Treatment of obstructive sleep apnea syndrome with a Kampo-formula, San'o-shashin-to: a case report.

The following describes a 76-year-old male with obstructive sleep apnea syndrome successfully treated with a Kampo-formula, San'o-shashin-to (Formula medicamentorum tres ad dispellendi cordis). Polysomnography, performed before and after administration of San'o-shashin-to, revealed that the apnea index decreased from 11.1 events/hour to 4.1 events/hour, and that the apnea plus hypopnea index decreased from 18.4 events/hour to 10.7 events/hour. The patient was normo-weight (body mass index: 20.4 kg/m2), and events of sleep apnea and hypopnea were mostly noted during a non-rapid eye movement sleep. It is possible that San'o-shashin-to has some alleviating effects on the upper airway resistance during sleep.

A case of subwakefulness syndrome.

We report a patient, a 30-year-old male Japanese-Brazilian migrant construction worker, suffering from excessive daytime sleepiness for at least 6 months. Electroencephalogram recordings during his waking states showed that 10-Hz and 60-microV alpha activity was present prominently in the occipital regions. From the multiple sleep latency test, it was found that stages 1-2 NREM sleep episodes appeared repetitively without any REM episodes, and that the mean sleep latency was 10.2 min. These findings support the diagnosis that this patient suffers from subwakefulness syndrome.

Chronic toxicity of indium arsenide and indium phosphide to the lungs of hamsters.

Chronic toxicity of indium arsenide (InAs) and indium phosphide (InP) was studied in male Syrian golden hamsters which received InAs or InP particles containing a total dose of 7.5 mg of arsenic or phosphorus by intratracheal instillations once a week for 15 weeks. As a control, hamsters were treated with the vehicle, phosphate buffer solution. During their total life span, the cumulative body weight gain of hamsters in the InAs group was suppressed significantly compared with that in the control group, but not in the InP group when compared with that in the control group. Concerning the histopathological findings of the lung, the incidence rates of proteinosis-like lesions, alveolar or bronchiolar cell hyperplasia, pneumonia, emphysema and metaplastic ossification observed in the InAs or InP group were significantly higher than those observed in the control group. From these results, it would seem that InAs and InP produced severe damage to the lungs of hamsters.

Chronic toxicity of tar from heavy-duty diesel exhaust following intratracheal instillations to the lungs of hamsters.

Chronic toxicity of tar from heavy-duty diesel exhaust (HD tar) was studied in male Syrian golden hamsters which received 15 mg, 7.5 mg or 1.5 mg of HD tar as the total dosages by intratracheal instillations once a week for 15 weeks. As a control group, hamsters were treated with the 0.1 ml of Tween 60: ethanol: phosphate buffer (pH 6.88, 0.25 M) solution (5.8: 8.7: 100 by volume) once a week in the same manner. The survival rate during the instillation period in the group given 15 mg of HD tar, the high-dose group of HD tar, was the lowest, and the effect was dose-dependent. However, the survival rates during the subsequent observation period showed no marked differences among HD tar treated groups. During their total life span, one papilloma in the larynx was seen in the 44 hamsters in the group given 1.5 mg of HD tar, one papilloma in the larynx was appeared in the 59 hamsters in the group given 1.5 mg of HD tar and one lung adenoma was developed in the 58 hamsters in the control group. There were no tumors in the respiratory tract in the group given 7.5 mg of HD tar. Concerning the histopathological findings of the lung, the incidence of alveolar cell or bronchiolar cell hyperplasia in the group given 1.5 mg of HD tar was significantly higher than that in the control group. From these results, although we could not observe any tumorigenicity or carcinogenic effect of HD tar, it would seem that HD tar caused weak but positive damage to the lungs of hamsters.

The frequency of spontaneously-occurring neoplasms in the male Syrian golden hamster.

The frequency of spontaneously-occurring neoplasms in the male Syrian golden hamster, often used as a control in carcinogenic studies, was examined. The hamsters were divided into 2 groups: Group 1 received 0.1 ml of the phosphate buffer vehicle intratracheally once a week for 15 w; Group 2 received 0.1 ml of Tween 60:ethanol:buffer (5.3:8.7:100 by volume) in the same manner. The mean survival days of hamsters' total life-span were 574.9 +/- 176.1 d in Group 1 and 427.7 +/- 178.1 d in Group 2. Tumor incidence rates were 10.6% (16/148) in Group 1 and 11.5% (13/113) in Group 2. The mean survival days for tumor-bearing hamsters in Group 1 was 692.0 +/- 80.7 d and was 650.8 +/- 74.2 d in Group 2. Most tumors increased with advancing hamster age. The most common neoplasm was adrenal gland tumors (Group 1 = 4.7%, Group 2 = 8.8%). The occurrence of other tumors in other organs was low. The Syrian golden hamster is a suitable animal model for evaluating chemical carcinogenicity.

Effects of glutathione depletion on the acute nephrotoxic potential of arsenite and on arsenic metabolism in hamsters.

Our previous study showed that pretreatment with buthionine sulfoximine (BSO), which inhibits glutathione synthesis, results in acute renal failure with oliguria in hamsters ingesting sodium arsenite (5 mg As/kg). For a deeper understanding of the relationship between arsenic metabolism and the subsequent development of nephrotoxicity, we studied excretion, tissue retention, biotransformation, pharmacokinetics, and histopathological events in the kidneys of hamsters both with and without BSO pretreatment. The total amount of arsenic excreted in the urine and feces within 72 hr of arsenite administration was more than fivefold lower in BSO-pretreated animals than in the controls without pretreatment (9.2 versus 53.4% of the arsenic dose). The persistence of high amounts of total arsenic was apparent in the blood, liver, and kidneys of BSO-pretreated hamsters, even though the content of inorganic arsenic steadily decreased with time. The disappearance of inorganic arsenic from the blood showed a biphasic elimination pattern characterized first by a rapid component with a half-life of 4.5 hr and second by a slower component with a half-life of 58.0 hr in the BSO-pretreated hamsters, while these half-lives were 0.6 and 11.0 hr, respectively, in the controls. BSO pretreatment not only impaired the excretion of inorganic arsenic, but also impaired its methylation. Combined BSO/arsenite treatment resulted in renal tubular necrosis which was prominent at 1 hr after arsenite administration. By 1 hr, the renal content of inorganic arsenic in the BSO-pretreated animals was 1.7 times higher than that in the controls. This study demonstrates that glutathione depletion elicits the nephrotoxic manifestations of arsenic poisoning.

Arsenic intake and excretion by Japanese adults: a 7-day duplicate diet study.

The amount of arsenic in the urine, faeces and in duplicate diets of two couples who had eaten customary Japanese meals were monitored for 7 days by arsine-generator atomic absorption spectrophotometry. For the four volunteers, the mean daily intake of arsenic from their diets was 182 micrograms (range 27 to 376 micrograms). The dietary arsenic was composed of 5.7% inorganic arsenic, 3.6% methylarsonic acid, 27.4% dimethylarsinic acid and 47.9% trimethylarsenic compounds. The mean amounts of arsenic eliminated daily in urine and faeces were 148 micrograms (50-416 micrograms) and 46 micrograms (0-138 micrograms), respectively. The urinary arsenic was composed of 1.4% inorganic arsenic, 3.5% methylarsonic acid, 33.6% dimethylarsinic acid and 61.4% trimethylarsenic compounds. The daily intake of arsenic influenced the total amount of arsenic excreted in the urine (r = 0.7302, P less than 0.01) and the amount eliminated in the faeces (r = 0.5900, P less than 0.01) the next day. Specifically, there was also a significant correlation between the daily intakes of trimethylarsenic compounds and dimethylarsinic acid and the amounts of these compounds found in the urine the following day (r = 0.6833, P less than 0.01 and r = 0.6630, P less than 0.01, respectively). Considering the amounts of arsenic compounds present in seafood and in other components of the diet together with the urinary elimination patterns of arsenic compounds, it seemed probable that the trimethylarsenic compounds in the urine originated largely from fish and shellfish, which contain mainly arsenobetaine. Trimethylarsenic compounds in the urine should therefore be the preferred indicator of arsenic arising from the ingestion of seafood, especially fish and shellfish. In this study, the mean daily intake of inorganic arsenic from the diet (0.18 micrograms/kg) did not exceed the FAO/WHO JECFA Tolerable Daily Intake of 2 micrograms inorganic arsenic kg.

Variation of trace metals in ancient and contemporary Japanese bones.

Excavated and contemporary bones (rib cortexes) of a mature age (40-60 yr) were analyzed by atomic absorption spectrometry for the concentration of seven elements, including Ca, Cd, Cu, Fe, Mn, Ni, and Pb, with a view to historically evaluating the chemical composition of the bones. Fifty-two well-preserved specimens, obtained from western Japan, were classified into six groups according to Japanese prehistoric and historic eras (Jomon, Yayoi, Kofun, Muromachi, Edo, and Contemporary). Average concentrations of Ca were 0.20-0.33 g/g in the excavated bones and 0.17 g/g in the contemporary bones. Among the trace metals, such as Cu, Fe, Mn, and Pb, which showed remarkably elevated concentrations in the Edo era bones, Cu, Fe, and Mn were found to be strongly associated with soil contamination. Lead levels only slightly increased between the Jomon and Kofun eras, but became abruptly elevated following the Edo era. In contrast, the concentrations of Cd increased abruptly in the Yayoi era to a level with an order of magnitude higher than the Edo era, and they have recently decreased to rather low contemporary levels. This tendency becomes clearer when comparing the molar ratio of trace metals to Ca. The cause of elevated Cd concentrations in early excavated bones is discussed in relation to the mineralization of bones and the surrounding environment.

A comparison of the carcinogenicity of N-nitrosodiethylamine and N-nitrosodimethylamine after intratracheal instillation into Syrian golden hamsters.

N-Nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA) were instilled intratracheally into male Syrian golden hamsters once a week for 15 wk. The total dosages were 1.5 mg and 7.5 mg of NDEA and 0.75 mg and 1.5 mg of NDMA. A control group simultaneously received phosphate buffer vehicle. Tumours related to instillation appeared principally in the respiratory tract and the liver. Over the entire lifespan of the animals tumour incidence rates in the respiratory tract were 100% in both the NDEA groups, 6% in both NDMA groups and 8% in the control group. The total incidences of liver tumours were 6% in the 0.75 mg NDMA group, 19% in the 1.5 mg NDMA group, zero in the NDEA groups, and 4% in the control group. These results indicate that, when administered by this route, NDEA is a much more potent carcinogen in the respiratory tract than is NDMA but NDMA alone seems to be carcinogenic to the liver, at a total dosage of 1.5 mg.

Comparative study on the carcinogenicity of N-nitrosodiethylamine, N-nitrosodimethylamine, N-nitrosomorpholine, N-nitrosopyrrolidine and N-nitrosodi-n-propylamine to the lung of Syrian golden hamsters following intermittent instillations to the trachea.

N-Nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), N-nitrosomorpholine (NMOR), N-nitrosopyrrolidine (NPYR) and N-nitrosodi-n-propylamine (NDPA) were instilled into the lungs of male Syrian golden hamsters by intratracheal instillations once a week for 15 weeks. The total doses given were 1.5 mg of each drug. As a control, hamsters were treated with the vehicle, phosphate buffer solution. During the total lifespan, tumor incidence rates in the respiratory organs were 100% in the NDEA group, 6% in the NDMA group, 43% in the NMOR group, 0% in the NPYR group, 72% in the NDPA group and 4% in the control group. The incidence rates in the liver were 19% in the NDMA group and 4% in the NPYR group. No liver tumors developed in the other groups. The carcinogenic potencies of these N-nitroso compounds to the respiratory organs was provisionally estimated to be in the following order: NDEA greater than NDPA greater than NMOR greater than NDMA = NPYR, at the 1.5 mg dosage level. However, the difference in the rates of tumor incidence between the NDMA or NPYR group and the control group was not significant.

Lead levels in ancient and contemporary Japanese bones.

During the past few centuries, lead production, consumption and emissions, to our total environment have increased remarkably. We have determined the concentrations of lead in 41 well-preserved ancient and 11 contemporary rib bones of a mature age (40-60 y), with a view of historically evaluating lead exposure in humans. The oldest Japanese bones (1000-300 B.C.) were found to contain a mean of 0.58 microgram Pb/g dry wt and a mean molar ratio of lead to calcium of 0.6 x 10(-6), compared with 4.7-5.2 x 10(-6) in the bones of the Edo era (1600-1867 A.D.) and contemporary residents in Japan. The mean molar ratios of female bones were always higher than those of male bones for each era. From this fact we may assume that facial cosmetics were one of the main routes of lead exposure among the ancient Japanese, especially those who lived during the Edo era.

Tumorigenicity of inorganic arsenic compounds following intratracheal instillations to the lungs of hamsters.

The tumorigenicity of arsenic trioxide (As2O3), calcium arsenate (Ca3(AsO4)2) and arsenic trisulfide (As2S3) was studied in male Syrian golden hamsters which received arsenic compounds containing a total dose of 3.75 mg arsenic by means of intratracheal instillations once a week for 15 weeks. As controls, some hamsters were treated with only the vehicle, phosphate buffer solution. During the animals' total life span, one lung adenocarcinoma was seen in the 17 hamsters in the As2O3 group, one lung adenocarcinoma and 6 lung adenomas in the 25 hamsters in the Ca3(AsO4)2 group, one lung adenoma in the 22 hamsters in the As2S3 group and one lung adenosquamous carcinoma in the 21 hamsters in the control group. From these results, we conclude that calcium arsenate is tumorigenic to the lungs of Syrian golden hamsters. The results concerning the other 2 arsenic compounds were not conclusive.

Some secular changes in body height and proportion of Japanese medical students.

Anthropometric dimensions of 738 medical students at Kyushu University in Japan were analyzed to determine secular changes of height and body proportions during a 20-year period. Since 1961, means of standing height, leg length, and ratio of leg length to standing height have increased, although the rate of increase from 1971 to 1981 has been rather slow. On the contrary, the mean sitting height X 100/standing height has declined during this same period. Compared with data on the Japanese general population, the medical students were considerably taller, but the difference has decreased.

Comparative study on the carcinogenicity of N-nitrosodiethylamine and benzo[a]pyrene to the lung of Syrian golden hamsters induced by intermittent instillations to the trachea.

N-Nitrosodiethylamine (NDEA) and benzo[a]pyrene (B[a]P) were intratracheally instilled into female Syrian golden hamsters 15 times weekly for about 4 months. The total dose given was 15 mg. The control hamsters were given only phosphate buffer solution. During the total life span, tumor incidence rates in the NDEA and B[a]P groups were 100% and 46%, respectively, and no tumor developed in the controls. We concluded that the high rate of carcinogenicity of NDEA seen in the respiratory organs of Syrian golden hamsters must be given increased attention.

Tumorigenicity of arsenic trioxide to the lung in Syrian golden hamsters by intermittent instillations.

The tumorigenicity of arsenic trioxide was investigated in female Syrian golden hamsters which were given a total of 5.25 mg or 3.75 mg as arsenic by intratracheal instillations once a week. As controls, hamsters were treated with the vehicle, phosphate buffer solution. During the total life span, 3 lung adenomas were manifested in 10 hamsters or 2 lung adenomas in another 20 hamsters after 15 instillations of arsenic, while no lung tumor was detected among 35 hamsters in 2 control groups. The results show that arsenic trioxide is tumorigenic to the lung of Syrian golden hamsters.

High speed rotating scanner for transesophageal cross-sectional echocardiography.

In conventional cross-sectional echocardiography, the configuration of the chest or the presence of excessive chest wall tissue or air-containing lung often limits the resolution and field of view. To increase the diagnostic capability of cross-sectional echocardiography, a transesophageal ultrasonic high speed rotating scanner that can obtain cardiac images without hindrance from ribs, sternum and lung was developed. The scanner uses a single small transducer with a flexible shaft to permit easy swallowing by adults and mechanically scans ultrasonic beams within the esophagus. The small transducer in the esophagus is rotated through a full 360 degrees at a rate of 15 to 50 cycles/s, and cardiac images obtained through the esophageal wall are displayed on a cathode ray tube in real time. The transesophageal scanning technique was evaluated in more than 50 adult patients. Aside from some slight gagging, no serious complications were encountered. In all patients, high quality images of most portions of the heart were obtained. There was little difference in the image quality among various patients.