Efficacy of incisional negative pressure therapy in preventing post-sternotomy wound complications.

BACKGROUND: Sternal wound infections represent a source of significant morbidity and mortality following median sternotomy. The use of incisional negative pressure wound therapy in prevention has yet to be elucidated. METHODS: A retrospective study was conducted before and after a universal wound care protocol was implemented including the prophylactic use of negative pressure wound therapy (NPWT). The primary endpoint was sternal infections within 90 days of the index operation. RESULTS: In the control period, there was a 3.0% rate of sternal infection within 90 days compared to 0.8% in the intervention period (p < 0.001). An odds ratio of 0.25 (95% confidence interval 0.11, 0.57; p < 0.001) in the intervention period as compared to the control period was demonstrated. CONCLUSIONS: The use of a standardized wound care protocol including the universal application of NPWT for patients undergoing cardiac surgery with median sternotomy was an independent predictor of decreased rates of sternal infection.

Synthesis, characterization and anticancer activity of gold(I) complexes that contain tri-tert-butylphosphine and dialkyl dithiocarbamate ligands.

Two new gold(I) complexes that contain tri-ter-butylphosphine and dialkyl dithiocarbamate ligands were synthesized and characterized by FTIR, NMR spectroscopy, Cyclic voltammetry, elemental analysis and X-ray diffraction. The in vitro cytotoxicity of both complexes was examined against A549 (lung cancer), MCF7 (breast cancer), and HeLa (cervical cancer) human cancer cell lines. Both complexes exhibit very strong in vitro cytotoxic effects against A549, MCF7 and HeLa cell lines. The screening of the cytotoxic activity based on IC50 data against the A549, MCF7, and HeLa lines shows that the synthesized gold(I) complexes are highly effective, particularly against HeLa cancer cell line. Based on IC50 data, the cytotoxic activity of both complexes is better than well-known commercial anticancer drug cisplatin against all the three cancer lines tested.

The quality of reporting of phase II and III trials for new antipsychotics: a systematic review.

BACKGROUND: The findings of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study and the Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS) called previous trials of antipsychotics into question, including pre-licensing trials. Concerns regarding methodological robustness and quality of reporting increased. This systematic review aimed to examine the quality of reporting of phase II and III trials for new antipsychotics in the aftermath of the CATIE and CUtLASS studies. METHOD: Electronic searches were conducted in EMBASE, Medline and Cochrane databases and also ClinicalTrials.gov for antipsychotic trials (published between January 2006 and February 2012). Phase II and III randomized controlled trials (RCTs) for iloperidone, asenapine, paliperidone, olanzapine, lurasidone and pomaglumetad methionil were selected for schizophrenia and schizoaffective disorder. The reporting of the methodology was evaluated in accordance with Consolidated Standards of Reporting Trials (CONSORT) guidelines. RESULTS: Thirty-one articles regarding 32 studies were included. There was insufficient reporting of design in 47% of studies and only 13% explicitly stated a primary hypothesis. Exclusion criteria were poorly reported for diagnosis in 22% of studies. Detail regarding comparators, particularly placebos, was suboptimal for 56% of studies, and permitted concomitant medication was often not reported (19%). Randomization methods were poorly described in 56% of studies and reporting on blinding was insufficient in 84% of studies. Sample size calculations were insufficiently reported in 59% of studies. CONCLUSIONS: The quality of reporting of phase II and III trials for new antipsychotics does not reach the standards outlined in the CONSORT guidelines. Authors often fail to adequately report design and methodological processes, potentially impeding the progress of research on antipsychotic efficacy. Both policymakers and clinicians require high quality reporting before decisions are made regarding licensing and prescribing of new antipsychotics.

Antidyslipidemic and antioxidant activity of the constituents isolated from the leaves of Calophyllum inophyllum.

In continuation of our drug discovery program on Indian medicinal plants, we isolated bioactive compounds (1-5) from the leaves of Calophyllum inophyllum and evaluated their antidyslipidemic activity in triton induced hyperlipidemia model. The calophyllic acid (1A) and isocalophyllic acid (1B) mixture, canophyllic acid (4) and amentoflavone (5) showed dose dependent lipid lowering activity in in vivo experiments. The compounds 1A+1B mixture and 3 also showed good in vitro antioxidant activity.

Synthesis of novel N-(2-hydroxy-2-p-tolylethyl)-amide and N-(2-oxo-2-p-tolylethyl)-amide derivatives and their antidyslipidemic and antioxidant activity.

In continuation of our drug discovery program on metabolic diseases, we identified an alkaloidal amide, that is, Aegeline (V) from the plant Aegle marmelos leaves as a dual acting agent (antihyperlipidemic and antihyperglycemic). We therefore synthesized a series of alkaloidal amides [N-(2-hydroxy-2-p-tolylethyl)-amides and N-(2-oxo-2-p-tolylethyl)-amide derivatives] related to Aegeline and screened for their in vivo antihyperlipidemic activity in Triton induced hyperlipidemia model. The synthetic compounds 4, 17 and 20 showed equipotent activity to the natural product, that is, Aegeline (V). These compounds also showed strong antioxidant activity, which support their antihyperlipidemic activity. Compound 12 showed better antihyperlipidemic and antioxidant profile than the natural product V.

Double blind placebo control trial of large neutral amino acids in treatment of PKU: effect on blood phenylalanine.

Large neutral amino acids (LNAA) have been used on a limited number of patients with phenylketonuria (PKU) with the purpose of decreasing the influx of phenylalanine (Phe) to the brain. In an open-label study using LNAA, a surprising decline of blood Phe concentration was found in patients with PKU in metabolic treatment centres in Russia, the Ukraine, and the United States. To validate the data obtained from this trial, a short-term double-blind placebo control study was done using LNAA in patients with PKU, with the participation of three additional metabolic centres--Milan, Padua and Rio de Janeiro. The results of the short trial showed significant lowering of blood Phe concentration by an average of 39% from baseline. The data from the double-blind placebo control are encouraging, establishing proof of principle of the role of orally administered LNAA in lowering blood Phe concentrations in patients with PKU. Long-term studies will be needed to validate the acceptability, efficacy and safety of such treatment.

Large neutral amino acids in the treatment of phenylketonuria (PKU).

Large neutral amino acids (LNAAs) have been used on a limited number of patients with phenylketonuria (PKU) with the purpose of decreasing the influx of phenylalanine (Phe) to the brain. In earlier studies on mice with PKU (ENU(2)/ENU(2)), LNAAs were given and a surprising decline in blood Phe concentrations was observed. The formula used in the mouse experiment (PreKUnil) lacked lysine. Therefore, a new formulation of LNAAs (NeoPhe) was developed, introducing changes in the concentration of some amino acids and adding lysine, so that such a mixture could be used in humans. The new formula was found to be effective in reducing blood Phe concentration in mice by about 50% of the elevated levels. Patients with PKU were given LNAAs and blood Phe concentrations were determined in an open-label study. Three centers--in Russia, the Ukraine and the USA--took part in the study. NeoPhe was given at 0.5 g/kg per day in three divided doses to eight subjects with PKU and at 1.0 g/kg per day to three patients, for one week. The NeoPhe resulted in decrease of elevated blood Phe by 50% in both groups. The preliminary data from this study are encouraging and a double blind placebo-controlled trial will be required to show long-term efficacy and tolerance of LNAAs in the treatment of PKU.

Elisa kit evaluation for IGG and IGM antibodies to A-60 tubercular protein antigen.

AIMS: The purpose of this study is to evaluate the A-60 antigen-based enzyme-linked immuno sorbent assay (ELISA) test for its sensitivity, specificity, and other related statistical parameters. SETTINGS AND DESIGN: Sera from 114 healthy volunteers, 105 bacteriologically confirmed cases of pulmonary tuberculosis (PTB), 59 sera from family contacts of PTB, and 40 sera from cases of lung infections other than tuberculosis collected from September to December 2003 were used for the kit evaluation. METHODS AND MATERIALS: Enzyme-linked immuno sorbent assay test using tuberculosis A-60 antigen-based kit manufactured by Anda Biologicals, France was used for the evaluation. STATISTICAL ANALYSIS: Differences in the optical density (OD) values for immunoglobulins G (IgG), and immunoglobulins M (IgM) antibodies in various groups were studied using t-test. RESULTS: On the basis of the findings the threshold value was setup as 400 U for IgG and mean OD for sera from healthy volunteers +2SD as the threshold for IgM. The sensitivity was 80% and specificity 95.8% for the IgG antibody test. The efficiency and predictive values were also high. The sensitivity for IgM was low (28.5%) but the specificity was high (95.7%). None of the 40 nontubercular lung infection cases were positive for the IgG and IgM antibody test for A-60, whereas five and three cases of 59 family contacts of PTB were positive for IgG and IgM antibody test. The test reproducibility was good for both IgG and IgM. CONCLUSION: IgG antibody test using A-60 antigen has good sensitivity and specificity, whereas IgM antibody test had high specificity but low sensitivity. Multicentric trials suggested evaluation of the diagnostic utility of the test for the extra-PTB.

Antidyslipidemic action of fenofibrate in dyslipidemic-diabetic hamster model.

Fenofibrate is the ligand for PPARalpha subtype that mediates the action of its agonists' in lipid metabolism. How fibrate exerts hypolipidemic effect? The mechanism is studied in a newly developed high-fat fructose enriched diet induced dyslipidemia-diabetic hamster model. Fenofibrate lowered the basal plasma lipids like TC, TG, PL, FFA, glycerol, VLDL, and LDL, but HDL was increased. The activity of lipoprotein lipase in liver, adipose tissue, and small intestine was upregulated. However, that of triglyceride lipase was downregulated in liver. It has also improved the insulin secretion and plasma glucose lowering, caused by impairment in insulin secretion due to high-fat load. The drug was found effective in reducing body weight and diet due to rise in leptin level. Fenofibrate also enhanced the fecal excretion of total lipids, cholic acid, and deoxycholic acid probably by the activation of 7alpha cholesterol hydroxylase enzyme. Thus, causing broad-spectrum lipid lowering along with inhibition of hepatic lipid biosynthesis and maintaining lipid-glucose homeostasis.

Patterns of use of unconventional therapies in the medical outpatient department of a tertiary care hospital in India.

Unconventional, alternative or unorthodox systems of treatment have become increasingly popular in recent years. We interviewed patients visiting the Internal Medicine outpatient department (OPD) for a period of 6 months regarding their use of unconventional therapies. Overall 76% of patients visiting the OPD had used one or more of the unconventional therapies in the past 1 year. Homeopathy was found to be the most frequently used alternative therapy (38.6%). A large number of patients used more than one unconventional therapy. Digestive problems, backache, joint pains and bronchial asthma were the most frequent conditions for which alternative therapies were used. Most patients who used alternative therapies used them on their own, without actually visiting a provider of such therapies. Because of the widespread use of alternative systems of medicine, efforts to enhance understanding about these forms of treatment have to be made.

Drug resistance among tubercle bacilli from pulmonary tuberculosis cases in central India.

An estimate of drug resistance is extremely important in the epidemiology and control of tuberculosis. Data on drug resistance among mycobacterial isolates from sputum samples analysed at Microbiology dept. of Choithram Hospital and Research Centre, Indore, M.P. is presented here. Drug sensitivity testing was carried out on 1426 Mycobacterial isolates by the method of proportion using critical concentration in Lowenstein Jensen medium. Resistance for Isoniazid, streptomycin, and pyrazinamide was found to be high (54.2%, 41.5% and 50% respectively) and was followed by resistance to rifampin (25%) and ethambutol (22%). Resistance for kanamycin, p-aminosalicylic acid, thiacetazone and ciprofloxacin was much lower (18%, 13%, 6.5% and 3.6% respectively). Only 12% of the isolates were sensitive to all the anti-TB drugs while resistance to two, three, and four or more drugs was in the range of 20-25%. Pattern wise, simultaneous resistance to INF and Rifampin with or without resistance to other drugs was observed in 8.1% while resistance for Isoniazid + pyrazinamide and Isoniazid + streptomycin was 11.9 and 11.5% respectively. Resistance for Isoniazid + ethambutol was the lowest (5.1%). Growing multiple drug resistance among tubercle bacilli warrant urgent attention in tuberculosis control programme.

Control of olefin geometry in the bryostatin B-ring through exploitation of a C(2)-symmetry breaking tactic and a Smith-Tietze coupling reaction.

A completely stereocontrolled asymmetric synthesis of an advanced B-ring synthon for the bryostatin family of antitumor agents is reported. Noteworthy features of our synthesis include the Smith-Tietze bis-alkylation reaction between 12 and 13 en route to C(2)-symmetrical ketone 10 and the totally stereoselective conversion of 10 into triol 18 via a Grignard addition tactic. Triol 18 was converted to epoxide 3 in nine steps, and an acid-catalyzed intramolecular Williamson etherification reaction completed the synthesis of 2.

Gastrointestinal tuberculosis: an eighteen-patient experience and review.

The diagnosis of gastrointestinal tuberculosis (GITB) is often delayed, increasing the morbidity associated with this treatable condition. In this case series, the clinical presentations and outcomes of 18 patients with GITB are reviewed. Our aim was to elucidate the presenting signs and symptoms of GITB so as to help physicians improve their ability to make this diagnosis. Cases were gathered retrospectively over an 8-year period from Santa Clara Valley Medical Center, San Jose, California. Sources of information included patient records from our TB clinic and our hospital from 1989 to 1997. Of the 18 patients, 16 had a definitive diagnosis of GITB made from histology and/or culture from an abdominal source. In the remaining two patients, a presumptive diagnosis of GITB was made based on the co-occurrence of abdominal signs and symptoms, response to antituberculous therapy, and Mycobacterium tuberculosis identified at a nonabdominal site. The most common clinical presentation was a triad of abdominal pain, fever, and weight loss. This triad was present in 8 of 18 patients. Seven patients presented with two of these signs and symptoms, two had abdominal pain alone, and one presented with other symptomatology. Time to diagnosis ranged from 2 days to 11 months, with a mean time to diagnosis of 50 days. These findings suggest that the diagnosis of GI and hepatic TB is often delayed. Possible reasons for delay include nonspecific signs and symptoms and failure to consider TB in the initial differential diagnosis. Once diagnosed, the outcome of GITB in this series was favorable.