Sexual dysfunctions and blood hormonal profile in men with focal epilepsy

PURPOSE: To evaluate the incidence of sexual dysfunction in men with focal epilepsy and to establish their hormonal profiles. METHODS: We prospectively analyzed sexual functions and hormone blood levels in 40 male patients (age ranged from 18 to 44 years, with an average age of 27.6+/-5.6 years) with refractory focal epilepsy. We used the Czech version of the structured questionnaire entitled International Inventory of Erectile Function (IIEF) to assess the patients' sexual functions. The subscales of this questionnaire separately evaluate erectile function (IIEF I), orgasmic function (IIEF II), sexual desire (IIEF III), intercourse satisfaction (IIEF IV), and overall satisfaction with sex life (IIEF V). In all of the patients, the following blood tests were performed: quantitative assessment of blood levels of prolactin (PRL), total testosterone (total-T), free androgen index (FAI), sexual hormone-binding globulin (SHBG), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), progesterone (PRG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). All these quantitative laboratory data were correlated with other clinical variables and with the results of the IIEF. chi2 and Wilcoxon tests were used for the statistical analysis. A p-value<0.05 was considered to be statistically significant. RESULTS: At least one of the types of sexual dysfunction, as defined by IIEF (IIEF I, II, and III), was found in 22 (55%) of the 40 patients (55%). Erectile dysfunction (IIEF I) was found in six (15%) of 40 patients, orgasmic dysfunction (IIEF II) in six (15%) of 40 patients, and loss of sexual desire (IIEF III) in 16 (40%) of 40 patients. According to other subscales of IIEF, 22 (55%) of 40 patients were not satisfied with sexual intercourse (IIEF IV), and 20 (50%) of 40 patients were not satisfied with their sex livee (IIEF V). None of the subscales of IIEF was significantly correlated with the age of the patients or with the duration of epilepsy. In patients with at least one of the sexual dysfunctions (IIEF I, II, and III), we found a statistically significant increase of FSH and SHBG, and a decrease of DHEAS and FAI in comparison with those in the patients with normal sexual functions. In patients with erectile dysfunction, we found the same changes and a significant increase of E2. In patients with orgasmic dysfunction, we found a statistically significant decrease of DHEAS. In patients with dysfunction of sexual desire, we noticed a significant increase of SHBG and a decrease of DHEAS and FAI. All patients with orgasmic dysfunction were being treated with carbamazepine (CBZ) in monotherapy or combination therapy. In patients with at least one type of sexual dysfunction (IIEF I, II, and III), we found a higher proportion of valproate treatment in monotherapy or combination therapy in comparison with CBZ. CONCLUSIONS: Our study showed a relatively high incidence of sexual dysfunction and dissatisfaction with sexual intercourse and sex life, as defined by the IIEF I-V questionnaire, in men with refractory focal epilepsy. The most frequent dysfunction in these patients is the impairment of sexual desire. However, our study indicates some specific hormonal changes related to various types of sexual dysfunction that are not related to antiepileptic drug treatment.     

Difficulties of motion-onset VEP interpretation in school-age children

Background

In adults, motion-onset visual evoked potentials (M-VEPs) with a dominant N2 peak represent a useful diagnostic tool. However, it is difficult to use this type of VEP in children because of the long maturation (up to 18 years) of M-VEPs, which is characterised by a gradual decrease in N2 peak latency and shape development. Moreover, in some children, M-VEPs are difficult to identify with standard stimuli.

Methods

We tested features of M-VEPs in 30 children (7–12 years) with the following set of standard stimuli used in our lab for examining adults (https://web.lfhk.cuni.cz/elf): low-contrast translation motion (TM) and expansion/contraction motion (ExCoM) in full field and in periphery (with central 20° masked). In 16 children, a high-contrast TM was also tested.

Results

With standard (low-contrast) stimuli, a common M-VEP to TM and to ExCoM was detected in 77 and 83 % of children, respectively. The M-VEPs to ExCoM in the periphery were detected in only 43 % of children. An abnormal dominant P1 peak was found in 9 % of VEPs to TM, 12 % of VEPs to full-field ExCoM and 14 % of VEPs to peripheral ExCoM. The M-VEPs to all low-contrast stimuli displayed large inter-individual latency variability (N2 peak latency differed for more than 100 ms). High contrast (more suitable for the non-mature magnocellular pathway) shortened M-VEP latencies and improved amplitudes.

Conclusions

Our findings show that the maturation of motion perception in children is inter-individually variable, which limits the diagnostic use of M-VEPs.     

Apelin is a positive regulator of ACE2 in failing hearts

Angiotensin converting enzyme 2 (ACE2) is a negative regulator of the renin-angiotensin system (RAS), catalyzing the conversion of Angiotensin II to Angiotensin 1-7. Apelin is a second catalytic substrate for ACE2 and functions as an inotropic and cardioprotective peptide. While an antagonistic relationship between the RAS and apelin has been proposed, such functional interplay remains elusive. Here we found that ACE2 was downregulated in apelin-deficient mice. Pharmacological or genetic inhibition of angiotensin II type 1 receptor (AT1R) rescued the impaired contractility and hypertrophy of apelin mutant mice, which was accompanied by restored ACE2 levels. Importantly, treatment with angiotensin 1-7 rescued hypertrophy and heart dysfunctions of apelin-knockout mice. Moreover, apelin, via activation of its receptor, APJ, increased ACE2 promoter activity in vitro and upregulated ACE2 expression in failing hearts in vivo. Apelin treatment also increased cardiac contractility and ACE2 levels in AT1R-deficient mice. These data demonstrate that ACE2 couples the RAS to the apelin system, adding a conceptual framework for the apelin-ACE2–angiotensin 1-7 axis as a therapeutic target for cardiovascular diseases.     

The long-term effectiveness of generic adult fixed-dose combination antiretroviral therapy for HIV-infected Ugandan children

Background

Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs.

Objective

To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment.

Methods

Clinical, immunologic, and virologic outcomes of HIV-infected ART-naïve children aged six months to 12 years, were evaluated up to 96 weeks post-ART initiation.

Results

From March 2004 to June 2006, 104 children were followed with a median age of 5.4 years, median CD4 cell percent and HIV-1 RNA were 11.0% (IQR 6.7–13.9) and 348,846copies/mL (IQR 160,941–681,313) respectively at baseline. Using Kaplan-Meir estimates, 75% of children had undetectable viral loads (<400copies/mL) at 96weeks of ART. Children with a baseline CD4 cell percent >15% were 3 times more likely to achieve viral load <400copies/mL than those with baseline CD4 cell percent <5% after adjusting for baseline age {aHR = 3.03 (1.10–8.32), p=0.03}; no difference was found among those with CD4 cell percent >5–14.9% and <5%.

Conclusion

Treatment with generic adult FDC for HIV-infected Ugandan children led to sustained clinical, immunologic and virologic response during 96 weeks of ART. Early initiation of ART is key to achieving virological success.