tbuckley/cabot-search huggingface dataset:
Noninvasive assessment of hepatic lipid composition: Advancing understanding and management of fatty liver disorders
Authors: Nathan A. Johnson, David W. Walton, Toos Sachinwalla, Campbell H. Thompson, Kate Smith, Patricia A. Ruell, Stephen R. Stannard, Jacob George
Journal: Hepatology (2008)

Nonalcoholic fatty liver is frequently observed in obese individuals, yet the factors that predict its development and progression to liver disease are poorly understood. We proposed that proton magnetic resonance spectroscopy (1H-MRS) might allow noninvasive assessment of hepatic lipid composition. Lipid saturation (SI) and polyunsaturation (PUI) indices measured by 1H-MRS were in agreement with those expected in oils of known composition. Hepatic triglyceride concentration (HTGC) and composition were then measured in healthy lean (LEAN) men, obese men with normal HTGC (OB), and obese men with hepatic steatosis (OB+HS). The effect of marked changes in dietary fat consumption on hepatic lipids were also compared in lean men after 67 hours of a normal mixed (NM) diet versus a low-carbohydrate, high-saturated-fat (LCHF) diet. SI was significantly higher in OB+HS (0.970 ± 0.004) and OB (0.944 ± 0.008) versus LEAN (0.818 ± 0.025) (P < 0.01 for both). PUI was significantly lower in OB+HS (0.003 ± 0.001) and OB (0.022 ± 0.005) versus LEAN (0.120 ± 0.021) (P < 0.01), and significantly lower in OB+HS versus OB (P < 0.05). LCHF diet did not alter HTGC, SI, or PUI (P > 0.05). The 1H-MRS method provides for rapid, qualitative assessment of lipid composition. Application of this technique in the liver produces results that are consistent with biopsy-based approaches demonstrating that relative hepatic lipid saturation increases and polyunsaturation decreases with obesity. Obesity-related hepatic steatosis is characterized by further depletion of polyunsaturated hepatic lipids. Conclusion: This readily available and noninvasive approach should promote further study into interactions between hepatic and whole-body lipid metabolism and help to elucidate the pathogenesis of disorders characterized by lipid accumulation within the liver. (HEPATOLOGY 2008.)
New lexicon and criteria for the diagnosis of Alzheimer's disease
Authors: Hamid R Sohrabi, Michael Weinborn, Johanna Badcock, Kristyn A Bates, Roger Clarnette, Darshan Trivedi, Giuseppe Verdile, Tom Sutton, Nat P Lenzo, Samuel E Gandy, Ralph N Martins
Journal: The Lancet Neurology (2011)
Coronary angioplasty. Statewide experience in California.
Authors: J L Ritchie, K A Phillips, H S Luft
Journal: Circulation (1993)

This report describes the in-hospital experience with percutaneous transluminal coronary angioplasty (PTCA) for the state of California in 1989. Data are derived from the statewide hospital discharge abstracts.A total of 24,883 PTCAs were performed; most patients (70%) were men and most procedures were single vessel (87%). About one fifth (19%) of patients had a principal diagnosis of acute myocardial infarction (AMI). Overall mortality was 1.4% and was higher in the AMI group (4.2%) versus the non-AMI group (0.8%, P = .0001). Mortality was higher for AMI patients having PTCA on the day of or day after admission (5.5%) versus those treated later (2.6%, P = .0001). Five percent of patients had coronary artery bypass surgery (CABG) after PTCA; CABG was performed on the same day as PTCA in 61.7% of cases. Patients presenting with AMI were more likely to have CABG (7.1%) than non-AMI patients (4.5%, P = .0001). Mortality associated with CABG was 7.3% and was higher in the AMI group (12.0%) than in the non-AMI group (5.5%, P = .0001). Factors predictive of increased mortality by bivariate analysis included age > 63 years (2.1% mortality versus 0.8% < or = 63, P = .01), female sex (1.9% versus 1.2% for men, P < .01), and the presence of diabetes (1.9% versus 1.3% for nondiabetics, P < .05). Multiple logistic regression showed that timings of PTCA with respect to admission (P = .004) and age (P = .05) were predictors of mortality, but female sex was predictive only in the non-AMI group (P = .03). Mean hospital charges were $19,597 (+/- SD, $18,213). Forty-two percent of the 110 hospitals performed more than the recommended minimum of 200 cases per year. The requirement for CABG during the same admission or the combined adverse outcome of CABG and/or death was increased in the lower-volume centers for both AMI and non-AMI patients (P < .001), although mortality alone was not.The mortality and need for CABG surgery in the statewide California PTCA experience is higher than that generally reported in the literature. In patients with an admitting diagnosis of AMI, the overall mortality was higher, as was the need for CABG and the associated CABG mortality. Most hospitals performed fewer than 200 PTCAs per year. Rates of CABG surgery and the combination of CABG and/or mortality, adjusted only for the presence or absence of AMI, were increased at the low-volume institutions.
Lymphatic removal of fluids and particles in the mammalian lung.
Authors: L V Leak
Journal: Environmental Health Perspectives (1980)

The structure and distribution of pulmonary lymphatics and their permeability to fluids and particulate materials have been investigated in the lungs of rats following fixation by combined intratracheal and vascular perfusion. In such preparations, the lymphatics remain in a distended state, and a close relationship to other structural components of the pulmonary interstitium is maintained. They were identified in regions with an abundant amount of connective tissue, forming an eleborate plexus within the pleura, the interlobular septum, peribronchial and perivascular areas. Recent data have shown that water-soluble molecules and particulate matter are removed from the interstitium along the lymphatic capillary (initial lymphatics) segment. It is distinguished by attenuated endothelial cells with extensively overlapping cell margins which are easily separated. We have studied this segment of the lymphatic vascular system following intratracheal injections of colloidal particles (ferritin and carbon) to determine the structural features responsible for the transport of large molecules and particulate materials across the lymphatic endothelial wall in the lung. The results showed that the tracer particles cross the lymphatic endothelial wall via the clefts of intercellular junctions. While the tracer particles were observed within vesicles, the question of transport across the lymphatic endothelium via plasmalemmal vesicles is still not settled since the number and size of vesicles containing tracer particles also increased with time. Intravascular injected dextran was also localized within the clefts of intercellular junctions and plasmalemmal vesicles. The results obtained with intratracheal and intravascular injected tracer substances are consistent with those observed in lymphatic capillaries for other tissues.
In liver fibrosis, dendritic cells govern hepatic inflammation in mice via TNF-α
Authors: Michael K. Connolly, Andrea S. Bedrosian, Jon Mallen-St. Clair, Aaron P. Mitchell, Junaid Ibrahim, Andrea Stroud, H. Leon Pachter, Dafna Bar-Sagi, Alan B. Frey, George Miller
Journal: Journal of Clinical Investigation (2009)

Hepatic fibrosis occurs during most chronic liver diseases and is driven by inflammatory responses to injured tissue. Because DCs are central to modulating liver immunity, we postulated that altered DC function contributes to immunologic changes in hepatic fibrosis and affects the pathologic inflammatory milieu within the fibrotic liver. Using mouse models, we determined the contribution of DCs to altered hepatic immunity in fibrosis and investigated the role of DCs in modulating the inflammatory environment within the fibrotic liver. We found that DC depletion completely abrogated the elevated levels of many inflammatory mediators that are produced in the fibrotic liver. DCs represented approximately 25% of the fibrotic hepatic leukocytes and showed an elevated CD11b+CD8– fraction, a lower B220+ plasmacytoid fraction, and increased expression of MHC II and CD40. Moreover, after liver injury, DCs gained a marked capacity to induce hepatic stellate cells, NK cells, and T cells to mediate inflammation, proliferation, and production of potent immune responses. The proinflammatory and immunogenic effects of fibrotic DCs were contingent on their production of TNF-α. Therefore, modulating DC function may be an attractive approach to experimental therapeutics in fibro-inflammatory liver disease.
Defending referrals between consultants
Authors: Michael Goodman
Journal: BMJ (2006)

T he NHS, at least in England, is currently afflicted by managerial interference in the referral of patients from one consultant to another and also in the scheduling of follow-up appointments in consultants' clinics.

Each inpatient and outpatient in NHS hospitals (with a few exceptions) is under the care of a medically or dentally qualified consultant, who needs access to a number of facilities so as to provide treatment and give advice. These facilities include investigations, operating theatres, and the services of other professionals such as physiotherapists. Consultants also need to be able to get opinions and interventions from other consultants—from colleagues in their own hospital and sometimes by referring to a consultant in another hospital. Access to this facility is as fundamental as access to the others.

In the NHS, capacity for prompt referral from one consultant to another is often lacking. Patients needing such referrals often have to join waiting lists for clinics to which general practitioners …
A Voluntary Board Will Not Accomplish the Result Desired.
Authors: L. W. Zwisohn
Journal: JAMA (1902)

New York, May 17, 1902. <h3>To the Editor:</h3> —I have read with great interest the article of Dr. Rodman in the issue ofThe Journalof the 10th inst. and your very able editorial on the same. You having invited a free expression of opinion pro and con, I take the liberty to analyze it and point out wherein I differ. The evil that this voluntary board of national examiners is expected to remedy is supposed to be this: that a graduate of a medical college of high standard, holding a certificate from a state board, is compelled to pass an examination in case of his removal to another state. Will this proposed board accomplish the result? Any state which demands an examination from one possessing credentials of registration in a state with a high medical standard, will also refuse to recognize a license of a national voluntary board; as
RELAPSED OR RESISTANT CLUBFOOT OF EARLY CHILDHOOD
Authors: BURT G. CHOLLETT
Journal: JAMA (1933)

There are three distinct types of deformity to which the title of congenital talipes equinovarus can be given: 1. The common variety, which, except in rare instances, occurs in otherwise normal infants. 2. A rare type associated with, and part of, a failure of development of the extremity as a whole, either of the lower limbs alone or of the upper limbs as well; also arthrogryposis. 3. A rare type associated with the absence of the tibia and some of the toes. If a real criterion is set for cured clubfoot, every clinic will have a certain number of disappointing results after all types of closed procedures have been exhausted. This is true even when treatment has been instituted early and efficiently carried out. Pathologic specimens of clubfoot in infancy are rare. Most of the descriptions in the literature on this subject and specimens in museums are of the adult
Precancerous lesions are more accurately termed "dysplasia"
Authors: J. P. Houghton
Journal: BMJ (2013)

Precancerous lesions, often detected by cancer screening programmes, fascinate histopathologists. Microscopic examination shows some of the architectural and cytological features of malignancy but no invasion of surrounding healthy tissue.

As a practising histopathologist, I have always felt uncomfortable that patients with these conditions, such as ductal carcinoma in situ of the breast, are often told …
The Genes and Brains of Mice and Men
Authors: Laurence H. Tecott
Journal: American Journal of Psychiatry (2003)

The elucidation of the human genome presents a challenge for psychiatry-determining the impact of thousands of genes on brain functions relevant to mental disorders. For both historical and practical reasons, the mouse has become the mammal of choice for applying molecular genetic approaches to gene function. A working draft of the mouse genome has led to estimates that a mouse version may be identified for 99% of human genes. In accord with their genomic homologies, humans and mice share numerous features of brain organization and behavioral responses to many pharmacological agents. Technologies enabling the precise experimental manipulation of the mouse genome provide unprecedented opportunities for exploring genetic contributions to the regulation of complex behavior and to the pathophysiology and treatment of psychiatric disease. The formidable array of mouse molecular genetic tools are applied for two general strategies: 1) exploring the function of particular genes by generating lines of mice with precise genetic alterations and 2) searching broadly for those genes that regulate a particular biological trait of interest. Essential to the effective use of these technologies is the implementation of sound strategies for discerning the impact of genetic manipulations on mouse behaviors relevant to psychiatric conditions. These approaches are having a major impact-examples relevant to psychiatric disorders are discussed. However, advances in implementing and interpreting behavioral assays have not kept pace with molecular genetic technologies. To maximize the extent to which the revolution in mammalian genetics may be effectively applied to psychiatric research, new technologies and strategies for mouse behavioral assessment must be developed.
Determination of synovial fluid hyaluronate concentration and polymerisation by high performance liquid chromatography.
Authors: H Saari, Y T Konttinen
Journal: Annals of the Rheumatic Diseases (1989)

High performance liquid chromatography (HPLC) with a size exclusion column and ultraviolet monitoring was used to study the effect of synovial fluid hyaluronate concentration and degree of polymerisation on viscosity and mucin clot formation. Rotational viscometry measurements showed an exponential relation between the synovial fluid hyaluronate concentration and relative viscosity, the viscosity increasing particularly steeply with hyaluronate concentrations exceeding 2-2.5 mg/ml. The scattering of individual values observed around the expected curve was eliminated when both the hyaluronate concentration and its degree of polymerisation were taken into account. Hyaluronate concentration and degree of polymerisation also correlated with the quality of mucin clot, though only HPLC provided more detailed quantitative information about this association. Because HPLC allows reproducible and rapid simultaneous analysis of the synovial fluid hyaluronate concentration and the degree of polymerisation in small volumes of unprocessed samples it can be used in well equipped rheumatological units to replace other methods used previously.
Ultrastructure of rat initial collecting tubule. Effect of adrenal corticosteroid treatment.
Authors: B Stanton, A Janzen, G Klein-Robbenhaar, R DeFronzo, G Giebisch, J Wade
Journal: Journal of Clinical Investigation (1985)

This study examines the effects of adrenalectomy and physiological replacement of mineralocorticoids and glucocorticoids on the cellular ultrastructure of the rat initial collecting tubule (late distal tubule). Animals were adrenalectomized (ADX) and for 10 d received by osmotic minipump either: vehicle, aldosterone (0.5 micrograms X 100 g-1 X d-1), aldosterone (2.0 micrograms X 100 g-1 X d-1), dexamethasone (1.2 micrograms X 100 g-1 X d-1), or aldosterone (0.5 micrograms X 100 g-1 X d-1) with dexamethasone (1.2 micrograms X 100 g-1 X d-1). Radioimmunoassay revealed that the low dose of aldosterone restored plasma aldosterone to control levels. The higher dose of aldosterone increased plasma levels by threefold. Morphometric techniques were used to measure membrane length of individual principal and intercalated cells in each condition. The basolateral membrane length of principal cells decreased by 35% in ADX animals. Low dose aldosterone replacement (0.5 micrograms X 100 g-1 X d-1) in ADX animals maintained membrane length at control values; at a higher level of aldosterone (2.0 micrograms X 100 g-1 X d-1) membrane length increased by 111% compared with control. Dexamethasone treatment, at a level that restored glomerular filtration rate to normal, had no effect on cellular ultrastructure. Combined aldosterone and dexamethasone replacement had no greater effect on basolateral membrane length than aldosterone alone. The length of the luminal membrane of the principal cell type was not affected by ADX or hormone treatment. Intercalated cell membrane length was not affected by ADX or hormone replacement. Thus, chronic aldosterone levels have an important, selective effect on the basolateral membrane of the principal cell. The correlation between these morphological results and the steroid hormone effects on renal electrolyte excretion, reported in the companion paper (15), suggests that basolateral membrane length is an important factor controlling the rate of sodium and potassium transport by the initial collecting tubule.
VISUAL ASSESSMENT OF ACL INJURY RISK: CAN EXPERTISE BE ACHIEVED?
Authors: E Petushek, E Cokely, P Ward, T Krosshaug, G Myer
Journal: British Journal of Sports Medicine (2014)

Background Identifying individuals with a high risk for ACL injury is important for injury prevention. Current screening methods exist but rely on expensive and time consuming biomechanical analysis, limiting large scale application. Objective The aim of this experiment was to investigate observational ACL injury risk assessment performance. Design Individual raters viewed 25 frontal plane video clips of female high school athletes performing a drop vertical jump. Five video clips were repeated. The decision task was to rate the athletes risk for an ACL injury on a 10 point scale (1=very low, 10=very high). Concurrent 3D peak knee abduction moment (KAM) was calculated for the video-taped athletes and served as the criterion for ACL injury risk level. Setting Raters viewed the video clips and responded using a computer. Participants A convenience sample of 40 allied health professionals/students served as raters. Risk factor assessment In order to perform signal detection analysis on the judgments, ratings greater than 5 were considered high risk. Main outcome measurements To assess judgment performance, Spearman rho (ρ), sensitivity ( A' ) and decision bias ( B D ) were calculated. Intra-rater consistency was assessed by calculating typical error between the 5 repeated video clips. Rater performance was also compared to the ACL Nomogram (KAM prediction model). Results Correlation between continuous KAM and subjective ratings ranged from −0.16 to 0.39 (Nomogram ρ=0.64). However, the best performer (M.S. Physiotherapist) displayed a sensitivity value of 0.85 ( B D =0.19) which was similar to the Nomogram measure of 0.97 ( B D =−0.48). In general, intra-rater consistency was sufficient with 83% of raters displaying typical error values less than 1. Conclusions Superior performance during visual assessment of ACL injury risk appears to be difficult but achievable. Research describing expertise mechanisms is warranted.
Role of the coagulation system in acetaminophen-induced hepatotoxicity in mice
Authors: Patricia E. Ganey, James P. Luyendyk, Sandra W. Newport, Theresa M. Eagle, Jane F. Maddox, Nigel Mackman, Robert A. Roth
Journal: Hepatology (2007)

Acetaminophen (N-acetyl-p-aminophenol [APAP]) is one of the leading causes of acute liver failure, and APAP hepatotoxicity is associated with coagulopathy in humans. We tested the hypothesis that activation of the coagulation system and downstream protease-activated receptor (PAR)-1 signaling contribute to APAP-induced liver injury. Fasted C57BL/J6 mice were treated with either saline or APAP (400 mg/kg intraperitoneally) and were euthanized 0.5-24 hours later. Hepatotoxicity and coagulation system activation occurred by 2 hours after administration of APAP. Treatment with APAP also caused a rapid and transient increase in liver procoagulant activity. In addition, significant deposition of fibrin was observed in the liver by 2 hours, and the concentration of plasminogen activator inhibitor-1 in plasma increased between 2 and 6 hours. Pretreatment with heparin attenuated the APAP-induced activation of the coagulation system and hepatocellular injury and diminished hepatic fibrin deposition at 6 hours. Loss of hepatocellular glutathione was similar in APAP-treated mice pretreated with saline or heparin, suggesting that heparin did not diminish bioactivation of APAP. In mice deficient in tissue factor, the principal cellular activator of coagulation, APAP-induced liver injury, activation of coagulation, and hepatic fibrin deposition were reduced at 6 hours. Formation of the tissue factor-factor VIIa complex leads to the generation of thrombin that can activate cells through cleavage of PAR-1. Mice lacking PAR-1 developed less injury and hepatic fibrin deposits at 6 hours in response to APAP than control mice.Activation of the coagulation system and PAR-1 signaling contribute significantly to APAP-induced liver injury.