tbuckley/cabot-search huggingface dataset:
5-year incidence of atherosclerotic vascular disease in relation to general risk factors, insulin level, and abnormalities in lipoprotein composition in non-insulin-dependent diabetic and nondiabetic subjects.
Authors: M I Uusitupa, L K Niskanen, O Siitonen, E Voutilainen, K Pyörälä
Journal: Circulation (1990)

The 5-year incidence of myocardial infarction and claudication was examined in a group of middle-aged patients (n = 133, 70 men and 63 women) with newly diagnosed non-insulin-dependent diabetes and nondiabetic control subjects (n = 144, 62 men and 82 women). The effects of general risk factors, plasma insulin level, and lipoprotein abnormalities on the incidence of myocardial infarction and claudication were also evaluated by univariate analyses in both diabetic patients and nondiabetic subjects and by multivariate analyses combining both groups. The age-adjusted incidence of myocardial infarction was higher both in diabetic men (19.4%) and diabetic women (11.0%) than in nondiabetic men (3.2%, p = 0.009) and nondiabetic women (3.0%, p = 0.047). Similarly, the age-adjusted incidence of claudication was higher among the diabetic patients (20.3% vs. 8.0% for men, p = 0.06; 21.8% vs. 4.2% for women, p = 0.003). None of the general risk factors (i.e., low density lipoprotein [LDL] cholesterol, blood pressure, smoking, and high density lipoprotein [HDL] cholesterol) showed an association with the risk of myocardial infarction either in the diabetic or nondiabetic groups of subjects, but an ischemic electrocardiographic abnormality at the baseline examination predicted myocardial infarction in diabetic men. In univariate analyses in diabetic subjects, high serum total cholesterol, low HDL cholesterol, high very low density lipoprotein (VLDL) cholesterol, and high total, LDL and VLDL triglycerides, and in nondiabetic subjects, high VLDL cholesterol and LDL triglycerides were associated with the appearance of claudication. In multivariate analyses including both diabetic and control subjects, only diabetes had an independent association with myocardial infarction, whereas smoking, high LDL triglycerides or VLDL cholesterol, and high fasting plasma insulin showed independent relations to claudication. The present results indicate that changes in lipoprotein composition characteristic of non-insulin-dependent diabetes are atherogenic and increase the risk of atherosclerotic vascular disease. Furthermore, high plasma insulin might also be involved in atherogenesis, independent of lipoprotein abnormalities.
Calculating excess lifetime risk in relative risk models.
Authors: M Vaeth, D A Pierce
Journal: Environmental Health Perspectives (1990)

When assessing the impact of radiation exposure it is common practice to present the final conclusions in terms of excess lifetime cancer risk in a population exposed to a given dose. The present investigation is mainly a methodological study focusing on some of the major issues and uncertainties involved in calculating such excess lifetime risks and related risk projection methods. The age-constant relative risk model used in the recent analyses of the cancer mortality that was observed in the follow-up of the cohort of A-bomb survivors in Hiroshima and Nagasaki is used to describe the effect of the exposure on the cancer mortality. In this type of model the excess relative risk is constant in age-at-risk, but depends on the age-at-exposure. Calculation of excess lifetime risks usually requires rather complicated life-table computations. In this paper we propose a simple approximation to the excess lifetime risk; the validity of the approximation for low levels of exposure is justified empirically as well as theoretically. This approximation provides important guidance in understanding the influence of the various factors involved in risk projections. Among the further topics considered are the influence of a latent period, the additional problems involved in calculations of site-specific excess lifetime cancer risks, the consequences of a leveling off or a plateau in the excess relative risk, and the uncertainties involved in transferring results from one population to another. The main part of this study relates to the situation with a single, instantaneous exposure, but a brief discussion is also given of the problem with a continuous exposure at a low-dose rate.
Androgen deprivation–induced NCoA2 promotes metastatic and castration-resistant prostate cancer
Authors: Jun Qin, Hui-Ju Lee, San-Pin Wu, Shih-Chieh Lin, Rainer B. Lanz, Chad J. Creighton, Francesco J. DeMayo, Sophia Y. Tsai, Ming-Jer Tsai
Journal: Journal of Clinical Investigation (2014)

A major clinical hurdle for the management of advanced prostate cancer (PCa) in patients is the resistance of tumors to androgen deprivation therapy (ADT) and their subsequent development into castration-resistant prostate cancer (CRPC). While recent studies have identified potential pathways involved in CRPC development, the drivers of CRPC remain largely undefined. Here we determined that nuclear receptor coactivator 2 (NCoA2, also known as SRC-2), which is frequently amplified or overexpressed in patients with metastatic PCa, mediates development of CRPC. In a murine model, overexpression of NCoA2 in the prostate epithelium resulted in neoplasia and, in combination with Pten deletion, promoted the development of metastasis-prone cancer. Moreover, depletion of NCoA2 in PTEN-deficient mice prevented the development of CRPC. In human androgen-sensitive prostate cancer cells, androgen signaling suppressed NCoA2 expression, and NCoA2 overexpression in murine prostate tumors resulted in hyperactivation of PI3K/AKT and MAPK signaling, promoting tumor malignance. Analysis of PCa patient samples revealed a strong correlation among NCoA2-mediated signaling, disease progression, and PCa recurrence. Taken together, our findings indicate that androgen deprivation induces NCoA2, which in turn mediates activation of PI3K signaling and promotes PCa metastasis and CRPC development. Moreover, these results suggest that the inhibition of NCoA2 has potential for PCa therapy.
Alterations of calcium-regulatory proteins in heart failure
Authors: Gerd Hasenfuss
Journal: Cardiovascular Research (1998)

Time for primary review 27 days.

During the last decade there was accumulating evidence that alterations of excitation-contraction (EC) coupling may play a critical role in the pathophysiology of myocardial failure. EC-coupling comprises processes involved in calcium activation of contractile proteins and the subsequent removal of calcium facilitating relaxation (for review see [1]). The initial event is depolarisation of the membrane which opens voltage-gated, dihydropyridine-sensitive sarcolemmal calcium channels (dihydropyridine receptors) allowing an influx of calcium into the myocyte. There is a close proximity between one or a few sarcolemmal calcium channels and one or a few calcium channels of the sarcoplasmic reticulum (ryanodine receptors). This may enable calcium influx through one opening of a single sarcolemmal calcium channel to increase a local pool of calcium sufficiently to open adjacent ryanodine receptors to release calcium. This local, punctate, increase of calcium is termed calcium spark according to its visualization by confocal microscopy [2]. It is the sum of these local calcium releases which generate a global cytoplasmic increase in calcium which causes activation of contractile proteins. The global increase in calcium is immediately followed by calcium removal resulting in subsequent deactivation of the contractile machinery. Calcium removal from the cytosol occurs by activity of the sarcoplasmic reticulum calcium pump and by exchange of calcium for sodium by the sarcolemmal Na+-Ca2+-exchanger [1].

Defective EC-coupling in heart failure may result from altered density or function of proteins relevant for calcium homeostasis. Knowledge of these alterations is a prerequisite for understanding the pathophysiology of myocardial failure and for the development of new strategies to treat patients with heart failure. This review focuses on expression and function of calcium-regulatory proteins in failing myocardium from animal models of heart failure and from failing human hearts.

Calcium entry through voltage-gated L-type … 

* Corresponding author. Tel. (+49-761) 270 3591; Fax (+49-761) 270 3788; E-mail: hasenfus@ruf.uni-freiburg.de
Carcinogenic Activity of Cigarette Smoke Condensate
Authors: George E. Moore
Journal: JAMA (1963)

To the Editor:  —Despite many disadvantages the value of using experimental animals to investigate various human diseases is evident. Dr. Needles apparently is unaware of the extent of the research into the human lung cancer-cigarette problem. The use of the entire respiratory membrane of the human in his calculations is not consistent with observations that smoke particles are not evenly distributed 1 2 throughout the bronchi and alveoli but localize on relatively small areas mainly at the divisions of the major bronchi. It has been estimated that the ratio of areas of experimental mouse skin to the human bronchial mucosa effectively exposed to cigarette smoke is 1 to 6. 2 In our experiments, the total amount of smoke tar painted on each mouse during the year which comprised the experiment was less than 50 gm. A heavy smoker may inhale 200 to 400 gm of smoke tar each year for
RIGHT VENTRICULAR OUTFLOW TRACT PACING LEADS TO BETTER LEFT VENTRICULAR STRAIN MECHANICS THAN CONVENTIONAL RIGHT HEART PACING: A STUDY IN OPEN-CHEST PIGS
Authors: David J. Sahn, Zhiwen Zhou, Ya-Wei Xu, Li Xiong, Muhammad Ashraf, Xiaokui Li, Da-yi Hu
Journal: Journal of the American College of Cardiology (2011)
Coarse particles and dust storm mortality.
Authors: D T Mage
Journal: Environmental Health Perspectives (2000)

In a paper titled "Episodes of High Coarse Partide Concentrations Are Not Associated with Increased Mortality," Schwartz et al. (1) concluded that "coarse particles from windblown dust are not associated with mortality risk."The authors seem to have overlooked the medical literature on the health effects of the historic U.S. dust storms of the dust bowl in 1935 (2-4).Brown et al. (2) reported that the dust ... was exceedingly irritating to the respi- ratory tract and materially increased the number of deaths from pneumonia and other complications....The storm that will be longest remembered came [to Dodge City, Kansas] on the afternoon of Sunday [April] the 14th at 2:40 p.m....No fttalities are known. They concluded thatThe "immediate" effects are shown in the [delayed] increase in morbidity and mortality from the acute infections of the respiratory tract.1) restricted their analysis to mortality occurring on "the day of the dust storm or the following day."Therefore, they may have not observed any delayed rise in mortality that could have occurred later because of the "immediate" exacerbation of acute respiratory infections in highly susceptible individuals, such as those with preexisting chronic obstructive pulmonary disease.Furthermore, improve- ments in modern medical treatments, such as the replacement of the sulfa drugs of the mid-1930s by penicillin and other drugs, could delay a mortal outcome beyond the lag observed in the 1930s. Schwartz et al. (
Hemodynamic Effects of Cerebral Arteriovenous Aneurysms
Authors: JOHN M. WALLACE, BLAINE S. NASHOLD, ANTHONY P. SLEWKA
Journal: Circulation (1965)

The hemodynamic alterations produced by large cerebral arteriovenous aneurysms are qualitatively similar to those caused by arteriovenous aneurysms elsewhere in the body. Congestive heart failure was not observed in our eight patients; it appears to be unusual in adult cases. By comparing cardiac outputs with a control group the mean aneurysm blood flow in six patients was estimated to be 2,804 ml. per minute at rest. Isoproterenol increased cardiac output relatively more than the estimated aneurysm flow. Implications of the present data with respect to the concept of "central" blood volume are discussed. Progressive mental and neurologic deterioration is the rule with large cerebral arteriovenous aneurysms. Repeated bleeding episodes, which may not be obvious clinically, appear to be partially responsible.
Developmental Origins of Health and Disease
Authors: Matthew W. Gillman
Journal: New England Journal of Medicine (2005)

At first glance, it may seem implausible that your mother's exposure to stress or toxins while she was pregnant with you, how she fed you when you were an infant, or how fast you grew during childhood can determine your risk for chronic disease as an adult. Mounting evidence, however, indicates that events occurring in the earliest stages of human development — even before birth — may influence the occurrence of diabetes, cardiovascular disease, asthma, cancers, osteoporosis, and neuropsychiatric disorders.More than 40 years ago, Widdowson and McCance1 discovered that rat pups that were undernourished during the three weeks of . . .
Mortality variations as a measure of general practitioner performance: implications of the Shipman case
Authors: S. Frankel
Journal: BMJ (2000)

Changes in the organisation of the NHS or in the management of health professionals are often made within the context of inquiries into specific medical catastrophes rather than through a measured process of policy formulation.Examples include changes in the scrutiny of psychiatric services after the Ely report into malpractice at a Cardiff hospital 1 and, more recently, changes in doctors' self regulation after the high mortality in Bristol paediatric cardiac surgery. 2 Harold Shipman's conviction for 15 murders committed during the course of his work as a general practitioner will result in several changes in the management of UK general practice.Some external monitoring of primary care is already routine.In the wake of the Shipman case there is pressure to introduce formal monitoring of mortality in general practitioners' patients. 3 Here we consider the potential value of such an approach to identifying aberrant practice.
Atropine Regimens for Amblyopia: Author reply
Authors: Michael X. Repka, Susan A. Cotter, Roy W. Beck, Raymond T. Kraker, Eileen E. Birch, Donald F. Everett, Richard W. Hertle, Jonathan M. Holmes, Graham E. Quinn, Nicholas A. Sala, Mitchell M. Scheiman, David R. Stager, David K. Wallace
Journal: Ophthalmology (2005)
NEW METHODS FOR THE APPLICATION OF OLD PRINCIPLES IN THE TREATMENT OF FRACTURES AND DEFORMITIES OF LIMBS.
Authors: JAMES G. HUGHES
Journal: JAMA (1901)

In all cases of fracture, to restore and maintain the limb in its normal position, extension and counterextension between bony prominences, or a flexed segment of the limb, above and below the fracture, must be employed.<sup>1</sup>To this must be added immobilization, when normal position of the limb is accurately secured. In addition to the above principles, the open dressing, in compound fractures, is of primary importance for obvious reasons. Every splint should permit of inspection, bathing, ventilation, etc. There should be no circular constriction of the limb to retard the circulation. The effects of impaired circulation, delayed union, ischemia, stiff joints, and in some cases non-union, can be ascribed to this interference. It is safe to say that fully one-half the fractures of the leg should be treated by the ambulatory method. Many patients assume the erect position in spite of the warnings of their medical attendant. The
Therapeutic Management of Small Cell Lung Cancer
Authors: Anne Kessinger, John F. Foley, Henry M. Lemon
Journal: JAMA (1983)

A treatment protocol for small cell lung cancer used attenuated drug dosages in an attempt to reduce toxic reactions without compromising effectiveness. Treatment consisted of cyclophosphamide, 50 mg orally daily, methotrexate, 1.25 mg orally daily, procarbazine hydrochloride, 50 mg orally daily, and vincristine sulfate, 10 μg/kg intravenously weekly, and was continued until relapse or for two years. Patients with limited disease were given concurrent radiation (4,000 to 5,000 rad, using standard fractionation) to the primary lesion and draining nodes. Fifty patients were evaluable for toxic reactions and survival: 22 with limited and 28 with extensive disease. Fifty-four percent of the patients with extensive disease responded; one (4%) had a complete response. Median survival of the patients with extensive disease was 20 weeks. Ninety-five percent of the patients with limited disease responded; 57% had a complete response. Median survival of these patients was 55 weeks; one-year survival was 59%, and 18-month survival was 36%. Three patients have discontinued therapy without relapse for 48, 22, and seven months. One patient remains disease free after undergoing therapy for 84 weeks. There were no treatment-related deaths, and only 4% of patients experienced WBC count nadirs of less than 1,000/cu mm. Patients with limited disease had long-term survivals comparable with those of other more toxic protocols. (<i>JAMA</i>1983;250:3188-3191)
Hope from despair
Authors: A. Danczak
Journal: BMJ (2013)

One of the hardest parts of being a GP is seeing people who you know well suffer.

I knew that the death of one of my patients would hit her husband hard. He seemed almost grey with grief. Nothing mattered to him. Her ashes were at home, and he could hardly bear to leave the house because it felt like abandoning her. After caring for her in chronic ill health for years, he now lacked both companionship and …
Misdiagnosis of Multiple Bone Metastases Due to Increased FDG Uptake in Polyostotic Fibrous Dysplasia
Authors: Chia-Hung Kao, Shung-Shung Sun, Yeh-You Shen, Yen-Kung Chen
Journal: Clinical Nuclear Medicine (2007)

It is well know that FDG is taken up by different tumor and active inflammation. Focal uptake of FDG may cause false-positive results in certain benign conditions. Fibrous dysplasia is a benign disorder of unknown cause in which the normal bone structure is replaced by fibrous connective tissue. X-ray CT and bone scan with technetium-99m-phosphate complexes has been used as a tool for diagnosing fibrous dysplasia. There have been very few reports of this, even if sometimes fibrous dysplasia showed increased FDG activity, it would be difficult to use PET to evaluate the disease because fibrous dysplasia does not always have increased metabolic activity. We report a rare case with polyostotic fibrous dysplasia which was misdiagnosed as multiple bone metastases due to increased FDG uptake in multiple foci of the whole body bones.
Short-term therapy with peroxisome proliferation-activator receptor-α agonist Wy-14,643 protects murine fatty liver against ischemia-reperfusion injury
Authors: Narci C. Teoh, Jacqueline Williams, Jennifer Hartley, Jun Yu, Robert S. McCuskey, Geoffrey C. Farrell
Journal: Hepatology (2009)

Steatosis increases operative morbidity/mortality from ischemia-reperfusion injury (IRI); few pharmacological approaches have been protective. Using novel genetic/dietary models of nonalcoholic steatohepatitis (NASH) and simple steatosis (SS) in Alms1 mutant (foz/foz) mice, we characterized severity of IRI in NASH versus SS and lean liver and tested our hypothesis that the lipid-lowering effects of the peroxisome proliferation-activator receptor (PPAR)-alpha agonist Wy-14,643 would be hepatoprotective. Mice were subjected to 60-minute partial hepatic IRI. Microvascular changes were assessed at 15-minute reperfusion by in vivo microscopy, injury at 24 hours by serum alanine aminotransferase (ALT), and hepatic necrosis area. Injury and inflammation mediators were determined by way of immunoblotting for intercellular cellular adhesion molecule, vascular cellular adhesion molecule, p38, c-jun N-terminal kinase, IkappaB-alpha, interleukin (IL)-1a, IL-12, tumor necrosis factor-alpha (TNF-alpha) and IL-6, cell cycle by cyclin D1 and proliferating cell nuclear antigen immunohistochemistry. In foz/foz mice fed a high-fat diet (HFD) to cause NASH or chow (SS), IRI was exacerbated compared with HFD-fed or chow-fed wild-type littermates by ALT release; corresponding necrotic areas were 60 +/- 22% NASH, 29 +/- 9% SS versus 7 +/- 1% lean. Microvasculature of NASH or SS livers was narrowed by enormous lipid-filled hepatocytes, significantly reducing numbers of perfused sinusoids, all exacerbated by IRI. Wy-14,643 reduced steatosis in NASH and SS livers, whereas PPAR-alpha stimulation conferred substantial hepatoprotection against IRI by ALT release, with reductions in vascular cellular adhesion molecule-1, IL-1a, TNF-alpha, IL-12, activated nuclear factor-kappaB (NF-kappaB), p38, IL-6 production and cell cycle entry.NASH and SS livers are both more susceptible to IRI. Mechanisms include possible distortion of the microvasculature by swollen fat-laden hepatocytes, and enhanced production of several cytokines. The beneficial effects of Wy-14,643 may be exerted by dampening adhesion molecule and cytokine responses, and activating NF-kappaB, IL-6 production, and p38 kinase to effect cell cycle entry.
Re: Tansu N, Öbek C, Önal B, Yalçın V, Öner A, Solok V. A simple position to provide better imaging of upper ureteral stones close to the crista iliaca during extracorporeal shock wave lithotripsy using the Siemens Lithostar. Eur Urol 2004;45:352–5
Authors: Chandra Shekhar Biyani, Vipan Bhatia
Journal: European Urology (2004)
Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes
Authors: Marie Scully, Mari Thomas, Mary Underwood, Henry Watson, Katherine Langley, Raymond S. Camilleri, Amanda Clark, Desmond Creagh, Rachel Rayment, Vickie Mcdonald, Ashok Roy, Gillian Evans, Siobhan McGuckin, Fionnuala Ni Ainle, Rhona Maclean, William Lester, Michael Nash, Rosemary Scott, Patrick O Brien
Journal: Blood (2014)
Bovine Spongiform Encephalopathy in the United States — An Epidemiologist's View
Authors: Christl A. Donnelly
Journal: New England Journal of Medicine (2004)

On December 9, 2003, a nonambulatory (“downer”) dairy cow was slaughtered in Washington State, and because the animal's condition was attributed to complications from calving, the animal was judged to be fit for human consumption (designated as “inspected and passed” by the U.S. Department of Agriculture [USDA]). Samples taken from this animal tested positive for bovine spongiform encephalopathy (BSE, also known as mad cow disease) on December 22; the USDA diagnosis was subsequently confirmed by the British world reference laboratory. The international response to the announcement of this result on December 23 was strong and swift, with bans being imposed . . .
Another View on Overviews-Reply
Authors: Andrew D. Oxman
Journal: JAMA (1995)

In Reply.  —We agree that an overview should be motivated by and rooted in an understanding of the clinical problem and the underlying biology. However, an overview is not a review of the overviews, as Dr McBride suggests—it is a review of relevant primary research. Overviews, like any other journal article, can be used as a platform for editorializing whether or not they are comprehensive. Completely reviewing the subject area often means covering a wide range of literature superficially and unsystematically and in no way provides protection against bias. To the contrary, it provides ample latitude for bias. McBride's last sentence refers to guidelines that use explicit methods and  literature reviews. If McBride means clinical practice guidelines, we agree entirely that the methods should be explicit and we address this in a subsequent Users' Guide. However, readers should be cautious about confusing extensive with systematic and valid. We would
Lithium carbonate and dental caries.
Authors: A Gillis
Journal: BMJ (1978)

cachexia-inducing tumours are encountered in mice; a chemically induced cachexia-producing murine gastric carcinoma has been described previously.2It is suggested that the use of such tumours would avoid the complications underlying the system developed by Dr Strain and his colleagues-that is, xenografts of a human hypernephroma in immunodepressed mice.In the case of our tumours the effect of diet modification would seem to provide a valuable opening for experimental investiga- tions relevant to clinical cancer cachexia.