Search

Shiga toxin, produced by Escherichia coli O157:H7, is important for the pathogenicity of the epidemic form of hemolytic uremic syndrome (HUS). This toxin has recently been found to stimulate endothelin-1 synthesis in cultured endothelial cells in vitro.We investigated endothelin and cytokine levels in sera during a large outbreak of E. coli O157:H7 infection in Osaka, Japan, in 1996. Eleven patients with HUS and 9 patients with hemorrhagic colitis at the onset of E. coli O157:H7 infection were studied.Serum IL-6 (p0.01), IL-8 (p0.05), IL-10 (p0.001) and endothelin (p0.001) levels were significantly increased in patients with HUS compared to those with colitis only. The serum thrombomodulin level, a molecular marker of endothelial damage, also showed a significant positive correlation with serum IL-6 (p0.01), IL-8 (p0.01), IL-10 (p0.01) and endothelin (p0.001) levels. In a HUS patient, the increase in serum IL-10 and endothelin levels reached a plateau prior to the peak of serum creatinine levels.Increased serum endothelin synthesis by Shiga toxin in vivo was proven in HUS secondary to E. coli O157:H7 infection. Increased serum endothelin and IL-10 levels were speculated to be associated with the development of HUS through vascular endothelial damage caused by E. coli O157:H7 infection.

Hypophosphatasia is associated with a defect of the tissue-nonspecific alkaline phosphatase (TNSALP) gene. The onset and clinical severity are usually correlated in hypophosphatasia; patients with perinatal hypophosphatasia die approximately at the time of birth. In contrast, we describe a male neonatal patient with hypophosphatasia who had no respiratory problems and survived. He was compound heterozygous for the conversion of Phe to Leu at codon 310 (F310L) and the deletion of a nucleotide T at 1735 (delT1735), causing the frame shift with the result of the addition of 80 amino acids at the C-terminal of the protein. Because the C-terminal portion of TNSALP is known to be important for TNSALP to bind to the plasma membrane, the localization of wild-type and mutated TNSALP proteins was analyzed using green fluorescent protein chimeras. The expression vectors containing the complementary DNA of fusion proteins consisting of signal peptide, green fluorescent protein, and wild-type or mutated TNSALP, caused by delT1735 or F310L mutation, were introduced transiently or stably in Saos-2 cells. The delT1735 mutant failed to localize at the cell surface membrane, whereas the wild-type and the F310L mutants were located in the plasma membrane and cytoplasm. The assay for enzymatic activity of TNSALP revealed that the delT1735 mutant lost the activity and that the F310L mutant exhibited an enzymatic activity level that was 72% of the normal level. The F310L mutation was also detected in another neonatal patient with relatively mild (nonlethal) hypophosphatasia (reported in J Clin Endocrinol Metab, 81:4458-4461, 1996), suggesting that residual ALP activity of the F310L mutant contributes to the less severe phenotype. The patient is unique, with respect to a discrepancy between onset and clinical severity in hypophosphatasia.

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.

The effects of three FK506 induction regimens on pediatric living-related liver transplantation (LRLT) were studied retrospectively in terms of patient survival and adverse side effects. The patients consisted of 120 children, ranging from 3 to 210 months of age, who underwent a total of 122 LRLTs with a minimum follow-up of 6 months. Immunosuppression consisted of FK506 and low-dose steroids. FK506 was given in 3 ways: (1) high-dose intravenous (i.v.) induction, with FK506 begun at a dose of 0.15 mg/kg/day for the first 16 patients; (2) low-dose i.v. induction, with FK506 begun at a dose of 0.06 mg/kg/day for the next 45 patients; and (3) per os (p.o.) induction, with FK506 begun orally from the day prior to LRLT and continued postoperatively. Whole-blood trough levels of FK506 were monitored daily. Trough levels in the high induction group were often as high as 100 ng/ml compared with the level of 20 ng/ml in the p.o. induction group. Patient survivals were 75%, 89%, and 80% in the high-i.v. vs. low-i.v. vs. p.o. groups. The incidences of acute rejection were 12.5%, 22.2%, and 26.4%, and the incidences of viral infection were 56%, 38%, and 11% in the respective groups. Major adverse effects occurred with higher frequency in the high-i.v. induction group. Oral FK506 induction therapy at a dose of 0.15 mg/kg/day starting from the day before LRLT was safer and associated with a lower incidence of viral infection than therapy with i.v. FK506.