Biomedical subjects
Publications and source records attributed to B Azzarelli.
An 8-year-old boy developed severe systemic hypertension during resection of an intramedullary tumor. The histological, ultrastructural and immunocytochemical characteristics of the tumor are those of a gangliocytoma. Based on the demonstration of tyrosine hydroxylase in neuronal tumor cells, it is postulated that catecholamine secretion was responsible for the systemic hypertension.
The Schwartz-Jampel syndrome (SJS) is a rare congenital multisystem disorder of unknown pathogenesis which is characterized by distinct faces, skeletal deformities, joint contractures, short stature, muscle hypertrophy, clinical myotonia, and continuous muscle fiber activity. The inheritance pattern of SJS has been assumed to be autosomal recessive. We report the occurrence of the classic SJS syndrome in both a father and son in a non-consanguineous family, suggesting that SJS has the potential for a dominant pattern of inheritance.
This report documents the occurrence of an extrarenal nephroblastoma from which a cerebellar metastasis developed in a four-year-old girl with spina bifida. The second tumor became symptomatic two years after the resection of the primary, suggesting a treatment effect as a factor for the delay in the growing of the metastatic neoplasm. Histologic and ultrastructural features of the metastasis were similar to those described in Wilms' tumors of the kidney. The pathogenesis of this exceptional association, including malformation, malignancy, and unusual site of metastasis, is discussed.
We present the clinical findings in affected members of a large kindred with Gerstmann-Sträussler-Scheinker disease. Sixty-four patients exhibited progressive ataxia, dementia, and parkinsonian features. Inheritance appears to be autosomal dominant. Impaired smooth-pursuit eye movements, defective short-term memory, clumsiness of the hands, and ataxia of gait develop in the late 30s to early 60s. Eye movement abnormalities are characteristic of cerebellar dysfunction. Dementia progresses gradually over several years. Later, rigidity and bradykinesia appear and, at this stage, there is often psychosis or severe depression with rapid weight loss. Death occurs in 6 months to 2 years after onset of rigidity. Magnetic resonance imaging in 2 affected individuals showed cerebellar atrophy. There is decreased T2 signal in the basal ganglia, consistent with iron deposition.
Azzarelli et al reported an Indiana kindred affected by a hereditary disorder, characterized clinically by ataxia, parkinsonism, and dementia. Recently, we studied neuropathologically the 3rd and 4th cases that came to autopsy among the patients of this family. As in 2 patients examined previously, amyloid plaques were widespread throughout the cerebrum and the cerebellum, whereas neurofibrillary tangles were numerous in the cerebral cortex, the hippocampus, and the substantia innominata. Amyloid plaques were not recognized by polyclonal antibodies against the Alzheimer's disease amyloid A4 protein, but did contain epitopes recognized by antibodies against a prion protein. Spongiform changes were occasionally observed and were mild. Our findings indicate that this familial disorder is a form of or is related to Gerstmann-Sträussler-Scheinker disease. The consistent presence of numerous neurofibrillary tangles may be important in differentiating a distinct subgroup of patients with familial Gerstmann-Sträussler-Scheinker disease, and indicates that a disturbance of the cytoskeleton might be part of the neuronal pathology of Gerstmann-Sträussler-Scheinker disease.
Gd-DTPA-enhanced MR images of experimental bacterial meningitis were obtained after Staphylococcus aureus was inoculated directly into the cisterna magna of four dogs. Each animal was studied with both unenhanced and enhanced MR and CT with Gd-DTPA and meglumine iothalamate, respectively. The enhancement patterns resulting from these techniques were compared and images were correlated with histopathology. All animals demonstrated abnormal leptomeningeal enhancement on MR with Gd-DTPA, but only one of four dogs exhibited abnormal contrast enhancement on CT. In these animals Gd-DTPA-enhanced MR also identified complications of meningitis, such as ventriculitis and cerebritis, more effectively than CT did. Unenhanced MR was not helpful in identifying meningitis. Histologic evaluation demonstrated that the abnormal areas of contrast enhancement on MR and CT correlated with inflammatory cell infiltration. However, some regions of mild leptomeningitis, ependymitis, and cerebritis identified histologically did not demonstrate abnormal enhancement. Since the animal model used was clinically and pathologically similar to human meningitis, we propose that Gd-DTPA-enhanced MR will subsequently be found more effective than unenhanced MR and IV contrast-enhanced CT for demonstrating meningitis and its complications in humans.
In some human and experimental leukemias and lymphomas, the pattern of metastasis can be correlated with the homing sites of the normal progenitor cells. In vitro binding assays and homing experiments with murine lymphoma cell lines suggest that the nonrandom distribution of metastasis could be determined by specificity of cell-endothelium binding. A single subcutaneous inoculum of L2C cells in strain II guinea pigs resulted in a predictable stereotyped pattern of metastasis. Leukemic cell infiltrates were mainly observed around veins at specific locations in each organ: in brain, the most superficial leptomeningeal veins; in liver, veins of the portal triads; in lung, peribronchial veins; in kidney, veins of the renal columns; in adrenal gland, capsular veins and veins of the medulla. Those vessels also showed intense leukemic cell binding and diapedesis. This would suggest that the leukemic infiltrates were the result of transvenular traffic in these regions. Because leukemic cells were both in the intra- and extravascular compartments, the direction of the cell migration could not be determined. When L2C cells were injected into the right auricle of normal guinea pigs, leukemic cell binding occurred almost exclusively in veins located in areas of metastasis predilection. In addition, extravasation by diapedesis occurred in high endothelial venules in lymphoid organs, peribronchial veins and veins in the portal triads. Neither leukemic cell binding nor diapedesis occurred at the sinusoidal or capillary levels; extravasation in these vessels results from intravascular proliferation and secondary damage of the vessel wall, not by diapedesis. Our data suggest the existence in several organs of the guinea pig of a widely distributed, yet discrete, system of venular endothelial cells specialized in the traffic of leukemic cells.
Glomus jugulare tumors have the ability to synthesize, store, and secrete biogenic amines. Although the majority of these tumors remain endocrinologically silent, on rare occasions they present either as a pheochromocytoma or with a carcinoid syndrome. We report a 20-year-old male with two intracranial tumors: an intrasellar neoplasm and a glomus jugulare tumor. Catecholamine catabolites in the urine were not increased, and blood pressure was always normal. The pituitary tumor was an adenoma, immunostaining positive for prolactin. The second patient, a 29-year-old hypertensive male, with a glomus jugulare tumor, had increased vanillylmandelic-acid excretion. In both cases, the paraganglioma tumor cells contained numerous dense-core vesicles (125 to 380 nm in diameter) in electron microscopy, and showed intense fluorescence by the sucrose-potassium phosphate-glyoxylic acid method. Using high-performance liquid chromatography and microspectrofluorometry we were able to establish the presence of large amounts of dopamine in the cytoplasm of the tumor cells.
Morphologic studies have thus far failed to demonstrate the nature of the vessel involved in the brain hemorrhages of patients with acute leukemia. A detailed study of such hemorrhages was carried out in a patient with leukemic phase of mycosis fungoides. Plastic-embedded lesions showed that blast cells blocked the lumen of the capillary, leading to severe dilation and rupture of the vessel. The rheologic properties of blast cells in vessels of critical diameters seem to be an important factor in the pathogenesis of intracerebral hemorrhages.
A case history illustrating the potential clinical significance of subependymoma is presented. Fine structural studies indicate that the tumor is composed of cells having the cytoplasmic features of ependyma, astrocytes, and transitional cells. Its composition and structure are alike those in the adult mammalian subependymal layer.
Pathologic changes and distribution of lesions of the spinal cord were studied in 16 patients who suffered from "anoxic" episodes. The lesions were symmetrical and limited to the gray matter. The vulnerability of the spinal cord was most marked in the lumbosacral region, although almost every nucleus throughout the spinal cord was subject to damage.
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Experimental allergic encephalomyelitis, a demyelinating disease with marked similarity to multiple sclerosis, was produced in two of 12 dogs. All dogs were studied with serial MR imaging. T1- and T2-weighted MR images were obtained both before and after IV Gd-DTPA. Multiple, new periventricular white matter demyelinating lesions were observed after each clinical episode of the disease. Like multiple sclerosis, the acute lesions of experimental allergic encephalomyelitis on T2-weighted MR images were indistinguishable from the older, more chronic lesions. However, after Gd-DTPA, there was bright paramagnetic enhancement of the acute lesions and, in one animal, no enhancement of the chronic lesions on T1-weighted MR images. At necropsy, the differences in the MR paramagnetic enhancement correlated well with the relative histologic age of the demyelinating lesions. Our results suggest that MR with Gd-DTPA may be used to differentiate acute, active demyelinating lesions from the more chronic, inactive lesions in this animal model.