Initial, continuous and intermittent bolus cardioplegia administration: efficacy of potassium-chloride and magnesium-sulfate as minimal additives for minimally-diluted blood cardioplegia.

AIM: The most effective delivery of blood cardioplegia (BCP) remains controversial, and a combination of initial continuous and intermittent bolus BCP seems to compensate each demerit. However, a large amount of crystalloid solution is infused into the myocardium in this method, which may nullify the advantages of BCP. We examined the hypothesis that minimally-diluted BCP resolves this issue and provides superior myocardial protective effects. METHODS: Seventy patients undergoing elective coronary revascularization between 1997-2001 (M:F=55:15, mean age 67.6+/-7.5 years) were randomly allocated into one of 2 groups: Group C (n=35) was given the standard 4:1-diluted blood-crystalloid BCP, and Group M (n=35) was given minimally-diluted BCP supplemented with potassium-chloride and magnesium-sulfate. The BCP temperature was maintained at 30 degrees C. Cardioplegic arrest was induced with 2 minutes of initial antegrade BCP infusion, followed by continuous retrograde BCP infusion. Intermittent antegrade BCP was infused every 30 minutes for 2 minutes. RESULTS: The time required for achieving cardioplegic arrest was significantly shorter in Group M (47.5+/-16.3 vs 62.5+/-17.6 s, p<0.0001) and the number of patients showing spontaneous heart-beat recovery after aortic unclamping was significantly larger in Group M (28 vs 15, p=0.0029). The number of patients suffering from atrial fibrillation during the postoperative period was significantly smaller in Group M (3 vs 11, p=0.034). The total amount of crystalloid solution infused as cardioplegia was significantly smaller in Group M (62.8+/-22.3 vs 733.6+/-382.6 mL, p<0.0001). Postoperative maximum dopamine dose (3.57+/-2.46 vs 5.44+/-2.23 mg/kg/min, p=0.0014) and peak creatine kinase-MB (19.5+/-8.5 vs 25.8+/-11.9 IU/L, p=0.0128) were significantly lower in Group M. The number of patients showing paradoxical movement of the ventricular septum by early postoperative echocardiography was significantly smaller in Group M (9 vs 24, p<0.0007). CONCLUSIONS: These results demonstrate that initial continuous and intermittent bolus administration of minimally-diluted BCP supplemented with potassium and magnesium can be a simple, reliable and effective technique of intraoperative myocardial protection.

Growth hormone prevents Fas-induced apoptosis in lymphocytes through modulation of Bcl-2 and caspase-3.

OBJECTIVE: Growth hormone (GH) has been reported to have a potent effect on the immune system. However, the detailed mechanism of the effect of GH on the immune system has not yet been clarified. This study was designed to investigate the nature of this mechanism. METHODS: In the present study, we investigated the effects of GH on the susceptibility of both human CEM/C7 lymphocytes and human IM-9 lymphocytes to Fas-induced apoptosis. RESULTS: Both cell lines expressed GH receptor mRNA. GH rescued Fas-induced suppression of [(3)H]-thymidine incorporation into each cell line. GH prevented Fas-induced apoptosis in each cell line without changing Fas antigen expression. We next investigated the mechanisms of the prevention of Fas-induced apoptosis, by focusing on intracellular molecules related to the apoptotic signal. Bcl-2 expression was increased by GH treatment in both CEM/C7 and IM-9 lymphocytes. GH also downregulated caspase-3 expression and inhibited activation of caspase-3 in both cell lines. CONCLUSION: These findings suggest that GH regulates the human immune system through inhibition of Fas-induced apoptosis in activated T and B lymphocytes.

Purification and characterization of poly(aspartic acid) hydrolase from Sphingomonas sp. KT-1.

Poly(aspartic acid) (PAA) hydrolase was purified from Sphingomonas sp. KT-1 (JCM10459). The purified hydrolase degraded thermally synthesized PAA to oligomers. The molecular mass of PAA hydrolase was 30 kDa and the isoelectric point was 8.9. The optimum values of pH and temperature for PAA degradation were 10.0 and 40 degrees C, respectively. The investigation of the effect of inhibitors for the PAA-degrading activities has revealed that the PAA hydrolase is a serine-type hydrolase. The structural analysis of PAA-degraded products using (1)H and (13)C nuclear magnetic resonances has indicated that the purified enzyme hydrolyzes selectively the beta-amide linkage connecting with beta-aspartic acid units in PAA.

[Bactericidal activity of biapenem against various bacteria].

The bactericidal activity of biapenem (BIPM), a new carbapenem agent, against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Serratia marcescens was compared with those of imipenem (IPM), panipenem (PAPM), meropenem (MEPM) and ceftazidime (CAZ). The bactericidal activity of BIPM against S. aureus was equal to those of IPM, PAPM and MEPM. Against E. coli and K. pneumoniae, BIPM showed higher bactericidal activity than IPM and PAPM. Against P. aeruginosa, BIPM showed excellent bactericidal activity campared with IPM. The killing speeds of BIPM and IPM were obviously the most rapid among four carbapenems. BIPM showed a strong bactericidal activity against 5 species of bacteria including P. aeruginosa.

Combined use of cyclosporine A and methotrexate in refractory polymyositis.

Polymyositis is an inflammatory muscle disease with unknown cause that is characterized by progressive weakness of the proximal muscles. Limited information is available concerning the effectiveness of the combination therapy with cyclosporine A and methotrexate in reducing myositis activity. We describe here a female patient with polymyositis who showed resistance to pulse corticosteroid therapy. Neither the combination of azathioprine (100 mg/day) nor methotrexate (10 mg/week) with corticosteroids decreased the value of creatine phosphokinase. Normalization of the creatine phosphokinase level as well as improvement of muscle strength was obtained only when low-dose cyclosporine A (3 mg/kg/day) was combined with methotrexate.

Comparison of two stimulus-delivery systems for measurement of nasal pungency thresholds.

Using representative members of each of three homologous series of chemicals-ketones, acetates and alcohols-we measured nasal pungency thresholds in anosmics via two stimulus-delivery systems. The first system consists of the fairly commonly used 270 ml, plastic 'squeeze bottles'. The second system consists of 1900 ml, glass vessels with Teflon tubing and nose-pieces. Although bulkier and more susceptible to mechanical breakage, the glass vessels possess advantages that can allow them to provide 'environmentally realistic' chemosensory thresholds, i.e. thresholds closer in absolute values to those that might be obtained under whole-body exposures. Such advantages include a larger volume of the vapor-source to accommodate whole sniffs, and a tight nose-nose-piece connection to avoid stimulus dilution. The outcome revealed that, for every chemical, the glass vessels provided nasal pungency thresholds significantly lower than those provided by the squeeze bottles. The difference amounted, on average, to a factor of 4.6, though the relative potency of the compounds remained the same under both systems. Additionally, when tested with the highest homologues used here, namely, octyl acetate and 1-octanol, anosmics using the glass vessels had little or no difficulty achieving the criterion for threshold whereas they did have difficulty when using the squeeze bottles.

Function of the catalytic domain of poly(3-hydroxybutyrate) depolymerase from Pseudomonas stutzeri.

The mechanism of enzymatic hydrolysis for (R)-3-hydroxybutyrate (3HB) oligomers with poly[(R)-3-hydroxybutyrate] [P(3HB)] depolymerase (PhaZpst) from Pseudomonas stutzeri was investigated by two deletion mutants lacking the substrate-binding domain and linker region, PhaZpst delta sbd and PhaZpstcore. The two deletion mutants had no ability for hydrolysis of water-insoluble P(3HB), while the hydrolysis activities of two deletion mutants for water-soluble 3HB oligomer and its derivatives (dimer, trimer, and tetramer) were identical with those of the wild type, indicating that the function of catalytic domain is independent of its substrate-binding domain and linker region. The hydrolyzed products analysis of 3HB oligomers by HPLC showed that the active site of catalytic domain recognizes at least two 3HB units for hydrolysis. The initial rates of hydrolysis of dimer derivative were lower by 2 orders of magnitude than those of trimer and tetramer derivatives, suggesting that 3HB oligomer derivatives larger than trimer are favorite substrates for PhaZpst.

[Asymptomatic pneumatosis cystoides intestinalis in a patient with systemic lupus erythematosus].

Pneumatosis cystoides intestinalis (PCI) is a rare condition characterized by the presence of gas-filled cysts in the submucosa or subserosa of gastrointestinal tract. PCI has been widely recognized as a late manifestation of systemic sclerosis but seldom reported to take place in patients with systemic lupus erythematosus (SLE). We reported here a 13-year-old female who had been diagnosed to have SLE based on the following findings; malar rash, discoid erythema, proteinuria, positive antinuclear antibody and anti-DNA antibody. She had been treated with various immunosuppressive drugs including pulse use of corticosteroid, cyclophosphamide and cyclosporin A. She was referred to our hospital because of proteinuria and numbness on her right fifth toe, refractory to above treatment. On admission, the activity of her disease was already low and she had no abdominal symptoms. Plain X-ray film showed multiple round translucencies along the wall of the ascending and transverse colon. Colonoscopy revealed multiple firm-walled cysts distributing in the terminal ileum as well. A diagnosis of PCI was made and she was successfully treated with oral antibiotics and laxatives. The association of PCI with SLE is reviewed briefly.

[Preparation of ketamine tablets for treatment of patients with neuropathic pain].

Ketamine is known to have distinguished analgesic effects without anesthetic when administered in a low dose. Since ketamine is not commercially available except injection forms, we prepared ketamine tablets for the home-care medication of patients with neuropathic pain. The direct compression or wet granulation method was employed to form 150 mg of tablets containing 50 mg of ketamine. The latter method was superior to the former one in terms of content uniformity, weight variation and disintegration tests of the tablets. Ketamine contents in the tablet prepared by the wet granulation method were unchanged for 12 weeks under the conditions of 25 degrees C and 75% relative humidity (RH). The Cmax and AUC0-3 h values for ketamine after administration of the tablet were slightly smaller than those of the syrup in a healthy volunteer. However, analgesic effects of the tablet was similar to that of the syrup in a patient with neuropathic pain. And the tablet was also effective for another four patients with neuropathic pain. These results indicate that ketamine tablets are useful for the home-care medication of patients with neuropathic pain.

Percutaneous revascularization of lesions with saphenous vein graft failure: influence of chronic total occlusion on early outcome.

The purpose of this study was to evaluate a therapeutic strategy of percutaneous transluminal coronary angioplasty (PTCA) in patients with recurrent angina following coronary artery bypass grafting. The study looked at 112 branches associated with graft failure, excluding new lesions in the native coronary artery (NCA). Chronic total occlusion (CTO) was observed in 50% of NCA (56/112) and in 68% of the grafts (76/112). Thirty-three branches (29%) showed CTO in both NCA and the graft. The overall success rate was 86% (96/112). The success rate on NCA was 98% (44/45) in non-CTO, while in CTO it was significantly lower at 62% (18/29). As to grafts, the success rate was 94% (32/34) in non-CTO, while it was 50% (2/4) in CTO. These characteristics, with respect to lesion morphology and the prevalence of CTO, exerted an influence on the selection of the access vessels for revascularization. Early outcome depended on the result of treatment of CTO.

Comparison of quantitative coronary angiographic results after directional coronary atherectomy and balloon angioplasty of protected left main coronary stenosis.

We compared the angiographic and clinical outcomes after directional coronary atherectomy (DCA, 13 patients) with those after conventional balloon angioplasty (BA, 21 patients) in patients with protected left main coronary artery stenosis. The initial success rate was 100% in the DCA group and 81% (17 of 21) in the BA group. Restenosis was present in 2 of 11 patients in the DCA group and 9 of 16 patients in the BA group (18% vs. 56%, P < 0.05). DCA and BA improved a minimal lumen diameter. The initial gain after DCA was greater than that after BA. At follow-up, the minimal lumen diameter was larger and the percentage diameter stenosis was smaller in the DCA group than in the BA group. The late loss and loss index were equivalent in both groups. Compared with conventional BA, DCA in protected left main coronary artery stenosis is associated with a higher angiographic success rate and provides a wider luminal diameter with reduced incidence of restenosis.

The coexistence of abdominal aortic aneurysm and advanced gastric cancer associated with recurrent angina after coronary artery bypass grafting.

A 76-year-old man with abdominal aortic aneurysm (AAA) and concomitant gastric cancer, who had undergone coronary artery bypass grafting (CABG), presented with recurrent exertional angina. Both lesions, the AAA and advanced gastric cancer, exhibited an absolute indication for urgent surgery. Coronary revascularization with percutaneous transluminal coronary angioplasty (PTCA) was carried out successfully before abdominal surgery. A one-stage abdominal operation was performed safely. The need for coronary revascularization complicates the treatment strategy for these patients with associated coronary artery disease. PTCA is the best option, especially if the patient presents with recurrent angina after prior CABG.

[Usefulness of percutaneous transluminal angioplasty of lesions in saphenous vein graft].

The purpose of this study is to evaluate the potential efficacy of saphenous vein graft (SVG) angioplasty. Angioplasty of 64 lesions in SVG was performed in 32 patients. (balloon angioplasty for 59 lesions and directional atherectomy for 5 lesions). The angioplasty site involved the proximal vein graft including aortic anastomosis in 9 lesions, the midportion of the graft in 32 lesions, and the distal anastomotic site in 17 lesions. Six grafts were totally occluded. The overall initial success rate was 89%, and restenosis rate was 57%. The initial success rate was lower in occluded grafts (75%) than in proximal (89%), midportion (94%), or distal lesions (88%). There were similar trend for restenosis (proximal 67%, midportion 50%, distal 56%, occluded 75%). The initial success rate was higher in vein graft < 1 year old compared with graft 1 to 5 years or > 5 years after operation (100% versus 87%, 82% respectively). The restenosis rate did not depend on graft age (< 1 year 53%, 1 to 5 years 75%, > 5 years 50%). There was no procedural death or emergent operation. Distal embolization occurred in two cases, both of which underwent directional atherectomy. Angioplasty of a non occlusive obstruction in saphenous vein graft had an initial success rate of approximately 90% and is a safe procedure. Angioplasty of chronic total occlusion was associated with poor acute result. Although the induced high restenosis rate remains a significant problem, angioplasty of saphenous vein graft is a reasonable alternative to revasculization.

[Combined resection of the descending aorta for lung cancer with aortic invasion].

Four lung cancer patients underwent left pneumonectomy combined with resection of the descending aorta. Their tumors arose from the superior segment (S6) of the left lower lobe and directly invaded the aorta. Their angles of contact with descending aorta were more than 130 degrees. There were two squamous cell carcinoma, and one each of large cell carcinoma, and adenosquamous carcinoma. In Case 1, the defect of the descending aorta was closed by patch graft using simple aortic cross-clamping. In the other three patients, the aorta was replaced by a 5-7 cm long woven Dacron tube graft under temporary bypass using Anthron tube. Their postoperative courses were uneventful. Although the follow-up period is too short at present, two cases (3 and 4) have been alive without recurrence for five and two months, respectively. The induction chemotherapy followed by extended surgery (Case 4) may become a feasible treatment modality to overcome the poor prognosis in patients with advanced lung cancer invading to the great vessels.

Percutaneous left ventricular assist system using a modification of the Dennis method: initial clinical evaluation and results.

A percutaneous left ventricular assist system (PLVAS) using a modification of the Dennis method was developed and implemented in 8 patients. Transseptal cannulation was performed under biplane fluoroscopy and/or transesophageal echocardiogram without encountering any problems. All the patients were in a state of severe cardiogenic shock, caused by acute myocardial infarction in 5, cardiomyopathy in 2, and postcardiotomy in 1, and were on intraaortic balloon pump support and/or percutaneous cardiopulmonary support (PCPS), in the form of partial cardiopulmonary bypass. Three patients who developed concomitant right heart failure required additional PCPS. All the patients were supported at 3.0 to 4.0 l/min for 76-284h for an average time of 159h. Three patients were successfully weaned from PLVAS and one of these patients, who had suffered an acute myocardial infarction, was discharged from hospital. The complications directly related to this system were minimal. Our observations led to the conclusion that PLVAS using our modification of the Dennis method is a simple, easy, and safe means of maintaining adequate systemic circulation in severely ill patients. As PLVAS is particularly effective for patients in cardiogenic shock following acute myocardial infarction, we believe that it will be applied routinely by many cardiac surgeons and cardiologists in the future.

[Planned combination therapy of coronary artery bypass and PTCA in ischemic heart disease].

Concomitant planned therapy consisting of a coronary artery bypass operation and percutaneous transluminal coronary angioplasty (PTCA) was attempted to shorten the period of cardiac arrest and make operations safer in patients undergoing emergency coronary artery bypass operations or coronary artery bypass operations in cases of significantly reduced left ventricle function or small perfusion lesions. The bypass operation was performed to treat only the main lesion and PTCA was undertaken 1-2 months later for coronary revascularization to treat secondary lesions. Finally, complete coronary revascularization was achieved. This concomitant method was performed on three cases. In all of these cases, two grafts were made and 1-2 lesions were dilated by PTCA. It was suggested that planned concomitant coronary artery bypass operations and PTCA provide a safer method of treatment in certain selected cases.

Successful surgery of malignant fibrous histiocytoma in the lung with gross extension into the right main pulmonary artery.

We report on successful surgical treatment of a 49-year-old female suffering from malignant fibrous histiocytoma which arose from the lower lobe of the right lung with gross extension into the right main pulmonary artery, mimicking pulmonary thromboembolism. With the aid of a percutaneous cardiopulmonary support system, right pneumonectomy with resection of the right main pulmonary artery and reconstruction of the pulmonary artery was performed. Surgical management and the unique clinicopathological features of this case are discussed.