Apparently increased trough levels of tacrolimus caused by acute infantile diarrhea in two infants with biliary atresia after liver transplantation

Two infants with biliary atresia who exhibited three-fold increased trough levels of tacrolimus and required reduced doses during episodes of acute infantile diarrhea within 5 months of liver transplantation are described. The cause of the increase was not explained simply by hemoconcentration as a result of significant loss of extracellular fluid during these episodes. It does highlight an important issue: that of the continuing need to carefully monitor the trough levels of tacrolimus in such infants.     

Acute heart failure and acute renal failure in Kawasaki disease

Acute renal failure and acute heart failure are rare in Kawasaki disease. We experienced two patients with Kawasaki disease who presented acute renal failure and acute heart failure. These two patients gave us an important insight into the understanding of water balance and fluid therapy in Kawasaki disease. One patient showed acute prerenal failure due to fluid exudation from the intravascular to the extravascular space, and subsequent acute heart failure. The other patient showed acute heart failure caused by fluid infusion for the treatment of dehydration. It is suggested that acute renal failure could be caused by a fluid shift from the intravascular to the extravascular space in Kawasaki disease. It is also demonstrated that the reserve of cardiac function could be decreased in patients with Kawasaki disease due to myocarditis even with normal echocardiography and chest X-rays.     

YF476 is a new potent and selective gastrin/cholecystokinin-B receptor antagonist in vitro and in vivo

Background : We newly synthesized YF476 ((R)-1-[2,3-dihydro-2-oxo-1-pivaloylmethyl-5-(2'-pyridyl)-1H-1,4-benzodiazepin-3-yl]-3-(3-methylamino-phenyl)urea) as a gastrin/cholecystokinin-B (CCK-B) receptor antagonist. We investigated the pharmacological profile of YF476 in vitro and in vivo .
Methods : We examined the binding properties of YF476 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, and the effect of YF476 on secretagogue-induced gastric acid secretion in rats and Heidenhain pouch dogs.
Results : YF476 replaced the specific binding of [¹²⁵I]CCK-8 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, with K _i values of 0.068, 0.62 and 0.19 n M , respectively. The affinity of YF476 for rat brain gastrin/CCK-B receptor was 4100-fold higher than that for rat pancreatic CCK-A receptor. In anaesthetized rats, intravenous YF476 inhibited pentagastrin-induced acid secretion with an ED ₅₀ value of 0.0086 μmol/kg, but did not affect histamine- and bethanechol-induced acid secretion at a dose of 10 μmol/kg. In Heidenhain pouch dogs, intravenous and oral YF476 inhibited pentagastrin-stimulated gastric acid secretion in a dose-dependent manner with ED ₅₀ values of 0.018 and 0.020 μmol/kg, respectively, but did not affect histamine-induced acid secretion.
Conclusion : These results suggest that YF476 is an extremely potent and highly selective gastrin/CCK-B receptor antagonist, and that the gastrin/CCK-B receptor is not involved in histamine- or bethanechol-induced gastric acid secretion in dogs or rats.     

Clinical features of Japanese children and adolescents with systemic lupus erythematosus: Results of 1980–1994 survey

Marked advances have been made in the past decade in the management of adults with systemic lupus erythematosus (SLE). Therefore, a nationwide retrospective survey was conducted between 1980 and 1994 to investigate the clinical manifestations of SLE in Japanese children and adolescents. Questionnaires were sent to 340 hospitals. Of 405 patients reported by 176 hospitals, 373 patients, diagnosed by the criteria established by the Pediatric Study Group of the Japanese Ministry of Health and Welfare in 1985, were enrolled in the study. Forty-nine of the 354 patients (13.8%) had relatives with a connective tissue disease within the third degree of consanguinity. The frequent manifestations in 373 patients were the presence of antinuclear antibody (98.9%), immunologic disorders (93.0%), hypocomplementemia (87.1%), malar rash (79.6%) and fever (74.0%). Lupus nephritis was present in 148 of the 309 patients (47.9%) at their first visit to a clinic, and 261 of the 373 patients (70.0%) developed renal involvement during the observation period. Of 370 patients, 92 patients (24.9%) exhibited central nervous system lupus. Of 368 patients, 192 patients (52.2%) were treated by methylprednisolone pulse therapy and 148 patients (40.2%) received immunosuppressants in combination with steroid therapy at some stage during the observation period. Survival rate at 5 years from onset was 95.9%. Management of infection, coagulopathies, and central nervous system involvement is essential to improve the prognosis of SLE in Japanese children and adolescents.     

Genetic analysis of hypophosphatasia

A review is presented of the recent advances in: (i) clinical features, (ii) biochemistry and molecular biology of alkaline phosphatase, (iii) genetic defect in hypophosphatasia, and (iv) prenatal diagnosis. Despite the recent progress, the pathogenesis of hypophosphatasia is far from being elucidated. More clinical cases and further characterization of the alkaline phosphatase gene mutations are needed for better understanding of the clinical spectrum of the entity.     

Three cases of pyogenic sacro-iliitis,and factors in the relapse of the disease

Pyogenic sacro-iliitis (PS) is a rare disease in childhood. Three cases of PS are reported that were difficult to diagnose. Scintigraphy and magnetic resonance imaging (MRI) were useful for diagnosis. One patient suffered from an episode of relapse. Seventeen other cases of PS were reviewed in the literature to investigate the incidence of abnormal imaging findings and various factors in disease relapse. It was found that the incidence of abnormal findings by scintigraphy was significantly higher than that by computed tomography (P = 0.0057). The duration of intravenous antibiotic administration of the relapse group (14.7 ± 4.7 days) was significantly shorter than that of the non-relapse group (24.3 ± 10.7 days; P = 0.0376). The statistical analysis suggested that intravenous antibiotic administration is necessary at least for 20 days to prevent a relapse of PS.     

Large infarct and high mortality by cerebral ischemia in mice carrying the factor V Leiden mutation

To cite this article : Kita T, Banno F, Yanamoto H, Nakajo Y, Iihara K, Miyata T. Large infarct and high mortality by cerebral ischemia in mice carrying the factor V Leiden mutation. J Thromb Haemost 2012; 10: 1453–5.     

Electron microscopic finding of eccrine sweat gland epithelial cells in a patient with Krabbe disease

A 13 month old boy was found to have severely reduced β-galactocerebrosidase activity suggesting infantile Krabbe disease. Clinically, the patient showed a progressive neurological deterioration with white-matter disease on radiological study. Axillary skin biopsy was performed to support the diagnosis. On electron microscopy, needle-like inclusions, which are the typical finding seen in the cytoplasm of astrocytes and Schwann cells in the classic infantile form, were present in eccrine sweat gland epithelial cells. This method is useful for diagnosis when nerve biopsy and biochemical analysis are not readily available.