Comparative cross-over study of sildenafil and apomorphine for treating erectile dysfunction

OBJECTIVE

To compare the effectiveness, safety and tolerability of sildenafil and apomorphine in Brazilian patients with erectile dysfunction (ED) of various causes.

PATIENTS AND METHODS

In all, 108 patients (mean age 55 years, sd 11) and documented ED for ≥6 months were included in 12 centres in Brazil. The patients were initially followed for 2 weeks and then randomized to initial treatment with apomorphine or sildenafil, taken before sexual intercourse, no more than once a day. The initial dose (2 mg apomorphine and 50 mg sildenafil) could be adjusted (to 3 mg apomorphine, or to 25 or 100 mg for sildenafil) depending on the effectiveness and tolerability during the first 4 weeks of treatment. The patients were re‐evaluated after 8 weeks on treatment and, after a wash‐out period of 2 weeks (no treatment), received the other study drug (other than that received in the first phase), and then had the same procedures as in the first phase.

RESULTS

In all, 97 patients were evaluated for therapeutic effectiveness, the overall effectiveness being assessed using two questions; sildenafil had a significantly higher proportion of affirmative answers for both (P < 0.001). Likewise, the estimates for the mean (sd ) proportion of successful sexual intercourse, of 83.3 (4.7)% vs 40.3 (4.7)% and the total ED Inventory of Treatment Satisfaction score, of 86.7 (2.9) vs 56.9 (2.9) (P < 0.001) were higher for sildenafil. At the end of the study, 93.8% of the patients randomized to initial therapy with apomorphine declared a preference for sildenafil, and 81.3% of those initially treated with sildenafil declared a preference for that drug. The two drugs were well tolerated, and the main adverse events for apomorphine were nausea, vomiting, headache, taste perversion and dizziness; for sildenafil they were headache, flushing or vasodilatation, abdominal pain or dyspepsia and nasal congestion.

CONCLUSIONS

Sildenafil is more effective than apomorphine for treating ED, in the domains of erectile function, satisfaction with sexual intercourse and overall satisfaction, and was the drug preferred by most of the patients.     

Alternative to the distal interphalangeal joint arthrodesis: lateral approach and plate fixation

PURPOSE: Several fixation techniques for distal interphalangeal (DIP) joint arthrodesis have been described, with good clinical results and complication rates between 10% and 20%. We propose an alternative technique and fixation method using a lateral approach and 1.3-mm plate and screws fixation. METHODS: Between March and September 2005, 11 patients, totaling 15 fingers, had DIP joint arthrodesis by the described technique. The indications were posttraumatic arthritis in 8 fingers, degenerative or rheumatoid arthritis in 5 fingers, and isolated flexor digitorum profundus tendon lesions in 2 fingers. Patients were analyzed for osseus union, pain relief, and functional mobility of the finger. RESULTS: Arthrodesis relieved pain and restored stability at the 12th week, on average, with osseous union in all patients. All patients maintained full proximal interphalangeal joint motion with pulp-to-palm distance of zero at 6 months of follow-up evaluation. There were no rotational or angular deformities, nail bed lesions, or skin complications. CONCLUSIONS: The lateral approach with plate and screws fixation is an option for DIP joint arthrodesis. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.     

Food intake increased after injection of adrenaline into the median raphe nucleus of free-feeding rats

The present study examined the effects of local injections of adrenaline (AD) or noradrenaline (NA) in equimolar doses (6, 20, and 60 nmol) into the median raphe nucleus (MRN) on ingestive and non-ingestive behaviors of free-feeding rats. The results showed that the treatment with AD at doses of 20 and 60 nmol increased food intake. While the hyperphagic response evoked by 60 nmol dose of AD was accompanied by a reduction of the latency to start feeding and an increase in the frequency of feeding, the 20 nmol dose of AD was unable to change these behavioral aspects of feeding response. The meal size and non-ingestive behaviors were not affected by AD treatment in the MRN. While water intake remained unchanged after the treatment with 20 nmol of AD in the MRN, this dose decreased the latency to start drinking. Feeding and drinking behaviors were not affected by treatment with NA in the MRN. These data suggest that adrenergic receptors of MRN participate in mechanisms that control food intake initiation or appetite. In addition, our results also indicate that the availability of energetic substrate could affect the adrenergic influence on MRN neurons since previous data indicated that the injection of AD into the MRN of food restricted rats decreased food intake.     

An easy and safe model of kidney transplantation in rats

A technical innovation of a novel ureter implantation technique on rat kidney allograft transplantation is described. The left kidney graft is transplanted heterotopically into the left infrarenal position, using vascular conduits from donor abdominal aorta and inferior vena cava in continuity to renal vessels, to perform arterial and venous end-to-side anastomoses to the recipient vessels. A new ureter implantation technique was employed by placing a purse-string suture around the uretero-vesical anastomosis and ligated at the end of the anastomosis to invaginate the ureter and relieve tension at its junction to the bladder. This functions as an anti-reflux procedure, also preventing urine leakage. Bilateral native kidneys nephrectomy of the recipient was performed a week post-transplant. This model of rat kidney transplantation was associated with high survival rate (87%) 2 weeks post-transplant with no evidence of vascular anastomoses complications or other technical failures. The technique is easy, reliable, and can be routinely applied to other microvascular transplantation procedures.     

Evaluation of renal defect healing, hemostasis, and urinary fistula after laparoscopic partial nephrectomy with oxidized cellulose

BACKGROUND AND PURPOSE: Laparoscopic partial nephrectomy (LPN) has been performed at several institutions using oxidized cellulose (OC) as a means of bleeding and urinary fistula (UF) prevention. However, a foreign-body reaction mimicking either abscess or tumor recurrence has been associated with the use of OC. We evaluated renal-defect healing after LPN with and without OC. MATERIALS AND METHODS: Sixteen female Landrace pigs underwent lower-pole excision; all the collecting systems were entered and then closed with absorbable running suture. In group 1, hemostatic U-shaped stitches were the only method of hemostasis. In group 2, a bolster of OC was added to the renal defect. The pigs were sacrificed at 1, 4, 7, or 21 days, and gross findings such as perirenal collection were observed. A catheter was advanced up to the kidney, and methylene blue was injected with collecting system pressure observation; burst pressure was defined as the appearance of extravasation. High risk for UF was defined as burst pressure <10 mm Hg. RESULTS: Neither hemorrhage nor urinoma was observed during sacrifice. One pig from group 2 had a burst pressure of 4 mm Hg At 7 days (high risk for UF). At 21 days in group 2, the tissue was grossly solid, apparently a granuloma. Suppuration tended to be greater in group 2. The foreign-body reaction was more intense in group 2 and was strongly present at 4, 7, and 21 days. CONCLUSIONS: The use of OC is associated with higher scores of suppuration and foreign-body reaction. After LPN with OC, postoperative day 7 might be a critical time for the development of urinary leakage.     

A naturalistic, 9-month follow-up, comparing olanzapine and conventional antipsychotics on sexual function and hormonal profile for males with schizophrenia

Second generation antipsychotics have less influence on prolactin levels than conventional antipsychotics (CA), which are commonly associated with sexual dysfunction and hyperprolactinaemia. However, only a few studies have been conducted assessing these newer antipsychotics and sexual function/dysfunction. The aim of this study is to evaluate the sexual function and hormonal profile of male schizophrenic patients taking olanzapine or CA. Sixty-three inpatients with acute episodes of schizophrenia were randomly assigned to take either olanzapine, or go on conventional antipsychotic treatment. The Dickson-Glazer sexual functioning questionnaire was used to assess sexual functioning where serum prolactin, luteinizing hormone, follicle-stimulating hormone, total testosterone, free testosterone, and sex hormone-binding globulin concentrations were measured. All measurements were taken on discharge from the inpatient unit (baseline), and again at 3 and 9 months after discharge. Prolactin levels in the olanzapine group decreased more rapidly and were significantly lower than in the CA group after 3 months (12.1+/-6.3 microg/l, p=0.01; 18.1+/-11.2 microg/l, p=0.564, respectively). After nine months, there was a tendency toward normal levels in both groups, and the frequency of sexual complaints did not differ between the groups. This study showed no difference between olanzapine and conventional antipsychotics regarding sexual complaints in the treatment of schizophrenia, but did show a difference in the hormone level normalization rate.     

Toxicological screening of Euphorbia tirucalli L.: developmental toxicity studies in rats

Euphorbia tirucalli (Euphorbiaceae family), an environmental risk factor for Burkitt's lymphoma, also presents pharmacological activities. In the northeast region of Brazil its latex is used as an antimicrobial, antiparasitic in the treatment of coughs, rheumatism, cancer and other maladies as folk remedy. The present work concerns its developmental toxicity in rats. Wistar rats on the first day post-coitum (dpc) were grouped as control (distilled water) and treated (latex aqueous solution) groups. Animals were treated by oral gavage from the 1st to the 4th (Experiment I) and from the 5th to 7th dpc (Experiment II) and killed on the 5th or 14th dpc, respectively. Maternal variables were: clinical signs of toxicity, body weight, ovaries, liver and kidneys weight and number of corpora lutea. The uterine tubes and cornua were washed for counting and identification of embryos. The embryos and placenta were weighed. Apart from the leucopenia and the higher placental weight observed in treated rats from Experiment II, there were no significant differences between the groups. It is possible to conclude that the latex aqueous solution of Euphorbia tirucalli did not interfere with tubaric embryo development or with implantation, but it seems to alter the placenta morphology.     

Expression and function of epithelial anoctamins

Endogenous Ca(2+)-activated Cl(-) currents (CaCCs) are abundant and present in very different cell types. Very good evidence has been provided that endogenous CaCC is produced by anoctamin 1 (Ano1) and Ano2. Insight into the physiological role of anoctamins has been provided for Ano1, Ano2 and Ano6; however, the physiological role of the other seven members of the anoctamin family remains obscure. Anoctamins 1 and 2 may operate as individual Ca(2+)-sensitive channel proteins or may require accessory subunits for complete function. We find that overexpressed Ano1 has properties resembling all those of endogenous CaCCs, although with some noticeable biophysical and regulatory differences when compared with endogenous channels. Apart from Ano1 and Ano2, expression of Ano6 also produces a Cl(-) conductance. Depending on the cellular background, Ano6 currents may have variable properties. Anoctamins 1 and 6 are frequent in epithelial cells, often coexpressed together with Ano8, Ano9 and Ano10. Most available data on anoctamins were obtained from mouse tissues and from cultured cells, which may not be representative of native human tissues.