Biomedical subjects

J C Kaufmann

Publications and source records attributed to J C Kaufmann.

At least 19 recordsLinked to original sources

PubMed1993

Primary cerebral fibrosarcomas. Clinicopathologic study and review of the literature.

BACKGROUND: Primary of the brain and meninges are uncommon tumors. Information regarding optimum treatment is limited due to their rarity, and the best form of therapy is not yet known. METHODS: Nine patients between the ages of 22 and 61 years with primary fibrosarcomas confined to the brain and meninges were studied clinicopathologically. Tumors were superficially located in five patients and intracerebrally or deep in four patients. Treatment consisted of maximum feasible surgical resection (seven patients, gross total; one, subtotal; one, no surgery before death) and radiation therapy (45-60 Gy conventional fractionation) in eight of nine patients. RESULTS: Fibrosarcomas were moderate or high grade in seven of nine patients (78%). Immunohistochemical reactions with antisera to glial fibrillary acid protein (GFAP), cytokeratin, vimentin, desmin, and S-100 demonstrated vimentin positivity in five of nine patients and cytokeratin positivity in two of nine patients. Individual GFAP-positive cells were seen in two cases, thought to represent trapped reactive astrocytes. None were S-100-positive or desmin-positive. Eight patients have died, with a median survival time of 7.5 months (range, 1 day-96 months). Local recurrence developed in eight patients and distant recurrence in six patients. Systemic metastases developed in four patients (50%) and meningeal seeding in four patients (50%). Longer survival was observed in superficially located tumors (range, 7.5 months-96 months) compared with intracerebral tumors (range, 1 day-9 months). CONCLUSIONS: Primary fibrosarcomas of the brain are uncommon tumors, usually of high histologic grade, with a high rate of local recurrence. Their propensity for meningeal and distant relapse distinguishes them from tumors of glial origin. Immunohistochemistry is of limited diagnostic value, although it may facilitate exclusion of other diagnoses. Because the prognosis after conventional surgery with 50-60 Gy external beam radiation therapy is relatively poor, the authors recommend more aggressive therapy with maximal feasible resection followed by external beam radiation therapy to doses of 64-66 Gy. When effective chemotherapy is established for soft tissue sarcomas of the extremities, this should be evaluated in view of the high incidence of distant metastases.

Adult↗

PubMed1991

Pathological and molecular biological features of a myelopathy associated with HTLV-1 infection.

We report the pathological and molecular biological findings of human T-cell lymphotropic virus type 1 (HTLV-1) infection of the spinal cord in a patient with a chronic progressive myelopathy. Light microscopy disclosed loss of myelin and axons, thickening of blood vessels and a lymphocytic cell infiltrate in the spinal cord especially at the cervical and thoracic levels. Electron microscopy confirmed the vascular appearance seen with light microscopy but virus particles were not observed. The HTLV-1 gag gene could be amplified (by polymerase chain reaction) from cervical spinal cord tissue while not from elsewhere in the neuroaxis. The presence of HTLV-1 genomic material in spinal cord tissue has not been previously reported.

DNA, Viral↗

PubMed1990

An immunohistochemical study of papillary tumors in the central nervous system.

An immunohistochemical study was performed on the paraffin sections of 25 tumors in the central nervous system (CNS) with prominent papillary configurations. These tumors included seven metastatic papillary carcinomas, six choroid plexus tumors, four papillary ependymomas, two myxopapillary ependymomas, two papillary pituitary adenomas, two astroblastomas, one papillary meningioma, and one anaplastic astrocytoma with significant papillary changes. The panel of antibodies applied included anti-glial fibrillary acidic protein (GFAP), anti-carcinoembryonic antigen (CEA), anti-vimentin (VM), anti-S-100 protein (S-100 P), anti-cytokeratin, and anti-prealbumin antisera. All ependymomas and astroblastomas examined expressed both VM and GFAP, which were either absent or focally expressed in choroid plexus tumors. In contrast, all choroid plexus tumors showed anti-cytokeratin immunoreactivity that was absent in the ependymomas and astroblastomas. Five choroid plexus tumors also expressed S-100 P, thus differentiating them from metastatic carcinoma that showed negative immunostaining. Anti-CEA antisera immunoreactivity was seen in six metastatic tumors, whereas none of the primary CNS tumors expressed CEA. Prealbumin was expressed in four choroid plexus tumors and two metastatic tumors. Immunohistochemical typing using a panel of antibodies has allowed the differentiation of most of the papillary tumors in the CNS examined in this study.

Astrocytoma↗

PubMed1990

Encephalopathy in liver transplantation: neuropathology and CMV infection.

The clinical histories and pathological findings of 27 autopsied cases of orthotopic liver transplantation (OLT) were reviewed. Fatal OLT was complicated in 93% of cases by neurological dysfunction, usually manifested by encephalopathy, with or without seizures. The etiology of the encephalopathy was largely multifactorial (44%) or undetermined (20%). Subarachnoid hemorrhage, central pontine myelinolysis, meningitis, brain infarction, polyclonal B cell lymphoma and spinal cord necrosis were common neuropathological findings. These diagnoses were often masked by other systemic illnesses. The role of cytomegalovirus (CMV) in neurologic dysfunction was explored with in situ hybridization and immunohistochemical techniques. OLT cases showed a significantly higher (89%) frequency of CMV genomic material in brain tissue compared to age-matched non immunocompromised (NIC) patients (23%). All OLT cases with encephalopathy of undetermined cause demonstrated usually prominent hybridization to the CMV probe. CMV may be an important cause of encephalopathy in such patients.

Adolescent↗

PubMed1990

The molecular mechanisms of scrapie encephalopathy and relevance to human neurodegenerative disease.

We have investigated alterations in the structure and function of nuclei isolated from normal and pathological brains in a number of neurodegenerative diseases including scrapie and Alzheimer's disease. Here we summarize both general and specific changes in chromatin structure, gene expression, and neuropathological features for each encephalopathy and compare them in terms of their molecular biological similarities and differences. While both scrapie and Alzheimer's disease share a number of common alterations in genomic organization and gene activity during the pathogenic process, each neurological disease appears to operate on fundamentally different mechanisms.

Alzheimer Disease↗

PubMed1989

Neuropathology of heart transplantation.

The neuropathology of 18 cardiac transplant recipients was reviewed with the clinical findings. Pathological changes were noted in the central nervous system (CNS) in 94% of the patients, the most frequent being cerebral vascular in origin (72%). Eight patients (44%) had multiple cerebral infarcts and morphologically, a large number of these antedated the transplantation. In addition 4 patients had acute focal ischemic changes which occurred after transplantation. Intracranial hemorrhage was noted in 5 patients (28%), including one case of fatal intracerebral hemorrhage following an acute hypertensive episode after the transplantation. While systemic infection was common (10 patients), there were only 5 cases of intracranial infection; including 3 cases of cytomegalovirus infection, one of candidiasis and one of aspergillosis. Post-transplant seizures, occurring in a third of the patients, were related to a variety of causative factors such as sepsis, intracranial hemorrhage, cerebral ischemia, metabolic encephalopathy and cyclosporin neurotoxicity. Of note in this series was the absence of CNS lymphoma or other systemic lymphoproliferative disorder.

Adolescent↗

PubMed1988

Fusiform intracranial aneurysms. Clinicopathologic features.

Seven fusiform aneurysms were found at autopsy in five patients (two males and three females) over a 13-year period. The subjects were between 56 and 65 years of age. The basilar trunk was the most frequent site. Four aneurysms were of giant proportions and contained laminated thrombi. Subarachnoid hemorrhage occurred in four patients. Microscopic examination of the aneurysm walls revealed atheromatous degeneration, focal wall attenuation, mural hemorrhage, rupture, and acute and chronic inflammatory cell infiltration. These findings suggest that rupture is not rare and that atherosclerosis is but one mechanism in the pathogenesis of these lesions.

Aged↗

PubMed1988

Jakob-Creutzfeldt disease associated with Wernicke encephalopathy.

Wernicke disease (WD) is a complication of alcoholism and malnutrition and usually presents acutely and is characterized by disturbances of consciousness, paralysis of the external ocular muscles, and ataxia. The disease results from deficiency of vitamin B 1, or thiamine, an essential coenzyme in intermediate carbohydrate metabolism. On the other hand, Jakob-Creutzfeldt disease (J-C) results from infection with an unconventional agent with a long incubation period and is characterized by a rapidly progressive dementia and histologically by a spongiform encephalopathy associated with neuronal destruction and pronounced astrogliosis. Combination of both diseases has not been reported in the literature previously and their relationship is uncertain. We present 3 cases with this interesting association and consider their relationship.

Aged↗

PubMed1988

Creutzfeldt-Jakob disease without periodic sharp wave complexes: a clinical, electroencephalographic, and pathologic study.

A comparison of clinical, EEG, and pathologic features was carried out on all cases of autopsy-proven Creutzfeldt-Jakob disease (CJD) studied over the last 10 years. Periodic sharp wave complexes (PSWCs) were present in three but absent in seven patients. Myoclonus was documented in two of the three with and in only one of the seven without PSWCs. The three with PSWCs had severe neocortical and at least mild thalamic involvement; those without PSWCs had more variable disease topography. The diagnosis of CJD should not be rejected if PSWCs are absent.

Aged↗

PubMed1987

A quantitative analysis of blood-brain barrier ultrastructure in the aging human.

The unique ultrastructure of brain endothelial cells restricts nonspecific leakage of blood-borne molecules across the blood-brain barrier (bbb). Human barrier ultrastructure has not been studied extensively because of the rapid ultrastructural degeneration that takes place after death. We have obtained living, structurally normal neocortex and underlying white matter at biopsy from patients of various ages, and have quantitated ultrastructural features that are associated with the bbb so that we could characterize human barrier ultrastructure and determine whether it changes with age. We found that gray matter capillaries have thinner walls than white matter capillaries, and that during aging white matter capillary walls became thinner until they approached the dimensions of those in gray matter. Thinning is due to loss of pericytes and thinning of the endothelial cytoplasm. The mitochondrial density was found to be higher in gray matter than in white matter, but this is a consequence of there being a smaller cytoplasmic volume and not more (or larger) mitochondria. The mitochondrial population did not change with age. Presumptive nonspecific permeability routes (endothelial vesicles, junctional gaps) did not change with age; therefore we found no morphological substrate for increased nonspecific bbb permeability in the aging human. The loss of pericytes, however, suggests that the bbb in the elderly may be less able to compensate for transient leaks.

Aging↗

PubMed1987

Prolonged progressive multifocal leukoencephalopathy without immunosuppression.

Atypical forms of progressive multifocal leukoencephalopathy (PML) may simulate other disorders. A previously healthy 70-year-old female developed unsteadiness of gait, dysarthria, dementia and weakness leading to inanition and death from bronchopneumonia over a 43 month period. The diagnosis of PML was not suspected prior to death. Neuropathologic examination of the brain disclosed characteristic findings of PML-deep bilateral cerebral demyelinative foci with enlarged gemistocytic astrocytes and swollen oligodendrocytes containing intranuclear inclusions. Electron microscopy identified papova virus particles within these inclusions. An underlying source of immunosuppression was not identified either premortem nor at the time of autopsy. The prolonged clinical course, simulating that of a primary degenerative disease, and the lack of apparent immunocompromise are unusual features of PML and lend credence to the suggestions that variations in its expression and course are to be expected.

Aged↗

PubMed1986

Long-term pathological follow-up of cerebral arteriovenous malformations treated by embolization with bucrylate.

We examined 17 intracranial arteriovenous malformations that were resected after treatment by embolization using bucrylate (isobutyl-2-cyanoacrylate). In nine specimens removed 5 days to 16 months after embolization therapy, a series of pathologic changes was seen, including patchy mural angionecrosis (adjacent to bucrylate fragments) up to six weeks after embolization, the presence of bucrylate in vessel walls and fibromuscular intimal cushions, and the occurrence (after several months) of entirely extravascular bucrylate. Occasional parts of recanalized vascular malformations were identified. Bucrylate was present within arteriovenous malformations as late as 16 months after embolization, although the amount appeared to be diminished. These findings suggest a specific sequence of events in the interaction between bucrylate and mural components within the malformations and may explain some important complications of embolization therapy (e.g., delayed hemorrhage after embolization).

Adolescent↗

PubMed1986

Gerstmann-Sträussler-Scheinker disease: autopsy study of a familial case.

Postmortem neuropathological findings in a patient with biopsy-proved familial Gerstmann-Sträussler-Scheinker disease of eight years' duration included severe spongy change in the neocortex, extensive and often large amyloid deposits throughout the cerebral hemispheres and cerebellum, and severe astrocytic gliosis throughout all areas of gray and white matter within the brain. The degree of cortical spongy change was much greater than that in relatives who died with a similar clinical history, indicating the phenotypic heterogeneity in this familial disorder.

Central Nervous System↗

PubMed1986

Severe cerebellar degeneration in a patient with T-cell lymphoma.

A 53-year-old man with an aggressive T-cell lymphoma was found at autopsy to have severe cerebellar degeneration, presumably as a 'remote' effect of malignancy. The degree of cerebellar atrophy was unusually pronounced and widespread, involving both Purkinje cell and granule cell layers, although patches of preserved and essentially normal cerebellar cortex were identified. This case is of particular interest in view of data which indicate that cerebellar Purkinje cells and T-lymphocytes share antigenic surface markers.

Atrophy↗

PubMed1986

Role of free radical scavenger in protection of spinal cord during ischemia.

Previous work in our laboratory established an experimental model for the production of paraplegia in the anesthetized normothermic adult mongrel dog. The current study involves 24 animals divided into two equal groups: Group 1 served as control, and Group 2 received treatment with scavenger agent. Vascular occlusive clamps were placed on the thoracic aorta proximal to the left subclavian artery, on the left subclavian artery at its origin, and on the distal thoracic aorta at the diaphragm for 30 minutes. In Group 1,200 ml of normal saline solution (37 degrees C) was perfused into the occluded aortic segment at the rate of 0.33 ml per kilogram of body weight per minute. In Group 2, 90% dimethyl sulfoxide (DMSO) in a dose of 0.1 gm/kg in normal saline solution (37 degrees C) for a total volume of 200 ml, was likewise injected into the occluded aortic segment at the same infusion rate. Animals were observed for evidence of paresis in the postoperative period. Microscopic analysis revealed evidence of ischemic myelopathy in the control group but none in the treated group. Under the conditions of this experiment, we conclude that the scavenger agent DMSO has a highly protective effect on the spinal cord during ischemic insult.

Animals↗

PubMed1986

An unusual form of motor neuron disease following a cat bite.

A case of motor neuron disease with clinical and pathological resemblance to amyotrophic lateral sclerosis (ALS) in a woman who was severely bitten on the ankle by a cat is described. Weakness first appeared at the ankles and relentlessly advanced proximally, terminating in death from pulmonary failure in a year. A number of unusual features that are uncharacteristic of ALS were found that included a markedly elevated antinuclear antibody titre in the serum and the presence of prominent oligoclonal bands in the cerebrospinal fluid. The spinal cord showed loss of anterior horn cells and pyramidal degeneration that are characteristic of ALS, but an extraordinary finding was the presence of transmural granulomatous inflammation of numerous small and medium sized vessels, especially veins, in the subarachnoid space around the cord. There were also inflammatory changes in the brainstem and spinal cord consisting of microglial and astrocytic nodules and perivenous cuffing by mononuclear cells. Ill-defined hyaline eosinophilic cytoplasmic inclusions were seen in some remaining anterior horn cells. No viral particles were found by electron microscopy despite an extensive search. Virological studies were inconclusive but there is reason to believe that this patient's illness was caused by an as yet unidentified virus.

Amyotrophic Lateral Sclerosis↗

PubMed1985

The histotoxicity of cyanoacrylates. A selective review.

Cyanoacrylates, a group of rapidly polymerizing adhesives, have found widespread uses in oral and general surgery as well as surgical subspecialties, for example as hemostatic and anastomotic agents. They have been utilized most recently as materials for embolotherapy of complex cerebral and extra-cerebral vascular anomalies. The histopathology that results from their deposition in human tissues is thus an important consideration, and the subject of this review. Particular attention is given to the fate of cyanoacrylates in cerebral lesions after iatrogenic embolization procedures. The apparent toxicity of these plastics on blood vessel walls is discussed in relation to experimental observations. It is imperative that clinicians who use this group of substances evaluate their potential functions in the light of the pathologic findings.

Animals↗

PubMed1985

Fatal intracranial arterial dissection: clinical pathological correlation.

The clinical pathological features of fatal arterial dissection confined to the intracranial vessels are described. Three patients with anterior circulation dissections presented with focal ischaemic neurological deficits and pathological examination of involved vessels revealed a dissection plane between internal elastic lamina and media accompanied by intravascular thrombosis. Three of four patients with posterior circulation dissections had clinical pathological features of subarachnoid haemorrhage and at necropsy had transmural dissections. In contrast to previous reports, primary vasculopathies either degenerative or inflammatory were not identified in affected vessels. The pathogenesis of intracranial arterial dissection is discussed and the clinical features are correlated with the pathological abnormalities.

Adolescent↗