Mikio Doi

Diphenylarsinic acid poisoning from chemical weapons in Kamisu, Japan

We noted a new clinical syndrome with prominent cerebellar symptoms in apartment building residents in Kamisu, Japan. The well that provided drinking water contained diphenylarsinic acid, a degradation product of diphenylcyanoarsine or diphenylchloroarsine, which were developed for use as chemical weapons, inducing severe vomiting and sneezing. Characteristics of diphenylarsinic acid poisoning include brainstem–cerebellar and cerebral symptoms. Mental retardation associated with brain atrophy in magnetic resonance images was evident in some infants. We must be vigilant to prevent or minimize the effects of further diphenylarsinic acid poisoning in Japan or elsewhere. Ann Neurol 2004;56:741–745

Calbindin-D 28k immunoreactivity in the cerebellum of spinocerebellar degeneration

We studied immunoreactivity for calbindin-D 28k (CaBP), an intracellular calcium-binding protein, in the cerebellum of control subjects and of patients with spinocerebellar degeneration (SCD) including sporadic olivopontocerebellar atrophy and familial cortical cerebellar atrophy. In the cerebellum, CaBP immunoreactivity was seen exclusively in the Purkinje cell in both SCD and control groups. However, the number of CaBP-immunoreactive Purkinje cells was significantly reduced in SCD. CaBP immunohistochemistry also disclosed abnormal morphological changes of Purkinje cells, which was not visualized on conventional strains or not clearly demonstrated on immunohistochemistry for neurofilaments. Moreover, reduced CaBP immunoreactivity was observed even in some remaining Purkinje cells of SCD suggesting that loss of CaBP precedes neuronal loss of Purkinje cell. We conclude that CaBP is a useful marker for Purkinje cell degeneration, and that reduced CaBP expression might have some association with the mechanism of the Purkinje cell degeneration in SCD.

Human H5N2 Avian Influenza Infection in Japan and the Factors Associated with High H5N2-Neutralizing Antibody Titer

Background H5N2 avian influenza virus infection of humans has not been reported thus far. The first H5N2 avian influenza infection of poultry in Japan occurred in Ibaraki. Methods The subjects were workers at 35 chicken farms in Ibaraki Prefecture, where the H5N2 virus or antibody was isolated from chickens. None of the subjects exhibited influenza symptoms. The H5N2-neutralizing antibody titers of the first and second paired sera samples were compared. To investigate the possible factors for this increase, the H5N2-neutralizing antibody titer (1:40 or more) was calculated for the second samples. A logistic regression analysis was performed to examine the association of these factors with H5N2-neutralizing antibody positivity. Results We performed Wilcoxon matched-pairs signed-ranked test on data collected from 257 subjects, and determined that the H5N2 antibody titers of the second paired sera samples were significantly higher than those of the first samples (P < 0.001). The H5N2 antibody titers of paired sera of 13 subjects without a history of seasonal influenza vaccination within the previous 12 months increased 4-fold or more. The percentage of antibody positivity was 32% for subjects with a history of seasonal influenza vaccination (28% of all subjects) and 13% for those without a history of the same. The adjusted odds ratio of H5N2-neutralizing antibody positivity was 4.6 (95% confidence interval: 1.6-13.7) for those aged over 40 and 3.1 (95% confidence interval: 1.6-6.1) for those with a history of seasonal influenza vaccination within the previous 12 months. Conclusion The results suggest that this may have been the first avian influenza H5N2 infection of poultry to affect humans. A history of seasonal influenza vaccination might be associated with H5N2-neutralizing antibody positivity.

Cerebral cortical pathology of sporadic olivopontocerebellar atrophy.

We examined the cerebral cortices of six brains from patients with sporadic olivopontocerebellar atrophy (s-OPCA), five control brains including four from patients who had died without neurological disease, and one from a patient with Holmes-type cerebellar cortical atrophy. Distinct laminar astrocytosis of the motor cortices in the fifth layer were demonstrated in 4 of 6 s-OPCA cases and in none of the control cases by immunohistochemistry for glial fibrillary acidic protein. The astrocytosis localized in the primary motor cortex and its distribution pattern were clearly different from those of so-called glial cytoplasmic inclusion. This cortical astrocytosis appears to be characteristic of s-OPCA and may reflect the pathology of the primary motor cortex.

Right ventricular damage due to pulmonary embolism: examination of the number of infiltrating macrophages.

To investigate the pathological changes in the heart induced by pulmonary embolism, 20 autopsy cases of pulmonary embolism and 10 control cases of acute death from traumatic injury were examined. Adding to the routine hematoxylin-eosin (HE) staining, immunostaining with CD68 pan-macrophage marker was performed on the specimens obtained from both right and left ventricular walls. The number of macrophages was counted semi-quantitatively in 100 random high-power fields (HPF). Although typical pathological findings of myocardial infarction was not observed in any of the cases, 16 of the 20 pulmonary embolism cases showed an increase in the number of macrophages, mainly in the right ventricular wall. Four cases showed massive macrophage infiltration in the entire right ventricular wall. It is speculated that ischemia due to pulmonary embolism may be connected to its pathogenesis.

Atypical adenomatous hyperplasia of the lung in autopsy cases

BACKGROUND Atypical adenomatous hyperplasia (AAH) is a possible precursor lesion of adenocarcinoma of the lung, but very few reports of AAH have focused on the autopsy lung. METHODS We intended to clarify the characteristics of AAH in the general population by using 207 autopsy cases, ranging in age from 0 to 90 years old. RESULTS A total of 179 eligible cases (86.5%) and 1265 tissue slides (7.0 per case) was examined independently by two pathologists. One hundred seventy-nine autopsy cases consisted of 125 males and 54 females, whose median ages were 38 (range 0-90) and 31 (range 0-81) years old, respectively. AAH was microscopically found in five of 179 autopsy cases (2.8%). The male/female ratio was 5/0 and age distribution was 52-63 years of age (median 57). One of five cases with AAH harbored esophageal carcinoma, but the others had no present or previous malignant neoplasm. One of five lesions was high grade and the others were low grade. All five cases showed positive immunoreactivity for proSP-C, a type II pneumocytes marker, but not for p53, Ki-67 or CEA. CONCLUSIONS The incidence of AAH was very low in the general autopsy cases, as compared with the previously reported surgically resected lung and senile autopsy cases, and AAH seems to occur after middle age in general.

Hepatic portal venous gas and hyper-dense aortic wall as postmortem computed tomography finding.

Postmortem computed tomography (PMCT) is useful for diagnosis of cause of death not only by emergency physicians but also medical examiners or police surgeons conducting postmortem studies. However, postmortem biological conditions are quite different from those in the living body. Hepatic portal venous gas (HPVG) and a hyperdense aortic wall (HDAW) are often found by PMCT, although no significant autopsy findings are evident in the liver or aorta. In this study we compared the findings of PMCT with those obtained at autopsy, and discussed the cause of these PMCT features. PMCT was conducted in 12 autopsy cases, comprising eight cases of natural death and four of unnatural death. HPVG was seen in five cases and HDAW in seven. In the cases showing HPVG, visceral abdominal injury, bowel distention or acute circulatory dysfunction was found at autopsy. In the cases showing HDAW, atherosclerosis or an increase in blood viscosity due to dehydration or postmortem changes was evident. Although the precise causes of these PMCT findings are not completely clear, the changes evident at autopsy provide some clues.

VENTRICULO‐CORONARY MICRO‐COMMUNICATIONS IN PULMONARY ATRESIA and SEQUENTIAL CHANGES OF CORONARY ARTERIES

In the present paper, numerous micro‐communications between myocardial sinusoids and small branches of coronary arteries are studied which existed in a rudimentary right ventricle of a female neonate with pulmonary atresia and an intact ventricular septum, who was born on the 40th week of gestation. Cardioangiography revealed a large fistulous subepicardial communication. At autopsy, myocardium of the right ventricle appeared spongy with extensive sinusoid slits. In addition to the large communication which was connecting a deeply extending sinusoid of the right ventricle to the main trunk of the anterior descending artery, numerous micro‐communications were found between myocardial sinusoids in the rudimentary right ventricle and intramural small branches of the coronary artery. Furthermore, mor‐phometrical analysis demonstrated that the medias of the intramural arteries in both ventricles of the present case were significantly hypertrophic, as compared with those in the control cases without communications (p<0.05). These facts indicate the significance of hemodynamic factors on the persistence of embryonic sinusoid‐coronary communication.

A Epidemiological Investigation of a Nosocomial Outbreak of Multidrug-Resistant Acinetobacter baumannii in a Critical Care Center in Japan, 2011–2012

In 2011, a multidrug-resistant Acinetobacter baumannii (MDRAB) outbreak occurred at a Japanese critical care center (CCC) in a tertiary care hospital. Multidrug-resistance in Japan is defined as resistance to the antimicrobials amikacin, carbapenem, and fluoroquinolone. We conducted a retrospective epidemiological investigation of this outbreak to identify the risk factors for MDRAB respiratory tract acquisition in this hospital. Cases were defined as hospitalized patients with MDRAB-positive cultures at least 3 days post admission to the CCC between June 1, 2011 and April 20, 2012. Fifteen MDRAB cases were identified, including 3 with infection and 12 with colonization. This case-control study demonstrated that hypoalbuminemia along with carbapenem administration were associated with MDRAB respiratory tract acquisition. Pulsed-field gel electrophoresis analysis and multilocus sequence typing using MDRAB isolates suggested a clonal dissemination of MDRAB strains with sequence type 74 occurred primarily among patients admitted to the CCC. From April 16, 2012, a decreased isolation rate of MDRAB in the hospital occurred after the implementation of the following infection control measures: closing the emergency room, discontinuing admission to the CCC, isolating patients with MDRAB colonization or infection to single room status, and conducting environmental cleaning. No MDRAB cases were detected between March 23 and April 20, 2012.

Pulmonary vasculature in idiopathic dilated cardiomyopathy: a morphometric study.

The pulmonary vascular alterations of seven patients with idiopathic dilated cardiomyopathy (IDC) were morphometri‐cally examined, and the relation between the vascular alterations and morphological status of the hearts was studied. Most patients with IDC showed not only fibrous thickening of small pulmonary veins but also intimal circumferential fibrosis and medial hypertrophy of small pulmonary muscular arteries to various degrees. The histo‐logical features of the pulmonary vessels were compatible with hypertensive vascular changes observed in patients with mitral stenosis. There was a significant correlation between medial hypertrophy of the pulmonary muscular arteries and right ventricular hypertrophy. The pulmonary vascular changes in IDC were always associated with left atrioventricular dilatation, but were only found in patients with prominent hypertrophy of the left ventricles. Medial hypertrophy of the pulmonary muscular arteries was related more to left ventricular hypertrophy than to left ventricular dilatation. These findings suggest that the pulmonary vascular changes in IDC are caused by venous pulmonary hypertension, which may be developed at the late stage when left ventricular hypertrophy predominates.