tbuckley/cabot-search huggingface dataset:
Abstract 16840: AMP-Activated Protein Kinase Prevents Myocardial Injury During Ischemia-Reperfusion by Suppressing the c-Jun Terminal Kinase Pathway and Inhibiting Mitochondrial Transition Permeability Pore Opening
Authors: Vlad G Zaha, Dake Qi, Monica Palmeri, Lawrence H Young
Journal: Circulation (2011)

AMP-activated kinase (AMPK) is a stress responsive kinase that coordinates energy conservation, activating catabolic pathways and inhibiting fuel storage and protein synthesis. In the heart, functional AMPK is essential to myocardial survival and functional recovery following ischemia-reperfusion. The mechanisms by which intrinsic AMPK activation protects against ischemic injury are not well understood. We investigated the role of AMPK in modulating mitogen activated protein kinase pathway and mitochondrial integrity during ischemia-reperfusion. Hearts from wild type (WT) and kinase dead AMPK (KD) mice were perfused with 7mM glucose, 0.4 mM oleate, 1% BSA and 10µU/mL insulin in vitro and subjected to 15 min of global ischemia and 10 min reperfusion. KD hearts had similar baseline contractile function, but markedly decreased recovery of left ventricular developed pressure (LVDP) after ischemia-reperfusion compared to WT (4.6±1.4 vs. 26.4±5.2% of baseline, n=9 and 11, p&lt;0.05). Mitochondria isolated from non-ischemic KD and WT hearts had similar calcium induced, cyclosporin-A inhibitable mitochondrial permeability transition pore (mPTP) opening (29.3±1.9 vs. 23.2±1.6µM calcium concentration at mPTP opening, n=4 per group). However, following ischemia-reperfusion mPTP opening was triggered by significantly less calcium in KD mitochondria compared to WT (9.0±0.6 vs. 12.6±1.3µM calcium, n=5 and 6, respectively, p&lt;0.05), indicating higher susceptibility of KD mitochondria to mPTP opening. KD hearts had increased phosphorylation of mitogen activated protein kinase kinase 4 (MKK4) and downstream c-Jun terminal kinase (JNK) during early reperfusion compared to WT hearts (p&lt;0.05). Pharmacologic inhibition of JNK during ischemia-reperfusion with SP600125 (10µM) resulted in improved recovery selectively in KD hearts (4.6±1.4 vs. 15.3±6.5%, of baseline, n=4 and 5, respectively, p&lt;0.05), without changes in WT. JNK inhibition also eliminated the increased susceptibility of mitochondria from KD hearts to mPTP opening. In conclusion, intrinsic AMPK activation prevents cardiac injury during ischemia-reperfusion, suppressing activation of signaling through the MKK4-JNK pathway and inhibiting mitochondrial transition pore opening.
Death from interventionist radiology: a cautionary tale
Authors: J D Miller, J F Shaw, A J W Steers, P Edmond, B Ashworth, R E Cull, E H Jellinek, J E Bell, A Gordon, R Sellar, J L Jenkinson, G L M Carmichael, D Child
Journal: BMJ (1986)

Even this consultation seems to be conducted with indecent haste.If others in the profession agree that the package is unacceptable I urge them to write to the DHSS.I realise that in rejecting the proposals we will be left with our present considerable manpower problems, but we of all people should know that there are times when the remedy is worse than the disease.
Transjugular liver biopsy in children
Authors: Katryn N. Furuya, Patricia E. Burrows, James M. Phillips, Eve A. Roberts
Journal: Hepatology (1992)

Transjugular liver biopsy is widely used in adult patients with liver disease when transthoracic needle liver biopsy is contraindicated by severe coagulopathy or ascites. It has not been used extensively in children. We report our experience with 30 consecutive transjugular liver biopsy procedures performed in 27 young patients at the Hospital for Sick Children in Toronto. Patient weights ranged from 14 to 91 kg (median = 42 kg); most patients had not yet attained adult size. A 9F catheter was used except in very small children, for whom we developed a 7F biopsy needle catheter. Most procedures were done with patients under general anesthesia. Specimens were obtained in all patients, and the procedure was tolerated well. A major complication occurred only once: perforation of the inferior vena cava, which was later repaired at liver transplantation. Minor complications included subcapsular extravasation of contrast agent in five patients and a small intrahepatic hematoma in one. Results of transjugular liver biopsy changed the diagnosis in 30% of patients and added valuable information about the disease process in most patients. Transjugular liver biopsy was an important component of emergency assessment for liver transplantation. Our results indicate that transjugular liver biopsy can be performed safely in children with liver disease if a skilled interventional radiologist and a well-equipped angiography suite are available. Histological studies in these patients enhance our understanding of the natural history of pediatric liver diseases.
DESTRUCTION OF LARVAE OF FLIES AND MYIASIS
Authors: Afilio Salinas
Journal: JAMA (1923)

<h3>To the Editor:</h3> —In the Spanish edition ofThe Journal, July 2, appears an abstract on the use of ethyl chorid for the destruction of larvae of flies that may exist in the nose, ears or other passages. In this connection, Dr. Filadelfo Masis, professor of the Salvador Faculty of Medicine, has for some time utilized insufflation of iodoform for the use of nasal myiasis. As this disease is found frequently in tropical countries, it might be advisable to call attention to this simple, economical and effective medicine.
Medical professionalism is under threat, say eight in 10 aspiring British doctors
Authors: Zosia Kmietowicz
Journal: BMJ (2005)

Most trainee doctors and medical students in the United Kingdom believe that high public expectations of what medicine can do and too many targets in the health service are reducing doctors' autonomy and will drive colleagues out of the profession, a survey has found.

The survey of more than 2000 trainee doctors and medical students, which was carried out by the trainees committee of the Royal College of Physicians, found that eight …
Associations between Prenatal Exposure to Polychlorinated Biphenyls and Neonatal Thyroid-Stimulating Hormone Levels in a Mexican-American Population, Salinas Valley, California
Authors: Jonathan Chevrier, Brenda Eskenazi, Asa Bradman, Laura Fenster, Dana B. Barr
Journal: Environmental Health Perspectives (2007)

BackgroundStudies have reported that prenatal exposure to polychlorinated biphenyls (PCBs) may alter neurodevelopment in both humans and animals. Furthermore, prenatal exposure to some PCB congeners and commercial mixtures has been shown to decrease free and total thyroxine (T4) blood levels in animals. Because thyroid hormones (TH) are essential for normal neurologic development, it has been suggested that the deleterious neurodevelopmental effect of PCBs may occur through TH disruption. PCBs may in turn affect TH levels by inducing the microsomal enzyme uridinediphosphate glucuronosyltransferase (UDP-GT), which is involved in TH elimination.ObjectivesOur goals were to group PCB congeners based on their potential to induce microsomal enzymes in animals, and to examine the relationship between neonatal TSH levels and prenatal exposure to PCB congeners grouped according to their structure and potential mechanisms of action.MethodsWe measured the concentration of 34 PCB congeners in serum samples collected from 285 pregnant women and the thyroid-stimulating hormone (TSH) levels in their children's blood collected shortly after birth.ResultsWe found no association between the sum of PCB congeners, the toxic equivalents, or structure-based groupings (mono- or di-ortho substituted congeners), and TSH blood concentration. However, we found a positive association between the sum of congeners suspected to be UDP-GT inducers (more specifically cytochrome P450 2B inducers) in animals and neonatal TSH levels. In individual congener analyses, PCBs 99, 138, 153, 180, 183, 187, 194, and 199 were positively associated with neonatal TSH levels after adjustment for covariates. PCBs 194 and 199 remained significant after adjustment for multiple hypothesis testing.ConclusionsOur results support grouping PCB congeners based on their potential mechanism of action of enzyme induction when investigating associations with TH. Findings also suggest that PCBs affect TH homeostasis even at the low background level of exposure found in the CHAMA-COS (Center for the Health Assessment of Mothers and Children of Salinas) population.
Determination and Modeling of Kinetics of Cancer Cell Killing by Doxorubicin and Doxorubicin Encapsulated in Targeted Liposomes
Authors: Rom E. Eliaz, Shlomo Nir, Cornelia Marty, Francis C. Szoka
Journal: Cancer Research (2004)

Abstract Various mathematical approaches have been devised to relate the cytotoxic effect of drugs in cell culture to the drug concentration added to the cell culture medium. Such approaches can satisfactorily account for drug response when the drugs are free in solution, but the approach becomes problematic when the drug is delivered in a drug delivery system, such as a liposome. To address this problem, we have developed a simple model that assumes that the cytotoxic potency of a drug is a function of the intracellular drug level in a critical compartment. Upon exposure to drug, cell death commences after a lag time, and the cell kill rate is dependent on the amount of drug in the critical intracellular compartment. The computed number of cells in culture, at any time after exposure to the drug, takes into account the cell proliferation rate, the cell kill rate, the average intracellular drug concentration, and a lag time for cell killing. We have applied this model to compare the cytotoxic effect of doxorubicin (DOX), or DOX encapsulated in a liposome that is targeted to CD44 on B16F10 melanoma cells in culture. CD44 is the surface receptor that binds to hyaluronan and is overexpressed on various cancer cells, including B16F10. We have shown previously that the drug encapsulated in hyaluronan-targeted liposomes was more potent than was the free drug. The model required the determination of the cell-associated DOX after the cells were incubated with various concentrations of the free or the encapsulated drug for 3 h, and the quantification of cell number at various times after exposure to the drug. The uptake of encapsulated drug was greater than that of the free drug, and the ratio of cell association of encapsulated:free drug was 1.3 at 0.5 μg/ml and increased to 3.3 at 20 μg/ml DOX. The results demonstrate that the enhanced potency of the encapsulated drug could stem from its enhanced uptake. However, in certain cases, where larger amounts of the free drug were added, such that the intracellular amounts of drug exceeded those obtained from the encapsulated drug, the numbers of viable cells were still significantly smaller for the encapsulated drug. This finding demonstrates that for given amounts of intracellular DOX, the encapsulated form was more efficient in killing B16F10 cells than the free drug. The outcome was expressed in the kinetic model as a 5–6-fold larger rate constant of cell killing potency for the encapsulated drug versus the free drug. The model provides a quantitative framework for comparing the cytotoxic effect in cultured cells when applying the drug in the free form or in a delivery system.
[551] HYPERHOMOCYSTEINEMIA IN CHRONIC HEPATITIS C: ROLE IN STEATOSIS, FIBROGENESIS AND RESPONSE TO ANTIVIRAL TREATMENT
Authors: X. Roblin, V. Ducros, M.N. Hilleret, N. Sturm, A. Plages, J.P. Zarski, V. Leroy
Journal: Journal of Hepatology (2007)
Toward a Basic Understanding of Diabetic Complications
Authors: Michael W. Steffes, S. Michael Mauer
Journal: New England Journal of Medicine (1991)

Diabetes mellitus presents a lifelong challenge to patients and their health care providers. Although Type I (insulin-dependent) and Type II (non-insulindependent) diabetes mellitus probably have different causes, patients with either form have an increased risk of microvascular, macrovascular, and neurologic complications. Many studies have examined or are addressing the relations between glycemic control (usually determined by levels of glycosylated hemoglobin) and the prevention or progression of these complications.1 Yet current therapy for patients with Type I or II diabetes rarely if ever normalizes blood glucose or glycosylated hemoglobin levels, and some patients will probably continue to have complications even when . . .
The impact of surveillance on hepatocellular carcinoma. Detection and survival of 417 patients with compensated cirrhosis: a 12-year prospective cohort study
Authors: Angelo Sangiovanni, Pierangelo Fasani, Guido Ronchi, Maria Francesca Donato, Cristina De Fazio, Ersilio Del Ninno, Pietro Lampertico, R. de Franchis, Massimo Colombo
Journal: Journal of Hepatology (2002)
Augmented Enterocystoplasty for Neurogenic Bladder Associated With Renal Transplantation: Appearance on Tc-99m MAG3 Renal Transplant Scan
Authors: BRUCE J. BARRON, SYED IMAM, LAMK LAMKI, MICHAEL D. REDWINE, JOSEPH A. NIGHTINGALE, BARRY KAHAN
Journal: Clinical Nuclear Medicine (1998)

Enterocystoplasty (bladder augmentation) is a method of increasing bladder capacity in patients with small or neurogenic bladders in order to prevent vesicoureteral reflux. In patients with poorly compliant bladders, enterocystoplasty, which consists of a segment of detubularized small bowel or a portion of the stomach attached to the bladder, often helps to reduce the intravesicular pressures, thus reducing the likelihood of infection. It is also useful in treating bladder dysfunction in children with end-stage renal disease who require renal transplantation. Radiographic evaluation of patients with a renal transplant and augmented bladder often can be confusing, and may suggest a urine leak or hematoma. We report a patient with a renal transplant, bladder augmentation, and rising serum creatinine who underwent renal scintigraphy and ultrasonography.
Abstract 695: The Quality Of Cell Isolation Determines Left Ventricular Contractile Recovery After Intracoronary Administration Of Bone Marrow-derived Progenitor Cells In Patients With AMI - Insights from the REPAIR-AMI Trial
Authors: Birgit Assmus, Volker Schachinger, Sandra Erbs, Albrecht Elsasser, Torsten Tonn, Stefanie Dimmeler, Andreas M Zeiher
Journal: Circulation (2007)

The REPAIR-AMI trial demonstrated that intracoronary (i.c.) infusion of bone marrow-derived progenitor cells (BMC) in patients (pts) with AMI is associated with a significantly greater recovery of ...
Alternative theories about AIDS should not be dismissed out of hand
Authors: R. Strohman
Journal: BMJ (1996)

EDITOR,—Stuart W G Derbyshire's review of Peter Duesberg's book Infectious AIDS: Have We Been Misled? is tendentious.1 He says that all Duesberg's supporters contend that Duesberg's ideas “were wilfully suppressed by AIDS investigators for reasons associated with ideology and personal gain.” Branding all supporters in this manner misses the point that many thoughtful scientists agree with Duesberg on many points while disagreeing on others. I wrote the preface to this book because I support openness in science and because I …
Interferon-γ Axis in Graft Arteriosclerosis
Authors: George Tellides, Jordan S. Pober
Journal: Circulation Research (2007)

Cardiac transplantation is the most effective treatment for advanced heart failure. Despite improvements in immunosuppression therapy that prevent acute rejection, cardiac allografts fail at rates of 3% to 5% per posttransplant year. The hallmark morphological lesion of chronically failing cardiac allografts, also seen in chronic renal and liver graft failure, is luminal stenosis of blood vessels, especially of conduit arteries. Late graft failure results from widespread secondary ischemic injury to the graft parenchyma rather than direct immune-mediated damage. Although this process affects the entire graft vasculature, graft arteriosclerosis is a suitable term to describe the problem because it applies to different types of failing organs and because it emphasizes the central feature, namely an accelerated form of arterial injury and remodeling. The precise pathogenesis of graft arteriosclerosis is unknown. In this review, we make the case that the signature T-helper type 1 cytokine, interferon (IFN)-γ, is a key effector in graft arteriosclerosis, which, together with the IFN-γ–inducing cytokine interleukin-12 and IFN-γ–inducible chemokines such as CXCR3 ligands, constitute a positive feedback loop for T-cell activation, differentiation, and recruitment that we refer to as the IFN-γ axis. We evaluate the evidence to support this hypothesis in clinical observational and experimental animal studies. Additionally, we examine the regulation of IFN-γ production within the artery wall, the effects of IFN-γ on vessel wall cells, and the outcome of therapeutic agents on IFN-γ production and signaling. These observations lead us to suggest that new therapies for graft arteriosclerosis should be optimized which focus on reducing IFN-γ synthesis or actions.
Transfer of Small Resting B Cells into Immunodeficient Hosts Results in the Selection of a Self-renewing Activated B Cell Population
Authors: Fabien Agenès, António A. Freitas
Journal: The Journal of Experimental Medicine (1999)

We studied the role of bone marrow B cell production in the renewal of peripheral B cells and the feedback mechanisms that control the entry of newly formed B cells into the peripheral B cell pools. When resting lymph node B cells are injected into B cell–deficient hosts, a fraction of the transferred cells expands and constitutes a highly selected population that survives for prolonged periods of time by continuous cell renewal at the periphery. Although the number of donor B cells recovered is low, a significant fraction shows an activated phenotype, and the serum immunoglobulin (Ig)M levels are as in normal mice. This population of activated B cells is resistant to replacement by a new cohort of B cells and is able to feedback regulate both the entry of newly formed B cells into the peripheral pool and terminal differentiation. These findings suggest that peripheral B cell selection follows the first come, first served rule and that IgM-secreting cells are generated from a pool of stable activated B cells with an independent homeostasis.
WILL AMERICAN MUNICIPALITIES PROFIT BY EXPERIENCE?
Authors: J. F. C. Luhan
Journal: JAMA (1918)

<h3>To the Editor:</h3> —Now is the time for American small municipalities to rise and demand health protection and pay for it. Thousands of able, educated, experienced young medical officers from the Army, Navy and Public Health Service will soon be discharged or will leave by resignation. Give these young, able men a chance to work as paid health officers in each community of, say, 5,000 inhabitants and above. Pay them living salaries and make them independent from the start. Place them in groups under older officers as supervisors, and let the U. S. Public Health Service do the general supervision and direction of the work so that uniform and advanced procedure may be maintained. Establish suitable, perhaps small, but still well equipped laboratories in some centrally located larger city for bacteriologic and biologic work, and place an efficient officer in charge. Build hospitals. Have an adequate staff of nurses on
Intrapleural t-PA plus DNase improved clinical outcomes in patients with pleural infection
Authors: Praveen N. Mathur
Journal: Annals of Internal Medicine (2011)

ACP Journal Club20 December 2011Intrapleural t-PA plus DNase improved clinical outcomes in patients with pleural infectionPraveen N. Mathur, MDPraveen N. Mathur, MDIndiana University School of Medicine, Indianapolis, Indiana, USA (P.N.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-12-201112200-02009 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationRahman NM, Maskell NA, West A, et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011;365:518-26. https://pubmed.ncbi.nlm.nih.gov/21830966Clinical Impact RatingsHospitalists: Infectious Disease: Pulmonology: References1 Maskell NA, Davies CW, Nunn AJ, et al; First Multicenter Intrapleural Sepsis Trial (MIST1) Group. U.K. controlled trial of intrapleural streptokinase for pleural infection. N Engl J Med. 2005;352:865-74. [PMID: 15745977] Google Scholar2 Colice GL, Curtis A, Deslauriers J, et al. Medical and surgical treatment of parapneumonic effusions: an evidence-based guideline. Chest. 2000;118:1158-71. [PMID: 11035692] Google Scholar Author, Article, and Disclosure InformationAuthors: Praveen N. Mathur, MDAffiliations: Indiana University School of Medicine, Indianapolis, Indiana, USA (P.N.M.)This article was published at Annals.org on 6 December 2011. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byIntra-pleural fibrinolytic therapy versus placebo, or a different fibrinolytic agent, in the treatment of adult parapneumonic effusions and empyema 20 December 2011Volume 155, Issue 12Page: JC6-9KeywordsBacterial culturesDeoxyribonucleaseDrug policyDrug therapyDrugsInfectious diseasesMortalityThoracic surgeryThoraxTissue plasminogen activator ePublished: 20 December 2011 Issue Published: 20 December 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Atrial Natriuretic Factor Binding to Its Receptor Is Dependent on Chloride Concentration
Authors: Kunio S. Misono
Journal: Circulation Research (2000)

Although considerable evidence indicates a role for atrial natriuretic factor (ANF) in renal salt regulation, other studies have found a lack of natriuretic response to high-plasma ANF under certain physiological and pathophysiological conditions. The mechanism for this apparent insensitivity to ANF is unknown. In the present study, it was found that ANF binding to its receptor requires the presence of chloride and occurs in a chloride concentration-dependent manner. ANF binding was measured using the purified recombinant hormone-binding domain of the ANF receptor in the presence of 0.1 mol/L NaCl or other selected salt. High specific binding was detected in the presence of NaCl, KCl, or NH(4)Cl. However, binding was undetectable when the salt was replaced with NaHCO(3), CH(3)COONa, or CH(3)COONH(4), indicating that binding requires the presence of chloride. Chloride dependence was also found with the native receptor in bovine adrenocortical membrane preparations. ANF binding to the recombinant protein was chloride concentration-dependent over a range from 0.05 to 10 mmol/L, and a half-maximum binding was attained at approximately 0.6 mmol/L equivalent chloride concentration. Competitive-binding assays at several fixed concentrations of NaCl showed that lowering chloride concentration caused a decrease in maximum binding but did not alter K(d) values, suggesting that a loss of chloride turns off ANF binding rather than reducing affinity for ANF. Saturation-binding studies showed that excess ANF cannot overcome loss of binding caused by low chloride. Chloride-dependent ANF-receptor binding may function as a feedback-control mechanism regulating the ANF-receptor action and, hence, renal sodium excretion.