tbuckley/cabot-search huggingface dataset:
Obesity in middle age and future risk of dementia: Authors' reply
Authors: Rachel Whitmer, Charles P Quesenberry, Kristine Yaffe
Journal: BMJ (2005)

Prognosis in obesity Older people should not be misinformed about being overweightEditor-With reference to the editorial by Lean on prognosis in obesity, 1 advising apparently overweight older people to lose weight may do more harm than good.Evidence suggests that the risks of being "overweight" decrease with increasing age.On the basis of mortality, the ideal body mass index (BMI) is higher in older than young adults, with an optimum BMI for people older than 65 in the young adult "overweight" range of 27-30 kg/m 2 . 2 In a systematic review, Heiat et al concluded that the relation between BMI and mortality in people older than 65 is a flat bottomed, Ushaped curve, with mortality rising only at BMI > 31 kg/m 2 and perhaps not at any BMI in people older than 75. 2 Weight loss is more common than weight gain in older people, and associated with poor outcomes, even when the weight loss is intentional and the person was "overweight" at baseline. [3]4][5] In the prospective cardiovascular health study of some 4700 community dwelling people older than 65, weight loss of more than 5% over three years was substantially more common than weight gain of more than 5%. 3 Weight loss, but not weight gain, was associated with a significantly increased risk of mortality (relative risk 1.67, 95% confidence interval 1.29 to 2.15). 3 The association of increased mortality with weight loss persisted even at the highest third of baseline weight. 3 In a study of older men with BMI ≥ 30 kg/m 2 , intentional weight loss was associated (P < 0.001) with a greater rate of hip bone loss ( -1.7%/year) than in men with no weight loss ( -0.1%/year) or weight gain (0.5%/year). 5 The indiscriminate application of evidence from studies in younger adults to the management of older people is hazardous.We believe that many older people are trying to lose weight inappropriately.There is a need to ensure that most of our elders are given appropriate advice: "Keep physically active, eat sensibly, and maintain weight."
FDG PET/CT Images Demonstrating Fournier Gangrene With Bilateral Pelvic Muscle Extension in a Patient With Recurrent Rectosigmoid Cancer
Authors: Chia-Tien Hsu, Pan-Fu Kao, Chi-Chou Huang, Hsin-Hui Huang, Jong-Kang Lee
Journal: Clinical Nuclear Medicine (2013)

A 71-year-old male patient with Parkinsonism was referred for an 18F-FDG PET/CT scan for suspicious recurrence of rectosigmoid adenocarcinoma. The FDG PET/CT scan revealed increased FDG uptakes in the lower pelvic region around the wall of the rectal stump, with extension to the bilateral pelvic sidewalls and the right gluteous minimus muscle. In addition, multiple small air bubbles were noted in the lesions on the attenuation CT images. Fournier gangrene was diagnosed. After treatment with intravenous antibiotics and debridement with sigmoidoscopic irrigation, the patient was discharged and remained uneventful during clinical follow-up for 50 days.
Systemic Therapy for Non–clear Cell Renal Cell Carcinomas: A Systematic Review and Meta-analysis
Authors: Francisco E. Vera-Badillo, Arnoud J. Templeton, Ignacio Duran, Alberto Ocana, Paulo de Gouveia, Priya Aneja, Jennifer J. Knox, Ian F. Tannock, Bernard Escudier, Eitan Amir
Journal: European Urology (2014)
EGFR Mutation-Induced Alternative Splicing of Max Contributes to Growth of Glycolytic Tumors in Brain Cancer
Authors: Ivan Babic, Erik S. Anderson, Kazuhiro Tanaka, Deliang Guo, Kenta Masui, Bing Li, Shaojun Zhu, Yuchao Gu, Genaro R. Villa, David Akhavan, David Nathanson, Beatrice Gini, Sergey Mareninov, Rui Li, Carolina Espindola Camacho, Siavash K. Kurdistani, Ascia Eskin, Stanley F. Nelson, William H. Yong, Webster K. Cavenee, Timothy F. Cloughesy, Heather R. Christofk, Douglas L. Black, Paul S. Mischel
Journal: Cell Metabolism (2013)
Witnessing Insanity: Madness and Mad-Doctors in the English Court
Authors: Harold J. Bursztajn
Journal: JAMA (1996)

This interesting work of intellectual history articulates a point of view with which I disagree, as will most physicians. Nonetheless, it is enjoyable, thought-provoking, and important. Its scope is far beyond its modest title.<i>Witnessing Insanity</i>has clear implications beyond psychiatry and forensic psychiatry for the practicing clinician coping daily with managed care receivers who question "medical necessity." Mr Eigen, a sociologist, has set out to systematically investigate medical testimony in British insanity trials from its beginnings in 1760 through 1843. It was in 1843 that the "McNaughton rule" for insanity was formulated, thereby setting forth a legal standard that medical testimony had to address. Perhaps most enlightening, one learns that the philosopher John Locke, so influential to the American revolutionary founding fathers as expressed in the Declaration of Independence and the Constitution, was also remarkably influential in the emerging field of medical psychology. Thus, writes Eigen, "Locke's schema and
Endoglin expression in blood and endothelium is differentially regulated by modular assembly of the Ets/Gata hemangioblast code
Authors: John E. Pimanda, Wan Y. I. Chan, Nicola K. Wilson, Aileen M. Smith, Sarah Kinston, Kathy Knezevic, Mary E. Janes, Josette-Renée Landry, Anja Kolb-Kokocinski, Jonathan Frampton, David Tannahill, Katrin Ottersbach, George A. Follows, Georges Lacaud, Valerie Kouskoff, Berthold Göttgens
Journal: Blood (2008)
Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis.
Authors: T A Guise, J J Yin, S D Taylor, Y Kumagai, M Dallas, B F Boyce, T Yoneda, G R Mundy
Journal: Journal of Clinical Investigation (1996)

Breast cancer almost invariably metastasizes to bone in patients with advanced disease and causes local osteolysis. Much of the morbidity of advanced breast cancer is a consequence of this process. Despite the importance of the problem, little is known of the pathophysiology of local osteolysis in the skeleton or its prevention and treatment. Observations in patients with bone metastases suggest that breast cancer cells in bone express parathyroid hormone-related protein (PTHrP) more frequently than in soft tissue sites of metastasis or in the primary tumor. Thus, the role of PTHrP in the causation of breast cancer metastases in bone was examined using human breast cancer cell lines. Four of eight established human breast cancer cell lines expressed PTHrP and one of these cell lines, MDA-MB-231, was studied in detail using an in vivo model of osteolytic metastases. Mice inoculated with MDA-MB-231 cells developed osteolytic bone metastasis without hypercalcemia or increased plasma PTHrP concentrations. PTHrP concentrations in bone marrow plasma from femurs affected with osteolytic lesions were increased 2.5-fold over corresponding plasma PTHrP concentrations. In a separate experiment, mice were treated with either a monoclonal antibody directed against PTHrP(1-34), control IgG, or nothing before tumor inoculation with MDA-MB-231 and twice per week for 26 d. Total area of osteolytic lesions was significantly lower in mice treated with PTHrP antibodies compared with mice receiving control IgG or no treatment. Histomorphometric analysis of bone revealed decreased osteoclast number per millimeter of tumor/bone interface and increased bone area, as well as decreased tumor area, in tumor-bearing animals treated with PTHrP antibodies compared with respective controls. These results indicate that tumor-produced PTHrP can cause local bone destruction in breast cancer metastatic to bone, even in the absence of hypercalcemia or increased circulating plasma concentrations of PTHrP. Thus, PTHrP may have an important pathogenetic role in the establishment of osteolytic bone lesions in breast cancer. Neutralizing antibodies to PTHrP may reduce the development of destructive bone lesions as well as the growth of tumor cells in bone.
Double contrast enema and colonoscopy in polyp detection.
Authors: F T Fork
Journal: Gut (1981)

The diagnostic accuracy of double contrast enema was assessed by colonoscopy of 250 consecutive patients with polypoid lesions that were observed at double contrast enema. The enema method detected 90% of all existing polypoid lesions, and gave false positive results in less than 3.5% Colonoscopy revealed 91% of the lesions. Double contrast enema is suitable as a screening procedure and, when used in combination with colonoscopy, only very few polyps will escape detection. The large number of neoplastic polyps detected in this retrospective series emphasises the necessity for a careful radiographic technique combined with colonoscopy to disclose and treat these potentially malignant lesions of the colon.
Market Forces and Unsponsored Research in Academic Health Centers
Authors: Joel S. Weissman
Journal: JAMA (1999)

ContextIncreased competitive pressures on academic health centers may result in reduced discretionary funds from patient care revenues to support the performance of unsponsored research, including institutionally funded and faculty-supported activities.ObjectiveTo measure the amount and distribution of unsponsored research activities and their outcomes.Design and SettingSurvey conducted in academic year 1996-1997 of 2336 research faculty in 117 medical schools. Responses were weighted to provide national estimates.Main Outcome MeasuresInstitutionally funded research as a proportion of total direct costs of research was compared across stages of market competition. Logistic regression was used to assess the relationship of performing unsponsored research to faculty characteristics and market stage.ResultsOverall, 43% of faculty received institutional funding for research. Young faculty were more likely than others to receive institutional support (adjusted odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.9; P = .004). The amount of institutional support as a proportion of total funding was more than twice as high in less competitive markets (6.1%) compared with the most competitive markets (2.5%; P = .05). Most faculty (55%) performed faculty-supported research. Clinical researchers (OR, 1.6; 95% CI, 1.1-2.3), principal investigators (OR, 4.3; 95% CI, 2.8-7.0), faculty with high levels of research effort (OR, 6.2; 95% CI, 4.0-9.5) or institutional funding (OR, 1.9; 95% CI, 1.4-2.6), and faculty in the most competitive markets (OR, 1.9; 95% CI, 1.4-2.5) were more likely than others to conduct faculty-supported research. When undertaken by clinical researchers, these activities were supported by clinical income, extra hours worked, and discretionary funds, and often led to publications (76%) or grant awards (51%).ConclusionsMany academic health center faculty receive institutional support to conduct their research or fund the research themselves. Market pressures may be affecting the level of institutional funding available to faculty.
Expression and localization of macrophage elastase (matrix metalloproteinase-12) in abdominal aortic aneurysms.
Authors: J A Curci, S Liao, M D Huffman, S D Shapiro, R W Thompson
Journal: Journal of Clinical Investigation (1998)

Elastolytic matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of abdominal aortic aneurysms (AAA), a disorder characterized by chronic aortic wall inflammation and destruction of medial elastin. The purpose of this study was to determine if human macrophage elastase (HME; MMP-12) might participate in this disease. By reverse transcription-polymerase chain reaction, HME mRNA was consistently demonstrated in AAA and atherosclerotic occlusive disease (AOD) tissues (six of six), but in only one of six normal aortas. Immunoreactive proteins corresponding to proHME and two products of extracellular processing were present in seven of seven AAA tissue extracts. Total HME recovered from AAA tissue was sevenfold greater than normal aorta (P < 0.001), and the extracted enzyme exhibited activity in vitro. Production of HME was demonstrated in the media of AAA tissues by in situ hybridization and immunohistochemistry, but HME was not detected within the media of normal or AOD specimens. Importantly, immunoreactive HME was specifically localized to residual elastin fragments within the media of AAA tissue, particularly areas adjacent to nondilated normal aorta. In vitro, the fraction of MMP-12 sequestered by insoluble elastin was two- to fivefold greater than other elastases found in AAA tissue. Therefore, HME is prominently expressed by aneurysm-infiltrating macrophages within the degenerating aortic media of AAA, where it is also bound to residual elastic fiber fragments. Because elastin represents a critical component of aortic wall structure and a matrix substrate for metalloelastases, HME may have a direct and singular role in the pathogenesis of aortic aneurysms.
AN IMPROVED AND SIMPLE OPERATING MASK
Authors: Ellice McDonald
Journal: JAMA (1925)

Lecturing during an operative clinic is difficult at the best, and is made more difficult by the voice being muffled by a mask. The ordinary gauze mask is a smothering affair, and the alternative, a wire chloroform mask type that hooks over the ears, is cumbrous. I have found that it is possible by sewing a strip of half inch rubber tube at the top of the mask, three-quarters inch from the upper border, to make a comfortable mask, which is yet simple. The rubber should be tied in the middle by a penetrating suture three-quarters inch from the angle. This suture is tied around the tube, and it maintains the angle and spring of the tube. The tube is then sewed to the material by stitches, one at each end and one in the middle. The cloth should be a little larger than the usual mask. The mask is
The Action of Insulin on Cells
Authors: William W. Engstrom
Journal: JAMA (1962)

The author has set as his task to review, "in current chemical terms, the effects of insulin upon carbohydrate, fat and nitrogen metabolism in the principal insulin-responsive tissues. After the individual effects have been identified, an attempt is made to devise a mechanism of action which will account for these separate effects." In this task, the author has reviewed the subject very well. He has not merely compiled isolated experiments, but has attempted, and generally succeeded in, intelligent interpretation of the results. His speculations on the possible fundamental action of insulin, in contrast to its observable effects, are interesting. Others have presented different hypotheses, and again others similar ones; while unproved, these speculations are useful in guiding future research. The first portion of the book is concerned with the effects of insulin on specific tissues, e.g., muscle, liver, adipose, and so forth. Next, the influence of insulin on permeability of
Dialogue in the degenerate case?
Authors: Patrick G. T. Healey
Journal: Behavioral and Brain Sciences (2004)

The interactive alignment model treats within- and between-individual co-ordination as essentially equivalent. It is argued that this leads to a conservative account of alignment that presupposes high levels of linguistic and conceptual co-ordination. Data from the maze task are used to argue that this approach is not sufficient to account for important co-ordination phenomena.
Confidence intervals for effect parameters common in cancer epidemiology.
Authors: T Sato
Journal: Environmental Health Perspectives (1990)

This paper reviews approximate confidence intervals for some effect parameters common in cancer epidemiology. These methods have computational feasibility and give nearly nominal coverage rates. In the analysis of crude data, the simplest type of epidemiologic analysis, parameters of interest are the odds ratio in case-control studies and the rate ratio and difference in cohort studies. These parameters can estimate the instantaneous-incidence-rate ratio and difference that are the most meaningful effect measures in cancer epidemiology. Approximate confidence intervals for these parameters including the classical Cornfield's method are mainly based on efficient scores. When some confounding factors exist, stratified analysis and summary measures for effect parameters are needed. Since the Mantel-Haenszel estimators have been widely used by epidemiologists as summary measures, confidence intervals based on the Mantel-Haenszel estimators are described. The paper also discusses recent developments in these methods.
Inhibition of SREBP by a Small Molecule, Betulin, Improves Hyperlipidemia and Insulin Resistance and Reduces Atherosclerotic Plaques
Authors: Jing-Jie Tang, Jia-Gui Li, Wei Qi, Wen-Wei Qiu, Pei-Shan Li, Bo-Liang Li, Bao-Liang Song
Journal: Cell Metabolism (2011)
cAMP and Calcemia
Authors: FRANCIS A. NEELON
Journal: Annals of Internal Medicine (1977)

Editorial Notes1 June 1977cAMP and CalcemiaFRANCIS A. NEELON, M.D.FRANCIS A. NEELON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-86-6-821 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptHypercalcemia is a common and vexing clinical problem. The clinician must decide whether serum calcium is raised because of hyperparathyroidism or one of eight or more other causes, each requiring remarkably different treatments. Over the past several decades a number of tests have been proposed to assist in the differential diagnosis of hypercalcemia. In general, each test has been greeted with enthusiasm only to fall into clinical disfavor because of difficulties in applying it in ambiguous cases. The measurement of parathyroid hormone (PTH) by radioimmunoassay is among the most sophisticated of such tests, but technical and biological problems appear to...References1. ARNAUDGOLDSMITHBORDIER CRP: Influence of immunoheterogeneity of circulating parathyroid hormone on results of radioimmunoassays of serum in man. Am J Med 56:785-793, 1974 CrossrefMedlineGoogle Scholar2. DREZNERNEELONCURTIS MFH: Renal cyclic adenosine monophosphate: an accurate index of parathyroid function. Metabolism 25:1103-1112, 1976 CrossrefMedlineGoogle Scholar3. KAMINSKYBROADUSHARDMAN NAJ: Effects of parathyroid hormone on plasma and urinary adenosine 3′,5′-monophosphate in man. J Clin Invest 49:2387-2395, 1970 CrossrefMedlineGoogle Scholar4. MURADPAK FC: Urinary excretion of adenosine 3′,5′-monophosphate and guanosine 3′,5′-monophosphate. N Engl J Med 286:1382-1387, 1972 CrossrefMedlineGoogle Scholar5. NEELONDREZNERBIRCH FMB: Urinary cyclic adenosine monophosphate as an aid in the diagnosis of hyperparathyroidism. Lancet 1:631-634, 1973 CrossrefMedlineGoogle Scholar6. MADSENBADAWIJØRGENSEN SIF: Urinary cyclic AMP. Acta Med Scand 200:195-199, 1976 CrossrefMedlineGoogle Scholar7. SHAWOLDHAMROSOFF JSL: Urinary cyclic AMP analyzed as a function of the serum calcium and parathyroid hormone in the differential diagnosis of hypercalcemia. J Clin Invest 59:14-21, 1977 CrossrefMedlineGoogle Scholar8. BABKABOWERSODE JRJ: Nephrogenous cyclic AMP levels in primary hyperparathyroidism. Arch Intern Med 136:1140-1144, 1976 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Medicine Duke University Medical Center Durham, North Carolina PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByBiochemical effects of oral sodium phosphateDiagnosis and Treatment of Primary HyperparathyroidismHypercalcemia of Malignancy 1 June 1977Volume 86, Issue 6Page: 821-822KeywordsCalciumCyclic adenosine monophosphateFallsHypercalcemiaHyperparathyroidismParathyroid hormoneRadioimmunoassays Issue Published: 1 June 1977 PDF DownloadLoading ...
Initial Misunderstanding Resulting From Title
Authors: Hugo S. Moreno
Journal: JAMA (1984)

To the Editor.—  I found the title of the article by Goffman et al 1 regarding a case of acute dyspnea in a young woman to be misleading. I do not see any relevance between the fact that the patient was  oral contraceptive pills and the final diagnosis of sarcoidosis.  Why did the authors not use the fact that the patient was blond or brunette, obese or slender, or tall or short instead of the phrase taking birth control pills?
"Go upstream, young man": lessons learned from the p38 saga
Authors: D Hammaker, G S Firestein
Journal: Annals of the Rheumatic Diseases (2009)

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor known with a poor survival rate despite current advances in the field of cancer. Additional research into the pathophysiology of GBM is urgently needed given the devastating nature of this disease. Recent studies have revealed the unique cellular physiology of GBM cells as compared with healthy astrocytes. Intriguingly, GBM cells are incapable of de novo cholesterol synthesis via the mevalonate pathway. Thus, the survival of GBM cells depends on cholesterol uptake via low-density lipoprotein receptors (LDLRs) in the form of apolipoprotein-E-containing lipoproteins and ATP-binding cassette transporter A1 (ABCA1) that efflux surplus cholesterol out of cells. Liver X receptors regulate intracellular cholesterol levels in neurons and healthy astrocytes through changes in the expression of LDLR and ABCA1 in response to cholesterol and its derivatives. In GBM cells, due to the dysregulation of this surveillance pathway, there is an accumulation of intracellular cholesterol. Furthermore, intracellular cholesterol regulates temozolomide-induced cell death in glioblastoma cells via accumulation and activation of death receptor 5 in plasma membrane lipid rafts. The mevalonate pathway and autophagy flux are also fundamentally related with implications for cell health and death. Thus, via cholesterol metabolism, the mevalonate pathway may be a crucial player in the pathogenesis and treatment of GBM where our current understanding is still lacking. Targeting cholesterol metabolism in GBM may hold promise as a novel adjunctive clinical therapy for this devastating cancer.
A Chaperone Enhances Blood α-Glucosidase Activity in Pompe Disease Patients Treated With Enzyme Replacement Therapy
Authors: Giancarlo Parenti, Simona Fecarotta, Giancarlo la Marca, Barbara Rossi, Serena Ascione, Maria Alice Donati, Lucia Ovidia Morandi, Sabrina Ravaglia, Anna Pichiecchio, Daniela Ombrone, Michele Sacchini, Maria Barbara Pasanisi, Paola De Filippi, Cesare Danesino, Roberto Della Casa, Alfonso Romano, Carmine Mollica, Margherita Rosa, Teresa Agovino, Edoardo Nusco, Caterina Porto, Generoso Andria
Journal: Molecular Therapy (2014)

Enzyme replacement therapy is currently the only approved treatment for Pompe disease, due to acid α-glucosidase deficiency. Clinical efficacy of this approach is variable, and more effective therapies are needed. We showed in preclinical studies that chaperones stabilize the recombinant enzyme used for enzyme replacement therapy. Here, we evaluated the effects of a combination of enzyme therapy and a chaperone on α-glucosidase activity in Pompe disease patients. α-Glucosidase activity was analyzed by tandem-mass spectrometry in dried blood spots from patients treated with enzyme replacement therapy, either alone or in combination with the chaperone N-butyldeoxynojirimycin given at the time of the enzyme infusion. Thirteen patients with different presentations (3 infantile-onset, 10 late-onset) were enrolled. In 11 patients, the combination treatment resulted in α-glucosidase activities greater than 1.85-fold the activities with enzyme replacement therapy alone. In the whole patient population, α-glucosidase activity was significantly increased at 12 hours (2.19-fold, P = 0.002), 24 hours (6.07-fold, P = 0.001), and 36 hours (3.95-fold, P = 0.003). The areas under the curve were also significantly increased (6.78-fold, P = 0.002). These results suggest improved stability of recombinant α-glucosidase in blood in the presence of the chaperone.