tbuckley/cabot-search huggingface dataset:
Acute anuric glomerulonephritis in monoclonal cryoglobulinaemia.
Authors: C Ponticelli, E Imbasciati, A Tarantino, M Pietrogrande
Journal: BMJ (1977)

Acute anuric glomerulonephritis in monoclonal cryoglobulinaemiaWhile proliferative glomerulonephritis with progressive renal failure is a common and often fatal complication of primary mixed cryo- globulinaemia,l the presence of monoclonal cryoglobulins is not usually associated with glomerular proliferative lesions.Nevertheless, a few well-documented cases of glomerulonephritis in patients with essential monoclonal IgG cryoglobulinaemia have been reported.-4In these cases the outcome of glomerulonephritis was generally favourable or very slowly progressive.We describe a further case of a woman with a primary monoclonal IgG cryoglobulinaemia who developed a diffuse proliferative glomerulonephritis.In this patient renal damage was particularly severe and prolonged anuria complicated the outcome.Despite the ominous prognosis attributed to acute renal failure in cryoglobulin- aemic nephritis, this patient's renal function recovered. Case reportA 42-year-old woman was admitted to our unit in December 1972.In July 1971 she had had a normal pregnancy, and in February 1972 she developed skin eruptions on her legs and arms, without fever or other symptoms.The skin lesions spontaneously disappeared but reappeared in subsequent episodes.In December 1972, during one of these episodes, we found that she had proteinuria and hypertension.After a few days she became oliguric and oedematous, and on admission she was pale, febrile, with oedema and haemorrhagic-papulo-necrotic lesions of the legs.Blood pressure was 165/100 mmHg.Serum creatinine was 831 tumol/l (9-4 mg/100 ml), blood urea 30 4 mmol/l (183 mg/100 ml), packed cell volume 28 %, haemo- globin 8-9 g/dl, white blood count 8-3 x 109/1, platelets 220 x 109/1.Serum C3 was 0-43 g/l, and tests for ANF and LE cells were negative.Her proteinuria amounted to 6 g daily and haematuria was present.In the serum cryo-
Children's dental health and medicines that contain sugar
Authors: I. C Mackie
Journal: BMJ (1995)

<h3>Objective</h3> Growth-differentiation factor 15 (GDF-15), a stress-responsive member of the transforming growth factor beta cytokine superfamily, has emerged as a biomarker of increased mortality in cardiovascular disease. However, the exact pathophysiological mechanisms of GDF-15 in the cardiovascular system and in acute ST-elevation myocardial infarction (STEMI) are not well defined. The aim of this study was to determine the relation between GDF-15 and myocardial damage assessed by cardiovascular magnetic resonance (CMR) imaging and to evaluate the prognostic value of GDF-15 in a high-risk STEMI population exclusively reperfused by primary angioplasty. <h3>Design, setting, patients</h3> GDF-15 concentrations were determined by an ELISA in 238 consecutive patients undergoing primary angioplasty in STEMI less than 12 h after symptom onset. Patients were categorised into two groups defined by the median GDF-15 value on admission. CMR was performed 3 days (IQR 2–4) after infarction for assessment of infarct size, myocardial salvage and microvascular obstruction. The primary clinical endpoint was mortality within 6 months after the index event. <h3>Results</h3> Elevated GDF-15 concentrations over and above the median on admission were a strong predictor of mortality (19 vs one death, p&lt;0.001) and major adverse cardiac events (27 vs nine events, p=0.001) at 6 months follow-up. Myocardial salvage was an inverse multivariable predictor of GDF-15 concentrations. <h3>Conclusions</h3> GDF-15 on admission is a strong predictor of mortality in patients with STEMI reperfused by primary angioplasty, which is associated with decreased myocardial salvage and subsequent adverse clinical outcome. <h3>Clinical trail registration number</h3> http://www.clinicaltrials.gov/NCT00463749.
Treatment of Common Parasitic Infections of Man Encountered in the United States
Authors: Harry Most
Journal: New England Journal of Medicine (1972)

During the past decade, the roster of drugs recommended for the treatment of human parasitic infections has undergone a striking metamorphosis. Some drugs have disappeared because of unacceptable serious toxicity; others, though still available, have lost their primacy as "drugs of choice," and several entirely new ones have entered the scene of antiparasitic chemotherapy.The purpose of this review is to relate specific infections to the most effective drug, indicating optimum dosage and method of administration. Although one can now assume that with few exceptions parasitic infections encountered in the United States, whether indigenous or imported, can be cured, one . . .
Cardiac Myocyte–Specific Expression of Inducible Nitric Oxide Synthase Protects Against Ischemia/Reperfusion Injury by Preventing Mitochondrial Permeability Transition
Authors: Matthew B. West, Gregg Rokosh, Detlef Obal, Murugesan Velayutham, Yu-Ting Xuan, Bradford G. Hill, Rachel J. Keith, Jürgen Schrader, Yiru Guo, Daniel J. Conklin, Sumanth D. Prabhu, Jay L. Zweier, Roberto Bolli, Aruni Bhatnagar
Journal: Circulation (2008)

Inducible nitric oxide synthase (iNOS) is an obligatory mediator of the late phase of ischemic preconditioning, but the mechanisms of its cardioprotective actions are unknown. In addition, it remains unclear whether sustained elevation of iNOS in myocytes provides chronic protection against ischemia/reperfusion injury.Constitutive overexpression of iNOS in transgenic mice (alpha-myosin heavy chain promoter) did not induce contractile dysfunction and did not affect mitochondrial respiration or biogenesis, but it profoundly decreased infarct size in mice subjected to 30 minutes of coronary occlusion and 24 hours of reperfusion. In comparison with wild-type hearts, isolated iNOS-transgenic hearts subjected to ischemia for 30 minutes followed by 40 minutes of reperfusion displayed better contractile recovery, smaller infarct size, and less mitochondrial entrapment of 2-deoxy-[(3)H]-glucose. Reperfusion-induced loss of NAD(+) and mitochondrial release of cytochrome c were attenuated in iNOS-transgenic hearts, indicating reduced mitochondrial permeability transition. The NO donor NOC-22 prevented permeability transition in isolated mitochondria, and mitochondrial permeability transition-induced NAD(+) loss was decreased in wild-type but not iNOS-null mice treated with the NO donor diethylene triamine/NO 24 hours before ischemia and reperfusion ex vivo. iNOS-mediated cardioprotection was not abolished by atractyloside. Reperfusion-induced production of oxygen-derived free radicals (measured by electron paramagnetic resonance spectroscopy) was attenuated in iNOS-transgenic hearts and was increased in wild-type hearts treated with the mitochondrial permeability transition inhibitor cyclosporin A.Cardiomyocyte-restricted expression of iNOS provides sustained cardioprotection. This cardioprotection is associated with a decrease in reperfusion-induced oxygen radicals and inhibition of mitochondrial swelling and permeability transition.
Abstract 1825: Sustained aerobic exercise alone does not counteract the tumor-promoting effects of a westernized diet on prostate cancer progression <i>in vivo</i>
Authors: Avi D. Vandersluis, Natalie A. Venier, Alex Kiss, Alexandra J. Colquhoun, Neil E. Fleshner, Laurence H. Klotz, Vasundara Venkateswaran
Journal: Cancer Research (2011)

Abstract Introduction: The influence of lifestyle behaviors on prostate cancer (PCa) is well established. Our lab has previously reported that diets high in both fat and carbohydrates – the “Westernized” diet – promote PCa tumor growth in vivo. Numerous studies have also found an inverse relationship between exercise and PCa progression. However, the exact relationships between diet, exercise and PCa, as well as their underlying mechanisms, are unclear. Herein we aim to investigate the effect of sustained aerobic exercise on PCa tumor growth in animals fed a “Westernized” diet or a normal diet. Methods: Athymic nude mice (n=46) were inoculated subcutaneously with LNCaP cells. Mice were fed ad libitum with either a high-fat/high-carbohydrate diet (HFHC) or a standard normal diet (Normal), and randomized into exercising (Ex) and non-exercising groups (No-Ex). Exercise was undertaken 3 days per week (3 × 15 mins; 2-min breaks between cycles; 2.0-7.0 m/min) for 8 weeks, using a forced exercise wheel. Body weights, tumor volumes, and food consumption were recorded tri-weekly. Comparisons between groups over time were performed using RANOVA Type 3 Tests of Fixed Effects. Results: There were no significant differences in body weight between the groups over time. The HFHC-Ex group (n=10) had the highest rate of tumor growth compared to all other groups (p&amp;lt;=0.0007). No significant differences were observed between the rate of tumor growth of the HFHC-No Ex group (n=11) and the Normal-No Ex group (n=12) or between the Normal-No Ex group and the Normal-Ex group (n=10). However, the rate of tumor growth of the Normal-Ex group was reduced compared to the HFHC-No Ex group (p&amp;lt;=0.0008). Food consumption analysis revealed significant differences (p&amp;lt;=0.012) in energy consumption (kcal) between each of the groups over time. Mice in HFHC-Ex group consumed the most energy compared to all other groups followed by HFHC-No Ex&amp;gt;Normal-Ex&amp;gt;Normal-No Ex groups. Conclusions: The results indicate that exercise stimulated an increase in food consumption. In mice fed a tumor-promoting “Westernized diet,” this enhanced the rate of tumor growth. However, in mice placed on a normal diet, this increase in energy consumption did not correspond with increased tumor growth over time, emphasizing the importance of both exercise and healthy diet in the progression of PCa. Further studies to examine the relationship between diet and exercise with respect to PCa progression are currently underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1825. doi:10.1158/1538-7445.AM2011-1825
The Management of Essential Hypertension
Authors: Brigadier William O'Brien
Journal: JAMA (1974)

HYPERTENSIVE disease exists if an elevated blood pressure is sufficient to cause objective abnormalities, such as retinopathy, renal disorders, cardiomegaly, or electrocardiographic evidence of left ventricular strain. Hypertensive disease requires drug therapy because it carries a significant mortality. The difference in five-year survival rates between treated and untreated patients is so great that the necessity of long-term antihypertensive therapy can scarcely be questioned.<sup>1</sup> <h3>Methyldopa and Thiazides</h3> The most popular antihypertensive drug in Britain today is<i>methyldopa</i>. Although its mode of action is not entirely clear, it is a decarboxylase inhibitor and originally was thought to act at the arteriolar wall nerve endings by causing a block in norepinephrine synthesis. Alpha-methylnorepinephrine has since been said to be synthesized as a "false transmitter." Neither of these two mechanisms entirely accounts for the action of the drug. Methyldopa has the advantage over most other potent antihypertensive drugs in its ability to control
Keratin 19, a Cancer Stem Cell Marker in Human Hepatocellular Carcinoma
Authors: Takayuki Kawai, Kentaro Yasuchika, Takamichi Ishii, Hokahiro Katayama, Elena Yukie Yoshitoshi, Satoshi Ogiso, Sadahiko Kita, Katsutaro Yasuda, Ken Fukumitsu, Masaki Mizumoto, Etsuro Hatano, Shinji Uemoto
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Keratin 19 (K19) is a known marker of poor prognosis and invasion in human hepatocellular carcinoma (HCC). However, the relationship between K19 and cancer stem cells (CSCs) is unclear. Here, we determined whether K19 can be used as a new CSC marker and therapeutic target in HCC. Experimental Design: HCC cell lines were transfected with a K19 promoter–driven enhanced green fluorescence protein gene. CSC characteristics, epithelial–mesenchymal transition (EMT), and TGFb/Smad signaling were examined in FACS-isolated K19+/K19− cells. K19 and TGFb receptor 1 (TGFbR1) expression in 166 consecutive human HCC surgical specimens was examined immunohistochemically. Results: FACS-isolated single K19+ cells showed self-renewal and differentiation into K19− cells, whereas single K19− cells did not produce K19+ cells. K19+ cells displayed high proliferation capacity and 5-fluorouracil resistance in vitro. Xenotransplantation into immunodeficient mice revealed that K19+ cells reproduced, differentiated into K19− cells, and generated large tumors at a high frequency in vivo. K19+ cells were found to be involved in EMT and the activation of TGFb/Smad signaling, and these properties were suppressed by K19 knockdown or treatment with a TGFbR1 inhibitor. The TGFbR1 inhibitor also showed high therapeutic effect against K19+ tumor in the mouse xenograft model. Immunohistochemistry of HCC specimens showed that compared with K19− patients, K19+ patients had significantly poorer recurrence-free survival and higher tumor TGFbR1 expression. Conclusions: K19 is a new CSC marker associated with EMT and TGFb/Smad signaling, and it would thus be a good therapeutic target for TGFbR1 inhibition. Clin Cancer Res; 21(13); 3081–91. ©2015 AACR.
Henry Matthew Adam
Authors: Keith Vickerman
Journal: BMJ (2004)

Psychiatrist and pioneer of the death-and-dying movementIn her groundbreaking bestseller On Death and Dying, Elisabeth Kübler-Ross overturned how physicians treat dying patients.When the book was published in 1969, death was a taboo subject and discussing it was considered morbid.Patients died alone in hospitals; physicians ignored them; and adequate pain medication was underused.The book brought these practices to the fore-and pressed for more humane treatment of the dying.The book rocked the medical profession-and at the same time also resulted in a public outcry for compassionate care of the dying.On Death and Dying is a classic work and is still in print around the world today.Kübler-Ross's work stemmed from the realisation that in her native Switzerland, death, like birth, was considered a normal part of the life cycle.In Switzerland people died at home surrounded by family and friends-and they were comfortable until the end of their lives.In contrast in the United States and other countries that placed a premium on high tech medicine, patients lay by the wayside.It was a practice she deplored.A hallmark of Kübler-Ross's work was her emphasis on communication.She stressed that patients truly wanted to review their lives, their deterioration, and imminent death.When patients and doctors could talk openly-and without fear-a good death could be achieved.In 1967 Kübler-Ross began interviewing dying patients at the University of Chicago's Billings Hospital, where she was a psychiatrist.She hoped to learn what patients were thinking as they lay dying.From her first hand research, she derived the famous five stage framework: denial, anger, bargaining, depression, and acceptance-or, as she called it, "one common denominator" of death and dying.The model outlined how patients with terminal illness grappled with their diagnosis, and their emotions along the way, right through to acceptance of their impending death.She appealed to the medical community to use it.Collin Murray Parkes, consultant psychiatrist at St Christopher's Hospice in London, credits Kübler-Ross's five stage framework and its high visibility as a driving force in stimulating research and changing
Case 44-1974
Authors: Richard C. Cabot, Robert E. Scully, Betty U. McNeely, Adolf W. Karchmer, Stanley J. Robboy
Journal: New England Journal of Medicine (1974)

Presentation of CaseA 46-year-old woman was admitted to the hospital because of rheumatic heart disease.Between six and 18 years of age she had 18 episodes of rheumatic fever. At the age of 32 years digitoxin therapy was begun because of atrial fibrillation. Seventeen months before admission she entered another hospital for treatment of congestive heart failure. Cardiac catheterization revealed severe mitral regurgitation and moderate aortic regurgitation.The patient complained of moderate fatigue and dyspnea, with occasional edema and chest pain. There was no history of cough, wheezing, orthopnea or hemoptysis.The temperature was 37°C, the pulse 96 and . . .
The cytokine profile in a transient variant of angioedema with eosinophilia
Authors: Y. Mizukawa, T. Shiohara
Journal: British Journal of Dermatology (2001)

Episodic angioedema with eosinophilia is characterized by recurrent angioedema, fever and weight gain with a remarkable eosinophilia. A transient type, predominantly reported in Japan, in which the disease is limited to a single attack, is usually less severe than the episodic type described in the U.S.A. and Europe, and provides an ideal disease model in which to study the mechanisms for resolution of eosinophilic inflammation. The aim of this study was to evaluate the relationship between cytokine responses and clinical course in three patients with the transient type. Serum levels of interleukin (IL) -5 were only marginally elevated even during an attack, unlike those in reported cases of the episodic type. Significant elevations in granulocyte-macrophage colony-stimulating factor levels were also noted during an attack in two cases in which it was measured. A dramatic increase in tumor necrosis factor (TNF) -α levels was subsequently observed in relation to resolution of clinical symptoms. No major changes in the serum levels of soluble Fas and soluble Fas ligand were found throughout the course. These results suggest that relatively lower levels of IL-5 and a subsequent increase in TNF-α levels are characteristic features of the transient type. The differences in clinical symptoms and course observed between the two types may be partly explained by the differences in the cytokine profiles.
p95HER2 Truncated Form in Resected Non-small Cell Lung Cancer
Authors: Federico Cappuzzo, Yong Gon Cho, Andrea Sacconi, Greta Alì, Olimpia Siclari, Matteo Incarbone, Annarita Destro, Luigi Terracciano, Gabriella Fontanini, Antonio Marchetti, Massimo Roncalli, Marileila Varella-Garcia
Journal: Journal of Thoracic Oncology (2012)
The effect of amorphous pyrophosphate on calcium phosphate cement resorption and bone generation
Authors: Liam M. Grover, Adrian J. Wright, Uwe Gbureck, Aminat Bolarinwa, Jiangfeng Song, Yong Liu, David F. Farrar, Graeme Howling, John Rose, Jake E. Barralet
Journal: Biomaterials (2013)

Pyrophosphate ions are both inhibitors of HA formation and substrates for phosphatase enzymes. Unlike polyphosphates their hydrolysis results simultaneously in the complete loss of mineral formation inhibition and a localised elevation in orthophosphate ion concentration. Despite recent advances in our knowledge of the role of the pyrophosphate ion, very little is known about the effects of pyrophosphate on bone formation and even less is known about its local delivery. In this work we first developed a self setting pyrophosphate based calcium cement system with appropriate handling properties and then compared its in vivo degradation properties with those of a non-pyrophosphate containing control. Contrary to expectation, the presence of the pyrophosphate phase in the cement matrix did not inhibit mineralisation of the healing bone around the implant, but actually appeared to stimulate it. In vitro evidence suggested that enzymatic action accelerated dissolution of the inorganic pyrophosphate ions, causing a simultaneous loss of their mineralisation inhibition and a localised rise in supersaturation with respect to HA. This is thought to be a rare example of a biologically responsive inorganic material and these materials seem to be worthy of further investigation. Bioceramics to date have mainly been limited to orthophosphate, silicate and carbonate salts of calcium, here we report the successful application of a pyrophosphate material as a degradable osteoconductive bone repair cement.
Stimulatory Autoantibodies to the PDGF Receptor in Systemic Sclerosis
Authors: Silvia Svegliati Baroni, Mariarosaria Santillo, Federica Bevilacqua, Michele Luchetti, Tatiana Spadoni, Matteo Mancini, Paolo Fraticelli, Paola Sambo, Ada Funaro, Andrius Kazlauskas, Enrico V. Avvedimento, Armando Gabrielli
Journal: New England Journal of Medicine (2006)

Systemic sclerosis (scleroderma) is characterized by immunologic abnormalities, injury of endothelial cells, and tissue fibrosis. Abnormal oxidative stress has been documented in scleroderma and linked to fibroblast activation. Since platelet-derived growth factor (PDGF) stimulates the production of reactive oxygen species (ROS) and since IgG from patients with scleroderma reacts with human fibroblasts, we tested the hypothesis that patients with scleroderma have serum autoantibodies that stimulate the PDGF receptor (PDGFR), activating collagen-gene expression.
IN VIVO TRANSMISSION OF DRUG RESISTANCE FACTORS BETWEEN STRAINS OF STAPHYLOCOCCUS AUREUS
Authors: Richard P. Novick, Stephen I. Morse
Journal: The Journal of Experimental Medicine (1967)

1. Multiply resistant strains of Staphylococcus aureus often harbor one or more extrachromosomal drug resistant factors as well as temperate prophages capable of mediating generalized transduction. 2. Spontaneous transduction occurs in mixed cultures of such staphylococcal strains, and the extrachromosomal resistance factors are involved more frequently than are chromosomal genes. 3. Spontaneous transduction of extrachromosomal determinants of erythromycin resistance and of linked penicillin-erythromycin resistance occurs in the kidneys of mice in which mixed infection has been induced.