The advanced lung cancer inflammation index predicts outcomes in patients with Crohn's disease after surgical resection.

AIM: Precise biomarkers for predicting prognosis could help to identify high-risk Crohn's disease (CD) patients to facilitate better follow-up during the postoperative course. In this study, the primary aim is the identification of the most reliable nutrition marker that predicts surgical relapse in CD patients. METHOD: We first evaluated the predictive value of various nutrition markers for postoperative surgical relapse in CD patients and identified the advanced lung cancer inflammation index (ALI) as a promising biomarker. Then, we assessed the clinical significance of preoperative ALI in CD patients using two cohorts. RESULTS: Preoperative ALI showed the highest correlation with reoperation rate compared with other nutritional parameters in CD patients receiving surgical resection (sensitivity 53%, specificity 86%, area under the curve 0.71). Lower levels of preoperative ALI were significantly correlated with the presence of perianal disease. A lower level of preoperative ALI was an independent prognostic factor for reoperation rate after an intestinal resection (hazard ratio 3.37, 95% CI 1.38-10.12, P = 0.006), and the prognostic impact of preoperative ALI was successfully validated in an independent cohort using the same cut-off value. CONCLUSION: Preoperative ALI might be useful for postoperative management of CD patients.

Iron limitation induces motility in uropathogenic E. coli CFT073 partially through action of LpdA.

More than half of women will experience a urinary tract infection (UTI) with most cases caused by uropathogenic Escherichia coli (UPEC). Bacterial swimming motility enhances UPEC pathogenicity, resulting in more severe disease outcomes including kidney infection. Surprisingly, the connection between motility and iron limitation is mostly unexplored despite the lack of free iron available in the host. We sought to investigate a potential connection between iron restriction and regulation of motility in UPEC. We cultured E. coli CFT073, a prototypical UPEC strain, under iron limitation and observed that CFT073 had elevated fliC (flagella) promoter activity, and this iron-specific response was repressed by the addition of exogenous iron. We confirmed increased flagellar expression in CFT073 by measuring fliC transcript, FliC protein, and surface-expressed flagella under iron-limited conditions. Interestingly, known motility regulator flhDC did not have altered transcription under these conditions. To define the regulatory mechanism of this response, we constructed single knockouts of eight master regulators and found the iron-regulated response was lost in crp, arcA, and fis mutants. Thus, we focused on the five genes regulated by all three regulators. Of the five genes knocked out, the iron-regulated motility response was most strongly dysregulated in the lpdA mutant, which also resulted in significantly lowered fitness in the murine model of ascending UTI, both against the WT and a non-motile fliC mutant. Collectively, we demonstrated that iron-mediated motility in CFT073 is partially regulated by lpdA, which contributes to the understanding of how uropathogens differentially regulate motility mechanisms in the iron-restricted host. IMPORTANCE: Urinary tract infections (UTIs) are ubiquitous and responsible for over five billion dollars in associated health care costs annually. Both iron acquisition and motility are highly studied virulence factors associated with uropathogenic Escherichia coli (UPEC), the main causative agent of uncomplicated UTI. This work is innovative by providing mechanistic insight into the synergistic relationship between these two critical virulence properties. Here, we demonstrate that iron limitation has pleiotropic effects with consequences that extend beyond metabolism and impact other virulence mechanisms. Indeed, targeting iron acquisition as a therapy may lead to an undesirable enhancement of UPEC pathogenesis through increased motility. It is vital to understand the full breadth of UPEC pathogenesis to adequately respond to this common infection, especially with the increase of antibiotic-resistant pathogens.

Brain-derived neurotrophic factor/tropomyosin-related kinase B pathway in gastric cancer.

BACKGROUND: Brain-derived neutrophic factor (BDNF) is a member of the neutrophin family that is known to activate the high-affinity tropomyosin-related receptor kinase B (TrkB). This study aimed to clarify the clinical and biological significance of the BDNF/TrkB pathway in gastric cancer. METHODS: We analysed BDNF and TrkB expression in gastric cancer samples by real-time reverse transcription PCR and immunohistochemistry. To investigate the biological role of BDNF/TrkB axis, recombinant human BDNF (rhBDNF) and the Trk antagonist K252a were used for in vitro and in vivo analysis. RESULTS: The BDNF expression at the invasive front of primary tumours was significantly elevated compared with that in the tumour core and adjacent normal mucosa. Increased BDNF expression at the invasive front was significantly correlated with factors reflecting disease progression, and poor prognosis. Increased co-expression of the BDNF/TrkB axis was significantly correlated with poor prognosis. Gastric cancer cells expressed BDNF, and administration of rhBDNF promoted proliferation, migration, invasion, and inhibition of anoikis. These effects were generally inhibited by K252a. In an in vivo assay, BDNF(+)/TrkB(+) gastric cancer cells injected into nude mice established peritoneal dissemination, whereas K252a inhibited tumour growth. CONCLUSION: The BDNF/TrkB pathway might be deeply involved in gastric cancer disease progression.

Altered motility in response to iron-limitation is regulated by lpdA in uropathogenic E. coli CFT073.

More than half of all women will experience a urinary tract infection (UTI) in their lifetime with most cases caused by uropathogenic Escherichia coli (UPEC). Bacterial motility enhances UPEC pathogenicity, resulting in more severe disease outcomes including kidney infection. Surprisingly, the connection between motility and iron limitation is mostly unexplored, despite the lack of free iron available in the host. Therefore, we sought to explore the potential connection between iron restriction and regulation of motility in UPEC. We cultured E. coli CFT073, a prototypical UPEC strain, in media containing an iron chelator. Under iron limitation, CFT073 had elevated fliC (flagella) promoter activity, driving motility on the leading edge of the colony. Furthermore, this iron-specific response was repressed by the addition of exogenous iron. We confirmed increased flagella expression in CFT073 by measuring fliC transcript, FliC protein, and surface-expressed flagella under iron-limited conditions. To define the regulatory mechanism, we constructed single knockouts of eight master regulators. The iron-regulated response was lost in crp, arcA, and fis mutants. Thus, we focused on the five genes regulated by all three transcription factors. Of the five genes knocked out, the iron-regulated motility response was most strongly dysregulated in an lpdA mutant, which also resulted in significantly lowered fitness in the murine model of ascending UTI. Collectively, we demonstrated that iron-mediated motility in CFT073 is regulated by lpdA , which contributes to the understanding of how uropathogens differentially regulate motility mechanisms in the iron-restricted host. Importance: Urinary tract infections (UTIs) are ubiquitous and responsible for over five billion dollars in associated health care costs annually. Both iron acquisition and motility are highly studied virulence factors associated with uropathogenic E. coli (UPEC), the main causative agent of uncomplicated UTI. This work is innovative by providing mechanistic insight into the synergistic relationship between these two critical virulence properties. Here, we demonstrate that iron limitation has pleiotropic effects with consequences that extend beyond metabolism, and impact other virulence mechanisms. Indeed, targeting iron acquisition as a therapy may lead to an undesirable enhancement of UPEC pathogenesis through increased motility. It is vital to understand the full breadth of UPEC pathogenesis to adequately respond to this common infection, especially with the increase of antibiotic resistant pathogens.

Mitotic checkpoint genes, hsMAD2 and BubR1, in oesophageal squamous cancer cells and their association with 5-fluorouracil and cisplatin-based radiochemotherapy.

AIMS: HsMAD2 and BubR1 are crucial components of a functional mitotic checkpoint. Recently, impaired mitotic checkpoints or decreased expression of mitotic checkpoint genes have been associated with sensitivity to certain anticancer drugs. The current study aimed to evaluate the association of hsMAD2 and BubR1 with sensitivity to various anticancer drugs in oesophageal squamous cell carcinoma (ESCC) cell lines. We also investigated responses to 5-fluorouracil and cisplatin-based radiochemotherapy in ESCC patients. MATERIALS AND METHODS: HsMAD2 and BubR1 mRNA levels in six ESCC cell lines and 21 ESCC patients were determined by real-time reverse transcription polymerase chain reaction. Responses to 5-fluorouracil, cisplatin, paclitaxel and docetaxel in human oesophageal cancer cell lines, TE1 and TE2, were evaluated by WST-8 colorimetric assay. HsMAD2 and BubR1 levels were compared with clinicopathological characteristics and responses to radiochemotherapy. RESULTS: TE1, with lower hsMAD2 and BubR1, showed greater sensitivity to paclitaxel and docetaxel compared with TE2, with higher hsMAD2 and BubR1. HsMAD2 and BubR1 were significantly higher in cancer tissue than in adjacent normal tissue (P < 0.01). Tumoral hsMAD2 and BubR1 were significantly decreased after radiochemotherapy (P < 0.01). There was a significantly strong positive association between hsMAD2 and BubR1 in cancer tissue (P < 0.01). Neither clinicopathological characteristics nor the response to radiochemotherapy was associated with hsMAD2 or BubR1. CONCLUSION: The mitotic checkpoint genes, hsMAD2 and BubR1, were co-ordinately overexpressed in ESCC. Low hsMAD2 and BubR1 was associated with sensitivity to paclitaxel and docetaxel. Decreased hsMAD2 and BubR1 after radiochemotherapy may indicate the potential efficacy of taxanes as second-line chemotherapy for recurrent and metastatic oesophageal cancer.

Changes in intra-abdominal visceral fat and serum leptin levels in patients with obstructive sleep apnea syndrome following nasal continuous positive airway pressure therapy.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a common disorder in obese subjects. Visceral fat accumulation (VFA) is a better predictor of coronary heart disease than body mass index. Leptin is a hormone involved in the control of body weight and fat distribution. The effect of nasal continuous positive airway pressure (NCPAP) treatment on VFA and serum leptin levels in OSAS patients has not been known. METHODS AND RESULTS: VFA and subcutaneous fat accumulation (SFA) were assessed by CT before and after NCPAP treatment in 22 OSAS patients (mean apnea and hypopnea index >50 episodes/h). Serum leptin levels of another 21 OSAS patients were measured before and after 3 to 4 days of NCPAP to gain insight into the mechanism by which NCPAP affects fat distribution. VFA and SFA decreased significantly after 6 months of NCPAP treatment (236+/-16 to 182+/-14cm(2), P=0.0003 and 215+/-21 to 189+/-18 cm(2), P=0.003, respectively). VFA decreased significantly in the body weight reduction group (n=9, P<0.01) and the no body weight reduction group (n=13, P<0.03). In contrast, SFA changed significantly in the body weight reduction group only (P<0.01). Leptin levels decreased significantly following 3 to 4 days of NCPAP (P<0.01), whereas body weight, fasting insulin, and cortisol levels did not change significantly. CONCLUSIONS: Correction of sleep disordered breathing by NCPAP may be used to reduce VFA in OSAS patients. OSAS may have significant effects on the serum leptin levels.

Distribution of involved abdominal lymph nodes is correlated with the distance from the esophagogastric junction to the distal end of the tumor in Siewert type II tumors.

BACKGROUND: The optimal surgical approach for Siewert type II adenocarcinoma of the esophagogastric junction (AEG) has not yet been agreed. Here we investigated whether the distance from the esophagogastric junction (EGJ) to the distal end of the tumor was related to the distribution of involved abdominal lymph nodes in Siewert type II tumors. METHODS: A total of 288 patients with pT2-4 AEG Siewert II, treated by R0 surgical resection at 7 institutions in Japan, were retrospectively investigated. The distribution of involved abdominal nodes was correlated with the distance from the EGJ to the distal end of the tumor. RESULTS: In patients where the distance from the EGJ to the distal end of the tumor was ≤30 mm, the frequency of nodal involvement along the greater curvature or antrum was low (2.2%). In contrast, in patients where the distance was >50 mm, the incidence of this nodal involvement was 20.0%. In patients where the distance was 30-50 mm incidence was intermediate (8.0%). Multivariate analyses showed that the distance from the EGJ to the distal end of the tumor was significantly related to lymph node involvement along the greater curvature or antrum (odds ratio 3.7, 95% confidence interval 1.3-11, p = 0.006). CONCLUSIONS: When the distance from the EGJ to the distal end of the tumor is ≤ 30 mm for Siewert II AEG, esophagectomy or proximal gastrectomy is sufficient from the point of view of abdominal lymphadenectomy. However, a total gastrectomy should be considered for abdominal lymphadenectomy when this distance is > 50 mm.

Effects of nasal continuous positive airway pressure on soluble cell adhesion molecules in patients with obstructive sleep apnea syndrome.

PURPOSE: Obstructive sleep apnea syndrome is common in middle-aged men and may be associated with an increased risk of cardiovascular disease. We investigated the effect of nasal continuous positive airway pressure (CPAP) treatment on levels of soluble cell adhesion molecules-which have been shown to be associated with the development of atherosclerosis-in these patients. SUBJECTS AND METHODS: We studied 23 patients with obstructive sleep apnea syndrome diagnosed by polysomnography who were treated with nasal CPAP. Serum soluble intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 levels were measured before nasal CPAP was started, and after 3 or 4 days (n = 19), 1 month (n = 23), or 6 months (n = 11) of treatment. RESULTS: After 3 to 4 days of nasal CPAP therapy, the mean (+/- SD) soluble E-selectin level had decreased from 89 +/- 44 ng/mL to 69 +/- 28 ng/mL (P = 0.002). After 1 month, the soluble intercellular adhesion molecule-1 level had decreased from 311 +/- 116 ng/mL to 249 +/- 74 ng/mL (P = 0.02). After 6 months, soluble vascular cell adhesion molecule-1 levels had not changed significantly, while the mean soluble intercellular adhesion molecule-1 level (212 +/- 59 ng/mL) had decreased further (P = 0.02). Before treatment, soluble intercellular adhesion molecule-1 levels and the apnea and hypopnea index were correlated (r = 0.43, P = 0.04). CONCLUSIONS: Obstructive sleep apnea and hypopnea have a significant adverse effect on serum soluble cell adhesion molecule-1 levels that may be reduced by nasal CPAP treatment.

Assessment of cardiac sympathetic function with iodine-123-MIBG imaging in obstructive sleep apnea syndrome.

UNLABELLED: Iodine-123-MIBG imaging has been used to evaluate myocardial sympathetic function in various cardiac diseases. In patients with obstructive sleep apnea syndrome (OSAS), increased sympathetic activity has been widely recognized, as assessed by measuring the plasma concentration and urinary excretion of catecholamines and by measuring muscle sympathetic nerve activity. However, these measurements are not specific indices of cardiac sympathetic function. Therefore, this study was undertaken to assess cardiac sympathetic function in patients with OSAS using MIBG cardiac scintigraphy. METHODS: This study consisted of 11 patients (10 men, 1 woman; mean age 43 +/- 16 yr) with a diagnosis of OSAS established by polysomnography, and 8 age-matched normal control subjects (7 men, 1 woman; mean age 45 +/- 18 yr). Early (15 min) and delayed (3 hr) planar images were taken after the injection of 111 MBq of [123I]MIBG. The mean counts of the whole heart and the mediastinum were obtained to calculate heart-to-mediastinum count ratios from the early images (H/Me) and from the delayed images (H/Md) and the myocardial washout rate (WR). Eight patients were restudied after 1 mo of nasal continuous positive airway pressure treatment. RESULTS: The H/Me and H/Md ratios were significantly lower in the patients than in the control subjects (H/Me, 2.49 +/- 0.32 versus 2.84 +/- 0.34, p = 0.0207; and H/Md, 2.33 +/- 0.30 versus 3.02 +/- 0.36, p = 0.0013). The WR was higher in the patients than in the control subjects (36.2 +/- 9.0% versus 23.6 +/- 4.9%, p = 0.0022). The H/Me and H/Md ratios in the patients were significantly correlated with the apnea-hypopnea index and the degree of hypoxemia during sleep. After treatment, H/Me and H/Md remained unchanged, but WR significantly recovered (from 34.9 +/- 10.4% to 26.3 +/- 7.7%, p = 0.0357). CONCLUSION: Cardiac sympathetic function and integrity are impaired in subjects with OSAS when compared with age-matched control subjects. MIBG cardiac imaging can be helpful in evaluating cardiac involvement and efficacy of therapy in OSAS.

Purification and characterization of tissue-type plasminogen activator in maxillary mucosa with chronic inflammation.

Tissue-type plasminogen activator (TPA) was purified from maxillary mucosa with chronic inflammation and compared with urokinase. Purification procedure consisted of the extraction from delipidated mucosa with 0.3M potassium acetate buffer (pH 4.2), 66% saturation of ammonium sulfate, zinc chelate-Sepharose, concanavalin A-Sepharose and Sephadex G-100 gel filtration chromatographies. The molecular weight of the TPA was approximately 58,000 +/- 3,000. Its activity was enhanced in the presence of fibrin and was quenched by placental urokinase inhibitor, but not quenched by anti-urokinase antibody. The TPA made no precipitin line against anti-urokinase antibody, while urokinase did. All these findings indicate that the TPA in maxillary mucosa with chronic inflammation is immunologically dissimilar to urokinase and in its affinity for fibrin.

Increase in bilirubin levels of patients with obstructive sleep apnea in the morning--a possible explanation of induced heme oxygenase-1.

STUDY OBJECTIVES: In the absence of heme oxygenase-1 (HO-1), which catalyzes the oxidation of heme to generate carbon monoxide and indirect bilirubin, hypoxia induces severe right ventricular dilation and infarction. Despite severe hypoxemia during sleep, patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) rarely die during sleep. We hypothesized that apnea-related hypoxemia would induce HO-1 and increase bilirubin levels in the morning in OSAHS patients. Therefore, bilirubin levels in OSAHS patients were analyzed before and after nasal continuous positive airway pressure (nCPAP) therapy. DESIGN: Bilirubin levels in the afternoon before sleep and in the morning immediately after sleep were determined before and after nCPAP treatment. SETTING: University Hospital in Kyoto, Japan. PATIENTS: The subjects were 22 patients with OSAHS (mean (SEM) apnea and hypopnea index of 60 (5)) who were treated with nCPAP and 13 controls. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Before nCPAP treatment, total after-sleep bilirubin level was significantly higher than the pre-sleep level (p<0.0001). The difference between the serum indirect bilirubin levels in the morning versus in the previous afternoon [D-(M-A)-IB] decreased significantly with nCPAP treatment (p<0.01). The magnitude of decrease in D-(M-A)-IB after nCPAP treatment correlated significantly with changes in the percent time spent with arterial O2 saturation below 90% (r=0.44; p=0.04) and 85% (r=0.49; p=0.02), respectively, during sleep after nCPAP treatment. CONCLUSIONS: The increase in bilirubin level by HO-1 might protect OSAHS patients from disorders related to hypoxemia.

Acute effect of nasal continuous positive airway pressure therapy on the systemic immunity of patients with obstructive sleep apnea syndrome.

OBJECTIVES: To investigate whether in patients with obstructive sleep apnea syndrome (OSAS) the systemic immunity is disturbed and whether it changes with nasal continuous positive airway pressure (NCPAP) therapy. DESIGN: Polysomnography was performed on 18 OSAS patients (Group A) before NCPAP was started and again on the first night of NCPAP. Blood samples were collected at 8:00PM, 1:00AM and 6:00AM during each polysomnography. Lymphocyte subsets, lymphocyte blastformation, and natural killer (NK) cell activity were determined. Six normal subjects were also studied. A different six OSAS patients were studied over 6 days of NCPAP. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The only immunological parameter that significantly differed between the Group A OSAS patients either before or on the first night of NCPAP, and the normal subjects was the epinephrine level. Among the Group A OSAS patients, the following immunological parameters were significantly lower at 6:00AM on the first night of NCPAP than before NCPAP was started: percentage (49.4+/-1.9% before NCPAP vs 45.7+/-2.0% with NCPAP, mean+/-SEM, p<0.005) and absolute count of CD4+ cells (944.1+/-63.8 vs 829.6+/-71.3/mm3, p<0.05); absolute count of CD4+HLA-DR+ cells (91.9+/-13.3 vs 75.1+/-8.9/mm3, p<0.05); CD4+/CD8+ ratio (2.13+/-0.21 vs 1.91+/-0.18, p<0.05). The reduction in the percentage of CD4+ cells at 6:00AM was significantly correlated with the change in apnea-hypopnea index (AHI) (r=0.729, p<0.01). The CD4+ cell count recovered after 6 days of NCPAP. The lymphocyte blasfformation and NK cell activity levels did not change with NCPAP. CONCLUSIONS: First-night NCPAP therapy reduced the CD4+ cell count after sleep, which recovered after one week of NCPAP. OSAS patients do not have immunological abnormalities.

Noninvasive method to assess cor pulmonale in patients with chronic obstructive pulmonary disease.

In our study of 15 patients with chronic obstructive pulmonary disease, we performed myocardial perfusion single-photon-emission computerized tomography (SPECT) with thallium-201 to quantitatively assess right ventricular hypertrophy. On the SPECT images, we determined the ratio of activity in the right-to-left ventricular wall as the thallium score. Right ventricular ejection fraction (RVEF) was measured by multigated equilibrium radionuclide ventriculography with krypton-81m. Both the thallium scores and RVEF values correlated well with pulmonary arterial pressure (r = 0.65 and r = -0.86, respectively) and permitted the structural and functional assessment of cor pulmonale. When the patients were classified according to the thallium scores and RVEF values, those who had both a high thallium score and reduced RVEF had a significantly high pulmonary arterial pressure and vice versa. The combined evaluation of the thallium score and RVEF enabled accurate noninvasive assessment of cor pulmonale.

Doxapram hydrochloride in the treatment of acute exacerbation of chronic respiratory failure. A patient with four episodes treated without use of a respirator.

A 51-year-old woman with chronic respiratory failure (status after tuberculosis) was given an infusion of doxapram hydrochloride (1 to 2 mg/kg of body weight per hour) for four episodes of acute exacerbation of her condition. Treatment with the drug prevented worsening of hypercapnia in the four episodes, when administration of 24 percent oxygen had occasioned rises in the arterial carbon dioxide tension of 23, 10, 9, and 7 mm Hg.

Hypoxic ventilatory response and breathlessness following hypocapnic and isocapnic hyperventilation.

STUDY OBJECTIVES: To investigate the etiology of posthyperventilation (post-HV) hypoxemia following voluntary hyperventilation (VHV), we examined the effects of hypocapnic (hypo-CO2) and isocapnic (iso-CO2) VHV on the hypoxic ventilatory response (O2-response) and on the sensation of breathlessness during the O2-response. METHODS: O2-responses and visual analog scale (VAS) scores for estimating breathlessness in 10 normal subjects during the O2-response under iso-CO2 conditions and under hypo-CO2 conditions immediately following voluntary maximal HV of 3 min duration were examined. RESULTS: Although there was no significant difference in the post-HV ventilation levels following hypo-CO2 vs iso-CO2 VHV, the VAS scores at the start of the O2-response following hypo-CO2 VHV (30.2+/-24.2 mm) were significantly higher (p<0.05) than the VAS scores at the start of the O2-response following iso-CO2 VHV (13.7+/-8.4 mm). However, VHV did not have a significant effect on the O2-response at 2 min after the VHV when the arterial O2 saturation (SaO2) was below 90%. The nonsteady-state hypo-CO2 induced by VHV greatly attenuated the O2-response below 90% SaO2 and VAS scores at 70% SaO2. CONCLUSIONS: Elevated VAS scores immediately following the hypo-CO2 VHV, which might be independent of actual breathing levels, and the attenuation of the O2-response following the hypo-CO2 VHV were not due to input from lung and chest wall mechanoreceptors induced by the hyperpnea itself, but rather to the hypo-CO2 induced by hyperpnea.

Ventilatory support during exercise in patients with pulmonary tuberculosis sequelae.

STUDY OBJECTIVE: The aim of this study was to determine whether intermittent positive pressure ventilation through a nasal mask (NIPPV) applied during exercise in patients with pulmonary tuberculosis sequelae (PTS) could improve arterial blood gas measurements, ameliorate breathlessness, and increase exercise endurance. PATIENTS: Seven PTS patients with a severe restrictive ventilatory defect (mean [SD] vital capacity, 1.02 [0.25] I) enrolled in this study had experienced NIPPV previously, and were familiar with the procedure. DESIGN: The patients underwent four constant-load cycle ergometer tests in the supine position to tolerance. The tests were performed with and without NIPPV, while breathing normoxic air (Air) or supplemental oxygen (O2; 35%). NIPPV was delivered during exercise in a controlled, volume-cycled mechanical ventilation mode, and the ventilator settings were modulated manually to meet patients' respiratory demands as estimated from the airway pressure waveform and the patient's breathlessness. RESULTS: All patients matched their breathing to the ventilator cycle during most of the exercise while receiving NIPPV. NIPPV significantly prolonged their exercise endurance time, from a mean (SD) of 180 (58) s to 310 (96) s in Air, and from 227 (64) s to 465 (201) s in O2. During exercise, NIPPV effectively decreased their breathlessness and significantly improved arterial blood gas measurements. CONCLUSIONS: NIPPV applied during exercise can effectively support ventilation, significantly ameliorate breathlessness, and consequently improve exercise endurance in patients with PTS.

Effects of nasal continuous positive airway pressure therapy on respiratory parameters of upper airway patency in patients with obstructive sleep apnea syndrome.

OBJECTIVES: To assess whether an initial treatment with nasal continuous positive airway pressure (NCPAP) therapy, applied for one night, had any effect on airway patency. METHODS: In 18 patients with obstructive sleep apnea syndrome (OSAS), we measured the total resistance of the respiratory system (Rrs) and their relevant lung functions before and after polysomnography, with and without NCPAP therapy. The Rrs was measured at 3 Hz with the forced oscillation technique. The overnight changes in the specific respiratory conductance (SGrs=reciprocal of the Rrs per unit lung volume) was also calculated in the sitting position. Since many reports have suggested that obesity, through fat deposits around the pharynx, can affect the mechanical and neuromuscular properties of the upper airway, we also investigated if the degree of obesity was related to the magnitude of improvement in these parameters. RESULTS: After the first night of NCPAP therapy, the Rrs decreased (sitting: 4.8+/-0.4 vs 4.3+/-0.4 cm H20/L/s, p < 0.05; lying: 6.5+/-0.4 vs 5.6+/-0.4 cm H20/L/s, p < 0.05) and the maximal voluntary ventilation increased in the morning (sitting: 101.6+/-5.8% vs 106.4+/-4.5%, p < 0.05; lying: 91.2+/-5.4% vs 97.9+/-4.7%, p < 0.05). The overnight difference in the SGrs showed a significant improvement after the initial treatment with NCPAP therapy (p < 0.05). However, the lung volume, flow volume loop, and closing volume in the morning did not change significantly after the therapy. An overnight decrease in the Rrs following NCPAP therapy is significantly correlated with the body mass index (sitting: r=0.54, p < 0.05; lying: r=0.61, p < 0.01). CONCLUSION: The improvements in Rrs without changes in spirometry may reflect improved upper airway patency after NCPAP therapy. The degree of obesity is suggested to be associated with the treatment effect on upper airway in patients with OSAS.

Breathing during sleep with mild hypoxia.

To investigate ventilatory response to mild hypoxia during non-rapid-eye-movement sleep, we administered approximately 16% O2 (which corresponds to concentrations found in commercial high altitude air craft) to 12 normal subjects by using a Venturi mask, which did not alter the breathing pattern during this study. Under mild hypoxia, inspiratory minute ventilation during sleep showed an initial rapid increase (P less than 0.001) but then declined significantly (P less than 0.001) and stabilized. Stable levels differed among individuals and, compared with those measured before hypoxia, were significantly lower in some subjects, higher in one, and essentially unchanged in the others. The initial rapid increase in minute ventilation after mild hypoxia during sleep correlated with the respective values of hypoxic ventilatory response during the awake state (P less than 0.01), but the final lowered levels did not. We conclude that the ventilatory response after mild hypoxia during sleep is biphasic and hypoxic depression exerts considerable influence on ventilation under mild hypoxia during sleep. So we should take hypoxic depression into consideration to evaluate the response to hypoxia during sleep.

Inhibitory effect of an intellectual task on breathing after voluntary hyperventilation.

We investigated the effects of an intellectual task on posthyperventilation (PHV) breathing by using a video game. Eight normal subjects were placed in a supine positions. The game task by itself led to increase ventilation compared with the control tasks via an increase in the average inspiratory flow rate (P < 0.01) and the respiratory frequency (P < 0.001). After hypocapnic voluntary hyperventilation (VHV), the task led to a decrease in the 1-min PHV breathing level compared with the control tasks after VHV [after VHV, first 60 s average minute ventilation while watching television and while playing a video game are 5.54 +/- 2.91 (SD) and 2.05 +/- 1.40 l/min, respectively; P < 0.01]. Only one subject showed PHV apnea for at least 10 s during the control protocol, whereas seven of the same eight subjects showed PHV apnea while performing the task. After isocapnic VHV, the task still led to a decrease in PHV breathing compared with the control tasks. However, this decrease was smaller than in the hypocapnic studies and was only significant during the first 15 s of recovery. These results suggest that increased activity in the higher centers of the central nervous system has an inhibitory effect on PHV breathing at a time when the effects of short-term potentiation after VHV, hypocapnia, and perhaps other mechanisms would be expected to be acting on breathing.

Hypoxaemia in patients with hyperventilation syndrome.

We assessed 12 patients with hyperventilation syndrome (HVS) who had experienced hypoxaemia (PaO2 < 60 Torr or SaO2 < 90%) despite the lack of any other organic disease and variability in their blood gas data. Hypoxic and hypercapnic ventilatory responses were measured in nine. Eight of the 12 patients had been referred from other hospitals to our institution for hypoxaemia of unknown origin. Mean PaO2 (n = 12) at rest (non-attack stage) was 87.3 +/- 7.5 Torr (mean +/- SD). Their (n = 9) hypoxic (-0.53 +/- 0.32 l/min/%; range 0.12-0.99) and hypercapnic (2.01 +/- 0.76 l/min/Torr; range 0.69-3.17) ventilatory responses were both within the normal range in our laboratory. The patients with HVS had variable blood gas data, and some of them also exhibited hypercapnia (PaCO2 > 45 Torr). Clinicians who treat patients with HVS should be aware of the possibility of hypoxaemia, even when ventilatory responses are normal. Physicians should also consider HVS as a diagnosis when treating patients with hypoxaemia of unknown origin.