Phase-II randomized study of pre-operative IL-2 administration in operable NSCLC.

Lymphocytopenia is a prognostic factor for shorter survival in advanced lung cancer and it is likely related to an interleukin-2 (IL-2) deficiency occurring during cancer progression. Major surgery itself for cancer is known to induce lymphocytopenia in the postoperative period. Postoperative lymphocyte decrease in colorectal cancer can be prevented by preoperative administration of recombinant human (rhIL-2), indicating that it is possible to drive appropriately important host defence agents during critical events, such as major surgery. The aim of this study is to verify if recombinant human interleukin-2 (rhIL-2) administered preoperatively is able to prevent the lymphocyte decrease occurring after radical surgery in operable lung cancer. This phase II study included 40 patients with operable NSCLC screened as stage II or IIIA, randomized to receive rhIL-2, 9000000 IU subcutaneously twice daily for 3 days before surgery (treated group, 20 patients) or not (control group, 20 patients). At baseline, there were no significant differences in total lymphocyte number and lymphocyte subsets (T-cell, T-helper, CD8+, natural killer, CD4/CD8 ratio) between groups. Postoperatively the control group showed a decrease in total lymphocyte count, T-lymphocyte count, T-helper cell number and CD4/CD8 ratio, significant at the 14th postoperative day relative to baseline values. In contrast, in the rhIL-2 treated group, at the 3rd and at the 14th postoperative days, a significant increase was observed over both baseline and control group values of total lymphocyte count, T-cells and T-helper cells. NK cell number increased significantly only over the control group. CD4/CD8 ratio was increased at the 14th postoperative day significantly over both baseline and control values. At pathological staging after surgery, four patients in the rhIL-2 group and four in the control group resulted in stage pIIIB; one patient in the rhIL-2 group resulted in stage IV (contralateral metastasis). Indeed, 15/20 rhIL-2 treated patients and 16/20 control patients were radically operated. After a 24-month follow-up, 12/20 rhIL-2 treated patients were alive and 8/15 radically operated were disease-free; 8/20 control patients were alive and 4/16 radically operated were disease-free. Toxicity was mild to moderate and easy manageable; treatment was suspended in one patient due to skin rash with hypotension grade II. The preoperative administration of rhIL-2 is feasible and prevents lymphocyte decrease occurring postoperatively after surgery for lung cancer. Further studies are required to assess the impact on survival.

Intrapleural administration of recombinant interleukin-2 in non-small cell lung cancer with neoplastic pleural effusion.

The aim of this study was to assess the feasibility and effectiveness of intrapleural administration of recombinant human interleukin-2 (rhIL-2) for treatment of malignant pleural effusions. From May 1993 to May 1995, 21 patients with non-small cell lung cancer (NSCLC) and cytologically documented malignant pleural effusion entered the study. After complete needle drainage of the effusion, a dose of 9 x 10(6) international units (IU) rhIL-2 was injected intracavitarily. The drug was injected on the first and second day each week for 3 weeks, in relation to the presence of effusion. Complete response (according to the criteria reported by Paladine st al.) was achieved in 7 of the 21 patients (33%), and partial response in 6 of the 21 patients (29%), with a median duration of 8 months (range 4-10 months). The treatment was well tolerated by all patients. Intracavitary administration of low-dose recombinant human interleukin-2 in malignant pleural effusion due to non-small cell lung cancer is an effective and well tolerated therapeutic strategy.

Clinical and bronchoscopic features of endobronchial tuberculosis.

Clinical and bronchoscopic features of endobronchial tuberculosis were retrospectively investigated in 24 patients. A barking cough was the most frequent chief complaint in 50% of patients. The typical apico-subclavian localization of pulmonary tuberculosis in adults was found in only 50% of patients; in one patient the lung fields were clear. Bronchoscopic features consisted of exudative lesions in 38% of cases, ulcerative lesions in 25%, granulomatous lesions in 25%, and ulcerative-granulomatous tumour-like lesions in 12%. In 12% of patients, a residual fibrotic stenosis was seen. It was concluded from our data that patients whose cough is barking and resistant to antitussive agents should be evaluated for endobronchial tuberculosis, and, therefore, the use of fibreoptic bronchoscopy is mandatory. We also conclude that diagnosis of endobronchial tuberculosis demands the use of corticosteroid therapy.

Efficacy and toxicity of vinorelbine-carboplatin combination in the treatment of advanced adenocarcinoma or large-cell carcinoma of the lung.

AIMS AND BACKGROUND: The aim of the study was to assess the activity and toxicity of the vinorelbine-carboplatin combination in advanced adenocarcinoma or large-cell carcinoma of the lung. The new vinca derivative, vinorelbine, shows promising activity when combined with cisplatin, but toxicity of the combination is substantial. METHODS: Accordingly, we substituted carboplatin for cisplatin in the combination in order to improve the therapeutic index. From March 1992 to March 1994, 55 untreated patients with undifferentiated unresectable or metastatic adenocarcinoma or large-cell carcinoma of the lung were recruited. The treatment consisted of a course of carboplatin (300 mg/m2) and vinorelbine (25 mg/m2) repeated every 4 weeks. The only grade 3 toxicity observed was 16 cases of grade 3 vomiting and 2 cases of grade 3 stomatitis. RESULTS: The positive response rate was 40% (partial response, 22 patients). In conclusion, the vinorelbine-carboplatin combination may be regarded as an active, safe regimen for the palliative treatment of advanced adenocarcinoma or large-cell carcinoma of the lung.

COPD patients and mechanical ventilation with positive end expiratory pressure (PEEP).

Application of positive and expiratory pressure (PEEP) is widely used in mechanically ventilated patients with acute respiratory failure (ARF) due to adult respiratory distress syndrome. Recent studies have suggested that application of PEEP can be useful in patients with chronic obstructive pulmonary disease (COPD) to reduce the mechanical inspiratory load due to intrinsic positive and expiratory pressure (PEEPi). In any ventilatory mode (controlled mechanical ventilation, assisted mechanical ventilation) and during weaning, application of moderate levels of PEEP replace in part PEEPi without adding to it and without significantly increasing lung volume.

Vinorelbine monochemotherapy in non-small-cell lung cancer: experience in patients with low performance status.

The aim of this study was to investigate the activity and safety of vinorelbine in patients with low performance status. From March 1992 to June 1993 we studied 14 untreated patients with Stage IV non-small-cell lung cancer (NSCLC) and a "performance status" lower than 70% of the Karnofsky score. Treatment was by means of an intravenous administration of vinorelbine (30 mg.m-2) repeated weekly. On the whole, the toxicity was mild. Of 150 cycles administered, we observed 10 cases of Grade 3 leucopenia and 4 cases of Grade 4 leucopenia. A peripheral neurotoxicity (Grade 2-3) was reported in two patients. The objective response rate was 36% partial response. Our data suggest that vinorelbine could be an active and safe treatment for those patients who cannot receive polychemotherapy because of low performance status, and justify further larger studies comparing vinorelbine, either as a single agent or in combination, to other analogues or to assess its efficacy in supportive care.

Clinical efficacy of azithromycin in lower respiratory tract infections.

A total of 51 patients with acute exacerbation of chronic bronchitis and pneumonia were enrolled: 27 treated with azithromycin (500 mg once a day for 3 days), and 24 with roxithromycin (150 mg every 12 hours for 7 days). The two regimens were equally effective, with clinical cure in 80% and 72% of patients respectively. Bacteriological eradication on day 19-23 was obtained in 7/11 cases (64%) and in 6/13 cases (46%) in the two groups, respectively. No side effects occurred in patients treated with azithromycin, while they occurred in the roxithromycin group (2 vomiting and 1 gastritis). Clinical and bacteriological efficacy, excellent tolerability, simplified dosage (single daily dose) and short-course (3 days) therapeutic regimen make azithromycin, in our experience, efficacious for the treatment of acute exacerbation of chronic bronchitis and community-acquired pneumonia.

Effectiveness and toxicity of "BELD" polychemotherapy in advanced malignant melanoma.

From January 1985 to December 1987, 17 patients with advanced malignant melanoma were treated with the polychemotherapy regimen BELD (bleomycin, 15 mg subcutaneously on day 1 and 4, vindesine 3 mg/m2 intravenously on day 1 and 5, CCNU 80 mg/m2 orally on day 1 and DTIC 200 mg/m2 intravenously on day 1 through 5) proposed as effective (CR + PR 45%) and tolerable. All patients were evaluable for toxicity and 14/17 also for response after 2 BELD cycles (total n. of cycles was 54). Criteria for response were just the same as those used by Young et al. A complete remission and a partial remission (2/14) have been observed at lymph nodal level, the unique sites of the disease in these two patients. Remission lasted 6 and 4 months, respectively. Two other patients showed a minimal response of 2 and 3 months duration (lymphonodal and cutis, respectively); 9 patients had stabilized disease of 5 months median duration. One case of progression of disease was observed. However, toxicity was relevant because of 2 early deaths after the first cycle, most probably therapy related, nausea and vomiting (82%), leukopenia (17%) and muscle rigors (11%).

[Cyclophosphamide, adriamycin and platinum (CAP) in the preoperative neoadjuvant phase and the therapy phase]. / Ciclofosfamide, adriamicina e platino (CAP) in fase neoadiuvante preoperatoria e in fase curativa.

Forty-two patients with metastasized, and 7 patients with locally advanced forms of carcinoma of the breast were treated with a combination of three drugs: CTX 200-400 mg/sq.m. on days 1, 3 and 5, ADM 40 mg/sq.m. on day 1, and DDP 30 mg/sq.m. on days 1, 3 and 5 (CAP), every 21 days. The 42 patients with metastasized carcinoma had already received substantial pre-treatment by surgery and with adjuvant polychemotherapy +/- chemotherapy on recurrence +/- hormonotherapy +/- radiotherapy. The disease sites were: bone (30%), skin (19%), lymph nodes (13.5%), pleura (12.5%), lung (12%) and liver (11%). The 7 patients with locally advanced carcinoma had not been pre-treated; they received the same chemotherapy in the pre-operative neo-adjuvant phase. Positive responses to CAP in the cases with metastasized carcinoma according to individual disease sites (37 pre-treated patients assessable after at least two courses of therapy) were as follows in percentage terms: 24% bone lesions, 56% skin lesions, 77% lymph node lesions, 30% liver lesions, 56% lung lesions, 22% pleural lesions. 3/37 patients (8%) showed complete remission in all disease sites, while 6/37 showed partial remission. This percentage (8 + 16 = 24%) is encouraging, as CAP, in these patients, represents on average the 3rd to 4th line of therapy. Responses to neo-adjuvant CAP therapy (7 patients assessable after at least two courses of therapy) were as follows: 5 patients showed partial remission after 3-6 courses, 1 complete remission, and 1 objective improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent advances of knowledge on the mechanism of action of drugs modifying the bronchial secretions.

In order to explain the mechanism of action of drugs modifying the bronchial secretions, their subdivision into agents with a direct or an indirect action seems justified: the former primarily modify already formed secretions, whilst the latter act on the bronchial structures originating mucus. In hypersecretive states with increased viscoelasticity of mucus, a widespread therapy is represented by the use of direct reducing drugs, which act by breaking the mucofibrillar network. Among them the most important are those with free sulphydryl groups (-SH), which can break the disulphide bonds of the bronchial secretions. The mechanism of action of substances such as acetylcysteine and tiopronin, that are included in those with a direct reducing action, was already verified by researches with the modified thrombo-elastograph (MTE) and has been recently confirmed by the present authors by employing a simple biochemical method, by which the action of such drugs on the structure of serum IgM can be studied in vitro. The same method permits the classification of carbocisteine and letosteine as amongst the drugs with indirect action. From the results obtained by such in vitro experiences, the necessity to examine more closely the consequences of secondary effects which direct mucolytic agents may cause by modifying the rheological, biochemical and immunological properties of bronchial secretions has been demonstrated.

Patients admitted for compulsory treatment to selected psychiatric units in Italy and in Sweden.

Eighty-five Italian and forty-nine Swedish patients consecutively admitted for compulsory treatment to either an Italian or a Swedish psychiatric unit in selected areas of the two countries have participated in an exploratory study aimed at assessing the main characteristics of compulsory admitted patients, and in particular, the immediate reason for admission. The two series proved to be quite similar as concerns most sociodemographic variables, and as concerns clinical diagnosis and severity of the morbid condition at admission as measured by means of a rating scale. More Swedish than Italian patients lived alone when admitted to hospital, and for more of them the request for admission was made by other people than relatives, and a larger proportion of them was accompanied to the hospital by medical or social welfare personnel. In both series the largest proportion had a low educational level and belonged to the lower social groups. The same proportion in the two series had previous admissions. The most common reason for admission was "odd or improper behaviour" for the Swedish patients, and "feared or manifest dangerousness" for the Italian patients. The Italian patients remained at hospital on average half the time than the Swedish patients.

[A case of primary orthostatic hypotension of the Bradbury-Eggleston type]. / Su di un caso di ipotensione ortostatica primitiva tipo Bradbury-Eggleston.

A patient with idiopathic orthostatic hypotension not accompanied by other neurologic disorders was examined. Pulmonary function tests demonstrated the failure of the autonomic innervation of airways. A syndrome of chronic primary alveolar hypoventilation was present, with the vocal cord paralysis. The symptoms of neurogenic bladder were also present. While recumbent, the patient had low levels of plasma norepinephrine, that failed to increase after standing and exercising. During Kaplan-Silah test the patient was proved to be supersensitive to intravenously administered norepinephrine and angiotensin. The finding was consistent with the view of peripheral denervation. The syndrome of orthostatic hypotension and other symptoms referable to peripheral autonomic dysfunction, without evidence of central nervous system involvement appears to represent a clinical entity distinct from the Shy-Drager syndrome. It can be defined Bradbury-Eggleston syndrome.

[Treatment of bronchial inflammatory disorders with guacetisal]. / Trattamento delle forme infiammatorie bronchiali con guacetisal.

A comparative trial conducted on 48 male and 9 female patients suitably selected in terms of indication consisted of a first stage in which a completely random, doubleblind comparison was made between acetylsalicylic acid, guacetisal and guaiacol carbonate (preparations A, B, and C) while in the second stage an association of bromexine, acetylsalicylic acid and codeine phosphate (preparation D) was examined in terms of activity and tolerance in an open trial. Statistical analysis showed the superiority of preparation B with respect to most of the parameters taken into consideration.

Double-blind cross-over clinical comparison of two 2'-chloro benzodiazepines: 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (chlordesmethyldiazepam) versus 7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (lorazepam) in neurotic anxiety.

A group of 20 female neurotic inpatients has been treated with 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one-(chlordesmethyldiazepan)- 7-chloro-5(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (lorazepam) according to a double-blind cross-over design. For each drug clinical evaluations were performed by means of Hamilton's rating scale for anxiety states and of Overall and Gorham's brief psychiatric rating scale, at the beginning, after the first week and at the end of the two-week period of treatment, in opposite sequence. A statistically greater efficacy of chlordesmethyldiazepam in comparison to lorazepam was observed. Results are discussed with regard to benzodiazepine structure-activity relationships.