Sexual Rehabilitation and Penile Pain Associated with Intracavernous Alprostadil after Radical Prostatectomy

IntroductionIntracavernous alprostadil injection (IAI) is widely used for sexual rehabilitation (SR) after radical prostatectomy (RP). However, the rate of spontaneous erection recovery with IAI remains unclear, and IAI causes pain that may hinder SR.AimsTo assess SR in IAI users after RP and to evaluate the course and impact on SR of postinjection penile pain.MethodsWe prospectively studied 87 patients who underwent nerve‐sparing laparoscopic RP, reported normal preoperative erectile function, and used IAI for 12 months. Patients started with 2.5 µg alprostadil and were advised to increase the dose gradually until erection hardness allowed vaginal penetration.Main Outcome MeasuresAt 6 and 12 months, the International Index of Erectile Function (IIEF‐15) and Erection Hardness Score (EHS) were determined with and without IAI, and injection‐related penile pain was assessed using a numeric rating scale. Correlations linking penile pain, IIEF‐15, and EHS scores were evaluated.ResultsThe mean alprostadil dose was 8.1 µg after 6 months and 9.9 µg after 12 months. With/without IAI, mean IIEF‐15 scores for erectile and orgasmic function and mean EHS score were 14.6/4.6, 4.1/2.1, and 2.5/0.4, respectively, after 6 months; and 17.2/5.4, 4.9/2.6, and 2.7/0.9 after 12 months. Pain scores were 3.2 ± 2.5/10 and 2.5 ± 2.5/10 after 6 and 12 months, respectively. Pain intensity correlated with erectile function (r = ?0.23), intercourse satisfaction (r = ?0.23), and overall satisfaction (r = ?0.24) after 6 months but not after 12 months. Follow‐up was short and only patients who used IAI for 12 months were included.ConclusionsIn patients who were willing and able to use IAI, erectile function improved after 1 year but remained below preoperative levels. The adverse impact of pain on SR was significant during the first 6 months and diminished over time. These data may help to counsel IAI users with painful erections. Yiou R, Cunin P, de la Taille A, Salomon L, Binhas M, Lingombet O, Paul M, and Abbou C. Sexual rehabilitation and penile pain associated with intracavernous alprostadil after radical prostatectomy.     

Stability of children's and adolescents' hemodynamic responses to psychological challenge: a three-year longitudinal study of a multiethnic cohort of boys and girls

This report evaluated (a) the temporal stability of hemodynamic responses to three tasks using impedance cardiography, and (b) the influence of aging on stress responses in a multi-ethnic pediatric sample. One hundred children 8 to 10 years old and 49 adolescents 15 to 17 years old were tested at study entry and on average 3 years later. Results showed that the composite task-induced changes in stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), and pre-ejection period (PEP) were moderately stable across 3 years (rs = .36 to .51), with children showing greater stability in task-induced CO change than did adolescents. However, the magnitude of the participant's stress responses changed over time, varied by task, age group, and gender. These results suggest that hemodynamic responses to stress change with aging during childhood and adolescence and that they can be measured reliably.     

Prevalence of genetic markers for thrombophilia in recurrent pregnancy loss

BACKGROUND: The genetic predispositions to venous thrombosis such as factor V Leiden (FVL) mutation (Arg 506 Gln), prothrombin (FII) gene mutation (G20210A), and mutation of the methylenetetrahydrofolate reductase (MTHFR) gene (C677T) have been reported to be associated with recurrent pregnancy loss. This paper examines the prevalence of markers for genetic thrombophilias in women with recurrent miscarriage. METHODS: The prevalence of FVL, FII G20210A and MTHFR C677T was compared in 108 women with three or more pregnancy losses either exclusively in the first trimester, or mixed first and second trimester losses, with the prevalence found in 82 fertile parous control women without miscarriages. Markers for the thrombophilias were assessed by PCR analysis. RESULTS: Twenty-three of the 108 patients (21.3%), had thrombophilia markers, which was similar to the proportion of patients in the control group (20.7%) with these markers. The prevalences of FVL and FII G20210A were lower in the study group than in the control group (3.7 versus 6.1% for FVL and 4.6 versus 6.1% for FII respectively); however, the difference was not statistically significant. In contrast, the prevalence of MTHFR C677T was higher in the study group than the control population (13 versus 8.5% respectively), but this difference was not statistically significant. There was no statistically significant prevalence of any particular thrombophilia in patients with previous first and second trimester pregnancy losses compared with patients with first trimester losses alone. CONCLUSION: Thrombophilia was not found to be associated with recurrent pregnancy loss.     

CC2D2A mutations in Meckel and Joubert syndromes indicate a genotype–phenotype correlation

Meckel-Gruber syndrome (MKS) is a lethal fetal disorder characterized by diffuse renal cystic dysplasia, polydactyly, a brain malformation that is usually occipital encephalocele, and/or vermian agenesis, with intrahepatic biliary duct proliferation. Joubert syndrome (JBS) is a viable neurological disorder with a characteristic “molar tooth sign” (MTS) on axial images reflecting cerebellar vermian hypoplasia/dysplasia. Both conditions are classified as ciliopathies with an autosomal recessive mode of inheritance. Allelism of MKS and JBS has been reported for TMEM67/MKS3, CEP290/MKS4, and RPGRIP1L/MKS5. Recently, one homozygous splice mutation with a founder effect was reported in the CC2D2A gene in Finnish fetuses with MKS, defining the 6th locus for MKS. Shortly thereafter, CC2D2A mutations were also reported in JBS. The analysis of the CC2D2A gene in our series of MKS fetuses, identified 14 novel truncating mutations in 11 cases. These results confirm the involvement of CC2D2A in MKS and reveal a major contribution of CC2D2A to the disease. We also identified three missense CC2D2A mutations in two JBS cases. Therefore, and in accordance with the data reported regarding RPGRIP1L, our results indicate phenotype–genotype correlations, as missense and presumably hypomorphic mutations lead to JBS while all null alleles lead to MKS. Hum Mutat 30:1–9, 2009. © 2009 Wiley-Liss, Inc.     

Mini Review

Amyotrophic lateral sclerosis (ALS) is characterized by loss of both upper and lower motor neurons. ALS progression is complex and likely due to cellular dysfunction at multiple levels, including mitochondrial dysfunction, glutamate excitotoxicity, oxidative stress, axonal dysfunction, reactive astrocytosis, and mutant superoxide dismutase expression, therefore, treatment must provide neuronal protection from multiple insults. A significant amount of ALS research focuses on growth factor-based therapies. Growth factors including insulin-like growth factor-I, vascular endothelial growth factor, brain-derived neurotrophic factor, and glial-derived neurotrophic factor exhibit robust neuroprotective effects on motor neurons in ALS models. Issues concerning growth factor delivery, stability and unwanted side effects slow the transfer of these treatments to human ALS patients. Stem cells represent a new therapeutic approach offering both cellular replacement and trophic support for the existing population. Combination therapy consisting of stem cells expressing beneficial growth factors may provide a comprehensive treatment for ALS.     

RSA fluctuation in major depressive disorder

Cardiac vagal control, as measured by indices of respiratory sinus arrhythmia (RSA), has been investigated as a marker of impaired self-regulation in mental disorders, including depression. Past work in depressed samples has focused on deficits in resting RSA levels, with mixed results. This study tested the hypothesis that depression involves abnormal RSA fluctuation. RSA was measured in depressed and healthy control participants during rest and during two reactivity tasks, each followed by a recovery period. Relative to controls, depressed persons exhibited lower resting RSA levels as well as less RSA fluctuation, primarily evidenced by a lack of task-related vagal suppression. Group differences in RSA fluctuation were not accounted for by differences in physical health or respiration, whereas group differences in resting RSA level did not survive covariate analyses. Depression may involve multiple deficits in cardiac vagal control.     

CD4+CD25+ regulatory/suppressor T cells prevent allogeneic fetus rejection in mice

Recent evidences indicate that naturally occurring CD4+CD25+ regulatory/suppressor T cells (T(reg)) regulate not only autoimmunity, but also alloreactivity. In mice, they notably control tolerance to allogeneic transplants and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Here, we studied the role of T(reg) in maternal tolerance to fetuses, i.e. natural semi-allogeneic grafts. We show that semi-allogeneic pregnancies in mice induce an expansion of T(reg), but not of activated CD4+ and CD8+ T cells, in para-aortic lymph nodes draining fetal antigens. The treatment of female mice with an anti-CD25 antibody before mating results in depletion of T(reg) and expansion of activated CD4+ and CD8+ T cells solely in the draining lymph nodes, ultimately leading to fetus rejection. These observations were not made in the context of syngeneic pregnancies. Thus, T(reg) play a major role in maternal-fetal tolerance.     

Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts at diagnosis of childhood acute lymphoblastic leukemia: a pilot prognostic factor analysis

Lymphoblasts in bone marrow samples, obtained from 43 children with acute lymphoblastic leukemia at diagnosis, were incubated with 1.0 mumols/L [3H] methotrexate for 24 hours in vitro. Nonexchangeable methotrexate and methotrexate polyglutamates were separated and quantitated. Event-free survival at 5 years was 38% +/- 9% for all 43 patients (27 failures), and 44% +/- 10% for the 35 with non-T, non-B- cell acute lymphoblastic leukemia (20 failures). Of these 35 children, those whose lymphoblasts accumulated more than 100 pmol methotrexate and 500 pmol methotrexate polyglutamates per billion cells experienced better 5-year event-free survival than those whose lymphoblasts did not (65% +/- 12% v 22% +/- 9%, P = .010). This difference characterized "good-risk" patients who were female (P = .014), less than age 7 at diagnosis (P = .005), or had low initial white blood cell counts (less than 20 X 10(9)/L, P = .018). Findings were similar for the 43 children with acute lymphoblastic leukemia and for the "good-risk" children in this total group. Thus, the ability of lymphoblasts to accumulate methotrexate and form methotrexate polyglutamates may be important to the curative properties of current therapy of acute lymphoblastic leukemia in children, particularly for "good-risk" patients. In such patients, inherent rather than acquired drug resistance may be the initial event leading to treatment failure.