The comparative evaluation of intravenous with intramuscular clonidine for suppression of hemodynamic changes in laparoscopic cholecystectomy.

BACKGROUND: Clonidine diminishes stress response by reducing circulating catecholamines and hence increases perioperative circulatory stability in patients undergoing laparoscopic surgeries. The aim of this study was to compare intravenous (IV) clonidine (2 µg/kg) with intramuscular (IM) clonidine (2 µg/kg) for attenuation of stress response in laproscopic surgeries. METHODS: Eighty adult patients classified as ASA physical status I or II, aged between 20 and 60 years undergoing elective cholecystectomy under general anesthesia were enrolled for a prospective, randomized, and double-blind controlled trial. They received either IV clonidine (2 µg/kg) 15 min prior to the scheduled surgery (Group I) or IM clonidine (2 µg/kg) 60-90 min prior to the scheduled surgery (Group II). Hemodynamic variables (Heart rate, systolic (SBP), diastolic (DBP), mean arterial pressure (MAP)), SpO2 and EtCO2 were recorded at specific times - baseline, prior to induction, 1 min after intubation, before CO2, insufflation, after CO2 insufflation at 1,5,10,20,30,45,60 min, after release of CO2, at 1 and 10 minutes after extubation. Secondary outcomes included evaluation of adverse effect profile of the two groups. RESULTS: No significant difference was observed in the HR throughout the intraoperative period in between the two groups (P>0.05). There was statistically significant difference in SBP between the two groups starting from 1 minute after induction till 1 min after extubation (P<0.05) but not in DBP except at 1 minute after intubation (P=0.042). Significant difference in MAP was noted at 1 minute after intubation (P=0.004) and then from 5 minutes after CO2 insufflation to 1 minute after extubation (P<0.05). Incidence of adverse effects were higher in group II (P=0.02) especially incidence of hypertension requiring treatment (0.006). CONCLUSION: We conclude that under the conditions of this study, hemodynamic parameters (SBP, DBP and MAP) were better maintained in the IV as compared to the IM route that had significantly higher incidence of hypertension requiring treatment.

Comparison of intrathecal bupivacaine-fentanyl and bupivacaine-butorphanol mixtures for lower limb orthopedic procedures.

CONTEXT: Intrathecal use of butorphanol is less explored in human subjects. AIMS: To compare the safety and efficacy of anesthesia and analgesia of intrathecal bupivacaine-butorphanol mixture with intrathecal bupivacaine-fentanyl mixture. SETTINGS AND DESIGN: Tertiary level, teaching hospital. Prospective, randomized, double-blind study. MATERIALS AND METHODS: Eighty patients aged above 18 years, of ASA physical status 1 or 2, undergoing lower limb orthopedic surgeries were randomly allocated to two groups of 40 patients each. Patients in group A and group B received intrathecal 2.5 ml of hyperbaric bupivacaine (0.5%), with 25 µg of fentanyl and 25 µg of butorphanol, respectively. STATISTICAL ANALYSIS USED: Fisher's exact test and Chi square tests. RESULTS: The times required for onset of sensory and motor blockade were comparable among the two groups. Significantly slower block regression to S2 level was observed in the group receiving intrathecal butorphanol as compared to intrathecal fentanyl (P=0.0230). A higher number of patients in group A requested for rescue analgesia during the postoperative period than in group B (9 versus 2; P=0.0238). The average times to first request for rescue analgesia were 308.6±14.9 minutes and 365.9±12.3 minutes in group A and B, respectively (P=0.0254). CONCLUSIONS: Both 25 µg fentanyl and 25 µg butorphanol given intrathecally along with 12.5 mg of hyperbaric bupivacaine provide effective anesthesia for lower limb surgeries. Intrathecal bupivacaine-butorphanol mixture provides longer duration of sensory blockade and superior analgesia than intrathecal fentanyl-bupivacaine mixture.

Mecamylamine suppresses Basal and nicotine-stimulated choroidal neovascularization.

PURPOSE: Nicotinic acetylcholine receptors (nAChR) are best known for their role in neurotransmission, but they have recently been demonstrated on vascular endothelial cells. Acetylcholine is their endogenous ligand, but they are also stimulated by nicotine. By stimulating nAChR, nicotine promotes tumor angiogenesis as well as atherosclerotic plaque neovascularization. In this study, the authors investigated the role of nAChR in the pathogenesis of choroidal neovascularization (CNV). METHODS: The effect of the nonselective nAChR antagonist mecamylamine was tested on human retinal and choroidal endothelial cells in vitro and in a murine model of CNV. RESULTS: Several nAChR isoforms were identified in retinal and choroidal microvascular endothelial cells, and the ability of these cells to form tubules when grown in growth factor-reduced basement membrane matrix and supplemented with VEGF was suppressed by the nAChR antagonist mecamylamine. Supplementation of the drinking water of mice with nicotine increased the size of CNV lesions at Bruch membrane rupture sites, an effect that was blocked by subcutaneous administration of mecamylamine (50 mg/kg/d) by an osmotic pump. In the absence of nicotine, CNV formation was suppressed by the infusion of 50 mg/kg/d mecamylamine or by topical application 0.1 or 1% mecamylamine to the cornea. CONCLUSIONS: These data suggest that endogenous activation of nAChR promotes CNV and that activation of nAChR by nicotine may contribute to the increased incidence of CNV seen in smokers with age-related macular degeneration (AMD). Topically administered mecamylamine could provide an appealing new treatment approach for CNV.

The alliance for cellular signaling plasmid collection: a flexible resource for protein localization studies and signaling pathway analysis.

Cellular responses to inputs that vary both temporally and spatially are determined by complex relationships between the components of cell signaling networks. Analysis of these relationships requires access to a wide range of experimental reagents and techniques, including the ability to express the protein components of the model cells in a variety of contexts. As part of the Alliance for Cellular Signaling, we developed a robust method for cloning large numbers of signaling ORFs into Gateway entry vectors, and we created a wide range of compatible expression platforms for proteomics applications. To date, we have generated over 3000 plasmids that are available to the scientific community via the American Type Culture Collection. We have established a website at www.signaling-gateway.org/data/plasmid/ that allows users to browse, search, and blast Alliance for Cellular Signaling plasmids. The collection primarily contains murine signaling ORFs with an emphasis on kinases and G protein signaling genes. Here we describe the cloning, databasing, and application of this proteomics resource for large scale subcellular localization screens in mammalian cell lines.

Primary vascular occlusion in IRVAN (idiopathic retinal vasculitis, aneurysms, neuroretinitis) syndrome.

IRVAN is a rare retinal vascular disease characterized by the presence of aneurysmal dilations along the retinal arteriolar tree. Visual loss occurs from sequelae to proliferative changes or due to severe macular exudation and rarely from secondary vascular occlusion following laser photocoagulation of the aneurysms. We herein report a patient with a primary vascular occlusion in a patient with IRVAN and suggest that such patients may already have a natural predisposition to develop a vascular occlusion.

Unravelling the signal-transduction network in B lymphocytes.

The Alliance for Cellular Signaling has chosen the mouse B lymphocyte as a model system to understand basic principles that govern cellular signalling. Progress to that end has focused initially on establishing a reproducible experimental cell system and characterizing essential signalling responses. Although unravelling this complex network will take years, findings revealed in the interim will prove immensely useful to the scientific community at large.