Antileishmanial activity of benzocycloalkyl azole oximino ethers: the conformationally constraint analogues of oxiconazole

Antileishmanial activities of 16 synthetic oximino benzocycloalkyl azoles against Leishmania donovani were evaluated in vitro against extracellular promastigotes and intracellular amastigotes. Based on SI (Selectivity Index), five compounds were tested further in vivo in hamster model. Out of these, three compounds have shown medium activity (53–58%) and one has shown significant inhibition of parasite multiplication (70%). Despite the fact that these compounds were better than the existing antileishmanials in respect to IC₅₀ and SI values, they were less active than miltefosine in vivo. The present study has helped us in identifying a new lead that could be exploited as a potential antileishmanial agent.     

Tracheocele--a case report

A tracheocele is a rarely encountered entity that may be congenital or acquired. This tracheal lesion is characterized by the presence of a single cystic pouch filled with air or a mixture of liquid and air. We recently managed a case of a large voluminous acquired tracheocele originating from the right posterolateral tracheal wall. A 39-year-old male patient presented with chronic cough and breathy voice. Rigid laryngoscopy revealed a right immobile vocal fold. Computed tomography scan revealed a tracheocele that was excised externally with recurrent laryngeal nerve preservation.     

Congenital malformations of the temporal bone

Congenital ear or temporal bone malformations are a diagnostic challenge to radiologists and surgeons alike. Newer imaging techniques can detect subtle changes in middle ear and cochlear anatomy. This information is invaluable with increasing use of hearing restoration surgeries and/or cochlear implants in such patients. This article discusses the embryogenesis, classification system, and salient imaging findings of congenital outer, middle ear, and inner ear anomalies in children. Both high-resolution computerized tomography and magnetic resonance imaging scans of the temporal bones are described.     

RETRACTED ARTICLE: Kearns Sayre Syndrome—Case Report with Review of Literature

Kearns-Sayre Syndrome is form of rare mitochondrial cytopathy, first described by Thomas P. Kearns and George Pomeroy Sayre in 1958 and is characterized by progressive external opthalmoplegia, cardiac conduction block, pigmentary retinal degeneration, variable number of red ragged fibers on muscle biopsy. It presents before the child reaches the age of twenty. Kearns-Sayre syndrome may affect many organ systems and additional features may include myopathy, dystonia, bulbar symptoms in the form of dysarthria and nasal regurgitation and bilateral facial weakness. Endocrine abnormalities (e.g., diabetes, growth retardation/short stature, and hypoparathyroidism), bilateral sensorineural deafness, dementia, cataracts, and proximal renal tubular acidosis, skeletal muscle weakness (proximal more than distal) and exercise intolerance are additional features. Kearns Sayre Syndrome occurs as a result of large-scale single deletions (or rearrangements) of mitochondrial DNA (mtDNA), which is usually not inherited but occurs spontaneously, probably at the germ-cell level or very early in embryonic development. No disease-modifying therapy is available for Kearns-Sayre syndrome (KSS). Management is supportive vigilance for detection of associated problems. In the future, potential treatment in patients with Kearns-Sayre syndrome may attempt to inhibit mutant mtDNA replication or encourage replication of wild-type mtDNA.     

Augmentation of antileishmanial efficacy of miltefosine in combination with tuftsin against experimental visceral leishmaniasis

Current drugs for the treatment of visceral leishmaniasis are inadequate, and their efficacies are also compromised due to suppression of immune function during the course of infection. Miltefosine is the only promising orally active antileishmanial drug, but due to its long half-life, there is risk of development of resistance. To overcome these problems, efforts are needed to develop combination therapy of miltefosine with effective immunostimulating agents where a decrease of parasitic burden and simultaneous enhancement of adaptive immunity can be achieved. In the present study, we have explored the antileishmanial efficacy of a subcurative dose of miltefosine in combination with free as well as liposomal palmitoyl tuftsin (p-tuftsin) using a Leishmania donovani/BALB/c mouse model. When miltefosine (2.5 mg/kg for 5 days) was given with free p-tuftsin, the inhibitory effect was significantly increased from 49.6% to 66% (P?相似文献   

Efficacy of safety signals in the epilepsy monitoring unit (EMU): should we worry?

There is little consensus regarding the critical safety measures to prevent harm in epilepsy monitoring units (EMUs). We sought to determine whether the safety signals (SS) triggered during EMU events differed by seizure type and the efficacy of SS in alerting responders. We screened 468 consecutive EMU admissions from January 2008 until April 2011 for definitive events to evaluate the first 50 events of complex partial seizures (CPS), generalized tonic-clonic seizures (GTC), and psychogenic non-epileptic seizures (PNES). Response to telemetry signal was slower than to push button (PB). When there was PB alarm, response time was slower in patients with PNES. A higher proportion of PNES were triggered by PB. A greater percentage of epileptic seizures were missed compared with PNES. Future studies investigating more effective techniques to capture every epileptic seizure are warranted as 24/7 monitoring by healthcare professionals is not feasible in many settings.     

Special requirements for electronic health records in dermatology

Government incentives and mandates to increase the meaningful use of electronic health records (EHR), with subsequent disincentives by Medicare, have made a significant push for dermatologists to adopt this technology into their practices. EHRs were originally developed for primary care physicians; however, owing to the unique features of dermatology, specialty-specific systems are a must. In this article, we discuss the special needs of dermatologists when choosing an EHR system.     

T cells raised against allogeneic HLA-A2/CD20 kill primary follicular lymphoma and acute lymphoblastic leukemia cells

T cells mediating a graft‐versus‐leukemia/lymphoma effects without causing graft‐versus‐host disease would greatly improve the safety and applicability of hematopoietic stem cell transplantation. We recently demonstrated that highly peptide‐ and HLA‐specific T cells can readily be generated against allogeneic HLA‐A*02:01 in complex with a peptide from the B cell‐restricted protein CD20. Here, we show that such CD20‐specific T cells can easily be induced from naïve precursors in cord blood, demonstrating that they do not represent cross‐reactive memory cells. The cells displayed high avidity and mediated potent cytotoxic effects on cells from patients with the CD20^pos B cell malignancies follicular lymphoma (FL) and acute lymphoblastic leukemia (ALL). However, the cytotoxicity was consistently lower for cells from two of the ALL patients. The ALL cells that were less efficiently killed did not display lower surface expression of CD20 or HLA‐A*02:01, or mutations in the CD20 sequence. Peptide pulsing fully restored the levels of cytotoxicity, indicating that they are indeed susceptible to T cell‐mediated killing. Adoptive transfer of CD20‐specific T cells to an HLA‐A*02:01^pos patient requires an HLA‐A*02:01^neg, but otherwise HLA identical, donor. A search clarified that donors meeting these criteria can be readily identified even for patients with rare haplotypes. The results bear further promise for the clinical utility of CD20‐specific T cells in B cell malignancies.