tbuckley/cabot-search huggingface dataset:
Improving Diabetes Processes of Care in Managed Care
Authors: Liza L. Ilag, Catherine L. Martin, Bahman P. Tabaei, Deanna J. M. Isaman, Ray Burke, Douglas A. Greene, William H. Herman
Journal: Diabetes Care (2003)

OBJECTIVE—To evaluate the impact of systematic patient evaluation and patient and provider feedback on the processes and intermediate outcomes of diabetes care in Independent Practice Association model internal medicine practices. RESEARCH DESIGN AND METHODS—Nine practices providing care to managed care patients were randomly assigned as intervention or comparison sites. Intervention-site subjects had Annual Diabetes Assessment Program (ADAP) assessments (HbA1c, blood pressure, lipids, smoking, retinal photos, urine microalbumin, and foot examination) at years 1 and 2. Comparison-site subjects had ADAP assessments at year 2. At Intervention sites, year 1 ADAP results were reviewed with subjects, mailed to providers, and incorporated into electronic medical records with guideline-generated suggestions for treatment and follow-up. Medical records were evaluated for both groups for the year before both the year 1 and year 2 ADAP assessments. Processes and intermediate outcomes were compared using linear and logistic mixed hierarchical models. RESULTS—Of 284 eligible subjects, 103 of 173 (60%) at the Intervention sites and 71 of 111 (64%) at the comparison sites participated; 83 of 103 (81%) of the intervention-site subjects returned for follow-up at year 2. Performance of the six recommended assessments improved in intervention-site subjects at year 2 compared with year 1 (5.8 vs. 4.3, P = 0.0001) and compared with comparison-site subjects at year 2 (4.2, P = 0.014). No significant changes were noted in intermediate outcomes. CONCLUSIONS—The ADAP significantly improved processes of care but not intermediate outcomes. Additional interventions are needed to improve intermediate outcomes.
Idiotypic cross-reactions of monoclonal human lupus autoantibodies.
Authors: Y Shoenfeld, D A Isenberg, J Rauch, M P Madaio, B D Stollar, R S Schwartz
Journal: The Journal of Experimental Medicine (1983)

Idiotypic cross-reactions were evaluated in 60 polynucleotide-binding monoclonal lupus autoantibodies produced by human-human hybridomas that were derived from seven unrelated patients with SLE. Three antiidiotype reagents were prepared by immunization of rabbits or a mouse with monoclonal autoantibodies from two patients. Binding of the three reagents to their corresponding idiotypes was inhibited by one or more polynucleotides, an indication that the antiidiotypes reacted with the variable regions of the autoantibodies. Each antiidiotype appeared to detect a different idiotypic determinant. Of the 60 monoclonal autoantibodies tested, 40 reacted in one or more competitive immunoassays; 15 reacted with one antiidiotype, 10 reacted with two antiidiotypes and 15 reacted with three antiidiotypes. A monoclonal antiidiotype reagent cross-reacted with autoantibodies from six of the seven patients. The idiotypic cross-reactions of immunoglobulins from unrelated patients suggest that the autoantibodies are derived from related families of germ line genes that are expressed by patients with SLE.
Interactions of Quinidine and Potassium on Atrioventricular Transmission
Authors: YOSHIO WATANABE, LEONARD S. DREIFUS
Journal: Circulation Research (1967)

The effects of quinidine and its interactions with potassium (K) on atrio-ventricular (A-V) conduction were studied in isolated, perfused rabbit hearts, utilizing microelectrode techniques. Quinidine gluconate (10 mg/liter) was added to perfusion fluid containing either normal [K + ] (4.5 mEq/liter), low [K + ] (1.5 mEq/liter), or high [K + ] (7.5 mEq/liter). The following observations were made: (A) The marked prolongation of A-V conduction time produced by quinidine was antagonized by low K + and enhanced by high K + concentration. (B) Quinidine or high K + concentration prolonged the A-V interval by slowing intra-atrial and His-Purkinje-ventricular conduction. (C) Low K + concentration depressed conduction in the N region of the A-V node. (D) Lowering K + concentration in the presence of quinidine shortened the A-V interval by enhancing His-Purkinje-ventricular conduction. (E) Quinidine and high K + concentration increased the action potential amplitude in the nodal and the node-His regions of the A-V node while low K + concentration showed opposite effects. Hence, different regions of the A-V conducting system were selectively influenced by these agents. A-V conduction in the presence of low K + and quinidine depends upon the net results of their antagonism within individual fiber types. The importance of these interrelationships in pharmacologic approach to A-V conduction disturbances is stressed.
Lactate Dehydrogenase 5 Expression in Operable Colorectal Cancer: Strong Association With Survival and Activated Vascular Endothelial Growth Factor Pathway—A Report of the Tumour Angiogenesis Research Group
Authors: Michael I. Koukourakis, Alexandra Giatromanolaki, Efthimios Sivridis, Kevin C. Gatter, Adrian L. Harris
Journal: Journal of Clinical Oncology (2006)

Purpose Lactate dehydrogenase 5 (LDH-5) regulates, under hypoxic conditions, the anaerobic transformation of pyruvate to lactate for energy acquisition. Several studies have shown that serum LDH may be an ominous prognostic marker in malignant tumors. The clinical significance of tissue LDH-5, however, remains largely unexplored. Patients and Methods We investigated the immunohistochemical expression of LDH-5 in a series of 128 stage II/III colorectal adenocarcinomas treated with surgery alone. In addition, markers of tumor hypoxia (hypoxia-inducible factor 1 alpha [HIF1α]), angiogenesis (vascular endothelial growth factor [VEGF] and phosporylated kinase domain receptor [pKDR]/flk-1 receptor) and the tumor vascular density (CD31 positive standard vascular density [sVD] and pKDR positive activated vascular density [aVD]) were assessed. Results The expression of LDH-5, together with that of HIF1α and pKDR, was both nuclear and cytoplasmic. Assessment, with minimal interobserver variability, was achieved using a previously described scoring system. LDH-5 was significantly associated with HIF1α (P = .01), aVD (P = .001) and, particularly, with pKDR expression in cancer cells (P = .0001). Tissue LDH-5 expression was linked with elevated serum LDH levels, but serum levels failed to reflect tissue expression in 71% of LDH-5 positive cases. In univariate analysis tissue LDH-5 was associated with poor survival (P = .0003, HR 15.1), whereas in multivariate analysis this isoenzyme was the strongest independent prognostic factor (P = .0009). VEGF, pKDR, aVD, sVD and vascular invasion were all significantly related to unfavorable prognosis. Conclusion The immunohistochemical assessment of tissue LDH-5 and pKDR provides important prognostic information in operable colorectal cancer. The strong association between LDH-5 and pKDR expression would justify their use as surrogate markers to screen patients for tyrosin kinase inhibitor therapy.
Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma
Authors: C. Haioun, N. Mounier, J.F. Emile, D. Ranta, B. Coiffier, H. Tilly, C. Récher, C. Fermé, J. Gabarre, R. Herbrecht, F. Morchhauser, C. Gisselbrecht
Journal: Annals of Oncology (2009)
Competing-Risk Analysis of ESRD and Death among Patients with Type 1 Diabetes and Macroalbuminuria
Authors: Carol Forsblom, Valma Harjutsalo, Lena M. Thorn, Johan Wadén, Nina Tolonen, Markku Saraheimo, Daniel Gordin, John L. Moran, Merlin C. Thomas, Per-Henrik Groop
Journal: Journal of the American Society of Nephrology (2011)

Patients with both type 1 diabetes and CKD have an increased risk of adverse outcomes. The competing risks of death and ESRD may confound the estimates of risk for each outcome. Here, we sought to determine the major predictors of the cumulative incidence of ESRD and pre-ESRD mortality in patients with type 1 diabetes and macroalbuminuria while incorporating the competing risk for the alternate outcome into a Fine-Gray competing-risks analysis. We followed 592 patients with macroalbuminuria for a median of 9.9 years. During this time, 56 (9.5%) patients died and 210 (35.5%) patients developed ESRD. Predictors of incident ESRD, taking baseline renal function and the competing risk for death into account, included an elevated HbA(1c), elevated LDL cholesterol, male sex, weight-adjusted insulin dose, and a shorter duration of diabetes. By contrast, predictors of pre-ESRD death, taking baseline renal function and the competing risk for ESRD into account, included only age, the presence of established macrovascular disease, and elevated cholesterol levels. This competing-risks approach has potential to highlight the appropriate targets and strategies for preventing premature mortality in patients with type 1 diabetes.
Evidence of Brain Overgrowth in the First Year of Life in Autism
Authors: Eric Courchesne
Journal: JAMA (2003)

ContextAutism most commonly appears by 2 to 3 years of life, at which time the brain is already abnormally large. This raises the possibility that brain overgrowth begins much earlier, perhaps before the first clinically noticeable behavioral symptoms.ObjectivesTo determine whether pathological brain overgrowth precedes the first clinical signs of autism spectrum disorder (ASD) and whether the rate of overgrowth during the first year is related to neuroanatomical and clinical outcome in early childhood.Design, Setting, and ParticipantsHead circumference (HC), body length, and body weight measurements during the first year were obtained from the medical records of 48 children with ASD aged 2 to 5 years who had participated in magnetic resonance imaging studies. Of these children, 15 (longitudinal group) had measurements at 4 periods during infancy: birth, 1 to 2 months, 3 to 5 months, and 6 to 14 months; and 33 (partial HC data group) had measurements at birth and 6 to 14 months (n = 7), and at birth only (n = 28).Main Outcome MeasuresAge-related changes in infants with ASD who had multiple-age measurements, and the relationship of these changes to brain anatomy and clinical and diagnostic outcome at 2 to 5 years were evaluated by using 2 nationally recognized normative databases: cross-sectional normative data from a national survey and longitudinal data of individual growth.ResultsCompared with normative data of healthy infants, birth HC in infants with ASD was significantly smaller (z = –0.66, P&lt;.001); after birth, HC increased 1.67 SDs and mean HC was at the 84th percentile by 6 to 14 months. Birth HC was related to cerebellar gray matter volume at 2 to 5 years, although the excessive increase in HC between birth and 6 to 14 months was related to greater cerebral cortex volume at 2 to 5 years. Within the ASD group, every child with autistic disorder had a greater increase in HC between birth and 6 to 14 months (mean [SD], 2.19 [0.98]) than infants with pervasive developmental disorder-not otherwise specified (0.58 [0.35]). Only 6% of the individual healthy infants in the longitudinal data showed accelerated HC growth trajectories (&gt;2.0 SDs) from birth to 6 to 14 months; 59% of infants with autistic disorder showed these accelerated growth trajectories.ConclusionsThe clinical onset of autism appears to be preceded by 2 phases of brain growth abnormality: a reduced head size at birth and a sudden and excessive increase in head size between 1 to 2 months and 6 to 14 months. Abnormally accelerated rate of growth may serve as an early warning signal of risk for autism.
PWE-037 Proton pump inhibitors and hypomagnesaemia
Authors: S Hebbar, N Sharma, P Wilson
Journal: Gut (2012)

<h3>Introduction</h3> Hypomagnesaemia is a rare and potentially serious complication of PPI therapy. About 30 cases of severe hypomagnesaemia have been reported in long term PPI users.<sup>1</sup> <h3>Methods</h3> We describe two cases recently admitted to our hospital with symptomatic hypomagnesaemia and a history of long term PPI usage. <h3>Results</h3> Patient 1—A 54-year-old female was admitted with nausea, vomiting and abdominal discomfort for few months. Patient was on lansoprazole for more than a year. On admission, magnesium level was 0.42 mmol/l. Patient was treated with magnesium supplements and was sent home with increased dose of lansoprazole. Over the next few weeks, magnesium level dropped to 0.4 mmol/l in spite of supplementation. On stopping PPI, magnesium returned to normal levels in 4 weeks time. Patient 2—A 75-year-old female was admitted with vomiting and lethargy. Patient was on PPI for more than 18 years. Magnesium level was 0.13 mmol/l and calcium 1.62 mmol/l. Patient was treated with intravenous supplements and discharged on oral magnesium. Within 2 months, patient was readmitted with similar complaints and magnesium level was again noted to be 0.13 mmol/l. OGD and CT abdomen were normal. Urinary magnesium levels were normal. Magnesium levels did not normalise in spite of supplementation. Omeprazole was stopped and magnesium started improving over the next 4 weeks. <h3>Conclusion</h3> Hypomagnesaemia is a under recognised complication of long term PPI therapy, which responds rapidly on stopping PPI. In few of the reported cases, a causal relationship with PPI use has been established by recurrence of hypomagnesaemia after rechallenge.<sup>2</sup> The cause of hypomagnesaemia is poorly understood. Mutation of TRPM 6/7 gene which is involved in the active transcellular pathway of intestinal absorption of magnesium is one of the postulated mechanism.<sup>2</sup> Monitoring magnesium levels in patients on long term PPI should be considered.<sup>3</sup> This rare complication might not even be so uncommon as more people become aware of the association. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Cundy T</b>, Mackay J. Proton pump inhibitors and severe hypomagnesaemia. <i>Curr Opin Gastroenterol</i> 2011;<b>27</b>:180–5. 2. <b>Negri AL</b>, Valle EE. Hypomagnesaemia/hypokalemia associated with the use of esomeprazole. <i>Curr Drug saf</i> 2011;<b>6</b>:204–6. 3. <b>FDA Drug Safety Communication</b>. <i>Low Magnesium Levels can be Associated with Long-Term use of Proton Pump Inhibitor drugs (PPIs)</i>.
Spectrometric analysis of mercury content in 549 skin-lightening products: Is mercury toxicity a hidden global health hazard?
Authors: Carsten R. Hamann, Waranya Boonchai, Liping Wen, Emi Nishijima Sakanashi, Chia-Yu Chu, Kylin Hamann, Curtis P. Hamann, Kumar Sinniah, Dathan Hamann
Journal: Journal of the American Academy of Dermatology (2013)
Rad GTPase Attenuates Vascular Lesion Formation by Inhibition of Vascular Smooth Muscle Cell Migration
Authors: Mingui Fu, Jifeng Zhang, Yu-Hua Tseng, Taixing Cui, Xiaojun Zhu, Yan Xiao, Yongshan Mou, Hector De Leon, Mary M.J. Chang, Yasuo Hamamori, C. Ronald Kahn, Yuqing E. Chen
Journal: Circulation (2005)

Rad (Ras associated with diabetes) GTPase is a prototypic member of a new subfamily of Ras-related GTPases with unique structural features, although its physiological role remains largely unknown. In the present study, we characterized the Rad function in vascular smooth muscle cells (VSMCs) and the influence of adenovirus-mediated Rad (Ad-Rad) gene delivery on vascular remodeling after experimental angioplasty.We documented for the first time that neointimal formation using balloon-injured rat carotid arteries was associated with a significant increase in Rad expression as determined by immunohistochemistry and quantitative real-time reverse-transcriptase polymerase chain reaction. The levels of Rad expression in VSMCs were highly induced by platelet-derived growth factor and tumor necrosis factor-alpha. Morphometric analyses 14 days after injury revealed significantly diminished neointimal formation in the Ad-Rad-treated carotid arteries compared with Ad-GFP or PBS controls, whereas the mutated form of Rad GTPase, which can bind GDP but not GTP, increased neointimal formation. Overexpression of Rad significantly inhibited the attachment and migration of VSMCs. In addition, Rad expression dramatically reduced the formation of focal contacts and stress fibers in VSMCs by blocking the Rho/ROK signaling pathway.Our data clearly identified Rad GTPase as a novel and critical mediator that inhibits vascular lesion formation. Manipulation of the Rad signaling pathway may provide new therapeutic approaches that will limit vascular pathological remodeling.
Thymidylate synthase inhibition after administration of fluorouracil with or without leucovorin in colon cancer patients: implications for treatment with fluorouracil.
Authors: G J Peters, C L van der Wilt, C J van Groeningen, K Smid, S Meijer, H M Pinedo
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine the time-dependence of fluorouracil (5FU)-induced thymidylate synthase (TS) inhibition in colon cancer patients, the effect of leucovorin (LV), and the relation to response. PATIENTS AND METHODS A 5FU injection (500 mg/m2) was given to 47 patients with advanced colorectal cancer; tumor biopsy specimens were obtained 1 to 72 hours after laparotomy. Eleven patients received LV (2-hour infusion of 500 mg/m2) with 5FU midinfusion; biopsies were obtained after 45 hours. TS inhibition was evaluated by comparing the number of total and free 5-fluoro-2'-deoxy-uridine-5'- monophosphate (UMP) (FdUMP) binding sites and the total and residual catalytic activity of TS. RESULTS The total catalytic TS activity varied from 0 to 621 pmol/h/mg protein and the total number of FdUMP binding sites varied from 0 to 976 fmol/mg protein. The residual catalytic TS activity after 2, 23, and 45 hours was 41%, 65%, and 74% of the total catalytic activity; the number of free FdUMP binding sites was 12%, 27%, and 49% of the total number, respectively. LV enhanced TS inhibition after 45 hours; the residual catalytic activity decreased from 74% to 49%, and the number of free FdUMP binding sites from 49% to 24%. Eleven of 19 patients treated with hepatic arterial infusion of 5FU had a partial response (PR). In the nonresponding patients, total TS activity was significantly higher (P &lt; .05) than in responding patients. A high TS activity with a poor inhibition correlated with no response. CONCLUSION Residual and total TS activity are predictive for response to 5FU. The findings may be applicable for treatment of patients with advanced disease and TS should be evaluated as a prognostic factor in adjuvant chemotherapy studies.
Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma
Authors: A. Baraniskin, J. Kuhnhenn, U. Schlegel, A. Maghnouj, H. Zollner, W. Schmiegel, S. Hahn, R. Schroers
Journal: Neuro-Oncology (2011)

Malignant gliomas are the most common and lethal primary intracranial tumors. To date, no reliable biomarkers for the detection and risk stratification of gliomas have been identified. Recently, we demonstrated significant levels of microRNAs (miRNAs) to be present in cerebrospinal fluid (CSF) samples from patients with primary CNS lymphoma. Because of the involvement of miRNA in carcinogenesis, miRNAs in CSF may serve as unique biomarkers for minimally invasive diagnosis of glioma. The objective of this pilot study was to identify differentially expressed microRNAs in CSF samples from patients with glioma as potential novel glioma biomarkers. With use of a candidate approach of miRNA quantification by reverse-transcriptase polymerase chain reaction (qRT-PCR), miRNAs with significant levels in CSF samples from patients with gliomas were identified. MiR-15b and miR-21 were differentially expressed in CSF samples from patients with gliomas, compared to control subjects with various neurologic disorders, including patients with primary CNS lymphoma and carcinomatous brain metastases. Receiver-operating characteristic analysis of miR-15b level revealed an area under the curve of 0.96 in discriminating patients with glioma from patients without glioma. Moreover, inclusion of miR-15b and miR-21 in combined expression analyses resulted in an increased diagnostic accuracy with 90% sensitivity and 100% specificity to distinguish patients with glioma from control subjects and patients with primary CNS lymphoma. In conclusion, the results of this pilot study demonstrate that miR-15b and miR-21 are markers for gliomas, which can be assessed in the CSF by means of qRT-PCR. Accordingly, miRNAs in the CSF have the potential to serve as novel biomarkers for the detection of gliomas.
Use of Exercise Testing for Diagnostic and Functional Evaluation of Patients with Arteriosclerotic Heart Disease
Authors: C. GUNNAR BLOMQVIST
Journal: Circulation (1971)

Myocardial oxygen demand generally increases with increasing levels of energy expenditure, but several factors which modify this relation must be considered, both in the design of the test methods and in interpretation of results of exercise tests in patients with arteriosclerotic heart disease (ASHD). A wide variety of exercise test methods are currently used. Master's test is simple to perform and requires no elaborate equipment. It has been more widely employed than any other test and much clinicopathologic and correlative data are available. However, Master's test provides little information on the patient's physical work capacity. Multistage tests, carried to a symptom-limited or maximal/near-maximal workload level, provide quantitative data on physical performance capacity and also result in fewer false-negative ECG responses among patients with ASHD. Follow-up studies of asymptomatic subjects have demonstrated that a horizontal S-T depression during or after exercise is associated with a high risk of developing clinical ASHD. The prognostic significance of the exercise test appears to be independent of other known risk factors. Studies correlating the ECG response to exercise with findings at coronary angiography have demonstrated an abnormal ECG response in 0-30% of patients with no demonstrable arterial disease. The number of patients with significant coronary artery disease and negative ECG response tends to be higher. Evaluation of physical performance capacity is the primary indication for exercise testing in patients with known ASHD. The results of the test form a basis for recommendations on occupational and recreational physical activity. Serial tests may be used to evaluate objectively the effect of medical and surgical therapy.
Sensing Tissue Ischemia
Authors: Hui-Lin Pan, Shao-Rui Chen
Journal: Circulation (2004)

Chest pain is a hallmark of myocardial ischemia, but its underlying signaling mechanisms remain poorly understood. The capsaicin receptor, vanilloid receptor-1 (VR1), is an important cation channel present on primary nociceptive neurons. We have shown that the VR1 is expressed on sensory nerve endings of the heart. In the present study, we determined the role of VR1s in activation of cardiac spinal afferent nerves caused by myocardial ischemia.Single-unit activity of cardiac afferents was recorded from the sympathetic chain of anesthetized ferrets. Cardiac afferents responded to 5 minutes of regional myocardial ischemia and topical application of 10 microg/mL bradykinin in a reproducible manner. Topical application of a specific VR1 antagonist, iodoresiniferatoxin (50 micromol/L), to the receptive field of afferents produced a large attenuation of the firing activity of cardiac afferents caused by myocardial ischemia. Iodoresiniferatoxin also significantly reduced the afferent response to bradykinin applied to the receptive field. Furthermore, treatment with a VR1 channel blocker, ruthenium red (200 micromol/L), had a similar inhibitory effect on the afferent responses to myocardial ischemia and bradykinin.This study provides the first functional evidence that ischemic stimulation of cardiac spinal afferent nerves is mediated through VR1s. The VR1 on the cardiac sensory nerve may function as a molecular sensor to detect tissue ischemia and activate cardiac nociceptors.