tbuckley/cabot-search huggingface dataset:
Urinary CTX-II and glucosyl-galactosyl-pyridinoline are associated with the presence and severity of radiographic knee osteoarthritis in men
Authors: Kelsey M Jordan, Holly E Syddall, Patrick Garnero, Evelyne Gineyts, Elaine Dennison, Avan Aihie Sayer, Pierre D Delmas, Cyrus Cooper, Nigel K Arden
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To investigate the association between biochemical markers of bone, cartilage, and synovial turnover with the presence and severity of knee osteoarthritis (OA) in men. <b>Methods:</b> 176 men aged 59–70 years from the MRC Hertfordshire Cohort were studied. Weightbearing anteroposterior and lateral semiflexed radiographs were taken of both knees. A lifestyle questionnaire including basic demographic details and a questionnaire detailing knee pain was completed. This random sample was stratified based on the Kellgren and Lawrence (K&amp;L) score, and the following biochemical markers were analysed: serum osteocalcin, serum C-terminal crosslinked telopeptide of type I collagen (CTX-I), urinary C-terminal crosslinked telopeptide of type II collagen (CTX-II), and urinary glucosyl-galactosyl-pyridinoline (Glc-Gal-Pyd). <b>Results:</b> Age, body mass index (BMI), social class, smoking, and alcohol consumption were similar across K&amp;L grades. Only one subject had a grade 4 K&amp;L score, and was amalgamated with grade 3 subjects. A strong significant association was found between the presence of knee OA and urinary CTX-II and urinary Glc-Gal-Pyd (p = 0.0001 and p = 0.009), which persisted after adjustment for age and BMI. A significant positive association was also found between urinary CTX-II and urinary Glc-Gal-Pyd and the severity of K&amp;L grade, joint space narrowing, and osteophytes scores, which persisted after adjustment for age and BMI. No associations between the presence and severity of knee OA were found for serum CTX-I or serum osteocalcin. <b>Conclusions:</b> Urinary CTX-II and Glc-Gal-Pyd, but not systemic markers of bone turnover, are strongly associated with disease severity and the presence of OA at the tibiofemoral and patellofemoral joints in men.
Prenatal origin of chromosomal translocations in acute childhood leukemia: Implications and future directions
Authors: Cliona M. McHale, Martyn T. Smith
Journal: American Journal of Hematology (2004)

Abstract We, and others, have demonstrated an in utero origin for translocations associated with childhood leukemia, with latency periods in some cases exceeding 10 years. The mechanism of generation of most of the translocations is thought to be aberrant repair following abortive apoptosis, rather than V(D)J recombination or exposure to topoisomerase II inhibitors. Folate supplementation may prevent some of the chromosome breakage leading to translocation formation. Translocations t(8;21) and t(12;21) have been shown to occur in the normal population (before birth) at a frequency that is 100‐fold greater than the risk of developing the corresponding leukemia. In most instances, additional genetic changes are required for progression to leukemia. Tyrosine kinase receptor (RTK) mutations, which give cells a survival/proliferative advantage, are proposed to act cooperatively with fusion genes, leading to transformation. However, translocations and cooperating RTK mutations have not been identified for all leukemia subtypes, particularly in acute myeloid leukemia. The core binding transcriptional pathway is frequently targeted by translocation in utero. We propose that this pathway is highly sensitive during fetal hematopoiesis and may be targeted by mechanisms other than translocation. For each leukemia subtype it is important to characterize the corresponding leukemic stem cell, which is thought to be the initial target for translocation. This would help to elucidate the molecular pathways involved in the progression from preleukemic clone harboring a translocation to fully disseminated leukemia. Am. J. Hematol. 75:254–257, 2004. © 2004 Wiley‐Liss, Inc.
Role of the Ras-Association Domain Family 1 Tumor Suppressor Gene in Human Cancers
Authors: Angelo Agathanggelou, Wendy N. Cooper, Farida Latif
Journal: Cancer Research (2005)

Abstract In recent years, the list of tumor suppressor genes (or candidate TSG) that are inactivated frequently by epigenetic events rather than classic mutation/deletion events has been growing. Unlike mutational inactivation, methylation is reversible and demethylating agents and inhibitors of histone deacetylases are being used in clinical trails. Highly sensitive and quantitative assays have been developed to assess methylation in tumor samples, early lesions, and bodily fluids. Hence, gene silencing by promoter hypermethylation has potential clinical benefits in early cancer diagnosis, prognosis, treatment, and prevention. The hunt for a TSG located at 3p21.3 resulted in the identification of the RAS-association domain family 1, isoform A gene (RASSF1A). RASSF1A falls into the category of genes frequently inactivated by methylation rather than mutational events. This gene is silenced and frequently inactivated by promoter region hypermethylation in many adult and childhood cancers, including lung, breast, kidney, gastric, bladder, neuroblastoma, medulloblastoma, gliomas and it has homology to a mammalian Ras effector (i.e., Nore1). RASSF1A inhibits tumor growth in both in vitro and in vivo systems, further supporting its role as a TSG. We and others identified the gene in 2000, but already there are over a 150 publications demonstrating RASSF1A methylation in a large number of human cancers. Many laboratories including ours are actively investigating the biology of this novel protein family. Thus far, it has been shown to play important roles in cell cycle regulation, apoptosis, and microtubule stability. This review summarizes our current knowledge on genetic, epigenetic, and functional analysis of RASSF1A tumor suppressor gene and its homologues.
MTAS or a tale of evidence heedless medicine
Authors: Parashkev Nachev
Journal: BMJ (2007)

The greatest achievement of modern medicine is arguably not any single therapeutic advance, but the development of a highly sophisticated framework for distinguishing a true advance from what merely looks like one. Evidence based medicine has completely transformed our profession to the extent to which no doctor—not even the most cavalier one—would countenance a change to current practice that has not been justified by a rigorous comparison between the old and the new. What constitutes a rigorous comparison is well established; indeed, agreement on the principles of designing and reporting therapeutic trials is so widespread that all good journals refuse to publish any study that does not fit the standard template. These principles are simple and incontestable: all comparisons between treatments should be fairly made, with meticulous attention to potential sources of bias, with clear outcome measures, and with inferences limited to only what is statistically justified by the data.

One might therefore have thought that the response of any competent physician to what I am about to describe would be predictably derisive. Imagine that the government proposed a radically new treatment (let's call it Effupin) for a complex and important condition that has hitherto been treated in an imperfect but largely satisfactory way. Effupin's mode of action is …
Incidence of Galactorrhea
Authors: Ekkehard Kemmann
Journal: JAMA (1976)

<h3>To the Editor.—</h3> I appreciated the review article by Drs Buckman and Peake entitled "Prolactin in Clinical Practice" (236:871, 1976). I can only emphasize their point about careful evaluation of galactorrhea. Yet their impression that "galactorrhea is commonly seen in women of childbearing age" needs some comment, as relevant studies have been done. Furthermore, if galactorrhea indeed would be common, the significance of this clinical finding would be minor. Canfield and Bates<sup>1</sup>state that galactorrhea is an "uncommon occurrence," and in their series, 6 of 16 women with galactorrhea showed evidence of a pituitary adenoma. Friedman and Goldfien examined normal women, not for galactorrhea but for any type of breast secretion, and found none in their group of 114 nulliparous women.<sup>2</sup>More than 800 anovulatory and ovulatory women were systematically evaluated by Jones and Gentile<sup>3</sup>; 3.6% of the anovulatory and 1% of the ovulatory were found to
PSYCHOTHERAPY AND CANCER
Authors: C. D. J. Generales
Journal: JAMA (1952)

<h3>To the Editor:—</h3> The case described in a letter by Dr. W. G. Eliasberg (Psychotherapy in Cancer Patients,<i>J. A. M. A.</i><b>147:</b>525 [Sept. 29] 1951) and also reported by Dr. Otto Kant (Deceptive Psychoneurosis,<i>Psychiatric Quarterly</i><b>20:</b>129 [Jan.] 1946) certainly needs further serious comment. Psychotherapy ostensibly suppressed the main symptoms of pain and improved the general attitude and behavior in this "mental" case, which autopsy ultimately proved to be carcinoma of the pancreas with widespread metastases and sudden death due to pulmonary embolism. It has been known for some time and it has again been recently stressed by Dr. Irving J. Sands, of the department of neurology at Columbia (Proceedings of 145th Annual Meeting of the Medical Society of the State of New York, Section on Neurology and Psychiatry, May 4, 1951,<i>N. Y. State J. M.</i><b>51:</b>2370 [Oct. 15] 1951) that true somatic disease may
High Risk Pregnancy: Management Options
Authors: Stephen R. Carr
Journal: JAMA (1995)

I do not envy editors of medical texts. The pace at which new information accrues is rapid and ever increasing. Pity the person who has to bring together information from so many sources in a manner sufficiently timely that it is not outdated by the time it is published. The editors of this weighty book (more than 1300 pages) have found a way to circumvent the problem of information being outdated by publication time— instead of giving minute detail for each pregnancy complication (detail that will undoubtedly change), they concentrate on an approach to management. Authors supply enough information to provide an understanding of our current state of knowledge about a particular pregnancy problem and to construct a paradigm for evaluation and treatment. The particular details concerning a disease state may change, but the paradigm, if well constructed, is more durable over time. This type of presentation helps to construct
Recovery of menstruation and pregnancy after liver transplantation.
Authors: T F Cundy, J G O'Grady, R Williams
Journal: Gut (1990)

The effect of successful liver transplantation on menstrual function was assessed by questionnaire in 44 women transplanted for various types of end stage liver disease, acute liver failure or malignant disease. Significant amenorrhoea (greater than one year) was present in 48% of women with chronic liver disease before transplantation, and was reversed within 10 months of surgery in all but one of the premenopausal patients who had primary amenorrhoea and hypogonadotrophic hypogonadism. Two patients became pregnant five months and 1.5 years after transplantation, but in one instance the pregnancy was unsuccessful, possibly as a consequence of cyclosporin related intrauterine growth retardation.
Evaluation of Percentage of Free Serum Prostate-Specific Antigen to Improve Specificity of Prostate Cancer Screening
Authors: William J. Catalona
Journal: JAMA (1995)

<h3>Objective.</h3> —To evaluate measurement of percentage of free prostate-specific antigen (PSA) in serum to improve the specificity of prostate cancer screening in men with serum PSA levels between 4.1 and 10.0 ng/mL. <h3>Design.</h3> —Retrospective, nonrandomized analysis using a research assay for measuring free PSA in frozen serum from men with a spectrum of prostate sizes and digital rectal examination results. <h3>Setting.</h3> —General community outpatient prostate cancer screening program at a university center. <h3>Patients.</h3> —One hundred thirteen men aged 50 years or older, 99% of whom were white, with serum PSA concentrations of 4.1 to 10.0 ng/mL, including 63 men with histologically confirmed benign prostatic hyperplasia, 30 with prostate cancer with an enlarged gland, and 20 with cancer with a normal-sized gland. All study volunteers had undergone prostatic ultrasonography and biopsy. <h3>Main Outcome Measures.</h3> —Percentage of free PSA in serum and percentage of free PSA cutoff that maintained at least 90% sensitivity for prostate cancer detection. <h3>Results.</h3> —Median percentage of free PSA was 9.2% in men with cancer and a normal-sized gland, 15.9% in men with cancer and an enlarged gland, and 18.8% in men with benign prostatic hyperplasia (<i>P</i>&lt;.001). The percentage of free PSA cutoff was higher in men with an enlarged gland and in those with a palpably benign gland. In men with an enlarged, palpably benign gland, a free PSA cutoff of 23.4% or lower detected at least 90% of cancers and would have eliminated 31.3% of negative biopsies. <h3>Conclusions.</h3> —Measurement of percentage of free serum PSA improves specificity of prostate cancer screening in selected men with elevated total serum PSA levels and can reduce unnecessary prostate biopsies with minimal effects on the cancer detection rate; however, further studies are needed to define optimal cutoffs. Final evaluation of PSA screening also must consider the ability of current treatments to improve the prognosis of screen-detected prostate cancer. (<i>JAMA</i>. 1995;274:1214-1220)
Portrait of Bernard's Grandmother
Authors: M. Therese Southgate
Journal: JAMA (2008)

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TREATMENT WITH WHOLE BODY PERIODIC ACCELERATION WITH A HORIZONTAL MOTION PLATFORM REVERSES LEFT VENTRICULAR REMODELING IN ANGINA PATIENTS WITH OLD MYOCARDIAL INFARCTION
Authors: Shoichi Miyamoto, Moriaki Inoko, Tetsuya Haruna, Muneo Oba, Yoshiaki Saji, Eisaku Nakane, Tomomi Abe, Ken-ichi Sasaki, Hidehiro Itoh, Terunobu Fukuda, Junji Nakashima, Nozomi Tanaka, Koji Ueyama, Ryuji Nohara, Masatoshi Fujita, Cardiovascular Center, Kitano Hospital
Journal: Journal of the American College of Cardiology (2010)
Left Ventricular Mechanics and Geometry in Patients With Congenital Complete Atrioventricular Block
Authors: Naomi J. Kertesz, Richard A. Friedman, Steven D. Colan, Edward P. Walsh, Robert J. Gajarski, Portia S. Gray, Ramona Shirley, Tal Geva
Journal: Circulation (1997)

Background Radiographic evidence of cardiomegaly is common in patients with congenital complete atrioventricular block (CCAVB). It has been speculated that left ventricular (LV) remodeling and increased stroke volume counteract the bradycardia, but the effects of slow heart rate and atrioventricular asynchrony on LV dimensions, geometry, wall stress, and function have not been examined in detail. Methods and Results Thirty patients with CCAVB without associated congenital heart disease (mean age, 8.5±5.3 years; range, 0.2 to 20 years) were included in a cross-sectional two-institution study. Thirty-five echocardiograms were performed using standard techniques. ECG and 24-hour ECG recordings were reviewed. Seven patients did not receive a pacemaker, whereas 23 patients underwent pacemaker implantation after the echocardiogram. Compared with normal control subjects, LV volume (Z score=1.5±1.3) and LV mass (Z=1.2±1.5) were significantly increased, whereas LV mass-to-volume ratio (1.1±0.3) and geometry (short-axis diameter/length ratio=0.65±0.09) were normal. LV end-systolic stress (ESS) (a measure of afterload) was normal (Z score=0.2±2.3), whereas shortening fraction (Z=3±2.9) and velocity of circumferential fiber shortening (VCF) (Z=3±3.1) were increased. The relationship between VCF and ESS (a preload-insensitive and afterload-adjusted index of contractility) was increased (Z=2.2±2) with only small increase in preload (Z=1.02±1.1). Regression analyses showed no significant change over age in LV mass, volume, geometry, loading conditions, or systolic function. Patients who ultimately met criteria for pacemaker implantation did not differ from those who did not in terms of heart rate or LV function but did have increased LV volume (Z score=1.8±1.4 versus 0.4±0.9, P =.03) and LV mass (Z score=1.7±1.2 versus 0.2±1.7, P =.001) compared to the unpaced group. Conclusions In most patients with CCAVB, the LV was enlarged with normal geometry and enhanced systolic function during the first two decades of life. The degree of LV dilation and enhanced function did not significantly change with age. In patients who ultimately underwent pacemaker implantation LV function did not differ from those who remained unpaced, but evidence of a slightly increased load manifested as increased end-diastolic volume and mass.
The Role of α-Cell Dysregulation in Fasting and Postprandial Hyperglycemia in Type 2 Diabetes and Therapeutic Implications
Authors: Beth Elaine Dunning, John E. Gerich
Journal: Endocrine Reviews (2007)

The hyperglycemic activity of pancreatic extracts was encountered some 80 yr ago during efforts to optimize methods for the purification of insulin. The hyperglycemic substance was named "glucagon," and it was subsequently determined that glucagon is a 29-amino acid peptide synthesized and released from pancreatic α-cells. This article begins with a brief overview of the discovery of glucagon and the contributions that somatostatin and a sensitive and selective assay for pancreatic (vs. gut) glucagon made to understanding the physiological and pathophysiological roles of glucagon. Studies utilizing these tools to establish the function of glucagon in normal nutrient homeostasis and to document a relative glucagon excess in type 2 diabetes mellitus (T2DM) and precursors thereof are then discussed. The evidence that glucagon excess contributes to the development and maintenance of fasting hyperglycemia and that failure to suppress glucagon secretion contributes to postprandial hyperglycemia is then reviewed. Although key human studies are emphasized, salient animal studies highlighting the importance of glucagon in normal and defective glucoregulation are also described. The past eight decades of research in this area have led to development of new therapeutic approaches to treating T2DM that have been shown to, or are expected to, improve glycemic control in patients with T2DM in part by improving α-cell function or by blocking glucagon action. Accordingly, this review ends with a discussion of the status and therapeutic potential of glucagon receptor antagonists, α-cell selective somatostatin agonists, glucagon-like peptide-1 agonists, and dipeptidyl peptidase-IV inhibitors. Our overall conclusions are that there is considerable evidence that relative hyperglucagonemia contributes to fasting and postprandial hyperglycemia in patients with T2DM, and there are several new and emerging pharmacotherapies that may improve glycemic control in part by ameliorating the hyperglycemic effects of this relative glucagon excess.
Partial Gastrectomy: Complications and Metabolic Consequences
Authors: Claude E. Welch
Journal: JAMA (1964)

In this very interesting book the authors have focused their attention upon the early and late complications and metabolic consequences of partial gastrectomy. Extensive original observations provide the basic material, though the discussion also includes a careful review of the literature. The senior author's descriptive terms (eg, "afferent loop syndrome," "loop-the-loop obstructions," "sumping") illuminate his great interest in the mechanical defects of Billroth II operations that often have been performed in a somewhat unorthodox fashion and referred to him for repair. When he converted to a Billroth I with vagotomy, the majority of his patients have been relieved completely. The late complications, "mechanical embarrassment of the afferent and efferent loops," "infection of the afferent loop," dumping, disturbances of fat metabolism leading to diarrhea, or malnutrition, iron deficiency, and defective calcium absorption) are all described in great detail. Severity of the sequelae are not under-emphasized; for example, anemia is estimated to
Molecular Fingerprint of Interferon-γ Signaling in Unstable Angina
Authors: Giovanna Liuzzo, Abbe N. Vallejo, Stephen L. Kopecky, Robert L. Frye, David R. Holmes, Jörg J. Goronzy, Cornelia M. Weyand
Journal: Circulation (2001)

Background —Activation of circulating monocytes in patients with acute coronary syndromes may reflect exposure to bacterial products or stimulation by cytokines such as IFN-γ. IFN-γ induces phosphorylation and nuclear translocation of transcription factor STAT-1, which initiates a specific program of gene induction. To explore whether monocyte activation is IFN-γ driven, patients with unstable (UA) or stable angina (SA) were compared for nuclear translocation of STAT-1 complexes and upregulation of IFN-γ–inducible genes CD64 and IP-10. Methods and Results —Peripheral blood mononuclear cells were stained for expression of CD64 on CD14 + monocytes and analyzed by PCR for transcription of IP-10. Expression of CD64 was significantly increased in patients with UA. Monocytes from UA patients remained responsive to IFN-γ in vitro, with accelerated transcriptional competency of CD64. IP-10–specific sequences were spontaneously detectable in 82% of the UA patients and 15% of SA patients ( P &lt;0.001). Most importantly, STAT-1 complexes were found in nuclear extracts prepared from freshly isolated monocytes of patients with UA, which provides compelling evidence for IFN-γ signaling in vivo. Conclusions —Monocytes from UA patients exhibit a molecular fingerprint of recent IFN-γ triggering, such as nuclear translocation of STAT-1 complexes and upregulation of IFN-γ–inducible genes CD64 and IP-10, which suggests that monocytes are activated, at least in part, by IFN-γ. IFN-γ may derive from stimulated T lymphocytes, which implicates specific immune responses in the pathogenesis of acute coronary syndromes.
Downward trend in dementia linked to better education and personal wealth, US study says
Authors: Janice Hopkins Tanne
Journal: BMJ (2008)

“Cognitive decline” is declining among Americans older than 70, a study of 11 000 elderly US residents carried out at the University of Michigan Medical School has found ( Alzheimer’s and Dementia 2008 http://alzheimersanddementia.org/webfiles/images/journals/jalz/JALZ_731.pdf).

Cognitive decline includes significant memory loss, dementia, and Alzheimer’s disease among people older than 70.

The study showed that higher education and higher net financial worth protected against cognitive impairment.

The authors used data from the health and retirement study, a nationally representative, population based longitudinal study of US adults. They compared two groups of people aged 70 and older—7406 in the 1993 cohort …