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.     

Triplet morbidity and mortality in a large case series.

OBJECTIVE: A significant increase in the triplet birth rate has occurred recently. This rise is of concern, as these infants are historically reported to be at risk of adverse outcome. Thus, we examined the outcome of triplet births in a large contemporary case series. STUDY DESIGN: Since 1993, detailed clinical data have been collected on all patients admitted to our Neonatal Intensive Care Unit. We retrospectively analyzed this database to examine triplet outcome. RESULTS: A total of 51 consecutive sets of triplets were born over a 9-year period. The mean birth weight for triplets was 1789+/-505 g, mean gestational age was 32.6+/-2.7 weeks, with discordancy present in 17.6% of neonates. Complications of prematurity were infrequent. Triplet survival to discharge was 96%. CONCLUSIONS: This large contemporary case series of triplets demonstrates excellent survival with low associated morbidity. These data suggest that there may no longer be medical justification for offering selective fetal reduction to parents with triplet pregnancies.     

Longitudinal,population-based study of racial/ethnic differences in colorectal cancer survival: impact of neighborhood socioeconomic status,treatment and comorbidity

Background  

Colorectal cancer, if detected early, has greater than 90% 5-year survival. However, survival has been shown to vary across racial/ethnic groups in the United States, despite the availability of early detection methods.     

Monitoring health care system performance in Iowa.

Monitoring the performance of the health care delivery system is a public health function that becomes more important as organized delivery systems begin to take control over larger portions of the medical care market. The study reported here illustrates how standard medical care epidemiology can be applied to analysis of health care system performance to aid governmental efforts to monitor new developments in the medical care market. In order to evaluate the efficiency of hospital care delivered in Iowa, age- and sex-adjusted population admission rates for five common procedures were generated for all 99 counties. The five common procedures were defined as follows: hernia, tonsillectomy, cesarean section, hysterectomy, and cholecystectomy. In addition, variations in 11 ambulatory care-sensitive condition rates were analyzed. Residents of at least 15 counties were at significantly greater than average risk of receiving each of the common procedures (chi 2 test, P < 0.05). Counties that had a high rate for one procedure tended to have a high rate for at least one other procedure. Several counties had more than twice the mean rate. Even a 10% reduction, when added across all five common procedures. amounts to well over 2,000 hospitalizations avoided. It is assumed that reductions would be concentrated in high-rate counties. If a 50% reduction could be achieved in only part of the ambulatory care-sensitive procedures, more than 10,000 hospital admissions could be avoided.     

Involvement of platelet activating factor and thromboxane A2 in the renal response to unilateral ureteral obstruction

Platelet activating factor (PAF) and thromboxane A2 (TxA2) are two vasoactive mediators which can decrease renal blood flow. Both are synthesized by various intrarenal cell types or by macrophages which may infiltrate the kidney during unilateral ureteral obstruction (UUO). In several experimental systems, PAF receptor activation is accompanied by TxA2 release; pharmacological modification of TxA2 synthesis or receptor activation modulates the response to PAF. The involvement of PAF in UUO has not been studied previously, and the role of TxA2 has not been clearly defined by previous investigations. The hemodynamic response to acute UUO is characterized by decreases in renal blood flow (RBF) and glomerular filtration rate and an acute increase in ureteral pressure. In the present experiments, the involvement of either PAF or TxA2 in the acute response to UUO was studied by determining if blockade of either the TxA2 or PAF receptor would affect the renal hemodynamic response to UUO. In addition, the effect of blockade of the TxA2 receptor on the renal response to PAF was determined. Our results indicate that only a small portion of the renal response to PAF is mediated by TxA2, and that neither PAF nor TxA2 can be implicated in the acute hemodynamic response to UUO. TxA2 or PAF involvement in the chronic response to UUO still remains to be determined.