Quantitative effects of osmotic diuresis following angiographic contrast administration

Osmotic diuresis resulting from the administration of angiographic contrast poses the potential threat of marked volume losses obligated by the renal excretion of non-reabsorbable solute. We prospectively assessed urinary excretion of solute and water following cardiac angiography in 14 euvolemic subjects without preexisting renal disease, by a protocol that allowed each patient to serve as his own control. During the initial 6 h after the beginning of angiography, contrast administration resulted in increased total osmolar excretion from a control rate of 0.79 +/- 0.09 to 1.09 +/- 0.09 mOsm/min (P less than .05) with a return to control values thereafter. Surprisingly, sodium, potassium, and chloride excretion rates did not differ significantly from control values. After subtraction of the molar contribution of electrolytes, urea, and creatinine from the total osmolar excretion rate, it was apparent that the "residual osmolar excretion rate" of 0.48 +/- 0.05 mOsm/min was markedly elevated over the control value of 0.11 +/- 0.05 mOsm/min (P less than .01), reflecting the excretion of contrast agent. Despite the marked osmotic diuresis, urine output during this period (3.9 +/- 0.2 cc/min) did not differ significantly from the control value of 4.0 +/- 0.3 cc/min. We conclude that marked volume losses are not a necessary concomitant of contrast-induced osmotic diuresis in the euvolemic cardiac patient without renal disease.     

From feedback to reciprocity. Developing a student-centered approach to course evaluation

Reforms to medical education have refocused curricula on the need to produce primary care physicians through a problem-based, student-centered, community-oriented, and integrated approach to instruction. Course evaluations, originally designed for traditional lecture-based, teacher-centered curricula, provide inadequate input from students to support curriculum planning and change and to determine appropriate mixes of educational methods. At the University of Toronto Faculty of Medicine, a unique community-centered course, called "Health, Illness and the Community," developed a student-centered course evaluation to provide adequate student input to support curriculum planning and change. A 35-item evaluation was developed to obtain data to identify student concerns, student learning styles, and preferred community agency utilization. The results suggest that student-centered course evaluation can play a role in managing and identifying key relationships in integrated and systematic courses as well as establishing a method for continual improvement.     

Surgical resection following interleukin 2 therapy for metastatic renal cell carcinoma prolongs remission.

Records of 399 patients with metastatic renal cell carcinoma treated with interleukin 2 with or without lymphokine-activated killer cell immunotherapy enrolled in 14 separate clinical trials from multiple institutions were reviewed to determine whether patients with a partial response to interleukin 2 therapy would benefit from surgical resection of residual tumor. Sixty-two patients demonstrated objective responses (15.5%), 18 (4.5%) complete and 44 (11.0%) partial. Eleven patients underwent resection of residual tumor in the lung, kidney, retroperitoneum, or pelvis so that they had "surgically no evidence of disease" (SNED). Of these, 10 had partial responses, and one patient with progressive disease had a complete response. Comparison of response duration showed no difference between the complete response and SNED groups, but there was a significant difference between each of these groups and the partial response group. At this writing, all 11 patients in the SNED group remained alive without evidence of disease (median follow-up, 21 months). In contrast, only 14 patients (76%) with complete responses and 15 patients (35%) with partial responses remained free of disease progression. Enhanced survival of the complete response and SNED groups compared with the partial response group borders on significance and awaits longer follow-up. These data suggest that surgical resection, if technically feasible, may benefit patients who show a partial response to interleukin 2 treatment for metastatic renal cell carcinoma.     

Biological response modifiers in the management of rheumatoid arthritis.

The management of rheumatoid arthritis (RA) with biological response modifiers (BRMs) is reviewed. RA, an autoimmune disorder affecting 1-2% of the world's population, is characterized by inflammation of synovial tissues, joint swelling, stiffness, and pain that may progress to joint erosion. There is strong evidence that inflammatory mediators, such as tissue necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1), play a critical role in the pathogenesis of this disorder. IL-1-receptor antagonist (IL-1Ra) is produced in healthy subjects and helps to protect against the adverse effects associated with IL-1 overexpression. Administration of IL-1Ra or similar agents may reduce the effects of IL-1 and ameliorate inflammatory conditions. Traditional treatment of RA has been based on symptomatic management with non-steroidal antiinflammatory drugs, disease-modifying antirheumatic drugs, and corticosteroids, each of which has substantial drawbacks in terms of effectiveness or adverse effects. Newer therapeutic strategies for blocking the biological effects of inflammatory cytokines include antibodies directed against TNF (e.g., infliximab), soluble receptors (e.g., etanercept) and receptor antagonists to IL-1 (anakinra) [corrected]. Clinical trials indicate that these BRMs may be more effective than traditional agents because they are able to alter joint remodeling in addition to attenuating symptoms. Anti-TNF therapies may be associated with increased risk for infections, sepsis, tuberculosis reactivation, demyelination disorders, and blood dyscrasias; anakinra appears to be safer. Combination therapy with BRMs may be more appropriate for RA than monotherapy. The role of BRMs in the treatment of RA will evolve as investigators learn more about the drugs and the disorder.