K. Yabuta

Kawasaki disease differs from anaphylactoid purpura and measles with regard to tumour necrosis factor-α and interleukin 6 in serum

It has been reported that tumour necrosis factor-α (TNF-α) is capable of inducing vascular injury, and interleukin 6 (IL-6) of inducing production of acute phase proteins and the maturation of megakaryocytes. Kawasaki disease (KD) is a systemic vasculitis with severe inflammation. We investigated whether TNF-α and IL-6 activities in serum from patients with KD differs from those in anaphylactoid purpura (AP) and measles. Serum TNF-α levels were measured by a sandwich enzyme immunoassay and IL-6 activities in serum were assessed by a colourimetric assay. Both KD and AP patients but not patients with measles had increased serum TNF-α levels during the acute stage. With respect to IL-6, patients with KD and measles, but not AP, had increased IL-6 activities in serum during the acute stage. IL-6 activities in serum of KD patients correlated with serum C-reactive protein levels and correlated to some extent with maximum platelet counts during the course of illness. These results suggest that KD differs from AP and measles regarding both cytokines. The combination of TNF-α, which may be responsible for severe vascular injury, and IL-6, which may be responsible for severe inflammation, may play an important role in acute KD.

Pentoxifylline and intravenous gamma globulin combination therapy for acute Kawasaki disease

We compared the efficacy of oral administration of pentoxifylline (PTX) and intravenous infusions of gamma globulin (IVGG) combination therapy with that of IVGG in reducing the frequency of coronary-artery lesions (CAL) in children with Kawasaki disease (KD), in a randomized trial. All patients with KD received acetylsalicylic acid (30 mg/kg per day), until the 30th day, after the onset of fever, followed by daily acetylsalicylic acid at a dose of 3-5 mg/kg per day there-after, and intravenous IVGG, 200 mg/kg per day, for 5 consecutive days. In addition, patients randomly assigned to PTX and IVGG combination therapy groups received oral PTX at a dosage of 10 mg/kg per day (low-dose) or 20 mg/kg per day (high-dose), in three divided doses until the 30th day. Patients with KD were all free from CAL prior to treatment. We assessed the presence of CAL by two-dimensional echocardiography which was also done prior to treatment and then twice a week after hospital admission. We detected CAL in 3 of 18 patients (16.7%) in the IVGG therapy group, as compared with 2 of 18 patients (11.1%) in the low-dose PTX and IVGG combination therapy group. There were no significant differences between the two groups. In the next study, we detected CAL in 3 of 21 patients (14.3%) in the IVGG therapy group, as compared with none of 22 patients (0%) in the high-dose PTX and IVGG combination therapy group (χ2 = 6.4, P < 0.02). No adverse side-effects were observed in 79 patients with KD.

Serum soluble CD4 and CD8 levels in Kawasaki disease

The levels of soluble CD4 (sCD4) and sCD8 in serum correlate with the T cell subset activation and may be important in monitoring and characterizing disease processes during immunological diseases. We compared acute Kawasaki disease (KD) with anaphylactoid purpura (AP) and acute febrile viral infections, such as measles and infectious mononucleosis (IM), in terms of serum sCD4 and sCD8 levels. The levels of serum sCD4 and sCD8 were measured by a sandwich enzyme immunoassay. In addition, peripheral blood mononuclear cell subsets were analysed by single and two‐colour flow‐cytometric analyses in KD and IM patients. The levels of serum sCD4 and sCD8 were significantly elevated in patients during acute stages of KD, measles and IM, but not AP. Peripheral blood CD4+, CD8+ and also HLA‐DR+ T cells count did not increase during the acute stage of KD; however, peripheral blood CD8+ and HLA‐DR+ T cell counts were increased during the acute stage of IM. Our results suggest that there is a low level of activation of peripheral blood T cells during acute KD, or that infiltrated T cells in some local tissues of KD patients contribute to the elevated levels of serum sCD4 and sCD8.

Evaluation of glomerular function in individual kidneys using dynamic magnetic resonance imaging

We used the fast field-echo technique of magnetic resonance (MR) imaging with an intravenous bolus injection of paramagnetic contrast agent to evaluate glomerular function. The time-dependent curves of changes in signal intensity observed in the renal cortex and renal medulla brought about by the paramagnetic contrast agent allowed insight into excretory kinetics. The time at which the cortical and medullary curves cross, the cortico-medullary (C-M) junction time, was delayed with a decrease in glomerular function. The mean C-M junction time in both kidneys showed a significant inverse correlation with total creatinine clearance (Ccr), indicating the glomerular filtration rate. The C-M junction time in an individual kidney also showed an inverse correlation with individual Ccr in each kidney. Results suggest that dynamic MR imaging is a useful tool in evaluating renal morphology and in evaluating semi-quantitatively the glomerular function of the kidneys, singly and together, in a manner analogous to radionuclide scintigraphy.

Carbamazepine-induced thrombocytopenia and leucopenia complicated by Henoch-Schönlein purpura symptoms

A rare case of carbamazepine-induced leucopenia and thrombocytopenia complicated by Henoch-Schönlein purpura (HSP) symptoms is presented. Laboratory findings suggested that leucopenia and thrombocytopenia could be due to bone marrow suppression and HSP symptoms to an allergic reaction to carbamazepine. To the best of our knowledge this is the first report that carbamazepine may cause haematological disorders associated with symptoms of HSP by different mechanisms at the same time in the same patient.

Abnormal contralateral kidney in unilateral multicystic dysplastic kidney disease

We performed a retrospective study of infants with unilateral multicystic dysplastic kidney (MCDK) in order to investigate the associated urological abnormalities. We examined the records of seven patients, in five of whom a diagnosis had been made prenatally using ultrasonography. Our investigation focused on the associated urological abnormalities, particularly on the contralateral side, and the results of voiding cystourethrography (VCUG). Four of the seven patients (57%) had urological abnormalities other than MCDK: three exhibited vesicoureteral reflux (VUR) of the contralateral side including one patient who also had an ipsilateral ectopic ureter, and the fourth patient had a ureterocele of the ipsilateral side. The results indicate that contralateral VUR, was the most common abnormality associated with MCDK. Two infants had high-grade VUR and underwent anti-reflux surgery soon after the diagnosis. Both have remained free of recurrent urinary tract infection.

Decrease in the concentrations of transforming growth factor-beta 1 in the sera of patients with Kawasaki disease.

Kawasaki disease (KD) is one of the most important forms of vasculitis, and is characterized by the initiation of a proinflammatory cytokine cascade. To further characterize the immunological profile of KD, we measured the serum levels of transforming growth factor-beta 1 (TGF-beta 1) as a regulatory cytokine. We determined the concentration of TGF-beta 1 in the sera of the patients with KD, anaphylactoid purpura (AP), and scarlet fever, using a sandwich enzyme linked immunosorbent assay. The serum levels of TGF-beta 1 were decreased in patients with KD, but not in patients with AP or scarlet fever during the acute stage. We found an inverse correlation between TGF-beta 1 and soluble tumor necrosis factor (TNF) receptor levels in KD patients during the acute and subacute stage. Decreased levels of TGF-beta 1, in particular to suppress TNF alpha (TNF-alpha) production, is an important part of the regulatory system of increased TNF-alpha production which cause vasculitis.

Transient depletion of T cells with bright CD11a/CD18 expression from peripheral circulation during acute Kawasaki disease

To clarify the activation of peripheral blood T cells in Kawasaki disease (KD) patients, we investigated whether expression of lymphocyte function‐associated antigen‐1 (LFA‐1, CD11a/CD18) and/or intercellular adhesion molecule‐1 (ICAM‐1, CDS4) on peripheral blood T cells increases during the acute stage. Expression of cellular adhesion molecules was measured using flow cytometry. There was a decrease in the percentage of CD3+ T cells in the bright LFA‐1α and LFA‐1β population and a concomitant increase in the dim population of LFA‐1α and LFA‐1β during the acute stage, in comparison with those of the convalescent stage. In addition, we observed no significant differences in ICAM‐1 expression during the acute stage compared with that of the convalescent stage. In our view the present data, in conjunction with previous reports on T‐cell function during acute KD, suggest that activated T cells are temporarily withdrawn from peripheral circulation during acute KD.

IgE levels in faecal extracts of patients with food allergy

IgE levels in faecal extracts (Copro‐IgE levels) were investigated in food allergy (EA) patients before and after the challenge test administration of food assay. In addition, the effects of administration of oral sodium cromoglycate (SCG) on the Copro‐IgE levels were studied. Copro‐IgE levels in patients with FA, who were placed on an elimination diet, did not differ from those of healthy children. After a challenge test immediate symptoms of urticaria and wheezing were observed in all FA patients. Copro‐IgE levels in each patients increased markedly within 24 h of the challenge test. Moreover, FA patients treated orally with SCG showed neither and increase in Copro‐IgE levels nor any remarkable symptoms after the challenge. Our results suggest that the increased Copro‐IgE levels may be a specific consequence of the local immune response to food allergen stimulation in the gut mucosa.

Sulfated and Nonsulfated Bile Acids in Urine of Patients with Biliary Atresia: Analysis of Bile Acids by High-Performance Liquid Chromatography

Summary To elucidate urinary bile acid patterns in patients with biliary atresia (BA), 15 sulfated and nonsulfated bile acids in urine were separately measured by high-performance liquid chromatography. This relatively simple technique for fluorescence detection utilizes the enzyme 3α-hydroxysteroid dehydrogenase (3α-HSD) to reveal urinary bile acid patterns. By this method, recovery rates of sulfated and nonsulfated bile acids in urine were satisfactory, and this analysis was shown to be applicable to clinical situations. In 10 patients with BA, the mean level of total bile acids in urine (23.35 ± 18.51 μmol/day) was seven times higher than the mean level in eight normal infants (3.05 ± 2.05 μmol/day). In the infants with BA, the mean level of total sulfated bile acids was about half of the total bile acid level. The main components of urinary nonsulfated bile acids in BA were glycocholic acid (6.21 ± 5.55 μmol/day) and taurocholic acid (2.28 ± 1.33 μmol/day), whereas the main components of the urinary sulfated bile acids were glycochenodeoxycholic acid (4.58 ± 6.97 μmol/day) and taurochenodeoxycholic acid (3.67 ± 3.54 μmol/day). Chenodeoxycholic acid, which is relatively toxic to the liver, may more easily be conjugated with sulfate and, hence, excreted into urine at a faster rate than cholic acid. Marked individual variations in urinary bile acid patterns were observed not only in BA patients but also in normal controls.