Takeshi Tomomasa

Prediction of Intravenous Immunoglobulin Unresponsiveness in Patients With Kawasaki Disease

Background— In the present study, we developed models to predict unresponsiveness to intravenous immunoglobulin (IVIG) in Kawasaki disease (KD). Methods and Results— We reviewed clinical records of 546 consecutive KD patients (development dataset) and 204 subsequent KD patients (validation dataset). All received IVIG for treatment of KD. IVIG nonresponders were defined by fever persisting beyond 24 hours or recrudescent fever associated with KD symptoms after an afebrile period. A 7-variable logistic model was constructed, including day of illness at initial treatment, age in months, percentage of white blood cells representing neutrophils, platelet count, and serum aspartate aminotransferase, sodium, and C-reactive protein, which generated an area under the receiver-operating-characteristics curve of 0.84 and 0.90 for the development and validation datasets, respectively. Using both datasets, the 7 variables were used to generate a simple scoring model that gave an area under the receiver-operating-characteristics curve of 0.85. For a cutoff of 0.15 or more in the logistic regression model and 4 points or more in the simple scoring model, sensitivity and specificity were 86% and 67% in the logistic model and 86% and 68% in the simple scoring model. The kappa statistic is 0.67, indicating good agreement between the logistic and simple scoring models. Conclusions— Our predictive models showed high sensitivity and specificity in identifying IVIG nonresponders among KD patients.

Erythromycin induces migrating motor complex in human gastrointestinal tract

Fifteen healthy subjects, fasted at least 8 hr, were studied by means of an infused manometric method. Twenty minutes after termination of the natural phase III activity in the duodenum, erythromycin or normal saline was administered intravenously for 15 min. When normal saline (N=5) was infused, the next migrating motor complex (MMC) was initiated 151.2±42.1 min after the infusion. On the other hand, when erythromycin was infused at a rate of 1.0 mg/kg/hr (N=5) or 3.0 mg/kg/hr (N=5), MMC-like contractions were initiated at shorter intervals, ie, 47.8±40.9 min (P<0.005) or 23.0±13.0 min (P <0.001), respectively. The duration, frequency, amplitude, and migrating velocity of the naturally occurring MMC (N-MMC) were not significantly different from those of the erythromycin-induced contractions except for the duration of the phase III contractions in the stomach; the duration (5.3±2.2 min) of the erythromycin-induced contractions being significantly (P<0.05) longer than that (3.2±0.9 min) of the naturally occurring MMC. The immunoreactive motilin (IRM) concentration did not increase significantly after the infusion of erythromycin, when compared to that after infusion of normal saline. It is concluded that erythromycin at a dose of 1–3 mg/kg/hr for 15 min during the interdigestive state, similar to motilin, has a significant influence upon the initiation of MMC in the human gastrointestinal tract, but further investigations are required to confirm whether endogenous motilin is involved or not.

Corticosteroids in the treatment of the acute phase of Kawasaki disease

OBJECTIVES Corticosteroids are considered to be contraindicated during the acute phase of Kawasaki disease (KD) based on unfavorable results in early studies. In our hospital, however, corticosteroids have been used in some cases of KD with satisfactory results. We analyzed outcomes of patients with KD treated with or without corticosteroids. STUDY DESIGN Medical records of 299 children with KD treated with one of the 4 regimens were reviewed retrospectively. Regimen 1 consisted of aspirin, dipyridamole, and propranolol; regimen 2 was regimen 1 plus prednisolone, 2 mg/kg/d, for 1 week, followed by tapering over 2 weeks; regimen 3 was regimen 1 plus intravenous gamma-globulin (IVGG), 200 or 400 mg/kg/d, for 5 consecutive days; and regimen 4 was regimen 1 plus both prednisolone and IVGG. RESULTS Although patients treated with regimens 2 and 4 were more ill at presentation than those treated with regimens 1 and 3, respectively, the duration of fever was shorter in the former patient groups (P =.0013). Coronary aneurysms developed least frequently in patients treated with regimen 4 and less frequently with regimen 2 than with regimen 1 (P =.0730). Multiple regression analysis showed significant reductions of fever and coronary aneurysm incidence with prednisolone (P <.0001 and P =.0307, respectively). CONCLUSION Our data suggest a possible role of corticosteroids in the treatment of the acute phase of KD.

Effect of corticosteroids in addition to intravenous gamma globulin therapy on serum cytokine levels in the acute phase of Kawasaki disease in children

OBJECTIVE The aim of this multicenter prospective and randomized study was to determine the effect of adding corticosteroids to intravenous gamma globulin (i.v.GG) therapy on serum cytokine levels, as well as to see its effect on the clinical course in children in the acute phase of Kawasaki disease (KD). STUDY DESIGN Patients with KD (n=32) were randomized to receive either i.v.GG alone (G group) or i.v.GG plus corticosteroids (G+S group). The clinical course and cytokine responses between groups were compared. RESULTS The pretreatment serum levels of interleukin (IL)-2, IL-6, IL-8, and IL-10 were significantly higher in patients with KD than in healthy controls. Although i.v.GG alone failed to reduce cytokine concentrations within 24 hours of i.v.GG administration, corticosteroids plus i.v.GG reduced IL-2, IL-6, IL-8, and IL-10 levels. The levels of IL-2, IL-6, IL-8, and IL-10 within 24 hours after initiating i.v.GG therapy were significantly lower in the G+S group than in the G group. The duration of fever was shorter, and the C-reactive protein concentration decreased more quickly in the G+S group than in the G group. CONCLUSIONS These findings suggest that corticosteroids rapidly ameliorate symptoms by reducing cytokine levels in children with KD.

Gastrointestinal sounds and migrating motor complex in fasted humans

Objective:We investigated the relationships among gastrointestinal sounds, gastrointestinal manometric findings, and small intestinal transit time in healthy fasted humans.Methods:Gastrointestinal sounds acquired with two microphones attached to the upper and lower abdominal walls of healthy subjects were quantified with a computer-aided sound analysis program. Antroduodenal contractions were recorded by manometry. Small intestinal transit time was measured by breath hydrogen testing after intraduodenal administration of lactulose.Results:The sum of the gastrointestinal sound amplitudes (sound index) in both the upper and lower abdomen changed with time, coinciding with the gastric phases of the migrating motor complex. The sound indices in the upper and lower abdomen were 59.0 ± 24.8 and 98.1 ± 21.6 mV/min in phase 1, 95.5 ± 27.9 and 127.4 ± 34.9 mV/min in phase 2, and 132.8 ± 12.4 and 188.5 ± 73.4 mV/min in phase 3, respectively. There were no significant differences among motility phases in terms of the mean duration or frequency of each sound event. Intravenous erythromycin induced phase 3 in the stomach and doubled the sound index. Somatostatin analogue induced phase-3–like clustered contractions in the duodenum, but inhibited antral contractions and decreased the sound index. The small intestinal transit time was shorter and the sound index increased after intravenous metoclopramide, compared with controls. Scopolamine delayed small intestinal transit time and decreased the sound index.Conclusions:This study is the first to document the relationships between gastrointestinal sounds and the migrating motor complex. The chronological relation between antral motility and gastrointestinal sounds, and the dissimilar effects of erythromycin and somatostatin, suggest that antral contractions increase gastrointestinal sounds, perhaps by supplying gas into the intestine.

Nonmigrating rhythmic activity in the stomach and duodenum of neonates.

We studied gastrointestinal motility in 20 infants, using a modified manometric method for neonates, and compared it to that in adults. Changes in the intragastric and intraduodenal pressures were recorded for 3 h after the ingestion of milk. Bands of contractions with the same rhythmicity as phase III activity in adults were frequently recorded. Some of them migrated caudally and were speculated to the equivalent of phase III activity of the interdigestive migrating complex (IMC) in adults. However, others did not migrate and showed some differences from phase III activity of adults and infants in the time of occurrence, duration and amplitude. The characteristic of gastroduodenal motility in infants was the frequent occurrence of these bands of nonmigrating rhythmic concentrations. Our findings indicated the following problems: (1) there are some differences in gastrointestinal motility between infants and adults and further investigations are required for the evaluation of the physiology or pathophysiology of this phenomenon; (2) in infants, many bands of rhythmic contractions of the alimentary tracts can exist without migration. This indicates the possibility that the occurrence of rhythmic contractions and their migration are regulated by different mechanisms.

Measurement of Tricuspid Annular Diastolic Velocities by Doppler Tissue Imaging to Assess Right Ventricular Function in Patients with Congenital Heart Disease

We assessed the clinical utility of using diastolic tricuspid annular velocities obtained by Doppler tissue imaging as a noninvasive index of right ventricular function in patients with congenital heart disease. Doppler tissue imaging at the tricuspid annulus and pulsed Doppler echocardiography of the right ventricular inflow were performed in 71 children with congenital heart disease, with and without elevated right ventricular pressure. Cardiac catheterization was performed in all patients with congenital heart disease, and the hemodynamic determinants of the tricuspid annular and inflow velocities were determined. In patients with congenital heart disease, the ratio of the late-to-early diastolic tricuspid annular velocity (Aa/Ea) showed a highly significant correlation with right ventricle pressure/left ventricle pressure (r = 0.79, p < 0.0001), right ventricular end diastolic pressure (r = 0.46, p < 0.0001), and the first derivatives of the change in right ventricle pressure during diastole (r = 0.72, p < 0.0001). However, the late-to-early diastolic tricuspid inflow velocity (A/E) did not correlate with any invasively measured index of right ventricular function. Aa/Ea, derived from tricuspid annular velocities as measured by Doppler tissue imaging, is a valuable, noninvasive tool for detecting an elevated right ventricular pressure in patients with congenital heart disease.

Living-related liver transplantation for type II citrullinemia using a graft from heterozygote donor.

BACKGROUND Type II citrullinemia (CTLN2) characterized by a liver-specific argininosuccinate synthetase deficiency is an adult onset genetical disorder caused by the mutation of SLC25A13 gene, which results in fulminant hyperammonemia often with poor prognosis. METHODS A 16-year-old Japanese boy presented fulminant hyperammonemia and encephalopathy and recovered after aggressive medical treatment. The patient was diagnosed as CTLN2 by plasma amino acid pattern and detection of the mutated SLC25A13 gene. We performed living-related liver transplantation (LRLT) using a graft from the genetically proven heterozygote father. RESULTS Serum amino acid concentration was normalized within a day after transplantation without protein restriction and medication. The patients postoperative course was natural. The patient is back in school 6 months after surgery. CONCLUSIONS Living-related liver transplantation using a graft from genetically proven heterozygote donors might be a permissible treatment modality for CTLN2. Long-term observation may be necessary to make a definite conclusion possible.

Plasmapheresis in fulminant acute disseminated encephalomyelitis

We report an 11-year-old girl with acute disseminated encephalomyelitis (ADEM) who developed respiratory failure and coma despite the use of corticosteroid and intravenous immunoglobulin. We performed plasmapheresis four times, which improved her level of consciousness, hyperesthesia, external ophthalmoplegia and muscle weakness, and led to the normalization of brain and spinal cord MRI. Plasmapheresis might be an effective treatment in cases of fulminant ADEM.

Endoscopic findings in pediatric patients with Henoch-Schonlein purpura and gastrointestinal symptoms

We report the gastrointestinal endoscopic findings in nine patients with Henoch-Schonlein purpura. Eight patients underwent upper gastrointestinal endoscopy, which revealed erosive gastritis in one patient, hemorrhagic-erosive duodenitis in four, and both findings in one. The rectum and the sigmoid colon were examined in six patients. Aphthoid ulcers were noted in two. In one of these patients, a rectal ulcer was also noted. Severe inflammatory changes and angiitis were found in the biopsy specimens obtained from the duodenum and the colon. The vascular abnormalities in the gastrointestinal mucosa are similar histologically to those found in the skin in Henoch-Schonlein purpura.