OBJECTIVE: To investigate the genetic contribution for myocardial infarction. METHODS: We investigated common polymorphisms of apolipoprotein E gene and angiotensin converting enzyme (ACE) gene in Japanese population. Subjects were 422 healthy people and 254 patients with myocardial infarction. We evaluated the 287 base pair (bp) insertion (I)/deletion (D) polymorphism in intron 16 of the ACE gene and a polymorphism in the apolipoprotein E gene by using the polymerase chain reaction. RESULTS: The ACE genotype prevalences for II, ID, and DD were 36.2, 46.1, and 17.7%, respectively, among the myocardial infarction patients. The prevalence of the D allele of the ACE gene among the myocardial infarction patients (0.593) exceeded that among the healthy controls (0.407). The prevalences of the epsilon 2, epsilon 3, and epsilon 4 alleles of the apolipoprotein E genotype among healthy controls were 0.024, 0.882, and 0.094, and those among survivors of myocardial infarction were 0.024, 0.834, and 0.142, respectively. Myocardial infarction patients had an excessive prevalence of the apolipoprotein E epsilon 4 allele (P < 0.05). Multiple regression analysis demonstrated that the independent risk factors for developing myocardial infarction were age, DD genotype of ACE gene, and apolipoprotein E epsilon 4 allele. Stenotic coronary vessels in myocardial infarction patients did not differ significantly among the patients with various ACE and apolipoprotein E genotypes in the present study. CONCLUSIONS: Among the Japanese, apolipoprotein E epsilon 4 carriers and subjects with ACE DD genotype are at an increased risk of myocardial infarction.

Aged↗

PubMed1998

Growth and quality of life after living-related liver transplantation in children.

Fifty-six consecutive pediatric recipients surviving more than 3 yr after living-related liver transplantation (LRLT) were evaluated in terms of growth, quality of life (QOL) and need for maintenance immunosuppression. Significant improvement in Z-score for height and weight were observed at last follow-up, ranging from 3 to 6 yr after transplantation, although catchup height gain lagged behind recovery in weight (height: -1.77 pre-transplant to -0.77 post-transplant, p<0.001; weight: -1.12 pre-transplant to -0.18 post-transplant, p<0.0001). 82% (46) recipients have remained in good health and have an excellent QOL as assessed in the most recent 6 months; these children lead similar daily lives to normal healthy children, with daily school attendance and full participation in activities including gymnastics and hiking. 3.6% (2) recipients attended school regularly but were unable to participate in sporting activities. 14% (8) recipients remain home or hospital-bound due to persistent complications in the past 6 months, with only minimal school attendance. Less than 10% of recipients were taking steroids by 2 yr post-transplantation, although approximately half of the children were receiving low-dose maintenance steroids at 1 yr. The mainstay immunosuppressant was tacrolimus, with 68% (38) recipients receiving daily therapy, 8.9% (5) alternate-day, 8.9% (5) twice a week, and 5.4% (3) a single dose weekly or alternate weeks. 7.1% (4) recipients were withdrawn completely from all immunosuppressants, including tacrolimus, for various reasons. 8.9% (5) patients have needed multiple immunosuppressive agents over the last 6 months. In conclusion, LRLT restores growth and offers excellent quality of life in pediatric recipients. The majority of recipients require minimal, steroid-free, immunosuppression by 2 yr post-transplant, but the occasional recipient still needs intensive longterm immunosuppression.

Adolescent↗

PubMed1998

University medical information network--past, present, and future.

The University Medical Information Network (UMIN), established in 1989, is a network service organization for national university hospitals in Japan. It has provided various medical information services to medical professionals, including database, electronic mail, and news services. Although its initial network was constructed as a closed network using N1 protocol, it now adopts TCP/IP protocol and is open to other medical professionals via the Internet. The next UMIN network system is planned to be constructed as a secure virtual closed network on the Internet, using cipher technology, and to provide secure information services to national university hospitals via the closed network, and to other medical professional via the Internet. User friendly interface and flexible system development were made possible by adopting TCP/IP, and the number of users dramatically increased accordingly. However, the database, software design, and human organizations developed in the N1 era have now proven to be of great value, and contribute to todayís flourishing state of the UMIN.

Computer Communication Networks↗

PubMed1998

Using a WWW-based mail user agent for secure electronic mail service for health care users.

WWW-based user interface is presented for secure electronic mail service for healthcare users. Using this method, communications between an electronic mail (WWW) server and users (WWW browsers) can be performed securely using Secure Socket Layer protocol-based Hypertext Transfer Protocol (SSL-HTTP). The mail can be encrypted, signed, and sent to the recipients and vice versa on the remote WWW server. The merit of this method is that many healthcare users can use a secure electronic mail system easily and immediately, because SSL-compatible WWW browsers are widely used and this system can be made available simply by installing a WWW-based mail user agent on a mail server. We implemented a WWW-based mail user agent which is compatible with PEM-based secure mail and made it available to about 16,000 healthcare users. We believe this approach is effective in facilitating secure network-based information exchange among medical professionals.

Computer Communication Networks↗

PubMed1998

Biliary complications in pediatric living related liver transplantation.

BACKGROUND: The goal of this study was to evaluate cause and outcome of biliary complications occurring after pediatric living related liver transplantation (LRLT). METHODS: A database of 205 pediatric patients (71 male and 134 female) undergoing 208 LRLT from June 1990 to April 1996 was reviewed. RESULTS: The overall incidence of bile duct complications was 13.9% (29 patients). There were 19 bile leaks, 7 anastomotic strictures, 8 intrahepatic biliary complications, and the bile duct was ligated inadvertently in 2 cases. Logistic regression analysis revealed hepatic artery thrombosis, ABO incompatible transplantation, intrapulmonary shunting in recipients, mode of artery reconstruction, and cytomegalovirus infection were all significant risk factors for biliary complications. CONCLUSIONS: Avoidance of ABO incompatible transplantation where possible, routine use of microvascular techniques for hepatic artery reconstruction to minimize the risk of artery thrombosis, earlier transplantation for patients with intrapulmonary shunt, and prophylaxis against cytomegalovirus infection should all reduce the rate of biliary complications after LRLT in pediatric recipients.

ABO Blood-Group System↗

PubMed1997

Hepatic artery thrombosis in living related liver transplantation.

BACKGROUND: Hepatic artery thrombosis (HAT) after orthotopic liver transplantation remains a significant cause of graft loss in pediatric patients. We previously reported that the microsurgical techniques for arterial anastomosis can reduce the incidence of HAT in living related liver transplantation (LRLT). The purpose of this study is to analyze the risk factors for HAT after LRLT. A total of 245 patients received 250 liver transplants. METHODS: Eight arteries in eight patients, reconstructed with the use of loupe magnification (HAT; 1/8, 12.5%), were excluded from this study. We observed HAT in 4 patients of the 242 transplants (1.7%, HAT group). Seventeen factors were compared between the HAT and the control group (those without HAT). RESULTS: HAT occurred in 3 of 33 grafts (9%) from ABO-incompatible donors, whereas it occurred in 1 of 209 grafts (0.5%) from identical or compatible donors (P=0.008). The corrected volume of fresh-frozen plasma intraoperatively transfused in the HAT group (46.9+/-30.3 ml/kg) was significantly (P=0.015) different from that in the control group (10.2+/-1.9 ml/mg). In all four patients with HAT, emergent revisions of the anastomosis were performed. Two patients with ABO-incompatible grafts died of hepatic failure and sepsis. CONCLUSIONS: Although microsurgical techniques can minimize the surgical risk factors for HAT, overtransfusion of fresh-frozen plasma in high-risk patients (ABO incompatible) may be a critical factor in the development of HAT in LRLT.

Arterial Occlusive Diseases↗

PubMed1997

Coexistence of a graft with the preserved native liver in auxiliary partial orthotopic liver transplantation from a living donor for ornithine transcarbamylase deficiency.

BACKGROUND: Auxiliary partial orthotopic liver transplantation (APOLT) has recently been performed in patients with noncirrhotic metabolic liver diseases. However, long-term outcomes for the preserved native liver and the transplanted liver graft have not been clearly established yet. METHODS: The recipient was a 36-month-old girl with ornithine transcarbamylase deficiency. She underwent APOLT, using her father's left lateral segment. RESULTS: Liver function was normalized soon after APOLT and the patient was able to ingest a normal diet without medication. Coexistence of the well-functioning native liver and graft was demonstrated in a computed tomography scan, Doppler ultrasonography, scintigraphy, and histological examination, during a relatively long-term follow-up period. CONCLUSIONS: APOLT seems to be most useful for the treatment of noncirrhotic metabolic liver diseases.

Biopsy↗

PubMed1997

A hepatic graft tuberculosis transmitted from a living-related donor.

Exclusion of occult diseases in the donor organ and prevention of infectious disease transmission are minimal requirements in organ transplantation. We report here a case of hepatic graft tuberculosis, which was most likely transmitted by the graft from the living-related donor. The course of the recipient included tuberculosis, rejection, and other infections, which led to vanishing bile duct syndrome. Due to various infections and tuberculosis, as well as a strong interaction between rifampicin and tacrolimus, the patient died of pneumonia on day 273 after transplantation. This case emphasizes the importance of care in the selection of a living-related donor for liver transplantation.

Adult↗

PubMed1997

Effects of hypoxemia on early postoperative course of liver transplantation in pediatric patients with intrapulmonary shunting.

Nine pediatric patients (mean age, 10 years) with biliary atresia, who had hypoxemia related to intrapulmonary shunting, underwent living related liver transplantation. The effects of hypoxemia during the early postoperative period after liver transplantation on cardiopulmonary and renal function, as well as on transplanted liver, were analyzed. Based on the degree of shunt ratio calculated by technetium-99m macroaggregated albumin scintigraphy, the nine patients were included in the moderate group (shunt ratio under 40%, n=4) or the severe group (shunt ratio over 40%, n=5). Partial pressure of arterial oxygen was maintained at normal range in the moderate group, while that in the severe group persistently had very low values (<50 mmHg), in spite of a high degree of oxygen supply. However, all patients in the severe group maintained stable cardiopulmonary vital signs, including systemic blood pressure, heart rate, respiratory rate, and cardiac index. They also demonstrated stable renal function. None of the patients died of cardiopulmonary or renal insufficiency after transplantation, but three patients died of portal vein thrombosis, sepsis, and intracranial hemorrhage (one each). The minimal adverse effect of hypoxemia on the transplanted liver was confirmed by a rapid increase of arterial ketone body ratio, low peak values (under 200 IU/L) of aspartate aminotransferase, and a steady decrease of serum total bilirubin. Four patients encountered surgical complications, including two bile leaks from the cut liver surface, two leaks from bilioenteric anastomosis, and one intestinal perforation. Six patients suffered from bacterial infections, including four wound infections, three right subphrenic abscesses, one cholangitis, and two systemic sepses. All patients in the moderate group recovered from hypoxemia, but four of five patients in the severe group have not recovered during the follow-up period between 4 and 9 months. It was concluded that the adverse effects of hypoxemia on cardiopulmonary and renal function and transplanted liver were minimal, so that patients with severe hypoxemia could tolerate the stress of liver transplantation without special management. However, the high incidence of surgical complication and infection suggested the adverse effects of hypoxemia on wound healing and resistance to bacteria infection.

Adolescent↗

PubMed1997

Efficiency of pentoxifylline in donor pretreatment in rat liver transplantation.

Donor pretreatment is a new concept in organ preservation. Pentoxifylline (PTX) has been reported to suppress the activation of Kupffer cells and to decrease injury to the hepatic graft after rat liver transplantation. We evaluated the efficiency of PTX pretreatment on the donor against hepatic injury following cold ischemia (CI) or warm ischemia (WI) using the rat liver transplantation model. Dose dependency: every rat was injected intraperitoneally with PTX (30, 50, or 80 mg/kg) or saline. One hour later, the portal vein (PV) and the hepatic artery (HA) were clamped for 30 min. Transplantation: the donor rat was injected intraperitoneally with 50 mg/kg PTX or saline, 1 hr before laparotomy. Animals were divided into two groups. In the CI group, grafts were preserved for 12 hr in University of Wisconsin solution at 4 degrees C and transplanted. In the WI group, the PV and the HA in the donor were clamped for 30 min before donor surgery, and the grafts were transplanted. Serum levels of tumor necrosis factor-alpha (TNF-alpha), glutathione S-transferase-alpha (GST-alpha), and aspartate transaminase (AST) were measured at 30 min, 3 hr, and 24 hr after reperfusion of the PV. Compared with those of a control group, the serum levels of TNF-alpha, GST-alpha, and AST in the PTX-pretreated groups were significantly lower after both CI and WI at 30 min and further suppressed in the WI group at 24 hr. These results indicate that PTX pretreatment on the donor is effective for suppression of hepatic injury after both CI and WI.

Alanine Transaminase↗

PubMed1997

Impact of the development of a liver transplant program on the treatment of biliary atresia in an institution in Japan.

Kasai operation for biliary atresia (BA) and living-related liver transplantation (LRLT) for failed Kasai cases have been performed by the same team in our hospital. Outcome of the treatment for BA in the pretransplantation and posttransplantation era in our institution were compared. As the "pre" group, 35 children first underwent the Kasai operation between 1982 and 1989. The "post" group consisted of 25 patients who underwent Kasai after introduction of the LRLT program in our hospital (1990). As for the reconstruction procedure after portal dissection during Kasai, jejunal interposition hepatic portoduodenostomy for the pre group was intentionally changed to Roux-en-Y procedure for the post group to decrease the risk of duodenal leakage after LRLT. Patients who needed revision of the Kasai decreased from 57% for the pre group to 28% for the post group. There was only one re-revision in the post group compared with seven in the pre group. In the pre group, 10 patients (28.6%) died at age 6 to 16 (mean, 8.5) months before the transplantation program was initiated. In the pre group, three patients could receive a cadaveric liver transplantation in other countries, and seven had LRLT in our hospital. Ten patients (40%) in the post group had LRLT at 7 to 22 (mean, 9.3) months old, and no deaths occurred in this group. When the patients who had liver dysfunction were excluded, the percentage of the patients who could be expected to survive and accomplish growth without undergoing liver transplantation was similar for the two groups, (31.4% v 36%). The change in the reconstruction procedure and the tendency for fewer revisions of Kasai procedure were effects of the start of the liver transplant program. As a general strategy for BA, Kasai operation should be the initial procedure, followed by liver transplantation for failed Kasai. In the late-diagnosed patients, primary LRLT can be considered if the liver has already been cirrhotic. LRLT in the infantile period is a significant component of this strategy for helping all patients to survive.

Biliary Atresia↗

PubMed1997

Effect of vitamin B12 on the sleep-wake rhythm following an 8-hour advance of the light-dark cycle in the rat.

We have studied the effect of vitamin B12 (VB12) on the sleep-wake rhythm following an 8-h advance of the light-dark (LD) cycle in the rat. The electroencephalogram and electromyogram were recorded on chart paper via a two-channel telemetry system. Infusion of VB12 (Mecobalamin; 0.25 microgram/h) or saline into the abdominal cavity was performed using an implanted miniosmotic pump. Before the phase shift, there was no significant difference between the two groups in terms of the mean daily amount of each vigilance stage. Following the phase advance, in the saline group, wake gradually decreased and nonrapid-eye-movement (NREM) sleep and REM sleep increased. In the VB12 group, no significant change was seen in any of the vigilance states, except for REM sleep on day 3. The results suggest that VB12 may maintain homeostasis of sleep and/or wake amount following an 8-h advance of the LD cycle in the rat.

Animals↗

PubMed1997

Hepatic vein reconstruction in 152 living-related donor liver transplantation patients.

BACKGROUND: Hepatic vein (HV) reconstruction is crucial in partial liver transplantation in which the inferior vena cava (IVC) is preserved. METHODS: We reviewed the medical records of 152 living-related donor liver transplantations (LRDLTs) in 150 children (45 left lobe grafts, 106 lateral segment grafts, and 1 right lobe graft) monitored for 12 months or longer. RESULTS: A standard technique was a wide end-to-side anastomosis between the donor HV and cuffs, consisting of the recipient middle and left HV and an incision to the IVC. In 15 of 22 partial grafts with two separated HVs the two vessels were reformed by back table surgery to have a common anastomotic orifice, and two separate anastomoses of the individual vessels were made for the remaining seven grafts. Four patients with an absence of infrahepatic IVCs and two with completely obstructed IVCs had end-to-end anastomoses with recipient IVCs. Four patients with stenotic IVCs had end-to-side anastomoses with new orifices on the IVCs. Two patients had acute HV obstruction caused by twisting of the HV that required laparotomy, and six had late-onset HV obstruction that required radiologic intervention. A tissue expander was placed prophylactically in the right subphrenic space in 10 patients to prevent the dislocation of the graft into the right subphrenic space. CONCLUSIONS: It is important in HV reconstruction in partial liver transplantation to make wide orifices and to adapt each graft to its orthotopic place, taking into consideration graft shape, size of the abdominal cavity of the recipient, and anatomic variations in vessels.

Adolescent↗