Efficacy of C.E.R.A. in Routine Clinical Practice for Correction of Anaemia and Maintenance of the Haemoglobin Levels in CKD Patients not on Dialysis.

INTRODUCTION: C.E.R.A. reported effective correction of anaemia and was well tolerated in International studies on CKD patients not on dialysis. OBJECTIVE: The study aimed to describe the management of renal anaemia in CKD patients not on dialysis with C.E.R.A. in routine clinical practice in India. METHODS: This was a prospective, single-arm, open-label, multi-centre, non-interventional, Phase IV study which followed 108 CKD Stage III-IV patients, not on dialysis with Hb < 10 g/dL for correction of anaemia with C.E.R.A. RESULTS: Of the 108 patients with Hb < 10 g/dL at baseline, 83 (90.2%) patients achieved target Hb of 10-12 g/dL and the time taken to achieve correction of anaemia was 9.6 weeks ± 6.13 weeks in the Intent-to-treat population. Haemoglobin concentration increased from 8.59 ± 0.808 g/dL pre-therapy to 10.91 ± 0.634 g/dL post-therapy. The change in mean ± SD Hb value was 2.32 ± 0.174 g/dL. Maintenance of Hb levels within the target range of Hb 10 - 12 g/dL was observed in 78.2% of ITT and 80.8% of the PP population for mean duration of 16.69 weeks. Four patients (3.7%) experienced 5 AEs and 2 patients (1.9%) experienced 3 SAEs in the safety population. As per the treating physician none of the AEs or SAEs was considered related to study drug. There were no deaths reported. CONCLUSIONS: This study demonstrated successful correction of anaemia in Indian patients with C.E.R.A. treatment as well as maintenance of Hb levels within the target range. C.E.R.A. was well tolerated with no new safety concerns specific to the Indian population. The less frequent up to monthly dosing schedule of C.E.R.A. may offer clinicians and patients a simplified regimen of anaemia management as compared to traditional frequently administered (thrice weekly to once weekly) ESAs.

MUC13 interaction with receptor tyrosine kinase HER2 drives pancreatic ductal adenocarcinoma progression.

Although MUC13, a transmembrane mucin, is aberrantly expressed in pancreatic ductal adenocarcinoma (PDAC) and generally correlates with increased expression of HER2, the underlying mechanism remains poorly understood. Herein, we found that MUC13 co-localizes and interacts with HER2 in PDAC cells (reciprocal co-immunoprecipitation, immunofluorescence, proximity ligation, co-capping assays) and tissues (immunohistofluorescence). The results from this study demonstrate that MUC13 functionally interacts and activates HER2 at p1248 in PDAC cells, leading to stimulation of HER2 signaling cascade, including ERK1/2, FAK, AKT and PAK1 as well as regulation of the growth, cytoskeleton remodeling and motility, invasion of PDAC cells-all collectively contributing to PDAC progression. Interestingly, all of these phenotypic effects of MUC13-HER2 co-localization could be effectively compromised by depleting MUC13 and mediated by the first and second EGF-like domains of MUC13. Further, MUC13-HER2 co-localization also holds true in PDAC tissues with a strong functional correlation with events contributing to increased degree of disorder and cancer aggressiveness. In brief, findings presented here provide compelling evidence of a functional ramification of MUC13-HER2: this interaction could be potentially exploited for targeted therapeutics in a subset of patients harboring an aggressive form of PDAC.

Cardiopulmonary exercise testing in evaluation of patients of chronic obstructive pulmonary disease.

BACKGROUND: Objective assessment of severity in patients with chronic obstructive pulmonary disease (COPD) is mainly limited to pulmonary function testing performed at rest. But, accurate assessment of exercise capacity in patients with COPD may be possible with cardiopulmonary exercise testing (CPET). METHODS: Forty-three patients with stable COPD were included and were divided into three groups based upon the spirometry data as per the Global Initiative for Obstructive Lung Disease (GOLD) guidelines as follows: Group A: mild COPD, Group B: moderately severe COPD and Group C: severe COPD. Symptom-limited CPET was performed using treadmill on incremental continuous ramp protocol in all of them. RESULTS: Five patients (11.6%) had mild COPD; 16 (37.2%) had moderately severe COPD and the remaining 22 (51.6%) patients had severe COPD. Anaerobic threshold was attained in all the 43 patients. The dominant symptom at peak exercise were dyspnoea (n = 19) and both dyspnoea and leg fatigue (n = 7). The other causes of exercise limitation included dyspnoea with significant oxygen desaturation (n = 6); and dyspnoea with severe oxygen desaturation (n = 2). Six patients complained only of leg fatigue at peak exercise. A significant correlation between forced expiratory volume in the first second (FEV1) percent predicted and the predicted maximum oxygen uptake (VO2 max % predicted) was observed in all the three groups (r = 0.39, p = 0.011) but with marked variability of peak VO2 for a given degree of airflow obstruction. Twenty-three (53.5%) patients with low anaerobic threshold (< 30%) were identified as potential group likely to benefit from exercise training for pulmonary rehabilitation. CONCLUSIONS: Cardiopulmonary exercise testing is useful to determine the causes of exercise limitation and to assess the maximal exercise capacity of patients with COPD.

Development of a heating reactor for a continuous flow-through application in urea measurement.

In most biochemical analyses, a flow-through heating arrangement is needed to reduce the reaction time or maintain a constant temperature. A rectangular reactor is described that is constructed of aluminium, is hollow inside and is filled with silicone oil. The glass coil through which the solution flows is immersed in the silicone oil. The heater, a Peltier-effect heat pump, on one side and the temperature sensor on the other side of the reactor body are embedded for heating and temperature control. The brief performance evaluation of the reactor is discussed by measuring the absorbance of urea concentration at different temperatures.

Development of a photometric system for continuous flow analysis.

Most chemical analyses carried out in a clinical laboratory are colorimetric. An improved photometric system is described where a tungsten lamp is the light source, a photo-diode is the detector and a microcontroller 8051 is used for processing and displaying absorbances. The performance characteristics of the instrument are reported. The parameters investigated are photometric linearity, precision and instrumental drift.

Development of a microprocessor-based biochemical sampler.

Modern medicine requires patients to be treated on the basis of precise data, which are often obtained from electronic equipment. An inexpensive and portable microprocessor-based sampler developed by the authors is described. It is comprised of the following units: sample plate assembly, probe-drive linkage system, wash fluid receptacle, timing system and 8085A microprocessor.

Outcomes in a consecutive series of 111 surgically treated plexal tumors: a review of the experience at the Louisiana State University Health Sciences Center.

OBJECT: The authors conducted a retrospective study of 107 consecutive patients with 111 brachial plexus tumors surgically treated at the Louisiana State University Health Sciences Center (LSUHSC). METHODS: During a 12-year period, from 1986 to 1998, 371 patients with lesions of the brachial plexus underwent surgery at LSUHSC. Among this group, 107 patients harbored 111 tumors of the brachial plexus. Neural sheath tumors were the most commonly found and included 33 neurofibromas (20 of which were associated with von Recklinghausen disease), 36 schwannomas, and 12 malignant neural sheath tumors. Of the non-neural sheath tumors, 13 were benign and 17 were malignant. Presenting symptoms included pain (59%), palpable mass (52%), paresthesias (30%), and paresis (29%). Anterior supraclavicular (82%) or posterior subscapular (18%) approaches were used to achieve gross-total (79%) or subtotal (21%) resection of tumor. The average follow-up period was 38.3 months or 3.2 years. Seventy percent of patients with benign neural sheath tumors became free from pain postoperatively or reported improvement in their preoperative pain status. Function remained intact or improved in 50% and remained stable postoperatively in another 20% of cases. Preservation of function was more likely in patients who presented intact and in those who had not undergone a previous attempted biopsy procedure or resection than in those in whom such manipulation had occurred. CONCLUSIONS: Resection of most plexal tumors is technically feasible and associated with acceptable morbidity and mortality rates.

Blood lead in children and its determinants in Nagpur, India.

In a community-based cross-sectional study of 297 children aged 6 months to 6 years in an Indian city, the authors assessed the prevalence of elevated (> or = 10 microg/dL) blood lead (PbB) levels, their risk factors, and the lead contents in potential environmental sources. Mean PbB was 18.4 microg/dL +/- 16.5. The prevalence of elevated PbB was 67%. Anticipated risk factors for elevated PbB were living in houses painted with lead-based paint, odds ratio (OR) 6.42 (1.75, 23.6; p = 0.005), recent exposures to lead-based paint, OR 2.61 (1.07, 6.66; p = 0.03), and the use of the eye cosmetic ma," OR 2.63 (1.24, 5.56; p = 0.01). Unanticipated results were effect of upper caste as a risk factor, OR (adjusted) 1.85 (95% CI = 0.96, 3.57; p = 0.06), and the lack of effect of traffic, parental occupational exposure, or nutritional status. Analysis of various environmental sources such as paint, pencils, crayons, and clay revealed high lead levels. These results demonstrate the existence of a major environmental health problem in Indian children, with risk factors that differ from those in other countries.

MEME-II supports the cooperative management of terminology.

Health care enterprises need enterprise-wide terminologies to compare, reuse and repurpose health care descriptions. But once they are created, these terminologies need to be maintained and enhanced to sustain their utility and that of the descriptions encoded with them. MEME II (Metathesaurus Enhancement and Maintenance Environment, Version II) supports the required activities and enables enterprises to leverage their investment in terminology and descriptions by permitting remote-extra-enterprise-enhancements to terminology to be incorporated locally, and local-intra-enterprise-enhancements to be shared remotely. MEME II represents all changes to terminologies as data, or "actions," that can be interpreted by an "action engine." These actions, or messages, represent semantic "units of work" that can be interpreted by other copies of MEME II. The exchange of update messages increases the likelihood that the comparability of terminology-based health care descriptions can be sustained.

Pharmacokinetics of cytomegalovirus specific IgG antibody following intravenous immunoglobulin in bone marrow transplant patients.

Cytomegalovirus (CMV) associated interstitial pneumonitis is a major cause of death among bone marrow transplant patients. A variety of intravenous immunoglobulin (IVIg) preparations have shown some promise in preventing this complication. As part of a multicenter trial of Sandoglobulin, the pharmacokinetics of CMV specific IgG was measured in order to guide future dosing schedules. A dose of 500 mg/kg was administered weekly beginning 1 week before transplant and continuing until day 98 following transplant. The half-life of CMV specific IgG was measured by an ELISA method after the first, third and fifth doses of IVIg. CMV seronegative patients received only screened CMV negative blood products, which permitted assessment of the half-life of IVIg CMV antibody. Peak titers achieved were comparable to those of the CMV seropositive patients averaging 1:2702 (range 1:596-1:10 514). Total IgG levels rose to a peak of about 75% above baseline. After the first dose of IVIg, the half-life of CMV IgG antibody was 3.4 +/- 2.0 (SD) days, although it lengthened to 6.1 +/- 5.1 days after the fifth dose of IVIg. The half-life of total IgG was estimated to be between 5 and 10 days, depending on the assumptions made regarding endogenous production. If high levels of IVIg are necessary for protection from CMV associated interstitial pneumonitis, weekly dosing will be important in order to maintain sufficient levels to be protective.

Reaginic sensitivity to Mus musculus extract in a group of Chicago urban asthmatics.

Thirty-nine out of 103 urban asthmatics reacted on prick test to rodent hair extract (MME). One out of 68 and one out of 50 reacted among suburban asthmatics and normal controls, respectively. Ten skin-test reactive and three non-reactive urban asthmatics underwent bronchial provocative challenge tests (BPT). Results were significant at p less than 0.001. Twenty-one out of 26 skin-reactive and one out of 25 skin non-reactive asthmatics had specific IgE antibody, p less than 0.001. These data suggest that rodent hair might be a relevant allergen in some urban asthmatics.

Serum IgE levels in healthy black American children: a case for environmental influences on IgE.

Serum IgE was determined in 115 healthy, non-atopic black American children, aged 0-16 years, living in Urban Chicago. The mean IgE level varied from 1.48 u/ml at birth to 70 u/ml at adolescence. These values are comparable to those observed in American whites but differ significantly from the IgE levels of both African blacks and European Caucasians. Thus, environmental factors apparently exert a strong influence on IgE production in non-atopic individual.