[Antimitotic effect of podophyllin derivatives on genital cancers].
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Antineoplastic Agents↗
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[Action of alkaloids from podophyllin on the response of pancreatic beta-cells of the rabbit to tolbutamide].
Some antineoplastic agents alter the microtubular-microfilamentous system involved in insulin release. The authors studied the effect of the podophyllotoxin derivate VM-26 and the epipodophyllotoxin derivative VP-16-213 on the insulin release by the pancreatic beta-cell after tolbutamide stimulation. VP-16-213 produced a slowing and partial inhibition of insulin release, and VM-26 inhibited the late stage of insulin release.
Animals↗
[Surgically treated supratentorial gliomas in the adult. Favourable action of a podophyllin derivative (VM 26) administered alone (author's transl)].
The action of VM 26 on cerebral glioblastomas was suggested by studies of phase II or protocols in which the drug was used in association. The randomised protocol presented here, involving 10 treated subjects and 11 controls, showed that VM 26 was active in terms of the duration of survival of patients undergoing surgery for a glioblastoma. The mean survival was 16.4 months as against 9.6 months in the controls (statistically significant difference at p less than 0.05). This activity would tend to characterise the drug as one of the essential factors in the chemotherapy of all malignant gliomas, in particular since it is itself free of all haematological complications, even at high doses, and causes scarcely any allergic problems.
Brain Neoplasms↗
Patients with genital warts: how are they managed by general practitioners?
This study was carried out to assess the management by general practitioners of patients with genital warts. An anonymized postal questionnaire was sent to 2060 general practitioners in the north west of England; 1260 (61.2%) completed questionnaires were returned. A total of 76.69% of GPs saw one or more cases per quarter. Of 468 (37.1%) GPs who managed patients in-house, 393 (83.9%) used podophyllin of concentration between 0.5 and 50%; 169 (43%) did not specify the podophyllin concentration and 112(23.9%) used podophyllotoxin. Of 395 GPs (31.3%) prescribing patient self-treatment, 259 (65.6%) prescribed podophyllin, but 60.23% did not specify the concentration; 134(33.9%) prescribed podophyllotoxin. Screening for selected sexually transmitted infections (STIs) was performed by 258/618 (41.7%) GPs. Only 74 (11.97%) screened for Chlamydia trachomatis and Neisseria gonorrhoeae and Trichomonas vaginalis. Partner notification was advised by 1138 (90.3%) and condom use by 1027 (81.5%). Only 333 (26.4%) referred all patients to GUM departments. Many GPs manage patients in-house, most using podophyllin solutions which vary in concentration, are non-standardized and potentially hazardous. Most GPs who instigate patient self-treatment prescribe podophyllin which is not licensed for this usage. Podophyllotoxin 0.5% is a safe, effective alternative. Few non-referring GPs screened for the 3 common STIs, thus putting patients at risk of complications such as pelvic inflammatory disease. Non-referral of patients with genital warts to GUM departments may have costly medical and financial consequences.
Condylomata Acuminata↗
Treatment of anogenital warts in genitourinary clinics in England and Wales.
A questionnaire on the treatment of anogenital warts was sent to 150 consultants in genitourinary medicine, 78 (52%) were returned completed. A wide range of treatments were used; podophyllin was the commonest first line treatment of multiple penile (60.3%), perianal (57.7%) and vulval (61.5%) warts. Cryotherapy was a popular choice for intrameatal warts (65.3%), small numbers of vulval warts (33.3%) and as second line therapy for penile (35.9%) and perianal (33.3%) warts. Vaginal warts were treated with podophyllin (39.7%) or cryotherapy (29.5%). Various combinations of podophyllin, trichloroacetic acid and cryotherapy were used (2.6%-24.3%) although there is no evidence this offers benefit over single therapy. Podophyllin is frequently used despite side effects, a poor clearance rate and in vaginal warts, difficult access. Initial therapy with more time-consuming procedures such as cryotherapy or electrocautery may be of benefit to selected patients.
Condylomata Acuminata↗
The cost effectiveness of treatment of genital warts with podophyllotoxin.
The cost effectiveness of 25% podophyllin resin and 0.5% podophyllotoxin solution in the treatment of genital warts in Genitourinary Medicine Clinic attenders was studied. Although the average treatment cost for a course of podophyllotoxin was more than that for podophyllin resin (20.75 pounds v. 14.95 pounds respectively) the overall cure rate with podophyllotoxin was 66% as opposed to 34.6% with podophyllin. When the costing of secondary treatment options was considered the cost per patient cured of warts with podophyllin resin was 27.15 pounds compared with 25.73 pounds for podophyllotoxin solution (not significant).
Adult↗
A cross-sectional survey of treatment choices for anogenital warts.
This was a cross-sectional survey that collected data relating to management of anogenital warts (AGW) during a single-patient visit only at genitourinary medicine clinics. Single-agent use of cryotherapy, podophyllotoxin and trichloroacetic acid (TCA) were the most common treatment modalities, accounting for over two-thirds of all modalities used. Podophyllin, alone or in combination with other agents, was used for about 20% of first-line treatments. Podophyllin was included in about 15% of all treatment modalities. Guidelines for the management of AGW continue to recommend the use of podophyllin, but this may need to be modified in the light of recent publications. Podophyllin, TCA, podophyllotoxin or combinations of these agents are commonly used to treat keratinized warts. About 11% of all treatments involved a combination of two or more agents.
Condylomata Acuminata↗
Autoimplantation technique in the treatment of anogenital warts: a clinico-immunological study.
An autoimplantation technique was adopted in the treatment of 50 cases of anogenital warts and was compared with the conventionally used podophyllin regimen in a matched group of 50 patients. They were assessed with 15 untreated subjects in a control group for the rate of clinical cure after 6 weeks, recurrence after 1 year follow up and for humoral and cell mediated immune responses before and after treatment. In the podophyllin group, 70% of patients were cured after 6 weeks while in autoimplantation, only 44% of patients were cured, and none in the control group had natural remission of warts without any treatment. After 1 year all the cured cases (100%) that completed follow up had recurrence of warts with podophyllin treatment, while none had recurrence of lesions in the autoimplantation group. Results of the humoral and cell mediated immune (CMI) response studies revealed that autoimplantation technique significantly augmented both humoral and CMI responses while there was not significant change in the immune status after podophyllin treatment (P > 0.001).
Anus Diseases↗
Pseudobowenoid change of the vulva: a histologic variant of untreated condylata acuminatum.
Vulvar condylomata are distinguished from vulvar intraepithelial neoplasia by orderly maturation, a low mitotic index, and the absence of nuclear atypia in the lower epithelial layers. Podophyllin therapy might produce changes in condylomata mimicking vulvar intraepithelial neoplasia but can be distinguished, particularly with a recent history of podophyllin use. This report describes five patients with vulvar condylomata that morphologically resemble both podophyllin effect and vulvar intraepithelial neoplasia. The mean age was 30.5 years. All lesions exhibited superficial keratinocytes in various stages of apoptosis, with a spectrum of nuclear degenerative changes characterized by absence of the nuclear membrane and dispersed nuclear chromatin. The characteristic finding was a perichromatin halo delineated by a rim of dense cytoplasm, beyond which a second zone of uniform clearing was observed, similar to changes noted in vulvar intraepithelial neoplasia. There was an absence, however, of either nuclear atypia in the lower cell layers or apoptosis and mitotic arrest observed in vulvar intraepithelial neoplasia and podophyllin therapy. Two (50%) of four lesions tested positive for human papillomavirus nuclei acids, one by polymerase chain reaction and the other by DNA-DNA in situ hybridization. No common human papillomavirus types were found. Pseudobowenoid change might represents a distinct type of vulvar condyloma, perhaps related to an unusual human papillomavirus.
Adult↗
Effects of the anti-inflammatory agents indomethacin, metiamide and acetylsalicylic acid on the induction of hyperplasia in hamster cheek-pouch epithelium and ear epidermis.
Previous studies have shown that agents such as indomethacin and hydrocortisone act to reduce the level of epidermal hyperplasia produced by various chemical, but little information is available about the effects of such anti-inflammatory agents on the induction of hyperplasia in oral mucosa. Hamster cheek-pouch epithelium and ear epidermis were treated with indomethacin, metiamide and acetylsalicylic acid prior to treatment with turpentine, podophyllin or TPA. The levels of hyperplasia induced were monitored by rates of epithelial glycolysis, protein synthesis and mitosis. The response of the metabolic assays to epinephrine was also examined. Alone, turpentine, podophyllin and TPA each caused a 3-5 fold increase in the metabolic assays and loss of the normal tissue response to epinephrine. Tissues pretreated with indomethacin showed significant reductions in the levels of hyperplasia produced and they retained a normal response to epinephrine. No reduction in hyperplasia was observed following pretreatment with acetylsalicylic acid, an alternative inhibitor or prostaglandin synthesis or with metiamide, a histamine blocker. The results indicate that the production of epithelial hyperplasia by turpentine, podophyllin and TPA can be inhibited by indomethacin.
Animals↗
5-Fluorouracil in the treatment of penile and urethral condylomata acuminata.
5-Fluorouracil (5-FU) cream was compared with podophyllin 25 percent in alcohol for treating genital and urethral condylomata acuminata. The cure rate after four weeks was found to be 6 of 18 patients treated with 5-FU and 10 of 19 treated with podophyllin. By changing the treatment for those not cured, warts regressed after four weeks in four more patients in each group. Patients were followed up for four to nine months; 10 of 27 treated with 5-FU and 14 of 31 treated with podophyllin remained in remission. It is not possible to support earlier reports on the successful treatment of meatal warts using 5-FU cream. More than half of the patients given 5-FU reported side effects after 10 to 14 days' treatment, which in some cases led them to stop using the cream. Twenty-one men considered to be treatment failures or relapses were examined by urethroscopy. No intraurethral condylomata were found but three cases of warts in the fossa navicularis were doscovered; this prompted us to introduce an instrument to examine the urethral meatus and the fossa navicularis.
Condylomata Acuminata↗
An audit of treatment of genital warts: opening the feedback loop.
An audit of the treatment of patients (100 men and 90 women) presenting with a first episode of anogenital warts to the Genitourinary Medicine Department at Leeds General Infirmary was performed. Treatment of patients was monitored for a period of 6 months from the time of presentation. The management of patients with genital warts lacked a clearly defined strategy and treatment was unselective and poorly monitored. Excluding patients who defaulted, at follow-up 44 (44%) men and 36 (38%) women still had genital warts at 3 months. Of those patients clear of warts at 3 months, the mean time to remission for men and women was 7.1 and 8.3 weeks respectively. Podophyllin 25% in tincture of benzoin was by far the predominant therapeutic modality used. A total of 96 (96%) men and 76 (84%) women received treatment with podophyllin. Both male and female patients had a mean of 5 treatments with podophyllin 25% (range 1-19 and 1-12 respectively). Physical methods of treatment i.e. cryotherapy and electrocautery, were underutilized, both as primary therapies and when topical agents had failed. Patients saw an average of 3 (range 1-7) doctors over the course of their treatment. Patients with warts affecting 2 or more sites, male patients with anal/perianal warts, and female patients with cervical and vaginal warts had higher failure rates from treatment at 3 months. On the basis of these findings, specific treatment protocols for the management of anogenital warts have been devised.
Adolescent↗
Induction of the deficient acid DNAse activity in mouse interfollicular epidermis by croton oil as a possible tumor promoting mechanism.
Histochemical activity of acid DNAse, intensity of nucleic acid staining and histological alterations in mouse interfollicular epidermis (I.F.E.) were investigated after a single dose or after chronic topical administration of two hyperplastic agents, of which one (croton oil) was a potent tumor promotor, and the other one (podophyllin) did not promote skin carcinogenesis. Podophyllin induced intense uniform I.F.E. hyperplasia without any proliferation of poorly differentiated basal cells, without increased nucleic acid staining and without any appreciably decreased acid DNAse activity. On the other hand, croton oil (as well as TPA) produced almost immediate, distinct hyperplasia of poorly differentiated basal cells with increased intensity in the staining of both nucleic acids and nearly complete deficiency in acid DNAse activity. Similar histochemical and histological patterns were observed at the sites of wounding hyperplasia in untreated control mice. Such wounding hyperplasia was thought also to be a tumor promoting factor. It was suggested that the decrease in acid DNAse activity which occurred almost immediately after administration of potent tumor promoters and which could not be induced by a hyperplastic agent without tumor promoting action may have a particular importance in the mechanisms of tumor promotion.
Animals↗
Autogenous vaccine: the best therapy for perianal condyloma acuminata?
PURPOSE: Treatment of perianal condyloma acuminata is frustrating because most treatment options are fraught with high recurrence rates and patient discomfort. We propose that surgical excision followed by vaccination with an autogenous condyloma acuminata vaccine is the most effective therapy available in primary and recurrent perianal condyloma acuminata. METHODS: Eighty-three patients with perianal condyloma acuminata were treated from 1985 to 1992. Treatment was divided for patients as follows: surgical excision, 20; bichloroacetic acid, 10; podophyllin and interferon A, 5; excision followed by autogenous condyloma acuminata vaccination twice weekly using 0.1 ml subcutaneously for three weeks increasing to 1.0 ml subcutaneously for seven weeks, 43. Syphilis was diagnosed in seven patients; two were human immunovirus-positive. All but three patients were male. Of those patients treated with the vaccination protocol, 25 had primary and 18 had recurrent disease. RESULTS: Recurrence rates were: excision alone and bichloroacetic acid, 50 percent; podophyllin and interferon A, 85 percent; whereas only 4.6 percent recurred when treated with excision and vaccination. Mean follow-up was 13 (range, 6-23) months. All patients treated with the vaccination protocol tolerated the full course of therapy. CONCLUSION: We believe that excision of perianal condyloma acuminata followed by autogenous condyloma acuminata vaccination for approximately ten weeks is the most effective and definitive treatment option and, moreover, should be considered in all patients with perianal condyloma acuminata.
Adult↗
Pattern of vulval warts at the University of Nigeria Teaching Hospital, Enugu, Nigeria.
A retrospective analysis of 45 cases of condyloma acuminata seen at the gynecology clinic of the University of Nigeria Teaching Hospital between January 1976 and December 1985 was carried out. The prevalence of condyloma acuminata was found to be highest in the single, young and sexually active age group. There was no definite trend in the yearly incidence of vulval warts. Marked association with moniliasis and trichomoniasis was found. Gonorrhea was detected in two patients, but there was no confirmed case of syphilis seen. The mainstay of treatment was the application of 25% podophyllin resin in benzoin tincture either alone or in combination with cold knife excision or diathermy excision. The overall response to all methods of treatment was 64% while treatment with podophyllin alone gave a success rate of 80% and 60% in mild and moderate cases, respectively. The overall incidence of condyloma acuminata was 2.7 per 1000 women seen.
Adult↗
Potato disc tumor induction assay: a multiple mode of drug action assay.
The study reported herein utilized the Agrobacterium tumefaciens-induced potato disc tumor assay. The objective was to verify the detection of antineoplastic activity in the potato disc tumor induction assay, regardless of the mode of antineoplastic drug action. Camptothecin, paclitaxel, podophyllin, vinblastine and vincristine were tested, each with a different mode of action. All drugs tested inhibited tumor induction. The order of activity was: camptothecin = paclitaxel = vinblastine < podophyllin = vincristine. No effect on the viability of the bacterium was detected. The A. tumefaciens-induced potato disc tumor assay was an effective indicator of antitumor activity regardless of the mechanism of drug action. Thus, this assay would be acceptable as a primary general screen for antineoplastic activity of various crude extracts, as well as for purified fractions, regardless of mode of inhibitory action on tumor formation.
Agrobacterium tumefaciens↗
Prevalence of human papilloma virus genital infections in sexually transmitted diseases clinic attendees in Ibadan.
All patients, who presented at the Sexually Transmitted Disease clinic of the University College Hospital, Ibadan, between the period of August 1996 and January 1998 were included in this study. They were examined for genital infections in order to determine the prevalence rate of Human papilloma virus genital infection (genital warts) among them. Out of the 1,373 patients seen in the clinic during the period, 861 (62.71%) had STD while the remaining 512 (37.29%) had other conditions. Out of these 861 cases, 69 (8.01%) had HPV genital infection, while the remaining 792 (91.9%) had other STDS. Of these 69 cases of genital warts, 35 (50.7%) were males while 34 (49.3%) were females. Their ages ranged between 17 and 74 years, with the peak incidence in the 20-29 years age group. 32 (46.4%) had concurrent genital infections with non-gonococcal urethritis and cervicitis 9(13%) constituting the most common type. The highest incidence (36.2%) of this condition was found among petty traders while the lowest was found among the business executives and applicants. In 67 (97%) of these patients, the nature of sexual intercourse was vaginal, while in 1 (1.5%) it was oral and another 1 (1.5%) both vaginal and oral. 26 (37.7%) of the patients had just one sexual partner, while 7 (8.1%) had 2 or more. Only 2 (2.9%) admitted to have had any sexual contact with commercial sex workers. The sites of warts in males include the shaft of the penis, the glans penis, perineum and intrameatum. In females, warts were found in the vulva, vagina, cervix, perineum and perianal regions. 42 (60.9%) of these patients were placed on 20% podophyllin on tincture of benzoin, 17 (24.6%) on cryotherapy and 1 (1.5%) on both. They all did well on the different treatment regimens except for 1 (1.5%) that had to change from podophyllin to cryotherapy when there was no reduction in size. 11 (15.9%) were however lost to follow up.
Adolescent↗
The epidemiology and treatment of anogenital warts in Singapore: a retrospective evaluation.
INTRODUCTION: A retrospective study in the referral centre for sexually transmitted infections (STIs) in Singapore to describe the epidemiology and treatment outcome of patients with anogenital warts. SUBJECTS AND METHODS: We reviewed the case records of 301 patients with anogenital warts who were seen over a 1-year period (1999). We also attempted to interview every patient by telephone to find out if they had any clinical recurrences for which treatment was sought elsewhere. RESULTS: There were 255 males and 46 females with a mean age of 34 years. Two hundred and nineteen (72.8%) presented with symptoms lasting 12 weeks or less. In males, warts occurred most frequently in the preputial cavity (52.5%) and on the penile shaft (40.8%). In females, they occurred most frequently on the external genitalia (91.3%). Two hundred and thirty-five males were treated with cryotherapy and 69% (95% CI, 62.6% to 74.8%) achieved clinical resolution after a mean of 6 treatment cycles. Seven males were treated with podophyllin 0.25% in ethanol and 71% (95% CI, 29.0% to 96.3%) were clinically cured after a mean of 4 treatment cycles. Thirty-nine females were treated with cryotherapy and 67% (95% CI, 49.8% to 80.9%) achieved clinical cure after a mean of 4 treatment cycles. Of the 290 patients treated at the centre, 212 (73%; 95% CI, 67.3% to 77.8%) patients (184 males, 28 females) achieved clinical cure after a mean of 7 weeks (range, 1 to 34 weeks); 90% (95% CI, 86.0% to 93.2%) of them by 15 weeks. Seven-two patients defaulted follow-up and 6 responded partially to treatment. Of the 212 patients who achieved clinical cure, 195 were interviewed by telephone, on an average, 17.7 months after clinical resolution. Thirty-seven (19%; 95% CI, 13.7% to 25.2%), all males, relapsed clinically after a mean of 100 days (range, 5 to 329 days); 90% (95% CI, 84.6% to 93.6%) relapsed by 228 days. CONCLUSIONS: Podophyllin 0.25% in ethanol was the most cost-effective treatment for males. One in 5 patients had a recurrence of their warts and most had their recurrence within 8 months of initial resolution.
Adolescent↗