Impact of a clinical pharmacist on antibiotic prescribing. A multicenter trial.

Within the past two decades, hospital pharmacists have become increasingly involved in providing consultation to physicians for drug management. Antibiotic use has become a complex and rapidly expanding discipline, complicated by the introduction of multiple new antimicrobial agents, each with unique features, and the pressures of prospective payment schemes. This study demonstrated that a team including a pharmacist had a positive impact on medical residents' utilization of antibiotics.     

Dipyridamole and RA-642 inhibit the production of superoxide anion and free radical damage to rat lens.

We studied the effects of dipyridamole and RA-642 on the production of superoxide anions and on oxygen radicals-induced lipid peroxidation in lens tissue homogenates from normal rats and rats given dipyridamole or RA-642 intraperitoneally. Superoxide production was evaluated by phenazine methosulphate (PMS)-induced nitroblue tetrazolium (NBT) reduction and lipid peroxidation by ferrous sulfate and ascorbic acid (FeAs)-induced malondialdehyde (MDA) production. Dipyridamole and RA-642 showed an inhibitory effect on both assays in the experiments with lens tissue homogenates from untreated or treated rats. The extent of inhibition, however, was significantly higher in pyrimidopyrimidinic-treated rats (range of inhibition at different times of incubation was 18% versus 23-57% for dipyridamole and 14% versus 73-80% for RA-642 in the assay of MDA production, and 10% versus 33-37% for dipyridamole and 2.5% versus 11-32% for RA-642 in the assay of NBT reduction). Concentrations of dipyridamole and RA-642 in lens tissue from treated animals could not be determined (less than 0.001 micrograms/mg of tissue). Although both compounds inhibited lipid peroxidation induced by oxygen free radicals, the mechanism of action might include the role of adenosine as a mediator.     

MR characteristics of iophendylate (Pantopaque)

Although iophendylate (Pantopaque) has been largely replaced by water soluble agents for myelography, retained intracranial or intraspinal Pantopaque remains a common occurrence. Pantopaque has signal characteristics similar to fat with both short T1 and T2 relaxation times. In vitro measurements revealed T1 = 170 ms and T2 = 27 ms. Spine radiography is recommended in patients with a history of previous myelography and magnetic resonance abnormalities similar to fat.     

Contributions of occipital and temporal brain regions to visual and acoustic imagery--a spect study

Regional cerebral blood flow (rCBF) was assessed by means of HMPAO-SPECT in two experimental groups. In a control condition both groups listened to abstract words, in the experimental condition they heard five names of objects. One group was advised to form visual images of the objects, the other group was advised to form acoustic images of the sounds made by these objects. Post-experimental questionnaires revealed that most of the subjects in the acoustic imagery condition had had visual images in addition to the acoustic ones. Both imagery conditions lead to approximately equal increases of rCBF in the left inferior occipital region and in the left thalamus. Flow increases in both hippocampal regions and the right inferior and superior temporal regions were larger in the acoustic than in the visual imagery condition. It is concluded that only the activation of left inferior occipital and left thalamic regions can be interpreted as being related to modality-specific visual aspects of imagery.     

The abdomen, thigh, and arm as sites for subcutaneous sodium heparin injections.

The purpose of this study was to evaluate three subcutaneous injection sites for low-dose heparin therapy (5,000 units). One hundred and one subjects were randomly placed in one of three groups. Group A received injections in the abdomen, Group B, in the thigh, and Group C in the arm. Each subject received three injections at the one site. Activated partial thromboplastin time (APTT) was measured prior to initiation of heparin and again four hours after the first injection. Bruising was measured at 48, 60, and 72 hours postinjection. There were no statistically significant differences among groups for either changes in APTT or bruising at 60 and 72 hours postinjection. Thus the clinical practice of utilizing the abdomen as the only or preferred site for subcutaneous heparin injections was not supported.     

Randomized trial of bilateral oophorectomy versus tamoxifen in premenopausal women with metastatic breast cancer

A randomized clinical trial was performed to compare the efficacy of bilateral oophorectomy with that of tamoxifen at a dose of 10 mg twice daily in premenopausal women with metastatic breast cancer, and to examine the efficacy of each as a crossover treatment. Initial treatment responses were seen in ten of 27 patients (37%) treated with oophorectomy and seven of 26 patients (27%) treated with tamoxifen. The difference was not statistically significant. Crossover responses were seen in five of 15 patients (33%) treated with oophorectomy, including three responses in ten prior tamoxifen nonresponders; and two of 18 patients (11%) treated with tamoxifen. Time to progression distributions were not significantly different during initial treatment, and no significant differences in survival were noted. Thus, there was no overall disadvantage to the use of tamoxifen as opposed to oophorectomy as initial hormonal therapy, and a failure to respond to tamoxifen did not preclude a response to subsequent oophorectomy. Exploratory data analysis within subsets indicated consistent differential treatment effects in the visceral dominant patients. Of the 16 such patients treated with oophorectomy, eight (50%) experienced objective responses but there were no responses in the 14 patients treated with tamoxifen. In the nine visceral dominant crossover patients who had not responded to initial tamoxifen, three (33%) subsequently responded to oophorectomy. Time to progression distributions within the visceral dominant subset appeared to be better for the patients treated initially with oophorectomy. However, one must be very cautious in drawing conclusions from exploratory subset analyses, especially with the small sample size. Further studies would be required to test any hypothesis of differential organ site responsiveness.     

Three-dimensional quantitative structure-activity relationship analysis of human CYP51 inhibitors.

CYP51 fulfills an essential requirement for all cells, by catalyzing three sequential mono-oxidations within the cholesterol biosynthesis cascade. Inhibition of fungal CYP51 is used as a therapy for treating fungal infections, whereas inhibition of human CYP51 has been considered as a pharmacological approach to treat dyslipidemia and some forms of cancer. To predict the interaction of inhibitors with the active site of human CYP51, a three-dimensional quantitative structure-activity relationship model was constructed. This pharmacophore model of the common structural features of CYP51 inhibitors was built using the program Catalyst from multiple inhibitors (n = 26) of recombinant human CYP51-mediated lanosterol 14alpha-demethylation. The pharmacophore, which consisted of one hydrophobe, one hydrogen bond acceptor, and two ring aromatic features, demonstrated a high correlation between observed and predicted IC(50) values (r = 0.92). Validation of this pharmacophore was performed by predicting the IC(50) of a test set of commercially available (n = 19) and CP-320626-related (n = 48) CYP51 inhibitors. Using predictions below 10 microM as a cutoff indicative of active inhibitors, 16 of 19 commercially available inhibitors (84%) and 38 of 48 CP-320626-related inhibitors (79.2%) were predicted correctly. To better understand how inhibitors fit into the enzyme, potent CYP51 inhibitors were used to build a Cerius(2) receptor surface model representing the volume of the active site. This study has demonstrated the potential for ligand-based computational pharmacophore modeling of human CYP51 and enables a high-throughput screening system for drug discovery and data base mining.