tbuckley/cabot-search huggingface dataset:
The Schorstein Lecture ON SOME CARDIAC PROBLEMS
Authors: T. W. Griffith
Journal: BMJ (1912)

To imce there lhas always been sometlling peculiarly fascinating about the anatomy, physiology, and diseases of the circulatory system.I have always been greatly impressed by the beauty of the cenitral organ with its mlarvellous adaptation of struLcture to function; by its ontogenetic and pllylogenetic development; by its mal- formations, and here the interest has been increased by an attempt to discrimlinate between
Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial
Authors: FT Cutts, SMA Zaman, G Enwere, S Jaffar, OS Levine, JB Okoko, C Oluwalana, A Vaughan, SK Obaro, A Leach, KP McAdam, E Biney, M Saaka, U Onwuchekwa, F Yallop, NF Pierce, BM Greenwood, RA Adegbola
Journal: The Lancet (2005)
The role of endotoxin during typhoid fever and tularemia in man
Authors: Sheldon E. Greisman, Richard B. Hornick, Henry N. Wagner, William E. Woodward, Theodore E. Woodward
Journal: Journal of Clinical Investigation (1969)

Volunteers infected with Salmonella typhosa develop a remarkable hyperreactivity to the pyrogenic and subjective toxic activities of homologous (S. typhos) and heterologous (Pseudomonas) endotoxins. The present studies quantitate this augmented reactivity and demonstrate by three differing approaches that significant tolerance to these endotoxins can be readily induced within the framework of the hyperreactive state. Thus, (a) tolerance induced before illness by repeated daily intravenous injections of the endotoxins remained demonstrable during overt illness, (b) daily intravenous injections of the endotoxins begun during overt illness evoked progressively increasing tolerance, and (c) continuous intravenous infusions of S. typhosa endotoxin during illness rapidly induced a pyrogenic refractory state. Despite unequivocal activation of the endotoxin tolerance mechanisms by any of the above methods, the febrile and toxic course of typhoid fever proceeded unabated. Similarly, in other volunteers with Pasteurella tularensis infection, continuous intravenous infusions of S. typhosa endotoxin evoked initial hyperreactive febrile and subjective toxic responses followed by rapid appearance of a pyrogenic refractory state without modification of the underlying clinical illness. These observations suggest that circulating endotoxin plays no major role in pathogenesis of the sustained fever and toxemia during typhoid fever and tularemia in man. The mechanisms responsible for the systemic hyperreactivity to endotoxin during typhoid fever and tularemia were further investigated. Low grade endotoxemia, nonspecific effects of tissue injury, impaired ability of the reticuloendothelial system to clear circulating endotoxin, and production of cytophilic antibodies capable of sensitizing leukocytes to endotoxin did not appear responsible. Inflammatory reactions to intradermal S. typhosa endotoxin increased significantly during typhoid fever. However, since no such dermal hyperreactivity developed to Pseudomonas endotoxin during typhoid fever nor to S. typhosa endotoxin during tularemia, the systemic hyperreactivity to bacterial endotoxins during typhoid fever and tularemia could not presently be ascribed to enhanced levels of acquired hypersensitivity.
Angiotensin II-Stimulated Nitric Oxide Release from Porcine Pulmonary Endothelium Is Mediated by Angiotensin IV
Authors: NATHALIE HILL-KAPTURCZAK, MATTHIAS H. KAPTURCZAK, EDWARD R. BLOCK, JAWAHARLAL M. PATEL, TADEUSZ MALINSKI, KIRSTEN M. MADSEN, C. CRAIG TISHER
Journal: Journal of the American Society of Nephrology (1999)

Abstract. In this study, a nitric oxide (NO) sensor was used to examine the ability of angiotensin II (AngII), AngIV, and bradykinin (Bk) to stimulate NO release from porcine pulmonary artery (PPAE) and porcine aortic endothelial (PAE) cells and to explore the mechanism of the AngII-stimulated NO release. Physiologic concentrations of AngII, but not Bk, caused release of NO from PPAE cells. In contrast, Bk, but not AngII, stimulated NO release from PAE cells. AngII-stimulated NO release from PPAE cells required extracellular L-arginine and was inhibited by L-nitro-arginine methyl ester. AT 1 and AT 2 receptor inhibition had no affect on AngII-mediated NO release or activation of NO synthase (NOS). AngIV, and AngII metabolite with binding sites that are pharmacologically distinct from the classic AngII receptors, stimulated considerably greater NO release and greater endothelial-type constitutive NOS activity than the same amount of AngII. The AngIV receptor antagonist, divalinal AngIV, blocked both AngII- and AngIV-mediated NO release as well as NOS activation. The results demonstrate that AngIV and the AngIV receptor are responsible, at least in part, for AngII-stimulated NO release and the associated endothelium-dependent vasorelaxation. Furthermore, these results suggest that differences exist in both AngII- and Bk-mediated NO release between PPAE and PAE cells, which may reflect important differences in response to these hormones between vascular beds.
Shaken baby syndrome
Authors: Brian Harding, R Anthony Risdon, Henry F Krous
Journal: BMJ (2004)

Pathological diagnosis rests on the combined triad, not on individual injuries 

Shaken baby syndrome is a form of physical non-accidental injury to infants, characterised by acute encephalopathy with subdural and retinal haemorrhages, occurring in a context of inappropriate or inconsistent history and commonly accompanied by other apparently inflicted injuries.1 2 Injuries to the neck and spinal cord may also be present. Controversy surrounds the precise causation of the brain injury, the retinal and subdural haemorrhages, as well as the degree of force required and whether impact in addition to whiplash forces is needed.1 3 4 Although most discussion has concerned fatal injuries of this nature, not all are lethal, but they may be associated with subsequent neurological disability of varying severity.

Expert medical evidence about inflicted injury must have scientific validity, but applying the evidence based criteria appropriate to clinical practice entails some difficulties.5 In clinical practice medical management of defined clinical problems can be compared and best practice distinguished by clinical outcomes. Conversely, in inflicted paediatric injuries, one is presented with the outcome, investigation follows rather than precedes that outcome, and the history may be incomplete or deliberately misleading. A need exists for …
Cardiac Autonomic Dysfunction in Brugada Syndrome
Authors: Thomas Wichter, Peter Matheja, Lars Eckardt, Peter Kies, Klaus Schäfers, Eric Schulze-Bahr, Wilhelm Haverkamp, Martin Borggrefe, Otmar Schober, Günter Breithardt, Michael Schäfers
Journal: Circulation (2002)

Background — Patients with Brugada syndrome present with characteristic ECG abnormalities (atypical right bundle-branch block and ST-segment elevation) and life-threatening ventricular tachyarrhythmias despite structurally normal hearts. Involvement of the autonomic nervous system is suggested by the occurrence of ventricular tachyarrhythmias and sudden death at rest or during sleep and by changes of typical ECG signs under pharmacological modulation of the myocardial autonomic tone. Methods and Results — This study investigated the presynaptic cardiac neuronal reuptake of norepinephrine (uptake 1) in 17 patients with Brugada syndrome and 10 age-matched control subjects with the use of the norepinephrine analogue [ 123 I] m -iodobenzylguanidine ( 123 I-MIBG), single-photon emission CT (SPECT), and quantitative 33-segment bull’s-eye analysis. Regionally reduced 123 I-MIBG uptake was present in 8 (47%) of 17 patients with Brugada syndrome but in none of the control subjects. Quantitative analysis showed segmental reduction of 123 I-MIBG uptake in the inferior and septal left ventricular wall in patients with Brugada syndrome compared with control subjects ( P &lt;0.05). No correlation was found between the findings of 123 I-MIBG-SPECT and clinical characteristics of the study patients. Conclusions — The present study demonstrated an abnormal 123 I-MIBG uptake in patients with Brugada syndrome, indicating presynaptic sympathetic dysfunction of the heart. These findings may have potential impact on the pathophysiology and arrhythmogenesis in patients with Brugada syndrome. Future quantitative investigations of the presynaptic and postsynaptic sympathetic and parasympathetic branches of the cardiac autonomic nervous system may clarify whether these observations represent a primary adrenergic dysfunction or an imbalance between sympathetic and parasympathetic innervation of the heart.
Fibronectin and immune complexes in rheumatic diseases.
Authors: K E Herbert, J S Coppock, A M Griffiths, A Williams, M W Robinson, D L Scott
Journal: Annals of the Rheumatic Diseases (1987)

The relation between fibronectin and immune complexes in rheumatic disease was examined in a series of linked studies. Fibronectin was present in immune complexes formed in vitro in the absence of C1q. Gel filtration chromatography showed complexed fibronectin was present in the serum of a patient with rheumatoid vasculitis, but not in normal serum; the complexed fibronectin coeluted with IgA and C3. Two dimensional immunoelectrophoresis showed a single fibronectin component was present in normal serum, but a number of components were present in serum from a rheumatoid patient. Polyacrylamide gel electrophoresis followed by immunoblotting for fibronectin showed that polyethylene glycol precipitates of synovial fluid contained immunoreactive components of a variety of sizes, indicating the presence of fragments of the molecule. An analysis of fibronectin in polyethylene glycol precipitates of paired serum and synovial fluid samples from 17 patients with rheumatoid arthritis and 16 with osteoarthritis showed more fibronectin was present in rheumatoid samples, especially in synovial fluid. More fibronectin was also present in synovial fluid than in serum polyethylene glycol precipitates; there was no direct relationship with C1q levels. All these results suggest that fibronectin is an integral component of immune complexes. This has potential pathogenic significance because it shows that a product of connective tissue cells may influence the functions of the immune system.
Serial 2-Point Ultrasonography Plus D-Dimer vs Whole-Leg Color-Coded Doppler Ultrasonography for Diagnosing Suspected Symptomatic Deep Vein Thrombosis
Authors: Enrico Bernardi
Journal: JAMA (2008)

Patients with suspected deep vein thrombosis (DVT) of the lower extremities are usually investigated with ultrasonography either by the proximal veins (2-point ultrasonography) or the entire deep vein system (whole-leg ultrasonography). The latter approach is thought to be better based on its ability to detect isolated calf vein thrombosis; however, it requires skilled operators and is mainly available only during working hours. No randomized comparisons are yet available evaluating the relative values of these 2 strategies.To assess if the 2 diagnostic strategies are equivalent for the management of symptomatic outpatients with suspected DVT of the lower extremities.A prospective, randomized, multicenter study of consecutive symptomatic outpatients (n = 2465) with a first episode of suspected DVT of the lower extremities who were randomized to undergo 2-point or whole-leg ultrasonography. Data were taken from ultrasound laboratories of 14 Italian universities or civic hospitals between January 1, 2003, and December 21, 2006. Patients with normal ultrasound findings were followed up for 3 months, with study completion on March 20, 2007.Objectively confirmed 3-month incidence of symptomatic venous thromboembolism in patients with an initially normal diagnostic workup.Of 2465 eligible patients, 345 met 1 or more exclusion criteria and 22 refused to participate; therefore, 2098 patients were randomized to either 2-point (n = 1045) or whole-leg (n = 1053) ultrasonography. Symptomatic venous thromboembolism occurred in 7 of 801 patients (incidence, 0.9%; 95% confidence interval [CI], 0.3%-1.8%) in the 2-point strategy group and in 9 of 763 patients (incidence, 1.2%; 95% CI, 0.5%-2.2%) in the whole-leg strategy group. This met the established equivalence criterion (observed difference, 0.3%;95% CI, -1.4% to 0.8%).The 2 diagnostic strategies are equivalent when used for the management of symptomatic outpatients with suspected DVT of the lower extremities.clinicaltrials.gov Identifier: NCT00353093.
Effect of Hydroxymethylglutaryl Coenzyme A Reductase Inhibitors on the Progression of Calcific Aortic Stenosis
Authors: Gian M. Novaro, Irving Y. Tiong, Gregory L. Pearce, Michael S. Lauer, Dennis L. Sprecher, Brian P. Griffin
Journal: Circulation (2001)

Recent studies have supported the hypothesis that calcific aortic stenosis is the product of an active inflammatory process, with similarities to atherosclerosis. We sought to determine whether therapy with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) might slow the progression of aortic stenosis.A retrospective study of 174 patients (mean age 68+/-12 years) with mild to moderate calcific aortic stenosis was conducted. Patients required normal left ventricular function, </=2+ aortic regurgitation, and >/=2 echocardiograms performed at least 12 months apart. Fifty-seven patients (33%) received treatment with a statin; the remaining 117 (67%) did not. The statin group was older and had a higher prevalence of hypertension, diabetes mellitus, and coronary disease. During a mean follow-up of 21 months, patients treated with statin had a smaller increase in peak and mean gradient and a smaller decrease in aortic valve area. When annualized, the decrease in aortic valve area for the nonstatin group was 0.11+/-0.18 cm(2) compared with 0.06+/-0.16 cm(2) for those treated with a statin (P=0.03). In multivariate analysis, statin usage was a significant independent predictor of a smaller decrease in valve area (P=0.01) and a lesser increase in peak gradient (P=0.02).Statin-treated patients, despite a higher risk profile for progression, had reduced aortic stenosis progression compared with those not treated with a statin. These data provide justification for a prospective randomized trial to substantiate whether statin therapy slows the progression of aortic stenosis.
Trust, competence, and the supervisor's role in postgraduate training
Authors: Olle ten Cate
Journal: BMJ (2006)

why should the decision to donate an organ be viewed differently?At the moment, kidneys are covertly transplanted in third world countries, from indigent donors into wealthy recipients.Bringing these activities out of the closet by introducing governmental supervision and funding will provide equity for the poor, who will get equal access to such transplants.It is appropriate that living donors, indigent or wealthy, share in the tangible benefits of their ethical concern for others.Not doing so, effectively restricting the disadvantaged, is unreasonably disingenuous.Contributors and sources: ALF is an American academic transplant surgeon with 15 years' experience in the specialty.She has three relatives with kidney failure, two of whom received kidney transplants, and has one relative who served as a live donor.Competing interests: ALF is paid for transplanting organs from live donors.
Is protective equipment useful in preventing concussion? A systematic review of the literature
Authors: B W Benson, G M Hamilton, W H Meeuwisse, P McCrory, J Dvorak
Journal: British Journal of Sports Medicine (2009)

Objective: To determine if there is evidence that equipment use reduces sport concussion risk and/or severity. Data sources: 12 electronic databases were searched using a combination of Medical Subject Headings and text words to identify relevant articles. Review methods: Specific inclusion and exclusion criteria were used to select studies for review. Data extracted included design, study population, exposure/outcome measures and results. The quality of evidence was assessed based on epidemiologic criteria regarding internal and external validity (ie, strength of design, sample size/power calculation, selection bias, misclassification bias, control of potential confounding and effect modification). Results: In total, 51 studies were selected for review. A comparison between studies was difficult due to the variability in research designs, definition of concussion, mouthguard/helmet/headgear/face shield types, measurements used to assess exposure and outcomes, and variety of sports assessed. The majority of studies were observational, with 23 analytical epidemiologic designs related to the subject area. Selection bias was a concern in the reviewed studies, as was the lack of measurement and control for potentially confounding variables. Conclusions: There is evidence that helmet use reduces head injury risk in skiing, snowboarding and bicycling, but the effect on concussion risk is inconclusive. No strong evidence exists for the use of mouthguards or face shields to reduce concussion risk. Evidence is provided to suggest that full facial protection in ice hockey may reduce concussion severity, as measured by time loss from competition.
Vitamin D plasma binding protein. Turnover and fate in the rabbit.
Authors: J G Haddad, D R Fraser, D E Lawson
Journal: Journal of Clinical Investigation (1981)

The metabolic disposition of the plasma binding protein (DBP) for vitamin D and its metabolites was studied in adult rabbits. Apo-DBP was purified from rabbit plasma and enzymatically labeled with radioiodine. The radioiodine-labeled protein retained its ability to bind vitamin D sterols and its physicochemical properties. When 125I-labeled DBP and 131I-labeled rabbit albumin were simultaneously injected intravenously, the 125I was cleared from plasma at a faster rate (t 1/2 = 1.7 d) than 131I (t 1/2 = 5 d) and 125I was present in excess of 131I in kidney, liver, skeletal muscle, heart, lung, intestine, testis, and bone 1 h after injection. In contrast to DBP, 25(OH)D3 was cleared more slowly (t 1/2 = 10.7 d). Compared to albumin, DBP radioactivity appeared earlier and in greater quantity in the urine of catheterized rabbits. Gel filtration analyses of plasma revealed most of the 125I to elute in the position of DBP, with only small amounts in the less than 1,000-dalton region. In contrast, almost all of the urine 125I eluted in this small molecular weight fraction. The molar ratio of DBP to 25(OH)D3 in normal rabbit plasma was 138/1. The extravascular pool of DBP was calculated to be 1.5-2.4 times larger than the intravascular DBP pool, and the molar replacement rate of DBP was 1,350-fold higher than that of 25(OH)D3. The plasma disappearance curves of holo-DBP, prepared either by saturating with 25(OH)D3 or by covalently linking 3 beta-bromoacetoxy-25(OH)D3, were very similar to that of apo-DBP. Neuraminidase treatment of DBP did not alter its plasma survival. These studies indicate that DBP or DBP-25(OH)D3 complex is removed from plasma by a variety of tissues, that the DBP moiety is degraded during this process, and that a significant recirculation of 25(OH)D3 probably occurs. The molar excess of DBP to 25(OH)D3 in plasma, and the relatively rapid turnover of DBP indicate that a high capacity, high affinity, and dynamic transport mechanism for vitamin D sterols exists in rabbit plasma.
Airway Inflammation in Nonobstructive and Obstructive Chronic Bronchitis with Chronic <i>Haemophilus influenzae</i> Airway Infection
Authors: PAUL BRESSER, THEO A. OUT, LOEK van ALPHEN, HENK M. JANSEN, RENÉ LUTTER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Nonencapsulated Haemophilus influenzae often causes chronic infections of the lower respiratory tract in both nonobstructive and obstructive chronic bronchitis. We assessed airway inflammation in clinically stable, chronically H. influenzae-infected patients with nonobstructive (CB–HI, n = 10) and in patients with obstructive chronic bronchitis (COPD–HI, n = 10) by analyses of the sol phase of spontaneously expectorated sputum (SSP). As compared with the CB–HI group, the COPD–HI group had significantly higher (p < 0.05) levels of myeloperoxidase (MPO) and tumor necrosis factor (TNF)- α in their SSP, whereas the degree of plasma protein leakage (SSP-to-serum ratio of plasma proteins) and the levels of interleukin (IL)-8, secretory IgA, and lactoferrin were similar in the two groups. These findings point to differences in pathophysiology in CB–HI and COPD–HI. The high level of TNF- α in the SSP of COPD-HI patients is in accord with the proposed role of TNF- α in the development of airway obstruction in COPD patients. In apparent contradiction, low levels of TNF- α were found in the SSP of noninfected but otherwise similar COPD patients (n = 9). This finding, however, does not exclude an exaggerated TNF- α response to infection or another stimulus in the airways of COPD patients. The SSP levels of MPO and IL-8, and the degree of plasma protein leakage in the COPD-HI group, were retrospectively compared with and found significantly higher than those of noninfected COPD patients, suggesting a more marked inflammatory response in COPD–HI. Whether this reflects a direct cause-and-effect relationship should be addressed in a future long-term prospective study involving repeated measurements in the same patients.
Deaths from chronic renal disease in U.S. battery and lead production workers.
Authors: W C Cooper
Journal: Environmental Health Perspectives (1988)

This report is based on an analysis of deaths in 4519 battery plant workers and 2300 lead production or smelter workers during the years 1947 to 1980. Causes were coded to the seventh (1955) revision of the International Classification of Diseases. There were significant excess deaths for
Protective effect of vagal stimulation on reperfusion arrhythmias in cats.
Authors: G Zuanetti, G M De Ferrari, S G Priori, P J Schwartz
Journal: Circulation Research (1987)

The role of the autonomic nervous system in modulating reperfusion arrhythmias is still unclear. Experiments with sympathetic denervation or alpha- and beta-adrenergic blocking agents have provided mixed results, while the effect of parasympathetic activation has not been investigated extensively. The effect of bilateral vagotomy and of vagal stimulation was studied, with and without attendant bradycardia, on the incidence of reperfusion arrhythmias in alpha-chloralose anesthetized cats. The left anterior descending coronary artery was occluded for 20 minutes, followed by reperfusion in 105 animals. The incidence and severity of reperfusion arrhythmias was compared in 1) neurally intact animals (heart rate 208 +/- 24 beats/min), 2) animals with acute bilateral vagotomy (heart rate 233 +/- 25 beats/min), 3) animals with vagal stimulation adjusted to maintain heart rate at 90-100 beats/min, and 4) animals with vagal stimulation + ventricular pacing to maintain heart rate at prestimulation values. All the neurally intact and vagotomized animals developed complex reperfusion arrhythmias, but these arrhythmias occurred in only 60 and 72%, respectively, of the animals with vagal stimulation and vagal stimulation + pacing (p less than 0.005 vs. neurally intact and p less than 0.02 vs. vagotomy). The incidence of ventricular fibrillation was similar in neurally intact (62%) and vagotomized (58%) animals; it was strikingly lower (7%, p less than 0.01) in animals with vagal stimulation when heart rate was allowed to decrease, and it was 48% when heart rate was kept constant during vagal stimulation. A selective protection from sustained (greater than 30 seconds duration) ventricular tachycardia was observed in animals with vagal stimulation independent of heart rate changes.(ABSTRACT TRUNCATED AT 250 WORDS)