Keloidal penile fibrosis: improvements with Centellicum® (Centella asiatica) and Pycnogenol® supplementation: a pilot registry.

BACKGROUND: The aim of this pilot study was to evaluate the effects of Pycnogenol® and CA (Centellicum®) on penile fibrosis and on associated signs and symptoms. METHODS: A group of 82 subjects with penile nodules and plaques was included in this registry study and followed up for 3 months; 32 were managed with standard management (SM) only. Twenty-four were managed with CA (Centellicum®: 3 capsules/day: 675 mg/day) in association with SM, and 26 subjects were managed with Pycnogenol® (150 mg/day) + CA (Centellicum® at the same dosage as in group 2) and SM. RESULTS: Subjects in the 3 groups were comparable, including the distribution of plaques. The occurrence of any previous catheterizations was also comparable. Safety and tolerability were optimal, no subjects had to stop supplementation. The percentage of subjects with improved symptoms evaluated with a Visual Analogue Scale line was significantly higher with both supplements in comparison with SM (P<0.05). The combined management with Pycnogenol® and Centellicum® was superior to the other 2 managements (P<0.05). Erectile function assessed by the Index of Erectile Fuction questionnaire (IIEF) was significantly higher with the combination Pycnogenol®+Centellicum (P<0.05). The number of plaques and microplaques, the average total sectional area of the plaques in each subject and the grey scale median were all better improved with the combination. Both supplementations were superior to SM at 12 weeks (P<0.05). Oxidative stress resulted significantly better (P<0.05) with the combination. All blood tests were normal at inclusion and at 12 weeks. The minimal, penile curvature at baseline was reduced in both the supplement groups at 12 weeks more than in the SM group (P<0.05). CONCLUSIONS: In conclusion Centellicum and Pycnogenol® appear to improve penile fibrosis reducing the keloidal aspects of penile plaques.

Fixed drug eruption due To 2,3-dimercapto-1-propanesulfonic acid (DMPS) treatment for mercury poisoning: a rare adverse effect.

BACKGROUND: Fixed drug eruptions (FDE) are characterized by recurrent, usually solitary erythematous or dark red macular, plaque or bullous lesions, all at the same site. Among the first choices for antidotal treatment in mercury exposure, 2,3-dimercapto-1-propanesulfonic acid (DMPS) is generally a drug with a low incidence of side effects. FDE due to DMPS was not detected in our literature research and so we aimed to present this rare case. CASE REPORT: Forty-eight-year-old male patient, gunpowder and explosives factory worker, was admitted to our hospital because of mercury exposure and we started DMPS treatment. On the second day of chelation treatment, swelling and felting on lips and complaints of wound formation in genital areas started. Annular, purple color plaque on penis with no angioedema was observed. Case was regarded as FDE. Systemic and topical steroid therapy was started after termination of chelation therapy and lesions regressed with steroids. DISCUSSION: Drug eruptions are substantially common dermatological problems and can be seen in about 2.2% of inpatients. The most common unexpected effects of DMPS are allergic skin reactions. The clinical state regress rapidly after the cessation of chelation therapy.

Role of inhibiting LIM-kinase2 in improving erectile function through suppression of corporal fibrosis in a rat model of cavernous nerve injury.

We evaluated whether LIM-kinase 2 inhibitor (LIMK2i) could improve erectile function by suppressing corporal fibrosis through the normalization of the Rho-associated coiled-coil protein kinase 1 (ROCK1)/LIMK2/Cofilin pathway in a rat model of cavernous nerve crush injury (CNCI). Sixty 11-week-old male Sprague-Dawley rats were divided equally into five groups: sham surgery (S), CNCI (I), and CNCI treated with low-dose (L), medium-dose (M), and high-dose (H) LIMK2i. The L, M, and H groups were treated with a daily intraperitoneal injection of LIMK2i (2.5, 5.0, and 10.0 mg kg-1 body weight, respectively) for 1 week after surgery. The erectile response was assessed using electrostimulation at 1 week, postoperatively. Penile tissues were processed for Masson's trichrome staining, double immunofluorescence, and Western blot assay. Erectile responses in the H group improved compared with the I group, while the M group showed only partial improvement. A significantly decreased smooth muscle/collagen ratio and an increased content of fibroblasts positive for phospho-LIMK2 were noted in the I group. The M and H groups revealed significant improvements in histological alterations and the dysregulated LIMK2/Cofilin pathway, except for LIMK2 phosphorylation in the M group. The inhibition of LIMK2 did not affect the ROCK1 protein expression. The content of fibroblasts positive for phospho-LIMK2 in the H group returned to the level found in the S group, whereas it did not in the M group. However, the L group did not exhibit such improvements. Our data suggest that the inhibition of LIMK2, particularly with administration of 10.0 mg kg-1 body weight LIMK2i, can improve corporal fibrosis and erectile function by normalizing the LIMK2/Cofilin pathway.

Penile calciphylaxis: a life-threatening condition successfully treated with sodium thiosulfate.

Calciphylaxis or calcific uremic arteriolopathy is a life-threatening condition that predominantly affects patients with end-stage renal disease on hemodialysis. A prevalence of up to 4% and a 6-month mortality rate of up to 80% have been reported in those with proximal disease (thighs, abdomen wall, and buttocks). Penile calciphylaxis is very rare but has a mortality rate of 69% within 6 months. Its treatment is controversial. For small lesions, conservative treatment with local wound care and debridement may suffice. Partial or complete penectomy may be needed for more extensive lesions, and especially those associated with signs of local infection. In addition to surgical intervention, as with any other case of calcific uremic arteriolopathy, the cornerstones of therapy should be to keep serum phosphorus <6 mg/dL, and a Ca × P product <55 mg²/dL². We report here the first case of penile calciphylaxis whereby intravenous sodium thiosulfate was used in addition to the standard medical and surgical therapy. Two months after surgery, the patient's wound completely healed and he has experienced no new lesions over the past 11 months.

[Laboratory research of the influence of keyouling on the proliferation of human prepuce epidermis cells and condyloma acuminatum cells].

OBJECTIVE: To discuss the mechanism of the Chinese medicine Keyouling in the treatment of condyloma axuminatum (CA). METHODS: Human prepuce epidermis cells and CA cells were primarily cultured and subcultured. We determined the proliferation of human prepuce epidermis cells and CA cells, and observed the influence of Keyouling with different concentrations on the proliferation of human prepuce epidermis cells and CA cells by means of MTT colourimetry assay. RESULTS: The absorbance was directly proportional to the numbers of human prepuce epidermis cells (r = 0.9850, P < 0.001) and CA cells (r = 0.9892, P < 0.001). Keyouling had no effect on proliferation of the human prepuce epidermis cells, but it had significant inhibition on CA cells. The concentrations of Keyouling bore negative correlation with the proliferation percentage of CA cells(r = -0.4124, P < 0.01). CONCLUSION: Keyouling can significantly restrain the growth and proliferation of CA cells but has no damaging effect on normal organic cuticle cells. It is suggested that Keyouling might have anti-HPV effect.

[Incidence and management of condylomata acuminata by French general physicians]. / Incidence et prise en charge des condylomes acuminés externes en médecine générale.

OBJECTIVES: Condylomata acuminata (or genital warts) are sexually transmitted diseases caused by human papillomavirus. Until now, there has been no available epidemiologic data about this disease in France. We conducted a prospective study among French general practitioners (GPs) to estimate the incidence of consultations for external condylomata acuminata in general practice. We also assessed the management of patients with external condylomata acuminata by French GP's. DESIGN: A panel of French general practitioners, members of the Sentinel network, had to fill-in prospectively a questionnaire for each patient with condylomata acuminata diagnosed between July and November 2000. RESULTS: The annual number of consultations for external condylomata acuminata with French GP's was estimated at 23,000 (CI (95 p. 100) 21,000-25,000) including 15,000 new cases (CI (95 p. 100) 13,000-17,000). Taking into account the estimations we made at the same time in office-based private dermatologists, we estimated the annual incidence of external condylomata acuminata in France at 107/100 000 inhabitants. The management of patients with external condylomata acuminata by French GP's was in accordance with the European guidelines in 54 to 78 p. 100 of cases. French GP's mostly prescribed chemical treatment. DISCUSSION: A proportion of cases of condylomata acuminata may have not been diagnosed. Similarly, some lesions may have been wrongly diagnosed as condylomata acuminata, but these proportions of false positive and false negative remain unknown. The incidence of external condylomata acuminata in France is similar to those estimated in others developed countries.

Comparing treatment response and complications between podophyllin 0.5%/0.25% in ethanol vs podophyllin 25% in tincture benzoin for penile warts.

AIM: The aims of this study were to: 1) ascertain if podophyllin resin in 0.5% [PE(0.5%)] and 0.25% [PE(0.25%)] in ethanol (PE) self-applied sequentially for 3 days with 4 days break cycle is as effective as supervised podophyllin 25% in tincture benzoin (PB) applied in the clinic biweekly in treating penile warts and 2) ascertain if PE causes less skin irritation than PB. METHODS AND RESULTS: The clearance rate of penile warts was 36.4% (4/11) in PE (0.5%) treated group, 66.7% (4/6) in the PE (0.25%) treated group and 33.3% (6/18) for PB treated group after 1 week (ns). The wart clearance rate at 6 weeks for PE (0.5%) treated group, PE (0.25%) treated group and PB treated group were 81.8% (9/11), 100% (6/6) and 83.3% (15/17) respectively (ns). There were 47 individual warts on the penis of the 17 patients in the PE treated group and 58 individual warts on the penis of the 18 patients in the PB treated group. Based on the response of individual warts to the 2 treatment regimens, the clearance rate was 42.6% (20/47) for the PE treated group and 25% (15/56) for the PB treated group after 1 week treatment (ns). At 6 weeks follow-up, the clearance rate for the PE treated group and the PB treated group were 85.1% (40/47) and 73.2% (41/56) respectively (ns). Skin irritation including superficial erosions, pain and itch were observed in 47% (8/17) in patients treated with PE compared to 38.9% (7/18) in patients treated with PB (ns) during the 6 weeks follow-up period. The clearance rate of patients treated with PE (0.25%) was compared to those treated with PE (0.5%). Four out of six of PE (0.25%) treated patients had clearance of warts after 1 week and 100% clearance at the end of 6 weeks. None experienced any skin irritation. CONCLUSION: This study demonstrates that 0.5% podophyllin (and possibly 0.25% podophyllin) in ethanol is effective in eradicating penile warts. It can be used by patients for self-treatment at home with greater convenience and is more cost effective than the conventional podophyllin 25% in tincture benzoin paint.

Podophyllin 0.5% or 2.0% v podophyllotoxin 0.5% for the self treatment of penile warts: a double blind randomised study.

OBJECTIVE: To compare the effectiveness and cost of self treatment of penile warts with a commercial preparation of podophyllotoxin 0.5% (PDX 0.5%) with podophyllin 0.5% and podophyllin 2.0% sourced from Podophyllum emodii. DESIGN: A prospective double blind randomised study. SUBJECTS: 315 patients with penile warts attending two departments of genitourinary medicine. MAIN OUTCOME MEASURES: Absence of warts, cessation of treatment due to severe side effects at 5 weeks. RESULTS: Of the 315 patients, 244 conformed to the protocol. Analysis was on an intention to treat basis. At 5 weeks no significant differences were found in the extent of healing of warts or in side effects for the three treatment groups. The costs of drug treatment (excluding staff time) are at least pounds 10.00 less for podophyllin than podophyllotoxin. A fourfold variation in the active constituents of the podophyllin preparations did not produce appreciably different clinical responses. In a subanalysis no evidence of deterioration in effectiveness of podophyllin over time was demonstrated. CONCLUSIONS: Penile warts in selected cases can be safely treated with 0.5-2.0% podophyllin self applied by the patient at a fraction of the cost of commercially available podophyllotoxin. The shelf life of the podophyllin extracts is at least 3 months. These findings may be especially relevant in countries where resources for health care are limited.

New therapies for the treatment of genital warts.

The treatment of genital warts with cytodestructive agents such as podophyllin and trichloroacetic acid continues to impose a heavy burden on the workload of genitourinary medicine clinics. Consequently clinics are now looking to new, economical treatments that will improve the management of patients with genital warts. The most promising of these new agents is podophyllotoxin, which is now available in pharmaceutically pure form tailored for the home treatment of external genital warts in males and females.

Long-term followup of subclinical human papillomavirus infection treated with the carbon dioxide laser and intraurethral 5-fluorouracil: a treatment protocol.

We evaluated 162 high risk male patients for the presence of subclinical anogenital human papillomavirus infection with magnified penile surface scanning. Infected patients were treated as outpatients with the carbon dioxide laser under local anesthesia. Of the patients 43 were followed for a mean of 8.7 months or 2.1 treatments after the initial treatment (range 3 to 30 months). A subset of 10 patients was followed for more than 20 months or 6.2 treatments. To date a 51% recurrence rate has been observed in the over-all population and a 50% recurrence rate was noted in the 20-month followup population. In a separate arm of this study a small number of patients (15) with deoxyribonucleic acid typed subclinical intraurethral disease plus subclinical skin lesions were treated with topical carbon dioxide laser therapy for the penile lesions and adjuvant intraurethral 5% 5-fluorouracil. Mean followup in the group was approximately 4 months. The addition of intraurethral therapy in this positive human papillomavirus reservoir group had no significant effect on the high rate of human papillomavirus recurrence.

Congenital hypopituitarism associated with neonatal hypoglycemia and microphallus: four cases secondary to hypothalamic hormone deficiencies.

The association of hypoglycemia and microphallus in the male neonate is presumptive evidence of congenital hypopituitarism. This was observed in four male infants with normal birth weight and length, optic discs, and intelligence, and without gross central nervous system malformations. Plasma and urinary cortisol values were low. Stimulation with metyrapone and insulin hypoglycemia failed to elicit a rise in plasma corticoids, but multiple doses of ACTH evoked a response. Growth hormone responses to arginine, insulin, sleep, L-dopa, and glucagon were uniformly less than 2.5 ng/ml. In three patients, however, length remained within 2 SD of the mean until two years of age; in one, there was a sharp decrease in growth by three months. Two patients had low plasma TSH and thyroxine concentrations within the first month of life. In the other two patients, whose thyroxine levels were measurable, intravenous administration of thyrotropin-releasing factor evoked a normal rise in plasma TSH; serum thyroxine decreased into the hypothyroid range in one after GH therapy was initiated. Plasma prolactin was normal in the first two patients receiving thyroxine replacement therapy. The other two patients had elevated baseline prolactin levels and had an augmented rise in plasma prolactin after administration of TRF. Human chorionic gonadotropin induced a 10- to 15-fold rise in plasma testosterone in the two patients tested. The changes in plasma FSH and LH after luteinizing hormone-releasing factor were either low or in the prepubertal range. In three patients, treated with testosterone enanthate intramuscularly, phallic growth occurred. In addition, all three had a transient increase in height but no acceleration of skeletal maturation. The data suggest a deficiency of hypothalamic hypophysiotropic hormones rather than a primary pituitary defect. Early recognition of this syndrome complex is critical for prompt treatment of the life-threatening cortisol deficiency. The diagnosis is more difficult in affected females because their external genitals are normal. The microphallus is a remediable manifestation of hypopituitarism.

Neutral red with photoinactivation in the treatment of herpes genitalis.

A clinical trial was undertaken to compare the efficacy of neutral red photodynamic inactivation treatment of genital herpes infections with that of a non-photoactive dye, phenol red, as a control. In a series of nineteen patients with virologically proven herpes genitalis who were adequately followed, eleven were treated with neutral red, and eight with phenol red; no difference in response to therapy was found between the two groups, and it is concluded that under the conditions of this trial neutral red with photoinactivation was not effective in the treatment of acute genital herpes infections. Approximately 75 per cent. of those with vulval lesions also had concurrent cervical infection, so that an effective topical treatment would need to be applicable to both anatomical sites.