Coronary Artery Disease in Patients with Ischemic Stroke and TIA

Background and ObjectivesIschemic stroke (IS) and coronary artery disease (CAD) share common risk factors and one may be the harbinger of the other. We aimed to study prevalence of symptomatic and asymptomatic CAD in a cohort of consecutive patients with IS and assess its relationship with intracranial and extracranial large artery cerebrovascular disease (LAD).MethodsAll consecutive eligible IS and Transient Ischemic Attack (TIA) patients were recruited into the study. Both clinically suspected and asymptomatic patients (N = 259) underwent myocardial Stress-rest Gated Technetium-99m (Tc99m) MIBI Myocardial Perfusion SPECT scan performed on a dual head SPECT-CT to estimate evidence of myocardial ischemia.ResultsThree hundred patients completed the study. Forty one patients were previously diagnosed cases of definitive CAD. Twelve patients were clinically suspected to have CAD and 247 patients were asymptomatic. Among these, 12 patients (4.81%) had a positive SPECT. The overall prevalence of CAD was 17.67% (n = 53). Presence of diabetes was an independent predictor of CAD (OR 1.98, 95% CI 1.07-3.67. P .02). No significant association was found between the presence of LAD and CAD in all subgroup comparisons. However, there was a suggestion of higher LAD among patients with known CAD compared with others.ConclusionsCAD is prevalent in patients with ischemic stroke. No definitive relationship was found between CAD and intracranial or extracranial LAD. Population based stratification tools are needed to further assess the need to detect subclinical CAD in patients with stroke.     

C11orf95‐RELA fusion present in a primary intracranial extra‐axial ependymoma: Report of a case with literature review

Ependymomas are gliomas that recapitulate the ependymal cells microscopically and ultrastructurally. They commonly occur along the ventricular surfaces and central canal of the brain and spinal cord. Intracranial extra‐axial ependymoma (IEAE) is a rare entity and is commonly misdiagnosed clinically and radiologically as a meningioma. The histogenesis of such IEAEs is obscure. A novel recurrent oncogenic fusion involving the C11orf95 and RELA genes was recently described in supratentorial ependymomas. A 9‐year‐old girl presented with a dural based parafalcine mass that, in addition to exhibiting classical immunohistochemical features of an ependymoma, also demonstrated C11orf95‐RELA fusion, characteristic of supratentorial ependymomas. We suggest that IEAEs share their histogenesis with their intra‐axial counterparts, arising either from dural extension of subcortical, subependymal rests or directly from ectopic dural rests.     

One-pot sequential multicomponent reaction between in situ generated aldimines and succinaldehyde: facile synthesis of substituted pyrrole-3-carbaldehydes and applications towards medicinally important fused heterocycles

An efficient sequential multi-component method for the synthesis of N-arylpyrrole-3-carbaldehydes has been developed. This reaction involved a proline-catalyzed direct Mannich reaction-cyclization sequence between succinaldehyde and in situ generated Ar/HetAr/indolyl-imines, followed by IBX-mediated oxidative aromatization in one-pot operation. The practical utility of this procedure is shown at gram-scale and the synthesis of diverse bioactive fused heterocyclic scaffolds such as pyrroloquinoline, pyrrolo-oxadiazole, dihydro pyrroloquinoline, and pyrrolo-phenanthridine.

An efficient sequential multi-component method for the synthesis of N-arylpyrrole-3-carbaldehydes has been developed.     

Inguinal hernia repair: Toward Asian guidelines

Groin hernias are very common, and surgical treatment is usually recommended. In fact, hernia repair is the most common surgical procedure performed worldwide. In countries such as the USA, China, and India, there may easily be over 1 million repairs every year. The need for this surgery has become an important socioeconomic problem and may affect health‐care providers, especially in aging societies. Surgical repair using mesh is recommended and widely employed in Western countries, but in many developing countries, tissue‐to‐tissue repair is still the preferred surgical procedure due to economic constraints. For these reason, the development and implementation of guidelines, consensus, or recommendations may aim to clarify issues related to best practices in inguinal hernia repair in Asia. A group of Asian experts in hernia repair gathered together to debate inguinal hernia treatments in Asia in an attempt to reach some consensus or develop recommendations on best practices in the region. The need for recommendations or guidelines was unanimously confirmed to help overcome the discrepancy in clinical practice between countries; the experts decided to focus mainly on the technical aspects of open repair, which is the most common surgery for hernia in our region. After the identification of 12 main topics for discussion (indication, age, and sex; symptomatic and asymptomatic hernia: type of hernia; type of treatment; hospital admission; preoperative care; anesthesia; surgical technique; perioperative care; postoperative care; early complications; and long‐term complications), a search of the literature was carried out according to the five levels of the Oxford Classification of Evidence and the four grades of recommendation.     

Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial.

This was a 6-week, randomized, double-blind, multicenter study evaluating the efficacy of pregabalin in the treatment of painful diabetic neuropathy. Two hundred forty-six men and women with painful diabetic neuropathy received pregabalin (150 or 600 mg/day by mouth) or placebo. The primary efficacy variable was mean pain score at the end of treatment. Efficacy results indicate that pregabalin 600 mg/day significantly decreased mean pain score to 4.3 (vs 5.6 for placebo, P = .0002) and increased the proportion of patients who had a > or =50% decrease from baseline pain (39% vs 15% for placebo, P = .002). Pregabalin also significantly reduced sleep interference, past week and present pain intensity, sensory and affective pain scores, and bodily pain and decreased by > or =50% the number of patients describing their pain as gnawing, sickening, fearful, and punishing-cruel. More patients receiving pregabalin 600 mg/day than placebo showed improvement, as rated on the Clinical and Patient Global Impression of Change scales, 73% vs 45% and 85% vs 47%, respectively. Pregabalin 150 mg/day was essentially no different from placebo. Dizziness was the most common side effect. These study results show pregabalin 600 mg/day to be safe and effective in reducing the pain and other associated symptoms of painful diabetic neuropathy. PERSPECTIVE: Painful diabetic peripheral neuropathy is a challenging neuropathic pain syndrome. This randomized controlled trial demonstrates that pregabalin, a new drug that interacts with the alpha2-delta protein subunit of the voltage-gated calcium channel, is an efficacious and safe treatment for the pain of this condition.     

A histidine protein kinase is involved in polar organelle development in Caulobacter crescentus.

Mutations having pleiotropic effects on polar organelle development (pod) in Caulobacter crescentus have been identified and shown to occur in at least 13 genes scattered throughout the genome. Mutations at each locus affect a unique combination of polar traits, suggesting that complex interactions occur among these genes. The DNA sequence of one of these genes, pleC, indicates that it is homologous to members of the family of histidine protein kinase genes. Membes of this family include the senor components of the bacterial two-component regulatory systems. Furthermore, in vitro experiments demonstrated that the PleC protein was capable of autophosphorylation. These results suggest that the PleC protein (and perhaps the proteins encoded by the other pod genes as well) regulates the expression of genes involved in polar organelle development through the phosphorylation of key regulatory proteins. The use of a phosphorelay system cued to internal changes in the cell would provide a mechanism for coordinating major changes in gene expression with the completion of specific cell cycle events.     

Adrenocorticotropic hormone-responsive guanylate cyclase in the particulate fraction of rat adrenal glands

Low concentrations of ACTH, 7 x 10(-12) M, caused a marked stimulation of the 100,000 x g particulate guanylate cyclase without any detectable change in the adenylate cyclase activity. The lowest concentration of the hormone that elicited adenylate cyclase stimulation was 7 x 10(-10) M, a concentration 100--fold higher than that required to stimulate the guanylate cyclase. Although calcium was found to be obligatory in the hormonally--dependent guanylate cyclase activity, calcium alone could not duplicate the ACTH effect. Sodium nitroprusside and ascorbic acid inhibited the particulate guanylate cyclase activity. While ACTH was unable to stimulate the soluble guanylate cyclase, sodium nitroprusside markedly stimulated this enzyme. From these data, we conclude that the adrenal guanylate cyclase exists in two forms, particulate and soluble. The particulate form is specifically responsive to ACTH, and calcium is one of the essential coupling factors of this hormonally--responsive guanylate cyclase.     

Oliguric and non-oliguric acute renal failure in malaria in west zone of rajasthan,India-A comparative study

ObjectiveTo report a comparative clinical and histopathological study on oliguric and non-oliguric acute renal failure (ARF) in malaria.Method311 consecutive cases of malaria out of which 74 (23.79%) had ARF as per WHO criteria were conducted. Mean age was 32.58 (range 15–60 years) and male: female was 2:1.ResultMost of the cases developed ARF within 10 d of onset. 18 cases (11 falciparum, 2 mixed, 5 vivax) presented with oliguric and 56 (41 falciparum, 6 mixed, 9 vivax) with non-oliguric renal failure. Associated major manifestations were jaundice (75.68%), cerebral malaria (41.89%), bleeding manifestations (32.43%), severe anemia (27.03%), hypotension (25.68%), multi-organ failure (18.92%), severe thrombocytopenia (12.16%), and ARDS (8.11%). Kidney biopsy (n=20) showed acute tubular necrosis (n=7), Mesangioproliferative glomerulonephritis (n=4) or both (n=9). Hemodialysis was done in 8 cases of oliguric renal failure out of which 4 survived (average no. of session 2.9).ConclusionMost of the cases recovered within 3 weeks. Total mortality was 28.38% (n=21) and mortality was more in oliguric renal failure (72.22%) as compare to non-oliguric renal failure (14.29%).     

STRL33, A Novel Chemokine Receptor–like Protein, Functions as a Fusion Cofactor for Both Macrophage-tropic and T Cell Line–tropic HIV-1

The chemokine receptors CXCR4, CCR2B, CCR3, and CCR5 have recently been shown to serve along with CD4 as coreceptors for HIV-1. The tropisms of HIV-1 strains for subgroups of CD4⁺ cells can be explained, at least partly, by the selective use of G protein–coupled receptors (GPCRs). We have identified a novel human gene, STRL33, located on chromosome 3 that encodes a GPCR with sequence similarity to chemokine receptors and to chemokine receptor–like orphan receptors. STRL33 is expressed in lymphoid tissues and activated T cells, and is induced in activated peripheral blood lymphocytes. When transfected into nonhuman NIH 3T3 cells expressing human CD4, the STRL33 cDNA rendered these cells competent to fuse with cells expressing HIV-1 envelope glycoproteins (Envs). Of greatest interest, STRL33, in contrast with CXCR4 or CCR5, was able to function as a cofactor for fusion mediated by Envs from both T cell line–tropic and macrophage-tropic HIV-1 strains. STRL33-transfected Jurkat cell lines also supported enhanced productive infection with HIV-1 compared with control Jurkat cells. Despite the sequence similarities between STRL33 and chemokine receptors, STRL33-transfected cell lines did not respond to any in a panel of chemokines. Based on the pattern of tissue expression of the STRL33 mRNA, and given the ability of STRL33 to function with Envs of differing tropisms, STRL33 may play a role in the establishment and/or progression of HIV-1 infection.