tbuckley/cabot-search huggingface dataset:
Fundal dysaccommodation in functional dyspepsia: head-to-head comparison between the barostat and three-dimensional ultrasonographic technique
Authors: M W Mundt, M Samsom
Journal: Gut (2006)

<b>Background:</b> Recently, non-invasive techniques such as 3 dimensional ultrasonography (3DUS) have been developed to assess gastric wall characteristics and to investigate their relationship with upper gastrointestinal sensations. To date, no head-to-head comparison has been carried out between the barostat and the 3DUS technique. <b>Aim:</b> To compare barostat and 3DUS and to investigate the relationship between gastric volumes and sensations in patients with functional dyspepsia and in healthy subjects. <b>Patients and methods:</b> Gastric accommodation was studied in 15 patients with functional dyspepsia and in 15 healthy subjects after ingestion of a liquid nutrient (300 kcal) using barostat and 3DUS in random order for 60 min. Proximal gastric relaxation was measured using barostat and gastric volume using 3DUS. Change in gastric volume, acquired by 3DUS, was expressed as total gastric volume/proximal volume ratio (TGV/PV) and compared with changes in barostat volume (fundal accommodation). <b>Results:</b> Patients with functional dyspepsia showed a smaller change in proximal gastric volume than healthy subjects using barostat (mean (SD) 82 (61) <i>v</i> 205 (79) ml, p&lt;0.01) and 3DUS (118 (41) <i>v</i> 199 (39) ml, p&lt;0.01). Dysaccommodation of the proximal stomach was observed in 7 of 15 (46%) patients using the barostat technique. 10 of 15 (67%) patients were found to have an abnormal change in proximal gastric volume using TGV/PV ratio. At 5 min postprandially, fullness was related to the change in distal gastric volume (r = 0.51, p = 0.006) in the 3DUS study, whereas no relationship was observed in the barostat study. <b>Conclusion:</b> 3DUS is a feasible non-invasive technique to measure gastric volumes and shows a distinct overlap with barostat data in healthy subjects and patients with functional dyspepsia. Fullness relates to distal gastric volumes when assessed by non-invasive 3DUS.
Elevation of 1-Hour Plasma Glucose During Oral Glucose Tolerance Testing Is Associated With Worse Pulmonary Function in Cystic Fibrosis
Authors: Jill Brodsky, Shayne Dougherty, Ramkrishna Makani, Ronald C. Rubenstein, Andrea Kelly
Journal: Diabetes Care (2011)

Cystic fibrosis (CF)-related diabetes (CFRD) is associated with declining pulmonary function and increased mortality. During oral glucose tolerance testing (OGTT), CFRD is defined by 2-h plasma glucose (PG2). We hypothesized PG elevations during OGTT resolving by 2 h, not meeting CFRD criteria, influence pulmonary function in CF. Thus we investigated the frequency of elevated 1-h OGTT PG (PG1) and its relationship with pulmonary function.Retrospective review of OGTTs was performed between August 2005 (annual screening initiation) and June 2008 at Children's Hospital of Philadelphia CF Center. First-time, well state OGTTs (PG0, PG1, PG2) were analyzed. Additional data collected were: percent predicted forced expiratory volume in 1 s (FEV(1)), BMI percentile, lung bacterial colonization, age, and sex. OGTTs were categorized as normal (PG2 <140 mg/dL), impaired glucose tolerance (IGT) (PG2 140-199 mg/dL), CFRD (PG2 ≥ 200 mg/dL), and indeterminate glycemia (INDET) (PG1 ≥ 200 mg/dL and PG2 <140 mg/dL). Frequency of PG1 ≥ 140 but <200 mg/dL was also noted. Multivariable linear regression was used to assess associations between percent predicted FEV(1), BMI percentile, and OGTT PG.OGTTs (101) were available (59 male/42 female; age 5.8-22 years, percent predicted FEV(1) = 94.5 ± 18%, BMI percentile = 52 ± 25%). With the use of PG2, 91 OGTT were normal, eight were IGT, and two were CFRD. With the use of PG1 (n = 89), 39 OGTT were normal, 36 were PG1 ≥ 140 <200 mg/dL, and 14 were PG1 ≥ 200 mg/dL. PG1 was negatively associated with percent predicted FEV(1), adjusting for BMI percentile (P = 0.009, R(2) 0.13). Percent predicted FEV(1) was not associated with PG0, PG2, age, sex, or lung bacterial colonization.PG elevations at nontraditional OGTT times are common in CF. The association of increasing PG1 with worse pulmonary function suggests early PG abnormalities may be deleterious or an early marker for worsening disease and will be missed if CFRD diagnosis focuses on PG2.
Review of Oncology and Hematology Drug Product Approvals at the US Food and Drug Administration Between July 2005 and December 2007
Authors: R. Sridhara, J. R. Johnson, R. Justice, P. Keegan, A. Chakravarty, R. Pazdur
Journal: JNCI Journal of the National Cancer Institute (2010)

The Office of Oncology Drug Products (OODP) in the Center for Drug Evaluation and Research at the US Food and Drug Administration began reviewing marketing applications for oncological and hematologic indications in July 2005. We conducted an overview of products that were reviewed by the OODP for marketing approval and the regulatory actions taken during July 2005 to December 2007. We identified all applications that were reviewed by the OODP from July 1, 2005, through December 31, 2007, and reviewed the actions that OODP took. We also sought the basis for the actions taken, including the clinical trial design, endpoints used, patient accrual in the trial(s) supporting approval, and the type of regulatory approval. During the study period, the OODP reviewed marketing applications for 60 new indications and took regulatory action on 58 indications. Regulatory action was based on a risk–benefit evaluation of the data submitted with each application. Products that demonstrated efficacy and had an acceptable risk–benefit ratio were granted either regular or accelerated marketing approval for use in the specific indication that was studied. Regular approval was based on endpoints that demonstrated that the drug provided clinical benefit as evidenced by a longer or better life or a favorable effect on an established surrogate for a longer or better life. Accelerated approval was based on a less well-established surrogate endpoint that was reasonably likely to predict a longer or better life. Of the 53 new indications that were approved during the study period, 39 received regular approval, nine received accelerated approval, and five were converted from accelerated to regular approval. Five applications were not approved, and two applications were withdrawn before any regulatory action was taken. Eighteen of the 53 indications that were approved were for new molecular entities. During the study period, regulatory action was taken on 58 of the 60 marketing applications. Fifty-three applications were approved. A variety of clinical trial endpoints were used in the approval trials.
Identification of the tyrosine phosphatase PTP1C as a B cell antigen receptor-associated protein involved in the regulation of B cell signaling.
Authors: G Pani, M Kozlowski, J C Cambier, G B Mills, K A Siminovitch
Journal: The Journal of Experimental Medicine (1995)

Recent data implicating loss of PTP1C tyrosine phosphatase activity in the genesis of the multiple hemopoietic cell defects found in systemic autoimmune/immunodeficient motheaten (me) and viable motheaten (mev) mice suggest that PTP1C plays an important role in modulating intracellular signaling events regulating cell activation and differentiation. To begin elucidating the role for this cytosolic phosphatase in lymphoid cell signal transduction, we have examined early signaling events and mitogenic responses induced by B cell antigen receptor (BCR) ligation in me and mev splenic B cells and in CD5+ CH12 lymphoma cells, which represent the lymphoid population amplified in motheaten mice. Despite their lack of functional PTP1C, me and mev B cells proliferated normally in response to LPS. However, compared with wild-type B cells, cells from the mutant mice were hyperresponsive to normally submitogenic concentrations of F(ab')2 anti-Ig antibody, and they exhibited reduced susceptibility to the inhibitory effects of Fc gamma IIRB cross-linking on BCR-induced proliferation. Additional studies of unstimulated CH12 and wild-type splenic B cells revealed the constitutive association of PTP1C with the resting BCR complex, as evidenced by coprecipitation of PTP1C protein and phosphatase activity with BCR components and the depletion of BCR-associated tyrosine phosphatase activity by anti-PTP1C antibodies. These results suggest a role for PTP1C in regulating the tyrosine phosphorylation state of the resting BCR complex components, a hypothesis supported by the observation that PTP1C specifically induces dephosphorylation of a 35-kD BCR-associated protein likely representing Ig-alpha. In contrast, whereas membrane Ig cross-linking was associated with an increase in the tyrosine phosphorylation of PTP1C and an approximately 140-kD coprecipitated protein, PTP1C was no longer detected in the BCR complex after receptor engagement, suggesting that PTP1C dissociates from the activated receptor complex. Together these results suggest a critical role for PTP1C in modulating BCR signaling capacity, and they indicate that the PTP1C influence on B cell signaling is likely to be realized in both resting and activated cells.
Breast Cancer Dormancy Can Be Maintained by Small Numbers of Micrometastases
Authors: Lisa Willis, Tomas Alarcón, George Elia, J. Louise Jones, Nick A. Wright, Ian P.M. Tomlinson, Trevor A. Graham, Karen M. Page
Journal: Cancer Research (2010)

Late relapse of breast cancer can occur more than 25 years after primary diagnosis. During the intervening years between initial treatment and relapse, occult cancers are maintained in an apparent state of dormancy that is poorly understood. In this study, we applied a probabilistic mathematical model to long-term follow-up studies of postresection patients to investigate the factors involved in mediating breast cancer dormancy. Our results suggest that long-term dormancy is maintained most often by just one growth-restricted dangerous micrometastasis. Analysis of the empirical data by Approximate Bayesian Computation indicated that patients in dormancy have between 1 and 5 micrometastases at 10 years postresection, when they escape growth restriction with a half-life of <69 years and are >0.4 mm in diameter. Before resection, primary tumors seed at most an average of 6 dangerous micrometastases that escape from growth restriction with a half-life of at least 12 years. Our findings suggest that effective preventive treatments will need to eliminate these small numbers of micrometastases, which may be preangiogenic and nonvascularized until they switch to growth due to one oncogenic mutation or tumor suppressor gene inactivation. In summary, breast cancer dormancy seems to be maintained by small numbers of sizeable micrometastases that escape from growth restriction with a half-life exceeding 12 years.
Vitamin Intake and Liver Cancer Risk: A Report From Two Cohort Studies in China
Authors: W. Zhang, X.-O. Shu, H. Li, G. Yang, H. Cai, B.-T. Ji, J. Gao, Y.-T. Gao, W. Zheng, Y.-B. Xiang
Journal: JNCI Journal of the National Cancer Institute (2012)

Epidemiologic studies on the relationship between vitamin intake and liver cancer risk are sparse and inconsistent. We evaluated vitamin intake from diet and supplements and risk of liver cancer in 132 837 women and men from China who were recruited into the Shanghai Women's Health Study from 1997 to 2000 or the Shanghai Men's Health Study from 2002 to 2006. In-person interviews, using a validated food-frequency questionnaire, were conducted to collect data on dietary habits. Follow-up consisted of in-person surveys and record linkage. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazard models with adjustment for potential confounders to compare liver cancer risk among participants with high vs low vitamin intake. All statistical tests were two-sided. After excluding the first 2 years of follow-up, 267 participants (including 118 women and 149 men) developed liver cancer during an average of 10.9 (Shanghai Women's Health Study) or 5.5 (Shanghai Men's Health Study) years of follow-up. Dietary vitamin E intake was inversely associated with liver cancer risk ( Ptrend = .01), as was vitamin E supplement use (hazard ratio = 0.52, 95% confidence interval = 0.30 to 0.90). This association was consistent among participants with and without self-reported liver disease or a family history of liver cancer. Vitamin C and multivitamin use was associated with increased risk among participants with self-reported liver disease or family history of liver cancer, whereas intake of vitamin C and other vitamins from dietary sources was unrelated to liver cancer risk. Vitamin E intake, either from diet or supplements, may reduce the risk of liver cancer.
Treatment of eosinophilic pustulosis of infancy with topical tacrolimus
Authors: N.P. Patel, B. Laguda, N.M. Roberts, N.D. Francis, K. Agnew
Journal: British Journal of Dermatology (2012)

Journal Article Treatment of eosinophilic pustulosis of infancy with topical tacrolimus Get access N.P. Patel, N.P. Patel Chelsea and Westminster Hospital NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, U.K. E‐mail: neilpatel14@yahoo.co.uk Search for other works by this author on: Oxford Academic Google Scholar B. Laguda, B. Laguda Chelsea and Westminster Hospital NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, U.K. E‐mail: neilpatel14@yahoo.co.uk Search for other works by this author on: Oxford Academic Google Scholar N.M. Roberts, N.M. Roberts Chelsea and Westminster Hospital NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, U.K. E‐mail: neilpatel14@yahoo.co.uk Search for other works by this author on: Oxford Academic Google Scholar N.D. Francis, N.D. Francis Chelsea and Westminster Hospital NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, U.K. E‐mail: neilpatel14@yahoo.co.uk Search for other works by this author on: Oxford Academic Google Scholar K. Agnew K. Agnew Chelsea and Westminster Hospital NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, U.K. E‐mail: neilpatel14@yahoo.co.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 167, Issue 5, 1 November 2012, Pages 1189–1191, https://doi.org/10.1111/j.1365-2133.2012.11045.x Published: 01 November 2012
Increased epithelial cell proliferation and abnormal extracellular matrix in rat polycystic kidney disease.
Authors: K Ramasubbu, N Gretz, S Bachmann
Journal: Journal of the American Society of Nephrology (1998)

Proliferation of renal tubular epithelial cells is considered a major factor leading to cyst formation in human polycystic kidney disease (PKD). The Han:SPRD rat model for inherited PKD permits a close scrutiny, especially for early stages of the disease, and shows numerous similarities to human autosomal dominant PKD (ADPKD). In this study, the exact in vivo proliferation rate in Han:SPRD rat kidneys was evaluated in a cell type-specific manner, using immunohistochemistry with antibody to proliferating cell nuclear antigen (PCNA). The proliferation index (PI; percentage of PCNA-positive cell nuclei) was determined in normal and cystically altered tissue, and a relationship between proliferative activity and alterations in extracellular matrix expression was established using in situ hybridization for collagen I and IV mRNA. Heterozygously affected rats (cy/+) showed strong increases of PI values in cystically altered nephron portions that were mostly derived from proximal tubule. Cell proliferation obviously preceded cyst formation, because early in the progression of the disease, the normal-appearing tubules from PKD kidneys had markedly increased PI values compared with healthy controls (14.1-fold in 3-mo-old rats and 11.9-fold in 12-mo-old rats; P < 0.05), whereas later stages revealed a more generalized cystic degeneration of the nephron, with increases in PI between 14- and 82-fold, depending on the respective category of cystic epithelia. In cysts with a distal phenotype, changes were less pronounced. No significant differences were encountered between the two age groups. Proliferation was also present in interstitial cells, whereas glomeruli were unchanged. Increases in epithelial and interstitial proliferation coincided with an overexpression of matrix compounds. For comparison, changes in homozygously affected rats (cy/cy) showed up to several hundred-fold elevated PI values. These results indicate that in the Han:SPRD model for ADPKD, cystic malformation of the nephron is preceded by and coincides with enhanced epithelial and interstitial cell proliferation. Altered cell-matrix interactions seem to be directly involved in the disruption of epithelial differentiation.
Long term remission of Sjogren's syndrome associated aggressive B cell non-Hodgkin's lymphomas following combined B cell depletion therapy and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)
Authors: M Voulgarelis
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Primary Sjögren's syndrome (SS) is associated with an increased frequency of non-Hodgkin's lymphomas (NHLs), mainly of low histological grade. However, aggressive diffuse large B cell lymphomas (DLBCL) characterised by poor treatment outcome can also be encountered in SS. It has recently been shown that rituxan has significant therapeutic activity in this type of lymphoma. <b>Objective:</b> To evaluate the efficacy of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) in combination with rituxan in SS patients with DLBCL, and to determine the outcome in such patients. <b>Methods:</b> In an open, single case trial, six SS patients with DLBCL were assigned to receive eight cycles of CHOP every three weeks plus rituxan given on day 1 of each cycle. In a retrospective study, conducted by the European Concerted Action for SS, nine cases were diagnosed as DLBCL, all of whom had been treated with CHOP alone. These patients were used as historical controls. <b>Results:</b> The difference in the overall survival between the two treatment groups was significant. The group treated with rituxan plus CHOP had a 100% two year overall survival rate, while the historical controls had only a 37% survival rate. Extraglandular manifestations serving as predictors for lymphoma development such as palpable purpura and peripheral neuropathy disappeared. The remission of these signs was accompanied by a decrease in both circulating monoclonal cryoglobulins and rheumatoid factor activity and an increase in C4 levels. Clinically relevant toxicity was not detected. <b>Conclusions:</b> The addition of rituxan to standard CHOP chemotherapy results in improved treatment outcome in SS patients with aggressive DLBCL, without increasing toxicity.
Response of livedoid vasculopathy to rivaroxaban
Authors: D.S. Winchester, L.A. Drage, M.D.P. Davis
Journal: British Journal of Dermatology (2014)

Journal Article Response of livedoid vasculopathy to rivaroxaban Get access D.S. Winchester, D.S. Winchester Department of Dermatology Mayo Clinic 200 First St SW Rochester MN 55905 U.S.A Search for other works by this author on: Oxford Academic Google Scholar L.A. Drage, L.A. Drage Department of Dermatology Mayo Clinic 200 First St SW Rochester MN 55905 U.S.A Search for other works by this author on: Oxford Academic Google Scholar M.D.P. Davis M.D.P. Davis Department of Dermatology Mayo Clinic 200 First St SW Rochester MN 55905 U.S.A Correspondence: Mark D.P. Davis. E‐mail: davis.mark2@mayo.edu Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 4, 1 April 2015, Pages 1148–1150, https://doi.org/10.1111/bjd.13428 Published: 01 April 2015
The Future of Radiation Oncology in the United States From 2010 to 2020: Will Supply Keep Pace With Demand?
Authors: Benjamin D. Smith, Bruce G. Haffty, Lynn D. Wilson, Grace L. Smith, Akshar N. Patel, Thomas A. Buchholz
Journal: Journal of Clinical Oncology (2010)

Prior studies forecasted an incipient shortage of medical oncologists as a result of the aging US population, but the radiation oncology workforce has not been studied. Accordingly, we projected demand for radiation therapy and supply of radiation oncologists in 2010 and 2020 to determine whether a similar shortage may exist for this specialty.Demand for radiation therapy in 2010 and 2020 was estimated by multiplying current radiation utilization rates (as calculated with Surveillance, Epidemiology, and End Results data) by population projections from the Census Bureau. Supply of radiation oncologists was projected using data from the American Board of Radiology inclusive of current radiation oncologists and active residents, accounting for variation in full-time equivalent status and expected survival by age and sex.Between 2010 and 2020, the total number of patients receiving radiation therapy during their initial treatment course is expected to increase by 22%, from 470,000 per year to 575,000 per year. In contrast, assuming that the current graduation rate of 140 residents per year remains constant, the number of full-time equivalent radiation oncologists is expected to increase by only 2%, from 3,943 to 4,022. The size of residency training classes for the years 2014 to 2019 would have to double to 280 residents per year in order for growth in supply of radiation oncologists to equal expected growth in demand.Demand for radiation therapy is expected to grow 10 times faster than supply between 2010 and 2020. Research is needed to explore strategies to enhance capacity to deliver quality radiation therapy despite increased patient loads.
A Predictive Model of Rectal Tumor Response to Preoperative Radiotherapy Using Classification and Regression Tree Methods
Authors: Inti Zlobec, Russell Steele, Nilima Nigam, Carolyn C. Compton
Journal: Clinical Cancer Research (2005)

The ability to predict rectal tumor response to preoperative radiotherapy before treatment would significantly impact patient selection. In this study, classification and regression tree (CART) methods were used to model tumor response to preoperative conformal high-dose rate brachytherapy by assessing the predictive value of vascular endothelial growth factor (VEGF), Bcl-2, p21, p53, and APAF-1.Immunohistochemistry was used to detect VEGF, Bcl-2, p21, p53, and APAF-1 from 62 pretreatment rectal tumor biopsies. Scores were assigned as percentages of positive tumor cell staining and were used in CART analysis to identify the proteins that best predicted response to radiotherapy. Ten-fold cross-validation was used to prevent overfitting and multiple cross-validation experiments were run to estimate the prediction error.Postoperative pathologic evaluation of the irradiated tumor bed revealed 43 responsive tumors [20 with complete response (T(0)) and 23 with partial response] and 19 nonresponsive tumors. The optimal tree resulting from CART analysis had five terminal nodes with a misclassification rate of 18%. Of the five proteins selected for their predictive value, VEGF and Bcl-2 contributed most to the classification of responsive and nonresponsive tumors. All 10 tumors with no VEGF were completely responsive (T(0)) to radiotherapy; 85% of those with VEGF and negative for Bcl-2 were responsive to therapy.VEGF and Bcl-2 status in pretreatment rectal tumor biopsies may be predictive of response to preoperative high-dose rate brachytherapy.