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ABSTRACT: Massive enlargement of an ovarian cyst is an uncommon cause of morbidity and a rare cause of mortality due in large to part to noninvasive imaging techniques that usually permit early detection. When an ovarian cyst reaches giant proportions, it produces abdominal enlargement often with a fluid wave resulting in a condition that mimics ascites, called pseudoascites. Despite their impressive appearances, such cysts often are operable for cure. We describe a case of a middle-aged woman who presented 3 years before her death with symptoms from an undiagnosed giant cyst and given a diagnosis of ascites of undetermined etiology. She subsequently died at home unexpectedly, and at autopsy, she was found to have a massively enlarged but otherwise benign mucinous cystadenoma.
The American journal of forensic medicine and pathology: official publication of the National Association of Medical Examiners 06/2011; · 0.71 Impact Factor
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Nicole S Yin,
Sebastian Benavides,
Sidney Starkman,
David S Liebeskind,
Jeffrey A Saver,
Noriko Salamon,
Reza Jahan,
Gary R Duckwiler,
Satoshi Tateshima,
Fernando Vinuela,
Paul M Vespa, Dennis J Chute,
Harry V Vinters
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ABSTRACT: Endovascular thrombectomy is an increasingly used treatment for arterial occlusion in acute stroke. Various devices (including most extensively the Mechanical Embolus Removal in Cerebral Ischemia [MERCI] Retriever device) have been used for this.
We review the neuropathologic findings in 5 patients (age range, 59 to 87 years) who died acutely or as late as 38 days after procedures using the MERCI (4 patients) and Penumbra (1 patient) devices were carried out to remove thromboemboli from the middle cerebral artery. Partial recanalization was achieved by thrombectomy in all 5 patients.
All patients showed extensive cerebral infarcts, 3 of 5 with clinical hemorrhagic transformations of the infarct or frank intraparenchymal hemorrhage after thrombectomy; in 1 case, this was judged to be at least partly on the basis of concomitant hypertensive microvascular disease. With 1 exception, basal arteries examined in detail by immunohistochemistry showed prominent, although usually nonocclusive (and generally nonulcerated), atheromata, often with significant luminal stenosis. One patient showed a subintimal dissection with resultant occlusion of the middle cerebral artery.
In this highly selected group of patients, the vascular pathological abnormalities affecting basal arteries were variable, but complicated atherosclerosis was a common finding. Extensive irreversible brain necrosis before therapeutic procedures may have contributed to deaths.
Stroke 04/2010; 41(5):938-47. · 5.73 Impact Factor
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ABSTRACT: As part of a review of substance abuse deaths in Dutchess County, New York, the Dutchess County Medical Examiner's Office identified 3 cases of angiocentric systemic foreign-body granulomatosis discovered at autopsy. Our investigation disclosed that in all 3 cases patients surreptitiously injected crushed oral prescription medication. Of the patients, 2 obtained intravenous access through central venous lines, the other patient was found to have injected herself intramuscularly. Autopsy demonstrated lung abnormalities due to diffuse deposits of foreign material within and around vessels, associated with foreign-body granulomatous reaction. We also identified a systemic distribution of this foreign material deposited beyond the lungs in the brain, heart, kidneys, and spleen. We present these cases along with a review of the literature of systemic embolization of foreign material in previously documented cases of deaths due to parenteral abuse of oral medications.
The American journal of forensic medicine and pathology: official publication of the National Association of Medical Examiners 02/2010; 31(2):146-50. · 0.71 Impact Factor
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ABSTRACT: Infantile perineal protrusion is a recently described dermatologic entity that resembles a skin tag and can be confused with evidence of sexual child abuse. Although well-described by the pediatric and dermatologic community in small case series and case reports, we found little reference to this abnormality in the forensic literature despite its medicolegal significance. Therefore, we present a case of a 3-month-old infant who had a representative example of this lesion.
The American journal of forensic medicine and pathology: official publication of the National Association of Medical Examiners 10/2009; 30(3):287-8. · 0.71 Impact Factor
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ABSTRACT: We report a case of sudden death due to a catastrophic spontaneous rupture of a urinary bladder associated with megacolon due to a fecal impaction (fecaloma). The massively distended rectum and sigmoid colon filled the pelvic cavity and pressed up against the posterior aspects of the uterus, vagina, and urinary bladder. This produced bladder outlet obstruction, followed by massive dilatation and rupture of the urinary bladder, bilateral hydronephrosis, and a 3.5 liter collection of urinary fluid within the abdominal cavity. Complications of chronic constipation, fecalomas, and rupture of the urinary bladder are reviewed.
The American journal of forensic medicine and pathology: official publication of the National Association of Medical Examiners 10/2009; 30(3):280-3. · 0.71 Impact Factor
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ABSTRACT: We discuss the autopsy findings of three medico-legal cases of sudden death associated with uncommon neuropathologic findings of which the general forensic pathologist may not be familiar. Case 1 was a 43-year-old man who died of a seizure due to malignant melanoma of the temporal lobe associated with neurocutaneous melanosis (NCM). Case 2 was a 57-year-old woman with a history of mental retardation and incoordination because of chronic lead poisoning, who died of a pulmonary thromboembolism due to deep venous thrombosis status post left leg fracture after a fall down a staircase. Autopsy revealed atrophy and gliosis of her cerebellum as a result of childhood lead poisoning. The third patient was a 75-year-old woman who died as a result of acute bacterial leptomeningitis at the cervico-medullary junction with acute inflammation of the connective tissue of her upper cervical spinal column associated with subluxation of her atlantoaxial (AA) joint, also known as Grisel's syndrome.
Journal of Forensic Sciences 06/2008; 53(3):734-8. · 1.23 Impact Factor
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Henry B Armah,
Guoji Wang,
Bennet I Omalu,
Robert B Tesh,
Kymberly A Gyure, Dennis J Chute,
Roger D Smith,
Paul Dulai,
Harry V Vinters,
Bette K Kleinschmidt-DeMasters,
Clayton A Wiley
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ABSTRACT: Rare cases of West Nile virus (WNV)-associated inflammation outside the central nervous system (CNS) have been reported. We evaluated the systemic distribution of WNV in postmortem tissues during encephalitis in six patients using immunohistochemistry. WNV antigens were detected in neurons of CNS (all 6 cases), kidney (4 cases), lungs (2 cases), pancreas (2 cases), thyroid (2 cases), intestine (2 cases), stomach (1 case), esophagus (1 case), bile duct (1 case), skin (1 case), prostate (1 case) and testis (1 case). In systemic organs epithelial cells were infected. In none of the six cases were viral antigens identified in hepatocytes, heart, adrenal gland, nerves, skeletal muscles, bone, vessels and fat. All cases in which viral antigens were identified in systemic organs in addition to CNS were severely immunocompromised transplant recipients. With the exception of testis and brain, most foci of infection were not associated with inflammation. While the absence of inflammation may in part be due to patient immunosuppression or to possible transient nature of any host response, compartmentalization of viral antigen to the luminal region of epithelial cells may sequester WNV from immune recognition. Comparison of our findings with previous reports suggests that patients with WNV encephalitis can have widespread systemic infection.
Brain Pathology 11/2007; 17(4):354-62. · 3.99 Impact Factor
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ABSTRACT: A new method for enhancing MRI contrast between gray matter (GM) and white matter (WM) in epilepsy surgery patients with symptomatic lesions is presented. This method uses the radiation damping feedback interaction in high-field MRI to amplify contrast due to small differences in resonance frequency in GM and WM corresponding to variations in tissue susceptibility. High-resolution radiation damping-enhanced (RD) images of in vitro brain tissue from five patients were acquired at 14 T and compared with corresponding conventional T(1)-, T(2) (*)-, and proton density (PD)-weighted images. The RD images yielded a six times better contrast-to-noise ratio (CNR = 44.8) on average than the best optimized T(1)-weighted (CNR = 7.92), T(2) (*)-weighted (CNR = 4.20), and PD-weighted images (CNR = 2.52). Regional analysis of the signal as a function of evolution time and initial pulse flip angle, and comparison with numerical simulations confirmed that radiation damping was responsible for the observed signal growth. The time evolution of the signal in different tissue regions was also used to identify subtle changes in tissue composition that were not revealed in conventional MR images. RD contrast is compared with conventional MR methods for separating different tissue types, and its value and limitations are discussed.
Magnetic Resonance in Medicine 11/2006; 56(4):776-86. · 2.96 Impact Factor
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Victor J Marder, Dennis J Chute,
Sidney Starkman,
Anna M Abolian,
Chelsea Kidwell,
David Liebeskind,
Bruce Ovbiagele,
Fernando Vinuela,
Gary Duckwiler,
Reza Jahan,
Paul M Vespa,
Scott Selco,
Venkatakrishna Rajajee,
Doojin Kim,
Nerses Sanossian,
Jeffrey L Saver
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ABSTRACT: Information regarding the histological structure of thromboemboli that cause acute stroke provides insight into pathogenesis and clinical management.
This report describes the histological analysis of thromboemboli retrieved by endovascular mechanical extraction from the middle cerebral artery (MCA) and intracranial carotid artery (ICA) of 25 patients with acute ischemic stroke.
The large majority (75%) of thromboemboli shared architectural features of random fibrin:platelet deposits interspersed with linear collections of nucleated cells (monocytes and neutrophils) and confined erythrocyte-rich regions. This histology was prevalent with both cardioembolic and atherosclerotic sources of embolism. "Red" clots composed uniquely of erythrocytes were uncommon and observed only with incomplete extractions, and cholesterol crystals were notably absent. The histology of thromboemboli that could not be retrieved from 29 concurrent patients may be different. No thrombus >3 mm wide caused stroke limited to the MCA, and no thrombus >5 mm wide was removed from the ICA. A mycotic embolus was successfully removed in 1 case, and a small atheroma and attached intima were removed without clinical consequence from another.
Thromboemboli retrieved from the MCA or intracranial ICA of patients with acute ischemic stroke have similar histological components, whether derived from cardiac or arterial sources. Embolus size determines ultimate destination, those >5 mm wide likely bypassing the cerebral vessels entirely. The fibrin:platelet pattern that dominates thromboembolic structure provides a foundation for both antiplatelet and anticoagulant treatment strategies in stroke prevention.
Stroke 09/2006; 37(8):2086-93. · 5.73 Impact Factor
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Noriko Salamon,
Marissa Andres, Dennis J Chute,
Snow T Nguyen,
Julia W Chang,
My N Huynh,
P Sarat Chandra,
Veronique M Andre,
Carlos Cepeda,
Michael S Levine,
Joao P Leite,
Luciano Neder,
Harry V Vinters,
Gary W Mathern
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ABSTRACT: In paediatric epilepsy surgery patients with hemimegalencephaly (HME; n = 23), this study compared clinical, neuroimaging and pathologic features to discern potential mechanisms for suboptimal post-hemispherectomy developmental outcomes and structural pathogenesis. MRI measured affected and non-affected cerebral hemisphere volumes for HME and non-HME cases, including monozygotic twins where one sibling had HME. Staining against neuronal nuclei (NeuN) determined grey and white matter cell densities and sizes in HME and autopsy cases, including the non-affected side of a HME surgical/autopsy case. By MRI, the affected hemisphere was larger and the non-affected side smaller in HME compared with non-HME children. The affected HME side showed enlarged abnormal deep grey and white matter structures and/or T2-weighted hypointensity in the subcortical white matter in 75% of cases, suggestive of excessive pre-natal neurogenesis and heterotopias. Histopathological examination of the affected HME side revealed immature-appearing neurons in 70%, polymicrogyria (PMG) in 61% and balloon cells in 45% of cases. Compared with autopsy cases, in HME children NeuN cell densities on the affected side were increased in the molecular layer and upper cortex (+244 to +18%), decreased in lower cortical layers (-35%) and increased in the white matter (+139 to +149%). Deep grey matter MRI abnormalities and/or T2-weighted white matter hypointensity correlated with the presence of immature-appearing neurons and PMG on histopathology, decreased NeuN cell densities in lower cortical layers and a positive history of infantile spasms. Post-surgery seizure control was associated with decreased NeuN densities in the molecular layer. In young children with HME and epilepsy, these findings indicate that there are bilateral cerebral hemispheric abnormalities and contralateral hemimicrencephaly is a likely explanation for poorer post-surgery seizure control and cognitive outcomes. In addition, our findings support the hypothesis that HME pathogenesis probably involves somatic mutations that affect each developing cerebral hemisphere differently with more neurons than expected on the HME side.
Brain 03/2006; 129(Pt 2):352-65. · 9.46 Impact Factor
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Ingo K Mellinghoff,
Maria Y Wang,
Igor Vivanco,
Daphne A Haas-Kogan,
Shaojun Zhu,
Ederlyn Q Dia,
Kan V Lu,
Koji Yoshimoto,
Julie H Y Huang, Dennis J Chute, [......],
P Nagesh Rao,
Rameen Beroukhim,
Timothy C Peck,
Jeffrey C Lee,
William R Sellers,
David Stokoe,
Michael Prados,
Timothy F Cloughesy,
Charles L Sawyers,
Paul S Mischel
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ABSTRACT: The epidermal growth factor receptor (EGFR) is frequently amplified, overexpressed, or mutated in glioblastomas, but only 10 to 20 percent of patients have a response to EGFR kinase inhibitors. The mechanism of responsiveness of glioblastomas to these inhibitors is unknown.
We sequenced kinase domains in the EGFR and human EGFR type 2 (Her2/neu) genes and analyzed the expression of EGFR, EGFR deletion mutant variant III (EGFRvIII), and the tumor-suppressor protein PTEN in recurrent malignant gliomas from patients who had received EGFR kinase inhibitors. We determined the molecular correlates of clinical response, validated them in an independent data set, and identified effects of the molecular abnormalities in vitro.
Of 49 patients with recurrent malignant glioma who were treated with EGFR kinase inhibitors, 9 had tumor shrinkage of at least 25 percent. Pretreatment tissue was available for molecular analysis from 26 patients, 7 of whom had had a response and 19 of whom had rapid progression during therapy. No mutations in EGFR or Her2/neu kinase domains were detected in the tumors. Coexpression of EGFRvIII and PTEN was significantly associated with a clinical response (P<0.001; odds ratio, 51; 95 percent confidence interval, 4 to 669). These findings were validated in 33 patients who received similar treatment for glioblastoma at a different institution (P=0.001; odds ratio, 40; 95 percent confidence interval, 3 to 468). In vitro, coexpression of EGFRvIII and PTEN sensitized glioblastoma cells to erlotinib.
Coexpression of EGFRvIII and PTEN by glioblastoma cells is associated with responsiveness to EGFR kinase inhibitors.
New England Journal of Medicine 12/2005; 353(19):2012-24. · 53.30 Impact Factor
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Linda M Liau,
Robert M Prins,
Sylvia M Kiertscher,
Sylvia K Odesa,
Thomas J Kremen,
Adrian J Giovannone,
Jia-Wei Lin, Dennis J Chute,
Paul S Mischel,
Timothy F Cloughesy,
Michael D Roth
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ABSTRACT: We previously reported that autologous dendritic cells pulsed with acid-eluted tumor peptides can stimulate T cell-mediated antitumor immune responses against brain tumors in animal models. As a next step in vaccine development, a phase I clinical trial was established to evaluate this strategy for its feasibility, safety, and induction of systemic and intracranial T-cell responses in patients with glioblastoma multiforme.
Twelve patients were enrolled into a multicohort dose-escalation study and treated with 1, 5, or 10 million autologous dendritic cells pulsed with constant amounts (100 mug per injection) of acid-eluted autologous tumor peptides. All patients had histologically proven glioblastoma multiforme. Three biweekly intradermal vaccinations were given; and patients were monitored for adverse events, survival, and immune responses. The follow-up period for this trial was almost 5 years.
Dendritic cell vaccinations were not associated with any evidence of dose-limiting toxicity or serious adverse effects. One patient had an objective clinical response documented by magnetic resonance imaging. Six patients developed measurable systemic antitumor CTL responses. However, the induction of systemic effector cells did not necessarily translate into objective clinical responses or increased survival, particularly for patients with actively progressing tumors and/or those with tumors expressing high levels of transforming growth factor beta(2) (TGF-beta(2)). Increased intratumoral infiltration by cytotoxic T cells was detected in four of eight patients who underwent reoperation after vaccination. The magnitude of the T-cell infiltration was inversely correlated with TGF-beta(2) expression within the tumors and positively correlated with clinical survival (P = 0.047).
Together, our results suggest that the absence of bulky, actively progressing tumor, coupled with low TGF-beta(2) expression, may identify a subgroup of glioma patients to target as potential responders in future clinical investigations of dendritic cell-based vaccines.
Clinical Cancer Research 09/2005; 11(15):5515-25. · 7.74 Impact Factor
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ABSTRACT: This article examines 3 contexts in which moderate or severe traumatic brain injury can be approached. The epidemiologic background of moderate and severe traumatic brain injury is presented, with particular attention paid to new findings from the study of a national hospital inpatient database. We review aspects of neuroimaging and how new imaging modalities can reveal fine detail about traumatic brain injury. Finally we examine the current state of neuropathologic evaluation of, and recent developments in, understanding of the neural disruptions that occur following traumatic brain injury, together with cellular reactions to these disruptions.
Brain Pathology 05/2004; 14(2):185-94. · 3.99 Impact Factor
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ABSTRACT: Intrathoracic extramedullary hematopoiesis (TEMH) is an unusual but well-described entity, which is typically found in patients who have chronic hemolytic anemias, myelofibrosis, or myeloproliferative disorders. It is seldom symptomatic, rarely fatal. We report a case of a 26-year-old African-American male with a past medical history of sickle cell trait/beta thalassemia who developed multiple intrathoracic nodules of extramedullary hematopoiesis. One of these nodules spontaneously ruptured and produced a fatal hemothorax.
American Journal of Forensic Medicine & Pathology 04/2004; 25(1):74-7. · 0.88 Impact Factor
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ABSTRACT: Lissencephaly with agenesis of the corpus callosum and rudimentary dysplastic cerebellum may represent a subset of lissencephaly with cerebellar hypoplasia (LCH) of unknown etiology, one that is distinct from other types of LCH. We present a detailed neuropathological description of an autopsy brain from a 7-day-old neonate born at 38-gestational weeks, presenting with this malformation. The brain was severely hydrocephalic and totally agyric. The corpus callosum was absent and deep gray matter structures indistinct. A rudimentary dysplastic cerebellum, dysplastic olivary nuclei and nearly complete absence of corticospinal tracts were also noted. Microscopic examination revealed various types of dysplastic and malformative features throughout the brain in addition to the classic four-layered neocortical structure characteristic of type I lissencephaly. Unique features in the present case were (1) bilateral periventricular undulating cortical ribbon-like structures mimicking fused gyri and sulci, associated with aberrant reelin expression, (2) large dysplastic neocortical neurons positive for phosphorylated neurofilament, calbindin-D28K, tuberin, hamartin, doublecortin, LIS1, reelin and Dab1, (3) derangement of radial glial fibers, and (4) disorganized cerebellar cortex and heterotopic gray matter composed exclusively of granule cells in the cerebellar deep white matter. The clinicopathological features in the present case are suggestive of a distinct category of lissencephaly with cerebellar involvement. We suggest a possible classification of this unique case among the LCH syndromes.
Acta Neuropathologica 02/2004; 107(1):69-81. · 9.32 Impact Factor
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ABSTRACT: There is a paucity of accurate postmortem data pertinent to comorbid medical conditions in patients with dementia, including Alzheimer disease.
The purposes of this study were (a) to examine general autopsy findings in patients with a dementia syndrome and (b) to establish patterns of central nervous system comorbidity in these patients.
Review of autopsy reports and selected case material from 202 demented patients who had "brain-only" autopsies during a 17-year period (1984-2000) and from 52 demented patients who had general autopsies during a 6-year period (1995-2000).
Large academic medical center performing approximately 200 autopsies per year.
Among the 52 patients who underwent complete autopsy, the most common cause of death was bronchopneumonia, which was found in 24 cases (46.1%). Other respiratory problems included emphysema, found in 19 (36.5%) of 52 patients, and pulmonary thromboembolism, found in 9 (17.3%) of 52 patients. In 6 cases, pulmonary thromboembolism was the proximate cause of death. Twenty-one (40.3%) of the 52 patients had evidence of a myocardial infarct (varying ages) and 38 (73.1%) had atherosclerotic cardiovascular disease, 27 of a moderate to severe degree. Four clinically unsuspected malignancies were found: 1 each of glioblastoma multiforme, diffusely infiltrative central nervous system lymphoma, pancreatic adenocarcinoma, and adenocarcinoma of the lung. One patient with frontotemporal dementia and amyotrophic lateral sclerosis died of severe meningoencephalitis/ventriculitis, probably secondary to seeding of the central nervous system by an infected cardiac valve. Of the 202 demented patients who underwent brain-only autopsies, the following types of dementia were found: 129 (63.8%) cases showed changes of severe Alzheimer disease, 21 (10.4%) showed combined neuropathologic abnormalities (Alzheimer disease plus another type of lesion, such as significant ischemic infarcts or diffuse Lewy body disease), 12 (5.9%) cases of relatively pure ischemic vascular dementia, 13 (6.4%) cases of diffuse Lewy body disease, and 8 (4.0%) cases of frontotemporal dementia. The remaining 19 (9.4%) patients showed miscellaneous neuropathologic diagnoses, including normal pressure hydrocephalus and progressive supranuclear palsy. Among the demented patients, 92 (45.5%) had cerebral atherosclerosis, which was moderate to severe in 65 patients (32.2%).
Some of the conditions found at autopsy, had they been known antemortem, would likely have affected clinical management of the patients. Autopsy findings may be used as a quality-of-care measure in patients who have been hospitalized in chronic care facilities for a neurodegenerative disorder.
Archives of pathology & laboratory medicine 02/2004; 128(1):32-8. · 2.58 Impact Factor
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ABSTRACT: We describe an 18-year-old male with an intramedullary spinal cord germinoma in whom the diagnosis was made two years after onset of a progressive myelopathy. Spinal cord germinomas are rare, most having been described in young Japanese adults. They often respond well to radiotherapy. A unique feature of this case was the prolonged time interval between onset of the patient's symptoms and ability to visualize the mass radiographically. A further interesting finding was the infiltrative nature of the tumor surrounding residual spinal cord neurons.
Journal of Neuro-Oncology 06/2003; 63(1):69-73. · 3.21 Impact Factor
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ABSTRACT: In this report, we describe ten cases of pseudo-subarachnoid hemorrhage on computer axial tomography (CT) scan of the head. A pseudo-subarachnoid hemorrhage is a false positive finding by CT of the head in which the scan is interpreted as being positive for a subarachnoid hemorrhage not substantiated by subsequent neuropathologic findings. This study is a retrospective review of postmortem cases brought into the Office of the Chief Medical Examiner for the State of Maryland over a three-year period (from 1997 to 2000). We compared the clinician's impression of the CT scan with the postmortem neuropathology. The clinical diagnosis of subarachnoid hemorrhage was based on misinterpretation of non-contrast CT scans of the head. In six of the ten cases, the reading was performed by a radiologist and in four cases by nonradiologist physicians (emergency room physician, neurologist, or neurosurgeon). All the patients survived between a few hours to a few days after being admitted to the hospital. For most of the cases (80%), the neuropathology showed hypoxic/ischemic encephalopathy. The most common cause of death (four out of ten cases) was narcotic intoxication. This report is submitted so that clinicians and pathologist become more familiar with this entity.
Journal of Forensic Sciences 04/2002; 47(2):360-5. · 1.23 Impact Factor
