Prothrombin gene mutation uncommon in pulmonary embolism.

BACKGROUND: Venous thrombosis followed by pulmonary embolism is one of the most common causes of sudden death among middle-aged adults. Several inherited polymorphisms are associated with heightened risk of venous thrombosis, including mutation at position 20210 of the prothrombin gene and mutation at codon 506 of the factor V gene. METHODS: We studied mutation prevalence in 67 individuals who died of pulmonary embolism and were autopsied in a medical examiner's facility over a 5-year period. Mutations were identified by polymerase chain reaction followed by allele-specific endonuclease digestion. RESULTS: Traditional risk factors for pulmonary embolism (eg, immobility, oral contraceptive use, cancer) were identified in 75%. Heterozygous mutation of the prothrombin gene was found in 3/67 (4%), and heterozygous mutation of the factor V gene was identified in 3/66 (4%). No homozygotes or compound heterozygotes were identified. The prevalence of mutation was not significantly different from that of the general population. CONCLUSIONS: Individuals who die suddenly from pulmonary embolism are not often affected by prothrombin or factor V gene mutations. Therefore, medical examiners need not routinely test for these mutations in individuals who die of pulmonary embolism.

Expression of renal and vascular angiotensin II receptor subtypes in children.

Angiotensin II (Ang II) AT1 receptors modulate most of the known physiological functions of Ang II in the kidney and cardiovascular structures. In contrast, the physiological role of AT2 receptors, which are abundantly expressed in fetal tissues, is not clearly defined. The changes that occur in the expression and distribution of AT2 receptors in the kidney and arteries during the first 2 years of life have not been studied. We have localized and characterized the expression of Ang II receptor subtypes, AT1 and AT2, in the kidney, interlobular arteries, thoracic aorta, and middle cerebral artery, in children during their first 2 years of life, using quantitative autoradiography. Renal glomeruli and middle cerebral arteries expressed exclusively AT1 receptors. In contrast, more than 80% of the Ang II receptors expressed in thoracic aorta and interlobular arteries belonged to the AT2 subtype. These findings demonstrate that the expression of Ang II receptor subtypes in different vascular structures in young children varies according to the tissue.

Muc-5/5ac mucin messenger RNA and protein expression is a marker of goblet cell metaplasia in murine airways.

Airway inflammation, hyperreactivity, increased number of goblet cells, and mucus overproduction characterize asthma. Respiratory challenge with ovalbumin (OVA) of sensitized mice has been shown by several laboratories to cause pulmonary pathology similar to that observed in human allergic asthma. Recently, interleukin (IL)-13 has been shown to be a central mediator in this process. Because the airways of healthy mice have few, if any, mucus-producing cells, an increase in the number of these cells likely reflects induction of mucin-gene expression. The purpose of this study was to identify mucin genes induced as a result of airway goblet-cell metaplasia (GCM) in mice sensitized and challenged with OVA or in mice treated with IL-13 alone. BALB/c mice were sensitized by intraperitoneal injection (Days 0, 4, 7, 11, and 14) and intranasal instillation (Day 14) of 100 microg of OVA in saline, and then challenged by intranasal instillation (Days 25, 26, and 27) of the same. IL-13-treated mice received 5 microg of IL-13 by intranasal instillation on three consecutive days. Control mice were given saline alone. All mice were studied 24 h after the last challenge. Histologic analysis of the lungs revealed both a striking peribronchial and perivascular lymphocytic and eosinophilic inflammation and airway GCM in OVA-treated mice, and also airway GCM without inflammation in IL-13-treated mice. Northern blot analysis of lung RNA demonstrated (1) expression of Muc-5/5ac messenger RNA (mRNA) in OVA-treated and IL-13-treated mice, but not in control mice; (2) expression of Muc-1 mRNA at comparable levels in all mice regardless of treatment; and (3) no expression of Muc-2 or Muc-3 mRNA in control or treated mice. Western blot analysis demonstrated the expression of Muc-5/5ac protein (both apomucin and glycosylated mucin) in lung lysates of OVA-treated (but not control) mice, and also the expression of Muc-5/5ac mucins in the bronchoalveolar lavage fluid of OVA-treated and IL-13-treated mice. These findings demonstrate that airway GCM is associated with the induction of pulmonary expression of Muc-5/5ac mRNA and mucin in murine models of allergic asthma.

Pancreatoblastoma: imaging findings in 10 patients and review of the literature.

PURPOSE: To describe the features of pancreatoblastoma at magnetic resonance (MR) imaging, computed tomography (CT), and ultrasonography (US). MATERIALS AND METHODS: Imaging and surgical findings in 10 patients (age range, 2-20 years; mean age, 6.8 years) with pathologically proved pancreatoblastoma were reviewed for tumor size, organ of origin, definition and quality of tumor margins, tumor heterogeneity, calcification, enhancement, ascites, biliary and/or pancreatic ductal dilatation, local invasion, adenopathy, vascular invasion, vascular encasement, metastases, and signal intensity on MR images. Results from 10 CT, seven US, and three MR imaging examinations were reviewed. RESULTS: Five of the 10 tumors were pancreatic; four others appeared to be pancreatic or hepatic. Most had well-defined margins (nine of 10), were heterogeneous (nine of 10), and enhanced (10 of 10). Other findings included calcification (two of 10), biliary and pancreatic ductal dilatation (one of 10), and ascites (three of 10). Hepatic (two patients) and pelvic (two patients) metastases were present. Adenopathy (two patients) and vascular invasion (one patient) were not identified radiologically. Tumors had low to intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images. CONCLUSION: Pancreatoblastoma is typically a heterogeneous tumor with well-defined margins that may appear to arise from the pancreas or liver. It may behave aggressively, with localized vascular or bowel invasion or with widespread metastatic disease. Although it is rare, it should be considered in the differential diagnosis of an upper abdominal mass in a child.

End-stage renal disease in two pediatric patients with Fechtner syndrome.

Fechtner syndrome, a disease in the spectrum of the hereditary nephridites, is a macrothrombocytopenia associated with sensorineural hearing loss, cataracts, nephritis, and characteristic leukocyte inclusions. Renal biopsy findings are consistent with those of Alport syndrome, and the associated renal disease is said to be unusual before mid to late adulthood. Here, we review the available literature on this disease and report two African-American pediatric patients with Fechtner syndrome who rapidly progressed to end-stage renal disease during adolescence. We conclude that chronic renal failure can occur at a young age in patients with Fechtner syndrome, with a possible relation to race/ethnicity. Fechtner syndrome, or other variants of Alport syndrome, need to be considered in patients presenting with proteinuria and thrombocytopenia.

Different vascular patterns of medulloblastoma and supratentorial primitive neuroectodermal tumors.

Astrocytoma vasculature patterns differ according to histological grade of malignancy with glioblastoma multiforme (WHO grade IV) showing most extensive endothelial proliferation. Here, we determined whether the vascular patterns of medulloblastoma and supratentorial primitive neuroectodermal tumors (PNETs), which can be hardly distinguished histopathologically, differ. We evaluated the spatial organization of vessels in medulloblastomas and PNETs using antibodies to von Willebrand factor (vWF) and CD34. Medulloblastoma capillaries showed slight endothelial cell hyperplasia. Microvessels sprouted from the capillaries and formed glomeruloid clusters. There were areas with chains of unopposed endothelial cells (3-10 cells). Supratentorial PNETs had highly branched capillaries with extensive endothelial cell hyperplasia. Glomeruloid arrays of microvessels extended from the capillaries. Small fragments of endothelial tubes were scattered throughout the tumor. Therefore, medulloblastomas and supratentorial PNETs showed different spatial organization of tumor vessels which can be used for differentiation of each tumor entity. These vascular patterns may reflect different tumor derived angiogenic stimuli.

Vasculopathy of small muscular arteries in pediatric patients after bone marrow transplantation.

Bone Marrow Transplant (BMT) is a critical therapeutic intervention for a variety of diseases occurring in the pediatric patient. Complications of allogeneic BMT include graft-versus-host disease (GVHD), infection, drug toxicity, thrombotic microangiopathy, and veno-occlusive disease. With solid organ transplantation, chronic vascular rejection has emerged as a major factor limiting long-term survival of the graft. We present a vasculopathy of small muscular arteries in 6 patients after allogeneic BMT. Cases include 4 boys and 2 girls ranging in age from 4 months to 13 years with full or partial human leukocyte antigen matching. Five of the 6 transplants were from related donors. The vasculopathy occurred 13 to 418 days after transplant and was noted in surgical specimens (2) and at autopsy (4). It was seen in the gastrointestinal tract and lung in 3 cases each. Vascular changes in small muscular arteries include concentric intimal or medial hyperplasia with luminal narrowing, prominent myxoid change, extravasated red blood cells, and presence of some foamy histiocytes with no evidence of thrombotic microangiopathy. Vasculopathy contributed to intestinal compromise requiring surgical intervention 3 times in 1 patient, and diffuse alveolar damage with hemorrhage in another. All 6 patients are dead. The cause of this unusual vasculopathy present in patients after BMT is likely to be multifactorial, involving effects of irradiation, chemotherapy, cyclosporine, and GVHD. Together these may create a negative synergy which produces an obliterative arteriopathy that should be recognized as a pathological entity and may be a harbinger of a poor prognosis.

Tissue distribution of tramadol and metabolites in an overdose fatality.

Tramadol (Ultram) is a centrally acting, synthetic analgesic agent. Although it has some affinity for the opiate receptors, tramadol is believed to exert its analgesic effect by inhibiting the re-uptake of norepinephrine and serotonin. There are several published cases of tramadol's involvement in drug-related deaths and impairment. Reports of deaths involving tramadol alone with associated tissue concentrations are rare. This report documents a case in which tramadol overdose was identified as the cause of death. The following tramadol concentrations were found in various tissues: blood, 20 mg/L; urine, 110.2 mg/L; liver, 68.9 mg/kg; and kidney, 37.5 mg/kg. Tissue distributions of the two primary metabolites, N-desmethyl and O-desmethyl tramadol, are also reported. In each tissue or fluid except urine, the tramadol concentration was greater than either metabolite, consistent with other reports of drug-impaired drivers and postmortem cases. The O-desmethyl metabolite concentration was greater than the N-desmethyl metabolite concentration in all tissues; this is in contrast to other postmortem reports, in which the majority of cases report concentrations of O-desmethyl as less than those of N-desmethyl. This may be useful as an indicator of time lapse between ingestion and death.

Accuracy of death certification in two tertiary care military hospitals.

To determine the number and type of errors in death certifications, death certificates and corresponding postmortem examination results for 98 patients were analyzed at two tertiary care military hospitals. Of the 98 death certificates, errors were found in 36 (37%). The most prevalent type of error was the use of a nonspecific diagnosis as the underlying cause of death (22 of 36 errors, 61%). No errors were found in the listed manner of death. Given the high prevalence of errors found in death certification, recommendations are made to ensure the proper completion of death certificates. In addition, it is suggested that for patients who are to undergo postmortem examination, the immediate, any intermediate, and the underlying cause of death may be listed as "pending" so that the clinician can use the autopsy results in the completion of the death certificate.

Mucin gene expression (MUC1, MUC2, and MUC5/5AC) in nasal epithelial cells of cystic fibrosis, allergic rhinitis, and normal individuals.

The early pathogenic events in cystic fibrosis (CF) include colonization of Pseudomonas in the lung, airway inflammation, and mucus hypersecretion with airway obstruction. The primary mechanisms leading to chronic infection and inflammation are not well understood. One possible explanation for this cascade of events is increased or altered expression of one or more mucin (MUC) genes by CF cells in the respiratory tract. We compared expression levels of three mucin genes, MUC1, MUC2, and MUC5/5AC, known to be expressed in the respiratory tract of CF, allergic rhinitis, and normal individuals. Mucin transcript levels in nasal epithelial cells free from inflammation were quantitated by an MUC mRNA slot-blot method. This study revealed three major findings: (1) MUC5/5AC mRNA was expressed at five- to tenfold greater levels than MUC2 or MUC1 for all subjects. (2) MUC2 mRNA levels were similar among all subject groups. (3) In CF subjects, there was a trend toward reduced MUC5/5AC expression. When normalized to the levels of MUC2 expression in individual specimens, MUC5/5AC expression was reduced significantly in CF cells compared with normal cells. These data suggest that mucin gene expression is altered in noninflamed CF nasal cells.

Human immunodeficiency virus (HIV)-associated nephropathy in children from the Washington, D.C. area: 12 years' experience.

Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is a clinicopathologic entity that includes proteinuria, azotemia, focal segmental glomerulosclerosis or mesangial hyperplasia, and tubulointerstitial disease. The incidence of HIVAN is increased in black patients and variable depending on the age and geographic area. The objective of this study was to describe relevant clinical and pathological findings in 30 children with HIVAN followed at the Children's National Medical Center in Washington, D.C. Our experience of the last 12 years showed a spectrum of HIVAN that seems to be coincident with the degree of acquired immunodeficiency syndrome (AIDS) symptomatology. By renal sonograms and frequent urinalysis, we identified children undergoing the early stages of HIVAN with enlarged echogenic kidneys, proteinuria, and "urine microcysts". HIVAN did not necessarily progress rapidly to end-stage renal disease. Nephrotic syndrome or chronic renal insufficiency were late manifestations of HIVAN. Children with HIVAN were likely to develop transient electrolyte disorders, heavy proteinuria, and acute renal failure due to systemic infectious episodes or nephrotoxic drugs. HIVAN was associated with other HIV-induced illnesses and high mortality rates. Early detection and careful clinical follow-up of children with HIVAN may reduce the incidence of renal-cardiovascular complications and improve their quality of life.

Sinus histiocytosis with massive lymphadenopathy: report of case.

A case of a five-year-old African American female with sinus histiocytosis with massive lymphadenopathy is presented. The epidemiology, morbidity, and management aspects of this condition are discussed.

Amebic osteomyelitis in a child with acquired immunodeficiency syndrome: a case report.

Disseminated Acanthamoeba infection has been described in immunocompromised or debilitated patients. The usual sites of involvement are skin, sinus, and brain. Sporadic reports of Acanthamoeba infection in patients infected with the human immunodeficiency virus are present in recent literature, predominantly in adults, and one case involving an 8-year-old child. We describe a case of amebic osteomyelitis, seen in a 6-year-old child with vertically acquired human immunodeficiency virus and a 6-month history of cutaneous Acanthamoeba infection.

Are endothelial cell patterns of astrocytomas indicative of grade?

BACKGROUND: The most common primary brain tumors in children and adults are of astrocytic origin. Classic histologic grading schemes for astrocytomas have included evaluating the presence or absence of nuclear abnormalities, mitoses, vascular endothelial proliferation, and tumor necrosis. MATERIALS AND METHODS: We evaluated the vascular pattern of 17 astrocytoma surgical specimens (seven from children and 10 from adults), and four normal brains obtained at autopsy, utilizing antibody to glial fibrillary acidic protein (GFAP) and von Willebrand factor (vWF) utilizing confocal microscopy. A modified WHO classification was used. RESULTS: All tumor cases showed cells positive for GFAP. Control tissues showed a few, widely separated vessels. Pilocytic astrocytomas (four cases) showed lacy clusters of small-to-medium sized vessels, with intact vessel wall integrity. Diffuse, low grade astrocytoma (three cases) showed a staining pattern similar to control tissue; intermediate grade (one case), anaplastic astrocytoma (three cases) and gliobastoma multiforme (six cases) showed an increased vessel density with multiple small vessels (glomeruloid clusters), some with prominent intimal hyperplasia, loss of vessel wall integrity, and with numerous vWF-positive single cells/microvessels within the tumor substance. CONCLUSIONS: Evaluation of astrocytomas utilizing antibody to vWF and confocal microscopy aids in the grading of these neoplasms.

Colonic diverticulitis causing partial bowel obstruction in a child with cystic fibrosis.

Children and adolescents with cystic fibrosis (CF) may manifest bowel pathology with resulting bowel obstruction. Recognized causes of bowel obstruction in CF patients include meconium ileus, intussusception, distal intestinal obstruction syndrome and postoperative adhesions. Additionally, the development of colonic strictures in children with CF has recently been described. We report an unusual cause of partial obstruction of the ascending colon in a child with CF due to pathologically proven diverticulitis.