Faculty Bibliography

Critically ill patients are predisposed to drug interactions because of the complexity of the drug regimens they receive in the intensive care setting. Drugs may affect the absorption, distribution, metabolism, and/or elimination of an object drug and consequently alter the intended pharmacologic response and potentially lead to an adverse event. Certain disease states that afflict critically ill patients may also amplify an intended pharmacologic response and potentially result in an unintended effect. A team approach is important to identify, prevent, and address drug interactions in the intensive care setting and optimize patient outcomes

PURPOSE: Platelet derived growth factor receptor inhibitor therapy improves the efficacy of taxane chemotherapy in preclinical models of prostate cancer. Men with high risk localized prostate cancer were treated with platelet derived growth factor receptor inhibitor therapy, docetaxel and hormone ablation in the preoperative setting, and clinicopathological outcomes were evaluated. MATERIALS AND METHODS: A total of 36 men with cT2 or greater disease, Gleason grade 8-10, serum prostate specific antigen more than 20 ng/ml or cT2b and prostate specific antigen more than 10 ng/ml and Gleason 7 disease, without radiological evidence of metastases, were scheduled to receive intramuscular leuprolide, 600 mg daily oral imatinib and 30 mg/m(2) weekly docetaxel x 4 every 42 days for 3 cycles before radical prostatectomy (beta [0.02, 1.98] prior on the possibility of pathological complete remission). Unresectable disease, postoperative prostate specific antigen 0.2 ng/ml or greater, or administration of postoperative radiation or hormones were defined as treatment failure. RESULTS: A total of 39 men were registered over 15 months. Median patient age was 57 years (range 44 to 71). Risk factors included T3 disease (22 of 39), Gleason 8-10 disease (31 of 39) and prostate specific antigen more than 20 ng/ml (12 of 39). Three men were ineligible or declined therapy, 29 of 36 (81%) received 3 cycles of therapy and 7 of 36 (19%) discontinued therapy related to toxicity. Grades 3-4 toxicity included rash (4), diarrhea (4), fatigue (6) and neutropenia (1). The surgical approach was feasible, without excessive or unusual complications such as wound dehiscence. No pathological complete remissions were defined. At a median followup of 39 months 53% were free from progression. CONCLUSIONS: Evidence for a favorable impact of platelet derived growth factor receptor inhibitor therapy on the efficacy of neoadjuvant docetaxel and hormonal ablation in high risk localized prostate cancer was not obtained

BACKGROUND: Stromal-epithelial signaling plays an important role in prostate development and cancer progression. Study of these interactions will be facilitated by the use of suitable prostate cell lines in appropriate model systems. METHODS: We have isolated an immortalized prostate mesenchymal cell line from the mouse E16 urogenital sinus (UGS). We characterized its expression of stromal differentiation markers, response to androgen stimulation, ability to induce and participate in prostate morphogenesis, response to Shh stimulation, and interaction with prostate epithelial cells. RESULTS: UGSM-2 cells express vimentin and smooth muscle actin, but not the mature smooth muscle markers myosin and desmin. This expression profile is consistent with a myofibroblast phenotype. Unlike other fibroblasts such as 3T3, UGSM-2 cells express androgen receptor mRNA and androgen stimulation increases proliferation. UGSM-2 cells are viable when grafted with embryonic UGS under the renal capsule and participate in glandular morphogenesis, but are not capable of inducing prostate morphogenesis of isolated UGS epithelium. Co-culture of UGSM-2 cells with human BPH-1 cells or co-grafting in vivo results in organized clusters of BPH-1 cells surrounded by a mantle of UGSM-2 cells. UGSM-2 cells are responsive to Sonic hedgehog (Shh), an important signaling factor in prostate development, and mimic the transcriptional response of the intact UGS mesenchyme. In co-cultures with BPH-1, UGSM-2 cells exhibit a robust transcriptional response to Shh secreted by BPH-1. CONCLUSIONS: UGSM-2 is a urogenital sinus mesenchyme cell line that can be used to study stromal-epithelial interactions that are important in prostate biology

Clinical pharmacy services in the critical care setting have expanded dramatically and include assisting physicians in pharmacotherapy decision making, providing pharmacokinetic consultations, monitoring patients for drug efficacy and safety, providing drug information, and offering medical education to physicians, nurses, and patients. Measurable clinical effects of these services include reduced drug errors and adverse drug events, decreased morbidity and mortality rates, and a positive pharmacoeconomic impact by decreasing overall health care costs

This case report describes a continuous i.v. infusion of glucagon used to reverse the cardiovascular manifestations of a nifedipine overdose in a patient who presented after a massive nifedipine extended-release tablet ingestion. In this patient, glucagon appeared to be effective in the management of this toxicologic emergency.

Hematogenous candidiasis is a life-threatening infection that occurs in critically ill patients. The incidence has increased dramatically over the past decade and Candida species are currently the fourth most common organism recovered from blood cultures in hospitalized patients. Numerous risk factors have been identified that predispose a patient to the development of hematogenous candidiasis. Diagnosis is often difficult in the clinical setting. Pharmacologic options for the management of hematogenous candidiasis includes amphotericin B, fluconazole, and flucytosine. Evidence from clinical trials indicate that fluconazole is as effective and better tolerated than amphotericin B for the management of hematogenous candidiasis in critically ill patients