ABSTRACT
One of the major challenges in prostate cancer (PCa) research is the identification of key players that control the progression of primary cancers to invasive and metastatic disease. The majority of metastatic PCa express wild-type p53, whereas loss of p63 expression, a p53 family member, is a common event. Here we identify inhibitor of apoptosis-stimulating protein of p53 (iASPP), a common cellular regulator of p53 and p63, as an important player of PCa progression. Detailed analysis of the prostate epithelium of iASPP transgenic mice, iASPP(Δ8/Δ8) mice, revealed that iASPP deficiency resulted in a reduction in the number of p63 expressing basal epithelial cells compared with that seen in wild-type mice. Nuclear and cytoplasmic iASPP expression was greater in PCa samples compared with benign epithelium. Importantly nuclear iASPP associated with p53 accumulation in vitro and in vivo. A pair of isogenic primary and metastatic PCa cell lines revealed that nuclear iASPP is enriched in the highly metastatic PCa cells. Nuclear iASPP is often detected in PCa cells located at the invasive leading edge in vivo. Increased iASPP expression associated with metastatic disease and PCa-specific death in a clinical cohort with long-term follow-up. These results suggest that iASPP function is required to maintain the expression of p63 in normal basal prostate epithelium, and nuclear iASPP may inactivate p53 function and facilitate PCa progression. Thus iASPP expression may act as a predictive marker of PCa progression.
Subject(s)
Cell Nucleus/metabolism , Disease Progression , Intracellular Signaling Peptides and Proteins/metabolism , Prostatic Neoplasms/pathology , Repressor Proteins/metabolism , Adult , Aged , Animals , Biomarkers, Tumor/metabolism , Cell Differentiation , Cell Line, Tumor , Coculture Techniques , Cohort Studies , Epithelium/metabolism , Epithelium/pathology , Humans , Male , Mice , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness , Phenotype , Phosphorylation , Prognosis , Prostate/metabolism , Prostatic Neoplasms/surgery , Tumor Suppressor Proteins/metabolismABSTRACT
We present the rare case of a ureteric hernia into the sciatic foramen. The presentation was that of a 59-year-old woman with urinary tract sepsis associated with an acute deterioration of renal function. The hernia was successfully repaired laparoscopically.
Subject(s)
Herniorrhaphy , Laparoscopy/methods , Proteus Infections/drug therapy , Sepsis/etiology , Ureteral Diseases/surgery , Abdominal Pain/etiology , Acute Kidney Injury/etiology , Acute Kidney Injury/surgery , Female , Hernia/complications , Humans , Middle Aged , Sepsis/drug therapy , Ureteral Diseases/complicationsABSTRACT
The concept of product line management has recently drawn much attention in the health care field. The impetus has come from both marketing and accounting professionals as they have sought to find solutions to identified problems. Examined here are the roots of product line management, the reasons for the growth in the application of the concept in health care, and whether it promises to solve the problems faced by health care organizations in the current highly competitive environment.
Subject(s)
Hospital Administration , Marketing of Health Services/methods , Women , Female , Hospital Departments , Humans , Planning Techniques , United StatesSubject(s)
Asthma/diagnosis , Bronchial Provocation Tests/methods , Methacholine Compounds , Adolescent , Adult , Female , Forced Expiratory Volume , Humans , Male , Methacholine ChlorideABSTRACT
To compete effectively, hospital administrators need to define their businesses and markets and assess their position within those markets. This article presents a system, developed at Forbes Health System, Pittsburgh, Pennsylvania, designed to accomplish this task. Included here are the three steps necessary to apply the strategic program unit technique.
Subject(s)
Hospital Planning/methods , Multi-Institutional Systems/organization & administration , Diagnosis-Related Groups , Economic Competition , Hospitals, Special/economics , Pennsylvania , Planning TechniquesABSTRACT
As Community Support Programs for the chronically mentally ill expand, it becomes increasingly important to determine the number of individuals qualifying for these services. Although national prevalence data are currently available, they have only limited usefulness for program planning at state and local levels. Given the distinctive circumstances affecting each community's chronically ill population, their number, and their need for services, the authors propose identifying a patient cohort that approximates the local prevalence of persons needing Community Support Programs by using one of three methods. The first method identifies persons who have been hospitalized previously and who currently require outpatient psychiatric care. The second identifies persons previously hospitalized who require another hospitalization during a specified period of time. And, the third method identifies persons who are currently in outpatient treatment with a diagnosis of schizophrenia. choice of method depends on definition of chronic mental illness, type of data available, local treatment philosophies, and health care system structure.
