Comparison of caudal epidural bupivacaine with bupivacaine plus tramadol and bupivacaine plus ketamine for postoperative analgesia in children

This study compared the effect of single-dose caudal epidural bupivacaine, bupivacaine plus ketamine and bupivacaine plus tramadol for postoperative pain management in children having surgery for inguinal hernia. Following ethics committee approval and informed parental consent, 75 children ASA PS I and II, between three and nine years of age and scheduled for elective unilateral inguinal hernia repair with general anaesthesia were recruited. The patients were randomly divided into three groups to receive 0.5 ml/kg caudal bupivacaine 0.25% (group B), bupivacaine 0.25% plus tramadol 1 mg/kg (group BT) or bupivacaine 0.25% plus ketamine 0.5 mg/kg (group BK). The injections were performed under general anaesthesia. Mean arterial pressure, heart rate, pulse oximetry, respiratory rate and sedation and pain scores were recorded at defined intervals following recovery from anaesthesia. The groups were similar in age, weight and duration of operation (P >0.05). No patient experienced hypotension, bradycardia or respiratory depression. Duration of analgesia was (mean+/-SD) 6.5+/-4.1 h in group B, 9.2+/-3.9 h in group BK, and 8.5+/-3.1 h in group BT (P <0.05). More patients in group B required supplementary analgesics in the first 24 h (P <0.05). Sedation scores were comparable in all groups. Incidence of emesis and pruritus was similar in all the groups. Caudally administered 0.5 ml/kg bupivacaine 0.25% plus ketamine or bupivacaine 0.25% plus tramadol 1 mg/kg provided significantly longer duration of analgesia without an increase in the adverse effects when compared to bupivacaine alone.     

Cyclophosphamide-induced agenesis of cerebral aqueduct resulting in hydrocephalus in mice

The present work was undertaken to reveal the mechanism of cerebral aqueduct agenesis found to result in hydrocephalus following intrauterine exposure to model teratogen, cyclophosphamide, in murine fetuses. A single dose of 10-mg/kg body weight cyclophosphamide was injected intaperitoneally to pregnant mice on day 10, 11 or 12 of gestation. Fetuses were collected through abdominal incision on day 18 and studied for various malformations of brain and cranium including hydrocephalus. Incomplete development and failure of canalization of the cerebral aqueduct were detected when serial sections of brain in coronal and transverse planes were studied under the microscope. Biotechnological investigations such as % DNA fragmentation, % viable cell count and cell proliferation assay were carried out on brain cells for further studies. Agenesis and non-canalization of the cerebral aqueduct resulted in increased pressure of CSF, which led to rupture of the aqueduct complicated by leakage and accumulation of CSF in brain substance forming a cavity containing CSF parallel and lateral to the unopened part of the cerebral aqueduct. Incomplete development along with non-canalization of the cerebral aqueduct resulted in blockage of CSF flow through the ventricles that manifest as internal hydrocephalus. External hydrocephalus on the other hand was detected where the CSF accumulated in the cavity formed inside the brain substance and established communication with the CSF in the subarachnoid space. Cyclophosphamide induced inhibition of mitosis and cell differentiation of ependymal cells reflecting a decreased % viable cell count and cell proliferation assay along with augmentation of apoptosis of brain cells quantified as increased % DNA fragmentation count, which were identified as the contributing factors underlying the agenesis and incomplete development of the cerebral aqueduct. The study also suggests that cell survival, proliferation, migration or differentiation of ependymal cells might have been affected, and we speculate that CSF may have an inducing role in the development and canalization of the cerebral aqueduct.     

Mechanisms underlying greater sensitivity of neonatal cardiac muscle to volatile anesthetics

BACKGROUND: In neonatal heart, plasma membrane Na+-Ca2+ exchange (NCX) and Ca2+ influx channels play greater roles in intracellular Ca2+ concentration [Ca2+]i regulation compared with the sarcoplasmic reticulum (SR). In neonatal (aged 0-3 days) and adult (aged 84 days) rat cardiac myocytes, we determined the mechanisms underlying greater sensitivity of the neonatal myocardium to inhibition by volatile anesthetics. METHODS: The effects of 1 and 2 minimum alveolar concentration halothane and sevoflurane on Ca2+ influx during electrical stimulation in the presence or blockade of NCX and the Ca2+ channel agonist BayK8644 were examined. [Ca2+]i responses to caffeine were used to examine anesthetic effects on SR Ca2+ release (via ryanodine receptor channels) and reuptake (via SR Ca2+ adenosine triphosphatase). Ca2+ influx via NCX was examined during rapid activation in the presence of the reversible SR Ca2+ adenosine triphosphatase inhibitor cyclopiazonic acid and ryanodine to inhibit the SR. Efflux mode NCX was examined during activation by extracellular Na+ in the absence of SR reuptake. RESULTS: Intracellular Ca2+ concentration transients during electrical stimulation were inhibited to a greater extent in neonates by halothane (80%) and sevoflurane (50%). Potentiation of [Ca2+]i responses by BayK8644 (160 and 120% control in neonates and adults, respectively) was also blunted by anesthetics to a greater extent in neonates. [Ca2+]i responses to caffeine in neonates ( approximately 30% adult responses) were inhibited to a lesser extent compared with adults (35 vs. 60% by halothane). Both anesthetics inhibited Ca2+ reuptake at 2 minimum alveolar concentration, again to a greater extent in adults. Reduction in NCX-mediated influx was more pronounced in neonates (90%) compared with adults (65%) but was comparable between anesthetics. Both anesthetics also reduced NCX-mediated efflux to a greater extent in neonates. Potentiation of NCX-mediated Ca2+ efflux by extracellular Na+ and NCX-mediated Ca2+ influx by intracellular Na+ were both prevented by halothane, especially in neonates. CONCLUSIONS: These data indicate that greater myocardial depression in neonates induced by volatile anesthetics may be mediated by inhibition of NCX and Ca2+ influx channels rather than inhibition of SR Ca2+ release.     

High prevalence of malnutrition and inflammation in undialyzed patients with chronic renal failure in developing countries: a single center experience from eastern India

BACKGROUND: Malnutrition is common in patients with chronic renal failure (CRF), and its prevalence before the initiation of dialysis is poorly characterized in these patients in developing countries. There is a paucity of data on the quantification of malnutrition and inflammation in undialyzed patients of CRF from India. This study analyzed the prevalence and causes of malnutrition in patients with CRF before the initiation of dialysis treatment. MATERIAL AND METHODS: In the present study, assessments of nutritional and inflammatory status were carried out in patients with CRF. Serum albumin, body mass index (BMI), triceps skin fold thickness (TST), mid-arm muscle circumference (MAMC), and subjective global assessment (SGA) scoring were used for assessment of nutritional parameters. Serum C-reactive protein and serum ferritin level were used to assess the inflammatory state of the patient. RESULTS: Two hundred and three (146 male, 57 female) patients with CRF were included in the study from August 2004 to April 2006. Overall, the prevalence of malnutrition was 65% (131/203). The age of malnourished patients (93 male, 38 female) ranged from 11-82, with mean age of 52 +/- 12.68 years. The mean serum total protein and albumin were also significantly lower in patients with malnutrition in comparison to non malnourished cases (5.50 +/- 0.40 gm/dL vs. 5.74 +/- 0.38 gm/dL; p < 0.05, and 3.18 +/- 0.58 gm/dL vs. 3.68 +/- 0.55 gm/dL; p < 0.05). The C-reactive protein and serum ferritin were significantly elevated in the malnourished group as compared to non-malnourished patients (63% vs. 33%; p < 0.05, and 301.2 +/- 127.1 mg/dL vs. 212.7 +/- 124.9 mg/dL; p < 0.05). CONCLUSION: Thus, malnutrition was common in patients with CRF before the commencement of dialysis. These data indicate that an emphasis should be placed on the assessment and prevention or correction of malnutrition in patients with CRF because of its documented adverse effect on the outcome on maintenance dialysis.     

Backside Wear in Modern Total Knee Designs

Although modularity affords various options to the orthopedic surgeon, these benefits come at a price. The unintended bearing surface between the back surface of the tibial insert and the metallic tray results in micromotion leading to polyethylene wear debris. The objective of this study was to examine the backside wear of tibial inserts from three modern total knee designs with very different locking mechanisms: Insall-Burstein II® (IB II®), Optetrak®, and Advance®. A random sample of 71 inserts were obtained from our institution’s retrieval collection and examined to assess the extent of wear, depth of wear, and wear damage modes. Patient records were also obtained to determine patient age, body mass index, length of implantation, and reason for revision. Modes of wear damage (abrasion, burnishing, scratching, delamination, third body debris, surface deformation, and pitting) were then scored in each zone from 0 to 3 (0 = 0%, 1 = 0–10%, 2 = 10–50%, and 3 = >50%). The depth of wear was subjectively identified as removal of manufacturing identification markings stamped onto the inferior surface of the polyethylene. Both Advance® and IB II® polyethylene inserts showed significantly higher scores for backside wear than the Optetrak® inserts. All IB II® and Advance® implants showed evidence of backside wear, whereas 17% (5 out of 30) of the retrieved Optetrak® implants had no observable wear. There were no significant differences when comparing the depth of wear score between designs. The locking mechanism greatly affects the propensity for wear and should be considered when choosing a knee implant system.Key words: polyethylene, wear, knee, backside, back surface, locking mechanism     

Laparoscopic Colonic Resection for Rectosigmoid Colonic Tumours: A Retrospective Analysis and Comparison with Open Resection

Laparoscopic approach for treatment of colorectal malignancy is gaining acceptance gradually; however the benefits of laparoscopic surgery in colonic and rectal tumours is still open to debate. This study aims at a retrospective analysis of operative and short term outcome of patients with rectosigmoid tumours. A retrospective analysis of operative, postoperative and short-term outcome of 62 patients who underwent laparoscopic colorectal resection for cancer of rectosigmoid region were compared with a same number of parameters-matched patients who underwent open colorectal resection. Blood transfusion requirement was significantly more in the open group compared to the laparoscopy group (38.7% versus 6.4%, p = 0.001). ICU stay was less in the laparoscopy group (p = <0.05) and they were started on oral liquid diet earlier (p = 0.013). The number of the lymph nodes retrieved, positive distal margin and radial involvement were similar in both groups. The hospital stay was significantly shorter in laparoscopy group (8.4 versus 13.8 days, p < 0.05). Radical operation for rectosigmoid tumors is technically feasible with laparoscopic surgery. Laparoscopic approach is associated with less blood loss, transfusion and significantly less ICU stay. Laparoscopic group recovers early and needs less hospital stay     

Protective effects of Eugenia jambolana extract versus N‐acetyl cysteine against cisplatin‐induced damage in rat testis

To assess the protective effects of Eugenia jambolana extract (EJE) or N‐acetyl cysteine (NAC) on testis, cisplatin (CIS, 5 mg kg^?1 bw, single dose) was administered either alone or along with EJE (25 mg kg^?1 bw, alternate day) or NAC (150 mg kg^?1 bw, Day 1 and 4) for 7 days. Significant alterations in serum LH, FSH and testosterone were observed in CIS group which were effectively modulated by EJE or NAC supplementation. Upregulation of 3β‐HSD gene indicated the rise in functional Leydig cells. This was further confirmed from the identical improvement in hCG‐stimulated testosterone production in isolated Leydig cells. Reduction in oxidative stress was associated with restoration of total antioxidant capacity and glutathione levels, and activation of antioxidant enzymes, SOD, catalase, glutathione s‐transferase (GST) and glutathione reductase (GR). CIS‐induced apoptosis of germ and Leydig cells was contained by both NAC and EJE intervention by effective modulation of apoptotic markers in the extrinsic, intrinsic and other pathways of metazoan apoptosis. Taken together, the study findings establish the potential of EJE as a therapeutically better antioxidant than NAC for use in curtailing the adverse effects of anticancer drugs on testicular function.     

Furlong Hydroxyapatite-Coated Hip Prosthesis vs the Charnley Cemented Hip Prosthesis

We report the results of a prospective trial comparing uncemented Furlong hydroxyapatite-coated total hip arthroplasty and cemented Charnley total hip arthroplasty. One hundred ninety-one patients were allocated into 2 groups depending on their year of birth. One group received a Furlong hydroxyapatite-coated total hip arthroplasty and the other group received a cemented Charnley total hip arthroplasty. At a mean follow-up of 14 years (12-16 years), Harris hip scores showed no difference between the 2 groups. The longitudinal multilevel model analysis shows that the mean slope of the change in the Harris hip score was −0.02 for the Furlong group and −0.05 for the Charnley group; the difference is 0.03 (P = .002). The survival analysis using Kaplan-Meier regression analysis (the log-rank test λ²₁ = 0.031, P = .58) does not show a significant difference between the 2 groups. Overall survival was 93.6% in the Furlong group and 94.8% in the Charnley group.     

Arcuate-legged Nonpenetrating Vascular Closure Staples (VCS): Early Experience

Vascular closure staples (VCS) provide a novel technique for fashioning vascular anastomoses, allowing a single operator to perform suture-less anastomoses. They may be used primarily or in an adjuvant role. When VCS are compared to a running suture, advantages include the avoidance of intimal damage, platelet aggregation and intimal hyperplasia at the anastomotic suture line, and a shorter time taken to complete the anastomosis. We report our early experience using VCS in an array of vascular anastomoses and conclude that VCS are a useful addition to the vascular surgeon's armamentarium. They help to decrease the time taken to construct an anastomosis, and are particularly useful in an adjuvant setting, complementing conventionally placed sutures.     

Impact of Common Variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the Risk of Type 2 Diabetes in 5,164 Indians

OBJECTIVE

Common variants in PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 genes have been shown to be associated with type 2 diabetes in European populations by genome-wide association studies. We have studied the association of common variants in these eight genes with type 2 diabetes and related traits in Indians by combining the data from two independent case–control studies.

RESEARCH DESIGN AND METHODS

We genotyped eight single nucleotide polymorphisms (PPARG-rs1801282, KCNJ11-rs5219, TCF7L2-rs7903146, SLC30A8-rs13266634, HHEX-rs1111875, CDKN2A-rs10811661, IGF2BP2-rs4402960, and CDKAL1-rs10946398) in 5,164 unrelated Indians of Indo-European ethnicity, including 2,486 type 2 diabetic patients and 2,678 ethnically matched control subjects.

RESULTS

We confirmed the association of all eight loci with type 2 diabetes with odds ratio (OR) ranging from 1.18 to 1.89 (P = 1.6 × 10⁻³ to 4.6 × 10⁻³⁴). The strongest association with the highest effect size was observed for TCF7L2 (OR 1.89 [95% CI 1.71–2.09], P = 4.6 × 10⁻³⁴). We also found significant association of PPARG and TCF7L2 with homeostasis model assessment of β-cell function (P = 6.9 × 10⁻⁸ and 3 × 10⁻⁴, respectively), which looked consistent with recessive and under-dominant models, respectively.

CONCLUSIONS

Our study replicates the association of well-established common variants with type 2 diabetes in Indians and shows larger effect size for most of them than those reported in Europeans.Type 2 diabetes is a complex metabolic disorder with both genetic and environmental factors such as food habits and lifestyle contributing to its pathogenesis (1). Due to its complex etiology, the progress of discovery of genetic components for type 2 diabetes had been very slow until the advent of high throughput genome-wide association (GWA) studies (2). Until recently, only a few common variants in PPARG (3), KCNJ11 (4), and TCF7L2 (5) were shown to be associated with type 2 diabetes. With the advent of GWA studies, there are at least 20 loci identified today that are associated with the risk of type 2 diabetes (6). The first GWA study in the French population revealed SLC30A8 and HHEX as new loci for type 2 diabetes in addition to replicating the strong association with TCF7L2 (7). Further, GWA studies added several new genes including CDKAL1, CDKN2A, IGF2BP2, and FTO to the list of type 2 diabetes–associated loci and confirmed the associations for PPARG, KCNJ11, and TCF7L2 (8–12).India harbors the maximum number of diabetic patients, which is projected to double by the year 2030 (13). Indians are diagnosed with diabetes a decade earlier and at a lower BMI than Europeans, which may be partly explained by their excess central obesity (14,15). Hence, determination of genetic risk factors predicting the risk of type 2 diabetes in the Indian population is highly desirable. Recent evidence suggests that the genetic basis of several diseases in Indians might be different from that of Europeans (16,17), which could be due to differences in the risk allele frequency and pattern of linkage disequilibrium. A report from the Indian Genome Variation Consortium also suggested that most of the populations in the Indian subcontinent are distinct from HapMap populations (18). Hence, genes associated with a disease in other populations need to be assessed for their role in the Indian population. The present study evaluated the association of eight most replicated and well-established genetic variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 with type 2 diabetes and related quantitative traits in Indians. We also performed allele dosage analysis of these variants and investigated their influence on quantitative metabolic traits related to type 2 diabetes.