Evaluations of hospitalizations associated with thiazide-associated hyponatremia

The prevalence of hypertension in the United States has grown dramatically in recent years. Thiazide diuretics have played a major role in the rising rate of blood pressure (BP) control. Accompanying this has been the appearance of adverse drug events, including hospitalizations associated with thiazide-associated hyponatremia (HTAH). Hyponatremia is a common yet often overlooked side effect of this drug class. Identification of HTAH risk factors may aid in creating strategies to prevent hospitalizations. This is a retrospective, case-controlled study of 10,805 patients (1802 cases, 9003 controls) examining HTAH risk factors within a group-model integrated-care organization. Multivariate analysis revealed that age (odds ratio [OR], 1.75; 95% confidence interval [CI], 1.58-1.93), angiotensin-converting enzyme (ACE) inhibitor use (OR, 1.53; 95% CI, 1.16-2.00), and hypokalemia (OR, 40.94; 95% CI, 26.46-66.33) were most associated with HTAH. Urinary tract infection (UTI), type 2 diabetes, hyperlipidemia, and gastroesophageal reflux disease (GERD) were also found to be HTAH risk factors. Potassium supplements (OR, 0.60; 95% CI, 0.44-0.83) and weight (OR, 0.91; 95% CI, 0.88-0.93) had protective effects. A predictive model was developed to determine overall HTAH risk given the presence of individual risk factors. Age, weight, hypokalemia, GERD, type 2 diabetes, UTI, and ACE inhibitor use independently correlated with an increased risk of HTAH. This model may be applied in clinical practice to guide thiazide prescribing.     

Type-I interferon receptor deficiency reduces lupus-like disease in NZB mice

Indirect evidence suggests that type-I interferons (IFN-alpha/beta) play a significant role in the pathogenesis of lupus. To directly examine the contribution of these pleiotropic molecules, we created congenic NZB mice lacking the alpha-chain of IFN-alpha/betaR, the common receptor for the multiple IFN-alpha/beta species. Compared with littermate controls, homozygous IFN-alpha/betaR-deleted NZB mice had significantly reduced anti-erythrocyte autoantibodies, erythroblastosis, hemolytic anemia, anti-DNA autoantibodies, kidney disease, and mortality. These reductions were intermediate in the heterozygous-deleted mice. The disease-ameliorating effects were accompanied by reductions in splenomegaly and in several immune cell subsets, including B-1 cells, the major producers of anti-erythrocyte autoantibodies. Decreases of B and T cell proliferation in vitro and in vivo, and of dendritic cell maturation and T cell stimulatory activity in vitro were also detected. Absence of signaling through the IFN-alpha/betaR, however, did not affect increased basal levels of the IFN-responsive p202 phosphoprotein, encoded by a polymorphic variant of the Ifi202 gene associated with the Nba2 predisposing locus in NZB mice. The data indicate that type-I IFNs are important mediators in the pathogenesis of murine lupus, and that reducing their activity in the human counterpart may be beneficial.     

Cell type and gender-dependent differential regulation of the p202 and Aim2 proteins: implications for the regulation of innate immune responses in SLE

Upon sensing cytosolic double-stranded DNA (dsDNA), the murine Aim2 (encoded by the Aim2 gene) protein forms an inflammasome and promotes the secretion of proinflammatory cytokines, such as IL-1β and IL-18. In contrast, the p202 protein (encoded by the Ifi202 gene) does not form an inflammasome. Previously, we have reported that the interferon (IFN) and female sex hormone-induced increased nuclear levels of p202 protein in immune cells are associated with increased susceptibility to develop a lupus-like disease. However, signaling pathways that regulate the expression of Aim2 protein remain unknown. Here we report that the expression of Aim2 gene is induced in bone marrow-derived macrophages (BMDMs) by IFN-α treatment and the expression is, in part, STAT1-dependent. However, treatment of splenic T or B cells with IFN-α or their stimulation, which induced the expression of Ifi202 gene, did not induce the expression of Aim2 gene. Furthermore, treatment of cells with the male hormone androgen increased levels of Aim2 mRNA and protein. Moreover, treatment of murine macrophage cell lines (RAW264.7 and J774A.1) with IFN-α differentially induced the expression of Aim2 and p202 proteins and regulated their sub-cellular localization. Additionally, activation of Toll-like receptors (TLR3, 4, and 9) in BMDMs and cell lines also differentially regulated the expression of Aim2 and Ifi202 genes. Our observations demonstrate that cell type and gender-dependent factors differentially regulate the expression of the Aim2 and p202 proteins, thus, suggesting opposing roles for these two proteins in innate immune responses in lupus disease.     

Antiplasmodial activity of [(aryl)arylsulfanylmethyl]Pyridine

A series of [(aryl)arylsufanylmethyl]pyridines (AASMP) have been synthesized. These compounds inhibited hemozoin formation, formed complexes (K(D) = 12 to 20 muM) with free heme (ferriprotoporphyrin IX) at a pH close to the pH of the parasite food vacuole, and exhibited antimalarial activity in vitro. The inhibition of hemozoin formation may develop oxidative stress in Plasmodium falciparum due to the accumulation of free heme. Interestingly, AASMP developed oxidative stress in the parasite, as evident from the decreased level of glutathione and increased formation of lipid peroxide, H(2)O(2), and hydroxyl radical (.OH) in P. falciparum. AASMP also caused mitochondrial dysfunction by decreasing mitochondrial potential (DeltaPsim) in malaria parasite, as measured by both flow cytometry and fluorescence microscopy. Furthermore, the generation of .OH may be mainly responsible for the antimalarial effect of AASMP since .OH scavengers such as mannitol, as well as spin trap alpha-phenyl-n-tertbutylnitrone, significantly protected P. falciparum from AASMP-mediated growth inhibition. Cytotoxicity testing of the active compounds showed selective activity against malaria parasite with selectivity indices greater than 100. AASMP also exhibited profound antimalarial activity in vivo against chloroquine resistant P. yoelii. Thus, AASMP represents a novel class of antimalarial.     

Comment on: The candidate lupus susceptibility gene Ifi202a is largely dispensable for B-cell function

SIR, We read with interest the letter by Bupp et al. [1] concerningthe candidate lupus susceptibility gene Ifi202a. They concludethat the Ifi202a gene is largely dispensable for B-cell function.However, we feel that Bupp et al. provided incomplete informationin their letter concerning Ifi202 genes. Moreover, before weconclude that the Ifi202a gene is largely dispensable for B-cellfunction, we feel there are a number of observations that needto be considered. A study by Wang et al. [2] revealed that Ifi202a gene     

Scrotal Hitch Procedure to Prevent Apical Necrosis of Scroto-perineal Flap for Urethroplasty

Objective To present our experience with scrotal hitch technique to prevent necrosis of apex of scroto-perineal flap during two staged open urethroplasty for long segment complex anterior urethral strictures. Patients and methods Over the past 6 years, 22 patients underwent two-staged urethroplasty at our institution. All the strictures were laid open during first stage along with scrotal hitch. The stitch was removed after 7 days. Results The flap was healthy in all 22 patients at the time of second stage. Neo-meatal stenosis was not seen in any of the patients. One patient had local site collection, which was cured by topical antibiotics. Conclusion This technique is simple, cost effective, which minimizes the drag over the flap by the shaft of the Foley catheter and thus prevents its pressure necrosis. The technique is particularly helpful in cases of thick, bulky scrotum and does not cause any morbidity, instead allows for early, comfortable ambulation and obviates the need of cumbersome scrotal supportive dressings.     

Measurement of entrance skin dose and estimation of organ dose during pediatric chest radiography

Entrance skin dose (ESD) was measured to calculate the organ doses from the anteroposterior (AP) and posteroanterior (PA) chest x-ray projections for pediatric patients in an Indian hospital. High sensitivity tissue-equivalent thermoluminescent dosimeters (TLD, LiF: Mg, Cu, P chips) were used for measuring entrance skin dose. The respective organ doses were calculated using the Monte Carlo method (MCNP 3.1) to simulate the examination set-up and a three-dimensional mathematical phantom for representing an average 5-y-old Indian child. Using this method, conversion coefficients were derived for translating the measured ESD to organ doses. The average measured ESDs for the chest AP and PA projections were 0.305 mGy and 0.171 mGy, respectively. The average calculated organ doses in the AP and the PA projections were 0.196 and 0.086 mSv for the thyroid, 0.167 and 0.045 mSv for the trachea, 0.078 and 0.043 mSv for the lungs, 0.110 and 0.013 mSv for the liver, 0.002 and 0.016 mSv for the bone marrow, 0.024 and 0.002 mSv for the kidneys, and 0.109 and 0.023 mSv for the heart, respectively. The ESD and organ doses can be reduced significantly with the proper radiological technique. According to these results, the chest PA projection should be preferred over the AP projection in pediatric patients. The estimated organ doses for the chest AP and PA projections can be used for the estimation of the associated risk.     

Supracardiac total anomalous pulmonary venous connection with cor triatriatum sinister: A rare diagnosis confirmed by saline contrast echocardiography

In cor triatriatum sinister, the left atrium is divided by a membrane into a proximal and a distal chamber. Usually proximal chamber receives all the pulmonary veins and drains through an opening in the dividing membrane into distal chamber, which empties into left ventricle through the mitral valve. Rarely, the two chambers lack a communication and there is associated total anomalous pulmonary venous connection (TAPVC). We report a 1-month-old infant with cyanosis and heart failure, who had cor triatriatum sinister associated with supracardiac TAPVC. The case is reported for rarity of the association with a focus on contrast echocardiographic imaging.