Introduction The obstructive sleep apnea–hypopnea syndrome (OSAHS) is associated with sexual dysfunction. Although successful treatment with continuous positive airway pressure (CPAP) has been demonstrated to improve sexual function, the effects of oral-appliance therapy are unknown. Aim The aims of this study were to determine to what extent untreated male OSAHS patients experience sexual dysfunctions compared with control subjects, and second, to evaluate the effects of oral-appliance and CPAP therapy on sexual functioning. Methods Sexual functioning was determined in 48 OSAHS patients with the Golombok Rust inventory of sexual satisfaction (GRISS) and a testosterone measurement. GRISS outcomes were compared with 48 age-matched male controls without any sexual problems. Patients were randomized for either oral-appliance or CPAP therapy. After 2–3 months of treatment, the GRISS and testosterone measurements were repeated. Main Outcome Measure The outcomes on the GRISS were used as the main outcome measure. Results Compared with controls, OSAHS patients had significantly more erectile dysfunction (mean ± standard deviation; OSAHS 8.7 ± 3.8 vs. controls 6.8 ± 2.6) and sexual dissatisfaction (mean ± standard deviation; OSAHS 9.7 ± 4.2 vs. controls 8.1 ± 2.6) as indicated by the GRISS. No significant changes in the GRISS or testosterone levels were observed in the 20 and 27 patients completing the follow-up review for oral-appliance and CPAP therapy. A correlation was demonstrated between the extent of erectile dysfunction at baseline and improvements in erectile function following treatment (r =−0.547, P =0.000). Conclusions This study confirms that male OSAHS patients show more sexual dysfunctions compared with age-matched control subjects. Although significant improvements in sexual functioning in neither the oral-appliance nor CPAP-treated group could be established, our findings suggest that untreated OSAHS patients with pronounced erectile dysfunction experience some improvement following treatment.

In our prospective inception cohort study derived from daily clinical practice, absolute agreement between sUS and salivary gland biopsies was slightly higher for parotid compared with labial gland biopsies. The combination of positive sUS and presence of anti-SSA/Ro antibodies highly predicts classification according to the AECG, ACR and ACR-EULAR classification criteria.

Ab binding to CD20 has been shown to induce apoptosis in B cells. In this study, we demonstrate that rituximab sensitizes lymphoma B cells to Fas-induced apoptosis in a caspase-8-dependent manner. To elucidate the mechanism by which Rituximab affects Fas-mediated cell death, we investigated rituximab-induced signaling and apoptosis pathways. Rituximab-induced apoptosis involved the death receptor pathway and proceeded in a caspase-8-dependent manner. Ectopic overexpression of FLIP (the physiological inhibitor of the death receptor pathway) or application of zIETD-fmk (specific inhibitor of caspase-8, the initiator-caspase of the death receptor pathway) both specifically reduced rituximab-induced apoptosis in Ramos B cells. Blocking the death receptor ligands Fas ligand or TRAIL, using neutralizing Abs, did not inhibit apoptosis, implying that a direct death receptor/ligand interaction is not involved in CD20-mediated cell death. Instead, we hypothesized that rituximab-induced apoptosis involves membrane clustering of Fas molecules that leads to formation of the death-inducing signaling complex (DISC) and downstream activation of the death receptor pathway. Indeed, Fas coimmune precipitation experiments showed that, upon CD20-cross-linking, Fas-associated death domain protein (FADD) and caspase-8 were recruited into the DISC. Additionally, rituximab induced CD20 and Fas translocation to raft-like domains on the cell surface. Further analysis revealed that, upon stimulation with rituximab, Fas, caspase-8, and FADD were found in sucrose-gradient raft fractions together with CD20. In conclusion, in this study, we present evidence for the involvement of the death receptor pathway in rituximab-induced apoptosis of Ramos B cells with concomitant sensitization of these cells to Fas-mediated apoptosis via Fas multimerization and recruitment of caspase-8 and FADD to the DISC.