Brain biopsy specimens from five patients with Alzheimer's disease obtained in the course of a trial of intracerebroventricular bethanechol were studied by immunohistochemical (antibody to A4 peptide) and ultrastructural techniques, with particular emphasis on the microvessels. In some cases, numbers of A4-immunoreactive lesions (senile plaques) correlated well with numbers of plaques demonstrable by silver stains. Prominent A4-immunoreactive amyloid angiopathy was seen in one patient. The patient with severe cerebral amyloid angiopathy (CAA) showed extensive arteriolar deposition of amyloid filaments with apparent destruction of the media but remarkably intact endothelium. A cell of origin for amyloid filaments was not apparent, although close proximity to smooth muscle cell remnants in the arteriolar media suggested this as one possible cell of origin. Frequent vessels showed medial or adventitial collagen deposition, even when the amount of amyloid was minimal or negligible. Thus relatively severe CAA can exist in the absence of overt endothelial injury, although related studies on this tissue indicate definite abnormalities of the blood-brain barrier. Conversely, destruction of smooth muscle cells and collagen deposition in vessel walls may be the cellular correlates of arteriolar weakening that can lead to CAA-related brain hemorrhage.
Fabry''s disease, a rare X-linked disorder of glycosphingolipid metabolism, can present as an insidious dementia in middle or later life. This genetic disorder produces a deficiency of α-galactosidase A which results in the deposition of glycosphingolipids in blood vessel walls in the brain as well as in the kidney, heart, peripheral nerves, and other organs. Among the cerebrovascular manifestations of this disorder is a vascular dementia from involvement of multiple small penetrating blood vessels. Fabry''s disease is a consideration in the work-up of an otherwise unexplained vascular dementia, particularly in males less than 65 years of age.
From March 1977 to December 1978, postmortem examination was performed at Wadsworth Veterans Administration Medical Center for 20 patients who had had nosocomially acquired Legionnaires' disease. Seventeen patients died during the acute illness due to Legionnaires' disease, and three patients died after clinical resolution of the acute process. The only consistent postmortem findings were limited to the lungs. Confluent bronchopneumonia, and less frequently lobar pneumonia, was present in most cases. Although a spectrum of microscopic pulmonary findings was observed, the characteristic histologic features of acute Legionnaires' disease were an extensive intra-alveolar exudation of macrophages and neutrophils in varying proportions, erythrocytes, and fibrin. Lysis of the inflammatory cells was frequently found. Areas of coagulative necrosis of the lung parenchyma and edematous thickening of the alveolar septa were typically seen. Microscopy of lung tissue from the three patients who died after clinical resolution of the acute process revealed organized pneumonia, with patchy organization of the intra-alveolar exudate and focal obliteration of the alveolar septal framework. Associated postmortem findings were fibrinous endocarditis in one case and hemorrhagic infarction of the adrenal glands in two cases. Electron-microscopic examination of the lungs revealed as many as 23 separate bacillary profiles within a single macrophage. Septate binary fission or spore-like structures were not observed.
Aluminum (Al) may cause both osteomalacia and encephalopathy in dialysis patients. Little is known about the biology of Al. This study examined the initial distribution kinetics of Al and its biological effects after injections of 1 mg/kg/day into dogs for 3 to 5 weeks. Following one intravenous dose, the plasma half-life (x +/- SE) was 276 +/- 51.8 min, with an apparent volume of distribution of 1.30 +/- 0.17 liters or 5.90 +/- 0.30% body wt; 10 to 21% of administered Al was excreted in the urine over 150 min, and the renal contribution to plasma clearance of Al correlated with GFR (r = 0.77, P less than 0.05). The total plasma clearance of Al (4.43 +/- 2.83 ml/min) exceeded the renal contribution to plasma clearance (1.94 +/- 0.36 ml/min) in each dog, and in only two instances did the renal contribution reach 50% of total plasma clearance. Serum calcium rose from 9.4 +/- 0.2 to 11.1 +/- 0.3 mg/dl and immunoreactive parathyroid hormone (iPTH) fell by 27 +/- 4% following one Al injection. With repeated Al injections, serum calcium increased from baseline levels of 10.2 +/- 0.07 mg/dl to 11.1 +/- 0.22 and 11.3 +/- 0.46 mg/dl after 1 and 2 weeks, respectively. Renal function declined in all dogs, and serum creatinine exceeded 3.5 mg/dl in four; over the 5 weeks of study, serum calcium correlated with serum creatinine (r = 0.91, P less than 0.001). Liver, kidney, and spleen showed the highest tissue content of Al, and there was substantial uptake by bone; the parathyroid content of Al was modest.(ABSTRACT TRUNCATED AT 250 WORDS)
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