Medroxyprogesterone acetate reduces the in vitro production of cytokines and serotonin involved in anorexia/cachexia and emesis by peripheral blood mononuclear cells of cancer patients.

Medroxyprogesterone acetate (MPA) is widely used in oncology both in the treatment of hormone-related cancers and as supportive therapy in anorexia/cachexia syndrome (ACS), but conclusive data are not yet available to explain its anticachectic effect. ACS is characterised by weight loss, changes in metabolism, reduction of appetite, nausea and vomiting. Several cytokines, mainly interleukin (IL)-1, IL-2, IL-6 and tumour necrosis factor alpha (TNF alpha), are involved in the pathogenesis of ACS. Additionally, nausea and vomiting can be mediated by factors inducing serotonin (5-HT) production and/or release by pleiotropic cells including activated T lymphocytes. In the present study, we report the effect of MPA on peripheral blood mononuclear cells (PBMC) from 10 cancer patients in advanced stage of disease (6 head and neck, 2 colon, 1 lung and 1 ovary). The proliferative response of PBMC to PHA, anti-CD3 monoclonal antibody (MAb) or recombinant IL-2 (rIL-2), the production of IL-1 beta, IL-2, IL-6, TNF alpha and 5-HT by PHA-stimulated PBMC and the expression of lymphocyte membrane-bound IL-2 receptor (IL-2R) subunities (CD25 and CD122) were studied. The addition of MPA significantly reduced the PBMC proliferative response to PHA and anti-CD3 MAb but not to rIL-2. MPA 0.2 microgram/ml was also capable of reducing the levels of IL-1 beta, IL-6, TNF alpha and 5-HT produced in culture by PHA-stimulated PBMC, whereas it did not induce any change in the percentage of PBMC expressing either CD25 or CD122 or both molecules after stimulation with PHA or anti-CD3 mAb.

Treatment of chronic idiopathic urticaria with topical preparations: controlled study of oxatomide gel versus dechlorpheniramine cream.

A controlled and completely randomized study was carried out with the aim of assessing the efficacy and safety of oxatomide gel in comparison with another preparation for topical use, dechlorpheniramine. Twenty-seven patients (sixteen F, eleven M) aged between 21 and 72 years (mean age 39) suffering from chronic idiopathic urticaria were treated for 15 days with oxatomide gel at 5% or dechlorpheniramine cream at 1%; 15 days of follow-up without therapy were then observed. Both the treatments allowed significant control of cutaneous symptoms. In particular, in the group treated with oxatomide there was a more marked reduction in itching and in the number of weals (p less than 0.01 between times), and in the dechlorpheniramine group in the severity of erythema (p less than 0.01 between times). During the follow-up period, a distinct flare-up of symptoms was observed only in the dechlorpheniramine group. Acceptability and safety, both clinical and biological, were good for both products.

[Effects of Hodgkin cytotoxic serum on electrophoretic mobility of normal and Hodgkin peripheral blood lymphocytes. (author's transl)]. / Effetto del siero citotossico di pazienti con malattia di Hodgkin sulla mobilità elettroforetica di linfociti periferici normali e hodgkiniani

The effect of Hodgkin patient cytotoxic sera on the electrophoretic mobility of normal and Hodgkin peripheral blood allo-lymphocytes has been studied. Contact with cytotoxic serum determined a significant decrease in the electrophoretic mobility of lymphocytes, due to the presence of cytotoxic antibody on the lymphocyte surface. The antibody seems to be directed against T-lymphocytes. The results are discussed in the light of the preceding data by the authors on the role of anti-T-autoantibodies in Hodgkin's disease.

Peripheral blood lymphocyte response to exogenous interleukin 2 by PHA-prestimulated and non-PHA-prestimulated cells in patients with cancer.

The study aims were to assess the response of peripheral blood lymphocytes (PBL) of cancer patients to exogenous Interleukin 2 (IL 2) either by PHA-prestimulated or non PHA-prestimulated PBL, and to carry out preliminary experiments for a direct quantitative evaluation of endogenous IL 2 production by PBL cultures of cancer patients in order to define the actual role of IL 2 in the disease. Analysis of PBL subsets was also carried out with monoclonal antibodies in a selected group of patients. A total of 134 patients entered the study. Cancer sites were: larynx 32, breast 36, lung (NSC) 24, colorectal 17 and gynecologic 25. In the former 3 cancer sites staging showed localized or only locally advanced disease, and in the last 2 sites disseminated disease. Our results provided evidence that cancer patients exhibit a T-cell functional immunodepression, which progresses during tumor growth, so that the localized disease shows a low-grade defect, and advanced disease a high-grade defect. Our data also clearly suggested that the factor involved with a primary role in this functional immune impairment is the IL 2 deficiency. A perspective may be drawn on the therapeutic administration in vivo of IL 2 and IL 2-activated lymphokine-activated killer cells in controlled clinical trials of selected groups of cancer patients.

[Effects of Hodgkin cytotoxic serum on blast transformation of normal and Hodgkin human peripheral blood lymphocytes]. / Effetto del siero citotossico di pazienti con malattia di Hodgkin sulla PHA-responsività in vitro di linfociti periferici umani

The PHA-resposiveness of normal and Hodgkin patient human peripheral blood lymphocytes has been studied before and after incubation with Hodgkin cytotoxic sera. The following conclusions have been reached: (a) Hodgkin cytotoxic serum is capable of decreasing the PHA-responsiveness of normal lymphocytes and of furtherly impairing the already defective PHA-responsiveness of Hodgkin lymphocytes. (b) The impaired PHA-responsiveness can be restored to the original levels by eluting the cytotoxic antibody. Control experiments in which normal and Hodgkin lymphocytes were put in contact with normal and Hodgkin non-cytotoxic serum showed no decrease of PHA-responsiveness. These data are in agreement with the hypothesis that the presence of serum cytotoxin is at least partly responsible for the immuno-incompetence of T-lymphocytes characteristic of Hodgkin's disease.

Prolonged treatment with acrivastine for seasonal allergic rhinitis.

In a double-blind, placebo-controlled multicentre study, the antihistamine acrivastine, was used over prolonged periods for the treatment of seasonal allergic rhinitis. After the initial treatment period of 10 days, 8 mg acrivastine three times daily was significantly superior to placebo in controlling the symptoms of sneezing, itchy nose, running nose, watery eyes, itchy eyes and itchy throat. The benefit from acrivastine was also apparent in the second (14 days) and third (28 days) treatment periods, although the difference no longer reached statistical significance. This was probably due to the large proportion of non-responders in the placebo group who withdrew from the study owing to lack of efficacy. The investigators rated symptom control with acrivastine to be 'good' in comparison to 'poor' control with placebo treatment (P = 0.01) for all three periods. There were no significant differences between acrivastine and placebo in the incidence of adverse experiences at the end of each treatment period. Acrivastine is effective and well tolerated over prolonged periods (up to 52 days) for the treatment of seasonal allergic rhinitis.

Total IgE in newborns treated prophylactically with conalbumin.

Conalbumin has been used as a prophylactic treatment in artificially fed babies to prevent enteritic infections. Conalbumin being a heterologous protein, it could have sensitizing properties. The trial here reported demonstrated that when conalbumin-treated milk was fed to 15 such babies for 60 days the values of total IgE, as determined by the radioimmunoassay method, remained within the normal range.

Effect of conalbumin on phytomitogen stimulation and E-rosette formation of human peripheral lymphocytes in normal subjects.

An immunological in vitro study was carried out on conalbumin, an iron binding protein structurally similar to lactoferrin, which is a well-known bacterial inhibitor in human milk. Conalbumin itself has been proved to have bacteriostatic activity against a broad spectrum of bacteria responsible for gastrointestinal infections. The activity of conalbumin on the in vitro response to PHA, PWM and Con A and on the E-rosette formation ability of peripheral lymphocytes of 10 normal subjects was studied. The results showed that conalbumin did not affect the lymphocytes' E-rosette formation ability and did not induce blastic transformation of lymphocytes. However, conalbumin was able to produce a significant increase in the in vitro response of lymphocytes to PHA and PWM, suggesting an action on both T and B lymphocytes.

Secondary immunodeficiency in advanced lung cancer: effects of chemotherapy plus thymostimulin in immunodepressed patients: updating results.

In order to evaluate the effect of an immunomodulator (thymostimulin-TS) added to a traditional combination chemotherapy (ADM, VCR, CTX, CCNU) in advanced lung cancer (oat cell excluded), we began a trial in immuno-depressed patients showing at least 2 out of three appropriate test criteria (see text). Of the 22 fully evaluable patients (all male), 12 in Arm A were given chemotherapy (CH) alone, and 10 in Arm B received chemotherapy (CH) plus TS (1.5 mg/kg/day, beginning the day after the end of the chemotherapeutic cycle). The mean age was 57 +/- 11 for Arm A and 58 +/- 8 for Arm B. The histological type was squamous for all 12 in Arm A and 9 of the 10 in Arm B. No significant differences were found between the mean survival of the two groups (8.1 +/- 3.6 Arm A and 12.1 +/- 84 Arm B); all the patients in Arm A died (maximum survival 12 months for 3 patients), and 2 patients of Arm B are still alive after 23 and 16 months respectively (one patient died after 23 months). Infections occurred on 2 occasions in 2 patients in Arm B, and 13 times in 5 patients in Arm A of which 2 died during a bronchopneumonia. Bone-marrow toxicity was lower in Arm B than in Arm A. Immunological tests failed to improve in the Arm-B patients receiving TS + CH although their resistance to infections seemed to be better than in patients treated by CH only. The quality of life remaining has been better in the patients of Arm B than in those of Arm A.

[Controlled trial of thymostimulin treatment of patients with primary carcinoma of the larynx resected surgically. Immunological and clinical evaluation and therapeutic prospects]. / Trial controllato di trattamento con timostimolina in pazienti con carcinoma primitivo della laringe sottoposti a sola chirurgia. Valutazione immunologica, clinica e prospettive terapeutiche.

The study aim was that of evaluate the effect of thymostimulin (Tp-1, Serono), either in vitro or in vivo, in patients with primary laryngeal carcinoma, treated only with surgery without any other complementary therapy. Nineteen patients have been studied: nine (mean age 62.5 years, range 48-70) have been treated with Tp-1 and ten patients (mean age 63.4 years, range 56-75) served as "controls". Tp-1 has been administered as follows: 60 mg/m2/daily i.m. days 1-15; 60 mg/m2 twice weekly i.m. days 16-30; 60 mg/m2 once weekly i.m. days 31-60. The treatment was stopped days 61-90. The same cycle was repeated until day 180. The treatment was stopped days 181-365. The following parameters have been assessed: clinical (at the protocol entry and after one year): Performance Status (PF, Karnofsky), local status, presence of relapses, incidence of chronic infections of the upper respiratory tract; immunological in vitro: 1) response to polyclonal mitogens, PHA, Con A and PWM, response to human recombinant Interleukin 2 (rIL 2) of PHA-prestimulated and non prestimulated peripheral blood lymphocytes. The immunological parameters also have been assessed at the protocol entry and after one year. Our results have shown that, in the group of patients treated with Tp-1, 5/9 patients (55.56%) exhibited a significant increase of the PHA response at the end of treatment as compared to pretreatment values, 3/9 (33.34%) showed a decrease and 1/9 (11.10%) an almost unchanged response. In the group of controls, 5/10 (50%) have shown a significant decrease of the response after one year, 3/10 (30%) an increase, 1/10 (10%) were unchanged and 1/10 (10%) exhibited a non univocal response.(ABSTRACT TRUNCATED AT 250 WORDS)

[p55 and p75 subunits of the IL 2 receptor, membrane bound and soluble, in peripheral lymphocytes in patients with solid tumors]. / Studio delle subunità p55 e p75 del recettore per l'IL 2, di membrana e solubile, sui linfociti periferici di pazienti con tumori solidi.

The aim of the investigation was to directly study the IL 2 receptor (IL 2 R) and its subunits, p55 and p75 chains, either membrane-bound or soluble, on peripheral blood mononuclear cells (PBMC) of patients with solid malignancies and, indirectly, the same patients' PBMC ability to produce IL 2. Fifty-eight cancer patients, 29 men and 29 women, were studied: their mean age was 57.3 years, range 35-79. Twenty-two healthy age-sex-matched subjects served as controls. The tumors were the most common and the most representative among human cancers, i.e. breast, lung, head and neck, digestive tract and liver, prostate and gynecologic cancers: they were generally in advanced stages and in 23 cases metastatic. The PBMC proliferative response to PHA, PHA plus IL 2 and IL 2 was evaluated along with the response to PHA in presence of anti-p55, anti-p75 monoclonal antibodies, or both. Moreover, membrane-bound IL 2 R, p55 and p75 chains, on PHA-stimulated PBMC were detected, along with soluble IL 2 R in the serum and in the culture supernatants. The conclusions suggest that in solid malignancies: the membrane-bound IL 2 R s, both p55 and p75 chains, are expressed normally, there is an high serum level of soluble IL 2 R, there is a normal release of soluble IL 2 R in culture, and there is an indirect evidence of a lack of IL 2 production. Therefore, no primary impairment of IL 2 R was found in solid tumors.(ABSTRACT TRUNCATED AT 250 WORDS)