Effects of Neurotropin on polysomnographic patterns in normal humans

The effects of Neurotropin, an analgesic drug, on polysomnographic patterns were investigated in 6 male healthy volunteers aged from 18 to 23 years (mean age 21.1 years). Polysomnographic recordings were made for 6 consecutive nights from each subject. An inert placebo, identical to the Neurotropin tablets, was given on the first 3 nights and on the sixth night. Forty-eight mg of Neurotropin (4 tablets containing 12 mg of Neurotropin each) was administered on the fourth and fifth nights. The drug and placebo were administered orally 30 min before starting the record of polysomnograms, i.e. around 22.00 h and continued until the natural awakening of the subjects the next morning. The polysomnographic record of the first night was discarded from the data, because of the first night effect. Neurotropin, given on the fourth night, significantly reduced total sleep time, stage 3 and percent of stage 3 as compared to those of the baseline placebo nights. Neurotropin given on the fifth night significantly decreased only total awakening time. These effects were not observed on the sixth placebo night (recovery night). As for the subjective assessments, no obvious changes were observed after administration of the drug. These results suggest that Neurotropin decreases total sleep time as well as stage 3 sleep. However, these effects are transient and unaccompanied by rebound phenomena. It is further suggested that Neurotropin seems to elevate slightly and transiently the arousal level.     

Comparative double-blind trial of dl-alpha-tocopheryl nicotinate on vibration disease.

Sixty inpatients with vibration disease were examined on the effect of dl-alpha-tocopheryl nicotinate by comparative double-blind study. The observed period was 6 weeks and the dose was 6 capsules a day (600 mg as dl-alpha-tocopheryl nicotinate, Juvela Nicotinate, referred to as EN). The physical exercise therapy was applied to all patients throughout the test period. EN group became better with a significant difference from P (placebo) group in the subjective symptoms, the clinical examinations and the collective improving rate (p less than 0.01, 0.05, 0.01), respectively. The improvement of the subjective symptoms of both groups was higher 6 weeks than 3 weeks after administration. Most items in EN group became better significantly (p less than 0.05) as compared with those in P group. The examinations of the peripheral functions in EN group showed a significant improvement 6 weeks after administration in comparison with those in P group. Blood chemistry, blood cell counts and serum electrolytes changed within normal range. Thus, this preparation would be a curative agent for patients with vibration disease.     

Automatic real-time analysis of human sleep stages by an interval histogram method

A new interval histogram method for automatic, all-night sleep stage scoring, simulated on a digital computer, is described. The system consists of a 2-step analysis. The first step is recognition of elementary patterns in EEG, EOG and EMG, and the second step is the determination of sleep stages based on these parameters. Correlation of this method with power spectral analysis of the dominant EEG patterns during each sleep stage supported the reliability of the first step analysis. Overall agreement (89.1%) between the computer and human judges was only 3% less than the agreement (92.1%) among the scorers, indicating considerable reliability of the second step. The primary areas of disagreement that arose in the identification of sleep stages occurred with stages 1, 2 and REM. To improve scoring accuracy, the system may require epoch sequence information. The profile of the elementary parameters of the EEG signals clearly illustrated the cyclic nature of these activities throughout the night. The alpha and delta 2 waves clearly separated the awake state from sleep stages. Beta 2 can discriminate stages 1 and REM from stage 2, and the best indicator for distincting stage 1 from REM was muscle activity. Sigma and spindles were prominent during stage 2 sleep. Both delta 2 and high voltage delta waves distinguished stage 3 from stage 4. On the other hand, delta 1 was evenly distributed and seemed to be common to all sleep stages.     

Effects of mianserin on negative symptoms in schizophrenia.

The efficacy of mianserin as a supplement in treating chronic schizophrenia was tested in 20 inpatients with schizophrenia who were receiving fixed doses of neuroleptics. Mianserin was given for six weeks with a starting dose of 60 mg/day. A brief psychiatric rating scale (BPRS) was completed before starting mianserin and thereafter BPRS scoring was carried out once weekly. The total BPRS score and the score for negative symptoms were decreased by mianserin treatment as compared to the pre-treatment values. Plasma 5-HIAA concentrations were increased after medication in both responding patients and nonresponding patients. However, the 5-HIAA values of responders were lower than those of nonresponders. Plasma HVA levels were slightly increased by mianserin in the responders. There were no significant changes in MHPG levels. These results suggest that the negative symptoms of schizophrenia may be improved by mianserin treatment.     

Cancer mortality of male workers exposed to benzidine and/or beta-naphthylamine

The risk of cancer was analysed in a cohort of 604 male workers who had been engaged in manufacturing and/or handling benzidine and/or beta-naphthylamine during the period 1945-71 at two factories located in the city of Osaka. The cohort was followed up from 1 January 1970 to the date of death or 31 December 1986. The mean follow-up time was 16.1 years. A total of 84 deaths was found compared with 112.66 expected based on the mortality of the Osaka population. Thirty-six were found to be dead of malignant neoplasms; 9 stomach, 2 colon, 1 rectum, 3 liver, 1 bile duct, 1 pancreas, 1 maxillary sinus, 6 lung, 8 bladder, and 2 ureter neoplasms as well as 1 case of myeloid leukemia. Seven cases were ascertained on death certificates as neoplasms of uncertain behaviour, all of which were tumors of genitourinary organs except for one case of brain tumor. Cancers of genitourinary organs and tumors of uncertain behaviour showed statistically significant increased standardized ratios (SMR = 12.20, 4.89). The mean age of death of those having genitourinary organs including cancer was 59 years old, and the latent period between the first exposure and the occurrence of the disease was 19.7 years on average. Non-significant increased risks of cancers of the colon, rectum, liver and lung were observed among the workers exposed to benzidine. Among the 7 histologically confirmed cases of these cancers, there were 2 adenocarcinomas of the lung, 1 adenocarcinoma of the rectum, 2 hepatocellular carcinoma and 1 adenocarcinoma of the bile duct. Seven patients with genitourinary tumors were found to have died of other primary cancers.     

Application of a stent splint to protect intraoral organs from radiation injury in a 97-year-old patient with multiple oral cancers who survived to over 100 years old

Radiation therapy had been used with increasing frequency in recent years in the management of oral cancers of advanced ages. In those cases we have to take good care to maintain the oral health of patients undergoing cancerocidal dose of radiation therapy. Using splints, as a tissue displacer, during radiation, we could treat a 99-year-old female patient without serious radiation sequelae, successfully she survived over 100 year-old. As she visited us at 97 year-old, the primary lesions located on the left upper lip, nose, upper and lower gums were diagnosed as multiple verrucous carcinoma histologically. Seventeen months after the first radiotherapy to the lip, nose and upper jaw, we planned again radiotherapy to the recurrent tumor of the lower gum. In order to eliminate and minimize side effects of the second irradiation for the contiguous intraoral organs, we devised a splint to exclude the tongue and upper gum apart from a radiation field. The splint, as tissue displacer, was made of heat-cured acrylic resin and divided into two pieces which were formed like full denture without artificial teeth. They were applied to the upper and lower jaws. The lower one had a large wing to exclude the tongue from irradiation field. After setting of the splint, she had been clenched slightly with an aid of chin cap. Then we could finish successfully the radiotherapy with 10 MV X-ray 40 Gy as scheduled without serious troubles.     

Development of stress-induced gastric lesions involves central adenosine A1-receptor stimulation

When rats were exposed to immobilization stress for 1-12 h, gastric lesions did not occur at 1-6 h but did at 12 h of immobilization. Exogenous adenosine increased stress-induced gastric lesions, and dipyridamole, a blocker of adenosine uptake, potentiated the action of adenosine. The selective adenosine A1-receptor stimulants N6-cyclohexyl adenosine (CHA) and N6-(L-phenylisopropyl) adenosine (L-PIA) produced gastric lesions even in non-stressed state and markedly potentiated in dose- and time-dependent manner in stressed state. The stimulatory effect of N6-(D-phenylisopropyl) adenosine (D-PIA) on ulceration was weaker than that of CHA or L-PIA. Furthermore, intracerebral ventricular (i.c.v.) injection of adenosine or adenosine analogues produced the most rapid and most potent exacerbation of stress-induced gastric lesions relative to those induced with subcutaneous (s.c.) injection. The stress lesions enhanced by CHA were not affected by phentolamine, yohimbine, prazosin, naloxone and cholecystokinin (CCK8) but were inhibited by caffeine, clonidine, morphine and beta-endorphin. The inhibitory effect of clonidine was not antagonized by yohimbine or prazosin. The inhibition by morphine was selectively antagonized by exogenous CCK8 as well as naloxone. These results suggest that endogenous adenosine is tonically active in stress lesion formation which is modulated by opiate systems. Clonidine as well as caffeine may function as a purinoceptor antagonist, and it seems unlikely that the inhibitory effect of clonidine on stress ulcer is due to activation of alpha-adrenoceptors.     

A case of advanced rectal cancer responding to oral UFT and Leucovorin-based preoperative chemoradiation therapy

We report a case of a 44-year-old male with advanced lower rectal cancer that showed a significant effect after preoperative chemoradiation therapy. Preoperative radiation and chemotherapy included whole pelvis irradiation (30 Gy in total), oral UFT (500 mg/day), and Leucovorin (75 mg/day) was administered daily for 4 weeks. Consequently, the patient underwent a total pelvic exenteration with lymph node dissection (D 3). Histopathological findings showed: invasion to peritoneum(Ai); stage IIIa with n(-); and histological grading, Grade 2. Preoperative chemoradiation therapy appears to be effective for locally advanced lower rectal cancer.