tbuckley/cabot-search huggingface dataset:
Combined Effects of HDL Cholesterol, Triglyceride, and Total Cholesterol Concentrations on 18-Year Risk of Atherosclerotic Disease
Authors: Cecil M. Burchfiel, Ami Laws, Richard Benfante, Robert J. Goldberg, Lie-Ju Hwang, Darryl Chiu, Beatriz L. Rodriguez, J. David Curb, Dan S. Sharp
Journal: Circulation (1995)

Background Whether the combination of a low level of HDL cholesterol (HDL-C) and high level of triglyceride (TG) confers increased risk of cardiovascular disease and whether risk varies across levels of total cholesterol (TC) are not well established. Combined effects of HDL-C, TG, and TC on the incidence of atherosclerotic disease were examined prospectively in Japanese-American men from the Honolulu Heart Program. Methods and Results Among 1646 men aged 51 to 72 years who were free of coronary heart disease (CHD), stroke, and cancer and were not taking lipid-lowering medication, 318 developed atherosclerotic events (angina, coronary insufficiency, aortic aneurysm, definite CHD, or thromboembolic stroke) and 170 developed definite CHD between 1970 and 1988. Subjects were stratified by TC level (desirable, &lt;200 mg/dL; borderline high, 200 to 239 mg/dL; high, ≥240 mg/dL), HDL-C level (&lt;35 and ≥35 mg/dL), and TG level (&lt;200 and ≥200 mg/dL). With Cox regression with high HDL-C and low TG as reference, age-adjusted relative risks (RR) of atherosclerotic events were significantly elevated in men with low HDL-C and high TG at borderline-high (RR, 2.46; 95% CI, 1.48 to 4.09) and high (RR, 2.21; 95% CI, 1.34 to 3.66) TC levels but not in men with desirable TC levels (RR, 0.89; 95% CI, 0.38 to 2.09). Elevated risks were independent of blood pressure, obesity, fat distribution, diabetes, smoking, and alcohol. Results were not materially altered by exclusion of subjects with angina alone and were similar but somewhat weaker for CHD. Conclusions Risk of atherosclerotic disease appears elevated in subjects with low HDL-C and high TG levels when TC is borderline high or high, independent of other cardiovascular risk factors. These findings support recent cholesterol screening recommendations and suggest that joint effects of HDL-C and TG may be important to consider.
The Pharmacology of Eating Behavior
Authors: J E Morley, A S Levine
Journal: The Annual Review of Pharmacology and Toxicology (1985)

Over the past two decades, deadly coronaviruses, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) 2019 pandemic, have majorly challenged public health. The path for virus invasion into humans and other ...Read More
Epstein-Barr Virus Infection in Renal Transplant Recipients
Authors: SARAH H. CHEESEMAN
Journal: Annals of Internal Medicine (1980)

We studied Epstein-Barr (EB) virus excretion and antibody in 41 renal transplant recipients enrolled in a placebocontrolled trial of human leukocyte interferon. Half the patients were also treated with antithymocyte globulin. Epstein-Barr virus excretion occurred more often in recipients of cadaver kidneys (P = 0.03) and those receiving antithymocyte globulin (P = 0.04) and less often in patients given interferon (P = 0.08). Antibody to viral capsid antigen increased fourfold or more in 12 of 22 patients treated with antithymocyte globulin and in none of the non-antithymocyte globulin-treated group (P = 0.0002). Antibody to the restricted component of early antigen rose fourfold or more in eight patients and appeared related to the occurrence of syndromes similar to those attributed to cytomegalovirus in transplant recipients. We conclude that increasing immunosuppression augments the rate of EB virus reactivation and that EB virus may be an important pathogen in heretofore ill-defined syndromes.
THE RÔLE OF THE "WAX" OF THE TUBERCLE BACILLUS IN ESTABLISHING DELAYED HYPERSENSITIVITY
Authors: Sidney Raffel, Louis E. Arnaud, C. Dean Dukes, Jwo S. Huang
Journal: The Journal of Experimental Medicine (1949)

Guinea pigs sensitized with egg albumin along with the purified wax fraction of the human tubercle bacillus respond with delayed hypersensitive reactivity to the protein antigen. Previous publications have reported a similar activity of the wax with respect to tuberculoprotein and picryl chloride. The effect is not referable to an ordinary adjuvant activity of the bacillary wax, since antibody titers are not increased in animals which receive it, and since a known adjuvant, water-in-oil emulsion, has no effect with respect to the induction of delayed hypersensitivity. This report further extends the rôle of the tubercle bacillary wax in the induction of delayed hypersensitive states.
Note on the 'Embolic Theory' of Chorea
Authors: J. H. Jackson
Journal: BMJ (1876)

parison of cases of chorea complicating pregnancy withi chorea inde- pendent of that condition enabled me to disprove the embolic theory of the cause of the disease: a theory since destroyed on other evidence by Ogle and Dickinson, and rejected by Bristowe."Many of the readers of this JOURNAL will doubtless feel inclined to adopt Dr. Basmes's opinion; for, so far from this hypothesis being, as Dr. Dickinson says, " somewhat attractive", it has, to the best of my observation, been considered by most medical men of little worth; many of those also who have some interest in it, will easily have their little faith destroyed by the rejection of it by such justly esteemed authorities as Ogle, Barnes, Wilks, Dickinson, and Bristowe.As, next to Parkes, I am the earliest propounder of the hypothesis (London Hospitol Reoorts, I564,* vol.i, p. 459, Lancct,t November 26th, I864, p. 6o6), I wvish to say something in favour of it.It may be that I labour under tvelve years of prejudice.I ask that Dr. Barnes's opinion as to the destruction of the embolic theory by Dr.Dickinson's researches should be accepted only after reading Dr.Dickinson's account of the pathological changes he found.It is right to grant that Dr. Dickinson has carefully distinguished the morbid changes after death from chorea from changes found in the brains of persons who have died of non-nervous diseases.+It shall be granted that they are, as Dr. Dickinson supposes, the real pathological chances causative of chorea; he points out, however, that " it is not possible but to connect them with those of a large group of nervous dis- orders, and prominently with those of diabetes".There are, he tells us, differences in the seats of the changes in chorea and in diabetes.Strange as it may seem, I think, as I said at the meeting after the reading of his paper, that the changes, " remarkably constant in kind and place" which he describes, are not unlike those admitted to result from the process of embolism.I would now say that they seem to me to be very like.Dr. Dickinson writes (Med.-C6hir.Tr-as., vol.59, p. 15)of what he found in all his cases, that " they were all connected w,vith vascular disturbance".This is a very important statement, in general harmony with the hypothesis of embolism, especially wvhen what he says on localisation of the changes (vide inf/-a) is taken into consideration.* I there quoted a summary of Dr. Kirkes's opinions from Dr.
Review of Kristin Zeiler and Lisa Folkmarson Käll, eds., <i>Feminist Phenomenology and Medicine</i><sup>1</sup>
Authors: Lauren Freeman
Journal: The American Journal of Bioethics (2015)

Feminist Phenomenology and Medicine is comprised of 13 chapters and an introduction and is the result of a conference of the same title that occurred in May 2011 at Uppsala University in Sweden. Th...
Skeletal muscle dysfunction: a ubiquitous outcome in chronic disease?
Authors: J. Nathan, J. Fuld
Journal: Thorax (2010)

Skeletal muscle wasting is a debilitating consequence of respiratory disease, particularly well characterised in individuals with chronic obstructive pulmonary disease (COPD). However, it remains controversial whether peripheral muscle dysfunction is an intrinsic part of the respiratory disease process, or a generalised response to multiple atrophy stimuli. Such debate has not only informed the subtleties of pathophysiology, but has also instigated detailed analyses of the molecular mechanisms involved in the induction of muscle atrophy, identifying the ubiquitin–proteasome system (UPS) as the predominant pathway required for the rapid proteolysis seen in muscle wasting.

In this issue of Thorax ( see page 113 ), Mainguy et al contribute to our knowledge of muscle weakness in chronic respiratory disease, characterising peripheral muscle function in patients with idiopathic pulmonary arterial hypertension (IPAH).1 Ten WHO functional class II–III patients with IPAH and 10 matched healthy controls underwent exercise capacity assessment, quadriceps strength testing and peripheral muscle morphology analysis. Patients with IPAH demonstrated a lower proportion of type I fibres in vastus lateralis muscle biopsies than healthy controls (38% vs 50%), and this was associated with reduced quadriceps strength and a relatively higher potential for anaerobic metabolism (enzymatic ratio of phosphofructokinase (PFK)/3-hydroxyacyl CoA dehydrogenase (HDAH)). While there was no correlation between the proportion of type I fibres and muscle strength with pulmonary haemodynamic parameters, a positive correlation was demonstrated for peripheral muscle strength and exercise capacity ( R 2=0.42, p=0.04). The authors conclude that peripheral muscle dysfunction may contribute to exercise intolerance in patients with IPAH. With relatively small numbers in the study groups, …
Adjuvant Chemotherapy for Stage II Colon Cancer With Poor Prognostic Features
Authors: Erin S. O'Connor, David Yu Greenblatt, Noelle K. LoConte, Ronald E. Gangnon, Jinn-Ing Liou, Charles P. Heise, Maureen A. Smith
Journal: Journal of Clinical Oncology (2011)

Adjuvant chemotherapy is typically considered for patients with stage II colon cancer characterized by poor prognostic features, including obstruction, perforation, emergent admission, T4 stage, resection of fewer than 12 lymph nodes, and poor histology. Despite frequent use, the survival advantage conferred on patients with stage II disease by chemotherapy is yet unproven. We sought to determine the overall survival benefit of chemotherapy among patients with stage II colon cancer having poor prognostic features.A total of 43,032 Medicare beneficiaries who underwent colectomy for stage II and III primary colon adenocarcinoma diagnosed from 1992 to 2005 were identified from the Surveillance, Epidemiology, and End Results (SEER) -Medicare database. χ(2) and two-way analysis of variance were used to assess differences in patient- and disease-related characteristics. Five-year overall survival was examined using Kaplan-Meier survival analysis and Cox proportional hazards regression with propensity score weighting.Of the 24,847 patients with stage II cancer, 75% had one or more poor prognostic features. Adjuvant chemotherapy was received by 20% of patients with stage II disease and 57% of patients with stage III disease. After adjustment, 5-year survival benefit from chemotherapy was observed only for patients with stage III disease (hazard ratio[HR], 0.64; 95% CI, 0.60 to 0.67). No survival benefit was observed for patients with stage II cancer with no poor prognostic features (HR, 1.02; 95% CI, 0.84 to 1.25) or stage II cancer with any poor prognostic features (HR, 1.03; 95% CI, 0.94 to 1.13).Among Medicare patients identified with stage II colon cancer, either with or without poor prognostic features, adjuvant chemotherapy did not substantially improve overall survival. This lack of benefit must be considered in treatment decisions for similar older adults with colon cancer.
A chalcone-related small molecule that induces methuosis, a novel form of non-apoptotic cell death, in glioblastoma cells
Authors: Jean H Overmeyer, Ashley M Young, Haymanti Bhanot, William A Maltese
Journal: Molecular Cancer (2011)

Abstract Background Methuosis is a unique form of non-apoptotic cell death triggered by alterations in the trafficking of clathrin-independent endosomes, ultimately leading to extreme vacuolization and rupture of the cell. Results Here we describe a novel chalcone-like molecule, 3-(2- m ethyl-1H- i ndol-3-yl)-1-(4- p yridinyl)-2- p ropen-1-one (MIPP) that induces cell death with the hallmarks of methuosis. MIPP causes rapid accumulation of vacuoles derived from macropinosomes, based on time-lapse microscopy and labeling with extracellular fluid phase tracers. Vacuolization can be blocked by the cholesterol-interacting compound, filipin, consistent with the origin of the vacuoles from non-clathrin endocytic compartments. Although the vacuoles rapidly acquire some characteristics of late endosomes (Rab7, LAMP1), they remain distinct from lysosomal and autophagosomal compartments, suggestive of a block at the late endosome/lysosome boundary. MIPP appears to target steps in the endosomal trafficking pathway involving Rab5 and Rab7, as evidenced by changes in the activation states of these GTPases. These effects are specific, as other GTPases (Rac1, Arf6) are unaffected by the compound. Cells treated with MIPP lose viability within 2-3 days, but their nuclei show no evidence of apoptotic changes. Inhibition of caspase activity does not protect the cells, consistent with a non-apoptotic death mechanism. U251 glioblastoma cells selected for temozolomide resistance showed sensitivity to MIPP-induced methuosis that was comparable to the parental cell line. Conclusions MIPP might serve as a prototype for new drugs that could be used to induce non-apoptotic death in cancers that have become refractory to agents that work through DNA damage and apoptotic mechanisms.
Atypical Antipsychotic Use in Patients With Dementia: Managing Safety Concerns
Authors: Martin Steinberg, Constantine G. Lyketsos
Journal: American Journal of Psychiatry (2012)

Neuropsychiatric symptoms such as agitation and delusions occur commonly in elderly patients with dementia and often cause significant distress. Data on treatment efficacy are strongest for atypical antipsychotics, but these agents must be used with great caution. Adverse effects in patients with dementia include an increased risk of mortality and cerebrovascular events, as well as metabolic effects, extrapyramidal symptoms, falls, cognitive worsening, cardiac arrhythmia, and pneumonia. Conventional antipsychotics may pose an even greater safety risk. No clear efficacy evidence exists to support the use of alternative psychotropic classes (e.g., antidepressants, anticonvulsants), although they may be safer options. An antipsychotic trial is warranted when nonpharmacological intervention is unsuccessful and neuropsychiatric symptoms or associated behaviors cause severe distress or pose a significant safety risk. Before an atypical antipsychotic is started, a comprehensive assessment should be performed to rule out medical causes of the neuropsychiatric symptoms and to ascertain whether any contributing environmental or caregiver factors are present. Risks, benefits, and alternatives should be discussed with the patient and surrogate decision maker, with an opportunity given to ask questions. Dosages should be the lowest necessary, and metabolic parameters should be regularly monitored. Face-to-face visits are important to monitor response, tolerance, and the need for continued treatment. For patients in whom neuropsychiatric symptoms have been much improved or have been in remission for 3–6 months, a discontinuation trial should be considered. Through careful selection of appropriate patients for treatment, education of patients and caregivers, and close monitoring, safety risks can be minimized.
Direct and Synergistic Interactions of 3,5,3′-Triiodothyronine and the Adrenergic System in Stimulating Sugar Transport by Rat Thymocytes
Authors: Joseph Segal, Sidney H. Ingbar
Journal: Journal of Clinical Investigation (1980)

Isolated rat thymocytes were preincubated with various catecholamines, alone and together with 3,5,3′-triiodothyronine (T3), and the accumulation of the glucose analogues, 2-deoxy-d-glucose (2-DG) and 3-O-methylglucose (3-O-MG), was then measured. Epinephrine induced a time- and dose-dependent increase in the 15-min accumulation of 2-DG; at a concentration of 100 μM epinephrine, the effect was evident after a preincubation period of only 5 min. The lowest concentration of epinephrine at which a significant effect was evident was 1 μM. Epinephrine also produced a dose-dependent increase in the accumulation of 3-O-MG, and the lowest concentration at which a significant effect was evident was again 1 μM. Isoproterenol, a β-adrenergic agonist, like epinephrine, increased the accumulation of 2-DG, whereas the α-agonist, phenylephrine, had no effect. The response to epinephrine was inhibited by the β-antagonist, alprenolol, but the α-antagonist, phentolamine, had no effect. As previously demonstrated, T3 increased 2-DG accumulation, and like epinephrine, its effect was blocked by alprenolol. Neither T3 (0.1 nM) nor epinephrine (0.1 μM) had any effect when acting alone, but when added together at these concentrations, they significantly increased the accumulation of both 2-DG and 3-O-MG. Neither T3 with isoproterenol nor T3 with phenylephrine produced a comparable synergistic effect. But T3 (0.1 nM) acting with isoproterenol (0.1 μM) and phenylephrine (0.1 μM) together, synergistically increased 2-DG accumulation. In addition, the α-antagonist, phentolamine, which alone had no effect, inhibited the synergistic effect induced by T3 and epinephrine. The effects of epinephrine and T3 alone, as well as their combined synergistic effect on 2-DG accumulation, were not blocked by the inhibitor of protein synthesis, puromycin.
Prospective Study of Trichomonas vaginalis Infection and Prostate Cancer Incidence and Mortality: Physicians' Health Study
Authors: Jennifer R. Stark, Gregory Judson, John F. Alderete, Vasanthakrishna Mundodi, Ashwini S. Kucknoor, Edward L. Giovannucci, Elizabeth A. Platz, Siobhan Sutcliffe, Katja Fall, Tobias Kurth, Jing Ma, Meir J. Stampfer, Lorelei A. Mucci
Journal: JNCI Journal of the National Cancer Institute (2009)

Background A recent nested case–control study found that the presence of antibodies against Trichomonas vaginalis , a common nonviral sexually transmitted infection, was positively associated with subsequent incidence of prostate cancer. We confirmed these findings in an independent population and related serostatus for antibodies against T vaginalis to prostate cancer incidence and mortality.
Is hypovitaminosis D a consequence rather than cause of disease?
Authors: Charles Shee
Journal: Thorax (2013)

Is hypovitaminosis D a consequence rather than cause of disease?Chalmers and colleagues 1 have shown that vitamin D deficiency is common in bronchiectasis and correlates with markers of disease severity.The authors comment that although the study has identified a strong association, this does not demonstrate causality, but the results justify a randomised controlled trial of vitamin D therapy to determine if supplementation can improve outcomes.They mention that reduced outdoor physical activity and reduced exposure to sunlight might contribute to vitamin D deficiency.One possibility that the authors have not considered is that hypovitaminosis D may be a consequence rather than cause of disease.Vitamin D deficiency has been associated with an ever-expanding list of diseases. 2These have largely been observational studies, and when the benefits of vitamin D supplementation have been tested in randomised controlled trials, they have often not been confirmed. 2Gama and colleagues 3 have produced evidence that vitamin D is a negative acute-phase reactant (APR), and there can be a marked fall in serum vitamin D levels during a systemic inflammatory response.This would suggest that serum vitamin D is an unreliable marker of true vitamin D status following an acute inflammatory insult, and also that hypovitaminosis D may be the consequence, rather than the widely purported cause, of a myriad of chronic diseases. 3PRs accompany both acute and chronic inflammatory states.One would, therefore, not be surprised to find a correlation between severity of bronchiectasis and a rise in positive APRs (eg, C-reactive protein or ferritin), and neither would it be surprising to see a correlation with a fall in levels of negative APRs (eg, albumin, transferrin or vitamin D).
Assessment and prevention of exercise-induced bronchoconstriction
Authors: Sandra D Anderson, Pascale Kippelen
Journal: British Journal of Sports Medicine (2012)

The assessment of exercise-induced bronchoconstriction (EIB) in athletes requires the measurement of forced expiratory volume in 1 s (FEV 1 ) before and after vigorous exercise or a surrogate of exercise such as eucapnic voluntary hyperpnoea (EVH) of dry air or mannitol dry powder. Exercise testing in a laboratory has a low sensitivity to identify EIB, and exercise testing in the field can be a challenge in itself particularly in cold weather athletes. The EVH test requires the subject to ventilate dry air containing ∼5% CO 2 for 6 min through a low-resistance circuit at a rate higher than that usually achieved on maximum exercise. A ≥10% reduction in FEV 1 is a positive response to exercise and EVH and, when sustained, is usually associated with release of inflammatory mediators of broncho constriction. Another surrogate, mannitol dry powder, given by inhalation in progressively increasing doses, is used to mimic the dehydrating stimulus of exercise hyperpnoea. A positive mannitol test is a 15% fall in FEV 1 at ≤635 mg and reveals potential for EIB. Mannitol has a high specificity for identifying a clinical diagnosis of asthma. Once a diagnosis of EIB is established, the athlete needs to know how to avoid EIB. Being treated daily with an inhaled corticosteroid to reduce airway inflammation, inhaling a β 2 agonist or a cromone immediately before exercise, or taking a leukotriene antagonist several hours before exercise, all inhibit or prevent EIB. Other strategies include warming up prior to exercise and reducing respiratory water and heat loss by using face masks or nasal breathing.
ARE THUMB INJURIES BECOMING MORE FREQUENT IN MEN'S LACROSSE?
Authors: M Webb, T Hoskins, J Price
Journal: British Journal of Sports Medicine (2013)

Men's lacrosse is a rapidly growing sport. The authors were concerned by the number of thumb injuries sustained while working with an international team at the 2012 European Championships. To compare data collected during immediate pre-tournament training camp and the European Championships with published reports. Data was gathered prospectively on all 23 players on the England Men's lacrosse team. An injury was defined as one that occurred during a team practice or game, and resulting in the player missing one or more further sessions. Over 15 days, 23 players participated in 17 athletic exposures each. This included 9 games and 8 practices. There were 3 thumb injuries (Rate=0.007673). 1 occurred from contact with an opponent, 1 from direct contact with an opponent's stick and another from a direct blow from the ball. 2 fractures of the proximal phalanx and 1 MCPJ sprain. The data was compared with published by Bowers et al . 1 They reported 276 thumb injuries in 1,019,222 athletic exposures (Rate=0.000271). A c2 test with Yates correction for continuity was performed. This yielded a Yates’ c2 value of 53.559 which is statistically significant (p&lt;0.001). Mechanism of injury corroborates with published reports. Lacrosse has become more popular and there has been a trend to develop lighter flexible equipment. Data needs to be collected to determine if thumb injuries can be attributed to equipment design. We would advise manufacturers to explore alternative designs to help protect the thumb more successfully.