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Current literature on neuropathies caused by metabolic defects and exogenous toxins is reviewed. Recent work on the molecular basis of hereditary amyloidosis is initially considered followed by various aspects of diabetic neuropathy and then the effects of ciguatoxin and podophyllin on peripheral nerves.
A case of squamous cell carcinoma developing in a perianal condyloma acuminatum in a 38-year-old man treated for over 5 years with podophyllin is presented. Although there are many reports of malignant transformation of condyloma acuminatum in the skin and mucosal surfaces of the male and female genitalia, it is quite rare in the perianal region. In this case there were foci of carcinoma in-situ and of frank invasion, as well as areas of squamous cell carcinoma in the large perianal condyloma. The lesion was widely excised, and completely removed, and the site covered with a split-thickness graft from the thigh. Later, repeated dilatations of the anus were required. Repeated histologic examinations of condyloma acuminatum are needed to diagnose possible malignant transformation.
In Northern Ireland in 1984 anogenital warts were diagnosed in 592 (352 male, 240 female) genitourinary medicine clinic attenders. Of these patients, 561 were heterosexual, 28 homosexual and three male bisexual. In the male patients 290 had penile warts, 67 meatal warts, 59 perianal warts, 25 anal canal warts and five rectal warts. In the female patients, 193 had vulval warts, 27 vaginal warts, 25 cervical warts, 107 perianal warts, 30 anal canal warts and one a rectal wart. Sexual partners were brought to the clinic by 345 patients and of these 93 male and 100 female partners had genital warts.The mean time from exposure to development of warts was 17 weeks SE +/- 1.5 (range 1 week - 12 months). As treatment, podophyllin 25% was used alone in 218 patients, and 132 were known to have had clearance of warts. At least one other sexually transmissible infection was found in 407 (69%) of patients. Cervical smears were taken in 164 women and were abnormal in 40 (24%). Cervical cytology was recorded in 89 regular sexual partners of male patients and was abnormal in 23 (26%).
Three major classes of interferons have been identified (alpha, beta, and gamma). All three have been tested in clinical trials in condylomata acuminata, or genital warts, with positive results. Administration by topical, intralesional, intramuscular, and subcutaneous routes results in regression of human papillomavirus genital disease. Significant reduction in measurable lesions occurs in some patients within days of initiation of therapy. Responses appear to be both time and dose dependent. Although disease resolution is highly variable from patient to patient, approximately 75 to 80 percent of all persons show clear clinical benefit at low doses. Biologic side effects of interferons are tolerated well at these doses and occur following systemic or local administration of interferon. In general, the interferons are emerging as active and safe therapeutic agents for genital human papillomavirus infections. This study reviews in detail the series of clinical trials conducted with one of these agents, interferon alpha n1. Results of four small and two major controlled trials in refractory genital warts have proved that this interferon provides significant clinical benefit for the majority of subjects with severe disease. Current studies show that it can be combined safely and effectively with other conventional treatment modalities, such as laser or podophyllin.
The histologic changes of podophyllin-treated condylomata acuminata were studied at 24-hour, 48-hour, and 7-day intervals. The 24-hour specimens had scattered individual atypical cells, whereas 48-hour specimens demonstrated small focal areas of atypia. Seven-day specimens exhibited very mild atypia of cells. All treated specimens had inflammation-necrosis ranging from scattered inflammatory cells to degeneration of the squamous epithelium.
The antineoplastic activity of 5 substances was tested in vivo and in vitro on four different tumours (plasmocytoma and melanoma Fortner III of the Syrian golden hamster, the Walker carcinosarkoma 256 and an adenocarcinoma of the rat). The substances involved were 2,3,5-triethyleniminobenzoquinone-(1,4) (triaziquone), actinomycin D, podophyllinic ethylhydrazide (mitopodozide), bleomycin and adriamycin hydrochloride. The effect of the substances in vivo was measured on the size of the tumour, and in vitro on the incorporation of 3-H-thymidine and 3-H-uridine in short-term incubations of tumour-cell suspensions. No correlation was observed between the 3-H-thymidine incorporation in vitro and the response of the tumours in vivo. On the other hand, the 3-H-uridine incorporation in the tumour-cell suspensions in vitro was in good agreement with the results of therapy in the animal experiments. This is compatible with the results of earlier experiments using other substances to investigate the possible correlation between tumour therapy and in vitro tests.
Condylomata acuminata are benign epitheliomas which are caused by the human papilloma virus. 8 subgroups (variants) of the virus are known up to now. Condylomata acuminata are infectious, the virus being transferred by direct contact with a lesion. Condylomata acuminata are found more often in males than in females and never occur in children prior to the age of two years. The peak incidence is between 19 and 22 years of age. Greatly proliferating condylomata acuminata (type Buschke-Löwenstein) may lead to malignant degeneration. There exists a broad spectrum of topical therapeutic modalities: cytotoxic substances such as podophyllin (10 to 25%), colchicine (8%), 5-fluorouracil (1 to 5%), cryotherapy (solid carbon dioxyde or liquid nitrogen), surgical treatment (excochleation, electrocautery or laser beam. Vaccination therapy may prove successful in certain cases in the future.
1. The primary problem in an effective treatment of a glioblastoma is the prevention of a recurrence. 2. For that purpose were the following therapeutical procedures undertaken: (a) Temporary implantation of radio cobalt in the brain itself (1957): (b) Clostridium butyricum M 55 was used to render the centre of the tumour fluid (1967): (c) Podophyllin was used to destroy the border of the tumour (1980); (d) The CO2 Laser beam (1975); (e) The electromagnetic heat induction deep in the brain (1973-1978). 3. In order to make the operation and postoperative phase safer for the patient, the following precautions were drawn upon or employed: (a) Hyperbaric oxygenisation in the pressure chamber (1971); (b) The anti-G-suit (1974); (c) the computer controlled automatic infusion pump (1980), and (d) the telemetric measurement of intra-cranial pressure (1975). 4. Apart from the pressure chamber, the mentioned devices were all supervised and developed in the department of the author. 5. The first successful means in the prevention of the recurrence of a glioblastoma multiform seems to be the telethermic method mentioned in 2 (e) above.
This article deals with surgical as well as with conservative treatment of condylomata acuminata, e.g. 10% podophyllin in liquid paraffin. Both methods are equally successful and may be combined in special cases.
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.
The incidence of condylomata acuminata infection has shown a steady increase for adults and children in recent years. With the discovery that the viral agents of this disease are potentially neoplastic, a disorder that was once considered a nuisance is now taking on new-found importance and concern. Furthermore, the knowledge that these lesions are often sexually transmitted and the ever-increasing concern over child abuse have combined to make the recognition and treatment of this disease in the pediatric population of even greater significance. Depending on location, podophyllum resin (podophyllin) is the initial therapy of choice. Available studies indicate a cure rate ranging from 22% to 98% depending on location of the warts, frequency of treatment, patient compliance, and freshness of the podophyllum resin preparation. Cure rates of 91% to 97% have been reported with cryotherapy and laser photocoagulation. Eradication of the viral agent and long-term follow-up are important.
Eighteen women and 6 of their male sexual partners with lower genital tract infections caused by various human papillomavirus (HPV) types were treated with systemic or topical interferon (IFN) application. All patients with vulvar or penile lesions had a history of podophyllin or surgical treatment. In the female group, 9 patients showed complete response, 8 patients partial response and 1 patient no response. In the male patients complete response was seen in all patients. The response rate appears to depend on the HPV type present. Women with an HPV 16/18 infection showed a lower response rate to IFN treatment (complete response in 5 out of 14 patients), whereas lesions caused by HPV 6(11) showed complete response in all 4 cases. During follow-up examinations (mean 7.5 months) no recurrence of disease was observed. Systemic treatment showed tolerable and temporary side-effects. Topical treatment yielded identical efficacy and no side-effects.
Certain enteric ailments are particularly common among homosexual men. They are primarily infectious diseases and include not only such common venereal diseases as gonorrhea and syphilis but also infections not usually regarded as being sexually transmitted. Among the latter are shigellosis, salmonellosis, giardiasis, and amebiasis. Patients' symptoms are non-specific and seldom helpful in diagnosing particular diseases. The practitioner must be prepared to identify a number of infections with similar presentations that may occur singly or together in gay men. Gonorrhea is probably the most common bacterial infection in gay men. Carriage rates as high as 50% have been reported, and extra-genital carriage is common; this necessitates culturing the urethra, rectum, and pharynx. Procaine penicillin G is the treatment of choice for most patients; spectinomycin is probably the drug of choice in penicillin-sensitive patients. In contrast to other venereal diseases, syphilis may have a characteristic protoscopic presentation. Benzathine penicillin G is the treatment of choice for most patients. Lymphogranuloma venereum causes penile lesions and inguinal lymphadenitis in heterosexual men, whereas homosexual men are more prone to proctitis. The disease may mimic Crohn's disease. Recommended treatment includes tetracycline or sulfamethoxazole-trimethoprim. Shigellosis usually presents as an acute diarrheal illness. Patients generally require only supportive treatment with fluids. Herpes simplex viral infection is difficult to diagnose and has several different presentations, including lumbosacral radiculomyelopathy. Symptomatic treatment with sitz baths, anesthetic ointment, and analgesics is recommended. Venereal warts are believed to be caused by the same virus that causes verrucous warts; they are usually found in the anal canal or around the anal orifice. They are commonly treated with 25% podophyllin solution. Parasitic infections include giardiasis, amebiasis, and pinworm infections. Metronidazole may be used in the treatment of symptomatic giardiasis and amebiasis, but it is not approved for the former indication; quinacrine is approved for giardiasis. Pinworm infestation may be treated with pyrantel pamoate or mebendazole. Cure of enteric diseases in homosexual men must be documented.
A 32-year-old woman was treated for Burkitt's lymphoma diagnosed during the 22nd week of pregnancy. Chemotherapy consisting of doxorubicin (Adriamycin), vincristine, teniposide (VM-26), cyclophosphamide, and prednisolone (AVTEP) was given each 2.5 to 3 weeks from the time of the diagnosis until delivery in the 37th week. Bleomycin and intrathecal methotrexate were also given from the 35th week. The infant was born after an assisted vaginal delivery and was fully developed and normal in all respects. This paper confirms prior reports that cytotoxic chemotherapy may safely be given during the second and third trimesters of pregnancy without adverse effects on the fetus. To our knowledge it is the first report of the use of teniposide, a new podophyllin derivative, during pregnancy.
A variety of epithelioproliferative benign neoplasms, both trivial and life-threatening, are caused by subtypes of human papillomaviruses. Interferons objectively regress HPV-induced warty disease and affect the regrowth of the transformed epithelium. Interferons effectively control the most serious and potentially life-threatening papillomavirus associated diseases, respiratory papillomatosis and genital warts, but not without the anticipated side effects associated with this potent biological weapon. It is entirely possible and even likely that individual species of interferons act preferentially on certain cells, tissues or organs in response to particular viruses. Combined therapies, such as surgery in combination with interferon, or podophyllin in conjunction with interferon alfa-n1, may prove most efficacious.
Condyloma acuminatum, CA or genital warts, are benign fibro-epithelial tumors with a predilection for moist environments, especially mucosal surfaces. This sexually transmitted disease (STD) is increasing rapidly in incidence. The lesions are associated with a number of human papillomavirus (HPV) types. Some HPV types are closely linked with genital (especially cervical) dysplasia and neoplasia. Treatment consists of such traditional modalities as podophyllin, cryotherapy or surgical excision and, more recently, administration of interferon (IFN).
The four lignans: podophyllotoxin, 4'-demethyl-podophyllotoxin, alpha-peltatin and beta-peltatin represent the podophyllin ingredients believed to exert lesional necrosis after application to condylomata acuminata. This study comparatively evaluates cutaneous cytodestructive potency of these drugs, as evaluated by measurement of epidermal and dermal 3H-thymidine incorporation and injury of dermal microcirculation at intervals in the range of 9--168 h after application to hairless mouse skin. Influence on DNA-synthesis was measured using a disc technique for isolation of standardized skin areas followed by alkali extraction of DNA from respective tissues after separation through potassium bromide incubation. Any capillary injury was demonstrated by visual assessment of leakage of i.v. injected trypan blue to test areas. An analytical method compensating for variations in DNA synthesis in individual controls is presented. Using 0.5% preparations of the lignans, podophyllotoxin most consistently influenced the variables indicating cytodestructive effect, while 4'-demethyl-podophyllotoxin exerted the weakest degree of damage.
The irritant and cytotoxic constituents of the latex of Euphorbia paralias L. were separated from the hydrocarbon fraction by means of solvent partition. 3 new ingenane esters were identified from the toxic ether fraction. The major compound was 3-angelyl-20-deoxyingenol and the 2 minor compounds were 3-hexanoyl-20-deoxyingenol and 3-angelyl-ingenol. These compounds were of a similar potency to podophyllin in the inhibition of 3H-thymidine uptake by TLX/5 mouse lymphoma cells. In addition the compounds produced a persistent erythema of the mouse ear in sub-microgram doses.