PubMed Health⌕ Search

Biomedical subjects

Chris McMahon

Publications and source records attributed to Chris McMahon.

7 recordsLinked to original sources
PubMed2006

Vardenafil improved erectile function in a "real-life" broad population study of men with moderate to severe erectile dysfunction in Australia and New Zealand.

INTRODUCTION: Phosphodiesterase type 5 inhibitor drugs produce vasodilatation by inhibiting the breakdown of cyclic guanosine monophosphate and have proven efficacy in treating erectile dysfunction (ED). AIM: To evaluate the efficacy, safety, and tolerability of vardenafil in men with moderate to severe ED of broad etiology. MAIN OUTCOME MEASURES: The erectile function (EF) domain score, the response to Questions 13 and 14 of the International Index of Erectile Function (IIEF) questionnaire, and the proportion of "yes" responses to questions 2 and 3 of the Sexual Encounter Profile (SEP), a Global Assessment (GAQ), and Global Satisfaction Questions (GSQ) were compared at baseline and at 12 weeks of treatment with as-needed vardenafil. METHODS: A total of 326 subjects with a mean age of 57.6 years and moderate to severe erectile dysfunction of various etiologies received vardenafil (5-20 mg) for 12 weeks in a prospective multicenter, open-label flexible-dose study. RESULTS: Compared with baseline, vardenafil was superior in all efficacy outcomes. A significant mean improvement of 13.4 (P < 0.001) in the EF domain from baseline was obtained at week 12. Subjects who received 5, 10, and 20 mg vardenafil at week 12 experienced improvements of 11.9, 15.1, and 12.9 respectively in the EF domain score. Sexual intercourse was successfully completed (SEP3) in 76.3%, 80.1%, and 74.3% of subjects receiving 5, 10, and 20 mg vardenafil compared with 25.9%, 17.9%, and 19.2% at baseline, respectively. For all doses combined at week 12, the change in SEP3 from baseline was 56.7% (P < 0.001). Treatment with vardenafil was well tolerated, and headaches, flushing, nasal congestion, and dyspepsia were the most frequently observed adverse events. CONCLUSIONS: Vardenafil was effective and well tolerated in men with moderate to severe erectile dysfunction. Treatment with vardenafil was associated with a significantly higher IIEF erectile function domain score and completion of successful intercourse rate compared with baseline.

Adult↗
PubMed2005

Proteolytic processing of myostatin is auto-regulated during myogenesis.

Myostatin, a potent negative regulator of myogenesis, is proteolytically processed by furin proteases into active mature myostatin before secretion from myoblasts. Here, we show that mature myostatin auto-regulates its processing during myogenesis. In a cell culture model of myogenesis, Northern blot analysis revealed no appreciable change in myostatin mRNA levels between proliferating myoblasts and differentiated myotubes. However, Western blot analysis confirmed a relative reduction in myostatin processing and secretion by differentiated myotubes as compared to proliferating myoblasts. Furthermore, in vivo results demonstrate a lower level of myostatin processing during fetal muscle development when compared to postnatal adult muscle. Consequently, high levels of circulatory mature myostatin were detected in postnatal serum, while fetal circulatory myostatin levels were undetectable. Since Furin proteases are important for proteolytically processing members of the TGF-beta superfamily, we therefore investigated the ability of myostatin to control the transcription of furin and auto-regulate the extent of its processing. Transfection experiments indicate that mature myostatin indeed regulates furin protease promoter activity. Based on these results, we propose a mechanism whereby myostatin negatively regulates its proteolytic processing during fetal development, ultimately facilitating the differentiation of myoblasts by controlling both furin protease gene expression and subsequent active concentrations of mature myostatin peptide.

Animals↗
PubMed2005

Comparison of efficacy, safety, and tolerability of on-demand tadalafil and daily dosed tadalafil for the treatment of erectile dysfunction.

OBJECTIVE: To assess and compare the efficacy of on-demand tadalafil and daily tadalafil in the treatment of erectile dysfunction. MATERIALS AND METHODS: A total of 145 men with a mean age of 57.3 years (range 19-82 years) and mild to severe erectile dysfunction of various etiologies were randomized to receive on-demand tadalafil (20 mg) or daily tadalafil (10 mg) taken without food or alcohol restrictions in a trial lasting 26 weeks. The three primary outcome measures were changes from baseline in the erectile function domain of the International Index of Erectile Function (IIEF), the proportion of "yes" responses to questions 2 and 3 of the Sexual Encounter Profile (SEP). Additional efficacy instruments included a Global Assessment Question administered at completion of the study. RESULTS: Compared with baseline, on-demand and daily tadalafil enhanced all efficacy outcomes. Patients receiving on-demand tadalafil (20 mg) and daily tadalafil (10 mg) experienced a significant mean improvement of 8.3 and 11.9, respectively, in the erectile function domain of the IIEF from baseline (P < 0.001). The mean change from baseline was significantly higher for daily dosed tadalafil than for on-demand tadalafil (P < 0.05). Sexual intercourse was successfully completed (SEP3) in 69% and 84% of patients taking on-demand tadalafil and daily tadalafil, respectively, compared with 30% at baseline (P < 0.001). Successful completion of sexual intercourse was statistically higher for daily tadalafil than for on-demand tadalafil (P < 0.05). Treatment with on-demand tadalafil or daily tadalafil was well tolerated, and headaches, facial flushing, and dyspepsia were the most frequently observed adverse events. CONCLUSION: Tadalafil was effective and well tolerated in this patient population. Treatment with daily tadalafil was associated with a significantly higher IIEF erectile function domain score and completion of successful intercourse compared with on-demand tadalafil.

Adult↗
PubMed2004

Efficacy and safety of daily tadalafil in men with erectile dysfunction previously unresponsive to on-demand tadalafil.

OBJECTIVE: To assess the efficacy and safety of daily tadalafil, a potent selective phosphodiesterase 5 inhibitor, for the treatment of erectile dysfunction (ED) in men previously unresponsive to on-demand tadalafil. MATERIALS AND METHODS: A total of 112 men with a mean age of 63 (range 21-79) and moderate to severe ED of various aetiologies were treated with tadalafil, taken on a daily basis at flexible daily doses of 10 and 20 mg for 12 weeks. The three primary outcomes were changes from the pretreatment and on-demand tadalafil baseline in the erectile function domain of the International Index of Erectile Function and the proportion of yes responses to questions 2 and 3 of the Sexual Encounter Profile. Additional efficacy instruments included a Global Assessment Question administered at completion of the study. RESULTS: Compared with pretreatment and on-demand tadalafil baseline, daily dosed tadalafil significantly enhanced all efficacy outcome variables. Patients receiving daily tadalafil (10 mg) experienced a significant mean improvement of 12.8 and 8.2 in the International Index of Erectile Function erectile function domain score from baseline (P < 0.001) and from on-demand tadalafil, respectively (P < 0.001). Fifty-eight percent of intercourse attempts (Sexual Encounter Profile question 3) were successfully completed (P < 0.001 vs. pretreatment baseline, P < 0.001 vs. on-demand tadalafil). Improved erections at end point were reported by 69% of men compared with 42% of men with on-demand tadalafil. Daily tadalafil was well tolerated with headache, dyspepsia, and facial flushing as the most frequent adverse events. CONCLUSION: Daily tadalafil (10/20 mg) was effective and well tolerated in this study population and is an effective salvage for previous on-demand tadalafil nonresponders.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

The myocardial protein S100A1 plays a role in the maintenance of normal gene expression in the adult heart.

S100A1 and S100B are members of a family of 20 kDa Ca2+-binding homodimers that play a role in signal transduction in mammalian cells. S100A1 is the major isoform in normal heart and S100B, normally a brain protein, is induced in hypertrophic myocardium and functions as an intrinsic negative modulator of the hypertrophic response. In order to examine the function of S100A1, we first showed that, in contrast to S100B, S100A1 was downregulated in rat experimental models of myocardial hypertrophy following myocardial infarction or pressure overload. Second, in co-transfection experiments in cultured neonatal rat cardiac myocytes, S100A1 inhibited the alpha1-adrenergic activation of promoters of genes induced during the hypertrophic response including the fetal genes skeletal alpha actin (skACT), and beta-myosin heavy chain (MHC) and S100B, but not the triiodothyronine (T3) activation of the promoter of the alpha-MHC gene, that is normally expressed in adult myocardium. These results suggest that S100A1 is involved in the maintenance of the genetic program that defines normal myocardial function and that its downregulation is permissive for the induction of genes that underlie myocardial hypertrophy.

Actins↗
PubMed2002

Lumican is a major proteoglycan component of the bone matrix.

MC3T3-E1 mouse calvaria cells are a clonal population of committed osteoprogenitors that in the presence of appropriate supplements form a mineralized bone matrix. The development of the MC3T3-E1 cells can be divided into three major stages, namely, proliferation, differentiation, and mineralization. Recently, using the cDNA microarray technology we found lumican to be abundantly expressed during the mineralization and differentiation stages of the MC3T3-E1 development and not during the proliferation stage. Lumican has been shown to play essential roles in regulating collagen fibril formation in different extracellular matrices but its expression in the developing bone matrix remains elusive. By examining the expression profile of this gene during the different stages of MC3T3-E1 development, utilizing the 'real-time' PCR technology, we observed that the expression of lumican increases as the osteoblast culture differentiates and matures, suggesting that lumican may be involved in regulating collagen fibrillogenesis in bone matrices. Using immunostaining, we observed that during the early embryonic development of mouse (E11 to E13), lumican is mainly expressed in the cartilaginous matrices. However, in the older embryos (E14 to E16), the expression of lumican is more prominent in the developing bone matrices. Our data suggest that lumican is a significant proteoglycan component of bone matrix, which is secreted by differentiating and mature osteoblasts only and therefore it can be used as a marker to distinguish proliferating pre-osteoblasts from the differentiating osteoblasts.

Animals↗