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Biomedical subjects

K Sarai

Publications and source records attributed to K Sarai.

At least 37 records · Page 2Linked to original sources

Molecular cloning of a fungal cDNA encoding protein disulfide isomerase.

Based on the partial amino acid sequences of a protein disulfide isomerase (PDI) from Humicola insolens, two primers were synthesized for reverse transcriptase mediated polymerase chain reaction (RT-PCR) of a fungal RNA. A 0.2-kbp fragment around the consensus sequence of PDIs was obtained and used as a probe for screening a fungal cDNA library. A cDNA clone of PDI from H. insolens was isolated and encoded a polypeptide consisting of 505 amino acids, which was characterized by a N-terminal signal sequence composed of 20 amino acids, a consensus sequence (WCGHCK) at two positions, and a C-terminal endoplasmic reticulum retention signal (HDEL). Bacillus brevis harboring an expression plasmid bearing the fungal PDI cDNA was prepared and its culture supernatant showed a significant PDI activity. This indicates that glycosylation of a fungal PDI is not essential for the enzymatic activity related to an interchange of disulfide bonds.

Amino Acid Sequence↗

[Masked depression].

Depressive disorders which masked by somatic symptoms is called masked depression. Masked depression is not a specific type of depression, but the general practitioners often misdiagnose it, because patients complain only somatic symptoms and most practitioners are not aware of it belongs to depression. Usually masked depression is mild, but is apt to chronic, and some patients become worse and might attempt suicide. The cause of depression is still obscure, but according to the results of many somatic tests, somatic findings are important. And differential diagnosis is also important. Concerning the treatment of mild depression, the patients dislike usual antidepressants because of the side effects. Then the author recommend to use a small dose of the drugs and some oriental herbal medicines. Oriental herbal medicines have fewer side effects, and effective for vegetative symptoms.

Antidepressive Agents↗

Studies of reperfusion injury in skeletal muscle: controlled limb reperfusion to reduce post-ischaemic syndrome.

Revascularization after prolonged complete limb ischaemia may result in both severe damage to skeletal muscle and various systemic manifestations of the postischaemic syndrome. Previous experimental studies performed by the authors have shown that these are caused, to a large extent, by normal reperfusion at normal systemic pressure and that this additional injury can be substantially reduced by controlled reperfusion of the revascularized limb before restoration of the normal circulation. This treatment includes control of the conditions of reperfusion and composition of the initial reperfusate. In the present study, this concept of controlled limb reperfusion was applied to patients with prolonged severe lower limb ischaemia. Controlled limb reperfusion was used in 11 patients after prolonged complete unilateral or bilateral ischaemia. The ischaemic interval ranged from 5 to 21 h. Two patients were in cardiogenic shock, ten had a history of associated cardiac disease and seven coexistent peripheral vascular disease. After systemic heparinization, thromboembolectomy was undertaken using a Fogarty catheter. Cannulas were placed in the iliac, profunda and superficial femoral arteries and connected to a reperfusion set. Oxygenated blood was drawn from the iliac artery and mixed with an asanguineous solution (ratio 6:1). This controlled reperfusate was returned to the profunda and superficial femoral arteries using a single roller pump. The system allows control of both the composition of the reperfusate (Ca2+, pH, osmolarity, glucose, substrate, PO2, free radical scavengers) and the conditions of reperfusion (pressure, flow, temperature). After 30 min of controlled limb reperfusion, the cannulas were removed, the arteriotomy closed and normal blood reperfusion started.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Changing patterns of patients undergoing emergency surgical revascularization for acute coronary occlusion. Importance of myocardial protection techniques.

Between 1977 and 1992 a total of 163 consecutive patients underwent emergency coronary artery bypass grafting after acute coronary occlusion (94% after failed angioplasty). Patients were divided into four groups according to the method used for myocardial protection. The crystalloid cardioplegia group included 30 patients operated on from 1977 to 1980; the hypothermic fibrillation group included 60 patients (1980 to 1986); the blood cardioplegia group included 36 patients (1986 to 1989); and the blood cardioplegia with controlled reperfusion group included 37 patients (1989 to 1992). Preoperative data, ischemic time interval, collateral blood flow, intraoperative data, regional wall motion, global ejection fraction, myocardial infarct-specific electrocardiographic changes, enzyme release, rhythm disturbances, mortality, prevalence of intraaortic balloon pumping, and inotropic support were assessed in this retrospective study. Our data indicate that the current spectrum of patients undergoing emergency coronary artery bypass grafting after acute coronary occlusion are at a significantly higher risk compared with those 15 years ago, that is, increase in age (53 +/- 1 versus 59 +/- 2 years; p < 0.05), three-vessel disease (38% versus 3%; p = 0.004), acute occlusion of the left main coronary artery (11% versus 0%; p = 0.02), preoperative cardiogenic shock (35% versus 3%; p = 0.007), prevalence of acute two-vessel occlusion (22% versus 3%; p = 0.05), prevalence of previous infarction (59% versus 23%; p = 0.04), and duration of ischemia (3.0 +/- 0.2 versus 4.1 +/- 0.3 hours; p < 0.05). Despite the increase in patients with severely compromised ventricular function during recent years, the overall hospital mortality decreased to 5% (2/37) when maximal protection of the ischemic and remote myocardium was performed (preoperative intraaortic balloon pump, combined antegrade/retrograde substrate-enriched blood cardioplegia, warm induction, controlled reperfusion, prolonged vented bypass). Single-vessel disease was always associated with a low mortality, whereas mortality could be reduced with controlled blood cardioplegia in patients with multivessel disease (6%) and cardiogenic shock (15%). The immediate return of regional contractility in the previously ischemic area after controlled reperfusion might serve as an explanation for these favorable results. After unmodified blood reperfusion, normokinesis or slight hypokinesis occurs in only 34% to 46% in the early postoperative period (1 to 4 weeks) in comparison with 86% after controlled blood cardioplegia reperfusion (p < 0.05). We conclude that there is a significant increase in risk factors in patients undergoing emergency coronary artery bypass grafting and that improved methods of intraoperative myocardial protection are needed for these compromised patients.

Acute Disease↗

[Surgical revascularization in patients with acute myocardial infarction].

This retrospective study was done to assess the results of emergency revascularization in patients with acute myocardial infarction. In addition, the influence of the mode of reperfusion was investigated in terms of morbidity and mortality. Between January 1987 and May 1992, 75 consecutive patients with acute coronary occlusion (in 87% PTCA-failure) received one of two different reperfusion protocols during emergency aortocoronary bypass operation. In 36 patients, the reperfusate was normal blood given at systemic pressure (uncontrolled reperfusion); in 39 patients, the ischemic area was initially reperfused for 20 minutes with a blood cardioplegic solution (substrate-enriched, hyperosmolar, hypocalcemic, alkalotic, diltiazem-enriched) given at 37 degrees C and at a perfusion pressure of 50 mmHg. Thereafter, the heart was kept in the beating empty state for 30 minutes before extra-corporeal circulation was discontinued (controlled reperfusion). Regional contractility (echocardiography, radionuclide ventriculography), electrocardiogram (ECG), release of creatine kinase and MB-isoenzyme of creatine kinase as well as hospital mortality were assessed. Quantification of regional contractility was done with a scoring system from 0 (normokinesis) to 4 (dyskinesis). Data are expressed as mean +/- standard error of the mean (SEM). Both groups were well matched for age, sex, and the distribution of the occluded artery. In the controlled reperfusion group, there was a higher incidence of additional significant stenosis (2.2 +/- 0.1 vs 1.7 +/- 0.1) and cardiogenic shock (36% vs 17%). Furthermore, the interval between coronary occlusion and reperfusion was longer in the controlled reperfusion group (4.1 +/- 0.3 vs 3.3 +/- 0.3 hrs; p > 0.05). Regional contractility returned to normal after controlled reperfusion (score 0.8 +/- 0.2; normokinesis = 0, slight hypokinesis = 1). In contrast, regional contractility remained depressed severely after uncontrolled reperfusion with normal blood (score 1.5 +/- 0.3; p < 0.05). Enzyme release and ECG-changes were similar in both groups postoperatively. While only 2 of 39 patients died in the controlled reperfusion group (5.1%), mortality increased to 11.1% (4/36) if normal blood is used as the primary reperfusate. Our data show, that the surgical revascularization during acute myocardial infarction can be performed with acceptable mortality and morbidity rates. Further improvement of the results can be obtained if controlled regional reperfusion for the previously ischemic area is used.

Angioplasty, Balloon, Coronary↗

Controlled reperfusion during emergency coronary artery bypass surgery after angioplasty failure restores immediate segmental contractility.

This study tests the hypothesis that careful control of the composition of the initial reperfusate and the conditions of the reperfusion during emergency CABG will restore immediate segmental contractility in the previously ischemia area despite ischemic intervals of greater than 2 hours. Between January 1987, and October 1990, 41 consecutive patients with acute coronary occlusion (90% due to PTCA failures) were reperfused during emergency myocardial revascularization according to one of two different protocols: in 25 patients the reperfusate was normal blood given at systemic pressure ("uncontrolled reperfusion"); in 16 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 mmHg. 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 CK and CK-MB enzymes, and hospital mortality were performed. Quantification of regional contractility was done 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 higher incidence of previous infarctions (50% vs 30%), additional significant stenosis (1.1 +/- 0.2 vs 0.8 +/- 0.1), and cardiogenic shock (38% vs 20%) as compared to uncontrolled reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗

Immediate functional benefits after controlled reperfusion during surgical revascularization for acute coronary occlusion.

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)

Aged↗

Pharmacokinetics of amitriptyline and its demethylated metabolite in serum and specific brain regions of rats after acute and chronic administration of amitriptyline.

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.

Amitriptyline↗

Clinical evaluation of hypothermic ventricular fibrillation, multi-dose blood cardioplegia, and single-dose Bretschneider cardioplegia in coronary surgery.

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)

Cardioplegic Solutions↗

New surgical repair for an anomalous origin of the left coronary artery adjacent to the pulmonary cusps with numerous large side branches.

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.

Adult↗

Prolonged abnormalities of LV regional wall motion after normal reperfusion in patients with preoperative cardiogenic shock.

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).

Coronary Disease↗

Adequate flow through the internal mammary artery graft achieved by a dilatation technique.

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.

Coronary Circulation↗

Comparison of the antimanic efficacy of carbamazepine and lithium carbonate by double-blind controlled study.

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.

Adolescent↗

Hypoproteinemia related with chronic lithium therapy in two patients.

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.

Adult↗

Clinical efficacy of carbamazepine in affective, schizoaffective, and schizophrenic disorders.

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.

Adult↗