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.     

Microbiology of adult cellulitis

Needle aspiration of cellulitis sites is commonly advocated to assist in the identification of causative organisms. Twenty-five nondiabetic, adult patients with a clinical diagnosis of cellulitis had site aspirations and blood cultures obtained before antibiotic therapy was initiated. Site cultures were positive in 6 of 25 patients. Blood cultures were positive in 4 of 25 patients. All organisms except one (Enterobacter agglomerans) were staphylococci or streptococci. The gram-negative bacilli were not believed to be a pathogen based on the patient's prompt response to nafcillin. In adult patients who do not have complications, the use of needle aspiration was not supported. Empiric treatment of cellulitis aimed at gram-positive cocci appears to be sufficient.     

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.     

Distribution and function of cholinergic receptors in the sheep detrusor muscle

The distribution of cholinergic nerve fibres, as well as the characterization of the muscarinic receptors responsible for the contraction, were determined in the detrusor smooth muscle of the sheep. The results obtained demonstrated a rich presence of acetylcholinesterase (AChE)-positive fibres distributed throughout the bladder body forming dense neuromuscular, subepithelial and perivascular plexuses. Furthermore, intramural ganglia containing AChE-positive cell bodies were identified. However, acetylcholine and carbachol induced a dose-dependent contraction of detrusor smooth muscle. The effect observed with carbachol was competitively antagonized by atropine (pA2: 8.94), pirenzepine (pA2: 7.38), AF-DX 116 (pA2: 7.35), 4-DAMP (pA2: 9.26) and hexahydroxiladifenidol (HHSiD) (pA2: 8.49). The pA2 value for pirenzepine is intermediate between M1- and M2-receptors which suggests that this antagonist does not act on M1- or M2-receptors, but that it does on M3-receptors. The pA2 value for AF-DX 116 is consistent with the presence of M2-receptors in this tissue. Moreover, the pA2 values obtained for both 4-DAMP and HHSiD are in agreement with the presence of M3-receptors, due to the lack of effect of pirenzepine on M1-muscarinic receptors. These results indicate the existence of a rich parasympathetic innervation in the sheep detrusor muscle and suggest that its contraction could be mediated by the stimulation of muscarinic receptors belonging to both M3- and M2-subtypes.     

Adenocarcinoma at an ileostomy site after colectomy for ulcerative colitis

In this article we present the tenth case, according to the literature, of adenocarcinoma occurring at a long standing ileostomy originally performed for ulcerative colitis. Study of this and previous cases demonstrates common factors such as a previous history of ulcerative colitis, a long interval until the appearance of symptoms, together with a similar clinical and pathological characterisation with invasion of neighbouring skin layers close to the ileostomy. Several pathogenic hypotheses are considered. We believe that local excision in oder to obtain the diagnosis is a better option than a sampling biopsy and that surgery should include a wide resection of the abdominal wall and intestine in order to comply with therapeutic criteria in malignant disease.