Simultaneous development of Kawasaki disease following acute human adenovirus infection in monozygotic twins: A case report.

BACKGROUND: The etiology of Kawasaki disease (KD) remains unknown. However, many studies have suggested that specific genetic factors and/or some infectious agents underlie the onset of KD. Previous studies have suggested that human adenovirus (HAdV) is one of the triggering pathogens of KD. Here, we report monozygotic twin boys who sequentially developed KD in conjunction with acute HAdV type 3 (HAdV-3) infection. CASE PRESENTATION: The patients were four-year-old monozygotic twin boys. The elder brother developed a high fever and was diagnosed with HAdV infection with an immunochromatographic kit for HAdV (IC-kit). He was transferred to our institute after persistent fever for 7 days. On admission, he already fulfilled all the diagnostic criteria for KD. His laboratory data were as follows: WBC, 9700/µl; CRP, 2.42 mg/dl; IFN-γ, 99.8 pg/ml; and TNF-α, 10.9 pg/ml. He received intravenous immunoglobulin (IVIG) and aspirin and responded well, with no coronary artery abnormalities. The younger brother, who was also IC-kit-positive, was hospitalized on the same day as his elder brother after persistent fever for 3 days. His data on admission were as follows: WBC, 12,600/µl; CRP, 5.54 mg/dl; IFN-γ, 105.0 pg/ml; and TNF-α, 33.6 pg/ml. Although he developed all of the typical KD symptoms by day 4, his fever subsided spontaneously on day 6 without IVIG or aspirin. However, he developed a dilation of the coronary artery in the region of the left circumflex artery bifurcation on day 10. His coronary artery dilation had resolved 3 months after onset. HAdV-3 DNA was detected with PCR in stool samples from both patients, and HAdV3 was isolated from the younger brother's stool sample. Serum neutralizing antibodies to AdV3 were also significantly elevated in both patients, suggesting seroconversion. CONCLUSIONS: There have been few reports of the simultaneous development of KD in monozygotic twins. Notably, both twins had an acute HAdV-3 infection immediately before they developed KD. These cases strongly suggest that KD was triggered by HAdV-3 infection, and they indicate that specific immune responses to some pathogens (such as HAdV-3), arising from genetic susceptibility, play a critical role in the pathogenesis of KD.

Late, Late-Onset Group B Streptococcus Cellulitis With Bacteremia.

Group B streptococcus (GBS) infection remains a leading cause of serious neonatal and early infantile infection. As the infection often presents with nonspecific symptoms, and is associated with underlying bacteremia, prompt investigation and treatment is required. We report a case of late, late-onset GBS infection with bacteremia in a 94-day-old boy experiencing cellulitis of the left hand. Although late-onset disease or late, late-onset disease has been reported to be common among infants with underlying conditions such as premature birth, immunocompromised status, trauma, or among those using medical devices, no such underlying medical condition predisposed this infant to invasive GBS infection. Recent reports including the present case underscore the risk of GBS infection among previously healthy infants beyond the neonatal period. Thus, clinicians should especially be aware of unusual presentations of GBS invasive disease with bacteremia.

Protective effects of influenza A (H1N1) pandemic 2009 vaccination against the onset of influenza-like illness and asthma exacerbation in Japanese children.

BACKGROUND: Vaccination against influenza A(H1N1)pdm09 in Japan started in October 2009. Children with asthma are considered as a high-risk group and are recommended to preferentially receive the vaccine. OBJECTIVE: To identify the clinical effects of vaccination in Japanese children with and without asthma. METHODS: We conducted a cross-sectional, questionnaire-based survey to compare vaccination rates, vaccine effectiveness against physician-diagnosed influenza A infection (PDIA), and consecutive asthma exacerbations between children with and without asthma. RESULTS: Of the 460 children included in this study, those with asthma had higher vaccination rates (46.5%, 67/144) than those without asthma (30.4%, 96/316). Influenza A infections were diagnosed in 28 of 163 vaccinated children (17.2%) compared to 164 of 297 unvaccinated children (55.2%, p < 0.001). Comparison of positive influenza diagnosis rates between vaccinated and unvaccinated children with and without asthma showed that unvaccinated children with asthma had an elevated odds ratio (13.235; 95% confidence interval [CI], 5.564-32.134) and that treatment for asthma exacerbations was needed in a larger proportion of unvaccinated children. Vaccine effectiveness against PDIA was 87% (95% CI, 78-93%) overall, 92% (95% CI, 81-96%) in children with asthma and 81% (95% CI, 63-91%) in children without asthma, respectively. CONCLUSIONS: The administration of an inactivated, split-virus, non-adjuvanted monovalent A(H1N1)pdm09 vaccine during the pandemic period reduced the number of physician-diagnosed influenza A infections and asthma exacerbations in children with asthma. Therefore, we strongly recommend that high-risk children with a history of asthma receive vaccines during pandemics.

[Urolithiasis induced by combined ACTH and zonisamide treatment in a patient with startle induced epilepsy].

A 5-year-old boy had periodic spasms and startle-induced drop attacks. Zonisamide (ZNS) was partially effective for the former seizures, and propranolol for the latter. An add-on therapy with ACTH resulted in a transient disappearance of seizures and an improvement of EEG. However, the patient developed urolithiasis with resultant hematuria and pyelectasis during ACTH therapy. ZNS can induce urolithiasis by increasing urinary pH and calcium (Ca) excretion, and ACTH may facilitate this rare adverse effect of ZNS by further increasing the urinary Ca. Hydrochlorothiazide could resolve the urolithiasis by decreasing the urinary Ca excretion.

Seizure-induced neuronal death in the immature brain.

The response of the developing brain to epileptic seizures and to status epilepticus is highly age-specific. Neonates with their low cerebral metabolic rate and fragmentary neuronal networks can tolerate relatively prolonged seizures without suffering massive cell death, but severe seizures in experimental animals inhibit brain growth, modify neuronal circuits, and can lead to behavioral deficits and to increases in neuronal excitability. Past infancy, the developing brain is characterized by high metabolic rate, exuberant neuronal and synaptic networks and overexpression of receptors and enzymes involved in excitotxic mechanisms. The outcome of seizures is highly model-dependent. Status epilepticus may produce massive neuronal death, behavioral deficits, synaptic reorganization and chronic epilepsy in some models, little damage in others. Long-term consequences are also highly age- and model-dependent. However, we now have some models which reliably lead to spontaneous seizures and chronic epilepsy in the vast majority of animals, demonstrating that seizure-induced epileptogenesis can occur in the developing brain. The mode cell death from status epilepticus is largely (but not exclusively) necrotic in adults, while the incidence of apoptosis increases at younger ages. Seizure-induced necrosis has many of the biochemical features of apoptosis, with early cytochrome release from mitochondria and capase activation. We speculate that this form of necrosis is associated with seizure-induced energy failure.

Short-term plasticity of hippocampal neuropeptides and neuronal circuitry in experimental status epilepticus.

PURPOSE: We used a model of self-staining status epilepticus (SSSE), induced by brief intermittent stimulation of the perforant path in unanesthetized rats, to study the mechanism of initiation and of maintenance of SSSE and the role of neuropeptides in those processes. METHODS: The perforant path was stimulated intermittently for 7 min (ineffective stimulation) or 30 min (generating SSSE). Peptides and their agonists and antagonists were delivered either intraperitoneally, or directly into the hippocampus through a implanted cannula. Behavior and electroencephalogram (EEG) were recorded through a videotape-telemetry system with automatic spike and seizures detection programs, which were supplemented by manual review of the records to confirm the diagnosis. Immunocytochemistry and enzyme-linked immunosorbent assay followed published methods. RESULTS: Initiation of SSSE was blocked by many agonists of inhibitory neurotransmitters or neuromodulators, and by many antagonists of excitatory synapses, and was facilitated by agents with the opposite action, suggesting the activation of a complex circuit with multiple potential entry points. Once SSSE was established, however, only N-methyl-d-aspartate (NMDA)-receptor ligands and a few neuropeptides had major effects on its maintenance. Galanin and dynorphin had powerful anticonvulsant roles in the maintenance phase of SSSE, whereas somatostatin and neuropeptide Y suppressed seizures only transiently. SSSE seemed to induce maladaptive changes in neuropeptides: it depleted the hippocampus of the galanin- and dynorphin-immunoreactive (IR) fibers, which normally function as endogenous anticonvulsants; whereas it induced overexpression of the proconvulsant neuropeptides substance P and neurokinin B; however, late in the course of SSSE, galanin-IR interneurons appeared in the dentate hilus. CONCLUSIONS: Initiation of SSSE seems to involve a circuit with many points of entry, and blockage of any point along this circuit inhibits the development of SSSE. Far fewer agents alter the maintenance phase of SSSE. Galanin, dynorphin, somatostatin, and neuropeptide Y have anticonvulsant roles, matching the previous described convulsant role of substance P and neurokinin B. Galanin and dynorphin seem to undergo maladaptive changes, which appear to play an important role of the maintenance phase of SSSE. Later, the de novo expression of inhibitory neuropeptides in novel cells in hippocampus coincides with the waning of seizures and may play a role in their termination.