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.     

Salvage therapy for prostate cancer recurrence after radiation therapy

Radiotherapy has been successful in treating localized prostate cancer; however, a subset of patients will experience disease recurrence. Determination of the recurrence location must be made using pretreatment and posttreatment clinical variables, imaging, and postradiotherapy biopsy. Patients presumed to have local-only recurrence, optimal clinical risk factors, and an extended life expectancy may be considered for salvage local treatment. Current options include salvage surgery, cryoablation, and brachytherapy. Although they are associated with higher morbidity than primary therapy, salvage treatments can be effective and can still provide patients with a good oncologic and functional outcome. As these modalities continue to improve and patient selection is optimized, better results will evolve.     

Results of speech perception and speech production training for three prelingually deaf patients using a multiple-electrode cochlear implant.

Five studies were conducted to measure changes in the perception and production of selected speech targets, with training, in three prelingually deaf patients. The two adults and one adolescent were implanted with the Cochlear (Nucleus) multiple-electrode prosthesis. The studies were perception and production of nasal consonants; perception of syllable-final consonants; perception and production of alveolar consonants; auditory-visual perception of alveolar consonants; and perception and production of vowels. Perceptual data were collected in the audition (implant)-alone condition, except for the auditory-visual perception of alveolar consonants where the audition-alone, vision-alone, and auditory-visual conditions were used. Speech perception data in the audition-alone condition were also collected from four postlingually deaf adult implant patients, without training, to indicate differences between the two classes of patients. The three prelingually deaf patients generally showed some improvements in speech production. In perception, improvements were recorded only for individual patients in some studies. The performance of the adolescent was better than that of the two adults in all cases. The perceptual performance of the postlingually deaf patients was superior to that of the prelingually deaf patients in all cases.     

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.