Treatment of premature ejaculation: New drugs and treatment strategies

This review discusses treatment options for men with premature ejaculation (PE), a common sexual dysfunction characterized by short ejaculatory latency, decreased sexual satisfaction, and distress. For a number of reasons, including embarrassment and the belief that PE is a normal part of aging, that it has no effective treatment, or that it will resolve itself, few men with PE seek treatment. Although several treatment options exist (eg, behavioral, cognitive, and sex therapy methods; desensitizing drugs; off-label use of antidepressants, phosphodiesterase type 5 inhibitors, or à-blockers), the majority of men with PE are not satisfied with their results. New pharmacologic drugs develped specifically for the treatment of PE are undergoing evaluation in clinical trials. For example, recent clinical research studies have revealed on-demand administration of one such drug, dapoxetine, which achieved significant improvements in ejaculatory latency, control over ejaculation, and satisfaction with sexual intercourse. In addition, partners of men who received dapoxetine likewise reported improved satisfaction with sexual intercourse. Future studies may reveal that integration of pharmacologic drugs with psychologic and/or behavioral therapy techniques may be the optimal approach to the management of PE. PE is a treatable condition, and new drugs in development may provide benefits over those available.     

IFN-alpha1,8 inhibits tumor-induced angiogenesis in murine angiosarcomas.

Interferon-alpha (IFN-alpha) has proved effective in the treatment of hemangiomas, hemangioblastomas, and Kaposi's sarcoma. To investigate the ability of IFNs to inhibit angiosarcoma, we used two transformed murine endothelial cell lines that form angiosarcomas in vivo. SVR and MS1-VEGF cell lines express oncogenic H-ras or vascular endothelial growth factor (VEGF), respectively. IFN-alpha1,8, which is active against murine and human cells, inhibited SVR and MS1-VEGF proliferation in vitro by 40% at 10(3) U/mL (p = 0.028). In vivo, IFN-alpha1,8 inhibited SVR tumor volume by 71% (p = 0.047) and MS1-VEGF volume by 79% (p = 0.003). Tumor-induced angiogenesis was decreased in SVR tumors by 52% (p = 0.005) and in MS1-VEGF tumors by 58% (p = 0.001). Sera from IFN-alpha1,8-treated mice bearing either SVR or MS1-VEGF tumors demonstrated a 5-fold increase in IP-10/CXCL10 (p = 0.001), an IFN-induced antiangiogenic protein. Both recombinant IP-10 and IFN-alpha1,8 inhibited human umbilical vein endothelial cell (HUVEC) vessel formation in the fibrin gel assay, a three-dimensional culture model of angiogenesis, by 56% at 25 ng/mL and 50% at 1.2 ng/mL, respectively (p < 0.001). An IP-10 blocking antibody restored vessel formation to 80% of untreated controls (p = 0.001). Given the magnitude of the in vivo response, these data suggested that the antitumor effects of IFN-alpha1,8 were likely mediated through angiogenesis inhibition rather than solely by direct inhibition of tumor cell proliferation.     

Primary hypothyroidism presenting as ovarian tumor and precocious puberty in a prepubertal girl.

We report a case of a prepubertal girl with juvenile primary hypothyroidism presenting as ovarian cysts and precocious puberty. The 7-year-old female was referred to our clinic because of a pelvic/abdominal mass and vaginal bleeding. Besides these findings, on physical examination we noticed the thyroid gland globally increased and the presence of secondary sexual characteristics. Based upon the clinical profile and investigations, the patient was diagnosed with juvenile primary hypothyroidism due to autoimmune thyroiditis. The cysts and precocious puberty resolved spontaneously after the simple replacement of thyroid hormone. It is important to bear in mind hypothyroidism in cases of girls presenting ovarian cysts and precocious puberty in order to avoid unnecessary surgery on the ovaries.     

Treatment of dysfunctional uterine bleeding in the perimenopause: the effects of adding combined estradiol/norethisterone acetate therapy to goserelin acetate treatment--a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: To assess the effects of adding combined estradiol/norethisterone acetate therapy (CENT) to goserelin acetate treatment (GA) of dysfunctional uterine bleeding (DUB) in perimenopausal women. METHODS: In a randomized, placebo-controlled, double-blind trial followed by an open follow-up study, 31 perimenopausal women with DUB were recruited from gynecological outpatient departments of two Dutch hospitals and randomized for treatment with either GA/placebo or GA/CENT for 6 months followed by 18 months of GA/CENT for all. The main outcome measures were abdominal pain, number of bleeding days, double-layer endometrial thickness (DET), Greene climacteric score (GCS), visual analog scale for well-being, bone mineral density (BMD) and mammographic density (BI-RAD score). RESULTS: Abdominal pain, number of bleeding days and DET decreased in both groups, the between-group difference in decrease not being statistically significant. GCS initially showed significant improvement in the GA/CENT group. BMD decreased significantly in the GA/placebo group (-4.1%) compared with the GA/CENT group (-0.3%). Another 18 months of GA/CENT did not result in a lasting difference in BMD between groups. BI-RAD scores did not differ significantly between or within the two groups. CONCLUSIONS: Adding CENT to GA treatment for DUB in perimenopausal women initially prevented BMD loss and improved climacteric complaints, while having no negative impact on vaginal bleeding, abdominal pain or BI-RAD scores. However, prolonged treatment did not result in a lasting prevention of bone loss.     

Effects of intranasal 17beta-estradiol and raloxifene on lipid profile and fibrinogen in hypercholesterolemic postmenopausal women: a randomized, placebo-controlled clinical trial.

AIM: To compare the effects of 17beta-estradiol given intranasally (intranasal E2) and raloxifene on serum lipid profile and fibrinogen in hypercholesterolemic postmenopausal women. METHODS: The study population consisted of 46 women after menopause. The placebo group (n = 11) was given calcium, while the intervention groups were given intranasal E2 (Aerodiol; Servier, Chambray-les-Tours, France) (n = 16) or raloxifene (Evista; Lilly SA, Madrid, Spain) (n = 19). Blood lipids and fibrinogen were compared between groups at baseline and after 3 months of treatment. RESULTS: The group receiving intranasal E2 showed a significant decrease in triglyceride levels (p<0.05) and a marked increase in high-density lipoprotein cholesterol levels (p<0.05). No changes in lipid profile were observed in the raloxifene and placebo groups. Raloxifene caused a significant decrease in fibrinogen levels (p<0.05). CONCLUSION: Intranasal E2 exerts significant effects on lipid profile in hypercholesterolemic postmenopausal women. Raloxifene has a greater impact on fibrinogen than intranasal E2 application.     

Rehabilitative Maßnahmen bei Patienten mit Pankreaskarzinom

Rehabilitative and palliative measures in the follow-up care of pancreatic cancer patients will remain the dominant medical focus as long as potentially curative measures (recurrence prophylaxis, early detection and therapy of recurrence) have failed to show a significant survival benefit. Rehabilitative measures are possible for patients undergoing potentially curative as well as palliative treatment. Their aim is to alleviate the negative effects of the cancer and its therapy, not only physically, but also psychologically, socially and vocationally. The spectrum of possible somatic handicaps ranges from metabolic disorders, malnutrition and under-nutrition, as well as gastrointestinal symptoms to pain. Assistance in coping with illness, alleviating fears and depression and strengthening compliance are the main areas which are dealt with in psycho-oncology. Assessment of vocational fitness and the capacity to work depends on tumor location, whether R0 or R1 resection has taken place, the extent of pancreas resection, accompanying illnesses, whether or not adjuvant therapy has been given, and the physical condition of the patient     

Freezing of gait in postmortem-confirmed atypical parkinsonism.

The frequency and pathophysiology of freezing of gait (FoG) in atypical parkinsonism is unknown. We analysed the frequency of FoG in postmortem-confirmed atypical parkinsonian disorders (APD) comprising corticobasal degeneration (CBD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Sixty-six patients with pathologically confirmed APD (CBD, n = 13; DLB, n = 14; MSA, n = 15; PSP, n = 24) formed the basis for a multicenter clinicopathological study. Clinical features at first and last clinical visit were abstracted from patient records on standardized forms following strict instructions. At the first visit (median 36 months after symptom onset), 24% of APD had FoG (CBD, 8%; DLB, 21%; PSP, 25%; MSA, 40%). Logistic regression analysis showed a significant association of FoG and urinary incontinence (P = 0.04) at first visit. At last visit, 47% of APD had FoG (CBD, 25%; PSP, 53%; DLB, 54%; MSA, 54%). Clinicopathological correlation based on routine postmortem examination failed to identify a consistent neuropathological substrate of FoG. This study demonstrates that (1) FoG is common in APD, and (2) urinary incontinence is significantly associated with FoG in these disorders. Whether FoG and urinary incontinence share similar neuropathological substrates remains to be determined by future studies.