tbuckley/cabot-search huggingface dataset:
Enhanced Cellular Proliferation in Intact Stenotic Lesions Derived From Human Arteriovenous Fistulas and Peripheral Bypass Grafts
Authors: Leo Hofstra, Jan H.M. Tordoir, Peter J.E.H.M. Kitslaar, Arnold P.G. Hoeks, Mat J.A.P. Daemen
Journal: Circulation (1996)

Background Vascular interventions are often complicated by the development of intimal thickening, leading to stenosis. Cellular proliferation is a key event in stenosis formation in animals, but the role of cell proliferation in intimal thickening in humans is still unclear. Furthermore, the relation between proliferation in human stenotic lesions and flow parameters has not been established. Methods and Results We studied the proliferation patterns of 35 anatomically intact human stenotic lesions derived from either peripheral bypasses (normal flow) or hemodialysis AV fistulas (high flow) with the use of Ki-67, a cell proliferation marker. Local flow parameters were assessed with ultrasound. Proliferation patterns were similar in AV fistula and bypass stenoses. In the intima, proliferation was highest in the area just below the endothelium (AV fistulas, 3.6%; bypasses, 3.5%; P =NS). In adjacent nonstenotic vessel segments that were used as controls, proliferation rate in the intima was 0.3%. Double-labeling studies revealed that subendothelial-intimal proliferation consisted mainly (90%) of vascular smooth muscle cells, whereas proliferation in the other layers of the vessel wall also consisted of endothelial cells and macrophages. Blood flow velocity was negatively correlated with subendothelial-intimal proliferation ( r =−.61, P &lt;.05). The endothelial cell coverage of the lumen was positively correlated with proliferation ( r =.85, P &lt;.01). Conclusions These data suggest enhanced cellular proliferation in human stenotic tissue derived from AV fistulas and peripheral bypass grafts. Furthermore, high proliferation rates seem to be associated with endothelial cell coverage of the lumen and low local flow velocities.
Pharmacogenetics and ethnically targeted therapies
Authors: Jonathan D Kahn
Journal: BMJ (2005)

Health inequalities under New Labour Relative rather than absolute gaps are important over time and placeEditor-We agree with Shaw et al that the method of measuring inequality in health outcomes used in setting the government targets is problematic (A Low, UKPHA (UK Public Health Association), 13th annual public health forum, Gateshead, April 2005). 1 However, the government's targets are based on reducing relative gaps in life expectancy and infant mortality. 2 The slope index of inequality (SII) used by Shaw et al measures absolute gaps.
Leptomeningeal melanoma and multiple cutaneous melanocytic naevi
Authors: J. Ponnampalam, J. Nicholson, D. Atherton
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, Neurocutaneous melanosis (NCM) is a rare disease characterized by congenital cutaneous melanocytic naevi with excess melanosis that continue to develop, favouring axial sites.1 Leptomeningeal melanoma, a known sequela of NCM, is an aggressive tumour with poor outcome and limited treatment options.2 It follows that in children with NCM, careful neurological as well as dermatological surveillance is essential. A striking feature of NCM is that melanomas favour axial sites and rarely develop in satellite lesions so that scrupulous monitoring of skin lesions is of limited value. Removal of skin lesions does not reduce the incidence of metastatic spread and laser or surgical treatment is of benefit only for cosmetic purposes. The presentation of NCM is variable. Children may present with developmental delay, weight loss, visual disturbances, flaccid paralysis, signs of raised intracranial pressure or even neuropsychiatric disturbances. Magnetic resonance imaging (MRI) of the nervous system may show thickened leptomeninges surrounding the brain and spinal cord with secondary hydrocephalus, or may show overt tumour. The abnormalities usually enhance postgadolinium.
The role of context and inhibition in ADHD
Authors: Petra Björne, Christian Balkenius
Journal: Behavioral and Brain Sciences (2005)

we have shown in a computational model that a poor memory for context could result in some of the behaviors associated with adhd, which is well in line with the dynamic developmental theory. given the important role of context in extinction, a weaker context due to a steeper delay-of-reinforcement gradient would result in impaired inhibition.
Challenging endoscopy reprocessing guidelines: a prospective study investigating the safe shelf life of flexible endoscopes in a tertiary gastroenterology unit
Authors: S. Osborne, S. Reynolds, N. George, F. Lindemayer, A. Gill, M. Chalmers
Journal: Endoscopy (2007)

Professional practice guidelines for endoscope reprocessing recommend reprocessing endoscopes between each case and proper storage following reprocessing after the last case of the list. There is limited empirical evidence to support the efficacy of endoscope reprocessing prior to use in the first case of the day; however, internationally, many guidelines continue to recommend this practice. The aim of this study is to estimate a safe shelf life for flexible endoscopes in a high-turnover gastroenterology unit.In a prospective observational study, all flexible endoscopes in active service during the 3-week study period were microbiologically sampled prior to reprocessing before the first case of the day (n = 200). The main outcome variables were culture status, organism cultured, and shelf life.Among the total number of useable samples (n = 194), the overall contamination rate was 15.5%, with a pathogenic contamination rate of 0.5%. Mean time between last case one day and reprocessing before the first case on the next day (that is, shelf life) was 37.62 h (SD 36.47). Median shelf life was 18.8 h (range 5.27-165.35 h). The most frequently identified organism was coagulase-negative Staphylococcus, an environmental nonpathogenic organism.When processed according to established guidelines, flexible endoscopes remain free from pathogenic organisms between last case and next day first case use. Significant reductions in the expenditure of time and resources on reprocessing endoscopes have the potential to reduce the restraints experienced by high-turnover endoscopy units and improve service delivery.
Effects of antisense p21 (WAF1/CIP1/MDA6) expression on the induction of differentiation and drug-mediated apoptosis in human myeloid leukemia cells (HL-60)
Authors: AJ Freemerman, JA Vrana, RM Tombes, H Jiang, SP Chellappan, PB Fisher, S Grant
Journal: Leukemia (1997)
Multilayered Heparin Hydrogel Microwells for Cultivation of Primary Hepatocytes
Authors: Jungmok You, Dong‐Sik Shin, Dipali Patel, Yandong Gao, Alexander Revzin
Journal: Advanced Healthcare Materials (2013)

Abstract The biomaterial scaffolds for regenerative medicine need to be rationally designed to achieve the desired cell fate and function. This paper describes the development of hydrogel microstructures for cultivation of primary hepatocytes. Four different micropatterned surfaces are tested: 1) poly(ethyelene glycol) (PEG) microwells patterned on glass, 2) heparin hydrogel microwells patterned on glass, 3) PEG microwells patterned on heparin hydrogel‐coated substrates, and 4) heparin hydrogel microwells patterned on heparin hydrogel‐coated substrates. The latter surfaces are constructed by a combination of micromolding and microcontact printing techniques to create microwells with both walls and floor composed of heparin hydrogel. Individual microwell dimensions are 200 μm diameter and 20 μm in height. In all cases, the floor of the microwells is modified with collagen I to promote cell adhesion. Cultivation of hepatocytes followed by analysis of hepatic markers (urea production, albumin synthesis, and E‐cadherin expression) reveals that the all‐heparin gel microwells are most conducive to hepatic phenotype maintenance. For example, ELISA analysis shows 2.3 to 13.1 times higher levels of albumin production in all‐heparin gel wells compared with other micropatterned surfaces. Importantly, hepatic phenotype expression can be further enhanced by culturing fibroblasts on the heparin gel walls of the microwells. In the future, multicomponent all‐heparin gel microstructures may be employed in designing hepatic niche for liver‐specific differentiation of stem cells.
Gentamicin Treatment of Staphylococcal Infections
Authors: Fred Richards
Journal: JAMA (1971)

<i>Sixteen infections caused</i>by Staphylococcus aureus<i>and six infections caused by</i>S albus<i>were treated with gentamicin sulfate. The antibiotic was effective in eradicating the</i>S<i>aureus infections in all but two patients. All six infections due to</i>S albus<i>were cured. No significant toxic effects were detected and superinfection developed in only one patient. The clinical efficacy of gentamicin correlated with its in vitro activity as determined by tube-dilution and disk-diffusion assays. All isolates of</i>S aureus<i>were inhibited by 3.1μg/ml or less of gentamicin; all isolates of</i>S albus<i>were inhibited by 0.78μg/ml or less of gentamicin. The bactericidal concentrations of gentamicin were never greater than twice the inhibitory concentrations</i>.
Correlation between hepatic morphology and immunoglobulins and antibodies to Escherichia coli in cirrhosis.
Authors: H Prytz, M Bjorneboe, P Christoffersen, H Poulsen, F Orskov
Journal: Gut (1977)

Increased antibody production and hypergammaglobulinaemia in cirrhosis are probably to a large extent due to decreased hepatic extraction of antigens. The deceased extraction is presumably related to changed microcirculation caused by damaged anatomical structure of the liver. It is therefore to be expected that immunoglobulin and antibody levels in serum in cirrhotic patients are related to the degree of certain morphological changes of the liver. This hypothesis has been tested. In 50 patients with cirrhosis, 28 alcoholics and 22 non-alcoholics, the degree of architectural destruction, the degree of fibrosis, the degree of fatty infiltration, and the degree of "activity" were compared with immunoglobulins G, A, and M and E. coli O antibody levels. The comparison was carried out within each of the aetiological groups. Identical relationships were found in both groups. Patients with completely destroyed lobular architecture had higher levels of E. coli O antibodies than patients with partly destroyed architecture. Patients with severe fibrosis had higher IgA and E. coli O antibody levels than patients with moderate or slight fibrosis. Patients with moderate and severe steatosis and patients with no or slight steatosis had the same immunoglobulin and E. coli O antibody levels. Patients with active cirrhosis had higher IgG levels than patients with inactive cirrhosis. When architectural destruction and fibrosis were combined significantly higher IgG, IgA, IgM, and E. coli antibodies were found in the group with the most severe changes. These findings support the hypothesis that immunoglobulin and antibody levels are related to the degree of morphological changes in the liver--namely, destruction of lobular architecture, fibrosis, and "activity".
Anorectal manometry in irritable bowel syndrome: differences between diarrhoea and constipation predominant subjects.
Authors: A Prior, D G Maxton, P J Whorwell
Journal: Gut (1990)

Anorectal manometry with balloon distension was performed on 28 patients with diarrhoea predominant irritable bowel syndrome, 27 patients with constipation predominant irritable bowel syndrome and 30 normal controls. In the diarrhoea predominant group balloon volumes required to perceive the sensations of gas, stool, urgency of defecation and discomfort were significantly lower than in controls or constipation predominant patients (p less than 0.001). Diarrhoea predominant patients also had a significantly lower rectal compliance than controls or constipation predominant patients (p less than 0.03) but showed no difference in motor activity induced by distension. When the constipation predominant patients were compared with controls the only significant difference that emerged was in the volume at which discomfort was perceived. No significant differences between constipated subjects and controls were found in the distension induced motor activity. Symptom severity and psychological parameters were also recorded and the diarrhoea predominant patients were found to be more anxious than those with constipation (p = 0.04). It proved possible (by comparison with the control group) to identify three abnormal rectal subtypes in patients with irritable bowel syndrome. These were a sensitive rectum (low sensation thresholds, normal or low rectal pressure), a stiff rectum (normal or low sensation thresholds, high pressure) and an insensitive rectum (high sensation thresholds, normal or high pressure) and their distribution varied considerably depending on bowel habit. Some form of rectal abnormality was identified in 75% of diarrhoea predominant patients compared with 30% of constipation predominant subjects (p = 0.002). A sensitive rectum was a particular feature of diarrhoea predominant patients being observed in 57% of patients compared with only 7% of the constipated group (p less than 0.001).
Molecular and cell biology in clinical medicine: introduction.
Authors: D Weatherall
Journal: BMJ (1987)

All this will require some rethinking ofmedical education and the way in which our clinical schools and postgraduate programmes are organised in the future; the profession will have to take on board and accommodate individuals with a much broader range of scientific skills than has been necessary hitherto.This will require some urgent thought by those who are concerned with training our doctors in the future.I hope that this new series will help to provide some of the background information on which we can develop an informed debate on how these changes might be made while, at the same time, maintaining high standards of patient care.
Impairing Loyalty: Corporate Responsibility for Clinical Misadventure
Authors: Kenneth Kipnis
Journal: The American Journal of Bioethics (2011)

A medical device manufacturer pays a surgeon to demonstrate a novel medical instrument in a live broadcast to an audience of specialists in another city. The surgical patient is unaware of the broadcast and unaware of the doctor's relationship with the manufacturer. It turns out that the patient required a different surgical approach to her condition—one that would not have allowed a demonstration of the instrument—and she later dies. The paper is an exploration of whether the manufacturer shares, along with the doctor, responsibility for the death of the patient. Three arguments for corporate responsibility are considered; two are criticized and the third is offered as sound.
A Switch in Time Saves a Statistical Bind
Authors: Elaine Blume
Journal: JAMA (1991)

To the Editor.  —In a review of breast cancer treatment in the student-edited Pulse section of JAMA , 1 the following statement was made: Each year one in ten women is confronted with breast cancer.... I think not. It's bad enough that the author is a former president of the American Cancer Society, but the Pulse editor also seems to have been asleep at the switch.
Respiratory impedance response to continuous negative airway pressure in awake controls and OSAS
Authors: A.M. Lorino, F. Lofaso, E. Dahan, A. Harf, H. Lorino
Journal: European Respiratory Journal (2001)

The aim of the study was to determine whether the response of respiratory impedance (Zrs) to decreasing levels of continuous negative airway pressure (CNAP) during wakefulness, differs in controls and subjects with obstructive sleep apnoea syndrome (OSAS). Zrs was measured by the forced oscillation technique (4-32 Hz) in 15 controls and 21 patients with OSAS (apnoea/hypopnoea index >20 per sleep hour) with normal lung function, in the basal state and with application of decreasing CNAP of -5, -10, and -15 hPa. Respiratory resistance was extrapolated to 0 Hz (R0) and estimated at 16 Hz (R16) by linear regression analysis of respiratory resistive impedance versus frequency. Respiratory elastance (Ers) and inertance (Irs) were estimated by multilinear regression analysis of respiratory reactance versus frequency, and resonance frequency (RF) was determined as RF=(1/2pi)(Ers/Irs)0.5. In both groups, R0, R16, Ers and RF significantly increased as the CNAP level decreased (p <0.0001 for all). R0, Ers, and RF increased significantly more in OSAS than in controls (p < 0.01, 0.001, and 0.0001, respectively), independently of the severity of obesity. Receiver operator characteristic curves showed that the parameter which best detected OSAS was RF, with a sensitivity of 81% and 93% specificity for the 13.6 Hz cut-off point. The results of the present study suggest that the response of respiratory impedance to decreasing continuous negative airway pressure levels, might allow detection of obstructive sleep apnoea syndrome in subjects with normal lung function.
TCT-260 Which is the Ideal Revascularization Strategy in Patients Presenting with Acute Coronary Syndrome and Proximal LAD Stenosis? Results from the ACUITY Study
Authors: Marco G. Mennuni, Roxana Mehran, George Dangas, Usman Baber, Ajay J. Kirtane, Philippe Genereux, Sorin Brener, Frederick Feit, A. Michael Lincoff, E. Magnus Ohman, Martial Hamon, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2013)
Pure Red Cell Aplasia Associated With Sodium Valproate Therapy
Authors: Lorna G. MacDougall
Journal: JAMA (1982)

Pure red cell aplasia developed in a 9-year-old girl receiving sodium valproate therapy. Infection with measles and chickenpox had occurred two months previously. Regeneration of bone marrow erythroid precursors was demonstrated one month after drug withdrawal. Readministration of sodium valproate resulted in a second episode of red cell aplasia that again resolved promptly after drug withdrawal. The respective roles of infection and drugs in the etiology of red cell aplasia are discussed.
Effect of Hypercholesterolemia on Expression and Function of Vascular Soluble Guanylyl Cyclase
Authors: Ute Laber, Thorsten Kober, Verena Schmitz, Astrid Schrammel, Wilfried Meyer, Bernd Mayer, Martina Weber, Georg Kojda
Journal: Circulation (2002)

Background — Vasorelaxation to endothelial NO is mediated by activation of soluble guanylyl cyclase (sGC) and impaired by hypercholesterolemia in animals and humans. We investigated whether hypercholesterolemia impacts expression and function of sGC. Methods and Results — White New Zealand rabbits (n=10 per group) received a standard diet for 16 weeks (SD16) (n=20) or 32 weeks (SD32) and a cholesterol diet (7.5 g/kg) for 16 weeks (CD16) (n=20) or 32 weeks (CD32), respectively. Another group received cholesterol diet for 16 weeks followed by standard diet for 16 weeks (CD/SD). Aortic expression of the α 1 -subunit of sGC (sGC-α 1 ) and β 1 -subunit of sGC (sGC-β 1 ) was assessed by Western blot. Function was measured by aortic relaxation to S-Nitroso- N -acetyl-D, L-penicillamine (SNAP) and sGC activity in aortic cytosols. Hypercholesterolemia induced an upregulation of sGC-β 1 in CD16 (3.5±0.4-fold, P &lt;0.001 versus SD16) and CD32 (4.0±0.4-fold, P &lt;0.001 versus SD32). A similar increase was found for sGC-α 1 . In striking contrast, basal and NO-stimulated sGC activities in aortic cytosols of CD16 were only slightly enhanced (1.4-fold, P &lt;0.05). Furthermore, the vasodilator potency of SNAP (EC 50 in −logM) was 10-fold lower in CD16 (6.76±0.09) than in SD16 (7.66±0.14, P &lt;0.01). The increase of sGC expression was completely reversible, as indicated by comparable sGC-β 1 amounts in SD32 and CD/SD (1.2±0.1-fold, P &gt;0.05). Immunohistochemical analysis suggests that a great portion of the overexpressed sGC is located in intimal lesions. Additional experiments showed that increased vascular superoxide production induced by 6-anilino-5,8-quinolinedione (LY85385) reduces sGC-activity but increases sGC-expression. Conclusions — These results suggest that hypercholesterolemia induces a reversible overexpression of a dysfunctional vascular sGC, which may contribute to the pathogenesis of atherosclerosis.
Persistence of hepatitis C virus in patients successfully treated for chronic hepatitis C
Authors: Marek Radkowski, Juan F. Gallegos-Orozco, Joanna Jablonska, Thomas V. Colby, Bozena Walewska-Zielecka, Joanna Kubicka, Jeffrey Wilkinson, Debra Adair, Jorge Rakela, Tomasz Laskus
Journal: Hepatology (2005)

It is unclear whether the current antiviral treatment for chronic hepatitis C virus (HCV) infection results in complete elimination of the virus, or whether small quantities of virus persist. Our study group comprised 17 patients with chronic HCV who had sustained virological response (SVR) after interferon/ribavirin treatment. Serum and peripheral blood mononudear cells were collected 2 to 3 times at 3- to 6-month intervals starting 40 to 109 months (mean, 64.2 +/- 18.5 months) after the end of therapy. In addition, lymphocyte and macrophage cultures were established at each point. In 11 patients, frozen liver tissue samples were available from follow-up biopsies performed 41 to 98 months (mean, 63.6 +/- 16.7 months) after therapy. Presence of HCV RNA was determined by sensitive reverse-transcriptase polymerase chain reaction, and concentration of positive and negative strands was determined by a novel quantitative real-time reverse transcriptase polymerase chain reaction. Only 2 of 17 patients remained consistently HCV RNA negative in all analyzed compartments. HCV RNA was detected in macrophages from 11 patients (65%) and in lymphocytes from 7 patients (41%). Viral sequences were also detected in 3 of 11 livers and in sera from 4 patients. Viral replicative forms were found in lymphocytes from 2 and in macrophages from 4 patients. In conclusion, our results suggest that in patients with SVR after therapy, small quantities of HCV RNA may persist in liver or macrophages and lymphocytes for up to 9 years. This continuous viral presence could result in persistence of humoral and cellular immunity for many years after therapy and could present a potential risk for infection reactivation.
Where next with revalidation?: Smart money is on using new communications technology effectively
Authors: Graeme M Mackenzie
Journal: BMJ (2005)

EDITOR—I assume that the survivalists of the profession will get into revalidation—better to be reporting on people than being reported on.1 The authorities need to look at practice in terms of how much daily evidence based peer review is going on in a team.

In our medium sized (non-training) practice journal articles are …
What Benefits Will Self-Employed Doctors Receive Under Social Security?
Authors: Robert J. Myers
Journal: JAMA (1966)

After many years of debate, a bill has been passed extending compulsory coverage under old-age, survivors, and disability insurance (OASDI), as well as a new program of hospital insurance (HI), to self-employed physicians. It is not the purpose of this report to argue the merits of such compulsory coverage. Rather, it is to point out the effects of coverage and the protection that is provided, and particularly to illustrate the benefits that accrue to the older doctors brought under the program. These advantages derive from liberalizations contained in the 1960 and 1961 amendments to the Social Security Act, as well as in the current amendments. This presentation is concerned only with male self-employed physicians and does not encompass the effect of any coverage secured through work as an employee. It is also assumed that annual earnings are at least equal to the maximum taxable earnings, $6,600 beginning in 1966 ($4,800