Seiichi Fukuda

Germinal matrix hemorrhage of venous origin in preterm neonates

The rupture point of germinal matrix hemorrhage in premature neonates was examined by postmortem angiography. Thirteen cases of germinal matrix hemorrhage were injected via artery (four cases), vein (five cases), and both artery and vein simultaneously (four cases). Only material injected via vein leaked into the hemorrhage, which was confirmed by stereomicroscopic and histologic examination. This study suggests that germinal matrix hemorrhage is venous in origin.

Thirty-One Autopsy Cases of Trisomy 18: Clinical Features and Pathological Findings

The clinical features and morphological findings in 31 Japanese infants with trisomy 18 are presented. The majority were small-for-date infants. There was no sex predominance in our series, as opposed to male:female ratios of 1:3 reported in the literature. The average age at death was greater in females than in males. Cardiovascular anomalies were consistently present; ventricular septar defect and patent ductus arteriosus being the most common malformations. Various other internal malformations including the Arnold-Chiari malformation were observed.

Neonatal subdural hematoma secondary to birth injury: clinical analysis of 48 survivors

In order to evaluate the treatment and prognosis of subdural hematoma in neonates, we analyzed 48 survivors in the 3-year period January 1979 to December 1981. Based on the CT findings, the hematomas were grouped into four types according to location: type I, localized around the posterior interhemispheral fissure (25 cases, 52%); type II, extending from the posterior interhemispheral fissure to the hemispheric convexity (5 cases, 10%); type III, extending from the incisura to the posterior fossa (15 cases, 31%); and type IV, subdural hematoma accompanied by intracerebral hemorrhage (3 cases, 7%). Intracranial pressure was measured via the anterior fontanel in 13 cases. In 10 cases of extensive hemorrhage, the pressure exceeded 200 mm H2O. The age of the patients was from 0 to 7 days. There were 36 mature (75%) and 12 premature (25%) infants. The mothers were primiparous in 27 cases (56%). Fetal presentation was cephalic in 38 cases (79%), in 10 of which (21%) suction delivery was performed, and breech in 11. The fundus oculi was examined in 32 cases. Retinal hemorrhage was noted in 12 cases; it did not correlate with the type of hematoma or the intracranial pressure. Operations were performed in 13 cases; 1 of type I, 4 of type II, 5 of type III, and 3 of type IV. Functional prognoses were found to be as follows: type I, normal 15, abnormal 4, undetermined 6; type II, normal 4, abnormal 1; type III, normal 13, abnormal 1, undetermined 1; type IV, normal 1, abnormal 2 cases.

Brief report: incidence of and risk factors for autistic disorder in neonatal intensive care unit survivors.

We investigated prospectively the incidence of autistic disorder (AD) in the neonatal intensive care unit and the risk factors associated with autistic development. The study population included the 5,271 children at St. Marys Hospital and the diagnosis of AD was performed using DSM-III-R criteria. A total of 36 prenatal, perinatal, and postnatal factors were evaluated in the patients with AD, 57 cerebral palsy (CP), and 214 controls. AD was identified in 18 of the 5,271 children and the incidence was 34 per 10,000 (0.34%). This value was more than twice the highest prevalence value previously reported in Japan. Children with AD had a significantly higher history of the meconium aspiration syndrome (p = .0010) than the controls. Autistic patients had different risk factors than CP.

Fatal hypertrophic cardiomyopathy associated with an A8296G mutation in the mitochondrial tRNALys gene

We describe an 8‐day‐old baby girl presenting a fatal infantile form of hypertrophic obstructive cardiomyopathy, associated with an A8296G mutation in the mitochondrial tRNALys gene. She was born from a healthy unrelated couple, and was the first infant of dizygotic twins. Soon after birth, she was noted to have tachypnea and generalized hypotonia. She had high levels of lactate and pyruvate, and was diagnosed as having hypertrophic cardiomyopathy using echocardiography. She died by cardiac failure. Mitochondrial DNA analysis was performed by sequencing after PCR‐subcloning methods, and the percentage of mutation was measured using PCR‐RFLP methods. In various tissues obtained at autopsy, analysis showed a heteroplasmic population of A8296G mutation in the mitochondrial tRNALys gene in all the tissues examined. Maternal inheritance was demonstrated in the family members. Our data demonstrated that an A8296G mutation in the mitochondrial tRNALys gene showed clinical heterogeneity from a milder form previously reported as mitochondrial diabetes mellitus, to a more severe form as hypertrophic obstructive cardiomyopathy, according to the spatial distribution of this mutation. Hum Mutat 15:382, 2000.

Herpes simplex viral infection in human neonates: An immunohistochemical and electron microscopic study

Specimens obtained at autopsy from six neonates with herpes simplex virus (HSV) infections were examined microscopically, electron microscopically, and immunohistochemically. Coagulative necrosis with inclusions was found in the livers and adrenal glands in all cases, as well as in various other organs, including the spleen, bone marrow, lungs, esophagus, tongue, and thymus, in some cases. Distinct hemorrhagic diathesis was found in three cases. No characteristic clinical findings, such as skin rashes or elevated titers of the antibody to HSV, were found, and clinical diagnosis was therefore difficult. In three cases isolation and typing of the causative virus were performed virologically, and type 1 HSV (HSV-1) was identified as the causative virus. Immunohistochemically, the type and distribution of the virus were evaluated in all cases with type-specific antisera to types 1 and 2 (HSV-2) antigens by the peroxidase-antiperoxidase method. In five cases the infections were found to be due to HSV-1 and in only one case to HSV-2. In the placenta in one case of HSV-2 infection, HSV antigen was demonstrated in the chorionic villi. Electron microscopic study confirmed the existence of viral particles in the placenta in that case and, thus, the possibility of a transplacental route of infection.

Nonimmunologic Hydrops Fetalis

Fifty cases of nonimmunologic hydrops fetalis found in Japanese infants are reported. Nonimmunologic hydrops fetalis is associated with various pathological conditions, twin transfusion syndrome including acardiac monsters, fetal heart diseases, congenital cystic adenomatoid malformation, pulmonary sequestration, pulmonary lymphangiectasia, intrauterine infections such as cytomegalovirus infection and neonatal hepatitis, congenital neuroblastoma, Kasabach-Merritt syndrome, cystic hygroma, and chromosomal aberrations. The mechanism of hydrops fetalis found in these conditions is discussed from various viewpoints. Despite a careful examination, no causative conditions were found in 14 cases. The placenta showed a proliferation of Hofbauer cells that were strongly positive for immunoreactive alpha 1-antichymotrypsin and there were other common findings such as edema of terminal villi and fibrin thrombi.

Primary causes of perinatal death. An autopsy study of 1000 cases in Japanese infants.

The primary causes of death in 1000 autopsy cases of perinatal death during the eight years from 1972 through 1979 are discussed. On the basis of the clinical data and gross and microscopic findings, each case was assigned to one of the following categories of primary causes of death: pulmonary hyaline membrane disease, infection, malformation, anoxia, immaturity, maternal causes, other causes, and unaccounted for. Definitions of perinatal infant diseases, essential points of diagnosis, and statistics relating to perinatal infant death are also discussed.

HYPOXIC‐ISCHEMIC BRAIN LESIONS FOUND IN ASPHYXIATING NEONATES

Early hypoxic‐ischemic brain lesions were examined regarding 26 autopsy cases which had severe asphyxia at birth and died within the first week. All cases were divided into three groups according to the birth weight: group A of less than 1,000 grams, group B of 1,001–2,500 grams, and group C of more than 2,501 grams. Neocortical and deep gray matter revealed pyknotic and karyorrhectic neuronal changes; however, in group A, these changes tended to be obscure. The hippocampus was the predictive site of the neuronal changes such as pyknotic neurons in Sommers sector and karyorrhectic neurons in subiculum. In 12 cases, pontosubicular‐type necrosis was found. White matter lesions were relatively characteristic and there was an early appearance of pathological astrocytes such as gemistocytic, Alzheimer‐type 2 and stellate astrocytes, periventricular leukomalacia with or without hemorrhage. The brain stem and cerebellar lesions were also found occasionally revealing neuronal or glial changes. We applied the immunoperoxidase method using antisera to glial fibrillary acidic protein (GFAP) and S‐100 protein for determination of pathological astrocytes. GFAP was a useful marker for pathological astrocytes in the subpial region and in the white matter. S‐100 protein was present in Bergmanns glia and satellite glia as well as pathological astrocytes.

PULMONARY ELASTIC FIBERS IN NORMAL HUMAN DEVELOPMENT AND IN PATHOLOGICAL CONDITIONS

Normal human pulmonary elastic fiber development and development in some pathological conditions were examined using elastic stains by light microscopy, electron microscopy, and immunohistochemistry. In normal development elastic fibers, composed mainly of microfibrils, first appeared around primitive bronchioles at 10 weeks of gestation. As they matured, their appearance became more amorphous, and they extended into the peripheral alveolar walls. Development of elastic fibers was retarded in the hypoplastic lungs of the oligohydramnios syndrome, diaphragmatic hernia, and hydrops fetalis. Elastic development was also retarded in congenital pulmonary lymphangiectasia and in focal areas of lungs with pulmonary dysplasia. Distribution of well-developed elastic fibers was found around the dilated bronchioles and alveoli in cases of congenital cystic adenomatoid malformation and extralobar pulmonary sequestration. Elastic fibers were distributed irregularly and unevenly in the lungs of bronchopulmonary dysplasia and ventilated cases of Wilson Mikity syndrome. In addition, four very immature infants who had progressively deteriorating respiratory function showed an almost total lack of elastic fibers in their alveolar walls.