the thrombus could be visualized en face also, and (3) identifying an area of increased mobility of a portion of the thrombus suggesting greater risk of embolization. (Echocardiography 2010;27:594‐596)     

High fat diet containing cholesterol induce aortic aneurysm through recruitment and proliferation of circulating agranulocytes in apoE knock out mice model

We studied and compared the efficiency of induction aneurysm in apo E mice by using high fat diet and Ang II. Aneurysm induced in 6 week old male apo E −/− mice by subcutaneous release of Ang II injection for 45 days. Also, aneurysm was induced in three month old male apo E by administration of high fat diet for a period of three months. No difference in body weight in Ang II treated mice. But, increase in body weight and mean arterial blood pressure observed in high fat diet group animals. Highly significant increase in total cholesterol, TG, LDL and significant decrease in HDL level were observed in Ang II treated animals. Significant increase in total cholesterol, but no changes in TG, LDL, HDL levels were observed in high fat diet group. Higher percentage of circulating monocytes was observed in ang II treated group but more number of circulating lymphocytes were observed in high fat diet group in FACS analysis. In histopathology, intimal layer of abdominal aorta was completely replaced by chronic inflammatory cells particularly macrophages (80%) which appeared as foam cells and lymphocytes (20%) in ang II treated animals. Degradation of elastin, infiltration of lymphocytes, chondrocytes and cellular migration towards media were observed in the abdominal aorta of high fat diet group. Real time analysis and immunofluorescence assay supports over expression of Vcam 1 Icam1, MCP 1and MMP2 genes were observed in Ang II treated animals. In immunofluorescence assay, over expression of Mac 3 protein specific for macrophages was observed in abdominal aorta of ang II treated animals, but over expression of CD45.1 & 45.2 proteins specific to lymphocytes were observed in high fat diet group. Based on our observations, Ang II induced aortic aneurysm by recruiting/ proliferating circulating monocytes by up regulating Icam-1, Vcam -1 and MCP-1. Also, ang II involved in degradation of elastin in the abdominal aorta by up regulation of MMP2 to promote agranulocytes migration in the intimal layers. Epithelial cell hyperplasia with accumulation of fatty fluids (cyst) was observed in seminal vesicle and ventral prostate of high fat treated animals. Fatty degeneration, germ cell apoptosis and infiltration giant cells were observed in the testes of high fat diet group. As per available literature these observations were not reported with high fat diet treatments with apo E models. High fat diet induced aneurysm prominently in abdominal, thoracic aorta and extensive plaque formation was observed in femoral and renal arteries. Administration of high fat diet containing cholesterol induced aneurysm in apo E mice model also efficient method to rule out the pathogenesis of aortic aneurysm when compared with angiotensin.     

Pseudointercondylar notch sign: manifestation of osteochondritis dissecans of the trochlea

Osteochondritis dissecans (OCD) is an idiopathic condition affecting the articular epiphysis. Initially described in the knee, this entity affects several other parts of the body such as the talar dome, tarsal navicular, and femoral capital epiphysis. OCD of the elbow primarily involves the capitellum. OCD involving the trochlea has rarely been reported. We describe an unusual and interesting case of OCD affecting the trochlea, mimicking a pseudointercondylar notch.     

Audit of short term outcomes of surgical and medical second trimester termination of pregnancy

Background  

As comparisons of modern medical and surgical second trimester termination of pregnancy (TOP) are limited, and the optimum method of termination is still debated, an audit of second trimester TOP was undertaken, with the objective of comparing the outcomes of modern medical and surgical methods.