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Drug Treatment (drug + treatment)
Kinds of Drug Treatment Terms modified by Drug Treatment Selected AbstractsKYNURENINE PATHWAY METABOLISM IN PATIENTS WITH OSTEOPOROSIS AFTER 2 YEARS OF DRUG TREATMENTCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2006Caroline M Forrest ABSTRACT 1Metabolism of tryptophan along the oxidative pathway via kynurenine results in the production of quinolinic acid and kynurenic acid, which can act on glutamate receptors in peripheral tissues. We have now measured the concentrations of kynurenine pathway metabolites in the plasma of patients with osteoporosis before treatment with drugs, throughout and after 2 years of treatment with the drugs raloxifene or etidronate. Oxidative stress was assessed by measuring levels of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal. Kynurenines were analysed by HPLC. Bone density was measured using dual-energy X-ray absorptiometry scans. 2Patients with osteoporosis showed significantly lower baseline levels of 3-hydroxyanthranilic acid compared with healthy controls, but significantly higher levels of anthranilic acid and lipid peroxidation products. After 2 years treatment with etidronate and calcium, we observed significant therapeutic responses quantified by bone densitometric scanning. Significant improvements were not seen in patients treated with raloxifene. 3In parallel, the levels of 3-hydroxyanthranilic acid, anthranilic acid and lipid peroxidation products were restored to control values by both drug treatments studied and tryptophan levels were increased significantly compared with baseline values. 4The results suggest that tryptophan metabolism is altered in osteoporosis in a manner that could contribute to the oxidative stress and, thus, to progress of the disease. The oxidative metabolism of tryptophan (the kynurenine pathway) could represent a novel target for the development of new drugs for the treatment of osteoporosis. In addition, we noted that etidronate is a more effective drug than raloxifene, but that the simultaneous use of non-steroidal anti-inflammatory drugs may reduce the efficacy of etidronate. [source] Drug Treatment: What Works?ADDICTION, Issue 3 2005STEVE ALLSOP No abstract is available for this article. [source] Coercive treatment for drug misuse: a dialogical junctureJOURNAL OF COMMUNITY & APPLIED SOCIAL PSYCHOLOGY, Issue 5 2004Christine Horrocks Abstract This article adopts a ,dialogical' relational perspective to explore the recently introduced initiative of coercive treatment for drug misuse in the UK. Conversational interviews were undertaken with 11 people who had been sentenced to the Drug Treatment and Testing Order. Receiving treatment for drug misuse is often storied within a motivational account that is expectant of a ,readiness to change'; such assumptions seem theoretically problematic when change is legally imposed. Therefore, moral and ethical concerns surround the introduction of this initiative, however the interview data illustrates the potential that participation might offer for the creation of ,counterstories' where a more moral self can be enacted. Our analysis suggests that this counterstory is co-constructed thus being an outcome of both self and other. Furthermore such stories appear fragile; constantly under assault from detrimental authoritative discourses that are not only part of wider social understandings around drug misuse but also permeate the policy and practice of coercive treatment. Copyright © 2004 John Wiley & Sons, Ltd. [source] The Majority of Men with Lifelong Premature Ejaculation Prefer Daily Drug Treatment: An Observation Study in a Consecutive Group of Dutch MenTHE JOURNAL OF SEXUAL MEDICINE, Issue 4i 2007Marcel D. Waldinger MD ABSTRACT Introduction., Whether men with lifelong premature ejaculation (PE) prefer on-demand drug treatment to delay ejaculation time to daily drug treatment, has never been studied as a separate study question. Aim., To study how men with lifelong PE feel about the use of serotonergic antidepressants, and which option they would prefer for themselves: either a daily drug, a drug to be used on demand, or a topical anesthetic cream to be applied on demand. Main Outcome Measures., Treatment preference was determined by questionnaire. Methods., An observational questionnaire survey in a clinical sample. Preferences of different treatment strategies were queried before and after standard efficacy and safety information. Results., A consecutive group of 88 men with lifelong PE who decided for themselves to be seen for rapid ejaculation was studied. The age was 37 ± 11 years (mean ± SD), range 18,64 years. None of these men was ever treated for PE and 21% used medication that did not affect sexual performance. Of them, 71 (81%) preferred a drug for daily use, 14 (16%) a drug on demand, while three men preferred topical anesthetic cream. Those men who initially preferred daily treatment did not change their view after standard information about efficacy and side effects, while 9 of 17 men who initially preferred on-demand drug treatment had switched their preferences to daily oral drug usage. Around 60% of men did not care about the nature of the drug, i.e., an antidepressant. The most frequently reported argument to prefer daily drug treatment was that this strategy would have the least effects toward the spontaneity of having sex. Conclusion., As opposed to agents that must be taken 4,6 hours prior to coitus and with the methods used here, this group of Dutch men with lifelong PE favor uninterrupted daily drug treatment to delay ejaculation mainly because daily treatment guarantees no interference with the spontaneity of having sex. Waldinger MD, Zwinderman AH, Olivier B, and Schweitzer DH. The majority of men with lifelong premature ejaculation prefer daily drug treatment: An observation study in a consecutive group of Dutch men. J Sex Med 2007;4:1028,1037. [source] The clinical impact of pharmacogenetics on the treatment of epilepsyEPILEPSIA, Issue 1 2009Wolfgang Löscher Summary Drug treatment of epilepsy is characterized by unpredictability of efficacy, adverse drug reactions, and optimal doses in individual patients, which, at least in part, is a consequence of genetic variation. Since genetic variability in drug metabolism was reported to affect the treatment with phenytoin more than 25 years ago, the ultimate goal of pharmacogenetics is to use the genetic makeup of an individual to predict drug response and efficacy, as well as potential adverse drug events. However, determining the practical relevance of pharmacogenetic variants remains difficult, in part because of problems with study design and replication. This article reviews the published work with particular emphasis on pharmacogenetic alterations that may affect efficacy, tolerability, and safety of antiepileptic drugs (AEDs), including variation in genes encoding drug target (SCN1A), drug transport (ABCB1), drug metabolizing (CYP2C9, CYP2C19), and human leucocyte antigen (HLA) proteins. Although the current studies associating particular genes and their variants with seizure control or adverse events have inherent weaknesses and have not provided unifying conclusions, several results, for example that Asian patients with a particular HLA allele, HLA-B*1502, are at a higher risk for Stevens-Johnson syndrome when using carbamazepine, are helpful to increase our knowledge how genetic variation affects the treatment of epilepsy. Although genetic testing raises ethical and social issues, a better understanding of the genetic influences on epilepsy outcome is key to developing the much needed new therapeutic strategies for individuals with epilepsy. [source] Atorvastatin prevents carbohydrate response element binding protein activation in the fructose-fed rat by activating protein kinase A,HEPATOLOGY, Issue 1 2009Ricardo Rodríguez-Calvo High fructose intake contributes to the overall epidemic of obesity and metabolic disease. Here we examined whether atorvastatin treatment blocks the activation of the carbohydrate response element binding protein (ChREBP) in the fructose-fed rat. Fructose feeding increased blood pressure (21%, P < 0.05), plasma free fatty acids (59%, P < 0.01), and plasma triglyceride levels (129%, P < 0.001) compared with control rats fed standard chow. These increases were prevented by atorvastatin. Rats fed the fructose-rich diet showed enhanced hepatic messenger RNA (mRNA) levels of glycerol-3-phosphate acyltransferase (Gpat1) (1.45-fold induction, P < 0.05), which is the rate-limiting enzyme for the synthesis of triglycerides, and liver triglyceride content (2.35-fold induction, P < 0.001). Drug treatment inhibited the induction of Gpat1 and increased the expression of liver-type carnitine palmitoyltransferase 1 (L-Cpt-1) (128%, P < 0.01). These observations indicate that atorvastatin diverts fatty acids from triglyceride synthesis to fatty acid oxidation, which is consistent with the reduction in liver triglyceride levels (28%, P < 0.01) observed after atorvastatin treatment. The expression of Gpat1 is regulated by ChREBP and sterol regulatory element binding protein-1c (SREBP-1c). Atorvastatin treatment prevented fructose-induced ChREBP translocation and the increase in ChREBP DNA-binding activity while reducing SREBP-1c DNA-binding activity. Statin treatment increased phospho-protein kinase A (PKA), which promotes nuclear exclusion of ChREBP and reduces its DNA-binding activity. Human HepG2 cells exposed to fructose showed enhanced ChREBP DNA-binding activity, which was not observed in the presence of atorvastatin. Furthermore, atorvastatin treatment increased the CPT-I mRNA levels in these cells. Interestingly, both effects of this drug were abolished in the presence of the PKA inhibitor H89. Conclusion: These findings indicate that atorvastatin inhibits fructose-induced ChREBP activity and increases CPT-I expression by activating PKA. (HEPATOLOGY > 2009;49:106-115.) [source] Drug treatment in dementiaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2001Roger Bullock No abstract is available for this article. [source] Management of heart failure in elderly peopleINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2008M. Imazio Summary Aims:, To review currently available knowledge on presentation, clinical features and management of heart failure (HF) in elderly people. Methods:, To review currently available evidence, we performed a thorough search of several evidence-based sources of information, including Cochrane Database of Systematic Reviews, Clinical Evidence, Evidence-based guidelines from National Guidelines Clearinghouse and a comprehensive MEDLINE search with the MeSH terms: ,heart failure', ,elderly' and ,management'. Results:, A number of features of ageing may predispose elderly people to HF, and may impair the ability to respond to injuries. Another hallmark of elderly patients is the increasing prevalence of multiple coexisting chronic conditions and geriatric syndromes that may complicate the clinical presentation and evolution of HF. Although diagnosis may be challenging, because atypical symptoms and presentations are common, and comorbid conditions may mimic or complicate the clinical picture, diagnostic criteria do not change in elderly people. Drug treatment is not significantly different from that recommended in younger patients, and largely remains empiric, because clinical trials have generally excluded elderly people and patients with comorbid conditions. Disease management programmes may have the potential to reduce morbidity and mortality for patients with HF. Conclusions:, Heart failure is the commonest reason for hospitalisation and readmission among older adults. HF shows peculiar features in elderly people, and is usually complicated by comorbidities, presenting a significant financial burden worldwide, nevertheless elderly people have been generally excluded from clinical trials, and thus management largely remains empiric and based on evidence from younger age groups. [source] Asthma patients with low perceived burden of illness: a challenge for guideline adherenceJOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 6 2007Antonius Schneider MD Abstract Rationale and aims, The reason why many patients seem to tolerate suffering from sub-optimal treated asthma remains unclear. The aim was to evaluate the guideline adherence combined with quality of life of patients with moderate to severe asthma. Methods, 256 asthma patients from 43 primary care practices in Saxony-Anhalt filled in a questionnaire including the Asthma Quality of Life Questionnaire (AQLQ), the Patient Health Questionnaire (PHQ-D) and questions evaluating the asthma severity, medication and self-management. Results, 43.4% suffered from moderate to severe asthma. Drug treatment accorded with guidelines in 36.9%, drug dosage of inhaled steroids was too low in 34.3%, and 21.5% were not treated according to guidelines. A total of 7.3% of the patients received end-of-dose therapy. AQLQ declined and depression rose with asthma severity and guideline non-adherence (P < 0.001). Only 29.1% received asthma education. However, 64.5% of the patients without education did not want to receive education. They had a higher quality of life, lower depression (P < 0.001) and lower use of steroids (P = 0.016). Higher depression scores where related with hospital admission (OR 3.29; 95% CI 1.57,6.87 for each quartile of PHQ-D) and unscheduled home visits or ambulatory care (OR 1.58; 1.07,2.33). Conclusion, There is a large variation of asthma severity which can partly be explained by the guideline adherence of medication and deficits of patients' management. The perceived burden of illness plays a more important role for education and self-management than the real severity of disease. Therefore, target-oriented interventions are needed to identify and motivate patients at risk. [source] Drug treatment of neonatal seizures by neonatologists and paediatric neurologistsJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 7 2005Kathryn Browning Carmo Objective:, To survey anti-epileptic drug (AED) treatment of early-onset neonatal seizures by neonatologists and paediatric neurologists. Methods:, A self-administered questionnaire was posted to Australian and New Zealand neonatologists and paediatric neurologists. Participants were given the hypothetical case of a full-term infant with early-onset seizures following perinatal asphyxia and asked to nominate their preferred AED for treatment of three seizure episodes during the first 24 h. Results:, One hundred and seven (57%) of 187 individuals answered the questionnaire: neonatologists responded more often than neurologists (,2 (1,187) = 7.18, P = 0.007). Phenobarbitone was used by 95% of the respondents to treat the first episode of seizures and 75% of them used an appropriate loading dose (20 mg/kg). Phenobarbitone was used by 84 and 40% of the respondents to treat the second- and third-seizure episodes, respectively. Neonatologists used phenobarbitone, phenytoin and a benzodiazepine with equal frequency to treat a third episode of seizures, whereas neurologists rarely used a benzodiazepine. Neonatologists used significantly larger total doses of phenobarbitone than neurologists. Very few respondents used pyridoxine to treat recurrent seizures that were historically linked to perinatal asphyxia and hypoxic,ischaemic encephalopathy. Neonatologists were more likely than neurologists to discontinue AED within a few days of seizure cessation (,2 (1,106) = 11.60, P = 0.0006). Conclusions:, Australian and New Zealand neonatologists and paediatric neurologists generally use phenobarbitone to treat neonatal seizures presumed to be owing to hypoxic,ischaemic encephalopathy, though they do not always use appropriate doses. Neonatologists use phenobarbitone, phenytoin or a benzodiazepine for second and third episodes of seizures, whereas neurologists tend not to use benzodiazepines. Neonatologists use larger total doses of phenobarbitone than neurologists in pursuit of seizure control. Neonatologists discontinue AED earlier than neurologists. [source] Latest news and product developmentsPRESCRIBER, Issue 8 2008Article first published online: 12 MAY 200 Glargine preferred to lispro as type 2 add-on Basal insulin glargine (Lantus) and insulin lispro (Humalog) at mealtimes improved glycaemic control equally well in patients with type 2 diabetes poorly controlled by oral agents, but patient satisfaction was greater with basal insulin (Lancet 2008;371:1073-84). The 44-week APOLLO trial, funded by Sanofi Aventis, was a nonblinded randomised comparison of basal and prandial insulin regimens added to oral treatment in 418 patients. It found similar reductions in HbA1C (,1.7 vs ,1.9 per cent respectively). Fasting and nocturnal glucose levels were lower with insulin glargine and postprandial levels were lower with insulin lispro. The basal regimen was associated with fewer hypoglycaemic events (5.2 vs 24 per patient per year), less weight gain (3.01 vs 3.54kg) and greater improvement in patient satisfaction scores. Treating hypertension cuts mortality in over-80s Treating hypertension in the over-80s reduces all-cause mortality by 21 per cent, the HYVET study has shown (N Engl J Med online: 31 March 2008; doi: 10.1056/NEJMoa 0801369). Compared with placebo, treatment with indapamide alone or with perindopril for an average of 1.8 years also reduced the incidence of fatal stroke by 39 per cent, cardiovascular death by 23 per cent and heart failure by 64 per cent. The incidence of stroke was reduced by 30 per cent but this was of borderline statistical significance. Fewer serious adverse events were reported with treatment than with placebo. New work for NICE The DoH has announced the 18th work programme for NICE. Seven public health interventions include preventing skin cancer, smoking by children and excess weight gain during pregnancy. Public health guidance will include the provision of contraceptive services for socially disadvantaged young people. Two new clinical guidelines are sedation in young people and management of fractured neck of femur. New technology appraisals may include eight therapies for cancer, two new monoclonal antibodies for psoriasis and rheumatoid arthritis, an oral retinoid for severe chronic hand eczema and methylnaltrexone for opioid-induced bowel dysfunction. Combinations no better against CV disease Taking ezetimibe and simvastatin (Inegy) does not appear to slow the progression of atherosclerosis more than high-dose simvastatin alone, say researchers from The Netherlands (N Engl J Med 2008;358: 1431-43). In patients with hypercholesterolaemia, there was no difference in regression or progression of atherosclerosis after two years' treatment with simvastatin 80mg per day alone or combined with ezetimibe 10mg per day. Adverse event rates were similar. In patients with vascular disease or high-risk diabetes, there was no difference between the ACE inhibitor ramipril 10mg per day or the ARB telmisartan (Micardis) 80mg per day as monotherapy, or their combination, in the risk of a composite outcome of cardiovascular death, MI, stroke and admission for heart failure (N Engl J Med 2008;358:1547-59). Combined treatment was associated with higher risks of hypotensive symptoms, syncope and renal dysfunction. Twice-daily celecoxib increases CV risk Taking celecoxib (Celebrex) twice daily carries a higher risk of cardiovascular events than the same total dose taken once daily, a metaanalysis suggests (Circulation 2008; doi: 10.1161/ CIRCULATIONAHA.108. 764530). The analysis of six placebo-controlled trials involving a total of 7950 patients taking celecoxib for indications other than rheumatoid arthritis found that the combined risk of cardiovascular death, myocardial infarction, stroke, heart failure or thromboembolic event increased with dose over the range 400-800mg per day. The risk was significantly greater with 200mg twice daily (HR 1.8) than 400mg once daily (HR 1.1). Patients at greatest baseline risk were at disproportionately increased risk from celecoxib. Long-term etanercept effective in AS An open-label study suggests that etanercept (Enbrel) remains effective in the treatment of ankylosing spondylitis in the long term (Ann Rheum Dis 2008;67:346-52). Of 257 patients who completed six months' treatment with etanercept and who entered the nonblinded extension study, 126 completed a total of 168-192 weeks' treatment. The commonest adverse events were injection-site reactions (22 per cent), headache (20 per cent) and diarrhoea (17.5 per cent). The annual rate of serious infections was 0.02 per person. Response and partial remission rates after 192 weeks were similar to those reported after 96 weeks. Metformin reduces risk Metformin reduces the risk of developing diabetes in individuals at increased risk, a meta-analysis suggests (Am J Med 2008;121:149-57.e2). The study included 31 mostly small, randomised, controlled trials involving a total of 4570 participants and lasting at least eight weeks (8267 patient-years of treatment). Metformin was associated with reductions in body mass (,5.3 per cent), fasting glucose (,4.5 per cent) and insulin resistance (,22.6 per cent); lipid profiles also improved. The odds of developing diabetes were reduced by 40 per cent,an absolute risk reduction of 6 per cent over 1.8 years. MHRA clarifies cough and colds advice Press reports mistakenly suggested that the MHRA had banned some cough and cold remedies when it issued new guidance on treating young children, the MHRA says. The Agency's advice followed a review of over-thecounter cough and cold medicines for children by the Commission on Human Medicines. Children under two are at increased risk of adverse reactions and should no longer be treated with products containing antihistamine (chlorphenamine, brompheniramine, diphenhydramine), antitussives (dextromethorphan, pholcodine), expectorants (guaifenesin, ipecacuanha) and decongestants (phenylephrine, pseudoephedrine, ephedrine, oxymetazoline and xylometazoline). The MHRA said these products, which are classified as general sale medicines, should be removed from open shelves until available in new packaging that complies with the advice. They may still be supplied by a pharmacist for the treatment of older children. Coughs and colds should be treated with paracetamol or ibuprofen for fever, a simple glycerol, honey or lemon syrup for cough, and vapour rubs and inhalant decongestants for stuffy nose. Saline drops can be used to thin and clear nasal secretions in young babies. Parents are being urged not to use more than one product at a time to avoid inadvertently administering the same constituent drug twice. Perindopril brand switch Servier Laboratories is replacing its current formulations of perindopril (Coversyl, Coversyl Plus) with a new product that is not bioequivalent. The current Coversyl brand contains perindopril erbumine (also known as tert -butylamine). The new formulation contains perindopril arginine; it will be distinguished by new brand names (Coversyl Arginine, Coversyl Arginine Plus) and new packaging. Coversyl 2, 4 and 8mg tablets are equivalent to Coversyl Arginine 2.5, 5 and 10mg. Servier says the change is part of the simplification and harmonisation of global manufacturing; the arginine salt is already used in other countries and offers greater stability and a longer shelf-life. Both Coversyl and Coversyl Arginine will be in the supply chain for the next few weeks. Generic perindopril will continue to be the erbumine salt and prescriptions for generic perindopril are not affected. New from NICE Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. Clinical Guidance No. 63, March 2008 This clinical guideline focuses on additional aspects of care for women with gestational diabetes (88 per cent of cases) or pre-existing diabetes (of which about 40 per cent is type 2 diabetes) and their babies. To date, insulin aspart (NovoRapid) is the only drug in the guideline specifically licensed for use in pregnancy and NICE advises obtaining informed consent to implement its recommendations for using other insulins and oral hypoglycaemic agents. As with other guidelines, NICE begins by stressing the importance of patient-centred care and involving women in decisions about their treatment. The guideline is divided into six sections, dealing with consecutive periods of pregnancy. Preconceptual planning should include empowering women to help them reduce risks, optimising glycaemic control (after retinal assessment) and increasing monitoring intensity, and providing information about the effects of pregnancy on diabetes. Metformin may be recommended as an adjunct or alternative to insulin, but other oral hypoglycaemic agents should be replaced with insulin, although glibenclamide is an option during pregnancy. Isophane insulin is the preferred long-acting insulin; lispro (Humalog) and aspart are considered safe to use. ACE inhibitors and angiotensin-II receptor blockers should be replaced with other antihypertensive agents and statins should be discontinued. Recommendations for screening and treatment of gestational diabetes build on previous guidance (CG62). Drug treatment will be needed by 10-20 per cent , this includes insulin (soluble, aspart or lispro) and/or metformin or glibenclamide, tailored to individual need. Antenatal care includes optimising glycaemic control. Insulin lispro or aspart should be considered in preference to soluble insulin. If glycaemic control cannot be achieved with insulin injections, an insulin pump may be indicated. The guideline includes a timetable for appointments and the care that should offered after each interval. Recommendations for intrapartum care, which supplement those in CG55, include frequent monitoring of blood glucose. Neonatal care includes recommendations for monitoring and screening the infant and the management of hypoglycaemia. Postnatal care (supplementing CG37) involves adjusting maternal treatment to avoid hypoglycaemia and recommendations for returning to community care. Metformin and glibenclamide are the only oral agents suitable for breastfeeding women. Women with gestational diabetes need advice about glycaemic control and planning for future pregnancies. Lifestyle advice and measurement of annual fasting plasma glucose should be offered. Inhaled corticosteroids for the treatment of chronic asthma in adults and in children aged 12 years and over. Technology Appraisal No. 138, March 2008 The latest technology appraisal of asthma treatments covers inhaled steroids for adults and children over 12 with chronic asthma. It makes only two recommendations. First, the cheapest appropriate option is recommended. Second, when a steroid and a long-acting beta2-agonist are indicated, the decision to prescribe a combined inhaler or separate devices should take into account therapeutic need and likely adherence. Combined inhalers are currently less expensive than separate devices, though they may not remain so. When a combined inhaler is chosen it should be the cheapest. NICE concludes that, at equivalent doses, there is little difference in the effectiveness or adverse event profile of the available steroids or the fixed-dose combinations. According to specialist advice, choosing the best device for an individual remains the overriding concern. Continuous positive airway pressure for the treatment of obstructive sleep apnoea/hypopnoea syndrome. Technology Appraisal No. 139, March 2008 NICE recommends continuous positive airway pressure (CPAP) for adults with moderate or severe obstructive sleep apnoea, and for those with a milder disorder if quality of life and functioning are impaired and alternative strategies such as lifestyle change have failed. Diagnosis and treatment is the responsibility of a specialist team. A CPAP device costs £250-£550 and lasts for seven years. Copyright © 2008 Wiley Interface Ltd [source] Pathology is alleviated by doxycycline in a laminin-,2,null model of congenital muscular dystrophyANNALS OF NEUROLOGY, Issue 1 2009Mahasweta Girgenrath PhD Objective Congenital muscular dystrophy type 1A is an autosomal recessive disease that is caused by loss-of-function mutations in the laminin-,2 gene, and results in motor nerve and skeletal muscle dysfunction. In a previous study, we used genetic modifications to show that inappropriate induction of apoptosis was a significant contributor to pathogenesis in a laminin-,2,deficient mouse model of congenital muscular dystrophy type 1A. To identify a possible pharmacological therapy for laminin-,2 deficiency, we designed this study to determine whether treatment with minocycline or doxycycline, which are tetracycline derivatives reported to have antiapoptotic effects in mammals, would significantly increase lifespan and improve neuromuscular function in laminin-,2,deficient mice. Methods Mice that were homozygous for a targeted, inactivating mutation of the laminin-,2 gene were placed into control, minocycline-treated, or doxycycline-treated groups. Drug treatment began within 2 weeks of birth, and the progression of disease was followed over time using behavioral, growth, histological, and molecular assays. Results We found that treatment with either minocycline or doxycycline increased the median lifespan of laminin-,2,null mice from approximately 32 days to approximately 70 days. Furthermore, doxycycline improved postnatal growth rate and delayed the onset of hind-limb paralysis. Doxycycline-treated laminin-,2,deficient muscles had increased Akt phosphorylation, decreased inflammation, and decreased levels of Bax protein, terminal deoxynucleotidyltransferase,mediated dUTP nick end labeling,positive myonuclei, and activated caspase-3. Interpretation Doxycycline or other drugs with similar functional profiles may be a possible route to improving neuromuscular dysfunction caused by laminin-,2-deficiency. Ann Neurol 2008 [source] Circulating endothelial cells as a therapeutic marker for thalidomide in combined therapy with chemotherapy drugs in a human prostate cancer modelBJU INTERNATIONAL, Issue 7 2008Haiqing Li OBJECTIVE To investigate how thalidomide confers its survival benefit in prostate cancer, by assessing its effect on circulating endothelial cells (CECs) and progenitors (CEPs) in a combined therapy of thalidomide and chemotherapy drugs in a human prostate cancer xenograft model, as in clinical trials patients treated with both thalidomide and docetaxel had a >50% decrease in prostate-specific antigen (PSA) levels and longer median overall survival than those treated with docetaxel monotherapy. MATERIALS AND METHODS A human prostate cancer xenograft model was used to evaluate the effect of either thalidomide, docetaxel or a combination of the two drugs on circulating ECs. Drug treatment was continued for 17 days, and tumours were measured two or three times a week. Blood samples were taken at three different time points: before the treatments, 4 days and 17 days into the treatments, and CECs and CEPs were measured by flow cytometry analysis. RESULTS There was an increased level of apoptotic/dead CECs shortly after the intravenous injection of docetaxel, and the addition of thalidomide further increased the apoptotic/dead CEC level, showing that thalidomide enhances the cytotoxicity of docetaxel against tumour vascular ECs. CONCLUSION Thalidomide increased the apoptotic/dead CEC level and enhanced the cytotoxicity of docetaxel against tumour vascular ECs, confirming its antiangiogenic property in vivo in combined anticancer treatments. In addition, there was a correlation between the increased apoptotic/dead CEC levels early in the treatment and antitumour efficacy later, suggesting that the apoptotic/dead CEC level could be used as a marker, at an early stage, to predict tumour response to antiangiogenic therapies. [source] Hyperventilation-stage electroencephalography in lateral temporal lobe epilepsyACTA NEUROPSYCHIATRICA, Issue 1 2007Shuichiro Asano Background:, To observe spike activity in electroencephalograms (EEGs), patients with symptomatic partial epilepsy are rarely monitored during the hyperventilation stages. Case:, A 38-year-old woman suffered from a ruptured arteriovenous malformation in the left temporal lobe. One and a half years later, the patient experienced her first generalized convulsion. EEG showed small spikes in the posterior of the left temporal lobe, which was observed during the hyperventilation and posthyperventilation stages. Because the location of the spikes correlated with the site of the lesion as observed from radiographic findings, she was diagnosed with lateral temporal lobe epilepsy. Drug treatment resulted in no further convulsive episodes and the patient has since returned to work. Conclusion:, EEG recordings during hyperventilation should be regarded as an effective technique in analyzing epilepsy because of its ease and cost-effectiveness compared with other methods such as single-photon emission computed tomography. [source] The clinical syndrome of Alzheimer's disease: aspects particularly relevant to clinical trialsGENES, BRAIN AND BEHAVIOR, Issue 3 2005R. C. Mohs This paper describes the natural history of the clinical syndrome of Alzheimer's disease (AD) including the cognitive deficit, the neuropsychiatric symptoms, impact on daily functioning, risk factors, medical complications and impact on the use of health-care resources. The clinical presentation of the disease varies greatly from the prodrome through end stage; instruments used to quantify the severity of each aspect of the disease have been developed and are described along with their use in clinical drug trials. Drug treatments for AD are usually developed by first showing a positive effect on the cognitive deficit, with later studies investigating drug effects on other clinical aspects of the disease. [source] Drug treatments and dementia.HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 3 2001Edited by Stephen Hopker. No abstract is available for this article. [source] Prostaglandin E2 -Mediated Anabolic Effect of a Novel Inhibitor of Phosphodiesterase 4, XT-611, in the In Vitro Bone Marrow Culture,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2003Ken-Ichi Miyamoto Abstract The mechanism of osteoblast formation by a novel PDE4 inhibitor, XT-611, was studied in the in vitro bone marrow culture system. The compound potentiated the osteoblast differentiation through accumulation of cyclic AMP after autocrine stimulation of EP4 receptor by PGE2 in pro-osteoblastic cells. Introduction: We previously reported that inhibitors of phosphodiesterase (PDE)4 isoenzyme increase osteoblast formation in an in vitro bone marrow culture system and inhibit bone loss in animal osteoporosis models. Here we investigated the mechanism of the effect of a novel PDE4 inhibitor, 3,4-dipropyl-4,5,7,8-tetrahydro-3H -imidazo[1,2- i]-purin-5-one (XT-611), on osteoblast formation in the in vitro bone marrow culture system. Materials and Methods: Rodent bone marrow cells were cultured in the presence of 0.2 mM ascorbic acid phosphate ester, 1 mM ,-glycerophosphate, and 10 nM dexamethasone for 10 days. Drug treatments were done for 24 h on day 3 of culture. Results: PDE4 inhibitors, including XT-611, but not PDE3 and PDE5 inhibitors, increased mineralized nodule formation in rat and mouse bone marrow cell cultures. During culture of the bone marrow cells, prostaglandin E2 (PGE2) production increased with a peak on day 4, but the increase was completely inhibited by indomethacin, an unselective cyclo-oxygenase (COX) inhibitor. Spontaneous and XT-611-induced mineralized-nodule formation was also inhibited by indomethacin and COX-2 inhibitors, in a similar potential. Alkaline phosphatase-positive nodule formation in the absence or presence of XT-611 was inhibited by an antagonist of EP4 receptor, AH23848B, and synergistically potentiated by 11-deoxy-PGE1, but it was not influenced by other EP antagonists and agonists examined. The expression of PDE4 and EP4 mRNAs was observed in bone marrow cells. The effect of XT-611 was also confirmed to involve an increase of cyclic AMP and the cyclic AMP-dependent protein kinase pathway. Conclusion: These results suggest that PGE2 stimulates differentiation of osteoblast progenitor cells through the EP4 receptor in an autocrine manner, and the PDE4 inhibitor potentiates the differentiation by inhibiting hydrolysis of cyclic AMP in the cells. [source] Anatomical characterisation of voltage gated sodium channels in the mammalian cochlear nerve spiral gangliaCLINICAL OTOLARYNGOLOGY, Issue 6 2006A. Prasai Introduction., There is evidence that Voltage Gated Sodium Channels (VGSC) may represent novel therapeutic targets for treatment of certain types of tinnitus and hearing loss. It is also known that the different VGSC types vary in their affinity for differing VGSC blockers. Parallels have been drawn with certain types of tinnitus, chronic pain and epilepsy (1) These conditions are thought to arise from pathological VGSC activity (2) There has also been empirical interest in the use of VGSC blockers as tinnitolytics, with the best known of these being intravenous lignocaine. Aim., The aim of this study was first begin to characterise VGSCs in the mammalian cochlear nerve spiral ganglion. Method., After sacrifice, guinea pigs were perfused with heparin and then 2% paraformaldehyde. The bony matrix of the cochleae was decalcified in buffer containing EGTA (8%). Decalcified tissues were embedded; frozen and 20-micron cryosections were made through the cochleae. Immunocytochemistry was then carried out using antibodies that selectively bind to individual sodium channel ,-subunits. Sections were then analysed and photographed using either an epifluorescence or a confocal microscope. Results and Conclusions., Sodium channel type 1.6 and 1.7 were shown to be expressed in the cochlear nerve spiral ganglion. Further work is being carried out to see if there are changes in the expression of these VGSC after ototrauma. These findings may help us to target our therapy to treat certain types of tinnitus and hearing loss. References 1 Smith P.F., Darlington C.L. (2005) Drug treatments for subjective tinnitus: serendipitous discovery versus rational drug design. Curr. Opin. Investig. Drugs.6, 712,716 2 Taylor C.P., Meldrum B.S. (1995) Na+ channels as targets for neuroprotective drugs. Trends. Pharmacol. Sci. 16, 309,315 [source] Relapse prevention with sex offenders: practice, theory and researchCRIMINAL BEHAVIOUR AND MENTAL HEALTH, Issue 1 2001Gilles Launay Head of Psychology Introduction Relapse prevention (RP) is now applied to sex offending. It has been questioned as to whether RP is worthwhile. This paper aims to evaluate this technique. The Rochester RP programme The purpose of the Rochester RP programme is to refine and strengthen skills gained in the prison department's sex offender treatment programme. The objective of the programme is to teach prisoners to recognize the chain of events leading up to their current offences and to practise strategies to interrupt this chain. Theoretical basis for RP Stopping an undesired behaviour and maintaining abstinence are two different problems. RP aims to address the maintenance problems. At the centre of RP theory is a study of the conditions that can turn lapse into relapse. Yet RP has been criticized as a lot of jargon saying very little. Ward and Hudson criticize RP constructs and their interaction. Such debates have few implications for clinical work and most of the criticism flies in the face of clinical experience. Research basis for RP Risk factors for sex offenders are being identified. Local evaluation of the Rochester programme suggests that prisoners do learn to identify risk factors and to develop coping strategies. As yet, however, there is no evidence as to whether RP works or not. Discussion A way to improve the efficacy of an RP programme may be to augment it with additional modules, e.g. behaviour therapy, drug treatment, continued work with the same prison staff and relaxation training. Conclusion RP theory is sound in essence but suffers from an overlay of cumbersome vocabulary. Reliable research is emerging. Copyright © 2001 Whurr Publishers Ltd. [source] EFFECTIVENESS OF DRUG TREATMENT COURTS: EVIDENCE FROM A RANDOMIZED TRIAL,CRIMINOLOGY AND PUBLIC POLICY, Issue 2 2003DENISE C. GOTTFREDSON Research Summary: Study randomly assigned 235 offenders to drug treatment court (DTC) or "treatment as usual." Analyses of official records collected over a two-year follow-up period show that DTC is reducing crime in a population of drug-addicted offenders. DTC subjects who participated in treatment were significantly less likely to recidivate than were both untreated drug court subjects and control subjects. Policy Implications: Continued enthusiasm for DTCs is warranted. Both sanctions and treatment are important elements of the DTC model. However, DTCs will not necessarily result in cost reductions because DTC and control cases are incarcerated for approximately equal numbers of days. Implementation fidelity is important, and DTCs can be strengthened if they engage a higher percentage of their clients in drug treatment. [source] Effect of gold nanoparticle on the microscopic morphology of white blood cellCYTOPATHOLOGY, Issue 2 2009V. Wiwanitkit Background:, In medicine, there is limited knowledge on the toxicity of nanoparticles. In medicine, there has been limited knowledge on the effect of nanoparticles on the white blood cell. Objective:, To evaluate the effect of gold nanoparticle on the microscopic morphology of white blood cell. Setting:, Chulalongkorn Univesity, Bangkok, Thailand. Method:, This study was performed as an experimental study. Mixture of gold nanoparticle solution and blood sample was prepared and analysed. Result:, This work revealed that after mixing the blood sample with gold nanoparticle solution, accumulation of gold nanoparticle in the white blood cell was observed. Conclusion:, The effect of gold nanoparticle on the white blood cell can be detected and this knowledge can be used in cytotoxic drug treatment. [source] Sturge,Weber syndrome and paroxysmal hemiparesis: epilepsy or ischaemia?DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 11 2004Floor E Jansen MD Transient neurological deficits experienced by patients with Sturge,Weber syndrome can be caused by epilepsy, or may result from temporary ischaemia of the cortex underlying the vascular malformation. To show the difficulty in distinguishing seizures from ischaemic symptoms, two male children with episodes of acute unilateral weakness are presented here as well as a review of the literature. The first child presented at 2 years of age with a sudden increase in his pre-existing right hemiparesis accompanied by screaming. Ictal epileptiform activity was recorded at the moment of the attack, and subsequent seizures were controlled by adjustment of antiepileptic drug treatment. The second child presented at 4 years of age with attacks of vomiting and a coinciding increase in the pre-existing paresis of the left leg. Electroencephalogram (EEG) recording did not show ictal epileptiform activity. The origin was presumed to be vascular. Treatment with aspirin led to control of these transient ischaemic attacks. Ictal EEG is needed to differentiate between an epileptic and an ischaemic origin of transient focal deficit. Treatment with aspirin should be considered if an ischaemic origin cannot be excluded. [source] Obesity, serious mental illness and antipsychotic drugsDIABETES OBESITY & METABOLISM, Issue 7 2009Richard I. G. Holt The prevalence of overweight and obesity is higher in people with mental illness than in the general population. Body weight is tightly regulated by a complex system involving the cortex and limbic system, the hypothalamus and the gastrointestinal tract. While there are justifiable concerns about the weight gain associated with antipsychotic medication, it is too simplistic to ascribe all obesity in people with serious mental illness (SMI) to their drug treatment. The development of obesity in SMI results from the complex interaction of the genotype and environment of the person with mental illness, the mental illness itself and antipsychotic medication. There are dysfunctional reward mechanisms in SMI that may contribute to poor food choices and overeating. While it is clear that antipsychotics have profound effects to stimulate appetite, no one receptor interaction provides an adequate explanation for this effect, and many mechanisms are likely to be involved. The complexity of the system regulating body weight allows us to start to understand why some individuals appear much more prone to weight gain and obesity than others. [source] Treatment of isolated systolic hypertension in diabetes mellitus type 2DIABETES OBESITY & METABOLISM, Issue 4 2006Ingrid Os Age-related arterial stiffness is more pronounced in diabetics compared to non-diabetics, which could explain the prevalence of isolated systolic hypertension (ISH, systolic blood pressure ,140 mmHg and diastolic blood pressure <90 mmHg) being approximately twice that of the general population without diabetes. Large-scale interventional outcome trials have also shown that diabetics usually have higher pulse pressure and higher systolic blood pressure than non-diabetics. Advanced glycation end-product formation has been implicated in vascular and cardiac complications of diabetes including loss of arterial elasticity, suggesting possibilities for new therapeutic options. With increasing age, there is a shift to from diastolic to systolic blood pressure and pulse pressure as predictors of cardiovascular disease. This may affect drug treatment as different antihypertensive drugs may have differential effects on arterial stiffness that can be dissociated from their effects on blood pressure. While thiazide diuretics are associated with little or no change in arterial stiffness despite a robust antihypertensive effect, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and calcium-channel blockers have been shown to reduce arterial stiffness. However, combination therapy is nearly always necessary to obtain adequate blood pressure control in diabetics. There are no randomized controlled trials looking specifically at treatment of ISH in diabetics. Recommendations regarding treatment of ISH in diabetes mellitus type 2 are based on extrapolation from studies in non-diabetics, post-hoc analyses and prespecified subgroup analysis in large-scale studies, and metaanalysis. These analyses have clearly demonstrated that blood pressure lowering in ISH confers improved prognosis and reduced cardiovascular and renal outcomes in both diabetics and non-diabetics. [source] Platelet hyperactivity in clinical depression and the beneficial effect of antidepressant drug treatment: how strong is the evidence?ACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2004R. Von Känel Objective:, Platelet hyperactivity is thought to contribute to the increased coronary artery disease (CAD) risk in depression. This study reviewed the evidence for hyperactive platelets and for effects of antidepressant drug treatment on platelet ,stickiness' in clinical depression. Method:, By means of PubMed electronic library search, 34 studies in English were identified (1983,2003) and critically reviewed. Results:, In depression, flow cytometry studies allowing detection of subtle platelet activation states consistently found at least one platelet activation marker to be increased, while the bulk of platelet aggregation studies did not suggest increased platelet aggregability. Platelets seem to be more activated in depressed patients with CAD than in depressed individuals without CAD. The selective serotonin reuptake inhibitors normalized platelet hyperactivity in four studies. Conclusion:, Data on platelet activity in depression are inconclusive. To resolve this issue and its clinical implications, studies in larger sample sizes controlling for confounders of platelet functioning and prospectively designed are needed. [source] New options for drug treatment of obesity in patients with Type 2 diabetesDIABETIC MEDICINE, Issue 2005R. L. Kennedy First page of article [source] Post-traumatic stress disorder: a review of psychobiology and pharmacotherapyACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2001I. Hageman Objective: To review the literature on the psychobiology and pharmacotherapy of PTSD. Method: Relevant studies were identified by literature searches (Pub-med, web of science) and through reference lists. The search was ended by May 2001. Results: There is evidence of involvement of opioid, glutamatergic, GABAergic, noradrenergic, serotonergic and neuroendocrine pathways in the pathophysiology of PTSD. Medications shown to be effective in double-blind placebo-controlled trials includes selective serotonin reuptake inhibitors, reversible and irreversible MAO-inhibitors, tricyclic antidepressants and the anticonvulsant lamotrigine. Still more agents appear promising in open-label trials. Conclusion: The complexity of the psychobiology is reflected by the difficulties in treating the disorder. According to the present knowledge, suggestions for drug treatment of PTSD are made. [source] Neuroleptic malignant syndrome during olanzapine and levomepromazine treatmentACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2000K. Järventausta Objective: To date only five reports of neuroleptic malignant syndrome (NMS) related to olanzapine exist. The first case report was published in November 1998. Method: We report the case of a 78-year-old woman suffering from chronic schizophrenia who developed a NMS while being treated with olanzapine and levomepromazine. Before this her medication had been unchanged for more than 2 years. Results: When treated with olanzapine and levomepromazine, the patient had a fulminant NMS which was complicated with pneumonia. When the neuroleptic drug treatment was discontinued, the patient recovered. However, when this combination was restarted later due to severe agitation and hallucinations, the symptoms of NMS reappeared. Conclusion: This case report shows that the neuroleptic malignant syndrome can occur during olanzapine treatment as well as during treatment with conventional neuroleptics. This syndrome may develop even after a long and stable neuroleptic treatment. [source] Youth retention: Factors associated with treatment drop-out from youth alcohol and other drug treatmentDRUG AND ALCOHOL REVIEW, Issue 6 2009RIA SCHRODER Abstract Introduction and Aims. This study examined factors associated with treatment drop-out among young people aged 13,19 years attending alcohol and other drug (AOD) treatment. Design and Methods. Data were gathered from structured interviews (n = 79) and a clinical file search of 184 randomly selected young people who had attended youth specific AOD treatment services in Aotearoa, New Zealand during 2003 or 2004. Results. The median length of stay was 2.7 months for those attending day/residential services (n = 42) and 4.0 sessions for those attending outpatient services (n = 37) 16.7% of participants from day/residential services dropped out of treatment early (within the first month) and 32.4% of participants from outpatient treatment services dropped out of treatment early (before the third session). Fixed client characteristics, such as age, sex, ethnicity, substance use and mental health diagnoses were not found to be associated with treatment retention. Dynamic client characteristics, such as motivation to attend treatment and expectations about treatment outcomes and program characteristics, such as positive experiences with treatment staff and feeling involved in the treatment process were found to be associated with treatment retention. Discussion and Conclusions. The findings of this study support previous research indicating that fixed client characteristics are not sufficient to explain youth retention in AOD treatment. Of more use are dynamic client characteristics and program variables. These findings stress the potential for improving treatment retention by creating more youth appropriate services.[Schroder R, Sellman D, Frampton C, Deering D. Youth retention: Factors associated with treatment drop-out from youth alcohol and other drug treatment. Drug Alcohol Rev 2009] [source] Validation of the World Health Organization Alcohol, Smoking and Substance Involvement Screening Test (ASSIST): report of results from the Australian siteDRUG AND ALCOHOL REVIEW, Issue 3 2005DAVID A. L. NEWCOMBE Abstract The concurrent, construct, discriminative and predictive validity of the World Health Organization's Alcohol Substance Involvement Screening Test (ASSIST) were examined in an Australian sample. One hundred and fifty participants, recruited from drug treatment (n = 50) and primary health care (PHC) settings (n = 100), were administered a battery of instruments at baseline and a modified battery at 3 months. Measures included the ASSIST; the Addiction Severity Index-Lite (ASI-Lite); the Severity of Dependence Scale (SDS); the MINI International Neuropsychiatric Interview (MINI-Plus); the Rating of Injection Site Condition (RISC); the Drug Abuse Screening Test (DAST); the Alcohol Use Disorders Identification Test (AUDIT); the Revised Fagerstrom Tolerance Questionnaire (RTQ); and the Maudsely Addiction Profile (MAP). Concurrent validity was demonstrated by significant correlations between ASSIST scores and scores from the ASI-lite, SDS, AUDIT and DAST; and significantly greater ASSIST scores for those with diagnoses of abuse or dependence. Construct validity was established by significant correlations between ASSIST scores and measures of risk factors for the development of drug and alcohol problems. Participants diagnosed with attention deficit/hyperactivity disorder or antisocial personality disorder had significantly higher ASSIST scores than those not diagnosed as such. Discriminative validity was established by the capacity of the ASSIST to discriminate between substance use, abuse and dependence. ROC analysis was able to establish cut-off scores for an Australian sample, with suitable specificities and sensitivities for most substances. Predictive validity was demonstrated by similarity in ASSIST scores obtained at baseline and at follow-up. The findings demonstrated that the ASSIST is a valid screening test for psychoactive substance use in individuals who use a number of substances and have varying degrees of substance use. [source] | ||||||||||||||||||||||||||||||||||||||||||||||