tbuckley/cabot-search huggingface dataset:
Calcineurin and hypertrophic heart disease: novel insights and remaining questions
Authors: Orlando F Bueno, Eva van Rooij, Jeffery D Molkentin, Pieter A Doevendans, Leon J De Windt
Journal: Cardiovascular Research (2002)

In the past 2 years, an emerging body of research has focused on a novel transcriptional pathway involved in the cardiac hypertrophic response. Ever since its introduction, the significance of the calcineurin–NFAT module has been subject of controversy. The aim of this review is to provide both an update on the current status of knowledge and discuss the remaining issues regarding the involvement of calcineurin in hypertrophic heart disease. To this end, the molecular biology of calcineurin and its direct downstream transcriptional effector NFAT are discussed in the context of the genetic studies that established the existence of this signaling paradigm in the heart. The pharmacological mode-of-action and specificity of the calcineurin inhibitors cyclosporine A (CsA) and FK506 is dicussed, as well as their inherent limitations to study the biology of calcineurin. A critical interpretation is given on studies aimed at analyzing the role of calcineurin in cardiac hypertrophy using systemic immunosuppression. To eliminate the controversy surrounding CsA/FK506 usage, recent studies employed genetic inhibitory strategies for calcineurin, which confirm the pivotal role for this signal transduction pathway in the ventricular hypertrophy response. Finally, unresolved issues concerning the role of calcineurin in cardiac pathobiology are discussed based upon the information available, including its controversial role in cardiomyocyte viability, the reciprocal relationship between myocyte Ca2+ homeostasis and calcineurin activity and the relative importance of calcineurin in relation to other hypertrophic signaling cascades.
New Frontiers in Genetic Medicine
Authors: LARRY J. SHAPIRO
Journal: Annals of Internal Medicine (1986)

Disorders determined wholly or in part by genetic factors constitute a substantial number of human diseases. This realization has grown during the past 2 decades with the recognition of many specific heritable conditions and the identification of familial risk factors for common disorders. New technologies, such as fetal visualization, chorionic villus sampling, molecular cloning methods, and gene transfer technology, provide a framework for dealing with genetically determined illness in unprecedented ways. Several current and potential applications of these methods are examined, as is the use of restriction fragment length polymorphisms to survey the variability within the genome and to generate markers permitting the prospective detection of genetic disorders. The promise and limitations of chorionic villus biopsy sampling are considered for early prenatal diagnosis. The future of gene therapy in hereditary diseases is examined, and some of the substantial social and ethical considerations engendered by these new developments are explored.
Can licorice lick colon cancer?
Authors: Paul M. Stewart, Stephen M. Prescott
Journal: Journal of Clinical Investigation (2009)

COX-2 promotes colon cancer. While both nonselective NSAIDs and selective COX-2 inhibitors reduce disease burden, their adverse gastrointestinal and cardiovascular side effects limit their therapeutic use. In this issue of the JCI, Zhang et al. used gene silencing and a derivative of licorice root to show that inhibition of the enzyme 11beta-hydroxysteroid dehydrogenase type II(11betaHSD2) reduces tumor COX-2 activity, tumor growth, and metastasis by increasing the tonic glucocorticoid-mediated suppression of the COX-2 signaling pathway without the adverse effects associated with NSAIDs and selective COX-2 inhibitors (see the related article beginning on page 876). Their findings suggest that 11betaHSD2 inhibition may be a potential therapeutic option in colon cancer, warranting further investigation.
US geriatric mental health workforce needs to expand, says Institute of Medicine
Authors: B. Roehr
Journal: BMJ (2012)

The “silver tsunami” of US baby boomers that is now entering retirement threatens to swamp the healthcare system, particularly mental health and substance misuse services, says a new report from the US Institute of Medicine, released on 10 July.1

The tidal wave comes from the convergence of two factors: the size of the cohort and its intense use of mental health services.

The US Census Bureau predicts that the number of persons aged over 65 will rise from 40.3 million in 2010 to 72.1 million in 2030.

Although the current cohort of senior citizens …
The Epidemiology of Diabetes and Pregnancy in the U.S., 1988
Authors: Michael M Engelgau, William H Herman, Philip J Smith, Robert R German, Ronald E Aubert
Journal: Diabetes Care (1995)

OBJECTIVE To determine the prevalence of pregnancy complicated by diabetes in a representative sample of the U.S. population. RESEARCH DESIGN AND METHODS We analyzed data from a multistaged cross-sectional probability sample of live births recorded in the U.S. in 1988 for women 15–49 years of age. The main outcome measure was pregnancy complicated by diabetes. RESULTS Diabetes was present in congruent to 154,000 (4%) of all pregnancies in the U.S. Gestational diabetes mellitus (GDM) accounted for 135,000 of such pregnancies (88%), non-insulin-dependent diabetes mellitus (NIDDM) for 12,000 (8%), and insulin-dependent diabetes mellitus for 7,000 (4%). On average, the mothers with NIDDM (29.6 years) and GDM (29.3 years) were older than mothers whose pregnancies were not complicated by diabetes (26.2 years; P &amp;lt; 0.05). In multivariate analyses, the odds of having a pregnancy complicated by GDM increased significantly with maternal age and body mass index. CONCLUSIONS Pregnancy is complicated by diabetes more often than was previously believed. More frequent testing may further increase the apparent prevalence of GDM.
Doctors should “just do it” to implement clinical visions
Authors: Robert Short
Journal: BMJ (2007)

Doctors have to seize the initiative and make the changes they think are needed if clinical excellence is to be put at the centre of NHS reforms, a conference was told last week. 

This idea was endorsed by several panel members at the conference, held to launch a report on clinicians' views of the NHS reforms to an audience of more than 100 NHS trust chief executives, clinical directors, medical directors, and representatives of primary care trusts.

The report, which contains “design rules” that are common to best practice, was …
Ethical Aspects of Surrogate Embryo Transfer
Authors: LeRoy Walters
Journal: JAMA (1983)

The article by Hodgen published in this issue ofThe Journal(p 2167) suggests that some infertile women who cannot produce fertilizable ova may one day be able to bear children. Such women may have ovaries that are functionally deficient in a critical respect, or they may lack ovaries entirely. For these women, bearing a child that is genetically "their own" is a physical impossibility. Any new technique that helps to reduce involuntary infertility is to be welcomed, provided that its benefits are not outweighed by safety considerations and social consequences. The present moment, when surrogate embryo transfer (SET) is being tested in primates and initially attempted in humans,<sup>1-3</sup>seems the appropriate time to inventory the ethical issues that the clinical use of this new technique may raise. Safety considerations in SET and accompanying techniques concern three biologic individuals—the oocyte or embryo donor, the embryo itself, and the embryo recipient.
Relationship between disease activity indices and colonoscopic findings in patients with colonic inflammatory bowel disease.
Authors: P Gomes, C du Boulay, C L Smith, G Holdstock
Journal: Gut (1986)

The Crohn's disease activity index, a similar index devised for patients with ulcerative colitis, and other commonly used laboratory indicators of disease activity have been studied in 50 patients with colonic inflammatory bowel disease undergoing routine colonoscopic assessment and compared with the histological extent and activity of disease. There was only poor correlation between the colonoscopic or histological findings and the indices of disease activity studied, showing that these are not reliable measures of disease activity or extent at the tissue level.
A Long-Term Study of Early Fluid Therapy in Severely Burned Adults
Authors: Manuel Bocanegra
Journal: JAMA (1966)

The effect of fluid therapy on shock mortality and late mortality has been studied in 308 severely burned adults. Two fluid regimens were compared simultaneously on an alternate-case basis. The results show (1) therapy with saline solutions alone was more effective than a fluid regimen deficient in electrolytes and (2) no additional advantage could be conclusively shown by combination of plasma with saline solutions. Furthermore, over a 14-year period there was only a 4% overall shock mortality in a total of 152 patients treated with saline solutions alone. There were no shock deaths in 127 patients with 10% to 50% surface-area burns. Late mortality, on the other hand, was not influenced by the early fluid therapy we employed.
Drug company threatens legal action over Canadian guidelines
Authors: M. Shuchman
Journal: BMJ (1999)

A pharmaceutical company has threatened legal action against an adviser to the Ontario Ministry of Health after taking issue with draft prescribing guidelines that she developed

Anne Holbrook, a pharmacist and practising physician at the Centre for the Evaluation of Medicines at McMaster University in Hamilton, Ontario, serves on several committees that make recommendations on prescribing issues. In 1997, Ontario's Ministry of Health asked her to lead a review of the drugs used …
An Analysis of Mechanisms of the Carcinoid Flush.
Authors: D. Joseph Demis
Journal: Annals of Internal Medicine (1964)

s1 February 1964An Analysis of Mechanisms of the Carcinoid Flush.D. Joseph Demis, M.D., James G. Zimmer, M.D.D. Joseph Demis, M.D.Search for more papers by this author, James G. Zimmer, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-2-329_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptFlushing has been accepted as an integral part of the carcinoid syndrome with its additional manifestations of diarrhea, right-sided valvular heart disease, and repiratory distress in the presence of metastatic carcinoid tumor. The transient flushes, usually involving the face, are among the most common manifestations and are certainly the most striking part of the syndrome. These cutaneous flushes have been classically described as patchy areas of erythema and cyanosis, though some have a purely erythematous flush. The flushes have been attributed to episodic release of serotonin from the tumor, and Schneckloth et al. (Circulation16: 523, 1957) have produced the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: D. Joseph Demis, M.D.; James G. Zimmer, M.D.Affiliations: Washington, D. C. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1964Volume 60, Issue 2_Part_1Page: 329-330KeywordsCarcinoid tumorCardiovascular therapyDiarrheaErythemaSerotonin ePublished: 1 December 2008 Issue Published: 1 February 1964 PDF downloadLoading ...
Increased risk for myelodysplastic syndromes in individuals with glutathione transferase theta 1 (GSTT1) gene defect
Authors: H.W Chen, D.P Sandler, J.A Taylor, D.A Bell, D.L Shore, E Liu, C.D Bloomfield, C.D Bloomfield, D.P Sandler, E Liu
Journal: The Lancet (1996)
Evaluation of a New Reflectance Photometer For Use in Home Blood Glucose Monitoring
Authors: William L Clarke, Terry W Melton, Marti Sachse, Jack M Schneider, Kathy D Schneider, Margaret C Yarborough
Journal: Diabetes Care (1981)

A new reflectance photometer (Glucometer, Ames Division, Miles Laboratories, Elkhart, Indiana) has been developed for use with the Dextrostix reagent strip. The device measures 8 × 17 cm, weighs 330 g, uses AA batteries, and requires no warm-up. High (330 mg/dl) and low (50 mg/dl) calibrations are stored in memory and need be repeated only when: (1) a control solution (100 mg/dl) reading is in error, (2) ambient temperature changes by more than 5°C, (3) a new bottle of Dextrostix is used, and (4) batteries are changed. A 60-s timer with alarm helps make timing of the procedure consistent. Nineteen insulin-dependent and one non-insulin-dependent diabetic subjects each performed a minimum of 20 blood glucose determinations over a 3-mo period in the investigators' laboratories. Simultaneous capillary blood samples were obtained for plasma glucose analysis by a comparative method. A total of 602 patient-determined glucose values ranging from 30 to 400 mg/dl were compared with simultaneous laboratory values. These values correlated significantly (r = 0.96, P &amp;lt; 0.0001, y = 2.6 + 0.92x). The Glucometer-Dextrostix System is an accurate and convenient method for home blood glucose monitoring by diabetic patients.
Inherited predisposition to hypertension confounds the effect of low birthweight
Authors: B. R Walker, G. C. Watt
Journal: BMJ (1999)

EDITOR—Our study showed that the relation between lower birthweight and subsequent higher blood pressure in adulthood may be confounded by parental blood pressure.1Mothers with higher blood pressure between 9 and 19 years after delivery had babies with lower birthweight who subsequently had higher blood pressure as adults.

Taylor …
Letter: Minimal brain dysfunction
Authors: R. J. Baumann
Journal: JAMA (1976)

<h3>To the Editor.—</h3> Dr Newton's editorial, "Minimal Brain Dysfunction" (235: 2524, 1976) emphasizes a major public health problem: evaluation of the cases of children who perform poorly in the traditional schoolroom. He is certainly correct in pointing out that the diagnostic criteria often used in evaluating these cases are "extremely confusing and in some cases, basically unscientific." It is disappointing that he then proceeds to endorse the concept of an entity called minimal brain dysfunction (MBD) and alleges that it is distinct from "hyperactivity, learning disability and behavior problems." Increasingly, workers in the field are coming to just the opposite conclusion: there is no such entity as MBD!<sup>1</sup>It is a ragtag hodgepodge term describing children with a striking variety of problems, due (in all probability) to a number of different etiologic mechanisms. Lumping all these diverse youngsters together in one group has greatly inhibited progress in this field.
Syndrome of Congenital Absence of the Spleen with Associated Cardiovascular and Gastroenteric Anomalies
Authors: MARY JANE AGUILAR, H. BRODIE STEPHENS, JACKSON T. CRANE
Journal: Circulation (1956)

Survey of 27 cases in the literature and the authors' 3 cases reveals a characteristic syndrome of congenital absence of the spleen with certain cardiovascular and gastrointestinal abnormalities. The hematologic and other findings permit a presumptive antemortem diagnosis. More accurate prognosis is made possible and valuable information is afforded the cardiac surgeon, since the cardiac anomalies often follow a predictable pattern.
Varicose Veins of Pregnancy
Authors: Robert A. Nabatoff
Journal: JAMA (1960)

Approximately 15 to 20 per cent of pregnant women develop varicose veins. These varices have a characteristic "scattered" distribution. The vulva is frequently involved. They are quite different from varices in the nonpregnant state. Susceptible women develop progressively larger varicosities with each succeeding pregnancy. Elastic bandages have been used to compress all varices from the time they appear until after delivery. An adjustable support has been devised to compress vulval varices. The use of simple leg exercises, in conjunction with these elastic supports, has proved effective in the management of varices of pregnancy. No injection treatment or surgery has been necessary. Tubal ligation has rarely been advised and therapeutic abortion has not been necessary thus far because even the largest varices and their complications have proved amenable to effective control during pregnancy.
Physician Assistants and Nurse Practitioners
Authors: Harold C. Sox Jr.
Journal: Annals of Internal Medicine (1995)

Letters1 August 1995Physician Assistants and Nurse PractitionersHarold C. Sox Jr., Jack A. Ginsburg, and H. Denman ScottHarold C. Sox Jr.Search for more papers by this author, Jack A. GinsburgSearch for more papers by this author, and H. Denman ScottSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-3-199508010-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Educational and certification requirements for registered nurses and nurse practitioners are not uniform. As our paper indicated, nurse practitioners are licensed registered nurses with advanced education ranging from 9 to 24 months of supervised clinical training, generally leading to a Master's degree. However, as Maffie-Lee and colleagues indicate, many nurses obtain advanced training to become nurse practitioners after already having completed educational and licensure requirements as registered nurses. The American Nurses Association has called for a minimum requirement of a Master's degree for certification of nurse practitioners by 1998.Certification is available from several sources, is generally voluntary, ...REFERENCE1. Washington Consulting Group. Final Report: Survey of Certified Nurse Practitioners and Clinical Nurse Specialists: December 1992. Washington, DC: Division of Nursing, Bureau of Health Professions. HRSA (240-91-0055); 1994. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1995Volume 123, Issue 3Page: 237-238KeywordsMedical servicesNursesNursing educationPatientsPharmacistsPrimary care ePublished: 15 August 2000 Issue Published: 1 August 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Great Expectations for a New Vaccine
Authors: Kathryn M. Edwards, Marie R. Griffin
Journal: New England Journal of Medicine (2003)

Despite the fact that a licensed pneumococcal capsular polysaccharide vaccine has been available for more than 30 years, Streptococcus pneumoniae continues to sicken and kill children and adults throughout the world each day. Pneumococcus-related illnesses including bacteremia, meningitis, and pneumonia affect both industrialized countries (see Figure) and developing countries. However, in developing countries the existence of a much larger burden of death from acute respiratory tract infection adds greater urgency to the situation. Although the polysaccharide vaccine was recently shown in the Journal 1 to have an efficacy of 44 percent for the prevention of bacteremic disease in older adults, in . . .
Comparison of Doppler echocardiographic peak frequency and turbulence parameters in the quantification of aortic stenosis in a pulsatile flow model.
Authors: S R Cannon, K L Richards, R G Morgann
Journal: Circulation (1985)

To test the relative accuracy of Doppler echocardiographic peak frequency and turbulence parameters in assessing aortic stenosis, we constructed a pulsatile flow model that simulated human left ventricular and aortic pressures, flow, and anatomy. Continuous wave-measured peak frequencies and pulsed Doppler-measured turbulence were determined in the model ascending aorta for nine stenotic valve areas for each of five different flow rates. The mean squared systolic peak frequency (MSPF) and turbulence spectral envelope area (SEA) were regressed against the mean systolic gradient (r = .94, SEE = 5.6 mm Hg; and r = .96, SEE = 1.2 mm Hg, respectively). SEA was more accurate than MSPF at moderate-to-high degrees of stenosis and exhibited a smaller standard error. MSPF was more accurate than SEA in mild stenoses, where SEA tended to overestimate gradients. When flow data were included in a multiple regression analysis, both MSPF and SEA provided fair predictions of actual effective valve areas (r = .90 and r = .94, respectively). Use of high pulse-repetition-frequency Doppler echocardiography significantly reduced aliasing problems common to pulsed Doppler techniques.
ATP7A Gene Addition to the Choroid Plexus Results in Long-term Rescue of the Lethal Copper Transport Defect in a Menkes Disease Mouse Model
Authors: Anthony Donsante, Ling Yi, Patricia M Zerfas, Lauren R Brinster, Patricia Sullivan, David S Goldstein, Joseph Prohaska, Jose A Centeno, Elisabeth Rushing, Stephen G Kaler
Journal: Molecular Therapy (2011)

Menkes disease is a lethal infantile neurodegenerative disorder of copper metabolism caused by mutations in a P-type ATPase, ATP7A. Currently available treatment (daily subcutaneous copper injections) is not entirely effective in the majority of affected individuals. The mottled-brindled (mo-br) mouse recapitulates the Menkes phenotype, including abnormal copper transport to the brain owing to mutation in the murine homolog, Atp7a, and dies by 14 days of age. We documented that mo-br mice on C57BL/6 background were not rescued by peripheral copper administration, and used this model to evaluate brain-directed therapies. Neonatal mo-br mice received lateral ventricle injections of either adeno-associated virus serotype 5 (AAV5) harboring a reduced-size human ATP7A (rsATP7A) complementary DNA (cDNA), copper chloride, or both. AAV5-rsATP7A showed selective transduction of choroid plexus epithelia and AAV5-rsATP7A plus copper combination treatment rescued mo-br mice; 86% survived to weaning (21 days), median survival increased to 43 days, 37% lived beyond 100 days, and 22% survived to the study end point (300 days). This synergistic treatment effect correlated with increased brain copper levels, enhanced activity of dopamine-β-hydroxylase, a copper-dependent enzyme, and correction of brain pathology. Our findings provide the first definitive evidence that gene therapy may have clinical utility in the treatment of Menkes disease.
Intestinal permeability and screening tests for coeliac disease.
Authors: I Cobden, J Rothwell, A T Axon
Journal: Gut (1980)

In disease states of the small intestine--for example, gluten-sensitive enteropathy--there is an increased permeability to large molecules. This increased permeability extends to polar molecules of intermediate size such as disaccharides, whereas small polar molecules are malabsorbed. A recently-developed oral test, based on the simultaneous administration of two test substances, cellobiose (a disaccharide) and mannitol (a small polar molecule) has been used to investigate permeability in a variety of gastrointestinal diseases, the result of the test being expressed as the ratio (cellobiose/mannitol) of the five hour urinary recoveries of the two probe molecules. Results for patients with pancreatic insufficiency, intestinal bacterial overgrowth, primary hypolactasia, ileocolic or colonic Crohn9s disease, and ulcerative colitis were comparable with those in normal controls, whereas in 23 out of 24 untreated coeliacs, and five out of eight patients with Crohn9s disease involving the more proximal small bowel, the cellobiose/mannitol ratio was clearly abnormal. A study of its application as a screening procedure for coeliac disease showed that the test was both sensitive and accurate, with fewer false-positive and false-negative results than other recognised screening tests--namely, the xylose test, reticulin antibodies, and blood folate estimations.