Biomedical subjects
Publications and source records attributed to K Sarai.
1. The advantage of oriental medicine are described. 2. For those whose anxious-depressive state are prolonged, despite several changes in combining drugs, five herbal medicines were introduced. Although their mechanism of action were still unknown, some effects were explained by modern pharmacological techniques.
This study tests the hypothesis that contractile dysfunction that often develops after acute coronary occlusion despite emergency revascularization can be avoided by careful control of the composition of the initial reperfusate and the conditions of the reperfusion. Between January 1987 and May 1989, 31 consecutive patients with acute coronary occlusion (90% resulting from percutaneous transluminal coronary angioplasty failures) were reperfused during emergency myocardial revascularization according to one of two different protocols. In 23 patients the reperfusate was normal blood given at systemic pressure ("uncontrolled reperfusion"); in eight patients the ischemic segment was reperfused during the first 20 minutes with a regional blood cardioplegic solution (substrate-enriched, hyperosmotic, hypocalcemic, alkalotic, diltiazem-containing) at 37 degrees C at a pressure of 50 mm Hg. Thereafter total bypass was prolonged for an additional 30 minutes before extracorporeal circulation was discontinued ("controlled reperfusion"). Assessment of regional contractility (echocardiography, radionuclide ventriculography), electrocardiographic evidence of myocardial infarction, release of creatine kinase and isoenzyme of creatine kinase, and hospital mortality was performed. Regional contractility was quantified with a scoring system from 0 (normokinesis) to 4 (dyskinesis). Data are expressed as mean +/- standard error of the mean. Both groups were well matched for age, sex, and the distribution of the occluded artery. In the controlled-reperfusion group there was a greater prevalence of previous infarctions (63% versus 43%), additional significant stenosis (1.3 +/- 0.2 versus 0.8 +/- 0.2), and cardiogenic shock (38% versus 17%) compared with the uncontrolled-reperfusion group. Furthermore, the interval between coronary occlusion and reperfusion was significantly longer in the controlled-reperfusion group (4.0 +/- 0.5 versus 2.3 +/- 0.3 hr; p less than 0.05). Regional contractility returned to normal in all patients treated by controlled reperfusion (wall motion score = 0.8 +/- 0.3, normokinesis = 0, slight hypokinesis = 1). In contrast, regional contractility remained severely depressed after uncontrolled reperfusion with normal blood (score 2.5 +/- 0.2; p less than 0.05), with only four of 23 patients with a score less than 2 (2 = severe hypokinesis). Postoperatively enzymes and electrocardiographic changes were similar in both groups. One patient died of mitral insufficiency in the controlled-reperfusion group, despite complete recovery of wall motion in the angioplasty-related artery. Conversely, the four of 23 deaths after uncontrolled reperfusion occurred in patients who sustained infarct in the area of the coronary occlusion (mortality 13% versus 17%). In conclusion, these preliminary clinical results indicate that immediate recovery of segmental contractility can be achieved after acute coronary occlusion if the initial reperfusion is controlled.(ABSTRACT TRUNCATED AT 400 WORDS)
The concentrations of amitriptyline (AMT) and its demethylated metabolite nortriptyline (NRT) in the serum and in specific brain regions were determined periodically after acute or chronic administration of 20 mg/kg of AMT in rats. Both AMT and NRT declined from the serum in a biexponential manner and were eliminated monoexponentially from the brain regions, with no significant difference in elimination among the eight brain regions examined. In the brain, both AMT and NRT were unevenly distributed after chronic administration, whereas an even distribution was observed after acute administration. The AUCbrain:AUCserum ratio of AMT was higher than that of NRT, indicating greater transport of AMT into the brain regions. The AUCAMT value in the serum increased 1.6 times after chronic administration, whereas no significant changes were observed in the brain regions. The AUCNRT values increased 9.0 times in the serum and 6.8 times in the brain, with the increase in the serum being greater. These results suggest inhibited distribution of the drugs into the tissues, including the brain regions, and enhanced metabolism of AMT.
37 patients undergoing coronary revascularization were randomly assigned to three protocols for intraoperative myocardial protection: hypothermic ventricular fibrillation (HF) (n = 13), multi-dose blood cardioplegia (BCP) (n = 12) and single-dose Bretschneider's crystalloid cardioplegia (CCP) (n = 12). As intraoperative markers of ischemic damage myocardial ultrastructure, ATP, and CP contents were determined in left ventricular biopsy specimens taken before and after cardiac arrest. Release of serum enzymes (CK, CK-MB, LDH, SGOT) was determined pre- and postoperatively. Hemodynamic data were assessed before, during, and after operation. The incidence of low cardiac output, positive inotropic support, intraaortic balloon counterpulsation, peri-operative myocardial infarction, rhythm disturbances, and the rate of spontaneous defibrillation was compared between groups. The results show a better preservation of high energy phosphates in the BCP group as compared to the HF and CCP groups. Myocardial ultrastructure showed moderate ischemic damage in the hypothermic fibrillation group; in contrast, only slightly deteriorated cells were seen after cardiac arrest, when cardioplegia was used. The incidence of rhythm disturbances was 25% for HF and 42% for CCP. In contrast, only 17% of new rhythm disturbances were seen in the BCP group. Functional recovery (i.e. CI and SWI) of hearts protected with BCP was generally greater as compared to HF and CCP. Release of MB-creatine-kinase isoenzyme was higher in the HF group as compared to cardioplegia. Clinical outcome in terms of incidence of peri-operative infarction, positive inotropic support and low cardiac output was superior in the BCP group but not significantly different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)
A new surgical procedure for anatomical correction of an anomalous origin of the left main coronary artery (LCA) from the pulmonary artery is described for those patients in whom the origin of the LCA is located adjacent to a pulmonary cusp and several side branches are arising immediately behind the ostium of the LCA. Hence the LCA can not be disconnected from the pulmonary artery for either coronary arterial transfer or bypass grafting. A tunnel-type repair may interfere with the movement of the pulmonary leaflets. In those cases our proposed surgical correction consists of an arteriotomy of the pulmonary trunk, end-to-end anastomosis of a vein graft to the ostium of the LCA and its implantation into the ascending aorta. The resulting defect in the pulmonary artery is closed with a pericardial patch avoiding kinking or stenosis of the pulmonary trunk.
The purpose of this clinical study was to (1) evaluate mortality rates after surgical interventions for patients in cardiogenic shock (CS) secondary to acute coronary occlusion, acute ventricular septal defect (VSD) or acute valvular heart disease, (2) determine the pre-operative regional wall motion, and (3) ascertain the recovery of preoperative regional wall motion abnormalities after surgical intervention. The hospital records of twenty-five consecutive patients in CS were reviewed retrospectively. Regional wall motion was assessed preoperatively by ventriculography and postoperatively by 2D echocardiography (Sonotron Kardio VUE 60) after 1 and 3 days and at the day of discharge from the surgical ward (7-10 days). The left ventricle was divided in three segments according to the blood supply: LAD artery (antero-lateral wall), circumflex artery (lateral wall), and right coronary artery (inferior and basal wall). Regional wall motion was analyzed with the use of a scoring system in which grading was from 0 to 4 according to the following criteria: 0 = hyperkinesia, 1 = normokinesia, 2 = hypokinesia, 3 = dyskinesia, 4 = akinesia. Postmortem examination was performed in 8/9 patients. Data are presented as mean +/- SD. Significant differences were defined as probabilities for each test of p less than 0.05. The hospital mortality was higher for patients with acute coronary occlusion as compared to those with acute valvular disease or VSD (54.5%, 27.3%, 0%, resp.). The cause of death was cardiac in 7/9 patients. However, postmortem examination revealed loss by infarction of only moderate quantities of myocardium which could not explain the severe postoperative heart failure in those patients. Previous myocardial infarctions and preoperative cardiac arrest were significant risk factors for hospital mortality. In all patients with acute coronary occlusion (11/11) at least one region of the left ventricle was either a- or dyskinetic in the region supplied by the acute occluded vessel. In addition five patients had akinetic regions due to previous infarctions. The remaining remote myocardium was hypocontractile due to significant stenosis in coronary arteries supplying remote areas. Of 10 dyskinetic segments before surgical intervention, 5 were akinetic postoperatively, and only 5 developed slight hypokinetic contractions. The overall hypokinetic regions were not different as compared to the preoperative data (36.4% vs 39.4%). The normokinetic segments increased from 9.1% to 33.% (p less than 0.05).
From Jan. 1984 to Dec. 1988 941 patients had internal mammary artery grafting alone or with vein grafts. There were 1705 associated vein grafts and 957 internal mammary grafts, for a total of 2 662 grafts (2.8 per patient). Use of the internal mammary artery was indicated in patients younger than 70 years with a significant stenosis of the main stem or the proximal left anterior descending artery in elective operations. The overall operative mortality was 3.4%, 2.9% for men and 6.2% for women. It rose to 9.6% in patients who were in New York Heart Association Class IV. Incidence of bleeding requiring reexploration was 5.5% and an intra-aortic balloon pump was implanted in 3% because of low cardiac output. At cardiac recatheterization (on average after 12 months) 88.3% of the internal mammary grafts and 63.3% of the vein grafts were patent. In investigation of, reasons for operative mortality, measuring the free flow of the internal mammary artery showed flow rates of 32-208 ml/min only slightly depending on the blood pressure. A technique of dilatation is described that significantly increases the flow rate up to 85%. The technique has been used regularly since Nov. 1987: from that date the IMA is only used if it has a flow rate of at least 60 ml/min.
A multi-institutional study comparing the antimanic effect of carbamazepine (CBZ) and lithium carbonate (Li) was performed using a double-blind group comparison design in a series of 105 patients with bipolar disorders. CBZ and Li were given for four weeks using a fixed-flexible method at an equipotent dose ratio of 1:1, starting from an initial dosage of 400 mg with a maximum dosage of 1200 mg. The final global improvement rate, based on the number of cases showing moderate to marked amelioration of manic symptoms, was 62% in the CBZ group and 59% in the Li group, with no significant difference being found between the two groups. Incidence of cutaneous side-effects was significantly higher in the CBZ group. The mean daily dosage and serum level of CBZ in the fourth week were 674 +/- 239 mg and 7.3 +/- 2.4 micrograms/ml respectively; these were within the therapeutic range. The daily dose and serum level of Li, however, were 710 +/- 239 mg and 0.46 +/- 0.22 mEq/l, and the Li level seemed to be too low to compare its therapeutic effect with that of CBZ. Prior to the present study, approximately 80% of the patients in both groups had been receiving antipsychotic medication, equivalent to 8.0 mg of haloperidol on average, without favorable response. This medication was maintained unchanged during treatment. While the shortcomings of the present study limit the interpretation of the data, it may be suggested that the usefulness of CBZ as a drug for the treatment of manic states is comparable to that of Li.
We present here two cases of reversible hypoproteinemia which could have occurred as an adverse effect of chronic lithium administration. In the present cases, protein losing a renal dysfunction, liver dysfunction and malabsorption syndrome were not observed, and the relationship between their dietary volume and serum protein levels was poor. The mechanism of hypoproteinemia in these cases was not identified from previously obtained data. We suggested that this type of hypoproteinemia might be a new adverse effect of lithium.
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The therapeutic effects of carbamazepine (CBZ) were evaluated in 103 patients with affective disorders, 54 with schizophrenic disorders, and 26 with schizoaffective disorders by a multi-institutional open study. The rate of marked and moderate improvement was 72.8% in affective disorders, 54.6% in schizophrenic disorders, and 61.5% in schizoaffective disorders. Symptom items of the Clinical Psychopharmacology Research Group rating scale for mania showed significant improvement in the patients with affective disorders as well as in those of the other two groups. In the Brief Psychiatric Rating Scale as applied to patients with schizophrenic or schizoaffective disorders, symptom items related to affect and emotion showed significant improvement. The antimanic efficacy of CBZ was also noted in many poor responders to lithium. Side-effects were observed in 82 patients (44.8%), and abnormal laboratory findings in 37 patients (44.8%), and abnormal laboratory findings in 37 patients. The present study seems to confirm the usefulness of CBZ for the treatment of affective disorders and in some cases, of schizophrenic and schizoaffective disorders.
A multi-institutional double-blind study comparing the therapeutic effect of adjunctive carbamazepine and placebo with standard neuroleptic treatment was performed on 162 patients with DSM-III diagnosis of schizophrenic (n = 127) or schizoaffective disorders (n = 35) who had excited states or aggressive/violent behavior that responded unsatisfactorily to neuroleptic treatment. The patients participated in a 4-week trial of carbamazepine plus neuroleptics (n = 82) or placebo plus neuroleptics (n = 80). The sum of patients with marked and moderate improvement was modestly larger in the carbamazepine group (48 vs. 30%, P less than 0.05). There was no significant difference between the carbamazepine and placebo groups in the changes of total BPRS scores, although the carbamazepine group showed more improvement on the items suspiciousness, uncooperativeness and excitement. The results suggest that carbamazepine, when used in combination with neuroleptics, is a useful drug for the treatment of excited states of patients with schizophrenic and schizoaffective disorders.
[3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) is thought to label a single population of serotonin (5-HT)1A receptor, but some reports implicate multiple binding sites exist. In addition, while 5-HT1A receptor activates or inhibits adenylate cyclase, 5-HT1A receptor high and low affinity states are not reported. In this experiment, we found that [3H]8-OH-DPAT had multiple binding sites, which contained 5-HT1A receptor high and low affinity states, in rat brain membranes. [3H]8-OH-DPAT saturation binding experiment revealed high and low affinity binding sites existed. High affinity binding site was dense in hippocampus and sparse in striatum. 5-HT agonist and antagonist biphasically displaced [3H]8-OH-DPAT binding in frontocortical, hippocampal, and striatal membranes. These drugs potently displaced high affinity [3H]8-OH-DPAT binding, but clomipramine (5-HT reuptake inhibitor) potently displaced low affinity binding. High affinity [3H]8-OH-DPAT binding site was decreased by guanosine triphosphate and Na+, but increased by divalent cations, implicating coupling with G protein(s). Low affinity [3H]8-OH-DPAT binding site was decreased by cations, especially by monovalent cations and Ca2+. After the destruction of 5-HT neuron by parachloroamphetamine, only the low affinity binding site decreased. These results indicate that [3H]8-OH-DPAT not only labels the 5-HT1A receptor high and low affinity states but has presynaptic binding site relating to 5-HT reuptake site.
Experiments were carried out on rats in order to find out the implications for psychiatry of the basic biological effects of rubidium (Rb). The forced swimming test (FST), used to evaluate the effects on rats of treatment with Rb, was conducted after 1 or 3 mEq/kg Rb was given chronically or subacutely. The weight of rats treated with 1 or 3 mEq/kg Rb, once daily, was observed daily for two weeks. Rb levels in the blood and brain of rats treated with Rb chronically or subacutely were determined by atomic absorption spectrophotometry. The rectal temperature was observed at 30, 60, 90, 120, 180, and 240 min after injections of 1 or 3 mEq/kg Rb. The increase in the mean body weight of treated rats was almost the same as that of the control. The rectal temperature in rats treated with Rb showed a hyperthermic response. With both the 1 and 3 mEq/kg Rb treatments, Rb levels in the brains were significantly higher in the chronic experiments than in the subacute experiments. The experiments conducted to determine the effect of chronic and subacute treatment of Rb are hereafter termed 'chronic experiment' and 'subacute experiment' respectively. Almost the same significant difference was also observed in the Rb levels in the blood. In the FST, a decrease in the mean immobility time was not observed in either the subacute or the chronic experiments. Thus, antidepressant effects, as judged from the FST, were not observed although Rb did actually accumulate in both brain and blood.
1. The serum levels of antidopaminergic (anti-D2), anti-alpha-adrenergic (anti-NA) and antiserotonergic (anti-5HT2) activities of neuroleptics were determined in schizophrenic patients on maintenance treatment. 2. The patients whose conditions remained stable had significantly higher serum levels of anti-D2 and anti-5HT2 activities than those who were considered to be in unstable conditions after a period of remission. 3. However, the serum levels of anti-5HT2 activity in patients whose conditions remained stable varied as much as those of anti-NA activities did, so it appeared that from a pharmacological viewpoint anti-D2 activity of neuroleptics was the most important in preventing a relapse in schizophrenic patient. 4. The serum levels of anti-D2 activity required to prevent relapses differed for each neuroleptic. 5. The frequency of side effects increased concordant with increasing serum levels of anti-D2, anti-NA and anti-5HT2 activities, and unfortunately even minimum effective serum levels of anti-D2 activity elicited slight side effects in the majority patients.
Zotepine and thiothixene were compared for clinical efficacy and safety in a double-blind trial. Using overall improvement ratings and Gorham's BPRS, zotepine rated higher improvement in motor retardation, suspiciousness, mannerisms and posturing symptoms, suggesting that it has both activating and antipsychotic activities. Thiothixene produced higher improvement ratings in symptoms such as hallucinatory behavior, somatic concerns, anxiety, guilt feelings, tension, depressive mood and uncooperativeness. As for side effects, there was a significantly lower frequency of dry mouth and insomnia with zotepine when compared with thiothixene. The lower incidence of insomnia is interesting in view of zotepine's clinical activating effects. There were no abnormal laboratory findings.
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