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Biomedical subjects

Y Cormier

Publications and source records attributed to Y Cormier.

At least 19 recordsLinked to original sources
PubMed1992

Influence of continuous positive airway pressure on sleep apnea-related desaturation in sleep apnea patients.

To investigate the influence of nasal continuous positive airway pressure (CPAP) on apnea-related desaturation, we compared the sleep apnea-related desaturations obtained during a polysomnographic study before and during nasal CPAP in 15 sleep apnea patients. An individual desaturation curve was determined with a regression analysis by plotting the lowest SaO2 value reached during each apnea against its duration; these data were collected throughout the night. At baseline, we only considered the apneas with a preapneic SaO2 value greater than 90% and a minimal SaO2 value above or equal to 60%. For the CPAP study, the preapneic SaO2 value also had to be within 2% the baseline value for the apneas to be retained. Due to the restriction criteria imposed to characterize apnea-related SaO2 falls, residual apneas still had to be recorded with CPAP. These data were analyzed separately for obstructive apnea for non-rapid eye movement (REM) and REM sleep stages. A desaturation curve was obtained from 10 sec to a variable upper limit that corresponded to the longest apnea duration commonly reached during both baseline and CPAP for a given apnea-type and sleep stage. The individual apnea-related SaO2 fall was characterized by measuring a desaturation area corresponding to the area under the curve. It was expressed in % SaO2/sec of apnea. CPAP reduced the number of apneas per hour of sleep from 37.5 +/- 6.5 (mean +/- SEM) to 14.3 +/- 3.7 (p = 0.001), and improved the whole night SaO2 level as estimated by a cumulative SaO2 curve. The mean apnea duration was reduced from 22.9 +/- 1.5 sec at baseline to 16.8 +/- 0.5 sec during CPAP therapy (p = 0.005). The preapneic SaO2 value was 94.8 +/- 0.3% at baseline and 95.5 +/- 0.2% during CPAP (p = 0.5). The desaturation area decreased from 267 +/- 48% SaO2/sec at baseline to 152 +/- 41% SaO2/sec during CPAP (p less than 0.001). We conclude that CPAP improves the apnea-related desaturation independently of the shortening of apneas and of any difference in the preapneic SaO2 value.

Female↗
PubMed1992

Effects of enhancing slow-wave sleep by gamma-hydroxybutyrate on obstructive sleep apnea.

Sleep apneas are rarely observed during slow-wave sleep (SWS), which is poorly represented in patients with obstructive sleep apnea (OSA). Gamma-hydroxybutyrate (gamma OH), a natural metabolite of the brainstem, increases the percentage of total sleep time (TST) spent in SWS. We evaluated the effects of gamma OH on sleep and breathing disorders in eight patients with OSA (age, 45 +/- 2 yr; body mass index, 35.0 +/- 1.5 kg/m2; mean +/- SEM). Three conventional sleep studies were done within a week; the first and third were control studies, and the second was the gamma OH study (30 mg/kg at bedtime and 3 h later). Because the effects of the drug last only 3 h, we analyzed and compared the results of the first 6 h of sleep recording. The percentage of TST spent in SWS increased with gamma OH (30.7 +/- 3.9%) compared with that in the control studies (12.5 +/- 1.1 and 11.0 +/- 2.1%) at the expense of stages I and II. There was no difference between apnea index obtained during the control studies (26.3 +/- 5.3 and 25.4 +/- 6.2/h) and that obtained during the gamma OH study (29.6 +/- 4.9/h). Most apneic events occurred during Stages I and II, and REM, but this proportion was less during the gamma OH study (77.9 +/- 8.9%) than during the control studies (92.3 +/- 1.9 and 95.9 +/- 2.2%), apneas occurring even during SWS with gamma OH.(ABSTRACT TRUNCATED AT 250 WORDS)

Electroencephalography↗
PubMed1992

Murine hypersensitivity pneumonitis: a study of cellular infiltrates and cytokine production and its modulation by cyclosporin A.

The progression of hypersensitivity pneumonitis (HP) was evaluated in mice repeatedly challenged with the actinomycete Faeni rectivirgula (Micropolyspora faeni) (90 or 180 micrograms), at the cellular level and at the mediator level. Instillation of F. rectivirgula by the intranasal route determined a granulomatous inflammation in the lungs of animals correlated with a dramatic increase (5- to 6-fold) in cellularity in the bronchoalveolar space and an increase in the percentage of lymphocytes. Disease in mice was also correlated with high spontaneous release of the cytokines interleukin-1 (IL-1) (60 U/ml), interleukin-6 (IL-6) (72 U/ml), and tumor necrosis factor-alpha (TNF-alpha) (56 U/ml) in the bronchoalveolar lavage (BAL) fluid, as well as by an enhanced capacity for cytokine release by macrophages upon stimulation with F. rectivirgula. It was also found that the pulmonary inflammation was correlated with a 60 to 70% increase in total lung weight after 4 wk and a significant lung fibrosis as seen by a 2-fold increase in lung hydroxyproline levels. Treatment of challenged mice with cyclosporin A (CyA) led to an abrogation of the disease as seen by an abrogation of the increase in lung index, lack of IL-1 and TNF-alpha release in the BAL. CyA did not, however, completely prevent the alveolitis as seen by the cellular infiltrate (2- to 3-fold in BAL cell increase). It also did not prevent the T-lymphocyte recruitment associated with HP, although these cells did not proliferate in response to the F. rectivirgula antigen, in contrast to BAL cells from F. rectivirgula-challenged mice treated with excipient only.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1992

T cells in hypersensitivity pneumonitis: effects of in vivo depletion of T cells in a mouse model.

C57BL/6 mice were given intranasal instillation of optimal doses of the actinomycete Faeni rectivirgula 150 micrograms/mouse 3 days/wk), an important offending agent causing hypersensitivity pneumonitis. This instillation was associated with a very significant increase in the lung weight of the mice and also a large increase (10-fold) in the number of cells recovered from the bronchoalveolar lavage (BAL) of instilled mice. Also, this instillation was associated with a very significant fibrosis at 4 and 8 wk (2-fold increase in hydroxyproline levels in the lungs). We determined the effect of depleting certain T-cell subsets on the progression of this inflammatory disease. Elimination of the L3T4 subset did not significantly affect the increase in the lung index, the lung cellular influx, or its profile. Fibrosis was also unaffected by this depletion of L3T4+ cells. Similarly, depletion of Lyt2+ (CD8+) cells did not lead to significant changes in these disease parameters. Depletion of all T cells (Thyl+) was also ineffective at modifying the number of infiltrating cells and the lung index score. However, identification of cell types in BAL showed that mice depleted of Thyl+ cells had a cellular influx that was almost exclusively neutrophilic throughout the instillation period, whereas control mice developed only a transient neutrophilic response to F. rectivirgula instillation, which was replaced by a recruitment of mononuclear cells, mostly macrophages. Also, depletion of Thyl+ cells before and during F. rectivirgula challenge had no effect on tumor necrosis factor-alpha levels in the BAL of treated mice (63 +/- 13 U/ml in anti-Thy1. 2 antibodies treated versus 52 +/- 10 U/ml in the BAL of control mice given F. rectivirgula).(ABSTRACT TRUNCATED AT 250 WORDS)

Actinomycetales Infections↗
PubMed1992

Mechanisms of the effectiveness of continuous positive airway pressure in obstructive sleep apnea.

Nasal continuous positive airway pressure (NCPAP) is considered the most effective treatment of obstructive sleep apnea. Its beneficial effects are related to the normalization of breathing during sleep and to the prevention of nocturnal desaturations. NCPAP interacts with the pathophysiologic mechanisms of sleep apnea onset and with the consequences of these apneas. Upper airway patency is maintained with NCPAP by a pneumatic splinting effect while changes in lung volume and pre-apnea SaO2 level may be implicated in the improvement of apnea-related desaturations. An improvement in central chemosensitivity could account for the improvement in diurnal oxygenation observed with long term NCPAP therapy.

Airway Resistance↗
PubMed1991

Influence of lung volume on collateral resistance in normal man.

We measured the influence of changing the end-expiratory lung volume (EELV) on collateral resistance (Rcoll) in 6 normal volunteers (5 male, 1 female, aged 23-45 years). With subjects lying supine in an iron lung, a 5.3 mm fibroscope was introduced under local anesthesia and wedged into a sub-segmental bronchus of the right lower lobe. A truncated 5f Swan-Ganz catheter was tightly fitted into the suction port of the fibroscope. One lumen of the catheter served to deliver a constant flow (200 ml/min) of 5% CO2 in air. The pressure in the wedged segment (Ps) was measured by the other channel. Airway pressure (used as alveolar pressure (Palv)) was determined with a low bias flow catheter taped to the side of the bronchoscope, its tip positioned 20 cm from the end of the bronchoscope. Rcoll was obtained by the formula: Rcoll = (Ps-Palv)/flow. EELV was passively changed by applying a constant extrathoracic pressure in the iron lung at 5 cm H2O steps from 0 to +15 and from 0 to -20 cm H2O. The changes obtained in Rcoll (% baseline, mean +/- SEM) at each extrathoracic pressure (ETP) were: -5 cm H2O, 73 +/- 4%; -10, 56 +/- 7%; -15, 56 +/- 9%; -20, 35 +/- 10%; +5, 118 +/- 6%; +10, 129 +/- 7%; +15, 118 +/- 11%. Rcoll progressively decreased with increasing EELV (negative ETP) and increased slightly as EELV was reduced (positive ETP). The relationship between the log Rcoll and delta EELV was linear; the slope of this line was 9.8%.

Adult↗
PubMed1991

Production of H2O2 by alveolar macrophages in experimental allergic alveolitis.

Experimental extrinsic allergic alveolitis (EAA) was induced in guinea pigs with Saccharopolyspora rectivirgula. Bronchoalveolar lavages were performed before inducing EAA (day 1, BAL 1), on day 23 (BAL 2), and on day 48 (BAL 3). The number of cells/ml in lavage fluid was increased at BAL 2 (4.79 x 10(6) and BAL 3 (4.29 x 10(6)) compared with BAL 1 (0.56 x 10(6)). The number of major cell types increased simultaneously, neutrophil becoming the predominant cell type over alveolar macrophages (AM). The production of H2O2 by AM was measured at the different phases of EAA. Adherent AM were either non-stimulated or triggered with phorbol myristate acetate (PMA), zymosan. S. rectivirgula opsonized with normal guinea pig serum (SRNS), or S. rectivirgula opsonized with guinea pig anti-S, rectivirgula serum (SRAS). Stimulated AM produced larger quantities of H2O2 than unstimulated cells, PMA being the most potent stimulus. At day 1, AM stimulated with S. rectivirgula and zymosan produced similar quantities of H2O2. After the induction of the disease, AM stimulated with S. rectivirgula produced larger quantities of H2O2 than with zymosan. Production of H2O2 by AM stimulated with S. rectivirgula or PMA, respectively, stayed the same at day 1 and 23, but increased sharply for both stimuli at day 48. There was no difference between H2O2 production by AM triggered with SRNS or with SRAS.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic↗
PubMed1991

Cephalometric measurements in snorers, non-snorers, and patients with sleep apnoea.

Cephalometry is often used to assess patients with sleep apnoea but whether these measurements differ from those in non-apnoeic snorers and how they are influenced by age is not clear. Cephalometric radiographs of patients with sleep apnoea were compared with those of snorers without sleep apnoea and those of non-snorers. Fifty two snorers with suspected sleep apnoea had a conventional sleep study and were divided into two groups: those with an apnoea-hypopnoea index greater than 10/h (n = 40, sleep apnoea group) and those whose apnoea-hypopnoea index was 10/h or less (n = 12, snorer group). The cephalometric measurements in these patients were compared with those of 34 non-snoring control subjects. Controls were subdivided into two groups: control group 1 included 17 subjects similar in age to the sleep apnoea and snorer groups (mean (SD) age 50.0 (10.9), 50.7 (9.4), and 50.6 (9.7) years); control group 2 included 15 young men (25.4 (2.6) years). The distance from the mandibular plane to the hyoid bone (MP-H) and the length of the soft palate were greater in the patients with sleep apnoea (28.7 (7.8) and 43.6 (5.0) mm) than in the snorers (23.7 (4.2) and 40.3 (4.9 mm). The MP-H was similar in snorers and age matched control subjects, but was significantly greater in the older than in the younger control subjects (22.1 (6.1) vs 17.0 (6.8]. The soft palate was longer in subjects who snored (both sleep apnoea patients and snorers) than in control subjects. The MP-H distance significantly correlated with age for all subjects (snorers and controls) and for the control subjects alone. This study shows that non-apnoeic snorers have cephalometric abnormalities that differ from those of patients with sleep apnoea and that cephalometric values are influenced by the subject's age.

Anthropometry↗
PubMed1991

Changes in upper airway resistance during progressive normocapnic hypoxia in normal men.

The effects of normocapnic progressive hypoxia on nasal and pharyngeal resistances were evaluated in nine normal men. To calculate resistances, upper airway pressures were measured with two low-bias flow catheters; one was placed at the tip of the epiglottis and the other in the posterior nasopharynx, and we measured flow with a Fleish no. 3 pneumotachograph connected to a tightly fitting mask. Both resistances were obtained during a baseline period and during progressive normocapnic hypoxia achieved by a rebreathing method. We collected the breath-by-breath values of upper airway resistances, minute ventilation, O2 and CO2 fractions, arterial O2 saturation (SaO2), and changes in functional residual capacity (inductance vest). The central respiratory drive was evaluated by the mouth occlusion pressure 0.1 s after the onset of inspiration (P0.1), and breath-by-breath P0.1 values were estimated by intrapolation from the linear relationship between P0.1 and SaO2. In each subject both resistances decreased during the hypoxic test. The slope of the decrease in resistance with decreasing SaO2 (%baseline/%SaO2) was steeper for pharyngeal resistance than for nasal resistance [2.67 +/- 0.29 and 1.61 +/- 0.25 (SE), respectively; P less than 0.05]. The slope of the decrease in resistance with increasing P0.1 (%baseline/cmH2O) was -0.24 +/- 0.05 for nasal resistance and -0.39 +/- 0.07 for pharyngeal resistance (P less than 0.05). Functional residual capacity progressively increased during the test, but the decrease in resistance was greater than expected from an isolated increase in lung volume. We conclude that nasal and pharyngeal resistances decrease during progressive normocapnic hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1991

Validity of diurnal sleep recording in the diagnosis of sleep apnea syndrome.

Two polysomnographic studies were performed in 35 subjects who had a clinical suspicion of sleep apnea syndrome: one study was done at night (N) (from 10:00 p.m. to 8:00 a.m.) and the other during the day (D) starting after lunch (from noon to 5:00 p.m.). N and D sleep studies were performed in random order at a minimal interval of 36 h. No treatment (drug, CPAP) was initiated between the two studies. Both studies included the recording of sleep stages (EEG, EOG, EMG), nasal and mouth flows, thoracoabdominal movements, electrocardiogram, and SaO2 (ear oximetry). D sleep was present in all but one subject. As expected, the total sleep time (TST) was significantly shorter during the D than during the N study (2.6 +/- 0.2 and 6.2 +/- 0.2 h, respectively, mean +/- SEM, p less than 0.001, Wilcoxon's signed-rank test). Stages III-IV and REM were significantly less represented during the D (13.1 +/- 2.4 and 7.7 +/- 1.3%, respectively) than during the N study (18.5 +/- 1.7 and 15.3 +/- 0.8%, p less than or equal to 0.005). From the results of the N study, the diagnosis of sleep apnea syndrome (apnea index greater than 5 and/or apnea + hypopnea index greater than 10) was made in 25 patients, and it was confirmed by the same criteria in 22 by the D sleep recording. There was a significant correlation between the N and D values for these indices (r greater than or equal to 0.9, p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian Rhythm↗
PubMed1991

Bronchoalveolar mast cells in normal farmers and subjects with farmer's lung. Diagnostic, prognostic, and physiologic significance.

To evaluate the specificity and significance of increased lavage mast cells in farmer's lung, we examined the lavage cell differentials of 89 farmers and 19 normal nonfarming control subjects. The farmers were divided into four groups: acute farmer's lung (n = 17), farmers with one or more prior episodes of farmer's lung who remained in daily contact with hay (n = 26) or quit farming (n = 14), and normal farmers (n = 36). A total of 14 of the subjects with prior episodes of farmer's lung and still farming and 15 normal farmers were evaluated twice at a 2-yr interval. The lavage mast cell numbers were significantly higher in acute farmer's lung (7.5 +/- 7.3 x 10(3)/ml, mean +/- SD) and ex-farmer's lung who were still farming (1.2 +/- 1.3 x 10(3)/ml) than in normal farmers (0.1 +/- 0.1 x 10(3)/ml) (p less than 0.01). A total of 8 of 14 exfarmer's lung patients who had quit farming and 18 of 36 normal farmers had an increased number of mast cells in lavage, but mast cell count never exceeded 0.5% of total recovered cells. In the acute farmer's lung and ex-farmer's lung-still farming groups, the mast cell count correlated with the lymphocyte count: r = 0.83 and r = 0.69 (p less than 0.001), respectively. In the two groups evaluated twice, mast cell numbers at the first study did not correlate with changes seen at the second study in chest roentgenogram and pulmonary functions. We conclude that an increase in lavage mast cells occurs commonly as a part of the immune response against thermophilic bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

Hypersensitivity pneumonitis: whole Micropolyspora faeni or antigens thereof stimulate the release of proinflammatory cytokines from macrophages.

Hypersensitivity pneumonitis (HP) is an allergic granulomatous interstitial lung disease resulting from a reaction of selected individuals to repeated inhalations of certain antigens. HP is characterized by chronic inflammation, and the development of the disease seems to be immunologically mediated. In farmer's lung, the source of provoking antigen has been found to be actinomycetes such as Micropolyspora faeni. In this study, we show that M. faeni, or antigens thereof, stimulate strong release of proinflammatory cytokines from blood monocytes and alveolar macrophages obtained from nonfarmer volunteers and naive mouse peritoneal macrophages. Interleukin-1 (IL-1) was produced by human alveolar macrophages and murine peritoneal macrophages in response to whole M. faeni and antigens thereof. IL-1 activity was detected in the supernatants at 12 h of incubation and was maximal by 24 to 36 h (200 to 400 U/ml of IL-1). A rabbit antiserum to IL-1 alpha and IL-1 beta neutralized the thymocyte-stimulating activity of the supernatants. Moreover, M. faeni (1 to 100 micrograms of antigen) elicited a strong secretion of tumor necrosis factor-alpha (TNF-alpha) from human alveolar macrophages and monocytes as well as mouse peritoneal macrophages, where 1 micrograms of M. faeni elicited the secretion of approximately 100 U of TNF-alpha from 2 x 10(5) macrophages, and 100 micrograms stimulated the release of approximately 1,000 U of bioactive TNF-alpha. One particle of whole M. faeni per cell was sufficient to induce copious release of TNF-alpha from macrophages or monocytes (100 U of bioactive TNF-alpha; 1,000 pg/ml of antigenic TNF-alpha as seen by radioimmunoassay). Both IL-1 and TNF-alpha productions stimulated by M. faeni were not abrogated by inclusion of polymyxin B. We propose that the direct stimulation of cytokines by M. faeni or antigens thereof may play an important role in HP.

Alveolitis, Extrinsic Allergic↗
PubMed1991

Tumor necrosis factor plays an essential role in determining hypersensitivity pneumonitis in a mouse model.

We examined the importance of the cytokine tumor necrosis factor-alpha (TNF-alpha) in a mouse model of hypersensitivity pneumonitis (HP). Mice of the C57BL/6 strain were instilled intranasally 3 days/wk for 3 wk with 150 micrograms of the actinomycete Faenia rectivirgula (Micropolyspora faeni) to induce HP as a model of farmer's lung. This experimental model was associated with a progressive inflammation in the lungs of challenged mice, seen histologically as cellular infiltrates of large quantities of macrophages and lymphocytes and some neutrophils. The disease in challenged mice treated with a control rabbit serum was also associated with a substantial release of tumor TNF-alpha (up to 80 U/ml of TNF-alpha in the bronchoalveolar lavage [BAL] at 3 wk after beginning of treatment) and interleukin-1, which peaked at 1 wk (approximately 300 U/ml) and diminished thereafter. A very large increase in BAL cell number (11-fold increase versus saline controls) and an enhanced release potential for TNF-alpha by alveolar macrophages was also seen. Lung fibrosis was also evident in challenged animals, as demonstrated by a 2-fold increase in hydroxyproline levels. Infusion of challenged mice with a rabbit polyclonal antibody against TNF-alpha (2 mg/wk) completely abrogated the disease, as mice so treated had normal lung histology. Anti-TNF-alpha blocked cellular recruitment in the lungs (only a 2-fold increase at week 3); it also completely abolished TNF-alpha secretion in the BAL and drastically reduced interleukin-1 levels in this fluid. Anti-TNF-alpha also abolished lung index increases and lung fibrosis, with both parameters similar to that of saline-instilled mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic↗
PubMed1991

Respiratory health of workers exposed to swine confinement buildings only or to both swine confinement buildings and dairy barns.

Swine building workers (N = 488) and nonfarming neighborhood referents (N = 216) were enrolled in this study. There was a slight but significant increase in the prevalence of chronic bronchitis (17.49 versus 11.57%) and more evidence of airflow obstruction (forced expiratory volume in 1 s/forced vital capacity 0.75 versus 0.78) among the swine workers when they were compared with the referents. The subjects who spent more than 3 h/d in the swine buildings had a higher prevalence of chronic bronchitis (21.94 versus 13.25%) and airflow obstruction (forced expiratory volume in 1 s/forced vital capacity 0.75 versus 0.76) than those with shorter daily contact. Swine building only workers had no precipitins to antigens found in their environment and no clinical evidence of extrinsic allergic alveolitis. The number of years on the farm, dual exposure with dairy cattle, positive skin prick tests, type of piggery, and type of feeding did not add to the respiratory health impact of swine buildings.

Agricultural Workers' Diseases↗
PubMed1990

Changes in upper airway resistance with lung inflation and positive airway pressure.

The influence of pulmonary inflation and positive airway pressure on nasal and pharyngeal resistance were studied in 10 normal subjects lying in an iron lung. Upper airway pressures were measured with two low-bias flow catheters while the subjects breathed by the nose through a Fleish no. 3 pneumotachograph into a spirometer. Resistances were calculated at isoflow rates in four different conditions: exclusive pulmonary inflation, achieved by applying a negative extra-thoracic pressure (NEP); expiratory positive airway pressure (EPAP), which was created by immersion of the expiratory line; continuous positive airway pressure (CPAP), realized by loading the bell of the spirometer; and CPAP without pulmonary inflation by simultaneously applying the same positive extrathoracic pressure (CPAP + PEP). Resistance measurements were obtained at 5- and 10-cmH2O pressure levels. Pharyngeal resistance (Rph) significantly decreased during each measurement; the decreases in nasal resistance were only significant with CPAP and CPAP + PEP; the deepest fall in Rph occurred with CPAP. It reached 70.8 +/- 5.5 and 54.8 +/- 6.5% (SE) of base-line values at 5 and 10 cmH2O, respectively. The changes in lung volume recorded with CPAP + PEP ranged from -180 to 120 ml at 5 cmH2O and from -240 to 120 ml at 10 cmH2O. Resistances tended to increase with CPAP + PEP compared with CPAP values, but these changes were not significant (Rph = 75.9 +/- 6.1 and 59.9 +/- 6.6% at 5 and 10 cmH2O of CPAP + PEP). We conclude that 1) the upper airway patency increases during pulmonary inflation, 2) the main effect of CPAP is related to pneumatic splinting, and 3) pulmonary inflation contributes little to the decrease in upper airways resistance observed with CPAP.

Adult↗
PubMed1990

Phase II study of amonafide: results of treatment and lessons learned from the study of an investigational agent in previously untreated patients with extensive small-cell lung cancer.

Thirteen previously untreated patients with extensive small-cell lung cancer (SCLC) were treated with the investigational agent amonafide in a dose of 300 mg/m2 intravenously (IV) over 1 hour daily for 5 consecutive days. No responses were seen in 12 eligible patients. Myelosuppression was only occasionally seen. Other toxicities included diaphoresis, chest pain, local irritation at the injection site, arthralgias, nausea and vomiting, and neuromuscular problems. There were two early deaths, both attributable to tumor progression with resultant obstruction of a vital structure. Ten patients crossed over to alternate active therapy (etoposide [VP-16]-cisplatin) and five responded. The median survival time (MST) of the whole group of treated patients was 31 weeks. In future trials of investigational new drugs in previously untreated SCLC, we recommend that patients with the following characteristics be excluded: Eastern Cooperative Oncology Group (ECOG) performance status 2, 3, and 4; superior vena cava (SVC) obstruction; any major paraneoplastic syndrome; serious comorbid illness; and extensive hepatic involvement by tumor. The trial design should include prompt crossover to active alternative therapy, such as VP-16 and cisplatin, for disease progression or for failure to respond after two treatment cycles. Also, the trial design should use an early stopping rule based on interest in identifying only very active agents with a minimum response rate of 30%.

Adenine↗
PubMed1990

Sequential bronchoalveolar lavages by endotracheal intubation in guineapigs.

We examined the feasibility of performing repeated bronchoalveolar lavage (BAL) on guineapigs. We also determined the influence of lavage volume on cell recovery in these animals, verified if the free cell populations were altered by repeated lavage, and compared the results with those obtained after euthanasia. Live animals were intubated orotracheally by direct vision laryngoscopy and lavaged, except for the last BAL which was done on isolated lungs after euthanasia. Each animal was lavaged weekly for 8 weeks: weeks 1-5 lavages were done with 5 aliquots of 2 ml of normal saline, week 6 with 3 aliquots of 1 ml, week 7 with 3 aliquots of 2 ml, and week 8 with 5 aliquots of 2 ml after euthanasia. The first 5 BAL gave similar results in volumes recovered, total number of cells, cell viability and differentials. The total cell yield of lavages 6 and 7 was less than that of the first 5 BAL and BAL 8; cell differentials with these smaller lavages were similar except for the percentage of neutrophils which was slightly higher than with the 10 ml lavage at week 3. The final lavage gave similar results as the first 5 BAL in terms of total cells recovered, cell viability, and differentials. We conclude that repeated BAL is feasible in live guineapigs, and that it gives a similar cells yield as lung lavage obtained after euthanasia.

Animals↗