Biphasic dissipation kinetics for dislodgeable foliar residues in estimating postapplication occupational exposures to endosulfan.

Agricultural workers are exposed to pesticide residues via dermal contact with foliage upon entry of treated fields. Restricted Entry Intervals (REIs) are established based on both toxicity and exposure. Key factors for estimation of potential worker exposures are dislodgeable foliar residues (DFRs) and the manner in which DFRs dissipate over time. DFR dissipation curves vary in form and shape, and are often biphasic, reflecting different rate processes, chemical-physical influences, and partitioning. Biphasic dissipation behavior for endosulfan [6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin 3-oxide] previously reported for tomatoes and peppers has been confirmed here for endosulfan on melon, grape, and peach foliage. Use of biphasic kinetics results in more robust r2 values for the regression curves that describe foliar dissipation of endosulfan compared to use of simple first-order kinetics. For endosulfan, the use of biphasic kinetics to describe the overall dissipation accurately predicts daily DFR values. In contrast, first order kinetics may overestimate DFRs and, potentially, postapplication worker exposures during the critical period when entry of treated fields is most likely to occur.

Mode of transformation of [1-15N]5-hydroxybenzimidazole and [1-15N]5-hydroxy-6-methylbenzimidazole into the 5,6-dimethylbenzimidazole moiety of vitamin B12.

The transformation of [1-15N]5-hydroxybenzimidazole and [1-15N]5-hydroxy-6-methylbenzimidazole into the 5,6-dimethylbenzimidazole moiety of vitamin B12 by Eubacterium limosum-cultures was studied. The vitamin B12 obtained was exclusively 15N-labeled in N-1 of the base part, as revealed by NMR-measurements. This indicates that either the unsubstituted 5,6-dimethylbenzimidazole presumably formed is not released from the enzyme until the ribose-5'-phosphate substituent is introduced, or that the precursors are first transformed into their alpha-nucleotide-5'-phosphates which then react to form 5,6-dimethylbenzimidazole-alpha-D-ribofuranoside- 5'-phosphate (alpha-ribazole-5'-phosphate).

How a longstanding P & T Committee identifies and meets current therapeutic challenges.

The P & T Committee at the University of Michigan, Ann Arbor, has run smoothly for some time. Nevertheless, it is not immune to today's fiscal and drug therapy challenges. In this exclusive Hospital Formulary interview, Dr. Jeoffrey Stross, chairman; Dr. Richard deLeon, secretary; and Dr. Burgunda Volger, a key University Hospital P & T Committee member, candidly describe their committee's philosophy and the mechanics by which it functions. This committee uses restriction to modify inappropriate prescribing, but it also carries out educational activities. As newer, more expensive, therapies become available, the responsibility to ensure efficacious, safe, economical therapy becomes increasingly complex. The following discussion highlights some of their strategies for success.

Alternatives in the treatment of memory loss in patients with Alzheimer's disease.

The pathophysiology, symptomatology, and treatment of memory loss in patients with Alzheimer's disease are described. Alzheimer's disease is characterized by cerebral cortical atrophy, neuronal loss, neurofibrillary tangles, and neuritic plaques. The primary neuropharmacologic defect involves reduced activity of the enzyme choline acetyltransferase, causing reduced synthesis of acetylcholine (ACh). Other neurotransmitters known to be compromised in patients with Alzheimer's disease include norepinephrine, serotonin, dopamine, and somatostatin. Initially components of short-term memory and immediate recall are lost. Eventually, memory loss is so severe that patients lose the ability to care for themselves. A definite diagnosis of Alzheimer's disease can be made only at autopsy. Three pharmacologic approaches to enhancing cholinergic function include increasing ACh production by increasing the availability of ACh precursors (lecithin, choline); inhibiting ACh degradation by inhibiting acetylcholinesterase (physostigmine, tacrine hydrochloride); and directly stimulating cholinergic receptors by using cholinomimetic agents (arecoline, RS-86). However, results of studies involving these agents are conflicting: no consistent benefit has been shown in patients with Alzheimer's disease. Although therapy with tacrine hydrochloride has been beneficial in some patients, it has not been effective in all cases and has the potential to cause serious adverse effects. Despite the research in patients with Alzheimer's disease, no agent has yet been found that produces consistent improvement in the memory loss associated with this disease.

Impact of a pharmacist education program on nonformulary drug use.

The effect of an educational program for pharmacists that included instructions for handling nonformulary drug requests and determining suitable formulary alternatives for frequently prescribed nonformulary drug requests was measured. Results indicate a significant increase in the number of appropriate nonformulary drug dispensings when the postintervention phase was compared with the preintervention phase. Other values, including the financial impact per nonformulary drug request, did not differ significantly between the two phases. Since all nonformulary drug requests require pharmacist time, a more cost-effective nonformulary drug policy might focus the pharmacist's efforts on nonformulary drug products that are more costly than their formulary alternatives.

Quality assurance program for a hospital investigational-drug service.

The development and implementation of a quality-assurance (QA) program for a pharmacy-based investigational-drug service are described. The objective of the QA program was to assess the quality of the activities in the areas of drug acquisition, inventory control, availability of drug data sheets and dispensing guidelines, provision of a quarterly drug accountability report, and documentation of drug dispensing to patients and decentralized pharmacy areas. The audit criteria were based on hospital policies and procedures and federal regulations for the handling of investigational drugs. Audits of four randomly selected protocols are conducted quarterly by a pharmacist who is not affiliated with the investigational drug service. The results of the first two audits have identified several areas for improvement, including the need for additional pharmacy staff education regarding study protocols, the importance of maintaining complete and accurate drug accountability records by decentralized pharmacists, and the need to provide a centralized source of study protocol information. The QA program has enabled the investigational-drug service to establish and enforce the policies and procedures for the appropriate handling of investigational drugs in this institution.

Retrospective evaluation of piperacillin use in a university hospital.

A retrospective review was conducted to evaluate the appropriateness of empiric and definitive piperacillin use and to determine if less expensive, more appropriate antibiotics could have been used. The criteria were approved by the chief of infectious diseases and the drug utilization review committee at this institution. One hundred courses of piperacillin use in adult patients were reviewed. Therapy was categorized as appropriate in 78 of the 100 courses: 21 were appropriate empiric, 32 were appropriate empiric changed to definitive due to culture and sensitivity reports, and 25 were appropriate definitive. Reasons for this high percentage of appropriate use include: 1) 40% of the infections involved Pseudomonas aeruginosa; 2) 18% of the organisms that were sensitive to piperacillin were resistant to ticarcillin and mezlocillin; and 3) 64% of the courses of therapy involved critically ill patients with diagnoses such as neutropenia secondary to cancer chemotherapy, burns, sepsis, and hospital-acquired pneumonia. Although only 19.7% of the 11,845 grams of piperacillin used were categorized as inappropriate, the cost is relatively high (annualized to $19,648) and cost savings could be realized if piperacillin use were monitored more closely.

Compliance with a restricted antimicrobial agent policy in a university hospital.

Compliance with a policy for use of antimicrobial agents that requires both oral approval from the infectious diseases service and completion of a restricted antimicrobial agent use form was evaluated in a 950-bed teaching hospital. The charts of patients for whom a restricted antimicrobial agent was ordered during four one-week periods between January 1987 and April 1987 were audited to determine whether completed use forms had accompanied orders for restricted antimicrobial agents. The validity of the information on completed forms was determined by comparing the information on the form with notes in patients' charts and through discussions with infectious diseases physicians. Two infectious diseases physician reviewers evaluated the appropriateness of prescribing of piperacillin and ceftazidime by analyzing data collected by pharmacists. Forms were submitted with 132 of 154 orders written for restricted agents; incomplete forms were received and accepted by pharmacists for 39 courses of therapy. The infectious disease service had not been contacted to approve use of a restricted agent in 25 cases. Eight of the 48 courses of piperacillin or ceftazidime therapy were deemed inappropriate despite initial infectious diseases approval. Compliance with a formal antimicrobial agent restriction policy at this institution has been good, but periodic re-education and follow-up monitoring appear to be necessary to ensure optimal use of restricted agents.

[Acute preoperative normovolemic hemodilution in gynecologic operations. A retrospective analysis]. / Die akute präoperative normovolämische Hämodilution bei gynäkologischen Operationen. Eine retrospektive Analyse.

In a retrospective analysis, a comparison of two groups of 100 patients each showed that in major breast surgery the need for heterogeneous banked blood can be considerably reduced by means of acute preoperative normovolemic hemodilution. The method involves replacing the blood withdrawn directly before or after anesthetization with a colloidal substitute solution, subsequently reinfusing it either intraoperatively, following hemostasis, or in the postoperative phase. Hemodilution could not be shown to influence the postoperative courses of HB, hexokinase or thrombocyte values. In contrast to major breast surgery, hemodilution was not found to have any advantages as regards reducing the requirement for heterogeneous blood in major abdominal wall grafting procedures.