Citations

Background and Purpose— Evidence supports a substantial genetic contribution to the risk of intracranial aneurysm (IA). The purpose of this study was to identify chromosomal regions likely to harbor genes that contribute to the risk of IA. Methods— Multiplex families having at least 2 individuals with “definite” or “probable” IA were ascertained through an international consortium. First-degree relatives of individuals with IA who were at increased risk of an IA because of a history of hypertension or present smoking were offered cerebral magnetic resonance angiography. A genome screen was completed using the Illumina 6K SNP system, and the resulting data from 192 families, containing 1155 genotyped individuals, were analyzed. Narrow and broad disease definitions were used when testing for linkage using multipoint model-independent methods. Ordered subset analysis was performed to test for a gene×smoking (pack-years) interaction. Results— The greatest evidence of linkage was found on chromosomes 4 (LOD=2.5; 156 cM), 7 (LOD=1.7; 183 cM), 8 (LOD=1.9; 70 cM), and 12 (LOD=1.6; 102 cM) using the broad disease definition. Using the average pack-years for the affected individuals in each family, the genes on chromosomes 4 (LOD=3.5; P =0.03), 7 (LOD=4.1; P =0.01) and 12 (LOD=3.6; P =0.02) all appear to be modulated by the degree of smoking in the affected members of the family. On chromosome 8, inclusion of smoking as a covariate did not significantly strengthen the linkage evidence, suggesting no interaction between the loci in this region and smoking. Conclusions— We have detected possible evidence of linkage to 4 chromosomal regions. There is potential evidence for a gene×smoking interaction with 3 of the loci.

Erectile dysfunction (ED) is frequently associated with cardiovascular disease. Epidemiological data on the frequency of ED in vascular surgery patients is rarely reported. We evaluated the prevalence of this comorbidity in patients consulting the vascular surgery outpatient clinic. Over a 6-month period, a short version of the International Index of Erectile Function (IIEF) questionnaire consisting of six EDrelevant questions was handed out to 440 vascular surgery outpatients. Clinical data were collected from patients' records. Linear regression models with forward selection were used to investigate associations between erectile function score and possible risk factors. The return rate was 31% (137 patients). Eight patients (6%) were taking phosphodiesterase inhibitors. ED, as defined by an erectile function score of 25 or less and/or use of phosphodiesterase inhibitors, was found in 90% (95% CI: 84% to 95%) of cases. Moderate or severe ED, as defined by an erectile function score of 16 or less and/or use of phosphodiesterase inhibitors, was found in 70% (95% CI: 62% to 78%) of cases. Increased age, abdominal aortic aneurysm, peripheral arterial disease, urologic disease, insulin-dependent diabetes mellitus, and use of beta-blockers were significantly associated with a lower erectile function score. In conclusion, erectile dysfunction is a frequent and often missed comorbidity in vascular surgery patients. While ED may have a profound impact on the patient's quality of life, attention should also be paid to the patient's preoperative sexual function, considering the availability of oral pharmacotherapies and possible consequences concerning liability in postoperative patients in whom pre-existing ED was not identified properly.

ABSTRACT Introduction Premature ejaculation (PE) and its individual and relationship consequences have been recognized in the literature for centuries. PE is one of the most common male sexual dysfunctions, affecting nearly one in three men worldwide between the ages of 18 and 59 years. Until recently, PE was believed to be a learned behavior predominantly managed with psychosexual therapy; however, the past few decades have seen significant advances in understanding its etiology, diagnosis, and management. There is, as yet, no one universally agreed upon definition of PE. Aim To review five currently published definitions of PE. Methods The Sexual Medicine Society of North America hosted a State of the Art Conference on Premature Ejaculation on June 24–26, 2005 in collaboration with the University of South Florida. The purpose was to have an open exchange of contemporary research and clinical information on PE. There were 16 invited presenters and discussants; the group focused on several educational objectives. Main Outcome Measure Data were utilized from the World Health Organization, the American Psychiatric Association, the European Association of Urology, the Second International Consultation on Sexual Dysfunctions, and the American Urological Association. Results The current published definitions of PE have many similarities; however, none of these provide a specific “time to ejaculation,” in part because of the absence of normative data on this subject. While investigators agree that men with PE have a shortened intravaginal ejaculatory latency time (IELT; i.e., time from vaginal penetration to ejaculation), there is now a greater appreciation of PE as a multidimensional dysfunction encompassing several components, including time and subjective parameters such as “control,”“satisfaction,” and “distress.” Conclusion There is a recent paradigm shift away from PE as a unidimensional disorder of IELT toward a multidimensional description of PE as a biologic dysfunction with psychosocial components.

Background and Purpose— Early hematoma expansion in spontaneous intracerebral hemorrhage (ICH) is associated with worse clinical outcome. We hypothesized that hemodynamic parameters are associated with the increase in hematoma volume owing to their relationship to blood vessel wall stresses. Methods— We performed a post hoc analysis of clinical and computed tomography (CT) data from patients enrolled in a prospective observational study of ICH patients presenting within 3 hours from symptom onset. Hematoma volumes were measured at hospital arrival and at 1 and 20 hours from presentation. Blood pressure and heart rate, recorded at 19 time points between presentation and 20 hours, were used to derive hemodynamic variables. Multivariable logistic-regression models were constructed to assess the relation between hemodynamic parameters and hematoma growth, adjusted for clinical covariates. Results— From the original study, 98 patients underwent baseline and 1-hour CT scans; of these, 65 had 20-hour CT scans. Substantial hematoma growth was observed in 28% within the first hour. Of the 65 patients not undergoing surgery within 20 hours, 37% experienced hematoma growth by 20 hours. Neither baseline or peak hemodynamic parameters nor changes in hemodynamic parameters were significantly associated with hematoma growth at either 1 or 20 hours. Conclusions— We found no blood pressure or heart rate parameters, individually or in combination, that were associated with hematoma growth. Our data suggest the influence of hemodynamic parameters on vessel wall stress to be an unlikely target for intervention in reducing the risk of early hematoma growth in ICH.

ABSTRACT Introduction Tadalafil, an inhibitor of phosphodiesterase 5 (PDE5), is indicated for treatment of erectile dysfunction. Most tadalafil clinical trials excluded patients with unsuccessful prior treatment with sildenafil citrate (sildenafil). Aim This retrospective analysis of pooled data from 14 tadalafil clinical trials examines the effect of this exclusion by comparing efficacy results in 1,349 patients without prior sildenafil use (naïve, presumably a mixture of potential responders and nonresponders) with efficacy results in 1,440 patients previously responsive to sildenafil (prior responders). Main Outcome Measures Efficacy measures included the International Index of Erectile Function (IIEF) erectile function (EF) domain, overall satisfaction (OS), and intercourse satisfaction (IS) domain scores; Sexual Encounter Profile (SEP) diary questions 2 through 5 (SEP2 [successful penetration], SEP3 [successful intercourse], SEP4 (satisfaction with hardness of erection), and SEP5 [overall satisfaction with the sexual experience]); and a Global Assessment Question (GAQ1) (13/14 trials) about erection improvement. Efficacy was compared using analysis of covariance (IIEF and SEP) and logistic regression (GAQ1) models. Methods After a 4-week, treatment-free, run-in period, patients in 14 double-blind, placebo-controlled, parallel-group trials were treated with tadalafil 10 mg, tadalafil 20 mg, or placebo for 12 weeks (dosed as needed before sexual activity, no more than once daily). Results Tadalafil improved erectile function compared with placebo (P < 0.001) in naïve patients and sildenafil prior responders for all efficacy measures. For most efficacy outcomes, responses in the naïve group (probable mix of responders and nonresponders) were not statistically different from responses in the prior-responder group (P ≥ 0.10). Conclusions The similar responses of these two patient groups observed in this post hoc analysis suggest, but do not confirm, that exclusion of sildenafil nonresponders in previously reported tadalafil clinical trials may not have substantially affected efficacy outcomes. Tadalafil improved erectile function in patients naïve to PDE5 inhibitor therapy and in patients who previously responded to sildenafil therapy.