Salt-wasting congenital adrenal hyperplasia: genotypical peculiarities in a Sicilian ethnic group.

Here we report for the first time the results of the molecular study of 17 unrelated patients with salt-wasting (SW) congenital adrenal hyperplasia (CAH) belonging to a Sicilian ethnic group, as corroborated by patients' pedigree taken to include 2 generations in the paternal and maternal lineage. The aim of this report was to confirm that genetic basis of CAH may be characterized by population differences. In our series, the overall predominant mutation was IVS2A/C>G, that was detected in 50% of alleles and in 58.8% of patients. The allelic and homozygous frequencies of IVS2A/C>G, Del8bpE3, and R356W mutations were significantly higher in our series than in other populations. Our study population included 2 cases with 2 different mutations that have been recently reported for the first time, 3 cases with a double mutation on the same allele, and 1 case with homozygous de novo mutation. We concluded that: a) in a Sicilian ethnic group the most frequent genotype in SW CAH is IVS2A/C>G homozygocity; b) surprisingly Del8bpE3 and R256W homozygocity are also well represented.

A randomized trial of adoptive immunotherapy with tumor-infiltrating lymphocytes and interleukin-2 versus standard therapy in the postoperative treatment of resected nonsmall cell lung carcinoma.

BACKGROUND: A previous pilot study from our group suggested that: (1) adoptive immunotherapy (A1) with tumor-infiltrating lymphocytes (TIL) and recombinant interleukin-2 (rIL-2) may be applied with safety to more than 80% of the patients who had surgery for Stage III nonsmall cell lung carcinoma (NSCLC); and (2) AI could be useful in patients with locally advanced disease. The present randomized study was planned to assess the efficacy of AI in the postoperative treatment of Stage II, IIIa, or IIIb NSCLC: METHODS: TIL were expanded in vitro from tissue samples obtained from the surgically removed specimens of 131 patients. Eighteen cultures yielded no growth of TIL. The remaining 113 patients were stratified according to disease stage and randomized to receive AI or standard chemoradiotherapy. TIL were infused intravenously 6 to 8 weeks after surgery, rIL-2 was administered subcutaneously at escalating doses for 2 weeks, and then at reduced doses for 2 weeks and then for 2 to 3 months. RESULTS: Three-year survival was significantly better (P < 0.05) for patients who underwent AI than for controls. AI was of no benefit to patients with Stage II NSCLC, potentially useful to patients with Stage IIIa NSCLC (P = 0.06), and significantly advantageous to patients with Stage IIIb (T4) NSCLC (P < 0.01). For patients with Stage III NSCLC, local relapse (but not distant relapse) was significantly reduced following AI (P < 0.05). CONCLUSIONS: AI should be considered when designing future adjuvant therapy protocols for the treatment of NSCLC:

Immunotherapy with the use of tumor-infiltrating lymphocytes and interleukin-2 as adjuvant treatment in stage III non-small-cell lung cancer. A pilot study.

This study assesses the feasibility and toxicity of adoptive immunotherapy with tumor infiltrating lymphocytes and recombinant interleukin-2 in 29 patients who underwent resection for stage III non-small-cell lung cancer. In five patients cultures yielded no growth of tumor infiltrating lymphocytes. In the remaining 24 patients (stage IIIa, 14 cases; stage IIIb, 10 cases) tumor infiltrating lymphocytes were in vitro expanded from surgically obtained tissue samples, including samples from both the tumor and surrounding lung. A number of tumor infiltrating lymphocytes, ranging from 4 to 70 billion cells, were reinfused intravenously 4 to 6 weeks after operation. Interleukin-2 was administered subcutaneously at escalating does for 2 weeks and then at reduced doses for 2 to 3 months. Median survival was 14 months, and the 2-year survival was 40%. Three patients remain alive and disease-free at more than 2 years after operation. Two of these patients did not have complete resection at thoracotomy. Multivariate analysis showed no correlation between the factor of incomplete resection and survival. Intrathoracic recurrence without concomitant distant failure was documented in two patients only and none of the patients with incomplete resection (12 cases) had relapse within the thorax. The present experience demonstrates that adoptive immunotherapy may be applied with safety in patients operated on for stage III non-small-cell lung cancer and suggests that it can be useful, notably in patients with locally advanced disease.

Benign cystic teratoma of the mediastinum presenting as recurrent pneumonia and simulating malignancy.

We describe a case in whom recurrent pneumonia was the presenting manifestation of a benign cystic teratoma of the mediastinum. Although the symptoms had developed over a 15-year period, the mass was not identified on the chest roentgenograrns up to the age of 22 years. CT demonstrated the extent of the mass, but failed in clarifying the cystic nature of the tumor and in providing diagnosis. The lesion could be safely approached through an antero-lateral thoracotomy, saving major chest wall muscles. However, surgical removal of the mass was difficult because of firm adherence to surrounding structures.

[Trials of the diagnostic potentials of TPA in tumorous and nontumorous lung pathologies in 303 cases]. / Sperimentazioni sulla potenzialità diagnostica del TPA nelle patologie tumorali e non del polmone in 303 casi.

Serum tissue polypeptide antigen (TPA) has been determined in 271 patients with pleural or pulmonary neoplastic diseases (131) or with benign lung diseases (140). Using a cut-off of 95 U/L, TPA has a sensitivity and specificity of 65%. Therefore, TPA serum determination can suggest a diagnosis of malignancy, but its evaluation, as a single test, is not useful to differentiate between malignant or benign disease. TPA can be useful as an ancillary test in the follow-up of lung cancer therapy.

Bacampicillin and the immune response.

To evaluate the possible influence of a bacampicillin on the immune response, 16 subjects, out of a group of 60 patients with bacterial respiratory tract infections, had various tests of immune function determined, before and after treatment. The peripheral mononuclear blastogenic index (ratio between PHA-induced and spontaneous proliferation), PHA-induced interferon-gamma production, percentages of T and B lymphocytes, serum immunoglobulins (IgG, IgM, IgA) levels, failed to show any significative differences before and after the treatment with bacampicillin. The PHA-induced interleukin-2 production increased after treatment but just failed to reach statistical significance (0.1 less than P less than 0.05; t = 1.9). The clinical condition of 56 of the sixty (93.3%) treated patients improved and neither side-effects nor alterations of liver or kidney function were observed. This study has shown no inhibitory effect of bacampicillin on the immune response while confirming its clinical efficacy.

Protective effect of Duovent versus salbutamol in long-term treatment.

The effect of the combination fenoterol-ipratropium bromide (Duovent) as a bronchodilator drug versus salbutamol and placebo was investigated in 20 patients with chronic obstructive lung disease in a random cross-over trial. Our study was performed not only to evaluate the bronchodilator response, but especially to quantify the possibly more prolonged action of Duovent versus salbutamol, based on registration of prevention of asthma attacks, time effects and protective activity, management and tolerance. Each patient received therapy for 3 weeks; in each week only one of the preparations: salbutamol, Duovent or placebo was used. Respiratory function tests were determined every week on the 3rd, 5th and 7th days at the same time exactly at 30 and 60 min after drug inhalation. Additionally we registered, for each patient, daily symptomatology (e.g., asthma attacks, cough, additional daily puff use, adverse reactions) by using a personal clinical diary. The results and analysis of the pulmonary tests (especially FEV1 and peak expiratory flow) confirmed the bronchodilator effect of both drugs, higher for Duovent but not sufficient to reach statistical significance. Clinical condition, regarding number, severity of asthma crises and additional puff use, showed a significant statistical variation for each symptom either as regards advantage of Duovent and salbutamol versus placebo, or advantage of Duovent versus salbutamol. Therefore, the results of this trial reveal an excellent bronchodilator effect of both drugs and confirm a higher clinical efficacy of Duovent if used in long-term treatment, with good tolerability.