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PubMed1990

Surgical management of anal condylomata in the HIV-positive patient.

A retrospective review of 677 patients who tested positive for the human immunodeficiency virus, evaluated from January 1986 to February 1988, demonstrated 119 patients (18 percent) with anal condylomata. Demographics of these patients were similar to the total human immunodeficiency virus group; ages ranged from 19 to 86 years (mean, 25 years). Ninety-four percent of patients were men, 62 percent were white, 30 percent were black, and 10 percent were other races, primarily Hispanic. Ten percent of the patients admitted to homosexual activity and 2 percent admitted to intravenous drug abuse. Sixty percent of the population had another sexually transmitted illness. The majority of patients were in early Walter Reed Classes (Stage I or II). With follow-up of 4 to 26 months (mean = 12 months), the recurrence rate for anal condylomata was 26 percent after local treatment with podophyllin and 4 percent after fulguration and excision. There were no operative complications. Our study confirmed that anal condylomata and sexually transmitted diseases are common in patients who test positive for the human immunodeficiency virus and that patients who test positive for the human immunodeficiency virus with early Walter Reed stages can be expected to do well with appropriate therapy.

Adult↗

PubMed1996

Induction of apoptosis in human HaCaT keratinocytes.

Although cell death by apoptosis has been recognized as an important control mechanism in the maintenance of tissue homeostasis and in the elimination of cells with damaged DNA, information on the induction and characteristics of apoptosis in keratinocytes is rather scarce. Apoptotic mechanisms may play an important role in normal and disturbed homeostasis of the skin. In the present study, we therefore investigated the effects of several potential inducers of apoptosis in the human keratinocyte cell line HaCaT. Apoptosis was assessed with respect to morphological changes by light and electron microscopic examinations and to DNA integrity by a specific ELISA. UVB irradiation induced the morphology and internucleosomal DNA fragmentation characteristic of apoptosis in a dose- and time-dependent manner. Interferon-gamma caused DNA cleavage at the linker regions without producing morphological features consistent with apoptotic cell death. In contrast, treatment with dithranol and NP-40 resulted in necrotic alterations in the keratinocytes. Treatment with the calcium ionophore A23187 caused morphological changes which were similar to the characteristics of 'nonapoptotic programmed cell death'. Dexamethasone, tumor necrosis factor-alpha, transforming growth factor-beta, TPA, retinoic acid, the podophyllin derivative etoposide, the thromboxane A2 analogue U46619, cycloheximide, and the nitric oxide donors sodium nitroprusside and S-nitroso-glutathione, which are all known to induce apoptosis in other cell types, did not affect HaCaT keratinocytes. These results demonstrate that apoptosis can be induced in keratinocytes in vitro but the apoptosis differs from that in other cell types, such as haematopoietic cells, with regard to the type of inducer and/or the sensitivity of the target cells. Since keratinocytes are affected by numerous external and internal stimuli, they might posses several protective mechanisms to prevent apoptosis and to ensure the structural integrity of the outermost barrier of the body.

Administration, Topical↗

PubMedDate not supplied

Genital infection with human papillomavirus in adolescents.

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections in adolescents. Such infection is associated with substantial health risks and is unpredictable in its resolution. Genital warts are the most common clinical manifestations of genital HPV infections. Most genital warts are caused by low risk HPV types (notably HPV-6 and -11). The majority of genital HPV infections are latent or subclinical. Although the outcome of a genital HPV infection is variable, the infection is usually transient and complete resolution is common. However, persistent infections with high-risk HPV types (notably HPV-16 and -18) are associated with the development of cervical intraepithelial dysplasia (CIN), which may progress to cervical cancer. Genital warts, generally diagnosed in the clinic, can be treated with imiquimod, podofilox, podophyllin, liquid nitrogen, bichloroacetic or trichloroacetic acid, or surgery. Cervical cytology screening is an ideal screening test for subclinical HPV infection with resultant CIN. Annual cervical cytology screening should begin approximately 3 years after initiation of sexual intercourse but no later than age 21 years. Because of the high rate of regression of low-grade squamous intraepithelial lesions (LSIL) in adolescents, the cytologic study should be repeated within 6 to 12 months. Colposcopy should be reserved for persistent LSIL. Patients with high-grade squamous intraepithelial lesions (HSIL) should be referred for colposcopy and biopsy. Confirmed HSIL should be treated with cryotherapy, laser therapy, or loop electrosurgical excisional procedure. The use of therapeutic vaccines is still experimental. HPV infection can be prevented, to a certain extent, by delaying the initiation of sexual activity, limiting the number of sexual partners, and using latex condoms. Several viruslike particle candidate vaccines are under development for the prevention of HPV. These vaccines have been proven safe, well tolerated, highly immunogenic, and highly efficacious. Such vaccines are urgently needed and ultimately may be an important preventive measure.

Adolescent↗

PubMed1990

Double-blind randomized clinical trial of self-administered podofilox solution versus vehicle in the treatment of genital warts.

PURPOSE: Genital warts are a highly prevalent and chronic sexually transmitted disease for which there is no completely satisfactory therapy. Conventional ablative therapy requires repeated treatment, often for months or years. This study was undertaken to evaluate the safety and efficacy of 0.5% podofilox in patient-administered treatment of penile warts. PATIENTS AND METHODS: Thirty-eight men with penile warts were randomly assigned to double-blind, self-administration of 0.5% podofilox solution or placebo, twice daily for 3 days per week for 4 weeks. Eleven podofilox and 15 placebo recipients with residual warts then received an additional 4 weeks of open-label treatment. RESULTS: By the end of treatment, podofilox recipients had their mean wart number and area reduced to 15.9% and 5.1% of baseline values, compared to 97.4% and 92.9% in the placebo group (p = 0.0001). Local adverse reactions were more common in the podofilox group, but were transient. Complete disappearance of warts was observed in 25 (53.3%) of 45 treatment courses, including open-label treatment. Recurrences of warts after therapy were frequent. Only 21% of patients remained free of warts 2 weeks after completing treatment, and subsequent recurrences were noted in all patients available for long-term follow-up, which is a common limitation of ablative therapy for genital warts. CONCLUSION: Podofilox 0.5% solution is effective in treating penile warts and is well tolerated in a self-administered regimen. Podofilox 0.5% offers potential advantages in safety and cost over podophyllin resin therapy of genital warts.

Adult↗

PubMed1994

Efficacy and safety of 0.5% podofilox solution in the treatment and suppression of anogenital warts.

PURPOSE: For the patient-administered treatment of anogenital warts, 0.5% podofilox (podophyllotoxin), one of the active compounds of podophyllin, has been shown to be more effective than the vehicle alone. This study was designed to evaluate the safety and efficacy of 0.5% podofilox treatment followed by prophylaxis. PATIENTS AND METHODS: A total of 103 patients were entered in stage 1 of the study. Stage 1 was an open label study, and patients self-administered 0.5% podofilox twice daily for 3 consecutive days per week for 4 weeks. A total of 100 patients remained available for efficacy and safety analyses. At the end of stage 1, patients who had a complete response proceeded to stage 2 of the study. Patients who had a 50% to 99% reduction in measured total wart area were offered cryotherapy every 10 days, up to 5 times. If cleared of warts, they were also entered into stage 2. A total of 57 patients were enrolled into stage 2, a double-blind, randomized, placebo-controlled prophylactic study of 0.5% podofilox self-administered once daily for 3 days per week for 8 weeks, on the sites of healed warts. A total of 45 patients in stage 2 were available for efficacy analysis. RESULTS: By the end of stage 1, 68% of the warts had disappeared, and 29 of 100 patients (29%) had a complete response. A total of 49 patients had a 50% or greater improvement in wart area and underwent cryotherapy. Rates of local side effects after 1 week of treatment were 57% for inflammation, 39% for erosion, 47% for pain, 48% for burning, and 44% for itching. However, these symptoms and signs were mostly mild to moderate in intensity and diminished over time. Therefore, overall treatment was well tolerated. In stage 2, only 4 of 21 patients (19%) in the podofilox group experienced a recurrence as opposed to 12 of 24 (50%) in the placebo group (P = 0.031). As in stage 1, the side effects were modest, and the drug was well tolerated. CONCLUSION: This study confirms the efficacy and good tolerance of 0.5% podofilox in the treatment of anogenital warts. It also establishes the safety and superior efficacy of patient-administered podofilox over the vehicle alone as prophylaxis against recurrence of lesions. Although long-term efficacy and tolerance remain to be established, podofilox appears to be a useful agent in the control of this disease.

Adult↗

PubMed1988

Verrucous carcinoma of the female genital tract: report of a case and review of the literature.

Verrucous carcinoma (VC) of the female genital tract is a rare lesion, primarily affecting postmenopausal women. A case of VC of the vulva is reported, bringing the total number of VC of the female genital tract to 89. VC is a slowly growing, locally "pushing" tumor with a rather benign histologic appearance, and the clinical and histologic characteristics are described on the basis of the present report and a review of the literature. The treatment of VC is still a matter of discussion. It seems logical to treat the tumor by wide local excision, taking the lack of proof of spontaneous metastasis into consideration. Radiation therapy should be contraindicated, and local application of podophyllin, bleomycin therapy, and cryosurgery are ineffective methods in the treatment of VC.

Aged↗

PubMed1985

Condyloma acuminata in children.

Condyloma Acuminata (venereal warts) are sexually transmitted involving the human papilloma virus. It has become commoner in adults in the last decade. While infection is most often by sexual intercourse, it can be transmitted at birth and with close contact with infected individuals. It is common in marked sexual promiscuity. Condyloma acuminata in children should alert the physician to the possibility of sexual abuse or early sexual activity. We report 14 cases of condyloma acuminata in children; from 6 months to 17 years. Sex incidence was equal. All had social and family problems in common, except for one who developed perianal condyloma after repeated rectal dilatations because of a pull through procedure for Hirschsprung's Disease. Two cases of sexual abuse were documented. Treatment methods included podophyllin, liquid nitrogen, 5 fluorouracil cream, fulguration and laser therapy. An adequate social history was available only in six cases. Investigations should include VDRL and cultures for Gonococcus, careful medical and social history for neglect or abuse.

Adolescent↗

PubMed2000

Podophyllotoxin.

Podophyllin, an ethanolic extract of Podophyllum peltatum L. or P. emodi Wall (syn. P. hexandnum Royle), is a good source of the aryltetralin-type lignan, podophyllotoxin. The latter compound, as well as its congeners and derivatives exhibit pronounced biological activity mainly as strong antiviral agents and as antineoplastic drugs. The podophyllotoxin derivatives etoposide, etopophos (etoposide phosphate), and teniposide are thus successfully utilized in the treatment of a variety of malignant conditions. Continued research on the Podophyllum lignans is currently focused on structure optimization to generate derivatives with superior pharmacological profiles and broader therapeutic scope, and the development of alternative and renewable sources of podophyllotoxin.

Podophyllotoxin↗

PubMedDate not supplied

Chinese herbal medicines revisited: a Hong Kong perspective.

Chinese herbal medicines (CHM) and Chinese proprietary medicines (CPM) are widely used by people of Chinese origin throughout the world. Although the use of these medicinal materials rarely causes significant toxic effects, cases of severe and even fatal poisoning have occurred after medication with herbs containing aconitine, podophyllin, and anticholinergic substances. Furthermore, CHM and CPM are often adulterated with substituted herbs, heavy metals, and western medicines; such contamination can have important clinical consequences. In Hong Kong, surveillance and legislation are required to control the use of some of these herbal preparations. In other countries, medical practitioners should also be aware of the possibility that these herbal-medicine-related remedies may cause significant clinical problems in their Chinese patients.

Drug Contamination↗

PubMed1998

Therapeutic evaluation of compounds in the SCID-RA papillomavirus model.

A previous study by Kreider (Kreider et al., 1979) indicated that rabbit skin, which had been transplanted to immunodeficient nude mice, could be successfully infected with cottontail rabbit papillomavirus (CRPV). We have extended this observation in developing a rodent model for evaluation of compounds for activity against the papillomaviruses. In this model (called the SCID-Ra model), rabbit ear skin is transplanted to the dorsum of SCID mice and allowed to heal for 3 weeks. Infection with CRPV by scarification leads to the growth of warty lesions within 2 3 weeks in >95% of the animals. Topical and/or systemic therapy can be initiated at various times post infection (PI). Weekly lesion scores are recorded and compounds are evaluated for their ability to suppress wart growth when compared to untreated control mice. Ribavirin, which has had a suppressive effect both in the clinic for the treatment of respiratory papillomatosis and on the growth of warts in the rabbit back model, was evaluated and showed significant anti-proliferative activity with oral dosing. Both antiviral and antiproliferative compounds including podophyllin and 5-fluorouracil, which have been used clinically for the treatment of human papillomavirus (HPV) infections, were evaluated in this model. The anti-mitotic compound, Navelbine (vinorelbine tartrate), which is used for the treatment of non-small cell lung carcinoma was evaluated in this system and showed significant inhibition of wart growth with somewhat less topical cytotoxicity when compared to podophyllotoxin.

Animals↗

PubMed1998

Etoposide: four decades of development of a topoisomerase II inhibitor.

Podophyllin-containing materials have been used as folk medicines for centuries. In the 1950s, scientists began a search to identify a more effective podophyllotoxin derivative. These efforts eventually resulted in the development of a new class of antineoplastic agents which target the DNA unwinding enzyme, topoisomerase II. The history of the development of one of the first identified topoisomerase II inhibitors, etoposide, is reviewed in this paper. Critical developments in etoposide's mechanism of action, pharmacology and administration schedule are summarised. The clinical benefits of the recently marketed etoposide prodrug, etoposide phosphate (Etopophos) are also detailed. The current status of other clinically approved anticancer agents which target topoisomerase II is briefly reviewed.

Administration, Oral↗

PubMed2001

Contact dermatitis from topical antiviral drugs.

The literature has been reviewed for contact dermatitis from topical antiviral drugs. 15 agents have been identified including acyclovir, imiquimod, podophyllin, podofilox, cidofovir, penciclovir, vidarabine, idoxuridine, trifluridine, tromantadine, lamivudine, interferon intralesional injections and ophthalmic solution, fomivirsen and foscarnet intravitreal injections and ganciclovir intraocular implants. Patch testing has been documented in certain individuals and cross-sensitization has been observed to contribute significantly to some allergic reactions.

Administration, Topical↗

PubMed1990

Direct effects of cytostatic therapy on the functional state of the thyroid gland and TBG in serum of patients.

This study analysed the concentrations of thyroid binding globulin (TBG) in the serum as well as the level of triiodothyronine (T3), thyroxine (T4), thyreostimulating hormone (TSH), thyroglobulin (Tg) and T4/TBG coefficient, before therapy and on the fifth day of therapy in 27 patients of both sexes suffering from neoplasia. The patients were treated with cytostatic antibiotics, alkylating agents and podophyllines derivates, by protocol. Serum T3 gains in concentration already after 5 days since the beginning of treatment (from 1.65 +/- 0.20 to 1.73 +/- 0.18 nmol/l), but it is retained within physiological ranges as well as TSH, rT3 and Tg. Thyroxine remains within the permitted ranges, but slightly decreased after therapy (64.00 +/- 11.00 nmol/l, mean +/- SEM) in comparison to the value before (71.00 +/- 19.00), p(F) less than 0.1. A reduction of concentrations in total serum proteins at an average 7.88% was found. The level of inter-alpha globulin, TBG, in patients with proved malignancy is low before therapy (14.97 +/- 4.73 micrograms/l, mean +/- SEM, in males and 14.83 +/- 3.70 in females) but, with application of cytostatics it decreases considerably to the level of 11.68 +/- 4.46 (p less than 0.05) in males and to 13.68 +/- 3.89 in females (NS). In view of these facts, T4/TBG coefficient remains normal and contributes to the maintenance of euthyroid gland function.

Adult↗

PubMedDate not supplied

[Results of long-term leukocyte interferon (alpha IFN) therapy using an individually determined dose schedule in recurrent laryngeal papillomatosis].

Out of 24 patients with laryngeal papillomatosis 6 (5 female, 1 male) suffered from repeated relapses and underwent long-term treatment with alpha-IFN-therapy. Age at onset of the disease: 1 5/12-16 2/12 years. Duration of illness: 1-7 years, with several relapses were treated surgically and with laser-coagulation. Three out of 6 patients had a tracheal cannula and were cauterized by podophylline at 2-4 week intervals. IFN was given in dosages of 5-20 X 10(4) U/kg 2 or 3 times a week. IFN-dosage for each patient was determined using the induction kinetics of (2'-5')-oligo(A)synthetase (OAS) in the mononuclear cells of the circulating blood of patients with laryngeal papillomatosis. A continuous effect could be achieved by the dose of IFN determined in the described way always before OAS activity decreased to its initial level. All 6 patients responded favorably to the alpha-IFN-therapy. Two patients treated only with IFN showed remission without relapses. In 2 cases IFN was successfully used to prevent relapses after surgical treatment and laser-coagulation. In 2 patients with papillomatosis extending into the main bronchi the disease could only be brought to a standstill, i.e. it was not necessary to remove the papillomas. Two out of 3 patients with laryngeal papillomatosis could be decannulated. Long-term therapy following the above described principles is efficient and without significant side-effects. Three patients are in treatment for more than 3 10/12 years.

Child↗

PubMed1980

[Bowenoid papulosis (author's transl)].

Bowenoid papulosis of the anogenital area was found in 3 women and 3 men aged 24 to 64 years. These were papulo-verrucous efflorescences with a tendency to multilocular recurrences despite cold cauterisation. Spontaneous healing was also observed. Histology showed acanthomas with varying degrees of dysplasia including carcinoma in situ. Light microscopic changes in the proliferating epidermis were found repeatedly which is taken as evidence for virus-induced origin. Thus the characteristic cell dysplasia of bowenoid papulosis is possibly the consequence of a viral anaplastic transformation. There is no definite histologic differentiation between dysplasia due to podophyllin in papillary condylomas and that of bowenoid papulosis.

Adult↗

PubMed2005

Look what I found! Poison hunting on eBay.

BACKGROUND: Many substances deemed too dangerous for commercial use are still available to the general public. The purchase of these substances may potentially place members of the general public at risk for serious poisonings. This study was designed to document the large variety of dangerous poisons readily available on a popular online auction Web site. Methods. Over a 10-month period, the online auction Web site eBays was searched daily using the terms "poison" and "contents." Product name, active ingredients, what form the product is in, amount in container, and relative toxicity rating (Clinical Toxicology of Commercial Products, Gosselin, et al.) were recorded. If available, pictures of the products were saved. RESULTS: One hundred twenty-one individual products were identified. Fifty-five were in solid/tablet form, 37 were powders, and 29 were liquids. Product containers were full for 56 items and partially full for 65. Twenty-four products contained ingredients rated as "supertoxic" and included strychnine (10), arsenic trioxide (8), cyanide (2) and nicotine, pilocarpine, phosphorus, powdered conium maculatum (1 each). Sixty-three products contained "extremely toxic" ingredients including thallium, picrotoxin, soluble barium, antimony, mercury, arsenates, podophyllin, fluoride, zinc phosphide, atropine, scopolamine, and plant extracts of gelsemium, aconite, larkspur, and croton. Twenty-one products contained "very toxic" ingredients including lead, copper, camphor, caffeine, theobromine, creosote, pyrogallic acid, sparteine, quinine, lindane, warfarin, phenol, and digitalis. The remaining 13 were "moderately-slightly toxic." CONCLUSION: While the viability of the labeled ingredients could not be verified, the transportation, handling, and potential utilization of these dangerous poisons by the general public could result in serious poisonings.

Agrochemicals↗

PubMed1970

The association of a class of saltatory movements with microtubules in cultured cells.

Particulate structures in the cytoplasm of HeLa and other cultured cells in interphase undergo rapid individual linear displacements (long saltatory movements, LSM). By the use of time-lapse microscopy to locate saltating particles prior to fixation and histochemical examination of the cells, structures of several kinds have been shown to move in this manner. Elements that show LSM include lysosomes, pinosomes, ingested carbon particles, lipoidal granules, and unidentified particles that appear as bright objects in positive phase contrast. The pattern of movement of the particles suggests the presence of linear guiding elements radially disposed from the cytocenter (centriole region). The participation of microtubules in these movements is inferred from the observation that LSM cease after treatment with drugs which depolymerize microtubules, i.e., colchicine, Vinblastine, and podophyllin. The directions of the microtubules in the cytoplasm of HeLa cells found by electron microscopy are consistent with the aster-like configuration predicted from study of LSM. Further support for this arrangement of cytoplasmic microtubules is provided by light microscope observations of colchicine-sensitive radial arrays of acid phosphatase granules in the cytoplasm of some cell lines.

Animals↗

PubMed1976

Verrucous carcinoma of the vagina.

Verrucous carcinoma of the vagina is a highly differentiated and rare variety of squamous-cell carcinoma. Two new cases are presented; a search for the literature revealed three other cases. This neoplasm is characterized by a warty verrucous pattern of growth of squamous epithelium. Histologically, this type of squamous-cell carcinoma is extremely well-differentiated, with minimal evidence of anaplasia of the cells. The neoplasm tends to grow slowly and to infiltrate, sometimes extensively, by pushing rather than by permeating the surrounding tissues. Surgical excision seems to provide the best cure at the present time as the tumor does not respond to irradiation or to podophyllin treatment. Lymph-node dissection is not usually necessary in view of the tendency of the tumor to spread locally rather than to metastasize. However, the value of resection of lymph nodes should be reassessed after enough cases have accumulated.

Carcinoma, Verrucous↗