[Surgical stratery for abdominal aortic aneurysm with coronary artery disease].

Coronary artery disease (CAD) and abdominal aortic aneurysm (AAA) frequently coexist. One-stage surgery of coronary artery bypass grafting (CABG) and AAA repair is recommended for the treatment of patients having a combination of severe CAD and large AAA. Fifty-three patients underwent simultaneous CABG and AAA repair. By operative methods, we classified them into 3 groups; on-pump CABG and AAA repair group (group A: n=13), AAA repair and off-pump CABG using partial sternotomy group (group B: n=23) and those using full sternotomy group (group C: n=16). It was evaluated which operative method was superior. Off-pump method was superior to on-pump method. A problem of simultaneous CABG and AAA repair was postoperative respiratory complication. This study suggests that the minimally invasive methods should be used for one-stage operation of CABG and AAA repair.

[Adult Bochdalek hernia with volvulus of the stomach].

We report a rare case of Bochdalek hernia, congenital posterolateral diaphragmatic hernia with volvulus of the stomach, in an adult A 74-year-old man was admitted to our hospital complaining of sudden abdominal pain and vomiting. Roentgenologic examination of the chest showed air above the left diaphragm, and the mediastinum was displaced to the right. Upper gastrointestinal series revealed volvulus of the stomach in which the pylorus was displaced to the left. The surgical repair was done through left thoracotomy with combining laparoscopy and thoracoscopy without surgical complications, 1 year later the patient is asymptomatic.

[Surgical strategy for acute type A aortic dissection with cerebral ischemia due to acute occlusion of aortic arch branches].

In the treatment of acute type A aortic dissection, it is important to cope effectively with cerebral ischemia due to preoperative acute occlusion of arch branches and intraoperative cerebral malperfusion under extracorporeal circulation. The validity of our surgical strategy for such cases was evaluated. Our surgical strategies are as follow; for cases with preoperative cerebral infarction and disturbance of consciousness total aortic arch replacement is performed after the improvement of brain edema, and for cases of transient cerebral ischemia, emergency operation is performed. In the emergency operation, selective cerebral perfusion through the carotid artery of the diseased side is initiated as soon as possible. In conclusion, our surgical strategy for acute type A aortic dissection with cerebral ischemia due to acute occlusion of aortic arch branches is acceptable. There was no significant difference between the cerebral ischemia group and the control group concerning hospital mortality, cerebral complication and the 5-year survival rate.

[Long-term results of total aortic arch replacement using selective cerebral perfusion].

From June 1994 to July 2001, 92 consecutive patients underwent total aortic arch replacement using hypothermic selective cerebral perfusion. Forty-four patients had nondissecting fusiform or saccular aneurysms (non-ruptured 34, ruptured 10), and 48 patients had dissection (acute 37, chronic 11). Hospital mortality rate was 6.8% in the nondissecting group and 6.3% in the dissecting group. No major operative cerebral complications were observed. There were 9 late deaths in the nondissecting group and 5 late deaths in the dissecting group. The actuarial survival rate was 61.6% after 100 months in the nondissecting group and 82.5% after 86 months in the dissecting group (p = 0.5128). In the postoperative aortic accidents, there were 2 cases of the descending aortic rupture and 2 cases of cholesterol crystal embolization in the nondissecting group and 3 cases of thoracoabdominal grafting, 2 cases of re-operation in the ascending aorta and 1 case of descending aortic rupture in the dissection group. The actuarial freedom from aortic accidents was 88% after 100 months in the nondissecting group and 80% after 86 months in the dissecting group (p = 0.6908). Our surgical outcome of total aortic arch replacement using hypothermic selective cerebral perfusion are satisfactory.

Effect of Sotalol in the prevention of atrial fibrillation following coronary artery bypass grafting.

OBJECTIVE: We assessed the efficacy of postoperatively administered oral Sotalol in preventing the occurrence of postoperative atrial fibrillation. METHODS: Subjects were 80 consecutive patients undergoing coronary artery bypass grafting (CABG) randomized alternately into a Sotalol group (40 patients) administered 80 mg of oral Sotalol daily starting on the postoperative day 1 and continued for 14 days, and a control group (40 patients) matched for age and gender. RESULTS: The incidence of postoperative atrial fibrillation (21 patients) was significantly lower in the Sotalol group (6/40 patients; 15%) than in controls (15/40; 37.5%) (p < 0.05). Significant bradycardia or hypotension, necessitating drug withdrawal, occurred in 3 of 40 (7.5%) patients in the Sotalol group. None in the Sotalol group developed Torsardes de Pointes or sustained ventricular arrhythmias or other severe side effects. The sinus heart rate increased in both groups but less in the Sotalol group. QT, QRS, and QTc durations did not differ between groups. Postoperative hospital stay did not differ between groups. CONCLUSIONS: Oral Sotalol administration of 80 mg daily was associated with a significant decrease in postoperative atrial fibrillation in patients undergoing CABG without appreciable side effects. Sotalol should thus be considered in preventing postoperative atrial fibrillation in patients undergoing CABG in the absence of heart failure and significant left ventricular dysfunction.

Patient survival after total knee arthroplasty.

The authors analyzed the 5-year and 9-year survival in 134 of 165 patients who underwent total knee arthroplasties from 1989 to 1996 in our department. Patients were followed until December 31, 1998, or until the time of death. Diagnoses were rheumatoid arthritis in 81 patients (132 knees) and osteoarthritis in 53 patients (79 knees). The survival of the patients was compared to that of the age- and sex-adjusted general population. Kaplan-Meier survival curves were constructed. Twenty-two patients in the study died before the end of the follow-up. The cumulative 5-year patient survival was 88.7%, and 9-year patient survival was 64.4% for total knee arthroplasty patients. The standardized mortality ratio was 0.11 (95% confidence interval: 0.02-0.40) for the patients with osteoarthritis, and 0.81 (95% confidence interval: 0.52-1.25) for the patients with rheumatoid arthritis. The Cox proportional hazards model showed that the factors of male sex and rheumatoid arthritis were related to a higher mortality rate in the total knee arthroplasty group.

Further studies on the site-specific protein modification by microbial transglutaminase.

A guinea pig liver transglutaminase (G-TGase)-mediated procedure for the site-specific modification of chimeric proteins was recently reported. Here, an alternative method with advantages over the recent approach is described. This protocol utilizes a microbial transglutaminase (M-TGase) instead of the G-TGase as the catalyst. M-TGase, which has rather broad structural requirements as compared to the G-TGase, tends to catalyze an acyl transfer reaction between the gamma-carboxamide group of a intact protein-bound glutamine residue and various primary amines. To demonstrate the applicability of the M-TGase-catalyzed protein modification in a drug delivery system, we have utilized recombinant human interleukin 2 (rhIL-2) as the target protein and two synthetic alkylamine derivatives of poly(ethyleneglycol) (PEG12; MW 12 kDa) and galactose-terminated triantennary glycosides ((Gal)(3))) as the modifiers. For the M-TGase-catalyzed reaction with PEG12 and (Gal)(3), 1 mol of alkylamine was incorporated per mole of rhIL-2, respectively. Peptide mapping of (Gal)(3)-modified rhIL-2 ((Gal)(3)-rhIL-2) by liquid chromatography-electrospray ionization mass spectrometry (LC-ESI/MS) suggested that the Gln74 residue in rhIL-2 was site specifically modified with (Gal)(3). The PEG12-rhIL-2 and (Gal)(3)-rhIL-2 conjugates retained full bioactivity relative to the unmodified rhIL-2. In pharmacokinetic studies, PEG12-rhIL-2 was eliminated more slowly from the circulation than rhIL-2, whereas (Gal)(3)-rhIL-2 accumulated in the liver via hepatic asialoglycoprotein receptor binding. The results of this study expand the applicability of the TGase-catalyzed methodology for the preparation of protein conjugates for clinical use.

Simultaneous coronary arterial bypass surgery using mini-sternotomy and off-pump methods and abdominal aneurysm repair.

A technique of combined minimally invasive coronary artery surgery and abdominal aneurysm repair is described. A mini-sternotomy and off-pump coronary artery bypasses to the left descending branch and right coronary arteries are conducted before abdominal aneurysm repair in a simultaneous operation.

Pulsatile cardiopulmonary bypass failed to prevent neuropsychological dysfunction.

To prevent neurological complications during cardiopulmonary bypass, cerebrovascular screenings by magnetic resonance angiography and computed tomographic scan of the brain were performed preoperatively in patients who had ischemic heart disease and all patients aged 60 years or older. From 1996 to 1999, 173 adult patients (mean age 65.1+/-7.7 y) were evaluated. Forty-one patients were considered to be at high risk from the screening tests and pulsatile cardiopulmonary bypass was applied. The remaining 132 patients were placed in the control group. Postoperative cerebral infarction caused by embolism was encountered in three patients (3/173, 1.7%), two in the high-risk group (2/41, 4.8%) and one in the control group (1/132, 0.8%), but the difference between these incidences was not statistically significant. Cerebral infarctions caused by brain hypoperfusion did not occur in this series. A neuropsychological test (Hasegawa's dementia scale, HDS) was done pre- and postoperatively. No one was diagnosed with dementia preoperatively, whereas 7 patients were diagnosed with dementia postoperatively. Among these 7 patients, 6 patients were in the high-risk group (17.1%, 6/35) and one patient was in the control group (0.9%, 1/113). Under these circumstances, using cerebrovascular screening and pulsatile cardiopulmonary bypass, cerebral infarction due to hypoperfusion did not occur, but cerebral infarction due to embolism was encountered, and neuropsychological dysfunction was not prevented.

Comparison of various reproductive status in Sika deer (Cervus nippon) using fecal steroid analysis.

The feasibility of fecal steroid analysis for pregnancy diagnosis and sex determination were tested in sika deer (Cervus nippon). Feces were collected from captive sika deer in June (non-breeding season and late-pregnancy period) and October (breeding season), and also from the rectum of 24 female sika deer (19 pregnant and 5 non-pregnant females) shot as part of programs for population control in February and March (mid-pregnancy period). In mid- and late-pregnancy periods, fecal progesterone concentrations were significantly higher in pregnant female than in male and non-pregnant female deer. In October, fecal testosterone concentrations were higher in adult male deer, and no difference was found between young males and females. These results suggest that fecal steroid analysis would be a useful means for estimating pregnancy status and for detecting adult male among wild deer.

Combined grafting of thoracic aortic aneurysm and cardiac repair using continuous cold-blood coronary perfusion.

OBJECTIVE: For patients diagnosed with combined thoracic aortic aneurysms and cardiac lesions, we conduct a 1-stage operation for ascending and aortic arch grafting. We studied surgical outcome comparatively with patients undergoing aortic grafting alone. For descending and thoracoabdominal aortic grafting, we choose a 2-stage operation. SUBJECTS AND METHODS: Subjects were 80 patients undergoing ascending and aortic arch aneurysm repair between June 1994 and March 1999. Group 1 consisted of 30 undergoing simultaneous cardiac repair. Concomitant cardiac procedures involved 21 valvular, 5 coronary arterial, and 4 valvular and coronary arterial surgeries. Group 2 consisted of 50 undergoing aortic grafting alone. We used crystalloid cardioplegia and additional antegrade continuous cold-blood coronary perfusion in Group 1, and crystalloid cardioplegia alone in Group 2. RESULTS: Hospital mortality was 10% in Group 1 and 2% in Group 2. Surgery length, cardiopulmonary bypass time, and aortic cross-clamping time in Group 1 were significantly longer than Group 2. Myocardial ischemic time did not differ significantly. Postoperative ICU stay, mechanical ventilation time and catecholamine support time did not differ significantly. Actuarial survival was 66.9 +/- 13.1% at 52 months in Group 1 and 87.2 +/- 4.8% at 57 months in Group 2 (p = 0.2918). CONCLUSION: Simultaneous cardiac repair and ascending and aortic arch aneurysm repair were conducted using continuous cold-blood coronary perfusion. Hospital mortality and mid-term survival did not differ significantly between groups.

Extended aortic grafting for acute ascending dissection after type B dissection.

A 31-year-old man was diagnosed with acute ascending aortic dissection and massive aortic regurgitation following acute type B dissection during drug treatment. Although the aortic arch was not dissected, we performed aortic replacement from the aortic root to the proximal portion of the descending aorta. The aim of the operation was the prevention of aortic arch dissection, and closure of initial entry of type B dissection.

Acute type A aortic dissection associated with an aortic annular abscess.

We describe a 66-year-old woman who underwent open heart surgery because of congestive heart failure. During operation, we found a Stanford type A dissection and an aortic ring abscess, which had burst into the aortic lumen. No other entries were found. Pathological examination showed excessive neutrophil infiltration in the aortic root. We strongly suspect that the abscess produced the intimal tear to cause the aortic dissection.

Individual base model of predator-prey system shows predator dominant dynamics.

Individual base model of predator-prey system is constructed. Both predator and prey species have age structure and cohorts of early reproductive age have competitive advantage. The model has linear functional response in predation behavior and includes the effect of interference among predators and delay of population growth from resource intake, not by functional response but by calculation procedure. Each foraging action is calculated successively and surplus or scarce of acquired resources is interpreted into population size through individual birth and death. This model shows that biomass of prey killed by predator is dependent on demand of predator and that heterogeneity in predator population is essential in persistency and stability of predator-prey system. Heterogeneity of predator makes predator individuals of less competing ability die rapidly. Rapid death of weak individuals causes rapid decrease of total demand of predator and that makes enough room for survived predators. Therefore, the biomass of killed prey is dependent on predator's demand. As young or infant population of predator are the more vulnerable to shortage of prey, and when many of them cannot survive to reproductive age, they can stabilize the system by wasting excessive prey with only temporal numerical increase of predator population.

Strategy for reduction of stroke incidence in coronary bypass patients with cerebral lesions. Early results and mid-term morbidity using pulsatile perfusion.

OBJECTIVES: Cerebral complication is an important factor affecting the outcome after coronary artery bypass surgery under cardiopulmonary bypass. One of the causes for cerebral complication is preoperative cerebrovascular stenotic lesion. Here, we have studied the effect of pulsatile perfusion on the rate of cerebral complication due to a cerebrovascular lesion in patients undergoing coronary arterial bypass graft under cardiopulmonary bypass. METHODS: 261 consecutive elective patients underwent operation using cardiopulmonary bypass for management of the atherosclerotic ascending aorta. Group 1 consisted of 62 patients with a cerebrovascular stenotic lesion (> or = 75%) identified on a magnetic resonance angiogram or multiple cerebral infarction diagnosed using a computer tomogram. Group 2 consisted of 199 patients diagnosed with no significant cerebral lesion. In Group 1, the systolic blood pressure during cardiopulmonary bypass was maintained at a level of 80 mmHg by means of pulsatile flow. In Group 2, non-pulsatile perfusion was used as usual. RESULTS: The overall hospital mortality was 1.5%, and no mortality was caused by a cerebral event. Only one patient in Group 1 suffered from temporary hemiparalysis. A cerebral complication occurred in only 1.6% in Group 1, and 0.4% overall. The actuarial freedom from cerebrovascular accident after 54 months was 84.4% in Group 1, and 96.2% in Group 2 (p = 0.0011). CONCLUSIONS: Management of the atherosclerotic ascending aorta and the use of pulsatile perfusion were helpful in preventing cerebral injury during CABG.

Aortic dissection complicated with aorto-right atrium fistula.

Aorto-right atrium fistula associated with aortic dissection is a very rare complication. Here report a case of successful surgical repair of ascending aortic dissection complicated with aorto-right atrium fistula. A 65-year-old man was presented with sudden chest pain and dyspnea. Fifteen years ago, he had aortic valve replacement. An aortic dissection with fistula to the right atrium was diagnosed by echocardiography and cardiac catheterization. At operation, dense adhesion of the aortic root due to the previous cardiac operation was confirmed, and this was suggested as the cause for this rare complication.

The effect of carbon dioxide tension on cerebral circulation during hypothermic selective cerebral perfusion.

BACKGROUND: Some reports have observed the response of cerebral blood flow to PaCO2 during hypothermic cardiopulmonary bypass. We studied the effect of PaCO2 on the cerebral circulation during hypothermic selective cerebral perfusion. METHODS: Between June 1992 and January 1998, 35 patients underwent aortic arch grafting using hypothermic selective cerebral perfusion (20 degrees C). In the earlier four patient (Group 1), carbon dioxide gas was not added. In the latter 31 patient (Group 2), carbon dioxide gas was added to the cerebral perfusion. The hemodynamics and rates of change in cerebral oxygen saturation were evaluated. RESULTS: In Group 1, the index of cerebral arterial resistance was 9.2+/-2.2 at the start of selective cerebral perfusion and increased to 15.7+/-0.1 at the re-warming stage (p<0.05), and there was a significant decrease in cerebral oxygen saturation at the re-warming stage (p<0.001). In Group 2, the index of cerebral arterial resistance was 4.7+/-1.7 at the start of selective cerebral perfusion and 4.3+/-1.5 at the re-warming stage, a non-significant change. The change in cerebral oxygen saturation was also nonsignificant between the start of selective cerebral perfusion and the re-warming stage. Among the neurological outcomes, there was only one small cerebral infarction in Group 2; however, no delayed conscious recovery was observed. CONCLUSIONS: The addition of CO2 to cerebral perfusion was a factor in inhibiting the increase in the cerebral vascular resistance at the re-warming stage.

Gene transfer into hepatoma cells mediated by galactose-modified alpha-helical peptides.

To develop a receptor-mediated gene delivery system into hepatoma cells using the cationic alpha-helical peptide as the gene carrier molecule, we modified an alpha-helical peptide, which is known to have transfection abilities into cells, with a multi-antennary ligand containing several galactose residues that provide efficient binding to the asialoglycoprotein receptor. The galactose-modified peptides formed complexes with a plasmid DNA and showed gene transfer abilities into HuH-7 cells, a human hepatoma cell line. The transfection efficiency of the peptide was increased by increasing the number of modified galactose residues on the peptide. Furthermore, considerable inhibition of the transfection efficiency by the addition of asialofetuin, which is a ligand for the asialoglycoprotein receptor, was observed in all galactose-modified peptides. Based on this result, we could confirm that the internalization of the galactose-modified peptides occurred by the receptor-mediated endocytosis pathway. In addition, to understand the transport route of the peptide-DNA complex in the cell, the effects on the transfection efficiencies with several endocytosis inhibitors were examined. As a result, it was suggested that the translocation of the peptide-DNA complex from the endocytic compartments to the cytosol mainly occurred during an early endosome step.

Transglutaminase-mediated dual and site-specific incorporation of poly(ethylene glycol) derivatives into a chimeric interleukin-2.

To expand the applications of poly(ethylene glycol) (PEG)-protein conjugates for clinical use, we have developed a novel method for dual and site-specific incorporations of PEG derivatives into proteins using a substrate peptide (AQQIVM, named TG2) and transglutaminase (TGase). In our previous studies, TG2 was shown to be a special peptide with two adjacent Gln substrates for guinea pig liver transglutaminase (G-TGase). We have now constructed a chimeric protein (named rTG2-IL-2) of human interleukin-2 (IL-2), in which TG2 was fused to the N-terminus of IL-2. For the G-TGase-catalyzed reaction, rTG2-IL-2 was dually and site-specifically modified with alkylamine derivatives of PEG (PEG10, average M(r) 10 kDa) at both the Gln2 and Gln3 residues in the appended tag. To demonstrate the effectiveness of the G-TGase-catalyzed PEG-incorporation, we have compared the characteristics and the biological properties of PEG10-rTG2-IL-2 species with two PEG10 molecules attached to rTG2-IL-2 [(PEG10)(2)-rTG2-IL-2] with that of (PEG10)(2)-rhIL-2(R), in which PEG10 was randomly incorporated into rhIL-2 by a general procedure using a N-hydroxysuccinimidyl ester of PEG (PEG10-COOSu) (M(r) 10 kDa). (PEG10)(2)-rTG2-IL-2 was found to be superior in its in vitro bioactivities and equivalent in its pharmacokinetic profiles to (PEG10)(2)-rhIL-2(R). Unlike most previous methods, this approach can place dual PEG chains at designed sites on chimeric proteins without decreasing their bioactivities. Thus, TGase-catalyzed PEG-incorporation would improve the therapeutic utility of PEG-protein conjugates.

Unique substrate specificities of two adjacent glutamine residues in EAQQIVM for transglutaminase: identification and characterization of the reaction products by electrospray ionization tandem mass spectrometry.

Reversed-phase HPLC (RP-HPLC) and electrospray ionization tandem mass spectrometry (ESI-MS/MS) were used to characterize the transglutaminase (TGase)-catalyzed dual modification of a peptide (EAQQIVM, named FibN) with monodansylcadaverine (MDC). The synthesized FibN peptide, which was derived from the N-terminal sequence of fibronectin, was used as the substrate for a guinea pig liver TGase (G-TGase). The time course of incorporation of MDC into FibN, detected by RP-HPLC, indicated two separate fluorescent product peaks. ESI-MS analysis of the isolated fractions indicated that products represented MDC-incorporated FibN molecules in molar ratios of 1:1 ((MDC)-FibN) and 2:1 ((MDC)2-FibN). A sequence analysis of MDC-FibN, using ESI-MS/MS, showed that the first modified residue in FibN was mainly Gln3. The kinetic analysis of MDC incorporation suggested that dual incorporation would occur by mainly one route. A one-dimensional 1H NMR comparison of MDC-FibN and unmodified FibN suggested that the first incorporation of MDC at Gln3 altered the substrate reactivity of the Gln4 residue in FibN for the G-TGase-catalyzed reaction. Thus, a detailed analysis of the peptide products using RP-HPLC and ESI-MS/MS should provide a powerful tool for exploring the mechanism of the substrate requirements of TGases.