Host defense against systemic infection with Streptococcus pneumoniae is impaired in E-, P-, and E-/P-selectin-deficient mice.

Endothelial selectins mediate rolling of leukocytes on endothelium, a crucial step for leukocyte firm adhesion and emigration into sites of tissue injury and infection. To characterize the role of the endothelial selectins during bacterial sepsis in vivo, Streptococcus pneumoniae (1-10 x 10(6) colony-forming units) was inoculated intraperitoneally into wild-type mice and mice with E-, P-, or E-/P-selectin deficiencies. Mice were followed 10 d for morbidity, survival, clearance of bacteremia, and leukocyte migration to the peritoneal cavity and organs 48 h after infection. All selectin-deficient mice showed a more pronounced morbidity, a significantly higher mortality associated with persistent bacteremia, and a higher bacterial load when compared with wild-type mice. These differences were most remarkable in the E-selectin-deficient mice, which showed the highest rate of mortality and bacteremia (P

Incessant ventricular tachycardia in infants: myocardial hamartomas and surgical cure.

Infants with incessant ventricular tachycardia (occurring greater than 10% of the day) have generally been described in pathologic studies. This report describes 21 patients with incessant ventricular tachycardia present greater than 90% of the day and night; the age at diagnosis ranged from birth to 30 months (mean 10.5 months). The most common clinical presentation was cardiac arrest (11 patients, in 5 after digitalis for presumed supraventricular tachycardia); another 6 patients had congestive heart failure and 4 were asymptomatic. Three patients had coexisting Wolff-Parkinson-White syndrome. The rate of incessant ventricular tachycardia ranged from 167 to 440 (mean 260 beats/min) and the QRS duration from 0.06 to 0.11 second. The most common electrocardiographic (ECG) pattern (10 of 21) was right bundle branch block with left axis deviation, but other right and left bundle branch block patterns were observed. Conventional and investigational antiarrhythmic agents (nine patients received amiodarone) failed to eliminate incessant ventricular tachycardia in all. Electrophysiologic studies localized incessant ventricular tachycardia to the left ventricle in 17 (to the apex in 2, the free wall in 9 and the septum in 6) and to the right ventricular septum in 4. No structural abnormalities were found on the echocardiogram or angiocardiogram. All 21 patients had surgery at an age of 3.5 to 31 months (mean 16). In 15 a tumor was found: 13 myocardial hamartomas (9 discrete, 4 diffuse throughout both ventricles) and 2 rhabdomyomas (1 multiple). Myocarditis was found in one patient (the oldest). In four, only myocardial fibrosis was found; results of one biopsy were normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Immature teratomas in children: pathologic considerations: a report from the combined Pediatric Oncology Group/Children's Cancer Group.

Pediatric germ cell tumors (n = 135) with a major component of immature teratoma (IT) registered on Pediatric Oncology Group/Children's Cancer Group treatment protocols from 1990 to 1995 were reviewed. Sixty cases were pure IT with no malignant component and 75 were mixed tumors with a major component of IT. Foci of yolk sac tumor (YST) were present in all 75 mixed tumors; additional malignant components were present in 15. The IT component was as follows: 47% grade 3, 29% grade 2, 24% grade 1. There were no significant correlations between tumor grade and patient age by specific subsets or overall (all p > 0.10). Significant correlations were detected between stage and the presence of foci of YST (p = 0.0145) and grade and the presence of foci of YST (p < 0.001). Serum alpha-fetoprotein concentrations were elevated at diagnosis in 96% of ovarian tumors with foci of YST and were mildly elevated (< 60 ng/dL) in only 16% of tumors without YST. Overall 2- to 6-year survival rate was 96% and was related to the presence of YST. Central pathologic review revealed aspects of morphologic diagnosis that were most frequently misinterpreted by contributing pathologists. These included the classification of differentiating tissues as immature and the failure to recognize two well-differentiated patterns of YST (the hepatoid pattern resembling fetal liver and the well-differentiated glandular pattern resembling fetal lung or intestine). Such foci were often overlooked. The authors conclude that the presence of microscopic foci of YST, rather than the grade of IT, per se, is the only valid predictor of recurrence in pediatric IT at any site.

Thoracoabdominal ectopia cordis with mosaic Turner's syndrome: Report of a case.

A child was treated for thoracoabdominal ectopia cordis and an associated chromosomal defect. Contrary to most cases in which death is due to the externally situated heart and abdominal viscera, this patient died from congenital heart disease.

Atrioventricular valve anular diameter: two-dimensional echocardiographic-autopsy correlation.

To study the accuracy of 2-dimensional echocardiography (2-D echo) in estimating mitral and tricuspid anular diameter, 2-D echo estimates were compared with autopsy measurements of anular diameter in 21 children studied by echo within 30 days of death. The mitral anulus was measured from the left parasternal long axis view and the apical or subcostal 4-chamber image and the tricuspid anulus from the 4-chamber view. Comparable measurements were made from the autopsy specimen with calipers. The correlation coefficient for echocardiographic vs autopsy measurements was 0.79 (standard error of the estimate 2.8 mm) (mitral long axis r = 0.76, mitral 4-chamber r = 0.85, tricuspid 4-chamber r = 0.76). Echo measurements exceeded the corresponding autopsy measurements by an average of 17%; this was at least partially attributed to shrinkage of the specimen during fixation. Thus, 2-D echo may be used to provide a reasonable estimate of mitral and tricuspid anular diameter.

Deletion of chromosome 22q11 and pseudohypoparathyroidism.

A newborn boy with complex congenital heart disease, unilateral renal agenesis, and hypocalcemia was found to have a submicroscopic deletion of 22q11.2 (DiGeorge anomaly). In evaluating the pathogenesis of the hypocalcemia, repeatedly elevated or normal levels of parathyroid hormone were found, consistent with a diagnosis of pseudohypoparathyroidism. Pseudohypoparathyroidism can be due to mutation of a GTP binding protein (Gs-alpha protein) located on chromosome 20. Since there is another G protein locus (Gz alpha) adjacent to the DiGeorge critical region of chromosome 22, we hypothesized that a more extensive deletion may lead to pseudohypoparathyroidism. Fluorescence in situ hybridization was performed using a probe containing the Gz alpha gene, but no deletion was detected. This patient emphasizes the importance of determining the pathogenesis of the hypocalcemia in cases of DiGeorge anomaly.

Malignant histiocytosis in childhood: morphologic considerations.

Eight cases diagnosed over a ten-year period as malignant histiocytosis (MH; histiocytic medullary reticulosis) were reviewed to clarify diagnostic criteria for the childhood disease and to identify sources of diagnostic confusion. Five of the eight cases met the authors' criteria for diagnosis; i.e., they were characterized by loose mixed infiltrates composed of three cell types--well-differentiated histiocytes, prohistiocytes, and malignant histiocytes--and they had no leukemic phase. Three cases did not share these features and were reclassified. The liver was found to be the organ most useful in premortem diagnosis, and immunoperoxidase staining for immunoglobulins and lysozyme was also helpful. The clinical and morphologic features of the five cases confirm the authors' view that diagnoses of MH should be limited to cases in which there is a loose pleomorphic population of all three types of histiocytes and that cases with monomorphous populations of aggregated malignant cells should be classified as lymphomas.

Nasopharyngeal carcinoma in children--a retrospective review and demonstration of Epstein-Barr viral genomes in tumor cell cytoplasm: a report of the Pediatric Oncology Group.

Twenty-seven nasopharyngeal carcinomas were entered in the Pediatric Oncology Group Rare Tumor Registry from 1973 to 1988 (15 males, 12 females; 10 white, 15 black, two unknown; aged 8 to 17 years). Eight tumors were non-keratinizing carcinomas (World Health Organization 2) and 19 were undifferentiated (World Health Organization 3). The overall 3-year survival rate was 70% (SE 11%). Nine children developed distant metastases and two were salvaged. We found that localized tumor (P = .02) and black race (P = .05) were associated with a better outcome. In situ hybridization using a biotinylated probe demonstrated Epstein-Barr virus DNA in the cytoplasm of the neoplastic epithelial cells in nine of 11 tumors examined, firmly establishing the presence of Epstein-Barr virus within the malignant cells of nasopharyngeal carcinomas of both World Health Organization 2 and World Health Organization 3 histology, rather than in the surrounding lymphocytes.

Germ cell tumors.

Germ cell tumors in children are different from those in adults and often differ from each other in the site of the tumor and the age of the child. The appropriate gross examination and processing of these tumors by pathologists are described, and differences according to site and/or age are highlighted. Useful special studies such as immunohistochemistry and cytogenetics are identified, and the appropriate methods for processing material for these studies are discussed. Handling of small biopsy specimens or fine-needle aspirates is also addressed. Staging of germ cell tumors by site according to Pediatric Oncology Group and Children's Cancer Study Group treatment protocols and the most recent adaptation of grading of immature teratomas are outlined.

Fat overload syndrome. An autopsy study with evaluation of the coagulopathy.

Fat overload syndrome is a rare complication of intravenous fat emulsion therapy. It is characterized by sudden elevation of the serum triglyceride level, fever, hepatosplenomegaly, coagulopathy, and variable end-organ dysfunction. The illness is generally discrete, and symptoms regress as the lipemia clears. The transient nature of the syndrome has allowed only speculation as to its pathogenesis. The authors report an autopsy study of a child who died during an acute episode of fat overload and document the causative role of fat sludging in the associated end-organ failure. In addition, they offer evidence that the coagulopathy, previously an enigma, results from primary fibrinolysis, possibly caused by release of tissue plasminogen activators from the damaged endothelial cells.

Graft-versus-host disease in the central nervous system. A real entity?

Graft-versus-host disease (GVHD) classically involves the skin, intestines, liver, esophagus, and tongue. clinically apparent disease involving the heart, lungs, kidneys, and central nervous system (CNS) is frequently secondary to other complicating factors. This report describes a case of an infant with severe combined immune deficiency (SCID) who developed unusual manifestations of GVHD following a bone marrow transplant (BMT). These were complete heart block and respiratory insufficiency in the absence of significant pulmonary disease. He lived 133 days post-transplantation. At autopsy, the brain showed focal lymphohistiocytic aggregates which may represent a hitherto unreported lesion of GVHD.

Infant cardiac fibroma with clonal t(1;9)(q32;q22) and review of benign fibrous tissue cytogenetics.

Cardiac fibromas are rare lesions which occur more frequently in infants and children than in the adult population. These tumors are nonmalignant proliferations of connective tissue most often found in the left ventricular myocardium or septal myocardium. No cytogenetic studies of cardiac fibromas have been reported. We report a case of an infant with a subepicardial tumor in whom the cytogenetic analysis showed a clonal reciprocal translocation, 46,XY,t(1;9)(q32;q22),inv(9)(p11q12)c. We review the literature regarding cardiac fibromas and briefly discuss the cytogenetics of benign fibrous neoplasias.

Renal function following cardiac arrest and resuscitation in the canine.

Organ malfunction often occurs following cardiac arrest and resuscitation. Renal function, inulin clearance (Cln), was examined in 27 dogs before and after (days 2, 4, and 6) cardiac arrest and resuscitation. Group A (n = 7) had no ventricular fibrillation (VF), but cardiopulmonary support was applied for 20 min, and three transthoracic countershocks were delivered. In groups B (n = 7), C (n = 7), and D (n = 6) VF was induced for 2.5, 5.0, and 7.5 min, respectively, followed by cardiopulmonary support for 20, 20, and 15 min, respectively. When necessary, epinephrine and sodium bicarbonate were given during resuscitation. Countershock was applied for defibrillation. Kidneys were examined histologically in groups C and D. Following cardiac arrest, Cln was significantly less in the arrested groups compared to the nonarrested group. Within group C, which received the most epinephrine, Cln correlated negatively with epinephrine administration, and with the energy applied for defibrillation. Histologically, group C showed the highest incidence of cortical tubular cytoplasmic vacuolization, regeneration, inflammation, and tubular casts. Groups C and D showed outer medullary tubular cytoplasmic vacuolization, renal vascular changes, and calcification. In conclusion, cardiac arrest and resuscitation may precipitate acute renal hypofunction as well as reversible and irreversible morphological changes in normal functioning canine kidneys. The confounding effect of pre-existing renal disease remains to be examined experimentally.

Mesangial IgG in childhood minimal change disease: clinical relevance.

The clinical courses of five children with the nephrotic syndrome and renal biopsies diagnosed as minimal change disease (MCD) by light microscopy but with mesangial immune deposits of IgG (> or = 2+) and no dominant or codominant IgA were reviewed retrospectively to determine if the presence of significant mesangial deposits of IgG has prognostic implications and to evaluate the treatment these patients received. All five of the children were steroid dependent or resistant initially, and four received cyclosporine or cytotoxic agents later. After a mean follow-up period of 2.9 years for four and 20 years for one, all are in remission. All have normal renal function with no hypertension. These results suggest that the deposition of IgG in the mesangium of biopsies from patients with MCD by light microscopy may predict a more difficult course initially and may require more aggressive treatment to achieve permanent remission.

Diagnostic and prognostic significance of glomerular epithelial cell vacuolization and podocyte effacement in children with minimal lesion nephrotic syndrome and focal segmental glomerulosclerosis: an ultrastructural study.

Children with minimal lesion nephrotic syndrome (MLNS) may later develop focal segmental glomerulosclerosis (FSGS). It has been suggested that a low percentage of epithelial podocyte effacement (EPE) and a high degree of epithelial cell vacuolization (ECV) in nonsclerotic glomeruli presage FSGS, and that extensive epithelial cell vacuolization in biopsies clearly showing FSGS predicts a poor clinical outcome. To investigate these contentions, we examined by electron microscopy three glomeruli from each of the first biopsies of 30 patients. Ten patients (group 1) had MLNS, 10 (group 2) had FSGS, and 10 (group 3) had MLNS which progressed to FSGS. Clinical data was obtained by retrospective review of medical records. The percent of epithelial podocyte effacement was calculated by computerized linear tracing and epithelial cell vacuolization was scored semiquantitatively from 0-3. (formula; see text) The percent podocyte effacement in each group was the same and does not distinguish MLNS from FSGS. Group 2 had more extensive epithelial cell vacuolization than group 1 (p less than 0.04) and the same as group 3 (p = 0.16). The combined ECV score for groups 2 and 3, however, was significantly greater than for group 1 (p less than 0.025) suggesting that epithelial cell vacuolization may indeed be a marker of FSGS. The extent of epithelial cell vacuolization did not correlate with creatinine clearance at latest follow-up, and thus does not predict clinical outcome.

Lymphocyte autofluorescence: a screening procedure for neurodegenerative diseases.

We examined the buffy coats from 12 consecutive patients with neurodegenerative diseases to determine the value of autofluorescence study by fluorescence microscopy in parallel with electron microscopy, as a rapid and inexpensive screening procedure for lymphocyte inclusions characteristic of neuronal ceroidlipofuscinoses. Four patients (3 with neuronal ceroidlipofuscinoses and 1 with Hallervorden-Spatz syndrome) had discrete, yellow-orange, 1-2 microns autofluorescent granules in the cytoplasm of some lymphocytes. These granules corresponded to characteristic inclusions of neuronal ceroidlipofuscinoses demonstrated by electron microscopy. Five patients (4 undiagnosed or nonspecific disease, and 1 with Leber congenital amaurosis) had hazy green cytoplasmic autofluorescence which correlated with parallel tubular arrays in lymphocytes. The 3 patients with no autofluorescence had no ultrastructural lymphocytic inclusions. We conclude that buffy coat autofluorescence is a rapid and inexpensive method of identifying specimens that require electron microscopic confirmation, and the absence of autofluorescence of lymphocytes in a buffy coat specimen eliminates the necessity for electron microscopic examination. However, characteristic ultrastructural inclusions associated with neurodegenerative diseases may occur in other tissues, such as skin and conjunctiva.

Yolk sac tumor identified at autopsy after surgical excision of immature sacrococcygeal teratoma.

Although the predictive value of immature elements in sacrococcygeal teratomas in unclear, there are reports of malignant recurrence after surgical resection of immature sacrococcygeal teratomas. The recurrent tumors are presumed to arise from small residual malignant foci not identified at the time of surgical resection. In this report a premature female infant was delivered at 29 week's gestation with a large sacrococcygeal teratoma. The tumor weighed 1,350 g. It was largely cystic with a focal nodular and variegated appearance. Histologically, the tumor was a grade 1 immature teratoma with a predominance of neuroglial elements. No malignant elements were identified in any of 26 sections examined. The infant died intraoperatively of cardiovascular complications related to the large vascular supply of the tumor but had a grossly complete resection of tumor. At autopsy, a small microscopic focus of yolk sac tumor was identified adjacent to the sacrum anteriorly. Had the infant survived, this focus might well have been a source for malignant recurrence.

Small bowel obstruction as a complication of Kawasaki disease.

A case of small bowel obstruction in an 8-month-old infant with Kawasaki disease is described. At laparotomy a discrete area of jejunal stricture with adhesions was noted. Microscopic examination revealed evidence of small artery thrombosis. Kawasaki disease results in a diffuse vasculitis, which may produce significant abnormalities in multiple organ systems. Serious abdominal complications can occur and should be considered when gastrointestinal symptoms develop in a patient with Kawasaki disease.