Focal sclerosis

It has been shown that subjects with renal diseases such as IgA nephropathy, membranous prohferative glomerulonephritis, focal sclerosis, and lupus nephritis have levels of endothelin that are significantly higher than those in healthy subjects [209]. Increased circulating ET-1 concentrations and urinary excretion of ET-1 have been observed in patients treated with the nephrotoxic immunosuppressive agents cyclosporine A and tacrolimus (FK-506) [210]. Other nephrotoxic agents, such as cisplatin, also increase urinary excretion of ET [211]. In patients with chronic renal disease, urinary excretion of ET-1 is significantly elevated when compared to normal values (Table 10). 

Studies regarding respiratory effects in animals following inhalation exposure to barium are limited to two reports (Hicks et al. 1986 Tarasenko et al. 1977). Pulmonary lesions (perivascular and peribronchial sclerosis and focal thickening of the interalveolar septa) were observed in rats following intermediate inhalation exposure to 3.6 mg barium/m as barium carbonate dust (Tarasenko et al. 1977). Bronchoconstriction was reportedly noted in guinea pigs following inhalation for an unspecified period of time to 0.06 mg barium/m /min as aerosolized barium chloride solution (Hicks et al. 1986). 

During each blood pressure measurement session, five measurements are recorded for each animal. The blood pressure is taken as the mean of the last 3 recordings. Urinary protein is determined by the Pyrogallol Red-molybdate method (RA-1000 Tech-nicon). Urinary sodium, creatinine and urea and serum electrolytes, creatinine, albumin, cholesterol and triacylglycerols are measured by a standard autoanalyser technique. Kidney samples are fixed in formalin and embedded in paraffin. Sections are stained with the periodic acid/Schiff technique. Focal glomerular sclerosis is scored semiquantitatively by light microscopy. 

Gradual onset of stroke over hours or days, rather than seconds or minutes, is unusual and is much more likely to occur in ischemic than in hemorrhagic stroke. If the onset is gradual, and not Ukely to be caused by low flow or migraine (Ch. 8), then a structural intracranial lesion must be excluded. In younger patients, multiple sclerosis should also be considered. However, focal neurological deficits that develop over hours, or up to two days, in elderly patients are still most likely to have a vascular cause since vascular disease is so common in older patients. 

Howland DS, Liu J, She Y, Goad B, MaragaMs NJ, Kim B, Erickson J, Kulik J, DeVito L, Psaltis G, DeGennaro LJ, Cleveland DW, Rothstein JD (2002) Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SODl mutant-mediated amyotrophic lateral sclerosis... 

Figure 18.1. MRI signal abnormalities in the brain and spinal cord in a 55-year-old woman with multiple sclerosis. (A) FLAIR (Fluid attenuated inversion recovery) image of axial brain image at the level of the lateral ventricles. Arrows point to hyperintense periventricular lesions demonstrating a characteristics MS demyelination pattern (B) T2W image of sagittal view of the spinal cord of the same individual, demonstrating focal bright signal (arrow) representing demyelination in the cervical spinal cord.

Mezaki T, Kaji R, Kohara N, Kimura J. Development of general weakness in a patient with amyotrophic lateral sclerosis after focal botulinum toxin injection. Neurology 1996 46(3) 845-6. 

Liver biopsies have been performed in some patients with chronic vitamin A intoxication. Perisinusoidal fibrosis and massive accumulation of lipid-storing cells were found. Impairment of blood flow by perisinusoidal fibrosis probably resulted in secondary alterations in hepato-cytes, including cellular atrophy and formation of cytoplasmic bullae. Histological examination also showed central vein sclerosis and focal congestion associated with perisinusoidal storage. The vitamin A concentration in the liver was increased (40-42). 

Th2 cells are pathogenic in gold salt-induced glomerulopathy in Brown-Norway (BN) rats (this part will be developed below). The analysis of mRNA obtained from kidneys of Buffalo/Mna rats that spontaneously develop a nephrotic syndrome associated with focal segmental glomerular sclerosis revealed an early Th2 biased profile of cytokine expression, consistent with the involvement of Th2 cells in this model of human idiopathic nephrotic syndrome [19]. In minimal change glomerulopathy, an association... 

The most frequent lesion described has been focal segmental glomerulosclerosis (FSGS) progressing to global sclerosis. This lesion has been classically referred to as "heroin nephropathy" and is the lesion seen in Black heroin addicts in the USA. Ninety percent of all... 

Stehman-Breen C, Alpers CE, Fleet WP, Johnson RJ. Focal segmental glomerular sclerosis among patients infected with hepatitis C virus. Nephron 1999 81 37-40. 

Grishman E, Churg J. Focal glomerular sclerosis In nephrotic patients. An electron microscope study of glomerular podocytes. Kidney Inti 975 7 111-122. 

The classic example of demyelination of the CNS is multiple sclerosis (MS), in which a chronic inflammatory lesion is characterised by a sharply demarcated plaque containing preserved axons denuded of myelin. Demyelination also occurs in infectious diseases such as progressive multifocal leucoencephalopathy and acute disseminated leucoencephalitis, but it is the disseminated focal form of MS that will be addressed in this review article. 

Acute renal toxicity may occur within days of initiating therapy. Serum creatinine concentration rises and creatinine clearance decreases. Hypertension, hyperkalemia, sodium avidity, and hypomagnesemia may occur. No urine sediment abnormalities are seen. Urinary enzyme excretions increase, but are not reliable indicators of toxicity. Renal biopsy reveals thickening of arterioles, mild focal glomerular sclerosis, proximal tubular epithelial cell vacuolization and atrophy, and interstitial fibrosis. Biopsy is useful to distinguish acute cyclosporine nephrotoxicity from renal allograft rejection, the latter being evidenced by cellular infiltration. ... 

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