tbuckley/cabot-search huggingface dataset:
Adverse Effects of Dabigatran
Authors: Patricio A. Pazmiño
Journal: Annals of Internal Medicine (2012)

Letters18 December 2012Adverse Effects of DabigatranPatricio A. Pazmiño, MD, PhDPatricio A. Pazmiño, MD, PhDFrom Nephrology, Internal Medicine and Hypertension Center, El Paso, TX 79902-3503.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-157-12-201212180-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read Radecki's article (1) with interest and agree with his concerns. Some of the potential harms stem from dabigatran's use for unapproved indications and in populations that have not been well-studied. The approval of dabigatran in the United States was based mostly on the results of the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial involving more than 18 000 patients (2). Unfortunately, this trial did not include patients with creatinine clearances less than 30 mL/min per 1.73 m2, which is common in the elderly and in patients with stage 4 or 5 chronic kidney disease.The ...References1. Radecki RP. Dabigatran: uncharted waters and potential harms. Ann Intern Med. 2012;157:66-8. [PMID: 22751762] LinkGoogle Scholar2. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51. [PMID: 19717844] CrossrefMedlineGoogle Scholar3. Pazmiño PA. Dabigatran associated acute renal failure (DAARF). El Paso Physician. 2011;34:7-9. Google Scholar4. Moore TJ, Furberg CD, Cohen MR. Anticoagulants the Leading Reported Drug Risk in 2011: May 31, 2012: New Data from 2011 Quarters 3-4. QuarterWatch 2012. Alexandria, VA: Institute for Safe Medicine Practices; 2012. Accessed at www.ismp.org/quarterwatch/pdfs/2011Q4.pdf on 15 November 2012. Google Scholar5. Pradaxa (prescribing information). Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals; 2011. Google Scholar Author, Article, and Disclosure InformationAffiliations: From Nephrology, Internal Medicine and Hypertension Center, El Paso, TX 79902-3503.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoDabigatran: Uncharted Waters and Potential Harms Ryan P. Radecki Adverse Effects of Dabigatran Ryan P. Radecki Metrics Cited ByFeatures of Electronic Health Records Necessary for the Delivery of Optimized Anticoagulant TherapyDabigatran: A Nephrological Way Out 18 December 2012Volume 157, Issue 12Page: 916KeywordsAcute renal failureChronic kidney diseaseCreatinineHeparinNephrologyPopulation statisticsProteinsStrokeUrine ePublished: 18 December 2012 Issue Published: 18 December 2012 CopyrightCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Metabolic Bone Disease and Clinically Related Disorders
Authors: Marshall R. Urist
Journal: JAMA (1991)

This monumental reference book is derived from a previous one-volume treatise published in 1977 and two volumes published in 1979. Now, 13 years after the first volume, the coverage is combined in an extraordinary multiauthored, detailed work encompassing the field of skeletal tissue systemic disorders in 24 chapters by 35 authors and coauthors. The first 10 chapters survey current knowledge of cellular physiology of bone turnover, mineralization, and the regulatory mechanisms of the gastrointestinal tract and kidney in calcium and phosphorus metabolism. The subsequent 14 chapters review clinical disorders, with special reference to diagnosis and treatment. The space allotted to research on etiology is relatively small. For example, nearly 155 pages are assigned to "The Female Osteoporotic Syndrome(s)," including 533 references to the literature. Since osteoporosis in postmenopausal women is the most common systemic bone disease, the amount of space is well justified. However, the emphasis is on diagnosis and
Esophageal staple transection as a salvage procedure after failure of acute injection sclerotherapy
Authors: Aiden P. McCormick, Graham L. Kaye, Lynda Greenslade, Fabrizio Cardin, Kenneth E. F. Hobbs, Neil McIntyre, Andrew K. Burroughs
Journal: Hepatology (1992)

It is not clear which therapy should be used in patients with bleeding esophageal varices that are not controlled by emergency sclerotherapy. This is a high-risk group with reported mortality rates of between 70% and 90%. We report our 7-yr experience with staple transection of the esophagus in this patient group. Of 168 patients (280 bleeding episodes) treated with sclerotherapy, 22 had emergency staple transection for failure to control bleeding. Bleeding was controlled in 20 patients (90%), and 10 patients (45%) survived to leave the hospital, including 4 of 10 patients (40%) with Pugh grade C liver disease. We suggest that emergency staple transection is an effective salvage treatment for this high-risk group.
1075 PHARMACOKINETIC-PHARMACODYNAMIC (PK-PD) ANALYSES OF TMC435 IN TREATMENT-NAIVE HEPATITIS C (HCV)-INFECTED PATIENTS IN THE OPERA-1 STUDY
Authors: V. Sekar, P. Vis, O. Lenz, P. Meyvisch, M. Peeters, G. De Smedt
Journal: Journal of Hepatology (2010)
Outcome of Pregnancy Among Immigrant Women With Diabetes
Authors: Siri Vangen, Camilla Stoltenberg, Synne Holan, Narve Moe, Per Magnus, Jennifer R. Harris, Babill Stray-Pedersen
Journal: Diabetes Care (2003)

OBJECTIVE—We studied outcome of pregnancy among immigrant women with diabetes. The women came from regions of the world with high incidence of impaired glucose tolerance and type 2 diabetes. Prevalences, secular trends, and sociodemographic risk factors of diabetes were also explored. RESEARCH DESIGN AND METHODS—Data from the Medical Birth Registry of Norway on all births from 1988 to 1998 for mothers born in South Asia and North Africa (11,268) and Norway (601,785) were analyzed. RESULTS—The prevalence of pregestational diabetes among the immigrants was 8.9/1,000 births, which was more than twice the rate among ethnic Norwegians (3.6/1,000). Time trends indicated increasing prevalences in both groups. Among the immigrants, diabetes was closely associated with maternal age. Maternal diabetes was associated with a significantly increased risk of pregnancy complications in both study groups. Increased risks were found for low birth weight, macrosomia, preterm birth, preeclampsia, and cesarean sections. Among ethnic Norwegians, maternal diabetes conferred a significantly increased risk of infant perinatal death (odds ratio 2.00, 95% CI 1,44–2.77). In the sample of immigrant women with predominantly type 2 diabetes, maternal diabetes was not significantly associated with perinatal death or congenital malformations in the offspring. CONCLUSIONS—The high prevalence of diabetes among immigrants from South Asia and North Africa represents a challenge for health care providers. To prevent adverse pregnancy outcomes and later cardiovascular and renal morbidity among these groups, early diagnosis of diabetes, adequate metabolic control, and relevant preventive measures are warranted.
Gold(III) Porphyrin 1a Induced Apoptosis by Mitochondrial Death Pathways Related to Reactive Oxygen Species
Authors: Ying Wang, Qing-Yu He, Raymond Wai-Yin Sun, Chi-Ming Che, Jen-Fu Chiu
Journal: Cancer Research (2005)

Abstract Apoptosis is a tightly controlled multistep mechanism of cell death, and mitochondria are considered to play a central role in this process. Mitochondria initiate two distinct apoptosis pathways, one caspase-dependent and the other caspase-independent. In addition, mitochondrial production of reactive oxygen species (ROS) seems to play a role in cell death. Most chemotherapeutic agents induce apoptosis through at least one of these pathways. The post-initiation mechanisms of gold(III) porphyrin 1a were investigated in this study. HONE1 cells exposed to gold(III) porphyrin 1a underwent apoptosis after 24 hours. Functional proteomic studies revealed the alteration of several cytoplasmic protein expressions in HONE1 cells after treatment with the drug. These proteins include enzymes participating in energy production and proteins involved in cellular redox balance. There was a quick attenuation of mitochondrial membrane potential (ΔΨm) with the alterations of Bcl-2 family proteins, the release of cytochrome c, and apoptosis-inducing factor (AIF) following gold(III) porphyrin 1a treatment. Cytochrome c in turn activated caspase-9 and caspase-3. Cotreatment with caspase inhibitor (zVAD-fmk) showed that the activated caspases worked in conjunction with AIF-initiated apoptosis pathways. Further study showed that ROS played a part in gold(III) porphyrin 1a–induced apoptosis by regulating ΔΨm. In summary, gold(III) porphyrin 1a induced apoptosis through both caspase-dependent and caspase-independent mitochondrial pathways, and intracellular oxidation affected gold(III) porphyrin 1a–induced apoptosis. These results support a role for gold(III) porphyrin 1a as a promising anticancer drug lead and as a possible novel therapeutic agent directed toward the mitochondria. (Cancer Res 2005; 65(24): 11553-64)
Cadmium exposure and nephropathy in a 28-year-old female metals worker.
Authors: Richard Wittman, Howard Hu
Journal: Environmental Health Perspectives (2002)

A 28-year-old female presented for evaluation of left flank pain and polyuria after having been exposed to cadmium in the jewelry manufacturing industry for approximately 3 years. This patient possessed both elevated 24-hr urinary ss2-microglobulin and elevated blood cadmium levels. Approximately 6 months after initial presentation, the patient resigned from her job due to shortness of breath, chest pain, and anxiety. Exposure to cadmium in the jewelry industry is a significant source of occupational cadmium exposure. Other occupational sources include the manufacture of nickel-cadmium batteries, metal plating, zinc and lead refining, smelting of cadmium and lead, and production of plastics. Cadmium is also an environmental pollutant that accumulates in leafy vegetables and plants, including tobacco. Major toxicities anticipated from cadmium exposure involve the renal, pulmonary, and, to a lesser extent, gastrointestinal systems. These include the development of renal proximal tubular dysfunction, glomerular damage with progressive renal disease, and respiratory symptoms including pneumonitis and emphysema. Low-level cadmium exposure has also been associated with increased urinary calcium excretion and direct bone toxicity, effects that recent research suggests may result in the development of osteoporosis. The body burden of cadmium, over half of which may reside in the kidneys, is most often measured through the use of urinary cadmium levels. Blood cadmium measurements generally reflect current or recent exposure and are especially useful in cases with a short exposure period and only minimal accumulation of cadmium in the kidneys. Both ss2-microglobulin and alpha1-microglobulin serve as organ-specific, early-effect biomarkers of tubular proteinuria and thus play a role in identifying early signs of cadmium-induced renal damage in those with potential exposures. In addition to ensuring workplace compliance with Occupational Safety and Health Administration-mandated monitoring and screening measures, it is prudent for those with cadmium exposure to maintain adequate intake of both iron and calcium, appropriate measures even in the absence of exposure.
Oral administration of specific antigens to allergy-prone infant dogs induces IL-10 and TGF-β expression and prevents allergy in adult life
Authors: Barbara Zemann, Christoph Schwaerzler, Monika Griot-Wenk, Marijke Nefzger, Peter Mayer, Heinz Schneider, Alain de Weck, José M. Carballido, Ekke Liehl
Journal: Journal of Allergy and Clinical Immunology (2003)
PTEN Has Tumor-Promoting Properties in the Setting of Gain-of-Function p53 Mutations
Authors: Yunqing Li, Fadila Guessous, Sherwin Kwon, Manish Kumar, Opeyemi Ibidapo, Lauren Fuller, Elizabeth Johnson, Bachchu Lal, Isa Hussaini, Yongde Bao, John Laterra, David Schiff, Roger Abounader
Journal: Cancer Research (2008)

Abstract We show, for the first time, that the tumor suppressor PTEN can have tumor-promoting properties. We show that PTEN acquires these unexpected properties by enhancing gain-of-function mutant p53 (mut-p53) protein levels. We find that PTEN restoration to cells harboring mut-p53 leads to induction of G1-S cell cycle progression and cell proliferation and to inhibition of cell death. Conversely, PTEN inhibition in cells expressing wild-type PTEN and mut-p53 leads to inhibition of cell proliferation and inhibition of in vivo tumor growth. We show the dependency of the tumor-promoting effects of PTEN on mut-p53 by showing that knockdown of mut-p53 expression inhibits or reverses the tumor-promoting effects of PTEN. Mechanistically, we show that PTEN expression enhances mut-p53 protein levels via inhibition of mut-p53 degradation by Mdm2 and possibly also via direct protein binding. These findings describe a novel function of PTEN and have important implications for experimental and therapeutic strategies that aim at manipulating PTEN or p53 in human tumors. They suggest that the mutational status of PTEN and p53 should be considered to achieve favorable therapeutic outcomes. The findings also provide an explanation for the low frequency of simultaneous mutations of PTEN and p53 in human cancer. [Cancer Res 2008;68(6):1723–31]
Homotypic and Endothelial Cell Adhesions via N-Cadherin Determine Polarity and Regulate Migration of Vascular Smooth Muscle Cells
Authors: Peter J.B. Sabatini, Ming Zhang, Rosalind Silverman-Gavrila, Michelle P. Bendeck, B. Lowell Langille
Journal: Circulation Research (2008)

Migration of smooth muscle cells from the arterial media to the intima is central to several vascular pathologies including restenosis. This study demonstrates that, like directional migration of other cells, smooth muscle migration is accompanied by a dramatic, polarized reorganization of the cell cytoskeleton that is accompanied by activation of the Rho GTPase Cdc42 and inactivation of glycogen synthase kinase-3β. We also show, for the first time, that signals generated at the posterior–lateral aspects of wound edge cells by the cell–cell adhesion molecule N-cadherin are required for polarization and rapid migration of vascular smooth muscle. Importantly, when a cohort of migrating smooth muscle cells encounter CHO cells or the A10 smooth muscle cell line, neither of which expresses N-cadherin, polarity is only slightly suppressed. However, when smooth muscle cells encounter stably transfected, N-cadherin–expressing A10 cells or (N-cadherin–expressing) vascular endothelium, they rapidly lose their polarized phenotype. The latter finding indicates that endothelial signaling to innermost smooth muscle cells via N-cadherin may be critical to normal vessel wall stability. We infer that asymmetrical distribution of N-cadherin is necessary for the establishment of cell polarity during migration and that N-cadherin ligation is highly effective in abrogating polarized migration. Finally, we showed that endothelial cell polarity does not depend on N-cadherin; therefore, this molecule may be an attractive target for therapies to prevent restenosis without suppressing endothelial repair and risking late thrombosis.
Effects of exercise- and pacing-induced tachycardia on coronary collateral flow in the awake dog.
Authors: J M Fedor, J C Rembert, D M McIntosh, J C Greenfield
Journal: Circulation Research (1980)

Collateral blood flow was studied in chronically instrumented awake dogs 11-12 weeks after implantation of ameroid constrictors on the right and left circumflex coronary arteries.Using 7-10 fim radionuclide-labeled microspheres, transmural myocardial blood flow was measured during resting conditions and at similar heart rates during ventricular pacing and treadmill exercise.The absence of significant myocardial fibrosis was verified histologically.Control transmural flow was distributed normally in all dogs.In five dogs a marked maldistribution of flow occurred in the collateral region during pacing and exercise.During pacing, flow to the epicardial layers increased while flow to the endocardial layers was unchanged, resulting in a marked endocardial perfusion deficit.During exercise, flow increased substantially to all transmural layers, but the endocardial perfusion deficit remained.Mean transmural blood flow increased similarly in the collateral and noncoUateral regions during pacing; however, during exercise, mean flow in the collateral region was significantly lower than in the noncollateral region.These data demonstrate that the collateral vessels became flow limiting and functioned inadequately during tachycardia produced by pacing and exercise; i.e., a marked perfusion deficit occurred in the endocardial layer.Blood flow to all layers in the collateraldependent region was higher during exercise than during pacing, possibly due to exercise-induced vasodilation of the collateral channels.Circ Res 46: 214-220, 1980AS MYOCARDIAL viability may depend on collateral channels in advanced occlusive coronary artery disease, a complete understanding of transmural myocardial perfusion in coronary artery disease must include a detailed knowledge of the determinants of flow through collateral vessels.Considerable effort has been devoted recently to developing a large animal model with a collateralized coronary circulation.Chronic gradual coronary artery occlusions, produced by hydroscopic ameroid constrictors in the dog, result in rapid growth of extensive intercoronary collateral channels which may prevent myocardial infarction.Several investigators have shown that these channels perfuse the myocardium adequately to meet metabolic needs during resting conditions (Becker and Pitt, 1971;Elliot et al., 1971;Schaper, 1971;Schaper et al., 1973).However, with the increased myocardial flow requirements of tachycardia or pharmacologically induced coronary vasodilation, these collateral
Multiple Concurrent Reverse Transcriptase and Protease Mutations and Multidrug Resistance of HIV-1 Isolates from Heavily Treated Patients
Authors: Robert W. Shafer
Journal: Annals of Internal Medicine (1998)

Background: Drug resistance of HIV-1 is an obstacle to the long-term efficacy of antiretroviral therapy. Objective: To characterize reverse transcriptase and protease genes of multidrug-resistant HIV-1 isolates. Design: Descriptive case series. Setting: Academic medical center. Patients: Four consecutive patients with HIV-1 infection were selected because they had previously received many antiretroviral drugs and had not achieved plasma HIV-1 RNA suppression despite treatment with several three-drug combinations. Measurements: Reverse transcriptase sequencing, protease sequencing, and drug susceptibility testing of HIV-1. Results: Isolates of HIV-1 from the four patients shared seven protease mutations and eight reverse transcriptase mutations. These mutations were present in biological clones and at three time points in three of the patients. Susceptibility testing showed high-level resistance (30-fold to >100-fold) to zidovudine, lamivudine, saquinavir, indinavir, and nelfinavir and lower-level resistance (3-fold to 5-fold) to didanosine, zalcitabine, and stavudine. Conclusions: Simultaneous resistance to almost all available antiretroviral drugs may occur in HIV-1. The concordance and persistence of mutations in drug-resistant HIV-1 isolates suggest that some combinations of reverse transcriptase and protease mutations give the virus a selective advantage in the presence of various drug combinations.
The Benefits of Metformin Therapy During Continuous Subcutaneous Insulin Infusion Treatment of Type 1 Diabetic Patients
Authors: Laurent Meyer, Philip Bohme, Irene Delbachian, Philippe Lehert, Nathalie Cugnardey, Pierre Drouin, Bruno Guerci
Journal: Diabetes Care (2002)

OBJECTIVE—This study was designed to assess the insulin-sparing effect of oral administration of metformin along with a continuous subcutaneous insulin infusion (CSII) for the treatment of type 1 diabetic patients. RESEARCH DESIGN AND METHODS—A total of 62 patients (25 women and 37 men) were studied in a monocenter, randomized, double-blind placebo-controlled study, comparing metformin (850 mg b.i.d.) with placebo in association with CSII during a 6-month period. RESULTS—Treatment with metformin was associated with a reduction in daily insulin requirements between V0 and V6 of −4.3 ± 9.9 units (−7.8 ± 18%) compared with an increase with placebo treatment of 1.7 ± 8.3 units (2.8 ± 12.7%) (P = 0.0043). A decrease in basal requirement of insulin was also observed in patients treated with metformin of −2.6 ± 3.2 units (−7.9 ± 23.8%) compared with an increase with placebo treatment of 1.9 ± 5.7 units (8.8 ± 27.1%) (P = 0.023). HbA1c remained unchanged in treatment with metformin and placebo between V0 and V6. The number of hypoglycemic events (&amp;lt;60 mg/dl) was similar in both groups. Significant reductions of total cholesterol (P = 0.04) and LDL cholesterol (P = 0.05) were observed in patients treated with metformin. Gastrointestinal events, including diarrhea and abdominal pain, were reported in three patients in the metformin group who discontinued the trial. Mild or moderate gastrointestinal side effects were also reported in eight patients treated with metformin and two patients treated with placebo (P = 0.069). CONCLUSIONS—Metformin was found to be a safe insulin-sparing agent, when used in combination with CSII for the treatment of type 1 diabetes.
Health promotion in general practice
Authors: M E Cupples, A McKnight
Journal: BMJ (1995)

stay and bed use factor are better than the average for Wales, where most hospitals have parallel systems for admitting acute medical and geriatric emergencies.The appointment of a bed manager, flexible use of all acute beds in the hospital, and protocols for early discharge and transfer have failed to prevent constant overflows into non-medical wards, waits on trolleys in the accident and emergency department, and temporary closures, even though some general practices have access to community type hospital beds.Brief analysis (to be audited in more detail) suggests that few of the admissions are inappropriate.Major factors include patients' increased demands and expectations and general practitioners' fear of complaints and litigation.Given this, it is difficult to envisage any reduction in beds, let alone the 30% predicted in acute district general hospitals,3 whose surgeons are already practising day case surgery to a maximum.General practitioners have neither the time nor, probably, the skill needed to treat most of our acute medical admissions, even if they were provided with more facilities.Planning must be modified to take account of these issues.