PubMed · 11198251
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
K Landow. 2001. OTC agents for ringworm?. https://doi.org/10.3810/pgm.2001.01.847
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
The aim of this study was to provide evidence for the peripheral effect of opioids in oromaxillary procedures and to investigate whether postoperative morphine sulfate plus lidocaine administered as a local spray achieve better analgesic efficacy than lidocaine applied alone. The double-blind randomized study included 60 patients. The patients exhibited neither preoperative pain nor inflammation (tooth extractions) and when pain occurred received as alternative medication diclofenac retard 50 mg or tramadol. Side effects were documented. No differences between the two groups were observed in the demographic data, visual and numeric analog scale in the first 24 h, or in the consumption of analgesics. Since the patients presented in a pain-free state at the time of surgery, apparently no activation of the peripheral opioid receptors occurs. Thus, a peripheral effect of opioids could not be demonstrated in this model.
Options for skin cancer treatment currently include surgery, radiotherapy, topical chemotherapy, cryosurgery, curettage, and electrodessication. Although effective, surgery is costly and unsuitable for certain patients. Radiotherapy can leave a poor cosmetic effect, and current chemotherapy is limited by low cure rates and extended treatment schedules. Here, we describe the preclinical activity of a novel topical chemotherapeutic agent for the treatment of skin cancer, 3-ingenyl angelate (PEP005), a hydrophobic diterpene ester isolated from the plant Euphorbia peplus. Three daily topical applications of 42 nmol (18 micro g) of PEP005 cured a series of s.c. mouse tumors (B16 melanoma, LK2 UV-induced squamous cell carcinoma, and Lewis lung carcinoma; n = >14 tumors/group) and human tumors (DO4 melanoma, HeLa cervical carcinoma, and PC3 and DU145 prostate carcinoma; n = >4 tumors/group) previously established (5-10 mm(3)) on C57BL/6 or Foxn1(nu) mice. The treatment produced a mild, short-term erythema and eschar formation but, ultimately, resulted in excellent skin cosmesis. The LD(90) for PEP005 for a panel of tumor cell lines was 180-220 micro M. Electron microscopy showed that treatment with PEP005 both in vitro (230 micro M) and in vivo (42 nmol) rapidly caused swelling of mitochondria and cell death by primary necrosis. (51)Cr release, uptake of propidium iodide, and staining with the mitochondria dye JC1, revealed that PEP005 (230 micro M) treatment of tumor cells in vitro resulted in a rapid plasma membrane perturbation and loss of mitochondrial membrane potential. PEP005 thus emerges as a new topical anti-skin cancer agent that has a novel mode of action involving plasma membrane and mitochondrial disruption and primary necrosis, ultimately resulting in an excellent cosmetic outcome.
PURPOSE: Topical therapies for anal fissure have largely focused on nitric-oxide donors (e.g., nitroglycerin), sometimes with undesirable side effects or inconsistent benefits. Topical phosphodiesterase inhibitors have theoretical merit but have never been reported in treatment of anal fissure. This article describes manometric analysis of the effects of a phosphodiesterase-5 inhibitor, topical sildenafil (Viagra) in 19 consecutive patients with chronic anal fissure with no previous treatment history. METHODS: Station pullthrough manometry was performed with patients in the left-lateral position. Maximum resting pressure (MRP1) was recorded, and 0.75 ml of 10 percent sildenafil was then instilled in the anal canal. Maximum resting pressure was repeated at the same distance from the anal verge. Thereafter, pressure was measured continuously. Time for initial relaxation (T1) and time to maximal relaxation (T2) were recorded. Average resting pressure (MRP2) was calculated. Results were analyzed by Student's t-test. RESULTS: Topical administration of 10 percent sildenafil was accompanied by significant reduction in anal sphincter pressure (18 percent; P < 0.01). Only one patient failed to respond. Average onset of action was less than three minutes, with maximum effect one minute later. MRP1: 119.3 +/- 18.7 cmH(2)O. MRP2: 97.8 +/- 21.3 cmH(2)O. MRP2 < MRP1, P < 0.01. MRP M vs. F, ns. T1: 168 +/- 67 seconds (M = 210 +/- 72, F = 130 +/- 53, P < 0.02). T2: 230 +/- 78 seconds (M = 271 +/- 63, F = 183 +/- 75, P < 0.02). Mild-to-moderate anal discomfort was reported by 26 percent of patients. No headaches or other side effects were reported. CONCLUSIONS: Topical administration of a phosphodiesterase-5 inhibitor (sildenafil, Viagra) significantly reduces anal sphincter pressure in patients with chronic anal fissure. A beneficial effect of nitric oxide on the spastic anal sphincter has been demonstrated previously. This study confirms that this effect need not be derived solely from nitric oxide donors. New therapeutic avenues for treatment of anal fissure through indirect enhancement of nitric oxide activity are suggested.