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Biomedical subjects

Culley C Carson

Publications and source records attributed to Culley C Carson.

At least 37 records · Page 2Linked to original sources

Phosphodiesterase type 5 inhibitors for erectile dysfunction.

The cyclic nucleotide signalling pathway mediates the smooth-muscle relaxing effects of nitric oxide necessary for normal erectile function. Down-regulation of this pathway is central to the pathophysiology of many forms of erectile dysfunction (ED), which is often associated with other chronic diseases (e.g. hypertension, type 2 diabetes mellitus) and treatments (e.g. certain drugs, radical prostatectomy). Conversely, selective inhibition of the enzyme that catalyses the degradation of cGMP (phosphodiesterase type 5, PDE-5) promotes erectile responses to sexual stimulation. The successful launch and commercialization of the selective PDE5 inhibitor (PDE5I) sildenafil transformed the treatment of ED, not only by providing an effective, well tolerated oral ED therapy, but also by fostering greater candour about the problem among men. Sildenafil is highly effective in promoting erectile responses across a wide spectrum of severity and causes of ED, including patients with ED that is often refractory to treatment. The recent advent of vardenafil, which has the highest in vitro potency of all available PDE5Is, and tadalafil, which has a prolonged half-life that may enable couples to have sexual activity with less planning, represent further advances. Other PDE5Is offering further potential improvements are under active investigation.

3',5'-Cyclic-GMP Phosphodiesterases↗

Urinary tract infections in women.

Urinary tract infections in female patients are exceedingly common. One third of all women with an initial UTI demonstrate recurrence, and one third of those recurrences are in the first 6 months. The potential morbidity of RUTIs is high, especially in infants, the elderly, and pregnant patients. Uropathogenic bacteria reside in the rectal vault, colonize the vagina, and then ascend per the urethra into the bladder. These bacteria avidly adhere to uroepithelial cells using pili and can further ascend to the kidneys. Empiric treatment of an initial uncomplicated UTI is acceptable, but recurrences warrant a urine culture and possible radiographic evaluation. Fluoroquinolones are now first-line medications for UTIs, except in geographic areas where resistance to TMP-SMX is still low. Response to therapy should govern the need for additional treatment. Certain motivated patients with three or more UTIs per year should be considered for prophylaxis therapy.

Adolescent↗

Efficacy of antibiotic impregnation of inflatable penile prostheses in decreasing infection in original implants.

PURPOSE: We compared infection rates in original inflatable penile prostheses implants between prostheses impregnated with InhibiZone (American Medical Systems, Minnetonka, Minnesota), an antibiotic surface treatment, and prostheses without antibiotic treatment. MATERIALS AND METHODS: We retrospectively reviewed patient information forms filed with the manufacturer following original implantation in the United States to implant AMS 700 series penile prostheses (American Medical Systems) between May 1, 2001 and April 30, 2003. We compared results in 4205 men, including 2261 with a mean age of 60.71 years who received prostheses with InhibiZone, a surface treatment combining rifampin and minocycline hydrochloride, and a control group of 1944 with a mean age of 61.04 years who received untreated prostheses. Followup in the treatment and control groups was 0 to 11.5 months (mean 5 and 8, respectively). In the treatment group only implants in which all components were treated were included. RESULTS: The reported incidence of infection after 60 days was 0.28% in the treated group and 1.59% in the control group (p = 0.0034). After 180 days the infection rate in the treated and control groups was 0.68% and 1.61%, respectively (p = 0.0047). The treated group had an infection rate that was 82.4% lower than in the control group after 60 days and 57.8% lower after 180 days. Erectile dysfunction etiologies occurred at statistically similar rates in the 2 groups and did not impact infection rate results. CONCLUSIONS: The use of InhibiZone to target postoperative infections results in a statistically significant decrease in penile prosthesis infection rates in original implants. Infection rates in the control group were consistent with those in the published literature.

Anti-Bacterial Agents↗

Penile prosthesis cultures during revision surgery: a multicenter study.

PURPOSE: Initial implantation of inflatable penile prosthesis has a 3% risk of infection. Reoperation of penile implants has a higher rate of infection, estimated between 10% and 18%. To explain the higher risk in revision surgery in this prospective study we cultured clinically uninfected prostheses requiring revision. Prosthesis pain was also investigated as a predictor of positive culture. MATERIALS AND METHODS: At 3 institutions cultures were prospectively obtained from 77 clinically uninfected penile prostheses at revision surgery. Immediately upon surgical exposure of the pump cultures were obtained. If a bacterial biofilm was noted on any component it was additionally cultured. All culture isolates positive for a staphylococcus species were tested for sensitivity to rifampin and tetracycline (minocycline). An implant is now available that is coated with these antibiotics. Patient history of chronic prosthesis pain was ascertained. RESULTS: Culture positive bacteria were found in 54 of 77 (70%) patients with clinically uninfected penile prostheses. In some patients more than 1 organism grew and, occasionally, the pump culture was negative but the biofilm was positive. Of 54 patients 49 had positive (90%) culture for staphylococcus genus with 10 different species. All staphylococcal species were sensitive to rifampin and/or tetracycline. We did not find a significant association between prosthesis related pain and culture laboratory results. CONCLUSIONS: The majority of clinically uninfected penile prostheses have organisms growing in the implant spaces at reoperation. Most of these organisms are staphylococcal species that are sensitive to rifampin/minocycline.

Aged↗

Erectile response with vardenafil in sildenafil nonresponders: a multicentre, double-blind, 12-week, flexible-dose, placebo-controlled erectile dysfunction clinical trial.

OBJECTIVE: To evaluate the efficacy of vardenafil in patients previously unresponsive to sildenafil. PATIENTS AND METHODS: A multicentre, double-blind, 12-week, flexible-dose, placebo-controlled trial was conducted, involving 463 men aged > or = 18 years with moderate-to-severe erectile dysfunction (ED) and who were unresponsive to sildenafil (by history). After a 4-week treatment-free run-in, patients received placebo or vardenafil 10 mg with the option to maintain current dose or to titrate by one dose level (5, 10 or 20 mg) based on efficacy and tolerability at 4 and 8 weeks. Outcome measures were the erectile function (EF) domain score of the International Index of Erectile Function, two Sexual Encounter Profile diary questions (vaginal penetration and maintenance of erection until successful completion of intercourse), and the Global Assessment Question (GAQ). RESULTS: There was significantly better EF with vardenafil than with placebo throughout the study. The least-square mean EF domain scores increased from 9.3 at baseline to 17.6 at the 'last' observation carried forward (LOCF) analysis with vardenafil (P < 0.001). Overall least-square mean per-patient success rates more than doubled for penetration (30.3% to 62.3%) and quadrupled for successful intercourse (10.5% to 46.1%) with vardenafil. Improved erections (positive response to the GAQ) were reported by 61.8% of patients receiving vardenafil and 14.7% of those receiving placebo at LOCF (P < 0.001). Normal EF (domain score > or = 26) was achieved by 30% of patients receiving vardenafil and 6% receiving placebo at LOCF (P < 0.001). Adverse events were infrequent and representative of the phosphodiesterase-5 inhibitor profile. CONCLUSION: Vardenafil is an effective and generally safe treatment for ED, even in men unresponsive to sildenafil (by history).

Administration, Oral↗

Sildenafil: a 4-year update in the treatment of 20 million erectile dysfunction patients.

Sildenafil citrate, the first internationally approved and widely used oral agent for the treatment of erectile dysfunction (ED), has revolutionized the treatment of ED throughout the past 5 years. This phosphodiesterase type-5 (PDE-5) inhibitor is selective for corpus cavernosum smooth muscle tissue and produces excellent erectile function. Its efficacy and safety over a wide variety of etiologies of ED and severities of ED demonstrates its usefulness in the clinical treatment of these patients. More than 20 million men have been treated worldwide with sildenafil with excellent results. ED caused by difficult-to-treat etiologies such as radical prostatectomy, severe diabetes, and spinal cord injury have demonstrated efficacy. Although sildenafil citrate, like all PDE-5 inhibitors, is contraindicated in patients taking nitrate medications for cardiac disease, it is effective and safe for those cardiovascular patients who are not taking nitrate medications. The incidence of adverse cardiovascular events in patients taking sildenafil does not differ from those of the general population. Investigations into the pharmacologic effect of sildenafil on coronary myocardial tissue further supports the safety of this medication. Sildenafil has been safe and effective in patients taking various medications including multiple antihypertensive drugs, selective serotonin reuptake inhibitors, cardiac, and diabetic medications.

3',5'-Cyclic-GMP Phosphodiesterases↗

Urologic manifestations of hematologic disease sickle cell, leukemia, and thromboembolic disease.

Advances in medicine are allowing patients with hematologic disease to live longer and healthier lives than ever before. As these patients age, however, manifestations of their disease processes may develop as complications in other organ systems. We discussed the major genitourinary complications of sickle cell anemia, leukemia, and thromboembolic disease. These range from the benign inability to concentrate urine that is seen in sickle cell disease to renal infarction that results from nephrotic syndrome. Our ability to treat and prevent these complications will improve as our understanding of these disease processes and their pathophysiology grows. Additionally, it is important for urologists to understand the underlying pathophysiology of hematologic disease to best serve the patients. For example, it may be the urologist who makes the diagnosis of ovarian vein thrombosis in a pregnant woman with right lower quadrant pain and fever. This diagnosis, with the proper treatment of antibiotics and anticoagulation, could prevent the potential development of septic thrombophlebitis. Urologists will increasingly be called upon to deal with the manifestations of these complex diseases as these patients are living longer. It is our duty to educate ourselves about these disease processes so that we can make the best clinical decisions for our patients.

Adrenergic alpha-Agonists↗

Long-term use of sildenafil.

The treatment of erectile dysfunction (ED) has been revolutionised by new agents to inhibit the enzyme PDE5. The scientific basis of this treatment of ED includes relaxation of the corpus cavernosum smooth muscle tissue by inhibition of PDE5 that breaks down cGMP, the key pathway for the production of erectile function in humans. Many clinical studies, both pre- and post-marketing, have demonstrated the clinical efficacy and safety of sildenafil (Viagra, Pfizer) - the first approved selective PDE inhibitor for the treatment of ED. Sildenafil is inhibitory of PDE5 at a rate tenfold higher than for the next PDE (PDE6), which produces visual changes through the retinal rods. Its clinical effectiveness has been well documented in the majority of men with ED irrespective of aetiology. The aetiology of ED, also, does not appear to effect the function of sildenafil in relaxing corpus cavernosum smooth muscle tissue. Adverse events are usually associated with the vascular changes from PDE5 inhibition. These include headache and flushing. Each of these adverse events, however, declines with medication use. With the use of sildenafil, it has been clearly, clinically demonstrated that the selective inhibition of PDE5 is an appropriate, effective, safe method for the treatment of ED of all aetiologies and severities.

Aged↗

The efficacy of sildenafil citrate (Viagra) in clinical populations: an update.

Although certain risk factors are known to be associated with erectile dysfunction (ED), the demographic and ED characteristics of the population of men with ED are quite diverse. We examined results from randomized trials of sildenafil citrate (Viagra) to ascertain if efficacy differed across various subgroups of men with ED. In addition, we reviewed findings from long-term extension studies and published accounts of sildenafil use in clinical practice to determine if effectiveness is maintained with long-term sildenafil treatment and to determine if effectiveness in the clinic practice setting is consistent with that reported in clinical trials. Data were pooled from 11 double-blind, placebo-controlled, flexible-dose (taken as needed) studies to assess efficacy (N = 2667) of sildenafil in men (aged 23 to 89 years) with ED of broad-spectrum etiology who were not receiving concomitant nitrate therapy. Efficacy evaluations included the International Index of Erectile Function, a global efficacy question ("Did treatment improve your erections?"), and a patient-recorded event log of sexual activity. Significantly improved erectile function was demonstrated for sildenafil compared with placebo for all efficacy parameters analyzed (P <0.02 to 0.0001), regardless of patient age, race, body mass index, ED etiology, ED severity, ED duration, or the presence of various comorbidities. Long-term effectiveness was assessed in 3 open-label extension studies. Of those who continued long-term therapy (1 to 3 years) with sildenafil, >95% of patients reported that they were satisfied with the effect of treatment on their erections, and that treatment had improved their ability to engage in sexual activity. Findings from published accounts of sildenafil use in the clinical practice setting further demonstrated that sildenafil is an effective treatment for a wide range of patients with ED.

Adult↗

Adult circumcision outcomes study: effect on erectile function, penile sensitivity, sexual activity and satisfaction.

PURPOSE: Evidence concerning the effect of circumcision on sexual function is lacking. Men circumcised as adults are potentially in a unique position to comment on the effect of a prepuce on sexual intercourse. We examine sexual function outcomes in men who have experienced sexual intercourse in the uncircumcised and circumcised states. MATERIALS AND METHODS: Men 18 years old or older when circumcised were identified by billing records during a 5-year period at an academic medical center. Medical charts were reviewed for confirmation of the procedure and to identify the indication(s). These men were surveyed to assess erectile function, penile sensitivity, sexual activity and overall satisfaction. Data were analyzed using paired t tests to compare category scores before and after circumcision. RESULTS: A total of 123 men were circumcised as adults. Indications for circumcision included phimosis in 64% of cases, balanitis in 17%, condyloma in 10%, redundant foreskin in 9% and elective in 7%. The response rate was 44% among potential responders. Mean age of responders was 42 years at circumcision and 46 years at survey. Adult circumcision appears to result in worsened erectile function (p = 0.01), decreased penile sensitivity (p = 0.08), no change in sexual activity (p = 0.22) and improved satisfaction (p = 0.04). Of the men 50% reported benefits and 38% reported harm. Overall, 62% of men were satisfied with having been circumcised. CONCLUSIONS: Our findings may help urologists better counsel men undergoing circumcision as adults. Prospective studies are needed to better understand the relationship between circumcision and sexual function.

Adult↗

The efficacy, safety and tolerability of intracavernous PNU-83757 for the treatment of erectile dysfunction.

PURPOSE: Despite the introduction of sildenafil citrate many men with erectile dysfunction remain dependent on intracavernous therapy. While the majority achieves satisfactory results with currently available intracavernous preparations, all preparations have undesirable side effects, including priapism, fibrosis and post-injection pain. We determined the efficacy, safety and tolerability of the erectogenic potassium channel opener PNU-83757. MATERIALS AND METHODS: We selected 66 men with erectile dysfunction of vascular etiology for intracavernous injection of PNU-83757 in a single dose, single blind, placebo controlled study. Of the 6 patients allocated into each of 11 dose groups 5 received active drug and 1 received placebo. Groups received progressive doses of PNU-83757 or placebo. Holter monitoring was performed at scheduled intervals. Heart rate, and systolic, diastolic and mean blood pressure were assessed at scheduled intervals. Blood samples were obtained for pharmacokinetic study. Patients were evaluated at regular intervals for adverse events. Investigators and patients evaluated efficacy. RESULTS: The first complete erection was observed at 10 mcg. Of the 25 patients receiving active drug in the 60 to 140 mcg. groups only 1 had no erectile response, 15 had partial erection and 9 had complete erection. No serious adverse events or cardiovascular effects were noted. CONCLUSIONS: The minimum effective dose for complete erection was 10 mcg. The erectile response reached a plateau between 60 and 140 mcg., suggesting minimal improvement in efficacy at higher doses. Patient evaluation of erectile quality corresponded well with that of investigators. PNU-83757 was efficacious and extremely well tolerated, and the only adverse events were mild. No cardiovascular side effects were observed at any dose. PNU-83757 intracavernous injections caused no post-injection pain in any patient, which may make PNU-83757 superior to alprostadil in a select group. Further study is required to evaluate the efficacy of PNU-83757 combined with other drugs and with sexual stimulation.

Adolescent↗

Therapeutic strategies for managing erectile dysfunction: a step-care approach.

During the past two decades, advances in the understanding of erectile dysfunction have provided primary care physicians, urologists, and other healthcare providers with additional treatment options. The introduction of sildenafil citrate, the first oral phosphodiesterase type 5 (PDE5) isoenzyme inhibitor, has helped to restore erectile function and improve overall health and quality of life. The step-care approach to the treatment of erectile dysfunction can be divided into first-, second-, and third-line modes of therapy. Most patients with erectile dysfunction will choose oral agents because of their simplicity and ease of administration. This article reviews all treatment strategies for erectile dysfunction, with a focus on PDE5 inhibitors, including novel agents that may optimize patient outcomes.

Counseling↗

Urological and medical evaluation of men with erectile dysfunction.

As the medical understanding of erectile dysfunction has evolved, the approach to its evaluation must also change. A good doctor/patient rapport is crucial to making patients more comfortable talking about their sexual function. Questionnaires help elicit specific information on which to base the diagnosis and find the etiology, along with examination of the genitals and hormone and other assays. If oral therapy is unsuccessful, other studies may find underlying conditions, leading to appropriate treatment.

Journal Article↗

Erectile dysfunction: evaluation and new treatment options.

OBJECTIVE: Erectile dysfunction (ED) is a common condition of aging men. Indeed as many as 50% of men over age 40 will suffer some degree of ED. This erectile dysfunction has substantial impact on interaction with their partners, families, and employment. ED may be a harbinger of more serious vascular events and is commonly associated with depression. METHODS: Evaluation of ED begins with a careful history, asking the patient about his sexual function during clinical visits. Once identified, ED must be carefully considered with full history, careful physical examination, and laboratory studies to include markers of vascular risk factors, diabetes, and hypogonadism. RESULTS: The treatment of ED was revolutionized by the introduction of phosphodiesterase type 5 (PDE5) inhibitors in 1998. Currently, 3 PDE5 inhibitors are available internationally with excellent expected results and somewhat unique profiles. Although these agents are safe in all patients who do not have severe cardiac disease or who are taking nitrate medications, they require some patient instruction and counseling to optimize results. In that small group of patients who do not respond to these oral medications, additional alternatives are available for patients motivated to pursue treatment of their ED. CONCLUSION: Currently available safe and effective alternatives for the treatment of ED can improve the lives of patients and partners and increase their quality of life.

Adult↗