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.     

A deep stop during decompression from 82 fsw (25 m) significantly reduces bubbles and fast tissue gas tensions.

In spite of many modifications to decompression algorithms, the incidence of decompression sickness (DCS) in scuba divers has changed very little. The success of stage, compared to linear ascents, is well described yet theoretical changes in decompression ratios have diminished the importance of fast tissue gas tensions as critical for bubble generation. The most serious signs and symptoms of DCS involve the spinal cord, with a tissue half time of only 12.5 minutes. It is proposed that present decompression schedules do not permit sufficient gas elimination from such fast tissues, resulting in bubble formation. Further, it is hypothesized that introduction of a deep stop will significantly reduce fast tissue bubble formation and neurological DCS risk. A total of 181 dives were made to 82 fsw (25 m) by 22 volunteers. Two dives of 25 min and 20 min were made, with a 3 hr 30 min surface interval and according to 8 different ascent protocols. Ascent rates of 10, 33 or 60 fsw/min (3, 10, 18 m/min) were combined with no stops or a shallow stop at 20 fsw (6 m) or a deep stop at 50 fsw (15 m) and a shallow at 20 fsw (6 m). The highest bubbles scores (8.78/9.97), using the Spencer Scale (SS) and Extended Spencer Scale (ESS) respectively, were with the slowest ascent rate. This also showed the highest 5 min and 10 min tissue loads of 48% and 75%. The lowest bubble scores (1.79/2.50) were with an ascent rate of 33 fsw (10 m/min) and stops for 5 min at 50 fsw (15 m) and 20 fsw (6 m). This also showed the lowest 5 and 10 min tissue loads at 25% and 52% respectively. Thus, introduction of a deep stop significantly reduced Doppler detected bubbles together with tissue gas tensions in the 5 and 10 min tissues, which has implications for reducing the incidence of neurological DCS in divers.     

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.     

Atypical fibroxanthoma and squamous cell carcinoma of the conjunctiva in xeroderma pigmentosum.

Patients with xeroderma pigmentosum (XP) have defective DNA repair and a high predisposition to developing abnormalities and neoplasia in the sun-exposed areas of the skin and mucous membranes. The most common tumors reported in patients with XP are squamous cell carcinomas, basal cell carcinomas, and melanomas. Atypical fibroxanthoma (AFX) is a pleomorphic tumor that arises predominantly in the sun-damaged skin of the head and neck regions of the elderly. We describe a unique case of a 6-year-old African American boy with XP who developed an atypical fibroxanthoma and 2 squamous cell carcinomas in the conjunctiva. The clinical and histopathologic findings of AFX are discussed.     

Partners in Growth: Implementing Family-Centered Changes in the Neonatal Intensive Care Unit

Although there are several forces driving changes with regard to parents within neonatal intensive care units (NICUs), they all culminate in the ideals represented in family-centered care. This article examined the variables that are perceived by parents to be barriers to their assumption of parental roles while their infants were hospitalized in the NICU. Data were used to support and implement pragmatic changes in program development and service delivery within the NICU.     

A novel mutation (deletion of Aalpha-Asn 80) in an abnormal fibrinogen: fibrinogen Caracas VI. Consequences of disruption of the coiled coil for the polymerization of fibrin: peculiar clot structure and diminished stiffness of the clot.

An abnormal fibrinogen was identified in a 10-year-old male with a mild bleeding tendency; several years later, the patient developed a thrombotic event. Fibrin polymerization of plasma from the propositus and his mother, as measured by turbidity, was impaired. Plasmin digestion of fibrinogen and thrombin bound to the clot were both normal. The structure of clots from both plasma and purified fibrinogen was characterized by permeability, scanning electron microscopy and rheological measurements. Permeability of patients' clots was abnormal, although some measurements were not reliable because the clots were not mechanically stable. Consistent with these results, the stiffness of patients' clots was decreased approximately two-fold. Electron microscopy revealed that the patients' clots were very heterogeneous in structure. DNA sequencing of the propositus and his mother revealed a new unique point mutation that gives rise to a fibrinogen molecule with a missing amino acid residue at Aalpha-Asn 80. This new mutation, which would disrupt the alpha-helical coiled-coil structure, emphasizes the importance of this part of the molecule for fibrin polymerization and clot structure. This abnormal fibrinogen has been named fibrinogen Caracas VI.