Recombinant interferon beta gel as an adjuvant in the treatment of recurrent genital warts: results of a placebo-controlled double-blind study in 120 patients.

BACKGROUND: Pilot studies of adjuvant therapy with topically applied interferons (IFN) have shown promising results in reducing the recurrence of condylomata acuminata (CA). OBJECTIVE: The aim of this multicenter placebo-controlled, double-blind study was to confirm the efficacy and safety of topically applied IFN in a large sample of patients. METHODS: After removal of CA by CO2 laser surgery, electrocautery or cryosurgery, 120 patients applied either recombinant IFN-beta (0.15 or 1.0 x 10(6) IU/g) or placebo gel to the affected areas 5 times daily for 4 weeks. The patients were followed for a total of 24 weeks or until recurrence of CA was observed, respectively. RESULTS: In the 105 patients evaluated for efficacy after 24 weeks, recurrence rates were 75% (27/36 patients) in the placebo group, 62% (21/34) in the 1.0 x 10(6) IU/g group (n.s.) and 54% (19/35) in the 0.15 x 10(6) IU/g group (p = 0.034). Only few mild adverse events were noted, which were almost limited to the application site. CONCLUSION: Topical application of gel containing 0.15 x 10(6) IU/g recombinant IFN-beta is safe and appears to reduce the recurrence of CA after surgical treatment.

Psychological factors influencing the surgical patients' consent to regional anaesthesia.

To investigate the preoperative attitude of surgical patients to regional anaesthesia, 162 subjects scheduled for elective surgery were studied. On the day before operation, patients were interviewed by an anaesthesiologist, using a semi-structured schedule. Topics investigated were sociodemographic variables and clinical correlates, such as past anaesthetic experience, information about anaesthesia and surgery, as well as questions and fears related to anaesthesia. Subjects were assessed for personality characteristics and emotional symptoms by Eysenck's Personality Questionnaire (EPQ), Zung's Self-rating Anxiety and Depression Rating Scales, Schalling-Sifneos' Personality Scale and the 43-item Life Events Inventory of Holmes and Rahe. Seventy-one patients (44%) consented to regional anaesthesia. Consent to regional anaesthesia was associated with advanced age, low neuroticism and high extroversion score in the EPQ, as well as longer duration of illness. The deniers of consent asked more questions and expressed more fears about anaesthesia. It is suggested that the patients' characteristics influence their preference, acceptance or refusal of regional anaesthesia.

Genital warts do not respond to systemic recombinant interferon alfa-2a treatment during cannabis consumption.

The case of a 22-year-old man suffering from genital warts is described. The lesions responded completely to recombinant interferon alfa-2a only after discontinuation of cannabis consumption. Cannabis was detected using the enzyme immunoassay/1-trans-tetrahydrocannabinoid method in urine. Southern blotting of frozen genital wart biopsy material revealed papillomavirus type 11 DNA, the amount of which increased significantly during interferon treatment. The final clearing of lesions after discontinuation of cannabis consumption implicates that the drug-induced impairment of cellular immunity was reversible. It is concluded that drug abuse and especially cannabis consumption may play some role in the world-wide increase in genital papillomavirus disease and in the high number of recalcitrant courses of genital warts.

Influence of psychological and clinical factors on postoperative pain and narcotic consumption.

Demographic, psychological and clinical factors influencing postoperative pain and narcotic analgesic requirements in 162 patients undergoing elective operations under general anesthesia were studied. Eysencks Personality Questionnaire, Foulds Hostility Questionnaire, Zung's Anxiety-Depression (self-rating) Scales and the 43 Item Life Events Inventory by Holmes and Rahe were used. Clinical correlates such as surgical department, outcome of the operation, patient's knowledge of the diagnosis, were studied. Using multiple regression analysis the following results were obtained: postoperative pain levels increase with higher score of extroverted hostility (p = 0.038), abdominal surgery (p = 0.004), longer stay at hospital postoperatively (p = 0.15) and higher educational status (p = 0.13). Postoperative narcotic requirements increase with increased postoperative pain levels (p = 0.039) and preoccupation with pain postoperatively (p = 0.025), preoperative analgesic drug use (p = 0.017), abdominal surgery (p = 0.009) and longer stay at hospital preoperatively (p = 0.016). Also the department in which the patients were hospitalized influenced narcotic consumption.

Efficacy of interferons on bowenoid papulosis and other precancerous lesions.

Preliminary results of an open randomized trial of recombinant interferon gamma in patients suffering from bowenoid papulosis are described. Recombinant interferon gamma was given subcutaneously to 12 patients at a daily dose of 4 X 10(6) I.U. by injection. Four patients each were assigned to one of three treatment groups consisting of continuous therapy (group A) with three subcutaneous injections per week for 13 weeks; intermittent block therapy (group B) with four six-week cycles consisting of five injections on days 1, 3, 5, 7, and 9 of each cycle; and intermittent single-dose therapy (group C) with six four-week cycles consisting of only one subcutaneous injection on day one of each cycle. At the twenty-sixth week after onset of therapy, complete responses were seen in three of four patients of treatment group A, whereas in the treatment groups B and C only one patient, respectively, responded partially. These results suggest that in contrast to condylomata acuminata bowenoid papulosis lesions respond better to continuous than to intermittent interferon gamma injections.

Recurrent vulvar Buschke-Löwenstein's tumor-like condylomata acuminata and Hodgkin's disease effectively treated with recombinant interferon-alpha 2c gel as adjuvant to electrosurgery.

The local application of recombinant interferon-alpha 2c hydrogel (1 x 10(6) IU IFN-alpha 2c per g) given as an adjuvant after electrosurgery led to a complete cure of previously recalcitrant untreatable giant Buschke-Löwenstein's tumor-like condylomata acuminata of a 19-year-old patient suffering from Hodgkin's disease (stage II/II). Interferon-alpha 2c hydrogel given as adjuvant with surgery may have more direct antiproliferative and antiviral activities than immunomodulating defects. This combined topical application is an effective and safe treatment which is recommended especially in immunocompromised individuals suffering from genital HPV disease nonresponsive against systemic interferon and conventional therapy modalities.

[Postoperative interferon hydrogel treatment. A method for the successful therapy of chronic persistent giant condylomas in an immunologically deficient patient with Hodgkin's disease]. / Die postoperative Interferon-Hydrogel-Behandlung. Methode zur erfolgreichen Therapie chronisch persistierender Riesenkondylome bei einer immundefekten Patientin mit Morbus Hodgkin.

The local application of recombinant interferon alpha 2c hydrogel (1.10(6) I.U. recombinant interferon alpha 2c/g hydrogel) given as an adjuvant therapy after electrosurgery led to a complete cure, without relapse, of previously recalcitrant giant condylomata acuminata similar in appearance to Buschke-Löwenstein's tumors in a 19-year-old female patient suffering from Hodgkin's disease (stage II/III). Recombinant interferon alpha 2c hydrogel given as an adjuvant therapy to surgery may have more antiviral and antiproliferative effects than immunomodulating activities. This combined topical application form of interferon alpha is a safe and effective treatment, which is recommended especially in immunocompromised individuals suffering from genital HPV infection unresponsive to systemic interferon treatment or conventional therapy modalities.

Epidermodysplasia verruciformis in a patient with Hodgkin's disease: characterization of a new papillomavirus type and interferon treatment.

A new human papillomavirus (HPV) was discovered in disseminated, macular, pityriasis versicolor-like lesions on the skin of the neck, face, scalp, and pubic region of a 42-year-old male suffering from Hodgkin's disease. Histopathology revealed features characteristic of epidermodysplasia verruciformis (ev). In contrast to classical ev, the lesions were almost exclusively seen in previously irradiated and UV-exposed skin areas. Papillomavirus capsid antigen was demonstrated with the genus-specific antiserum and the patient's serum, which had IgM and IgG antibody titers. HPV DNA was isolated from biopsies and cloned into the vector pIC20H. It proved to be related to ev-associated viruses, showing 23% cross-hybridization with DNA of the closest relative HPV14. The new HPV type was named HPV46. The genome was physically mapped and colinearly aligned with HPV8 DNA to establish its gene organization. Interferon treatment of the patient did not significantly change the clinical picture nor was the concentration of viral DNA per lesion affected. However, no virus capsid antigen was detectable after starting treatment.

[Alpha interferon in condylomata acuminata and juvenile diabetes mellitus]. / Interferon-alpha bei Condylomata acuminata und juvenilem Diabetes mellitus.

Persistent condylomata acuminata in a 21-year-old patient with diabetes mellitus were treated with highly purified interferon-alpha (IFN-alpha) obtained by recombinant DNA technology. Daily dose was 1.5 X 10(6) IU, given subcutaneously. Already during treatment the condylomata regressed. Two weeks after the end of therapy, i.e. after a total dose of 10.5 X 10(6) IU IFN-alpha, all condylomata had completely receded. Blood glucose levels remained constant with concomitant insulin therapy. Toxic side-effects or antibodies to IFN-alpha were not observed.

Systemic treatment of condylomata acuminata with recombinant interferon-alpha-2a: low-dose superior to the high-dose regimen.

Fourteen patients with chronic genital warts were entered in a pair-matched crossover trial of recombinant interferon-alpha-2a. They received daily doses of either 1.5 X 10(6) U or 18 X 10(6) U interferon for one week by the subcutaneous route (abdominal skin). After an observation period of 4 weeks in case of no change or partial response, patients of the low-dose group were given 18 X 10(6) U and those of the high-dose group 3 X 10(6) U daily for another 7 days. Eight of 14 patients had a complete remission by the end of the therapy-free interval of 4 weeks, 5 patients of the low-dose group and 3 patients of the high-dose group. Acute side-effects consisted of a transient influenza-like syndrome. Remissions have been maintained for 6 to over 10 months. The data implicate that recombinant interferon-alpha-2a is highly effective in patients with human papillomavirus-related genital warts and that the low-dose regimen is at least equivalent to the high-dose treatment.