Loss of breast cancer metastasis suppressor 1 protein expression predicts reduced disease-free survival in subsets of breast cancer patients.

PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors.     

The Effect of Flurbiprofen on Steady-State Plasma Lithium Levels

Study Objective . To evaluate the effects of flurbiprofen therapy on the pharmacokinetics of lithium. Design . Placebo-controlled, single-blind, crossover study. Setting . University-affiliated hospital. Patients . Eleven healthy women with bipolar disorder. Interventions . The subjects received therapeutic doses of lithium administered as an immediate-release capsule every 12 hours. In addition, they received one placebo tablet every 12 hours during phase I and flurbiprofen 100 mg every 12 hours during phase II of the study. Measurements and Main Results . Steady-state pharmacokinetic parameters were measured for each phase. Lithium trough plasma concentration (C_min) and area under the curve were statistically significantly increased (p<0.05) when patients received flurbiprofen. Flurbiprofen also caused decreases in lithium clearance and 24-hour lithium urine excretion, although the changes did not reach statistical significance. Clinically significant increases in C_min appeared to be associated with a greater than 1000-μg/24 hour decrease in urinary excretion of prostaglandin E₂. Conclusion . Patients with clinically normal renal function may experience an increase in lithium levels with the initiation of flurbiprofen therapy.     

The Future of Clinical Psychology: Board Certification

The present article presents the future of clinical psychology board certification. With the increasing specialization in the field of professional psychology and the generic nature of state licensure, clinical psychology as a specialty will develop into a specialty area in a similar fashion as have specialties in medicine. A brief history of board certification in professional psychology by the American Board of Professional Psychology is reviewed and the process of becoming board certified in either clinical psychology or clinical child and adolescent psychology is discussed.     

Production of a human monoclonal anti-epithelial cell surface antibody derived from a patient with pemphigus vulgaris.

The production of monoclonal autoantibodies derived from individuals with autoimmune diseases constitutes a powerful tool to analyse an autoimmune process at both the antigen and antibody levels. We established a human anti-epithelial cell surface monoclonal antibody by applying hybridoma technology using peripheral blood lymphocytes from a patient with pemphigus vulgaris using a heteromyeloma as the fusion partner. The F12 monoclonal antibody displays four major characteristics: (1) it belongs to the IgM, kappa class; (2) it binds to the cell surface of stratified squamous and simple epithelia; (3) it recognizes an antigenic determinant associated with the desmosomal complex as demonstrated by indirect immunoelectron microscopy; (4) by immunoblotting analysis, it reacts with a 185 kDa polypeptide which was also recognized by a few pemphigus vulgaris sera. Although the F12 monoclonal antibody does not have the immunochemical properties of classical pemphigus vulgaris autoantibodies, several arguments suggest its relevance to the pemphigus vulgaris autoimmune response and, therefore, the heterogeneity of the antigen/antibody systems involved in this autoimmune disorder.     

Adhesive properties of Haemophilus influenzae to different human cells

The adhesion of 19 nontypable strains and 3 typable (type b) Haemophilus influenzae to human cells was examined using buccal epithelial cells (BEC), the continuous HEp-2 cell line and human 0 erythrocytes. The strains were classified into three phenotypes, according to their adhesive properties. Phenotype 1 consists of strains that adhere to both buccal epithelial cells and HEp-2 cells. Phenotype 2 consists of strains that adhere to both buccal epithelial cells and erythrocytes and strains belonging to phenotype 3 adhere to none of the three cell types used. Among 22 strains studied, 18 (81.8%) belonged to phenotype 1, 2 (9.1%) to phenotype 2 and 2 (9.1%) to phenotype 3. Fimbriae were observed for 11 (61%) among the 18 adherent strains belonging to phenotype 1. The 7 nonpiliated strains adhered with a significant adhesion index, thus this results would indicate that a non fimbrial adhesin exists.     

Endoscopic diagnosis and treatment of Mirizzi's syndrome.

Mirizzi's syndrome is the name given to common bile duct obstruction secondary to a stone in the cystic duct. The cause of the biliary obstruction is often difficult to establish before operation. We report two cases of Mirizzi's syndrome, diagnosed endoscopically and treated without surgery. One of the patients was treated by drainage of both the common bile duct and the gallbladder associated with monooctanoin dissolution of the gallstone. The other was treated by common bile duct stenting.     

Analysing managerial responses in face-to-face contacts

Executive nurse managers, as well as other nurse managers, spend much time responding verbally to people. Whether or not their responses are effective in these situations remains an unexplored area in nursing administration. The author describes a research-based framework to analyse managerial actions. Five types of actions, three non-exploratory and two exploratory, were identified through previous research using Orlando's theory as the framework. Subsequent research suggests nurses prefer that their managers use exploratory action. The article contains discussion on how specific types of actions facilitate or thwart problem identification.