Influence of diabetes on manifestations and treatment outcome of pulmonary TB patients.

OBJECTIVE: To understand the influence of diabetes on the clinical and bacteriological aspects and treatment outcome of pulmonary tuberculosis (PTB) patients. SETTING AND DESIGN: Records of 692 consecutive smear-positive PTB patients admitted to a referral hospital in Riyadh, Saudi Arabia, were reviewed retrospectively. The characteristics of 187 patients with diabetes mellitus (PTB-DM group) were compared to 505 patients without DM (PTB group). RESULTS: In the PTB-DM group, 65.2% of the patients had numerous acid-fast bacilli (AFB) on sputum smear examination compared to 54.1% in the control group (P = 0.008). Among new cases, PTB-DM patients had a lower prevalence of resistance to any anti-tuberculosis drug (6.4% vs. 16.0%, P = 0.007) and achieved higher sputum conversion rates at the end of 3 months of treatment (98.9% vs. 94.7%, P = 0.013). Favourable outcomes (cured/treatment completed), failure, death and default were comparable in both groups (P = 0.7005). CONCLUSIONS: PTB-DM patients have a higher pre-treatment bacillary load, a lower prevalence of anti-tuberculosis drug resistance and achieve slightly higher sputum conversion by the end of 3 months of treatment compared to non-diabetic patients. The association of diabetes does not alter the final treatment outcome among PTB patients.     

Antiarrhythmic potential of chloroquine: new use for an old drug

Amiodarone and chlorpromazine are phospholipase inhibitors which produce cytoplasmic inclusion bodies and have important electrophysiologic properties. Chloroquine also inhibits phospholipase activity, resulting in similar inclusion bodies, but electrophysiologic information about this drug is lacking. In this study, the cellular electrophysiologic effects of two doses of chloroquine were examined in sheep Purkinje fibres and ventricular muscle cells. Both concentrations produced a significant reduction in maximum velocity of upstroke of the action potential and prolongation of the action potential duration and refractory period in Purkinje fibres. These effects were observed in the absence of significant changes in threshold of stimulation or action potential amplitude and were partially reversible following washout of the lower drug concentration. In addition to these experimental data, clinical evidence of antiarrhythmic action was determined by administering 500 mg chloroquine daily over nine weeks to six subjects with frequent asymptomatic ventricular premature complexes. In four patients there was a reduction in ventricular ectopy, which recurred when the drug was discontinued, while a fifth patient reverted to sinus rhythm from atrial fibrillation previously resistant to other antiarrhythmic medication. Thus, chloroquine has important electrophysiologic properties. The underlying mechanism of this action remains unproven at the present time.     

Hepatic artery stenosis after liver transplant, managed with percutaneous angioplasty and stent placement.

Hepatic artery stenosis is a recognized vascular complication of orthotopic liver transplant that carries significant morbidity and mortality. The authors present a case of hepatic artery stenosis in a 50-year-old female successfully treated with balloon angioplasty and stent. This case report highlights the importance of percutaneous intervention as a preferred treatment option in patients with hepatic artery stenosis post-orthotopic liver transplant.     

Ultrastructural changes of ischemic injury due to coronary artery occlusion in the porcine heart

Using the ultrastructural criteria established by Schaper et al. 1979 [27] for distinguishing between different degrees of ischemic change in dog myocardium, slight ischemic changes are observed in the pig suboendocardium as early as 1 min after occlusion of the LAD artery. Moderate change throughout the thickness of the myocardium is seen after 6 to 12 min of ischemia and continues to be found up until 20 min after commencement of the ischemic period. 20 to 30 min ischemia produces severe ischemic damage and more than 30 min leads to irreversible damage. The changes are uniform at all stages of ischemia and there is no evidence of a transmural gradient of ultrastructural damage. Of particular interest in the early part of the ischemic period is the observation of ultrastructural changes in the subendocardial specialized conducting tissue. In these specialized cells, although morphological features consistent with slight and moderate ischemia are found as early as 1 to 2 min after occlusion, spontaneous recovery occurs and is complete by 15 min. This biphasic time course parallels the electro-physiological changes known to occur in ischemic Purkinje fibres.     

Pd nanoparticles on green support as dip-catalyst: a facile transfer hydrogenation of olefins and N-heteroarenes in water

Chemo- and regioselective hydrogenation methods using highly green sources, particularly from metal nanoparticles on plant stem as support and water, is an intensive research area, which is highly relevant to the development of green chemistry and technology in the 21^st century. Here, the synthesis and activity of a heterogeneous catalytic system (called “dip-catalyst”) for the transfer hydrogenation of a series of styrenyl, unfunctionalized olefins, quinoline and other N-heteroarenes, are presented. It consists of Pd nanoparticles (15–20 nm) anchored on bio-processed jute plant (Corchorus genus) stem as the support. Pd nanoparticles were decorated on the green support (GS) jute stem by the in situ reduction of K₂PdCl₄ in aqueous medium at 70 °C, using formic acid as the reductant. The Pd@GS was characterized using SEM, EDS, XRD, FTIR, XPS and TEM. Elemental mapping revealed uniform distribution of Pd on the cellulose matrix of the jute stem. The catalyst was successfully applied to the chemoselective transfer hydrogenation of numerous styrenyl, unfunctionalized olefins. Its high functional group tolerance was investigated during the olefins hydrogenation in water. Furthermore, Pd@GS was capable of quantitative hydrogenation to selectively produce 1,2,3,4-tetrahydroquinoline (THQ) in water using stoichiometric amounts of tetrahydroxydiboron (THDB) at 60 °C with turn over frequency (TOF) 4938 h⁻¹. This system is stable in water and displays excellent recyclability; it could be used for 32 consecutive cycles, without losing its original crystallinity or requiring replenishment.

A dip catalyst consisting of Pd nanoparticles immobilized on the surface of thin slices of jute-stem was fabricated. Its versatility as a hydrogen transfer agent for styrenyl, cyclic and unfunctionalized olefins and N-heterocycles was investigated.     

Collaborative Biomedicine in the Age of Big Data: The Case of Cancer

Biomedicine is undergoing a revolution driven by high throughput and connective computing that is transforming medical research and practice. Using oncology as an example, the speed and capacity of genomic sequencing technologies is advancing the utility of individual genetic profiles for anticipating risk and targeting therapeutics. The goal is to enable an era of “P4” medicine that will become increasingly more predictive, personalized, preemptive, and participative over time. This vision hinges on leveraging potentially innovative and disruptive technologies in medicine to accelerate discovery and to reorient clinical practice for patient-centered care. Based on a panel discussion at the Medicine 2.0 conference in Boston with representatives from the National Cancer Institute, Moffitt Cancer Center, and Stanford University School of Medicine, this paper explores how emerging sociotechnical frameworks, informatics platforms, and health-related policy can be used to encourage data liquidity and innovation. This builds on the Institute of Medicine’s vision for a “rapid learning health care system” to enable an open source, population-based approach to cancer prevention and control.     

SNP array mapping of chromosome 20p deletions: Genotypes,phenotypes, and copy number variation

The use of array technology to define chromosome deletions and duplications is bringing us closer to establishing a genotype/phenotype map of genomic copy number alterations. We studied 21 patients and five relatives with deletions of the short arm of chromosome 20 using the Illumina HumanHap550 SNP array to: 1) more accurately determine the deletion sizes; 2) identify and compare breakpoints; 3) establish genotype/phenotype correlations; and 4) investigate the use of the HumanHap550 platform for analysis of chromosome deletions. Deletions ranged from 95 kb to 14.62 Mb, and all of the breakpoints were unique. Eleven patients had deletions between 95 kb and 4 Mb and these individuals had normal development, with no anomalies outside of those associated with Alagille syndrome (AGS). The proximal and distal boundaries of these 11 deletions constitute a 5.4‐Mb region, and we propose that haploinsufficiency for only 1 of the 12 genes in this region causes phenotypic abnormalities. This defines the JAG1‐associated critical region, in which deletions do not confer findings other than those associated with AGS. The other 10 patients had deletions between 3.28 Mb and 14.62 Mb, which extended outside the critical region, and, notably, all of these patients had developmental delay. This group had other findings such as autism, scoliosis, and bifid uvula. We identified 47 additional polymorphic genome‐wide copy number variants (>20 SNPs), with 0 to 5 variants called per patient. Deletions of the short arm of chromosome 20 are associated with relatively mild and limited clinical anomalies. The use of SNP arrays provides accurate high‐resolution definition of genomic abnormalities. Hum Mutat 0,1–8, 2008. © 2008 Wiley‐Liss, Inc.