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Biomedical subjects

I A Cohen

Publications and source records attributed to I A Cohen.

At least 19 recordsLinked to original sources

Activities, functions, and structure of pharmacy and therapeutics committees in large teaching hospitals.

The results of a survey on the activities and functions of hospital-based pharmacy and therapeutics (P&T) committees are presented. Questionnaires were mailed to the pharmacy director or the person responsible for the pharmacy's drug information service at 267 teaching hospitals throughout the United States in 1994 and 1995. The survey questions covered P&T committee composition, functions, roles of members, policies and procedures, and formulary-maintenance activities. The overall response rate was 70%. The mean number of members on the P&T committees was 19.3, of whom 91% were allowed to vote. There was an average of 12.3 physicians on the committees. Each P&T committee had at least one pharmacist member, with an average of 3.2 pharmacist members; 69.5% of the institutions reported having a committee secretary, who was almost always a pharmacist. On almost all committees, pharmacists wrote the minutes, prepared the formulary review documents, and were responsible for monitoring formulary activities outside the meeting. The P&T committee functioned in a very formal manner. Most (87.7%) of the respondents reported that their institutions had a closed formulary. At all hospitals, the attending medical staff could request additions to the formulary, but at only 62.4% of the hospitals could pharmacy staff make a similar request. The committees were active in changing the formulary. P&T committees in large teaching hospitals are active in formulary management, are large and diverse, and consist mainly of physicians, although pharmacists play an important role in the meetings.

Formularies, Hospital as Topic↗

A new flap for nasal tip reconstruction.

Aesthetic reconstruction of tumor defects of the nasal tip and supratip areas remains a challenge. Because of our dissatisfaction with the current reconstructive options, we have developed a modification of the nasalis flap based on the angular artery for the management of nasal tip defects. This is an axial flap-pattern that rotates toward the midline and nasal tip, leaving donor scars in the nasojugal and alar creases. A second rotation flap from the alar groove fills the donor defect in the nasojugal region to minimize scarring. We have utilized this flap 19 times in 18 consecutive patients with nasal tip and supratip tumor defects with follow-up ranging from 10 to 72 months. Donor scars are well concealed and nasal contour is minimally altered. Color and texture matches are excellent, and the pincushion deformity has been eliminated. On the basis of these results, we believe the modified nasalis flap is ideally suited for nasal tip reconstruction.

Aged↗

Phase I clinical evaluation of [SP-4-3(R)]-[1,1-cyclobutanedicarboxylato(2-)](2-methyl-1,4- butanediamine-N,N1) platinum in patients with metastatic solid tumors.

The development of clinically useful drugs is a priority of clinical cancer research. CI-973, [SP-4-3(R)]-[1,1-cyclobutanedicarboxylato(2-)](2-methyl-1,4- butanediamine-N,N1) platinum, has been shown in preclinical murine and human tumor models to have activity equivalent or superior to that of cisplatin and carboplatin and to exert activity against cisplatin-resistant cell lines. In addition, preclinical testing suggests a reduced toxicity profile for CI-973 as compared with currently available drugs, especially decreased nephrotoxicity, ototoxicity, and gastrointestinal toxicity. A total of 29 (28 evaluable) patients with solid tumors were treated with intravenous CI-973 given over 30 min every 4 weeks. No routine pre- or post-treatment hydration or antiemetic program was used. The CI-973 doses given were 75, 150, 170, 188, 230, and 290 mg/m2. The dose-limiting toxicity was granulocytopenia. Nausea and vomiting occurred in the majority of patients but was mild to moderate in severity. No renal or auditory toxicity was seen. The maximum tolerated dose (MTD) for patients who had a good performance status, had not received prior radiation therapy to bone marrow, and had not previously been exposed to platinum or stem-cell toxin was 290 mg/m2. For those who had received prior radiation therapy, had a performance status of 2 or worse, or had previously been exposed to platinum or stem-cell toxin, the MTD was 230 mg/m2. The recommended phase II starting doses for these groups of patients are 230 and 190 mg/m2, respectively. No clinical tumor response was seen in this phase I study.

Adult↗

Persistent immune deficiency in patients with alcoholic hepatitis.

T-lymphocyte subset numbers, recall-antigen skin test responses and mitogen-induced lymphocyte proliferation assays were investigated in 12 patients with severe alcoholic hepatitis (AH). Serial studies of these parameters were obtained at intervals of 1 or 2 wk. Patients with AH had lower peripheral blood lymphocyte counts with corresponding decreases in T-cell subset numbers that were persistent in the serial evaluations. T8 cells were disproportionately decreased, with a significant resultant increase in the T4:T8 ratios. Compared with controls, AH patients had significantly smaller cutaneous responses to Candida albicans antigen (p less than 0.05) and mumps antigen (p less than 0.005). Fifty-eight percent of patients were anergic when tested with a battery of four antigens. Patients with AH had increased concanavalin A-, but not phytohemagglutinin-induced lymphocyte proliferative responses. These serial analyses confirm previous observations of cell-mediated immune dysfunction in patients with severe AH. Moreover, there is a persistence of these abnormalities for at least 6 wk after withdrawal from alcohol.

Hepatitis, Alcoholic↗

Investigational drug practices in Michigan hospitals.

All 188 acute-care hospitals in Michigan with licensed pharmacies were surveyed to assess compliance with recommendations of ASHP, FDA, and the Joint Commission on Accreditation of Healthcare Organizations related to investigational drug use; other practice issues related to investigational drugs but not covered in those guidelines were also studied. Pharmacy directors were questioned about their practices for approving, prescribing, procuring, storing, and labeling investigational drugs; preparation, content, and use of investigational drug data sheets; record keeping; personnel issues; and other investigational drug services provided by the pharmacy department. The response rate was 84.5% (159 completed questionnaires returned), but only 44 respondents (27.7%) indicated that investigational drugs were currently used in their institutions. Written investigational drug policies and procedures were available in 116 (73.0%) of the responding pharmacy departments. Respondents currently handling investigational drugs had high rates of adherence for the following practice guidelines: preparation of data sheets (75.0%), storage (97.7%), monitoring of investigational drug use and stock levels (79.5%), and maintaining perpetual inventories (79.5%). Areas with relatively poor adherence rates included pharmacy department preparation of investigational drug patient-information sheets (20.5%), maintaining information within the pharmacy on minimum stock levels (53.9%), mode of shipment (30.8%), time to receive investigational drugs after order placed (38.5%), acceptance of nursing transcriptions of oral orders (56.8%), including "investigational drug" on the dispensing label (55.8%), and approval of data sheets by the investigator and the institutional review board (40.5% and 37.8%, respectively). Pharmacy departments, regardless of hospital size, should improve their adherence to ASHP, FDA, and Joint Commission guidelines for handling investigational drugs.

Documentation↗

Compatibility of premixed theophylline and methylprednisolone sodium succinate intravenous admixtures.

The stability of theophylline supplied as a premixed injection and of methylprednisolone sodium succinate in admixtures containing both drugs was studied. Solutions containing theophylline in concentrations of 4.0 mg/mL and 0.4 mg/mL were used. Methylprednisolone sodium succinate was added to each solution to produce a final concentration of 0.5 mg/mL and 2.0 mg/mL of methylprednisolone alcohol, a pharmacologically active form of methylprednisolone sodium succinate. Each admixture was prepared in triplicate, and samples were kept at room temperature in glass containers. Immediately after admixture and at 3, 6, 12, and 24 hours, samples were visually inspected, tested for pH, filtered, and assayed in duplicate by high-performance liquid chromatography for theophylline concentration and for both methylprednisolone sodium succinate and methylprednisolone alcohol content. Control solutions containing only one of the two drugs were also tested. No visual changes were observed. The addition of theophylline in 5% dextrose injection to the methylprednisolone sodium succinate solutions resulted in decreased pH values for all solutions, which did not vary significantly throughout the study period. Theophylline concentrations did not change significantly compared with baseline. In solutions containing theophylline 0.4 mg/mL with either 2.0 or 0.5 mg/mL of methylprednisolone sodium succinate, less than 90% of the initial methylprednisolone sodium succinate concentrations remained at 24 hours. However, within three hours after admixture preparation, methylprednisolone alcohol was detected in those solutions in increasing concentrations. A commercial preparation of premixed theophylline in 5% dextrose injection in a concentration of 4 mg/mL or less can be mixed with methylprednisolone sodium succinate in a final concentration of 2 mg/mL or less and administered intravenously within 24 hours after mixing.

Chromatography, High Pressure Liquid↗

Injectable-antineoplastic-drug practices in Michigan hospitals.

Practices related to parenteral (injectable) antineoplastic drugs (PADs) in Michigan hospitals were surveyed. All hospitals in Michigan were surveyed to assess compliance with American Society of Hospital Pharmacists (ASHP) and Occupational Safety and Health Administration (OSHA) recommendations related to PADs. Other PAD-related practice issues not covered within those guidelines were also studied. Surveys were mailed to the pharmacy directors of the state's 192 acute-care hospitals. Included were questions concerning policies and procedures for ordering, storing, preparing, handling, labeling, transporting, administering, and disposing of PADs. Questions concerning staff education, spill cleanup, and personnel issues were also included. A total of 169 questionnaires were returned, yielding a response rate of 88%. Of those respondents, 132 indicated that they prepare PAD doses for inpatients. Adherence rates were high for several of the PAD-preparation recommendations, including handwashing (97%) and gloving (98.5%). Rates for gowning (71.2%), labeling of PAD doses as biohazards (chemical hazards) (73.5%), and use of Class II biological-safety cabinets (71.2%) were less favorable. Practice areas with relatively poor adherence rates included use of plastic-backed absorbent pads under PAD preparation areas (53.8%), storing PADs separately from other drugs (48.5%), informing prospective employees of potential risks of handling PADs (36.4%), availability of spill kits (36.4%), and attaching and priming i.v. tubing before adding PADs to i.v. containers (5.4%). Many pharmacy departments in Michigan hospitals can substantially improve their adherence to ASHP and OSHA recommendations related to PADs.

Antineoplastic Agents↗

Compatibility of aminophylline and methylprednisolone sodium succinate intravenous admixtures.

The stability of aminophylline and methylprednisolone sodium succinate in admixtures containing both drugs was studied. Admixtures containing aminophylline 1.0 mg/mL and methylprednisolone sodium succinate 2.0 and 0.5 mg/mL were prepared in both 5% dextrose injection and 0.9% sodium chloride injection. Each admixture was prepared in triplicate and samples were kept at room temperature in glass. Immediately after admixture and at one, two, and three hours, samples were visually inspected, tested for pH, filtered, and assayed in duplicate by high-performance liquid chromatography for theophylline concentration and for both methylprednisolone sodium succinate and methylprednisolone alcohol. Control solutions containing only one of the two drugs were also tested. No visual changes were observed. The admixtures had higher pH values after aminophylline was added, but pH of the samples did not change significantly. Aminophylline concentrations did not change significantly throughout the study period. In 0.9% sodium chloride admixtures with methylprednisolone sodium succinate 0.5 mg/mL, less than 90% of the initial methylprednisolone concentration remained at two hours at the 2.0 mg/mL initial concentration, less than 90% remained at three hours. However, methylprednisolone alcohol (a pharmacologically active form of methylprednisolone sodium succinate) was detected in increasing concentrations after the first hour. Aminophylline in a final concentration of 1.0 mg/mL or less can be mixed with methylprednisolone sodium succinate in a final concentration of 2.0 mg/mL or less in 5% dextrose injection or 0.9% sodium chloride injection and administered intravenously within three hours after mixing.

Aminophylline↗

Evaluation of a pharmacist-managed anticoagulation clinic.

Medical records were retrospectively analyzed to evaluate the success of a pharmacist-managed Anticoagulation Surveillance Clinic (ASC). The 78 patients in group I were followed by the ASC. The 17 patients in Group II were followed by other Veterans Administration Medical Center clinics. Demographic characteristics, warfarin indication and potentially complicating conditions were comparable between the groups. Group I patients had shorter intervals between visits to the clinic than Group II patients. Although not statistically different compared to Group II, Group I patients had better prothrombin time control. Group I patients also had fewer complications per treatment year (6.9% vs 9.0%) and received fewer potentially interacting drugs. The ASC was at least as successful as the other clinics in managing patients on warfarin, and results compared very favorably to those reported in the literature for other anticoagulation clinics.

Ambulatory Care Facilities↗

Effect of various storage conditions on a fluorescence polarization immunoassay for tobramycin.

The effects of various storage conditions on the results of a fluorescence polarization immunoassay for tobramycin were studied. Two venous blood samples (150 mL each) were drawn one hour and six hours after a single intramuscular dose of tobramycin. From each of these samples, which represented peak (6 micrograms/mL) and trough (1 microgram/mL) concentrations, aliquots of whole blood and of serum were prepared and stored in both glass and polypropylene containers. Serum samples were stored at -20 degrees C and assayed for tobramycin at intervals of 1-372 days. Samples of serum and whole blood were stored at 4 and 25 degrees C and assayed on days 1, 3, and 7. Mean tobramycin concentrations over time and between-run coefficients of variation were calculated for each set of samples. There was no substantial variation in tobramycin concentrations over time. Significant differences between tobramycin concentrations were noted only for peak serum samples in glass versus plastic containers at -20 degrees C and for trough serum samples stored in glass at -20 degrees C versus 25 degrees C. However, these differences were small and are unlikely to be clinically important. Under the conditions tested, the results of a fluorescence polarization immunoassay for tobramycin do not appear to be affected by storage time, storage temperature, container material, or storage medium (whole blood versus serum).

Adult↗

Cimetidine-theophylline interaction: effects of age and cimetidine dose.

Influences of cimetidine dose and age on the cimetidine-theophylline interaction were evaluated. Group Y consisted of nine young adults, aged 22-35 years, and Group O of nine elderly adults, aged 60-74 years. Each subject completed three study phases in this randomized crossover study. During Phase A, oral dosing of 5 mg/kg theophylline was followed by 14 serial blood samples drawn over 36 h. Phases B and C involved the same procedures, but with oral cimetidine treatment of either 200 or 300 mg every 6 h, respectively. Theophylline pharmacokinetic parameters for Group Y, Group O, and Groups Y + O were calculated. Analyses of variance (ANOVA) for crossover design were performed for each variable. Intragroup interphase ANOVA results were interpreted using multiple range tests (Tukey's Q). Comparisons between groups were performed using two-sided Student's t tests (alpha = 0.05). Within each phase, the area under the concentration-time curve (AUC), elimination half-life (t1/2 el), clearance (Clp), and volume of distribution (Vd) of theophylline for the elderly subjects were not significantly different from those of the younger adults. Mean changes in AUC, t1/2 el, and Clp between Phases A and B for both Groups Y and O were highly significant (29.2 vs. 40.4, 36.7 vs. 44.8, and 25.9 vs. 29.8%, respectively). Further significant changes in those parameters were associated with 1.2 g/day of cimetidine (Phase C). Alterations of theophylline pharmacokinetics by cimetidine appear to be dose-related and are of similar magnitude in elderly and young healthy adults.

Administration, Oral↗

Stability of theophylline in human serum and whole blood.

The effect of various storage conditions on serum theophylline results using a fluorescence polarization immunoassay (FPI) method was studied. Two human subjects received sufficient oral theophylline to produce low and high therapeutic serum theophylline concentrations. Aliquots of venous whole blood (without anti-coagulant) and serum from each subject were sealed in polypropylene plastic and glass containers and stored at 4 degrees C and 25 degrees C. Additional aliquots of serum from each subject were stored in glass and polypropylene containers at -20 degrees C. FPI assays were performed on days 0 and 3 for room temperature serum samples, days 3 and 7 for refrigerated serum samples, and days 3, 7, 14, 28, 56, 168, and 336 for frozen serum samples. All whole blood samples were assayed on day 3 after removal of the clot. Some samples were tested using FPI for 1,3-dimethyluric acid, a metabolite of theophylline, and results from spiked samples and samples tested with high-pressure liquid chromatography were compared with FPI results to determine cross-reactivity of the metabolite. No appreciable change in the assayed theophylline values occurred under any storage temperature, nor was there any difference in results from samples stored in glass versus polypropylene containers. At a concentration of 20 micrograms/ml, 1,3-dimethyluric acid produced a cross-reactivity of 3.5% with the FPI system. The FPI method is not affected by storage of samples under the specified conditions over the time period studied.

Adult↗

Relationship between cimetidine plasma levels and gastric acidity in acutely ill patients.

The relationship between cimetidine plasma levels and gastric acidity was studied in acutely ill patients. Patients in surgical intensive care for stress ulcer who were being managed with nasogastric suction were studied. Nine patients (Group 1) received 300 mg of intravenous cimetidine over 30 minutes every six hours. Titratable acidity and pH of gastric aspirates and plasma cimetidine levels were measured at peak (1.5--2.5 hours) and trough (5--6 hours) times following cimetidine administration, in Group 1. Titratable acidity and pH were measured for nine Group 2 patients (control) who did not receive cimetidine. In Group 1, mean gastric acid output was significantly lower (p less than 0.05) and mean pH was significantly higher (p less than 0.005) than in Group 2. In Group 1, plasma cimetidine concentration correlated poorly with gastric pH and gastric acid output (r = 0.21). The study indicates that the correlation between plasma cimetidine levels and gastric acid secretion is poor, but that the cimetidine dosage used suppressed acid output during the entire dosing interval.

Adult↗