Collagenase Clostridium histolyticum for the Treatment of Peyronie's Disease: The Development of This Novel Pharmacologic Approach.

INTRODUCTION: The conception of collagenase Clostridium histolyticum (CCH) as treatment for Peyronie's disease (PD) was a vital first step in providing a nonsurgical, minimally invasive FDA-approved treatment for men with PD. AIM: To review the origins, clinical research history, and ultimately FDA approval of collagenase as PD treatment. METHODS: A PubMed search using (Peyronie's or Peyronie) AND collagenase, and limited to clinical research studies, returned nine papers that were examined in the current review. RESULTS: Collagenase as a PD treatment arose in response to a lack of effective nonsurgical treatments and the incomplete understanding of underlying PD etiology. Awareness of dense collagen in PD scarring and parallel initial exploration of collagenase to treat herniated lumbar discs coincided with and inspired laboratory-based investigation of collagenase effects on excised PD plaque tissue. The foundational conceptual work and the critical development of purified injectable collagenase allowed the pursuit of clinical studies. Progression of clinical studies into large-scale robust trials culminated in two important outcomes: development of the first validated, PD-specific measure of psychosexual function, the Peyronie's Disease Questionnaire, and the first FDA-approved treatment for PD. CONCLUSIONS: Collagenase therapy began as an attempt to modify the structure of PD-related tunica albuginea scarring, despite the lack of a fundamental understanding of the scar's origin. If we wish to advance PD treatment beyond this first effective step, the future needs to bring us full circle to the starting point: We need a greater understanding of the control of collagen deposition and wound healing in men with PD.

Lubiprostone: chloride channel activator for chronic constipation.

BACKGROUND: Chronic constipation is a common and costly health problem occurring in approximately 4.5 million Americans. Current management of constipation is suboptimal and requires a stepwise approach using a combination of laxatives to decrease symptoms. OBJECTIVE: The objective of this review was to describe the efficacy and safety of a new therapeutic entity, lubiprostone, recently approved by the US Food and Drug Administration for the treatment of chronic idiopathic constipation. METHODS: Computerized searches of MEDLINE and International Pharmaceutical Abstracts were conducted (1966-July 10, 2006). Search terms utilized were lubiprostone, RU-0211, and chronic constipation. References of selected articles were searched for additional articles or abstracts. All relevant published literature regarding lubiprostone was included in this review. Pertinent abstracts presented at meetings of the American College of Gastroenterology and Digestive Diseases Week were also included. RESULTS: Lubiprostone activates a chloride channel (ie, subtype 2) and increases chloride and fluid secretion into the intestines, resulting in relief of constipation. It is poorly absorbed after oral administration, and its metabolism occurs primarily in the stomach and jejunum. Lubiprostone was evaluated in 6 placebo-controlled, double-blind, randomized Phase II or III clinical trials. Overall, in clinical trials, >1400 patients were exposed to 24 mug of lubiprostone BID for up to 48 weeks. It improved the number of bowel movements, stool consistency, bloating, and global assessment of constipation compared with placebo (P < 0.05). Nausea was the most common adverse effect reported in clinical trials, occurring in 30.9% of patients. However, nausea was dose dependent and decreased when lubiprostone was given with food. CONCLUSIONS: Lubiprostone is the first in its class of chloride channel activators that results in improvement of symptoms of constipation. It has not been compared with other laxatives but, based on the available placebo-controlled studies, its efficacy is superior to placebo and its safety is acceptable. Considering the currently available laxatives, lubiprostone will become an additional option for the treatment of patients with chronic constipation.

Use of biological based therapy in patients with cardiovascular diseases in a university-hospital in New York City.

BACKGROUND: The use of complementary and alternative products including Biological Based Therapy (BBT) has increased among patients with various medical illnesses and conditions. The studies assessing the prevalence of BBT use among patients with cardiovascular diseases are limited. Therefore, an evaluation of BBT in this patient population would be beneficial. This was a survey designed to determine the effects of demographics on the use of Biological Based Therapy (BBT) in patients with cardiovascular diseases. The objective of this study was to determine the effect of the education level on the use of BBT in cardiovascular patients. This survey also assessed the perceptions of users regarding the safety/efficacy of BBT, types of BBT used and potential BBT-drug interactions. METHOD: The survey instrument was designed to assess the findings. Patients were interviewed from February 2001 to December 2002. 198 inpatients with cardiovascular diseases (94 BBT users and 104 non-users) in a university hospital were included in the study. RESULTS: Users had a significantly higher level of education than non-users (college graduate: 28 [30%] versus 12 [12%], p = 0.003). Top 10 BBT products used were vitamin E [41(43.6%)], vitamin C [30(31.9%)], multivitamins [24(25.5%)], calcium [19(20.2%)], vitamin B complex [17(18.1%)], fish oil [12(12.8%)], coenzyme Q10 [11(11.7%)], glucosamine [10(10.6%)], magnesium [8(8.5%)] and vitamin D [6(6.4%)]. Sixty percent of users' physicians knew of the BBT use. Compared to non-users, users believed BBT to be safer (p < 0.001) and more effective (p < 0.001) than prescription drugs. Forty-two potential drug-BBT interactions were identified. CONCLUSION: Incidence of use of BBT in cardiovascular patients is high (47.5%), as is the risk of potential drug interaction. Health care providers need to monitor BBT use in patients with cardiovascular diseases.

Use of alternative pharmacotherapy in management of cardiovascular diseases.

OBJECTIVES: To review use of alternative pharmacotherapy (AP) in patients with cardiovascular disease (CVD) and significant drug interactions between AP and traditional CVD medications. STUDY DESIGN: A literature search of MEDLINE and the National Complementary and Alternative Medicine database was done using these search terms: supplements, vitamins, garlic, fish oil, L-arginine, soy, coenzyme Q10, herbs, phytosterols, chelation therapy, alternative medicine, and CVD. PATIENTS AND METHODS: English human clinical trials measuring surrogate and clinical end points. RESULTS: Antioxidants have not been consistently proven beneficial in reducing cardiovascular mortality. Fish oils may be beneficial in patients with hypertension and hypercholesterolemia, but therapeutic doses need to be defined. Use of coenzyme Q10 in patients with heart failure has not demonstrated consistent benefits. Garlic may lower blood pressure and cholesterol levels, but also may increase bleeding, so its use in CVD patients should be monitored. Clinical studies with small sample sizes have demonstrated that L-arginine may be useful to prevent and treat CVD. The Food and Drug Administration recommends 25 g/day of soy protein as part of a diet low in saturated fats for cholesterol reduction. Plant sterols are recommended by the American Heart Association and the National Cholesterol Education Program Expert Panel as adjunct therapy to reduce low-density lipoprotein. No data support use of chelation therapy. Some APs interact with common prescription CVD medications (eg, gingko and ginseng with warfarin, St. John's Wort with digoxin). CONCLUSIONS: The benefits of APs as part of the treatment for CVD are controversial. Routine use is not recommended.