TGF-beta promotes the establishment of renal cell carcinoma bone metastasis.

Bone metastases develop in approximately 30% of patients with RCC, and the mechanisms responsible for this phenomenon are unknown. We found that TGF-beta1 stimulation of RCC bone metastasis cells promotes tumor growth and bone destruction possibly by stimulating paracrine interactions between tumor cells and the bone. INTRODUCTION: Bone metastasis is a frequent complication and causes marked morbidity in patients with renal cell carcinoma (RCC). Surprisingly, the specific mechanisms of RCC interaction with bone have been scarcely studied despite the inability to prevent or effectively treat bone metastasis. Bone is a reservoir for various growth factors including the pleiotropic cytokine TGF-beta1. TGF-beta1 has been shown to have tumor-supportive effects on advanced cancers and evidence suggests its involvement in promoting the development of breast cancer bone metastasis. Here, we studied the potential role of TGF-beta1 in the growth of RCC bone metastasis (RBM). MATERIALS AND METHODS: To inhibit TGF-beta1 signaling, RBM cells stably expressing a dominant-negative (DN) TGF-betaRII cDNA were generated. The in vivo effect of TGF-beta1 on RBM tumor growth and osteolysis was determined by histological and radiographic analysis, respectively, of athymic nude mice after intratibial injection of parental, empty vector, or DN RBM cells. The in vitro effect of TGF-beta1 on RBM cell growth was determined after TGF-beta1 treatment by MTT assay. RESULTS: TGF-beta1 and the TGF-beta receptors I and II (TGF-betaRI/II) were consistently expressed in both RBM tissues and cell lines. Inhibition of TGF-beta1 signaling in RBM cells significantly reduced tumor establishment and osteolysis observed in vivo after injection into the murine tibia, although no effect on tumor establishment was observed after injection of RBM cells subcutaneously or into the renal subcapsule. Treatment of five RBM cell lines with TGF-beta1 in vitro either had no effect (2/5) or resulted in a significant inhibition (3/5) of cell growth, suggesting that TGF-beta1 may promote RBM tumor growth indirectly in vivo. CONCLUSIONS: TGF-beta1 stimulation of RBM cells plays a role in promoting tumor growth and subsequent osteolysis in vivo, likely through the initiation of tumor-promoting paracrine interactions between tumor cells and the bone microenvironment. These data suggest that inhibition of TGF-beta1 signaling may be useful in the treatment of RBM.     

Enteric hyperoxaluria, nephrolithiasis, and oxalate nephropathy: potentially serious and unappreciated complications of Roux-en-Y gastric bypass.

BACKGROUND: Neither the presence nor prevalence of enteric hyperoxaluria has been recognized after Roux-en-Y gastric bypass (RYGBP). We have noted a high rate of oxalate nephrolithiasis and even 2 patients with oxalate nephropathy in this patient population postoperatively. Our aim was to determine the frequency of the occurrence and effects of enteric hyperoxaluria after RYGBP. METHODS: Retrospective review of all patients at our institution diagnosed with calcium oxalate nephrolithiasis or oxalate nephropathy after standard (n = 14) or distal (n = 9) RYGBP. The mean postoperative follow-up was 55 months. RESULTS: A total of 23 patients (14 men and 9 women; mean age 45 years; mean preoperative body mass index 55 kg/m(2)) developed enteric hyperoxaluria after RYGBP, defined by the presence of oxalate nephropathy (n = 2) or calcium oxalate nephrolithiasis (n = 21) and increased 24-hour excretion of urinary oxalate and/or calcium oxalate supersaturation. Enteric hyperoxaluria was recognized after a mean weight loss of 46 kg at 29 months (range 2-85) after RYGBP. Two patients developed renal failure and required chronic hemodialysis. Of the 21 patients with nephrolithiasis, 14 had no history of nephrolithiasis preoperatively, and 19 of 21 required lithotripsy or other intervention. Of the 23 patients, 20 tested had increased oxalate excretion, and 14 of 15 tested had high urine calcium oxalate supersaturation. CONCLUSION: Enteric hyperoxaluria, nephrolithiasis, and oxalate nephropathy must be considered with the other risks of RYGBP. Efforts should be made to identify factors that predispose patients to developing hyperoxaluria.     

Integrating disability management into strategic plans: creating healthy organizations.

The integration of disability management into the strategic planning of a corporation ensures a work environment is created that motivates employees to consistently meet customer expectations. Disability management strategies can achieve significant decreases to the human and financial cost of workers' compensation, sick leave or short term disability, and long-term disability. The business case for disability management including effective return to work programs clearly supports program implementation to enhance employee engagement, delivery of corporate priorities, and improvement to the company's bottom line.     

Routine postoperative chest x-ray following laparoscopic nephrectomy.

PURPOSE: To determine whether a routine postoperative chest x-ray is required following uneventful laparoscopic nephrectomy to rule out pneumothorax. METHODS: From June 1999 to May 2003, 308 laparoscopic nephrectomy cases were performed by 5 different surgeons. This consisted of 121 radical nephrectomies, 106 donor nephrectomies, 29 simple nephrectomies, 29 partial nephrectomies, and 23 nephroureterectomies. Of the 308 procedures, 186 postoperative chest x-ray s were obtained in the recovery room: 183 routinely and 3 for known intraoperative diaphragmatic injuries. Routine chest x-rays were not obtained in 122 cases due to the individual surgeon's preference. Of these 122 patients, 15 underwent chest x-ray performed while hospitalized secondary to pulmonary issues or fever. RESULTS: Of the 308 cases, 4 pneumothoraces were identified on chest x-ray. Three were identified in the patients who had intraoperative identification of diaphragmatic injury. The fourth pneumothorax was identified in a patient who did not have a routine postoperative chest x-ray but did have a chest x-ray obtained due to postoperative shoulder pain. The pneumothorax in this patient resolved spontaneously. No incidental findings existed of pneumothorax in any patient who underwent routine postoperative chest x-ray. CONCLUSION: In our series, a pneumothorax was identified either intraoperatively or based on postoperative clinical findings. None of the 183 routine postoperative chest x-rays changed patient management. Routine postoperative chest x-ray is not necessary in uncomplicated laparoscopic nephrectomy.     

Performance measures for evaluating services for people with a first episode of psychosis

Aim: The purpose of this project was to operationalize and apply a previously identified set of performance measures designed to evaluate services for those experiencing a first episode of a schizophrenia spectrum disorder. Methods: Operational definitions were developed for previously identified measures through an iterative process of discussions between clinical experts and health‐care evaluators. Data were collected from existing sources including corporate databases, clinical databases and chart review. Results: Definitions were developed for 44 measures covering seven of eight domains recommended for service level evaluation by the Canadian Institute for Health Information domains. Forty measures could be calculated. Conclusions: The measures represent a comprehensive set of performance measures suitable for the evaluation of services for people with a first‐episode psychosis. The measures could be used by other services in order to establish standards and norms for routine clinical practice.     

Outcomes of Project Wall Talk: an HIV/AIDS peer education program implemented within the Texas State Prison system.

We report select outcomes from an evaluation of Project Wall Talk, a community-based, peer-led HIV prevention education program implemented in 36 Texas State prison units. Peer educators completed questionnaires prior to receipt of a 40-hour intensive training (N = 590) and at 9-month follow-up (N = 257). Students (N = 2506) completed questionnaires pre- and post-receipt of peer educator-led HIV education sessions. Peer educators and their students showed significant increases in HIV-related knowledge. Peer educators showed significant increases in assessment of their skills as educators. For both peer educators and students, significant differences in HIV-related knowledge were indicated across categories of prior educational level attained and race/ethnicity; no such differences were indicated at follow-up. Compared with baseline, a significantly greater proportion of peer educators reported ever having had an HIV test. After receiving peer-led education, a significantly smaller proportion of students reported they knew their HIV status and more indicated plans to take an HIV test. Additionally, in months 12 and 18 following program implementation, the numbers of HIV tests at the five units that implemented the peer education program were roughly twice that of five, matched comparison units without the peer education program. Based on peer educator reports, we projected that peer educators (N = 257) may have as many as 84,000 or more annual opportunities to share HIV-related knowledge with other prisoners outside the classroom.     

Intentional mis-reporting of food consumption and its relationship with body mass index and psychological scores in women

BACKGROUND: The reasons for mis-reporting food consumption warrant investigation. OBJECTIVE: To document intention to mis-report food consumption and its associations with psychological measures in women. DESIGN: A total of 184 female volunteers aged 18-65 years, comprising 50 seeking help in primary care to lose weight with a body mass index (BMI) >/=30 kg m(-2) (obese-clinical group) and 134 nurses (nonclinical groups) (BMI <25 kg m(-2), n = 52; BMI 25-29.9 kg m(-2), n = 45; BMI >/=30 kg m(-2), n = 37) were studied. A questionnaire was administered containing three psychological tests (self-esteem, psychological well-being and Stunkard's three-factor eating questionnaire) and new items to address food intake mis-reporting. RESULTS: Overall, 68% of participants declared an inclination to mis-report (64% nonclinical, 78% clinical). Inclination to under-report was 29, 33 and 51% in the three nonclinical groups; and 46% among the obese clinical patients. Among the same groups, inclination to over-report were 39, 29, 11 and 32%. After adjusting for social deprivation and BMI, women inclined to mis-report had higher hunger (P = 0.008) and disinhibition (P = 0.005) scores than those intending to report accurately. These variables were associated with current dieting, frequency of dieting, self-reported bingeing and dissatisfaction with body weight. CONCLUSIONS: These findings indicate that intentional under-reporting and over-reporting of food consumption are common in women of all BMI categories and are associated with eating behaviour. Current dieting, frequency of dieting in the past, self-reported bingeing and dissatisfaction with body weight seem to mediate this relationship.