The diversity of its causes, the unpredictability of its clinical course, and our expanding knowledge of the conditions that may exacerbate or retard its progression suggest that glomerular sclerosis cannot be attributed to a single aberration in glomerular physiology. Nonetheless, the welter of clinical and experimental observations is beginning to yield a pattern. Agents or conditions injurious to glomerular epithelium tend to cause glomerular sclerosis. Agents or conditions that induce short-term or long-term activation of mesangial cells may lead to glomerular sclerosis. Indeed, one contribution of the healthy epithelium may be to serve as a tonic inhibitor of the intraglomerular processes arising from mesangial-cell activation. Long-term activation of the mesangium is associated with the proliferation and infiltration of cells and with the expansion of the mesangial matrix--the antecedents of sclerosis. We anticipate that different diseases associated with glomerular sclerosis will be found to depend to varying extents on these two potential mechanisms of sclerosis. Beyond a certain threshold of glomerular injury, glomerular diseases share an additional factor: the capacity of both intrinsic cells and infiltrating cells to alter the microenvironment of the glomerulus so that sclerosis progresses inexorably long after the disappearance of the initiating insult. Several potential risk factors may contribute to the progression of chronic renal disease. These factors include systemic hypertension, proteinuria, hyperlipidemia, high protein intake, and probably conditions that lead to glomerular hypertrophy. Interventions designed to minimize the potential contribution of these factors to the progression of renal insufficiency may halt or slow the loss of function of the kidney. Clinical trials designed to examine the effects of these factors on the progressive course of renal insufficiency will help to establish their role and relative importance in humans.

As a long-term dialysis therapy, CAPD has attractive features for use in children (in whom access to the circulation and immobility are often problems), adults in whom blood access is difficult, patients with diabetes, patients prone to hypotension, and patients seeking independence from a machine or medical facility. CAPD and related procedures are still evolving and improving. Efforts to reduce the rates of peritonitis are ongoing and should decrease the rates of treatment dropout and increase the use of this alternative method of dialysis. Continued research toward improvements in catheter configuration and connection devices and the tailoring of technique to meet the particular needs of patients have made peritoneal dialysis an acceptable replacement therapy in patients with end-stage renal disease. Neither peritoneal dialysis nor hemodialysis is the superior long-term dialysis therapy for all patients; the choice depends on numerous medical, social, geographic, and life-style considerations.

Many knee injuries that previously caused disability can now be diagnosed accurately and treated successfully. Arthroscopy has been instrumental in this progress. The anterior cruciate ligament, which is an important stabilizer of the knee, is commonly injured. Disruption of the restraint provided by the ligament results in an unstable knee that can give way during pivoting motions. Early reconstruction is usually effective in restoring stability and improving function. Considerable progress has been made in knee bracing. However, prophylactic bracing has not been demonstrated to be effective in preventing knee injuries.

Carotid endarterectomy is a commonly performed but controversial procedure. We developed from the literature a list of 864 possible reasons for performing carotid endarterectomy, and asked a panel of nationally known experts to rate the appropriateness of each indication using a modified Delphi technique. On the basis of the panel's ratings, we determined the appropriateness of carotid endarterectomy in a random sample of 1302 Medicare patients in three geographic areas who had had the procedure in 1981. Thirty-five percent of the patients in our sample had carotid endarterectomy for appropriate reasons, 32 percent for equivocal reasons, and 32 percent for inappropriate reasons. Of the patients having inappropriate surgery, 48 percent had less than 50 percent stenosis of the carotid artery that was operated on. Fifty-four percent of all the procedures were performed in patients without transient ischemic attacks in the carotid distribution. Of these procedures, 18 percent were judged appropriate, as compared with 55 percent judged appropriate in patients with transient ischemic attacks in the carotid distribution. After carotid endarterectomy, 9.8 percent of patients had a major complication (stroke with residual deficit at the time of hospital discharge or death within 30 days of surgery). We conclude that carotid endarterectomy was substantially overused in the three geographic areas we studied. Furthermore, in situations in which the complication rate is equal to or above the study's aggregate rate, carotid endarterectomy would not be warranted, even in cases with an appropriate indication, because the risks would almost certainly outweigh the benefits.