Urine steroid profile of judo competitors affected by acute physical exercises.

A heterogeneous group of 10 male and 15 female judo players are utilized in this study. The subjects complete a standardized maximal treadmill exercise test. Urine samples are collected at the pre- and postexercise stages. The urine steroids are measured using a gas chromatography-mass spectrometry instrument. In rest and after exercise, significantly higher testosterone and epitestosterone concentrations in males (p < 0.01) are found. The etiocholanolone-dehydroepiandrosterone (DHEA) ratio is significantly lower in males than females (p < 0.05). In both males and females, etiocholanolone concentration significantly decreases with the effect of exercise (p < 0.05). 11-OH etiocholanolone concentration also significantly decreases, but only in females (p < 0.05). Positive correlation is found between the changes of the etiocholanolone and epitestosterone concentration caused by exercise.

[Interferon in the treatment of solid tumors]. / Interferon u lijecenju solidnih tumora.

Discovered almost four decades ago, interferons were being investigated as potential anticancer agents from early sixties, because of their antiviral antiproliferative and immunomodulating properties and their relatively modest toxicity. Unlike very good effects on some lymphoproliferative disorders where complete durable remissions were observed, results of their application in solid tumors are not so unambiguous. Among large number of tumors investigated so far, the best, reproducible, although modest, activity was found against melanoma, renal cell carcinoma and Kaposi's sarcoma. There are still many doubts concerning their optimal doses, sequencing and schedules, most probably in combination with other biological response modifiers and/or cytotoxic agents, which have to be clarified in further clinical trials, together with investigation of more reliable biological indicators of response to interferons in vivo.

Addition of IFN-alpha to treatment of malignant brain tumors.

Despite many attempts to improve the survival after surgery of patients with malignant astrocytoma the prognosis is poor. We have used natural IFN-alpha in 16 patients with malignant astrocytoma treated between 1987 and 1990; 6 for recurrent tumors. Radiation therapy was given in 2 Gy fractions daily to a total dose of 50 Gy in the tumor area, 5 fractions per week and IFN twice per week, cisplatinum 60 mg/m2 i.v. every second week and vincristine 2 mg every week in 12-h i.v. infusions. Eight patients were reoperated when clinical deterioration suggested recurrent tumor; histological examination showed no residual tumor in 7 of them. Of these 8 patients 3 are alive and well, 2 of them after more than 5 years. The study suggests that malignant astrocytoma can be successfully eradicated with surgery, irradiation, IFN-alpha and chemotherapy. The treatment had, however, unacceptably high neurotoxicity. Earlier removal of the tumor necrosis, before clinical deterioration, could possibly diminish the high complication rate and consequently improve survival.

Intrapleural application of natural IFN alpha in breast cancer patients with pleural carcinomatosis. Monitoring of immunotherapy by assaying serum interferon levels.

For resistant local recurrence, e.g. in breast cancer, or metastatic spread, local infiltration of IFN may be an interesting new approach. The aim of this study was to find out if intrapleurally administered interferon, in breast cancer patients with pleural carcinomatosis, can cause measurable serum concentrations and how soon after administration. Serum IFN concentrations were compared with those in the pleural fluid, and correlated with the presence of malignant cells in the pleural fluid. To uncover possible rhythmicity of serum interferon levels and its relationship to the timing of therapy, natural leukocyte interferon was administered intrapleurally at 10 a.m. Data on pharmacokinetics were obtained from blood samples drawn at -2, 0, 2, 8, 14, 22 and 46 h during the course of treatment. In contrast to our previous observations in healthy volunteers, levels of serum IFN before therapy had no circadian rhythmicity. Daily pharmacokinetic profile of individual patients on interferon therapy has shown that serum IFN peaks 8 h after intrapleurally administered IFN alpha. The peak depended on frequency and number of applied doses. During treatment with IFN alpha, malignant cells degenerated and finally disappeared from pleural fluid. At the same time reactive cells appeared. This effect is rather uniformly observed, but varies in degree. The number of patients is too small, however, to permit conclusions in regard to correlation of this clinical effect and the levels of serum IFN alpha.

Human leukocyte interferon alpha (HLI-alpha) for treatment of pleural effusion caused by non small cell lung cancer. A pilot study.

Fourteen patients with ipsilateral pleural effusion from non small cell cancer of the lung, 10 of them with generalized metastasis, were treated with local application of HLI-alpha in addition to other symptomatic treatment. Cytology of pleural fluid at the beginning of treatment yielded cancer cells in all but one. HLI-alpha, 2 x 10(6) International Units (I.U.) diluted in 20 ml of distilled water was injected intrapleurally each time. The mean survival of the HLI-alpha treated patients, measured from the first treatment of the pleural effusion, was 10.8 months. The performance status improved in 9 patients following HLI-alpha treatment. The pleural effusion eventually ceased accumulating in all patients. To judge from cytology of tapped pleural fluid, the cancer cells disappeared during treatment with HLI-alpha in 11 patients.

[The effect of vaginal administration of interferon on squamous intraepithelial cervical lesions]. / Utjecaj vaginaleta interferona na cervikalnu skvamoznu intraepitelnu leziju.

Human papillomavirus vaginal and/or cervical infections were found in 1.98 percent of mostly younger female general populations and in 26.6 percent of cases with abnormal Pap smears. Antiviral treatment with human leukocyte interferon (HLI-alpha) vaginalettes was introduced at the beginning of 1987. In 30 cases a daily dose of 1 x 10(6) IU HLI during two 21-day menstrual cycles was applied. In 137 controls without therapy and the treated group a 12-month follow-up was performed. Every third month the regression, persistence or progression of the cervical squamous intraepithelial lesion (SIL) was determined by cytology and colposcopy. Most of the cases with progression were histologically confirmed. For ethical reasons the placebo treatment of the control group with an identical spectrum of disease was not feasible. Therefore, a secondary analysis and the 2 test were used. Up to now the results show a significant regression (21 out of 30, X2 = 4.51, P less than 0.05) in the treated group and progression (23 out of 137, X2 = 18.41, P less than 0.01) in controls. HLI vaginalettes are easily applicable, without any side-effects.

Intrapleural application of human leukocyte interferon (HLI) in breast cancer patients with ipsilateral pleural carcinomatosis.

Seven patients with ipsilateral pleural carcinomatosis from breast cancer were treated by intrapleural application of a crude interferon-alpha (IFN-alpha) preparation (HLI). In 4 patients, previous systemic treatment had been without effect, and 3 patients had recurrence after initial remission. Pleural carcinomatosis was confirmed by cytology in 6 patients and by histology in 1 patient. HLI was given in doses of 2.2 X 10(6) IU two to six times. The effect was evaluated by cytological examination of the pleural fluid; malignant cells disappeared in all six patients who were evaluable. Pleural fluid, while not totally resolving, did not accumulate further after HLI. Disseminated tumor was present in all at the time of eventual death. No tumor was found in the pleura at autopsy of 2 patients and the pleural fluid was free of malignant cells at the time of last follow-up examination in the 4 others. These results seem to justify further investigation on larger groups of patients with better technique of application.

Histopathologic and histoenzymatic observations in carcinomas treated with human leukocyte interferon.

In this study histologic and histochemical examinations were performed on the bioptic material of 30 cases of head and neck tumors and 34 cases of uterocervical carcinomas after treatment with human leukocyte interferon (HLI). Particular attention was paid to the interaction between stromal and neoplastic cells as a possible host response to the treatment with interferon. In addition to tumor biopsies, regional lymph nodes were also examined microscopically. Stromal cells (macrophages, T and B lymphocytes, and granulocytes) were detected by enzyme-histochemical methods. Histologic and histochemical criteria for classification of tumor biopsies into five groups included the frequency, the cellular composition of peritumoral stroma, the grade of macrophage infiltration into the tumor (expressed quantitatively), and cytologic changes, followed by the regression of tumor. The overall appraisal of patients with cervical carcinoma based on histopathologic and chemical criteria showed the positive effect of HLI therapy in 70% of the cases; observations of head and neck carcinoma treated with HLI showed positive effects in 82% of the cases.

The clinical use of human leukocyte interferon in viral infections.

This review presents the results of the clinical use of human leukocyte interferon (HLI) in certain diseases with viral etiology. Viral infections with manifestations in the eye, skin, and/or mucous membranes and in the respiratory system were treated with HLI by local application. HLI was incorporated into ointment, oil suspension, powder, dilution for inhalation, and dilution for subcutaneous and subconjunctival injections. The treatment in some of the diseases yielded statistical results that were highly significant in favor of interferon.

Topical application of human leukocyte interferon in stasis ulcers and deep burns.

Human leukocyte interferon (HLI) incorporated in ointment (4,000 units/g) applied topically for 4 weeks induced the process of "scavenging" granulation and epithelialization of stasis ulcers. This therapy had a better effect than that of the other combined local and general therapy also given in the study. A comparison of the effects of both therapies was made on nine pairs of stasis ulcers. A favorable effect of HLI on granulation and epithelialization was observed in a patient with deep burns, who had been given HLI topically in the form of powder and solution. This type of HLI activity calls for further clinical trials, especially as regards deep burns.

Application of human leucocyte interferon in patients with tumours of the head and neck.

Local administration of crude human leucocyte interferon (HLI) produced substantial or total remission in patients with cancers of the head and neck. At the end of HLI therapy 10 of 30 patients were considered completely cured. In 10 patients unepithelialised skin lesions were hardly visible, in 5 the tumours were significantly reduced in size and had clear-cut borders, in 2 the tumours showed a tendency towards regression, and in 3 there was no effect. Application of HLI close to the tumour site appears to prevent dispersal of tumour cells during surgical removal of the tumour. It also inhibits metastatic spread, thereby reducing the likelihood of recurrence.

Application of human leucocyte interferon in patients with urinary bladder papillomatosis, breast cancer, and melanoma.

Eight patients with malignant papillomaosis of the bladder, four with breast cancer, and two with malignant melanoma, all of whom had a poor prognosis, were treated with injection of crude human leucocyte interferon (HLI) into the tumour or the adjacent tissue and in some cases with intramuscular HLI injection also. All tumours showed complete or partial regression after treatment for up to 6 months. One patient with breast cancer died from distant metastases; all other patients in the trial were recurrence-free after 3--30 months of follow-up.

Application of human leucocyte interferon in patients with carcinoma of the uterine cervix.

15 patients with invasive squamous-cell carcinoma of the uterine cervix were treated with crude human leucocyte interferon (HLI) for 3 weeks before surgical removal of the tumour. 9 patients were given HLI topically and intramuscularly and 6 topically only. In 3 patients the surgical material was free from tumour cells, in 3 it showed a lower grade of carcinoma, and in 9 the findings remained unchanged. In only 1 patient the tumour metastasised to the lymph nodes. Typically a tumour regressed to about a third of its original size. There was a sharp distinction between the tumour mass and the healthy tissue manifested in the formation of a fibrous wall. On the basis of the scores--i.e., stromal response, relation between tumour-cell and macrophage activity and reactivity, and reactivity of the original lymph nodes--the overall appraisal of the response caused by HLI therapy was as follows: in 6 patients excellent, in 5 very good, in 1 moderate, in 2 poor, and in 1 no response. It is suggested that HLI is suitable for administration both before and after surgery in patients with cervical cancer of grade I or II. If stroma cannot be induced to respond within 21 days of treatment, HLI application should be discontinued.

Effect of interferon in therapy of skin and head and neck tumors.

The clinical experimental model of HLI application in the therapy of skin and mucosal cancers of the head and neck has opened new prospects in HLI utilization. Based on clinical observations and research it may be concluded that HLI, if applied topically in the area of the tumor, may induce its disappearance or regression. If applied presurgically, it blocks the dispersion of neocytes during surgery. Also, HLI inhibits metastatic dissemination of malignant tumors and therefore might reduce the percentage of patients with recurrence, decreasing the chance of survival of any other primary tumor.

Interferon treatment of uterine cervical precancerosis.

Human leukocyte interferon (HLI) was used in a randomized study of patients with precancerous states on the uterine cervix. The daily dose of HLI was 10(6) units and its was applied by the contraceptive pessary technique. In patients how had had only viral alterations on the cervix the treatment lasted 14 days (Singer et al. 1979) and in those with changed cytologic findings 21 days. The cytologic findings of the interferon treated patients showed no progression of the pathologic process during the ensuing 2 years. In the control group, however, they showed the aggravation of the process and the patients were directed to surgical therapy. The control of cytologic findings has been continued and in now performed at 3 month intervals.

Influence of human leukocyte interferon on squamous cell carcinoma of uterine cervix: clinical, histological, and histochemical observations. III. Communication.

Fifteen patients with invasive squamous cell carcinoma of the uterine cervix were treated with human leukocyte interferon (HLI). HLI was applied topically and i.m. to nine patients, and only topically to six. After therapy, surgical material was free from tumor cells in three patients, tumor cells were identified as invasive carcinoma in one patient and as CA in situ in two patients. Findings remained unchanged in nine patients. Tumor metastases in the lymph nodes were found in only one patient. The patients' overall response to therapy was assessed on the basis of stromal response, relation of tumor cells and macrophage activity, and the reactivity of lymph nodes.

Human leukocyte interferon in therapy of patients with urinary bladder papillomatosis, breast cancer, and melanoma.

The authors report the result of local and parenteral applications of human leukocyte crude interferon in the therapy of eight patients with urinary bladder papillomatosis, four patients with breast cancer, and two patients with melanoma. The doses and effects of treatment are presented in tables. Clinical application of human leukocyte interferon (HLI) to these three types of malignant tumors has yielded encouraging results. The authors believe that investigations on HLI applications to some malignant tumors should continue because the results obtained indicate that interferon possesses not only an antiviral but also an antitumor activity.