[Clinical efficacy of arbekacin on MRSA pneumonia].

Arbekacin sulfate (ABK) was administered by intravenous drip to pneumonia patients infected with methicillin-resistant Staphylococcus aureus (MRSA), and the efficacy and the safety were objectively evaluated by the executive committee. The daily dose was determined in principle as 150-200 mg, two times a day, 30-90 minutes drip infusion, and the dose was to be changed at each special occasion. Combined therapy with other antibiotics was scheduled in severe cases at a decision of the physician in charge. Data of 18 cases were accumulated. The efficacy could be evaluated for 12 cases (4 cases with ABK alone, and 8 cases with combined therapy), and the safety was evaluated for 18 cases. The clinical efficacy was: excellent, 1; good, 4; fair, 5; and poor, 2. The efficacy rate was 41.7%. The bacteriological effect was: eradicated, 2 (16.7%); decreased, 2; and no change, 8. There found no side effects except 3 cases of abnormal laboratory data, two abnormal renal functions(11.1%) and one abnormal hepatic function (5.5%). In one of the renal disorders, decreased dose of ABK improved the function. In the other case, the impaired renal function lasted until death by heart failure. In the case of abnormal function, discontinuing the ABK therapy improved the hepatic function. In the 4 out of 5 cases that showed excellent or good clinical efficacy, patients recovered within relatively early days of ABK therapy. The average days for recovery was 7.8.

[Epidemiological study of snoring--a questionnaire survey in factory workers].

There has been no epidemiological study of snoring in Japan, and we therefore performed a questionnaire survey (in about 7,000 adult men working at a steel-making factory at the time of the yearly health examination, and investigated the relationship between the severity of snoring and 17 items including age, obesity, family history of snoring, daytime hypersomnolence, hypertension, smoking, alcohol intake and traffic accidents. We classified all the subjects into three groups, no snoring, mild snoring, and severe snoring group. We defined severe snorers as persons who snored loudly in both inspiratory and expiratory phases and those who snored loudly with apnea. We found that aging, obesity, smoking and alcohol intake are risk factors for snoring. Compared with non-snorers, severe snorers were found to have a high incidence of family history of snoring, daytime hypersomnolence, and history of treatment of hypertension. No relationship was found between the severity of snoring and the occurrence of automobile accidents. The proportion of severe snorers over 40 years old with obesity, daytime hypersomnolence and morning headache was 0.25%, representing the group that may have obstructive sleep apnea syndrome. The probable incidence of sleep apnea syndrome in men may be considerably lower in Japan compared with that in either U.S.A. or Europe.

[A case of obstructive sleep apnea syndrome remarkably improved by gastric restriction surgery].

A 23-year-man with morbid obesity and obstructive sleep apnea syndrome (OSAS) was admitted. He was 170 cm in height and 170 kg in weight. He underwent dietary treatment several times, but his weight returned to its original level, or even higher, within a short period. A diagnosis of OSAS was made by nocturnal polysomnography. In this morbidly obese patient with OSAS a nocturnal sleep apnea study was performed before and after weight reduction surgery (gastric restriction). The postoperative findings revealed a dramatic body weight reduction. At the same time, the results of apnea and oxygen desaturation were remarkably improved too. These results indicate that weight reduction surgery is a definitely effective treatment for morbid obesity associated with OSAS.

[Clinical evaluation of cefteram pivoxil in respiratory tract infections].

The usefulness of cefteram pivoxil (CFTM-PI) was evaluated in 99 cases with respiratory tract infections: 32 cases with acute bronchitis, 51 cases with infectious exacerbations of chronic respiratory diseases and 16 cases with pneumonia. 1. The clinical efficacies included marked improvement in 27 cases, improvement in 51 cases, moderate improvement in 9 cases, no change in 10 cases and deterioration in 2 cases. The improvement rate was 78.8%. 2. Overall effects were excellent in 12 cases, good in 9 cases and fair in 5 cases. There was no case in which efficacy was not observed and the efficacy rate was 80.8%. 3. Bacteriological effects were classified according to the causative organisms. Eradication rate was 80.8% (21 of 26 strains), indicating an excellent antibacterial action of CFTM-PI. In particular, MICs of cefteram were below 0.05 microgram/ml against all 10 strains of Haemophilus influenzae regardless of beta-lactamase production even with an inoculum of 10(8) or 10(6) cells/ml. 4. Side effects rarely occurred and included a slight gastrointestinal irritation in 4 of 99 cases (4%). Two cases which had abnormal elevations of GOT and GPT had abnormal values prior to administration of CFTM-PI. The elevations were slight and it was possible to continue administration. The GOT and GPT values were improved after the end of administration. The above results indicate the usefulness of CFTM-PI in acute respiratory infections and infectious exacerbation of chronic respiratory diseases.

[Indications for home oxygen therapy in cases of sleep oxygen desaturation].

Home oxygen therapy is now considered indicated in cases of severe sleep oxygen desaturation. To explore whether we could choose cases with severe sleep desaturation by measurement of waking physiological parameters, we examined the relationship between arterial blood gases, lung functions and pulmonary artery pressure while awake and the degree of sleep oxygen desaturation in 21 patients with chronic obstructive pulmonary disease and 22 cases with a past history of pulmonary tuberculosis. There were significant correlations between waking PaO2, PaCO2 and pulmonary artery mean pressure and sleep lowest SaO2, respectively, whereas no significant relation was found between %VC or FEV1.0% and sleep lowest SaO2. However, we found wide ranges of PaO2 and PaCO2 in cases who had 10 min or more with SaO2 below 85% during sleep. This was also true in the patients who underwent 60 min or more with SaO2 below 85% while a sleep. These results suggest that it may be difficult to find out the indications for cases with severe sleep desaturation by evaluation of arterial blood gases while awake.

[Open loop gain of the CO2-ventilation feedback control system in chronic obstructive pulmonary disease].

To evaluate the stability of the CO2-ventilation feedback system, we measured its open loop gain (G) in 12 patients with chronic obstructive pulmonary disease (COPD) and 15 control subjects. Then, we compared G to the conventional slope of the CO2-ventilation response line (S) and that of the metabolic hyperbola (SL). G was determined as the ratio of S to SL by applying external dead space of 250 and 500 ml. G, S and 1/SL in the control and the COPD were +17.1 +/- 7.2 (Mean +/- SD), 1.70 +/- 0.75 L.min-1.Torr-1 and -10.4 +/- 2.0 L-1.min.Torr, and -7.2 +/- 3.3, 0.48 +/- 0.27 L.min-1.Torr-1 and -16.1 +/- 6.4 L-1.min.Torr, respectively. G was significantly correlated with S in both groups, but that was not the case in 1/SL. The magnitude of G and S in COPD was about 42% and 28% of the control, indicating that G was maintained more stable than S. These data suggest that the decreased G in the COPD resulted from insufficient compensation of ventilatory drive, whereas 1/SL increased higher than the control. We conclude that G can be used to indicate the stability of the CO2-ventilation feedback system better than S.

Progesterone therapy for sleep apnea syndrome evaluated by occlusion pressure responses to exogenous loading.

We investigated the mechanisms of the beneficial effect derived from progesterone therapy for sleep apnea syndrome (SAS). Nine patients with SAS were treated for 7 days with chlormadinone acetate (CMA), a respiratory stimulant known to increase not only CO2 and hypoxic chemosensitivity but also respiratory drive response for ventilatory loading. They were examined as to sleep events and ventilatory control during wakefulness before and during CMA treatment. Apnea-hypopnea index was significantly reduced from 51.1 +/- 5.7 to 43.6 +/- 8.1 episodes/h (p less than 0.05). The ratio of desaturation time with more than 4% SaO2 fall to total sleep time was diminished in seven of nine patients, and its mean value decreased from 44.9 +/- 8.6 to 28.7 +/- 8.1% (p less than 0.05). Both hypercapnic ventilatory response (HCVR) and load response during wakefulness were significantly increased, although isocapnic hypoxic ventilatory response (HVR) was not significantly enhanced by CMA. The degree of augmentation in awake load response as well as in HCVR was positively correlated with that of improvement in sleep-disordered breathing. Moreover, patients who did not show amelioration in oxygen desaturation were found to be incapable of increasing load response despite increased HCVR. We conclude that CMA therapy for sleep apnea syndrome is effective in the patients whose load response as well as respiratory control activity are augmented during wakefulness.

Arterial oxygen desaturation during sleep in interstitial pulmonary disease. Correlation with chemical control of breathing during wakefulness.

Patients with IPD often develop oxygen desaturation during sleep. We investigated whether or not the degree of falls in SaO2 during sleep were correlated with the daytime data of pulmonary function tests, arterial blood gas tensions, or ventilatory responses to chemical stimuli. Fourteen patients with IPD who had restrictive ventilatory impairment were studied to evaluate these relationships. The magnitude of SaO2 depression from awake to REM sleep was inversely correlated with the level of baseline SaO2. Hypercapnic ventilatory response was inversely related to the amount of maximal desaturation in both REM and NREM sleep. These results indicate that patients with IPD who have insufficient ventilatory response to hypercapnia reveal larger falls in SaO2 during sleep, particularly if they have lower baseline SaO2.

Periodic breathing at high altitude and ventilatory responses to O2 and CO2.

To determine the relationship between periodic breathing (PB) during sleep at high altitude and ventilatory chemosensitivities, we studied nine Japanese climbers who participated in the expedition to the Kunlun Mountains (7,167 m) in China in 1986. At sea level, ventilatory response to hypoxia (HVR) by isocapnic progressive hypoxia test and to hypercapnia (HCVR) by Read's method were examined. At altitude 5,360 m, respiratory movements of the chest and abdominal wall, SaO2, ECG, and HR were monitored. Seven climbers manifested PB during sleep. There was a significant correlation between PB during sleep and HVR and HCVR (p less than 0.05). All the climbers showed severe desaturation during sleep. There was a significant negative correlation between degree of desaturation during sleep and HVR (p less than 0.05). A negative correlation was also detected between PB and the degree of desaturation during sleep. We concluded that ventilatory chemosensitivities play an important role in eliciting PB and that climbers with high HVR can maintain their arterial oxygenation during sleep, due to hyperventilation induced by PB, which is considered an advantageous adaptation for lowland sojourners.

Abnormal breathing during sleep and chemical control of breathing during wakefulness in patients with sleep apnea syndrome.

The possible role of ventilatory control in relation to sleep apnea has not yet been clarified. We investigated the relationship between awake ventilatory drives to hypoxia and hypercapnia and sleep-disordered breathing in 21 subjects with sleep apnea syndrome. The awake hypoxic ventilatory drive, which was evaluated by occlusion pressure responses, was inversely correlated with the magnitude of maximal oxygen desaturation during sleep as well as the ratio of duration with more than 4 and 10% oxygen desaturation to total sleep time. On the other hand, the awake hypercapnic ventilatory drive was not correlated with these parameters of sleep desaturation. Apnea index and duration were not correlated with the degree of hypoxic or hypercapnic ventilatory drive, respectively. Our study concluded that sleep desaturation is better correlated with hypoxic ventilatory drive than with hypercapnic ventilatory drive in patients with sleep apnea syndrome. These results are different from the results obtained in the patients with COPD in our previous study.

Obese patients with sleep apnea syndrome treated by progesterone.

Two obese patients with sleep apnea syndrome were administered chlormadinone acetate (CMA), a synthetic progesterone, known as a potent respiratory stimulant to augment load compensation response as well as CO2 chemosensitivity. Before CMA administration, both cases showed normal chemosensitivity of hypoxic and hypercapnic ventilatory responses (HVR and HCVR) at daytime, although marked oxygen desaturation with sleep apnea was observed. During CMA administration for 7 days, HVR, HCVR and occlusion pressure response to flow-resistive loading were altogether augmented. In one case obstructive sleep apnea (OSA) was altered to obstructive hypopnea, and in the other case central apnea disappeared completely, resulting in remarkable improvement of oxygen desaturation at sleep and daytime somnolence in both cases. We conclude that CMA might be useful in the treatment of sleep apnea syndrome.

Sex differences in awake ventilatory drive and abnormal breathing during sleep in eucapnic obesity.

We studied hypoxic and hypercapnic ventilatory drives in 22 eucapnic obese subjects (14 female and eight male subjects) referred for weight reduction therapy and 23 normal subjects (eight female and 15 male subjects). In the female subjects, both occlusion pressure, currently used as an indicator of ventilatory drive, and ventilatory responses to hypoxia, as well as occlusion pressure response to hypercapnia, were significantly greater in the obese than in the normal subjects; however, no significant differences in these responses between male obese and male normal subjects were observed, except for the hypoxic occlusion pressure response. We also studied disordered breathing during sleep in the obese subjects, and male predominance in abnormal breathing and oxygen desaturation was noted. These results showed that obese female subjects increased their hypoxic and hypercapnic chemosensitivities against their body mass loading, which was not evident in obese male subjects. The relatively depressed chemosensitivities of the latter may be related to disordered breathing and oxygen desaturation during sleep.

Effects of acetazolamide in patients with the sleep apnoea syndrome.

There is as yet no convincing evidence that acetazolamide, a carbonic anhydrase inhibitor, is effective in obstructive sleep apnoea. A study was therefore designed to examine the effect of acetazolamide (250 mg/day) on sleep events and ventilatory control during wakefulness in nine patients with the sleep apnoea syndrome. In eight of the nine patients the apnoea index and the total duration of apnoea were reduced by acetazolamide, and the mean (SEM) apnoea index of all patients changed from 25.0 (6.7) to 18.1 (5.8) episodes an hour. Furthermore, the total time of arterial oxygen desaturation (SaO2)--more than 4% depression in SaO2 from the baseline sleeping level--divided by total sleep time was also significantly decreased and its mean (SEM) value improved from 24.1 (7.9) to 13.6 (4.8)% of total sleep time. Five of the seven patients with varying degrees of daytime hypersomnolence had their symptoms obviously improved. There was no patient whose predominant type of apnoea was converted from the obstructive to the central type, or vice versa. In the studies of wakefulness, metabolic acidosis, an increase of arterial oxygen tension (PaO2) and a decrease of arterial carbon dioxide tension (PaCO2) were observed. The slopes of the occlusion pressure response and the ventilatory response to carbon dioxide increased, and the carbon dioxide ventilatory response line shifted to the left. It is suggested that acetazolamide cannot remove apnoea completely but has a beneficial effect in mild cases of obstructive sleep apnoea through an augmentation of central (CO2, H+) drive and a stabilising effect on ventilatory control.

Effect of chlormadinone acetate on sleep arterial oxygen desaturation in patients with chronic obstructive pulmonary disease.

Twelve patients with chronic obstructive pulmonary disease (COPD) were studied in order to evaluate the effect of chlormadinone acetate (CMA), a potent synthetic progesterone, on the degree of hypoxemia during sleep. In patients designated as "correctors," in whom an increase in minute ventilation (VI) during wakefulness was brought about mainly by an increase in tidal volume (VT) and PaCO2 was effectively decreased by the administration of CMA, this agent also proved to be effective during sleep, with hypoxemia improved during both NREM and REM sleep. On the other hand, in patients called "noncorrectors" in whom a decrease in PaCO2 was not seen during wakefulness with CMA, there was also no effect during sleep. These results indicate that CMA is effective in certain selected patients with COPD.