Tubulin, BRCA1, ERCC1, Abraxas, RAP80 mRNA expression, p53/p21 immunohistochemistry and clinical outcome in patients with advanced non small-cell lung cancer receiving first-line platinum-gemcitabine chemotherapy.

BACKGROUND: The aim of this study was to assess the predictive value of tumor expression of nine genes on clinical outcome in patients with advanced NSCLC receiving platinum-gemcitabine chemotherapy. METHODS: Quantitative PCR or immunohistochemistry were used to analyze the expression of ß-tubuline IIA (TUBB2A), ß-tubuline III (TUBB3), BRCA1, ERCC1, Abraxas (ABRX) and RAP80 in mRNA isolated from paraffin-embedded tumor biopsies of 45 NSCLC patients treated as part of a larger observational trial. All patients received first-line platinum-gemcitabine chemotherapy for stage IIIB or IV NSCLC. RESULTS: Median progression-free survival (PFS) was 7 months, overall survival (OS) 12 months. A partial treatment response was found in 14 patients (33%). Patients with low ERCC1 or ABRX expression had a significantly better response to chemotherapy (R=-0.45, p<0.01 for ERCC1; R=-0.40, p=0.016 for ABRX). A significant correlation was found between the individual time for PFS and the expression of both ERCC1 (R=-0.36, p=0.015) and ABRX (R=-0.46, p=0.001). Patients with low ERCC1 expression had a longer OS as compared to patients with high ERCC1 expression (HR=0.26, log-rank p=0.02). CONCLUSIONS: The study confirms tumor expression of ERCC1 as a predictor for clinical outcome in patients with advanced NSCLC receiving platinum-based chemotherapy, and found ABRX expression to be similarly predictive of clinical outcome. Prospective validation is warranted and - if confirmed - non platinum-containing chemotherapy should be explored as the preferred treatment in patients with high ERCC1 or ABRX expression and no activating mutations of EGFR.

Using pharmacists' documentation of clinical activities to reclaim employees and reposition the department.

The use of documentation on pharmacist clinical activities to encourage greater hospital investment in a department is described. From 1983 through 1988, the number of full-time-equivalent (FTE) positions in the pharmacy department at a 468-bed medical center was reduced from 63 to 39.4. To cope with the challenge of a sharply reduced staff, the department established a permanent pharmacy-nursing task force, developed a pharmacy strategic plan, used total quality management, recruited the best staff possible when openings appeared, and held staff retreats. In addition, measures were taken to begin documenting all pharmacist clinical activities online. As data were accumulated, it became clear that more pharmacist involvement in patient care areas was needed and that more resources would be necessary to achieve that. Presentations were made to hospital administration to demonstrate the existing and potential contributions of the department; the presentations drew heavily on the clinical documentation. Formal reports were also submitted. As a result, the department received approval for a pharmacist career ladder, an increase of 1.6 pharmacist FTEs for the evening shift, a large salary-range adjustment for staff pharmacists, and an increase of 1 pharmacist FTE to focus on antimicrobial use. A pharmacy department successfully used documentation of its clinical activities to make a case to administration for reclaiming some of the pharmacist FTEs lost through downsizing.

Development of a methylprednisolone protocol for use in acute spinal cord injuries.

Acute spinal cord injury is a serious medical condition that results in 10,000 new cases of paralysis each year. Initial physical damage to the spinal cord is followed by chemical damage, resulting in cell death and scar tissue formation. Methylprednisolone therapy has proven effective in suppressing the chemical damage, particularly when started within 8 hours of injury. A protocol developed by the Pharmacy Department at Methodist Medical Center in Dallas, Texas, is described. This protocol facilitates accurate, efficient preparation and administration of this emergency therapy. The protocol takes advantage of the pharmacist's unique expertise to lessen the risk of calculation errors and mistakes in preparation, by providing a tailored drug admixture for administration at a fixed flow rate. The protocol and a sample of the pharmacy work sheet are presented.

Methotrexate in rheumatoid arthritis: an update.

Methotrexate, a folic acid antagonist, is being employed more frequently in an attempt to control rheumatoid arthritis that has not responded adequately to conventional therapies. Systemic administration of 7.5-15 mg weekly in a pulse fashion appears to be effective without precipitating serious adverse effects. Concern over potentially serious adverse effects and lack of well-controlled clinical trials have limited its use to severe, refractory disease. Its use in the future is likely to increase in these patients because of its ease of administration and the high response rate noted in clinical studies.

The use of methotrexate in rheumatoid arthritis.

The use of methotrexate in rheumatoid arthritis is reviewed. Methotrexate, a folic acid antagonist, is sometimes employed in an attempt to symptomatically control patients whose disease does not respond adequately to conventional therapies. Systemic administration of 7.5-15 mg/wk in a "pulse" fashion appears to be effective without precipitating severe adverse effects. However, concern over potentially serious side effects and a lack of well-controlled clinical trials have limited its use to severe, refractory disease. Further studies are needed before its role in rheumatoid arthritis can justifiably be expanded.

Failure of nifedipine and reperfusion to reduce infarct size relative to region at risk as measured by NADH fluorophotography.

In this report we describe a new technique for the measurement of region at risk after coronary artery ligation in the rabbit by NADH fluorophotography. We also describe the application of this technique to a study of nifedipine combined with reperfusion in experimental myocardial infarction. In 16 untreated rabbits the epicardial surface area of NADH fluorescence immediately after coronary ligation correlated with infarct size at 24 hr after coronary occlusion, as measured by nitro blue tetrazolium staining (r = .84, p less than .001). In 24 rabbits we studied the effect of nifedipine administered immediately after coronary ligation and combined with reperfusion at 1 hr after occlusion. Nifedipine had no significant effect on region at risk or infarct size.

Effect of TRH on plasma arginine vasopressin.

Effect of thyrotropic releasing hormone (TRH) on plasma arginine vasopressin (AVP) was studied in human subjects. All 7 normal controls and 2 hypothyrotropic hypothyroid subjects failed to show any rise of AVP on TRH administration. The 4 primary hypothyroid subjects had elevated basal AVP level and showed further elevation on TRH administration. Our data suggests that elevated TRH in primary hypothyroid subjects may act directly as a nonosmotic stimulus or modulate the osmoreceptor and hypothalamic neurohypophyseal system for AVP release.