End-stage disease

Monster TB, Janssen WM, de Jong PE, de Jong-van den Berg LTPrevention of Renal Vascular End Stage Disease Study Group. Oral contraceptive use and hormone replacement therapy are associated with microalbuminuria. Arch Intern Med 2001 161(16) 2000-5. 

Poorly understood, dose-responsive biomarkers in 1 toxicology species Poorly understood, monitorable Repeat, escalating dose in end stage disease population... 

Because the phase 1 study was planned in end-stage disease patients, the in vitro receptor affinity was similar between monkey and human, and the NOAEL was 10-fold higher than the MABEL/PAD a 3-fold safety margin was applied to the MABEL/PAD-based HED resulting in a safe first-inhuman dose of l.Opg/kg. 

In one study, no pharmacokinetic differences were noted when a single 0.15 mg/kg intravenous dose was given to six cirrhotic patients and six healthy subjects. However, tbe cirrhotic patients had no manifestations of end-stage disease, normal prothrombin times and relatively normal liver function tests. Four had experienced prior encephalopathy [58]. 

The main adverse effect associated with intravenous cidofovir is renal tubular damage (12), although it is usually mild. However, cases of acute renal insufficiency leading to end-stage disease have been reported (13,14). Acute renal insufficiency has also been attributed to topical cidofovir (15). 

In the United States, CHF is the only cardiovascular disease with an increasing incidence. The National Heart, Lung, Blood Institute estimates that current prevalence is 4.9 mfilion Americans with CHF, with an incidence of approximately 400,000 new cases each year. CHF is the leading cause of hospitalization in individuals 65 years and older. Current prognosis is dependent on disease severity, but overall it is poor. Five-year mortality is approximately 10% in mild CHF, 20% to 30% in moderate CHF, and up to 80% in end-stage disease. These poor outcomes are not without substantial cost, estimated at 18.8 billion per year in the U.S. ... 

Yang, M., Pariza, M.W., and Cook, M.E. (2000) Dietary Conjugated Linoleic Acid Protects Against End Stage Disease of Systemic Lupus Erythematosus in the NZB/W FI Mouse, Immunopharmacol. Immunotoxicol. 22, 433 449. 

Keratoprostheses or artificial corneas have been developed for restoring minimal comeal function [104]. However, most of these devices are manufactured from synthetic materials that are not bioresorbable and are therefore outside the scope of this review. In addition, their use is reserved for end-stage disease. 

Usually, the disease progresses very slowly, but can result in cardiac and pulmonary failure. There is no known treatment, except lung transplantation in end-stage disease. 

In contrast to HCC, increased bilirubin levels in metastatic liver disease arise more from biliary obstruction in infiltrative and end-stage disease than from chemotherapy toxicity (Coin et al. 2005). 

Secondary PH with the clinical features of right ventricular strain is common in end-stage disease, but PH also occurs as a primary pulmonary vascular process. Moderate to severe PH is frequently associated with SSc-BLD (54,93,94). In one study, PH presence in SSc-ILD was 17.9% and was strongly associated with a low Pa02, regardless of the extent of fibrosis mean pulmonary artery pressure (PAP) was disproportionate to PFT impairment in 33% of patients (94). 

Kelly K, Hertz ML Obliterative bronchiolitis. In Maurer JR, ed. Surgical approaches to end-stage disease Lung transplantation and volume reduction. Philadelphia WB Saunders, 1997 319-338. 

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