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T J Pysher

Publications and source records attributed to T J Pysher.

At least 19 recordsLinked to original sources
PubMed2000

Therapy associated changes in childhood tumors.

Contemporary treatment regimens for the common solid tumors of childhood have led to increased numbers of post-treatment pathologic specimens from survivors. Current therapeutic strategies for childhood cancers in North America require an accurate pathologic diagnosis and stratify patients based on combinations of clinical, biological, and pathologic features. In several tumor systems, the pathologic response to therapy also modifies the treatment regimen. Accurate pathologic interpretation of such specimens is critical in providing useful prognostic information for therapeutic decisions. Standardized handling of post-therapy pathologic specimens, appropriate use of molecular and genetic studies, consideration of the differential diagnoses, and assessment of the potential biologic significance of therapy-induced pathologic changes are, therefore, critical for patient management and determination of treatment protocols.

Adolescent↗
PubMed1999

Characterization of the baboon responses to Shiga-like toxin: descriptive study of a new primate model of toxic responses to Stx-1.

The baboon response to intravenous infusion of Shiga toxin 1 (Stx-1) varied from acute renal failure, proteinuria, hyperkalemia, and melena with minimal perturbation of host inflammatory and hemostatic systems (high-dose group, 2.0 microg/kg; n = 5) to renal failure with hematuria, proteinuria, thrombocytopenia, schistocytosis, anemia, and melena (low-dose group, 0.05 to 0.2 microg/kg; n = 8). Both groups exhibited renal shutdown and died in 57 hours or less. Both groups produced urine that was positive for tumor necrosis factor and interleukin-6 although neither of these cytokines was detectable (</=5 ng/ml) in the general circulation. Light and electron microscopy showed organelle disintegration and necrosis of the renal proximal tubular epithelium and of the intestinal mucosal epithelium at the tips of the microvilli, both of which were previously shown to bear Gb3 receptors. The renal distal tubular epithelium was spared. The renal proximal tubular epithelial changes were accompanied by swelling of visceral epithelial cells (podocytes) and by swelling and detachment of endothelial cells of the glomerular capillaries. In addition, all of the animals receiving low-dose Stx-1 showed microvascular fibrin deposition and thrombosis in renal glomerular and peritubular capillaries in association with a fall in hematocrit and platelet count and a rise in schistocyte count. The gastrointestinal villous tip lesions were accompanied by varying degrees of mucosal and submucosal congestion, hemorrhage, or necrosis. Electron microscopic images of cerebral cortex and cerebellum showed diffuse unraveling of myelin sheaths with occasional disintegration of neuronal cell bodies. In contrast to the gastrointestinal mucosal and renal proximal tubular epithelium, the Gb3 receptor glycolipid of the renal glomerular and neuronal tissues as determined using toxin overlay thin-layer chromatography plates was below the limit of detection (<13 pM/g wet tissue). We conclude that, depending on the status of the host and amount of toxin infused, Stx-1 can produce a variety of responses ranging from damage to cells carrying the Gb3 receptor (renal proximal tubular epithelial cells and gastrointestinal mucosa) to damage to renal glomerular tissues with microvascular thrombosis as a result of the host's inflammatory response localized to the kidney. We conclude that this thrombotic coagulopathy arises from local changes in the kidney because the appearance of host inflammatory mediators was limited to the urine. This suggests that the initial host response is localized in the kidney, and that the systemic thrombocytopenia, anemia, and schistocytosis may arise secondarily.

Animals↗
PubMed1998

ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma.

Congenital mesoblastic nephroma (CMN) is an infantile spindle cell tumor of the kidney that is subdivided into "classical" and "cellular" forms based on the degree of cellularity and mitotic activity. The histogenesis of CMN remains obscure, but relationships to other pediatric renal neoplasms have been proposed. However, cellular CMN is virtually identical histologically to congenital fibrosarcoma (CFS), a malignant tumor of fibroblasts in children of the same age group. Moreover, cytogenetic studies have reported common trisomies in CFS and cellular CMN, particularly of chromosome 11. We show here that t(12;15)(p13;q25)-associated ETV6-NTRK3 gene fusions described in CFS are also present in cellular CMN. ETV6-NTRK3 chimeric transcripts were detected in 8 of 9 cellular CMNs and 2 of 2 mixed CMNs. In contrast, all of the four classical CMNs tested were negative, as were cases of Wilms' tumor and clear cell sarcoma of the kidney. Moreover, we found trisomy 11 only in cellular or mixed CMNs with the ETV6-NTRK3 gene fusion. Our studies indicate that classical and cellular CMN have different genetic features and support the concept that cellular CMN is histogenetically related to CFS. They also provide insight into potential mechanisms involved in the transformation of the classical into the cellular form of CMN.

Child, Preschool↗
PubMed1998

Pulmonary vascular resistance of children treated with nitrogen during early infancy.

BACKGROUND: We have empirically used supplemental nitrogen in newborns with a functional single ventricle and ductal-dependent systemic perfusion to prevent pulmonary vasodilation and deliver a greater proportion of flow to the systemic circulation. Thus, we reviewed patient outcome to determine whether adverse pulmonary vascular effects may be associated with this therapy. METHODS: From December 1991 to December 1995, the fraction of inspired oxygen was adjusted, with supplemental nitrogen if necessary, to maintain an oxygen saturation near 75% in 20 newborns awaiting heart transplantation. Medical records were reviewed to evaluate (1) the duration of nitrogen therapy, (2) pulmonary vascular histology, (3) postoperative pulmonary hemodynamics, and (4) survival. RESULTS: Thirteen patients underwent heart transplantation, 4 patients died without surgical intervention, and 3 patients underwent late aortic reconstruction. Supplemental nitrogen was used without exceeding a fraction of inspired oxygen of 0.21 for 38 +/- 6 days. One patient had evidence of changes of potentially irreversible pulmonary vascular disease. Pulmonary vascular resistance was not increased long-term in surviving patients. CONCLUSIONS: Supplemental nitrogen can be used to maintain a systemic oxygen saturation near 75% for an extended period in newborns with ductal-dependent systemic perfusion with no long-term adverse effect on pulmonary vascular resistance.

Administration, Inhalation↗
PubMed1997

Xq28-linked noncompaction of the left ventricular myocardium: prenatal diagnosis and pathologic analysis of affected individuals.

Isolated noncompaction of the left ventricular myocardium (INVM) is characterized by the presence of numerous prominent trabeculations and deep intertrabecular recesses within the left ventricle, sometimes also affecting the right ventricle and interventricular septum. Familial occurrence of this disorder was described previously. We present a family in which 6 affected individuals demonstrated X-linked recessive inheritance of this trait. Affected relatives presented postnatally with left ventricular failure and arrhythmias, associated with the pathognomonic echocardiographic findings of INVM. The usual findings of Barth syndrome (neutropenia, growth retardation, elevated urinary organic acids, low carnitine levels, and mitochondrial abnormalities) were either absent or found inconsistently. Fetal echocardiograms obtained between 24-30 weeks of gestation in 3 of the affected males showed a dilated left ventricle in one heart, but were not otherwise diagnostic of INVM in any of the cases. Four of the affected individuals died during infancy, one is in cardiac failure at age 8 months, and one is alive following cardiac transplant at age 9 months. The hearts from infants who died or underwent transplantation appeared, on gross examination, to be enlarged, with coarse, deep ventricular trabeculations and prominent endocardial fibroelastosis. Histologically, there were loosely organized fascicles of myocytes in subepicardial and midmyocardial zones of both ventricles, and the myocytes showed thin, often angulated fibers with prominent central clearing and reduced numbers of filaments. Markedly elongated mitochondria were present in some ventricular myocytes from one specimen, but this finding was not reproducible. Genetic linkage analysis has localized INVM to the Xq28 region, where other myopathies with cardiac involvement have been located.

Adolescent↗
PubMed1997

Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome.

Loss-of-function mutations in the G4.5 gene have been shown to cause Barth syndrome (BTHS), an X-linked disorder characterized by cardiac and skeletal myopathy, short stature, and neutropenia. We recently reported a family with a severe X-linked cardiomyopathy described as isolated noncompaction of the left ventricular myocardium (INVM). Other findings associated with BTHS (skeletal myopathy, neutropenia, growth retardation, elevated urinary organic acids, and mitochondrial abnormalities) were either absent or inconsistent. A linkage study of the X chromosome localized INVM to the Xq28 region near the BTHS locus, suggesting that these disorders are allelic. We screened the G4.5 gene for mutations in this family with SSCP and direct sequencing and found a novel glycine-to-arginine substitution at position 197. This position is conserved in a homologous Caenorhabditis elegans protein. We conclude that INVM is a severe allelic variant of BTHS with a specific effect on the heart. This finding provides further structure-function information about the G4.5 gene product and has implications for unexplained cases of severe infantile hypertrophic cardiomyopathy in males.

Abnormalities, Multiple↗
PubMed1997

Acute renal failure in idiopathic nephrotic syndrome.

Acute renal failure (ARF) associated with idiopathic nephrotic syndrome has been reported in adults with advanced age but is a rare event in children. We have reviewed the literature on this subject and report an additional pediatric case. The pathogenetic mechanisms which may lead to ARF during the course of idiopathic nephrotic syndrome are reviewed with a brief discussion of the role of angiotensin II and angiotensin converting enzyme inhibition in this setting. Although no consensus has emerged for the prevention and treatment of ARF in patients with nephrotic syndrome, a combination of salt-poor albumin and diuretics to reduce interstitial edema may be beneficial as a preventive measure. Once acute tubular necrosis is diagnosed, dialysis may be indicated. In the majority of reports the prognosis for recovery of renal function has been good even in patients in whom long-term dialysis was required.

Acute Kidney Injury↗
PubMed1996

Aprosencephaly and cerebellar dysgenesis in sibs.

Aprosencephaly is a rare, lethal malformation sequence of the central nervous system that has been attributed to a postneuralation encephaloclastic process. We describe autopsy findings consistent with aprosencephaly in 2 fetuses conceived from a consanguineous mating (first cousins). Both showed anencephalic manifestations; however, the crania were intact, with fused sutures. The neuropathologic findings were essentially identical. Each fetus had complete absence of the telecephalon and pyramidal tracts, rudimentary diencephalic and mesencephalic structures, primitive cerebellar hemispheres, posterolateral clusters of primitive neural cells in the medullas suggesting an abnormality of neural migration, a normally-formed spinal cord, and retinal dysplasia within normally-formed globes. In addition, both fetuses manifested a peculiar perivascular mesenchymal proliferation seen only within the central nervous system. The similarity of these cases, coupled with parental consanguinity, suggests a primary malformation in brain development due to the homozygous representation of a mutant allele. We hypothesize that these patients may represent a defect in a gene important in brain development, the nature of which has yet to be elucidated.

Abnormalities, Multiple↗
PubMed1994

Atelencephalic aprosencephaly.

Absence of the telencephalon and diencephalon characterizes the syndrome of aprosencephaly, while in atelencephaly, only the telencephalon is absent. Atelencephalic aprosencephaly is characterized by the presence of at least a rudimentary diencephalon. Embryologically, aprosencephaly is thought to occur after the optic vesicles form but before the cerebral vesicles appear. The syndrome is quite rare, with only 10 cases previously reported. We describe two fetuses with atelencephalic aprosencephaly. A 25-week estimated gestational age fetus was born to first-cousin parents and had a prenatal ultrasonographic diagnosis of anencephaly. The second, a 19-week estimated gestational age fetus, was thought to have semilobar holoprosencephaly by prenatal ultrasound. At autopsy, neuropathologic examination in both cases showed virtual absence of the cerebral hemispheres with an incomplete diencephalon. Microscopic examination in one case revealed disorganized neuropil with a proliferative vasculopathy. The optic globes were completely formed and attached to hypoplastic optic nerves, but retinal dysplasia was apparent histologically in both cases, and bilateral colobomata were present in one case. The findings in these cases demonstrate a spectrum of congenital variations that lie between the syndromes of atelencephaly and aprosencephaly, underscoring the complexity of the congenital anomalies.

Abnormalities, Multiple↗
PubMed1993

Renal disease in adolescents with type I diabetes mellitus: a report of the Southwest Pediatric Nephrology Study Group.

Although 30% to 40% of patients with type I diabetes mellitus develop diabetic nephropathy, the usual signs of clinical nephropathy are often thought to be delayed until adulthood. We studied 13 adolescents with type I diabetes mellitus for 5 to 14 years who had renal biopsies completed because of clinical problems, including proteinuria, hematuria, or hematuria plus proteinuria. Changes typical of diabetes were seen by light and immunofluorescence microscopy; evidence of other renal diseases was not noted. On electron microscopy evaluation, glomerular basement membrane width was increased in 11 patients. In seven patients, mesangial volume was elevated above the normal range. Peripheral capillary filtration surface density was diminished below the normal range in five patients. Thus, several of these adolescents had severe glomerular lesions that were indicative of overt diabetic nephropathy. Within 2 to 3 years after biopsy, at least two patients were dialysis dependent. Thus, the adolescent diabetic patient with a relatively short duration of diabetes may be developing progressive diabetic renal lesions, and the clinical signs and symptoms at presentation may not be those typically seen in diabetic nephropathy.

Adolescent↗
PubMed1990

Chronic encephalitis, epilepsy, and cerebrovascular immune complex deposits.

Refractory epilepsy, electroencephalographic abnormalities, progressive hemiplegia, and contralateral hemicerebral atrophy developed in a previously healthy 3-year, 9-month-old girl. Extensive laboratory testing showed elevated serum antinuclear antibody titers, cerebrospinal fluid oligoclonal bands, and elevated immunoglobulin G (IgG): albumin ratio, IgG index, and IgG synthesis rate. Pathological study of a subtotal hemispherectomy specimen revealed widespread cerebral vasculitis with immunofluorescence staining for IgG, IgM, IgA, C3, and Clq, and ultrastructural evidence of vascular injury in addition to severe cortical atrophy with marked neuronal loss. Cerebrospinal fluid abnormalities in other reported patients suggest that immunological abnormalities may not be unique to this girl. These data suggest possible immunopathogenetic mechanisms in these patients.

Antibodies, Antinuclear↗
PubMed1990

A clinicopathological study of 24 children with hemolytic uremic syndrome. A report of the Southwest Pediatric Nephrology Study Group.

This study reports the pattern of renal injury in 24 North American children with hemolytic uremic syndrome (HUS), and the extent of extrarenal involvement in 9 of these children examined at autopsy. Fifteen of the 24 children were studied during the first 16 days of hospitalization; their renal specimens demonstrated glomerular thrombotic microangiopathy (TMA) in 8 children, cortical necrosis in 1, and varying degrees of glomerular TMA and cortical necrosis in 6 children. Nine of the children were studied after 16 or more days of hospitalization; these patients had prominent renal arterial lesions. Of 9 children examined at autopsy, extrarenal microthrombi were identified in 8. In 4 children who died during the acute phase of the disease, hemorrhagic colonic necrosis (3 children) and pancreatic islet cell necrosis (2 children) were the principal extrarenal lesions encountered. Rare microthrombi were present in the brains of the 3 children who manifested seizures.

Aging↗
PubMed1989

Serial renal function in an ovine model of unilateral fetal urinary tract obstruction.

Renal tubular and glomerular function following ovine fetal urinary tract obstruction has been studied predominantly in anesthetized, exteriorized fetuses immediately after relief of obstruction. Since surgery and anesthesia may alter fetal cardiovascular and renal physiology, we developed a chronically catheterized, ovine model of unilateral fetal urinary tract obstruction to compare function of the unobstructed and obstructed kidneys repeatedly after relief of obstruction. Split renal function of the previously obstructed kidneys and unobstructed kidneys was measured serially in 7 fetal sheep after obstruction at 55 to 85 days per 147 days of gestation for 30 to 49 days. Seventy-five split clearances were determined on days 1, 2, 3 to 4 and 5 to 6 postoperatively. Not every fetus was studied each day. By 2-way ANOVA, renal function was stable on day 1 after surgery and did not change with time. Previously obstructed kidneys had lower creatinine clearance (0.16 versus 0.71 ml. per minute, p equals 0.0001), higher fractional sodium excretion (33.04 versus 6.02 per cent, p equals 0.0001) and higher urine sodium/creatinine ratio (4.80 versus 0.90 mEq. per mg., p equals 0.0001). Urine flow in the unobstructed kidneys did not differ significantly from that of the obstructed kidneys (0.122 versus 0.083 ml. per minute, p equals 0.35). Obstruction reduced kidney weight (4.7 versus 9.7 gm., p equals 0.0006), cortical thickness (-39 per cent) and nephrogenic zone (-59 per cent), and it increased collecting duct dilatation and medullary fibrosis. No cysts or dysplasia was noted. Fetal urinary tract obstruction for 39.7 days alters renal histology, glomerular function and tubular function. Renal function is stable by 1 day after catheterization and does not change from days 1 to 6 following relief of obstruction.

Animals↗
PubMed1989

The pediatric office laboratory. A look at recent trends.

The office laboratory has experienced an explosive growth in this decade as a result of technological advances and changes in reimbursement and regulatory practices. An evaluation of currently available methods, however, suggests that tests appropriate for the pediatric office laboratory today are similar to those recommended in a critical appraisal of pediatric laboratory medicine in 1974. This underscores the fact that the patient and not the technology dictates the tests to be performed.

Clinical Laboratory Techniques↗
PubMed1989

Hemolytic uremic syndrome associated with glomerular disease.

Secondary hemolytic uremic syndrome (HUS) is uncommon. When it occurs, it is usually in association with pregnancy, malignancy, severe hypertension, drugs, or collagen vascular diseases. It has rarely been reported in patients with glomerular disease. Two such patients with secondary HUS are described. A 17-month-old girl with hematuria and the nephrotic syndrome, negative antistreptolycin O (ASO) titer, and low serum levels of C3 and C4 developed oliguria, progressive azotemia, thrombocytopenia, and microangiopathic hemolytic anemia. A kidney biopsy showed fibrin in glomerular capillaries and cresentic membranoproliferative glomerulonephritis. A 22-year-old man with a 16-year history of relapsing minimal change nephrotic syndrome had been in remission for 5 years when he experienced nephrotic syndrome relapse and developed thrombocytopenia, microangiopathic hemolytic anemia, and renal failure. A kidney biopsy revealed foot process fusion and obstruction of glomerular capillaries with fibrin and platelets. These cases illustrate that HUS can occur in association with other glomerular diseases and should be considered when thrombocytopenia and hemolytic anemia occur in a nephritic or nephrotic patient.

Adult↗