Dextrocardia, situs inversus and severe mitral stenosis in a pregnant woman: successful closed commissurotomy

A 16-weeks' pregnant woman with situs inversus and dextrocardia underwent successful closed commissurotomy for severe mitral stenosis. The electrocardiogram revealed sinus rhythm with right axis deviation and progressive diminishing of QRS amplitude towards the left precordial leads. The chest X-ray showed dextrocardia with situs inversus. Doppler echocardiography depicted severe mitral stenosis; the mitral valve area increased from 0.9 cm2 pre-operatively to 1.8 cm2 post-operatively with mild increase of mitral regurgitation from grade I to II post-valvotomy. She also had associated mild functional tricuspid insufficiency and moderate pulmonary hypertension. No thrombo-embolic complications occurred intra- or post-operatively. There was no evidence of either clinical or Doppler restenosis. The course of pregnancy was uneventful. At 39 weeks a healthy baby was vaginally delivered. The patient is still free of cardiac symptoms.     

Splenic infarction secondary to acute pancreatitis

BACKGROUND AND OBJECTIVE: the close anatomic relationship of the pancreas with the splenic vessels and the spleen is responsible for splenic complications in the course of acute pancreatitis. Our objective was to report two cases of severe acute pancreatitis complicated by splenic infarction. PATIENTS: in a three-month period of time two patients were diagnosed with splenic infarction secondary to acute pancreatitis. In both cases splenic infarction diagnosis and follow-up were carried out using computed tomography. RESULTS: in the first case images clearly showed a narrowing of the splenic artery due to the inflammatory pancreatic condition. In the second case no involvement of the splenic vessels could be demonstrated, hence the only possible etiological explanation was a hypercoagulability state generated by pancreatitis. CONCLUSIONS: it would be advisable that splenic complications were added to the list of relevant extrapancreatic manifestations. CT is very useful for the diagnosis and follow-up of splenic complications arising in acute pancreatitis.     

Short-term Effects of Alfacalcidol on Hospital Length of Stay in Patients Undergoing Valve Replacement Surgery: A Randomized Clinical Trial

PurposeVitamin D deficiency is highly prevalent in critically ill patients, and has been associated with more prolonged length of hospital stay and poor prognosis. Patients undergoing open-heart surgery are at higher risk due to the associated life-threatening postoperative complications. This study investigated the effect of alfacalcidol treatment on the length of hospital stay in patients undergoing valve-replacement surgery.MethodsThis single-center, randomized, open-label, controlled trial was conducted at El-Demerdash Cardiac Academy Hospital (Cairo, Egypt), from April 2017 to January 2018. This study included adult patients undergoing valve-replacement surgery who were randomized to the intervention group (n = 47; alfacalcidol 2 μg/d started 48 h before surgery and continued throughout the hospital stay) or to the control group (n = 42). The primary end points were lengths of stay (LOS) in the intensive care unit (ICU) and in the hospital. Secondary end points were the prevalence of postoperative hospital-acquired infections, cardiac complications, and in-hospital mortality.FindingsA total of 86 patients were included in the final analysis, with 51 (59.3%) being vitamin D deficient on hospital admission. Treatment with alfacalcidol was associated with a statistically significant decrease in ICU LOS (hazard ratio = 1.61; 95% CI, 1.77–2.81; P = 0.041) and hospital LOS (hazard ratio = 1.63; 95% CI, 1.04–2.55; P = 0.034). Treated patients had a significantly lower postoperative infection rate than did the control group (35.5% vs 56.1%; P = 0.017). The median epinephrine dose was lower in the intervention group compared to that in the control group (5.9 vs 8.2 mg; P = 0.019). The rate of in-hospital mortality was not significantly different between the 2 groups.ImplicationsEarly treatment with 2 μg of alfacalcidol in patients undergoing valve-replacement surgery is promising and well tolerated. This effect may be attributed to its immunomodulatory and cardioprotective mechanisms. ClinicalTrials.gov identifier: NCT04085770.     

Impact of IL12B Gene rs 3212227 Polymorphism on Fibrosis,Liver Inflammation,and Response to Treatment in Genotype 4 Egyptian Hepatitis C Patients

Introduction. Hepatitis C virus (HCV) infection affects almost 3% of the world''s population with the highest prevalence in Egypt (15%). The standard therapy; pegylated interferon (PEG-IFN) and ribavirin, is effective in only 60% of Egyptian patients; moreover it is costly, prolonged, and has severe side effects, so prediction of response is essential to reduce burden of unfavorable treatment. Several viral and host factors have been proved to affect response to the treatment PEG-IFN and ribavirin; the strongest of them is polymorphisms near IL28B; nonetheless, nonresponse in patients with favorable IL28B is still unexplained, which implies the importance of studying other immunological factors that may correlate with response. Interleukin 12 (IL-12) is one of the most important proinflammatory cytokine presented with the initiation of immune response, determining Th1 and Th2 differentiation. A functional single nucleotide polymorphism (A/C) at the 3′ untranslated region (3′UTR) at position 1188 (NCBI SNP database no 3212227) was reported to be associated with responding more efficiently to antiviral combination therapy in HCV genotype 1 infected patients. The present study aims to evaluate association between this polymorphism with fibrosis stages, necroinflammation activity, response to the combined therapy, and gender in Egyptian HCV genotype 4. Material and Methods. A total of 133 Egyptian chronic HCV (CHCV) patients were treated with IFN/RBV and were followed up. IL12B 1188 A/C genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PRC-RFLP) analysis. Results. A nonsignificant trend for higher sustained virological response (SVR) was observed in patients homozygote for IL12B 1188 A/C SNP CC genotype (69% SVR versus 30.8% NR) only but not in AC and AA genotypes. No association was detected between IL12B 1188 A/C polymorphism and less severe fibrosis or less liver activity. By stratification of response according to gender genotype, a significant difference in response between males and females was seen among AA genotype carriers only due to high number of non responder females. Conclusion. IL12B CC genotype appears to have some influence on SVR achievement but not on severe fibrosis and severe necroinflamation activity. Females carrying A/A genotype of IL12B 1188 A/C SNP achieve less SVR than those carrying AC and CC genotypes.     

The ‘quadriceps angle’: correlation between clinical and radiographic measurements from a study in North Bengal

Introduction: Quadriceps angle (Q angle) is one of the most important indicators of stability of patello-femoral joint. Orthopedic surgeons often measure the Q angle clinically in patients suffering from patello-femoral joint dysfunction or in subjects particularly young active sportspersons who are prone to injury of this joint. But the clinical method of measurement of Q angle is not standardized, and its value depends on various methods used. But the radiological method of measurement of Q angle is more accurate. However, due to the expense and time involved, the clinical method is preferred over the radiological one in practice. Aim: This study was aimed at studying the correlation and regression between the radiographic Q-angle values and the clinical ones, so that the former can be predicted easily from the latter. Materials and methods: Q angle was measured both clinically and radiographically in both knee joints of 93 adult subjects in North Bengal Medical College and Hospital. Result: Statistically significant correlation followed by the regression analysis could reveal simple linear regression equations for predicting the radiological Q-angle values from the clinical Q angle, derived separately in both males and females in right and left sides, separately. Conclusion: Thus, from a known clinical Q-angle value, we can derive the respective radiological Q angle, indirectly avoiding the entire troublesome maneuver in regular practice. So the present study recommends this method in clinical fields because this is a more rational and ideal approach to estimate the radiological Q angle. Increase in the Q angle beyond 20–22° predisposes to patellar dislocation which should be kept in mind while screening athletes, especially females. This tendency can be countered by quadriceps exercises and appropriate footwear.     

Lipopolysaccharide Causes an Increase in Intestinal Tight Junction Permeability in Vitro and in Vivo by Inducing Enterocyte Membrane Expression and Localization of TLR-4 and CD14

Bacterial-derived lipopolysaccharides (LPS) play an essential role in the inflammatory process of inflammatory bowel disease. A defective intestinal tight junction (TJ) barrier is an important pathogenic factor of inflammatory bowel disease and other inflammatory conditions of the gut. Despite its importance in mediating intestinal inflammation, the physiological effects of LPS on the intestinal epithelial barrier remain unclear. The major aims of this study were to determine the effects of physiologically relevant concentrations of LPS (0 to 1 ng/mL) on intestinal barrier function using an in vitro (filter-grown Caco-2 monolayers) and an in vivo (mouse intestinal perfusion) intestinal epithelial model system. LPS, at physiologically relevant concentrations (0 to 1 ng/mL), in the basolateral compartment produced a time-dependent increase in Caco-2 TJ permeability without inducing cell death. Intraperitoneal injection of LPS (0.1 mg/kg), leading to clinically relevant plasma concentrations, also caused a time-dependent increase in intestinal permeability in vivo. The LPS-induced increase in intestinal TJ permeability was mediated by an increase in enterocyte membrane TLR-4 expression and a TLR-4–dependent increase in membrane colocalization of membrane-associated protein CD14. In conclusion, these studies show for the first time that LPS causes an increase in intestinal permeability via an intracellular mechanism involving TLR-4–dependent up-regulation of CD14 membrane expression.An integral function of intestinal epithelial cells is to act as a physical barrier, separating the noxious luminal environment from the underlying lamina propria and the deeper intestinal layers.^1,2 The apically located tight junctions (TJs) form a paracellular seal between the lateral membranes of adjacent intestinal epithelial cells, and act as a structural and functional barrier against paracellular flux of luminal substances. Defective intestinal epithelial TJ barrier has been shown to be an important pathogenic factor of inflammatory bowel disease (IBD) and necrotizing enterocolitis (NEC) by allowing paracellular permeation of luminal antigens that elicit and promote inflammatory response.^1,2 Both clinical and animal studies have shown the importance of a defective intestinal TJ barrier in the development and prolongation of intestinal inflammation in IBD and NEC.^1–5 These studies have shown that normalization of intestinal barrier in patients with active Crohn’s disease predicts prolonged clinical remission, whereas a persistent increase in intestinal permeability portends poor clinical outcome with rapid recurrence of the disease.^6,7 Additionally, animal studies have also shown that a primary defect in intestinal junctional complexes was sufficient to induce or aggravate intestinal inflammation in murine models of IBD,^8,9 whereas therapeutic tightening or enhancement of the intestinal TJ barrier prevented the development of intestinal inflammation.^3,10The terms endotoxin and lipopolysaccharide (LPS) are used interchangeably and refer to the major cell wall component of Gram-negative bacteria.^11,12 LPS are complex amphiphilic molecules having a hydrophobic (consisting of lipid A) and a hydrophilic (consisting of carbohydrate core and polysaccharide O-antigen) component and are released from bacterial cell wall by shedding or through bacterial lysis.^11–13 LPS concentrations are highest in the gut lumen, where many trillions of commensal bacteria reside. Normally, LPS in the gut lumen do not penetrate across the healthy intestinal epithelium^14,15; however, in intestinal permeability disorders, the defective TJ barrier allows paracellular flux of LPS and other luminal antigens.^{11–13,16–19} The intestinal tissue and circulating LPS levels are markedly elevated in IBD and NEC, and play an important role in mediating inflammatory response.^{11–13,16–18} The involvement of LPS in the initiation and propagation of intestinal inflammation in IBD and NEC has been well demonstrated.^20–23 These studies have shown LPS to be an important contributing factor of intestinal inflammation, and removal of circulating LPS accelerated the clinical improvement of IBD and NEC.^20,22,23 Despite the importance of a defective intestinal barrier in the accentuation and prolongation of intestinal inflammation in IBD and NEC,^3,6,9,20,22 the effects of circulating levels of LPS on the intestinal epithelial barrier remain unknown. Because LPS levels are markedly elevated in these diseases and play an important role in the inflammatory process, understanding the effects of LPS on intestinal barrier function has important potential clinical significance.In normal healthy individuals, plasma concentrations of LPS range from undetectable levels up to 0.2 ng/mL.^11,12,20,22 A variety of physiological factors such as prolonged physical exertion, high-fat diet, physiological stresses, or heat can lead to elevated plasma LPS levels as high as 1 to 2 ng/mL.^24–27 Patients with intestinal permeability disorders such as Crohn’s disease, NEC, acute pancreatitis, alcoholic liver disease, and critical illnesses also have elevated plasma LPS levels ranging up to 2 to 10 ng/mL.^{11–13,20,22,28} Based on these reports, we consider LPS levels of 0 to 1.0 ng/mL to be physiologically relevant and 0 to 10 ng/mL to be clinically relevant. (For reference, the concentration of LPS in the gut lumen has been reported to be 1.8 μg/mL in the rat distal ileum.^29,30) Inexplicably, in most of the published studies, extreme pharmacological concentrations of LPS ranging between 50 and 1000 μg/mL, which exceed the physiologically achievable concentrations by 10⁴- to 10⁷-fold, have been used to assess various biological responses.^30–34 At these extreme concentrations, LPS causes rapid cell death in various cell types studied, including in intestinal and immune cells,^30,33–35 and does not provide accurate depiction of biological activity of LPS. Herein, we show that LPS, at physiologically and clinically relevant concentrations (0 to 10 ng/mL), does not cause intestinal epithelial cell death, but causes a selective increase in intestinal TJ permeability in vitro and in vivo. These studies also show for the first time that pattern recognition receptors Toll-like receptor 4 (TLR-4) and CD14 play a central role in the modulation of the intestinal epithelial TJ barrier.     

The Misuse of Prescribed Drugs During the Syrian Crisis: a Cross-sectional Study

International Journal of Mental Health and Addiction -     

Effect of Mirazid in Schistosoma japonicum-infected mice: parasitological and pathological assessment

Conflicting reports are found in the literature about the antischistosomal efficacy of Mirazid (MZ), which is a special formulation of myrrh obtained from the stem of the plant Commiphora molmol. This initiated the present study to assess this drug for the first time in experimental schistosomiasis japonicum. Mice were divided into four groups: infected untreated control (I); infected treated with MZ, 500 mg/kg (II); infected treated with MZ, 250 mg/kg (III); and infected treated with praziquantel (PZQ), 200 mg/kg (IV). The drugs were given 7 weeks post-infection for five successive days. All animals were killed 3 weeks posttreatment. Results showed no signs of antibilharzial activity of MZ. Total worms, total tissue egg load, egg developmental stages, and granuloma area were not affected by any of the MZ treatment regimens as compared to the infected untreated group (P?>?0.05 for all variables). These results were in contrast to those obtained in PZQ-treated animals in which 82.82 % total worm reduction, 94.62 % egg reduction, and 86.35 % granuloma area reduction were observed. Also, it significantly increased the percentage of dead ova and decreased the percentage of mature ova with complete absence of immature ones in comparison with the control group (P?<?0.01 for all variables). In conclusion, the results of the current study raise serious doubts about the antischistosomal activity of MZ.