Behavioral treatment for chronic insomnia]

The efficacy of non-pharmacological intervention for chronic insomnia has been proven by several meta-analytic reviews, an NIH report, an American Academy of Sleep Medicine review, and numerous clinical trials. Behavior therapy for chronic insomnia consists of relaxation, stimulus control, sleep restriction, cognitive restructuring and sleep hygiene education, which has produced reliable and durable changes in total sleep time, sleep onset latency, number and duration of awakening. These studies also showed that the post-treatment effect of behavior therapy is equal to that of hypnotic therapy, and that these effects were maintained for 6 months on follow-up assessment. Elderly insomniac patients would gain considerable benefit from behavioral treatments because there are no adverse physical effects as there are from pharmacological therapy. The authors present the basic theory, techniques of behavior therapy for insomnia, and the results of two important key meta-analytic reviews. Any behavioral approach such as convenient education, self-care enhancement by bibliotherapy, and individual face-to-face counseling, seem to be fruitful not only for American but also Japanese insomnia patients. Nonetheless, there are no currently actual intervention studies using behavior therapy in Japan. We have discussed the methodology of intervention study and published a behavioral self-help manual for people with sleep problems. Development of a behavioral approach to chronic insomnia seemed to be very beneficial and a useful contribution to mental health services.     

Combined operation for renovascular hypertension and ischemic heart disease

We have experienced two patients of ischemic heart disease associated with renovascular hypertension. Patient 1 (60-year-old man) underwent LV aneurysmectomy and triple aortocoronary bypass grafting (saphenous vein to diagonal branch, left internal mammary artery to obtuse marginal branch, and right gastroepiploic artery to right coronary artery). Seventy five days after the initial cardiac surgery endarterectomy for the left renal artery and bifurcated Dacron graft implantation for the iliac artery obstruction were performed. Patient 2 (62-year-old woman) underwent simultaneous operation of both right nephrectomy and triple aortocoronary bypass grafting (saphenous vein grafts to obtuse marginal branch and right coronary artery, and left internal mammary artery to left anterior descending artery). Their postoperative courses were uneventful except unstable and high blood pressure for four to seven days after the operation. It appears that it should be decided to achieve either simultaneous or two stage approach for ischemic heart disease associated with renovascular hypertension based on the preoperative cardiac function. And both postoperative cardiac function and hypertension should be carefully managed until the blood pressure becomes stable after the surgery.     

Successful Treatment of Adult T-cell Leukemia/Lymphoma with MACOP-B,M-FEPA and VEPP-B Combination Chemotherapy

A 45-year-old man was referred to our department in March of 1989. Physical examination showed erythroderma, palmo-plantar hyperkeratosis, generalized lymphadenopathy, hepatosplenomegaly, and leukemic manifestation. The lymphocyte count in the peripheral blood before treatment was 1.7 × 10⁴ cells/mm³. Atypical lymphocytes such as flower cells and lobulated cells were seen in the peripheral blood. A sample excised from a lymph node showed immunoblastic, pleomorphic T cells by a modified classification scheme of the Working Formulation. A high level of serum LDH was detected (2.1 times the upper normal limit). Anti HTLV-1 antibody was also detected in the serum. The atypical lymphocytes were positive for CD3, CD4, CD5, CD7 and HLA-DR, and negative for CD8. Thus, the clinical, pathologic and immunologic features were those of typical acute-type ATL. The patient was treated with VEPA-M for three months starting in March of 1989. Because of poor response, the patient was then treated with MACOP-B, M-FEPA, and VEPP-B for about one year from June of 1989 and has been free of disease up to the time of writing, March of 1993.     

Effect of KB-2796, a new diphenylpiperazine Ca antagonist, on voltage-dependent Ca currents and oxidative metabolism in dissociated mammalian CNS neurons

The effects of KB-2796, 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine-2HCl, on the low- and high-voltage activated Ca²⁺ currents (LVA and HVA I_Ca, respectively) and on oxidative metabolism were studied in neurons freshly dissociated from rat brain. KB-2796 reduced the peak amplitude of LVA I_Ca in a concentration-dependent manner with a threshold concentration of 10⁻⁷ M when the LVA I_Ca was elicited every 30 s in the external solution with 10 mM Ca²⁺. The concentration for half-maximum inhibition (IC₅₀) was 1.9 × 10⁻⁶M. At 10⁻⁵ M or more of KB-2796, a complete suppression of the LVA I_Ca was observed in the majority of neurons tested. There was no apparent effect on the current-voltage (I-V) relationship and the current kinetics. KB-2796 delayed the reactivation and enhanced the inactivation of the Ca²⁺ channel for LVA I_Ca voltage- and time-dependently, suggesting that KB-2796 preferentially binds to the inactivated Ca²⁺ channel. KB-2796 at a concentration of3.0 × 10⁻⁶M also decreased the peak amplitude of the HVA I_Ca without shifting the I-V relationship. In addition, KB-2796 reduced the oxidative metabolism (the formation of reactive oxygen species) of the neuron in a concentration-dependent manner with a threshold concentration of3 × 10⁻⁶M. It is suggested that the inhibitory action of KB-2796 on the neuronal Ca²⁺ influx and the oxidative metabolism, in combination with a cerebral vasodilatory action, may reduce ischemic brain damage.     

Effects of fasting on biperiden pharmacokinetics in the rat

The effects of fasting on the pharmacokinetics of biperiden in rats were examined. Total clearance of biperiden was greater than 90% ascribable to hepatic clearance and was essentially blood-flow dependent. The number of compartments in the preferred pharmacokinetic model of biperiden changed from three (for normal rats) to two (for fasted rats). The smaller mean residence time (MRT) values found for fasted rats were attributable to decreases in distribution volume. Biperiden showed much higher lipophilicity than haloperidol, thiopental, and hexobarbital, and its tissue-to-plasma partition coefficient in adipose tissue was 20-fold higher than that in muscle. The influence of changes in volumes of adipose tissue and muscle on distribution volume (Vdss/BW) was evaluated from tissue-to-plasma partition coefficients. The value of Vdss/BW was predicted to decrease with decrease of adipose tissue, and to increase with decrease of muscle tissue. These results suggest that the observed decrease of Vdss/BW in fasted rats reflects reduced capacity to trap biperiden in the body, especially in adipose tissue. Possible clinical implications of these results are discussed.     

Neuropsychological test for the detection of dementia in elderly individuals: the Nishimura Dementia Test

Background: Progression of the core and accessory symptoms of dementia can be slowed if drug therapies and psychosocial interventions are administered at an early stage. The aim of this study was to develop and standardize a neuropsychological test for the elderly that can detect dementia at an early stage with high sensitivity and can evaluate a wide range of severities of dementia based on assessments of various cognitive functions. Methods: A preliminary test consisting of 23 items and the Nishimura Mental State Scale for the Elderly (NM Scale), which evaluates the mental functions of elderly individuals by observing their actual behaviors in daily life, were administered to 448 elderly subjects. After applying Hayashi’s quantification theory type I to the results, we revised the preliminary test to construct a neuropsychological test for the elderly, which we named the Nishimura Dementia Test (ND Test), and standardized it. Then, we examined its validity and test–retest reliability. Results: Among the 448 subjects, there was a strong correlation between the ND Test scores and NM Scale scores. The ND Test showed a good general agreement rate for the discrimination of the severity of dementia, and good sensitivity and specificity of discrimination of dementia when compared with the actual NM Scale. Using different groups of elderly subjects, the ND Test showed validity and test–retest reliability, and the ND Test scores showed strong correlations with the Revised Hasegawa Dementia Scale scores and the Mini‐Mental State Examination scores. Conclusions: The ND Test is based on assessment of a variety of cognitive functions and can evaluate a wide range of severities of dementia with good validity and reliability.     

Safety and usefulness of a novel eMotion electric mesh nebulizer in children with asthma.

BACKGROUND: A new electronic mesh nebulizer, eMotion is known to have higher performance compared to conventional nebulizers. However, there are some concerns about whether too much delivered dose might cause side effects with higher frequency. METHODS: To evaluate the safety and usefulness of the nebulizer, we measured changes in heart rates and lung functions of 73 asthmatic children when they inhaled 1 microg/kg of procaterol with eMotion or a conventional nebulizer, Junior BOY. RESULTS: In 34 children with mild asthma exacerbation, physical findings, lung function and transcutaneous oxygen saturation levels were improved after inhalation using both nebulizers. No adverse effects including significant increase of heart rate were found. Improvements in the rates of the parameters were comparable. When response to beta2-agonist inhalation was checked in 39 children in stable condition, similar degrees of improvement in lung function were observed, and heart rates did not change after inhalation with either nebulizers. CONCLUSIONS: Safety and efficacy was comparable between eMotion and a conventional nebulizer when it was used to administer beta2-agonists in asthmatic children. However, from the fact that eMotion needs only 3-4 minutes to inhale 2 mL solution, eMotion could be more useful for most children who usually do not prefer longer inhalation time with conventional compressor nebulizers.     

A differentiation-inducing factor produced by the osteoblastic cell line MC3T3-E1 stimulates bone resorption by promoting osteoclast formation

We have reported that the differentiation-inducing factor (DIF) is present in conditioned medium of mouse osteoblast-like cell (MC3T3-E1) cultures. In the present study, the DIF from conditioned medium of MC3T3-E1 cells was partially purified and its biologic activity was examined. The DIF was purified by monitoring the induction of phagocytic activity of mouse myeloblastic leukemia cells (M1). The DIF induced differentiation of not only M1 cells but also mouse myelomonocytic cells (WEHI-3). Furthermore, the DIF increased the in vitro bone-resorbing activity and the osteoclast number in mouse calvaria. The increases were inhibited by the addition of either salmon calcitonin or indomethacin. When mouse bone marrow cells were cultured with the DIF for 8 days, formation of osteoclast-like multinucleated cells was stimulated dose dependently. The DIF from MC3T3-E1 cells appeared to be different from interleukin-1 (IL-1), tumor necrosis factor (TNF), and transforming growth factor beta (TGF-beta). These results suggest that the DIF partially purified from osteoblast-like cell cultures stimulates osteoclastic bone resorption by promoting differentiation and fusion of osteoclast progenitors to form multinucleated osteoclasts.     

Prolidase Activity in Chronic Wound and Blister Fluids

We investigated prolidase activity in samples derived from wound fluid as well as blister fluid. Prolidase activity was elevated in fluid samples collected from wounds over the levels in sera collected from patients with chronic wounds (P<0.05). Prolidase activity was also present in samples taken from blister diseases. However, prolidase activity in blister fluid was not higher than that in sera collected from patients with blister diseases. Our results indicate that prolidase may play a role in wound healing.