Search

100 patients were treated either with heparin 5,000 i.u. every 12 hours or placebo in a double-blind, randomized, prospective trial. The treatment was commenced 1-3 hours before surgery and was continued for 6 1/2 days. The criteria for the selection of patients and the principles on which the treatment and investigation schedules were based corresponded generally to those laid down by Kakkar et al. (1972). The incidence of deep-vein thrombosis of the lower extremities was 6% in the group treated with heparin and 20% in the placebo group. The decisive diagnosis of thrombosis was based on the scanning of the lower extremities after administration of I125-fibrinogen. No case of pulmonary embolism occurred and no complications because of the treatment were noted. We propose to institute investigations on a larger scale to evaluate the prophylactic value of small heparin doses with respect to pulmonary embolism.

The human vasoconstrictor bioassay was used to assess the potency of open applications of Synemol cream (0.025%), Diprosone cream (0.05%), Aristocort-A cream (0.5%), and Valisone cream (0.1%). Intensity of vasoconstriction was determined eight, twenty-four, and thirty-two hours after application. Results obtained from the average intensity scores of the three determinations indicated that Synemol cream (0.025%) is actually a more active compound than are Diprosone cream (0.05%), Aristocort-A cream (0.5%), and Valisone cream (0.1%), and that its activity is longer acting.

The profession of pharmacy has applied the term "documentation" to count activities that more closely approximate descriptive protocols or administrative reports. This extended nonclinical use of the term documentation has resulted in the profession losing sight of a necessary step in the development, justification, and successful implementation of clinical pharmacy services. An instrument that helps to standardize the documentation of a clinical pharmacist's database, patient-care activities, and therapeutic plans is presented. This process, the pharmacist's workup of drug therapy (PWDT), consists of the following six interrelated steps: (1) establish a comprehensive patient-specific database; (2) identify patient-specific, drug-related problems; (3) describe desired therapeutic outcomes; (4) list all therapeutic alternatives that might produce the desired outcomes; (5) select the drug recommendation(s) that most likely will result in the desired outcomes; and (6) establish a plan for therapeutic drug monitoring that documents that desired effects occur and undesired effects are minimized. A formative method of documenting the clinical pharmacist's activities such as the PWDT must be functional on a daily basis in order to generate meaningful summative management reports.

To study the influence of hypoglycaemia and starvation on mental functions eight healthy male students age 25-34 years with an ideal body mass of 99.9% +/- 2.5% (mean +/- SEM) were recruited. Hypoglycaemia was induced in random order by an insulin-glucose clamp technique (insulin: 2.4 mU/kg/min + glucose at variable rate) keeping the venous blood glucose at 2.2 mmol/l both after an overnight fast and after 72 h fasting. Mental alertness was assessed by measuring the recognition time, moving time and total reaction time to a visual signal and by a verbal mental clearness test and a synonym learning test during normo- as well as hypoglycaemia. Hypoglycaemia prolonged the total reaction time (p less than 0.05) and the time required for the mental clearness test (p less than 0.05). Compared with a control study performed at normoglycaemia the learning effect of the synonym test was reduced by hypoglycaemia. Fasting, which resulted in a body weight reduction of 2.6 +/- 0.3 kg and ketonuria prolonged the total reaction time (p less than 0.005) by increasing the moving time but did not affect the mental clearness test. When hypoglycaemia was preceded by 72 h fasting it did not increase the total reaction time, nor did it modify the mental clearness test. Moreover, the learning effect of the synonym test was less impaired. In conclusion, mental alertness was reduced by moderate hypoglycaemia after an overnight fast while similar hypoglycaemia did not reduce mental alertness after prolonged fasting. This may illustrate a decrease of the glucose dependency of the central nervous system during prolonged fasting.

The use of isotretinoin over a 2-year period was retrospectively studied in Saskatchewan. The database of the Saskatchewan Prescription Drug Plan was used to obtain the names of physicians who prescribed isotretinoin as well as the names of patients for whom it was prescribed. Of the 861 such patients 161 had been instructed to use the drug for at least 4 months by 42 physicians. Questionnaires were returned by 86 of the 161 patients and 22 of the 42 physicians. The responses confirmed that isotretinoin therapy is highly effective for acne. However, at least half of the patients for whom the agent was prescribed apparently did not complete a full 4- to 5-month course of treatment, and of the 34 women (average age 28 years) who responded to the questionnaire 12 (35%) did not use a method of contraception, which is a matter of concern in view of isotretinoin's teratogenic effects.

Radioimmunoassay (RIA) and fluorescent polarization immunoassay (FPI) methods for quantitative gentamicin serum concentration assay have been shown to be comparable. The purpose of this study was to determine if serum concentration-time data from the same patients assayed by RIA and FPI would provide the same estimates for half-life, elimination rate constant, distribution volume, drug clearance, and gentamicin dose. A total of 99 pre-and postinfusion serum samples were obtained from 30 patients. Samples were divided and assayed by RIA or FPI, and the resultant serum concentration-time data were fitted to a standard one-compartment model. The correlation between the two assay methods was 0.99 (p less than 0.005). A mean difference of 10% was seen in distribution volume, gentamicin clearance, and gentamicin dose from quantitative data from the two methods. These differences were significant (p less than 0.01). Although the two methods appear to be interchangeable, based on in vitro comparison, differences in calculated pharmacokinetic parameters resulted in significant differences in dose recommendations.

Synchronous cultures of Chlamydomonas reinhardii have been examined for the total amounts of carotenoid and chlorophyll present throughout a 12 hrs light -- 4 hrs dark life cycle. Variations in the carotenoid distribution at different points within the cell cycle have been found. During the greater part of the light period all major carotenoids increased at a proportionally similar rate. However, the increases in lutein and violaxanthin preceded those in beta-carotene and neoxanthin by some 2 hrs and that in loroxanthin, and algal xanthophyll, by abour 3 hrs. A marked drop in total carotenoid accumulation, corresponding to similar temporary falling away in the accumulation of beta-carotene, lutein and violaxanthin occurred at 9 hrs. The correspondence of this with the established drop in RNA accumulation and the break-up of the nucleolus was pointed out. Considerable redistribution among the carotenoids occurred during the dark period, notably the amount of beta-carotene increased relative to the total xanthophylls. The full significance of these results can not be estimated in the absence of comparative data on related organisms.

Newer nonsteroidal antiinflammatory agents (NSAI's) such as ibuprofen, neproxen, fenoprofen, and tolmetin have broadened the therapeutic choice and increased the chances of providing optimum arthritis control, but require careful assessment of the possibilities for unwanted drug effects when long-term therapy is required. A review of the literature on the gastrointestinal effects of the promising newer NSAIs, as compared with the older agents, aspirin, indomethacin, and phenylbutazone, is presented, highlighting animal toxicology and human adverse reaction surveillance data and the evidence for various suggested pathophysiological mechanisms.

1. The metabolism of vanillin, isovanillin and the corresponding alcohols and acids in rats was investigated using t.l.c., g.l.c. and combined g.l.c.-mass spectrometry. 2. Oral dosage (100 mg/kg) of the aldehyde resulted in urinary excretion of most metabolites within 24 h, mainly as glucuronide and/or sulphate conjugates although the acids formed were also excreted free and as their glycine conjugates. In 48 h 94% of the dose of vanillin was accounted for as follows (%) : vanillin (7), vanillyl alcohol (19), vanillic acid (47), vanilloylglycine (10), catechol (8), 4-methylcatechol (2), guaiacol (0-5) and 4-methylguaiacol (0-6). Similarly, 89% of the dose of isovanillin was accounted for as follows: isovanillin (19), isovanillyl alcohol (10), isovanillic acid (22), vanillic acid (11), isovanilloylglycine (19), catechol(7) and 4-methylcatechol (1). Protocatechuic acid was also formed from both aldehydes. 3. By means of (a) investigation of biliary metabolites, (b) prevention of biliary excretion, (c) suppression of intestinal bacteria with neomycin sulphate and (d) inhibition of intestinal beta-glucuronidase with saccharo-1,4-lactone, it was found that glucuronides of the aldehydes and their respective alcohol and acid derivatives are excreted in the bile and that the conjugates are metabolized by the intestinal bacteria to toluene derivatives and decarboxylated products.

Three hundred and twenty-four patients presenting to Wellington Women's Hospital with symptoms suspicious of an ectopic pregnancy were first studied by testing serum for HCG using a new simple and sensitive (25 mIU/mL) ICON pregnancy test. One hundred and thirty ICON tests were positive. Subsequent management: (a) Immediate laparoscopy noted 3 intrauterine and 15 ectopic pregnancies. (b) Twenty-five patients discharged on revised clinical grounds without pregnancies. (c) An immediate ultrasound examination of 87 women showed 58 intrauterine pregnancies (including 1 misdiagnosed ectopic pregnancy) and 29 ectopic pregnancies which were later confirmed at laparoscopy. One hundred and ninety-four ICON tests were negative including two false negative results in patients with ectopic pregnancies. To avoid both unnecessary laparoscopy or the discharge of patients with a possible ectopic pregnancy, patients with symptoms and signs suspicious of an ectopic pregnancy and who present to hospital should have a rapid sensitive HCG assay. Then, if the test is positive (sensitivity 96%), an ultrasound examination can assist in determining the likely site of the pregnancy.

Polygalacturonase (EC 3.2.1.15) produced by Fursarium oxysporum f. sp. lycopersici was purified by chromatography on DEAE-cellulose, CM-cellulose, and hydroxyapatite. The purified enzyme consisted of two electrophoretically distinct "isozymes", that behaved as charge isomers during electrophoresis in several different concentrations of polyacrylamide gel. The two isozymes had similar "endo" modes of action on polygalacturonic acid, as determined by comparison of viscosity reduction, reducing group release, and thin-layer chromatography of oligomeric hydrolysis products. Both isozymes hydrolzyed 5% of the substrate bonds in reaching 50% viscosity reduction. The amino acid compositions of the isozymes were similar and their molecular weights were about 37000 as determined by sedimentation equilibrium. Removal of large amounts of carbohydrate during purification did not affect heat stability of the enzymes. A large proportion of the remaining carbohydrate appeared to be covalently linked to the enzyme protein.

Pharmacy department costs for preparing and administering intermittent i.v. drug doses using a piggyback bottle system and a syringe pump system were predicted and compared. Centralized i.v. admixture service personnel time for preparation of small-volume injections in piggyback bottles was recorded for 14 days. After a four-week orientation of personnel to the syringe pump system, personnel time for preparation of doses in this system was recorded for 14 days. Material costs were itemized for each system and annual costs were predicted. Costs were calculated on the basis of the previous year's purchasing data, assuming that 80% of intermittent i.v. drug doses could be given by the syringe pump system. Syringe pump system costs were calculated for administration of one to eight drug doses through each secondary infusion set; 5-mL and 10-mL syringes were used. Preparation time was slightly longer for the syringe pump system than for the piggyback bottle system; the annualized personnel cost difference was $0.012 per dose. Based on one dose per secondary infusion set, material costs were higher for the syringe pump system. Based on administration of four doses through each secondary infusion set, overall costs were lower for the syringe pump system. Lower material acquisition costs for the syringe pump system could result in pharmacy department cost savings if at least four intermittent i.v. drug doses were administered through each secondary administration set.

The bioavailability of cloprednol, a new systemic corticosteroid, was examined in a 12-subject crossover study in which two capsules, a tablet, and a solution were tested. Plasma was analyzed for cloprednol by a GLC-mass spectrometric method. The biological half-life, peak plasma concentration, peak time, plasma concentration at all sampling times, and plasma areas were evaluated for differences (p less than or equal to 0.05) in comparisons of pairs among the four formulations. An analysis of variance revealed that cloprednol was absorbed to the same extent from all formulations and rapidly cleared from the plasma with a half-life of 1.86 +/- 0.36 (SD) hr. All plasma profile parameters from the solid dose formulations were the same, demonstrating bioequivalence in both rate and extent of absorption. Significant differences were observed between the solution and solid dose formulations with respect to peak time, 15-min plasma concentration, and 0-30 min area, indicative of faster absorption from the solution; however, total plasma areas were the same for all four formulations. Comparison of plasma cloprednol levels in this study to those of a prior intravenous-oral dose study suggests that cloprednol was completely bioavailable from all formulations.

The personnel time and costs involved in manually developing a master drug file are described. This system was designed independently by the pharmacy personnel of a 550-bed medical center to support the computer programs for drug purchasing, inventory control, outpatient services, i.v. admixture services, and pharmacy management reports. The master drug file was created to contain data on every drug and nondrug line item used in the pharmaceutical services of the medical center. The process of manually developing the drug file and entering the data into the computer system required six weeks, 732 pharmacy staff hours, 120 hours of supervision by administrative pharmacy personnel, 50 hours of program planning and organization of computerized programs, and cost a total of $8451. The drug file contains 1138 drug formulary line items; 0.88 hours were consumed per line item, at a development cost of $7.43 per line item. Although a commercially available drug file could have provided 35,000 records at half the cost, it was concluded that the independent development of the master drug file was justified in terms of meeting this medical center's specific information needs.

The relationships between serum and saliva concentrations were evaluated in 18 patients after single doses of three theophylline preparations. Simultaneous multiple saliva and serum samples were obtained after theophylline ingestion and were analyzed for theophylline content by the modified Schack and Waxler spectrophotometric method. Significant variability was observed in the data for those saliva/serum ratio sets obtained within 30 min of dosage. The mean correlation coefficient for saliva/serum sample sets obtained at and after 30 min was 0.86. Pearson product moment correlation coefficients determined for saliva/serum ratios at 2,4,6, and 8 hr ranged from 0.84 to 0.89, leaving 26% of the variance unexplained. Serum concentrations were calculated from a randomly selected saliva/serum ratio for each patient. Predicted serum concentrations were +/- 2 micrograms/ml of measured concentrations in only 143 of the 196 determinations (73%). Therefore, the use of saliva concentrations to predict serum values has substantial error in specific patients and may lead to incorrect dosage adjustments.

Purified polygalacturonases from two fungi released proteins from wall fractions prepared from three plant species. Peroxidase activity was associated with the proteins released from the cell walls, and several of the protein fractions released contained hydroxyproline. Cellulase, purified free of pectic enzyme activity, was ineffective in releasing cell wall proteins. Specific inhibition of endopolygalacturonase activity prevented release of the proteins.

Pharmacy directors and pharmacists in charge of clinical services at 46 medium-sized hospitals were surveyed to identify possible explanations for previously documented inconsistency in the implementation of clinical pharmaceutical services. There were three study objectives: to determine the extent to which basic structural and functional management prerequisites have been implemented at these institutions; to determine whether a relationship exists between the kind and number of clinical services offered and implementation of these prerequisites; and to identify discrepancies between responses of the pharmacy director and the pharmacist in charge of clinical services at the same hospital to the same questions. One hundred hospitals providing clinical pharmaceutical services were randomly selected from a master list of 190 hospitals that had been grouped into nine geographic areas. Of 17 functional and structural prerequisites studied, 4 to 13 of them had been implemented at the hospitals surveyed. Only 24% of the hospitals had implemented the basic functional prerequisites of unit dose drug distribution and decentralized pharmaceutical services. Of nine clinical pharmaceutical services, one to eight were being delivered. A weak correlation between the number of prerequisites implemented and the number of clinical services provided was found. Significant disagreement was found between the directors and their pharmacists about which prerequisites and clinical services were being implemented. This pilot study suggests that pharmacy directors and clinical pharmacists need to assess how effectively basic management prerequisites are being put into practice in the delivery of clinical pharmaceutical services.

Hepatic conversion of porphobilinogen to porphyrins was less than 50% of control levels in human subjects with the genetic disease, intermittent acute porphyria. This relative block in heme biosynthesis may be relevant to a concomitant 6- to 10-fold elevation in delta-aminolevulinic acid synthetase activity, since this first and rate-controlling enzyme in the biosynthetic pathway is subject to negative feedback regulation by the end product, heme. A micro-radio-chemical assay of delta-aminolevulinic acid synthetase, and some of its applications, are described.