Mechanisms of long-lasting effects of benidipine on Ca current in guinea-pig ventricular cells.

1. Benidipine (KW-3049), a new derivative of 1,4-dihydropyridine (DHP), showed dose-dependent inhibition of Ca current (ICa) which was elicited by depolarization from -40 mV to +10 mV at 0.2 Hz in single cardiac cells isolated from guinea-pig ventricle under whole cell voltage clamp. Half inhibition doses (IC50) of benidipine and nifedipine for the peak ICa at +10 mV were 2.7 nM and 63.1 nM, respectively. 2. A change in holding potential from -40 to -75 mV partially removed the block induced by both 10 nM benidipine and 100 nM nifedipine. The block of ICa by benidipine strongly depended upon holding potentials as did that induced by nifedipine. 3. The effect of 100 nM nifedipine was mostly removed when the cells were kept quiescent at holding potentials negative to -75 mV for 5 min after withdrawal of nifedipine. In contrast, hyperpolarization for several minutes did not significantly accelerate the removal of benidipine-induced block after withdrawal of the drug. Effects of 10 nM benidipine could not be washed out for up to 30 min regardless of the holding potentials. 4. It is suggested that the dissociation of benidipine from the DHP binding site, like that of nifedipine, is greatly accelerated by hyperpolarization. Benidipine but not nifedipine may have an additional interaction with the channel or lipid membrane and cannot be washed away even after the dissociation. Alternatively, the dissociation of benidipine from the DHP binding site may be too slow to occur substantially during the limited period of hyperpolarization in the present study (less than 30 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

A patient with severe ventricular tachycardia who was saved by prolonged extracorporeal lung and heart assist]

A 47-y-o man had been suffering from cardiac failure due to refractory ventricular tachycardia (VT) after myocardial infarction. He underwent resection of the left ventricular aneurysm and cryocoagulation of the arrhythmogenic foci. On the 2nd post-operative day, VT often recurred in spite of repeated cardioversion and drug therapy, and threatened his life, even under IABP. Therefore, a veno-arterial bypass route was made and extracorporeal lung and heart assist, ECLHA, was started with a heparin bonded Maxima lung on the following day. Even under ECLHA, VT continued to recur. Cryocoagulation of the VT foci was tried again, without immediate success. A record high dose of beta-blockers, given under the circulatory support by ECLHA, stopped VT on the following day. The patient was weaned from the ECLHA circuit 12 days after the first operation, then from IABP on the 14th day. During the 10 day course of surgeries and ECLHA, the patient had almost 100 defibrillations. But for ECLHA, we may say that the patient couldn't have survived two open heart surgeries, administration of a great amount of beta-blockers, and repeated cardiac arrest without neurological sequelae.     

Different origin of leiomyoblastoma by immunohistochemical study.

Leiomyoblastoma has been regarded as a neoplasm of smooth muscle origin. With recent progress in immunohistostaining techniques, many clinicopathological discrepancies have been pointed out about the origin of leiomyoblastoma. It has been claimed that gastrointestinal non-epithelial tumors should be regarded as stromal tumors in order to study their origin. In the present study, we performed various forms of immunohistostaining in seven cases of leiomyoblastoma to determine their origin. One case expressed desmine and muscle specific actin and was considered to be derived from smooth muscle. Four neoplasms expressed X-100 protein (two cases were also NSE positive) and were thought to be derived from the nerve. Two cases were of unknown derivation. These results suggest that the cells of leiomyoblastoma may arise from a primitive to totipotential cell of neural lineages that may anomalously express smooth muscle filaments.     

Deep vein thrombosis in the psychiatric patients under physical restraint]

Pulmonary thromboembolism induced by deep vein thrombosis (DVT), which is known as economy-class syndrome, is one of sudden death in psychiatric patients under physical restraint. (1) A decrease in venous blood flow, (2) damage to vessel walls, and (3) the enhancement of blood clotting are the major risk factors for DVT (Virchow triad). It has been speculated that physical restraint inhibits venous blood flow, and that antipsychotic drugs facilitate blood clotting. In order to prevent sudden death due to DVT, prophylactic measures and early diagnosis are crucial. Whereas Doppler ultrasonography and contrast venography are the gold standards for the diagnosis of DVT, more simplified methods are now under development. Of those, D-dimer measurement, which can be conducted with a small blood sample, is the most potent candidate for the biochemical diagnosis of DVT. Although there are many prophylactic measures, including anticoagulant medications and physical therapies, it is not clear which is the most effective and suitable in psychiatric practice. Psychiatric professionals should pay closer attention to DVT in psychiatric patients under physical restraint.     

Investigation of where schizophrenic patients receive treatment

Schizophrenic patients receiving treatment in Kagawa Prefecture were studied as to where treatment was obtained. Analysis showed that there was a tendency by schizophrenic patients to seek treatment in institutions distant from their place of residence. The direction in which a patient proceeded to seek treatment varied and showed no pattern. Analysis by age groups showed that patients in the 15 to 39 years age group were most likely to seek treatment in locations other than where they lived and traveled the longest distance. The tendency to seek treatment away from their place of residence decreased with increasing age. However even among the elderly there were patients who traveled long distances for treatment. Factors associated with geographical or social relationships between the cities/towns could not explain the tendency observed. Neither was there a relationship to specialized medical care. Factors such as the related to the mental health care system, including prejudice and lack of societal understanding were inferred to be associated to this problem. Results of this study indicate a need to organize the community mental health system to serve districts with wider areas than that established for other diseases. However in the future there should be a gradual narrowing of the district area, a broadening of services offered, and a removal of societal prejudice against psychiatric patients.     

Hepatocellular carcinoma: Efficacy of transcatheter oily chemoembolization in relation to macroscopic and microscopic patterns of tumor growth among 100 patients with partial hepatectomy

Purpose: To evaluate the efficacy of transcatheter oily chemoembolization (TOCE) for hepatoceliular carcinoma (HCC) on the basis of microscopic and macroscopic findings postembolization. Methods: HCCs ranging in size from 0.5 to 13 cm (mean 3.6 cm) were obtained from partial hepatectomies of 100 consecutive patients who had undergone TOCE between 20 and 246 days (mean 59.5 days) prior to surgery. The efficacy of TOCE was assessed on the basis of the necrotic to live cell ratio of the tumors. The microscopic pattern of tumor growth was grouped into expanding type (complete capsule formation) and replacing type (incomplete or no capsule). There were five types of macroscopic groupings: single nodule, single nodule with extranodular growth (SNE), contiguous and noncontiguous multinodular, and massive growth type. Results: Among 79 cases with the expanding type, 29 (37%) had 100% HCC necrosis, but none with 100% necrosis were in the replacing type. By macroscopic grouping, the efficacy of TOCE decreased from the single nodule type (50% of patients had 100% necrosis) to the SNE type (21%), and the other types (9%).     

The distribution of antigen in flare up reaction in contact sensitivity to DNCB

The distribution of DNP groups in various tissues of guinea-pigs following intravenous injection of DNBSO3Na was investigated by an immunofluorescent method using FITC-labelled anti-DNP antibody. DNP groups were detected either in the cytoplasms of epidermal cells or on/in lymphoid tissue cells. The epidermal distribution of DNP groups was shown in the skin obtained from 5 min to 3 days after injection. There was no fundamental difference in the epidermal localization of DNP groups between at the previously tested site and at virgin site in DNCB sensitized animals. Unreacted DNBSO3Na was demonstrated in the blood plasma of DNBSO3Na injected animals. The injection of either DNP-lysine or 2,4-dinitrophenol was found incapable of inducing flare up reaction and no epidermal localization of DNP groups in the sensitized animals was observed. A possibility that intravenously injected DNBSO3Na forms a complete antigen by conjugation with epidermal proteins and sensitized cells, which have been indicated by Polak, Turk & Frey (1973) to remain at the site of old contact reaction, react with the antigen resulting in flare up reaction, is suggested.     

Cartilage regeneration using slow release of bone morphogenetic protein-2 from a gelatin sponge to treat experimental canine tracheomalacia: a preliminary report

We investigated whether saber sheath-type tracheomalacia could be treated by the slow release of bone morphogenetic protein (BMP)-2 from a gelatin sponge. A 1 cm gap was made in the middle portion of each of 10 consecutive tracheal cartilage rings in the canine cervix (control group, n = 3), then a gelatin sponge containing 12 microg of BMP-2 solution was implanted in the gap (12 microg group, n = 3). In another group (120 microg + P group, n = 3), the implanted gelatin sponge contained 120 microg of BMP-2 solution, and the gap was covered with periosteum. All of the control dogs developed saber sheath-type tracheomalacia, whereas tracheomalacia was not observed in the 12 microg and 120 microg + P groups. In the 12 microg group, fibrous cartilage was observed at the ends of the cartilage stumps. In the 120 microg + P group, newly formed bone and cartilage were observed to form a bridge between the cartilage stumps. The regeneration of cartilage or bone induced by the slow release of BMP-2 from a gelatin sponge might be useful for treatment of tracheomalacia.