Showing papers by "Jewish Hospital published in 2010"

EWSR1‐POU5F1 fusion in soft tissue myoepithelial tumors. A molecular analysis of sixty‐six cases, including soft tissue, bone, and visceral lesions, showing common involvement of the EWSR1 gene

Abstract: The diagnosis of myoepithelial (ME) tumors outside salivary glands remains challenging, especially in unusual clinical presentations, such as bone or visceral locations. A few reports have indicated EWSR1 gene rearrangement in soft tissue ME tumors, and, in one case each, the fusion partner was identified as either PBX1 or ZNF444. However, larger studies to investigate whether these genetic abnormalities are recurrent or restricted to tumors in soft tissue locations are lacking. Sixty-six ME tumors mainly from soft tissue (71%), but also from skin, bone, and visceral locations, characterized by classic morphological features and supporting immunoprofile were studied. Gene rearrangements in EWSR1, FUS, PBX1, and ZNF444 were investigated by fluorescence in situ hybridization. EWSR1 gene rearrangement was detected in 45% of the cases. A EWSR1-POU5F1 fusion was identified in a pediatric soft tissue tumor by 3'Rapid Amplification of cDNA Euds (RACE) and subsequently confirmed in four additional soft tissue tumors in children and young adults. An EWSR1-PBX1 fusion was seen in five cases, whereas EWSR1-ZNF444 and FUS gene rearrangement was noted in one pulmonary tumor each. In conclusion, EWSR1 gene rearrangement is a common event in ME tumors arising outside salivary glands, irrespective of anatomical location. EWSR1-negative tumors were more often benign, superficially located, and showed ductal differentiation, suggesting the possibility of genetically distinct groups. A subset of soft tissue ME tumors with clear cell morphology harbor an EWSR1-POU5F1 fusion, which can be used as a molecular diagnostic test in difficult cases. These findings do not support a pathogenetic relationship between soft tissue ME tumors and their salivary gland counterparts.

Teduglutide, a novel mucosally active analog of glucagon-like peptide-2 (GLP-2) for the treatment of moderate to severe Crohn's disease.

Abstract: Background: Teduglutide, an analog of glucagon-like peptide-2 (GLP-2), is associated with trophic effects on gut mucosa. Its role in the treatment of active Crohn's disease (CD) was assessed in a pilot, randomized, placebo-controlled, double-blinded, dose-ranging study. Methods: Subjects with moderate-to-severe CD were randomized 1:1:1:1 to placebo or 1 of 3 doses of teduglutide (0.05, 0.10, or 0.20 mg/kg daily) delivered as a daily subcutaneous injection for 8 weeks. The primary outcome measure was the percentage of subjects in each group that responded to treatment, defined as a decrease in Crohn's Disease Activity Index (CDAI) score to 100 points. At week 8 there was an optional 12-week open-label period of treatment with teduglutide 0.10 mg/kg/d. Results: One hundred subjects were enrolled and 71 completed the study. The mean baseline CDAI score was 290.8 ± 57.6 and was similar across groups. There were numerically higher response and remission rates in all teduglutide-treated groups as compared with placebo, although the percentage of subjects who achieved a clinical response or remission was more substantial, and seen as early as week 2 of treatment in the highest dose (0.2 mg/kg/d) group (44% response and 32% remission versus 32% response and 20% remission in the placebo group). Of subjects who had not achieved remission during the 8-week placebo-controlled phase in the higher-dose group, 50% achieved remission during the more prolonged, open-label treatment phase. Plasma citrulline was similar across groups at baseline, but increased substantially over time in all teduglutide groups when compared with placebo at week 8. Adverse events were not different between placebo and active treatment groups. Conclusions: Teduglutide is a novel and potentially effective therapy for inducing remission and mucosal healing in patients with active moderate-to-severe CD. Further clinical investigation of this growth factor is warranted. Inflamm Bowel Dis 2009

No evidence for switching the antidepressant: systematic review and meta-analysis of RCTs of a common therapeutic strategy.

Abstract: Bschor T, Baethge C. No evidence for switching the antidepressant: systematic review and meta-analysis of RCTs of a common therapeutic strategy. Objective: Switching antidepressants is a common strategy for managing treatment-resistant depressed patients. However, no systematic reviews have been conducted to date. Method: We systematically searched MEDLINE/EMBASE/Cochrane Central Register of Controlled Trials and additional sources. We included double-blind studies of patients with depressive symptomatology who were not responding to initial antidepressant monotherapy and were subsequently randomized to another antidepressant or to continue the same antidepressant. Results were pooled for meta-analysis of response + remission rates using a fixed-effects model. Results: A total of three studies were included. Switching to another antidepressant was not superior to continuing the initial antidepressant in any of these studies. Our meta-analysis showed no significant advantages to either strategy and no significant heterogeneity of results [OR for response rates: 0.85 (95% CI: 0.55–1.30) favoring continuing]. Conclusion: There is a discrepancy between the published evidence and the frequent decision to switch antidepressants, indicating an urgent need for more controlled studies. Pending such studies we recommend that physicians rely on more thoroughly evaluated strategies.

Provision of preventive health care in systemic lupus erythematosus: data from a large observational cohort study

Abstract: Cancer and infections are leading causes of mortality in systemic lupus erythematosus (SLE) after diseases of the circulatory system, and therefore preventing these complications is important. In this study, we examined two categories of preventive services in SLE: cancer surveillance (cervical, breast, and colon) and immunizations (influenza and pneumococcal). We compared the receipt of these services in SLE to the general population, and identified subgroups of patients who were less likely to receive these services. We compared preventive services reported by insured women with SLE enrolled in the University of California, San Francisco Lupus Outcomes Study (n = 685) to two representative samples derived from a statewide health interview survey, a general population sample (n = 18,013) and a sample with non-rheumatic chronic conditions (n = 4,515). In addition, using data from the cohort in both men and women (n = 742), we applied multivariate regression analyses to determine whether characteristics of individuals (for example, sociodemographic and disease factors), health systems (for example, number of visits, involvement of generalists or rheumatologists in care, type of health insurance) or neighborhoods (neighborhood poverty) influenced the receipt of services. The receipt of preventive care in SLE was similar to both comparison samples. For cancer surveillance, 70% of eligible respondents reported receipt of cervical cancer screening and mammography, and 62% reported colon cancer screening. For immunizations, 59% of eligible respondents reported influenza immunization, and 60% reported pneumococcal immunization. In multivariate regression analyses, several factors were associated with a lower likelihood of receiving preventive services, including younger age and lower educational attainment. We did not observe any effects by neighborhood poverty. A higher number of physician visits and involvement of generalist providers in care was associated with a higher likelihood of receiving most services. Although receipt of cancer screening procedures and immunizations in our cohort was comparable to the general population, we observed significant variability by sociodemographic factors such as age and educational attainment. Further research is needed to identify the physician, patient or health system factors contributing to this observed variation in order to develop effective quality improvement interventions.

Diagnostic value of MR elastography in addition to contrast-enhanced MR imaging of the breast—initial clinical results

Abstract: The purpose of the study was to assess the additional value of magnetic resonance (MR) elastography (MRE) to contrast-enhanced (ce) MR imaging (MRI) for breast lesion characterisation. Fifty-seven suspected breast lesions in 57 patients (mean age 52.4 years) were examined by ce MRI and MRE. All lesions were classified into BI-RADS categories. Viscoelastic parameters, e.g. α0 as an indicator of tissue stiffness, were calculated. Histology of the lesions was correlated with BI-RADS and viscoelastic properties. The positive predictive value (PPV) for malignancy, and the sensitivity and specificity of ce MRI were calculated. Receiver-operating characteristics (ROC) curves were separately calculated for both ce MRI and viscoelastic properties and conjoined to analyse the accuracy of diagnostic performance. The lesions (mean size 27.6 mm) were malignant in 64.9% (n = 37) of cases. The PPV for malignancy was significantly (p < 0.0001) dependent on BI-RADS classification. The sensitivity of ce MRI for breast cancer detection was 97.3% (36/37), whereas specificity was 55% (11/20). If ce MRI was combined with α0, the diagnostic accuracy could be significantly increased (p < 0.05; AUCceMRI = 0.93, AUCcombined = 0.96). In this study, the combination of MRE and ce MRI could increase the diagnostic performance of breast MRI. Further investigations of larger cohorts and smaller lesions (in particular those only visible on MRI) are necessary to validate these results.

Bone healing with an in situ-formed bioresorbable polyethylene glycol hydrogel membrane in rabbit calvarial defects.

Abstract: Objectives. The aims of this study were to test whether or not the application of an in situ–formed synthetic polyethylene glycol hydrogel (PEG) used as a biodegradable membrane for guided bone regeneration with a variety of graft materials and ambient oxygen or hyperbaric oxygen (HBO) environments would result in enhanced bone regeneration, and to observe the histologic and histomorphometric aspects of bone healing of the calvarial defects with and without a PEG membrane. Study design. Thirty adult, skeletally mature, male New Zealand white rabbits were randomly divided into 3 groups of 10 animals each. Bilateral 15-mm-diameter critical-size defects were created in the parietal bones of each animal. Group 1 served as a control with unfilled bilateral calvarial defects, group 2 had bilateral calvarial defects filled with morcelized autogenous calvarial bone, and group 3 had bilateral calvarial defects filled with a biphasic calcium phosphate ceramic. One of the calvarial defects was randomly protected with a PEG resorbable liquid membrane in each animal. Five animals from each group underwent a course of HBO treatment (2.4 ATA 100% oxygen for 90 minutes 5 days a week for 4 weeks) and the other 5 served as control and did not receive any supplemental oxygen (normobaric). The animals were killed 6 weeks after their surgery, and their parietal bones were harvested. The specimens were analyzed with microscopic computerized tomography (microCT) scans and histomorphometrics. Results. The unfilled normobaric control bony defects did not heal, proving the critical-size nature of these defects. The presence of autogenous bone or bone ceramic in the defects increased the bone volume fraction and bone mineral density of the defects (P .001). The presence of a membrane in the ungrafted and autogenous bone grafted defects resulted in a decrease in the corrected bone volume fraction (P .002) but not in the bone ceramic grafted defects (P .580). Bony healing of defects where the membrane was unsupported was compromised; the membrane did not maintain the desired bone regeneration volume with the unfilled and autogenous bone grafted groups. The PEG resorbable liquid membrane worked best with the bone ceramic material. HBO did not ameliorate the healing of the autogenous bone graft or ceramic filled defects in the 6week time period of this study. Conclusions. Although the PEG resorbable liquid membrane is easy to use and forms an occlusive layer, caution is recommended when using the membrane over an unsupported defect. HBO did not ameliorate bony healing with the membrane at the early 6-week time point. The authors recommend future assessment with HBO at the 12-week time

Toward precise pulmonary nodule descriptors for nodule type classification

Abstract: A framework for nodule feature-based extraction is presented to classify lung nodules in low-dose CT slices (LDCT) into four categories: juxta, well-circumscribed, vascularized and pleural-tail, based on the extracted information. The Scale Invariant Feature Transform (SIFT) and an adaptation to Daugman's Iris Recognition algorithm are used for analysis. The SIFT descriptor results are projected to lower-dimensional subspaces using PCA and LDA. Complex Gabor wavelet nodule response obtained from an adopted Daugman Iris Recognition algorithm revealed improvements from the original Daugman binary iris code. This showed that binarized nodule responses (codes) are inadequate for classification since nodules lack texture concentration as seen in the iris, while the SIFT algorithm projected using PCA showed robustness and precision in classification.

A systematic review and meta-analysis of bone metabolism in prostate adenocarcinoma

Abstract: Osteoporosis could be associated with the hormone therapy for metastatic prostate carcinoma (PCa) and with PCa per se. The objective of this review is to determine the incidence of bone loss and osteoporosis in patients with PCa who are or are not treated with hormone therapy (ADT). The Medline, Embase, Cancerlit, and American Society of Clinical Oncology Abstract databases were searched for published studies on prostate cancer and bone metabolism. The outcomes assessed were: fracture, osteoporosis and osteopenia. Thirty-two articles (116,911 participants) were included in the meta-analysis. PCa patients under ADT had a higher risk of osteoporosis (RR, 1.30; p < 0.00001) and a higher risk of fractures (RR, 1.17; p < 0.00001) as compared to patients not under ADT. The total bone mineral density was lower in patients under ADT when compared with patients not under ADT (p = 0.031) but it was similar to bone mineral density found in healthy controls (p = 0.895). The time of androgen deprivation therapy correlated negatively with lumbar spine and total hip bone mineral density (Spearman's rho = -0.490 and -0.773; p = 0.028 and 0.001, respectively) and with total hip t score (Spearman's rho = -0.900; p = 0.037). We found consistent evidence that the use of androgen deprivation therapy in patients with PCa reduces bone mineral density, increasing the risk of fractures in these patients.

Appearance analysis for diagnosing malignant lung nodules

Abstract: An alternative method of diagnosing malignant lung nodules by their visual appearance rather than conventional growth rate is proposed. Spatial distribution of image intensities (or Hounsfield values) comprising the malignant nodule appearance is accurately modeled with a rotation invariant second-order Markov-Gibbs random field. Its neighborhood system and potentials are analytically learned from a training set of nodule images with normalized intensity ranges. Preliminary experiments on 109 lung nodules (51 malignant and 58 benign ones) resulted in the 96.3% correct classification (for the 95% confidence interval), showing the proposed method is a promising supplement to current technologies for early diagnostics of lung cancer.

Comparison of bone removed during total hip arthroplasty with a resurfacing or conventional femoral component: a cadaveric study.

Abstract: We sought to examine the amount of bone removed during total hip arthroplasty with a resurfacing femoral component, compared to with a conventional, stemmed femoral component, by using 6 male and 4 female cadaveric pelves with attached bilateral proximal femora. Using randomized assignment and order, a total hip arthroplasty with a resurfacing femoral implant was performed on one side, and total hip arthroplasty with a cementless, stemmed femoral implant was performed on the contralateral side. The relationship between native femoral head diameter and the implanted acetabular socket was on average within 2 mm for both procedures. No significant difference was observed in the amount of acetabular bone removed (9.8 g for hip resurfacing vs 8.8 g). However, a resurfacing component resulted in approximated 3 x less bone removal from the femur (25.8 g vs 75.1 g). This study shows that the preservation of femoral bone with a resurfacing femoral component does not result in an increased removal of acetabular bone when compared to the use of a conventional, stemmed femoral component.

Physiological assessment of renal artery stenosis: comparisons of resting with hyperemic renal pressure measurements.

Abstract: OBJECTIVES We compared resting and hyperemic pressure gradients induced by intrarenal papaverine for the assessment of renal artery stenosis (RAS). We also investigated the incidence of the QT interval prolongation and ventricular arrhythmias. BACKGROUND In the coronary circulation, maximal hyperemia is essential in determining the significance of a stenosis. In the renal circulation, the role of maximal hyperemia for the assessment of RAS has not been established. METHODS In 55 patients with RAS (67 RAS), resting P(d)/P(a) ratio (the ratio between distal renal pressure to the aortic pressure), renal fractional flow reserve (FFR), and resting and hyperemic systolic gradients (RSG and HSG, respectively) were measured with a pressure guidewire. In a subset of 16 patients, renal vein renin activity (RVRA) was measured. RESULTS HSG was significantly greater than RSG (20 ± 14 mm Hg vs. 9.0 ± 13 mm Hg, respectively; P < 0.001). Renal FFR was significantly lower than baseline P(d)/P(a) ratio (0.91 ± 0.06 vs. 0.94 ± 0.06 vs. respectively; P < 0.001). RVRA increased from 50 ± 66% at rest to 122 ± 112% at hyperemia, P < 0.01. At HSG of 21 mm Hg or renal FFR of 0.90, RVRA increased markedly (120%), but RVRA increased modestly (18%) when RSG was 16 mm Hg or resting P(d)/P(a) ratio was 0.93. The corrected QT intervals at baseline vs. hyperemia were not significantly different (433 ± 26 vs. 436 ± 25 msec, respectively; P = NS); no episodes of ventricular arrhythmias were noted. CONCLUSIONS Renin production, an index of renal ischemia, was markedly greater at hyperemia than at rest, suggesting that RAS, with either an HSG of 21 mm Hg or a renal FFR of 0.90, can be considered a hemodynamically significant stenosis. Intrarenal papaverine neither prolonged the QT interval nor induced ventricular arrhythmias and the safety of which will need to be corroborated in a large study. © 2010 Wiley-Liss, Inc.

Severe cutaneous candida infection during natalizumab therapy in multiple sclerosis

Abstract: Natalizumab is a humanized monoclonal antibody against alpha-4 integrin. It prevents inflammatory cells from crossing vascular endothelial cells into the CNS and mucosal organs.1 Natalizumab is approved for the treatment of relapsing multiple sclerosis (MS).2 There are reports of opportunistic infections that can limit its use.3 The diploid fungus Candida albicans may cause opportunistic cutaneous infections, with an estimated prevalence of 0.2% in a healthy European population4 and 3.7% in a sample of immunocompromised patients.5 Severe cutaneous Candida infections may occur in immunocompromised patients, such as those with HIV, chemotherapy, cancer, or organ transplantation.5 We report a 61-year-old woman with relapsing MS who presented with a severe cutaneous Candida infection during treatment with natalizumab. ### Level of evidence. This is a single case report of severe adverse event. It is level IV evidence. ### Case report. In August 2008, a 61-year-old woman with MS developed an itchy redness in her inguinal, genital, axillary, and lumbar regions, a few days after her 11th natalizumab infusion. This was diagnosed as cutaneous Candida infection. Within 14 days, over 30% of her body surface was covered by Candida , with multiple ulcerations in the infected gluteal region. In August 2007, the patient had been diagnosed with relapsing-remitting MS with an Expanded Disability Status Scale score of 5.5. …

Molecular oncogenesis of prostate adenocarcinoma: role of the human epidermal growth factor receptor 2 (HER-2/neu).

Abstract: The potential mechanisms involving the genesis and growth of androgen-independent prostate cancer include super-expression of the androgen receptor (AR), in an attempt to compensate for the low androgenic plasma levels and mutations of this specific receptor, which could determine resistance to anti-androgenic therapy. However, most advanced prostate tumors have no mutations or amplifications of the AR, suggesting a potential role of non-androgenic growth factors, including epidermal growth factor (EGF), transforming growth factor alpha, insulin-like growth factor (IGF-1) and fibroblast growth factor. More specifically, these factors, and their receptors like EGFR (HER-1) and HER-2/neu, through paracrine and autocrine mechanisms, may contribute to the proliferation and growth of prostate cancer.

The Comparative Use of Ventricular Assist Devices: Differences between Europe and the United States

Abstract: In the field of mechanical circulatory support and transplantation, there are several differences between Europe and the United States. The population of Europe is 731,000,000 and the population of the U.S. (2008 U.S. Census Bureau estimate) is 305,529,237. Currently, the estimated total number of long-term devices implanted in the U.S. per year is over 1,700, compared with over 430 per year in Europe. Europe's multiple countries are very diverse in their levels of wealth and in their philosophies towards healthcare. An estimate of the population of European and nearby countries is shown in Table I; those that currently play an important role in the ventricular assist device (VAD) field appear in bold type. TABLE I. The Populations of Major European (and Nearby) Countries Of course, the funding and regulation of device implantations in each country significantly affects that country's role in the field. There are many European countries in which long-term VADs are funded only as a bridge to transplantation, often with only limited numbers funded; and in other countries, funding for destination therapy is present but very limited. Many countries have no formal VAD funding at all. The European numbers are currently dominated by Germany, which does not limit funding by indication for either bridge-to-transplantation or destination therapy and is able to implant devices, with good reimbursement, in all patients who need one. Of the 3 large German centers (Berlin, Bad Oeynhausen, and Hannover), each of the first 2 has implanted devices in more than 1,000 patients. In France, the government has recently doubled the number of devices funded. Bridge to Transplantation Only The United Kingdom limits funding to bridge to transplantation, which changes not just the number of devices implanted and patients treated, but the whole approach to the patient. Although the population of the U.K. stands at almost 62 million, the heart transplantation numbers (as in other countries) have decreased significantly—to fewer than 100 adult transplants per year, in the whole of the U.K. This is totally inadequate to treat the number of patients with heart failure requiring transplantation. When only a bridge-to-transplantation program is funded, every patient has to be either a transplant candidate or a potential transplant candidate (that is, after a period of VAD support). We know from Interagency Registry for Mechanically Assisted Circulatory Support data that eligibility for heart transplantation is difficult to predict and that many destination-therapy patients later become candidates for transplantation. Hence, the bridge-to-transplantation-only program leads to palliative care for some patients who would have become good transplant candidates following a period of VAD support. Moreover, this approach limits the number of devices that can be justified: when patients receive implants only as a bridge to transplantation, the number of implants is limited by the number of transplants, which continues to fall. This approach is counterproductive if the goal of VAD therapy is to treat more patients who have advanced heart failure. In addition, under the constraints of bridge-to-transplantation-only funding, many cardiologists delay referrals for VAD implantations in the hope of directly obtaining a heart transplant for the patient, thereby avoiding a 2nd operation; in the meanwhile, the patient often deteriorates (on inotropic support), waiting for heart transplantation. By the time such patients receive their VADs, they often have developed right-heart failure (leaving patients in left-heart failure often leads to right-heart failure), infection, or multiorgan failure, due to the prolonged wait for a heart. These higher-risk patients are prone to longer lengths of stay, higher complication rates after VAD implantation, more postoperative infections, and a higher rate of perioperative right-VAD support. In addition, the proportion of urgent transplants (for patients on inotropic support, intra-aortic balloon pumps, etc.) has increased in the U.K. Today, 60% of heart transplantations are urgent cases, rather than the previous 20%. This translates to transplantations for sicker patients, resulting in worse outcomes. Furthermore, because of the donor-heart shortage, most U.K. centers are using more marginal donors, which further compromises transplant outcomes. Bridge-to-transplantation patients are younger than destination-therapy patients, but the body mass index of patients accepted for bridge to transplantation is limited to the body mass index in the donor pool. Finally, since referral for left-VAD implantation is often delayed until patients deteriorate, there is increased use of short-term support devices prior to the implantation of long-term devices. Wider Use of Ventricular Assist Devices In the U.S., the indications are for bridge to transplantation or destination therapy, which fosters more appropriate timing of implantation to meet the patient's clinical need. The main limitation to wider use of VADs in many European countries is cost. To determine the coverage of high-technology therapies, funding bodies in Europe closely evaluate the cost per Quality-Adjusted Life Years (QALY) gained. Demonstration of a reduced cost per QALY would encourage European governments to fund more devices and to expand the destination-therapy indication. In the Netherlands, there is only bridge-to-transplantation funding, but the number of bridge-to-transplantation implants is not capped by the number of transplants—hence, it does not limit patient care so much. Differences in Transplantation The trend toward decreased heart transplantation is more noticeable in Europe than in the U.S. Although the numbers of donors have decreased everywhere, they are decreasing more in Europe, as indicated by the more dramatic decline in transplants (Fig. 1).1 Furthermore, the proportion of younger donors is still higher in the U.S. (Fig. 2).1 In Europe, there is a higher proportion of older donors with poor organ quality, due to the lower number of traumatic deaths in young people—which in turn can be explained by the European use of seat belts, speed cameras, crash helmets, etc. In the U.S., the recipient age is higher and the donor age lower. Recently, non-heart-beating lung donation has been introduced in some countries; it may be that relatives prefer this option, and hearts are being lost as a consequence. Fig. 1 Number of heart transplants per year in Europe, North America, and elsewhere. Fig. 2 Donor age distribution in Europe, North America, and elsewhere. Myocardial Recovery The approach to myocardial recovery is also affected by the 2 different systems. In bridge-to-transplantation-only funded programs, some governments, such as that of the U.K., initially refused to fund a patient's implant once the myocardium recovered, stating that the funding was for bridge to transplantation only. However, after the first few VADs were explanted, the U.K. changed this policy. The advent of myocardial recovery after VAD support then prompted the U.K. to increase its cap on bridge-to-transplantation devices, but the number of devices funded is still less than the number of transplants performed annually. In the U.S., the challenges to promoting recovery are different. First, the proportion of ischemic heart disease patients receiving VADs is higher, and these patients are less likely to recover; and second, cost limits the number of diagnostic tests that can be performed on patients who receive VADs—so their recovery is more difficult to evaluate. Third, it is more difficult in the U.S. to study investigational drugs in combination with investigational VADs, in order to promote recovery. Destination therapy removes the pressure to transplant, but VAD programs might suffer financially because hospitals lose the profit margin associated with heart transplantation. Finally, destination therapy enables VAD implantation to be independent of heart transplantation, and we are nearing the point where VADs are becoming the primary alternative to transplantation. However, the growing population of VAD patients will render even more important the need of a rescue strategy for the few patients who develop life-threatening complications from their VADs. The best bailout for these patients will be transplantation; hence, the number of transplants will once again become an important rate-limiting factor for each program.

Endothelial nitric oxide synthase T-786C mutation, a reversible etiology of Prinzmetal's angina pectoris.

Abstract: Because the endothelial nitric oxide synthase (eNOS) T-786C polymorphism is associated with reduced nitric oxide production and coronary artery spasm in Japanese patients, we speculated that it might be reversibly associated with Prinzmetal's variant angina in white Americans. Polymerase chain reaction analyses of eNOS T-786C and stromelysin 5A6A polymorphisms were done in 31 women and 12 men (42 white and 1 black American, median age 50 years), with well-documented Prinzmetal's variant angina. We matched each case with 1 healthy control by race and gender. Of the 43 cases, 21 (49%) were homozygous for wild-type normal eNOS, 19 (44%) were T-786C heterozygotes, and 3 (7%) were T-786C homozygotes. Of the 43 controls, 31 (72%) were homozygous for wild-type normal eNOS, 12 (28%) were T-786C heterozygotes, and 0 (0%) were T-786C homozygotes (p = .013). The mutant eNOS T-786C allele frequency in patients was 25 (29%) of 86 vs 12 (14%) of 86 in the controls (p = 0.016). Patients did not differ from controls for the distribution of the stromelysin 6A mutation (p = 0.66) or for the mutant 6A allele frequency (53% in cases, 50% in controls; p = 0.65). Nineteen patients took nitric oxide-elevating l-arginine (9.2 g/day, orally). Of these 19 patients, 10 (53%) became free of angina, 3 (16%) were improved but not angina free, and 6 (32%) had no change in their angina. Using l-arginine, the physical ability score (Seattle Angina Questionnaire) increased from a median of 42 to 72 of a total possible score of 100 (p = 0.011), satisfaction with symptom reduction increased from 53 to 61 (p = 0.004), and the perception of quality of life as acceptable increased from 29 to 50 (p = 0.001). In conclusion, the eNOS T-786C mutation appears to be a reversible etiology of Prinzmetal's variant angina in white Americans whose angina might be ameliorated by l-arginine.

A new validation approach for the growth rate measurement using elastic phantoms generated by state-of-the-art microfluidics technology

Abstract: Our long-term research goal is to develop a fully automated, image-based diagnostic system for early diagnosis of pulmonary nodules that may lead to lung cancer. This paper focuses on validating our approach for monitoring the development of lung nodules detected in successive chest low dose computed tomography (LDCT) scans of a patient. Our methodology for monitoring the detected lung nodules includes 3-D LDCT data registration, which is non-rigid and involves two steps: (i) global target-to-prototype alignment of one scan to another using the learned prior appearance model followed by (ii) local alignment in order to correct for intricate relative deformations. This approach has been validated on elastic lung phantoms constructed using state-of-the-art microfluidics technology. The elastic lung phantoms are fabricated from a flexible transparent polymer, i.e., polydimethylsiloxane (PDMS). These Phantoms mimic the contractions and expansions of the lung and nodules seen during normal breathing. Experiments confirm the high accuracy of the proposed approach for measuring the growth rate of the detected lung nodules.

Phosphonate analogs of cephalin

Abstract: Two ester-phosphonate analogs of cephalin of the type Structure (I). have been synthesized in the L-dipalmitoyl (R C15H31) and DL-distearoyl (R C17H35) forms. 2-Phthalimidoethylphosphonic acid was prepared by hydrogen bromide cleavage of its crude diethyl ester. Reaction of D-αβ-dipalmitin or DL-αβ-distearin with 2-phthalimidoethylphosphonyl dichloride gave, after hydrazinolysis and purification of the product on a silicic acid column, the corresponding phosphono-cephalins (I). A diether-phosphonate analog of cephalin, was prepared in high yield by condensation of with 2-hydroxyethylphthalimide and trichloroacetonitrile, followed by hydrazinolysis of the phthalyl diether phosphonocephalin.

Constrained Acetabular Liners Cemented Into Cages During Total Hip Revision Arthroplasty

Abstract: The combination of acetabular bone loss and hip instability is challenging. Sixteen patients underwent revision total hip arthroplasty using constrained acetabular liners cemented into cages. The average follow-up was 28 months (range, 24-60 months). Clinical evaluation was obtained using the Harris hip score along with radiographic data. At latest follow-up, 13 patients were available for evaluation. Although the average postoperative Harris hip score was 62 points, which was better than the preoperative score of 27 points, the overall radiographic failure rate was 23%. The combination of poor acetabular bone stock and altered stresses from the increased constraint likely led to the poor outcome. We would only recommend use of a cemented, constrained acetabular liner in combination with a protrusio cage as a bail out or salvage procedure.

Preteen insulin levels interact with caloric intake to predict increases in obesity at ages 18 to 19 years: a 10-year prospective study of black and white girls.

Abstract: We evaluated the associations of teenage insulin and adolescent diet with 10-year weight gain in an analysis sample of black and white girls matched for pubertal stage, body mass index (BMI) (or fat mass), and insulin at ages 9 to 10 years. We hypothesized that preteen insulin and insulin resistance would interact with dietary factors to positively predict increases in BMI. Furthermore, we hypothesized that increased insulin and insulin resistance, interacting with higher caloric intake during adolescence, would lead to greater increments in BMI in black girls than in white girls. Prospective 10-year follow-up was performed on 215 pairs of black and white schoolgirls matched at baseline by BMI (or fat mass), insulin, and pubertal stage, with repeated measures of body habitus, insulin, and dietary intake. When matched for BMI, black girls had higher fat-free mass and white girls had higher fat mass at ages 9 to 10 years. Black-white differences in caloric intake were not significant at ages 9 to 10 years, but black girls consumed more calories at age 19 years. Black girls consumed a greater percentage of calories from fat throughout. At age 19 years, black girls had higher BMI, fat mass index, and insulin. When matched at ages 9 to 10 years for fat mass, black girls were heavier, had higher BMI, and had greater fat-free mass. By ages 18 to 19 years, black girls continued to have higher BMI, but had accrued higher fat mass and a higher percentage of body fat. By stepwise multiple regression, 10-year increases in BMI were predicted by ages 9 to 10 years BMI, 10-year change in insulin, and a 3-way interaction between ages 9 to 10 years insulin, adolescent caloric intake, and race (higher in black girls) (all Ps < .0001). Insulin at ages 9 to 10 years interacts with caloric intake to increase BMI by age 19 years. There appear to be intrinsic black-white metabolic differences that lead to greater gains in fat during adolescence in black girls. Evaluating BMI and insulin at ages 9 to 10 years could identify girls (particularly black) who would optimally benefit from dietary and exercise interventions to avoid obesity.

T-786C polymorphism of the endothelial nitric oxide synthase gene and neuralgia-inducing cavitational osteonecrosis of the jaws.

Abstract: Objective We hypothesized that, similar to idiopathic hip osteonecrosis, the T−786C mutation of the endothelial nitric oxide synthase (eNOS) gene affecting nitric oxide (NO) production was associated with neuralgia-inducing cavitational osteonecrosis of the jaws (NICO). Design In 22 NICO patients, not having taken bisphosphonates, mutations affecting NO production (eNOS T−786C, stromelysin 5A6A) were measured by polymerase chain reaction. Two healthy normal control subjects were matched per case by race and gender. Results Homozygosity for the mutant eNOS allele (TT) was present in 6 out of 22 patients (27%) with NICO compared with 0 out of 44 (0%) race and gender–matched control subjects; heterozygosity (TC) was present in 8 patients (36%) versus 15 control subjects (34%); and the wild-type normal genotype (CC) was present in 9 patients (36%) versus 29 controls (66%) (P = .0008). The mutant eNOS T−786C allele was more common in cases (20 out of 44 [45%]) than in control subjects (15 out of 88 [17%]) (P = .0005). The distribution of the stromelysin 5A6A genotype in cases did not differ from control subjects (P = .13). Conclusions The eNOS T−786C polymorphism affecting NO production is associated with NICO, may contribute to the pathogenesis of NICO, and may open therapeutic medical approaches to treatment of NICO through provision of L-arginine, the amino-acid precursor of NO.

Systemic chemotherapy‐induced microsatellite instability in the mononuclear cell fraction of women with breast cancer can be reproduced in vitro and abrogated by amifostine

Abstract: Objectives Microsatellite instability (MSI) induction by alkylating agent-based chemotherapy (ACHT) may underlie both tumor resistance to chemotherapy and secondary leukaemias in cancer patients. We investigated if ACHT could induce MSI in tumor-derived plasma-circulating DNA (pfDNA) and in normal peripheral blood mononuclear (PBMN) cells. We also evaluated if amifostine could interfere with this process in an in-vitro model. Methods MSI was determined in pfDNA, PBMN cells and urine cell-free DNA (ufDNA) of 33 breast cancer patients before and after ACHT. MCF-7 cells and PBMN from normal donors were exposed in vitro to melphalan, with or without amifostine. Results We observed at least one MSI event in PBMN cells, pfDNA or ufDNA of 87, 80 and 80% of patients, respectively. In vitro, melphalan induced MSI in both MCF-7 and normal PBMN cells. In PBMN cells, ACHT-induced MSI occurred together with a significant decrease in the expression of the DNA mismatch repair gene hMSH2. Amifostine decreased hMSH2 expression and also prevented MSI induction only in normal PBMN cells. Conclusions ACHT induced MSI in PBMN cells and in tumour-derived pfDNA. Because of its protective effect against ACHT induction of MSI in normal PBMN cells in vitro, amifostine may be a potential agent for preventing secondary leukaemias in patients exposed to ACHT.

Feature-based lung nodule classification

Abstract: Model-based detection and classification of nodules are two major steps in CAD systems design and evaluation. This paper examines feature-based nodule description for the purpose of classification in low dose CT scanning. After candidate nodules are detected, a process of classification of these nodules into types is needed. The SURF and the LBP descriptors are used to generate the features that describe the texture of common lung nodules. These features were optimized and the resultant set was used for classification of lung nodules into four categories: juxta-pleural, well-circumscribed, vascularized and pleural-tail, based on the extracted information. Experimental results illustrate the efficiency of using multi-resolution feature descriptors, such as the SURF and LBP algorithms, in lung nodule classification.

Successful implementation of intelligent infusion technology in a multihospital setting: nursing perspective.

Abstract: Complexities of today's medications and greater use of high-risk medications place the patient at an increased risk for nursing errors. The purpose of this case report is to present, from a nursing perspective, the successful experience of a multihospital healthcare system's quest to decrease or eliminate medication administration errors through implementation of intelligent pumps. This case report focuses on the vital role that nursing services played, including the selection of pumps, development of the drug library, education of end users, and strategies employed to achieve a high compliance rate. Also described are the ongoing educational efforts, lessons learned, and specific results in intercepting significant medication administration errors.