Size-dependent grain-growth kinetics observed in nanocrystalline Fe.

Measurements of grain growth in nanocrystalline Fe reveal a linear dependence of the grain size on annealing time, contradicting studies in coarser-grained materials, which find a parabolic (or power-law) dependence. When the grain size exceeds approximately 150 nm, a smooth transition from linear to nonlinear growth kinetics occurs, suggesting that the rate-controlling mechanism for grain growth depends on the grain size. The linear-stage growth rate agrees quantitatively with a model in which boundary migration is controlled by the redistribution of excess volume localized in the boundary cores.

Linkage of familial Wilms' tumor predisposition to chromosome 19 and a two-locus model for the etiology of familial tumors.

Familial predisposition to Wilms' tumor (WT), a childhood kidney tumor, is inherited as an autosomal dominant trait. For most WT families studied, the 11p13 gene WT1 and genomic regions implicated in tumorigenesis in a subset of tumors can be ruled out as the site of the familial predisposition gene. Following a genome-wide genetic linkage scan, we have obtained strong evidence (log of the odds ratio = 4.0) in five families for an inherited WT predisposition gene (FWT2) at 19q13.3-q13.4. In addition, we observed loss of heterozygosity at 19q in tumors from individuals from two families in which 19q can be ruled out as the site of the inherited predisposing mutation. From these data, we hypothesize that alterations at two distinct loci are critical rate-limiting steps in the etiology of familial WTs.

Adrenal calcification: an incidental finding or not?

When the adrenal gland is calcified but no mass is found, the calcification is usually assumed to be due to prior adrenal hemorrhage. We report a case of adrenal calcification without a noncalcified mass in a child who subsequently presented with neuroblastoma elsewhere. This case has implications for the investigation of children with adrenal calcification.

Evidence for genetic heterogeneity in familial Wilms' tumor.

Wilms' tumor (WT), a childhood kidney cancer, occurs both sporadically and, less frequently, in a familial context. Genetic linkage studies of several large WT families have excluded the one cloned WT gene, WT1, as the locus responsible for familial predisposition. These data demonstrate the existence of a familial predisposition gene distinct from WT1 and, more broadly, imply that the genetic etiology of WT is heterogenous. However, it has been unknown whether the predisposition observed in large WT families is also heterogenous or perhaps is due to mutations at a single locus. Recently, examination of a large French-Canadian WT family has demonstrated genetic linkage to 17q12-q21. We report here the results from a genetic linkage study of six WT pedigrees. Analyses of genotype data from eight loci within the 17q12-q21 region in these families resulted in cumulative lod scores of <-4.0 through the region, thereby excluding linkage. The ability to rule out the 17q region as the site of a predisposition gene in several of these pedigrees individually demonstrates the existence of more than one gene that predisposes to WT in large pedigrees and again emphasizes that the etiology of WT is genetically heterogenous.

Cytosine arabinoside and mitoxantrone induction chemotherapy followed by bone marrow transplantation or chemotherapy for relapsed or refractory pediatric acute myeloid leukemia.

The purpose of this study was to determine the induction rate, duration of response and toxicity of cytosine arabinoside (1.0 gm/m2 i.v. over 2 h q 12 h x 8 doses days 1 through 4) and mitoxantrone (12 mg/m2 over 1 h daily x 4 doses days 3 through 6) in pediatric patients with acute myeloid leukemia (AML). Patients achieving a complete remission received either bone marrow transplantation or further chemotherapy. Twenty-seven of 37 evaluable patients (73% (95% confidence interval 59-87%)) achieved a complete remission. For all responding patients, the projected median time to relapse is 12 months. The projected 1 and 2 year disease-free survival is 47% (28-66) and 41% (21-61) with a range of follow-up of 0 to 48+ months. The major toxicity was bone marrow suppression and infection. This therapy is very active in pediatric AML and has acceptable toxicity. Some patients treated achieve prolonged survival.

Cytosine arabinoside and mitoxantrone treatment of relapsed or refractory childhood leukemia: initial response and relationship to multidrug resistance gene 1.

The objective of this study was to determine the response rate and toxicity of high-dose cytosine arabinoside (AC) and mitoxantrone (M) in relapsed or refractory childhood acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) and to correlate response with the expression of the multidrug resistance gene 1 (mdr1). Twenty-nine patients were treated with AC 1.0 g/m2 infused over 2 h every 12 h for eight doses (days 1-4) and M 12 mg/m2 infused over 1 h (days 3-6). Mdr1 expression was determined by a polymerase chain reaction (pcr) assay. Ten of 15 patients (67%) with AML obtained a complete remission (CR) of 3 to 30+ months duration. Eight of 14 (57%) ALL patients obtained a CR of 1 to 23+ months duration. The major toxicities were hematopoietic and infectious. Seventy-nine per cent of patients developed a documented infection during induction. Mdr1 did not correlate with a lower induction rate. This AC/M regimen is active in childhood AML and ALL.

Fusarium meningoencephalitis in a child with acute leukemia.

A 15-year-old boy with acute lymphoblastic leukemia (ALL) developed disseminated fusarium infection with meningoencephalitis following a contaminated skin wound. With antifungal therapy, the cutaneous lesions cleared but central nervous system (CNS) infection persisted causing a fibrosing meningitis and a brain granuloma. Fusaria are soil saprophytes that are more commonly associated with superficial eye and skin lesions, but may also cause severe systemic infections with CNS involvement in immuno-compromised patients. The organism may be confused with Aspergillus in tissue sections, and can only be diagnosed by culture.

Methemoglobinemia due to ingestion of N,N-dimethyl-p-toluidine, a component used in the fabrication of artificial fingernails.

An acute cyanotic episode due to methemoglobinemia occurred in a 16-month old girl following the ingestion of N,N-dimethyl-p-toluidine, a commercially available component used in the production of artificial fingernails. The amount of the parent compound ingested was about 6 mg/kg of body weight. Administration of methylene blue was effective in the reversal of the methemoglobinemia. In vitro studies suggest that the activity of the compound was probably due to its biochemical transformation to the toxic metabolite p-methylphenylhydroxylamine. We expand the list of aromatic amino or nitro compounds and their derivatives capable of producing methemoglobinemia and call attention to the hazard of their ingestion.

Tumors of skeletal muscle.

The most common tumors arising in muscle are soft tissue sarcomas, fibromatoses, and hemangiomas. Rhabdomyosarcoma is primarily a tumor of childhood and adolescence and arises most commonly in extramuscular sites. Most intramuscular rhabdomyosarcomas are alveolar. Increased diagnostic accuracy and the recognition of malignant fibrous histiocytoma have changed understanding of adult, intramuscular, pleomorphic rhabdomyosarcoma. Immunohistochemistry is playing an increasingly important role in the diagnosis of rhabdomyosarcoma, and the correlation between the histologic features and clinical behavior of rhabdomyosarcoma is under investigation. Because of their diversity and overlapping histologic features, muscle tumors are a challenge for the pathologist and require intensive study by current techniques.

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.

Relationship of iron status to urinary norepinephrine excretion in children 7-12 years of age.

In a group of 7- to 12-year-old children without manifest clinical iron deficiency, urinary excretion of free norepinephrine was found to have substantial positive correlation with measure of total iron-binding capacity and negative correlation with serum ferritin. Results support earlier reports of an inverse contingency between iron status and urinary norepinephrine level as observed with severe iron lack, findings consistent with speculation that monoamine oxidase activity may be modified by iron availability.