tbuckley/cabot-search huggingface dataset:
Gargoylism: hydrolysis of β-galactosides and tissue accumulation of galactose- and mannose-containing compounds
Authors: Björn Hultberg, Per-Arne ϖckerman, Arne Dahlqvist
Journal: Journal of Clinical Investigation (1970)

The sugars present in hydrolyzed extracts of human liver and brain were analyzed by gasliquid chromatography after conversion to their alditol acetates. The samples analyzed were obtained from control subjects, patients with gargoylism, and patients with a few other kinds of storage disorders. Accumulation of galactose was demonstrated in the liver and the brain of two patients with gargoylism, and in the liver samples, high levels of mannose were found too. We also studied the hydrolysis of a number of galactosides by homogenates from different tissues in the control subjects and in the patients. Separation methods and kinetic studies demonstrated the presence in normal human tissues of two different beta-galactosidases, which we call enzyme A and enzyme B, respectively. Enzyme A hydrolyzed all the beta-galactosides tested. Enzyme B hydrolyzed the synthetic substrates tested (4-methylumbelliferyl-, p-nitrophenyl-, o-nitrophenyl-, and phenyl-beta-galactoside) but not the natural substrates tested (ceramide-beta-galactoside, ceramide lactoside, transferrin glycopeptide, and keratan sulfate). Enzyme B also exerted beta-glucosidase activity. In various tissues from patients with gargoylism, deficiency of beta-galactosidase A could be demonstrated. It is suggested that the high level of galactose found in the hydrolyzed extracts of tissues from gargoylism patients is due to storage of galactose-rich glycosaminoglycans and glycopeptides, and that this storage is a result of the deficiency of beta-galactosidase A. The high level of mannose in the liver from gargoylism patients seems to indicate storage of glycopeptide, adding a new group of substances to those known to be stored in gargoylism.
Detection of a frequent restriction fragment length polymorphism in the human T cell antigen receptor beta chain locus. A potential diagnostic tool.
Authors: N Berliner, A D Duby, C C Morton, P Leder, J G Seidman
Journal: Journal of Clinical Investigation (1985)

Abnormal T cell function is a feature of a spectrum of inherited and acquired diseases. We have detected a frequent restriction fragment length polymorphism in the human T cell antigen receptor beta-chain locus that may aid in the analysis of these disorders. A study of a panel of 18 normal individuals, testing for the presence of the polymorphism, showed it to account for 36% of the alleles in that group. In view of the fact that the T cell receptor beta-chain locus has been mapped to chromosome 7, and that the disease ataxia telangiectasia (AT) is associated both with abnormal T cell function and with chromosomal abnormalities of the same region of chromosome 7, we investigated the possibility that the polymorphism could demonstrate linkage of the T cell receptor locus to the gene for that disease. We demonstrated that the mutation causing AT did not lie within the beta-chain locus itself, and that there was preliminary evidence that the two loci were not closely linked. This polymorphism may provide a useful tool for the study of other genetic disorders associated with abnormalities of T cell function, as well as disorders associated with inherited or acquired abnormalities of chromosome 7.
Glial Cell Line–Derived Neurotrophic Factor in the Vitreous of Patients With Proliferative Diabetic Retinopathy
Authors: Nami Nishikiori, Yoshinori Mitamura, Asako Tashimo, Yasushi Nakamura, Takayuki Harada, Makoto Osanai, Norimasa Sawada, Kenji Ohtsuka
Journal: Diabetes Care (2005)

Glial cell line–derived neurotrophic factor (GDNF) belongs to the neurotrophic factor family. GDNF functions are not restricted to neurons but are also implicated in glial cell development (1). We observed high expression levels of GDNF receptor family α-component 2 (GFRα2) in epiretinal membranes (ERMs) in proliferative diabetic retinopathy (PDR), indicating the involvement of GFRα2 in ERM formation in PDR (2). Here, we examined the vitreous of patients with PDR for the presence of GDNF.

We assayed GDNF levels in …
Road traffic injuries are a global public health problem
Authors: M. Peden
Journal: BMJ (2002)

EDITOR—Road traffic crashes and their sequelae are a scourge in all societies, both developed and developing. Each year over a million people are killed in road traffic collisions worldwide and some 10 million people are injured or disabled by these events,1 predominantly in low and middle income countries.2

Despite what is known about road traffic crashes and their health consequences, policymakers worldwide show little awareness of their contribution to the burden of disease; consequently they are neglected …
P131 What is the Evidence For Pharmacological and Non-Pharmacological Interventions in Improving Dyspnoea, Other Symptoms and Quality of Life in Progressive Idiopathic Fibrotic Interstitial Lung Disease?- A Systematic Review of the Literature
Authors: S Bajwah, JR Ross, JL Peacock, IJ Higginson, AU Wells, A Patel, J Koffman, J Riley
Journal: Thorax (2012)

<h3>Background</h3> Patients with Progressive Idiopathic Fibrotic Interstitial Lung Diseases (PIF-ILD) such as idiopathic pulmonary fibrosis have a short disease trajectory and have a similar prognosis to lung cancer patients. They have clear symptom control and quality of life (Qol) needs. The objective of this review was to evaluate the evidence for the use of pharmacological and non-pharmacological methods in improving dyspnoea, other symptoms and Qol for patients with PIF-ILD. In addition we assessed the use of outcome scales and economic evaluation of interventions. <h3>Methods</h3> Studies were identified by searching eleven databases, relevant websites and hand searching key journals. Relevant studies were selected, assessed and data extracted independently by two researchers using standardised proformas. Meta-analyses were performed where appropriate and results presented as pooled mean difference with 95%CI. Effect sizes were also calculated where possible. A descriptive summary of other studies has been given. <h3>Results</h3> 35 papers with 18 interventions were included. Meta-analyses were only possible for 3 interventions. Meta-analysis showed no significant treatment effect of IFN gamma 1b or sildenafil on 6MWD or dyspnea. A positive treatment effect of pulmonary rehabilitation on 6MWD (effect size (95% CI) 27.4 (4.1, 50.7) p=0.02) was seen. Separate analysis showed a positive effect of pulmonary rehabilitation on dyspnea and a trend towards significant results for pulmonary rehabilitation and sildenafil in improving quality of life. There was weak evidence for the improvement of 6MWD using oxygen, dyspnea using prednisolone, diamorphine, D-pencillamine and colchicine, cough using interferon alpha and thalidomide, anxiety using diamorphine, fatigue using pulmonary rehabilitation and Qol using thalidomide and doxycycline which warrants further research. There were a wide range of outcome scales used and no studies with economic evaluation. <h3>Conclusion</h3> There is strong evidence for the use of pulmonary rehabilitation to improve 6MWD and moderate evidence for its use in improving dyspnoea and Qol. In addition, there is moderate evidence for sildenafil in improving Qol. There is weak evidence for a number of other interventions. Further research using economic evaluation and uniform outcome measures is needed.
The Hematopoietic Microenvironment
Authors: Dane R. Boggs
Journal: New England Journal of Medicine (1980)

IN this issue of the Journal, Ershler et al. present the most compelling evidence to date for the existence of a naturally occurring human disease of the hematopoietic microenvironment. Their patient had long-standing and probably congenital anemia due to failure of maturation of erythroid precursors in the marrow. However, when her marrow cells were aspirated and dispersed in culture systems, erythroid precursors proved to be abundant, and they matured and synthesized heme. Conversely, a nondispersed section of marrow obtained by means of biopsy failed to synthesize heme when placed in culture, although a similar sample of marrow from a . . .
Speakers convince debate that NHS efficiencies can be achieved without jeopardising quality
Authors: J. Hayes
Journal: BMJ (2010)

Delegates attending a debate on the cuts proposed for the NHS were convinced by speakers that the health service can reduce its expenditure without a drop in the quality of care delivered to patients.

Before the debate, which was hosted jointly by the King’s Fund and the BMJ , 58% of 100 delegates disagreed with the motion, “This house believes that the NHS will not be able to cut costs without substantially damaging the quality of health care.”

But after arguments from Rebecca Rosen, a GP and senior fellow at the Nuffield Trust, and Paul Corrigan, a management consultant and executive coach, the proportion of the doctors, managers, and health policy strategists in the audience voting against the motion increased to 71%.

Dr Rosen and Professor Corrigan argued that the NHS needs integration rather than investment, and that the future of the NHS looks rosy compared with other public sectors.

Speaking for the motion James Drife, professor of …
Electrocardiographic Signs of Chronic Cor Pulmonale
Authors: Raffaele Antonelli Incalzi, Leonello Fuso, Marino De Rosa, Anteo Di Napoli, Salvatore Basso, Gabriella Pagliari, Riccardo Pistelli
Journal: Circulation (1999)

Background —Chronic cor pulmonale (CCP) is a strong predictor of death in chronic obstructive pulmonary disease (COPD). The aims of this study were to assess the prognostic role of individual ECG signs of CCP and of the interaction between these signs and abnormal arterial blood gases. Methods and Results —Two hundred sixty-three patients (217 men) with COPD, mean age 67±9 years, were grouped according to whether they had no ECG signs (group 1, n=100) or ≥1 ECG signs (group 2, n=163) of CCP and were followed up for 13 years after an exacerbation of respiratory failure. The median survival was significantly shorter in group 2 than in group 1 (2.58 versus 3.45 years, respectively; Mantel-Cox test, 9.58; P =0.002). The Cox regression analysis identified S 1 S 2 S 3 pattern, right atrial overload (RAO), and alveolar-arterial oxygen gradient (P ao 2 −Pa o 2 ) &gt;48 mm Hg during oxygen therapy as the strongest predictors of death, with hazard rate (HR)=1.81 (95% CI, 1.22 to 2.69), HR=1.58 (95% CI, 1.15 to 2.18), and HR=1.96 (95% CI, 1.19 to 3.25), respectively. The median survivals of patients having both S 1 S 2 S 3 pattern and RAO (n=14) and of patients having either S 1 S 2 S 3 pattern or RAO (n=77) were 1.33 and 2.70 years, respectively ( P =0.022). Group 2 patients had a 3-year survival of 18% or 53%, depending on whether their P ao 2 −Pa o 2 during oxygen therapy was or was not &gt;48 mm Hg. Conclusions —Some ECG signs of CCP and P ao 2 −Pa o 2 &gt;48 mm Hg during oxygen therapy qualified as a simple and inexpensive tool for targeting subsets of COPD patients with severe or very severe short-term prognosis.
Coffee reduces liver damage in a rat model of steatohepatitis: The underlying mechanisms and the role of polyphenols and melanoidins
Authors: Paola Vitaglione, Filomena Morisco, Giovanna Mazzone, Daniela Caterina Amoruso, Maria Teresa Ribecco, Antonietta Romano, Vincenzo Fogliano, Nicola Caporaso, Giuseppe D'Argenio
Journal: Hepatology (2010)

Epidemiological data associate coffee consumption with a lower prevalence of chronic liver disease and a reduced risk of elevated liver enzyme levels (γ glutamyl transpeptidase and alanine aminotransferase), advanced liver disease and its complications, and hepatocellular carcinoma. Knowledge of the mechanisms underlying these effects and the coffee components responsible for these properties is still lacking. In this study, 1.5 mL/day of decaffeinated coffee or its polyphenols or melanoidins (corresponding to approximately 2 cups of filtered coffee or 6 cups of espresso coffee for a 70-kg person) were added for 8 weeks to the drinking water of rats who were being fed a high-fat, high-calorie solid diet (HFD) for the previous 4 weeks. At week 12, HFD + water rats showed a clinical picture typical of advanced nonalcoholic steatohepatitis compared with control rats (normal diet + water). In comparison, HFD + coffee rats showed: (1) reduced hepatic fat and collagen, as well as reduced serum alanine aminotransferase and triglycerides; (2) a two-fold reduced/oxidized glutathione ratio in both serum and liver; (3) reduced serum malondialdehyde (lipid peroxidation) and increased ferric reducing antioxidant power (reducing activity); (4) reduced expression of tumor necrosis factor α (TNF-α), tissue transglutaminase, and transforming growth factor β and increased expression of adiponectin receptor and peroxisome proliferator-activated receptor α in liver tissue; and (5) reduced hepatic concentrations of proinflammatory TNF-α and interferon-γ and increased anti-inflammatory interleukin-4 and interleukin-10. Conclusion: Our data demonstrate that coffee consumption protects the liver from damage caused by a high-fat diet. This effect was mediated by a reduction in hepatic fat accumulation (through increased fatty acid β-oxidation); systemic and liver oxidative stress (through the glutathione system); liver inflammation (through modulation of genes); and expression and concentrations of proteins and cytokines related to inflammation. (Hepatology 2010;52:1652-1661)
Lower Myocardial Perfusion Reserve Is Associated With Decreased Regional Left Ventricular Function in Asymptomatic Participants of the Multi-Ethnic Study of Atherosclerosis
Authors: Boaz D. Rosen, João A.C. Lima, Khurram Nasir, Thor Edvardsen, Aaron R. Folsom, Shenghan Lai, David A. Bluemke, Michael Jerosch-Herold
Journal: Circulation (2006)

Background— Myocardial ischemia is an important determinant of regional left ventricular systolic function. Myocardial blood flow reserve may be impaired by cardiovascular disease before alterations of myocardial perfusion at rest become manifest. Nevertheless, the relation between flow reserve and regional myocardial function has not been studied in individuals without a history of clinical heart disease. Methods and Results— Seventy-four participants (66±9 years, mean±SD) of the Multi-Ethnic Study of Atherosclerosis (MESA) underwent myocardial magnetic resonance tagging and contrast-enhanced perfusion studies. Regional myocardial function was evaluated as peak systolic circumferential strain (Ecc) in the three main coronary territories (left anterior descending [LAD], left circumflex, and right coronary artery [RCA]). Myocardial blood flow at rest and during adenosine-induced hyperemia was quantified by contrast-enhanced magnetic resonance imaging, to study the relation between regional flow and function after multivariable adjustment for age, gender, body mass index, left ventricular mass, and traditional risk factors. Lower regional myocardial blood flow during hyperemia was associated with reduced regional left ventricular function expressed as lower Ecc in the RCA ( P &lt;0.01) and left circumflex regions ( P &lt;0.05) measured in the subendocardium, mid-wall, and subepicardium. In contrast, no significant association was seen in the LAD territory ( P =0.16). In addition, segmental function in LAD and RCA regions was reduced when individuals in the lowest 10th percentile for regional myocardial flow reserve were compared with the other participants. Absolute decreases in mid-wall Ecc LAD and RCA and global Ecc were 3.0%, 3.4%, and 2.8%, respectively ( P &lt;0.05 for all regions). Conclusions— Lower myocardial flow reserve is related to reduced regional function in asymptomatic individuals.
Corrigendum to: “Re: The Efficacy and Safety of Degarelix: A 12-Month, Comparative, Randomized, Open-Label, Parallel-Group Phase III Study in Patients with Prostate Cancer” by Dieter Jocham and Christian Doehn [Eur Urol 2009;55:1488–9]
Authors: Bo-Eric Persson
Journal: European Urology (2009)
Chronology of Histological Changes after Band Ligation of Esophageal Varices in Humans
Authors: J.M. Polski, E.M. Brunt, None Z.A. Saeed
Journal: Endoscopy (2001)

While the histological effects of endoscopic sclerotherapy in humans have been extensively described, the effects of endoscopic ligation have been reported in only two cases. The purpose of this study was to reconstruct the chronological sequence of histological changes after ligation of esophageal varices.Autopsy specimens from six patients who received ligation of varices from nine hours to 22 months ante-mortem were evaluated for gross and microscopic changes.Early after ligation, the appearance was that of a polyp with its base compressed by the band. Variceal thrombosis was seen on day 2. Varying degrees of ischemic necrosis of the polyp were present on days 0-5. If the bands did not remain in situ for two days (premature loss), necrosis of the polyp and dilated variceal vessels were seen. On day 22, superficial ulcers were observed. After complete healing, fibrosis was seen in the submucosa.The changes seen in the present study are similar to those described in animals. The delay in ulcer healing, compared with the gross changes reported during follow-up endoscopic examinations, may be related to the severity of the underlying illness and the compromised immune status of patients in the present series.
Pharmacological evidence for a role of ATP-dependent potassium channels in myocardial stunning.
Authors: J A Auchampach, M Maruyama, I Cavero, G J Gross
Journal: Circulation (1992)

BACKGROUND Several recent studies suggest that activation of ATP-dependent potassium (K(ATP)) channels in the myocardium plays an important cardioprotective role during ischemia. The present study was undertaken to examine further the role of this ion channel in vivo in a model of "stunned" myocardium. METHODS AND RESULTS Barbital-anesthetized dogs were subjected to 15 minutes of left anterior descending (LAD) coronary artery occlusion followed by 3 hours of reperfusion. Regional myocardial blood flow was measured by radioactive microspheres and segment function by sonomicrometry. Intravenous administration of the potassium channel opener aprikalim (RP 52891) at a dose that produced no significant systemic hemodynamic effects (10 micrograms/kg plus 0.1 microgram/kg/min) resulted in a marked improvement in segment shortening in the ischemic/reperfused myocardium compared with control animals (p less than 0.05) when given before the ischemic insult. However, administration of aprikalim immediately before reperfusion had no beneficial effect. Furthermore, pretreatment with the K(ATP) channel antagonist glibenclamide antagonized the recovery of contractile function afforded by aprikalim when administered at a low dose (0.3 mg/kg) that alone had no effect on postischemic recovery. In contrast, pretreatment with either a higher dose of glibenclamide (1.0 mg/kg) or the related sulfonylurea K(ATP) channel antagonist tolbutamide (100 mg/kg) resulted in a worsening of segment function after reperfusion. The ability of aprikalim and the K(ATP) channel antagonists to alter postischemic wall function occurred independently of differences in systemic hemodynamics, area at risk, and collateral blood flow during occlusion, the major determinants of the extent of myocardial stunning. CONCLUSIONS These results suggest that opening myocardial K(ATP) channels in the ischemic heart results in a marked cardioprotective effect in stunned myocardium and that these channels may serve an endogenous function, which is to provide protection from ischemic insults.
THE ETIOLOGY OF PRIMARY GRANULOCYTOPENIA (AGRANULOCYTIC ANGINA)
Authors: FREDERICK W. MADISON
Journal: JAMA (1934)

In 1922, when Schultz<sup>1</sup>described the syndrome which he called "agranulocytosis" and which later was called "agranulocytic angina,"<sup>2</sup>he suggested that it might be the result of a depressant effect on the bone marrow of an unknown micro-organism or possibly of an unknown chemical agent. Extensive search for an organism capable of producing such an effect has met little success. Salmonella suipestifer,<sup>3</sup>Bacillus pyocyaneus<sup>4</sup>and occasional organisms isolated from human cases have produced leukopenia with granulopenia in experimental animals but not in a manner entirely comparable to the syndrome seen in the human being. Nor has any organism thus far been found to occur constantly or even frequently in the clinical cases. Recently Dennis<sup>5</sup>has attempted to incriminate focal infections by introducing various organisms in the experimental animal in a manner intended to simulate that type of infection in man and has found a tendency
Agricultural and residential pesticides in wipe samples from farmworker family residences in North Carolina and Virginia.
Authors: Sara A Quandt, Thomas A Arcury, Pamela Rao, Beverly M Snively, David E Camann, Alicia M Doran, Alice Y Yau, Jane A Hoppin, David S Jackson
Journal: Environmental Health Perspectives (2003)

Children of farmworkers can be exposed to pesticides through multiple pathways, including agricultural take-home and drift as well as residential applications. Because farmworker families often live in poor-quality housing, the exposure from residential pesticide use may be substantial. We measured eight locally reported agricultural pesticides and 13 pesticides commonly found in U.S. houses in residences of 41 farmworker families with at least one child &lt; 7 years of age in western North Carolina and Virginia. Wipe samples were taken from floor surfaces, toys, and children's hands. We also collected interview data on possible predictors of pesticide presence, including characteristics of the household residents, cleaning practices, and characteristics of the home. All families were Spanish-speaking, primarily from Mexico. Results indicate that six agricultural and 11 residential pesticides were found in the homes, with agricultural, residential, or both present in 95% of homes sampled. In general, residential pesticides were more commonly found. Presence of both types of pesticides on the floor was positively associated with detection on toys or hands. Agricultural pesticide detection was associated with housing adjacent to agricultural fields. Residential pesticide detection was associated with houses judged difficult to clean. Although the likelihood of agricultural pesticide exposure has been considered high for farmworker families, these results indicate that residential pesticide use and exposure in this population merit further study.
BLOOD COUNTS AND LONG-TERM ANTIBIOTIC THERAPY
Authors: Victor H. Witten
Journal: JAMA (1960)

The charts of 100 dermatological patients seen in private practice, who had received one or more antibiotic agents systematically for more than two months, were drawn at random from the authors' files and reviewed. Minor variations from what is considered normal in peripheral blood counts occurred in 54 of the patients. Leukocytosis was noted in 34, leukopenia in 7, and reversal of the polymorphonuclear leukocyte—lymphocyte ratio in 19. Other changes included eosinophilia, presence of atypical lymphocytes, and toxic granulations. Therapy of anemia was indicated in only one patient. The changes in this series may or may not be attributable to the antibiotics or sulfonamides; they were never dangerous, though patients should be made to understand that antibacterial agents should never be taken indiscriminately or without regular medical examination.