End-linked homodimers in fibrinogen Osaka VI with a B beta-chain extension lead to fragile clot structure.

The authors have identified a 12-residue carboxyl-terminal extension of Lys-Ser-Pro-Met-Arg-Arg-Phe-Leu-Leu-Phe-Cys-Met in a dysfibrinogen derived from a woman heterozygotic for this abnormality and associated with severe bleeding. This extension is due to a T-to-A mutation that creates AAG encoding Lys at the stop (TAG) codon, thus translating 36 base pairs in the noncoding region of the Bbeta gene. The extra Cys residues appear to be involved in 1 or 2 disulfide bonds between 2 adjacent abnormal fibrinogen molecules, forming a fibrinogen homodimer as indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Indeed, about half of the fibrinogen molecules exist as end-linked dimers oriented in parallel or with an angle, as observed by transmission electron microscopy. These end-linked dimers may well alter the conformations of D and DD regions on fibrin assembly, leading to increased fiber branching at their sites in the growing protofibrils. By scanning electron microscopy, the Osaka VI fibrin network appears to have a lacelike structure composed of highly branched, thinner fibers than the normal fibrin architecture. Such fibrin networks may be easily damaged to form large pores when fluids are allowed to pass through the gels. The fragility of Osaka VI fibrin clots, further confirmed by permeation and compaction studies, may account for the massive bleeding observed in this patient. (Blood. 2000;96:3779-3785)

Application of nitric oxide for a case of veno-occlusive disease after peripheral blood stem cell transplantation.

A 5-year-old girl at high risk for acute lymphoblastic leukemia was treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation (PBSCT). However, her condition was complicated by veno-occlusive disease of the liver (VOD) after PBSCT. For treatment of VOD, transdermal isosorbide tape was applied as a nitric oxide (NO) donor. The signs of VOD improved immediately after NO treatment was initiated, and the patient showed no side effects from the transdermal isosorbide tape.

A case of hemolytic uremic syndrome improved with nitric oxide.

Hemolytic uremic syndrome (HUS) after transplantation is difficult to treat, and there is no consensus regarding optimal mode of treatment. We attached transdermal isosorbide tape as a nitric oxide (NO) donor to patients with HUS after bone marrow transplantation (BMT). This was very effective in ameliorating the hemolysis and increasing platelet numbers. We report here the successful use of an isosorbide in a patient with HUS after transplantation. Bone Marrow Transplantation (2000) 25, 109-110.

A case of myelodysplastic syndrome complicated by pulmonary alveolar proteinosis with a high serum KL-6 level.

Serious hematological diseases often cause respiratory disorders. Because these are related to the prognoses of patients with hematological diseases, their early diagnosis is necessary. This study describes a 6-year-old girl with myelodysplastic syndrome complicated by pulmonary alveolar proteinosis who showed a remarkable increase in her serum KL-6 level. Three years and 2 months after the end of therapy for neonatal melanoma, a diagnosis of myelodysplastic syndrome with leukemic change was made. Ten months after the onset of leukemia, she had respiratory distress with an increased serum KL-6 level of 75,000 U/mL (reference range; < 500 U/mL). Despite various treatments for pulmonary complications, she died 3 months after developing respiratory distress. A diagnosis of pulmonary alveolar proteinosis was made at autopsy. Earlier treatment of respiratory distress could be achieved if serum KL-6 levels were examined earlier.

Endoscopic retrograde cholangiopancreatography in paediatric patients with biliary disorders.

Endoscopic retrograde cholangiopancreatography (ERCP) has long been used in children. The usefulness of ERCP in paediatric patients with various biliary disorders, however, has not been well documented. Thirty-two sessions of ERCP performed in 29 paediatric patients ranging in age from 1 month to 15 years were evaluated. Endoscopic retrograde cholangiopancreatography was to confirm diagnosis or to obtain detailed information about their pancreaticobiliary system. Cannulation was successful in all patients. Opacification of the biliary tracts was also successful in all except for three patients with extrahepatic biliary atresia. Endoscopic retrograde cholangiopancreatography was assessed to be successful in making a differential diagnosis of neonatal hepatitis from extrahepatic biliary atresia, and in having a confirmed diagnosis of anomalous arrangement of the pancreaticobiliary ductal system associated with choledochal cyst. The procedure was also useful for obtaining detailed information on the pancreaticobiliary system in the other children. No accidents occurred during the endoscopic procedures in any of the paediatric patients. When a confirmed diagnosis or detailed information is needed in paediatric patients with biliary disorders, ERCP is a useful and safe technique.

Assessment of hepatic vitamin E status in adult patients with liver disease.

No published reports compare hepatic alpha-tocopherol (adjusted for hepatic lipid content) with indicators of blood alpha-tocopherol in adult patients with various liver diseases. alpha-Tocopherol was simultaneously measured in liver biopsy tissues and blood from 66 subjects (9 comparison patients hospitalized for biliary tract surgery, 13 with chronic persistent hepatitis, 9 with chronic aggressive hepatitis, 10 with acute hepatitis, 10 with cirrhosis, 7 with both cirrhosis and hepatic cell carcinoma, and 8 with fatty liver). Hepatic, erythrocyte, and plasma alpha-tocopherol concentrations were measured, as were hepatic and serum lipids. The ratios of alpha-tocopherol to total lipid concentrations (Toc/TL ratios) in plasma and liver were calculated. In both comparison patients and patients with chronic persistent hepatitis and fatty liver, hepatic alpha-tocopherol concentrations were strongly correlated with hepatic triglyceride and total lipid concentrations (r = .72, P < .001; and r = .75, P < .001, respectively); the relationships (slopes) when hepatic alpha-tocopherol concentrations were compared with hepatic triglyceride and total lipid concentrations were similar in these patients and in all subjects. No strong correlations were found between hepatic and blood alpha-tocopherol parameters in all subjects. These results suggest that hepatic alpha-tocopherol is present at similar concentrations in triglycerides as well as total cholesterol and phospholipids and that neither plasma Toc/TL ratios nor erythrocyte alpha-tocopherol concentrations are useful indicators of hepatic vitamin E status. The hepatic Toc/TL ratio may be useful to assess total hepatic vitamin E status.

Diurnal variation in intragastric pH in children with and without peptic ulcers.

Diurnal variation in intragastric pH in children with peptic ulcers has not been previously reported. Therefore, we monitored intragastric pH during a 24-h period in 82 subjects (10 children with gastric ulcers, 9 children with duodenal ulcers, 58 non-ulcer (comparison group) children, and 5 healthy adults) using a monopolar glass pH electrode. The percent of readings below pH 2, 3, 4, and 5 for each subject was calculated and compared between the comparison group and the two ulcer groups using means and slopes (i.e. changes in percent with age for each group) of percent readings for each pH analysis. In the comparison group children, gastric acidity increased with age and reached adult levels by 14 y. Mean readings for all pH analyses in gastric ulcer children were lower than those in age-adjusted comparison children (p < 0.05). The slopes of the relationships between age and the percent time below any pH for the gastric ulcer group were different from those in the comparison group (p < 0.05) and were negative for all pH analyses. The mean time below pH 2 in children with duodenal ulcers was greater than that in age-adjusted comparison children (p = 0.002). The slope of the relationship between age and the percent time below pH 2 in the duodenal ulcer group was different from that in the comparison group (p < 0.05). Gastric acidity in children with primary gastric ulcers was reduced during childhood, but in children with primary duodenal ulcer, gastric acidity was at or above adult levels.

Management and ultrasonographic appearance of infantile hypertrophic pyloric stenosis with intravenous atropine sulfate.

Some infants with hypertrophic pyloric stenosis (HPS) have responded to oral atropine treatment. To achieve sufficient effect of atropine, it must be administered intravenously (i.v.). Therefore, with ultrasonography, we studied the changes in the pyloric muscle in HPS during and after intravenous administration of atropine. Twenty-three infants were studied. Atropine sulfate was initially administered at a dose of 0.04 mg/kg day i.v., and the dose was increased by 0.01 mg/kg/day until vomiting ceased. When vomiting ceased after administration of intravenous atropine sulfate, the infants received oral atropine sulfate at twice the effective intravenous dose; this was continued for 2 weeks. Ultrasonography was repeated until pyloric muscles normalized. Twenty-two infants were free from vomiting after 1-8 days of intravenous atropine sulfate (dosages of 0.04-0.11 mg/kg/day). In 21 infants, weight gain continued after atropine treatment even though no change in thickness of the pyloric muscles was demonstrated ultrasonographically. Only 2 infants required pyloromyotomy because of prolonged treatment or a mistake in underdosing of oral atropine. All of the 21 infants who recovered after intravenous atropine without surgery had normalization of pyloric muscle caliber, as shown by ultrasonography 4-12 months after treatment. Atropine is an effective medicine for HPS. Regression of pyloric thickening after vomiting has been controlled implies that pyloric muscle hypertrophy could be worsened by the spasm that occurs in HPS.

Pharmacokinetics and pharmacodynamics of famotidine in children with gastroduodenal ulcers.

We treated 14 boys, six with gastric ulcers and eight with duodenal ulcers, to determine famotidine pharmacokinetics and its inhibition of gastric acid secretion (pharmacodynamics). Famotidine (1 mg/kg/day) was administered either intravenously or orally at a dose of 0.5 mg/kg twice a day (maximum: 40 mg/day). Blood samples were collected from all subjects and the intragastric pH monitored in eight. Pharmacokinetic parameters were calculated assuming a one-compartment model. Volume of distribution, elimination half-life, and area under the serum concentration-time curve were 1.52 +/- 0.37 l/kg, 2.29 +/- 0.38 h, and 1.14 +/- 0.32 ng.h/ml, respectively. The mean oral bioavailability of famotidine was 50.6%. Both intravenously and orally administered famotidine neutralized gastric acidity during sleep but failed to continuously maintain the intragastric pH > 5.0. All subjects' ulcers healed within 8 weeks. There were no side effects noted during famotidine treatment. Twice daily administration of 0.5 mg/kg famotidine for 8 weeks appears to be a tolerated and effective treatment of children with gastroduodenal ulcers.

Ultrasonographic diagnosis of juvenile colonic polyps.

To reduce the risks of air-contrast barium enemas and colonoscopy, we studied the use of saline enemas for ultrasonographic examination of children with rectal bleeding. Thirty-nine children, from 2 years 8 months to 8 years 3 months of age, were examined. Juvenile colonic polyps were ultrasonographically demonstrated and histologically confirmed in 25 children; all the polyps were solitary and pedunculated, and were located in the splenic flexure in 3 children, the descending colon in 6, the sigmoid colon in 12, and the rectum in 4. Ultrasonographic findings by hydrocolonic ultrasonography were identical to those obtained by immersion ultrasonography of removed specimens. Hypoechoic areas within more hyperechoic polyps were shown histologically to be dilated glandular canals. The 14 children in whom no abnormal ultrasonographic findings were shown had no further rectal bleeding after resuming regular defecation, and 5 of these 14 had negative colonoscopic findings. No adverse reactions were noted in any child during or after the saline enema examination. We conclude that ultrasonographic examination with a saline enema is a safe and accurate method of assessing children with rectal bleeding, especially for the diagnosis of juvenile colonic polyps.

Relationship between red blood cell and liver tocopherol concentration after administration and depletion of vitamin E.

As the assessment of the nutritional status of vitamin E, the validity of red blood cell (RBC) tocopherol concentration was examined in relation to tocopherol concentration in the liver and in its subcellular fractions. When 10 mg/kg of dl-alpha-tocopherol was injected intramuscularly to vitamin E deficient rats, plasma tocopherol reached a maximum level earlier than did RBC tocopherol and liver tocopherol. However, as the correlation in tocopherol concentrations between RBC and plasma and between RBC and tissue homogenate or its subcellular fractions was examined with respect to all the values examines during the study courses, a moderately close correlation was observed between RBC and liver tissue and between RBC and the subcellular fractions while a lack of correlation was found between RBC and plasma. When rats sufficient in vitamin E were depleted for 8 weeks by a vitamin E deficient diet, tocopherol concentrations decreased in a similar pattern in the plasma, RBC, and liver and its subcellular fractions. In this case, a very close correlation in the tocopherol concentrations was observed between RBC and other subjects, i.e., the plasma, liver homogenate and its subcellular fractions.