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Inhibitor Treatment (inhibitor + treatment)

Distribution by Scientific Domains

Medical Sciences	82%
Life Sciences	15%

Distribution within Medical Sciences

Gastroenterology & Hepatology	20%
Neurology	18%
Allergy & Clinical Immunology	14%
Oncology & Radiotherapy	6%
10 Other Subdomains	36%

Selected Abstracts

Efficacy of Phosphodiesterase Type 5 Inhibitor Treatment in Men with Erectile Dysfunction and Dyslipidemia: A Post Hoc Analysis of the Vardenafil Statin Study

THE JOURNAL OF SEXUAL MEDICINE, Issue 5 2010
Martin M. Miner MD
ABSTRACT Introduction., Dyslipidemia occurs often in subjects with erectile dysfunction (ED), but there is little information about how this condition affects ED treatment responses. Aim., To determine whether low-density lipoprotein cholesterol (LDL-C) levels, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio; or the presence of metabolic syndrome influenced efficacy of vardenafil in men with ED and dyslipidemia. Methods., Post hoc subgroup analysis of a 12-week study of the influence of lipid levels and presence of metabolic syndrome on the efficacy of vardenafil as measured by International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, responses to Sexual Encounter Profile (SEP) SEP2 and SEP3 questions, duration of erection leading to successful intercourse, and erection duration regardless of the answer to SEP3. Lipid values were obtained at study start, after patients had received at least 3 months of therapy with a statin. Main Outcome Measures., Outcomes in subjects with LDL-C <100, ,100 to <130, or ,130 mg/dL [<2.59, ,2.59 to <3.36, or ,3.36 mmol/L]; TC/HDL-C ratio <3.5 vs. ,3.5, and presence or absence of metabolic syndrome. Results., Vardenafil improved all endpoints evaluated compared with placebo in all subgroups, however, nominally significant treatment by subgroup interaction terms did not follow a distinct pattern. Increasing LDL-C (P = 0.033), but not TC/HDL-C ratio or metabolic syndrome, was associated with an increase in treatment response measured by the IIEF-EF domain score. Responses to SEP3 were nominally influenced by LDL-C levels (P = 0.019), but were not significantly influenced by TC/HDL-C ratio, or the metabolic syndrome. Only higher TC/HDL-C ratios (,3.5) were associated with larger treatment differences in duration of erection leading to successful intercourse (P = 0.028). Conclusions., Vardenafil was effective in men with dyslipidemia regardless of LDL-C levels, TC/HDL-C ratio, and/or presence of metabolic syndrome. Despite the known presence of ED and dyslipidemia, other cardiovascular risk factors were apparently not aggressively managed. Miner MM, Barnes A, and Janning S. Efficacy of phosphodiesterase type 5 inhibitor treatment in men with erectile dysfunction and dyslipidemia: A post hoc analysis of the vardenafil statin study. J Sex Med 2010;7:1937,1947. [source]

Citalopram treatment of social anxiety disorder with comorbid major depression

DEPRESSION AND ANXIETY, Issue 4 2003
Franklin R. Schneier M.D.
Abstract Treatment of patients with both social anxiety disorder and major depression has been little studied although social anxiety disorder and depression frequently co-occur. Each disorder has been shown to respond to serotonin reuptake inhibitor treatment. Objectives of this study were to characterize a sample of these comorbid patients and to assess response to treatment with citalopram. Patients with primary DSM-IV generalized subtype of social anxiety disorder and comorbid major depression (N = 21) were assessed for symptoms of each disorder, including atypical depressive features, and functional impairment. Patients were treated with a flexible dose of open label citalopram for 12 weeks. Response rates for the intention-to-treat sample at week 12 were 14/21 (66.7%) for social anxiety disorder and 16/21 (76.2%) for depression. All continuous measures of social anxiety, depression, and functional impairment improved significantly with treatment, but depression symptoms responded more rapidly and more completely than social anxiety symptoms. Mean dose of citalopram at study endpoint was 37.6 mg/day. Only three patients (14.3%) fulfilled DSM-IV criteria for atypical features of depression, although 18 (85.7%) fulfilled the criterion for interpersonal rejection sensitivity. Citalopram treatment may benefit patients with primary social anxiety disorder and comorbid major depression, and it should be further studied in controlled trials. Improvement in social anxiety disorder symptoms lagged behind improvement in depression, and greater than 12 weeks of treatment may be required to assess full social anxiety response in patients with comorbid depression. The overlap of social anxiety disorder with atypical features of depression may primarily be due to the shared feature of rejection sensitivity. Depression and Anxiety 17:191,196, 2003. © 2003 Wiley-Liss, Inc. [source]

Age-dependent differential expression of genes involved in steroid signalling pathway in the brain of protandrous black porgy, Acanthopagrus schlegeli

DEVELOPMENTAL NEUROBIOLOGY, Issue 5 2009
Sherly Tomy
Abstract The mechanisms underlying brain sex differentiation in animals are poorly understood. In the present study, using black porgy, Acanthopagrus schlegeli, as primary experimental model, we investigated the temporal expression patterns of receptors for androgen (ar) and estrogen (esr1 and esr2a) in the brain during posthatching ages and analyzed them against the timing of gonadal germ cell development. We hypothesized that endogenous estrogens naturally masculinize the brain of black porgy. The expression of sex steroid receptors was studied in relation to a wider suite of other related genes (nr5a2, nr0b1, star, and cyp19a1b) to provide some insight into the monomale sex differentiation pattern observed in this species. Our results revealed a highly significant increase in esr1 together with the increase in esr2a at 120 dph (days posthatching), suggesting a significant role for esr in sex differentiation in this species. Temporal expression patterns of nr5a2, nr0b1, star, sex steroid receptors, and cyp19a1b in the brain provided evidence for their physiological roles in the monomale sex differentiation in this species. The expression of nr5a2, star, ar, esr1, esr2a, and cyp19a1b increased at 120 dph, a period when brain sex differentiation probably occurs in this species. The study also suggests that neurosteroidogenesis in black porgy may be regulated by both nr5a2 -dependent and nr5a2 -independent mechanisms. The results demonstrated striking differences in the abundance of the gene transcripts in discrete brain region throughout ontogeny. In addition, the sex steroid hormone levels and aromatase activity in brain at different developmental states and the changes in the gene expression patterns in response to aromatase inhibitor treatment are also discussed. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source]

Transthyretin as a potential CSF biomarker for Alzheimer's disease and dementia with Lewy bodies: effects of treatment with cholinesterase inhibitors

EUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2010
K. Schultz
Background:, Previous studies have indicated that transthyretin (TTR) levels in cerebrospinal fluid (CSF) are altered in depression and dementia. The present study aimed to investigate whether CSF TTR can be used to discriminate between patients with Alzheimer's disease (AD) and patients with dementia with Lewy bodies (DLB) with or without medication, as well as to reveal whether CSF TTR correlates with depression in dementia. Methods:, CSF samples from 59 patients with AD, 13 patients with DLB and 13 healthy controls were collected, and biochemical analysis was performed. Subjects were assessed for the presence of depression. Results:, No significant differences in CSF TTR were found between AD, DLB, and control subjects or between depressed and non-depressed dementia patients. Interestingly, we found a significant reduction in CSF TTR (14%) in AD patients who were medicated with cholinesterase inhibitors compared to those AD patients who were not. Conclusions:, Significant reductions in CSF TTR were found after cholinesterase inhibitor treatment in patients with AD compared to untreated individuals. CSF TTR was unaltered in patients with DLB and had no relationship to depression in the present cohort with dementias. [source]

A tripartite motif protein TRIM11 binds and destabilizes Humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2003
Takako Niikura
Abstract Humanin (HN) is a newly identified neuroprotective peptide that specifically suppresses Alzheimer's disease (AD)-related neurotoxicity. HN peptide has been detected in the human AD brain as well as in mouse testis and colon by immunoblot and immunohistochemical analyses. By means of yeast two-hybrid screening, we identified TRIM11 as a novel HN-interacting protein. TRIM11, which is a member of protein family containing a tripartite motif (TRIM), is composed of a RING finger domain, which is a putative E3 ubiquitin ligase, a B-box domain, a coiled-coil domain and a B30.2 domain. Deletion of the B30.2 domain in TRIM11 abolished the interaction with HN, whereas the B30.2 domain alone did not interact with HN. For their interaction, at least the coiled-coil domain was indispensable together with the B30.2 domain. The intracellular level of glutathione S -transferase-fused or EGFP-fused HN peptides or plain HN was drastically reduced by the coexpression of TRIM11. Disruption of the RING finger domain by deleting the first consensus cysteine or proteasome inhibitor treatment significantly diminished the effect of TRIM11 on the intracellular level of HN. These results suggest that TRIM11 plays a role in the regulation of intracellular HN level through ubiquitin-mediated protein degradation pathways. [source]

Molecular basis of resistance to cytochrome bc1 inhibitors

FEMS YEAST RESEARCH, Issue 2 2008
Nick Fisher
Abstract Inhibitors of the mitochondrial respiratory chain enzyme cytochrome bc1 (respiratory complex III) have been developed as antimicrobial agents. They are used in agriculture to control plant pathogenic fungi and in medicine against human pathogens, such as the malaria parasite Plasmodium falciparum, or Pneumocystis jiroveci (an opportunistic pathogenic fungus life-threatening in immuno-compromised patients). These respiratory inhibitors are thus effective against a broad range of important pathogens. Unfortunately, the problem of acquired resistance has rapidly emerged. A growing number of pathogen isolates resistant to inhibitor treatment have been reported, and this resistance is often linked to mutation within cytochrome b, one of the essential catalytic subunits of the complex. Saccharomyces cerevisiae is an invaluable model in order to assess the impact of the mutations on the sensitivity to the drugs, on the respiratory capacity and the fitness of cells. In this minireview, the inhibitors, their mode of action, and the mutations implicated in resistance and studied in yeast are briefly reviewed. Four mutations that are of particular importance in medicine and in agriculture are briefly reviewed and described in more detail and the molecular basis of resistance and of evolution of the mutations is discussed succinctly. [source]

Genetics of dermatofibrosarcoma protuberans family of tumors: From ring chromosomes to tyrosine kinase inhibitor treatment

GENES, CHROMOSOMES AND CANCER, Issue 1 2003
Nicolas Sirvent
Dermatofibrosarcoma protuberans (DP) is a rare, slow-growing, infiltrating dermal neoplasm of intermediate malignancy, made up of spindle-shaped tumor cells often positive for CD34. The preferred treatment is wide surgical excision with pathologically negative margins. At the cytogenetic level, DP cells are characterized by either supernumerary ring chromosomes, which have been shown by using fluorescence in situ hybridization techniques to be derived from chromosome 22 and to contain low-level amplified sequences from 17q22-qter and 22q10,q13.1, or t(17;22), that are most often unbalanced. Both the rings and linear der(22) contain a specific fusion of COL1A1 with PDGFB. Similar to other tumors, the COL1A1-PDGFB fusion is occasionally cryptic, associated with complex chromosomal rearrangements. Although rings have been mainly observed in adults, translocations have been reported in all pediatric cases. DP is therefore a unique example of a tumor in which (i) the same molecular event occurs either on rings or linear translocation derivatives, (ii) the chromosomal abnormalities display an age-related pattern, and (iii) the presence of the specific fusion gene is associated with the gain of chromosomal segments, probably taking advantage of gene dosage effects. In all DP cases that underwent molecular investigations, the breakpoint localization in PDGFB was found to be remarkably constant, placing exon 2 under the control of the COL1A1 promoter. In contrast, the COL1A1 breakpoint was found to be variably located within the exons of the ,-helical coding region (exons 6,49). No preferential COL1A1 breakpoint and no correlation between the breakpoint location and the age of the patient or any clinical or histological particularity have been described. The COL1A1-PDGFB fusion is detectable by multiplex RT-PCR with a combination of forward primers designed from a variety of COL1A1 exons and one reverse primer from PDGFB exon 2. Recent studies have determined the molecular identity of "classical" DP, giant cell fibroblastoma, Bednar tumor, adult superficial fibrosarcoma, and the granular cell variant of DP. In approximately 8% of DP cases, the COL1A1-PDGFB fusion is not found, suggesting that genes other than COL1A1 or PDGFB might be involved in a subset of cases. It has been proposed that PDGFB acts as a mitogen in DP cells by autocrine stimulation of the PDGF receptor. It is encouraging that inhibitory effects of the PDGF receptor tyrosine kinase antagonist imatinib mesylate have been demonstrated in vivo; such targeted therapies might be warranted in the near future for treatment of the few DP cases not manageable by surgery. © 2003 Wiley-Liss, Inc. [source]

The Effects of Cyclooxygenase2,ProstaglandinE2 Pathway on Helicobacter pylori -Induced Urokinase-Type Plasminogen Activator System in the Gastric Cancer Cells

HELICOBACTER, Issue 3 2008
Junichi Iwamoto
Abstract Background:, Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an important role in the destruction of the extracellular matrix and basement membrane. The induction of uPA and uPAR in the gastric cancer cells with H. pylori has been demonstrated previously. The involvement of COX-2-PGE2 pathway in the uPA system (uPA and uPAR) expression is unclear. Methods:, Gastric cancer cells (MKN45) were co-cultured with H. pylori standard strain (NCTC11637). The specific inductions of uPA and uPAR mRNA were examined by reverse transcription-polymerase chain reaction amplification. The secreted uPA antigen was measured by ELISA. To evaluate the involvement of COX-2 and PGE2 pathway in H. pylori -induced uPA and uPAR expressions, we examined the effects of COX-2 inhibitor and PGE2 receptor antagonist on H. pylori -induced uPA and uPAR expression in the gastric cancer cells. Results:, The expressions of both uPA and uPAR mRNAs in the gastric cancer cells increased obviously (12-fold and 3-fold, respectively) with H. pylori stimulation. The amount of uPA antigen into the culture medium increased dramatically with H. pylori stimulation. The COX-2 expression level in the gastric cancer cells increased remarkably with H. pylori stimulation. H. pylori -induced uPA and uPAR expression levels were suppressed with COX2 inhibitor treatment. The amount of PGE2 antigen into the culture medium increased dramatically 24 hours after H. pylori stimulation. The gastric cancer cells expressed EP2 and EP4 subtypes. EP2 receptor antagonist suppressed the H. pylori -induced uPA and uPAR expressions in the gastric cancer cells. Conclusions:, Our results indicated that COX2-PGE2 pathway may be involved in H. pylori- associated uPA and uPAR induction, and that COX-2 inhibitor or EP2 receptor antagonist may inhibit angiogenesis and tumor invasion via suppression of the uPA system. [source]

Factors associated with virological response in HIV-infected patients failing antiretroviral therapy: a prospective cohort study

HIV MEDICINE, Issue 2 2005
S Fournier
Objectives To assess the antiviral response to optimized therapy following genotypic resistance testing and to identify factors associated with virological response in HIV-1-infected patients failing antiretroviral therapy. Methods A prospective cohort study was conducted in 344 HIV-1-infected patients who underwent genotypic resistance testing because of virological failure. Virological response was defined as a plasma HIV RNA level below 200 HIV-1 RNA copies/mL or a drop of plasma viral load from baseline of more than 1 log10. A multivariate logistic regression analysis was performed to identify factors associated with virological response. Results The median age of the patients was 40 years, with a male to female ratio of 4:1. Fifty-one per cent of patients had received the three major classes of antiretrovirals and the median duration of previous antiretroviral therapy was 4.6 years. At baseline, the median plasma HIV RNA level was 4.4 log10 copies/mL and the median CD4 cell count was 274 cells/,L. At 3 months, 55% of patients (188 of 344) had a virological response, which was sustained at 6 months (53%). Predictors of virological response were exposure to two or fewer protease inhibitors [odds ratio (OR) 1.8; P=0.046], and use in optimized therapy of a new class of antiretrovirals (OR 2.9; P=0.006), of more than two new drugs (OR 3.0; P<0.0001), of abacavir (OR 1.9; P=0.03), or of lopinavir/ritonavir (OR 3.7; P=0.0002). Conclusions A high proportion of patients achieved a short-term virological response in this cohort study. Patients with the least experience of protease inhibitor treatment and in whom a new class of antiretroviral, more than two new drugs, abacavir or lopinavir/ritonavir was used in optimized therapy had the best virological outcome. [source]

99mTc-MIBI imaging for prediction of therapeutic effects of second-generation MDR1 inhibitors in malignant brain tumors

INTERNATIONAL JOURNAL OF CANCER, Issue 12 2007
Toshio Sasajima
Abstract The aim of this study was to explore whether 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) is suitable to elucidate multidrug resistance and prediction of potentiation of antitumor agents by second-generation MDR1 inhibitors (PSC833, MS-209) in malignant brain tumors in rat. Malignant tumor cells (RG2 and C6 gliomas, Walker 256 carcinoma) were incubated with low dose vincristine (VCR) to induce multidrug resistance. MTT assay demonstrated a significant increase of surviving fractions in VCR-resistant sublines compared to those of drug-naive cells. Reverse transcriptase polymerase chain reaction revealed higher expression of MDR1 mRNA in VCR-resistant cells than drug-naive cells in each line. Volume distribution (Vd) of 99mTc-MIBI was negatively correlated with MDR1 mRNA expression among drug-naive and VCR-resistant cells. MDR1 inhibitors decreased surviving fractions and increased Vd of 99mTc-MIBI significantly in VCR-resistant sublines, whereas MDR1 mRNA expression was unchanged. These findings indicate that 99mTc-MIBI efflux was functionally suppressed by MDR1 inhibitors. Autoradiographic images of 99mTc-MIBI revealed higher uptake in drug-naive cells at basal ganglia compared with VCR-resistant cells at the opposite basal ganglia of rats. Oral administration of the second-generation MDR1 inhibitors significantly increased 99mTc-MIBI accumulation of both tumors. Therapeutic effects of VCR with or without the MDR1 inhibitors were also evaluated autoradiographically using 14C-methyl- L -methionine (14C-Met) and MIB-5 index. 14C-Met uptake and MIB-5 index of both tumors treated with VCR following the MDR1 inhibitor treatment significantly decreased compared with tumors treated with VCR alone. Analysis of 99mTc-MIBI accumulation is considered informative for detecting MDR1-mediated drug resistance and for monitoring the therapeutic effects of MDR1 inhibitors in malignant brain tumors. © 2007 Wiley-Liss, Inc. [source]

Hypertension, white matter change and response to cholinesterase inhibitors in Alzheimer's disease

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 7 2005
Peter J. Connelly
Abstract Background Cholinesterase inhibitors are used to treat mild to moderate Alzheimer's disease. Their role in patients with concurrent cerebrovascular disease has been less well studied, and the influence of vascular risk factors on response to treatment is uncertain. We investigated the effect of hypertension and white matter lesions (WML) on response. Methods A retrospective sample of 160 consecutive out-patients who had blood pressure measured and the presence or absence of WML recorded at baseline and who completed six months treatment with a cholinesterase inhibitor was studied. Subjects scored either zero or one on the Modified Hachinski Ischaemic Scale. Subjects were assessed using the Mini-Mental State Examination (MMSE), the Digit Symbol Substitution test (DSST) and both the Instrumental Activities of Daily Living (IADL) and Social Behaviour (SB) sub-scales of the Nurses Observation Scale for Geriatric Patients (NOSGER). Results 43.9% of the total study population were classified as good responders using our criteria. Neither the presence of hypertension nor the presence of WML alone influenced outcome. However, there was a statistically significant interaction between blood pressure and WML on outcome variables on multiple analysis of variance (MANOVA) (F(4,,139),=,5.60, p,<,0.0005). Subjects with both hypertension and WML deteriorate to a significantly greater extent in IADL and SB scores than any other group (p,<,0.05 in each case). This effect could not be explained by age or by smoking status. Conclusion Our results support the hypothesis that there is an interaction between hypertension and WML that adversely influences functional change during cholinesterase inhibitor treatment. Our results are a contrast to suggestions that subjects with vascular disease show a better response to cholinesterase inhibitors. We recommend careful exploration of factors that may influence outcome. Copyright © 2005 John Wiley & Sons, Ltd. [source]

BACE1 inhibition reduces endogenous Abeta and alters APP processing in wild-type mice,

JOURNAL OF NEUROCHEMISTRY, Issue 6 2006
Kouhei Nishitomi
Abstract Accumulation of amyloid beta peptide (Abeta) in brain is a hallmark of Alzheimer's disease (AD). Inhibition of beta-site amyloid precursor protein (APP)-cleaving enzyme-1 (BACE1), the enzyme that initiates Abeta production, and other Abeta-lowering strategies are commonly tested in transgenic mice overexpressing mutant APP. However, sporadic AD cases, which represent the majority of AD patients, are free from the mutation and do not necessarily have overproduction of APP. In addition, the commonly used Swedish mutant APP alters APP cleavage. Therefore, testing Abeta-lowering strategies in transgenic mice may not be optimal. In this study, we investigated the impact of BACE1 inhibition in non-transgenic mice with physiologically relevant APP expression. Existing Abeta ELISAs are either relatively insensitive to mouse Abeta or not specific to full-length Abeta. A newly developed ELISA detected a significant reduction of full-length soluble Abeta 1,40 in mice with the BACE1 homozygous gene deletion or BACE1 inhibitor treatment, while the level of x-40 Abeta was moderately reduced due to detection of non-full-length Abeta and compensatory activation of alpha-secretase. These results confirmed the feasibility of Abeta reduction through BACE1 inhibition under physiological conditions. Studies using our new ELISA in non-transgenic mice provide more accurate evaluation of Abeta-reducing strategies than was previously feasible. [source]

Review article: gastro-oesophageal reflux disease and psychological comorbidity

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009
I. MIZYED
Summary Background, A growing number of studies have shown the impact of psychological comorbidities on gastro-oesophageal reflux disease (GERD) patients' symptom reports and healthcare-seeking behaviour. Aim, To review the reported relationship between GERD and psychological comorbidity. Methods, Review of the literature on GERD and psychological comorbidity. Results, Psychological comorbidity is common among GERD patients and appears to afflict all GERD phenotypes. Sexual and physical abuse is also common in GERD patients. Stress enhances perception of oesophageal acid exposure. Treatment for GERD, especially in those who are not responsive to antireflux treatment, may require further evaluation for psychological comorbidity. Conclusions, Psychological comorbidity is very common in GERD patients and is likely to play an important role in response, or failure of response, to proton pump inhibitor treatment. [source]

Symptom overlap in patients with upper gastrointestinal complaints in the Canadian confirmatory acid suppression test (CAST) study: further psychometric validation of the reflux disease questionnaire

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2007
S. V. VAN ZANTEN
Summary Background The reflux disease questionnaire (RDQ) is a short, patient-completed instrument. Aims To investigate the psychometric characteristics of the RDQ in patients with heartburn-predominant (HB) and non-heartburn predominant (NHB) dyspepsia. Methods HB (n = 388) and NHB (n = 733) patients were randomized to esomeprazole 40 mg daily or twice daily for 1 week, followed by 3 weeks of esomeprazole 40 mg daily. Results High factor loadings (0.78,0.86) supported the ,regurgitation' dimension of the RDQ. Overlapping factor loadings in the ,heartburn' and ,dyspepsia' dimensions suggested symptom overlap. All dimensions demonstrated high internal consistency (Cronbach's alpha: 0.79,0.90). Intra-class correlation coefficients over 4 weeks were good (0.66,0.85). The RDQ showed good responsiveness over 4 weeks of treatment, with high effect sizes (,0.80). Moderate or large symptom improvements were reported by 90% and 77% of HB and NHB patients, respectively, following treatment. Patients who responded to acid suppression also experienced symptom benefits in all RDQ dimensions. Conclusions The RDQ is reliable, valid and responsive to change in HB and NHB patients. The symptom overlap is important but need not play a major role in determining treatment strategy as both patient groups benefited from proton pump inhibitor treatment. [source]

Improved diagnosis of gastro-oesophageal reflux in patients with unexplained chronic cough

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2007
K. BLONDEAU
Summary Background Symptoms, oesophageal pHmetry and proton pump inhibitor treatment are used for diagnosing gastro-oesophageal reflux-related cough. Weakly acidic reflux is now increasingly associated with reflux symptoms such as regurgitation or chest pain. Aim To study the association between weakly acidic reflux and cough in a selected, large group of patients with unexplained chronic cough. Methods A total of 100 patients with chronic cough (77 ,off' and 23 ,on' a proton pump inhibitor) were studied using impedance-pHmetry for reflux detection and manometry for objective cough monitoring. Symptom Association Probability (SAP) Analysis characterized the reflux,cough association. Results Acid reflux could be a potential mechanism for cough in 45 patients (with either heartburn, high acid exposure or +SAP for acid reflux). Weakly acidic reflux could be a potential mechanism for cough in 24 patients (with either increased oesophageal volume exposure, increased number of weakly acidic reflux or +SAP for weakly acidic reflux). Reflux could not be identified as a potential mechanism for cough in 31 patients. Conclusion A positive association between cough and weakly acidic reflux was found in a significant subgroup of patients with unexplained chronic cough. Impedance-pH-manometry identified patients in whom cough can be related to reflux that would have been disregarded using the standard diagnostic criteria for acid reflux. [source]

Frequency analyses of gastric pH in control and gastro-oesophageal reflux disease subjects treated with a proton-pump inhibitor

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11-12 2004
J. D. Gardner
Summary Background :,We are unaware of any solid theoretical or pathophysiological basis for selecting pH 4 or any other pH value to assess gastric acidity. Aim :,To examine the frequency of different gastric pH values in control and GERD subjects. Methods :,Gastric pH was measured for 24 h in 26 control subjects, 26 gastro-oesophageal reflux disease subjects at baseline and the same 26 gastro-oesophageal reflux disease subjects during treatment with a proton-pump inhibitor. Histograms were constructed using the 21 600 values generated from each recording and bins of 0.25 pH units. Results :,The distribution of gastric pH values in gastro-oesophageal reflux disease subjects was significantly different from that in controls and in some instances the distributions detected significant differences that were not detected by integrated acidity. Proton-pump inhibitor treatment significantly altered the distribution of gastric pH values and the nature of this alteration during the postprandial period was different from that during the nocturnal period. Using time pH,4 can significantly underestimate the magnitude of inhibition of gastric acidity caused by a proton-pump inhibitor. Conclusions :,The distribution of gastric pH values provides a rationale for selecting a particular pH value to assess gastric acidity. In some instances, the distribution of gastric pH values detects significant differences between gastro-oesophageal reflux disease and normal subjects that are not detected by integrated acidity. [source]

Treatment with a proton pump inhibitor promotes corpus gastritis in patients with Helicobacter pylori -infected antrum-predominant gastritis

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2002
M. Suzuki
Background: Proton pump inhibitors have been reported to modify the level of Helicobacter pylori gastritis. Aim: To quantitatively investigate the effect of a proton pump inhibitor on the mucosal neutrophil reaction. Methods: Forty-six H. pylori -infected patients (17 duodenal ulcer, 29 gastric ulcer) were enrolled. During endoscopic examination, biopsy samples were obtained from the antrum and the corpus. The tissue content of neutrophil myeloperoxidase was measured by enzyme-linked immunoabsorbent assay, and H. pylori infection was histologically assessed. A proton pump inhibitor was administered orally for 8 weeks. Results: In the patients as a whole, antral myeloperoxidase decreased significantly after proton pump inhibitor treatment, but corpus myeloperoxidase remained largely unchanged. In duodenal ulcer patients, myeloperoxidase significantly decreased in the antrum, but increased in the corpus. In gastric ulcer patients, a significant reduction was observed in antral myeloperoxidase, but corpus myeloperoxidase remained unchanged. In the antral myeloperoxidase > corpus myeloperoxidase subgroup (n=24), antral myeloperoxidase significantly decreased, whereas corpus myeloperoxidase increased. No changes were observed at either site in the corpus myeloperoxidase > antral myeloperoxidase subgroup. Histology showed that the antral bacterial load of H. pylori decreased in all subgroups, but that it was mostly unchanged in the corpus. Conclusions: Proton pump inhibitor treatment stimulated the neutrophil reaction in the corpus mucosa of duodenal ulcer patients and of patients in whom antral neutrophil accumulation was more predominant than that of the corpus. This phenomenon may not be caused by increased bacterial density. [source]

Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2000
Laine
This review examines the evidence for the development of adverse effects due to prolonged gastric acid suppression with proton pump inhibitors. Potential areas of concern regarding long-term proton pump inhibitor use have included: carcinoid formation; development of gastric adenocarcinoma (especially in patients with Helicobacter pylori infection); bacterial overgrowth; enteric infections; and malabsorption of fat, minerals, and vitamins. Prolonged proton pump inhibitor use may lead to enterochromaffin-like cell hyperplasia, but has not been demonstrated to increase the risk of carcinoid formation. Long-term proton pump inhibitor treatment has not been documented to hasten the development or the progression of atrophic gastritis to intestinal metaplasia and gastric cancer, although long-term studies are required to allow definitive conclusions. At present, we do not recommend that patients be tested routinely for H. pylori infection when using proton pump inhibitors for prolonged periods. Gastric bacterial overgrowth does increase with acid suppression, but important clinical sequelae, such a higher rate of gastric adenocarcinoma, have not been seen. The risk of enteric infection may increase with acid suppression, although this does not seem to be a common clinical problem with prolonged proton pump inhibitor use. The absorption of fats and minerals does not appear to be significantly impaired with chronic acid suppression. However, vitamin B12 concentration may be decreased when gastric acid is markedly suppressed for prolonged periods (e.g. Zolllinger,Ellison syndrome), and vitamin B12 levels should probably be assessed in patients taking high-dose proton pump inhibitors for many years. Thus, current evidence suggests that prolonged gastric acid suppression with proton pump inhibitors rarely, if ever, produces adverse events. Nevertheless, continued follow-up of patients taking proton pump inhibitors for extended periods will provide greater experience regarding the potential gastrointestinal adverse effects of long-term acid suppression. [source]

A viral PAMP double-stranded RNA induces allergen-specific Th17 cell response in the airways which is dependent on VEGF and IL-6

ALLERGY, Issue 10 2010
J.-P. Choi
To cite this article: Choi J-P, Kim Y-S, Tae Y-M, Choi E-J, Hong B-S, Jeon SG, Gho YS, Zhu Z, Kim Y-K. A viral PAMP double-stranded RNA induces allergen-specific Th17 cell response in the airways which is dependent on VEGF and IL-6. Allergy 2010; 65: 1322,1330. Abstract Background:, Innate immune response by a viral pathogen-associated molecular pattern dsRNA modulates the subsequent development of adaptive immune responses. Although virus-associated asthma is characterized by noneosinophilic inflammation, the role of Th17 cell response in the development of virus-associated asthma is still unknown. Objective:, To evaluate the role of the Th17 cell response and its underlying polarizing mechanisms in the development of an experimental virus-associated asthma. Methods:, An experimental virus-associated asthma was created via airway sensitization with ovalbumin (OVA, 75 ,g) and a low (0.1 ,g) or a high (10 ,g) doses of synthetic dsRNA [polyinosine,polycytidylic acid; poly(I:C)]. Transgenic (IL-17-, IL-6-deficient mice) and pharmacologic [a vascular endothelial growth factor receptor (VEGFR) inhibitor] approaches were used to evaluate the roles of Th17 cell responses. Results:, After cosensitization with OVA and low-dose poly(I:C), but not with high-dose poly(I:C), inflammation scores after allergen challenge were lower in IL-17-deficient mice than in wild-type (WT) mice. Moreover, inflammation enhanced by low-dose poly(I:C), but not by high-dose poly(I:C), was impaired in IL-6-deficient mice; this phenotype was accompanied by the down-regulation of IL-17 production from T cells from both lymph nodes and lung tissues. Airway exposure of low-dose poly(I:C) enhanced the production of VEGF and IL-6, and the production of IL-6 was blocked by treatment with a VEGFR inhibitor (SU5416). Moreover, the allergen-specific Th17 cell response and subsequent inflammation in the low-dose poly(I:C) model were impaired by the VEGFR inhibitor treatment during sensitization. Conclusions:, Airway exposure of low-level dsRNA induces an allergen-specific Th17 cell response, which is mainly dependent on VEGF and IL-6. [source]

Investigations of an ethanolamine-based corrosion inhibitor system for surface treatment of reinforced concrete

MATERIALS AND CORROSION/WERKSTOFFE UND KORROSION, Issue 7 2004
V. T. Ngala
Abstract Laboratory investigations were performed to assess the efficacy of a proprietary ethanolamine-based corrosion inhibitor system when applied to the surface of reinforced concrete specimens that were chloride-contaminated to varying extents in the presence or absence of carbonation. The corrosion responses of embedded steel bars at various depths of cover were monitored electrochemically during a controlled programme of cyclic wetting and drying undertaken for several months prior to the inhibitor treatment and for approximately eighteen months thereafter. Gravimetric measurements of the quantities and distribution of corrosion on the steel were also made on completion of the exposure tests. Analysis of aqueous extracts from treated concrete revealed that the ethanolamine component of the inhibitor system penetrated to depths of more than 15 mm within the concrete. It was found that, for inhibitor-treated specimens, there was some reduction in the corrosion rate of pre-corroding steel at low cover depths in non-carbonated concrete with modest levels of chloride contamination. At higher levels of chloride contamination and in carbonated specimens, however, the ethanolamine-based inhibitor was apparently ineffective under the conditions investigated. [source]

Renal ACE2 expression in human kidney disease,

THE JOURNAL OF PATHOLOGY, Issue 5 2004
AT Lely
Abstract Angiotensin-converting enzyme 2 (ACE2) is a recently discovered homologue of angiotensin-converting enzyme (ACE) that is thought to counterbalance ACE. ACE2 cleaves angiotensin I and angiotensin II into the inactive angiotensin 1,9, and the vasodilator and anti-proliferative angiotensin 1,7, respectively. ACE2 is known to be present in human kidney, but no data on renal disease are available to date. Renal biopsies from 58 patients with diverse primary and secondary renal diseases were studied (hypertensive nephropathy n = 5, IgA glomerulopathy n = 8, minimal change nephropathy n = 7, diabetic nephropathy n = 8, focal glomerulosclerosis n = 5, vasculitis n = 7, and membranous glomerulopathy n = 18) in addition to 17 renal transplants and 18 samples from normal renal tissue. Immunohistochemical staining for ACE2 was scored semi-quantitatively. In control kidneys, ACE2 was present in tubular and glomerular epithelium and in vascular smooth muscle cells and the endothelium of interlobular arteries. In all primary and secondary renal diseases, and renal transplants, neo-expression of ACE2 was found in glomerular and peritubular capillary endothelium. There were no differences between the various renal disorders, or between acute and chronic rejection and control transplants. ACE inhibitor treatment did not alter ACE2 expression. In primary and secondary renal disease, and in transplanted kidneys, neo-expression of ACE2 occurs in glomerular and peritubular capillary endothelium. Further studies should elucidate the possible protective mechanisms involved in the de novo expression of ACE2 in renal disease. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Efficacy of Phosphodiesterase Type 5 Inhibitor Treatment in Men with Erectile Dysfunction and Dyslipidemia: A Post Hoc Analysis of the Vardenafil Statin Study

Timing of Dose Relative to Sexual Intercourse Attempt in Previous Sildenafil Citrate Users Treated with Tadalafil: A Geographical Comparison from a Single Arm, Open-Label Study

THE JOURNAL OF SEXUAL MEDICINE, Issue 10 2009
Eusebio Rubio-Aurioles MD
ABSTRACT Introduction., Previous research has demonstrated that sildenafil citrate users alter dosing-sexual attempt behavior when switched to tadalafil. The impact of geography and culture on sexual behavior with phosphodiesterase type 5 (PDE5) inhibitor treatment has not been fully investigated. Aim., To describe and compare the changes in dosing-sexual attempt behavior with sildenafil citrate vs. tadalafil treatment across four distinct geographies: Asia, Australia/New Zealand (ANZ), Central Eastern Europe/Middle East (CEE/ME), and Latin America (LA). Methods., Data from a single-arm, open-label clinical trial conducted in 21 countries from November 2002 to May 2004 were used in this analysis. Men with erectile dysfunction and a history of ,6-week prior sildenafil citrate use continued sildenafil citrate treatment for 4 weeks then switched to tadalafil for 8 weeks. Dosing instructions were provided. Main Outcomes Measures., Timing of dose and sexual intercourse was assessed through patient diaries for the final 4 weeks of each treatment period. Results., A total of 2,760 men were enrolled: Asia 15.8%; ANZ 29.4%; CEE/ME 19.7%; LA 35.1%. The median time from dosing to intercourse was significantly increased during tadalafil treatment across all geographical regions; however, the magnitude of increase differed significantly by geography (P < 0.0001). The Asian cohort demonstrated the shortest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the least upon switching to tadalafil. The ANZ cohort demonstrated the longest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the most upon switching to tadalafil. Conclusion., Men with a history of established sildenafil citrate use alter their dose-attempt behavior when treated with tadalafil irrespective of geography. However, the extent to which sexual behavior alters is not uniform across geographical regions, suggesting that dosing instructions and duration of drug effectiveness, in combination with personal and cultural preferences, may determine sexual behavior with PDE5 inhibitor use. Rubio-Aurioles E, Glina S, Abdo CHN, Hernandez-Serrano R, Rampazzo C, Sotomayor M, West TM, Gallagher GL, and Lenero E. Timing of dose relative to sexual intercourse attempt in previous sildenafil citrate users treated with tadalafil: A geographical comparison from a single arm, open-label study. J Sex Med 2009;6:2836,2850. [source]

Feasibility of the Use of Phosphodiesterase Type 5 Inhibitors in a Pharmacologic Prevention Program for Recurrent Priapism

THE JOURNAL OF SEXUAL MEDICINE, Issue 6 2006
Arthur L. Burnett MD
ABSTRACT Introduction., Recurrent ischemic priapism is an enigmatic erectile disorder in need of improved clinical interventions to avert its known, potentially serious complications. Aim., To evaluate the use of a long-term, continuous phosphodiesterase type 5 (PDE5) inhibitor therapeutic regimen in controlling recurrent ischemic priapism and its feasibility in a clinical management program for the disorder. Main Outcome Measures., The main outcome measure was reduction in frequency or duration of priapism episodes. A secondary outcome measure was preservation of erectile ability. Methods., We retrospectively evaluated the clinical progress of seven patients (age 22,37 years) with sickle cell disease-associated "stuttering" priapism (N = 4) and idiopathic recurrent priapism (N = 3), who were counseled and consented to the "off-label" use of the PDE5 inhibitors sildenafil citrate and tadalafil. The medications were administered according to a specified therapeutic regimen based on scientific evidence that chronic PDE5 inhibitor administration in priapism contexts effectively reconditions PDE5 regulatory function in the penis. The duration of clinical follow-up extended through 2 years. Results., All seven patients were confirmed to have recurrent ischemic priapism without identifiable pharmacologic, traumatic, or neoplastic disease associations based on clinical history, physical examination, laboratory testing, and penile diagnostics. PDE5 inhibitor treatment was successful in alleviating or resolving priapism recurrences in six of the seven patients. Erectile function was unchanged in six patients and improved in one patient at last follow-up compared with baseline status. All the patients reported that PDE5 inhibitor therapy was well tolerated and did not cause any adverse effects limiting their continued use of the medication. Conclusions., Because of their efficacy, safety, and tolerability as shown in this case series, PDE5 inhibitors would appear to have a possible role in a rigorously implemented clinical management program to control recurrent priapism. However, completion of a controlled clinical trial is necessary to confirm the utility of this treatment. Burnett AL, Bivalacqua TJ, Champion HC, and Musicki B. Feasibility of the use of phosphodiesterase type 5 inhibitors in a pharmacologic prevention program for recurrent priapism. J Sex Med 2006;3:1077,1084. [source]

ORIGINAL ARTICLE: Treatment with Tumor Necrosis Factor Inhibitors and Intravenous Immunoglobulin Improves Live Birth Rates in Women with Recurrent Spontaneous Abortion

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2008
Edward E. Winger
Problem, The purpose of this study was to investigate whether treatment with tumor necrosis factor (TNF) inhibitors combined with intravenous immunoglobulin (IVIG) increases live birth rates among women with recurrent spontaneous abortion (RSA) concurrently treated with anticoagulants (AC). Method of study, Seventy-five pregnancies in patients with a history of RSA were retrospectively evaluated. The population was divided into three groups: group I: 21 patients treated with AC (anticoagulants), group II: 37 patients treated with AC and IVIG, and group III: 17 patients treated with AC, IVIG and the TNF inhibitor Etanercept (Enbrel®) or Adalimumab (Humira®). In groups II and III, IVIG was administered at least once during the cycle of conception and/or at least once after a positive pregnancy test. In group III, either Adalimumab or Etanercept was administered by subcutaneous injection according to standard protocols. Statistical analysis of pregnancy outcome was performed using Fisher's exact test. Results, Patient populations in the three treatment groups were similar in terms of age, past miscarriages, inherited thrombophilia and autoimmunity. The live birth rate was 19% (4/21) in group I, 54% (20/37) in group II, and 71% (12/17) in group III. There was significant improvement in pregnancy outcome in group II versus group I (P = 0.0127) and in group III versus group I (P = 0.0026). The live birth rate in group III compared to group II was not significantly different (P = 0.3723). Side effects of AC, IVIG and TNF inhibitor treatment were minimal in these patients, and no birth defects were identified in their offspring. Conclusion, In women with RSA, addition of either IVIG or a TNF inhibitor + IVIG to the AC regimen appears to improve live birth rates compared to the treatment with AC alone. The positive effect of IVIG and TNF inhibitor therapy on pregnancy outcome merits further study in prospective clinical trials. [source]

Sustained improvement of spinal muscular atrophy mice treated with trichostatin a plus nutrition

ANNALS OF NEUROLOGY, Issue 4 2008
Heather L. Narver VMD
Early treatment with the histone deacetylase inhibitor, trichostatin A, plus nutritional support extended median survival of spinal muscular atrophy mice by 170%. Treated mice continued to gain weight, maintained stable motor function, and retained intact neuromuscular junctions long after trichostatin A was discontinued. In many cases, ultimate decline of mice appeared to result from vascular necrosis, raising the possibility that vascular dysfunction is part of the clinical spectrum of severe spinal muscular atrophy. Early spinal muscular atrophy disease detection and treatment initiation combined with aggressive ancillary care may be integral to the optimization of histone deacetylase inhibitor treatment in human patients. Ann Neurol 2008; 64:465,470 [source]

Gastric fundic gland polyps: a clinico-pathological study from North West Tasmania

ANZ JOURNAL OF SURGERY, Issue 6 2009
Inian Samarasam
Abstract Background:, Fundic gland polyps (FGPs) of the stomach were originally described in association with familial polyposis syndromes. It is now known that the majority of these polyps occur in the sporadic setting and are incidentally seen in up to 1.9% of routine upper gastrointestinal endoscopes. The aim of this study was to look at the clinico-pathological features of the FGPs and to analyse their relationship to Helicobacter pylori infection, proton pump inhibitor treatment, colonic polyps and malignancy. Methods:, A search of the histopathology records for a period of 10 years from 1997 to 2006 identified 120 patients with a histologically confirmed diagnosis of FGPs. The clinical history, upper gastrointestinal endoscopy findings, histopathology and colonoscopy findings were recorded from the medical records and analysed. Results:, FGPs were seen in 3.2% of patients undergoing routine upper gastrointestinal endoscopes. There was a definite association with long-term proton pump inhibitor treatment. There was a strikingly low incidence of H. pylori infection in the study population. Although there was no dysplasia or malignancy in any of these polyps, one patient had concomitant adenocarcinoma of the stomach. In the subgroup of patients who also had colonoscopy during the study period, 19% had associated colonic polyps and 6% had associated colonic malignancies. Conclusions:, Every new patient diagnosed with FGPs should have a thorough clinico-pathological study to see if the polyps are part of a sporadic or syndromic setting. A long-term follow-up study of patients with FGPs and its association with colonic polyps may be warranted. [source]

Arthritis develops but fails to resolve during inhibition of cyclooxygenase 2 in a murine model of lyme disease

ARTHRITIS & RHEUMATISM, Issue 5 2008
Victoria A. Blaho
Objective Recent studies have implicated products of cyclooxygenase 2 (COX-2) in not only induction but also resolution of the inflammatory response; however, the contribution of COX-2 products to the in vivo response to infection is unknown. The aim of this study was to determine the contribution of COX-2 to temporal regulation of the inflammatory response to infection in a murine model of Lyme arthritis. Methods Experimental Lyme disease was induced in both arthritis-resistant DBA/2J and arthritis-susceptible C3H/HeJ mice by inoculation in the hind footpads with Borrelia burgdorferi. COX-2 inhibitors were administered daily, and their effect on arthritis pathology was assessed at various time points postinfection. The COX-2 deficiency was also backcrossed onto both DBA and C3H backgrounds to confirm the findings from COX-2 inhibitor,treated mice. Results In COX-2 inhibitor,treated or COX-2,/, C3H mice, arthritis developed normally but did not resolve. Cessation of COX-2 inhibitor treatment on day 14 postinfection did not induce resolution of arthritis, indicating an early onset for the molecular mechanisms governing resolution. The lack of resolution of arthritis correlated with altered COX-2 and cytosolic phospholipase A2 messenger RNA levels in the joints of C3H mice. In addition, the proresolution lipid molecule 15-deoxy-,12,14 -prostaglandin J2 was produced in response to B burgdorferi infection, and its production was attenuated by the inhibition of COX-2. Conclusion Our results demonstrate that early production of COX-2 products is necessary for resolution of the inflammatory arthritis induced by Borrelia infection, and that COX-2 inhibition may result in prolonged inflammatory states, possibly by inhibition of proresolution eicosanoids. [source]

Role of Network Branching in Eliciting Differential Short-Term Signaling Responses in the Hypersensitive Epidermal Growth Factor Receptor Mutants Implicated in Lung Cancer

BIOTECHNOLOGY PROGRESS, Issue 3 2008
Jeremy Purvis
We study the effects of EGFR inhibition in wild-type and mutant cell lines upon tyrosine kinase inhibitor TKI treatment through a systems level deterministic and spatially homogeneous model to help characterize the hypersensitive response of the cancer cell lines harboring constitutively active mutant kinases to inhibitor treatment. By introducing a molecularly resolved branched network systems model (the molecular resolution is introduced for EGFR reactions and interactions in order to distinguish differences in activation between wild-type and mutants), we are able to quantify differences in (1) short-term signaling in downstream ERK and Akt activation, (2) the changes in the cellular inhibition EC50 associated with receptor phosphorylation (i.e., 50% inhibition of receptor phosphorylation in the cellular context), and (3) EC50 for the inhibition of activated downstream markers ERK-(p) and Akt-(p), where (p) denotes phosphorylated, upon treatment with the inhibitors in cell lines carrying both wild-type and mutant forms of the receptor. Using the branched signaling model, we illustrate a possible mechanism for preferential Akt activation in the cell lines harboring the oncogenic mutants of EGFR implicated in non-small-cell lung cancer and the enhanced efficacy of the inhibitor erlotinib especially in ablating the cellular Akt-(p) response. Using a simple phenomenological model to describe the effect of Akt activation on cellular decisions, we discuss how this preferential Akt activation is conducive to cellular oncogene addiction and how its disruption can lead to dramatic apoptotic response and hence remarkable inhibitor efficacies. We also identify key network nodes of our branched signaling model through sensitivity analysis as those rendering the network hypersensitive to enhanced ERK-(p) and Akt-(p); intriguingly, the identified nodes have a strong correlation with species implicated in oncogenic transformations in human cancers as well as in drug resistance mechanisms identified for the inhibitors in non-small-cell lung cancer therapy. [source]

Tadalafil and vardenafil vs sildenafil: a review of patient-preference studies

BJU INTERNATIONAL, Issue 9 2009
Vincenzo Mirone
The immediate objective of phosphodiesterase type 5 (PDE5) inhibitor treatment is to restore the ability of a man to achieve and/or maintain an erection adequate for sexual intercourse. As erectile dysfunction (ED) generally develops in the second half of life, the ultimate objective generally is not procreation, but quality of sexual life. Indeed, ED is known to impair quality of life considerably; two-thirds of men report that ED has impaired their self-esteem and nearly a third claim that it has damaged the relationship with their partner. It follows that the therapeutic success of PDE5 inhibition has an important subjective component, which is compounded by the subjective nature and complexity of sexual life in humans. This makes it very difficult for physicians to be certain that they have selected the optimal therapy for a couple, even after a thorough evaluation. The 2007 European Association of Urology Guidelines stress the importance of educating the patient and claim that ,the patient will choose the final drug after his own experience'. However, PDE5 inhibitors are typically used twice a week, so a patient would have to spend ,3 months trying the various compounds and dosages to achieve adequate exposure to all three PDE5 inhibitors; this would seem an unrealistic strategy in normal clinical practice. The acknowledgement that the patient has an important role in therapeutic decisions for ED has fuelled interest in the concept of patient preference. It has been established that patient preference depends on three factors, i.e. personal characteristics, e.g. age, duration of ED, frequency and dynamics of sexual relations, and the characteristics of their partners, e.g. age, menopausal status and level of interest in sexual activity and medication profile. Medication features of interest include efficacy in terms of quality of erection, consistency of effects, rapid onset of action, long duration of action, side-effect profile and route of administration; drug costs must also be considered if the medicinal product is not reimbursed. [source]