[Swallowing rehabilitation in two elderly patients with cerebral infarction].

We report two cases of cerebral infarction in which swallowing function improved following swallowing rehabilitation. Patient 1 was an 82-year-old man, who was admitted due to rheumatoid arthritis and multiple cerebral infarction, suffering from aspiration pneumonia. The abnormality of swallowing was assessed by the water swallowing test and videofluorography. It has been reported that videofluorography is useful in the diagnosis of aspiration. Three weeks after the start of swallowing rehabilitation, the serum level of inflammatory markers and the chest X-ray had returned to normal. His score on the water swallowing test had improved. Patient 2 was a 68-year-old [correction of 62] man, who was admitted with severe hemiplegia, dysphagia and dysarthria. One month after the swallowing rehabilitation, videofluorography showed that the magnitude of aspiration into the trachea had decreased and the pooling of barium in the piriform sinus had disappeared. The patient could begin taking a little food by mouth. These results suggest that swallowing rehabilitation will be affect the clinical improvement of swallowing function and help preventing aspiration pneumonia in our hospital.

[The effects of pulmonary rehabilitation with chronic obstructive pulmonary disease (COPD)].

It is controversial whether pulmonary rehabilitation is effective in patients with chronic obstructive pulmonary disease (COPD). To test the effect of pulmonary rehabilitation, 7 patients with COPD (aged 76.0 +/- 2.6 years) were enrolled in pulmonary rehabilitation program for 6 weeks. The program consisted of relaxation, pursed lip breathing, diaphragmatic breathing, panic control, muscle stretch gymnastics, and exercise training. The distance of the 6-minute walking test increased significantly from 246.4 +/- 38.0 (m) to 304.3 +/- 28.4 (m) (p < 0.05). The minimum SpO2 during the 6-minute walking test increased from 86.0 +/- 2.8 (%) to 90.1 +/- 1.3 (%) and dyspnea as measured with Borg scale decreased from 5.6 +/- 1.1 to 4.6 +/- 0.5, although they were not significantly different. These results suggest that pulmonary rehabilitation might improve exercise tolerance in elderly patients with COPD.

Effects of dextran sulfate on tracheal mucociliary velocity in dogs.

We have shown that low molecular weight dextran, as a potential mucolytic agent, reduced the viscoelasticity and spinnability of cystic fibrosis (CF) sputum and improved its ciliary transportability in vitro; it also reduced viscoelasticity of healthy dog mucus in in vitro testing. In anesthetized dogs, dextran administered by aerosol at 65 mg/mL increased tracheal mucus velocity, but this increase was not sustained for higher concentrations. The purpose of the present study is to evaluate whether low mol. wt. dextran sulfate, a charged oligosaccharide, exhibits similar effects to previously tested neutral dextran when administered by aerosol to anesthetized dogs in terms of mucus rheology and mucociliary clearance rate. Healthy mongrel dogs were anesthetized with pentobarbital and intubated. Aerosols of Ringer's solution or dextran sulfate (m.w. 5000) dissolved in Ringer's were generated by Pari LC STAR nebulizer, and delivered during 30-min periods of spontaneous breathing. Tracheal transepithelial potential difference (PD, using agar filled electrodes) and tracheal mucociliary velocity (TMV, by charcoal marker particle transport) were measured under bronchoscopic control, and mucus for viscoelasticity analysis by magnetic rheometry was collected by the endotracheal tube method. We performed experiments in seven dogs, involving 30-min administrations of aerosol, separated by 30-min periods of no aerosol. All dogs received inhalations of 6.5 mg/mL, 20 mg/mL, and 65 mg/mL dextran sulfate. Tracheal mucus viscoelasticity (average log G* over 1-100 rad/s) decreased progressively with increasing dose of dextran sulfate; for the highest concentration (65 mg/mL), log G* decreased by a factor of 2.61 (p = 0.021). A modest increase in the TMV was observed for the first dose of dextran sulfate (128% of baseline at 6.5 mg/mL, p = 0.066); thereafter TMV was stable. PD increased significantly at each concentration of dextran sulfate compared with Ringer control; however, there was no additional change between the three groups. The solids content of collected airway fluid (%SC) was gradually increased during successive 30-min dextran sulfate aerosols, indicating a significant residence time for the dextran in the mucus, and correlating with the decrease in viscoelasticity. These results suggest that dextran sulfate may be potentially of therapeutic value as a mucolytic agent, assisting mucus clearance by cough and physiotherapy, although whether it stimulates mucociliary clearance remains to be proven.

[Sleep apnea syndrome and hypertension using desaturation index].

To examine the roles of obstructive apnea (OA) and central apnea (CA) in oxygen desaturation on hypertension and sleep apnea syndrome (SAS), we performed a sleep study on 41 elderly subjects (mean age 69.5 +/- 6.8 years, male:female = 31:10). Nocturnal oxygen desaturation was documented with a pulse oximeter and apneas (OA and CA) were diagnosed on the basis of results of respiratory inductive plethysmography and oronasal flow. Significant desaturation (SDS, greater than 5% drop in SpO2 from baseline value) and desaturation index (DI; epsilon SDS (%) x duration (hour)) were calculated using the continuous nocturnal monitoring system with a pulse oximeter. We defined central type apnea above 50% as the central type group (n = 8, mean age 58.6 +/- 2.9, mean BMI 21.3 +/- 1.0, male:female = 7:1), and obstructive type and mixed type apnea above 50% as the obstructive type group (n = 21, mean age 70.0 +/- 3.2, mean BMI 25.3 +/- 1.0, male:female = 17:4). Other subjects were assigned to the control group (n = 12, mean age 64.3 +/- 2.3, mean BMI 23.8 +/- 1.2, male:female = 7:5). The DI (delta 5%) of the central type was 0.34 +/- 0.17, and that of the obstructive type was 1.78 +/- 0.7 showing a significant increase in the latter compared to the control group (p < 0.02). The DI (< 90%) of the central type was 0.14 +/- 0.07, and that of the obstructive type was 1.72 +/- 0.75, and that of the obstructive type was significantly greater than in the control group (p < 0.05) and central type (p < 0.05). There were 4 cases (33.3%) with hypertension in the control group and 4 cases (50.0%) with hypertension in the central type group, but there were 15 cases (71.4%) with hypertension in the obstructive type group. Hypertensive prevalence in the obstructive group was significantly more than in the control group (p < 0.05). No significant difference in body mass index or age were seen in the obstructive group and control group. There was a significant correlation between mean blood pressure and apnea index (AI). The AI of the hypertensive group was significantly higher than that of the normotensive group (p < 0.001). These results suggest that subjects with significant obstructive apneas may be at greater risk for hypertension than subjects with central apneas and that hypertension in the pathogenesis of SAS may be related to the severity of apneas rather than oxyhemoglobin desaturation.

Effects of methacholine and uridine 5'-triphosphate on tracheal mucus rheology in mice.

We compared the action of methacholine (MCh) and uridine 5'-triphosphate (UTP) with and without pretreatment with the chloride channel blocker 4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS) on the transepithelial potential difference (PD), the mucus collection rate (MCR), and tracheal mucus rheology using anesthetized C57BL/6 mice. The cystic fibrosis transmembrane conductance regulator (CFTR) blocker 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB) was also used as a pretreatment for MCh. After collecting baseline mucus for 1.5 h, mucus secretion was stimulated by instilling 5 microl of 10(-2) M MCh or UTP around the upper trachea. There was a significant increase in PD after MCh or UTP stimulation (-21.3+/-2.0 mV MCh versus -14.1+/-1.6 mV control; -25.4+/-2.5 mV UTP versus -19.2+/-1.9 mV control). When UTP administration was preceded by DIDS, PD shifted from -15.2+/-2.9 to -12.0+/-2.2 mV. When MCh was preceded by DIDS or by NPPB, there was no change in PD. There was a significant decrease in mucus rigidity index, logG*, with MCh (2.54+/-0.09 versus 2.99+/-0.14 for control), similar to that previously reported in other species. With UTP, 14 of 16 mice responded in terms of PD becoming more negative, and of these, there was a significant difference in logG* after UTP administration (2.29 +/-0.10 versus 2.57+/-0.10 for control), whereas there was no change in logG* with DIDS administration before UTP. When DIDS administration preceded MCh, there was a diminished but still significant decrease in logG* from control, whereas there was no change in logG* when NPPB was preadministered. The control mucus collection rate was 0.19+/-0.09 mg/h, whereas after MCh stimulation, it increased to 2.83+/-0.78 mg/h. No significant difference was measured in the MCR after either UTP or DIDS+UTP stimulation. DIDS+MCh and NPPB+MCh both resulted in significant increases in MCR, but of a much smaller magnitude than that for MCh alone. We conclude that hypersecretion owing to UTP in C57BL/6 mice is less vigorous than with MCh, reflecting the limited population of Ca(2+)-dependent Cl(-) channels stimulated by UTP P(2) receptors. The action of MCh on tracheal mucus secretion in mice appears to involve both CFTR- and non-CFTR-dependent chloride channels.

Impaired swallowing reflex in patients with obstructive sleep apnea syndrome.

BACKGROUND: The swallowing reflex is well coordinated with breathing patterns in normal humans. However, patients with obstructive sleep apnea syndrome (OSAS) may have a swallowing disorder that reflects the abnormal function of nerves and muscles in the suprapharynx. OBJECTIVE: To examine the relationship between the swallowing function and sleep-disordered breathing in patients with OSAS. PARTICIPANTS: Twenty patients with OSAS with a mean (+/-SD) age of 53.4+/-8.9 years old, and 20 age-matched control subjects with a mean age of 51.4+/-9.1 years old. METHODS: OSAS was diagnosed using the recordings of overnight polysomnography. The swallowing function in the subject was tested using a swallowing provocation test. The swallowing reflex was determined according to the following criteria: latent time (LT), the time following a bolus injection of distilled water at the suprapharynx to the onset of swallowing; inspiratory suppression time (IST), the time from the termination of swallowing to the next onset of inspiration; and threshold volume, the minimum volume of water (range, 0.4 to 2 mL) that could evoke the swallowing response. RESULTS: Whereas the LT values in patients with OSAS were larger than the LT values in the control subjects, the IST values (which may reflect the switching mechanism from deglutition apnea to breathing) were actually shorter. In addition, a greater bolus volume was necessary to elicit swallowing in patients with OSAS than was necessary in the control subjects. CONCLUSION: Patients with OSAS are likely to exhibit an impaired swallowing reflex, probably due to the perturbed neural and muscular function of the upper airways.

Effects of dextran on tracheal mucociliary velocity in dogs in vivo.

We have previously shown that dextran (molecular weight 4kDa) is a potential mucolytic agent, reducing the viscoelasticity and spinnability of cystic fibrosis (CF) sputum and improving its mucociliary clearability during in vitro testing. We wished to see whether low molecular weight (LMW) dextran had similar effects on mucus rheology when administered by aerosol to living dogs, and whether the administration of dextran increased the rate of mucociliary clearance. Healthy mongrel dogs were anesthetized with pentobarbital and intubated. After a 30-min Ringer aerosol delivery during spontaneous breathing, tracheal mucociliary velocity (TMV by charcoal marker particle transport) was measured under bronchoscopic control, and mucus for viscoelasticity analysis (magnetic rheometer) was collected by the endotracheal tube method. Then LMW dextran in Ringer vehicle was delivered by aerosol via the endotracheal tube, followed by the same procedures. We performed eight experiments in eight dogs, involving 30 min administrations of dextran aerosol; all dogs received inhalations of 20 mg/ml, 65 mg/ml, and 200 mg/ml dextran. Compared with Ringer control, TMV increased to 145% of control (P=0.0417) at 65 mg/ml dextran. Mucus viscoelasticity (G*) significantly decreased to 19% of control (P=0.0426) at 65 mg/ml. This in vivo study supports our previous in vitro testing, that LMW dextran decreases the mucus viscoelasticity and increases the rate of mucociliary clearance. We estimate the dosage received by aerosol at 65 mg/ml to be within the effective concentration range studied in vitro, i.e. 10-15 mg/ml final concentration. The results are consistent with the proposed mechanism that the saccharide moieties in LMW dextran compete for hydrogen bonding sites with other mucous glycoproteins. These new hydrogen bonds are structurally and rheologically ineffective, thus reducing the overall cross-link density, and making the mucus more easily cleared by ciliary and cough mechanisms.

ICAM-1 mediates lung leukocyte recruitment but not pulmonary fibrosis in a murine model of bleomycin-induced lung injury.

Bleomycin-induced lung injury has been extensively used as a model of interstitial pneumonia and pulmonary fibrosis. Intercellular adhesion molecule (ICAM)-1 is a ligand for lymphocyte function-associated antigen (LFA)-1alpha and has been shown to be required for leukocyte migration into inflamed areas. The purpose of this report was to investigate the role of the ICAM-1/LFA-1alpha pathway in a murine model of bleomycin-induced lung injury. Animals received 75 mg x kg(-1) bleomycin (BLM) i.v. followed by treatment with phosphate-buffered saline (BLM group), anti-ICAM-1 and LFA-1alpha monoclonal antibodies (mAb) (BLM+mAb group). Inflammatory cell counts of bronchoalveolar lavage (BAL) fluid, hydroxyproline content and histological findings were compared between these groups. In the BLM group, significant increases in total cell count, macrophage count and neutrophil count of BAL fluid were observed on days 7 and 14. In the BLM+mAb group, bleomycin-induced accumulation of neutrophils was significantly reduced on days 7 and 14 (p<0.01). However, the administration of mAb to ICAM-1 and LFA-1alpha did not decrease the lung hydroxyproline content or the histopathological fibrosis grading score, indicating that the antagonism of ICAM-I and LFA-1alpha did not attenuate bleomycin-induced pulmonary fibrosis. This study suggests that the intercellular adhesion molecule-1/lymphocyte function-associated antigen-1alpha pathway mediates the accumulation of inflammatory cells in the injured lung caused by bleomycin; however, other mechanisms are important for the subsequent development of pulmonary fibrosis.

[Swallowing rehabilitation in an elderly patient with Wallenberg's syndrome--role of videofluorography and the swallowing provocation test].

A 65-year-old man was admitted to our department due to severe dysphagia, dysarthria, and aspiration pneumonia. Dysphagia and dysarthria were caused by lateral medullary infarction (Wallenberg' s syndrome). After the patient recovered from pneumonia, the abnormality of swallowing was assessed by a swallowing provocation test and videofluorography. Two months after the start of swallowing training, a swallowing provocation test showed that the swallowing reflex had improved and videofluorography showed that the magnitude of aspiration to the trachea had decreased. The patient began taking food by mouth. These tests are useful for quantitative assessment of dysphagia and for deciding when to start oral intake in elderly patients.

[Two elderly patients with Rhabdomyolysis and respiratory infection with Streptococcus pneumoniae].

Rhabdomyolysis is not common in the elderly. Two elderly patients with rhabdomyolysis and respiratory infection with Streptococcus pneumoniae. The first patient was a 71-year-old woman with bronchiectasis who admitted to our hospital due to pneumonia. The second patient was an 84-year-old man who was admitted because of appetite loss, fever, and a cough producing of yellowish sputum. In both patients, sputum cultures were positive for S. pneumoniae, but blood cultures were not. The serum creatine kinase levels peaked on the day of admission at levels ten to thirty times higher than fold above the upper limit of normal; the serum lactate dehydrogenase levels were 1.5 times higher than the upper limit of normal. The creatine kinase levels returned to normal 5 to 7 days after admission, treated with antibiotics and recovered from pneumonia. The cases of these two patients, along with those described in previous reports of rhabdomyolysis associated with pneumococcal pneumonia indicate that measuring the serum creatine kinase level is important in detecting rhabdomyolysis, especially in elderly patients with respiratory infection caused by S. pneumoniae, and detection may help to prevent renal failure.

[The effects of pulmonary rehabilitation combined with inspiratory muscle training on pulmonary function and inspiratory muscle strength in elderly patients with chronic obstructive pulmonary disease].

It has been suggested that pulmonary rehabilitation compined with inspiratory muscle training (IMT) might improve pulmonary function and respiratory muscle strength in elderly patients with chronic obstructive pulmonary disease (COPD). To test this hypothesis, inspiratory muscle strength (PImax), expiratory muscle strength (PEmax) and resting pulmonary function were measured in 13 elderly patients with COPD (aged 70.3 +/- 2.7 years). Inspiratory muscle training (IMT) was performed for 15 min twice a day, using a pressure threshold device, for a total of 12 weeks. The inspiratory threshold was set at 15% of maximal inspiratory pressure (PImax) for each individual. Pulmonary rehabilitation was performed for 12-h sessions over a 12-week period. Patients with COPD were assigned randomly to two groups: pulmonary rehabilitation combined with IMT (group A) (n = 7), and conventional pulmonary rehabilitation only (group B) (n = 6). Functional residual capacity (FRC) decreased significantly from 4.3 +/- 0.4 L at baseline to 3.9 +/- 0.4 L after rehabilitation (p < 0.01), Vp significantly increased from 4.6 +/- 0.8 L/sec at baseline to 5.1 +/- 0.7 L/sec after rehabilitation (p < 0.05) and the PImax increased significantly from 51.5 +/- 5.4 cmH2O at baseline to 80.9 +/- 7.0 cmH2O after rehabilitation (p < 0.02) in group A. However, these variables did not change in group B. There was no improvement in the 10-minutes walking distance of group A, but there was a significant increase in that of group B. It can be concluded that pulmonary rehabilitation combined with IMT improves pulmonary function and inspiratory muscle strength in elderly patients with COPD.

[Duration of effect of pulmonary rehabilitation in elderly patients with chronic obstructive pulmonary disease].

Pulmonary rehabilitation has been reported to be effective in patients with chronic obstructive pulmonary disease (COPD). To investigate the effect of a moderate period of pulmonary rehabilitation combined with inspiratory muscle training (IMT) in elderly patients with COPD, we instituted pulmonary rehabilitation for 60 weeks in five elderly patients (age: 65.4 +/- 3.7 SE years). IMT was performed for 15 min twice daily using a pressure threshold device. The inspiratory threshold was set at 15% of the maximal inspiratory pressure (PImax) of each individual. Maximal peak flow significantly increased from 3.0 +/- 0.6 (L/s) at baseline to 4.1 +/- 0.7 (L/s) after 12 weeks (p < 0.02) and was maintained at that level for 60 weeks. PImax increased significantly from 49.9 +/- 6.4 cmH2O at baseline to 67.3 +/- 3.0 cmH2O after 12 weeks (p < 0.05) and to 72.8 +/- 3.5 cmH2O (p < 0.02) after 60 weeks of rehabilitation. The 10-minute walking distance increased from 666.6 +/- 55.0 to 764.0 +/- 49.9 m (p < 0.05) after 12 weeks and was maintained at the same level. We conclude that pulmonary rehabilitation combined with IMT improves pulmonary function and inspiratory muscle strength in elderly patients with COPD between for 12 weeks after commencement, but occurs that no significant increase on lung function or 10-minute walking distance from 12 to 60 weeks. Respiratory muscle strength may further increase after 60 weeks.

[Age-related changes in static maximal inspiratory and expiratory pressures].

We evaluated 240 consecutive subjects (aged 20-91) without cardiopulmonary, endocrine or, neuromuscular disease consecutively regarding pulmonary function (TLC, VC, FEV1, RV) and static maximal inspiratory (PImax) and expiratory (PEmax) pressures. PImax and PEmax declined with advancing age. PImax correlated with grip strength, VC, FEV1, height, weight, and RV/TLC. PEmax also correlated with grip strength, TLC, VC, FEV1, height, and weight. Age, height, weight, and grip strength were entered stepwise into multiple linear regression models with PImax or PEmax as the dependent variable. Stepwise regression analysis revealed that grip strength was an independent predictor for both PImax and PEmax. However, age itself was not an independent predictor for PImax or PEmax. These results suggest that static maximal respiratory pressures decrease with aging, and that age-dependent changes in respiratory muscle function may depend on other factors, including lung volume, skeletal muscle status, and body composition.

Roles of calcitonin gene-related peptide (CGRP) in hyperpnea-induced constriction in guinea pigs.

It has been reported that hyperpnea-induced bronchoconstriction in guinea pigs is a potential model for exercise-induced asthma in humans. We hypothesized that calcitonin gene-related peptide (CGRP) could modulate leukotriene D4 (LTD4)-induced responses and be involved in the pathophysiology in this asthma model. We measured tracheal (Ptr) and alveolar pressure (PA) using alveolar capsules in open-chested, mechanically ventilated (f = 1 Hz, VT = 9 ml/kg, PEEP = 4 cm H2O) guinea pigs. Animals were intravenously pretreated with saline (SAL), CGRP(8-37) (CGRP receptor antagonist), CGRP, MK-571 (LTD4 receptor antagonist), MK-886 (5-lipoxygenase inhibitor), or CGRP(8-37) + MK-571, and then underwent dry gas hyperpnea challenge (HC, 95% 02-5% CO2, 150 breaths/min, 7 min). We calculated resistance of lung (RL), tissue (Rti), and airway (Raw). HC increased RL, Rti, and Raw in SAL controls (322 +/- 27, 430 +/- 59, 299 +/- 23% baseline, respectively). MK-571, MK-886, and CGRP significantly reduced the responses to HC, while CGRP(8-37) enhanced HC-induced responses. Pretreatment with CGRP(8-37) and MK-571 in combination attenuated HC-induced constriction. In addition, pretreatment with CGRP reduced responses induced by intravenous administration of LTD4. These observations suggest that CGRP might be involved in the pathophysiology of hyperpnea-induced constriction in guinea pigs via modulation of LTD4-elicited responses.

Long-term effects of inhaled anticholinergic drug on lung function, dyspnea, and exercise capacity in patients with chronic obstructive pulmonary disease.

To investigate the long-term effects of the inhaled anticholinergic bronchodilator, oxitropium bromide (OTB), on lung function, exercise capacity, and dyspnea in patients with chronic obstructive pulmonary disease (COPD), spirometry and symptom-limited exercise testing before and 1, 6, and 12 months after the regular use of OTB (600 micrograms/day) were performed in 12 patients with the use of OTB (mean age 69.9 +/- 3.1 years; FEV1/FVC 53.3 +/- 1.6%) as well as in 12 control patients who were not treated with OTB (Mean age 68.8 +/- 2.8 years; FEV1/FVC 52.6 +/- 1.9%). The dyspnea was evaluated by the slope of the regression line between Borg scale and oxygen uptake (Vo2) during exercise (Borg scale slope: BSS). At 1, 6, and 12 months after the start of OTB, the forced expiratory volume in one second (FEV1) and the exercise capacity (maximal Vo2) were greater than the pretreatment values and the dyspnea index (BSS) was significantly improved compared with the pretreatment value, while these parameters slightly worsened in the control patients over one year. In conclusion, the chronic use of an inhaled anticholinergic bronchodilator may provide beneficial improvements in expiratory flow rate, exercise performance, and dyspnea in mild to moderate COPD patients over one year.

Intercellular adhesion molecule-1 mediates acid aspiration-induced lung injury.

Acid-aspiration-induced injury is one of the leading causes of adult respiratory distress syndrome. Intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte-function-associated antigen-1 alpha (LFA-1 alpha), and it has been shown to be required for leukocyte migration into inflamed areas. The purpose of this report was to investigate the role of the ICAM-1/LFA-1 alpha pathway in a rat model of acid-aspiration-induced injury. Animals received 3.0 ml/kg HCI (0.1N; pH, 1.0) intratracheally pretreated with control monoclonal antibodies (mAbs) (HCI group) or anti-ICAM-1 and LFA-1 alpha mAbs (Test group). In the HCI group, increases in lung resistance (RL) (229 +/- 23% baseline), lung wet-to-dry weight ratio (W/D) (11.9 +/- 0.4), protein concentration (TP) (0.447 +/- 0.054 mg/ml), and the number of neutrophils (PMN) (159.0 +/- 19.4 x 10(4)) of bronchoalveolar lavage fluid were observed. In the Test group, HCI-induced injury was significantly reduced (RL, 122 +/- 7% baseline; W/D, 7.2 +/- 0.1; TP, 0.277 +/- 0.016 mg/ml; PMN, 8.8 +/- 0.8 x 10(4)). The administration of mAbs to ICAM-1 and LFA-1 alpha after HCI instillation partially attenuated HCI-induced responses. These observations suggest that the ICAM-1/LFA-1 alpha pathway might be involved in the pathogenesis of adult respiratory distress syndrome caused by acid aspiration.

Effects of lung volume on airway resistance during induced constriction in papain-treated rabbits.

It has been reported that both the elasticity of the cartilage and airway-parenchymal interdependence can modify shortening of the airway smooth muscle and airway narrowing during induced constriction. We hypothesized that induced softening of the cartilage could alter airway compliance and/or the forces of mechanical interdependence, resulting in an increased degree of airway narrowing in response to a contractile stimulus. To test this hypothesis, we compared the effects of changing lung volume on airway resistance (Raw) under baseline conditions and during methacholine (MCh)-induced constriction in papain-treated (n = 6) and control rabbits (n = 6). With use of the alveolar capsule technique, Raw was directly measured under baseline conditions at different levels of end-expiratory transpulmonary pressure (Ptp = 4-12 cmH2O). Then aerosolized MCh was delivered (0.2-25 mg/ml) and measurements were performed at different levels of Ptp (4 and 12 cmH2O). From measured tracheal flow and tracheal and alveolar pressure in open-chest animals during mechanical ventilation (tidal volume = 6 ml/kg, breathing frequency = 1 Hz), we calculated Raw by subtracting tissue resistance from lung resistance. Papain treatment significantly increased Raw both under baseline conditions and after induced constriction. We found that increasing Ptp decreased Raw before and after MCh in both groups; however, the effects of changing Ptp on Raw were less in papain-treated animals. These observations suggest that both cartilage elasticity and mechanical interdependence are important determinants of airway smooth muscle shortening. The observation that volume dependence of Raw was less in papain-treated animals is consistent with the hypothesis that papain effects significant changes in the parenchymal attachments.

Detection of human T lymphotropic virus type I proviral DNA in patients with diffuse panbronchiolitis.

In Japan a number of reported cases of diffuse panbronchiolitis (DPB) have been associated with human T lymphotropic virus type I (HTLV-I) infection. In this study the hypothesis that HTLV-I proviral DNA may be prevalent in DPB was examined using polymerase chain reaction (PCR) for the region of env or the two-step PCR for the pX region of this virus. The presence of HTLV-I proviral DNA was studied in the peripheral blood mononuclear cells (PBMC) obtained from 10 patients with DPB. The presence of proviral DNA in PBMC in 12 patients with chronic obstructive pulmonary disease (COPD), eight patients with idiopathic interstitial pneumonia (IIP), four patients disease were also studied as relevant controls. The lung tissue obtained from 11 patients with DPB, 12 patients with diffuse aspiration bronchiolitis (DAB) at autopsy, and the surgical lung samples obtained from 12 patients with bronchogenic cancer were also studied. Peripheral blood mononuclear cells obtained from one DPB patient and one bronchogenic carcinoma patient were positive for the HTLV-I pX region. The presence of the pX region was also found in the lung tissue of three DPB patients (27.3%) and one DAB patient (8.3%). None of other subjects were positive for HTLV-I proviral DNA, In conclusion, HTLV-I is not the causative virus in the pathogenesis of COPD, IIP, bronchiectasis and bronchogenic carcinoma. There is a likelihood that HTLV-I infection is associated with some cases of DPB; however this association needs further verification.

[Nocturnal pulmonary hypertension in an elderly patient with sleep apnea syndrome].

We report a case of sleep apnea syndrome (SAS) with nocturnal pulmonary hypertension (NPH) in a 71-year-old man suffering from dyspnea during sleep. Severe snoring at night and daytime sleepiness were noticed before admission by his wife. Nocturnal oxygen desaturation (NOD) was documented with a pulse oximeter and severe sleep apnea syndrome was diagnosed on the basis of results of respiratory inductive plethysmography, an apnea index (AI) > 20, minimum SpO2 56%. NPH was diagnosed by Swan-Ganz catheter. The levels of NPH were severe. Elevation of systolic pulmonary arterial pressure (PAP) above 40 mmHg was observed 137 episodes at night. Both NPH and NOD were improved by 1 L/min of nasal oxygen therapy. A number of episodes of systolic PAP above 40 mmHg with oxygen therapy was 55 episodes. Peak mean PAP was 36 mmHg in room air vs 33 mmHg in oxygen therapy. Minimum SpO2 with oxygen therapy was improved to 69%. Total time of SpO2 < 90% at night was 153 minutes in room air vs 37 minutes in oxygen therapy. In this case, NPH and NOD due to severe SAS were remarkably improved by oxygen therapy.

[A case of pulmonary infiltration with eosinophilia (PIE) syndrome associated with syndrome of inappropriate secretion of ADH (SIADH) in the elderly patient].

A 76-year-old woman was admitted to our hospital because of productive cough, fever and anorexia in January 1995. She had suffered from bronchial asthma for 25 years. From 1983, exacerbation of PIE was recorded three times, on which occasions prednisolone and antibiotics were quite effective. On admission, marked leukocytosis (28,000/microliters) and eosinophilia (18,000/microliters) were found. However, plasma IgE level was normal, and specific antigen for eosinophilia was not detected by RAST or the skin allergic reaction test. Chest X-ray film and CT scan revealed extensive bilateral pulmonary infiltration. Increase in eosinophils (33%) was demonstrated in bronchoalveolar lavage. Furthermore, biopsy specimen of the affected lung revealed diffuse infiltration of eosinophils into alveolar septa. On the basis of these findings, the patient was diagnosed as chronic eosinophilic pneumonia (PIE syndrome). Hyponatremia (117 mEq/l) was persistent after the hydration with normal saline. Plasma ADH was not suppressed (2.29 pg/ml) in spite of hypoosmolality of plasma. Laboratory examination showed that renal, adrenal and thyroid function as well as plasma renin activity were normal. Taking these findings together, she was diagnosed as having SIADH. Treatment with prednisolone improved not only the PIE syndrome but also SIADH.