Urinary tract infections per se do not cause end-stage kidney disease

The objective of this study was to determine the frequency with which urinary tract infection (UTI) in the absence of concomitant underlying abnormalities caused end-stage renal disease (ESRD). The records of 102 patients with ESRD (disease necessitating dialysis and/or transplant) seen at Children’s Mercy Hospital during a 10-year period (1986 – 1995) were reviewed. Obstructive uropathy, aplastic/hypoplastic/dysplastic kidneys, polycystic kidney disease, congenital nephrotic syndrome, acquired glomerulonephritis, idiopathic interstitial nephritis, hemolytic uremic syndrome, and a variety of systemic conditions were the cause of ESRD in 99 children; 3 children had reflux nephropathy, 1 of whom had no history of a UTI and another who had a single, afebrile UTI. A girl with a history of recurrent UTIs since 4 years of age had an elevated serum creatinine and grade II – III bilateral vesicoureteric reflux when evaluated at 8 years of age. She had ureteral reimplantations and control of the infections, but progressed to ESRD. This child appears to be the only 1 of 102 children who developed ESRD because of acquired renal injury in which UTIs were an important contributing factor. Received July 29, 1997; received in revised form October 22, 1997; accepted October 26, 1997     

Rapid evolution of Cse4p-rich centromeric DNA sequences in closely related pathogenic yeasts, Candida albicans and Candida dubliniensis

The Cse4p-containing centromere regions of Candida albicans have unique and different DNA sequences on each of the eight chromosomes. In a closely related yeast, C. dubliniensis, we have identified the centromeric histone, CdCse4p, and shown that it is localized at the kinetochore. We have identified putative centromeric regions, orthologous to the C. albicans centromeres, in each of the eight C. dubliniensis chromosomes by bioinformatic analysis. Chromatin immunoprecipitation followed by PCR using a specific set of primers confirmed that these regions bind CdCse4p in vivo. As in C. albicans, the CdCse4p-associated core centromeric regions are 3–5 kb in length and show no sequence similarity to one another. Comparative sequence analysis suggests that the Cse4p-rich centromere DNA sequences in these two species have diverged faster than other orthologous intergenic regions and even faster than our best estimated “neutral” mutation rate. However, the location of the centromere and the relative position of Cse4p-rich centromeric chromatin in the orthologous regions with respect to adjacent ORFs are conserved in both species, suggesting that centromere identity is not solely determined by DNA sequence. Unlike known point and regional centromeres of other organisms, centromeres in C. albicans and C. dubliniensis have no common centromere-specific sequence motifs or repeats except some of the chromosome-specific pericentric repeats that are found to be similar in these two species. We propose that centromeres of these two Candida species are of an intermediate type between point and regional centromeres.     

Effect of Nickel on Some Aspects of Protein Metabolism in Selected Organs of the Freshwater of the Freshwater Mussel Lamellidens marginalis

The levels of soluble, structural and total proteins, and the activities of A1AT and AAT decreased along with an increase in the levels of free amino acids and the activity of protease in the ctenidium, hepatopancreas and foot of the freshwater mussel L. marginalis after 1, 2, 3 and 4 d of exposure to a lethal concentration (115 mg.L-1) of nickel. But the activity of GDH and the level of urea decreased in the hepatopancreas and increased in the ctenidium and foot. A reverse trend was observed in the level of ammonia. In a sublethal concentration (23 mg.L-1), the levels of soluble, structural and total proteins and ammonia decreased in these three organs of the mussel after 1, 5, 10 and 15 d of exposures, with an increase in the levels of free aminoacids, urea and in the activities of protease, A1AT, AAT and GDH. The extent of these changes differed in degree depending on exposure period in the lethal and sublethal concentrations. The results are discussed in order to arrive at the degree of metal stress on the overall nitrogen metabolism of the mussel according to the period of exposure to lethal and sublethal concentrations of nickel.     

Serum IGF-1 concentrations in a sample of patients with traumatic brain injury as a diagnostic marker of growth hormone secretory response to glucagon stimulation testing

Objective The diagnosis of growth hormone deficiency (GHD) in adults is established through growth hormone (GH) stimulation testing, which is often complex, expensive, time‐consuming and may be associated with adverse side effects. The decision to perform GH provocative testing is influenced by clinical findings, medical history and biochemical evidence. We report in this study our experience using the glucagon stimulation test (GST) in assessing GHD in adult patients with traumatic brain injury (TBI) as it relates to baseline serum insulin‐like growth factor‐1 (IGF‐1) concentrations. Design A receiver operating characteristic (ROC) curve analysis was performed to determine the optimal IGF‐1 cut‐off for diagnosis of GHD at different potential diagnostic GST cut‐off values (<3, <5, & <10 μg/l). Patients One hundred and thirty‐eight patients (98 men and 40 women) with a documented history of moderate to severe TBI were assessed for GHD using serum IGF‐1 concentrations and the GST. Measurements IGF‐1 values were compared with peak GH values obtained following the GST. Results An IGF‐1 cut‐off value of 175 μg/l minimized the misclassification of GHD patients and GH‐sufficient patients and provided a sensitivity of 83% and specificity of 40%, as well as a negative predictive power of 90% considering a criterion for peak GH response of <3 μg/l. Conclusions Our current findings are consistent with previous work assessing peak GH response using the insulin tolerance test (ITT) in a non‐TBI sample, suggesting that diagnostic accuracy may be optimized if the GST is used when obtained serum IGF‐1 concentrations are below 175 μg/l. While the decision to perform provocative testing to assess GHD in adult patients should be based on the clinician’s clinical impression, the findings from this retrospective study can provide useful clinical information and serve as a guide.     

An indigenously developed method for sweat collection and estimation of chloride for diagnosis of cystic fibrosis

An indigenously developed method for sweat collection and titration method for estimation of chloride was validated. The mean difference in estimated chloride value from the known strength of saline in 50 samples was -1.04 +/- 4.13 mEq/L (95% CI: -0.07 to 2.28). The mean difference in the estimated chloride values between two observers when the test was performed on known strengths of saline solution was -2.5 +/- 4.24 mEq/L (95% CI: -3.67 to 1.33). The inter observer variability between two observers when the test was performed on sweat samples obtained from 50 individuals was -1.12 +/- 4.34 mEq/L (95% CI: -2.23 to 0.8 ). Sweat weight of more than 100 mg could be collected in first attempt in 602 of 757 (80%) patient with an average sweat weight of 230 mg. This inexpensive method of sweat collection and chloride estimation has acceptable accuracy and repeatability and can be used in resource poor setting for making a diagnosis of cystic fibrosis.     

Inhibition of the mitochondrial calcium uniporter rescues dopaminergic neurons in pink1−/− zebrafish

Mutations in PTEN‐induced putative kinase 1 (PINK1) are a cause of early onset Parkinson's disease (PD). Loss of PINK1 function causes dysregulation of mitochondrial calcium homeostasis, resulting in mitochondrial dysfunction and neuronal cell death. We report that both genetic and pharmacological inactivation of the mitochondrial calcium uniporter (MCU), located in the inner mitochondrial membrane, prevents dopaminergic neuronal cell loss in pink1^Y431* mutant zebrafish (Danio rerio) via rescue of mitochondrial respiratory chain function. In contrast, genetic inactivation of the voltage dependent anion channel 1 (VDAC1), located in the outer mitochondrial membrane, did not rescue dopaminergic neurons in PINK1 deficient D. rerio. Subsequent gene expression studies revealed specific upregulation of the mcu regulator micu1 in pink1^Y431* mutant zebrafish larvae and inactivation of micu1 also results in rescue of dopaminergic neurons. The functional consequences of PINK1 deficiency and modified MCU activity were confirmed using a dynamic in silico model of Ca²⁺ triggered mitochondrial activity. Our data suggest modulation of MCU‐mediated mitochondrial calcium homeostasis as a possible neuroprotective strategy in PINK1 mutant PD.     

A Systematic Review and Meta-Analysis on the Efficacy of Curcumin/Turmeric for the Prevention and Amelioration of Radiotherapy/Radiochemotherapy Induced Oral Mucositis in Head and Neck Cancer Patients

Background: Oral Mucositis(OM) is an acute debilitating dose limiting toxicity of Radiotherapy/Radiochemotherapy(RT/RCT) in management of Head and Neck Cancer (HNC). Curcumin/Turmeric may reduce OM in patients. Aim: Efficacy of Curcumin/Turmeric for preventing and ameliorating the onset and severity of RT/RCT induced OM was analysed in this review. Methods: A systematic literature search with meta-analysis were performed using Mesh terms in PubMed, Google scholar, Science Direct, Cochrane library and manual searching, articles published from 2010 to April 2021 were included. Clinical trials that studied the efficacy/effects of turmeric / curcumin in management of RT/RCT induced OM in HNC patients were included. Statistical Analysis were done to calculate the pooled Risk ratio at 95%confidence interval with significance at p     

Right Ventricular Tissue Doppler and Strain Imaging: Ready for Clinical Use?

Although tissue Doppler (TD) imaging of the left ventricle is now commonly used in clinical settings, TD imaging of the right ventricle (RV) is not routinely practiced. Yet, there are significant data on clinical uses of RV TD imaging, including established normal values using both color and spectral TD. In acute left ventricular (LV) inferior wall myocardial infarction, depressed RV TD velocities have been shown to correlate with the presence of RV impairment, and with patient outcome. In patients with LV heart failure, TD imaging has been correlated to RV ejection fraction by radionuclide angiography, and is an independent predictor of outcome. In patients with congenital heart disease, RV TD has been especially valuable for assessing RV function, and has been correlated to invasive hemodynamic indices, and RV ejection fraction by magnetic resonance imaging. The RV performance (Tei) index has been calculated and validated using TD-derived, rather than conventional pulsed Doppler time intervals. RV TD indices have been shown to be useful in the detection of subclinical and clinical disease in morbid obesity, chronic pulmonary, and systemic disease. TD-derived RV strain imaging can detect segmental myocardial dysfunction, overcoming limitations to conventional TD imaging resulting from tethering. For both TD velocity and strain imaging, however, appreciation of the limitations of these techniques is necessary for their appropriate use. Given its rapid acquisition times, reproducibility, and ease of addition to standard transthoracic echocardiographic protocols, RV TD and strain imaging are important additional modalities in the comprehensive echo-Doppler assessment of RV function.