Single nucleotide polymorphisms: discovery of the genetic causes of male infertility.

We carried out single nucleotide polymorphism (SNP) and mutation analyses of haploid germ cell-specific genes. An analysis of 13 genes associated with male infertility in approximately 300 infertile male patients and approximately 300 male volunteers with proven fertility revealed two mutations that might produce male infertility, and three SNP/mutations associated with male infertility in 13 germ cell-specific genes. These findings strongly support the hypothesis that dysfunction of germ cell-specific genes causes idiopathic human male infertility.

Disulfide bond formation in refolding of thermophilic fungal protein disulfide isomerase.

Disulfide bond formation in the refolding of thermophilic fungal protein disulfide isomerase (PDI) was investigated. It was revealed that (i) a disulfide bond buried inside the molecule is preferentially formed and contributes to the thermal stability and the isomerizing power of PDI, and (ii) formation of disulfide bonds in active sites located on the molecular surface causes deformation of the optimum conformation resulting in a decrease in the thermal stability.

Angioscopic evaluation of stabilizing effects of bezafibrate on coronary plaques in patients with coronary artery disease.

Background Since long-term administrations of anti-hyperlipidemic agents result in reduction in % stenosis or increase in minimum lumen diameter (MLD) of stenotic coronary segments, it is generally believed that anti-hyperlipidemic agents stabilize vulnerable coronary plaques. However, recent pathologic and angioscopic studies revealed that vulnerability of coronary plaques is not related to severity of stenosis and the rims rather than top of the plaques disrupt, and therefore, angiography is not adequate for evaluation of vulnerability.Angioscopy enables macroscopic pathological evaluation of the coronary plaques. Therefore, we carried out a prospective angioscopic open trial for evaluation of the stabilizing effects of bezafibrate on coronary plaques.Methods From April, 1997 to December, 1998, 24 patients underwent coronary angioscopy of the plaques in the non-targeted vessels during coronary interventions and 6 months later. The patients were divided into control (10 patients, 14 plaques) and bezafibrat (14 patients, 21 plaques) groups. Oral administration of bezafibrate (Bezatol SR, 400mg/day) was started immediately after the interventions and was continued for 6 months. The vulnerability score was determined based on angioscopic characteristics of plaques and it was compared before and 6 months later.Results Six months later, vulnerability score was reduced (from 1.6 to 0.8;p < 0.05) in bezafibrate group and unchanged (from 1.4 to 1.3; NS) in control group. In bezafibrate group, the changes in vulnerability score was not correlated with those in % stenosis or MLD. Conclusion The results indicate that bezafibrate can stabilize coronary plaques.

Percutaneous dye image cardioscopy for detection of endocardial lesions.

Endocardial lesions are caused not only by inflammatory processes but also by myocardial ischemia, resulting in endocardial thrombosis and cerebral embolism. We deviced a method for direct visualization of endocardial damages by a novel dye image cardioscopy with Evans blue and examined its feasibility in patients with heart disease. The dye was injected into the left ventricle before and after endomyocardial biopsy. Endocardial surface was stained in dark blue in 63% of patients with angina pectoris before biopsy. After biopsy, the biopsied portions were stained in blue in all. The results indicate that endocardium is damaged even in apparently intact LV in patients with ischemic heart disease and that endomyocardial biopsy causes severe endocardial damages.

Evaluation of Annuloaortic Ectasia by Angioscopy and IVUS "Report of 2 cases".

We attempted combined use of angioscopy and intravascular ultrasonography (IVUS) to localize the coronary ostia and determine the aortic segment to be replaced in patients with annuloaortic ectasia, because these preoperative informations are important for selection of an appropriate technique for reconstructing the coronary artery, to prevent complications, and also to postoperative follow-up. Two cases with annuloaortic ectasia underwent angioscopy and IVUS both pre- and post-operatively. Structure of aortic cusps, position of coronary ostia, the extent of ectasia with very thin wall were clearly observed by IVUS. Angioscopy showed milky white luminal surface of the ectasic segment. After Cabrol's operation, the sutured portion of native aorta and graft was clearly identified by IVUS and mural thrombus and naked surface of graft were observed by angioscopy. Complications were observed in none. The results indicate feasibility of combined use of angioscopy and IVUS for determination of surgical approach and follow-up in patients with AAE.

Preventive effects of an antiallergic drug, pemirolast potassium, on restenosis after percutaneous transluminal coronary angioplasty.

BACKGROUND: We recently confirmed that pemirolast potassium, an antiallergic agent, markedly inhibits migration and proliferation of vascular smooth muscle cells. It has also been reported that pemirolast inhibits intimal hyperplasia in animal experiments. METHODS AND RESULTS: To elucidate the preventive effects of pemirolast on restenosis after percutaneous transluminal coronary angioplasty (PTCA), 227 patients were enrolled in this prospective, randomized trial. A total of 205 patients who were compatible with the protocol were analyzed (pemirolast group, 104 patients with 140 lesions; control group, 101 patients with 133 lesions). Patients in the pemirolast group received 20 mg/d of pemirolast from 1 week before PTCA until the time of follow-up angiography (4 months after PTCA). Angiographic restenosis was defined as diameter stenosis >/=50% at follow-up. Restenosis rates were significantly lower in the pemirolast group than in the control group (24.0% vs 46.5% of patients, 18.6% vs 35.3% of lesions, P <.01, respectively). During 8 months of follow-up, there were no coronary events (death, myocardial infarction, coronary artery bypass surgery, or repeated PTCA) in 81.7% of the pemirolast group and in 63.4% of the control group (P =.013). CONCLUSIONS: This study suggested that pemirolast would be useful in the clinical setting to prevent restenosis after PTCA.

Application of cryoprecipitate as a hematostatic glue.

BACKGROUND: The effectiveness of cryoprecipitate, harvested from a patient's own fresh frozen plasma, for use in cardiac surgery as a hematostatic glue was studied in 32 randomized elective adult cardiac surgery patients from January 1993 to July 1994. MATERIALS AND METHODS: Patients from the Toho Sakura Hospital were randomly allocated to two groups: Group 1 (n=11) received conventional fibrin glue presently available in our institution; while Group 2 (n=21) received autologous cryoprecipitate as a hematostatic glue. Surgical procedures broken down by group were as follows: Group 1: 4 CABG, 5 valvular surgeries and 2 other. Group 2: 11 CABG, 6 valvular surgery, 4 other. We preserved the patient's own blood and stored pure red cell and fresh frozen plasma (FFP). Cryoprecipitate was prepared from the FFP and preserved until required. RESULTS: Cryoprecipitate had a 5-fold increase in fibrinogen activity (1190+/-311 mg/dl vs 238+/-34 mg/dl p<0.001), a 10-fold increase in factor VIII activity (362+/-219% vs 34+/-11%, p=0.001), and 4.5-fold increase in factor XIII activity (538+/-213% vs 119+/-50%, p<0.001), compared to serum. The amount of bleeding postoperatively was slightly lower in the cryoprecipitate glue group compared to the conventional glue group, but this was not significantly different. CONCLUSIONS: We conclude that autologous samples of human cryoprecipitate prepared from a patient's own FFP had a strong hematostatic effect compared to conventional fibrin glue and was a very valuable hematostatic agent during cardiac surgery.

[Effects of repetitive myocardial ischemia on collateral circulation, ST deviation and epicardial wall motion].

The effects of repetitive myocardial ischemia on collateral circulation, ST deviation and epicardial wall motion were examined in 12 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) for single left anterior descending artery disease. Rentrop collateral filling grade was assessed using contrast injection to the contralateral artery during the first and final episodes of coronary occlusion. ST deviation was measured by intracoronary electrocardiography. Epicardial wall motion (%pre PTCA) was measured by guide wire motion analysis according to the centerline method. Collateral filling grade was assessed 30 sec after balloon inflation. The ST segment and the epicardial wall motion were measured 60 sec after balloon inflation and deflation, respectively. There was no change in the collateral filling grade between the first and final episode of coronary occlusion. Patients with collateral filling grade I (R-I group, n = 4), II (R-II group, n = 3) and III (R-III group, n = 5) during coronary occlusion showed mean ST segment shifts of 13.2, 9.4, and 0.9 mm, respectively, and mean epicardial wall motion of 41.4%, 67.2%, and 78.5%, respectively. The collateral filling grade correlated with ST deviation and epicardial wall motion, and there was a significant correlation between epicardial wall motion and ST deviation (r = -0.67). Comparison of the R-I group or severe ischemia (n = 4) and the R-III group or slight ischemia (n = 4) during coronary occlusion for the fourth time showed the effect of preconditioning was obtained in R-I group. More R-III group patients than R-I group had hyperkinetic epicardial wall motion during coronary reperfusion. Stunned myocardium was demonstrated in both R-I group and R-III group patients. Epicardial wall motion was poorer in the R-I group than R-III group. We concluded the following: There is no change in the grade of collaterals during repetitive coronary occlusion, and there is a relationship between the grade of collateral and degree of myocardial protection; there is good correlation between ST segment and epicardial wall motion; ischemic preconditioning is obtained during repetitive severe myocardial ischemia; recovery from brief episodes of slight myocardial ischemia is associated with hyperkinesia of epicardial wall motion; the reduction of stunned myocardium is related to the degree of premyocardial ischemia; preconditioning is sufficient to cause myocardial stunning, but myocardial stunning is insufficient to cause preconditioning.

[A successful surgical replacement for mitral regurgitation after cardiac arrest due to widely ruptured chordae tendineae].

A 47-year-old woman, who has mitral regurgitation previously diagnosed in another hospital, was transferred to our intensive care unit for acute congestive heart failure. Just after admission, her respiratory state became worse and she suddenly fell into cardiac arrest. Five minutes later she recovered through cardiopulmonary resuscitation. The pulmonary artery pressure, however, which reached 85/43 mmHg with a Swan-Ganz catheter, had been exceeding systemic pressure. On echocardiography ruptured chordae tendineae of the mitral anterior leaflet was most suspected. Five days after the intensive treatment with a use of IABP, we operated upon her. On the operative findings most rough zone chordae of both leaflets including two strut chordae were ruptured with severe prolapsing. Thus we chose prosthetic valve replacement rather than mitral valve repair. We replaced the mitral valve with a Carbomedix 25 mm. Postoperatively the mean pulmonary artery pressure remained still high as 40 mmHg. With a continuous intravenous administration of prostaglandin E1, the pulmonary artery pressure became lower gradually. The patient was able to wean from respirator on the 18th postoperative day. The patient was discharged on the 49th postoperative day. The mitral valve removed at operation showed myxomatous degeneration and idiopathic ruptured chordae tendineae on the pathological examination. In summary a 47-year-old woman underwent mitral valve replacement 5 days after cardiac arrest from acute severe mitral regurgitation due to widely ruptured chordae tendineae of both leaflets. She survived the operation and got well. The mitral valve showed myxomatous degeneration on pathological examination.

[Successful surgical treatment of total cavopulmonary connection on a 4-year-old boy with complete transposition of the great arteries and hypoplastic left ventricle].

A four-year-old boy with complete transposition of the great arteries, intact ventricular septum and hypoplastic left ventricle, underwent total cavopulmonary connection after two palliative operations; B-T shunt and central shunt. He had undergone cardiac catheterization three times; four months after birth, and at two and four years of age. LVEDV (% normal) were calculated 31%, 26%, 27%, and RVEDV (% normal) were 226%, 115%, 105% respectively. PA index increased from 178 to 230 and further to 380. This case indicates that intracardiac repair is possible, if appropriate palliative operations suitable for patient's cardiac function and pulmonary artery morphology are applied.

[Impending rupture of a pseudoaneurysm in the descending thoracic aorta: a rare clinical course].

A sixty-year-old male manifested high fever, bloody sputa and an abnormal shadow in the left hilus on chest X-ray film. He was treated with antibiotics as for a infections lung disease. But back pain which he had been suffered from didn't improve. He was referred to the second hospital with suspicion of lung neoplasm. He underwent radiation therapy. The shadow in the left hilus had been increasing in size with the radiation therapy. On CT scanning, the shadow was recognized as an impending aneurysm along the descending thoracic aorta. He was referred to our hospital and operated upon in emergency basis. On operative findings, the aortic aneurysm located from the distal portion of the left common carotid artery and was huge sacklar shape. In surgical procedure, the entrance in the descending aorta was closed with a vascular patch graft because the aortic wall around the entrance was normal and unaffected. Postoperative course was uneventful. We should learn some warning from this case.

[A case report of complex cardiac malformation treated with total cavopulmonary connection after pulmonary artery banding].

A two-year-old boy with cardiac malformation including hypoplastic right ventricle, severe stenosis of the tricuspid valve, atrial primum defect and ventricular septal defect underwent total cavopulmonary connection after pulmonary artery banding, which was done to tract cardial failure at six months after birth. Under cardiopulmonary bypass, an intraatrial cavocaval channel was constructed with a prosthetic patch of expanded polytetrafluoroethylene (EPTFE). The superior vena cava was transected and each end of the superior vena cava was anastomosed to the pulmonary artery in an end-to-side fashion. Pulmonary artery pressure registered 15 mmHg on cardiac catheterization after operation, and angiography showed smooth blood flow to the pulmonary artery from the vena cava. We suggest that a Fontan-type operation could be indicated for the patients younger than 4-year-old having acceptable pulmonary resistance if the symptoms of hemoconcentration and hypoxia are life-threatening.

[A case of mitral valve replacement in the first three months of life for congenital mitral valve regurgitation].

Mitral valve replacement with 19 mm St. Jude Medical mechanical valve was successfully performed for congenital mitral regurgitation in an infant aged 3 months. The infant had undergone ligation of ductus arteriosus at the first month of age. Ten days after the operation, he was discharged, though having systolic murmurs. One month later, however, he was re-admitted for progressive heart failure. After hospitalization, he had to be supported mechanical ventilation. The second operation was needed for intractable heart failure, that was considered to be caused by mitral regurgitation, on an emergency basis without cardiac catheterization. The mitral valve was hypoplastic and the leaflet and chordae were gelatinous. Therefore, mitral valvuloplasty was considered to be impossible, and consequently mitral valve replacement was chosen. Postoperatively the patient's condition remarkably improved. Anticoagulation therapy with sodium warfarin and dipyridamole was maintained after operation. At present the patient is growing without any symptom.

[An emergency coronary artery bypass for failed percutaneous transluminal coronary angioplasty with intractable ventricular tachycardia and fibrillation].

A 73-year-old man with effort angina after myocardial infarction is admitted for percutaneous transluminal coronary angioplasty (PTCA). During PTCA, the left anterior descending artery (LAD) was completely occluded. He was suffered from severe cardiogenic shock with systemic cyanosis and loss of consciousness. Under assist of intraaortic balloon pump (IABP) and cardiac massage, he was transferred to an operating room. Before the start of operation, cardioversion were required 13 times because of repeat attacks of ventricular tachycardia and fibrillation. Coronary artery bypass was completed in 177 minutes after total occlusion of the LAD. At the 5th postoperative day, IABP could be discontinued, and at the 8th postoperative day, the patient was weaned from mechanical ventilation. He was transferred to the prior hospital for rehabilitation on the 65 days after operation. We must try to perform CABG for salvage of myocardium, even if a patient falls in severe cardiogenic shock presenting intractable ventricular tachycardia and fibrillation.

[Surgical repair for pulmonary artery sling on a 46-day-old infant].

Surgical repair on a 46-day-old girl with pulmonary artery sling is reported. She was suffered from dypnea and admitted to a hospital on 12 days after her birth. On chest roentgenogram atelectasis of right lung was found. She had been on respirator since 21 days after her birth. On bronchogram and pulmonary arteriogram, the trachea and right bronchus were compressed and shifted with the anomalous origin of left pulmonary artery which originated from the right pulmonary artery and passed between the trachea and esophagus. These results confirmed the diagnosis of pulmonary artery sling. Hence, she was referred to our hospital for surgical treatment. She underwent surgical repair on 46-day-old. In operation, we chose a mid-sternal splitting incision, and excised 5 mm of ductus arteriosus. Under extracorporeal circulation, the left pulmonary artery was amptated from the right pulmonary artery and pulled back to left side between the trachea and the esophagus. The left pulmonary artery was anastomosed to the main pulmonary artery at the anterior to the left bronchus. She weaned from respirator, and was extubated on the 3rd day after procedure. She recovered uneventfully in post-operative course. On the 24th day after operation she discharged from hospital. On pulmonary perfusion scanning and pulmonary arteriography performed one year after operation, the left pulmonary artery was patient with slightly decreased perfusion in the left lung. Surgical repair for pulmonary artery sling was recognized as high mortality because of frequently associated tracheobronchial anomalies. In the Japanese literature, only 4 patients survived surgically and lived in late stage.(ABSTRACT TRUNCATED AT 250 WORDS)

[A successful surgical repair of anomalous right pulmonary venous connection with Goldenhar syndrome].

A ten-year-old girl with Goldenhar syndrome underwent intracardial repair for partial anomalous right pulmonary venous connection into the superior vena cava. In surgical procedure the proximal tract of superior vena cava was reconstructed into double floor, low floor was tract for anomalous pulmonary venous blood drained into left atrium through the atrial septal defect which was made with resection of prinum septum, upper floor was a real tract for superior venous blood. After operation, arrhythmia did not detect. One month after operation, no stenosis along the superior vena cava or right pulmonary vein were evidenced in catheterization. This surgical technique is superior to using baffle for preventing thrombogenesis. The result suggested that this surgical technique is preferable to the reconstruction of baffle in superior vena cava.

[Clinical assessment of myocardial protection with blood-GIK solution].

Since Jan, 1984, three different types of myocardial protection have been tried in coronary bypass surgery. These are GIK (1984. 1-1984. 12), Young+GIK (1985. 1-1986. 8), and blood GIK (1986. 9-until present). In this study we tried to demonstrate the advantage of myocardial protection induced with blood GIK solution in comparison with that with GIK alone or Young + GIK. (Materials and methods) Eighty-three patients undergone coronary bypass surgery in that period, were evaluated and divided into three groups: Group I had myocardial protection with GIK alone in 24 patients, group II had myocardial protection with Young + GIK in 28 patients, and group III had myocardial protection with Young + blood GIK in 31 patients. Among these groups, the changes of serum enzymes and hemodynamics in postoperative period were compared. (Results) In the hemodynamic changes, cardiac index at 24 hours after operation in group III, was higher than that in the other two groups (p < 0.05). The peak value of MB-CPK in all groups appeared 12 hours after operation, however, 21.9 +/- 19.72 IU/ml in group III was significantly lower than 33.4 +/- 25.5 in group I, or 36.9 +/- 26.8 in group II (p < 0.01). The results demonstrates that the myocardial protection induced with blood GIK are superior to these with the other two method.