[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.

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.

Portable measurement of maximum mouth pressures.

We have compared a small portable mouth pressure meter (MPM) to our laboratory standard (LS) pressure recording equipment in order to evaluate this new device. The mouth pressure meter measures and displays as a digital read-out peak pressure for inspiratory and expiratory efforts. It samples the signal at 16 Hz, and an integral microprocessor is programmed to determine and display the maximum pressure averaged over one second both during inspiratory and expiratory manoeuvres (PImax and PEmax, respectively). A fine bore catheter connecting the mouthpiece of the mouth pressure meter to a Validyne pressure transducer enabled simultaneous measurement of pressure, which was analysed by LabVIEW, running on a Macintosh Quadra 700 computer. We studied 13 normal subjects and 11 patients with respiratory disease. Each subject performed inspiratory and five expiratory efforts. The values displayed from the mouth pressure meter were manually recorded. The mouth pressure meter reliably and accurately measured peak pressure and maximal pressure both for inspiratory and expiratory efforts in normals and patients. The mean +/- SD difference when compared with the Validyne method was 0.19 +/- 0.12 and -0.04 +/- 0.12 kPa, for PImax and PEmax, respectively. This portable device should be useful to measure mouth pressures, not only in the routine lung function laboratory but also at the bedside and in the clinic.

A comparison of different modes of noninvasive ventilatory support: effects on ventilation and inspiratory muscle effort.

The aims of noninvasive ventilation include the correction of hypoventilation and unloading of inspiratory muscles. Volume cycled flow generators, bi-level positive airway pressure and continuous positive airway pressure techniques have all been used with face and nasal masks. We have compared these modes of ventilatory support, administered by a nasal mask in stable, awake outpatients with chronic obstructive pulmonary disease or neuromusculo-skeletal disease in respect of their effects on ventilation, inspiratory muscle effort and oxygen saturation. There were no clinically significant differences between the volume cycled flow generator and bi-level positive airway pressure methods; compared to spontaneous ventilation, oxygen saturation increased and inspiratory muscle effort decreased. Tidal volume increased and respiratory rate reduced, the largest changes occurring with bi-level positive airway pressure. Only the volume cycled flow generator increased minute ventilation significantly. Ventilation and inspiratory muscle effort were unaffected by continuous positive airway pressure but oxygen saturation was lower than during spontaneous ventilation. In awake, stable outpatients acclimatised to nasal ventilation there were no clinically significant differences between volume cycled flow generator and bi-level positive airway pressure techniques, but continuous positive airway pressure was less effective.

Diaphragmatic dysfunction in neuralgic amyotrophy: an electrophysiologic evaluation of 16 patients presenting with dyspnea.

We report 16 adult men (age, 41 to 75 yr) with neuralgic amyotrophy (NA) who presented with dyspnea due to involvement of the diaphragm. All patients developed breathlessness after a prodrome of acute severe neck and shoulder pain. Bilateral diaphragm paralysis (BDP) was confirmed in 12 patients and unilateral diaphragm paralysis (UDP) in four by the absence of electrical and mechanical responses to percutaneous phrenic nerve stimulation. Global expiratory muscle strength was well preserved in all patients, but inspiratory muscle strength was reduced in proportion to the extent of diaphragmatic involvement. Lung function showed low lung volumes with preservation of carbon monoxide transfer coefficient in all patients. Two BDP patients were hypoxic (PaO2 = 67 and 54 mm Hg, respectively) on daytime arterial blood gas analysis; the latter patient with pre-existing chronic obstructive pulmonary disease and marked obesity also had borderline hypercapnia (PaO2 = 49 mm Hg). Overnight sleep studies in three BDP and two UDP patients showed frequent intermittent arterial oxygen desaturations apparently caused by obstructive sleep apneas, but there was no evidence of alveolar hypoventilation. Follow-up muscle studies in five BDP and four UDP patients between 2 and 4 yr after initial referral showed complete recovery of diaphragmatic function in only two UDP patients, one of whom relapsed a year later. We postulate that NA may be an important but underrecognized cause of diaphragmatic paralysis in otherwise normal patients. Diaphragmatic strength returns very slowly, if at all.

Comparison of cervical magnetic stimulation and bilateral percutaneous electrical stimulation of the phrenic nerves in normal subjects.

Cervical magnetic stimulation is a new technique for stimulating the phrenic nerves, and may offer an alternative to percutaneous electrical stimulation for assessing diaphragmatic strength in normal subjects and patients in whom electrical stimulation is technically difficult or poorly tolerated. We compared cervical magnetic stimulation with conventional supramaximal bilateral percutaneous electrical stimulation in nine normal subjects. We measured oesophageal pressure (Poes), gastric pressure (Pgas) and transdiaphragmatic pressure (Pdi). The maximal relaxation rate (MRR) was also measured. The mean magnetic twitch Pdi was 36.5 cmH2O (range 27-48 cmH2O), significantly larger than electrical twitch Pdi, mean 29.7 cmH2O (range 22-40 cmH2O). The difference in twitch Pdi was explained entirely by twitch Poes, and it is possible that the magnetic technique stimulates some of the nerves to the upper chest wall muscles as well as the phrenic nerves. We compared bilateral, rectified, integrated, diaphragm surface electromyographic (EMG) responses in three subjects and found results within 10% in each subject, indicating similar diaphragmatic activation. The within occasion coefficient of variation, i.e. same subject/same session, was 6.7% both for magnetic and electrical twitch Pdi. The between occasion coefficient of variation, i.e. same subject/different days, was 6.6% for magnetic stimulation and 8.8% for electrical. There was no difference between relaxation rates measured with either technique. We conclude that magnetic stimulation is a reproducible and acceptable technique for stimulating the phrenic nerves, and that it provides a potentially useful alternative to conventional electrical stimulation as a nonvolitional test of diaphragm strength.

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.

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:

Remifentanil reduces auditory and somatosensory evoked responses during isoflurane anaesthesia in a dose-dependent manner.

We studied 60 patients during stable isoflurane anaesthesia (0.4 MAC) after premedication with temazepam. Patients were allocated randomly to one of three dose regimens of remifentanil: 1 microgram kg-1 i.v. over 1 min and an infusion of 0.2 microgram kg-1 min-1 (low dose); 2.5 micrograms kg-1 and 0.5 microgram kg-1 min-1 (medium dose); and 5 micrograms kg-1 and 1 microgram kg-1 min-1 (high dose). The auditory (AER) and median nerve somatosensory (SER) responses were elicited throughout, and recorded before and after tracheal intubation, and surgical incision, together with systolic and diastolic arterial pressure and heart rate. Venous blood concentrations of remifentanil were measured at the above times. After administration of remifentanil, Pa and Nb amplitudes of the AER increased at the low dose, remained constant at the medium dose and decreased at the high dose. This dose-related effect was linear and significant (P = 0.012, P = 0.05). Pa amplitude correlated inversely with remifentanil blood concentrations before and after intubation and incision (P = 0.002, P < 0.001, P < 0.001 and P < 0.001). In the SER, P15-N20 amplitudes decreased after administration of remifentanil (P < 0.001), whereas P25-N35 and N35-P45 amplitudes increased at all dose concentrations (P < 0.001 and P < 0.001). After intubation, P15-N20 and N35-P45 amplitudes increased at the low dose, did not change at the medium dose and decreased at the high dose (P = 0.001, P = 0.027). After remifentanil, systolic and diastolic arterial pressure and heart rate decreased in a linearly dose-related manner (P = 0.033, P < 0.001, P < 0.001). At all doses the three variables increased after intubation (P = 0.001, P < 0.001, P < 0.01), and systolic and diastolic arterial pressure increased after incision (P = 0.027, P = 0.039).