Assessment of zinc inadequacy among tribal adolescent population of central India - A cross-sectional study

Background & objectives: Zinc is a crucial micronutrient in adolescence, required for promoting growth and sexual maturation. Adolescents of some tribes may be at high risk of zinc deficiency due to dietary inadequacy and poor bioavailability of zinc from plant-based diets. This study aimed to evaluate the risk of zinc deficiency by estimating prevalence of inadequate zinc intake, prevalence of low serum zinc and stunting among tribal adolescents. Methods: A cross-sectional community-based survey was conducted among adolescents (10-19 yr) in three purposively selected districts where Bhil, Korku and Gond tribes were in majority. Structured data collection instrument comprising information about sociodemographic characteristics and dietary recall data was used. Anthropometric assessment was conducted by standardized weighing scales and anthropometry tapes, and blood sample was collected from antecubital vein into trace element-free vacutainers. Serum zinc was estimated using an atomic absorption spectrophotometer. Results: A total of 2310 households were approached for participation in the study, of which 2224 households having 5151 adolescents participated. Out of these enlisted adolescents, 4673 responded to dietary recall (90.7% response rate). Anthropometry of 2437 participants was carried out, and serum zinc was analyzed in 844 adolescents. The overall prevalence of dietary zinc inadequacy was 42.6 per cent [95% confidence interval (CI) 41.2 to 44.1] with reference to the estimated average requirement suggested by International Zinc Nutrition Consultative Group (IZiNCG) and 64.8 per cent (95% CI 63.4 to 66.2) with Indian Council of Medical Research-recommended requirements. Stunting was observed in 29 per cent (95% CI 27.2 to 30.8) participants. According to IZiNCG cut-offs, low serum zinc was detected in 57.5 per cent (95% CI 54.1 to 60.8) of adolescents, whereas it was 34.4 per cent (95% CI: 31.2-37.5) according to the national level cut-off. Interpretation & conclusions: Risk of dietary zinc inadequacy and low serum zinc concentration amongst adolescents of the Gond, Bhil and Korku tribes is a public health concern.

Disfunção hepática em pacientes de unidade de terapia intensiva médica prevê desfecho desfavorável / Hepatic dysfunction in medical intensive careunit patients predicts poor outcome

ABSTRACT Background: A large number of patients admitted to the medical intensive care unit (MICU) have abnormal liver function tests (LFT). This includes patients with critical illness with or without preexisting liver disease and patients with acute primary liver injury. There are very few studies which have investigated the spectrum of liver disease, clinical profile and outcome in patients admitted to the MICU. Objective To evaluate the occurrence, etiology, clinical profile, laboratory profile and outcome of hepatic dysfunction in patients admitted to the MICU. To evaluate the utility of model for end-stage liver disease (MELD) score on admission as a predictor of adverse short term outcome in patients with hepatic dysfunction admitted in MICU. Methods: It was a prospective observational study, conducted from December 2017 to December 2018 in a tertiary care hospital. Two hundred and two patients admitted to the MICU with LFTs as per the inclusion criteria were analyzed and their short-term outcome at 7 days was studied in relation to various parameters. Results: LFT abnormalities were present in 202/1126 (17.9%) of the patients admitted to MICU. Critical illness associated liver dysfunction was found in 172 (85.2%) patients, chronic liver disease in 11 (5.4%) patients and acute viral hepatitis in 19 (9.4%) patients. Most common symptom was fever (68.3%) followed by vomiting (48.0%). Among LFT abnormalities, elevated transaminases, raised international normalized ratio and high MELD score on admission correlated with poor short-term outcome. Requirement for inotropes and mechanical ventilation correlated with poor short-term outcome. Mortality did not differ significantly between patients with chronic liver disease, patients with acute viral hepatitis and patients with critical illness associated hepatic dysfunction. Hepatic dysfunction in MICU was associated with poor outcome and a high short-term mortality of 56.4% (114/202). Conclusion: Liver function abnormality is common in patients who are admitted to the MICU and its presence is an indicator of poor short-term outcome.

RESUMO Contexto: Um grande número de pacientes internados na unidade de terapia intensiva (UTI) tem testes de função hepática anormais (TFH). Isso inclui pacientes com doença crítica com ou sem doença hepática pré-existente e pacientes com lesão hepática primária aguda. Há poucos estudos que têm investigado o espectro da doença hepática, perfil clínico e desfecho em pacientes admitidos em UTI. Objetivo Avaliar a ocorrência, etiologia, perfil clínico, perfil laboratorial e desfecho de disfunção hepática em pacientes internados na UTI médica. Avaliar a utilidade do modelo para doença hepática em estágio terminal (MELD). Escore na admissão como preditor de desfecho adverso a curto prazo em pacientes com disfunção hepática admitida em UTI. Métodos: Foi realizado um estudo observacional prospectivo, de dezembro de 2017 a dezembro de 2018 em um hospital de atenção terciária. Foram analisados 202 pacientes internados na UTI com TFH conforme os critérios de inclusão e seu desfecho a curto prazo de 7 dias foi estudado em relação a diversos parâmetros. Resultados: Anormalidades dos testes estiveram presentes em 202/1126 (17,9%) dos pacientes internados na UTI. Doença crítica associada à disfunção hepática foi encontrada em 172 (85,2%) pacientes, doença hepática crônica em 11 (5,4%) pacientes e hepatite viral aguda em 19 (9,4%) pacientes. O sintoma mais comum foi a febre (68,3%), seguido de vômito (48,0%) casos. Entre as anormalidades do TFH, transaminases elevadas, INR e escore MELD elevados na admissão correlacionaram-se com desfecho ruim de curto prazo. Exigência de inotrópicos e ventilação mecânica correlacionaram-se com desfecho de curto prazo ruim. A mortalidade não diferiu significativamente entre pacientes com doença hepática crônica, pacientes com hepatite viral aguda e pacientes com doença crítica associada à disfunção hepática. A disfunção hepática em UTI esteve associada a um desfecho ruim e à uma alta mortalidade a curto prazo de 114/202 (56,4%). Conclusão: A anormalidade da função hepática é comum em pacientes que são admitidos nas unidades de tratamento intensivo e sua presença é um indicador de desfecho de curto prazo ruim.

Morphological patterns of endometrium in infertile woman-a prospective study.

Background and Objective: Infertility is a global health problem because 8-12% of all couples worldwide, around 80 million are infertile. Endometrium is the most sensitive indicator of ovarian function. Endometrial biopsy with routine hematoxylin and eosin staining is an important investigation in the Indian Scenario. Therefore the present study has undertaken to investigate the morphological patterns of endometrium in infertile women. Materials and Methods: This study was carried out in the Department of Pathology, Bangalore Medical College after the ethical clearance from the institutional ethics committee. The study included 90 cases with complaints of infertility (primary / secondary). The premenstrual D & C was done to obtain endometrial biopsy. The endometrial tissue was fixed; processed, sectioned and performed Hematoxylin & Eosin stain for morphology of endometrium, dating of endometrium and Ziehl-Neelsen (ZN) stain for acid fast bacilli was also performed. In this descriptive analysis, values are mentioned as percentages. Result: In the present study, we also observed 2 cases of Tuberculosis (TB), 5 cases exhibited cystic hyperplasia and only a single case of endometrial polyp was seen. But, the percentage of cases of secretory phase was more. Simple cystic hyperplasia was seen in 3 cases of primary and 2 cases of secondary infertility. Conclusion: In the present study we concluded that the anovulatory endometrium, simple cystic hyperplasia and luteal phase defect formed the major etiological basis of many cases of infertility and the tuberculosis endometritis and endometrial polyp formed the minor group of etiology.

Hepatoprotective activity of six polyherbal formulations in paracetamol induced liver toxicity in mice.

Background & objective: Polyherbal formulations available with a wide range of indications like protective to liver, appetite and growth promoters, gastrointestinal and hepatic regulator, as treatment for hepatic dysfunction, for hepatic regeneration as well as liver stimulant and tonic. Despite the widespread use, there is a lack of scientifi c evidence on their effi cacy and safety. This study was undertaken to evaluate the hepatoprotective activity of six commercially available formulations, namely Liv 52, Livergen, Livokin, Octogen, Stimuliv and Tefroliv in acute liver toxicity in mice model induced by paracetamol (PCM). Methods: Swiss albino mice of either sex were used, divided in 28 groups with six in each group. The dose of the polyherbal formulations was calculated from human dose (20 ml/day) using a standard conversion table. They were given as pretreatment (2.60 ml/kg/day) for 7 days by oral route twice a day prior to PCM administration. Hepatotoxicity was induced by administering a single oral dose of PCM (500 mg/kg bw) on day 8. The study parameters were conducted on day 9. The biochemical parameters included liver enzyme levels alanine tranaminases (ALT), aspartate transaminases (AST) and alkaline phosphatase (ALP). The pharmacological and pathological parameters were phenobarbitone sleeping time and macroscopic and microscopic changes of liver tissues respectively. Results: PCM toxicity signifi cantly increased ALT, AST and ALP (321.00 ± 87.93, 273.17 ± 45.68, 257.50 ± 17.64 IU/l vs normal control, 33.33 ± 0.61, 89.33 ± 9.50, 152.17 ± 11.40 IU/l respectively, P<0.05), prolonged phenobarbitone induced sleeping time (from 277.50 ± 8.04 min to 335.83 ± 7.00 min, P<0.05). When PCM higher dose (1g/kg p.o. single dose) was used, the liver tissue, in macroscopic appearance, showed extensive necrosis associated with haemorrhages. Low dose (500 mg/kg p.o. single dose) showed punctate haemorrhagic necrosis of liver tissue. In the microscopic studies, PCM induced toxicity showed haemorrhages, fatty changes and necrosis. The pretreatment in low doses (2.6 ml/kg/day) with liquid formulations of Liv 52 and Livergen reversed the PCM induced liver toxicity. At higher doses (5.2 ml/ kg/day), all the six herbal formulations conclusively showed marked benefi cial effects in the studied pharmacological, biochemical and histological parameters. Interpretation & conclusion: The present fi ndings demonstrated the effi cacy of polyherbal liquid formulations at two dose levels in PCM induced hepatotoxicity in mice. However, it suggests that a dose adjustment may be necessary to optimize the effects in clinical settings.

Hepatoprotective activity of six polyherbal formulations in CCl4-induced liver toxicity in mice.

To evaluate pretreatment of six polyherbal liquid formulations (PLFs) commercially available in India, on CCl4-induced liver injury, Swiss albino mice were treated for 7 days with distilled water or PLFs (2.6 and 5.2 ml/kg body weight/day, po) followed by single sc injection of 50% (v/v) CCl4 in arachis oil at a dose of 1 ml/kg. The serum biochemical parameters such as alanine transaminases, aspartate transaminases and alkaline phosphatase were estimated. Phenobarbitone-induced sleeping time and liver histopathology were also carried out. CCl4-treated animals showed significant increase in the levels of liver enzymes, phenobarbitone-induced sleeping time and revealed fatty changes and centrizonal necrosis on histological examination of liver indicating hepatic damage. When pretreated with PLFs at a dose of 5.2 ml/kg body weight/day, the CCl4-induced changes were significantly reversed. The pretreatment with PLFs can prevent acute liver damage induced by CCl4 only at a higher dose. Therefore, it is suggested that a dose adjustment of these PLFs may be necessary for their optimal effects in human liver diseases.

Evaluation of the efficacy, safety and tolerability of miglitol in adult Indian patients with uncomplicated type 2 diabetes mellitus.

Postprandial hyperglycaemia and spikes have deleterious effects on Insulin secretion and sensitivity. The present study was undertaken to evaluate the efficacy, safety and tolerability of miglitol 50 mg three times daily for 12 weeks in 129 patients with type 2 diabetes mellitus, inadequately managed with diet and exercise therapy alone for 3 months after obtaining their written informed consent. The primary efficacy variables were per cent change from baseline at week 12 in fasting and postprandial plasma glucose concentrations and glycosylated haemoglobin (HbA(1C)) levels. After treatment at the end of 12 weeks mean reduction in fasting plasma glucose levels was 35.7% and 44.33% in postprandial plasma glucose levels while the mean HbA(1C) was significantly reduced by 0.88% (p<0.05). Total cholesterol, HDL, LDL and TC/HDL ratio did not showed any significant change but a non-significant reduction in triglyceride levels was observed in some patients. The mean body mass index was reduced non-significantly by 8% from baseline values. A total 19.5% patients treated with miglitol reported adverse events like flatulence, abdominal pain, nausea/vomiting, diarrhoea and dyspepsia. Only one patient reported hypoglycaemia. The results of the present study indicate that miglitol reduces fasting and postprandial plasma glucose levels, Improving glycaemic control, which is reflected in a reduced HbA(1C) level in patients with type 2 diabetes mellitus. It could be a useful first-line therapy in patients with type 2 diabetes mellitus inadequately controlled by diet alone and as adjuvant therapy in patients who are inadequately controlled with diet and sulfonylureas.

Aprepitant: a substance P antagonist for chemotherapy induced nausea and vomiting.

The episodes of nausea and vomiting which follow each cycle of chemotherapy are the most troublesome side effect experienced by cancer patients. Introduction of ondansetron was a definite therapeutic advance in treating chemotherapy induced nausea and vomiting (CINV) with more effectiveness with corticosteroids. However, the protection remained largely limited to acute phase of CINV with little or no effect over delayed phase. Aprepitant, a drug that antagonizes the effect of substance P on neurokinin type 1 receptor showed promising results in controlling both phases of CINV. This drug is well absorbed orally with a t max of about four hours. The addition of aprepitant to ondansetron and dexamethasone was found to be superior to ondansetron and dexamethasone alone in clinical trials with patients taking high and moderate emetogenic chemotherapy. This drug also showed a good safety profile, but its inhibitory effect on CYP3A4 may result in clinically significant drug interactions needing dose modifications of co-administered drugs. The National Comprehensive Cancer Network guidelines for CINV recommends the use of aprepitant with high and moderately emetogenic anticancer drugs. Results of ongoing clinical trials with aprepitant and other agents of this new class of antiemetics are awaited and may alleviate the sufferings of cancer patients.

Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine.

Silymarin, a flavonolignan from 'milk thistle' (Silybum marianum) plant is used almost exclusively for hepatoprotection and amounts to 180 million US dollars business in Germany alone. In this review we discuss about its safety, efficacy and future uses in liver diseases. The use of silymarin may replace the polyherbal formulations and will avoid the major problems of standardization, quality control and contamination with heavy metals or bacterial toxins. Silymarin consists of four flavonolignan isomers namely--silybin, isosilybin, silydianin and silychristin. Among them, silybin being the most active and commonly used. Silymarin is orally absorbed and is excreted mainly through bile as sulphates and conjugates. Silymarin offers good protection in various toxic models of experimental liver diseases in laboratory animals. It acts by antioxidative, anti-lipid peroxidative, antifibrotic, anti-inflammatory, membrane stabilizing, immunomodulatory and liver regenerating mechanisms. Silymarin has clinical applications in alcoholic liver diseases, liver cirrhosis, Amanita mushroom poisoning, viral hepatitis, toxic and drug induced liver diseases and in diabetic patients. Though silymarin does not have antiviral properties against hepatitis virus, it promotes protein synthesis, helps in regenerating liver tissue, controls inflammation, enhances glucuronidation and protects against glutathione depletion. Silymarin may prove to be a useful drug for hepatoprotection in hepatobiliary diseases and in hepatotoxicity due to drugs. The non traditional use of silymarin may make a breakthrough as a new approach to protect other organs in addition to liver. As it is having a good safety profile, better patient tolerability and an effective drug at an affordable price, in near future new derivatives or new combinations of this drug may prove to be useful.

Newer insulin analogues and inhaled insulin.

Diabetes is a metabolic disease with high prevalence worldwide. Exogenous insulin is used in the management of this condition. The development of human insulin has provided tighter control of glycaemia in diabetic patients. Insulin analogues like insulin lispro and aspart were developed to closely match its profile with physiological secretion. The newer additions to this armamentarium are insulin glulisine, insulin detemir and albulin.Insulin glulisine is a short acting analogue with a rapid onset of action. The antiapoptotic property, mediated through insulin substrate receptor-2 has a favourable protective action on beta cells. Insulin detemir is a long acting analogue, soluble at neutral pH, which reversibly binds to albumin in plasma, prolonging its action. Its lower affinity for insulin receptors necessitates higher doses compared to human insulin. The reduction in body weight is an additional advantage of detemir. A major concern about all newer insulin analogues is their altered mitogenic properties and resultant risk of carcinogenicity on long term use. Albulin is a latest addition of insulin analogue which is under various in vitro and in vivo studies. Inhaled insulin in powder form (Exubera) is recently approved by FDA and appears promising.

Assessment of efficacy, safety and tolerability of fixed dose combination of telmisartan 40mg and hydrochlorothiazide 12.5mg in adult Indian patients with mild to moderate hypertension.

The objective of the study was to assess the efficacy, safety and tolerability of a fixed dose combination of telmisartan 40 mg and hydrochlorothiazide 12.5 mg in adult Indian patients with mild to moderate hypertension. A prospective, multicentric, open-label, non-comparative, phase IV study was conducted. A total of 353 patients of either sex, between 18- 65 years of age with supine blood pressure (BP) levels of systolic BP (SBP) of 140-200 mmHg and diastolic BP (DBP) of 95-114 mmHg were included. After a placebo run-in period of 2 weeks, each patient received a fixed dose combination of telmisartan/hydrochlorothiazide (40mg/12.5mg) once daily, for 8 weeks. Supine BP was assessed at the end of every 2 weeks. Tolerability and safety were assessed by physical examination, laboratory parameters and evaluation of adverse events. A total of 339 patients completed the study with 14 drop-out cases because of loss to follow-up. There was a significant fall (p<0.05) in both the SBP and DBP starting from the second week as compared to the baseline. Mean SBP had a significant reduction of 23.55 mmHg (15.0%) and 27.79 mmHg (18%) at the end of 6th and 8th week respectively, compared to baseline values. Mean DBP had also had a significant reduction of 12.51 mmHg (12.6%) and 15.17 mmHg (15.3%) at the end of 6th and 8th week respectively, compared to baseline values. This combination was well tolerated with only 3.9% of the total cases reporting mild adverse events like fatigue, dizziness, nausea, diarrhoea etc. The laboratory values were within normal limits. Fixed dose combination of telmisartan/hydrochlorothiazide (40 mg/12.5 mg) once daily has a significant therapeutic effect and a good tolerability profile in adult Indian patients with mild to moderate hypertension.

Non-cirrhotic portal fibrosis in children.

BACKGROUND AND OBJECTIVES: Non-cirrhotic portal fibrosis (NCPF) is an infrequent cause of portal hypertension in children. We report 11 children with NCPF, from among 338 with portal hypertension, seen over 6.5 years. METHODS: The diagnosis was based on patent splenoportal axis on ultrasonography and/or splenoportal venography and liver biopsy showing no evidence of cirrhosis or other diagnosis, in children with portal hypertension. Those with variceal bleed were managed with endoscopic sclerotherapy and/or shunt surgery. RESULTS: The median age was 11 years (range 5 to 14), and 8 were boys. Presentation was with variceal bleed in 6, lump in left upper abdomen in 5 (though all children had splenomegaly) and esophageal varices on endoscopy. The median spleen enlargement was 8.5 cm; 8 also had hepatomegaly. Hypersplenism was present in 7, and two had developed ascites after bleed. Of 6 children presenting with bleed, variceal obliteration was achieved on sclerotherapy (average 5.6 sessions) in 4 while two underwent shunt surgery for associated hypersplenism. After median follow up of 57.5 months (range 12-78) all are alive and well. CONCLUSION: NCPF is an uncommon cause of portal hypertension in Indian children. Presentation with variceal bleed is less common than in adults; sclerotherapy is effective.