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Bone marrow transplantation (BMT) is discussed in terms of immunology, procedures, and complications and their treatment. Any patient with a disorder of the hematopoietic or immune system or a disease in which a transferable hematopoietic cell can supply a missing enzyme is a candidate for BMT. A priority in allogeneic BMT is the identification of a compatible donor through matching of human lymphocyte antigens (HLAs). The greater the disparity in HLAs, the greater the chance of rejection. The ideal donor is a monozygotic twin or an HLA-matched sibling, but only 30% of patients have such a donor. Before receiving the bone marrow infusion, patients must be conditioned to create space in the marrow for donor cells, suppress the immune system, and eradicate any tumor in patients with malignancies. Conditioning is achieved by the combination of total body irradiation and cyclophosphamide treatment; busulfan, etoposide, and cytarabine have also been used. For patients given unmanipulated marrow, the number of nucleated cells infused is about 3 X 10(8) per kilogram. Signs of engraftment are usually seen 14-21 days later. Toxic effects related to conditioning appear during this period and include infection, gastroenteritis, mucositis, and congestive heart failure. The most serious complication is graft-versus-host disease (GVHD), which can affect multiple organ systems. Prednisone, methylprednisolone, methotrexate, antithymocyte globulin, and cyclosporine have been used in an effort to prevent or treat GVHD. Bone marrow transplantation offers the chance of long-term survival to many patients with terminal disease, but associated morbidity and mortality rates remain high. Research is needed to address the problems of infection, leukemic relapse, and GVHD and the difficulty in obtaining and matching donors.

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The predictive value of the Cockcroft-Gault equation in patients with Cushing's syndrome was evaluated in 23 patients. Patients were subdivided based on total body weight into two groups, obese and nonobese. Estimated creatinine clearance (EClcr) values were obtained by the Cockcroft-Gault method using ideal body weight (IBW) and total body weight (TBW). These values were then compared with a 24-hour measured creatinine clearance (MClcr). EClcr values based on TBW consistently overestimated measured values in all patients (p less than 0.05). In obese patients with Cushing's syndrome IBW predictions were not statistically different. However, linear regression analysis revealed a poor correlation (r = 0.32). Daily creatinine production rates (Ucr) were calculated and contrasted with an appropriate historical control for obese and nonobese subjects. Nonobese patients revealed a marked reduction in total Ucr compared with normal-weight controls (p less than 0.05). Obese patients also showed a reduction in Ucr when compared with a normal obese control population (p less than 0.05). Difficulty in predicting creatinine clearance in patients with Cushing's syndrome appears to be related to alterations in Ucr. These data suggest that the pathophysiologic changes that accompany Cushing's syndrome are sufficient to alter Ucr and may limit the usefulness of existing methods to predict creatinine clearance and renal function in these patients.

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The justification, establishment, and evaluation of a full-service cancer center pharmacy satellite for a university hospital are described. Providing efficient and effective pharmaceutical services was difficult because (1) the cancer center is housed in a freestanding building adjacent to the hospital and (2) there are special considerations inherent in the ordering and preparation of antineoplastic medications. Data collected and presented by the pharmacy, along with letters of support from nursing and medical staff, provided justification of the need to establish an oncology satellite pharmacy. The satellite, open 8.0 hours per day Monday through Friday, is primarily responsible for preparing antineoplastic agents and dispensing first doses of other intravenous and oral medications for the cancer center. Satellite staffing consists of 1.2 full-time-equivalent (FTE) pharmacists and 2.0 FTE technicians. A technician works in the satellite the same number of hours as the pharmacist but is also available to prepare antineoplastic drugs in the central pharmacy on weekends. Pharmacist activities also include providing drug and dosing information to the medical and nursing staff, as well as handling investigational drugs. The satellite pharmacy has decreased medication turnaround time by one-half and has improved pharmaceutical services to the nursing staff.

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Conditioning chemoradiotherapy damages the mucosal barrier of the mouth and throat and often produces severe oral inflammation and infection. In a prospective, double-blind, randomized study, we examined the use of a chlorhexidine digluconate mouthrinse for prophylaxis against oral mucosal complications in 51 bone marrow transplant patients. Use of chlorhexidine mouthrinse produced significant reductions in the incidence and severity of oral mucositis. Mucositis also resolved more quickly in patients receiving chlorhexidine. Concomitant reductions in total oral streptococci (p less than 0.02-p less than 0.001) and oral candida (p less than 0.004) were seen in patients using chlorhexidine. Persistent clinical oral candidiasis (thrush) was observed in 15 to 27 control group patients (56%), but only transiently in two (8%) of 24 patients who used chlorhexidine rinse (p less than 0.001). Five of 27 control group patients (19%) had candidemia, while no candidemia was observed in the chlorhexidine group (p less than 0.03). Three deaths from disseminated candidiasis occurred in the placebo group; none occurred in patients who received chlorhexidine. Prophylactic use of chlorhexidine mouthrinse produces reductions in oral soft tissue disease and oral microbial burden in patients undergoing bone marrow transplantation. The reductions in mucositis and in oral candida infections observed with prophylactic chlorhexidine mouthrinse represent a significant advantage for patients undergoing marrow transplantation.

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A retrospective review of 114 patient charts was conducted at three geographically different hospitals to compare the costs of ceftazidime (CTZ) with the combination of tobramycin and ticarcillin (T/T) in the treatment of hospital-acquired pneumonias and/or septicemias. Variables analyzed to determine the cost of the therapy included duration of treatment, dosage and number of doses administered, side effects, and laboratory tests. Time and motion studies were also performed and the results included in the algorithm. In two of the three hospitals, the computer-calculated cost of CTZ therapy was significantly less than for T/T therapy ($1194 vs. $1668 and $93 vs $629). In the third hospital there was no significant difference in the costs of the two treatments ($1079 for CTZ vs. $1066 for T/T). The cost of each regimen per patient day followed a similar pattern, with CTZ therapy being significantly less expensive in the same two hospitals. Patients receiving CTZ therapy realized an average cost savings of $29.70 per day at the three institutions. These savings appeared to be due to a reduction in laboratory and administration costs resulting from the decreased frequency of CTZ administration. We conclude that CTZ therapy was less costly than T/T therapy at three geographically different institutions when the cost of supplies, laboratory tests, and personnel time were taken into account.

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A 33-year-old obese, hypothyroid, white male with several medical problems was admitted to University Hospital in September 1984 for treatment of drug intoxication. Admitting medications included ethchlorvynol in addition to other central nervous system depressants. Initial serum concentrations were reported at 70 micrograms/ml in this somnolent yet totally conscious adult. Established therapeutic concentrations are 2-8 micrograms/ml, with toxic exceeding 20 micrograms/ml. A tolerance phenomenon seemed evident. Serum ethchlorvynol concentrations were monitored daily during early hospitalization and continued to be substantially greater than reported toxic concentrations. Kinetic values were as follows: total body clearance 9.92 ml/min, volume of distribution 68.0 liters, and half-life 78 hours. These values are unique in that they were calculated from a patient who had not suffered an acute overdose, thereby differing markedly from previously published values. The influence of hypothyroidism and hyperlipidemia on these markedly different values appears to be significant. Ethchlorvynol should probably be added to the list of drugs influenced by thyroid disease.

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The development, production, limitations, and uses of monoclonal antibody (MoAb) technology are presented. The first MoAbs were developed in 1975 using a process whereby the antibody-producing spleen cells of mice that had been immunized against sheep red blood cells were fused with the cells of a mouse myeloma cell line, producing hybridomas. These hybridoma cells are used to produce MoAbs, which are antibodies that will bind to only one specific target site on an antigen. Large quantities of MoAbs are grown, either in cell cultures or in the peritoneum of mice, and harvested. Although large quantities of MoAbs can be produced, these techniques are limited because of the potential for contamination by mouse viruses and the inability of the hybridomas to yield sufficient quantities of MoAbs. MoAbs are currently used in diagnostic techniques, including pregnancy tests and drug assays, as well as in tests for detecting viral and bacterial infections and cancer. MoAbs, coupled with dyes or radioactive isotopes, can be used in imaging techniques. Other possible applications of MoAbs include tissue typing, purification, therapy of cancer and autoimmune diseases, and treatment of drug toxicities. As the use of MoAbs in health care increases, pharmacists will need to have a good understanding of the functions and applications of these agents.

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The components and functions of the immune system are described, and the clinical applications of agents that affect the immune system are discussed. Through both nonspecific and specific responses, the immune system recognizes and destroys or eliminates harmful foreign substances with which a host comes into contact. Nonspecific responses are usually associated with the first introduction of a foreign substance into the body and consist mainly of phagocytosis and inflammation. When the same substance, or antigen, is introduced into the body on subsequent occasions, antibodies specific for that antigen combine with the antigen and activate a complex network of specialized cells and soluble cellular secretions that eliminate the substance from the body. Certain antigens are inherited and are found on the cells and tissues of the body; these antigens play a major role in human allotransplantation, blood transfusions, and certain disease states. Recent advances in biotechnology have made it possible to alter an individual's immunologic response with such agents as azathioprine, cyclosporine, or monoclonal antibodies or to augment an individual's antitumor defenses with immunopotentiators. As the products of biotechnology are used more frequently in the hospital setting to treat or prevent disease, pharmacists will need to have a good understanding of the immune system to appreciate the functional capacity of and the problems that may exist with these agents.

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A computer program for estimating and comparing the costs of intravenous antibiotic therapy is described, and a cost comparison of two antibiotic regimens using the program is demonstrated. Data unique to each antibiotic (e.g., dosage regimen, duration of therapy, need for pharmacokinetic monitoring, and acquisition cost per dose) are entered into the first part of the program (ABDATA) and combined with preprogrammed hospital-specific data, such as personnel and material costs, to produce an itemized list of the total cost of therapy. With the second part of the computer program (ABCOMP), antibiotic regimen costs that have been entered into ABDATA can be compared. Cost comparisons are made with the assumption that the antibiotic regimens have similar efficacy and toxicity. A sample cost comparison was performed using data from a recent study comparing the use of ceftazidime or tobramycin-ticarcillin therapy in the treatment of nosocomial pneumonia and bacteremia. The computer-generated cost comparison showed that although the unit cost of ceftazidime was more than the combined unit cost of tobramycin and ticarcillin, the total cost of a 10-day course of therapy with ceftazidime (which included personnel and material costs) was less than the cost of therapy with a combination of tobramycin and ticarcillin. A computer program that incorporates hospital-specific personnel and material costs with unit drug costs can be used to facilitate comparisons of the overall cost of intravenous antibiotic regimens.

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The stability of amino acids in total parenteral nutrient (TPN) solutions stored for 30 days and the potential for stored TPN solutions to support growth of microbial contaminants were studied. Solutions of 3.5% crystalline amino acids and 25% dextrose with electrolytes were prepared either by using a commercially available amino acid solution with electrolytes or by adding electrolytes individually to a base TPN solution. Solutions were stored in polyvinyl chloride bags at refrigerated (4 degrees C) or room (25 degrees C) temperature for 30 days. Some bags were inoculated with Candida albicans or Pseudomonas maltophilia before storage to serve as positive controls for evaluation of microbial contamination. At appropriate intervals, bags of each type of solution under each storage condition were analyzed for amino acid content. Microbial growth was evaluated by filtering the contents of each bag and incubating the filter in brain-heart infusion broth. No microbial growth was detected in any of the study solutions, but all solutions inoculated with C. albicans and 2 of 16 solutions inoculated with Ps. maltophilia had evidence of growth. No significant decreases in the concentrations of any of the amino acids were noted for solutions stored at refrigerated temperature, but significant decreases in the concentrations of arginine and methionine were noted for solutions stored at room temperature. Total parenteral nutrient solutions can be stored for up to 30 days if they are kept at refrigerated temperatures and protected from light; however, quality assurance measures for these solutions should include end-product microbiologic testing.

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Total costs, drug and supply costs, and personnel costs for 14 days of therapy with seven therapeutically equivalent i.v. antibiotic combinations were calculated for a simulated febrile neutropenic patient. The cost for each antibiotic regimen was calculated using a previously developed computerized model that included the cost elements involved in preparation, administration, and pharmacokinetic monitoring of i.v. antibiotic therapy. Comparative costs for the seven antibiotic regimens were determined by inserting the costs of the individual elements into the model. Total costs for the 14 days of therapy varied greatly among the seven regimens, ranging from $908 to $2543. Antibiotics constituted the greatest percentage of total expenditures for each regimen (64-92%). Costs were increased substantially when a third-generation cephalosporin was included in the regimen. Antibiotic costs correlated strongly with total costs, while personnel costs correlated poorly with total costs and accounted for only 6-30% of the total expenditures. Computerized analysis of all costs involved in antimicrobial therapy for this simulated neutropenic patient showed that total costs varied widely in direct proportion to antibiotic costs. In selecting antimicrobial agents for high-risk patients, costs should be considered along with efficacy.

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