Effect of intraperitoneal bupivacaine on postoperative pain and sympathoadrenal response following laproscopic cholecystectomy

Background: Pain after laproscopic surgeries is highest in the upper abdomen. Pain is greatest after operation and decreases within 24 hours. Due to adverse effects of opoids, multimodal analgesia with smaller doses of opoids, local anaesthatics and NSAIDS is given. The aim of postoperative pain relief is to provide subjective comfort and to blunt the autonomic and somatic responces to pain to inhance restore normal function.so that patient can go home early.Methods: 30 Patients each of study group (bupivacine) and control group (normal saline) of class 1 and class 2 of American society of anaesthiology of either sex were taken. 20cc of bupivacine or normal saline sprayed in gall blader fossa. Vital parameter visual analog scale score and blood sugar was noted.Results: The two groups were comparable regarding age, sex and body mass index. VAS score was significantly reduced in study group. Mean blood sugar showed no significant difference in two groups.Conclusions: Intraperitonial instillation of bupivacine is safe and reduces pain in early postoperative period

Differences in peripheral noradrenergic function among actively drinking and abstinent alcohol-dependent individuals.

We examined whether excessive alcohol consumption was related to changes in plasma levels of noradrenaline (NA) and whether these changes recover following abstinence. We also explored whether there were differences in NA levels between Type I and Type II alcoholics and controls during active drinking and abstinence. Plasma concentrations of NA were determined in (1) 27 Caucasian men with alcohol dependence who were regularly drinking (active drinkers) within 24 hours of hospitalization, (2) 29 Caucasian alcohol-dependent men who were in remission (abstinent for a minimum of three months), and (3) 28 race- and gender-matched healthy controls. NA concentrations were significantly higher in actively drinking alcohol-dependent subjects compared to those in remission and controls. While Type I and Type II alcoholic individuals differed across clinical measures, NA levels were similar in the two subtypes. Both subtypes showed an elevation in NA levels during active drinking compared to controls, but NA levels did not differ between the two subtypes and controls during remission. The findings indicate that chronic exposure to alcohol may lead to disturbances in NA activity that may manifest in early abstinence. However, the changes in NA activity appears to normalize after a longer period of abstinence. Alterations in NA activity do not seem to be specific for Type I or Type II subtypes of alcoholism

Clonidine as an adjuvant to local anesthetic in supraclavicular brachial plexus block: a randomized, double blinded placebo controlled study

Background: Many drugs have been studied as adjuvants to local anesthetic agents with the aim of improving the quality of anesthesia and to provide profound analgesia. Clonidine has also been used as an adjunct to local anesthetic agents in various regional techniques. The studies regarding clonidine in brachial plexus block have given mixed results. Aim was to determine whether addition of clonidine to the local anesthetic solution for brachial plexus block by supraclavicular approach, prolongs sensory and motor blockade and improves postoperative analgesia. Also to observe side effects if any.Methods: 60 patients aged 18-60 years, were randomly allocated into two groups. Group A received 2 µg / kg of Clonidine diluted to 1 ml with saline and group B received 1 ml of saline added to bupivacaine (10 ml 0.5%) and lignocaine (20 ml 2 %) solution, in the supraclavicular block. The onset and duration of sensory and motor block was compared along with the duration of analgesia, sedation in both the groups. Patients’ pulse rate, blood pressure, saturation was also recorded.Results: Addition of clonidine had no effect on the onset of the block, but was found to increase the duration of sensory and motor block along with the increase in the duration of analgesia. Visual analogue score for pain was significantly lower in the group receiving clonidine.Conclusions: Clonidine 2 µg / kg added to 10 ml of 0.5 % Bupivacaine + 20 ml of 2% lignocaine with adrenaline (1:200000) is a good option for improving the quality and duration of supraclavicular brachial plexus block

Fantastic Sources Of Tumor Heterogeneity And How To Characterize Them

Cancer constantly evolves to evade the host immune system and resist different treatments. As a consequence, we see a wide range of inter and intra-tumor heterogeneity. In this PhD thesis, we present a collection of computational methods that characterize this heterogeneity from diverse perspectives. First, we developed computational frameworks for predicting functional re-wiring events in cancer and imputing the functional effects of protein-protein interactions given genome-wide transcriptomics and genetic perturbation data. Second, we developed a computational framework to characterize intra-tumor genetic heterogeneity in melanoma from bulk sequencing data and study its effects on the host immune response and patient survival independently of the overall mutation burden. Third, we analyzed publicly available genome-wide copy number, expression and methylation data of distinct cancer types and their normal tissues of origin to systematically uncover factors driving the acquisition of cancer type-specific chromosomal aneuploidies. Lastly, we developed a new computational tool: CODEFACS (COnfident Deconvolution For All Cell Subsets) to dissect the cellular heterogeneity of each patient’s tumor microenvironment (TME) from bulk RNA sequencing data, and LIRICS (LIgand Receptor Interactions between Cell Subsets): a supporting statistical framework to discover clinically relevant cellular immune crosstalk. Taken together, the methods presented in this thesis offer a way to study tumor heterogeneity in large patient cohorts using widely available bulk sequencing data and obtain new insights on tumor progression

A comparative study of ropivacaine 0.75% and bupivacaine 0.5% for segmental epidural anaesthesia in patients undergoing percutaneous nephrolithotomy

Background: Percutaneous nephrolithotomy (PCNL) is used for fragmentation and removal of stones from pelvicalyceal system using a nephroscope passed into the kidneys through a track created in the patients back. PCNL is the treatment of choice for larger renal stones of size more than 20 to 30 mm, staghorn stones and stones that are multiple or resistant to extra corporeal shock.Methods: This prospective, randomized, open, controlled trial was carried out in 60 adult patients undergoing elective surgical procedure. The patients were randomly divided into two groups of 30 each. Each group underwent PCNL under segmental epidural.Results: Both the groups were comparable with respect to their demographic data, duration of surgery, size of stone and baseline vital parameters. Nine patients in Ropivacaine group and seven patients in Bupivacaine group developed clinically significant hypotension. The incidence of complications was similar in both the group. The fall in haemoglobin was similar in both the groups and none of the patients required blood transfusion.Conclusions: Segmental epidural anaesthesia is a safe alternative technique to general anesthesia for PCNL. Both the drugs ropivacine and bupivacaine were safe and clinically comparable in segmental epidural for PCNL.

A comparative study of combined spinal epidural anaesthesia and general anaesthesia in patients undergoing percutaneous nephrolithotomy

Background: Our primary aim was to study the efficacy, safety, hemodynamic stability, postoperative pain relief, and complication with combined spinal epidural anaesthesia (CSE) and to compare it with general anaesthesia (GA) for percutaneous nephrolithotomy (PCNL).  Methods: The present study was a prospective, randomized, open, controlled trial to compare the effects of CSE and GA in patients undergoing PCNL. Study was carried out in 100 adult patients, who were randomly divided into two groups of 50 each, Group GA and Group CSE. Post-operative pain relief and amount rescue analgesia required were noted. Postoperatively samples were collected for haemoglobin and arterial blood gases. Incidence of complications were noted and compared among both the groups.Results: Mean arterial pressure in CSE group was less compared to GA group during the procedure. 30 % patients in group GA required first rescue analgesia within first hour of completion of surgery whereas no patient in group CSE required analgesia within first hour indicating better pain relief in CSE group. Mean haemoglobin and the fall in haemoglobin between the groups were comparable. 48.0% of the cases among GA group and 14.0% of the cases among CSE group had postoperative nausea and vomiting. Mean pH in GA group was 7.33±0.05 and in CSE group was 7.36±0.04. There was one case of hydrothorax post operatively.Conclusions: We conclude that CSE is a safe alternative to GA for PCNL with better pain relief, less PONV. Hypotension due to sympathetic blockade is always a possibility

Medical symptoms associated with tobacco smoking with and without marijuana abuse among crack cocaine-dependent patients.

Despite the widespread use of tobacco and marijuana by cocaine abusers, it remains unclear whether combined tobacco and marijuana smoking is more harmful than tobacco smoking alone in cocaine abusers. We investigated the differences in medical symptoms reported among 34 crack cocaine abusers who did not smoke tobacco or marijuana (C), 86 crack cocaine abusers who also smoked tobacco (C + T), and 48 crack abusers who smoked both tobacco and marijuana (C + T + M). Medical symptoms were recorded using a 134-item self-report instrument (MILCOM), and drug use was assessed using the Addiction Severity Index (ASI). After controlling for clinical and demographic differences, the C + T + M group reported significantly more total symptoms on the MILCOM as well as on the respiratory, digestive, general, and nose/throat subscales than the C + T or C groups. The C + T group reported higher total and respiratory and nose/throat symptoms than the C group. HOwever, the C group had the highest number of mood symptoms among the three groups. The C + T and C + T + M groups were comparable in number of cigarettes smoked and ASI scores. Although tobacco smoking is associated with higher reports of medical problems in crack abusers, smoking both marijuana and tobacco seems to be associated with greater medical problems than smoking tobacco alone. Tobacco smoking was not related to changes in cocaine use. Also, marijuana smoking does not appear to be associated with a reduction in tobacco or cocaine use

The Effects of C-terminal Modifications on the Opioid Activity of [N-BenzylTyr1]Dynorphin A-(1-11) Analogs

Structural modifications affecting the efficacy of analogs of the endogenous opioid peptide dynorphin (Dyn) A have focused on the N-terminal “message” sequence, based on the “messageaddress” concept. To test the hypothesis that changes in the C-terminal “address” domain could affect efficacy, modified amino acids and cyclic constraints were incorporated into this region of the partial agonist [N-benzylTyr1]Dyn A-(1-11). Modifications in the C-terminal domain of [NbenzylTyr1] Dyn A-(1-11)NH2 resulted in increased kappa opioid receptor (KOR) affinity for all of the linear analogs, but did not affect the efficacy of these peptides at KOR. Cyclization between positions 5 and 8 yielded [N-benzylTyr1,cyclo(D-Asp5,Dap8)]Dyn A-(1-11)NH2 (13) (Patkar et al. J. Med. Chem. 2005, 48, 4500-4503) with high selectivity for KOR. In contrast to the linear peptides, this peptide exhibits negligible efficacy in the AC assay and is a KOR antagonist. These data are consistent with our hypothesis that appropriate modifications in the “address” domain of Dyn A analogs may affect efficacy

Relationship of serum prolactin with severity of drug use and treatment outcome in cocaine dependence.

RATIONALE: Alteration in serum prolactin (PRL) levels may reflect changes in central dopamine activity, which modulates the behavioral effects of cocaine. Therefore, serum PRL may have a potential role as a biological marker of drug severity and treatment outcome in cocaine dependence. OBJECTIVE: We investigated whether serum PRL levels differed between cocaine-dependent (CD) subjects and controls, and whether PRL levels were associated with severity of drug use and treatment outcome in CD subjects. METHODS: Basal PRL concentrations were assayed in 141 African-American (AA) CD patients attending an outpatient treatment program and 60 AA controls. Severity of drug use was assessed using the Addiction Severity Index (ASI). Measures of abstinence and retention during 12 weeks of treatment and at 6-month follow-up were employed as outcome variables. RESULTS: The basal PRL (ng/ml) in CD patients (9.28+/-4.13) was significantly higher than controls (7.33+/-2.94) (t=3.77, P\u3c0.01). At baseline, PRL was positively correlated with ASI-drug (r=0.38, P\u3c0.01), ASI-alcohol (r=0.19, P\u3c0.05), and ASI-psychological (r=0.25, P\u3c0.01) composite scores, and with the quantity of cocaine use (r=0.18, P\u3c0.05). However, PRL levels were not significantly associated with number of negative urine screens, days in treatment, number of sessions attended, dropout rate or changes in ASI scores during treatment and at follow-up. Also, basal PRL did not significantly contribute toward the variance in predicting any of the outcome measures. CONCLUSION: Although cocaine use seems to influence PRL levels, it does not appear that PRL is a predictor of treatment outcome in cocaine dependence