The clinical significance of extracellular matrix in gangliogliomas.

Based on in vitro studies which demonstrate that collagen IV and laminin inhibit the proliferation and invasiveness of glioma cells, we investigated the clinical significance of these extracellular matrix proteins (ECM) in patients with gangliogliomas, tumors in which ECM is often a prominent feature. Our study compared the relative presence and deposition pattern of collagen IV and laminin in 19 gangliogliomas and in 18 gliomas without ganglion cell differentiation (8 low-grade astrocytomas, 7 anaplastic astrocytomas, and 3 anaplastic mixed gliomas). We also examined whether the presence of collagen IV and laminin correlated with other features often observed in gangliogliomas, including perivascular lymphocytic inflammation, granular bodies, microcalcification, and subarachnoid extension, and whether any of these features were associated with the patient's clinical course. Significant deposition of collagen IV and laminin was found in 9 gangliogliomas (47%), but in none of the other gliomas. The presence of these extracellular proteins in gangliogliomas correlated with both perivascular inflammation (P = 0.003), and involvement of the leptomeninges by tumor (P = 0.008). The duration of symptoms prior to surgical resection was significantly longer for patients whose tumors showed extracellular deposition of collagen IV and laminin than for patients whose tumors lacked deposition of these proteins (mean 13.7 vs 5.1 years; P = 0.02). In addition, the duration of symptoms was significantly longer for patients whose tumors exhibited perivascular inflammation than for patients whose tumors displayed little or no perivascular inflammation (mean 14.8 vs 4.8 years; P = 0.01). These findings suggests that collagen IV and laminin and perivascular inflammation are related to the indolent behavior of gangliogliomas.

Increased vulnerability to demyelination in streptozotocin diabetic rats.

Demyelination is a prominent feature in nerve biopsies of patients with diabetic neuropathy. The mechanism is unknown because diabetic rodents, unlike humans, do not consistently develop segmental demyelination. We examined how diabetes influences toxicant-induced demyelination, remyelination, Schwann cell nerve growth factor receptor (p75) expression, and endoneurial macrophage apolipoprotein E (apo E) synthesis in diabetic rats. Postnatal day 17 (P17) rats were given 110 mg/kg streptozotocin intraperitoneally and then fed a diet containing metallic tellurium (Te) from P20 to P27 to induce demyelination. Transverse electron micrographs and immunostained longitudinal cryosections were prepared from sciatic nerve during demyelination and remyelination. Diabetic rats had a mean serum glucose concentration of 490 mg/dl and consumed equivalent doses of peroral Te. The number of demyelinated fibers in electron micrographs was increased significantly by 17% (P < .0011). Endoneurial density of p75-stained Schwann cells was increased in diabetic rats in proportion to the increased number of injured internodes. Density of apo E- and ED1-positive macrophages also was significantly increased in diabetes. There was no delay in macrophage myelin clearance. and remyelination was not compromised. Increased Schwann cell vulnerability to stress, by increasing the turnover rate of myelinated units, may explain why myelin defects accumulate after long-standing diabetes.

Escherichia coli lobar pneumonia: fatal infection in a patient with mental retardation.

Lobar pneumonia due to Escherichia coli is rare. Most lobar pneumonias are caused by either Streptococcus pneumoniae or Klebsiella pneumoniae, and most E coli pneumonias are bronchopneumonias. We report an acute fulminant course of E coli lobar pneumonia in a 37-year-old patient who was profoundly retarded, institutionalized, and nonimmunosuppressed and who died within 2 days of developing initial symptoms. Antemortem blood and postmortem blood and lung specimens isolated pure cultures of E coli. The source of infection in E coli lobar pneumonia is not clear in this patient or in the few cases that have been reported. We postulate that nasopharyngeal colonization of E coli in those who are institutionalized with mental retardation may predispose these patients to E coli pneumonia. Our case illustrates features of pneumonias that are unique in the institutionalized, mentally retarded patient population (ie, the relatively high prevalence of nasopharyngeal colonization of E coli, a higher incidence of E coli pneumonia than in other institutionalized populations, the often fulminant course of the disease), as well as the need for early, aggressive treatment including antibiotics effective against gram-negative bacteria.

Blast-like cells in the cerebrospinal fluid of young infants: further characterization of clinical setting, morphology and origin.

Blast-like cells in the cerebrospinal fluid (CSF) of neonates have been identified and previously suggested to be of germinal matrix origin. Twelve additional CSF specimens with blast-like cells collected at the University of Texas Medical Branch, Galveston, between 1985-1992 were analyzed. The cytological features of the blast-like cells as well as their associated clinical setting were further characterized by the authors. All patients in the study were young infants with hydrocephalus and nearly all underwent placement of a ventriculoperitoneal (VP) shunt at the time the CSF specimen was collected. In addition, a cytologic preparation of germinal matrix cells obtained from an autopsy specimen was analyzed, which closely resembled the blast-like cells. These data provide additional evidence that blast-like cells originate from the germinal matrix.

Retinoblastoma-like phenotype expressed in medulloblastomas.

The previous demonstration of rod-opsin and S-antigen (S-Ag), a protein which arrests visual phototransduction, in retinoblastomas and in a subgroup of medulloblastomas has suggested a relationship between these tumors. We examined 17 medulloblastomas for the presence of a retinoblastoma-like phenotype. Overall 41% of the tumors were immunoreactive for S-Ag. Two tumors with well-differentiated Flexner-Wintersteiner rosettes were also immunoreactive for S-Ag, but not for epithelial membrane antigen (EMA). In contrast, most ependymal rosettes in two ependymomas stained positive for EMA along the luminal surface, consistent with a previous study, and were negative for S-Ag. Because calcification in areas of necrosis is a near constant finding in retinoblastomas, the medulloblastomas were evaluated for the presence of calcification, using Von Kossa staining. Forty-one percent showed calcification in areas of necrosis and 29% were positive for both calcification and S-Ag immunoreactivity. There was a statistically significant concordance between calcification and S-Ag immunoreactivity in the medulloblastomas (p < 0.05). Despite similar phenotypic features, a shared mechanism of tumori-genesis for retinoblastomas and the subgroup of medulloblastomas with photoreceptor differentiation could not be identified since all 17 medulloblastomas were found to express functional Rb protein, as indicated by positive nuclear immunoreactivity.

Disseminated Conidiobolus infection with endocarditis in a cocaine abuser.

A crack cocaine abuser developed disseminated infection caused by a species of Conidiobolus not known to cause disease in vertebrates. The fungus gained entry via skin abrasions on the lower extremities, spread through the hematogenous route, and caused endocarditis. There was evidence of fungal infection in the lungs, heart, kidneys, skeletal muscles, and brain. An additional complication was extensive rhabdomyolysis, with a marked elevation of creatine kinase of up to 1.2 million U/L.