Marvin S. Platt

Retrospective biochemical screening of fatty acid oxidation disorders in postmortem livers of 418 cases of sudden death in the first year of life

OBJECTIVE Fatty acid oxidation (FAO) disorders are frequently reported as the cause of sudden and unexpected death, but their postmortem recognition remains difficult. We have devised a biochemical protocol in which informative findings in liver tissue are microvesicular steatosis, elevated concentrations of C8-C16 fatty acids, glucose depletion, and low carnitine concentration. STUDY DESIGN We analyzed 27 cases representing five FAO disorders and compared the results with those obtained in a retrospective blinded analysis of 418 cases of sudden infant death (313 SIDS, 45 infections, and 34 accidents and abuse). RESULTS All cases of accidents and abuse correctly tested negative. Among the others, 25 (6%) showed at least two abnormal findings. Of these, 14 closely matched the biochemical profiles seen in specific FAO disorders. These included 2 cases with medium-chain acyl-CoA dehydrogenase deficiency, 4 cases consistent with glutaric acidemia type 2, 4 cases with either very long-chain acylcoenzyme A dehydrogenase deficiency or long-chain 3-hydroxy-acyl-coenzyme A dehydrogenase deficiency, and 4 cases predicted to be affected with carnitine uptake defect. CONCLUSION The results of this study support the view that approximately 5% of all cases of sudden infant death are likely caused by an FAO disorder.

Histologic Analysis of Placental Tissue in First Trimester Abortions

The value of histologic evaluation in the analysis of material from first trimester abortions is not completely defined. We prospectively analyzed placenta and decidua from 75 first trimester, spontaneous abortions to ascertain if morphologic features were predictive of karyotype. The histologic features analyzed included hydropic villus change, villus fibrosis, villus scalloping with trophoblastic invaginations, atypical stromal cells, aggregates of lymphocytes in placenta or decidua, and acute inflammation of placenta or decidua. Normal karyotypes were observed in 44 cases and abnormal karyotypes were demonstrated in 31. The presence of villus scalloping with trophoblastic invagination was significantly associated with abnormal karyotypes, particularly triploidy, and the demonstration of acute inflammation was seen significantly more often in cases with normal karyotypes. We conclude that histology can provide only a suggestion as to the likelihood of an abnormal karyotype; the findings are not specific enough to obviate the need for karyotyping in the individual case.

Neonatal Hemophilus vaginalis (Corynebacterium vaginalis) Infection

Two cases of neonatal Hemophilus vagi nalis (Corynebacterium vaginalis) infection are presented. In addition, eight recent neonatal-maternal cases have been sum marized. The data obtained from these cases strongly suggest that the organism is a matemal, fetal and neonatal pathogen. Measures which promote successful isola tion and identification are outlined.

Significance of Placental Findings in Early-Onset Group B Streptococcal Neonatal Sepsis

Assessment of placental pathology and its relationship to historical data, initial laboratory parameters, and outcome was undertaken in 22 cases of early-onset group B streptococcal sepsis of the neonate. Fourteen (64%) of the placentas demonstrated chorioamnionitis, six (27%) funisitis, and in nine (41%) gram stain demonstrated organisms within the membranes. Focal villous edema was observed in five (23%) cases and diffuse villous edema in four (18%). No placenta demonstrated chorangiosis. Placental inflammation was significantly (p < 0.05) associated with prematurity, prolonged rupture of membranes, and onset of symptoms at less than 3 hours of age. No placental change was significantly associated with outcome or with neutropenia, which was the only parameter assessed that appeared to have prognostic value.

Evaluation of a latex particle agglutination kit in pneumococcal disease

Latex particle agglutination for Streptococcus pneumoniae was evaluated in 76 patients. Fifteen of these patients had invasive disease due to S. pneumoniae including 12 with meningitis, 2 with occult bacteremia and 1 with suppurative arthritis. Five of the patients with meningitis also had bacteremia. Pneumococcal antigen was detected in the cerebrospinal fluid of 9 of the 12 patients with meningitis (sensitivity 75%). However, antigen was detected in the serum of only two of the six patients with bacteremia (sensitivity 33%) and was detected in the urine of none of five patients with bacteremia (sensitivity 0%). Consequently latex particle agglutination appears to be useful when cerebrospinal fluid is examined in patients with pneumococcal meningitis but does not appear to be sufficiently sensitive to warrant its use with serum or urine in patients with invasive disease due to S. pneumoniae. The specificity of the system used here appeared satisfactory, since pneumococcal antigen was not detected in any of the body fluids from the 61 patients without evidence of invasive pneumococcal disease (specificity 100%).

Macrophage migration inhibitory factor in thymus.

Summary and Conclusion Saline extracts of the thymus of immunologically experienced animals (pig, calf, and guinea pig) have been shown by a new and very sensitive method to contain a macrophage migration inhibitory factor whose properties are similar to that of MIF obtained from the supernatant of transforming lymphocytes in vitro. This MIF activity could not be demonstrated in guinea pig or calf thymus until these animals had been immunologically stimulated by either soluble antigen or whole bacteria, however.

Arnold-Chiari Malformation: Report of a Case with Contamination of Ventricular and Subarachnoid Spaces by Amniotic Sac Contents

An infant with the Arnold-Chiari malformation had a lumbosacral amniotic-central nervous system fistula that allowed massive amounts of squamous cells and lanugo hair to enter the ventricular and subarachnoid spaces causing blockage, gliosis, and fibrosis. This rare complication can be diagnosed by cytologic examination of cerebrospinal fluid and should be considered in the prognosis of Arnold-Chiari malformation and selection of cases for treatment.

Occult hepatic sinusoid tumor of infancy simulating neuroblastoma

Two infants with hepatosplenomegaly and an occult tumor of hepatic sinusoids are reported. Although secretion of biogenic amines of neuroblastoma was not elevated, infrequent neurosecretory granules were observed by electron microscopy in the cytoplasmic processes of the tumor cells. The infants responded to vincristine and prednisone therapy and are tumor free 8 and 2 years later, respectively. The clinical, radiographic, biochemical, and microscopic findings of these cases are presented. The distinction from other infantile hepatic sinusoid small round cell tumors is based on the light and electron microscopic findings. This neuroepithelial tumor is either an unusual form of neuroblastoma or a neoplasm of APUD cell origin. If chemotherapy is utilized, it should be selective and limited.