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Similar Toxicity (similar + toxicity)
Selected AbstractsLatest news and product developmentsPRESCRIBER, Issue 10 2007Article first published online: 13 SEP 200 Sitagliptin: novel drug for type 2 diabetes Sitagliptin (Januvia), the first dipeptidyl peptidase-4 (DPP-4) inhibitor, has been introduced for the treatment of type 2 diabetes in combination with metformin or a glitazone when either agent plus exercise and diet fail to control blood glucose. Inhibition of DPP-4 prevents the breakdown of incretin hormones that promote insulin release from pancreatic beta cells. In trials lasting up to 24 weeks, adding sitagliptin to established therapy reduced HbA1C by 0.67-0.90 per cent. It is contraindicated in patients with moderate or more severe renal impairment. At the recommended dose of 100mg per day, a month's treatment with sitagliptin costs £33.36. Guide to treating mentalillness in primary care A new guide from the Centre for Clinical and Academic Workforce Innovation aims to help health professionals and others treating people with mental illness. A Complete Guide to Primary Care Mental Health, a toolkit presented as a reference book and CD, covers aspects of treatment, the law and working with the voluntary sector and includes training materials compatible with evidence-based guidance. Copies are available from amazon.co.uk. Follow-up improves statin adherence Patients may take long holidays from statin treatment but a visit to the doctor is among the most effective ways to improve adherence, a US study shows (Arch Intern Med 2007;167:847,52). Observation of 239 911 patients who began statin treatment during a seven-year period showed that 54 per cent stopped their treatment for at least 90 days. Of these, 48 per cent restarted within one year and 60 per cent within two years. Factors associated with restarting treatment were a visit to the doctor who prescribed the statin (odds ratio, OR, 6.1) or a visit to a different doctor (OR 2.9). A cholesterol test and hospital admission for a cardiovascular event were also significant factors. Pharmacist MUR does not reduce heart failure deaths Medication review by trained community pharmacists does not reduce admissions or deaths among patients with heart failure, according to a study from East Anglia (BMJ online: 23 April 2007; doi:10.1136/bmj.39164.568183.AE). Patients admitted as emergencies with heart failure were randomised to usual care or two home visits by a community pharmacist within two and eight weeks after discharge. Pharmacists reviewed medication and advised on self-management of symptoms and lifestyle. There were no significant differences in hospital admissions over the next six months (rate ratio 1.15 for pharmacist vs control) or deaths (rate ratio 1.18); quality of life scores were similar in the two groups. The authors speculate that the interventions may have been too brief or too late (lifestyle changes having been made already), or disadvantaged by not adjusting beta-blocker doses. A Cardiff study of pharmacist medication reviews for elderly patients (BMJ online: 20 April 2007; doi:10.1136/bmj.39171. 577106.55), found that their advice had the potential to undermine patients' ,confidence, integrity and self-governanc'. The study found that pharmacists gave advice unnecessarily and uninvited. CHD targets met early The national programme to tackle heart disease has made substantial progress towards it targets, the Department of Health says in a 10-year report, and a 40 per cent cut in mortality will be achieved ahead of the deadline of 2010. Coronary Heart Disease Ten Years On: Improving Heart Care, a report by Professor Roger Boyle, National Director for Heart Disease and Stroke, states that 7 per cent of the population is now taking statins, resulting in 9700 deaths avoided annually. The prevalence of untreated hypertension fell from 32 to 24 per cent between 1998 and 2003. The report also summarises changes in service delivery, nutrition and smoking cessation. HRT: ovarian cancer risk The MHRA has not altered its advice on the use of HRT following news that five years' use increases ovarian cancer risk in women over 50. The Million Women Study revealed an approximately 20 per cent increased risk of ovarian cancer or death among women still using HRT after five or more years. There was no difference in risk between oestrogen-only and combined formulations. The MHRA says HRT is still indicated for relieving symptoms of the menopause for short-term use; as an alternative for women over 50 who cannot take other treatments to prevent osteoporosis, or when such options fail; and in women under 50 who experience a premature menopause. Poor angina treatment Over half of patients with angina continue to experience attacks despite treatment, according to a survey by the British Cardiac Patients Association. The survey of 600 patients with angina also found that twot-hirds of respondents reported that angina had a moderate to severe impact on their lives. Half said that the adverse effects of their treatment negatively affected their work, two-thirds reported an adverse impact on sex, and almost three-quarters of patients taking beta-blockers reported fatigue. A second survey of 2000 adults revealed widespread ignorance about the prevalence and symptoms of angina. The surveys were sponsored by Servier Laboratories Limited and conducted in collaboration with Research Quorum. Cabergoline restriction Indications for the dopamine agonist cabergoline (Cabaser) are being restricted to match those of pergolide (Celance), the MHRA has announced. Pergolide was recently withdrawn in the United States and its use in the EU is limited because of the risk of cardiac valvular damage. Similar toxicity has been reported with cabergolide, which is now restricted to second-line use when a nonergot treatment for Parkinson's disease has failed. It is contraindicated in patients with valvular damage or a history of fibrotic disorders and requires patient monitoring. Sodium reduction cuts CV events Long-term reduction in dietary sodium may reduce cardiovascular events by 25 per cent, US epidemiologists say (BMJ online: 20 April 2007; doi:10.1136/bmj.39147.604896.55). Participants in the two Trials of Hypertension Prevention (TOHP I and II) reduced their sodium intake by 44 and 33mmol per 24hr. After 10,15 years' follow-up of 2415 participants, the adjusted relative risk of cardiovascular events was 0.75 compared with controls. There was a nonsignificant 20 per cent reduction in mortality. Copyright © 2007 Wiley Interface Ltd [source] Effects of eight polycyclic aromatic compounds on the survival and reproduction of the springtail Folsomia fimetaria L. (collembola, isotomidae)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2001Line E. Sverdrup Abstract The effects of eight polycyclic aromatic compounds on the survival and reproduction of the collembolan Folsomia fimetaria L. were investigated in a well-characterized Danish agricultural soil. With the exception of acridine, polycyclic aromatic hydrocarbons (PAHs) and neutral N-, S-, and O-monosubstituted analogues showed similar toxicities to soil collembolans when the results were expressed in relation to total soil concentrations (mg/kg). The estimated concentrations resulting in a 10% reduction of reproductive output (EC10 values) were based on measured initial concentrations and were for acridine 290 mg/kg, carbazole 10 mg/kg, dibenzofuran 19 mg/kg, dibenzothiophene 7.8 mg/kg, fluoranthene 37 mg/kg, fluorene 7.7 mg/kg, phenantrene 23 mg/kg, and pyrene 10 mg/kg. When the EC10 values were converted to soil pore-water concentrations, they showed a highly significant correlation (r2 = 0.71, p < 0.01) to no-observed-effect concentrations for the freshwater crustacean Daphnia magna, as estimated by a quantitative structure activity relation (QSAR) for baseline toxicity (nonpolar narcosis). Only carbazole and acridine were more than two times more toxic (4.9 and 3.1, respectively) than expected from the Daphnia QSAR data. The latter result indicates that the toxicity of the tested substances is close to that expected for compounds with nonpolar narcosis as the mode of action. However, the relatively large uncertainties in the extrapolation method prevent final conclusions from being drawn. [source] Differential toxicity on monocytes and monocyte-derived dendritic Cells: a new tool to differentiate allergens from irritants?INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 5 2007Laetitia Furio Phenotypic activation of monocyte-derived dendritic cells has been proposed as an in vitro alternative assay to discriminate potential sensitizers from irritants, but the sensitivity of the assay remains controversial. In this study, we first determined the dynamic range of expression of activation/maturation markers on human monocyte-derived dendritic cells cultured in the presence or absence of transforming growth factor ß (TGF,)? On day three of culture, most monocytes had already differentiated into dendritic cells that expressed low levels of costimulatory molecules especially in the presence TGF,-treatment of 3-day-old TGF,-treated monocyte-derived dendritic cells with several chemicals at sub-toxic concentrations induced significant phenotypic changes for all the strong and mild sensitizers tested, whereas the irritant sodium lauryl sulfate had no effect. However, a very large variability was observed among the experiments. Most interestingly, we could show here for the first time that at concentrations sub-toxic for monocyte-derived dendritic cells all the allergens tested induced monocyte apoptosis within 2 days of culture. In contrast, sodium lauryl sulfate displayed similar toxicity on monocytes and monocyte-derived dendritic cells and these results were confirmed with other irritants such as benzoic acid or methylsalicylate. Although testing of far more chemicals is required, these results indicate that differential toxicity of chemicals to monocytes and monocyte-derived dendritic cells could be a rapid, simple and valuable tool to differentiate sensitizers from irritants. [source] Effect of amyloid ,-peptide on permeability transition pore: A comparative studyJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2002Paula I. Moreira Abstract A potentially central factor in neurodegeneration is the permeability transition pore (PTP). Because of the tissue-specific differences in pore properties, we directly compared isolated brain and liver mitochondria responses to the neurotoxic A, peptides. For this purpose, the following parameters were examined: mitochondrial membrane potential (,,m), respiration, swelling, ultrastructural morphology, and content of cytochrome c. Both peptides, A,25,35 (50 ,M) and A,1,40 (2 ,M), had a similar toxicity, exacerbating the effects of Ca2+, although, per se, they did not induce (PTP). In liver mitochondria, A, led to a drop in ,,m and potentiated matrix swelling and disruption induced by Ca2+. In contrast, brain mitochondria, exposed to the same conditions, demonstrated a higher capacity to accumulate Ca2+ before the ,,m drop and a slight increase of mitochondrial swelling compared with liver mitochondria. Furthermore, mitochondrial respiratory state 3 was depressed in the presence of A,, whereas state 4 was unaltered, resulting in an uncoupling of respiration. In both types of mitochondria, A, did not affect the content of cytochrome c. The ,,m drop was reversed when Ca2+ was removed by EGTA or when ADP plus oligomycin was present. Pretreatment with cyclosporin A or ADP plus oligomycin prevented the deleterious effects promoted by A, and/or Ca2+. It can be concluded that brain and liver mitochondria show a different susceptibility to the deleterious effect of A, peptide, brain mitochondria being more resistant to the potentiation by A, of Ca2+ -induced PTP. © 2002 Wiley-Liss, Inc. [source] Resistance to cyfluthrin and tetrachlorvinphos in the lesser mealworm, Alphitobius diaperinus, collected from the eastern United StatesPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 7 2006Ronda L Hamm Abstract The lesser mealworm, Alphitobius diaperinus (Panzer), is an important pest in poultry facilities. The toxicity of cyfluthrin and tetrachlorvinphos to five strains of the lesser mealworm was compared with the toxicity to a susceptible laboratory strain. Bioassays were carried out with both larvae and adults. For the susceptible strain, cyfluthrin and tetrachlorvinphos had similar toxicity to adults, but cyfluthrin was 5 times more toxic to larvae when compared with tetrachlorvinphos. High levels of resistance to tetrachlorvinphos in two beetle strains were detected in both larvae and adults, although these strains were heterogeneous and still contained susceptible individuals. Resistance to cyfluthrin ranged from 1.7- to 9.5-fold for adults and from 0.5- to 29-fold for larvae at the LC95. Overall, the patterns of resistance did not mirror the insecticide use patterns reported at these facilities. The implications of these results to management of the lesser mealworms are discussed. Copyright © 2006 Society of Chemical Industry [source] Randomized phase II trial of gemcitabine and either day 1 or day 8 carboplatin for advanced non-small-cell lung cancer: Is thrombocytopenia predictable?ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2009Cathy CROMBIE Abstract Aim: Two 21-day gemcitabine,carboplatin schedules were evaluated in patients with advanced non-small cell lung cancer in order to assess the effect of timing of the carboplatin dose on toxicity and efficacy. Methods: Patients were randomized to gemcitabine (1000 mg/m2 on days 1 and 8 of a 21-day cycle) and carboplatin (AUC 5, on day 1) (Carbo d1 arm) or the same gemcitabine schedule with carboplatin given on day 8 (Carbo d8 arm). Twenty patients with Stage IIIB or IV non-small-cell lung cancer were enrolled in each arm. Results: The achieved dose intensities of both gemcitabine and carboplatin were significantly higher in the Carbo d1 arm. The total rates of grade 3 or 4 hematological and non-hematological toxicities (any toxicity, any cycle) were 80% and 65%, respectively, with no significant differences between the two arms. Nine patients in the Carbo d1 arm, but only one patient in the Carbo d8 arm, required a platelet transfusion. There were 10 partial responses (four Carbo d1 arm, six Carbo d8 arm), giving an overall response rate of 25% (95% CI 13,41%). Conclusion: Administration of carboplatin on day 8 of this regimen confers no clear advantage compared with day 1 carboplatin, with similar toxicity but lower dose intensity. A formula for the prediction of thrombocytopenia is proposed. [source] Speed of action and in vitro efficacy of spinosad against sheep body lice, Bovicola ovis (Schrank) (Phthiraptera: Trichodectidae), resistant to pyrethroid, organophosphate or insect growth regulator insecticidesAUSTRALIAN JOURNAL OF ENTOMOLOGY, Issue 3 2008Garry Levot Abstract, Results of laboratory bioassays indicated that spinosad was equally effective against sheep lice populations that were susceptible to insecticides or resistant to pyrethroid, organophosphorus or insect growth regulator (IGR) insecticides. Spinosad had similar toxicity against susceptible strains of lice to that previously reported for diazinon, but lower toxicity than cypermethrin. Lethal concentrations of spinosad and diazinon caused knock down of lice within 6 h of exposure and death within 24 h. Prior to the current phasing out of diazinon as a sheep dip, most wool producers, needing to control pyrethroid- or IGR-resistant lice infestations in short-wool, would have chosen to use diazinon. Our results suggest that spinosad is an effective alternative for treatment of lice resistant to other chemical groups. [source] Six of the Best, Colorectal 21BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue S1 2002I. Taylor Aims: Intrahepatic arterial (IHA) therapy should deliver higher doses of drug to the liver with reduced overall systemic exposure. An IHA regimen was designed which used the same drugs and schedule, and achieved similar toxicity and steady-state venous 5FU levels as the standard de Gramont IV regimen. Patients with advanced colorectal liver metastases were randomized to either IV or IHA. Methods: In total 290 patients were randomized from 16 centres in 6 years. The median age was 62 years, 70 per cent were male, 68 per cent had colon cancer. Of the 145 patients allocated to IV, 14 per cent did not receive any allocated therapy, but 78 per cent received six cycles of chemotherapy. Of the 145 IHA patients, 37 per cent did not start and only 35 per cent received six cycles. The additional problems in the IHA group were inability to insert the catheter, or infected, leaking, or blocked catheters. Of the patients who did not receive six cycles of IHA therapy, 52 per cent switched to IV therapy. Similar levels of toxicity and quality of life were reported in both arms. Results: There was no clear evidence of a difference in progression-free survival (HR 0.90, 95 per cent CI: 0.71,1.16; P = 0.42) or overall survival (HR 1.03, 95 per cent CI: 0.79,1.33; P = 0.85). From randomization median, and estimated 1- and 2-year survival were 14.1 months in both groups, and 60 and 57 per cent, and 26 and 22 per cent for IV and IHA, respectively. Conclusions: This trial suggests that there is no obvious role for this IHA regimen in the management of hepatic metastatic colorectal cancer. [source] Toxicity and efficacy of combined radioimmunotherapy and bevacizumab in a mouse model of medullary thyroid carcinoma,CANCER, Issue S4 2010Pierre-Yves Salaun MD Abstract BACKGROUND: Significant antitumor effects were previously observed with radioimmunotherapy (RIT) using an anti-carcinoembryonic antigen (CEA) monoclonal antibody (F6) labeled with iodine-131 in medullary thyroid cancer (MTC)-bearing nude mice. Nevertheless, no complete response was achieved. Because angiogenesis is critical for tumor growth, bevacizumab is used to treat solid tumor in clinical practice. The present pilot study evaluated toxicity and efficacy of RIT combined with bevacizumab in mice subcutaneously grafted with TT MTC cells. METHODS: Groups of 4-6 nude mice were treated with 5 ,g/g bevacizumab twice weekly during 4 weeks and/or 100 MBq of 131I-F6. For combined therapy, bevacizumab was given at Day 0 followed by 131I-F6 at Day 30. The control group received no treatment. Animal weight, hematological toxicity, tumor volume, and serum calcitonin were monitored for 2 or 4 months. RESULTS: Bevacizumab alone induced no cytopenia and no significant weight loss. A weight loss of 12 ± 1% and 15 ± 2% was observed in mice treated by RIT alone or bevacizumab + RIT, respectively. RIT alone and combined treatment induced leukopenia and anemia. RIT alone and RIT plus bevacizumab induced tumor responses with minimum relative tumor volume of 0.38 ± 0.24 and 0.15 ± 0.07%, respectively, and time to progression of 35 ± 5 and 56 ± 11 days, respectively. CONCLUSIONS: Pretreatment with bevacizumab improved RIT efficacy, with similar toxicity as compared as RIT alone. Cancer 2010;116(4 suppl):1053,8. © 2010 American Cancer Society. [source] | |||||||||||||