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Robotic assisted laparoscopic pyeloplasty is an emerging, minimally invasive alternative to open pyeloplasty in children for ureteropelvic junction obstruction. The procedure is associated with smaller incisions and shorter hospital stays. To our knowledge previous outcome analyses have not included human capital calculations, especially regarding loss of parental workdays. We compared perioperative factors in patients who underwent robotic assisted laparoscopic and open pyeloplasty at a single institution, especially in regard to human capital changes, in an institutional cost analysis.A total of 44 patients 2 years old or older from a single institution underwent robotic assisted (37) or open (7) pyeloplasty from 2008 to 2010. We retrospectively reviewed the charts to collect demographic and perioperative data. The human capital approach was used to calculate parental productivity losses.Patients who underwent robotic assisted laparoscopic pyeloplasty had a significantly shorter average hospital length of stay (1.6 vs 2.8 days, p0.05). This correlated with an average savings of lost parental wages of $90.01 and hospitalization expenses of $612.80 per patient when excluding amortized robot costs. However, cost savings were not achieved by varying length of stay when amortized costs were included.Robotic assisted laparoscopic pyeloplasty in children is associated with human capital gains, eg decreased lost parental wages, and lower hospitalization expenses. Future comparative outcome analyses in children should include financial factors such as human capital loss, which can be especially important for families with young children.

Adult men accumulate greater intra-abdominal fat (IAF) than adult women, a difference closely related to gender differences in cardiometabolic disease risk in the elderly. However, the time when this gender difference appears is a matter of controversy.We examine the influence of gender on IAF deposition in lean, overweight and obese teenagers and young adults.We measured subcutaneous abdominal fat (SAF) and IAF in 505 healthy sexually mature teenagers and young adults (254 males, 251 females; 15-22 years) using a single CT scan at the level of the umbilicus.Regardless of body size, young females had greater SAF values than young males. Although lean females had higher IAF values than lean males (13.7 ± 7.8 vs. 11.2 ± 5.4; P = 0.001), overweight and obese females and males had strikingly similar IAF values (23.4 ± 11.1 vs. 23.1 ± 9.5; P = 0.88 and 36.5 ± 20.4 vs. 38.8 ± 13.2; P = 0.59, respectively). In contrast, the ratio of IAF/SAF was greater in males than females, except in the very obese. Multiple regression analysis indicated that while gender was a strong predictor of SAF in lean and overweight subjects (P's 0.0001), it did not influence IAF after adjusting for height and weight (P = 0.35 and 0.65, respectively) in overweight and obese subjects.Overweight and obese young women have similar absolute amounts of IAF as young men.

Genetic susceptibility research and testing is leading to an era of personalized medicine. Genetic counselors act as liaisons between the medical genetics community and the public. Understanding the opinions of genetic counselors will be important in developing testing guidelines. Attitudes towards genetic susceptibility testing in children were assessed for 216 NSGC members. Genetic counselors were likely to support testing if the results would determine: disease progression or prognosis, likelihood of survival after a specific treatment, or risk for an adverse drug reaction. Genetic counselors were unlikely to support testing to determine susceptibility to later disease development or in the absence of available intervention. There was a strong positive correlation between attitudes associated with desire to test their own child, if at risk and their support for genetic testing in any child at risk. Respondents strongly favored parent/guardian and child's rights over doctor or insurance rights. They indicated assent should be obtained prior to testing, when appropriate, and that a copy of results should be kept in a permanent medical record. Respondents expressed concerns about insurance discrimination, testing in the absence of medical necessity, and taking away a child's autonomy.

Adenosine deaminase (ADA)–deficient severe combined immune deficiency (SCID) may be treated by allogeneic hematopoietic stem cell transplantation without prior cytoreductive conditioning, although the mechanism of immune reconstitution is unclear. We studied this process in a murine gene knockout model of ADA-deficient SCID. Newborn ADA-deficient pups received transplants of intravenous infusion of normal congenic bone marrow, without prior cytoreductive conditioning, which resulted in long-term survival, multisystem correction, and nearly normal lymphocyte numbers and mitogenic proliferative responses. Only 1% to 3% of lymphocytes and myeloid cells were of donor origin without a selective expansion of donor-derived lymphocytes; immune reconstitution was by endogenous, host-derived ADA-deficient lymphocytes. Preconditioning of neonates with 100 to 400 cGy of total body irradiation before normal donor marrow transplant increased the levels of engrafted donor cells in a radiation dose–dependent manner, but the chimerism levels were similar for lymphoid and myeloid cells. The absence of selective reconstitution by donor T lymphocytes in the ADA-deficient mice indicates that restoration of immune function occurred by rescue of endogenous ADA-deficient lymphocytes through cross-correction from the engrafted ADA-replete donor cells. Thus, ADA-deficient SCID is unique in its responses to nonmyeloablative bone marrow transplantation, which has implications for clinical bone marrow transplantation or gene therapy.

Patients who are treated with steroids for immunosuppression after solid organ transplant are at risk for development of osteonecrosis. The purpose of this study was to determine the prevalence of symptomatic osteonecrosis of the hip and knee in patients who were treated with corticosteroids after cardiac transplantation and to determine if there was a relationship between steroid dose and the development of osteonecrosis. We retrospectively evaluated 204 patients who underwent cardiac transplantation and noted that only 6 (3%) of 204 patients developed symptomatic osteonecrosis of the hip or knee. The osteonecrosis was diagnosed an average of 38.5 months (range, 21-52 months) after transplantation. There was no association noted between steroid dose and the development of symptomatic osteonecrosis. The low prevalence of osteonecrosis supports the hypothesis that the development of osteonecrosis in these patients is an idiosyncratic response to steroids, perhaps related to an underlying hypercoagulable state or hypofibrinolysis.

The Wnt signaling transduction pathway plays a critical role in the pathogenesis of several murine and human epithelial cancers. Here, we have used mouse mammary tumor virus (MMTV)-Wnt1 transgenic mice, which develop spontaneous mammary adenocarcinoma, to examine whether matrix metalloproteinases (MMPs)—a family of extracellular proteases implicated in multiple steps of cancer progression—contributed to Wnt1-induced tumorigenesis. An analysis of the expression of several MMPs by RT-PCR and in situ hybridization revealed an increase in the expression of MMP-2, MMP-3, MMP-9, MMP-13, and MT1-MMP (MMP-14) in hyperplastic glands and in mammary tumors of MMTV-Wnt1 transgenic mice. Interestingly, whereas MMP-2, MMP-3, and MMP-9 were exclusively expressed by stromal cells in mammary tumors, MMP-13 and MT1-MMP were expressed by transformed epithelial cells in addition to the tumor stroma. To determine whether these MMPs contributed to tumorigenesis, MMTV-Wnt1 mice were crossed with transgenic mice overexpressing tissue inhibitor of metalloproteinase-2—a natural MMP inhibitor—in the mammary gland. In the double MMTV-Wnt1/tissue inhibitor of metalloproteinases-2 transgenic mice, we observed an increase in tumor latency and a 26.3% reduction in tumor formation. Furthermore, these tumors grew at a slower rate, exhibited an 18% decrease in proliferative rate, and a 12.2% increase in apoptotic rate of the tumor cells in association with a deficit in angiogenesis when compared with tumors from MMTV-Wnt1 mice. Thus, for the first time, the data provides evidence for the active role of MMPs in Wnt1-induced mammary tumorigenesis. (Cancer Res 2006; 66(5): 2691-9)

To examine the relationship between age and biochemical failure after radical prostatectomy (RP), controlling for the year of surgery. Prior studies have suggested that younger men have lower prostate-specific antigen recurrence rates after RP, although none of the prior studies had controlled for the year of surgery.We examined the data from 1753 men treated with RP between 1988 and 2002 at five equal access medical centers. We compared age, as a categorical variable according to decade of life (50 years old or younger, 51 to 60, 61 to 70, and older than 70 years), with the clinical and pathologic variables at RP, as well as the time to biochemical recurrence, using a multivariate Cox proportional hazards model.Age was significantly related to the year of surgery, with the more recently treated patients being younger than less recently treated patients (P0.001). After controlling for the year of surgery, the younger men had smaller prostates, fewer high-grade tumors on biopsy, and less lymph node metastasis, but a greater percentage of cores with cancer. On multivariate analysis, men 50 years old or younger had significantly lower recurrence rates than did the older men. Moreover, men older than 70 years had significantly greater prostate-specific antigen failure rates than men aged 51 to 70 years or men aged 50 years or younger.The average age of men undergoing RP has decreased with time. Independent of this, young men have more favorable outcomes after RP than older men. Continued screening to detect prostate cancer among younger men when it is most curable appears warranted.

Recent studies have suggested that the percent of positive cores in the prostate needle biopsy is a significant predictor of outcome among men undergoing radical prostatectomy or radiation therapy for prostate cancer. We evaluate whether either percent of cores with cancer or percent of cores positive from the most and least involved side of the prostate needle biopsy was associated with a worse outcome among men treated with radical prostatectomy.A retrospective survey of 1,094 patients from the SEARCH Database treated with radical prostatectomy at 4 different equal access medical centers in California between 1988 and 2002 was undertaken. We used multivariate analysis to examine whether total percent of prostate needle biopsy cores with cancer, percent of cores positive from each side of the prostate and other clinical variables were significant predictors of adverse pathology and time to prostate specific antigen (PSA) recurrence following radical prostatectomy.On multivariate analysis serum PSA and percent of positive cores were significant predictors of positive surgical margins, nonorgan confined disease and seminal vesicle invasion. Percent of positive cores (p0.001), serum PSA (p = 0.008) and biopsy Gleason score (p = 0.014) were significant independent predictors of time to biochemical recurrence. On a separate multivariate analysis that included the variables of total percent of positive cores, percent of positive cores from the most involved side of the biopsy, percent of positive cores from the least involved side of the biopsy and whether the biopsy was positive unilaterally or bilaterally, only the percent of positive cores from the most involved side of the biopsy was a significant independent predictor of PSA failure following radical prostatectomy. Percent of positive cores was used to separate patients into a low risk (less than 34%), intermediate risk (34% to 50%) and high risk (greater than 50%) groups, which provided significant preoperative risk stratification for PSA recurrence following radical prostatectomy (p0.001). Percent of positive cores cut points were able to further risk stratify men who were at low (p = 0.001) or intermediate (p = 0.036) but not high (p = 0.674) risk for biochemical failure based on serum PSA and biopsy Gleason score.Percent of positive cores in the prostate needle biopsy was a significant predictor of adverse pathology and biochemical failure following radical prostatectomy, and the cut points of less than 34%, 34% to 50% and greater than 50% can be used to risk stratify patients preoperatively. The finding that percent of positive cores from the most involved side of the biopsy was a stronger predictor of PSA failure than the total percent of cores involved suggests that multiple positive biopsies from a single side might be a better predictor of a larger total cancer volume and thus correlate with clinical outcome.

A number of studies have failed to show significant differences in outcome following radical prostatectomy between men with palpable, clinically localized prostate cancer (cT2) and those whose tumors are not palpable (cT1c). We determined whether we could improve the prognostic value of the TNM staging system in men with cT1c and cT2 cancers by including information on whether prostate needle biopsy was unilaterally or bilaterally positive.A retrospective survey of 992 patients from the SEARCH (Shared Equal Access Regional Cancer Hospital) Database treated with radical prostatectomy at 4 equal access medical centers between 1988 and 2002 was done. TNM 1992 clinical stage was T1c in 421 patients, T2a in 287, T2b in 202 and T2c in 82. Multivariate analysis was used to examine whether biopsy laterality and clinical stage were significant predictors of surgical margin status, nonorgan confined disease, seminal vesicle invasion, and time to prostate specific antigen (PSA) recurrence following radical prostatectomy.Patients with clinical stages T2b and T2c cancers had similar rates of PSA recurrence, which were significantly higher than in patients with T1c and T2a disease, who also had similar rates of PSA recurrence. Bilateral positive biopsy further stratified patients with T1c and T2a disease (p = 0.01) but not those with T2b and T2c cancers (p = 0.207). Grouping these 1992 clinical stages with biopsy laterality resulted in a new clinical staging system, which was a significant predictor of PSA recurrence following radical prostatectomy (p0.001). On multivariate analysis whether TNM clinical stage was evaluated as a categorical or continuous variable only PSA, biopsy Gleason score and the new clinical staging system (1992 TNM stage groupings combined with biopsy laterality) were significant independent predictors of time to biochemical recurrence following radical prostatectomy.Combining low (T1c and T2a) and high (T2b and T2c) risk 1992 clinical stages with biopsy laterality (unilateral versus bilateral positive) resulted in a new clinical staging system that was a stronger predictor of PSA recurrence following radical prostatectomy than the 1992 or 1997 TNM clinical staging system. If confirmed at other centers and in men who undergo with other treatment modalities, consideration should be given to revising the current TNM staging system to reflect these findings.

Prostate specific antigen (PSA) density based on the surgical weight of the radical prostatectomy specimen has previously been shown to be an independent predictor of biochemical recurrence after radical prostatectomy. We determined whether preoperative PSA density calculated using transrectal ultrasound prostate volume was a better predictor of advanced pathological findings or biochemical recurrence after radical prostatectomy relative to PSA.We examined 552 men from the newly established Shared Equal Access Regional Cancer Hospital data base of men treated with radical prostatectomy at equal access medical centers to determine whether preoperative PSA density was a significant predictor of an adverse pathological condition or PSA recurrence after radical prostatectomy. Models using PSA density were compared with models using PSA to determine whether PSA density improved risk stratification relative to PSA. PSA density was examined as a continuous and a categorical variable using cutoffs to separate patients into groups at different risks for PSA failure.PSA density and PSA were significant predictors of adverse pathological findings on univariate analysis. Using PSA density in the multivariate model resulted in slightly better but statistically insignificant improvement in prediction of positive surgical margins (p = 0.134) and extracapsular extension (p = 0.771) relative to using PSA in the model. Neither PSA nor PSA density were significant independent predictors of seminal vesicle invasion. Area under the ROC curves for predicting biochemical recurrence for PSA and PSA density were not significantly different (0.589 and 0.58, respectively, p = 0.691). On separate multivariate analyses PSA density and PSA were significant independent predictors of biochemical failure. The multivariate model using PSA density provided only slight improvement in risk assessment relative to the model using PSA (index C = 0.589 and 0.581, respectively). To determine whether using PSA density as a categorical variable would result in improved prognostication we evaluated PSA density to determine the cutoff points that would provide the greatest risk stratification. PSA density cutoffs of less than 0.4, 0.4 to 1 and greater than 1 ng./ml./cc separated patients into 3 distinct groups at increasing risk for biochemical failure (p0.001). While these cutoffs provided better risk stratification than when PSA density was examined as a continuous variable (index C = 0.684 versus 0.58), they provided only marginal improvement relative to the standard PSA cutoffs of less than 10, 10 to 20 and greater than 20 ng./ml. (index C = 0.676).The use of preoperative PSA density relative to PSA provided only slight improvement for predicting adverse pathological findings and biochemical recurrence after radical prostatectomy. The minimal and statistically insignificant improvement in preoperative risk assessment provided by PSA density does not justify the time and effort necessary to calculate this value.

Pulmonary embolism poses a risk to patients undergoing total knee arthroplasty. The selection of an appropriate prophylaxis agent and its implementation have been influenced by decreased duration of hospital stay and the pressures of cost containment. The purpose of this study was to determine the inpatient and outpatient pulmonary embolism rates, the number of days required to attain the target level of anticoagulation, and complications associated with the use of a low-dose warfarin prophylaxis protocol after primary and revision total knee arthroplasty. Between 1984 and 1993, there were 815 primary and revision total knee arthroplasties that received low-dose warfarin prophylaxis at our institution. The average time to attainment of the target level of anticoagulation was 3 days. The average duration of warfarin prophylaxis was 12 days. Overall, there were a total of three symptomatic pulmonary embolisms (0.3%; 95% confidence interval, 0.08%-1.1%). There were eight (1%) symptomatic deep vein thromboses (all distal). There were two deaths (0.3%), but neither one was secondary to a pulmonary embolism. Seventeen knees (2.5%) developed a hematoma after surgery, and two of these patients required drainage of the knee. Low-dose warfarin prophylaxis is safe and effective in preventing symptomatic pulmonary embolism after total knee arthroplasty.

To compare the perioperative parameters of paediatric patients who underwent nephrectomy via laparo-endoscopic single site (LESS) surgery (also known as single incision laparoscopic surgery or SILS) with those who underwent nephrectomy via conventional laparoscopy (LAP), robotic-assisted laparoscopy (RALN), and open surgery (OPEN).The medical records of 69 paediatric patients at a single institution who underwent nephrectomies for non-functioning kidneys in 72 renal units (39 OPEN, 11 LAP, 11 RALN and 11 LESS) were reviewed for patient demographics and perioperative clinical parameters.The minimally invasive modalities in children, including LESS nephrectomy, were associated with shorter lengths of hospital stay (P0.001) and decreased postoperative pain medication usage (P0.001) than with open surgery. Similar surgical times were noted with LESS and the other minimally invasive modalities (LAP and RALN) (P= 0.056). However, the minimally invasive modalities (LESS, LAP and RALN) were associated with slightly longer surgical times when compared with open surgery (P0.001), which may, in part, be secondary to learning curve factors. No differences were noted among the minimally invasive modalities for postoperative pain medication usage (P= 0.354) and length of hospital stay (P= 0.86).The minimally invasive modalities for nephrectomy in children, including LESS nephrectomy, are associated with shorter lengths of hospital stay and decreased postoperative pain medication use when compared with open surgery. LESS nephrectomy in children is associated with similar surgical times, lengths of hospital stay and postoperative pain medication use as the other minimally invasive modalities (LAP and RALN). Slightly longer surgical times are noted with the minimally invasive modalities, including LESS nephrectomy, when compared with open surgery, which may, in part, be secondary to learning curve factors.

Recent studies suggest a close local link between bone marrow adiposity and endosteal bone formation. Using magnetic resonance imaging, we examined whether the relation between the amount of marrow fat and cortical bone is present at multiple sites along the diaphyses of the long bones of young and old males and females.The relations between values for cortical bone area and percent marrow fat in each 5-mm section along the midthird of both femoral shafts were determined using magnetic resonance imaging in eight healthy young (aged25 yr), and nine healthy old (aged55 yr) men and women.Strong inverse correlations were observed between values for cortical bone area and percent marrow fat along the shafts of all 34 femurs; r values between -0.54 to -0.97; all P values = 0.01-0.0001. The strength of this local association was comparable in the young and the elderly and in males and females.Our results underscore the strength of the local connections between bone and marrow adiposity. Increasing our understanding of the mechanism for this association could lead to better diagnosis and treatment approaches for osteoporosis.

Matrix metalloproteinases (MMPs) play a well-defined role in later stages of tumor progression. However, there has been evidence that they also contribute to earlier stages of malignant transformation. The Wnt signaling transduction pathway plays a critical role in development and in the pathogenesis of many epithelial cancers. Here we have used Wnt1-induced epithelial-mesenchymal transition (EMT) in C57MG murine mammary epithelial cells to study the role of MMPs in this early step of malignant progression. Overexpression of Wnt1 in C57MG cells promoted EMT, the translocation of β-catenin from the cell membrane to the nucleus and its transcriptional activity, cell proliferation and cell motility. Simultaneously, we observed an increased expression of stromelysin-1 (MMP-3) and a 5.5-fold increase in MMP-3 promoter activity in C57MG cells expressing Wnt1 compared with C57MG cells. Treatment of Wnt-overexpressing cells with MMP inhibitor AG3340 decreased MMP-3 expression. We also found evidence that MMP-3 and Wnt3a cooperate in enhancing the transcriptional activity of β-catenin in C57MG cells. Consistently, the effects of Wnt1 on EMT, proliferation and migration were inhibited by MMP inhibitors, or upon downregulation of MMP-3 by siRNA. These results suggest that MMP-3 is both a direct transcriptional target and a necessary contributor of the Wnt/β-catenin signaling pathway.

Context: Considerable evidence indicates that osteoblasts and adipocytes share a common progenitor cell in the bone marrow that is capable of mutually exclusive differentiation into the cell lineages responsible for bone and fat formation. Objective: The purpose of this study was to examine the relation between bone acquisition and changes in marrow adiposity. Design: This was a longitudinal study. Outcome Measures and Subjects: Computed tomography measurements of femoral cortical bone area (CBA), cross-sectional area (CSA), and marrow density, and dual-energy x-ray absorptiometry (DXA) measurements of total body fat and lean mass (LM) were obtained in 39 healthy females (15–20 yr of age) at baseline and 18–24 months later. Results: Marrow adiposity was inversely related to CBA at baseline and follow-up (r = 0.39 and 0.33; P = 0.015 and 0.039, respectively) but was not associated to CSA (r = 0.19 and 0.17; P = 0.24 and 0.32, respectively). The association between marrow fat and CBA persisted, even after controlling for body mass and DXA values of LM and femoral CSA. Gains in CBA during the course of the study were related to decreases in marrow fat (r = 0.41; P = 0.009), a relation that persisted, even after accounting for changes in bone size. Marrow fat was not associated to anthropometric measures or DXA values of body fat and LM (all r's between −0.15 and 0.19; P > 0.05). Conclusions: Bone acquisition in the appendicular skeleton of healthy young females is inversely related to changes in marrow adiposity. These results provide support for the growing body of evidence indicating an inversely coupled relationship between osteogenesis and adipogenesis in the skeleton.

Nitric oxide has been identified as an endothelium-derived relaxing factor in blood vessels. We tried to determine whether it is involved in the relaxation of the corpus cavernosum that allows penile erection. The relaxation of this smooth muscle is known to occur in response to stimulation by nonadrenergic, noncholinergic neurons.We studied strips of corpus cavernosum tissue obtained from 21 men in whom penile prostheses were inserted because of impotence. The mounted smooth-muscle specimens were pretreated with guanethidine and atropine and submaximally contracted with phenylephrine. We then studied the smooth-muscle relaxant responses to stimulation by an electrical field and to nitric oxide.Electrical-field stimulation caused a marked, transient, frequency-dependent relaxation of the corpus cavernosum that was inhibited in the presence of N-nitro-L-arginine and N-amino-L-arginine, which selectively inhibit the biosynthesis of nitric oxide from L-arginine. The addition of excess L-arginine, but not D-arginine, largely reversed these inhibitory effects. The specific liberation of nitric oxide (by S-nitroso-N-acetylpenicillamine) caused rapid, complete, and concentration-dependent relaxation of the corpus cavernosum. The relaxation caused by either electrical stimulation or nitric oxide was enhanced by a selective inhibitor of cyclic guanosine monophosphate (GMP) phosphodiesterase (MB 22,948). Relaxation was inhibited by methylene blue, which inhibits cyclic GMP synthesis.Our findings support the hypothesis that nitric oxide is involved in the nonadrenergic, noncholinergic neurotransmission that leads to the smooth-muscle relaxation in the corpus cavernosum that permits penile erection. Defects in this pathway may cause some forms of impotence.

It has generally been believed that adiposity contributes to bone health and protects against osteoporosis. A number of studies have shown a positive association between body weight or body mass index and bone mass. In recent years, however, this long-held viewpoint has been challenged by reports suggesting that there is no positive association of fat mass and/or that there may be a negative relationship. There is accumulating evidence that the regional distribution pattern of fat deposition into the subcutaneous and visceral abdominal compartments may explain these conflicting data. Measurements of fat deposition into these 2 compartments may be a more meaningful predictor of disease risk than overall fat mass. The possible independent effects of subcutaneous abdominal fat (SAF) and visceral abdominal fat (VAF) on bone health have not been previously investigated. This study investigated the effect of differential deposition of SAF and VAF on bone structure and/or bone strength in the appendicular skeleton of 100 healthy young females 15 to 25 years of age, computed tomography was used for measurements of fat, bone, and muscle phenotypes. Calculations of cross-sectional area, cortical bone area, maximum and minimum principal moments of inertia, and polar moment of inertia, were made using multiple linear regression analysis. After adjusting for leg length and thigh musculature, the data showed that both SAF and VAF had strong and independent associations with femoral cross-sectional area, cortical bone area, maximum and minimum principal moments of inertia, and polar moment of inertia (P < 0.03 for all comparisons). Although a positive predictive value was found for SAF with all femoral bone phenotypes, there was a similar but negative effect between VAF and these measures (P < 0.01 for all comparisons). These findings indicate that SAF and VAF have opposing effects on the structure and strength of bone in young women. SAF has a strong beneficial effect on parameters of bone structure and strength, whereas VAF has a negative association with all bone phenotypes.

Intrapatient consistency and relative utility of TDI as well as other echocardiographic parameters are incompletely understood in pediatric HTx recipients. We sought to evaluate the relative strength of common echocardiographic parameters used in the evaluation of pediatric HTx recipients, including TDI. We reviewed 388 echocardiograms and 73 catheterizations from 34 pediatric HTx recipients without coronary disease over an 18-month period. Data included systolic and diastolic parameters, with VCFc and mitral annular TDI velocities. We used descriptive statistics, and analyzed intrapatient variability using MSR from one-way anova. Echocardiographic data were compared with invasively measured hemodynamic data. For most echocardiographic parameters, including TDI velocities, intrapatient variability was smaller than total population variability. VCFc was higher than normal in most patients. TDI parameters were approximately 10% slower than in previously published studies of normal subjects. Pediatric HTx normal ranges are not the same as healthy population norms, and the range of findings in healthy HTx recipients without rejection is relatively broad. Serial assessment is important when interpreting echocardiograms in pediatric HTx recipients.

Title Turnover intention in new graduate nurses: a multivariate analysis Aim This paper is a report of a study to determine the relationship of new nurse turnover intent with individual characteristics, work environment variables and organizational factors and to compare new nurse turnover with actual turnover in the 18 months of employment following completion of a residency. Background Because of their influence on patient safety and health outcomes nurse turnover and turnover intent have received considerable attention worldwide. When nurse staffing is inadequate, especially during nursing shortages, unfavourable clinical outcomes have been documented. Method Prospective data collection took place from 1999 to 2006 with 889 new paediatric nurses who completed the same residency. Scores on study instruments were related to likelihood of turnover intent using logistic regression analysis models. Relationships between turnover intent and actual turnover were compared using Kaplan–Meier survivorship. Results The final model demonstrated that older respondents were more likely to have turnover intent if they did not get their ward choice. Also higher scores on work environment and organizational characteristics contributed to likelihood that the new nurse would not be in the turnover intent group. These factors distinguish a new nurse with turnover intent from one without 79% of the time. Increased seeking of social support was related to turnover intent and older new graduates were more likely to be in the turnover intent group if they did not get their ward choice. Conclusion When new graduate nurses are satisfied with their jobs and pay and feel committed to the organization, the odds against turnover intent decrease. What is already known about this topic There is concern in many countries about nurse turnover and the resulting effects on patient safety and quality of care. Decreasing ability to recruit experienced nurses has increased the emphasis on recruitment of new graduate nurses, particularly in the United States of America. Historically, new graduate nurses have a high turnover rate within the first year of employment. What this paper adds When new graduate nurses are satisfied with their jobs and pay and feel committed to the organization, the odds of turnover intent decrease. Increased seeking social support to cope with the transition from student to competent Registered Nurse is related to turnover intent. Older graduates (>30) are 4·5 times more likely to have turnover intent if they do not get their ward of choice.

Background The Gillette Gait Index (GGI) is a summary measure incorporating 16 clinically important kinematic and temporal parameters. The purpose of this study was to compare GGI scores from computerized gait analysis versus qualitative visual assessments of overall gait to assess the validity of the GGI as a summary score for gait analysis. Methods The GGI was calculated for 25 children with cerebral palsy who underwent computerized gait analysis before and 1 year after lower extremity surgery to correct gait problems. Twelve observers reviewed video recordings from the gait analysis to assess the severity of each patient's gait impairment preoperatively and postoperatively and the amount of preoperative to postoperative change. Variability of the video ratings was assessed, and GGI scores were compared with the mean video ratings. Results The individual ratings showed some variability, with moderate intrarater agreement (weighted kappa = 0.49-0.56) and slight to fair interrater agreement (kappa = 0.11-0.25). However, the mean scores from all raters were much more consistent, as demonstrated by a highly significant relationship in preoperative to postoperative change viewing the videos separately versus together (r2 = 0.62; P = 0.0001). GGI scores were correlated with these mean scores preoperatively (r2 = 0.34; P = 0.003), postoperatively (r2 = 0.30; P= 0.005), and in preoperative to postoperative change (r2 = 0.30, P = 0.006 for absolute change; r2 = 0.22, P = 0.02 for percentage change). Conclusions These results support the validity of GGI as a gait analysis summary score and suggest that GGI may be a useful outcome measure in patients undergoing gait analysis. Clinical relevance Clinicians and researchers should consider using the GGI as a quantitative outcome measure for assessing overall gait.

ContextProstate safety is a primary concern when aging men receive testosterone replacement therapy (TRT), but little information is available regarding the effects of TRT on prostate tissue in men.ObjectiveTo determine the effects of TRT on prostate tissue of aging men with low serum testosterone levels.Design, Setting, and ParticipantsRandomized, double-blind, placebo-controlled trial of 44 men, aged 44 to 78 years, with screening serum testosterone levels lower than 300 ng/dL (

The potential for brief periods of low-magnitude, high-frequency mechanical signals to enhance the musculoskeletal system was evaluated in young women with low BMD. Twelve months of this noninvasive signal, induced as whole body vibration for at least 2 minutes each day, increased bone and muscle mass in the axial skeleton and lower extremities compared with controls. Introduction: The incidence of osteoporosis, a disease that manifests in the elderly, may be reduced by increasing peak bone mass in the young. Preliminary data indicate that extremely low-level mechanical signals are anabolic to bone tissue, and their ability to enhance bone and muscle mass in young women was inves- tigated in this study. Materials and Methods: A 12-month trial was conducted in 48 young women (15-20 years) with low BMD and a history of at least one skeletal fracture. One half of the subjects underwent brief (10 minutes requested), daily, low-level whole body vibration (30 Hz, 0.3g); the remaining women served as controls. Quantitative CT performed at baseline and at the end of study was used to establish changes in muscle and bone mass in the weight-bearing skeleton. Results: Using an intention-to-treat (ITT) analysis, cancellous bone in the lumbar vertebrae and cortical bone in the femoral midshaft of the experimental group increased by 2.1% ( p 0.025) and 3.4% ( p < 0.001), respectively, compared with 0.1% ( p 0.74) and 1.1% ( p 0.14), in controls. Increases in cancellous and cortical bone were 2.0% ( p 0.06) and 2.3% ( p 0.04) greater, respectively, in the experimental group compared with controls. Cross-sectional area of paraspinous musculature was 4.9% greater ( p 0.002) in the experimental group versus controls. When a per protocol analysis was considered, gains in both muscle and bone were strongly correlated to a threshold in compliance, where the benefit of the mechanical intervention compared with controls was realized once subjects used the device for at least 2 minute/day (n 18), as reflected by a 3.9% increase in cancellous bone of the spine ( p 0.007), 2.9% increase in cortical bone of the femur ( p 0.009), and 7.2% increase in musculature of the spine ( p 0.001) compared with controls and low compliers (n 30). Conclusions: Short bouts of extremely low-level mechanical signals, several orders of magnitude below that associated with vigorous exercise, increased bone and muscle mass in the weight-bearing skeleton of young adult females with low BMD. Should these musculoskeletal enhancements be preserved through adulthood, this intervention may prove to be a deterrent to osteoporosis in the elderly.

Aim. This paper reports data from an evaluation study to determine whether new graduate nurses: (1) were satisfactorily matched with mentors; (2) received guidance and support; (3) attained socialization into the nursing profession; (4) benefited from having a role model for acquisition of professional behaviours; (5) maintained contact with mentors; and (6) were satisfied with the mentorship. Background. The literature indicates that mentorship facilitates transition of new graduate nurses into the workplace and social culture of the organization. In addition, mentoring increases staff retention by decreasing stress and promoting positive self-esteem and confidence. Methods. Data were generated from participant responses to survey items about mentoring from 1999 to 2005. Item responses were summarized with descriptive statistics, and then logistic regression was performed to see whether demographic variables predicted successful programme outcomes. In addition, content analysis was performed on respondents’ comments on survey items. Results. For participants who met with their mentors on a regular basis (54%), the mentor provided guidance and support for more than 90% and facilitated stress reduction for the majority. On the other hand, comments raised several concerns that apparently contributed to lack of connection between mentor and mentee. These included possible lack of commitment and time, and scheduling constraints of mentor and mentee. Inadequacy of both mentor and mentee in their roles was also apparent, especially in relation to socialization/career advice. Diversity of new graduates, including educational level, age and choice of nursing unit, were shown to add or decrease stress and influence the mentoring relationship. Conclusion. A successful relationship between mentor and resident-mentee requires adequate time for the connection to grow through face-to-face meetings on a regular basis. Obstacles to meeting regularly and adequate role training of both mentors and mentees must be addressed in mentorship programmes for new graduate nurses.

Objective Nonmyeloablative cytoreduction is used in clinical hematopoietic stem cell gene therapy trials to increase engraftment of gene-modified cells. We utilized an infant rhesus monkey model to identify an optimal dosage of busulfan that results in efficient long-term gene marking with minimal toxicities. Methods Bone marrow (BM) was harvested, followed by a single 2-hour intravenous infusion of busulfan at escalating dosages of 0 to 160 mg/m 2 . CD34 + cells were immunoselected from BM, transduced overnight with a simian immunodeficiency virus–based lentiviral vector carrying a nonexpressed marker gene, and injected intravenously 48 hours post–busulfan administration. Pharmacokinetics were assessed, as well as adverse effects and peripheral blood and BM gene marking. Results Increasing dosages of busulfan resulted in increased area-under-the-curve (AUC) with some variability at each dosage level, suggesting interindividual variation in clearance. Blood chemistries were normal and no adverse effects were observed as a result of busulfan infusion. At 120 and 160 mg/m 2 , transient neutropenia and thrombocytopenia were noted but not lymphopenia. Over the 6 months of study posttransplantation, a busulfan dosage-related increase in gene marking was observed ranging from undetectable (no busulfan) up to 0.1% gene-containing cells in animals achieving the highest busulfan AUC. This corresponds to a more than 100-fold increase in gene marking over the busulfan dosage range studied. Conclusions These data indicate that increased gene marking of hematopoietic stem cells can be achieved by escalating busulfan dosages from 40 to 160 mg/m 2 without significant toxicity in infant nonhuman primates.

ContextThe natural history of biochemical recurrence after radical prostatectomy can be long but variable. Better risk assessment models are needed to identify men who are at high risk for prostate cancer death early and who may benefit from aggressive salvage treatment and to identify men who are at low risk for prostate cancer death and can be safely observed.ObjectivesTo define risk factors for prostate cancer death following radical prostatectomy and to develop tables to risk stratify for prostate cancer–specific survival.Design, Setting, and PatientsRetrospective cohort study of 379 men who had undergone radical prostatectomy at an urban tertiary care hospital between 1982 and 2000 and who had a biochemical recurrence and after biochemical failure had at least 2 prostate-specific antigen (PSA) values at least 3 months apart in order to calculate PSA doubling time (PSADT). The mean (SD) follow-up after surgery was 10.3 (4.7) years and median follow-up was 10 years (range, 1-20 years).Main Outcome MeasureProstate cancer–specific mortality.ResultsMedian survival had not been reached after 16 years of follow-up after biochemical recurrence. Prostate-specific doubling time (3 years) were all significant risk factors for time to prostate-specific mortality. Using these 3 variables, tables were constructed to estimate the risk of prostate cancer–specific survival at year 15 after biochemical recurrence.ConclusionClinical parameters (PSADT, pathological Gleason score, and time from surgery to biochemical recurrence) can help risk stratify patients for prostate cancer–specific mortality following biochemical recurrence after radical prostatectomy. These preliminary findings may serve as useful guides to patients and their physicians to identify patients at high risk for prostate cancer–specific mortality following biochemical recurrence after radical prostatectomy to enroll them in early aggressive treatment trials. In addition, these preliminary findings highlight that survival in low-risk patients can be quite prolonged.

To determine the ideal cutpoint for defining prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). Although various cutpoints have been used, a recent study suggested that 0.4 ng/mL may be the most appropriate.A retrospective survey of 358 men undergoing RP at the West Los Angeles Veterans Affairs Medical Center between 1991 and 2001 was undertaken. The 3-year and 5-year risk of PSA recurrence was estimated by Kaplan-Meier analyses using various cutpoints of postoperative PSA to define recurrence: greater than 0.1, greater than 0.2, greater than 0.3, greater than 0.4, and greater than 0.5 ng/mL. The 1 and 3-year risk of PSA progression after a detectable PSA level (PSA rising to a higher cutpoint) was evaluated for each definition of PSA recurrence using Kaplan-Meier analyses. Multivariate analysis using a Cox proportional hazards model was used to determine the clinical variables that were significant independent predictors of PSA recurrence at each cutpoint.For patients with a detectable postoperative PSA value from 0.11 to 0.2 ng/mL, the 1 and 3-year risk of PSA progression was 64% (95% confidence interval [CI] 46% to 82%) and 93% (95% CI 74% to 99%), respectively. For patients with a PSA value from 0.21 to 0.3 ng/mL, the 1 and 3-year risk of PSA progression was 86% (95% CI 69% to 97%) and 100% (95% CI 87% to 100%), respectively. The use of higher PSA cutpoints to define recurrence resulted in a lower 5-year risk of PSA recurrence. The 5-year risk of PSA recurrence using a greater than 0.1 ng/mL cutpoint resulted in a 43% (95% CI 36% to 50%) risk of recurrence compared with only 23% (95% CI 18% to 30%) for a greater than 0.5 ng/mL cutpoint. In multivariate analysis, PSA and biopsy Gleason score were significant independent predictors of biochemical recurrence, regardless of the definition of PSA recurrence used (Por=0.002).PSA and biopsy Gleason score were significant predictors of biochemical failure, regardless of the definition of failure used. However, the definition of PSA recurrence dramatically affected the perceived success of therapy. Patients with a postoperative PSA value greater than 0.2 ng/mL are at very high risk of developing an additional rise in PSA. On the basis of this finding, a PSA value greater than 0.2 ng/mL is an appropriate cutpoint to define PSA recurrence after RP.

We examined whether cytoreductive nephrectomy in patients with venous tumor thrombus and metastatic disease is associated with more complications than in those with thrombus without metastatic disease.Between 1989 and 2000, 74 patients with renal vein extension, 87 with inferior vena caval extension and 491 without tumor thrombus underwent nephrectomy at our institution. Metastatic and nonmetastatic renal vein extension in 51 and 23 cases, inferior vena caval extension in 54 and 33, and nontumor thrombus in 171 and 320, respectively, were compared for symptoms at presentation, surgical data, mortality and complications.For nonmetastatic and metastatic inferior vena caval extension presenting symptoms, hospital stay, surgical time and the number of patients undergoing thoraco-abdominal incision, lymph node dissection, venacavotomy alone for thrombus and adrenal sparing surgery were similar. Five patients with thrombus died intraoperatively or postoperatively, including 3.1% with and 0.8% without thrombus (p = 0.03), while 3 had metastatic (2.3%) and 2 (2.6%) had nonmetastatic disease. The rate of postoperative complications was higher in thrombus cases overall but there was no difference in nonmetastatic and metastatic disease with thrombus. On multivariate analysis inferior vena caval thrombus (odds ratio 10.5), adjacent organ resection due to locally advanced tumor (odds ratio 6), partial nephrectomy (odds ratio 3.8), regional lymph node involvement (odds ratio 1.7) and lower preoperative hemoglobin (odds ratio 1.6) were independent variables predicting bleeding requiring transfusion. Inferior vena caval thrombus (odds ratio 1.7) and adjacent organ resection (odds ratio 2) were also associated with nonhemorrhagic complications. Systemic metastasis was not an independent risk factor in either analysis.To our knowledge there are no published data comparing surgical complications in patients with metastatic and nonmetastatic renal cell carcinoma who have gross tumor thrombus. Cytoreductive surgery in patients with thrombus and metastasis is not associated with an increase in the extent of surgery, morbidity or mortality compared with their counterparts with nonmetastatic disease.

To improve on current staging and monitoring methods for prostate cancer, we applied the technique of quantitative polymerase chain reaction to measure the degree of tumor burden in the circulation and correlate this with pathological tumor stage. A reproducible, highly sensitive and specific, reverse transcriptase-polymerase chain reaction amplification technique to quantify prostate specific antigen (PSA) and prostate specific membrane antigen gene expression in the peripheral circulation was developed. Using a 32phosphorus-gamma-adenosine triphosphate-5'PSA and prostate specific membrane antigen primer incorporation assay, the ribonucleic acid signal extracted from a single neoplastic cell (LNCaP) premixed in 10 cc normal whole blood could be amplified. PSA and prostate specific membrane antigen polymerase chain reaction indexes have been created for clinical application.From September 1994 through July 1995 specimens from 121 patients were prospectively analyzed for PSA and prostate specific membrane antigen signals.Circulating PSA producing cells were present in 29 of 33 patients (88%) with metastatic prostate cancer. Two of 19 patients (11%) with no known prostate cancer exhibited positive signals (1 later had prostate cancer), establishing a sensitivity of 88% and specificity of 94% for our assay. Positive PSA polymerase chain reaction signals were detected in 30 of 51 patients (59%) with stages pT1 and pT2 disease and in 13 of 18 (72%) with stage pT3 cancer. No statistically significant relationship of a positive PSA polymerase chain reaction signal to pathological stage, tumor grade, apical involvement or positive surgical margins was found, and no benefit was derived by measuring the quantity of circulating PSA polymerase chain reaction signals. Circulating prostate specific membrane antigen polymerase chain reaction signals were identified mostly in patients with advanced prostate cancer and offered no benefit to preoperative staging.Given the high incidence of false positive signals in patients with pathologically determined localized disease, in our experience polymerase chain reaction based assays offer no immediate benefit for preoperative prostate cancer staging. The prognostic significance of detecting circulating prostate specific signals awaits longer followup in this cohort of patients, which is currently under study.

Twenty-seven total knee arthroplasties (TKAs) were performed in 24 patients using the total condylar III knee prosthesis (TCP III) and were evaluated clinically and radiographically with a mean follow-up period of 4 years. Eighteen were revision TKAs, and nine were primary knee arthroplasties. Evaluations were made using the Hospital for Special Surgery (HSS) knee scale as well as the Knee Society radiographic evaluation method. Clinical results for all knees were 11% (3 of 27) excellent, 70% (19 of 27) good, 15% (4 of 27) fair, and 4% (1 of 27) poor. The one poor rating resulted from an intraoperative vascular injury. The results showed no statistical difference between revision and primary TKA. After operation, pain relief, range of motion, walking, function, and activity level improved in both the primary and revision patients. Radiolucencies 2 mm or greater in width were found in 6 of the 27 tibial components, in none of the 27 femoral components, and in 1 of the 19 patellar components. Only two tibial implants showed progressive radiolucencies. No correlation was found between the radiographic position of the implants and the clinical results. The authors conclude that the TCP III is a satisfactory choice for TKA in selected knees in which there is significant instability and in which intramedullary fixation is required.

Cells of the human acute promyelocytic cell line HL-60 undergo differentiation when exposed to dimethyl sulfoxide (DMSO); in this report, amiloride, an inhibitor of passive intracellular Na+ flux, potentiated the DMSO-induced differentiation of HL-60 cells. This effect was seen at several concentrations of DMSO. Amiloride alone did not affect HL-60 differentiation. Various analogues of amiloride were tested for their ability to potentiate differentiation of HL-60 cells. The synergistic induction of myeloid differentiation by a membrane solvent (DMSO) and an Na+ transport inhibitor (amiloride) suggested membrane cation flux as being important in initiating differentiation.