Hisanori Uchida

Pure red cell aplasia caused by parvovirus B19 infection in a renal transplant recipient

To the Editor: Human parvovirus B 19, which is the etiologic agent of transient aplastic crisis in hemolytic anemia, is known to cause chronic bone marrow failure in immunocompromised hosts (1-4). To our knowledge, there have been 2 previous case reports describing parvovirus B 19 infection in renal transplant recipients (5 ,6 ) . We report here another case of severe anemia caused by parvovirus B 19 infection in a renal transplant recipient. Although humoral immune response to the virus was absent for a while due to immunosuppressive therapy, treatment with a regimen of intravenous commercial immunoglobulin resulted in rapid elevation of the reticulocyte count and resolution of the anemia. A 48-year-old man with chronic renal failure secondary to diabetic nephropathy, who had been undergoing chronic hemodialysis and administration of recombinant human erythropoietin (rhEPO) for the treatment of renal anemia, was hospitalized to receive a cadaveric kidney transplant. On the 1st hospital day (d 0), he underwent cadaver donor kidney transplantation, and immunosuppressive therapy with cyclosporin (3 mg/kg/d), prednisolone (70 mg/d), mizoribine (200 mg/d), and antilymphocyte globulin (1000 mg/d) was started. The donor was a 52-year-old man who had died of subarachnoid hemorrhage. Laboratory examination of the recipient on admission showed a white blood cell count of 5300/mm3, a hemoglobin level of 10.6 g/dl, and a platelet count of 204 000/mm3. After transplantation, his anemia began to progress without improvement after rhEPO treatment. On d 18, his hemoglobin level dropped to 5.0 g/dl, reticulocyte count was 0.08 %, white blood cell count was 2500/mm3, and platelet count was 172000/mm3. Bone marrow aspiration revealed severe erythroid hypoplasia with the appearance of many giant proerythroblasts, suggesting the presence of parvovirus B 19 infection. Thereafter, rhEPO was discontinued and the patient was treated with a 7-d course of intravenous commercial immunoglobulin preparations ( 5 g/d) and red cell transfusion. Thereafter, the reticulocyte count increased and his anemia improved. Normal hematopoiesis was observed on bone marrow examination on d 38. The serial serum specimens during the course of illness were subjected to enzyme-linked immunosorbent assay (ELISA) for detection of virus antigen, and polymerase chain reaction (PCR) for detection of virus DNA. B19 antigen became positive on d 2, reached a peak on d 5 , and lasted 18 d. However, viral DNA was detected by PCR in the serum specimen taken just before transplantation, and was negative or faintly positive on d 48. Interestingly, the amount of viral DNA was transiently elevated on d 153 (Fig. 1). The presence of a replicative form of B 19 virus was demonstrated by Southern blot analysis in the bone marrow specimen (Fig. 2) (7). In the serum specimen from the donor, viral DNA was not detected. The assay of virusspecific antibody revealed that IgM and IgG response was not observed until d 153 while the appearance of IgG response was detected in the sample

Successful resection of a large hepatoblastoma in a young adult: Report of a case

Hepatoblastoma (HB) rarely occurs in adults, and very few cases of successful resection have been documented. We report herein the unusual case of a 22-year-old, otherwise healthy woman with no history of liver disease who presented with upper abdominal pain and hepatomegaly. Tests for hepatitis B virus (HBV) and hepatitis C virus (HCV) were negative, but the AFP was mildly elevated at 77 ng/ml, the normal being <20. There was no evidence of liver cirrhosis on either the laboratory or histologic examinations. A well-demarcated solid mass of 14cm in diameter, which was lobulated and partly necrotic, was detected in the liver by computed tomography (CT). The lesion was echogenic on ultrasound, slightly hypodense on CT, and mildly hyper-vascular on arteriogram. The entire tumor was resected by extensive hepatectomy preserving only the lateral segment and part of the posterior segment of the liver. Histologically, the neoplasm was diagnosed as a pure epithelial HB of the fetal type. Following the operation, the patient has been well and free of recurrence for 38 months, maintaining low alpha-fetoprotein (AFP) levels at around 5 ng/ml. To our knowledge, this is the longest reported survival of an adult following surgical resection of an epithelial HB.

Hepatocellular carcinoma with a solitary adrenal metastasis and poor hepatic functional reserve: Report of a case

A 54-year-old man with a 15-year history of liver disease, was found by his family physician to have multiple tumors in the right lobe of the liver and a large right retroperitoneal tumor. He was referred and admitted to our institute where a preoperative diagnosis of liver cirrhosis complicated by hepatocellular carcinoma and probable right adrenal metastasis was made. Because his hepatic functional reserve was so poor, only resection of the right adrenal tumor with a splenectomy for hypersplenism and a cholecystectomy for the prevention of cholecystitis secondary to the scheduled transcatheter arterial embolization was performed. The patient was discharged in good clinical condition 5 weeks after surgery.

Two subtypes of HLA-B51 differing by substitution at position 171 of the α2 helix

Newly defined antigens of the B5, B35 cross-reacting group have been found in Japanese and North American Indians. Nucleotide sequencing of the alleles encoding the Japanese B5.35 antigen and the variant B5 antigen from the Piman Indians show them to be identical. This new allele, B*5102, differs from B*5101 by a single nucleotide substitution that changes residue 171 from histidine to tyrosine. Residue 171, which is part of the α2 helix, is believed to contribute directly to peptide interaction in the A pocket of the binding groove and is either histidine or tyrosine in all HLA-A, B, C heavy chains. Tyrosine 171 is shared by B*5102, B*3501, B*3502, and B*5301 and must be responsible for the serological cross-reactivities of these molecules not shared with B*5101. Stimulation of lymphocytes from a B*5101 positive donor with B*5102 positive cells failed to generate cytotoxic T cells with specificity for the difference between these molecules. However, one out of five clones of cytotoxic T cells raised against B*5101 failed to lyse targets expressing B*5102. Substitution of histidine for tyrosine at residue 171 affected recognition of HLA-B35-restricted human minor histocompatibility antigen-specific T cell clones.

Spontaneous rupture of hepatocellular carcinoma: An approach with delayed hepatectomy

Two cirrhotic patients with ruptured hepatocellular carcinoma (HCC), presenting with hemoperitoneum, were successfully treated by elective hepatectomy. Both of these patients, a 67-year-old female and a 76-year-old male, had first been taken to other primary hospitals by ambulance due to hypovolemic shock. They were then found to have a mass of approximately 5 cm in the cirrhotic liver. In the initial management, however, neither any direct hemostasis by surgery nor indirect measures such as transcatheter hepatic arterial embolization were performed in either case. Instead, conservative treatment consisting mainly of fresh blood and plasma transfusions were continued for more than a month until the liver function stabilized. In both hepatectomies, the use of a microwave tissue coagulator resulted in minimal intra-operative blood loss and an appreciably excellent post-operative course. These cases point to the effectiveness of a “wait and see” policy for selected patients with ruptured HCC.

Effect of anti-ICAM-1 and anti-LFA-1 antibodies on rat liver transplantation.

The effect of the anti-cell adhesion molecule anti-bodies, anti-ICAM-1 (1A29) and anti-LFA-1 (WT1), on rat liver transplantation was investigated. Livers from ACI rats were transplanted into Lewis rats by Kamadas method and during the recipient operation 1A29 1 mg/kg, and WT1 1 mg/kg were administered intravenously to one group of rats (treated group). The survival time of the treated group was significantly longer than that of the untreated group, but permanent unresponsiveness could not be induced. Postmortem examination revealed little histological evidence of acute rejection in the treated rats, in which the main cause of death was thought to be chronic rejection.

A NONSPECIFIC COLONIC ULCER OCCURRING AFTER HEPATECTOMY : REPORT OF A CASE

We herein report the case of a 53-year-old man with a nonspecific acute colonic ulcer whose liver function deteriorated after he had undergone hepatectomy. He was referred to our hospital for a hepatoma caused by hepatitis B virus and a right hemihepatectomy was performed. His liver function was poor after the operation, and minor complications such as pleural effusion and biliary fistula developed. A large amount of melena was seen 29 days after the hepatectomy and he developed hemorrhagic shock. Superior mesenteric arteriography revealed pooling of blood in both the hepatic flexure of the ascending colon and the cecum. An emergency right hemicolectomy was performed. There was a 5 x 1-mm ulcer 18 cm distal to the ileocecal valve. Numerous erosions were observed to be scattered throughout the colonic mucosa. The patient recovered slowly and was discharged 6 months after the hepatectomy. This is the first report of an acute colonic ulcer that could have been caused by liver dysfunction.

Esophageal Transection Using a Biofragmentable Anastomosis Ring in Dogs

Since the first publication on the new anastomosis technique using a biofragmentable anastomosis ring (BAR) by Hardy in 1985, various studies have been performed to investigate the superiority of this type of anastomosis, and it has since been reported that the BAR was safely used not only in large and small bowel anastomosis, but in cholecystojejunal and gastrojejunal anastomosis as well. In this study, the feasibility of the BAR for esophageal transection was investigated. Seven dogs were operated on, and one died of intraabdominal bleeding on the operative day while another died of leakage at the site of gastrotomy on the 3rd postoperative day. These deaths were all considered to be due to simple technical errors not directly related to the use of the BAR. The postoperative recovery of the other five dogs was uneventful, and the ring eventually disintegrated into several small fragments that passed out of the body in the faces between the 14th and 21st postoperative days. The dogs were killed on the 28th postoperative day, and both gross and histological examinations, revealed that the transection had been successful. Neither leakage nor significant stenosis at the site of transection was found. Our results suggested that the BAR could be used for esophageal transection and is thus recommended as an easy-to-learn, time-saving, and safe technique for esophageal operations.

The synergistic effect of bactobolamine and tacrolimus on in vitro and in vivo experiments

The aim of this study was to examine the immunosuppressive effect of bactobolamine (BBL) alone and in combination with tacrolimus (FK) using in vitro proliferation assays on human peripheral blood lymphocytes (PBLs) and in vivo liver allografts in rats. In the latter setting, the immunosuppressive activity of BBL alone and in combination with FK was compared to that of mizoribine (MIZ). The interactions between BBL and FK and between MIZ and FK were assessed by the combination index (CI) proposed by Chou and Kahan. In the in vitro study, the combination of BBL and FK displayed stronger inhibitory effects on T-cell proliferation than when each drug was applied alone. The mean CI values for the BBL/FK combination were below 1.0, rangin from 0.19 to 0.86, indicating synergism between BBL and FK. In the in vivo study, 50–200 mg/kg/day BBL monotherapy significantly prolonged survival compared with a control group, and the effect was dose-dependent. Conversely, the efficacy of MIZ monotherapy at 2.5–10 mg/kg/day did not increase dose-dependently. The CIs for MIZ at doses of 2.5 and 5.0 mg/kg/day with FK 0.08 mg/kg/day were 0.48 and 0.42, respectively, indicating therapeutic synergism between MIZ and FK. The CI for BBL 100mg/kg/day with FK was 0.26, which indicated further synergism between BBL and FK.

Case report of ten adults who underwent or desired to undergo liver transplantation abroad.

肝移植が末期肝不全に対する標準的な治療法として世界で確立されている現在, 日本でも肝移植が普及することが予想されるが, 臨床面での問題点も多い. そこで, 海外で肝移植を受けることを希望した成人10例の臨床経過を検討したので報告をする. 原疾患の内訳は, 肝硬変7例, 慢性活動性肝炎, 原発性胆汁性肝硬変, 薬剤性肝炎各1例であった. 実際に肝移植を受けた5例のうち2例は術後に肝不全または敗血症のために死亡した. 4例は肝移植を受けることができずに死亡し, 薬剤性肝炎の1例は待機中に肝機能が軽快したため肝移植を受けずに生存している. 肝移植術後生存中の3例はいずれも肝炎ウイルスの再感染を認めた. 今後日本国内で脳死肝移植が可能となっても, 適応疾患の選択, ウイルス性肝炎や肝癌などの原疾患の再発, 待機中の死亡, 拒絶反応や免疫能低下による感染症の発生の問題など, なお解決せねばならない諸問題が残されている.