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Yekosani Mitala,1 Abraham Birungi,1 Branchard Mushabe,2 John Manzi,3 Brian Ssenkumba,1 Raymond Atwine,1 Siyadora Ankunda2,4 1Department of Pathology, Mbarara University of Science and Technology, Mbarara City, Uganda; 2Department of Pediatrics, Kabale University, Kabale, Uganda; 3Department of Surgery, Mbarara University of Science and Technology, Mbarara City, Uganda; 4Department of Pediatrics, Mbarara Regional Referral Hospital, Mbarara City, UgandaCorrespondence: Yekosani Mitala, Email yekomitala@gmail.comIntroduction: Gaucher disease is a rare autosomal recessive lysosomal storage disease with unknown prevalence in Africa and no record of the disease exists in Uganda.Case Presentation: We report a case of a 12-year-old female, the last born of 6 from a family with no known familial disease who presented with non-neuronopathic Gaucher disease and superimposed malaria. The disease was initially misdiagnosed as hyperreactive malarial splenomegaly but was subsequently confirmed by examination of the bone marrow smear and core. The disease was managed supportively and splenectomy was done due to worsening hematological parameters. She currently takes morphine for bone pains in addition to physiotherapy.Conclusion: Always HMS is a common complication in malaria endemic areas, other causes of hepatosplenomegaly need to be excluded before the diagnosis is made. Diagnosis and treatment of patients with rare conditions like GD is still a challenge in developing countries. Although splenectomy is indicated in GD, it should only be done when it is absolutely necessary.Keywords: type 1 Gaucher’s disease, case report, Uganda

The actin cytoskeleton shapes cells and also organizes internal membranous compartments. In particular, it interacts with membranes for intracellular transport of material in mammalian cells, yeast, or plant cells. Tubular membrane intermediates, pulled along microtubule tracks, are formed during this process and destabilize into vesicles. While the role of actin in tubule destabilization through scission is suggested, literature also provides examples of actin-mediated stabilization of membranous structures. To directly address this apparent contradiction, we mimic the geometry of tubular intermediates with preformed membrane tubes. The growth of an actin sleeve at the tube surface is monitored spatiotemporally. Depending on network cohesiveness, actin is able to entirely stabilize or locally maintain membrane tubes under pulling. On a single tube, thicker portions correlate with the presence of actin. These structures relax over several minutes and may provide enough time and curvature geometries for other proteins to act on tube stability.

Background: Inflammation and hemostasis may increase the risk of kidney function decline; however, data from prospective studies are sparse.Study Design: The Atherosclerosis Risk in Communities (ARIC) Study, a prospective observational cohort.Setting& Participants: We used data from 14,854 middle-aged adults from 4 different US communities.Predictor: Markers of inflammation and hemostasis were examined.Outcomes& Measurements: The risk of kidney function decrease associated with these markers was studied. Glomerular filtration rate (GFR) was calculated from serum creatinine levels using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. Chronic kidney disease (CKD) was defined as: (1) a decrease in estimated GFR to less than 60 mL/min/1.73 m2 from greater than 60 mL/min/1.73 m2 at baseline, or (2) a hospitalization discharge or death coded for CKD. Serum creatinine was measured at baseline and the 3- and 9-year follow-up visits. Hazard ratios (HRs) of CKD associated with increased levels of inflammatory and hemostatic variables were estimated by using multivariate Cox proportional hazards regression.Results: 1,787 cases of CKD developed between 1987 and 2004. After adjusting for demographics, smoking, blood pressure, diabetes, lipid levels, prior myocardial infarction, antihypertensive use, alcohol use, year of marker measurement, and baseline renal function using estimated GFR, the risk of incident CKD increased with increasing quartiles of white blood cell count (HR quartile 4 versus quartile 1, 1.30; 95% confidence interval [CI], 1.12 to 1.50; P trend = 0.001), fibrinogen (HR, 1.25; 95% CI, 1.09 to 1.44; P < 0.001), von Willebrand factor (HR, 1.46; 95% CI, 1.26 to 1.68; P < 0.001), and factor VIIIc (HR, 1.39; 95% CI, 1.20 to 1.60; P < 0.001). A strong inverse association was found between serum albumin level and risk of CKD (HR, 0.63; 95% CI, 0.55 to 0.72; P < 0.001). No independent association was found with factor VIIc level.Limitations: Although we lacked a direct measure of kidney function, associations were robust to case definitions.Conclusions: Markers of inflammation and hemostasis are associated with greater risk of kidney function decrease. Findings suggest that inflammation and hemostasis are antecedent pathways for CKD. [ABSTRACT FROM AUTHOR]

Background: The calibration of serum creatinine values to standardized creatinine and the commutability of serum creatinine across surveys are essential to the correct use of National Health and Nutrition Examination Survey (NHANES) data for kidney function and for generating estimates of the burden of kidney disease in the United States.Study Design: Calibration study of serum creatinine in NHANES III (1988-1994) and NHANES 1999-2000, 2001-2002, and 2003-2004 to directly compare creatinine measurements from the original surveys with standard creatinine measured using an assay traceable to known gold-standard methods. We also assessed predictors of differences between methods (potential interferences) in this general population.Setting& Participants: The NHANES are ongoing cross-sectional surveys of the civilian noninstitutionalized population of the United States. We selected random samples of approximately 200 stored specimens from persons aged 60 years or older from each survey (NHANES III, 1999-2000, 2001-2002, and 2003-2004).Measurements: Stored serum specimens from the 4 NHANES surveys were analyzed for serum creatinine by using a Roche enzymatic assay implemented at the Cleveland Clinic Research Laboratory (CCRL). The Roche assay is traceable to gold-standard reference methods. The original NHANES serum creatinine values were obtained using the Jaffé method (kinetic alkaline picrate) implemented in several different laboratories.Results: Overall agreement between the original NHANES values (Jaffé method) and CCRL measurements (Roche enzymatic) was high, but substantial biases were observed in NHANES III and 1999-2000. No bias was observed in NHANES 2001-2002 and 2003-2004. Final calibration equations to correct serum creatinine values in the relevant surveys are provided. Assay differences were independent of sex, race/ethnicity, and bilirubin and triglyceride levels, but weakly related to age and glucose concentration.Limitations: We were not able to examine drift in measurements over time within each survey or directly evaluate freeze-thaw effects.Conclusions: The magnitude of differences in serum creatinine measurements in NHANES III and 1999-2000 from standard creatinine would result in large differences in estimates of kidney function (10% to 20%). Thus, correction of original creatinine values in NHANES III and 1999-2000 is essential, but no correction is needed for NHANES 2001-2002 or 2003-2004. [ABSTRACT FROM AUTHOR]

BACKGROUND: Variation in performance of glomerular filtration rate (GFR) estimating equations is related to variation in calibration of the creatinine assay across clinical laboratories. STUDY DESIGN: Cross-sectional analysis. SETTING & PARTICIPANTS: 6 research studies and 4 clinical populations including 5,504 participants who had GFR measured using urinary clearance of iothalamate. MEASUREMENTS: Standardized serum creatinine values obtained by means of calibration to the Cleveland Clinic Research Laboratory using frozen specimens, a calibration panel, and/or survey results from the College of American Pathologists. PREDICTOR: Noncalibrated serum creatinine assayed in research and clinical laboratories compared with standardized serum creatinine. OUTCOME: Difference between measured GFR versus GFR estimated from the Modification of Diet in Renal Disease (MDRD) Study and Cockcroft-Gault equations. RESULTS: For a noncalibrated serum creatinine value of 1 mg/dL (88.4 micromol/L), standardized serum creatinine value was 0.07 mg/dL (6.2 micromol/L) less than noncalibrated values. In the pooled data set, for the MDRD Study equation, calibration improved median percentage of difference between measured and estimated GFR from 9.0% (interquartile range [IQR], 28%) to 5.8% (IQR, 28%) and improved the percentage of estimates within 30% of measured GFR (P30) from 80% to 83%. The effect of calibration was greater at higher levels of GFR and varied across studies. For the Cockcroft-Gault equation, calibration worsened the median percentage of difference from -2.0% (IQR, 38%) to -11.4% (IQR, 39%), and the P30, from 74% to 69%. LIMITATIONS: College of American Pathologist samples were used for calibration of clinical populations; calibration factors do not account for drift over time in the serum creatinine assay; calibration cannot account for variation in assay performance among individuals. CONCLUSION: Calibration improves the performance of the MDRD Study equation. After calibration, larger errors remain for GFR estimates greater than 60 mL/min/1.73 m2 (>1 mL/s/1.73 m2).Copyright © 2007 by National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]