tbuckley/cabot-search huggingface dataset:
Aging is associated with increased lipid peroxidation in human hearts, but not with mitochondrial respiratory chain enzyme defects
Authors: O Miró, J Casademont, E Casals, M Perea, A Urbano-Márquez, P Rustin, F Cardellach
Journal: Cardiovascular Research (2000)

Background: Aging is associated with increased oxidative damage at multiple cellular and tissular levels. A decrease in mitochondrial function has repeatedly been advocated as a primary key event, especially on the basis of analysis of skeletal muscle mitochondria. However, some doubts on this issue have arisen when confounding variables (such as physical activity or smoking habit) have been taken into account in the analysis of mitochondrial respiratory chain (MRC) enzyme activities or when additional analytical parameters such as enzyme ratios have been considered. Objective: To determine whether oxidative damage and enzyme activities of the MRC are influenced by the aging process in human hearts. Patients and methods: We studied cardiac muscle obtained from 59 organ donors (age: 56±12 years, 75% men). Oxidative membrane damage was evaluated through the assessment of lipid peroxidation. Absolute and relative enzyme activities (AEA and REA, respectively) of complex I, II, III and IV of the MRC were spectrophotometrically measured. Stoichiometric relationships among MRC complexes were also assessed through calculating MRC ratios. Linear regression analyses were employed to disclose any potential correlation between mitochondrial dysfunction and aging. Results: We found a progressive, significant increase of heart membrane lipid peroxidation with aging (P<0.05). Conversely, neither AEA nor REA decreased with age (P=n.s. for all complexes). Similarly to observations in other tissues, we found that stoichiometry of the MRC enzymes is maintained within a narrow range in human hearts. When the effects of aging on MRC ratios were explored, we failed again in demonstrating any subtle disarray. Conclusion: MRC enzymes remain preserved in heart with aging, and thus they cannot be considered the main cause of the increased oxidative damage associated with aging.
POTENTIATED BLOOD PRESSURE RESPONSES TO ENERGY DRINK INTAKE IN CAFFEINE NAïVE HEALTHY ADULTS: A DOUBLE BLIND RANDOMIZED CONTROLLED STUDY
Authors: Anna Svatikova, Naima Covassin, Krishen Somers, Filip Soucek, Tomas Kara, Lukas Ruzek, Jan Bukartyk
Journal: Journal of the American College of Cardiology (2015)
Disseminated Mycobacterium Kansasii Infection Complicating Hairy Cell Leukemia
Authors: Jose L. Manes
Journal: JAMA (1976)

<i>Mycobacterium kansasii</i>was isolated from the spleen of a patient with "hairy cell leukemia" (HCL) who had caseating necrosis in the spleen and in the liver. The disseminated infection in this patient suggests a cellular immunity deficit. Despite intensive investigations, the nature of the cell of origin in HCL remains unknown. (<i>JAMA</i>236:1878-1879, 1976)
Report predicts 20 million AIDS orphans in Africa by 2010
Authors: F. Fleck
Journal: BMJ (2003)

The number of children left as orphans because their parents have died from AIDS related diseases in sub-Saharan Africa is expected to almost double–to 20 million–over the next seven years and could account for as many as 12% of all the region's children, says a new Unicef report.

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John, aged 9, whose parents died of AIDS related TB, sits with his grandmother Alim a Niymku at her home in Tanzania

Credit: GIACOMO PIROZZI/UNICEF

The report, Africa's Orphaned Generations , published this week, said that …

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Embolism from mural thrombus in the thoracic aorta.
Authors: D. O. Oliver
Journal: BMJ (1967)

Mural thrombus in the internal carotid artery is a source of emboli to the retinal and cerebral arteries, causing transient or permanent blindness and hemiplegia (Gunning et al., 1946b); thrombi in subclavian arteries damaged by cervical ribs form emboli which lodge in the digital arteries, inducing ischaemia of the fingers and thickened intima (Gunning et al., 1964a).Emboli from mural thrombi in the popliteal artery have been implicated in gangrene of the great toe (Ross, 1936).Mural thrombi on plaques of nodular arteriosclerosis are common in the abdominal aorta, but the frequency with which they form emboli to the abdominal or leg arteries is unknown, the paucity of published cases suggesting the event is either uncommon or unrecognized.Gross examples of a phenomenon are important because they are easily recognized and may be the extreme variants of events which are commonly unspectacular or undetectable.It is with this possibility in mind that a case in which mural thrombus in the thoracic aorta formed emboli to the abdominal and leg arteries is reported. CASE REPORTAn unmarried woman (U.O.H. 363216) aged 67 had for many years noticed slight breathlessness and constricting pain in the centre of the chest when walking.She was admitted to a cottage hospital complaining of pain in the right loin, vomiting, and weakness for nine days.Her temperature was 99.60 F. (37.60 C.) and blood- pressure 190/90 mm.Hg.No abnormalities were found in the abdomen or chest.The urine contained moderate quantities of protein, but the centrifuged deposit showed neither red nor white cells.The blood urea was 53 mg./100 ml.Her pain continued for five days and several examinations failed to establish its cause.She was transferred to the Radcliffe Infirmary, where examination showed a sinus rhythm of 96/minute.The only pulses in the legs were the femorals; her blood-pressure was 125/80 mm.Hg.Crepitations were present in both lungs, but there were no cardiac murmurs and no abdominal abnormalities.The urine had a specific gravity of 1018, it contained between 300 and 1,000 mg. of protein per litre, and the centrifuged deposit had 8 white cells and several hyaline and granular casts per high-power field.The blood urea was 48 mg./100 ml.; plasma sodium 130, potassium 4.2, chloride 90, and bicarbonate 20 mEq/l.The plasma amylase was 7 units.The haemoglobin was 99%; white cells 20,000/cu.mm.-a neutrophil leucocytosis; the sedimentation rate was 97 mm./hour.The next day her loin pain increased and she complained of pain in the legs.Examination revealed tenderness in the right hypo- chrondrium.The following day her legs were cold and white, and bowel sounds were absent.On the third day she sweated profusely, the pulse was 120/minute and the systolic blood-pressure 50 mm.Hg, despite metaraminol and hydrocortisone.Faeculent material was aspirated from the stomach.She died on the seventeenth day
Government refuses to fund flexible training in England
Authors: Rhona MacDonald
Journal: BMJ (2001)

Last week the government announced that no additional central funding would be given to trusts in England to support flexible trainees (junior doctors who work part time), despite its claimed commitment to improve the working lives of NHS staff and support a family friendly NHS.

Under the new banding system for junior doctors, trusts in England have had to increase their financial contributions to fund flexible trainees, which has provided a disincentive to employing such trainees. Consequently, the BMA's Junior Doctors Committee has been in discussion with the government for almost a year to improve funding.

The problem has arisen because of the new pay deal relating to certain patterns of work for junior …
Radiotherapy units should be seen as shared resource in EU
Authors: I. Kunkler
Journal: BMJ (2001)

EDITOR—In his news item on the ruling of the European Court of Justice in Luxemburg Watson cites the cases of a Belgian and two Dutch citizens in which refusal to sanction treatment in another member state of the European Union (EU) was judged unlawful.1 On this basis the plaintiffs covered by social insurance were eligible to have their costs reimbursed by the country that denied them treatment.

How this ruling would apply to British patients waiting in excess of …
Inactivation or Loss of TTP Promotes Invasion in Head and Neck Cancer via Transcript Stabilization and Secretion of MMP9, MMP2, and IL-6
Authors: Elizabeth A. Van Tubergen, Rajat Banerjee, Min Liu, Robert Vander Broek, Emily Light, Shiuhyang Kuo, Stephen E. Feinberg, Amanda L. Willis, Gregory Wolf, Thomas Carey, Carol Bradford, Mark Prince, Francis P. Worden, Keith L. Kirkwood, Nisha J. D'Silva
Journal: Clinical Cancer Research (2013)

Invasion is the critical step in progression of a precancerous lesion to squamous cell carcinoma of the head and neck (HNSCC). Invasion is regulated by multiple proinflammatory mediators. Tristetraprolin (TTP) is an mRNA-degrading protein that regulates multiple proinflammatory mediators. TTP may serve as an excellent treatment target. Rap1 is a ras-like oncoprotein that induces critical signaling pathways. In this study, the role of rap1 in TTP-mediated invasion was investigated.Using complementary approaches, we modulated TTP and altered expression of interleukin (IL)-6 and matrix metalloproteinase (MMP) 2/9, which were quantified by ELISA and zymogram. Invasion was evaluated in vitro using the oral-cancer-equivalent (OCE) three-dimensional model and in vivo in the chick chorioallantoic membrane (CAM). The role of rap1 and p38 were established using knockdown strategies.Downregulation of TTP significantly increased invasion via secretion of MMP9/2 and IL-6. In the novel OCE and CAM invasion models of HNSCC, cells with downregulated TTP destroyed the basement membrane to invade the underlying connective tissue. Rap1 induces p38 mitogen-activated protein kinase (p38)-mediated inactivation of TTP. Inactive TTP enhances transcript stability via binding to the 3'-untranslated region (UTR). High IL-6 and MMP9 are prognostic for poor clinical outcomes in patients with HNSCC.Targeting the rap1-p38-TTP cascade is an attractive novel treatment strategy in HNSCC to concurrently suppress multiple mediators of invasion.
Risk Models to Predict Chronic Kidney Disease and Its Progression: A Systematic Review
Authors: Justin B. Echouffo-Tcheugui, Andre P. Kengne
Journal: PLoS Medicine (2012)

Background Chronic kidney disease (CKD) is common, and associated with increased risk of cardiovascular disease and end-stage renal disease, which are potentially preventable through early identification and treatment of individuals at risk. Although risk factors for occurrence and progression of CKD have been identified, their utility for CKD risk stratification through prediction models remains unclear. We critically assessed risk models to predict CKD and its progression, and evaluated their suitability for clinical use. Methods and Findings We systematically searched MEDLINE and Embase (1 January 1980 to 20 June 2012). Dual review was conducted to identify studies that reported on the development, validation, or impact assessment of a model constructed to predict the occurrence/presence of CKD or progression to advanced stages. Data were extracted on study characteristics, risk predictors, discrimination, calibration, and reclassification performance of models, as well as validation and impact analyses. We included 26 publications reporting on 30 CKD occurrence prediction risk scores and 17 CKD progression prediction risk scores. The vast majority of CKD risk models had acceptable-to-good discriminatory performance (area under the receiver operating characteristic curve>0.70) in the derivation sample. Calibration was less commonly assessed, but overall was found to be acceptable. Only eight CKD occurrence and five CKD progression risk models have been externally validated, displaying modest-to-acceptable discrimination. Whether novel biomarkers of CKD (circulatory or genetic) can improve prediction largely remains unclear, and impact studies of CKD prediction models have not yet been conducted. Limitations of risk models include the lack of ethnic diversity in derivation samples, and the scarcity of validation studies. The review is limited by the lack of an agreed-on system for rating prediction models, and the difficulty of assessing publication bias. Conclusions The development and clinical application of renal risk scores is in its infancy; however, the discriminatory performance of existing tools is acceptable. The effect of using these models in practice is still to be explored. Please see later in the article for the Editors' Summary
FDG Injection Site Extravasation
Authors: Luke I. Sonoda, Subhadip Ghosh-Ray, Bal Sanghera, Jeanette Dickson, Wai Lup Wong
Journal: Clinical Nuclear Medicine (2012)

18F-FDG PET/CT plays an important role in the management of non-small-cell lung cancers (NSCLC). The treatment options for NSCLC depend upon the initial staging of the disease. The authors report a case with a potential pitfall of overlooking a site of FDG uptake as radiopharmaceutical extravasation at an injection site. The PET/CT demonstrated a T2a N2 bronchial carcinoma, with a solitary focus of FDG uptake at the left antecubital fossa where FDG was administered. Careful interpretation of the images reveals a solitary skeletal metastasis in the left proximal ulna, which makes the disease stage IV rather than IIIA, leading to a significant difference in treatment.
Mechanism of Methacholine Dose-Response Plateaus in Normal Subjects
Authors: B. J. MOORE, G. G. KING, Y. D'YACHKOVA, H. R. AHMAD, PETER D. PARÉ
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Normal subjects develop plateaus on dose-response curves produced from inhalation challenge tests with bronchoconstricting agonists. These plateaus occur after only mild degrees of airway narrowing despite the fact that, if unloaded, maximally activated airway smooth muscle (ASM) should be able to cause airway closure. Plateaus may develop because, despite maximal activation, the muscle load provided by lung parenchymal recoil and tidal swings in airway transmural pressure are sufficient to prevent further ASM shortening. Alternatively, progressive ASM activation may occur throughout the plateau, but progressive hyperinflation and/or parenchymal stiffening could increase parenchymal load and attenuate further airway narrowing. In the first case, maximal ASM activation causes the plateau and in the second case the plateau is caused by progressive activation balanced by progressive loading. To test which of these mechanisms is responsible for the plateau, we measured pulmonary resistance (Rl) and the maximal, minimal, and mean pulmonary elastic recoil pressure (Pel max, Pel min, and Pel mean) during tidal breathing throughout methacholine challenge in 10 normal subjects. Pel mean served as our measure of ASM afterload. Subjects swallowed an esophageal balloon and inhaled doubling concentrations of methacholine (1 to 256 mg/ml). Rl was measured after each dose, as was Pel. All subjects developed a plateau on the dose-response curve defined by < 25% change in Rl over three successive doses. During the Rl plateau, there was no significant further increase in Pel mean, i.e., Pel mean also plateaued. These data are consistent with the hypothesis that maximal activation of ASM is balanced by an equal afterload at the maximal dose-response plateau. Airway hyperresponsiveness could result from a failure of afterload to attenuate muscle shortening after maximal activation.
Primary Hyperparathyroidism, Psychiatric Manifestations, Diagnosis and Management
Authors: Baruch Spivak, Marguerite Radvan, Richard Ohring, Abraham Weizman
Journal: Psychotherapy and Psychosomatics (1989)

Mental manifestations of primary hyperparathyroidism simulate a wide spectrum of psychiatric disorders. Definitive surgical treatment results in long-lasting full recovery. The 2 cases presented demonstrate this. The clinical diagnostic and therapeutic aspects of primary hyperparathyroidism, with an emphasis on neuropsychiatric manifestations, are discussed. Early diagnosis of hypercalcemia can prevent unnecessary and potentially harmful treatment with antidepressive, anxiolytic or antipsychotic drugs, which can further depress the cognitive state of the patients, and can aggravate the mental symptoms.
Evidence of Apoptosis in Arrhythmogenic Right Ventricular Dysplasia
Authors: Ziad Mallat, Alain Tedgui, Fabrice Fontaliran, Robert Frank, Michel Durigon, Guy Fontaine
Journal: New England Journal of Medicine (1996)

Arrhythmogenic right ventricular dysplasia, a disorder that may lead to severe ventricular arrhythmias and sudden death, is characterized by the progressive replacement of myocardial cells by fat and fibrous tissue. We examined whether the loss of myocardial cells in this disease could result from cell death by apoptosis (programmed cell death).
Ackerman and del Regato's Cancer: Diagnosis, Treatment, and Prognosis
Authors: Walter G. Gunn
Journal: JAMA (1985)

The first edition of this classic text on cancer appeared in the late 1940s. In a field as rapidly changing as that of cancer, to have successive editions from the same source after 20 years would be remarkable. Here we have a work that has survived twice as long. Why? Most texts on clinical cancer are either so general as to have little meaning for the physician who needs information on a specific problem or so detailed with recipes for treatment that they become little more than extended progress reports, obsolete almost from the time of printing. Ackerman and del Regato's original concept was to give the medical student, resident, and practitioner the background information to enable a coherent approach to the cancer patient or problem. They wrote the entire text themselves, selected excellent anatomical sketches, photographs, and microphotographs to illustrate main points, included complete and pertinent references, and prepared
Endoscopic Findings in Tangier Disease
Authors: Th. Gheorghiu, G. Assmann, H. Schaefer
Journal: Endoscopy (1976)

Tangier disease is a rare familial metabolic disorder due to the absence of normal plasma HDL. Gholesteryl esters are stored in various tissues, mostly in reticulo-endothelial foam-cells; enlarged tonsils, (hepato) splenomegaly and polyneuro-pathy are the principal clinical manifestations. The very unusual endoscopical findings in a recently observed patient might contribute to the detection of this disease: the uneven surface of the liver has a salmon-bright red, strawberry-like color; the enlarged spleen is covered by numerous minute, yellowish, subcapsular "stipples" and some isolated, irregular, yolk-yellow patches; the rectal, and even more the colonie mucosa, presents itself with round, brownish-red spots, diffusely scattered on a yellow-orange back-ground ("cheetah fur-like").
7-Ketocholesterol induces reversible cytochrome c release in smooth muscle cells in absence of mitochondrial swelling
Authors: C SEYE
Journal: Cardiovascular Research (2004)

7-Ketocholesterol, a major oxysterol in oxidized low-density lipoproteins in advanced atherosclerotic plaques, induces vascular smooth muscle cell (SMC) death. We investigated whether cytochrome c release participated in SMC death induced by 7-ketocholesterol and whether the processes were reversible.SMC cultures derived from the rabbit aorta were exposed to 25 microM 7-ketocholesterol. Cytochrome c and Bax were studied by means of immunofluorescence and immunoblotting, apoptosis by the TUNEL technique and mitochondrial structure by transmission electron microscopy.7-Ketocholesterol induced rapid upregulation of the proapoptotic protein Bax and its translocation from cytosol into the mitochondria (4 h). This was followed by mitochondrial cytochrome c release (65% at 8 h) into the cytosol, which was almost complete at 16 h. The mitochondria became spherical and ultracondensed, without showing signs of lysis. They clustered around the nucleus and were wrapped by wide cisternae of the rough endoplasmic reticulum. Cytochrome c release was not blocked by the pan-caspase inhibitor zVAD-fmk, in contrast to DNA fragmentation and SMC loss. Interestingly, upon removal of 7-ketocholesterol after 16 h and re-exposure to serum for 24 h, the mitochondrial cytochrome c content, their transmembrane potential and TUNEL labelling normalised and SMC loss decreased. However, none of these cell death markers was rescued when the SMCs had been exposed to the oxysterol for 24 h.The results indicate that cytochrome c release during oxysterol-induced SMC apoptosis is not caspase-dependent and occurs as a result of a reversible mitochondrial conformational change rather than swelling and rupture of the outer membrane. The reversibility of these events suggests that the apoptotic cascade could be arrested before a point of no return.
Early biochemical responses of the small intestine of coeliac patients to wheat gluten.
Authors: D S Bailey, A R Freedman, S C Price, D Chescoe, P J Ciclitira
Journal: Gut (1989)

The pathogenesis of coeliac disease has been investigated by studying the response of small intestinal hydrolases in patients with coeliac disease subject to gluten challenge. Small intestinal biopsies taken before and two and a half hours after a gluten challenge in five patients with coeliac disease who had been maintained on a gluten free diet were examined by a combination of electron and light microscopy, organ culture, pulse chase biosynthetic labelling, SDS-PAGE and autoradiography. Before the challenge, the small intestinal biopsies showed nearly normal morphology. Two and a half hours after the challenge there was deterioration in villus architecture, distortion of microvillus structure, disorganisation of the intermicrovillus pit region, an increase in lysosome like bodies in the apical cytoplasm of the luminal enterocytes and pronounced hypertrophy of the rough endoplasmic reticulum of these cells. SDS-PAGE of small intestinal biopsies from four treated coeliac patients before gluten challenge revealed normal microvillus membrane and hydrolase composition. There was a generalised reduction but no specific alteration in the pattern of polypeptide synthesis in the mucosa of the small intestine in these subjects two and a half hours after the gluten challenge. These results suggest that the generalised reduction in small intestinal brush border enzymes in coeliac patients is not the primary pathogenetic mechanism and represents a secondary effect.
Acute megakaryo-monocytic leukemia with acute myelofibrosis
Authors: Tohru Murayama, Shion Imoto, Hiroshi Matsuoka, Nobuko Iwata, Taizo Taniguchi, Mitsuhiro Ito, Kazuo Chihara, Toshimitsu Matsui, Yoshitake Hayashi, Chiho Obayashi
Journal: American Journal of Hematology (1996)
Alpine climate treatment of atopic dermatitis: a systematic review
Authors: K. B. Fieten, A. C. G. Weststrate, E. J. van Zuuren, C. A. Bruijnzeel-Koomen, S. G. M. A. Pasmans
Journal: Allergy (2014)

Climate therapy has been used for decades in the treatment of atopic dermatitis (AD), but evidence of its effectiveness has not yet been assessed systematically. A systematic literature search in Medline, Embase, and the Cochrane library was performed to identify all original studies concerning alpine climate treatment. The risk of bias of individual studies was assessed following the Cochrane Handbook, and level of evidence was rated using GRADE guidelines. Fifteen observational studies were included concerning 40 148 patients. Four studies concerning 2670 patients presented follow-up data over a period of 1 year. Disease activity decreased in the majority of patients during treatment (96% of n = 39 006) and 12-month follow-up (64% of n = 2670). Topical corticosteroid use could often be reduced or stopped during treatment (82% of n = 1178) and during 12-month follow-up (72% of n = 3008). Quality assessment showed serious study limitations, therefore resulting in a very low level of evidence for the described outcomes. Randomized controlled trials designed with a follow-up period including well-defined patient populations, detailed description and measurement of applied interventions during climate therapy and using validated outcomes including cost-effectiveness parameters, are required to improve the evidence for alpine climate therapy as an effective treatment for patients with AD.