Osteopontin regulates multiple functions contributing to human colon cancer development and progression.

Osteopontin (OPN) is a secreted phosphoglycoprotein known to interact with a number of integrin receptors. While increased OPN expression has been reported in a number of human cancers, and its cognate receptors (alphav-beta3, alphav-beta5, and alphav-beta1 integrins and CD44) have been identified, its role in colon cancer development and progression has not been extensively studied. We previously identified, using a combination of gene expression and tissue microarrays, that increased OPN expression is concordant with tumor stage. The current study examined the functional role of OPN in colon cancer progression and metastatic potential. The principal findings of this study were that both endogenous OPN expression (via stable transfection) as well as exogenous OPN (added to culture medium) enhanced the motility and invasive capacity of human colon cancer cells in vitro. OPN appeared to regulate motility though interaction with CD44. OPN expression also reduced intercellular (homotypic) adhesion, an important characteristic of metastatic cancer cells. Stable transfection of four poorly tumorigenic human colon cancer cell lines with OPN also resulted in enhanced tumorigenicity in vivo with increased proliferation and increased CD31 positive microvessel counts, concordant with the degree of OPN expression. Collectively, these results suggest that OPN may affect multiple functional components contributing to human colon cancer progression and solidifies its role in this process.

Beyond health care cost containment: creating collaborative arrangements among the stakeholders.

The causes of escalating healthcare costs in the United States and many other industrial countries are well documented. Less evident are the structural factors that underlie the increases and their implications for the future. This paper discusses these structural factors, puts them in the context of the healthcare marketplace, and proposes a way to address them using a collaborative arrangement among all stakeholders in a healthcare system, called value-based partnering. To be successful, the effort must include not only final purchasers (such as employers or Medicare in the USA) but all stakeholders in a healthcare system. Each stakeholder must develop a value equation in terms that are meaningful to the others, and must identify opportunities for value-enhancing partnerships. The paper also identifies some of the impediments to value-based partnering and discusses ways to overcome them, including the need for senior management intervention within some stakeholder groups, and the importance of collaborative discussions among all stakeholders.

Value-based partnering in health care.

Many companies are beginning to focus on value in their health care purchasing decisions, and some are going beyond value-based purchasing to value-based partnering. Value-based partnering recognizes the interdependencies among stakeholder groups in the health care system and creates a strategic reason for them to exchange information and create long-term strategic alliances. This article discusses the principles of value-based partnering, impediments to practicing it and its future role in the health care system.

Value-based partnering in healthcare: a framework for analysis.

Value-based partnering is designed to move the healthcare system beyond cost-based competition. It recognizes that the healthcare "product" is not a commodity and that much of the value in the system comes from relationships between and among four stakeholders: consumers, providers, health plans, and employers. Given the difficulty of measuring such benefits as quality of care, improved health status, and increased employee productivity, stakeholders within the system traditionally have focused on easily measurable financial considerations such as premium rates. This focus has led to a system that defines relationships in purely financial terms. In contrast, the value-based partnering model presented in this article recognizes the range of factors that stakeholders consider in their relationships with each other. This approach has the potential to change the nature of competition and presents opportunities for those organizations that can effectively partner with other stakeholders and demonstrate value, rather than just lower cost. Moreover, by recognizing the interdependencies among stakeholder groups, the approach creates a strategic reason for employers, health plans, providers, and consumers to exchange information and create long-term alliances.

Aligning physician financial incentives in a mixed-payment environment.

Under a shadow-pricing approach to physician compensation, physicians who deliver healthcare services to a mix of fee-for-service (FFS) and capitated patients are compensated for services via a payment schedule that treats all patients as if they were capitated. By encouraging physicians to adopt the same care-management approach for all patients, shadow pricing helps a group practice prepare for a larger share of revenues to be derived from capitation, thereby making the organization more attractive to many managed care payers. An apparent drawback of shadow pricing is that it gives physicians an incentive to reduce FFS utilization, resulting in a loss of potential revenue to the healthcare organization. This loss can be strategically justified, however, as an investment in the organization's ability to remain viable under capitation and to retain patients for whom payment may shift from FFS to capitation. In developing a shadow-pricing compensation approach, healthcare organizations can include incentives that encourage physicians to meet specific utilization targets, establish review procedures to identify physicians who deviate from the targets, and account for differences in acuity levels among different physicians' patient panels.

Myometrial tissue in uterine septa.

STUDY OBJECTIVE: To assess the frequency of myometrial tissue in the septa of septate uteri. DESIGN: Retrospective review (Canadian Task Force classification II-2). SETTING: University-affiliated tertiary referral center. PATIENTS: Twenty-nine consecutive women with uterine septa diagnosed by magnetic resonance imaging (MRI). INTERVENTIONS: The MRI examination was performed with a 1.5 Tesla scanner using high-resolution phased array coils with multiplanar fast-spin echo and T1-weighted sequences. Of resected septa, tissue was available in four for histologic evaluation for the presence of myometrial tissue. MEASUREMENTS AND MAIN RESULTS: In 17 women MRI showed a partial septum, all containing myometrium. The 12 patients with complete septum had evidence of myometrium in the upper part of the septum, with fibrous tissue constituting the lower part. Histology reviewed from four resected septa (2 partial, 2 complete) reported myometrial tissue. CONCLUSION: Uterine septa are frequently composed of myometrial tissue.

Nonmetastatic gestational trophoblastic neoplasia. Role of ultrasonography and magnetic resonance imaging.

OBJECTIVE: To determine whether routine imaging using grey-scale ultrasound, pulse and color Doppler flow, endovaginal ultrasound and magnetic resonance imaging (MRI) provide information that significantly helps determine therapy in patients with nonmetastatic gestational trophoblastic disease. STUDY DESIGN: A literature search was performed to seek all publications in English and German that reported on investigations of imaging by ultrasound and MRI in patients with a diagnosis of trophoblastic tumor without evidence of metastases. Studies performed to make a diagnosis of hydatidiform mole were excluded. Included were studies that investigated the clinical usefulness and efficacy of these imaging methods in the diagnosis of invasive mole as a visual confirmation of the diagnosis based on human chorionic gonadotropin (hCG) and histology. Furthermore, the usefulness and efficiency of imaging in determining the effectiveness of chemotherapy were investigated. RESULTS: Analysis of these reports showed that lesions are detectable by imaging modalities at relatively high levels of hCG but may not be visualized at lower levels of hCG, when chemotherapy is nevertheless indicated and the diagnosis of neoplasia is fully justified. Moreover, myometrial lesions have been observed by MRI in patients who subsequently achieved spontaneous resolution of their disease without chemotherapy. At lower levels of hCG (< 700 mIU/mL), intramyometrial lesions may not be visualized by either ultrasound or MRI. Myometrial abnormalities may persist with resolution of the tumor. Thus, the sensitivity of either method is no better than 70% and the specificity is even lower. CONCLUSION: Weekly serial levels of serum hCG remain the most accurate, reliable and definitive arbiter of treatment management. Pelvic ultrasound or MRI need not be an integral part of pretreatment assessment. Imaging techniques are expensive yet not decisive in managing nonmetastatic trophoblastic disease. This finding applies to nonmetastatic disease only. With metastases, ultrasound, MRI and computed tomography do play an integral role in diagnosis, staging and management.

Clinical stage I endometrial carcinoma: pitfalls in preoperative assessment with MR imaging. Work in progress.

PURPOSE: To identify potential pitfalls in using magnetic resonance (MR) imaging to determine the depth of myometrial invasion in patients with clinical stage I endometrial carcinoma. MATERIALS AND METHODS: Forty women with clinical stage I endometrial carcinoma underwent preoperative pelvic MR imaging. Uterine length, tumor signal intensity, appearance of the junctional zone, presence of large polypoid tumors, leiomyomata, and congenital uterine anomalies were analyzed. Univariate logistic-regression analysis was performed to identify associations between incorrect MR staging and these variables. RESULTS: MR staging of IA, IB, and IC disease was 55% accurate (22 of 40 cases); MR differentiation of deep myometrial invasion (stage IC) from superficial disease (stages IA and IB) was 78% accurate (31 of 40 cases). Older age (P = .025), presence of polypoid tumors (P = .025), and difficulty in pathologic staging (P < .005) were significantly associated with incorrect MR assessment. CONCLUSION: When present, large polypoid tumors, leiomyomata, congenital anomalies, small uteri, and indistinct zonal anatomy may make it difficult to assess myometrial invasion at MR imaging.

Cost effectiveness of magnetic resonance imaging of the knee.

When compared to diagnostic arthroscopy in patients with knee complaints consistent with internal derangement, MR imaging emerges as a cost effective diagnostic supplement to clinical examination. This article concludes that the results of MR imaging can be used as a guide for the management of knee pain.

MR evaluation of clinically suspected adnexal masses.

OBJECTIVE: Our goal was to determine the sensitivity, specificity, predictive value, and accuracy of pelvic MRI in the prospective evaluation of women with a clinically suspected pelvic mass. MATERIALS AND METHODS: One-hundred three patients with clinically suspected pelvic masses were prospectively evaluated by pelvic MRI. Masses were analyzed for size, location, morphological characteristics, and signal behavior. Masses were classified as benign, malignant, or indeterminate and in every case an attempt was made to generate a specific diagnosis according to previously reported characteristic MR appearances. Surgical follow-up was obtained within 3 months of MRI examination for all patients, excepting 11 patients with typically appearing leiomyomas. RESULTS: One hundred twenty pelvic masses were confirmed. Magnetic resonance was 100% sensitive and 99% specific in prospectively diagnosing dermoids, 96% sensitive and 100% specific in diagnosing subserosal leiomyomas, and 92% sensitive and 91% specific in diagnosing endometriomas. CONCLUSION: When physical examination or ultrasound examination is inconclusive, pelvic MRI can aid in the evaluation of women with a suspected pelvic mass. By identifying these common benign gynecologic conditions, unnecessary surgery can be avoided.

Comprehensive care of the child with a chronic condition. Part 1. Understanding chronic conditions in childhood.

Understanding the care of children with chronic illnesses and disabilities is an important part of the practice of pediatrics. Children with special health care needs and their families benefit from the support which comprehensive, coordinated, accessible, and responsive services provide. Although the primary care pediatrician is often most appropriate to serve as the overall coordinator of such services, many challenges to providing such care exist. Part 2, "Primary Care Management," will suggest guiding principles and management structures that allow the pediatrician to respond most effectively over time to the needs of children with chronic conditions and their families.

Comparison of MRI with postcontrast CT for the evaluation of acute abdominal trauma.

We compared the ability of MRI and CT to detect and characterize abdominal visceral injury. Seven patients with contrast-enhanced abdominal CT interpreted as showing definite (five patients) or possible (two) solid organ injury following blunt abdominal trauma were referred for abdominal MRI with a mean interval of 3 days between modalities. T1-weighted and T2-weighted spin echo sequences were obtained in all patients. Gradient-recalled echo (GRE) sequences (22-25/12-13/60 degrees flip angle) were obtained in five cases. Both CT and MR allowed detection of complex splenic lacerations in two patients and complex hepatic injuries in three other patients. A sixth patient had subtle periportal hypodensity noted on CT which was not detected prospectively on MRI. One patient had a right adrenal hematoma detected on MRI but not on CT. Relative lesion conspicuity and extent were judged equal on CT and T2-weighted imaging. The T1-weighted and GRE imaging were judged inferior to CT. We conclude that MRI offers no significant advantage over CT for the routine evaluation of acute abdominal trauma.

Zonal anatomy of the cervix: correlation of MR imaging and histologic examination of hysterectomy specimens.

High-resolution magnetic resonance (MR) images of nine hysterectomy specimens were correlated with light microscopy, computer-aided image analysis, and immunohistochemical examination to investigate the histologic counterparts of the zonal anatomy of the cervix. A central stripe of high signal intensity, a surrounding middle layer of low signal intensity, and an outer layer of intermediate signal intensity were found in all specimens. Histologic correlation indicated that the central stripe most likely represents the secretions in the canal, the cervical mucosa, and the plicae palmatae; the other two layers represent fibromuscular stroma. The percentage of nuclear area in the inner zone of the fibromuscular stroma is 2.5 times greater than in the outer zone, which may account for the lower signal intensity of the inner zone. No difference in distribution of collagen, laminin, and fibronectin (common components of the extracellular matrix) was found between the two zones of the cervical fibromuscular stroma.

Pelvic MR imaging findings in gestational trophoblastic disease, incomplete abortion, and ectopic pregnancy: are they specific?

Thirty-nine patients with abnormally elevated levels of serum beta subunit of human chorionic gonadotropin (beta-hCG) were studied to determine whether findings at magnetic resonance (MR) imaging are specific for primary molar disease, persistent gestational trophoblastic disease (GTD), incomplete abortion, and ectopic pregnancy. Among the latter three groups, the only significant differences were a higher prevalence of endometrial distention in the group with incomplete abortion (P < .0035) and the absence of junctional zone disruption in the group with ectopic pregnancy (P < .05). In the group with primary molar disease, total intrauterine volume was significantly increased (P < .001), and endometrial distention and presence of an endometrial mass had a significantly higher prevalence than that in the persistent GTD groups with (P < .04) or without (P < .001) metastases. Myometrial or extrauterine disease was identified in 65% of the patients with persistent disease and a beta-hCG level greater than 500 mIU/mL (500 IU/L). Thus, although MR imaging findings in persistent GTD, incomplete abortion, and ectopic pregnancy are relatively nonspecific, MR imaging can depict invasive disease that may alter therapeutic management in patients with documented GTD.

A case illustration of family management style.

Chronic illness management is a way of life for many children and their families. For these chronically ill children, the ability of the family to respond to the daily relentless demands of management dictates the quality of the child's and family's life. In an effort to better understand how a family responds to a chronic illness, Knafl and Deatrick's Family Management Style (FMS) model is applied to a family with a child with type I diabetes using a case-study analysis. Gallo derived dimensions of the model's components in an earlier application. These dimensions are applied to interview data obtained on the same family 1 year later to address the dynamic nature of family management style.

Diagnosis of uterine anomalies: relative accuracy of MR imaging, endovaginal sonography, and hysterosalpingography.

The purpose of this study was to compare the relative accuracy of magnetic resonance (MR) imaging (n = 26), endovaginal sonography (EVS) (n = 14), and hysterosalpingography (HSG) (n = 20) in the classification of müllerian duct anomalies in 26 patients. There were 24 cases of surgically proved anomaly, and two patients had normal uteri (one with a vaginal septum). MR imaging allowed diagnosis of 24 of 24 cases (accuracy, 100%), and EVS was correct in 11 of 12 cases (accuracy, 92%). HSG was correct in only four cases. In the diagnosis of septate uterus, MR imaging demonstrated a sensitivity and specificity of 100% and EVS demonstrated a sensitivity of 100% and a specificity of 80%. Both MR imaging and EVS demonstrated a sensitivity and specificity of 100% in distinguishing those anomalies that did not require surgery. The high accuracy of MR imaging and EVS permit noninvasive differentiation of uterine anomalies and can spare women diagnostic laparoscopy, promoting cost-effective diagnosis.