Tadashi Abe

Respiratory muscle electromyogram and mouth pressure during isometric contraction.

When extra-diaphragmatic muscles are activated progressively under approximately isometric conditions, we expect a corresponding increase in respiratory muscle output. Therefore, we examined relative recruitment shown as the latency to onset of EMG activity, and the relationship between mouth pressure and electromyogram activity of the neck accessory and transversus abdominis (TRANS) muscles during respiratory maneuvers against occlusion. Fine wire electrodes were inserted into the scalene (SCLN), sternocleidomastoid (STERNO), trapezius (TRAPZ) and TRANS in six awake, healthy subjects. Mouth pressure, raw and moving average EMG signals were recorded during gradual production of expiratory or inspiratory mouth pressure to maximum (MPmax) at FRC in the standing posture. Group mean linear regression lines of EMG activity versus mouth pressure were strongly significant for SCLN and TRANS, less for STERNO, and least for TRAPZ. The SCLN and STERNO showed EMG activities with low, and TRAPZ showed EMG activity only with high, mouth pressure. At 90% MPmax, TRAPZ was much less active compared with TRANS, SCLN, or STERNO. These results suggest that over a wide range of respiratory effort there is a significant difference in the relationship between mouth pressure and EMG activity in the accessory muscles, with differential recruitment of individual respiratory muscles.

Neck and abdominal muscle activity during a sniff

Measurement of sniff nasal inspiratory pressure (SNIP) is now used widely as a simple, non-invasive assessment of global respiratory muscle strength, even though the technique evolved originally from measurements of trans-diaphragmatic pressure (Pdi) that reflect the status of the diaphragm. The relative participation of major respiratory muscles, apart from the diaphragm, in the generation of SNIP is not known. Therefore, we examined the activity during a sniff of both neck and abdominal accessory muscles. In seven young adults we implanted fine wire EMG electrodes under direct vision with high-resolution ultrasound into scalene, sternocleidomastoid, trapezius, and transversus abdominis. SNIP was measured during sniffs that were short and sharp, from low to maximal intensity, in both standing and supine postures. Mean maximum SNIP was -105.6cmH2O (SD 32.9) in supine and -94.5cmH2O (26.6) in the standing posture, (difference NS). In every subject, scalene activity appeared even at the lowest SNIP, and increased linearly with increasing SNIP. Sternomastoid activity appeared at higher SNIP levels in three of seven subjects. By contrast, trapezius activity was never present at low SNIP, and appeared in only 2 subjects at maximum SNIP. Sniff abdominal expiratory activity was inconsistent with no activity of transversus in four of seven subjects even at greatest SNIP. Thus, we observed differential activation among these non-diaphragm respiratory muscles during SNIP; while some accessory muscles were very active, others were unlikely to contribute to generation of SNIP. Clinically, this indicates SNIP will be impacted unequally by loss of function of specific respiratory muscles.

Analysis of the oligosaccharide chain of human serum immunoglobulin G in patients with localized or metastatic cancer

A quantitative imbalance between matrix metalloproteinases produced by cancer cells and tissue inhibitors of metalloproteinases produced by fibroblasts and other types of cells has been demonstrated to be a causative factor in invasion and metastasis of cancer cells. On the other hand, it is reported that sugar chains of adhesion molecules such as integrins and CD44 also influence the metastasis of cancer cells. Here, alterations of serum IgG oligosaccharide chain structure were investigated during tumor progression using the new method of fluorophore-assisted carbohydrate electrophoresis (FACE). The structure of serum IgG oligosaccharide chains from 22 cancer patients (11 localized cancer, 11 metastatic cancer) and 10 healthy controls was evaluated by FACE. It was clearly demonstrated that serum IgG oligosaccharide chains without galactose (agalactosyl IgG oligosaccharide) significantly increased with tumor progression of lung and gastric cancers. It is concluded that a marked increase of agalactosyl IgG oligosaccharide in these cancer patients is associated with carcinogenesis and metastasis. Therefore, the analysis of serum IgG oligosaccharide chain structure by FACE may be useful for evaluating diagnosis and prognosis in patients with these carcinomas.

Phase I and pharmacologic study of irinotecan and amrubicin in advanced non-small cell lung cancer.

PurposeWe conducted a Phase I trial of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with amrubicin, a topoisomerase II inhibitor. The aim was to determine the maximum tolerated dose (MTD) of amrubicin combined with a fixed dose of CPT-11 as well as the dose-limiting toxicities (DLT) of this combination in patients with advanced non-small cell lung cancer.Patients and methodsEleven patients with stage IIIB or IV disease were treated at 3-week intervals with amrubicin (5-min intravenous injection on daysxa01–3) plus 60xa0mg/m2 of CPT-11 (90-min intravenous infusion on daysxa01 and 8). The starting dose of amrubicin was 25xa0mg/m2, and it was escalated in 5xa0mg/m2 increments until the maximum tolerated dose was reached.ResultsThe 30xa0mg/m2 of amrubicin dose was one dose level above the MTD, since three of the five patients experienced DLT during the first cycle of treatment at this dose level. Diarrhea and leukopenia were the DLT, while thrombocytopenia was only a moderate problem. Amrubicin did not affect the pharmacokinetics of CPT-11, SN-38 or SN-38 glucuronide. Except for one patient, the biliary index on day-1 correlated well with the percentage decrease of neutrophils in a sigmoid Emax model. There were five partial responses among 11 patients for an overall response rate of 45%.ConclusionThe combination of amrubicin and CPT-11 seems to be active against non-small cell lung cancer with acceptable toxicity. The recommended dose for Phase II studies is 60xa0mg/m2 of CPT-11 (days 1 and 8) and 25xa0mg/m2 of amrubicin (days 1–3) administered every 21xa0days.

Differential function of the costal and crural diaphragm during emesis in canines.

In six mongrel dogs under thiopental anesthesia, piezoelectric transducers and bipolar electromyographic (EMG) wires were installed onto left costal, medial crural and lateral crural segments of the diaphragm. During CO2 rebreathing, shortening and EMG activity increased significantly in all three regions of the diaphragm compared to resting breathing. During emesis, (1) both shortening and EMG activity significantly increased compared to resting in costal segment; however, (2) lateral crural shortening was not increased in spite of significant increase in EMG activity; furthermore, (3) the medial crural segment lengthened without any increased EMG activity. These results demonstrate a differential recruitment of costal and crural diaphragm segments, and an additional differential activity within the crural segment between medial and lateral crural regions, during emesis. This activity of the canine diaphragm is consistent with a central influence of emesis upon individual regions of the diaphragm.

Aminophylline increases parasternal intercostal muscle activity during hypoxia in humans.

To clarify the mechanism of action of aminophylline on the hypoxic ventilatory response in humans, we analyzed the effects of aminophylline on respiratory neural output. To evaluate the respiratory neural output, we analyzed the electromyogram (EMG) of the parasternal intercostal muscle, one of the major inspiratory muscles, in eight healthy subjects. Both before and during aminophylline administration, measurements of ventilatory parameters with EMG recordings were conducted in room air, mild hypoxia (F(I)(o)(2) 0.15), and severe hypoxia (F(I)(o)(2) 0.11). Before administering aminophylline, hypoxic stimulation elicited ventilatory augmentation in a hypoxia-intensity dependent manner. Administration of aminophylline caused significant increases in ventilation (V (I)), tidal volume (V(T)), respiratory frequency (f(R)), and the respiration-related phasic moving averaged EMG amplitude (tidal EMG), at corresponding levels of hypoxia compared to before aminophylline. Augmentation patterns of hypoxia-induced increases in V(T) and tidal EMG showed close similarity. These results indicate that augmentation of hypoxic ventilatory response by aminophylline is mainly mediated by an increase in the respiratory neural drive in healthy humans.

Hyperventilation and finger exercise increase venous-arterial Pco2 and pH differences

INTRODUCTIONnSince the invention of the pulse oximeter, physicians often or even routinely perform venous blood gas analysis (VBGA). However, it has not been generally agreed that the application of VBGA is practically meaningful in routine clinical situations such as in an ED.nnnMETHODSnWe measured venous-arterial Pco(2) difference ((v-a)Pco(2)) and arterial-venous pH difference ((a-v)pH), and analyzed the physiological factors that affect these differences in healthy volunteers and hyperventilation patients.nnnRESULTSnIn healthy volunteers, both (v-a)Pco(2) and (a-v)pH increased during finger exercise or hyperventilation in an intensity-dependent manner. Doppler echography indicated that increases in (v-a)Pco(2) and (a-v)pH during hyperventilation are induced by reduction of peripheral blood flow. Approximately 40% of patients with untreated respiratory alkalosis were found to be incorrectly diagnosed if based only on VBGA.nnnCONCLUSIONSnIt must be noted that VBGA may lead to overestimation of acidosis and to underestimation of respiratory alkalosis when extremities muscles are active or patients are hyperventilating. Physicians should keep these limitations in mind when conducting VBGA.

Interactive Simulation System for Artificial Ventilation on the Internet: Virtual Ventilator

Objective. To develop an interactive simulation system “virtual ventilator” that demonstrates the dynamics of pressure and flow in the respiratory system under the combination of spontaneous breathing, ventilation modes, and ventilator options. The simulation system was designed to be used by unexperienced health care professionals as a self-training tool. Methods. The system consists of a simulation controller and three modules: respiratory, spontaneous breath, and ventilator. The respiratory module models the respiratory system by three resistances representing the main airway, the right and left lungs, and two compliances also representing the right and left lungs. The spontaneous breath module generates inspiratory negative pressure produced by a patient. The ventilator module generates driving force of pressure or flow according to the combination of the ventilation mode and options. These forces are given to the respiratory module through the simulation controller. Results. The simulation system was developed using HTML, VBScript (3000 lines, 100 kB) and ActiveX control (120 kB), and runs on Internet Explorer (5.5 or higher). The spontaneous breath is defined by a frequency, amplitude and inspiratory patterns in the spontaneous breath module. The user can construct a ventilation mode by setting a control variable, phase variables (trigger, limit, and cycle), and options. Available ventilation modes are: controlled mechanical ventilation (CMV), continuous positive airway pressure, synchronized intermittent mandatory ventilation (SIMV), pressure support ventilation (PSV), SIMV + PSV, pressure-controlled ventilation (PCV), pressure-regulated volume control (PRVC), proportional assisted ventilation, mandatory minute ventilation (MMV), bilevel positive airway pressure (BiPAP). The simulation system demonstrates in a graph and animation the airway pressure, flow, and volume of the respiratory system during mechanical ventilation both with and without spontaneous breathing. Conclusions. We developed a web application that demonstrated the respiratory mechanics and the basic theory of ventilation mode.

Hepatopulmonary syndrome associated with autoimmune liver cirrhosis.

A 46‐year‐old woman presented for evaluation of liver dysfunction and dyspnoea. Laboratory examination showed high levels of γ‐globulin, immunoglobulin (Ig)G, and antinuclear antibodies. Laparoscopy demonstrated hepatic cirrhosis. Despite normal spirometry, hypoxaemia (which was worse in standing position) and a low diffusing capacity were present. The shunt ratio calculated using arterial blood gas was 6.4%, but was 40% when measured using 99mTc‐macroaggregated albumin scanning. The discrepancy between the ratios indicated that hypoxaemia was caused by intrapulmonary vascular dilatation. The patient was diagnosed with hepatopulmonary syndrome associated with autoimmune liver cirrhosis.

Abdominal Muscle Function with Change in Posture or CO2 Rebreathing in Humans.

The relative respiratory function of the individual abdominal muscles in humans is not well defined. Abdominal muscles have been reported to act as a single unit during breathing1, yet others have reported differential activation of specific abdominal muscles during respiration2.