Prediction of weight of Indian children aged upto two years based on foot-length: implications for emergency areas

BACKGROUND: Children presenting in critical care department might receive improper drug doses, as their weight and length cannot be determined while they are being resuscitated. AIMS: To determine if there is a correlation between foot-length and weight, length and surface area and to compare the drug doses calculated as per predicted weight (determined on the basis of foot-length) with those calculated on the basis of actual weight. MATERIAL AND METHODS: Weight, length and foot-length of children aged up to 24 months were determined in the prospective study. Analysis was done using simple linear regression analysis and by determination of coefficient of determination. The dosages of emergency medications (epinephrine, atropine, Ringers lactate and diazepam) were calculated on the basis of actual weight and dosages given in standard text and were then compared with dosages likely to be administered on the basis of weight predicted by foot-length measurement. RESULTS: Five hundred subjects were enrolled in the study that demonstrated a significant linear relationship between foot-length and body weight (r2 = 0.88), total length (r2 = 0.88), and body surface area (r2 = 0.84). The weight could be predicted on the basis of the following formula Weight (kg)= [1.35 x foot-length (cm)] -5.15. The doses of drugs calculated on the basis of weight predicted from foot length were exceeded the standard dose by 2.35 to 2.40%. CONCLUSIONS: In children aged up to 2 years, foot-length can be used to predict weight and calculate doses of emergency drugs.     

Metabolic syndrome and hepatic resection: improving outcome

ObjectiveA review of the peri-operative risk associated with hepatic resection in patients with metabolic syndrome (MetS) and identification of measures for the improvement of cardiometabolic disturbances and liver-related mortality.BackgroundMetS and its hepatic manifestation non-alcoholic fatty liver disease (NAFLD) are associated with an increased operative mortality in spite of a significant improvement in peri-operative outcome after hepatic resection.MethodsA review of the English literature on MetS, liver resection and steatosis was performed from 1980 to 2011 using the MEDLINE and PubMed databases.ResultsMetS is a predictor of NAFLD and patients with multiple metabolic risk factors may harbour non-alcoholic steatohepatitis (NASH) predictive of operative and cardiovascular mortality. Pre-operative diagnosis of unsuspected NASH with the selective use of a liver biopsy can modify the operative strategy by limiting the extent of hepatic resection, avoiding or altering the pre-operative chemotherapy regimen and the utilization of portal vein embolization. Thiazolidinediones are therapeutic for MetS and NASH and Vitamin E for active NASH; however, their utility in improving the peri-operative outcome after hepatic resection is unknown. A short-term regimen for weight loss improves post-operative patient and liver-related outcomes in patients with >30% steatosis. Cardiovascular disease associated with MetS or NAFLD should be managed aggressively. Peri-operative measures to minimize thrombotic events and acute renal injury secondary to the pro-inflammatory, prothrombotic state of MetS may further improve the outcome.ConclusionPotential candidates for hepatic resection should be screened for MetS as the pre-operative identification of NASH, short-term treatment of significant steatosis, cardiovascular risk assessment and optimization of each component of MetS may improve the peri-operative outcome in this high-risk subset of patients.     

Unequal allotment of patients in phase III oncology clinical trials

Patient enrollment in cancer clinical trials has traditionally been limited to an equal distribution between cases and controls, however recently some clinical trials have utilized an unequal distribution between the case and control arms. Trends and proportion of phase 3 cancer clinical trials that have an unequal allocation between the years 2010 and 2019 were studied from data extracted from clinicaltrials.gov. 323 trials with two arms and 35 trials with 3 arms were identified as randomized control trials with the primary purpose of a cancer-related treatment that provided allocation data. Amongst the trials with two arms, 238 trials had equal allocation and 85 trials had unequal allocation. Therefore, cancer clinical trials with unequal allocation represent about one in four 2-arm phase 3 trials. Amongst the eligible trials with three arms, 26 trials had equal allocation and 9 trials had unequal allocation. There was no significant difference in the annual proportion of trials with unequal allocation from 2010 to 2019. The categories of cancer which had the highest number of unequally allotted two-arm clinical trials were: gastrointestinal, breast, and genitourinary malignancies. This shift may represent a new trend in clinical trial design to help enhance closer monitoring of adverse events despite higher costs and lower statistical power attached to this method.     

Caveolin-1 and Altered Neuregulin Signaling Contribute to the Pathophysiological Progression of Diabetic Peripheral Neuropathy

OBJECTIVE

Evaluate if Erb B2 activation and the loss of caveolin-1 (Cav1) contribute to the pathophysiological progression of diabetic peripheral neuropathy (DPN).

RESEARCH DESIGN AND METHODS

Cav1 knockout and wild-type C57BL/6 mice were rendered diabetic with streptozotocin, and changes in motor nerve conduction velocity (MNCV), mechanical and thermal hypoalgesia, Erb B2 phosphorylation (pErb B2), and epidermal nerve fiber density were assessed. The contribution of Erb B2 to DPN was assessed using the Erb B2 inhibitors PKI 166 and erlotinib and a conditional bitransgenic mouse that expressed a constitutively active form of Erb B2 in myelinated Schwann cells (SCs).

RESULTS

Diabetic mice exhibited decreased MNCV and mechanical and thermal sensitivity, but the extent of these deficits was more severe in diabetic Cav1 knockout mice. Diabetes increased pErb B2 levels in both genotypes, but the absence of Cav1 correlated with a greater increase in pErb B2. Erb B2 activation contributed to the mechanical hypoalgesia and MNCV deficits in both diabetic genotypes because treatment with erlotinib or PKI 166 improved these indexes of DPN. Similarly, induction of a constitutively active Erb B2 in myelinated SCs was sufficient to decrease MNCV and induce a mechanical hypoalgesia in the absence of diabetes.

CONCLUSIONS

Increased Erb B2 activity contributes to specific indexes of DPN, and Cav1 may be an endogenous regulator of Erb B2 signaling. Altered Erb B2 signaling is a novel mechanism that contributes to SC dysfunction in diabetes, and inhibiting Erb B2 may ameliorate deficits of tactile sensitivity in DPN.Diabetic peripheral neuropathy (DPN) is a common complication of diabetes (1). Although hyperglycemia is the definitive cause of DPN (2), the vascular, glial, and neuronal damage that underlies the progressive axonopathy in DPN has a complex biochemical etiology involving oxidative stress (3,4), protein glycation (5), protein kinase C activation (6), polyol synthesis (7), and the hexosamine pathway (8). Altered neurotrophic support also contributes to sensory neuron dysfunction in DPN (9), but whether diabetes may alter growth factor signaling in Schwann cells (SCs), which also undergo substantial degeneration in diabetes, is poorly defined.Neuregulins are growth factors that control SC growth, survival, and differentiation via their interaction with Erb B receptors (10). Although Erb B2 signaling promotes developmental myelination and is clearly trophic for SCs, pharmacological evidence supports that pathologic activation of Erb B2 after axotomy (11) or infection with leprosy bacilli (12) is sufficient to induce SC dedifferentiation and demyelination. Additionally, genetic evidence supports that Erb B2 can promote the development of sensory neuropathies independent of diabetes because expression of a dominant-negative Erb B4 in nonmyelinating (13) or myelinating (14) SCs induced a temperature or mechanical sensory neuropathy, respectively. Given the contribution of Erb B2 to the degeneration of SCs, endogenous proteins that regulate Erb B2 activity may influence the development of certain aspects of sensory neuropathies.The interaction of Erb B2 with the protein caveolin-1 (Cav1) inhibits the intrinsic tyrosine kinase activity of the receptor (15). Cav1 is highly expressed in mature, myelinated SCs (16), and we have shown that prolonged hyperglycemia promoted the downregulation of Cav1 in SCs of sciatic nerve (17). Cav1 may regulate Erb B2 signaling in SCs because its forced downregulation was sufficient to enhance neuregulin-induced demyelination of SC–dorsal root ganglion (DRG) neuron cocultures (18). However, it is unknown whether an increase in Erb B2 activity may contribute to the pathophysiological development of DPN and if changes in Cav1 expression may alter Erb B2 activation in diabetic nerve.In the current study, we demonstrate that diabetic Cav1 knockout mice showed an increased activation of Erb B2 and developed greater motor nerve conduction velocity (MNCV) deficits relative to their wild-type counterparts. Inhibition of Erb B2 with two structurally diverse inhibitors corrected the MNCV deficits and mechanical hypoalgesia evident after 6 or 15 weeks of diabetes. Also, induction of a constitutively active Erb B2 in myelinated SCs of adult mice was sufficient to recapitulate the MNCV and mechanical sensitivity deficits observed in the diabetic mice. These studies provide the first evidence that activation of Erb B2 contributes to deficits associated with myelinated fiber function in diabetic nerve and suggest that Cav1 may serve as an endogenous regulator of Erb B2.     

Surgical Management and Outcome in Primary Adenocarcinoma of the Small Bowel

Background Primary adenocarcinoma of the small bowel is a rare malignancy and is associated with poor survival outcome. Patient, tumor and treatment-related factors were analyzed for their association with recurrence and survival. Methods Between 1971 and 2005, 64 patients with primary adenocarcinoma of the small bowel were treated at our institution. Clinico-pathologic data, operative details, postoperative treatment, recurrence pattern and survival were reviewed. Results The most common clinical features at presentation included abdominal pain (n = 33; 51.6%) or bowel obstruction (n = 20; 31.3%). The most frequently involved portion of the small bowel was the duodenum (n = 41; 64%). A segmental bowel resection was performed in 30 patients and pancreaticoduodenectomy in 14 patients. Postoperative mortality and morbidity rates were 3.6% (n = 2) and 14.5% (n = 8), respectively. Of the 55 patients who underwent operative intervention, a curative resection was performed in 30 (54.5%). The most common sites of recurrence following a curative resection were the liver and lung. Median survival for all 64 patients was 18 months with a 5-year survival of 21.1%. On multivariate analysis, absence of distant metastatic disease (5-year survival 30.4%), curative resection (5-year survival 44.8%) and pathological T stage 1-3 (5-year survival 39.2%) were identified as independent predictors of survival. Conclusions A curative resection in the absence of both distant metastases and pathological T4 tumor provides the best survival outcome. Recurrence at distant sites is the predominant pattern of failure following a curative resection, suggesting a role for adjuvant therapy.     

Using a smokeless tobacco control mass media campaign and other synergistic elements to address social inequalities in India

The burden of tobacco-related morbidity and mortality in India is substantial, with smokeless tobacco being the predominant form of tobacco use. Use of smokeless tobacco (for example gutkha, paan, khaini, and pan masala) is linked to a host of socioeconomic and cultural factors including gender, regional differences, educational level, and income disparities. Given the scale of the problem, a national social marketing campaign was developed and implemented. The creative approach used testimonials from a surgeon and patients at Tata Memorial Hospital in Mumbai. The communication message approach was designed to reflect the realities of disfiguring, disabling, and fatal cancers caused by smokeless tobacco. Evaluation of the campaign identified significant differences across a range of campaign behavioral predictors by audience segments aware of the campaign versus those who were “campaign unaware”. Significant findings were also identified regarding vulnerable groups by gender (female/male) and rural/urban disparities. Findings are discussed in relation to the powerful impact of using graphic, emotive, and testimonial imagery for tobacco control with socially disadvantaged groups.