Modified blalock-taussig shunt in palliative cardiac surgery

Background: Cyanotic congenital heart diseases present early in life with poor general condition of the patient. Majority of deaths occurs within one year of life before surgical intervention due to severe cyanosis and metabolic acidosis. Modified Blalock-Taussig Shunt (MBTS) is one of the palliative cardiac surgeries done for cyanotic congenital heart diseases. It improves the general condition of the patient before definitive surgery is done. The aim of this study was to determine the commonest indications, post-operative anticoagulation and early complications following MBTS at CARE Hospital, India.Methods: This was a retrospective study from January 2004 to December 2006 including all patients who underwent Posterolateral Thoracotomy for MBTS. All patients had deep cyanosis, oxygen saturation of 65% or less and small pulmonary vasculature due to congenital heart defects. Acyanotic patients and those with oxygen saturation more than 65% were excluded from the study. All patients received a single dose of heparin intra-operatively and oral aspirin as anticoagulant regimen post-operatively. No heparin given postoperatively.Results: A total of 20 children with a mean age of 27.4 months were studied. Two patients had pre-operative ICU admission due to severe cyanosis (both had oxygen saturation of 35%), hypotension and severe body weakness. The commonest indications for MBTS included Tetralogy of Fallot (70%), pulmonary atresia (10%) with or without Ventricular Septal Defect (VSD), tricuspid atresia (10%) with pulmonary atresia or stenosis and Double Outlet Right Ventricle (DOVR) with pulmonary atresia or stenosis (10%). Mean duration of ICU stay was 2 days, mean duration of mechanical ventilation was four and half hours, mean duration of hospital stay was 7 days and mean systemic oxygen saturation improved significantly from 46% to 84% ( x2 = 7.03, p = 0.0080). No post-operative bleeding, seroma, shunt thrombosis or death occurred in this study.Conclusion: The commonest indication for MBTS is TOF. Intra-operative single dose of heparin followed by post-operative oral aspirin as anticoagulant regimen was not associated with a major complication in terms of bleeding, seroma, shunt thrombosis, or death

Clinico-Surgical Outcome of Repair of Isolated Atrial Septal Defect At Care Hospital, Banjara Hills-Hyderabad India, 2004-2006

No Abstract

Design, Synthesis, and Structure−Activity Relationship Exploration of 1-Substituted 4-Aroyl-3-hydroxy-5-phenyl-1H-pyrrol-2(5H)-one Analogues as Inhibitors of the Annexin A2−S100A10 Protein Interaction

This research was supported by grants from Cancer Research UK. H.K.M. was funded by a Biotechnology and Biological Sciences Research Council studentship.S100 proteins are small adaptors that regulate the activity of partner proteins by virtue of direct protein interactions. Here, we describe the first small molecule blockers of the interaction between S100A10 and annexin A2. Molecular docking yielded candidate blockers that were screened for competition of the binding of an annexin A2 peptide to S100A10. Several inhibitory clusters were identified with some containing compounds with potency in the lower micromolar range. We chose 3-hydroxy-1-(2-hydroxypropyl)-5-(4-isopropylphenyl)-4-(4-methylbenzoyl)-1H-pyrrol-2(5H)-one (1a) as a starting point for structure-activity studies. These confirmed the hypothetical binding mode from the virtual screen for this series of molecules. Selected compounds disrupted the physiological complex of annexin A2 and S100A10, both in a broken cell preparation and inside MDA-MB-231 breast cancer cells. Thus, this class of compounds has promising properties as inhibitors of the interaction between annexin A2 and S100A10 and may help to elucidate the cellular function of this protein interaction.Peer reviewe

Giardia Flagellar Motility Is Not Directly Required to Maintain Attachment to Surfaces

Giardia trophozoites attach to the intestinal microvilli (or inert surfaces) using an undefined “suction-based” mechanism, and remain attached during cell division to avoid peristalsis. Flagellar motility is a key factor in Giardia's pathogenesis and colonization of the host small intestine. Specifically, the beating of the ventral flagella, one of four pairs of motile flagella, has been proposed to generate a hydrodynamic force that results in suction-based attachment via the adjacent ventral disc. We aimed to test this prevailing “hydrodynamic model” of attachment mediated by flagellar motility. We defined four distinct stages of attachment by assessing surface contacts of the trophozoite with the substrate during attachment using TIRF microscopy (TIRFM). The lateral crest of the ventral disc forms a continuous perimeter seal with the substrate, a cytological indication that trophozoites are fully attached. Using trophozoites with two types of molecularly engineered defects in flagellar beating, we determined that neither ventral flagellar beating, nor any flagellar beating, is necessary for the maintenance of attachment. Following a morpholino-based knockdown of PF16, a central pair protein, both the beating and morphology of flagella were defective, but trophozoites could still initiate proper surface contacts as seen using TIRFM and could maintain attachment in several biophysical assays. Trophozoites with impaired motility were able to attach as well as motile cells. We also generated a strain with defects in the ventral flagellar waveform by overexpressing a dominant negative form of alpha2-annexin::GFP (D122A, D275A). This dominant negative alpha2-annexin strain could initiate attachment and had only a slight decrease in the ability to withstand normal and shear forces. The time needed for attachment did increase in trophozoites with overall defective flagellar beating, however. Thus while not directly required for attachment, flagellar motility is important for positioning and orienting trophozoites prior to attachment. Drugs affecting flagellar motility may result in lower levels of attachment by indirectly limiting the number of parasites that can position the ventral disc properly against a surface and against peristaltic flow