Characterization of epithelial cell shedding from human small intestine.

Intestinal epithelial cells migrate from the base of the crypt to the villi where they are shed. However, little is known about the cell shedding process. We have studied the role of apoptosis and wound healing mechanisms in cell shedding from human small intestinal epithelium. A method preparing paraffin sections of human small intestine that preserves cell shedding was developed. A total of 14 417 villus sections were studied. The relationship of cell shedding to leukocytes (CD45), macrophages (CD68) and blood vessels (CD34) were studied by immunohistochemistry. Apoptotic cells were identified using the M30 antibody against cleaved cytokeratin 18 and an antibody against cleaved caspase-3. Potential wound healing mechanisms were studied using antibodies against Zona Occludens-1 (ZO-1) and phosphorylated myosin light chains (MLCs). We found that 5.3% of villus sections contained a shedding cell. An eosin-positive gap was often seen within the epithelial monolayer beneath shedding cells. Shedding was not associated with leukocytes, macrophages or blood vessels. Cells always underwent apoptosis during ejection from the monolayer. Apoptotic bodies were never seen in the monolayer but morphologically normal cells that were positive for M30 or cleaved caspase-3 were often seen. ZO-1 protein was usually (41/42) localized to the apical pole of cells neighboring a shedding event. Phosphorylated MLCs could be identified in 50% of shedding events. In conclusion, cell shedding is associated with apoptosis though it remains unclear whether apoptosis initiates shedding. It is also associated with phosphorylation of MLCs; a process associated previously with wound healing.

Ribosomal protein l19 is a prognostic marker for human prostate cancer.

Microquantity differential display analysis of gene expression profiles between benign (PNT2) and malignant (PC3M) human prostate cell lines identified the gene encoding ribosomal protein L19 (RPL19) to be overexpressed in the malignant cells. Northern blot hybridization analysis done on a wide range of human cell lines and tissues confirmed the level of RPL19 mRNA to be 5-fold higher in malignant cell lines and 8-fold higher in malignant tissues, when compared with their benign counterparts. Analysis of RPL19 mRNA expression by in situ hybridization revealed a significant increase of RPL19 expression in a substantial number of prostate cancers. All of the eight normal prostatic tissues were unstained (100%). Of 32 benign prostatic hyperplasia (BPH) tissues, 15 (46.9%) were unstained, 9 (28.1%) stained weakly, and 8 (25%) stained moderately. Among 87 carcinomas, only 7 (8.1%) were unstained, whereas 22 (25.2%) stained weakly, 21 (24.1%) stained moderately, and 37 (42.61%) stained strongly. The intensity of staining of the malignant specimens was significantly higher than that of normal and BPH specimens (chi(2): n = 127, P < 0.001). Gleason scores of the carcinomas correlated with RPL19 expression (chi(2): n = 87, P < 0.001). Kaplan-Meier survival analysis confirmed increased RPL19 expression to be highly predictive of shorter patient survival (P < 0.05), revealing RPL19 to be a sensitive predictor of prostate cancer progression. Expression of this protein could be a valuable marker in prostate cancer diagnosis and patient management.

Medicare coverage and reimbursement of outpatient prescription drugs in the US: history, recent changes and outlook for the future.

US Medicare provides health insurance to 41.5 million disabled and elderly Americans. Outpatient coverage, including a limited pharmacy benefit, is provided by Medicare Part B. Even with very restrictive criteria, Part B incurs 8.5 billion US dollars annually for outpatient prescription medications. Prior to passage of the Medicare Prescription Drug and Improvement Modernization Act (MMA) 2003, the Part B pharmacy benefit was criticised for its limited coverage criteria and flawed reimbursement practices. Despite the changes made under the MMA, these two issues continue to be concerns for the Medicare Part B outpatient prescription drug programme because (a) the criteria for selection of drugs for coverage do not necessarily reflect valuable advances in medicine, and the extent to which the new private-sector style 2006 Medicare Part D drug benefit will correct this is unknown; and (b) although pre-MMA average wholesale price-based reimbursement practices were clearly flawed, MMA changes such as use of the average sales price and providing increased reimbursement to physicians for drug administration may or may not be successful, and could lead to new problems. The extent to which the MMA and its associated Part D drug benefit address concerns and advance towards better, more cost-effective healthcare is reviewed and recommendations made.

Understanding the underlying drivers of inpatient cost growth: a literature review.

BACKGROUND: After the declining growth in inpatient hospital spending that occurred from 1994 through 1998, the recent trend in increased spending has been of concern to many. Understanding the underlying reasons for this new growth will aid decision makers in finding best means to manage inpatient costs. OBJECTIVE: To identify potential contributors to recent growth in inpatient spending. STUDY DESIGN: Literature review. METHODS: Healthcare and economic databases, prominent Web sites, and key journals were searched to identify potential drivers for the 1999-2001 rise in inpatient spending. Initial literature review and state-level regression analyses published in a companion paper were used to identify key explanatory factors, which were further explored. RESULTS: Although many of the contributors to the rise in inpatient costs overlap and are interrelated, the major cost drivers were identified as (1) workforce shortage; (2) new technology; (3) less tightly managed care; and (4) shifting hospital business directions. Underlying factors such as legislation, quality of care, limited access to noninpatient care, pressures on the safety net, population aging, and increasing chronic illness prevalence were found to influence the contributors and healthcare spending in general. CONCLUSIONS: Future trends in inpatient spending will depend on the response of the healthcare system to these cost drivers and underlying factors. Potential avenues to control inpatient spending include expanding access to primary care, encouraging cost-effective technology and more efficient hospital market structures, and developing incentives for the healthcare workforce.