Non-invasive measurement of the mean alveolar O(2) tension from the oxygen uptake versus tidal volume curve.

AIMS: The classical equations for measuring the mean and the ideal alveolar O(2) tension are based on assumptions, which are shown to be invalid. So we thought to develop a new, non-invasive method for measuring the mean alveolar P,O(2) within the volume domain (PA,O(2(Bohr))). This method is based on the oxygen uptake vs. tidal volume curve (VO(2) vs. VT) obtained during tidal breathing of room air and/or air enriched with oxygen. METHODS: PA,O(2(Bohr)) and the ideal alveolar PO(2) (PA,O(2(ideal))) were simultaneously measured in 10 healthy subjects and 34 patients suffering from chronic obstructive pulmonary disease (COPD) breathing tidally room air at rest. Additionally, 10 subjects (three healthy subjects and seven COPD patients) were studied while breathing initially room air and subsequently air enriched with oxygen. RESULTS: According to the results, PA,O(2(Bohr)) considerably differed from PA,O(2(ideal)) (P = 0.004). The cause of the difference, at the individual's R, is: (1) the difference between the arterial and Bohr's alveolar CO(2) tension, mainly in COPD patients, and (2) the inequality between Bohr's alveolar part of the tidal volume for CO(2) and O(2). Furthermore, end-tidal gas tension (PET,CO(2) and PET,O(2)) differed from Pa,CO(2) and PA,O(2(Bohr)) respectively. CONCLUSION: The deviation of PA,O(2(Bohr)) from PA,O(2(ideal)) has a definite impact on Bohr's dead space ratio for O(2) and CO(2), and on the alveolar-arterial O(2) difference. The difference (PA,O(2(Bohr)) - PA,O(2(ideal))) is not related to the pathology of the disease. So, gas exchange within the lungs should be assessed at the subject's R from PA,O(2(Bohr)) and PA,CO(2(Bohr)) but not from PA,O(2(ideal)) nor Pa,CO(2).

Unevenness of ventilation assessed by the expired CO(2) gas volume versus V(T) curve in asthmatic patients.

Recently, we have shown that the expired CO2 gas volume versus tidal volume (VCO2-VT) curve is a useful tool for assessing unevenness of ventilation because it allows the separation of tidal volume into three functional compartments: (a) the CO2-free expired air (V0), (b) the transitional volume (Vtr), (c) the alveolar volume (VA) and the measurement of alveolar FCO2 during resting breathing in normal subjects and patients with COPD. In this paper, we have investigated whether changes pertaining to unevenness of ventilation taking place immediately after the administration of methacholine can be assessed using the VCO2-VT curve in asthmatic patients. The VCO2-VT curve was obtained during tidal breathing from 16 stable asthmatic patients who underwent a methacholine challenge test. It has been found that the Vtr, and hence Bohr's dead space (VD,Bohr = V0 + Vtr), over tidal volume ratios were significantly increased immediately after the methacholine administration, whilst the V0 over tidal volume ratio was not affected. The change of the above ratios was not related to the percentage decrease of FEV1.0 following methacholine administration.

Tidal expiratory flow limitation, dyspnoea and exercise capacity in patients with bilateral bronchiectasis.

In this study the authors investigated whether expiratory flow limitation (FL) is present during tidal breathing in patients with bilateral bronchiectasis (BB) and whether it is related to the severity of chronic dyspnoea (Medical Research Council (MRC) dyspnoea scale), exercise capacity (maximal mechanical power output (WRmax)) and severity of the disease, as assessed by high-resolution computed tomography (HRCT) scoring. Lung function, MRC dyspnoea, HRCT score, WRmax and FL were assessed in 23 stable caucasian patients (six males) aged 56 +/- 17 yrs. FL was assessed at rest both in seated and supine positions. To detect FL, the negative expiratory pressure (NEP) technique was used. The degree of FL was rated using a five-point FL score. WRmax was measured using a cyclo-ergometer. According to the NEP technique, five patients were FL during resting breathing when supine but not seated, four were FL both seated and supine, and 14 were NFL both seated and supine. Furthermore, it was shown that: 1) in stable BB patients FL during resting breathing is common, especially in the supine position; 2) the degree of MRC dyspnoea is closely related to the five-point FL score; 3) WRmax (% pred) is more closely correlated with the MRC dyspnoea score than with the five-point FL score; and 4) HRCT score is closely related to forced expiratory volume in one second % pred but not five-point FL score. In conclusion, flow limitation is common at rest in sitting and supine positions in patients with bilateral bronchiectasis. Flow limitation and reduced exercise capacity are both associated with more severe dyspnoea. Finally, high-resolution computed tomography scoring correlates best with forced expiratory volume in one second.

Evidence for left ventricular dysfunction in patients with obstructive sleep apnoea syndrome.

There is limited information on the development of left ventricular (LV) dysfunction in patients with obstructive sleep apnoea (OSA) in the absence of lung and cardiac comorbidity. This study aimed to investigate whether OSA patients without heart morbidity develop LV dysfunction, and to assess the effect of continuous positive airway pressure (CPAP) on LV function. Twenty-nine OSA patients and 12 control subjects were studied using technetium-99m ventriculography to estimate LV ejection fraction (LVEF), LV peak emptying rate (LVPER), time to peak emptying rate (TPER), peak filling rate (LVPFR) and time to peak filling rate (TPFR) before and after 6 months of treatment with CPAP. A significantly lower LVEF was found in OSA patients, compared to control subjects, (53+/-7 versus 61+/-6%) along with a reduced LVPER (2.82+/-0.58 versus 3.82+/-0.77 end-diastolic volumes x s(-1)). Furthermore, OSA patients had significantly lower LVPFR (2.67+/-0.71 versus 3.93+/-0.58 end-diastolic volumes x s(-1)) and delayed TPFR (0.19+/-0.04 versus 0.15+/-0.03 s) in comparison with the control group. Six-months of CPAP treatment was effective in significantly improving LVEF, LVPER, LVPFR and TPFR. In conclusion, obstructive sleep apnoea patients without any cardiovascular disease seem to develop left ventricular systolic and diastolic dysfunction, which may be reversed, either partially or completely, after 6 months of continuous positive airway pressure treatment.

Noninvasive measurement of mean alveolar carbon dioxide tension and Bohr's dead space during tidal breathing.

The lack of methodology for measuring the alveolar carbon dioxide tension (PA,CO2) has forced investigators to make several assumptions, such as that PA,CO2 is equal to end-tidal (PET,CO2) and arterial CO2 tension (Pa,CO2). The present study measured the mean PA,CO2 and Bohr's dead space ratio (Bohr's dead space/tidal volume (VD,Bohr/VT)) during tidal breathing. The method used is a new, simple and noninvasive technique, based on the analysis of the expired CO2 volume per breath (VCO2) versus the exhaled VT. This curve was analysed in 21 normal, healthy subjects and 35 chronic obstructive pulmonary disease (COPD) patients breathing tidally through a mouthpiece apparatus in the sitting position. It is shown that: 1) PA,CO2 is similar to Pa,CO2 in normal subjects, whilst it is significantly lower than Pa,CO2 in COPD patients; 2) PA,CO2 is significantly higher than PET,CO2 in all subjects, especially in COPD patients; 3) VD,Bohr/VT is increased in COPD patients as compared to normal subjects; and 4) VD,Bohr/VT is lower than the "physiological" dead space ratio (VD,phys/VT) in COPD patients. It is concluded that the expired carbon dioxide versus tidal volume curve is a useful tool for research and clinical work, because it permits the noninvasive and accurate measurement of Bohr's dead space and mean alveolar carbon dioxide tension accurately during spontaneous breathing.

A multicenter randomized clinical trial comparing paclitaxel-cisplatin-etoposide versus cisplatin-etoposide as first-line treatment in patients with small-cell lung cancer.

BACKGROUND: Previous phase I-II studies have shown that the combination of paclitaxel-cisplatin-etoposide (TEP) is very active and well tolerated in patients with small-cell lung cancer (SCLC). In order to compare the TEP combination to cisplatin etoposide (EP) regimen as front-line treatment in patients with SCLC, we conducted a randomised multicenter study. PATIENTS AND METHODS: One hundred thirty-three chemotherapy-naïve patients with histologically proven limited or extensive stage SCLC were randomised to receive either paclitaxel 175 mg/m2 i.v. three-hour infusion on day 1 and cisplatin 80 mg/m2 i.v. on day 2 and etoposide 80 mg/m2 i.v. on days 2-4 with G-CSF support (5 mcg/kg s.c. days 5-15) or cisplatin 80 mg/m2 i.v. on day 1 and etoposide 120 mg/m2 i.v. on days 1-3 in cycles every twenty-eight days. RESULTS: Due to excessive toxicity and mortality observed in the TEP arm, an early interim analysis was performed and the study was closed. Sixty-two patients received two hundred sixty-one cycles of TEP and seventy-one patients three hundred twenty-three cycles of EP The two patient groups were well balanced for age, sex, performance status, stage of disease and the presence of abnormal LDH at diagnosis. In an intention-to-treat overall analysis both regimens were equally active with a complete and partial response rate of 50% (95% confidence interval (CI): 37.5%-62.4%) for TEP and 48% (95%) CI: 36.2%-59.5%) for EP (P = 0.8). The median time to disease progression was 11 months for TEP and 9 months for EP (P = 0.02). The duration of response, one-year survival and overall survival were similar in the two arms. Similarly, in an intention-to-treat subgroup analysis of patients with limited or extensive stage disease, there was no difference in the activity between the two regimens except of a longer median time to disease progression in the extensive stage in favour of the TEP regimen, eight versus six months (P = 0.04). However, there were eight toxic deaths in the TEP arm versus none in the EP arm (P = 0.001). Moreover, the TEP regimen was associated with more severe toxicity than the EP regimen in terms of grade 4 neutropenia (P = 0.04), grade 3-4 thrombocytopenia (P = 0.02), febrile neutropenia (P = 0.08), grade 3-4 diarrhea (P = 0.01), grade 3-4 asthenia (P = 0.05) and grade 3 neurotoxicity (P = 0.06). CONCLUSIONS: In this early terminated study, the TEP regimen was significantly more toxic than the EP regimen. The TEP regimen is associated with significant toxicity and mortality, and should not be used outside of a protocol setting. For future investigations, dose and schedule modifications are necessary to reduce toxicity.

Combined expression of p53, Bcl-2, and p21WAF-1 proteins in lung cancer and premalignant lesions: association with clinical characteristics.

We examined p53, p21WAF-1, and Bcl-2 protein expression in malignant and nonmalignant bronchial specimens obtained during bronchoscopy from 60 lung cancer patients. Twenty-six (43.3%), 36 (60%), and 20 (33.3%) of the tumors were p53, p21WAF-1, and Bcl-2 positive, respectively. High-level p53 and Bcl-2 expression characterized advanced preneoplastic lesions, while hyperplasias, squamous metaplasias, and mild dysplasias exhibited low levels of expression. There was no difference between early and advanced preneoplastic lesions in the level of p21WAF-1, expression. A history of heavy smoking was associated with p21WAF-1, expression in preneoplastic lesions (p = 0.022) and tumors (p = 0.032). p53(-)/p21WAF-1(++)/bcl-2(-) was the only significant independent predictor of lower clinical stage (OR: 0.88, p = 0.038). In univariate analysis, survival of NSCLC patients was affected by disease stage (p <0.001) and tumor histology (p = 0.018). While single-protein expression was not associated with prognosis, the combined immunophenotype p53(-)/p21WAF-1(++)/bcl-2(-) predicted longer survival (p = 0.03). In multivariate analysis, only the TNM stage was found to be a prognostic factor for NSCLC. We conclude that p53 and Bcl-2 alterations may happen early in bronchial carcinogenesis and that absence of these alterations in combination with p21WAF-1, overexpression may be associated with a less aggressive tumor behavior.

Daytime pulmonary hypertension in patients with obstructive sleep apnea: the effect of continuous positive airway pressure on pulmonary hemodynamics.

BACKGROUND: Limited information exists regarding the development of pulmonary hypertension in patients with obstructive sleep apnea (OSA) in the absence of lung and heart comorbidity. OBJECTIVES: The aims of this study were to investigate whether OSA patients without any other cardiac or lung disease develop pulmonary hypertension, and to assess the effect of continuous positive airway pressure (CPAP) treatment on pulmonary artery pressure (P(PA)). METHODS: Twenty-nine patients aged 51 +/- 10 years with OSA and 12 control subjects were studied with pulsed-wave Doppler echocardiography for estimation of P(PA) before and after 6-month effective treatment with CPAP. RESULTS: A significantly higher mean P(PA) was found in OSA patients as compared to control subjects (17.2 +/- 5.2 vs. 12.1 +/- 1.9 mm Hg, p < 0.001). Six out of the 29 OSA patients had mild pulmonary hypertension (P(PA) > or = 20 mm Hg). Significant differences were observed between pulmonary hypertensive and normotensive OSA patients with respect to age (62 +/- 4 vs. 48 +/- 15 years, respectively, p < 0.05), body mass index (41 +/- 7 vs. 32 +/- 4 kg/m(2), p < 0.02) and daytime P(a)O(2) (81 +/- 9 vs. 92 +/- 9 mm Hg, p < 0.05). CPAP treatment was effective in reducing mean P(PA) in both groups of pulmonary hypertensive and normotensive OSA patients (decreases in P(PA) from 25.6 +/- 4.0 to 19.5 +/- 1.5 mm Hg, p < 0.001; from 14.9 +/- 2.2 to 11.5 +/- 2.0 mm Hg, respectively, p < 0.001). CONCLUSIONS: A proportion (20.7%) of OSA patients without any other lung or heart disease and characterized by older age, greater obesity and lower daytime oxygenation develop mild pulmonary hypertension which has been partially or completely reversed after 6-month CPAP treatment. In conclusion, OSA alone constitutes an independent risk factor for the development of pulmonary hypertension.

Left ventricular function in patients with obstructive sleep apnoea syndrome before and after treatment with nasal continuous positive airway pressure.

BACKGROUND: Previous studies have yielded disparate results regarding the effect of obstructive sleep apnoea (OSA) syndrome on left ventricular (LV) function. OBJECTIVES: In order to clarify this, we performed a prospective study investigating OSA patients with no history of systemic hypertension, coronary artery disease, myocardial, pericardial or valvular problems, asthma or chronic obstructive pulmonary disease before and after treatment with nasal continuous positive airway pressure (nCPAP). METHODS: Fifteen patients (3 women, 12 men) with an apnoea/hypopnoea index >15 (mean +/- SD = 52 +/- 21) were studied with complete polysomnography, ambulatory blood pressure monitoring, M-mode two-dimensional echocardiography and pulsed Doppler echocardiography in two phases, i.e. before and after 12-14 weeks of nCPAP therapy. We measured systolic and diastolic blood pressure (BP) separately in the daytime and night-time, isovolumic relaxation time (IVRT), the ratio of peak early filling velocity (E) to peak late velocity (A) diastolic transmitral flow (E/A), posterior wall thickness (PWT) and septal thickness (IVST). The shortening fraction (SF) was also calculated. Eleven overweight non-apnoeic normal subjects matched for age were used as the control group. RESULTS: Our results showed that the patient group exhibited, before treatment, LV diastolic, but not systolic, dysfunction compared with the normal group (IVRT = 94.3 +/- 11.6 ms, p < 0.05; E/A = 0.94 +/- 0.26, p < 0.02; SF = 39.9 +/- 4.1%, not significant (NS); IVST = 9.9 +/- 1.2 mm, NS; PWT = 8.3 +/- 1.2 mm, NS). Moreover, the patient group developed diastolic hypertension both in the daytime and night-time (BP/diastolic/daytime = 93.3 +/- 9.2 mm Hg, BP/diastolic/night-time = 90.3 +/- 10.7 mm Hg). After 12-14 weeks of nCPAP treatment (no change in body mass index), significant improvement in LV diastolic function and a drop in blood pressure were noticed (IVRT = 85.6 +/- 8.8 ms, p < 0.05; E/A = 1.07 +/- 0.3, p < 0.05; BP/diastolic/daytime = 86.3 +/- 5.5 mm Hg, p < 0.02; BP/diastolic/night-time = 83.9 +/- 8. 6 mm Hg, p < 0.05) in our patient group. CONCLUSIONS: We conclude that repetitive apnoeas/hypopnoeas are very important factors in the development of both LV diastolic dysfunction and diastolic systemic hypertension in patients with OSA syndrome. Treatment with nCPAP leads to significant improvement in both ventricular function and systemic hypertension.

Eosinophils are a feature of upper and lower airway pathology in non-atopic asthma, irrespective of the presence of rhinitis.

BACKGROUND: Asthma and rhinitis often co-exist and there are data to suggest that they may be two ends of the same disease spectrum. Immunohistochemical studies have shown that eosinophilia in the airways is a feature of rhinitic patients without asthma. OBJECTIVE: The aim of our study was to examine whether cellular infiltration exists in the nasal mucosa of asthmatics even in the absence of symptoms and signs of rhinitis. METHODS: Nasal mucosa biopsies were taken from 27 non-atopic subjects and comprised nine asthmatic rhinitic patients (AR), eight asthmatic non-rhinitic patients (ANR) and 10 healthy control subjects (N). Bronchial mucosa biopsies were also taken simultaneously from some of the patients (n = 10) to determine whether there was an association between cellular infiltration in the nose and the lungs. The alkaline phosphatase-anti-alkaline phosphatase (APAAP) method was used on 6 microm thick cryostat sections using monoclonal antibodies against T cells (CD4, CD8), eosinophils (EG2) and mast cells (mast cell tryptase). Slides were counted blind and results expressed as cells per field. RESULTS: The results showed that eosinophil counts were higher in both asthma groups compared with control nasal biopsies (median values AR 8.3, ANR 9.2, N 2.1 cells per field, P < 0.01). Furthermore, there was a significant correlation between eosinophil cell counts in the nose and the airways (r = 0.851 P < 0.001). No differences in eosinophil numbers were detected between the two groups of asthmatics. Also, no differences were noted for any other cell type (i.e. CD4, CD8, tryptase) among the three study groups. CONCLUSIONS: These results show that eosinophil infiltration was present in the nasal mucosa of asthmatic patients even in the absence of rhinitis, and add further support to the hypothesis that asthma and rhinitis are clinical expressions of the same disease entity.

Expression of mdm-2 protein in neoplastic, preneoplastic, and normal bronchial mucosa specimens: comparative study with p53 expression.

Loss of function of the p53 tumor supressor gene is involved in nearly all human cancer. Recently a cellular oncogene product, mdm2, has been shown to bind to p53 and eliminate its ability to function as a transcription factor. mdm2 and p53 immunohistochemical protein expression was studied in tumor tissues, preneoplastic lesions, and normal bronchial mucosa. The specimens were obtained during diagnostic bronchoscopy from 53 patients with lung cancer. In the tumor specimens, p53 nuclear staining was detected in 26 (49%) cases, mdm2 in 11 (20.7%), and simultaneous expression of both proteins in 6 (11.3%) cases. Thirty-five sections with preneoplastic lesions were found in 21 patients. p53 nuclear staining was found in 11 of 35 and mdm2 in 6 of 35 sections. In normal cells, mdm2 positive staining was found in 18 and p53 in 12 specimens. Simultaneous p53 and mdm2 expression was found in 4 specimens. Our results indicate that p53 expression is more frequent than mdm2 expression in lung cancer tissues. Alterations in these proteins are early events and may represent alternative pathways in carcinogenesis.

Optimal duration of chemotherapy in small cell lung cancer: a randomized study of 4 versus 6 cycles of cisplatin-etoposide.

With the purpose of investigating whether the 6-course standard dose treatment of etoposide-platinum (EP) in small cell lung cancer could be reduced to 4 courses without compromising patient's survival, 70 patients were randomized to receive either 4 or 6 cycles of etoposide 120 mg/m2 i.v. days 1-3 and cisplatin 80 mg/m2 day 1. With the intention of comparing these two durations as primary treatment policies, patients were randomized on admission and not after the fourth course. From the 69 evaluable patients 34 received EPx4 cycles and 35 EPx6 cycles. Objective response for EPx4 was achieved by 21 patients (62%, 95% CI 44%-78%) compared to 24 patients (69%, 95% CI 51%-83%) of the EPx6 group. Median times to progression were 6 mo (4-19) and 7 mo (4-40) respectively (P=0.06) in the two groups. Median survivals were 8.5 mo (4-28.5) and 9.5 mo (4-51) (p=0.04) respectively. No differences in the survival of limited-disease patients were shown with 10.5 mo (6-28.5) and 12 mo (8-51) respectively, in the two groups. Patients with extensive disease had a trend favoring prolonged chemotherapy with a median survival of 9 mo (5-16) versus 6.5 mo (4-16.5) for those in the EPx4 group (p=0.09). Toxicity was not significantly more severe in the EPx6 group. In conclusion, patients achieving complete response within 4 cycles may not need continued chemotherapy, but patients with extensive disease may benefit from 2 more cycles.

Immunohistochemical detection of p53 protein in neoplastic, preneoplastic and normal bronchial mucosa specimens obtained during diagnostic bronchoscopy.

The expression of p53 protein was evaluated immunochemically in cancer tissue, preneoplastic lesions and normal bronchial mucosa obtained during diagnostic bronchoscopy from 53 patients with lung cancer and 12 patients with benign lung diseases. In lung cancer patients, positive p53 staining was detected in 26/53 (49%) of the tumour specimens. In preneoplastic lesions p53 positive staining was found in 8 of 24 (33.3%) squamous metaplasia, 1 of 4 hyperplasia and 1 of 3 dysplasia lesions. In the same group of patients, 12 cases were found with positive p53 cells in normal bronchial mucosa. In patients with benign diseases, positive p53 staining was found in 1 of 4 cases with squamous metaplasia and in one normal mucosa. Our results provide evidence that somatic genetic alterations may occur in early stages of lung tumorigenesis, raising the possibility that molecular analyses is useful in the early diagnosis of precancerous lesions of the bronchial mucosa, and results indicate that p53 expression can be studied in small tissue specimens obtained during bronchoscopy.

Adenosine deaminase activity and lysozyme levels in bronchoalveolar lavage fluid in patients with pulmonary tuberculosis.

SETTING: The estimations of adenosine deaminase (ADA) activity and lysozyme (LYS) levels in pleural fluid have been proved useful tools in the diagnosis of tuberculous pleural effusions. Little is known about their usefulness when estimated in bronchoalveolar lavage fluid (BALF). OBJECTIVE: To evaluate whether both ADA activity and LYS levels in BALF could be employed in the diagnosis of pulmonary tuberculosis, and especially in active but acid fast bacilli (AFB) smear negative cases. DESIGN: ADA activity and LYS levels were determined in BALF and serum obtained on the same day in 28 patients with tuberculosis, 21 with interstitial lung diseases, 14 with lung cancer and 13 with infectious diseases. RESULTS: Patients with pulmonary tuberculosis had significantly higher ADA activity in BALF than patients with non-tuberculous lung diseases (P < 0.001). High BALF ADA activity in pulmonary tuberculosis patients suggests increased local production. In contrast, in this group of patients BALF LYS levels were not significantly higher than in the other groups of patients, but were in the group with interstitial lung diseases. CONCLUSION: BALF ADA activity seems to be a useful tool in the differentiation of tuberculosis from other lung diseases. Its estimation can be restricted to the detection of cases with AFB negative smears.

Phrenic nerve dysfunction after cardiac operations: electrophysiologic evaluation of risk factors.

BACKGROUND AND STUDY OBJECTIVE: Phrenic nerve injury may occur after cardiac surgery; however, its cause has not been extensively investigated with electrophysiology. The purpose of this study was to determine by electrophysiologic means the importance of various possible risk factors in the development of phrenic nerve dysfunction after cardiac surgical operations. DESIGN: A prospective study was conducted. SETTING: A tertiary teaching hospital provided the background for the study. PATIENTS: Sixty-three cardiac surgery patients on whom surgical operations were performed by the same surgical team constituted the study group. Mean (+/-SD) age and ejection fraction were 63+/-5 years and 50+/-10%, respectively. INTERVENTIONS: Measurement of phrenic nerve conduction latency time after transcutaneous stimulation preoperatively and at 24 h and 7 and 30 days postoperatively. RESULTS: Thirteen patients had abnormal phrenic nerve function postsurgery, 12 on the left side and one bilaterally. Logistic regression analysis revealed that among the potential risk factors investigated, use of ice slush for myocardial preservation was the only independent risk factor related to phrenic nerve dysfunction (p=0.01), carrying an 8-fold higher incidence for this complication. In contrast, age, ejection fraction of the left ventricle, operative/bypass/aortic cross-clamp time, left internal mammary artery use, and diabetes mellitus were not found to be associated with phrenic neuropathy. The postoperative outcome of patients who received ice slush compared with that of those who had cold saline solution did not differ in terms of early morbidity and mortality. CONCLUSION: Among the risk factors investigated, only the use of ice slush was significantly associated with postoperative phrenic nerve dysfunction. Therefore, ice should be avoided in cardiac surgery, since it does not seem to provide additional myocardial protection.

Dependence of forced vital capacity manoeuvre on time course of preceding inspiration in patients with restrictive lung disease.

In normal subjects and patients with airway obstruction, flows during a forced vital capacity (FVC) manoeuvre are higher after a fast inspiration without an end-inspiratory pause (manoeuvre 1) as compared to a slow inspiration with an end-expiratory pause of approximately 5 s (manoeuvre 2). In this study, we investigated the influence of these manoeuvres on maximal expiratory volume-time and flow-volume curves in patients with restrictive lung disease. Eleven patients with restrictive lung disease were studied. Their average (+/-SD) lung function test results were: FVC=55+/-12% predicted value, forced expiratory volume in one second (FEV1) 52+/-20% pred, FEV1/FVC 85+/-6%, total lung capacity 55+/-8% pred, and carbon monoxide transfer factor 47+/-18% pred. The patients performed the two FVC manoeuvres in random order. We compared the ensuing spirograms and maximal expiratory flow-volume curves from which peak expiratory flow, FEV1, FEV1/FVC, maximal mid-expiratory flow, and maximal flows were computed. All spirometric indices were significantly higher with manoeuvre 1 than 2. Maximal expiratory flows at the same lung volume were also significantly higher with manoeuvre 1 than 2, in all patients. Routine spirometric indices, obtained during a forced vital capacity manoeuvre depend on the time course of the preceding inspiration in patients with restrictive lung disease. Therefore, the forced vital capacity manoeuvre should be standardized if used in clinical, epidemiological and research studies.

Clinical and microbiological evaluation of pefloxacin in lower respiratory tract infections.

Patients with Gram-negative lower respiratory tract infections (acute exacerbation of chronic bronchitis (n = 23), pneumonia (n = 4), and bronchiectasis (n = 5) were treated with pefloxacin, 400 mg twice daily, given either intravenously or orally. Symptoms, signs and sputum volume and colour were monitored daily. Chest X-rays, sputum culture and Gram-stain examinations were carried out on days 1 and 5, and immediately after the end of the treatment. There was a clinical improvement, as indicated by the incidence of cough, dyspnoea and rales, and by sputum volume and colour in 31 patients (97%). Microbiological improvement, as indicated by the complete elimination of sputum pathogens and pus cells, was achieved in 28 of the patients (88%). In one patient, an adverse effect, renal failure, occurred. These results suggest that pefloxacin is both clinically and microbiologically effective for the treatment of Gram-negative lower respiratory tract infections.

Evaluation of CYFRA 21-1 in malignant and benign pleural effusions.

CYFRA 21-1 was evaluated in 115 untreated patients with malignant pleural effusions (96 with primary lung cancer and 19 with non lung cancer) and 99 patients with benign pleural effusions. The levels of pleural fluid CYFRA 21-1 were from 1 to 385 times higher than those in serum, in all the examined patients. The mean level of pleural fluid CYFRA 21-1 was significantly higher in cancer patients than in patients with benign pleural effusion (96.1 ng/ml vs 26.2 ng/ml, p < 0.001). At 92% specificity for benign pleural effusion (> 50 ng/ml) the overall sensitivity of CYFRA 21-1 in malignant pleural effusions was 69.6%. When the histology was considered the highest sensitivity was found in squamous cell lung cancer (90%), followed by adenocarcinoma cell lung cancer (74%), non lung cancer (54%) and small cell lung cancer (25%). These results indicate that CYFRA 21-1 could be a useful pleural fluid marker in discriminating benign from malignant pleural effusion and particularly from those due to squamous and adenocarcinoma cell lung cancer.