Synthesis and anti-mycobacterial activity of 4-(4-phenyl-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-1-yl)salicylhydrazones: revitalizing an old drug

The antitubercular drug; para-aminosalicylic acid (PAS) was used as the core scaffold for the design of a series of 1H-1,2,3-triazolylsalicylhydrazones upon coupling with triazole and arylhydrazone moietis to furnish a single molecular architecture. The obtained derivatives were screened against Mycobacterium tuberculosis H37Rv revealing good to high activity for the active compounds (MIC values of 0.39–1.5 μg/mL) compared to the marketed drugs isoniazid, rifampicin and ethambutol. Moreover, the most active analogue N-(1-(4-chlorobenzyl)-2-oxoindolin-3-ylidene)-2-hydroxy-4-(4-phenyl-1H-1,2,3-triazol-1-yl)-benzohydrazide (20) was found to be ten-fold more potent than PAS and equipotent to rifampicin (MIC 0.39 µg/mL), while exhibiting low cytotoxicity with a selectivity index of >128. In addition, this compound was shown to be active against persistent forms of mycobacteria comparable to standard drugs in nutrient starvation model. Accordingly, we introduce compound 20 as a valuable lead for further development. A 3D-QSAR study was also conducted to help in explaining the observed activity and to serve as a tool for further development.     

Management of Failed External Fixation by Two‐Staged Internal Osteosynthesis in the Lower Limb

ObjectiveThis study aims to evaluate the result of a two‐stage (delayed conversion) management of nonunion after failed external fixation of the lower limb.MethodsA case series of 25 patients (19 males and six females) enrolled in this study between February 2008 and October 2016, mean age 33.4 years (range, 22–65 years). Eight had femoral fractures, and 17 had tibial fractures. All were due to high‐energy trauma and were open fractures. All cases were presented by non‐union after external fixation in the lower limb long bones. All patients were managed by two stages (delayed conversion) osteosynthesis. The patients have been assessed for rate and time for union, range of motion of adjacent joints, the Modified functional outcome score of Karlstrom‐Olerud, and Trauma outcomes measure score.ResultsThe mean follow‐up was 36.5 months (range 24–54 months). Twenty‐two cases (88%) were fully united on an average of 5.3 months. According to the Karlstrom‐Olerud scores, the final functional outcome score was excellent 12 cases, good 9 cases, accepted 2 cases, and poor in two cases. As regards the trauma outcome measure score, the mean TOM after 3 months was 26.1 (25.3–27.3), 30.4 (29.3–32.1) after 12 months, and 33.4 (32.3–40) after 24 months.ConclusionsThe technique of two‐stage treatment of nonunions of long bone after external fixation is a successful tool to achieve bony union. It could be a favorable option with a low risk of complications and a high level of functional outcomes.     

Multichannel intra-luminal impedance signals variability during gastro-oesophageal activities

Multichannel intra-luminal impedance (MII) technique has been proven to be a successful diagnostic tool in detecting and displaying activities inside the oesophagus. It improves the diagnostic capability of oesophageal disorders since it gives accurate and more in-depth information about the activities inside the oesophagus, especially reflux episodes. A comparison is presented between normal and abnormal adults in terms of variability in MII signals during baselines and reflux episodes. A comparative study of episode duration for normal and abnormal subjects is presented. The characteristics of MII signals during gastro-oesophageal reflux episodes as well as during baselines are investigated. These characteristics show different responses between normal and abnormal individuals which help improving MII analysis capability in evaluating patients with gastro-oesophageal reflux disease and enhances the automatic detection of the oesophageal activities. Baselines from normal and abnormal samples were fitted to gamma distributions as a trial to distinguish between normal and abnormal samples.     

Spectral Doppler Interrogation of the Patent Foramen Ovale–A Window to Left Heart Hemodynamics

Spectral Doppler interrogation of flow across a patent foramen ovale (PFO) allows recording of the instantaneous pressure gradient between left and right atrium (RA). The assessment of RA pressure using the size and collapsibility of the inferior vena cava would thus allow estimation of left atrial (LA) pressure. In this article, we illustrate the value of spectral Doppler interrogation of flow across the PFO by transthoracic echocardiography as a novel and simple tool for the assessment of LA pressure and left cardiac hemodynamics in addition to the conventional noninvasive parameters.     

Ventricular Function in Patients with End‐Stage Renal Disease Starting Dialysis Therapy: A Tissue Doppler Imaging Study

Background: Heart failure is prevalent in end‐stage renal disease (ESRD) patients on long‐term dialysis. Detection of right ventricular (RV) dysfunction before starting dialysis may help to identify patients at a higher risk of developing heart failure. Aim: To assess RV function in predialysis patients using tissue Doppler imaging (TDI) derived myocardial performance index of RV (MPI‐RV). Methods: Echocardiography including pulsed TDI of lateral tricuspid annulus was performed in 41 patients with ESRD before starting dialysis therapy and 12 age and gender matched healthy controls. RV dysfunction was defined as MPI > 0.4; a value above the median MPI in controls. Results: Compared to controls, ESRD patients had significantly higher blood pressure and lower hemoglobin level. MPI‐RV was significantly impaired in ESRD patients compared to control (0.6 vs. 0.4, P < 0.001). RV dysfunction was identified in 23 ESRD patients (56%). ESRD patients had significantly lower e’ velocity and e’/a’ ratio as compared with controls. Pulmonary hypertension was detected in 15 (36.5%) patients. Among ESRD patients, no correlation was detected between MPI‐RV and calculated mean pulmonary artery pressure (r =–0.13, P = 0.47), pulmonary artery systolic pressure (r =–0.12, P = 0.6), left ventricular ejection fraction (r = 0.294, P = 0.06), or MPI of left ventricle (r = 0.3, P = 0.065). ESRD patients with and without pulmonary hypertension had similar MPI‐RV (0.6 vs.0.62, P = 0.32). Conclusion: Subclinical RV dysfunction—as estimated by TDI derived MPI—is highly prevalent among ESRD patients even before starting dialysis therapy. Pulmonary hypertension is not significantly associated with RV dysfunction in these patients.     

A Novel Mutation of the Ornithine Transcarbamylase Gene Leading to Fatal Hyperammonemia in a Liver Transplant Recipient

Ornithine transcarbamylase (OTC) deficiency (OTCD) is an X‐linked urea cycle disorder. Being an X‐linked disease, the onset and severity of the disease may vary among female carriers. Some of them start to develop the disease early in life, whereas others remain asymptomatic throughout their lives. Our patient was a 42‐year‐old man who developed severe hyperammonemia and fatal brain edema after receiving a right lobe graft from an asymptomatic female living donor with unrecognized OTCD. The donor developed hyperammonemia and disturbed level of consciousness that was managed successfully by hemodialysis. Molecular testing of the OTC gene in the donor revealed a heterozygous nonsense mutation (c.429T > A) in exon 5.     

Maternal serum leptin as a marker of preeclampsia

Purpose

To assess maternal leptin levels as a marker for preeclampsia (PE) and to explore the possibility of leptin being a marker of severity of preeclampsia.

Participants and methods

Comparative prospective study was conducted among a total of 72 pregnant women at 28–38 weeks of gestation. They were divided into two groups (control and study) according to the absence or presence of clinical parameters of preeclampsia. Leptin was measured for both groups at the time of presentation, once weekly and at the termination of pregnancy.

Results

Leptin levels were found to be significantly higher among all preeclampsia patients when compared to the control group; whether at admission or at the time of delivery. Mean serum leptin level at admission in control group was 9.8?ng/ml versus 10.9 ng/ml in mild cases and 17.6 ng/ml in severe cases. At the time of delivery, mean serum leptin in control group decreased to 4.7 ng/ml while in preeclampsia patients it increased up to 22 ng/ml in mild cases and 42.6 ng/ml in severe cases. ROC curve analysis has shown that a cut off value >13.7 ng/ml can be used to detect presence of preeclampsia with a sensitivity of 91 % and specificity 100 % while a cut off value >22.5 ng/ml can be used to detect severity of preeclampsia with a sensitivity of 85 % and specificity 100 %.

Conclusion

Maternal serum leptin is significantly elevated in preeclampsia, also it can be used as a marker for the presence of preeclampsia and to differentiate patients with mild preeclampsia from those with severe disease.     

Efficacy of vitamin D replacement therapy in restless legs syndrome: a randomized control trial

Sleep and Breathing - Restless legs syndrome is a movement sleep disorder that may be linked to dopaminergic dysfunction and in which vitamin D may play a role. This 12-week randomized,...