A case of Kawasaki disease associated with syndrome of inappropriate secretion of antidiuretic hormone.

UNLABELLED: Kawasaki disease (KD) is an acute vasculitis of unknown aetiology with varied clinical manifestations. Although coronary arteritis is common in the course of KD, central nervous system involvement is rare. We report a case of KD in an infant who developed convulsions and apnoea during his illness associated with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). CONCLUSION: The possibility of severe hyponatraemia should be anticipated in children with KD. Infants with KD are at risk of SIADH and should be monitored closely for its development.

Differential diagnosis and clinical course of autoimmune neutropenia in infancy: comparison with congenital neutropenia.

AIM: Autoimmune neutropenia in infancy (AIN) is caused by granulocyte-specific autoantibodies. Clinical presentation and diagnosis have not been well studied, resulting in cumbersome diagnostic investigations and unnecessary treatment such as granulocyte colony-stimulating factor (G-CSF) therapy. METHODS: Clinical, laboratory and immunological data of 18 infants with AIN were evaluated. Granulocyte-specific autoantibodies were detected by the direct granulocyte immunofluorescence test (D-GIFT), indirect granulocyte immunofluorescence test (I-GIFT) and immunoblotting. RESULTS: The average age of onset and resolution of neutropenia in AIN was 7.4 +/- 3.4 mo (mean +/- SD) and 20.4 +/- 4.9 mo, respectively. Sixteen of the 18 patients presented with mild infectious symptoms; the other 2 patients were detected by chance and presented with no infectious symptoms. D-GIFT was positive in all patients, and I-GIFT was positive in 17 of these 18 patients. Most patients showed preferential binding to neutrophils from NA(1 + 2-)-phenotyped donors by 1-GIFT and immunoblotting. An antibiotic (sulfamethoxazole-trimethoprim) was given to 15 patients for prophylaxis. G-CSF was given to only one infectious patient. CONCLUSION: A combination of diagnostic tests for the detection of granulocyte-specific autoantibodies was useful in diagnosing AIN, thus avoiding unnecessary investigations. Continuous treatment with G-CSF was not necessary for prophylaxis, even if neutrophil counts were extremely low.

Role of reactive oxygen species in neutrophil apoptosis following ingestion of heat-killed Staphylococcus aureus.

Neutrophils, short-lived leucocytes that die by apoptosis, play an important role in the first stage of defense against bacterial infections. It has been reported that phagocytosis of intact bacteria or Candida albicans can accelerate neutrophil apoptosis. However, the mechanism of phagocytosis-mediated neutrophil apoptosis is not well characterized. In this study, we evaluated whether ingestion of heat-killed Staphylococcus aureus (S. aureus) enhances neutrophil apoptosis and whether this type of apoptosis is mediated by oxidative stress by using antioxidants and polymorphonuclear leucocytes (PMNs) from patients with chronic granulomatous disease (CGD). Co-culture of PMNs with varying doses of S. aureus resulted in accelerated PMN death in a dose- and time-dependent manner. Increased PMN apoptosis was observed by both Annexin V and PI staining. Similar results were observed in PMNs of CGD patients. Dimethyl sulphoxide (DMSO, an OH* scavenger) did not significantly inhibit either S. aureus-ingested PMN apoptosis or spontaneous PMN apoptosis. On the other hand glutathione (GSH, an H2O2 scavenger) significantly inhibited both types of apoptosis. Our findings suggest that oxygen-independent pathways may mainly operate in the process of phagocytosis-induced apoptosis.

FcgammaRIII b and FcgammaRIIa polymorphism may affect the production of specific NA1 autoantibody and clinical course of autoimmune neutropenia of infancy.

We studied 18 children with autoimmune neutropenia (AIN) to evaluate whether there was a possible relationship between the specificity of granulocyte autoantibodies (anti-NA1,2) and the phenotype of the NA system. Direct granulocyte immunofluorescence test (D-GIFT) was positive in all patients, and indirect granulocyte immunofluorescence test (I-GIFT) was positive in 17 of these 18 patients, respectively. Fourteen of 18 patients showed preferential binding to neutrophils from NA(1+2-) phenotyped donors. Immunoblotting with anti-FcgammaRIIImAb showed that IgG prepared from 7 of 12 patients precipitated both FcgammaRIIIb from NA1 and NA2 neutrophil lysate, whereas the other 5 precipitated only NA1. Patients' IgG did not react with purified FcgammaRIIa. FcgammaRIIIb genotype were NA(1+2-) in 15 of 18 patients and NA(1+2+) in the other 3. FcgammaRIIa type of all patients were (H+R-). These distributions were significantly different from those of healthy Japanese blood donors (n = 608). The genotype of FcgammaRIIIb and FcgammaRIIa may affect the production of neutrophil specific auto-antibodies in AIN of infancy and influence its clinical course.

[Clinical and bacteriological studies of ceftriaxone (CTRX) once daily administration in pediatric patients with respiratory tract infections].

Clinical studies of ceftriaxone (CTRX) were performed at a dose of 40 mg/kg once daily to evaluate its pharmacokinetics, and clinical and bacteriological efficacies in pediatric patients with respiratory tract infections. The following results were obtained. 1. Of 45 patients, clinical responses to CTRX were excellent in 34 (75.6%), good in 9 (20.0%) and poor in 2 (4.4%), indicating the overall efficacy rate of 95.6%. 2. Haemophilus influenzae (23 strains), Streptococcus pneumoniae (20 strains) and Moraxella catarrhalis (17 strains) were isolated from the patients as the main causative organisms. MIC90 of CTRX against these detected bacteria was < or = 0.06 microgram/ml with H. influenzae [beta-lactamase (-)/ABPC (S)], 0.25 microgram/ml with H. influenzae (BLNAR), 0.05 microgram/ml with PSSP, 1.0 microgram/ml with PISP/PRSP and 2.0 micrograms/ml with M. catarrhalis, respectively. 3. The eradication rate of causative organisms was 90.0% (27/30). 4. Serum levels of CTRX after administration of a 1-hour intravenous drip infusion of 40 mg/kg were investigated in 12 patients. Mean serum level at 24 hours after the administration was 9.4 +/- 2.8 micrograms/ml, which covered the level of MIC90 throughout the 24 hours. 5. No adverse reactions related to CTRX were observed. As the approved dosage of CTRX in pediatric patients is twice daily, while it is once daily in adults, there have been few reports on the efficacy of once-daily CTRX in pediatrics. According to the results of the study, it is suggested that once-daily CTRX for the pediatric patients with respiratory tract infections is useful. Further studies might be required to establish outpatient parenteral antibiotic therapy (OPAT) in pediatric infections.

Two cases of autoimmune neutropenia possibly induced by beta-lactam antibiotics in infants.

This report describes two infants who had neutropenia develop after treatment with beta-lactam antibiotics. The first patient, a 9-month-old girl, was administered flomoxef (FMOX); the second patient, a 14-month-old boy, was administered cefotiam (CTM). Both infants were found to have neutropenia 4 to 5 days after they were placed on respective antibiotics, and neutropenia had persisted despite antibiotics withdrawal for 1 to 3 months. Drug-induced lymphocyte stimulation test (DLST), granulocyte-bound antibodies, serum granulocyte antibodies, and immunoblotting analysis indicated that beta-lactam antibiotics possibly triggered production of granulocyte autoantibody with resultant autoimmune neutropenia.

Dizygotic twin sisters with myelokathexis: mechanism of its neutropenia.

Dizygotic twin sisters were first found to have neutropenia at 1 year of age when evaluated for recurrent pulmonary infections. Since then they have remained neutropenic (0.05 approximately 0.5 x 10(9)/l). Despite of their neutropenia, myeloid hyperplasia was evident on a marrow smear examination, and a number of cells were hypersegmented with fine interlobular bridging with chromatin strands and cytoplasmic vacuolation. Electron microscopy showed apoptotic cells with condensed nuclei and apoptotic bodies in the cytoplasm. Although life span, hydrogen peroxide production, phagocytosis, spreading, and chemotaxis of peripheral neutrophils were normal, the survival of bone marrow neutrophils in both infants was markedly decreased when compared with that of normal bone marrow neutrophils. During the bone marrow culture apoptotic neutrophils were observed at an earlier stage in both patients than in normal controls, biochemically and morphologically. Morphology of bone marrow neutrophils in both patients resembled that of cultured control bone marrow neutrophils. Peripheral neutropenia and appearance of characteristic neutrophils in the bone marrow in myelokathexis are considered to be an expression of apoptosis of bone marrow neutrophils.

Chronic granulomatous disease in Japan: incidence and natural history. The Study Group of Phagocyte Disorders of Japan.

PURPOSE: To analyze the incidence and causes of fatality of patients with chronic granulomatous disease (CGD) in Japan and to provide an opportunity for comparison with reports from other countries. METHODS: The Study Group of Phagocytic Disorders in Japan conducted a questionnaire survey on CGD patients in Japan, results of which formed the basis of the study. RESULTS: Clinical details of 221 patients were analyzed: 194 male and 27 female (ratio: 7.2/1), 152 living, 51 dead and 18 unknown. The prevalence of CGD was estimated to be 1/287,709 live births. The fatality rate was 23.1%. The mean age of the surviving patients increased from 8 years 4 months in 1985 to 16 years 0 months in 1998. Although the mean age of death was advanced by 4 years 11 months during the same period of time, the fatality rate has remained practically unchanged during the past 13 years. The number of living adult patients has tended to increase (32.1%). At the time of study, approximately 90% of patients had been placed on sulfamethoxazole-trimethoprim prophylactically or therapeutically, either singly or in combination with other modalities, including interferon-gamma, antifungal agents and various antibiotics. Pulmonary infections were responsible for 58.3% of fatalities. CONCLUSIONS: With early diagnosis and prompt institution of appropriate therapy, the mean age of CGD patients in Japan has been increasing, but the fatality rate has remained practically unchanged during the last 13 years, mostly due to the fungal infections.

Heterogeneity in F-actin polymerization of cord blood polymorphonuclear leukocytes stimulated by N-formyl-methionyl-leucyl-phenylalanine.

BACKGROUND: To elucidate the mechanism responsible for defects of polymorphonuclear leukocyte (PMNL) chemotaxis of neonates, we determined actin polymerization of NBD (7-nitrobenz-2-oxa-diazol)-phallacidin-stained PMNL following stimulation with either N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate (PMA) in cord blood and adult controls. METHODS: We measured F-actin content in PMNL stained with NBD-phallacidin using flow cytometry. RESULTS: Relative F-actin polymerization, that is, a ratio of stimulated F-actin to basal F-actin, was significantly decreased in cord blood PMNL when compared with that of adult PMNL. Distribution of fMLP-stimulated F-actin showed a bimodal pattern, while adult PMNL disclosed a single pattern. Following stimulation with PMA, however, F-actin levels were equal in both cord and adult PMNL. A fluorescein isothiocyanate-conjugated fMLP receptor assay showed no significant difference in binding capacity of fMLP receptors between adult and cord PMNL. CONCLUSION: These results indicate that a deficiency of PMNL chemotaxis in neonates may be due, in part, to decreased relative F-actin polymerization, which may be caused by functional heterogeneity in cord blood PMNL.

[Effects of a vitamin K2 preparation in severely handicapped patients complicated by osteopenia].

The efficacy and side effects of oral vitamin K2 therapy were examined in 20 children and adults with probable secondary osteoporosis who had been hospitalized for a long period, due to severe mental and/or physical handicaps. Vitamin K2 was given for 12 months. Bone mineral density significantly increased 4 months after starting oral vitamin K2 therapy (p = 0.0038) and it retained the elevated level after 12 months of treatment. This therapy was particularly effective in patients with severe locomotor dysfunction. Serum total protein levels significantly decreased following the start of this therapy (p = 0.0012). The reasons of this decrease and its causal relationship to the administration of vitamin K2 are unknown, and should be investigated further.

[A case of pacemaker implantation for complete atrioventricular block associated with Duchenne muscular dystrophy].

We report here a case of Duchenne muscular dystrophy (DMD) who underwent pacemaker implantation for complete atrioventricular block. This 30 year-old male had the deletion of exon 45-52 in the dystrophin gene and complained of palpitation and precordial oppression. Because his electrocardiogram showed complete atrioventricular block, a permanent pacemaker was implanted. He has been doing well for 15 months after implantation. There have been few reports about pacemaker implantation for patients with DMD. As these patients survive longer by mechanical ventilation with chest respirators or nasal intermittent positive pressure ventilators, an increasing number of cases may require pacemaker implantation.

[Prevalence of serum anti-Helicobacter pylori IgG antibody in persons with severe motor and intellectual disabilities--comparison between institutionalized persons and persons living at home].

The seroprevalence of an anti-Helicobacter pylori antibody (ELISA) was investigated in institutionalized persons with severe motor and intellectual disabilities (SMID). The rate of seropositivity was significantly higher in persons with SMID under 29 years of age than in age-matched controls and in institutionalized patients with muscular dystrophy. No difference in seropositivity among SMID patients was found between those in our and other institutions. Therefore, it is speculated that Helicobacter pylori infection occurs soon after the institutionalization of SMID patients. Persons with SMID living at home, in their teens and twenties, had lower seropositivity than that of institutionalized patients but higher than controls. These data implicate the life style of persons with SMID and long-term institutionalization as one of important risk factors of Helicobacter pylori infection.

Effects of coronary blood flow, myocardial contractility, and heart rate on cardiac lymph circulation in open-chest dogs. Use of a direct cannulation method for subepicardial lymph vessel.

The study was conducted to evaluate the effects of increased coronary blood flow (CBF), myocardial contractility, and heart rate on cardiac lymph circulation using a subepicardial lymph channel in anesthetized open-chest dogs. A subepicardial lymph vessel along the left anterior descending coronary artery (LAD) was cannulated directly with a small polyethylene tube, and lymph flow (LF) and protein concentration of lymph (PC) were measured. Coronary blood flow (CBF) was increased with intracoronary infusion of adenosine, and myocardial contractility with isoproterenol (isoprenaline) infusion. Effects of an increase in CBF using a constant flow system were also studied. Heart rate was increased by atrial pacing. The control cardiac LF in 17 adult mongrel dogs varied from 5.3 to 12.6 microliters/min (mean 8.4 +/- 2.8). With an increase in CBF, LF and protein efflux to lymph (PEF) increased both adenosine and isoproterenol infusion, while PC was decreased by adenosine and increased by isoproterenol. The increase in CBF using the constant flow system elicited the essentially similar extent of changes in LF and PC in relation to a change in CBF as those during infusion of adenosine. The increase in LF and PEF was significantly smaller during the infusion of adenosine than isoproterenol infusion in relation to a change in CBF. In contrast, pacing-induced tachycardia which caused a relative shortening of the diastolic phase in the heart cycle reduced LF and PEF despite of a slight increase in CBF. These findings suggest that CBF and relative duration of diastole in the heart cycle play an important role in regulation of lymph circulation, and isoproterenol can change capillary permeability in addition to increasing CBF.

[Abnormal metabolism of fatty acids and ketone bodies in Duchenne muscular dystrophy, and the effect of biotin on these abnormalities].

It has been reported that serum levels of ketone bodies often elevate in patients with Duchenne muscular dystrophy (DMD). The cause of this abnormal metabolism, however, has not been elucidated. In this study, serum levels of ketone bodies were measured in the early morning in patients with DMD, congenital muscular dystrophy and cerebral palsy. Serum free fatty acids (FFA), glucose, and thickness of subcutaneous fat were also measured. Ketone bodies elevated in most DMD patients, but not elevated in patients with the other disorders. Hyperketonemia in the DMD patients was accompanied by elevation of the FFA level, but no correlation was seen between hyperketonemia and the creatine kinase level or the severity of muscle involvement. No differences were found between DMD patients and others in the levels of FFA, glucose and thickness of subcutaneous fat. These results indicate that DMD patients are more prone to ketosis than the others. The effect of biotin administration (2 mg/day) on hyperketonemia also was investigated in 11 patients with DMD. The levels of total ketone bodies decreased by biotin administration for 2 weeks. These data suggest that the utilization of FFA and ketone bodies may be impaired in DMD patients. Biotin treatment will be useful for improving the abnormal metabolism of ketone bodies in DMD patients.

[Identification of impaired cholesterol biosynthesis in a Japanese patient of Smith-Lemli-Opitz syndrome].

We reported the decreased level of cholesterol as well as the elevated levels of 7- and 8-dehydrocholesterol in the serum and erythrocytes of a Japanese patient with Smith-Lemli-Opitz syndrome. These findings suggested that the detection of these precursors of cholesterol synthesis should become an important biochemical parameter for this syndrome in which clinical features are not always obvious.

In vitro antiviral activities of sulfated polysaccharides from a marine microalga (Cochlodinium polykrikoides) against human immunodeficiency virus and other enveloped viruses.

A marine microalga, Cochlodinium polykrikoides, produces extracellular sulfated polysaccharides. Isolation and purification of the polysaccharides were accomplished by precipitation with ethanol and Cetavlon, followed by DEAE-cellulose column chromatography (polysaccharides A1 and A2). These polysaccharides, which were homogeneous when analysed by both ultracentrifugal and electrophoretic methods, were composed of mannose, galactose, glucose and uronic acid, together with sulfate groups (S = 7-8% w/w). Both A1 and A2 inhibited the cytopathic effect of influenza virus types A and B in MDCK cells, that of respiratory syncytial virus types A and B in HEp-2 cells, that of human immunodeficiency virus type 1 in MT-4 cells; and, except A1 for herpes simplex virus type 1 and A2 for parainfluenza virus type 2 in HMV-2 cells, the cochlodinium polysaccharides showed no antiviral activity against parainfluenza virus types 2 and 3, measles virus, mumps virus or herpes simplex virus type 1 in HMV-2 cells. No cytotoxicity for host cells was observed with these polysaccharides at a concentration of 100 micrograms ml-1. Inhibitory effects on various viruses were achieved at concentrations that were not markedly inhibitory to the blood coagulation process.

[Increased gamma delta T cells in peripheral blood of patients with severe neurologic impairment].

We examined peripheral gamma delta T cells in patients with severe neurologic impairment. The gamma delta T cells in these patients significantly increased as compared with those in healthy adults (P < 0.0001). These cells expressed the V gamma 9/V delta 2 phenotype which was reported to proliferate by infections. When patients with severe neurologic impairment and patients with Duchenne muscular dystrophy (DMD) were divided into frequent and non-frequent infectious groups, the gamma delta T cells increased significantly in the frequent infectious group of DMD (P < 0.005), but not significantly in the frequent infectious group of patients with severe neurologic impairment. These results indicated that the gamma delta T cells of patients with severe neurologic impairment increased in frequent infections and other factor(s).