The American journal of medicine
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Review Comparative Study Clinical Trial
Comparative review of combination therapy: two beta-lactams versus beta-lactam plus aminoglycoside.
Febrile neutropenic patients are usually treated with a combination of a beta-lactam and an aminoglycoside. Since Pseudomonas aeruginosa is an important pathogen in these patients, the empiric use of possibly synergistic combinations against that organism has been traditionally recommended. The recent appearance of beta-lactams more active against P. aeruginosa and the well-known nephrotoxicity of aminoglycosides have led some to advocate the use of beta-lactam combinations for empiric treatment of fever in neutropenic cancer patients. ⋯ Overall, these results show that response rates with a combination of two beta-lactams are similar to those obtained with the combinations of a beta-lactam and an aminoglycoside for infections in patients with serious underlying disease and compromised mechanisms of defense. They also suggest that the steady emergence of resistance of pathogens to beta-lactams has often been overcome by the use of newer drugs in regard to infections caused by the Enterobacteriaceae but much less effectively in regard to P. aeruginosa. There are still important theoretic reasons for preferring an aminoglycoside-containing combination as empiric therapy in febrile neutropenic patients, and our overall conclusion is that it would be appropriate to conduct a large-scale trial comparing beta-lactam combinations with the traditional beta-lactam plus aminoglycoside regimens in that setting.
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Renal lesions in lymphoid malignancies are rare, with most lesions observed in association with Hodgkin's disease. In two large series of patients with Hodgkin's disease, only 0.4 percent had minimal-change lesion whereas 0.1 percent had amyloidosis. The non-Hodgkin's lymphomas and leukemias comprise large and heterogeneous groups with equally diverse renal lesions. ⋯ Also recognized are rare reports of renal disease associated with the atypical lymphoid proliferations of angioimmunoblastic lymphadenopathy, giant lymph node hyperplasia syndrome, and acquired immune deficiency syndrome. Broad generalizations regarding the pathogenesis of renal disease in these syndromes are difficult, partly due to the paucity and sporadic reporting of such cases. Mechanisms proposed to explain the renal pathologic findings include autologous nontumor antigens, tumor antigens, fetal antigen expression, immune complex deposition, viral antigens, and disordered T cell function.
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Many functional, biochemical, and morphologic changes occur in diabetes in animal models and in humans. The responses of humans and animals to treatment with insulin indicate that these changes are induced by the diabetic milieu and are indirect or direct consequences of insulin deficiency and/or hyperglycemia. Guidelines for acceptable laboratory values in controlling diabetes are presented, as is evidence supporting a metabolic basis for vascular complications of the disease. On the basis of the results of a recently published prospective study of 59 patients with diabetes, fluorophotometry is cited as a technique that may predict development of retinopathy.
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Studies throughout the world demonstrate the effectiveness of prophylactic antibiotics in vaginal hysterectomy and cesarean section. Febrile morbidity is reduced by more than one half, and pelvic infections are reduced one third to one fifth, respectively. Prophylactic antibiotics are most beneficial in high-risk cesarean section, such as in patients in labor and with ruptured membranes. ⋯ First- and second-generation cephalosporins are the antibiotics most frequently used. In vaginal hysterectomies, a single preoperative dose, and in cesarean section, three perioperative doses seem to be adequate. Infections occurring despite prophylactic antibiotics are often caused by resistant organisms.
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In human subjects, ceftriaxone exhibits an exceptionally long elimination half-life (5.8 to 8.7 hours) and a small degree of nonlinearity in its pharmacokinetics which can be ignored in its clinical applications. Thirty-three to 67 percent of a dose is excreted in the urine as unchanged drug, and the remainder is secreted in the bile and ultimately is found in the feces as microbiologically inactive compounds. Ceftriaxone is rapidly and completely absorbed following intramuscular administration. ⋯ Small changes in the pharmacokinetics of ceftriaxone in elderly subjects or patients with renal or hepatic dysfunction are such that dose adjustments should not be necessary with a ceftriaxone dosage up to 2 g per day. Ceftriaxone was not removed to any significant extent from plasma by hemodialysis. In a small percentage of patients, on dialysis, the elimination rate of ceftriaxone was significantly reduced, suggesting that plasma concentrations of ceftriaxone should be monitored in these patients to determine if dosage adjustments are necessary.