tbuckley/cabot-search huggingface dataset:
Tracking Early Decline in Cognitive Function in Older Individuals at Risk for Alzheimer Disease Dementia
Authors: Rebecca E. Amariglio, Michael C. Donohue, Gad A. Marshall, Dorene M. Rentz, David P. Salmon, Steven H. Ferris, Stella Karantzoulis, Paul S. Aisen, Reisa A. Sperling
Journal: JAMA Neurology (2015)

<h3>Importance</h3> Several large-scale Alzheimer disease (AD) secondary prevention trials have begun to target individuals at the preclinical stage. The success of these trials depends on validated outcome measures that are sensitive to early clinical progression in individuals who are initially asymptomatic. <h3>Objective</h3> To investigate the utility of the Cognitive Function Instrument (CFI) to track early changes in cognitive function in older individuals without clinical impairment at baseline. <h3>Design, Setting, and Participants</h3> Longitudinal study from February 2002 through February 2007 at participating Alzheimer's Disease Cooperative Study sites. Individuals were followed up annually for 48 months after the baseline visit. The study included 468 healthy older individuals (Clinical Dementia Rating scale [CDR] global scores of 0, above cutoff on the modified Mini-Mental State Examination and Free and Cued Selective Reminding Test) (mean [SD] age, 79.4 [3.6] years; age range, 75.0-93.8 years). All study participants and their study partners completed the self and partner CFIs annually. Individuals also underwent concurrent annual neuropsychological assessment and<i>APOE</i>genotyping. <h3>Main Outcomes and Measures</h3> The CFI scores between clinical progressors (CDR score, ≥0.5) and nonprogressors (CDR score, 0) and between<i>APOE </i>ε4 carriers and noncarriers were compared. Correlations of change between the CFI scores and neuropsychological performance were assessed longitudinally. <h3>Results</h3> At 48 months, group differences between clinical progressors and non-progressors were significant for self (2.13, SE=0.45,<i>P</i> &lt; .001), partner (5.08, SE=0.59,<i>P</i> &lt; .001), and self plus partner (7.04, SE=0.83,<i>P</i> &lt; .001) CFI total scores. At month 48,<i>APOE</i>ε4 carriers had greater progression than noncarriers on the partner (1.10, SE=0.44,<i>P</i> &lt; .012) and self plus partner (1.56, SE=0.63,<i>P</i> &lt; .014) CFI scores. Both self and partner CFI change were associated with longitudinal cognitive decline (self, ρ=0.32, 95% CI, 0.13 to 0.46; partner, ρ=0.56, 95% CI, 0.42 to 0.68), although findings suggest self-report may be more accurate early in the process, whereas accuracy of partner report improves when there is progression to cognitive impairment. <h3>Conclusions and Relevance</h3> Demonstrating long-term clinical benefit will be critical for the success of recently launched secondary prevention trials. The CFI appears to be a brief, but informative potential outcome measure that provides insight into functional abilities at the earliest stages of disease.
6-YEAR OUTCOMES OF PATIENTS TREATED WITH DES, BMS OR MEDICAL THERAPY IN THE OAT TRIAL
Authors: Xavier Freixa, Sandra A. Forman, James M. Rankin, Cristopher E. Buller, Warren J. Cantor, Witold Ruzyllo, Gervasio A. Lamas, Judith S. Hochman, Vladimir Džavík
Journal: Journal of the American College of Cardiology (2011)
Opening of Specialty Cardiac Hospitals and Use of Coronary Revascularization in Medicare Beneficiaries
Authors: Brahmajee K. Nallamothu
Journal: JAMA (2007)

ContextAlthough proponents argue that specialty cardiac hospitals provide high-quality cost-efficient care, strong financial incentives for physicians at these facilities could result in greater procedure utilization.ObjectiveTo determine whether the opening of cardiac hospitals was associated with increasing population-based rates of coronary revascularization.Design, Setting, and PatientsIn a study of Medicare beneficiaries from 1995 through 2003, we calculated annual population-based rates for total revascularization (coronary artery bypass graft [CABG] plus percutaneous coronary intervention [PCI]), CABG, and PCI. Hospital referral regions (HRRs) were used to categorize health care markets into those where (1) cardiac hospitals opened (n = 13), (2) new cardiac programs opened at general hospitals (n = 142), and (3) no new programs opened (n = 151).Main Outcome MeasuresRates of change in total revascularization, CABG, and PCI using multivariable linear regression models with generalized estimating equations.ResultsOverall, rates of change for total revascularization were higher in HRRs after cardiac hospitals opened when compared with HRRs where new cardiac programs opened at general hospitals and HRRs with no new programs (P&lt;.001 for both comparisons). Four years after their opening, the relative increase in adjusted rates was more than 2-fold higher in HRRs where cardiac hospitals opened (19.2% [95% confidence interval {CI}, 6.1%-32.2%], P&lt;.001) when compared with HRRs where new cardiac programs opened at general hospitals (6.5% [95% CI, 3.2%-9.9%], P&lt;.001) and HRRs with no new programs (7.4% [95% CI, 3.2%-11.5%], P&lt;.001). These findings were consistent when rates for CABG and PCI were considered separately. For PCI, this growth appeared largely driven by increased utilization among patients without acute myocardial infarction (42.1% [95% CI, 21.4%-62.9%], P&lt;.001).ConclusionThe opening of a cardiac hospital within an HRR is associated with increasing population-based rates of coronary revascularization in Medicare beneficiaries.
Assessment of training in psychosexual medicine
Authors: N Mathers, M Bramley, K Draper, S Snead, A Tobert
Journal: BMJ (1994)

The Institute of Psychosexual Medicine offers training in the treatment of psychosexual problems to medically qualified doctors. Training takes place in fortnightly seminars in which trainees present and discuss real cases. Assessment of cases presented at the beginning and end of the six term basic training showed appreciable improvement in doctors' abilities. The proportion of doctors meeting each of the 14 predetermined clinical objectives rose. Factors which affected the amount of improvement were the initial score, the number of cases presented at the seminars, the occupation of the leader, and the duration of training. Accreditation by the Institute of Psychosexual Medicine was shown to be an appropriate outcome measure for the achievement of the required standards for practising psychosexual medicine.
Physiologic Aspects of Prolonged Weightlessness
Authors: Michael McCally, Duane E. Graveline
Journal: New England Journal of Medicine (1963)

JUST as we are accustomed to think of the physiology of exercise, we should be thinking too about the pathology of inactivity and disuse."1 For as long as man has contemplated space flight his imagination has been captured by the state of zero gravity or weightlessness. In this biologic never-never land speculation has often outstripped the collection of data. Because the zero-gravity state cannot yet be effectively created or maintained for more than brief seconds on earth the physiologic effects of prolonged weightlessness remain unknown. This essay is presented to acquaint the general medical reader with some of the speculations . . .
Ethical Foundations of Health System Reform
Authors: Nancy K. O'Connor
Journal: JAMA (1994)

To the Editor.  —There are several reasons that I am not reassured by Drs Brock and Daniels' 1 discussion of the ethical basis for President Clinton's health care plan.  First, having worked in the Indian Health Service, I am familiar with how government budgetary restraints can interfere with patient care. Right now, if a utilization clerk denies payment for medical care, physicians and hospitals usually ignore the clerk's decision and do it anyway, keeping themselves solvent by overcharging other patients. In President Clinton's plan, we will all be working for the government/ health care alliances. The pressure to conform will be severe. Since nonalliance health care would be forbidden, we may be unable to ignore the clerk's decision and may be unable to give care until the appeal is heard, by which time, of course, some patients will no longer need the care.  Second, there is an underlying public distrust
Taste Dysfunction and Penicillamine-Reply
Authors: Robert I. Henkin
Journal: JAMA (1976)

Taste dysfunction (hypogeusia and dysgeusia) following the administration of penicillamine is a disturbing and oftimes unexpected side effect observed in approximately one third of patients with rheumatoid arthritis, scleroderma, or cystinuria who have received this durg. 1,2 However, these symptoms rarely develop in patients with Wilson disease who have been given penicillamine, possibly because of their elevated levels of total body copper and the inability of penicillamine to mobilize and assist in the rapid excretion of their large copper body burden. 1   The comparison of changes in blood and urine copper levels in patients without Wilson disease, who developed taste dysfunction after the administration of penicillamine, indicates a significant hypocupremia and hypercupruria. 1,2 These symptoms were corrected by the oral administration of copper salts, whether or not penicillamine therapy was continued. 1,2 These data suggested that the taste dysfunction was directly related to the copper depletion that commonly
New paradigms in the treatment of hepatic cholestasis: From UDCA to FXR, PXR and beyond
Authors: Ulrich Beuers, Michael Trauner, Peter Jansen, Raoul Poupon
Journal: Journal of Hepatology (2015)

Cholestasis is an impairment of bile formation/flow at the level of the hepatocyte and/or cholangiocyte. The first, and for the moment, most established medical treatment is the natural bile acid (BA) ursodeoxycholic acid (UDCA). This secretagogue improves, e.g. in intrahepatic cholestasis of pregnancy or early stage primary biliary cirrhosis, impaired hepatocellular and cholangiocellular bile formation mainly by complex post-transcriptional mechanisms. The limited efficacy of UDCA in various cholestatic conditions urges for development of novel therapeutic approaches. These include nuclear and membrane receptor agonists and BA derivatives. The nuclear receptors farnesoid X receptor (FXR), retinoid X receptor (RXR), peroxisome proliferator-activated receptor α (PPARα), and pregnane X receptor (PXR) are transcriptional modifiers of bile formation and at present are under investigation as promising targets for therapeutic interventions in cholestatic disorders. The membrane receptors fibroblast growth factor receptor 4 (FGFR4) and apical sodium BA transporter (ASBT) deserve attention as additional therapeutic targets, as does the potential therapeutic agent norUDCA, a 23-C homologue of UDCA. Here, we provide an overview on established and future promising therapeutic agents and their potential molecular mechanisms and sites of action in cholestatic diseases.
Complete Heart Block Complicating Hyperthyroidism
Authors: Michael P. Stern
Journal: JAMA (1970)

Acute rheumatic fever and third-degree heart block developed in a 23-year-old man with hyperthyroidism. Although cardiac arrhythmias frequently complicate hyperthyroidism, third-degree heart block occurs only rarely in this disorder. Prolonged atrioventricular conduction has been noted in a significant number of hyperthyroid patients. Available information indicates that higher degrees of heart block may occur in hyperthyroidism when additional factors are present which can independently impair atrioventricular conduction.
Cognitive impairment and death in the elderly.
Authors: R Ramsay, C Bielawska, C Katona
Journal: BMJ (1990)

to account for death.In contrast, in children with fewer injuries a pathologist will be searching for features to account for death and would be tempted to record the presence of gastric contents to reflect probable importance as a cause of death.It is potentially misleading to equate the presence of gastric contents in the airways at necropsy with appreciable hypoxia before death, without details of the quality of pathological examinations under- taken with respect to detailed neuropathology.
Islet Cell Antibodies Are Less Predictive of IDDM Among Unaffected Children in the General Population Than in Sibs of Children With Diabetes
Authors: Mikael Knip, Jukka Karjalainen, Hans K Åkerblom
Journal: Diabetes Care (1998)

OBJECTIVE To examine the controversial issue of whether islet cell antibodies (ICAs) have a higher predictive value for progression to clinical IDDM in first-degree relatives of patients with diabetes than in the general population. RESEARCH DESIGN AND METHODS ICAs were analyzed with standard immunofluorescence in two population-based groups: 765 sibs of children with recent-onset diabetes and 1,212 unaffected Finnish children &amp;lt;20 years of age at initial screening. Those positive for ICAs were additionally tested for antibodies to GAD (GADAs) and the protein tyrosine phosphatase-related 1A-2 antigen (IA-2As). Subsequently, these subjects were observed for the manifestation of clinical IDDM over the next 7 years. RESULTS The frequency of both detectable ICAs and ICA levels ≥20 Juvenile Diabetes Foundation units (JDF U) was significantly higher among the sibs than in the general population (7.8 vs. 4.1% and 4.8 vs. 2.0%, respectively; P &amp;lt; 0.001). The prevalence of GADAs (37/60 vs. 3/48; P &amp;lt; 0.001) and IA-2As (31/60 vs. 0/48; P &amp;lt; 0.001) was increased among ICA-positive sibs compared with ICA-positive individuals from the background population. Over the next 7 years, 24 sibs (3.1%) and 3 unrelated children positive for ICAs (0.3%) progressed to clinical diabetes. The positive predictive value of ICAs was thus 6% in the general population and 40% among the sibs (P &amp;lt; 0.001), or 13 and 59%, respectively (P &amp;lt; 0.001), with an antibody cutoff level of 20 JDF U. The positive predictive value was related to the number of positive autoantibodies in sibs, which was 57% in those with three antibodies, 50% in those with two antibodies, and only 6% in those with ICAs alone. CONCLUSIONS These data show that the frequency of multiple autoantibodies is substantially lower in ICA-positive children representing the general population than in ICA-positive sibs of children with IDDM. As a consequence, the predictive value of ICAs for IDDM is higher in sibs of affected children than in the general population. This finding must be taken into account when planning intervention trials aimed at preventing or delaying the manifestation of clinical diabetes in individuals from the general population who test positive for ICAs.
Disability evaluation: a fledgling science?
Authors: Terra Ziporyn
Journal: JAMA (1983)

Although medicine and law often operate from incompatible bases, physicians must occasionally work with lawyers and in the process reconcile medicine to the legal world. Nowhere is this more evident than in disability evaluation. Indeed, explains Talmage G. Hiebert, PhD, MD, medical director of the American Disability Evaluation Research Institute (ADERI) and the National Association of Disability Evaluating Physicians (NADEP), Ann Arbor, Mich, while disability is a legal term, each year American physicians receive hundreds of thousands of requests to determine it. In fact, almost every physician at some point in his career will be called on to do so. But physician misunderstanding of disability evaluation is rampant, say Hiebert and others, and this in turn invites accusations of bias, lackeyism, and malpractice. Such misunderstanding has been plaguing groups like the American Academy of Compensation Medicine (AACM), the American Academy of Occupational Medicine, and the American Occupational Medicine Association for
Improved P50 Auditory Gating With Ondansetron in Medicated Schizophrenia Patients
Authors: Lawrence E. Adler, Ellen M. Cawthra, Kara A. Donovan, Josette G. Harris, Herbert T. Nagamoto, Ann Olincy, Merilyne C. Waldo
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Most schizophrenia patients have a deficit in auditory sensory gating, which appears to be mediated by the α-7 nicotinic receptor, that is not improved with conventional antipsychotic treatment. This study examined the effects of ondansetron, a highly selective 5-HT3 antagonist, on the P50 auditory evoked potential. METHOD: Eight medicated outpatients with schizophrenia were given either ondansetron (16 mg) or placebo in a double-blind, placebo-controlled design. Evoked potentials were recorded at baseline and 1 hour, 2 hours, and 3 hours after receipt of drug. RESULTS: There was a highly significant improvement in P50 gating after ondansetron treatment. The maximal treatment difference was at 2 hours posttreatment (ondansetron: mean=41.4%, SD=39.7%; placebo: mean=80.2%, SD=21.3%). CONCLUSIONS: Ondansetron significantly enhanced P50 auditory gating in schizophrenia patients treated with typical antipsychotics.
Restricted immunoglobulin VH usage and VDJ combinations in the human response to Haemophilus influenzae type b capsular polysaccharide. Nucleotide sequences of monospecific anti-Haemophilus antibodies and polyspecific antibodies cross-reacting with self antigens.
Authors: E E Adderson, P G Shackelford, A Quinn, P M Wilson, M W Cunningham, R A Insel, W L Carroll
Journal: Journal of Clinical Investigation (1993)

To examine the human antibody repertoire generated against a biologically significant antigen we have obtained sequences of heavy chain variable region genes (IgVH) from 15 monoclonal antibodies specific for the capsular polysaccharide of Haemophilus influenzae type b (Hib PS). All VH segments are members of the VH3 family and 9 of 15 are members of the smaller VH3b subfamily. Restriction is evident by the shared use of certain VDJ joints in independent hybridomas from different subjects. Two hybridomas generated from the same subject demonstrate identical heavy chain variable region gene sequences but differ in isotype and rearrange alternative light chain variable region genes (IgVL), suggesting that in a normal immune response, a single pre-B cell clone may use different light chain rearrangements and give rise to progeny capable of reacting with antigen. Using a polymerase chain reaction assay optimized to detect base pair differences among VH genes we demonstrate that at least a portion of expressed anti-Hib PS VH genes have undergone somatic mutation. Anti-Hib PS heavy chain genes are homologous to VH segments encoding autoantibodies and two hybridomas secrete anti-Hib PS antibody that cross-reacts with self antigens (double-stranded DNA and single-stranded DNA). Comparison of VH regions of self-reactive and monospecific anti-Hib PS Ab demonstrates no consistent structural feature correlating with fine antigen specificity. These data demonstrate significant restriction in VH usage and VDJ recombination in the anti-Hib PS response and confirm that autoantibodies may be elicited during normal immune responses.
THE HOST RESPONSE TO CALMETTE-GUÉRIN BACILLUS INFECTION IN MICE
Authors: R. V. Blanden, M. J. Lefford, G. B. Mackaness
Journal: The Journal of Experimental Medicine (1969)

Heterologous organisms (L. monocytogenes and S. typhimurium) were used to study the rate of development, magnitude, and persistence of the antimicrobial resistance engendered in mice by vaccination with BCG. These same methods were used to investigate the influence of prior vaccination on the host response to reinfection. The rate of onset and magnitude of the resistance produced by BCG varied with the vaccinating dose. Increased resistance was detected within 48 hr of injecting large numbers of BCG (approximately 10(8) viable units), but concurrent treatment with isoniazid interrupted its further development. An equal number of heat-killed organisms failed to influence host resistance significantly. The development of tuberculin sensitivity was also dependent upon the continued survival of the immunizing population of BCG. When vaccinated mice were reinfected with BCG, host resistance in spleen and liver was rapidly augmented to the accompaniment of striking changes in the morphology and microbicidal activity of the peritoneal macrophages. These changes occurred most rapidly in mice with a high level of delayed hypersensitivity at the time of reinfection.
Myocardial perfusion and ventricular function measurements during total coronary artery occlusion in humans. A comparison with rest and exercise radionuclide studies.
Authors: S Borges-Neto, J Puma, R H Jones, M H Sketch, R Stack, M W Hanson, R E Coleman
Journal: Circulation (1994)

BACKGROUND The purpose of this investigation was to compare the magnitude of change in myocardial perfusion and function during exercise with that obtained during total coronary artery occlusion. Radionuclide studies are widely used for the diagnosis and determination of prognosis in patients with suspected or known coronary artery disease. These studies are based on the premise that the relative deficit of coronary blood flow, which is induced by exercise and recognized as increased demand, relates to the jeopardy experienced by the decrease or sudden absolute interruption of coronary blood flow that is recognized as decreased supply and is associated with coronary stenosis or total coronary artery occlusion. The magnitude of exercise-induced perfusion and function abnormalities compared with those induced by total coronary artery occlusion in humans has not been previously reported. METHODS AND RESULTS We prospectively studied 20 patients with &gt; or = 50% diameter stenosis documented by quantitative coronary angiography in at least one vessel. A same-day rest/exercise sestamibi myocardial function and perfusion study was performed within 24 hours before percutaneous transluminal coronary angioplasty. At 1 minute after balloon inflation, while the vessel was occluded, sestamibi was injected, and a myocardial perfusion and function study was performed. Perfusion defect size was greater during occlusion (28 +/- 3%) than during exercise (13 +/- 2%) (P &lt; .01). Ejection fraction was greater during exercise (53 +/- 3%) compared with values measured during occlusion (41 +/- 2%) (P &lt; .01). CONCLUSIONS Physiological abnormalities induced by coronary occlusion are greater than those that occur during exercise, thereby indicating that stress-induced ischemia may not reflect the total potential myocardium in jeopardy from a stenotic lesion, if sudden occlusion occurs.
Regulate unhealthy food like cigarettes, campaigners urge
Authors: A. Gulland
Journal: BMJ (2014)

The World Health Organization is being urged to introduce a “tobacco style” response to unhealthy food in a bid to curb the global epidemic of obesity.

The World Obesity Federation and Consumers International are calling on this week’s World Health Assembly in Geneva, WHO’s decision making body, to develop a global convention on food regulation, similar to the international Framework Convention on Tobacco Control.

They described the tobacco convention as among the fastest treaties in history to be negotiated, adopted, and entered into force but added that “unhealthy dietary patterns now rank above tobacco as the …