tbuckley/cabot-search huggingface dataset:
Identification of longitudinally dynamic biomarkers in Alzheimer’s disease cerebrospinal fluid by targeted proteomics
Authors: Kristin R Wildsmith, Stephen P Schauer, Ashley M Smith, David Arnott, Yuda Zhu, Joshua Haznedar, Surinder Kaur, W Mathews, Lee A Honigberg
Journal: Molecular Neurodegeneration (2014)

Alzheimer's disease (AD) is the leading cause of dementia affecting greater than 26 million people worldwide. Although cerebrospinal fluid (CSF) levels of Aβ42, tau, and p-tau181 are well established as diagnostic biomarkers of AD, there is a need for additional CSF biomarkers of neuronal function that continue to change during disease progression and could be used as pharmacodynamic measures in clinical trials. Multiple proteomic discovery experiments have reported a range of CSF biomarkers that differ between AD and control subjects. These potential biomarkers represent multiple aspects of the disease pathology. The performance of these markers has not been compared with each other, and their performance has not been evaluated longitudinally. We developed a targeted-proteomic, multiple reaction monitoring (MRM) assay for the absolute quantitation of 39 peptides corresponding to 30 proteins. We evaluated the candidate biomarkers in longitudinal CSF samples collected from aged, cognitively-normal control (n = 10), MCI (n = 5), and AD (n = 45) individuals (age > 60 years). We evaluated each biomarker for diagnostic sensitivity, longitudinal consistency, and compared with CSF Aβ42, tau, and p-tau181. Four of 28 quantifiable CSF proteins were significantly different between aged, cognitively-normal controls and AD subjects including chitinase-3-like protein 1, reproducing published results. Four CSF markers demonstrated significant longitudinal change in AD: Amyloid precursor protein, Neuronal pentraxin receptor, NrCAM and Chromogranin A. Robust correlations were observed within some subgroups of proteins including the potential disease progression markers. Using a targeted proteomics approach, we confirmed previous findings for a subset of markers, defined longitudinal performance of our panel of markers, and established a flexible proteomics method for robust multiplexed analyses.
Clinical Inertia in People With Type 2 Diabetes
Authors: Kamlesh Khunti, Michael L. Wolden, Brian Larsen Thorsted, Marc Andersen, Melanie J. Davies
Journal: Diabetes Care (2013)

To determine time to treatment intensification in people with type 2 diabetes treated with one, two, or three oral antidiabetes drugs (OADs) and associated levels of glycemic control.This was a retrospective cohort study based on 81,573 people with type 2 diabetes in the U.K. Clinical Practice Research Datalink between January 2004 and December 2006, with follow-up until April 2011.In people with HbA1c ≥7.0, ≥7.5, or ≥8.0% (≥53, ≥58, or ≥64 mmol/mol), median time from above HbA1c cutoff to intensification with an additional OAD was 2.9, 1.9, or 1.6 years, respectively, for those taking one OAD and >7.2, >7.2, and >6.9 years for those taking two OADs. Median time to intensification with insulin was >7.1, >6.1, or 6.0 years for those taking one, two, or three OADs. Mean HbA1c at intensification with an OAD or insulin for people taking one, two, or three OADs was 8.7, 9.1, and 9.7%. In patients taking one, two, or three OADs, median time from treatment initiation to intensification with an OAD or insulin exceeded the maximum follow-up time of 7.2 years. The probability of patients with poor glycemic control taking one, two, or three OADs, intensifying at end of follow-up with an OAD, was 21.1-43.6% and with insulin 5.1-12.0%.There are delays in treatment intensification in people with type 2 diabetes despite suboptimal glycemic control. A substantial proportion of people remain in poor glycemic control for several years before intensification with OADs and insulin.
The electrocardiogram during sinus rhythm and tachycardia in patients with Mahaim fibers
Authors: Eduardo Back Sternick, Carl Timmermans, Eduardo Sosa, Fernando E.S. Cruz, Luz-Maria Rodriguez, Márcio Fagundes, Luiz M. Gerken, Hein J.J. Wellens
Journal: Journal of the American College of Cardiology (2004)
Image Registered Gastroscopic Ultrasound (IRGUS) in human subjects: a pilot study to assess feasibility
Authors: K. Obstein, R. Estépar, J. Jayender, V. Patil, I. Spofford, M. Ryan, B. Lengyel, R. Shams, K. Vosburgh, C. Thompson
Journal: Endoscopy (2011)

Endoscopic ultrasound (EUS) is a complex procedure due to the subtleties of ultrasound interpretation, the small field of observation, and the uncertainty of probe position and orientation. Animal studies demonstrated that Image Registered Gastroscopic Ultrasound (IRGUS) is feasible and may be superior to conventional EUS in efficiency and image interpretation. This study explores whether these attributes of IRGUS will be evident in human subjects, with the aim of assessing the feasibility, effectiveness, and efficiency of IRGUS in patients with suspected pancreatic lesions.This was a prospective feasibility study at a tertiary care academic medical center in human patients with pancreatic lesions on computed tomography (CT) scan. Patients who were scheduled to undergo conventional EUS were randomly chosen to undergo their procedure with IRGUS. Main outcome measures included feasibility, ease of use, system function, validated task load (TLX) assessment instrument, and IRGUS experience questionnaire.Five patients underwent IRGUS without complication. Localization of pancreatic lesions was accomplished efficiently and accurately (TLX temporal demand 3.7 %; TLX effort 8.6 %). Image synchronization and registration was accomplished in real time without procedure delay. The mean assessment score for endoscopist experience with IRGUS was positive (66.6 ± 29.4). Real-time display of CT images in the EUS plane and echoendoscope orientation were the most beneficial characteristics.IRGUS appears feasible and safe in human subjects, and efficient and accurate at identification of probe position and image interpretation. IRGUS has the potential to broaden the adoption of EUS techniques and shorten EUS learning curves. Clinical studies comparing IRGUS with conventional EUS are ongoing.
Evaluation of the Optimal Number of Lesions Needed for Tumor Evaluation Using the Response Evaluation Criteria in Solid Tumors: A North Central Cancer Treatment Group Investigation
Authors: Shauna L. Hillman, Ming-Wen An, Michael J. O'Connell, Richard M. Goldberg, Paul Schaefer, Jan C. Buckner, Daniel J. Sargent
Journal: Journal of Clinical Oncology (2009)

PURPOSE In February 2000, the criteria for measuring tumor shrinkage as an indicator of antitumor activity were redefined by the Response Evaluation Criteria in Solid Tumors (RECIST). This resulted in simplifying bidimensional to unidimensional measurement of lesions. Under RECIST, all lesions, up to 10, must be measured. Scanning and measuring multiple lesions is costly, time-consuming, and a disincentive to participation in clinical trials. We investigated whether fewer than 10 lesions can be measured without compromising the accuracy of assessing a regimen's activity. PATIENTS AND METHODS Thirty-two North Central Cancer Treatment Group trials including 2,374 patients were analyzed. Twelve studies were conducted before RECIST; 20 were conducted post-RECIST. Agreement between objective status by cycle, confirmed response, overall response rate, and time to progression (TTP) was evaluated based on all 10 versus the largest one through five lesions. Results The median number of lesions reported on RECIST trials did not differ from pre-RECIST trials (median = 2.0). One lesion at baseline was reported in 49% of patients, two lesions in 28% of patients, three lesions in 12% of patients, four lesions in 6% of patients, and five lesions in 5% of patients in post-RECIST trials. Utilizing the largest two lesions produced excellent concordance with that using all lesions for all end points. In no trial did the overall response rate differ by more than 3% when two versus all lesions were considered. Evaluating more than two lesions did not significantly improve agreement. CONCLUSION Based on these trials, the assessment of more than two lesions did not alter the conclusions regarding a treatment's efficacy as judged by response rate or TTP.
Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison
Authors: Jan J. Cornelissen, Bronno van der Holt, Gregor E. G. Verhoef, Mars B. van 't Veer, Marinus H. J. van Oers, Harry C. Schouten, Gert Ossenkoppele, Pieter Sonneveld, Johan Maertens, Marinus van Marwijk Kooy, Martijn R. Schaafsma, Pierre W. Wijermans, Douwe H. Biesma, Shulamit Wittebol, Paul J. Voogt, Joke W. Baars, Pierre Zachée, Leo F. Verdonck, Bob Löwenberg, Adriaan W. Dekker
Journal: Blood (2008)
Erythrocytic galactose-1-phosphate uridyl transferase levels in hepatic cirrhosis
Authors: M. M. Fisher, S. Spear, E. Samols, S. Sherlock
Journal: Gut (1964)

EDITORIAL SYNOPSIS Hereditary galactosaemia is an inborn error of metabolism and may lead to the development of hepatic cirrhosis.The diagnosis may be established by finding very low or no levels of 'transferase' in the red cells.No examples of this disease were found among the patients studied and, it must be a rare cause of cirrhosis in Great Britain.It would seem adequate to screen cirrhotic patients by 'transferase' assay only if they showed other features suggesting galactosaemia.These include subnormal mentality, cataracts, a family or past history of intolerance to milk, or a family history of cirrhosis.on August 22,
Marked, Homogeneous, and Early [<sup>18</sup>F]Fluorodeoxyglucose–Positron Emission Tomography Responses to Vemurafenib in <i>BRAF</i>-Mutant Advanced Melanoma
Authors: Grant A. McArthur, Igor Puzanov, Ravi Amaravadi, Antoni Ribas, Paul Chapman, Kevin B. Kim, Jeffrey A. Sosman, Richard J. Lee, Keith Nolop, Keith T. Flaherty, Jason Callahan, Rodney J. Hicks
Journal: Journal of Clinical Oncology (2012)

Imaging with [(18)F]fluorodeoxyglucose (FDG) -positron emission tomography (PET) allows early recognition of a response to agents that target key driver mutations in human cancer. We aimed to determine the metabolic response rate to vemurafenib in patients with advanced BRAF-mutant melanoma.Baseline and day 15 FDG-PET was evaluated in 31 patients with advanced melanoma treated in a phase I study of dose escalation of vemurafenib (PLX06-02), which included four patients treated at subtherapeutic doses and 24 patients treated at 960 mg twice a day, which is the maximum-tolerated dose of vemurafenib.All 27 patients treated at potentially therapeutic levels had at least a partial metabolic response, and three patients achieved a complete metabolic response. In the 27 patients, there was an 80% ± 3% reduction in the maximum standardized uptake value (SUVmax) of target lesions and an 87% ± 3% decrease in the percentage of injected dose (%ID) in all identified disease sites. There was a positive correlation between %ID in all identified disease and target-lesion SUVmax (r(2) = 0.66; P < .001) that indicated a significant homogeneity of the response between lesions in individual patients. Although no relationship was found between the reduction in target lesion SUVmax and best response according to RECIST (Response Evaluation Criteria in Solid Tumors), there was a trend for patients with greater reductions in uptake of FDG to have longer progression-free survival.FDG-PET is a useful marker of an early biologic response to vemurafenib. Little variability in PET response was found between lesions in individual patients, which suggested minimal intrapatient molecular heterogeneity. FDG-PET is a useful tool for the evaluation of the biologic impact of inhibiting mutant BRAF and may allow for the more effective development of novel agents.
Ontogeny of type 1 angiotensin II receptor gene expression in the rat.
Authors: A Tufro-McReddie, J K Harrison, A D Everett, R A Gomez
Journal: Journal of Clinical Investigation (1993)

To determine whether the expression of the type 1 angiotensin II receptor (AT1) gene is developmentally regulated and whether the regulation is tissue specific, AT1 mRNA levels were determined by Northern blot analysis in livers and kidneys from fetal, newborn, and adult rats, using a 1133-bp rat AT1 cDNA. In the liver, AT1 mRNA levels increased fivefold from 15 d gestation to 5 d of age. Liver AT1 mRNA levels at 5 d of age were similar to those of adult rats. In the kidney, AT1 mRNA levels were higher in immature than in adult animals. The intrarenal distribution of AT1 mRNA was assessed by in situ hybridization to a 35S-labeled 24 residues oligonucleotide complementary to rat AT1 mRNA. In the adult, AT1 mRNA was present in glomeruli, arteries, and vasa recta, whereas in the newborn AT1 mRNA was observed also over the nephrogenic area of the cortex. We conclude that: (a) fetal kidney and liver express the AT1 gene; (b) the AT1 gene expression is developmentally regulated in a tissue-specific manner; (c) during maturation, localization of AT1 mRNA in the kidney shifts from a widespread distribution in the nephrogenic cortex to specific sites in glomeruli, arteries, and vasa recta, suggesting a role for the angiotensin receptor in nephron growth and development.
Racial/Ethnic Differences in Dementia Risk Among Older Type 2 Diabetic Patients: The Diabetes and Aging Study
Authors: Elizabeth R. Mayeda, Andrew J. Karter, Elbert S. Huang, Howard H. Moffet, Mary N. Haan, Rachel A. Whitmer
Journal: Diabetes Care (2013)

OBJECTIVE Although patients with type 2 diabetes have double the risk of dementia, potential racial/ethnic differences in dementia risk have not been explored in this population. We evaluated racial/ethnic differences in dementia and potential explanatory factors among older diabetic patients. RESEARCH DESIGN AND METHODS We identified 22,171 diabetic patients without preexisting dementia aged ≥60 years (14,546 non-Hispanic whites, 2,484 African Americans, 2,363 Latinos, 2,262 Asians, 516 Native Americans) from the Kaiser Permanente Northern California Diabetes Registry. We abstracted prevalent medical history (1 January 1996 to 31 December 1997) and dementia incidence (1 January 1998 to 31 December 2007) from medical records and calculated age-adjusted incidence densities. We fit Cox proportional hazards models adjusted for age, sex, education, diabetes duration, and markers of clinical control. RESULTS Dementia was diagnosed in 3,796 (17.1%) patients. Age-adjusted dementia incidence densities were highest among Native Americans (34/1,000 person-years) and African Americans (27/1,000 person-years) and lowest among Asians (19/1,000 person-years). In the fully adjusted model, hazard ratios (95% CIs) (relative to Asians) were 1.64 (1.30-2.06) for Native Americans, 1.44 (1.24-1.67) for African Americans, 1.30 (1.15-1.47) for non-Hispanic whites, and 1.19 (1.02-1.40) for Latinos. Adjustment for diabetes-related complications and neighborhood deprivation index did not change the results. CONCLUSIONS Among type 2 diabetic patients followed for 10 years, African Americans and Native Americans had a 40-60% greater risk of dementia compared with Asians, and risk was intermediate for non-Hispanic whites and Latinos. Adjustment for sociodemographics, diabetes-related complications, and markers of clinical control did not explain observed differences. Future studies should investigate why these differences exist and ways to reduce them.
STUDIES ON THE GENERALIZED SHWARTZMAN REACTION
Authors: Lewis Thomas, Robert A. Good
Journal: The Journal of Experimental Medicine (1952)

Certain factors involved in the production of the generalized Shwartzman reaction with meningococcal toxin in rabbits were investigated. The optimal amounts of toxin for the preparing and provoking injections, and the optimal time interval between injections were determined. Under suitable conditions of dosage and timing, bilateral cortical necrosis of the kidneys was produced in a high proportion of animals. When excessive amounts of toxin were used for preparation the incidence of the reaction was reduced. Animals undergoing the generalized Shwartzman reaction became severely prostrated within several hours after the provoking injection of toxin. The renal lesion became fully developed within 24 hours, and its occurrence was associated with a rise of the blood non-protein nitrogen. Edema and petechial hemorrhages in the ears were observed in rabbits with advanced renal lesions. The earliest change in the kidneys in the generalized Shwartzman reaction was the appearance of homogeneous, eosinophilic material, resembling fibrinoid, within the lumen of the glomerular capillaries. Occlusion of the capillaries by this material was regarded as the cause of subsequent tubular necrosis in the renal cortex. The material appeared to be derived from the blood, rather than from the capillary walls. Cortisone enhanced the lethal effect of a single, large dose of meningococcal toxin, as well as causing bilateral renal cortical necrosis. The generalized Shwartzman reaction produced by two injections of toxin was aggravated by cortisone and ACTH. Profound polymorphonuclear leukopenia was produced by both the preparing and provoking injections of toxin. When leukopenia was produced before the preparing injection of toxin, by treatment with nitrogen mustard, the generalized Shwartzman reaction was inhibited. During the intervals before and after leukopenia, and when leukopenia was prevented by shielding the femoral bone marrow from the action of nitrogen mustard, no inhibition of the generalized Shwartzman phenomenon was demonstrable. Various colloidal and particulate materials, which are capable of provoking the local skin Shwartzman reaction when injected intravenously, failed to provoke the generalized Shwartzman reaction. A working hypothesis was set up to account for certain events in the generalized Shwartzman reaction.
Ethnic-Specific Criteria for the Metabolic Syndrome
Authors: Jing Liu, Scott M. Grundy, Wei Wang, Sidney C. Smith, Gloria Lena Vega, Zhaosu Wu, Zhechun Zeng, Wenhua Wang, Dong Zhao
Journal: Diabetes Care (2006)

The metabolic syndrome is a constellation of interrelated abnormalities, including dyslipidemia, elevated blood pressure and glucose, and prothrombotic and proinflammatory states (1). Because of the growing prevalence of the metabolic syndrome, several organizations have attempted to set forth clinical criteria for its diagnosis (1–5). The most recent are those proposed by the International Diabetes Federation (IDF) definition (5) and the American Heart Association’s National Heart, Lung, and Blood Institute (1). The latter updated the National Cholesterol Education Program Adult Treatment Panel III (ATPIII) criteria (2). Both IDF and updated ATPIII criteria emphasized the importance of adiposity in the etiology of the metabolic syndrome and recommended specific thresholds for central obesity in different ethnic groups. Thresholds in the two reports were identical for Asian populations. A significant difference between the two criteria is that the IDF makes central obesity necessary for diagnosis, whereas updated ATPIII criteria did not. Whether the prerequisite of central obesity has any impact on the prevalence or the classification of the syndrome in the Chinese population is unknown. The objective of this study is to assess the prevalence of the metabolic syndrome in the Chinese population using the ethnic-specific …
Changes in malaria indices between 1999 and 2007 in The Gambia: a retrospective analysis
Authors: Serign J Ceesay, Climent Casals-Pascual, Jamie Erskine, Samuel E Anya, Nancy O Duah, Anthony JC Fulford, Sanie SS Sesay, Ismaela Abubakar, Samuel Dunyo, Omar Sey, Ayo Palmer, Malang Fofana, Tumani Corrah, Kalifa A Bojang, Hilton C Whittle, Brian M Greenwood, David J Conway
Journal: The Lancet (2008)
INCIDENCE, CHARACTERISTIC AND RISK FACTORS OF CEREBRAL THROMBOEMBOLIC COMPLICATIONS FOLLOWING HIGH-FREQUENCY CATHETER ABLATION OF ATRIAL FIBRILLATION: EXPERIENCE OF 3,360 PROCEDURES
Authors: Andreas Bollmann, Jedrzej Kosiuk, Jelena Kornej, Krzysztof Myrda, Arash Arya, Thomas Gaspar, Christopher Piorkowski, Philipp Sommer, Gerhard Hindricks, Gregory Lip
Journal: Journal of the American College of Cardiology (2013)
Morphologic and functional consequences of immune-mediated mesangiolysis
Authors: R A Stahl, F Thaiss, U Wenzel, U Helmchen
Journal: Journal of the American Society of Nephrology (1992)

The i.v. injection of a rabbit anti-rat thymocyte serum (ATS) induces mesangiolysis in rats, followed by a mesangioproliferative glomerulonephritis (4 to 7 days after antibody). This proliferative lesion disappears 4 to 6 wks after antibody. In order to induce an antibody-mediated sclerotic glomerular disease, uninephrectomized rats received ATS twice at 6-wk interval. At 6 months after the first antibody injection, albuminuria, arterial blood pressure, and inulin clearances were evaluated and renal morphologic studies were performed. At the time of evaluation, mean arterial blood pressure and inulin clearances were not different between animals that received the antibody and uninephrectomized controls. Rats that were injected with antibody, however, had significantly higher albuminuria compared with that of controls. Glomeruli of rats with ATS revealed expansion of the glomerular mesangial matrix and focal sclerosis. A semiquantitative morphologic analysis revealed an increased incidence of glomerular lesions and a higher glomerular damage index in kidneys of nephritic rats. These data demonstrate that the repetitive injection of ATS to unilaterally nephrectomized rats induces a model of chronic glomerular sclerosis.
Reasons for delay in primary treatment of British patients with malignant melanoma
Authors: Valerie Doherty, J. Ashworth, J. English, Rona Mackie
Journal: British Journal of Dermatology (1985)

Patients with ‘thin’ malignant melanoma (I mm thick) have excellent prospects for survival while those with tumours thicker than 3 mm have 5-year survival figures of under 40%. It is logical to assume that the first group receive treatment more rapidly than the latter. Delay in therapy may be due to the patient, the family doctor or the specialist. Of 1300 primary melanomas studied in Scotland from 1979 to 1983, 390 (30%) were < 1–5 mm in thickness. This contrasts with Australia where at present 80% of melanomas are in this thin, good prognosis group. We have conducted a detailed study of 115 Glasgow patients to establish the reason for the low percentage of good prognosis tumours. Records were studied and patients interviewed to establish the reasons for delay. One hundred patients (87%) had delayed for 3 months or longer in seeking treatment for a new or changing pigmented lesion and 38 (33%) had delayed for over a year. In only three patients (26%) was there family doctor delay, and there was no hospital delay. Patient delay was virtually always due to lack of knowledge rather than fear. Following this study, the West of Scotland Pigmented Lesion Education Project has been organized and will be described, as will the methods of measuring its impact.