Amiodarone induced pulmonary toxicity in a case of atrial fibrillation.

Pulmonary opacities have many causes we are presenting a case of pulmonary opacity in a patient of breathlessness; who was on amiodarone for atrial fibrillation (AF).

Occurrence, biochemical profile of vascular endothelial growth factor (VEGF) isoforms and their functions in endochondral ossification.

Vascular endothelial growth factor (VEGF), initially detected in bovine pituitary follicular cells, is widely localized in hypertrophic zones of chondrocytes in various tissues where focus is on bone growth. Similarly, VEGF found in chondrocytes of articular cartilage of osteo-arthritic/rheumato-arthritic joints reflected need for bone repair. Members of VEGF family of human origin are seven homo-dimeric, heparin-binding glyco-proteins, encoded by different genes located on different chromosomes. They encode seven isoforms: VEGF-A, -B, -C, -D, -E, -F, and PLGF, each catalyzing distinct functions. They are compared with VEGFs derived from bovine origin in biochemical composition and functions. Each isoform and subtype has specific receptors for binding, necessary for expression of specific functions in bone growth or repair. VEGF control is by diffusion of isoforms, hypoxic conditions, and bone (mandibular) positioning. Thus, transformation of cartilage into bone involves proliferation of mesenchymal cells, hypertrophy in chondrocytes, capillary invasion, and calcification by extra cellular matrix (ECM). Inherent limitations of in vitro/in vivo models and chronology of appearance of different isoforms have eluded precise mechanism of VEGF action and regulation. Nonetheless, central role of VEGF in bone growth is quite obvious.

An update on transforming growth factor-ß (TGF-ß): sources, types, functions and clinical applicability for cartilage/bone healing.

Transforming growth factor-ß (TGF-ß) has been reviewed for its sources, types of isoforms, biochemical effects on cartilage formation/repair, and its possible clinical applications. Purification of three isoforms (TGF-ß-1, ß-2 and ß-3) and their biochemical characterization revealed mainly their homo-dimer nature, with heterodimers in traces, each monomer comprised of 112 amino acids and MW. of 12 500 Da. While histo-chemical staining by a variety of dyes has revealed precise localization of TGF-ß in tissues, immune-blot technique has thrown light on their expression as a function of age (neonatal vs. adult), as also on its quantum in an active and latent state. X-ray crystallographic studies and nuclear magnetic resonance (NMR) analysis have unraveled mysteries of their three-dimensional structures, essential for understanding their functions. Their similarities have led to interchangeability in assays, while differences have led to their specialized clinical applicability. For this purpose, their latent (inactive) form is changed to an active form through enzymatic processes of phosphorylation/glycosylation/transamination/proteolytic degradation. Their functions encompass differentiation and de-differentiation of chondrocytes, synthesis of collagen and proteoglycans (PGs) and thereby maintain homeostasis of cartilage in several degenerative diseases and repair through cell cycle signaling and physiological control. While several factors affecting their performance are already identified, their interplay and chronology of sequences of functions is yet to be understood. For its success in clinical applications, challenges in judicious dealing with the factors and their interplay need to be understood.

Host control over infection and proliferation of a cheater symbiont.

Host control mechanisms are thought to be critical for selecting against cheater mutants in symbiont populations. Here, we provide the first experimental test of a legume host's ability to constrain the infection and proliferation of a native-occurring rhizobial cheater. Lotus strigosus hosts were experimentally inoculated with pairs of Bradyrhizobium strains that naturally vary in symbiotic benefit, including a cheater strain that proliferates in the roots of singly infected hosts, yet provides zero growth benefits. Within co-infected hosts, the cheater exhibited lower infection rates than competing beneficial strains and grew to smaller population sizes within those nodules. In vitro assays revealed that infection-rate differences among competing strains were not caused by variation in rhizobial growth rate or interstrain toxicity. These results can explain how a rapidly growing cheater symbiont--that exhibits a massive fitness advantage in single infections--can be prevented from sweeping through a beneficial population of symbionts.

Anterior uterocervical angle measurement improves prediction of cerclage failure.

OBJECTIVE: To compare the anterior uterocervical angle and cervical length as predictors of spontaneous preterm delivery in patients with transvaginal cerclage. STUDY DESIGN: We retrospectively evaluated a cohort of 142 pregnant women with transvaginal cerclage placed over a 5-year period (2010 to 2015) were evaluated. Cervical morphology characteristics were measured from endovaginal imaging, including cervical length, cerclage height, funnel volume and anterior uterocervical angle prior to cerclage placement (UCA 1), shortly after cerclage placement (UCA 2) and the last image prior to delivery (UCA 3). Cerclage failure was defined as delivery prior to 36 weeks. Univariate analysis, receiver operator characteristic curves and binary logistic regression were used for statistical analysis. Statistical significance was defined as a P<0.05. RESULTS: Among the 142 women with a transvaginal cerclage, 38% had cerclage failure. The mean gestational age at birth was 29.3±5.2 weeks in the failure group compared with 37.9±2.8 weeks in those that did not fail (P<0.001). Univariate analysis identified cervical length (P=0.034) and UCA 3 (P<0.001) as significantly associated with gestational age at birth. Receiver operator characteristic curves demonstrated improved prediction of delivery prior to 34 weeks at UCA 3=108o (97% sensitivity, 65% specificity) compared to a cervical length of 25 mm. At <28 weeks, optimal performance of UCA 3 was found at 112o (100% sensitivity, 62% specificity) compared with cervical length of 25 mm (29% sensitivity, 39% specificity). Binary logistic regression revealed UCA 3>108o conferred an OR 35.1 (95% CI 7.7 to 160.3) for delivery prior to 34 weeks, and UCA 3>112o an OR 42.0 (95% CI 5.3 to 332.1) for delivery prior to 28 weeks. In comparison, CL<25 mm had an OR 4.7 (95% CI 1.8 to 12.2) for delivery prior to 34 weeks and OR 6.0 (95% CI 1.9 to 19.3) prior to 28 weeks. CONCLUSIONS: In patients with transvaginal cerclage, an increasingly obtuse anterior uterocervical angle reflects an increased risk of cerclage failure in the mid-trimester. Utilization of UCA measurement as a surveillance tool may improve identification of patients at risk for cerclage failure.

Perioperative complications of esophagectomy: Postneoadjuvant treatment versus primary surgery - Our experience and review of literature.

AIMS: : To compare perioperative complications in esophagectomy after neoadjuvant therapy v/s primary surgery. SETTINGS AND DESIGN: : Retrospective analysis of perioperative complications in a prospectively maintained data base of patients who underwent esophagectomy as Primary surgery or after neoadjuvant therapy was done. METHODS AND MATERIAL: : 238 cases of esophagectomies performed for esophageal carcinoma were analysed and compared, out of which 125(52.5%) were given neoadjuvant therapy followed by surgery and 113(47.5%) underwent primary surgery. Surgical procedure was standard for both the groups. All the cases were analysed for perioperative complications. STATISTICAL ANALYSIS USED: : Data was analysed using Open Epi soft ware. Association between the two study group was assessed with Chi square test. RESULTS: : On comparison, both the groups were comparable in demographic profile and type of surgery performed. However, tumour stage was higher for cases who received neoadjuvant therapy as expected. On analysis there was no significant difference in overall morbidity and 30 days mortality. CONCLUSIONS: : Neoadjuvant Chemo/chemoradiotherapy is a feasible option in esophageal carcinoma without increase in incidence of peri operative morbidity or mortality.

Implementation of a pharmacogenomics consult service to support the INGENIOUS trial.

Hospital systems increasingly utilize pharmacogenomic testing to inform clinical prescribing. Successful implementation efforts have been modeled at many academic centers. In contrast, this report provides insights into the formation of a pharmacogenomics consultation service at a safety-net hospital, which predominantly serves low-income, uninsured, and vulnerable populations. The report describes the INdiana GENomics Implementation: an Opportunity for the UnderServed (INGENIOUS) trial and addresses concerns of adjudication, credentialing, and funding.

Current perception threshold screening for carpal tunnel syndrome.

Screening for the onset of carpal tunnel syndrome (CTS), which is associated with excess ergonomic stresses of the wrist and hand, is a major concern in occupational medicine. CTS questionnaires, physical examinations, and quantitative sensory function determination through neuroselective current perception threshold (CPT) measurements were obtained from the median digital nerves of 16 assembly line workers who were symptomatic with hand pain. Median nerve evaluations by CPT detected sensory abnormalities in 75% of the workers, and abnormalities in 50% of the workers were detected by clinical evaluations (p less than .05, df = 22). CPT abnormalities were characterized as "hypoesthetic" in 25% and hyperesthesic in 42% of the workers. The noninvasive, nonaversive CPT technique provided sensitive and easily obtained quantitative measures. Regular use of this procedure in the occupational setting may assist in preventing the development of advanced CTS for it provides early detection of median nerve abnormalities.

Poly propyl ether imine (PETIM) dendrimer: a novel non-toxic dendrimer for sustained drug delivery.

In the present study, an attempt was made to study the acute and sub-acute toxicity profile of G3-COOH Poly (propyl ether imine) [PETIM] dendrimer and its use as a carrier for sustained delivery of model drug ketoprofen. Drug-dendrimer complex was prepared and characterized by FTIR, solubility and in vitro drug release study. PETIM dendrimer was found to have significantly less toxicity in A541 cells compared to Poly amido amine (PAMAM) dendrimer. Further, acute and 28 days sub-acute toxicity measurement in mice showed no mortality, hematological, biochemical or histopathological changes up to 80 mg/kg dose of PETIM dendrimer. The results of study demonstrated that G3-COOH PETIM dendrimer can be used as a safe and efficient vehicle for sustained drug delivery.