Whole blood viscosity is associated with baseline cerebral perfusion in acute ischemic stroke

Neurological Sciences - Whole blood viscosity (WBV) is the intrinsic resistance to flow developed due to the frictional force between adjacent layers of flowing blood. Elevated WBV is an...     

Correlation of Flexor Pollicis Longus Tendon Status by Ultrasonography with Plate Position on Radiographs Following Volar Plate Fixation of Distal Radius Fractures with Pronator Quadratus Repair

BackgroundPurpose was to correlate flexor pollicis longus tendon (FPL) attrition using Ultrasonography with plate position on radiographs following volar locked compression plate fixation (LCP) in patients who have undergone pronator quadratus (PQ) repair for distal radius fractures.MethodsStatus of flexor pollicis longus tendon was analyzed by ultrasonography in patients who underwent volar locked compression plating with pronator quadratus repair at a minimum of one year follow up. Soong’s criteria was used to assess the plate position and then correlated the ultrasonography findings of flexor pollicis longus.ResultsThere were 33 patients included in our study, of which 15 belonged to Soong’s grade zero, 10 were grade one and eight were grade two. Flexor pollicis longus attrition was noted in all cases with grade two plating.ConclusionPronator quadratus repair may not prevent attritional changes in higher grades of Soong’s, hence follow up may be required in these patients to identify attritional changes and early implant removal to prevent complications.     

Spironolactone prevents the inducibility of ventricular tachyarrhythmia in rats with aldosteronism

Myocardial fibrosis is considered a substrate for fatal ventricular arrhythmias (VAs). In rats receiving aldosterone/salt treatment (ALDOST) for ≥4 weeks, foci of myocardial scarring that replace necrotic cardiomyocytes appear scattered throughout the right and left sides of the heart. We hypothesized that this adverse structural remodeling would promote the inducibility of VA, which could be prevented by cotreatment with spironolactone (A+Spiro), an aldosterone receptor antagonist and cardioprotective agent. In controls and each treatment group, we monitored: (1) electrocardiogram, ventricular electrogram, and arterial pressure before, during, and after bipolar electrical stimulation of the right ventricular outflow tract and apex at a strength 3× the pacing threshold, using both programmed stimulation with premature extra stimuli and 50-Hz burst pacing for 3 different durations; and (2) myocardial collagen volume fraction (CVF) as a marker of cardiac fibrosis. We found that VA (duration >200 ms accompanied by declining arterial pressure) was more inducible (P < 0.05) at 4 weeks (4 of 6) and with even greater frequency at 6 weeks (9 of 10) of ALDOST versus controls (0 of 6) and A+Spiro for 6 weeks (2 of 11). CVF (%) was proportionally increased (P < 0.05) at 4 and 6 weeks (8.4 ± 0.74 and 13.9 ± 1.9, respectively) of ALDOST compared with control group (2.6 ± 0.4) and A+Spiro group (5.3 ± 0.7). However, the effective refractory period was indistinguishable between groups, whereas the probability of VA was nonlinearly related to CVF. Thus, in rats with aldosteronism, in which a reduction in effective refractory period was not evident, the mechanism for VA susceptibility is presumably linked to a decrease in conduction velocity and/or increased dispersion of refractoriness, probably caused by consequential myocardial fibrosis.     

SMAC mimetics as potential cancer therapeutics in myeloid malignancies

Evasion of apoptosis has been identified as one of the essential hallmarks of cancer. Inhibitor of apoptosis proteins (IAPs) are implicated in a host of myeloid malignancies, providing the rationale for strategies aimed at neutralizing IAPs to lower the cancer cell apoptosis threshold. Modes of IAP antagonism may include down-regulating IAP expression, up-regulating endogenous pro-apoptotic proteins, such as tumour necrosis factor-α or Fas ligand, or directly antagonizing IAP activity against caspases. Direct targeting of IAPs using mimetics of the second mitochondria-derived activator of caspase (SMAC) protein has shown therapeutic promise by sensitizing the effect of chemotherapy on malignant cells. In pre-clinical studies, SMAC mimetics have demonstrated broad synergistic activity with a wide range of therapeutics, including cytotoxic chemotherapy, receptor tyrosine kinase inhibitors, agents targeting death receptors and alternative mechanisms of cell death, such as necroptosis or autophagy and immune check point blockade. SMAC mimetics represent a novel approach for further investigation in patients with high-risk, chemo-refractory blood cancers, as single agents or in thoughtfully selected combinations. In this review, we discuss the development and therapeutic rationale of small molecule SMAC mimetics, with an emphasis on agents in clinical development for myeloid malignancies.     

Cutaneous leishmaniasis: A case report of a diagnostic dilemma

Cutaneous leishmaniasis (CL) is the most prevalent clinical form of leishmaniasis and is caused by vector‐borne protozoan parasite. Variation in diagnostic accuracy exists. A 54‐year‐old female farmer by occupation presented with lesion over right thigh for 8 months. Lesion evolved over period of 2–3 months and progressed to form ulcer with surrounding redness. On examination, solitary plaque with crateriform ulcer 3 * 2 cm in size roughly oval in shape was present. Ulcer floor was moist, smooth shiny with serous discharge, and well‐defined raised erythematous margin was present. Biopsy was done which showed features suggestive of lupus vulgaris, for which anti‐tubercular treatment (ATT) was started. There was persistence of ulcer despite 4 months of ATT, for which diagnosis was reconsidered and fine‐needle aspiration cytology (FNAC) was performed. FNAC showed numerous intra‐ and extracellular amastigotes suggestive of leishmaniasis which was treated with complete disappearance of ulcer over 4 months.