tbuckley/cabot-search huggingface dataset:
Blood eosinophil guided prednisolone therapy for exacerbations of COPD: a further analysis
Authors: M. Bafadhel, L. Davies, P. M. A. Calverley, S. D. Aaron, C. E. Brightling, I. D. Pavord
Journal: European Respiratory Journal (2014)

To the Editor: 

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with significant morbidity and mortality [1]. Current guidelines advocate the use of systemic corticosteroids in addition to antibiotics to treat an exacerbation [2, 3], but these treatments are not universally effective and are not without harm [4]. Individualised treatment may, therefore, be an advance. Recently we showed that patients with a peripheral blood eosinophil count of ≥2% at the onset of an outpatient managed exacerbation respond promptly and completely to prednisolone, whereas those with a count of <2% had a higher rate of treatment failure compared with placebo [5]. Whether these findings can be replicated in a larger population, including patients hospitalised with exacerbations of COPD remains unclear. We set out to address these questions in a further analysis of randomised controlled studies comparing outcomes in patients with exacerbations of COPD treated with prednisolone or non-prednisolone (placebo or equivalent). We investigated the rates of treatment failures in patients stratified by the peripheral blood eosinophil count measured at the time of exacerbation.

A literature search of the Medline, EMBASE and PubMed databases was performed using the MeSH terms: 1) chronic obstructive pulmonary disease; 2) exacerbations; 3) oral corticosteroid/prednisolone; and 4) randomised clinical trials. Six trials fulfilled these criteria and the authors were contacted about data sharing. Of these studies, the peripheral blood eosinophil count at the onset …
Biopsy of the Rectum as an Aid to the Diagnosis of Amyloidosis
Authors: P. H. Fentem, L. A. Turnberg, K. G. Wormsley
Journal: BMJ (1962)

The relation between prognosis and lineage specific surface antigen expression on peripheral blood granulocytes and monocytes was studied using monoclonal antibodies and flow cytometry in 37 patients with myelodysplastic syndromes (MDS). Abnormalities in antigen expression were summarised as a score, and cases were divided into low (few abnormalities) and high (many abnormalities) groups. Survival was significantly worse in the "high" group (logrank chi 2 = 5.793, p = 0.016), this group having a median survival of 31 weeks, compared with more than 67 weeks in the "low" group. No correlations were found between the score and any of the following: peripheral blood platelet and granulocyte count; FAB subtype; bone marrow blast cells and sideroblast count, or erythroid and myeloid progenitor growth. Antigen expression was also studied in six further cases of MDS before and after six weeks of treatment with 13-cis retinoic acid (CRA), 20 mg given orally, and a comparison was made with six untreated patients studied before and after a similar time interval. In the treated group 58% of initially abnormal measurements reverted to normal, compared with 24% in the untreated group. Five of the six treated patients showed a decrease in the score, whereas only two of the six improved in the untreated group. The data indicate that myeloid antigen expression is a useful indicator of prognosis in MDS, and that antigen expression may be affected by treatment.
The context: investigation into hypertension and cardiac hypertrophy
Authors: S Sen
Journal: Cardiovascular Research (2000)

From the 1940s to the late 1960s, The Cleveland Clinic Foundation's Division of Research was a hub of advanced laboratory and clinical hypertension studies. Irvine H. Page, M.D., first chairman of Research, whose “mosaic theory of hypertension” outlined the multifactorial cardiovascular aspects of hypertension, was concentrating on the renin–angiotensin system in Clinic patients with both essential and renal hypertension. Page (and the City of Cleveland) became central to scientific interchange by founding the National Foundation for High Blood Pressure (precursor to the Council for High Blood Pressure Research of the American Heart Association).

Page had recruited F. Merlin Bumpus, Ph.D., in 1949 to investigate angiotensin and its antagonists; then, when high blood pressure was thought to be a ‘good’ response of the heart to stress, no one knew that the renin–angiotensin system was a control mechanism in hypertension. By 1969 Bumpus had synthesized angiotensin II, making that vasopressor peptide commercially available for all subsequent research. These studies of some 30 years ago ‘provided the basis for the development and application of major new classes antihypertensive agents, such as converting enzyme, and angiotensin II-receptor blockers.’

In 1968 I joined these world-class hypertension research efforts. American science was rapidly changing, with a most significant change being research funding. It was not until the 1970s that funding from the National Institutes of Health became the prime source of competitively awarded research funding. The Clinic's laboratories, with proven scientific innovations, were well positioned to compete, and one of the first successful awards was made to the Cleveland Clinic group for hypertension research. In particular, our work was to find out why hypertensive humans showed normal cardiac output in the setting of increased vascular resistance. We were finding that hypertrophy occurred early in hypertension; we began to see the heart as an active participant, rather …
Moderate wine drinking reduces all cause mortality
Authors: A. Dorozynski
Journal: BMJ (1998)

Drinking three glasses of wine a day reduces the risk of death from all causes by about 30%, according to the first prospective study on the health effects of moderate drinking, which was carried out in France. Mortality from cardiovascular disease was reduced by 35% and from cancer by 20%.

The study included 34000 men aged 40-60 years who had received a complete health checkup between 1978 and 1983 in Nancy, a town in eastern France. This group was re-evaluated in 1993, by which time 2642 of …
Anaesthetists do not need separate consent before surgery
Authors: R. Dobson
Journal: BMJ (1999)

New guidelines on obtaining consent for anaesthesia recommend that consent from patients specifically for a general anaesthetic is not needed The guidelines, produced by a working party of the Association of Anaesthetists of Great Britain and Ireland, say that there is no virtue in getting the patient to sign a separate consent form.

“The Department of Health recommends that written consent …
Information Quality in Regulatory Decision Making: Peer Review versus Good Laboratory Practice
Authors: Lynn S. McCarty, Christopher J. Borgert, Ellen M. Mihaich
Journal: Environmental Health Perspectives (2012)

There is an ongoing discussion on the provenance of toxicity testing data regarding how best to ensure its validity and credibility. A central argument is whether journal peer-review procedures are superior to Good Laboratory Practice (GLP) standards employed for compliance with regulatory mandates.
The Utility of Duplex Ultrasound Scanning of the Renal Arteries for Diagnosing Significant Renal Artery Stenosis
Authors: Jeffrey W. Olin
Journal: Annals of Internal Medicine (1995)

Objective: To determine the utility of duplex ultrasound scanning of the renal arteries in identifying patients with renal artery stenosis of 60% or more and in excluding patients with either normal renal arteries or renal artery stenosis of less than 60%. Design: A prospective, blinded study. Setting: Large tertiary referral center. Patients: 102 consecutive patients (44 men and 58 women with a mean age [±SD] of 63.3 ±13.4 years) who had both duplex ultrasound scanning of the renal arteries and renal arteriography. All patients who were studied had hypertension that was difficult to control, unexplained azotemia, or associated peripheral vascular disease (alone or in combination), giving them a high pretest likelihood of renovascular disease. Main Outcome Measurements: Peak systolic and end diastolic velocities, renal-aortic ratios, resistive index, and kidney sizes. Results: Sixty-two of 63 arteries with stenosis of less than 60% using arteriography were correctly identified by duplex ultrasound scanning. Thirty-one of 32 arteries with 60% to 79% stenosis using arteriography were correctly identified as having 60% to 99% stenosis on duplex ultrasound, whereas 67 of 69 arteries with 80% to 99% stenosis on arteriography were correctly identified as having 60% to 99% stenosis on ultrasound. Twenty-two of 23 arteries with total occlusion on arteriography were correctly identified by duplex ultrasound. The overall sensitivity of duplex ultrasound compared with arteriography was 0.98, the specificity was 0.98, the positive predictive value was 0.99, and the negative predictive value was 0.97. Conclusion: Duplex ultrasound scanning of the renal arteries is an ideal screening test because it is noninvasive and can predict the presence or absence of renal artery stenosis with a high degree of accuracy.
Beyond Recommendation and Mediation: Moral Case Deliberation as Moral Learning in Dialogue
Authors: Suzanne Metselaar, Bert Molewijk, Guy Widdershoven
Journal: The American Journal of Bioethics (2015)

In “Neglected Ends: Clinical Ethics Consultation and the Prospects for Closure,” Autumn Fiester (2015) rightly criticizes the “Recommendation-Focused Model” (RFM) in clinical ethics consultations (...
103. A Screen for Host Cellular Proteins That Interact with Adeno-Associated Virus Capsid Proteins Reveals Proteins Involved in AAV8 Transduction
Authors: Bassel Akache, Sally Fuess, Dirk Grimm, Mark A. Kay
Journal: Molecular Therapy (2006)

Vectors from adeno-associated virus (AAV) appear very promising for use in some gene therapy applications, due to their relative safety and sustained gene expression. Different serotypes of AAV have been isolated, each having different properties. For example, it has been shown that AAV-8 uncoats more readily than AAV-2 in the nuclei of hepatocytes in mouse liver, possibly explaining the more robust transduction efficiencies of AAV-8 (Thomas et al., Journal of Virology, 2004, 78 (6) p. 3110-3224). Our goal is to better understand the mechanisms behind AAV-8 transduction by identifying cellular proteins that interact with the capsid, and that are necessary for optimal transduction. Towards this end, we used a yeast two-hybrid screen to identify cellular proteins that interact with different domains of the AAV-8 capsid. Using a portion of the AAV capsid protein VP3 as bait against a mouse liver cDNA library, we recovered around 700 clones. Analysis of the sequence of these clones revealed that over 100 genes had multiple hits, indicating that the interactions might be genuine. These included genes encoding many different types of proteins that may be involved in viral binding, entry and trafficking. In particular, some clones contained portions of cathepsins B and L, lysosomal proteases shown to be important in the uncoating of reovirus and the Ebola virus. These clones did interact with the corresponding portion of the AAV-2 capsid, but not AAV-5, when using the same two-hybrid system. Infection of murine fibroblast NIH-3T3 cells by AAV-2 and AAV-8 was severely inhibited by treating the cells with the cathepsin B inhibitor Ca-074Me. In addition, capsid proteins from assembled AAV-2 and AAV-8, but not AAV-5, were cleaved specifically when incubated with purified cathepsin B protein, which was consistent with our two-hybrid data. Cathe sin B seems to be involved in the uncoating of both AAV-2 and 8. This data confirms that some of the roteins isolated in the screen are indeed involved in AAV transduction, and further analysis of the other genes recovered in our screen may hel reveal other cellular roteins im ortant for AAV8-mediated gene transfer.
Statins and Ischemic Stroke—Reply
Authors: Paul Muntner, George Howard, Monika M. Safford
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Hepatic loss of survivin impairs postnatal liver development and promotes expansion of hepatic progenitor cells in mice
Authors: Dan Li, Jin Cen, Xiaotao Chen, Edward M. Conway, Yuan Ji, Lijian Hui
Journal: Hepatology (2013)

Hepatocytes possess a remarkable capacity to regenerate and reconstitute the parenchyma after liver damage. However, in the case of chronic injury, their proliferative potential is impaired and hepatic progenitor cells (HPCs) are activated, resulting in a ductular reaction known as oval cell response. Proapoptotic and survival signals maintain a precise balance to spare hepatocytes and progenitors from hyperplasia and cell death during regeneration. Survivin, a member of the family of inhibitor of apoptosis proteins (IAPs), plays key roles in the proliferation and apoptosis of various cell types. Here, we characterized the in vivo function of Survivin in regulating postnatal liver development and homeostasis using mice carrying conditional Survivin alleles. Hepatic perinatal loss of Survivin causes impaired mitosis, increased genome ploidy, and enlarged cell size in postnatal livers, which eventually leads to hepatocyte apoptosis and triggers tissue damage and inflammation. Subsequently, HPCs that retain genomic Survivin alleles are activated, which finally differentiate into hepatocytes and reconstitute the whole liver. By contrast, inducible ablation of Survivin in adult hepatocytes does not affect HPC activation and liver homeostasis during a long-life period.Perinatal Survivin deletion impairs hepatic mitosis in postnatal liver development, which induces HPC activation and reconstitution in the liver, therefore providing a novel HPC induction model.
Totally implantable intravenous catheters in the management of sickle cell anemia
Authors: George Phillips, Craig Slingluff, John Hartman, Patricia Thomas, Onye Akwari
Journal: American Journal of Hematology (1988)

Abstract Totally implantable catheters (TICs) have recently been employed for long‐term central venous access in patients with sickle cell disease (SCD). We have reviewed our experience with 10 TICs inserted in patients with SCD. These were compared to 33 TICs inserted in patients without SCD (controls). The primary diagnosis was malignancy in most of the controls. The SCD patients experienced a marked increase in total complications (70 vs. 24%), as well as in complications requiring catheter removal (50 vs. 3%). No variable explained these differences except the presence of SCD. The complications requiring catheter removal from SCD patients were infections, catheter thrombosis, and venous thrombosis. The increased risk of these complications must be considered before a catheter is inserted; however, the average useful life of these catheters exceeded 12 months. They remained useful in the care of patients with poor venous access and multiple complications of SCD.
Reversible Renal Tubular Defects in Gluten Enteropathy with Osteomalacia
Authors: A. C. MacCuish, J. F. Munro, W. L. Lamb
Journal: BMJ (1970)

BDI JOURNAL a stage of Bames's myopathy.If the present patient had Barnes's myopathy it would have been in the hypertrophic stage, whereas the father is now in the atrophic stage.The onset of hyperyrexia was quicker in the present case than in most of those described.A possible explanation is that the patient was pyrexial before induction of anaesthesia was begun.We had hoped to pursue the family history in the present case to see if there was any connexion with the family described by Barnes.So far it has not been possible to obtain the necessary data.No definite relation between Barnes's myopathy and ful- minating hyperpyrexia has been established, but the occur- rence of two such rare conditions in the same family is worth recording.
Abstract 4984: Contribution of MMP13 to tumor development in the steatotic liver microenvironment
Authors: Alisha Maria Mendonsa, Michael N. VanSaun, Lee Gorden
Journal: Cancer Research (2014)

Abstract With the rising prevalence of obesity there has been a marked increase in the incidence of non alcoholic fatty liver disease (NAFLD). Epidemiologically, NAFLD has been linked to an increased risk for development of primary liver cancer (HCC), however the mechanisms involved are not known. The liver is also a frequent site of metastasis for several types of cancers. To determine the effect of steatosis (fatty liver) on tumor metastasis to the liver, we used a mouse model of diet induced steatosis coupled with the splenic injection model of metastasis to the liver and found a significant increase in the number of tumors in the steatotic livers. To evaluate what molecular changes distinguish the steatotic liver from normal liver, microarray analysis was performed and demonstrated that MMP13, a member of the Matrix Metalloproteinase family recognized to be involved in liver disease and cancer progression, is significantly upregulated in the steatotic liver compared to normal livers of mice. We evaluated MMP13 expression in human patients with NAFLD and found that MMP13 is elevated with the progression of NAFLD. We hypothesize that increased MMP13 levels in the steatotic liver contribute to a more permissive microenvironment for the establishment of liver tumors. To test this hypothesis, mice genetically deficient in MMP13 or control wildtype mice, with and without steatosis, were injected with syngeneic MC38 colon cancer cells. Examination of the two groups demonstrated a significant decrease in the number of tumors in the MMP13 null mice (P &amp;lt;0.01). Additionally, since the tumor cells themselves express MMP13, wildtype mice were injected with either shRNA control or MMP13 knockdown MC38 colon cancer cells to determine the role of tumor cell derived MMP13. Using transwell migration assay and the platypus invasion system with parental and MMP13 shRNA knockdown MC38 cells we found that loss of MMP13 decreases the invasive and migratory properties of the metastatic cancer cells in vitro. In conclusion, we found that MMP13 is elevated in the setting of steatosis and that loss of both stromal and tumor derived MMP13 lead to decreased number of metastatic foci in the liver. Tumor derived MMP13 effects tumor cell migration and invasion invitro. MMP13 may thus be a potential target to control initiation and growth of metastatic cancer of the liver. Citation Format: Alisha Maria Mendonsa, Michael N. VanSaun, Lee Gorden. Contribution of MMP13 to tumor development in the steatotic liver microenvironment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4984. doi:10.1158/1538-7445.AM2014-4984
Association Between Duration of Overall and Abdominal Obesity Beginning in Young Adulthood and Coronary Artery Calcification in Middle Age
Authors: Jared P. Reis, Catherine M. Loria, Cora E. Lewis, Tiffany M. Powell-Wiley, Gina S. Wei, J. Jeffrey Carr, James G. Terry, Kiang Liu
Journal: JAMA (2013)

Younger individuals are experiencing a greater cumulative exposure to excess adiposity over their lifetime. However, few studies have determined the consequences of long-term obesity.To examine whether the duration of overall and abdominal obesity was associated with the presence and 10-year progression of coronary artery calcification (CAC), a subclinical predictor of coronary heart disease.Prospective study of 3275 white and black adults aged 18 to 30 years at baseline in 1985-1986 who did not initially have overall obesity (body mass index [BMI] ≥30) or abdominal obesity (men: waist circumference [WC] >102 cm; women: >88 cm) in the multicenter, community-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants completed computed tomography scanning for the presence of CAC during the 15-, 20-, or 25-year follow-up examinations. Duration of overall and abdominal obesity was calculated using repeat measurements of BMI and WC, respectively, performed 2, 5, 7, 10, 15, 20, and 25 years after baseline.Presence of CAC was measured by computed tomography at the year 15 (2000-2001), year 20 (2005-2006), or year 25 (2010-2011) follow-up examinations. Ten-year progression of CAC (2000-2001 to 2010-2011) was defined as incident CAC in 2010-2011 or an increase in CAC score of 20 Agatston units or greater.During follow-up, 40.4% and 41.0% developed overall and abdominal obesity, respectively. Rates of CAC per 1000 person-years were higher for those who experienced more than 20 years vs 0 years of overall obesity (16.0 vs 11.0, respectively) and abdominal obesity (16.7 vs 11.0). Approximately 25.2% and 27.7% of those with more than 20 years of overall and abdominal obesity, respectively, experienced progression of CAC vs 20.2% and 19.5% of those with 0 years. After adjustment for BMI or WC and potential confounders, the hazard ratios for CAC for each additional year of overall or abdominal obesity were 1.02 (95% CI, 1.01-1.03) and 1.03 (95% CI, 1.02-1.05), respectively. The adjusted odds ratios for CAC progression were 1.04 (95% CI, 1.01-1.06) and 1.04 (95% CI, 1.01-1.07), respectively. Associations were attenuated but largely persisted following additional adjustment for potential intermediate metabolic factors during follow-up.Longer duration of overall and abdominal obesity was associated with subclinical coronary heart disease and its progression through midlife independent of the degree of adiposity. Preventing or at least delaying the onset of obesity in young adulthood may lower the risk of developing atherosclerosis through middle age.