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Drug Therapy (drug + therapy)
Kinds of Drug Therapy Selected AbstractsCurrent literature in diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2009Article first published online: 13 FEB 200 In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 26 sections: 1 Reviews; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Obesity; 7 Prediction and Prevention; 8 Intervention: a) General; b) Care; c) Drug Therapy; d)Economics; e) Gene therapy; f) Nursing; g) Nutrition; h) Surgery; i) Transplantation; 9 Pathology and Complications: a) General; b) Cardiovascular; c) Eye disease; d) Gestational and fetal; e) Neurological; f) Podiatrical; g) Renal; 10 Endocrinology & Metabolism; 11 Experimental Studies; 12 Diagnosis and Techniques. Within each section, articles are listed in alphabetical order with respect to author [source] Current literature in diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 7 2008Article first published online: 29 SEP 200 In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 26 sections: 1 Reviews; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Obesity; 7 Prediction and Prevention; 8 Intervention: a) General; b) Care; c) Drug Therapy; d)Economics; e) Gene therapy; f) Nursing; g) Nutrition; h) Surgery; i) Transplantation; 9 Pathology and Complications: a) General; b) Cardiovascular; c) Eye disease; d) Gestational and fetal; e) Neurological; f) Podiatrical; g) Renal; 10 Endocrinology & Metabolism; 11 Experimental Studies; 12 Diagnosis and Techniques. Within each section, articles are listed in alphabetical order with respect to author [source] Current literature in diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2008Article first published online: 21 AUG 200 In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 26 sections: 1 Reviews; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Obesity; 7 Prediction and Prevention; 8 Intervention: a) General; b) Care; c) Drug Therapy; d)Economics; e) Gene therapy; f) Nursing; g) Nutrition; h) Surgery; i) Transplantation; 9 Pathology and Complications: a) General; b) Cardiovascular; c) Eye disease; d) Gestational and fetal; e) Neurological; f) Podiatrical; g) Renal; 10 Endocrinology & Metabolism; 11 Experimental Studies; 12 Diagnosis and Techniques. Within each section, articles are listed in alphabetical order with respect to author [source] Current literature in diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2008Article first published online: 8 JUL 200 In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 26 sections: 1 Reviews; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Obesity; 7 Prediction and Prevention; 8 Intervention: a) General; b) Care; c) Drug Therapy; d)Economics; e) Gene therapy; f) Nursing; g) Nutrition; h) Surgery; i) Transplantation; 9 Pathology and Complications: a) General; b) Cardiovascular; c) Eye disease; d) Gestational and fetal; e) Neurological; f) Podiatrical; g) Renal; 10 Endocrinology & Metabolism; 11 Experimental Studies; 12 Diagnosis and Techniques. Within each section, articles are listed in alphabetical order with respect to author [source] Current literature in diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2008Article first published online: 24 APR 200 In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 26 sections: 1 Reviews; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Obesity; 7 Prediction and Prevention; 8 Intervention: a) General; b) Care; c) Drug Therapy; d)Economics; e) Gene therapy; f) Nursing; g) Nutrition; h) Surgery; i) Transplantation; 9 Pathology and Complications: a) General; b) Cardiovascular; c) Eye disease; d) Gestational and fetal; e) Neurological; f) Podiatrical; g) Renal; 10 Endocrinology & Metabolism; 11 Experimental Studies; 12 Diagnosis and Techniques. Within each section, articles are listed in alphabetical order with respect to author [source] Current literature in diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2008Article first published online: 25 FEB 200 In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 26 sections: 1 Reviews; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Obesity; 7 Prediction and Prevention; 8 Intervention: a) General; b) Care; c) Drug Therapy; d)Economics; e) Gene therapy; f) Nursing; g) Nutrition; h) Surgery; i) Transplantation; 9 Pathology and Complications: a) General; b) Cardiovascular; c) Eye disease; d) Gestational and fetal; e) Neurological; f) Podiatrical; g) Renal; 10 Endocrinology & Metabolism; 11 Experimental Studies; 12 Diagnosis and Techniques. Within each section, articles are listed in alphabetical order with respect to author [source] Current literature in diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2008Article first published online: 11 DEC 200 In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 26 sections: 1 Reviews; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Obesity; 7 Prediction and Prevention; 8 Intervention: a) General; b) Care; c) Drug Therapy; d)Economics; e) Gene therapy; f) Nursing; g) Nutrition; h) Surgery; i) Transplantation; 9 Pathology and Complications: a) General; b) Cardiovascular; c) Eye disease; d) Gestational and fetal; e) Neurological; f) Podiatrical; g) Renal; 10 Endocrinology & Metabolism; 11 Experimental Studies; 12 Diagnosis and Techniques. Within each section, articles are listed in alphabetical order with respect to author [source] Current literature in diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2007Article first published online: 28 AUG 200 In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 26 sections: 1 Reviews; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Obesity; 7 Prediction and Prevention; 8 Intervention: a) General; b) Care; c) Drug Therapy; d)Economics; e) Gene therapy; f) Nursing; g) Nutrition; h) Surgery; i) Transplantation; 9 Pathology and Complications: a) General; b) Cardiovascular; c) Eye disease; d) Gestational and fetal; e) Neurological; f) Podiatrical; g) Renal; 10 Endocrinology & Metabolism; 11 Experimental Studies; 12 Diagnosis and Techniques. Within each section, articles are listed in alphabetical order with respect to author [source] Current literature in diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2007Article first published online: 23 FEB 200 In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 26 sections: 1 Reviews; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Obesity; 7 Prediction and Prevention; 8 Intervention: a) General; b) Care; c) Drug Therapy; d)Economics; e) Gene therapy; f) Nursing; g) Nutrition; h) Surgery; i) Transplantation; 9 Pathology and Complications: a) General; b) Cardiovascular; c) Eye disease; d) Gestational and fetal; e) Neurological; f) Podiatrical; g) Renal; 10 Endocrinology & Metabolism; 11 Experimental Studies; 12 Diagnosis and Techniques. Within each section, articles are listed in alphabetical order with respect to author [source] Current literature in diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2006Article first published online: 29 AUG 200 In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 26 sections: 1 Reviews & Symposia; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Obesity; 7 Prediction and Prevention; 8 Intervention: a) General; b) Care; c) Drug Therapy; d)Economics; e) Gene therapy; f) Nursing; g) Nutrition; h) Surgery; i) Transplantation; 9 Pathology and Complications: a) General; b) Cardiovascular; c) Eye disease; d) Gestational and fetal; e) Neurological; f) Podiatrical; g) Renal; 10 Endocrinology & Metabolism; 11 Experimental Studies; 12 Diagnosis and Techniques. Within each section, articles are listed in alphabetical order with respect to author [source] Current literature in diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2006Article first published online: 16 JUN 200 In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 26 sections: 1 Reviews & Symposia; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Obesity; 7 Prediction and Prevention; 8 Intervention: a) General; b) Care; c) Drug Therapy; d)Economics; e) Gene therapy; f) Nursing; g) Nutrition; h) Surgery; i) Transplantation; 9 Pathology and Complications: a) General; b) Cardiovascular; c) Eye disease; d) Gestational and fetal; e) Neurological; f) Podiatrical; g) Renal; 10 Endocrinology & Metabolism; 11 Experimental Studies; 12 Diagnosis and Techniques. Within each section, articles are listed in alphabetical order with respect to author [source] 40 abstracts relating to the Meeting of European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy & 3rd World Conference of International Academy of Cardiovascular Sciences June 18,19, 2009,Copenhagen, DenmarkFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2010Article first published online: 4 JAN 2010 First page of article [source] Antidiabetic Drug Therapy of African-American and White Community-Dwelling Elderly Over a 10-Year PeriodJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 12 2003Catherine I. Lindblad PharmD Objectives: To determine the prevalence and predictors of antidiabetic medication use over a 10-year period in a general population of African-American and white community-dwelling elderly. Design: Survey. Setting: Five adjacent counties (one urban and four rural) in the Piedmont area of North Carolina. Participants: Those aged 65 and older present at the baseline (n=4,136), second (n=3,234), third (n=2,508), and fourth (n=1,633) in-person waves of the Duke Established Populations for Epidemiologic Studies of the Elderly. Measurements: The use of six discrete categories of antidiabetic medications (insulin, first-generation oral sulfonylureas, second-generation oral sulfonylureas, metformin, oral combination therapy, and insulin combination therapy) was determined. Multivariate analyses, using weighted data adjusted for sampling design, were conducted to assess the association between antidiabetic medication use and race and other sociodemographic, health-status, and access-to-healthcare factors at baseline and 10 years later. Results: Antidiabetic medications were taken by 21.4% of the population at baseline; this increased to 28.1% at the 10-year follow-up (P<.001). Insulin was the most commonly used drug at baseline (7.9%). The use of second-generation sulfonylureas increased, and use of first-generation sulfonylureas decreased over the 10-year time period. Combination antidiabetic therapy and metformin use was infrequent throughout the study. Multivariate analyses revealed that, at baseline, African Americans were nearly twice as likely (adjusted odds ratio (AOR)=1.93, 95% confidence interval (CI)=1.46,2.54) to receive any antidiabetic medication as their white counterparts. Other significant (P<.05) factors were hypertension (AOR=1.38, 95% CI=1.03,1.84), stroke (AOR=1.98, 95% CI=1.43,2.73), one or more mobility difficulties (AOR=1.29, 95% CI=1.01,1.66), continuity of care (AOR=1.74, 95% CI=1.20,2.54), and multiple doctor visits (1,4 visits, AOR=1.69, 95% CI=1.08,2.65; ,5 visits, AOR=3.15, 95% CI=1.95,5.07). Being underweight (AOR=0.45, 95% CI=0.30,0.67) and being cognitively impaired (AOR=0.60, 95% CI=0.41,0.87) were factors significantly (P<.05) associated with a decreased risk of antidiabetic medication use. At the 10-year follow-up, similar trends were seen associating these sociodemographic, health-status, and access-to-healthcare factors with antidiabetic medication use. Conclusion: Antidiabetic medication use is common and increases over time for community-dwelling elderly. Race is significantly associated with antidiabetic medication use, even after controlling for other sociodemographic, health-status, and access-to-healthcare variables. [source] Total Atrioventricular Nodal Ablation Increases Atrial Fibrillation Burden in Patients with Paroxysmal Atrial Fibrillation Despite Continuation of Antiarrhythmic Drug TherapyJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 12 2003RIK WILLEMS M.D. Introduction: Total atrioventricular nodal (TAVN) ablation and pacing is an accepted and safe treatment for patients with drug-refractory paroxysmal atrial fibrillation (AF). Many patients develop permanent AF within the first 6 months after TAVN ablation. This usually is ascribed to the cessation of antiarrhythmic drug therapy. We hypothesized that TAVN ablation itself creates an atrial substrate prone to AF. Methods and Results: Patients participating in the Atrial Pacing Periablation for Paroxysmal Atrial Fibrillation (PA3) study who remained on stable antiarrhythmic drug therapy throughout follow-up were included in this analysis. AF burden and the development of persistent AF in the preablation period were compared to two consecutive postablation periods. Echocardiographic changes also were evaluated. Twenty-two patients remained on stable drug therapy (9 men and 13 women, age 59 ± 3 years). One patient developed persistent AF preablation compared to 10 postablation (P < 0.05). AF burden preablation was 3.0 ± 1.2 hours/day and increased to 10.4 ± 2.2 hours/day and 11.8 ± 2.3 hours/day in the two postablation follow-up periods (P < 0.05). In patients with fractional shortening (FS) >30% prior to ablation, FS decreased significantly from 39.4%± 1.3% to 36.4%± 1.7% (P < 0.05). In contrast, in patients with a FS ,30% prior to ablation, FS increased from 27%± 0.8% to 33.6 ± 1.7% (P < 0.05). Conclusion: TAVN ablation increases AF burden and facilitates the development of persistent AF in patients with paroxysmal AF despite the continuation of antiarrhythmic drugs. Loss of AV and/or interventricular synchrony may lead to altered cardiac hemodynamics resulting in atrial stretch and increasing AF burden. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1296-1301, December 2003) [source] Intrathecal Drug Therapy for Cancer Pain: Time for a Boost!PAIN PRACTICE, Issue 5 2009Marc A. Huntoon MD No abstract is available for this article. [source] A Novel Drug Therapy for Recurrent Laryngeal Nerve Injury Using T-588,THE LARYNGOSCOPE, Issue 7 2007Yuko Mori MD Abstract Objectives/Hypothesis: We have previously shown that gene therapy using Insulin-like growth factor (IGF)-I, glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF), or a combination of these trophic factors, is a treatment option for recurrent laryngeal nerve (RLN) palsy. However, there remain some difficulties preventing this option from becoming a common clinical therapy for RLN injury. Thus, we need to develop novel treatment option that overcomes the problems of gene therapy. R(,)-1-(benzothiophen-5-yl)-2-[2-N,N-diethylamino]ethoxy]ethanol hydrochloride (T-588), a synthetic compound, is known to have neuroprotective effects on neural cells. In the present study, the possibility of new drug treatments using T-588 for RLN injury was assessed using rat models. Study Design: Animal study. Methods: Animals were administered T-588 for 4 weeks. The neuroprotective effects of T-588 administration after vagal nerve avulsion and neurofunctional recovery after recurrent laryngeal nerve crush were studied using motoneuron cell counting, evaluation of choline acetyltransferase immunoreactivity, the electrophysiologic examination, and the re-mobilization of the vocal fold. Results: T-588 administration successfully prevented motoneuron loss and ameliorated the choline acetyltransferase immunoreactivity in the ipsilateral nucleus ambiguus after vagal nerve avulsion. Significant improvements of motor nerve conduction velocity of the RLN and vocal fold movement were observed in the treatment group when compared to controls. Conclusion: These results indicate that oral administration of T-588 might be a promising therapeutic option in treating peripheral nerve injury. [source] Liver disease and the renin,angiotensin system: Recent discoveries and clinical implicationsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2008John S Lubel Abstract The renin,angiotensin system (RAS) is a key regulator of vascular resistance, sodium and water homeostasis and the response to tissue injury. Historically, angiotensin II (Ang II) was thought to be the primary effector peptide of this system. Ang II is produced predominantly by the effect of angiotensin converting enzyme (ACE) on angiotensin I (Ang I). Ang II acts mainly through the angiotensin II type-1 receptor (AT1) and, together with ACE, these components represent the ,classical' axis of the RAS. Drug therapies targeting the RAS by inhibiting Ang II formation (ACE inhibitors) or binding to its receptor (angiotensin receptor blockers) are now in widespread clinical use and have been shown to reduce tissue injury and fibrosis in cardiac and renal disease independently of their effects on blood pressure. In 2000, two groups using different methodologies identified a homolog of ACE, called ACE2, which cleaves Ang II to form the biologically active heptapeptide, Ang-(1,7). Conceptually, ACE2, Ang-(1,7), and its putative receptor, the mas receptor represent an ,alternative' axis of the RAS capable of opposing the often deleterious actions of Ang II. Interestingly, ACE inhibitors and angiotensin receptor blockers increase Ang-(1,7) production and it has been proposed that some of the beneficial effects of these drugs are mediated through upregulation of Ang-(1,7) rather than inhibition of Ang II production or receptor binding. The present review focuses on the novel components and pathways of the RAS with particular reference to their potential contribution towards the pathophysiology of liver disease. [source] Hard palate perforation: an unusual finding in paracoccidioidomycosisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 4 2001Luiz G. M. Castro MD A 36-year-old black man presented to his dermatologist in May 1996 complaining of mucosal lesions in the mouth, as well as perforation of the hard palate. The lesions had started approximately 7 months before and had worsened gradually. Other complaints included odynophagia, dysphagia, mild dyspnea, and dry cough. The patient was in good general health, but reported a 3 kg weight loss over the previous semester. The hard and soft palate presented erythematous ulcers with a finely granulated base and irregular, but clearly defined margins. A perforation (diameter, 0.5 cm) of the hard palate was seen in the center of the ulcerated region (Fig. 1). Direct examination of 10% KOH cleared specimens showed typical double-walled, multiple budding yeast structures. Paracoccidioidomycosis (PCM) serologic reactions tested positive for double immunodiffusion (DI), complement fixation (CF) 1 : 256 and counterimmunoelectrophoresis (CIE) 1 : 128. Hematoxylin and eosin-stained sections of oral lesions showed an ulcer covered by a fibrous leukocytic crust, with a lymphoplasmacytic infiltrate, as well as multinuclear giant cells containing round bodies with a double membrane. Gomori,Grocott staining showed budding and blastoconidia suggestive of PCM. Lung computed tomography (CT) exhibited findings consistent with pulmonary PCM. Diagnosis of the chronic multifocal form of PCM with oral and pulmonary manifestations was established. Drug therapy was initiated with ketoconazole (KCZ) 200 mg twice daily, which led to clinical cure in approximately 2 months. Serum antibody values rose 30 days after institution of therapy (CIE 1 : 256; CF 1 : 512), peaking at day 60 (CIE 1 : 1024; CF 1 : 1024). Three months later the daily dose was reduced to 200 mg and titers declined slowly. The diameter of the perforation remained unchanged (Fig. 2). The hard palate perforation was corrected with a palatoplasty 27 months after initiation of drug therapy (Fig. 3). KCZ was discontinued when serologic cure was achieved after 34 months of treatment (DI weakly positive; CIE 1 : 8; CF not measurable). The patient was discharged 46 months after the first visit. Figure 1. Ulcers with a finely granulated base on the hard palate with irregular but clearly defined margins. A perforation (diameter, 0.5 cm) of the hard palate is seen in the center of the ulcerated region Figure 2. Clinical aspect after 2 months of oral ketoconazole 200 mg twice daily. Resolution of ulceration was evident, but the diameter of the perforation remained unchanged Figure 3. Final result of palatoplasty to cover hard palate perforation [source] Drug therapy of primary biliary diseases: classical and modern strategiesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2001Julia Schlichting [source] Inappropriate prescribing in the elderlyJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2007P. Gallagher MB MRCPI Summary Background and objective:, Drug therapy is necessary to treat acute illness, maintain current health and prevent further decline. However, optimizing drug therapy for older patients is challenging and sometimes, drug therapy can do more harm than good. Drug utilization review tools can highlight instances of potentially inappropriate prescribing to those involved in elderly pharmacotherapy, i.e. doctors, nurses and pharmacists. We aim to provide a review of the literature on potentially inappropriate prescribing in the elderly and also to review the explicit criteria that have been designed to detect potentially inappropriate prescribing in the elderly. Methods:, We performed an electronic search of the PUBMED database for articles published between 1991 and 2006 and a manual search through major journals for articles referenced in those located through PUBMED. Search terms were elderly, inappropriate prescribing, prescriptions, prevalence, Beers criteria, health outcomes and Europe. Results and discussion:, Prescription of potentially inappropriate medications to older people is highly prevalent in the United States and Europe, ranging from 12% in community-dwelling elderly to 40% in nursing home residents. Inappropriate prescribing is associated with adverse drug events. Limited data exists on health outcomes from use of inappropriate medications. There are no prospective randomized controlled studies that test the tangible clinical benefit to patients of using drug utilization review tools. Existing drug utilization review tools have been designed on the basis of North American and Canadian drug formularies and may not be appropriate for use in European countries because of the differences in national drug formularies and prescribing attitudes. Conclusion:, Given the high prevalence of inappropriate prescribing despite the widespread use of drug-utilization review tools, prospective randomized controlled trials are necessary to identify useful interventions. Drug utilization review tools should be designed on the basis of a country's national drug formulary and should be evidence based. [source] Drug therapy tailored for the individual patient,search for the holy grailCLINICAL CARDIOLOGY, Issue 3 2001C. Richard Conti M.D., M.A.C.C. Editor-in-Chief No abstract is available for this article. [source] Reflecting on Type 2 Diabetes Prevention: More Questions than Answers!DIABETES OBESITY & METABOLISM, Issue 2007J. Rosenstock Given the enormous public health and economic burden posed by the global epidemic of type 2 diabetes mellitus (T2DM), intervention in the prediabetes stage of disease to prevent progression to T2DM and its vascular complications seems the most sensible approach. Precisely how best to intervene remains the subject of much debate. Prudent lifestyle changes have been shown to significantly reduce the risk of progression in individuals with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Although lifestyle modifications are notoriously difficult to maintain, there is evidence that intensive intervention results in continued preventive benefit after the stopping of structured counselling. A number of drug therapies, including metformin, acarbose, orlistat and rosiglitazone, have also been proven effective in preventing progression from IFG/IGT, but unresolved issues still remain. Specifically, whether large numbers of individuals with glucose dysregulation who may never progress to T2DM should be exposed to the risk of pharmacological adverse effects is a topic of discussion and debate. Furthermore, there are limited data on the effectiveness of implementing interventions during the prediabetic state to prevent cardiovascular complications that may be hyperglycaemia related. A recent American Diabetes Association (ADA) consensus statement on IFG/IGT recommends lifestyle modification for individuals with IFG or IGT. Of note, the ADA consensus statement introduces the option of adding metformin treatment to lifestyle changes in those individuals who have combined IFG/IGT plus an additional risk factor for progression and who also have some features that increase the likelihood of benefiting from metformin treatment. The dipeptidyl peptidase-4 inhibitors are a new class of oral antidiabetic agents that, in addition to being effective in improving glycaemic control, may exert beneficial effects in preserving ,-cell function. These characteristics, combined with a low risk of hypoglycaemia, weight neutrality and what appears , so far , to be a relatively benign tolerability profile, make these agents intriguing candidates for preventive treatment. [source] Short Report: Safe and rapid resolution of severe hypertriglyceridaemia in two patients with intravenous insulinDIABETIC MEDICINE, Issue 9 2010J. M. Triay Diabet. Med. 27, 1080,1083 (2010) Abstract Aim, To rapidly reduce serum triglyceride to a safe serum level. Severe hypertriglyceridaemia is associated with uncontrolled diabetes, obesity and poor physical activity. Even moderate increases in triglyceride levels (> 5mmol/L) confer an increased risk of pancreatitis and coronary artery disease. We present two patients with diabetes and serum triglyceride levels of greater than 85mmol/L despite polypharmacy intervention. Method, 72-hour intravenous insulin infusion was administered. Results, Serum triglyceride levels fell to 9.4 and 4.6 mmol/L respectively, without adverse events and sustained effect over several months. Conclusion, We suggest the use of intravenous insulin infusion where lifestyle and oral drug therapies have failed can impact on severe hypertriglyceridaemia. [source] Genotypic and phenotypic classification of cancer: How should the impact of the two diagnostic approaches best be balanced?GENES, CHROMOSOMES AND CANCER, Issue 9 2010Petter Brandal Neoplastic tumors are traditionally named based on their differentiation (i.e., which normal cells and tissues they resemble) and bodily site. In recent years, knowledge about the genetic basis of tumorigenesis has grown rapidly, and the new information has in several instances been incorporated into the very definition of cancerous entities. The proper contribution of the diseases' phenotype and genotype to what they are called and how they are delineated from one another has rarely been subjected to explicit reasoning, however, nor is it often made clear whether existing naming practices are founded on ontological or utilitarian grounds. We look at several examples of how the new cytogenetic and molecular genetic understanding of tumorigenesis has impacted oncological nomenclature in a significant manner, but also at counterexamples where no similar change has taken place. In all likelihood, more and more neoplastic diseases will in the future be defined and named based on their pathogenesis rather than their phenotype, not least because effective and specific drug therapies directed against the molecular change at the very heart of oncogenesis will increasingly become available. The fact that this shift in emphasis is primarily guided by utilitarian considerations rather than any perception of acquired genetic changes as somehow being more ontologically "profound" or "important" in tumorigenesis, is as it should be; both the phenotype and the genotype of tumors are key parameters across most of oncology and are likely to be retained as the basis of coexisting disease classifications for as long as we can foresee. © 2010 Wiley-Liss, Inc. [source] Phosphoinositide 3-kinase signalling in lung disease: leucocytes and beyondIMMUNOLOGY, Issue 4 2007David A. Medina-Tato Summary The family of lipid kinases termed phosphoinositide-3-kinase (PI3K) is known to contribute at multiple levels to innate and adaptive immune responses, and is hence an attractive target for drug discovery in inflammatory and autoimmune disease, including respiratory diseases. The development of isoform-selective pharmacological inhibitors, targeted gene manipulation and short interfering RNA (siRNA) target validation have facilitated a better understanding of the role that each member of this family of kinases plays in the physiology and pathology of the respiratory system. In this review, we will evaluate the evidence for the roles of specific PI3K isoforms in the lung and airways, and discuss their potential as targets for novel drug therapies. [source] Regulation of gene expression in inflammatory bowel disease and correlation with IBD drugs.INFLAMMATORY BOWEL DISEASES, Issue 1 2004Screening by DNA microarrays Abstract Potential biomarkers for Crohn's disease (CD) and ulcerative colitis (UC) were identified from two sets of full thickness pathologic samples utilizing DermArray® and PharmArray® DNA microarrays relative to uninvolved (Un) colon or normal colon. Seven of the over-expressed genes were verified using quantitative RT-PCR (i.e., TMPT, FABP1, IFI27, LCN2, COL11A2, HXB, and metallothionein). By correlating gene expression profiles between inflammatory bowel disease (IBD) tissue samples and IBD drug-treated cell cultures it might be possible to identify new candidate molecular target genes for IBD therapy and drug discovery. Potential biomarkers for CaCo2 cell cultures, which are routinely used as a GI tract surrogate model for in vitro pharmacokinetic studies, treated with azathioprine, 5-aminosalicylic acid, metronidazole, and prednisone were also identified from another experiment. Metallothionein mRNA expression was found to be down-regulated in azathioprine-treated CaCo2 cells, and was coincidentally up-regulated in the CD sample, thus resulting in an anti-correlation. These results suggest that this new screening methodology is feasible, that metallothioneins might be biomarkers for azathioprine therapy in vivo in CD, and that azathioprine might mechanistically down-regulate metallothionein gene expression. Correlations were also observed between IBD samples and either metronidazole- or 5-aminosalicylic acid-treated CaCo2 cells. Similar comparisons of disease tissue samples in vivo vs drug-treated cell cultures in vitro might reveal new mechanistic insights concerning established or experimental drug therapies. This affordable in vitro methodology is promising for expanded studies of IBD and other diseases. [source] Potentially Inappropriate Prescribing in Ontario Community-Dwelling Older Adults and Nursing Home ResidentsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2004Christopher J. Lane BASc Objectives: To compare patterns of potentially inappropriate drug therapy prescribing in community-dwelling older adults and nursing home residents in Ontario, Canada. Design: A retrospective cohort study using administrative databases. Setting: Ontario community and nursing home facilities. Participants: All 1,275,619 older adults aged 66 and older in Ontario (1,216,900 community-dwelling and 58,719 nursing home residents) who were dispensed at least one prescription from the comprehensive provincial drug plan in 2001. In Ontario, the provision of clinical pharmacy services is mandated in the nursing home setting. No comparable program exists for older adults in the community setting. Measurements: Potentially inappropriate drug prescribing was compared between community-dwelling and nursing home residents in two categories: those to always avoid and therapies considered rarely appropriate to prescribe. Results: Of the 1,275,619 adults in the cohort, nursing home residents were older (mean age±standard deviation=84.2±7.6 vs 75.0±6.5, P<.001), included more women (73.3% vs 57.7%, P<.001), had higher comorbidity scores (measured by the number of distinct drug therapies dispensed in the prior year (10.7±6.8 vs 7.2±5.7, P<.001) and Charlson comorbidity scores (1.4±1.6 vs 0.9±1.5, P<.001)) than community-dwelling individuals. Community-dwelling older adults were significantly more likely to be dispensed at least one drug therapy in the always avoid or rarely appropriate category than nursing home residents (3.3% vs 2.3%, P<.001). Using a logistic regression model that controlled for age, sex, and comorbidity (number of distinct drug therapies dispensed in the prior year), nursing home residents were close to half as likely to be dispensed one of these potentially inappropriate drug therapies as community-dwelling older adults (odds ratio=0.52, 95% confidence interval=0.49,0.55, P<.001). Conclusion: Potentially inappropriate drug therapy in the always avoid and rarely indicated categories is dispensed less often to nursing home residents than to older community-dwelling adults. Clinical pharmacist services, which are mandated in the nursing home setting, may be responsible for these differences in Ontario, Canada. [source] The Role of Benzodiazepines in the Treatment of InsomniaJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2001Meta-Analysis of Benzodiazepine Use in the Treatment of Insomnia PURPOSE: To obtain a precise estimate of the efficacy and common adverse effects of benzodiazepines for the treatment of insomnia compared with those of placebo and other treatments. BACKGROUND: Insomnia, also referred to as disorder of initiating or maintaining sleep, is a common problem and its prevalence among older people is estimated to be 23% to 34%.1 The total direct cost in the United States for insomnia in 1995 was estimated to be $13.9 billion.2 The complaint of insomnia in older people is associated with chronic medical conditions; psychiatric problems, mainly depression, chronic pain, and poor perceived general condition;1,3,4 and use of sleep medications.5 Thus in most cases, insomnia is due to some other underlying problem and is not just a consequence of aging.6 Accordingly, the management of insomnia should focus on addressing the primary problem and not just short-term treatment of the insomnia. Benzodiazepines belong to the drug class of choice for the symptomatic treatment of primary insomnia.7 This abstract will appraise a meta-analysis that compared the effect of benzodiazepines for short-term treatment of primary insomnia with placebo or other treatment. DATA SOURCES: Data sources included articles listed in Medline from 1966 to December 1998 and the Cochrane Controlled Trials Registry. The medical subject heading (MeSH) search terms used were "benzodiazepine" (exploded) or "benzodiazepine tranquillizers" (exploded) or "clonazepam,""drug therapy,""randomized controlled trial" or "random allocation" or "all random,""human," and "English language." In addition, bibliographies of retrieved articles were scanned for additional articles and manufacturers of brand-name benzodiazepines were asked for reports of early trials not published in the literature. STUDY SELECTION CRITERIA: Reports of randomized controlled trials of benzodiazepine therapy for primary insomnia were considered for the meta-analysis if they compared a benzodiazepine with a placebo or an alternative active drug. DATA EXTRACTION: Data were abstracted from 45 randomized controlled trials representing 2,672 patients, 47% of whom were women. Fifteen studies included patients age 65 and older and four studies involved exclusively older patients. Twenty-five studies were based in the community and nine involved inpatients. The duration of the studies ranged from 1 day to 6 weeks, with a mean of 12.2 days and median of 7.5 days. The primary outcome measures analyzed were sleep latency and total sleep duration after a sleep study, subjects' estimates of sleep latency and sleep duration, and subjects' report of adverse effects. Interrater reliability was checked through duplicate, independent abstraction of the first 21 articles. Overall agreement was between 95% and 98% (kappa value of 0.90 and 0.95 accordingly) for classification of the studies and validity of therapy, and 76% (kappa value of 0.51) for study of harmful effects. A scale of 0 to 5 was used to rate the individual reports, taking into account the quality of randomization, blinding, follow-up, and control for baseline differences between groups. Tests for homogeneity were applied across the individual studies and, when studies were found to be heterogeneous, subgroup analysis according to a predefined group was performed. MAIN RESULTS: The drugs used in the meta-analysis included triazolam in 16 studies; flurazepam in 14 studies; temazepam in 13 studies; midazolam in five studies; nitrazepam in four studies; and estazolam, lorazepam, and diazepam in two studies each. Alternative drug therapies included zopiclone in 13 studies and diphenhydramine, glutethimide, and promethazine in one study each. Only one article reported on a nonpharmacological treatment (behavioral therapy). The mean age of patients was reported in 33 of the 45 studies and ranged between 29 and 82. SLEEP LATENCY: In four studies involving 159 subjects, there was sleep-record latency (time to fall asleep) data for analysis. The pooled difference indicated that the latency to sleep for patients receiving a benzodiazepine was 4.2 minutes (95% CI = (,0.7) (,9.2)) shorter than for those receiving placebo. Patient's estimates of sleep latency examined in eight studies showed a difference of 14.3 minutes (95% CI = 10.6,18.0) in favor of benzodiazepines over placebo. TOTAL SLEEP DURATION: Analysis of two studies involving 35 patients in which total sleep duration using sleep-record results was compared indicated that patients in the benzodiazepine groups slept for an average of 61.8 minutes (95% CI = 37.4,86.2) longer than those in the placebo groups. Patient's estimates of sleep duration from eight studies (566 points) showed total sleep duration to be 48.4 minutes (95% CI = 39.6,57.1) longer for patients taking benzodiazepines than for those on placebo. ADVERSE EFFECTS: Analysis of eight studies (889 subjects) showed that those in the benzodiazepine groups were more likely than those in the placebo groups to complain of daytime drowsiness (odds ratio (OR) 2.4, 95% confidence interval (CI) = 1.8,3.4). Analysis of four studies (326 subjects) also showed that subjects in the benzodiazepine groups were more likely to complain of dizziness or lightheadedness than the placebo groups. (OR 2.6, 95% CI = 0.7,10.3). Despite the increased reported side effects in the benzodiazepine groups, drop-out rates were similar in the benzodiazepine and placebo groups. For patient reported outcome, there was no strong correlation found for sleep latency data, (r = 0.4, 95% CI = (,0.3) (,0.9)) or for sleep duration (r = 0.2, 95% CI = ,0.8,0.4) between benzodiazepine dose and outcome. COMPARISON WITH OTHER DRUGS AND TREATMENTS: In three trials with 96 subjects, meta-analysis of the results comparing benzodiazepines with zopiclone, did not show significant difference in sleep latency in the benzodiazepine and placebo groups, but the benzodiazepine groups had increased total sleep duration (23.1 min. 95% CI = 5.6,40.6). In four trials with 252 subjects, the side effect profile did not show a statistically significant difference (OR 1.5, CI 0.8,2.9). There was only one study comparing the effect of behavioral therapy with triazolam. The result showed that triazolam was more effective than behavioral therapy in decreasing sleep latency, but its efficacy declined by the second week of treatment. Behavioral therapy remained effective throughout the 9-week follow-up period. There were four small trials that involved older patients exclusively, with three of the studies having less than 2 weeks of follow-up. The results were mixed regarding benefits and adverse effects were poorly reported. CONCLUSION: The result of the meta-analysis shows that the use of benzodiazepines results in a decrease in sleep latency and a significant increase in total sleep time as compared with placebo. There was also a report of significantly increased side effects, but this did not result in increased discontinuation rate. There was no dose-response relationship for beneficial effect seen with the use of benzodiazepines, although the data are scant. Zopiclone was the only alternative pharmacological therapy that could be studied with any precision. There was no significant difference in the outcome when benzodiazepines were compared with zopiclone. There was only one study that compared the effect of benzodiazepines with nonpharmacological therapy; thus available data are insufficient to comment. [source] Interleukin-6 Levels are Inversely Correlated with Heart Rate Variability in Patients with Decompensated Heart FailureJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2001DORON ARONSON M.D. Interleukin-6 and Heart Rate Variability.Introduction: Increased local and systemic elaboration of cytokines have an important role in the pathogenesis of congestive heart failure (CHF) through diverse mechanisms. Because cytokines are known to act at the neuronal level in both the peripheral and central nervous system, we sought to determine whether increased cytokine levels are associated with the autonomic dysfunction that characterizes CHF. Methods and Results: We studied 64 patients admitted for decompensated CHF (mean age 59 ± 12 years). Autonomic function was assessed using time, and frequency-domain heart rate variability (HRV) measures, obtained from 24-hour Holter recordings. In addition, norepinephrine, tumor necrosis factor-, (TNF-,), and interleukin-6 (IL-6) were measured in all patients. TNF-, levels did not correlate with any of the HRV measures. IL-6 inversely correlated with the time-domain parameters of standard deviation of RR intervals (SDNN) (r =,0.36, P = 0.004) and standard deviation of all 5,minute mean RR intervals (SDANN) (r =,0.39, P = 0.001), and with the frequency-domain parameters of total power (TP) (r =,0.37, P = 0.003) and ultralow-frequency (ULF) power (r =,0.43, P = 0.001). No correlation was found between IL-6 and indices of parasympathetic modulation. Using multiple linear regression models, adjusting for clinical variables and drug therapies, the strong inverse relationship between IL-6 and SDNN (P = 0.006), SDANN (P = 0.001), TP (P = 0.04), and ULF power (P = 0.0007) persisted. Conclusion: Reduction of long-term HRV indices is associated with increased levels of IL-6 in patients with decompensated heart failure. The ability of long-term HRV parameters to better reflect activation of diverse hormonal systems may explain their greater prognostic power for risk stratification in patients with CHF. [source] EDTA enhances high-throughput two-dimensional bioprinting by inhibiting salt scaling and cell aggregation at the nozzle surfaceJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 4 2009Cheryl A. Parzel Abstract Tissue-engineering strategies may be employed in the development of in vitro breast tissue models for use in testing regimens of drug therapies and vaccines. The physical and chemical interactions that occur among cells and extracellular matrix components can also be elucidated with these models to gain an understanding of the progression of transformed epithelial cells into tumours and the ultimate metastases of tumour cells. The modified inkjet printer may be a useful tool for creating three-dimensional (3D) in vitro models, because it offers an inexpensive and high-throughput solution to microfabrication, and because the printer can be easily manipulated to produce varying tissue attributes. We hypothesized, however, that when ink is replaced with a biologically based fluid (i.e. a ,bio-ink'), specifically a serum-free cell culture medium, printer nozzle failure can result from salt scale build-up as fluid evaporates on the printhead surface. In this study, ethylene diamine tetra-acetic acid (EDTA) was used as a culture medium additive to prevent salt scaling and cell aggregation during the bioprinting process. The results showed that EDTA, at a concentration typically found in commercially available trypsin solutions (0.53 mM), prevented nozzle failure when a serum-free culture medium was printed from a nozzle at 1000 drops/s. Furthermore, increasing concentrations of EDTA appeared to mildly decrease aggregation of 4T07 cells. Cell viability studies were performed to demonstrate that addition of EDTA did not result in significant cell death. In conclusion, it is recommended that EDTA be incorporated into bio-ink solutions containing salts that could lead to nozzle failure. Copyright © 2009 John Wiley & Sons, Ltd. [source] |