Bone marrow mononuclear cell therapy in ischaemic stroke: a systematic review.

Bone marrow mononuclear cell (BM-MNC) therapy has emerged as a potential therapy for the treatment of stroke. We performed a systematic review of published studies using BM-MNC therapy in patients with ischaemic stroke (IS). Literature was searched using MEDLINE, PubMed, EMBASE, Trip Database, Cochrane library and clinicaltrial.gov to identify studies on BM-MNC therapy in IS till June, 2016. Data were extracted independently by two reviewers. STATA version 13 was used for carrying out meta-analysis. We included non-randomized open-label, single-arm and non-randomized comparative studies or randomized controlled trials (RCTs) if BM-MNCs were used to treat patients with IS in any phase after the index stroke. One randomized trial, two non-randomized comparative trials and four single-arm open-label trials (total seven studies) involving 227 subjects (137 patients and 90 controls) were included in the systematic review and meta-analysis. The pooled proportion for favourable clinical outcome (modified Rankin Scale score ≤2) in six studies involving 122 subjects was 29% (95% CI 0.16-0.43) who were exposed to BM-MNCs and pooled proportion for favourable clinical outcome of 69 subjects (taken from two trials) who did not receive BM-MNCs was 20% (95% CI 0.12-0.32). The pooled difference in the safety outcomes was not significant between both the groups. Our systematic review suggests that BM-MNC therapy is safe up to 1 year post-intervention and is feasible; however, its efficacy in the case of IS patients is debatable. Well-designed randomized controlled trials are required to provide more information on the efficacy of BM-MNC transplantation in patients with IS.

Association of pollution and climate with atopic eczema in US children.

BACKGROUND: We sought to determine the relationship between childhood eczema, climate, and environmental pollutants. METHODS: We analyzed data from the 2007-2008 National Survey of Children's Health including a representative sample of 91,642 children age 0-17 years and the 2006-2007 Environmental Protection Agency measurements of carbon monoxide (CO), nitrate (NO3 ), nitrogen dioxide (NO2 ), organic carbon (OC), sulfate (SO3 ), sulfur dioxide (SO2 ), particulate matter ≤2.5 µm (PM-2.5) and <10 µm (PM-10), and tropospheric ozone levels, and the National Climate Data Center measurements of relative humidity (%), issued UV index, outdoor air temperature, and precipitation levels. RESULTS: In multivariate survey logistic regression models controlling for age, sex, race/ethnicity, household income, US birthplace, and history of moving to a new location, eczema was associated with higher mean annual NO2 (p = 0.008), SO2 (p = 0.006), SO3 (p = 0.0002), arsenic (p = 0.0007), nickel (p = 0.0002), lead (p = 0.03), vanadium (p < 0.0001), and zinc (p = 0.003), but lower NO3 (p = 0.002), OC (p = 0.03), PM-2.5 (p = 0.006), cadmium (p < 0.0001), copper (p = 0.004), and potassium (p < 0.0001). In contrast, moderate-severe eczema was associated with higher NO3 (p = 0.03), OC (p = 0.008) and PM-2.5 (p = 0.01), copper (p = 0.04), lead (p = 0.008), and zinc (p = 0.01), but lower CO (p = 0.03). Principal component analysis was used and identified 4 combinations of pollutants and climate factors occurring in the USA, of which 1 was associated with higher prevalence and two were associated with lower prevalences of eczema (p < 0.05). CONCLUSIONS: Pollutants in conjunction with climate factors may differentially impact eczema prevalence and severity, some with apparent harmful effects.

Biomarkers to enhance accuracy and precision of prediction of short-term and long-term outcome after spontaneous intracerebral haemorrhage: a study protocol for a prospective cohort study.

BACKGROUND: Several studies reported prognostic value of biomarker in intracerebral hemorrhagic (ICH) but they are either preliminary observation or inadequately powered to analyse independent contribution of biomarkers over and above clinical and neuroimaging data. OBJECTIVE: To examine whether the biomarker can significantly add to the predictive accuracy of prognosis of ICH. METHOD/DESIGN: In a multi-centric prospective cohort study, 1020 patients with ICH within 72 hours of onset are being recruited. After obtaining written informed consent from patients/proxy, venous blood sample (10 ml) is being collected and analysed for C-reactive protein (CRP) level, S100B, Glial fibrillary acidic protein (GFAP), Troponin, change in leukocyte count and Copeptin levels. The patients are telephonically followed using stroke scales (Barthel Index and modified Rankin Scale) at 3, 6, 12 months and 2 years after the recruitment. DISCUSSION: This protocol will aim at predicting the short term or long term prognosis with the use of clinical, neuroimaging and biomarkers in order to help clinician to stratify patients for early referral or intervention.

Sitting occupations are an independent risk factor for Ischemic stroke in North Indian population.

Stroke is a multi-factorial disease and is influenced by complex environmental interactions. The purpose of this case-control study was to determine the relationship of sitting occupations with ischemic stroke in the North Indian population. In a hospital-based case-control study, age- and sex-matched controls were recruited from the outpatient department and the neurology ward of All India Institute of Medical Sciences, New Delhi. Occupation along with other demographic and risk factor variables was measured in-person interview in standardized case record form. The multivariate logistic regression model was used to estimate the odds ratio associated with ischemic stroke. Two hundred and twenty-four people post-stroke and 224 control participants were recruited from the period of February 2009 to February 2012. Mean age of cases and controls was 53.47 ± 14 and 52.92 ± 13.4, respectively. The occupations which involve sitting at work were independently associated with the risk of ischemic stroke after adjustment for demographic and risk factor variables (OR 2.2, 95% CI 1.12-3.8). The result of this study has shown an independent association between the sitting occupations and ischemic stroke in North Indian population. The present study supports the workplace health initiative to implement workplace physical activity policy and encourages employee to reduce the amount of time they spend sitting throughout the day.

Effect of dialysis modality and membrane transport characteristics on dialysate protein losses of patients on peritoneal dialysis.

OBJECTIVE: To determine if peritoneal dialysis modality has an impact on protein losses in dialysate. DESIGN: Retrospective, cross-sectional study. PATIENTS: 190 patients who had selected peritoneal dialysis were classified into one of four transport categories (high, high-average, low-average, or low) based on standard peritoneal equilibration test results. Patients were then assigned to continuous ambulatory peritoneal dialysis (CAPD) or nightly intermittent peritoneal dialysis (NIPD) based on membrane transport characteristics and individual preferences. RESULTS: Patients with similar membrane transport characteristics had essentially no differences in dialysate protein and albumin losses whether treated with CAPD or NIPD. CONCLUSIONS: Although high transporters may be better managed with short-dwell therapies such as nocturnal intermittent peritoneal dialysis or daily ambulatory peritoneal dialysis, consistent marked decreases in protein losses cannot be cited as a benefit of NIPD over CAPD.

Calculation of 6-hour D/P creatinine ratio from the 4-hour peritoneal equilibration test. The effect of dwell duration on the results.

OBJECTIVES: Since the introduction of the peritoneal equilibration test (PET), the 4-hour dialysate/plasma creatinine (D/P Cr) has been used by several authors for determining continuous ambulatory peritoneal dialysis (CAPD) prescriptions. However, the results have been unsatisfactory because the 4-hr D/P Cr does not accurately reflect the D/P Cr in 24-hr collections. The PET and the 24-hr dialysate collections differ in the duration of dwell and the tonicity and volume of dialysate, all of which influence the equilibrated D/P Cr. It can be assumed that the D/P Cr in 24-hr collections in these patients is closer to a 6-hr D/P Cr. Because a 6-hr PET is inconvenient, we developed a mathematical model to calculate the 5- and 6-hr D/P using the results of a standard PET. DESIGN: In a retrospective analysis, D/P Cr ratios in 24-hr collections and D/P Cr ratios calculated from a mathematical formula were correlated. Using a mathematical model, the data collected fit an exponential relation of the type D/P = a(1-e-t/tau). The values of a and tau are unique for a given patient and were determined using a nonlinear regression technique. The formula performed well on our published data-the true and predicted 6-hr D/P Cr being 0.696 and 0.71, respectively. SETTING: The University Hospital and Clinics, Dalton Cardiovascular Research Center and Dialysis Clinic, Inc., Columbia, Missouri. PATIENTS: All CAPD patients on four 2-L exchanges/day at the time of the 24-hr collections were included. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Closeness of 4-hr and 6-hr D/P Cr values to those of 24-hr ratios. RESULTS: The study group comprised 74 patients (age, mean +/- SEM: 56.4 +/- 1.8 yr) with 80 PETs and 145 (24-hr) collections. The interval between the two tests was 8.3 +/- 0.9 months (0-48.7 months). The median 24-hr D/P Cr of 0.760 did not differ significantly from the predicted median 6-hr D/P Cr of 0.755. A subgroup analysis, based on transport type, showed that this relationship was most precise in the high-average transporters. The predicted 6-hr D/P Cr was within 10% of the 24-hr D/P Cr in 48% of patients and within 20% in 77% of patients. The margin of error was greatest in the low transporters. CONCLUSIONS: To conclude, the 4-hr D/P Cr from a PET cannot be used interchangeably with the D/P Cr in the 24-hr dialysate collections, hence, the clearances calculated thereof will be inaccurate. Using the proposed model, it is feasible to use the 4-hr PET results to obtain 5- and 6-hr D/P Cr values. In our study, using this model, the extrapolated 6-hr D/P Cr is similar to the D/P Cr in 24-hr dialysate collections only in the high-average transporters. Hence, the best way to determine clearances in peritoneal dialysis patients is still by collecting 24-hr dialysates.

Gastrointestinal complications after renal transplantation. 10 Year data from a North Indian Transplant Center.

Gastrointestinal complications are responsible for substantial morbidity and mortality among renal allograft recipients in developing countries. During a 10 year period, 166 (62.6%) of 265 allograft recipients developed gastrointestinal complications. This figure reflects the high incidence of infectious complications, especially acute diarrheas. Also notable was the incidence of esophageal candidiasis (7.2%), ischemic colitis (2.6%), and gastrointestinal and peritoneal tuberculosis (3.0%). Almost one quarter of the complications developed in the first 6 months after transplantation. Mortality was the highest with acute ischemic colitis (100%), pancreatitis (60%), and upper gastrointestinal hemorrhage (40%). Improvements in standards of living and sanitary conditions, pre transplant evaluation and assessment of risk factors, prophylaxis with anti ulcer drugs, early diagnosis, and appropriate treatment are needed to decrease the frequency and severity of gastrointestinal complications in renal allograft recipients.

Temporary stoppage of peritoneal dialysis when laparoscopic procedures are performed on patients undergoing CAPD/CCPD: a change in policy.

Laparoscopic surgery has been gaining in popularity. Prior to 1995, whenever our patients had a laparoscopic procedure it was carried out with the standard precautions, and the patient stayed on peritoneal dialysis (PD). We noticed a high incidence (71.4%) of peritonitis post laparoscopic surgery. Four of the peritonitis patients had cholecystectomies and 1 had a gastrostomy for placement of a feeding tube laparoscopically. The patients' ages ranged from 31 to 74 years; 4 (80%) were females. They had been on PD for a mean of 24 months (range 6-48 months). Peritonitis was diagnosed within a mean of 22.2 hours (r: 12-36 h) post procedure. The causative organisms were Klebsiella in two cases, Staph. aureus in one, Pseudomonas in one, with no growth observed in one. Following this, we instituted a deliberate policy of temporary cessation of PD for 2 weeks post laparoscopic procedure, maintaining the patient on hemodialysis during this period. Since the adoption of this policy, we have had no peritonitis in 7 patients who have undergone laparoscopic procedures.

Preliminary evaluation of silver-coated peritoneal catheters in rats.

Silver is known to have powerful antibacterial properties against a variety of micro-organisms and has a low toxicity and a favorable biocompatibility profile. This study was designed to evaluate the effectiveness of silver-coated catheters in preventing early exit-site infection and to assess tunnel morphology. Seven male Sprague-Dawley rats underwent simultaneous implantation of two double-cuffed, silver-coated silicone rubber and standard silicone rubber catheters. Weekly observations and photographs documented exit-site characteristics. The animals were sacrificed and catheters removed and processed for histopathology of the external tunnel at 5 weeks. Exit sites of silver-coated catheters tended to have less inflammation and infection and healed better than those of uncoated catheters; however, these data did not achieve significance using the Wilcoxon signed-rank test. Sections of the external tunnel of well-healing exit sites showed an epithelialized tract with granulation tissue near the cuff and significant invasion of the external cuff by collagen with a mild neutrophilic inflammatory response. In contrast, the histology of the external tunnel of infected exists revealed exudate overlying inflammatory granulation tissue and a variable degree of fibrosis of the cuff. When the exit sites appeared similar, no significant histopathological differences in sinus tract and cuff morphology were noted with either silver or standard catheters. In conclusion, these findings suggest that silver coating of catheters may decrease the incidence of early exit-site infections and allow better ingrowth of the catheter.

The effect of peritonitis on the peritoneal membrane transport properties in patients on CAPD.

Peritonitis is known to acutely affect the transport characteristics of the peritoneal membrane, however, the long-term effects are not known. We studied the effect of peritoneal inflammation on mean dialysate-to-plasma creatinine concentration ratio (D/P), dialysate protein losses (DPL, g/week), and dialysate albumin losses (DAL, g/week), done at six weeks or more postepisode, in 152 patients [102 (67%) males, mean age 57 years (range 21-91)]. These patients were on continuous ambulatory peritoneal dialysis for a mean of twelve months (range 1-97). A total of 94 distinct peritonitis episodes were managed in 47 patients (31%). The number of patients with 0, 1, 2, 3, 4, and 5 episodes of peritonitis were 105, 29, 3, 6, 4, and 5. These episodes were treated with a standard protocol. There were no statistically significant differences between the D/P, DPL, or DAL between the groups. The parameters did not show any correlation to time on dialysis. Thus, in conclusion, peritonitis, if promptly treated, does not cause any permanent change in D/P, DAL, or DPL.

Evaluation of healing and external tunnel histology of silver-coated peritoneal catheters in rats.

A previous study showed that silver-coating peritoneal catheters tended to decrease the incidence of early exit-site infections in rats. This study was designed to further evaluate the healing, biocompatability, and external tunnel morphology of standard and silver-coated catheters. Catheters were coated with silver by an ion beam-assisted process. Fourteen male Sprague-Dawley rats underwent implantation of either a standard or silver-coated double-cuff peritoneal catheter. Weekly observation and photographs documented exit-site characteristics. Erythema, exudate, loose fit, and poor hair growth were evidence of an inflamed exit. Overt infection was indicated by the presence of three or more of the following: erythema, purulent exudate, exuberant granulation tissue, loose fit, and poor hair growth. Animals were sacrificed at six weeks, and catheters were removed and processed for histology of the external tunnel. Multiple measurements were taken using a Filar eyepiece, and data were expressed as a mean of several readings. Inflammation, vascularity, and fibrosis were judged semiquantitatively. At the end of six weeks, six of the seven exits of the silver catheters showed excellent healing, while one exit site had signs of excessive inflammation. Four of the exit sites of the standard catheters healed well, two were inflamed, and one was overtly infected. The sinus tract of the standard and silver catheters had similar characteristics: keratinized and nonkeratinized epithelium lined the external part of the sinus tract and merged into granulation tissue. A fibrous sheath was noted in some sinus tracts between the granulation tissue and the cuff. The cuff evoked a foreign body reaction, with fibrosis, multiple giant cells, and vascularization. Poorly healing or infected sinus tracts had highly vascular granulation tissue with overlying exudate. The cuff of these catheters had marked inflammation and scanty giant cells, although collagen bundle thickness was similar to the well-healing catheters. In conclusion, silver-coating potentially enhances healing of the exit sites of peritoneal catheters. Additionally, the similarity of the tunnel histomorphology of standard and silver catheters confirms the favorable biocompatibility of silver.

Total serum immunoglobulin E levels in a case-control study in asthmatic/allergic patients, their family members, and healthy subjects from India.

BACKGROUND: Total immunoglobulin E (IgE) is an important indicator of allergic disorders. However, its role in allergic patients in India has not been evaluated in relation to atopic status for a reference range as compared with healthy subjects. OBJECTIVE: The aim of the study was to establish serum IgE levels in a diseased group, study its relationship with atopy, and to compare the same with healthy volunteers in Indian subjects. METHODS: Four hundred and eighty asthmatics/allergic patients, 100 first-degree relatives of asthmatics, and 120 unrelated normal healthy volunteers from Delhi region were recruited for the study. Atopy was established by family history and skin test to common indigenous allergens and, total and specific IgE measurements. Statistical analysis was performed with the help of SPSS software program. RESULTS: The mean IgE levels were the highest in asthmatic patients and the lowest in the control healthy group. IgE was significantly high in the male than the female healthy volunteers (P<0.05), but not in the diseased group. Prosopis juliflora among pollen allergens and Alternaria alternata among fungal allergens were important sensitizers in allergic patients with 34.7% and 17.7% skin positivity, respectively. Atopic status and asthma were found to be the best predictor of IgE, which was highly significant (r(2)=0.239, P<0.00001). However, at 95% confidence interval as many as 50% of asthmatic patients had their IgE values in the normal range. CONCLUSION: The IgE levels in Indian allergic patients is significantly related to atopy, but due to wide overlap of IgE levels in patients and healthy subjects, its diagnostic significance in Indian population seems to be limited.

Hypokalemic metabolic alkalosis with hypomagnesuric hypermagnesemia and severe hypocalciuria: a new syndrome?

Bartter's and Gitelman's syndromes are characterized by hypokalemia, urinary potassium wasting, elevated plasma renin activity and aldosterone levels, normotension, and prostaglandinuria. They differ in that hypomagnesemia and hypocalciuria are universal in Gitelman's syndrome; 20% of cases of Bartter's syndrome have hypomagnesemia and hypercalciuria. We present a 44-year-old white man referred for hypokalemia. Clinical evaluation was unremarkable. He had hypokalemia (P(K), 2.8 to 3.0 mEq/L), hypochloremic metabolic alkalosis, mild azotemia (serum creatinine, 1.4 to 1.8 mg/dL; creatinine clearance, 59 mL/min), normocalcemia, marked persistent hypocalciuria (FE(Ca), 0.08% to 0.09%), and normal intact parathyroid hormone levels (51 pg/mL) and glucosuria. He had persistent hypermagnesemia (P(Mg), 2.1 to 2.8 mEq/L) with relative hypomagnesuria (FE(Mg), 3.2% to 5.2%) given the level of renal impairment and hypermagnesemia. Supine plasma renin activity and aldosterone levels were high (11 ng/mL/hr and 43 ng/dL, respectively). An excessive dietary intake of magnesium, including medications, was excluded. Studies were performed after withdrawing all medications for 8 days. A maximum water diuresis was established (an oral load of 20 mL/kg; stable Uosm, 120 mOsm/kg), and free water and solute clearances were studied at baseline and after sequential intravenous injections of 125 mg chlorothiazide and 40 mg furosemide. The patient had moderate renal impairment (technetium diethylene triamine pentacetic acid [DTPA] clearance, 35.4 mL/min/1.73 m2) and, in contradistinction to Bartter's and Gitelman's syndromes, sodium and water handling in the thick ascending limb of the loop of Henle and the distal tubule (fractional distal solute reabsorption) was normal, but there was evidence of a defect in the proximal tubule reabsorption (glucosuria, supranormal C(H2O) and high distal delivery). Hypomagnesuria and hypocalciuria appeared to be secondary to an increase in their absorption in the loop of Henle (increased excretion following furosemide). In conclusion, this combination of metabolic abnormalities has never been described. We postulate a proximal tubular defect in the absorption of NaCl leading to hypocalciuria, hypomagnesuria, and potassium wasting. Whether the tubular defect is primary or secondary to a renal parenchymal disease is, however, unclear.

Pancreatic pseudocyst. A rare complication of polyarteritis nodosa.

An 18-year-old male who developed a pancreatic pseudocyst during the active phase of polyarteritis nodosa is described. Cytotoxic therapy with cyclophosphamide and prednisolone was unable to control the manifestation of this disease, and he required percutaneous drainage of the pseudocyst. The drainage resulted in complete resolution.

Renal mucormycosis: computerized tomographic findings and their diagnostic significance.

Isolated renal involvement by mucormycosis has been reported rarely in immunocompromised individuals. We describe four patients with mucormycosis confined to the kidneys, three of whom did not exhibit any predisposing factors. Only one patient had acute viral hepatitis with fulminant hepatic failure as the preceding disease. Two patients presented with oliguric renal failure of undetermined etiology and investigations revealed bilateral extensive involvement of the kidneys. Computerized tomography showed diffuse enlargement of the kidneys and multiple low-density areas. Treatment included systemic amphotericin B therapy in all four patients and nephrectomy in three patients. Two patients recovered completely. Our experience emphasizes the need for a high index of suspicion and recognition of computed tomographic scan appearances for making a prompt diagnosis. Early surgical intervention and systemic antifungal therapy are necessary for survival in this life-threatening condition.