Sildenafil citrate (Viagra) in erectile dysfunction: near normalization in men with broad-spectrum erectile dysfunction compared with age-matched healthy control subjects

OBJECTIVES: To evaluate the efficacy, safety, and tolerability of sildenafil in men with broad-spectrum erectile dysfunction (ED), with reference to age-matched healthy control subjects. METHODS: One hundred eleven patients were enrolled in a randomized, double-blind, placebo-controlled, parallel-group, 12-week, flexible-dose study. Efficacy assessments included the International Index of Erectile Function (IIEF), a global assessment question, and patient event log data. In a separate, nontreatment study, 109 control subjects also completed the IIEF. RESULTS: Mean IIEF scores at baseline were significantly lower for patients with ED than for control subjects without a history of ED. After treatment, mean IIEF scores for patients receiving sildenafil approached values observed in control subjects and were significantly higher than mean scores for patients receiving placebo (P<0.01). Responses to the global assessment question and patient log data corroborated the IIEF results. Sildenafil was well tolerated, with no discontinuations because of adverse events. CONCLUSIONS: The results indicate that sildenafil, an effective oral therapy for the treatment of broad-spectrum ED, is associated with a near normalization of patient erectile function.     

Posttraumatic stress disorder in injured adults: etiology by path analysis

OBJECTIVE: Posttraumatic Stress Disorder (PTSD) impairs outcome from injury. We present a path analysis of factors related to the development of PTSD in injured adults. METHODS: A prospective cohort of 250 patients without severe neurotrauma was evaluated by interview during admission and by mailed self-report 6 months later. Data were gathered from the trauma registry (age, injury mechanism, and Injury Severity Score), social history (gender, income, education, and social support), and survey instruments. Baseline assessment used the Michigan Critical Events Perception Scale (peritraumatic dissociation and subjective threat to life), the Life Experience Survey (stressful exposure history), and the SF36 (general and mental health). PTSD at 6 months was identified with the civilian Mississippi Scale for PTSD. Data are listed as mean +/- SEM or percent (%). Path analysis was conducted by linear regression and significant (p<0.05) variables are shown. Factors are listed with the standardized beta. A negative beta suggests a protective effect. RESULTS: The 176 patients (72%) who completed the 6-month follow-up were 37.7+/-0.88 years old; 75% were men; and blunt (70%), penetrating (13.5%), and burn (16.4%) mechanisms caused the injuries. Assault was involved in 14.5% of the cases. Average income was $44,300+/-2,700/yr, education was 13.0+/-0.15 years, and Injury Severity Score was 13.9+/-0.50. A total of 42.3% of the patients developed PTSD. The 39.7% of the variance in PTSD explained by the model was due to intentional injury (beta = 0.27), male gender (beta = -0.21), age (beta = -0.20), peritraumatic dissociation (beta = 0.174), baseline mental health (beta = -0.21), and prior life-threatening illness (beta = -0.29). Peritraumatic dissociation was due to the patient's sense of threat to life (beta = -0.47), and threat was related to Injury Severity Score (beta = 0.2), assault(beta = 0.14), education (beta = -0.15), and age (beta = -0.19). Baseline SF36 mental health was related to social support (beta = 0.27) and income (beta = 0.21). Income was contingent on education (beta = 0.21). CONCLUSION: PTSD occurred in 42.3% of injured adults 6 months after trauma and was related to assault, dissociation, female gender, youth, poor mental health, and prior illness. By modeling PTSD, we may learn more of the etiology, risk stratification, and potentials for the treatment of this common and important morbidity of injury.     

A sociodemographic and economic comparison of breast reconstruction, mastectomy, and conservative surgery

BACKGROUND: There are a variety of surgical choices for women with early-stage breast cancer, including breast-conserving surgery, mastectomy, or mastectomy plus reconstructive surgery. This report examines some of the factors that affect these choices and the costs of the various treatment options. METHODS: Data from the Virginia Cancer Registry were linked to insurance claims from the Trigon Blue Cross and Blue Shield Company for women with local and regional staged breast cancer from 1989 to 1991 in Virginia. Multivariate analyses and cost studies were performed. RESULTS: There were 592 women who underwent breast-conserving surgery (BCS, 26%), mastectomy (58%), or mastectomy plus reconstruction (16%). Increasing age reduced the use of reconstruction. The choice of reconstruction was not affected by tumor size, nodal status, or race. Sixty percent of women had immediate breast reconstruction at the time of mastectomy; the majority had the implant procedure. The cost of BCS ($21,582) was higher than that of mastectomy ($16,122, P < .01). The costs for BCS and mastectomy were significantly lower than for mastectomy plus reconstruction ($31,047, P < .05). The 2-year cost for immediate reconstruction was $8200 less than for delayed procedures and was similar to the cost of BCS. CONCLUSIONS: Age was the driving force in reconstruction decisions. Clinical factors such as tumor size and nodal status were more important for the choice between BCS and mastectomy. There are significant cost differences between the various procedures. For a similar cosmetic outcome, BCS is less expensive than breast reconstruction. When reconstruction is required, a simultaneous procedure is less expensive.     

Diagnosis and management of BK polyomavirus interstitial nephritis in renal transplant recipients

BACKGROUND: Interstitial nephritis caused by BK polyomavirus is a recognized complication of renal transplantation. A study of renal transplant recipients at Duke University Medical Center was undertaken to evaluate diagnostic modalities and assess clinical outcomes in transplant polyomavirus infections. METHODS: Polyomavirus nephritis was identified in 6 of 240 patients who received renal transplants between January 1996 and June 1998 and an additional patient who underwent transplantation in 1995. The clinical records of these seven patients were reviewed, as were all renal biopsy and nephrectomy specimens. Electron microscopy (EM) was performed on negatively stained urine samples from 6 patients with polyomavirus infection and 23 patients with other diagnoses. RESULTS: Patients with polyomavirus infection shared several clinical features, including ureteral obstruction (5/7 patients), lymphocele (3/7), bacterial urinary tract infection (3/7), hematuria (3/7), cytomegalovirus infection (3/7), and immunosuppression with mycophenolate mofetil (6/7). All patients experienced elevations in serum creatinine, which stabilized or decreased in four patients with altered or decreased immunosuppression. The diagnosis of polyomavirus infection was established by renal biopsy and EM of urine in five patients, by biopsy alone in one, and by EM alone in one. Sequential examinations of urine by EM were used to monitor the course of infection in six patients. CONCLUSIONS: Interstitial nephritis due to BK polyomavirus occurred in 2.5% of patients receiving renal transplants at our center since 1996. Polyomavirus infection can cause transplant dysfunction and graft loss, but progression of the infection can frequently be abrogated with alterations in immunosuppressive therapy. Both renal biopsy and EM of urine samples are useful in the diagnosis and monitoring of polyomavirus infections.     

Heparin-induced skin necrosis and low molecular weight heparins

Heparin-induced skin necrosis is a rare but potentially devastating side-effect of low molecular weight heparins. These agents are widely used in surgical practice and doctors prescribing them should be aware of the condition, as failure to recognise it may increase morbidity. An unusually severe case is presented with a review of the literature.     

Campath IH allows low-dose cyclosporine monotherapy in 31 cadaveric renal allograft recipients

BACKGROUND: Campath 1H is a depleting, humanized anti-CD52 monoclonal antibody that has now been used in 31 renal allograft recipients. The results have been very encouraging and are presented herein. METHODS: Campath 1H was administered, intravenously, in a dose of 20 mg, on day 0 and day 1 after renal transplant. Low-dose cyclosporine (Neoral) was then initiated at 72 hr after transplant. These patients were maintained on low-dose monotherapy with cyclosporine. RESULTS: At present, the mean follow-up is 21 months (range: 15-28 months). All but one patient are alive and 29 have intact functioning grafts. There have been six separate episodes of steroid-responsive rejection. One patient has had a recurrence of her original disease. Two patients have suffered from opportunistic infections, which responded to therapy. One patient has died secondary to ischemic cardiac failure. CONCLUSIONS: Campath 1H has resulted in acceptable outcomes in this group of renal allograft recipients. This novel therapy is of equal efficacy compared to conventional triple therapy, but allows the patient to be steroid-free and to be maintained on very-low-dose immunosuppressive monotherapy.     

Motility potential of macaque epididymal sperm: the role of protein phosphatase and glycogen synthase kinase-3 activities

Human and monkey ejaculated sperm contain protein phosphatase-1 (PP1), PP1 inhibitor 2 (12), and glycogen synthase kinase-3 (GSK-3). Inhibition of ejaculated human sperm protein phosphatase (PP) activity with calyculin-a (CL-A) significantly stimulates motility, implicating protein dephosphorylation in motility regulation. The present experiments were conducted to characterize and compare PP and GSK-3 activity in monkey caput and caudal epididymal sperm, to determine the cellular distribution of these enzymes, and to test the thesis that epididymal sperm PP activity is inversely related to motility. Caput epididymal sperm populations, (8.8% motile) contained levels of PP activity that were >3 times as high as those of caudal spermatozoa. This PP activity was further identified by inhibitor response profiles as PP1. In both caput and caudal sperm, the majority of this PP1 activity was localized in 100,000 x g soluble fractions. Western blot analysis indicated that a portion of this difference was the result of elevated amounts of PP1 in caput compared with caudal epididymal sperm. The presence of GSK-3 activity was undetectable in 100,000 x g insoluble fractions of epididymal sperm, whereas both caput and caudal sperm soluble fractions contained GSK-3 activity, which was approximately threefold higher in caput sperm compared with caudal populations. Treatment of caput epididymal sperm from the rhesus macaque with the PP inhibitor CL-A resulted in a significant, dose-dependent increase from 8 to 38% motile cells (without any effect on their path velocity). In contrast, CL-A had no significant influence on either percent motility or path velocity of caudal epididymal sperm. Cytosolic PP1 and GSK-3 activities appear to be inversely related to the motility of monkey epididymal sperm and may have a regulatory role in the development of the potential for motility in epididymal sperm.     

The vagaries of self-reports of physical activity: a problem revisited and addressed in a study of exercise promotion in the over 65s in general practice.

BACKGROUND: The assessment of levels of physical activity relies upon suitable measurement tools. OBJECTIVE: We aimed to investigate whether a practice nurse, using a motivational interview technique, could encourage older patients to increase their physical activity. METHODS: Health and well-being were monitored at baseline and 8 weeks following intervention. Physical activity levels were ascertained using both a self-report measure and ambulatory heart-rate monitoring. RESULTS: Whilst patients reported higher levels of physical activity at follow-up, this finding was not confirmed by the heart-rate data. CONCLUSION: The study concludes that patients tend to overestimate the amount of physical activity undertaken and that ambulatory heart-rate monitoring may be more useful for verifying actual behaviour.