tbuckley/cabot-search huggingface dataset:
Indian researchers accused of violating ethical guidelines
Authors: Ganapati Mudur
Journal: BMJ (2005)

Medical experts in India have accused government doctors of violating national guidelines on clinical ethics by treating patients in Mumbai with a new and unproved treatment developed abroad without insisting on parallel studies outside India. Wary of India's attractiveness as a site for clinical trials, the Indian government has maintained a policy of rejecting clinical trials of unproved treatments developed outside India when they are carried out only on Indian patients.

But doctors at the Institute of Immunohaematology, a centre of the Indian Council of Medical Research, used a stem cell therapy developed by a biotechnology firm based in Dublin and London to treat four patients with aplastic anaemia …
Renal Cell Carcinoma with Nodal Metastases in the Absence of Distant Metastatic Disease: Prognostic Indicators of Disease-Specific Survival
Authors: Pierre I. Karakiewicz, Quoc-Dien Trinh, Naeem Bhojani, Karim Bensalah, Laurent Salomon, Alexandre de la Taille, Jacques Tostain, Luca Cindolo, Vincenzo Altieri, Vincenzo Ficarra, Luigi Schips, Richard Zigeuner, Peter F.A. Mulders, Antoine Valeri, Jean-Luc Descotes, Arnaud Mejean, Jean-Jacques Patard
Journal: European Urology (2006)
Post-bulbar and coexisting ulceration: unique features of peptic ulcer in Hyderabad.
Authors: S S Rao, K V Murthy
Journal: Gut (1993)

<h3>Abstract</h3> Phylodynamic methods reveal the spatial and temporal dynamics of viral geographic spread, and have featured prominently in studies of the COVID-19 pandemic. Virtually all such studies are based on phylodynamic models that assume—despite direct and compelling evidence to the contrary—that rates of viral geographic dispersal are constant through time. Here, we: (1) extend phylodynamic models to allow both the average and relative rates of viral dispersal to vary independently between pre-specified time intervals; (2) implement methods to infer the number and timing of viral dispersal events between areas; and (3) develop statistics to assess the absolute fit of discrete-geographic phylodynamic models to empirical datasets. We first validate our new methods using simulations, and then apply them to a SARS-CoV-2 dataset from the early phase of the COVID-19 pandemic. We show that: (1) under simulation, failure to accommodate interval-specific variation in the study data will severely bias parameter estimates; (2) in practice, our interval-specific discrete-geographic phylodynamic models can significantly improve the relative and absolute fit to empirical data; and (3) the increased realism of our interval-specific models provides qualitatively different inferences regarding key aspects of the COVID-19 pandemic—revealing significant temporal variation in global viral dispersal rates, viral dispersal routes, and the number of viral dispersal events between areas—and alters interpretations regarding the efficacy of intervention measures to mitigate the pandemic.
First clinical results with a real time, electronic imager as an aid to colonoscopy.
Authors: B P Saunders, G D Bell, C B Williams, J S Bladen, A P Anderson
Journal: Gut (1995)

The early clinical results are described of a real time, electromagnetic imaging system as an aid to colonoscopy. After gaining experience with the use of the system, one experienced endoscopist was randomised to perform consecutive colonoscopies either with (n = 29) or without (n = 26) the imager view. All procedures were recorded on computer disk and replayed for retrospective analysis. Total colonoscopy was achieved in all patients except one (imager view not available). Comparing intubation time and duration of loop formation per patient, there was no significant difference between the two study groups. The number of attempts taken to straighten the colonoscope pre patient, however, was less when the endoscopist was able to see the imager view, p = 0.03. Hand pressure was also more effective when the endoscopist and endoscopy assistant could see the imager display, p = 0.02. Preliminary experience suggests that real time, electronic imaging of colonoscopy is safe, effective, and will improve the accuracy of the procedure.
Vasopressin versus epinephrine for inhospital cardiac arrest: a randomised controlled trial
Authors: Ian G Stiell, Paul C Hébert, George A Wells, Katherine L Vandemheen, Anthony SL Tang, Lyall AJ Higginson, Jonathan F Dreyer, Catherine Clement, Erica Battram, Irene Watpool, Sharon Mason, Terry Klassen, Brian N Weitzman
Journal: The Lancet (2001)
The Influence of Insulin Use on Glycemic Control
Authors: Joyce A. Cramer, Mary Jo Pugh
Journal: Diabetes Care (2005)

OBJECTIVE—The purposes of this study were to determine the relationship between insulin self-management and glycemic control and to identify patient characteristics associated with better control. RESEARCH DESIGN AND METHODS—A Department of Veterans Affairs regional database was used to identify patients with diabetes on chronic insulin therapy (n = 6,222) with dose defined as number of units and doses. The rate of insulin use during a 2-year period was calculated using pharmacy data. Regression analyses were used 1) to predict compliance with prescribed insulin regimens using demographic variables, HbA1c levels, and a measure of diabetes management intensity and 2) to predict HbA1c levels using demographic variables and rates of insulin use. RESULTS—Insulin use was 77.44 ± 17% of prescribed amounts, including wastage; HbA1c levels were 7.98 ± 1.66%. Concomitant oral hypoglycemic agent use (84.89 ± 16%) was higher than insulin use (P &amp;lt; 0.0001) but correlated with insulin use (r = 0.189, P &amp;lt; 0.0001). Ordinary least-squares regression showed that race, HbA1c levels, and intensity of diabetes management were significant predictors of insulin use. Age, race, and insulin use were significant predictors of HbA1c levels. CONCLUSIONS—Adults prescribed a specific insulin regimen averaged using 77% of prescribed doses, demonstrating good intention to follow the prescription. However, HbA1c higher than the recommended level suggested that the rate of insulin use, the prescribed regimen, or both were inadequate to achieve good glycemic control in patients with long-term insulin use.
ALK1 as a Novel Therapeutic Target for CD30+ T-Anaplastic Large Cell Lymphoma
Authors: J. W. Hsu, N. H. Dang
Journal: JNCI Journal of the National Cancer Institute (2014)

Anaplastic large cell lymphoma (ALCL) is one of the more common subtypes of peripheral T-cell lymphomas (PTCL), comprising approximately 15% of cases, and is characterized by the expression by CD30, an activation marker for B and T cells (1).It can present in either the primary cutaneous form, where the disease is restricted to the skin, or as systemic disease, involving the lymph nodes and organs.ALK1 is a useful prognostic indicator for ALCL.Although ALK1 + ALCL generally has a better prognosis than AKL1 -ALCL, the prognosis for relapsed ALK1 + ALCL is poor (2).Several therapeutic options exist for the treatment of relapsed PTCL, including ALCL.Pralatrexate was approved for use in relapsed/refractory PTCL as a single agent based on a study of 115 patients (including 17 with ALCL) with an overall response rate of 29% and a median duration of response of 10.1 months (3).The HDAC inhibitor romidepsin was studied in 130 patients with relapsed/refractory PTCL (including 21 patients with ALK - ALCL) and was found to have an overall response rate of 25% with a median duration of response of 17 months (4).Gemcitabine has shown reasonable activity in ALCL both as a single agent (5) and in combination (6).Therapies targeting surface antigens have also been developed for the management of relapsed ALCL.Denileukin diftitox was tested in 27 patients with relapsed/refractory PTCL (including 2 ALK1 -and 1 ALK1 + ALCL) and demonstrated an overall response rate of 48.1% and a median duration of response of 6 months (7).A study of 58 patients with relapsed/refractory ALCL (42 ALK1 -, 16 ALK1 -) treated with brentuximab vedotin (an anti-CD30 antibody conjugate) found an objective response rate of 86% with a median duration of 12.6 months (8).There was no statistically significant difference in objective response rate (88% for ALK1 -vs 81% for ALK1 + ) or complete response (52% for ALK1 -vs 69% for ALK1 + ) between the ALK1 -and ALK1 + ALCL subgroups.There were also no statistically significant differences in median duration of response and progression-free survival.Crizotinib adds another option for the treatment of relapsed ALK1 + ALCL.In this issue of the Journal, Passerini et al. treated 11 patients with relapsed ALK1 + ALCL and found an overall response rate of 91% with a 2-year progression-free survival of 73% (9).Of note is the fact that crizotinib therapy can be successfully administered before and after allogeneic transplant.Importantly, the toxicity profile of crizotinib appears to be very benign, with all toxicities being grade 1 or 2. Exposure to crizotinib did not seem to affect CD30 expression, as one patient who progressed on crizotinib subsequently responded to brentuximab vedotin.Given its specific
Inactivation of c-Cbl Reverses Neonatal Lethality and T Cell Developmental Arrest of SLP-76–deficient Mice
Authors: Y. Jeffrey Chiang, Connie L. Sommers, Martha S. Jordan, Hua Gu, Lawrence E. Samelson, Gary A. Koretzky, Richard J. Hodes
Journal: The Journal of Experimental Medicine (2004)

c-Cbl is an adaptor protein that negatively regulates signal transduction events involved in thymic-positive selection. To further characterize the function of c-Cbl in T cell development, we analyzed the effect of c-Cbl inactivation in mice deficient in the scaffolding molecule SLP-76. SLP-76–deficient mice show a high frequency of neonatal lethality; and in surviving mice, T cell development is blocked at the DN3 stage. Inactivation of c-cbl completely reversed the neonatal lethality seen in SLP-76–deficient mice and partially reversed the T cell development arrest in these mice. SLP-76−/− Cbl−/− mice exhibited marked expansion of polarized T helper type (Th)1 and Th2 cell peripheral CD4+ T cells, lymphoid infiltrates of parenchymal organs, and premature death. This rescue of T cell development is T cell receptor dependent because it does not occur in recombination activating gene 2−/− SLP-76−/− Cbl−/− triple knockout mice. Analysis of the signal transduction properties of SLP-76−/− Cbl−/− T cells reveals a novel SLP-76– and linker for activation of T cells–independent pathway of extracellular signal–regulated kinase activation, which is normally down-regulated by c-Cbl.
Paying attention to the preciseness of conclusion
Authors: Kai Yuan, Jianxin Chen, Tiangang Li, Anlong Xu
Journal: Annals of the Rheumatic Diseases (2014)

We focus with significant interest on the report by Lv et al ,1 which was related to comparison of Tripterygium wilfordii Hook F (TwHF) with methotrexate (MTX) in the treatment of active rheumatoid arthritis. Lv et al found that TwHF monotherapy was not inferior to, and MTX+TwHF was better than, MTX monotherapy in patients with active RA.

However, we think that there are still several critical questions in this research, and one of them should be treated carefully in revealing the results of this trial.

First, the trial was an open-label study. Patients were aware of the corresponding treatment with …
Diabetes and Impaired Glucose Tolerance Among the Inuit Population of Greenland
Authors: Marit E. Jørgensen, Peter Bjeregaard, Knut Borch-Johnsen, Vibeke Backer, Ulrik Becker, Torben Jørgensen, Gert Mulvad
Journal: Diabetes Care (2002)

OBJECTIVE—To assess the prevalence of diabetes and impaired glucose tolerance (IGT) among the Inuit population of Greenland and to determine risk factors for developing glucose intolerance. RESEARCH DESIGN AND METHODS—This cross-sectional study included 917 randomly selected adult Inuit subjects living in three areas of Greenland. Diabetes and IGT were diagnosed using the oral glucose tolerance test. BMI and waist-to-hip ratio were measured and blood samples were taken from each subject. Sociodemographic characteristics were investigated using a questionnaire. RESULTS—The age-standardized prevalences of diabetes and IGT were 10.8 and 9.4% among men and 8.8 and 14.1% among women, respectively. Of those with diabetes, 70% had not been previously diagnosed. Significant risk factors for diabetes were family history of diabetes, age, BMI, and high alcohol consumption, whereas frequent intake of fresh fruit and seal meat were inversely associated with diabetic status. Age, BMI, family history of diabetes, sedentary lifestyle, and place of residence were significant predictors of IGT. CONCLUSIONS—The prevalence of diabetes is high among the Inuit of Greenland. Heredity was a major factor, while obesity and diet were important environmental factors. The high proportion of unknown cases suggests a need for increased diabetes awareness in Greenland.
Malignancy in unrecognised coeliac disease: a nail in the coffin for mass screening?
Authors: R. F A Logan
Journal: Gut (2009)

Fear of malignancy has been the driver of many of the recommendations and guidelines on the investigation and management of coeliac disease since the malignant complications of coeliac disease were first recognised in the 1960s.1 2 What these early papers variously called reticulum cell sarcoma, intestinal reticulosis or malignant histiocytosis is now labelled as an enteropathy-associated T cell lymphoma (EATL). Cases can present acutely with obstruction or perforation, or chronically with diarrhoea, abdominal pain and weight loss, or, if coeliac disease has been previously diagnosed, a clinical relapse after responding to treatment with a gluten-free diet (GFD). It has a poor prognosis, generally following an intractable downhill course, with fewer than 20% surviving for >3 years.3–5

Initial estimates suggested that the relative risk of EATL might be 40–100 times higher than in the general population and that 10% of patients with coeliac disease diagnosed over age 50 would be harbouring a lymphoma.6–8 Furthermore, in one of the most cited papers ever to appear in Gut , Holmes et al reported that the long-term follow-up of a cohort of 210 patients with coeliac disease showed that the risks of developing EATL were much lower in those taking a strict GFD.9 These findings have been widely used to justify the need for a strict GFD, although the term ‘strict’ was not clearly defined in their paper.

As larger studies have appeared, based on populations rather than hospital series, …
Viruses and Bacteria in Bronchial Samples from Patients with Primary Hypogammaglobulinemia
Authors: LEENA KAINULAINEN, JUKKA NIKOSKELAINEN, TYTTI VUORINEN, KALLE TEVOLA, KARI LIIPPO, OLLI RUUSKANEN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Viruses and bacteria in bronchoalveolar lavage fluids, protected specimen brush samples, and bronchial biopsies from 14 patients with primary hypogammaglobulinemia (11 patients with common variable immunodeficiency [CVID] and three patients with X-linked agammaglobulinemia [XLA]) were analyzed. At the time of the study, the patients had no signs of acute respiratory infections, and no antibiotics were administered. In addition to routine bacterial and viral cultures, polymerase chain reaction tests were used for the detection of adenovirus, cytomegalovirus (CMV), herpes simplex virus 1, enterovirus, rhinovirus, Borrelia burgdorferi, Chlamydia pneumoniae, Legionella spp., Mycoplasma pneumoniae, Pneumocystis carinii, and Ureaplasma urealyticum. Viruses (four adenoviruses, one CMV, and one rhinovirus) were detected in four of the 11 (36%) CVID patients. No viruses were found in the three patients with XLA or in 13 control patients. Bacteria from the lower respiratory tract were detected in nine of the 14 (64%) patients with hypogammaglobulinemia and three of the 13 (23%) control patients. Haemophilus influenzae was the most prevalent bacterium (43%) in the hypogammaglobulinemia patients. The study shows that patients with CVID harbor viral and bacterial infections in the lower respiratory tract, which may predispose to the development of changes in the respiratory tract.
Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10 117 patients: a multicentre observational study by the French ERMETIC-IFCT network
Authors: M. Beau-Faller, N. Prim, A.-M. Ruppert, I. Nanni-Metéllus, R. Lacave, L. Lacroix, F. Escande, S. Lizard, J.-L. Pretet, I. Rouquette, P. de Crémoux, J. Solassol, F. de Fraipont, I. Bièche, A. Cayre, E. Favre-Guillevin, P. Tomasini, M. Wislez, B. Besse, M. Legrain, A.-C. Voegeli, L. Baudrin, F. Morin, G. Zalcman, E. Quoix, H. Blons, J. Cadranel
Journal: Annals of Oncology (2013)
Some determinants of the effects of VAL-5-angiotensin II amide on glomerular filtration rate and sodium excretion in dogs
Authors: John C. McGiff, James R. Lynch, Jeffrey A. Leinicke, James C. Strand, Ali Aboosi
Journal: Journal of Clinical Investigation (1969)

In 12 dogs anesthetized with chloralose, angiotensin (angiotensin II amide) given intravenously increased the glomerular filtration rate (GFR) of an ischemic kidney while simultaneously having little effect on the GFR of the contralateral kidney. In the ischemic kidney, in 14 of 30 observations, increments of GFR greater than 100% of mean control GFR (9 ml/min) occurred in response to angiotensin. The magnitude of the increase in GFR produced by angiotensin was independent of dose (range 0.005-0.050 mug/kg per min), the degree of accompanying pressor response, and alterations in renal blood flow (RBF) (electromagnetic flow-meter). In the ischemic kidney, increments of GFR could be produced by sub-pressor doses of angiotensin. Dissociations between increments of GFR and sodium excretion occurred. Equivalent increments of GFR in the ischemic kidney in dogs receiving either 5% glucose in water or 10% mannitol in 0.3% saline were associated with natriuresis only in the latter group: a) as an initial response of the contralateral kidney to renal arterial constriction (RAC) in spite of a concomitant reduction in RBF and an unchanged GFR; b) in the ischemic kidney on giving angiotensin. The natriuresis produced by angiotensin was independent of the magnitude of elevations in blood pressure, altered filtration fraction, and was associated with a further reduction in RBF. After release of RAC in the dogs receiving mannitol, an antinatriuresis was again observed in response to angiotensin. The presence of unilateral renal ischemia allowed the demonstration of a differential action of angiotensin on the GFR of an ischemic and nonischemic kidney. The natriuresis in response to angiotensin requires, in addition to mannitol, the participation of undefined factors invoked by unilateral renal ischemia.
Processing of <i>Mycobacterium tuberculosis</i> Antigen 85B Involves Intraphagosomal Formation of Peptide–Major Histocompatibility Complex II Complexes and Is Inhibited by Live Bacilli that Decrease Phagosome Maturation
Authors: Lakshmi Ramachandra, Erika Noss, W. Henry Boom, Clifford V. Harding
Journal: The Journal of Experimental Medicine (2001)

Mycobacterium tuberculosis (MTB) inhibits phagosomal maturation to promote its survival inside macrophages. Control of MTB infection requires CD4 T cell responses and major histocompatibility complex (MHC) class II (MHC-II) processing of MTB antigens (Ags). To investigate phagosomal processing of MTB Ags, phagosomes containing heat-killed (HK) or live MTB were purified from interferon-γ (IFN-γ)–activated macrophages by differential centrifugation and Percoll density gradient subcellular fractionation. Flow organellometry and Western blot analysis showed that MTB phagosomes acquired lysosome-associated membrane protein-1 (LAMP-1), MHC-II, and H2-DM. T hybridoma cells were used to detect MTB Ag 85B(241–256)–I-Ab complexes in isolated phagosomes and other subcellular fractions. These complexes appeared initially (within 20 min) in phagosomes and subsequently (&amp;gt;20 min) on the plasma membrane, but never within late endocytic compartments. Macrophages processed HK MTB more rapidly and efficiently than live MTB; phagosomes containing live MTB expressed fewer Ag 85B(241–256)–I-Ab complexes than phagosomes containing HK MTB. This is the first study of bacterial Ag processing to directly show that peptide–MHC-II complexes are formed within phagosomes and not after export of bacterial Ags from phagosomes to endocytic Ag processing compartments. Live MTB can alter phagosome maturation and decrease MHC-II Ag processing, providing a mechanism for MTB to evade immune surveillance and enhance its survival within the host.
Alveolar liquid pressure measured by micropuncture in isolated lungs of mature and immature fetal rabbits.
Authors: J U Raj
Journal: Journal of Clinical Investigation (1987)

Increased alveolar surface tension due to surfactant deficiency is thought to result in a negative pressure surrounding pulmonary capillaries and to promote fluid filtration. To test this hypothesis, alveolar liquid pressure (Pliquid) was measured by micropuncture in isolated lungs of mature and immature fetal rabbits (with and without surfactant replacement) at different air inflation pressures (Pairway). Lung maturity was assessed by air pressure-volume (P-V) curves. Pliquid was correlated with surfactant content in the lungs and with alveolar size. Pliquid was lower in immature (2.3 +/- 0.7 cmH2O) than in mature (8.4 +/- 1.0 cmH2O) lungs at comparable Pairway (25 cmH2O) (P less than 0.01). The mean linear intercept, a measure of airspace dimensions was similar in all lungs (42.1 +/- 2.0 micron), but alveolar wash phospholipid/g wet lung was lower in immature than in mature lungs (0.05 +/- 0.01 vs. 0.49 +/- 0.30 mg) (P less than 0.01). Surfactant replacement in immature lungs resulted in P-V curves and Pliquid similar to those of mature lungs. If pericapillary interstitial liquid pressure approximates Pliquid, surfactant deficiency will predispose preterm infants to pulmonary edema.