tbuckley/cabot-search huggingface dataset:
RADIOASSAY OF SERUM VITAMIN B12 BY QUANTITATING THE COMPETITION BETWEEN Co57B12 AND UNLABELED B12 FOR THE BINDING SITES OF INTRINSIC FACTOR*
Authors: Sheldon P. Rothenberg
Journal: Journal of Clinical Investigation (1963)

The extremely low concentration of vitamin B,2 in normal and B.2-deficient blood has, heretofore, necessitated the use of microbiologic methods for its assay.Such bioassays are not only indirect and time consuming, but also require particular bacteriologic skills.In an earlier report from this laboratory (1) preliminary data were pre- sented describing a simplified method for assaying this vitamin based on the competition between unlabeled vitamin B12 and isotopically labeled vitamin B12 for the binding sites of intrinsic factor.This investigation was prompted by the obser- vation that the electrophoretic mobility of Co60B1, could be altered by prior incubation with intrinsic factor (IF).Similar findings had been made by Schilling and Deiss (2) using human gastric juice instead of IF. Figure 1 is a diagrammatic il- lustration of radioelectroplhoretograms of free and IF-bound Co6OB12.Whereas free Co60B12 has essentially no electrophoretic mobility (Figure 1A), when bound to IF, it migrates toward the anode (Figure 1B).If the IF is incubated with a mixture of Co60BJ, and unlabeled B12, less of the Co60B,, will be bound because of the competition now present for the binding sites of IF.Two peaks of radioactivity appear, the free unbound Co60B,, at the origin and that bound to the IF (Figure 1C) .These findings are similar to those reported by Berson and co-workers (3) on the binding of in- sulin-I131 by specific anti-insulin antibodies in studies employing paper electrophoresis.As they exploited their observations in developing an im- munoassay for insulin (4, 5), so it seemed possible that the inverse relationship between the ratio of bound to free Co60B,2 and total concen-
Surveillance of work related and occupational respiratory disease--SWORD.
Authors: A Seaton
Journal: Thorax (1991)

Surveillance of work related and occupational respiratory disease-SWORDThe burden borne by society in the management of respiratory disease is a large one, and in no comparable range of illnesses is the influence of the environment so much greater than that of genetic factors.From the recognition of the causes of tuberculosis and pneumonia to the appreciation of the influences of cigarette smoking on health, physicians interested in lung-disease have been closely associated with important opportunities to ameliorate adverse environmental effects and so prevent disease.So far most important advances in the prevention of lung disease have stemmed from epidemiological research.For long we have been familiar with statistical information on tuberculosis and lung cancer.We have watched with satisfaction the decline of the former disease in the West and have debated the value of further preven- tive measures in the light of knowledge of the statistics.We continue to view with concern worldwide trends in lung cancer mortality, and plan strategies to counter the com- mercial activities of the cigarette industry on.the basis of
Hereditary deficiency of the sixth component of complement in man. I. Immunochemical, biologic, and family studies.
Authors: J P Leddy, M M Frank, T Gaither, J Baum, M R Klemperer
Journal: Journal of Clinical Investigation (1974)

An 18-yr-old black woman in good general health was found to lack serum hemolytic complement activity. The sixth component of complement (C6) was undetectable by functional assay of serum or plasma and by immunoprecipitin analysis of serum. Functional titers of all other complement components were normal. The absence of C6 in the patient's serum could not be accounted for by a circulating C6 inhibitor, and addition of functionally pure C6 to the patient's serum restored hemolytic activity to normal. Both parents of the proband and five of six available siblings had approximately half the normal levels of functional C6. The other sibling had a normal C6 level. These data suggest that both parents and five siblings are heterozygous for C6 deficiency, while the proband is homozygous and one sibling is normal. Thus, C6 deficiency appears to follow classic mendelian inheritance, with all three possible genotypes recognizable within the family. Functional properties of the proband's C6-deficient serum included total absence of bactericidal activity against Salmonella typhi 0 901 and Hemophilus influenzae, type b, and inability to mediate lysis of red blood cells from patients with paroxysmal nocturnal hemoglobinuria in either the acidified serum or "sugar water" tests. The proband's serum did, however, exhibit a normal capacity (a) to generate chemotactic activity during incubation with bacterial endotoxin or aggregated IgG, (b) to mediate the immune adherence phenomenon, and (c) to coat human red blood cells, sensitized by cold agglutinins, with C4 and C3.
Genotoxic Effects in Swimmers Exposed to Disinfection By-products in Indoor Swimming Pools
Authors: Manolis Kogevinas, Cristina M. Villanueva, Laia Font-Ribera, Danae Liviac, Mariona Bustamante, Felicidad Espinoza, Mark J. Nieuwenhuijsen, Aina Espinosa, Pilar Fernandez, David M. DeMarini, Joan O. Grimalt, Tamara Grummt, Ricard Marcos
Journal: Environmental Health Perspectives (2010)

BackgroundExposure to disinfection by-products (DBPs) in drinking water has been associated with cancer risk. A recent study (Villanueva et al. 2007; Am J Epidemiol 165:148–156) found an increased bladder cancer risk among subjects attending swimming pools relative to those not attending.ObjectivesWe evaluated adults who swam in chlorinated pools to determine whether exposure to DBPs in pool water is associated with biomarkers of genotoxicity.MethodsWe collected blood, urine, and exhaled air samples from 49 nonsmoking adult volunteers before and after they swam for 40 min in an indoor chlorinated pool. We estimated associations between the concentrations of four trihalomethanes (THMs) in exhaled breath and changes in micronuclei (MN) and DNA damage (comet assay) in peripheral blood lymphocytes before and 1 hr after swimming; urine mutagenicity (Ames assay) before and 2 hr after swimming; and MN in exfoliated urothelial cells before and 2 weeks after swimming. We also estimated associations and interactions with polymorphisms in genes related to DNA repair or to DBP metabolism.ResultsAfter swimming, the total concentration of the four THMs in exhaled breath was seven times higher than before swimming. The change in the frequency of micronucleated lymphocytes after swimming increased in association with higher exhaled concentrations of the brominated THMs (p = 0.03 for bromodichloromethane, p = 0.05 for chlorodibromomethane, p = 0.01 for bromoform) but not chloroform. Swimming was not associated with DNA damage detectable by the comet assay. Urine mutagenicity increased significantly after swimming, in association with the higher concentration of exhaled bromoform (p = 0.004). We found no significant associations with changes in micronucleated urothelial cells.ConclusionsOur findings support potential genotoxic effects of exposure to DBPs from swimming pools. The positive health effects gained by swimming could be increased by reducing the potential health risks of pool water.
One more thing for GPs
Authors: K. Challen
Journal: BMJ (2010)

Dormandy’s group showed a mean gestational age at screening uptake of around 16 weeks, despite ongoing engagement with participating GP practices and significantly higher offer rates of screening before 10 weeks.1 This highlights structural problems in antenatal services little changed since the Confidential Enquiry into Genetic Counselling by Non-geneticists …
Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipients
Authors: Tak Mao Chan, Guo Xiang Fang, Colin S. O. Tang, Ignatius K. P. Cheng, Kar Neng Lai, Stephen K. N. Ho
Journal: Hepatology (2002)

Hepatitis B surface antigen (HBsAg)-positive kidney transplant recipients have increased liver-related mortality. The impact of lamivudine treatment on patient survival, the optimal time to start treatment, and the feasibility of discontinuing treatment have not been determined. This study examined these issues with a novel management protocol. Serum hepatitis B virus (HBV) DNA levels were measured serially in HBsAg-positive kidney transplant recipients, and lamivudine was administered preemptively to patients with increasing HBV DNA levels with or without elevation of aminotransferase levels. Outcomes of patients who underwent transplantation before or after institution of this preemptive management strategy (in January 1996) were compared. Eleven de novo patients (91.7%) who underwent transplantation between 1996 and 2000 and 15 existing patients (39.5%) who underwent transplantation between 1983 and 1995 received preemptive lamivudine therapy for 32.6 ± 13.3 months. The treatment criteria were met by de novo patients at 8.4 ± 6.2 months (range, 1-18 months) after transplantation. Suppression of HBV DNA and normalization of aminotransferase levels were achieved in all treated patients, and 21.4% had hepatitis B e antigen (HBeAg) seroconversion. The survival of preemptively managed de novo transplant patients was similar to that of HBsAg-negative controls, whereas HBsAg-positive patients who underwent transplantation before January 1996 had inferior survival (relative risk of death, 9.7 [ P &lt; .001]; relative risk of liver-related mortality, 68.0 [ P &lt; .0001]). Eleven patients (40.7%) developed lamivudine resistance. Discontinuation of lamivudine was attempted in 12 low-risk patients after stabilization and was successful in 5 (41.7%). In conclusion, preemptive lamivudine therapy based on serial HBV DNA levels and clinical monitoring improved the survival of HBsAg-positive renal allograft recipients. Treatment can be discontinued safely in selected patients after stabilization to minimize the selection of drug-resistant HBV mutants.
Scope of surgery for intracranial aneurysm in the elderly: a preliminary report.
Authors: R P Sengupta, L P Lassman, J Hankinson
Journal: BMJ (1978)

Thirty-two elderly patients were reviewed six months to six years after intracranial surgery for subarachnoid haemorrhage. Out of 24 patients whose surgical outcome had been satisfactory, one had died from an unrelated illness and the remainder were well and leading normal lives. Eight patients had a poor outcome, which in some cases was due to factors other than age. In only three could a poor outcome be attributed to early surgery and advanced age. The results confirm that in at least three-quarters of patients aged 60-65 the risk of further haemorrhage can be removed by surgery without causing a major neurological deficit.
Enhanced proliferation and osteocalcin production by human osteoblast-like MG63 cells on silicon nitride ceramic discs
Authors: R. Kue, A. Sohrabi, D. Nagle, C. Frondoza, D. Hungerford
Journal: Biomaterials (1999)

The biocompatibility of silicon nitride (Si3N4) was assessed in an in vitro model using the human osteoblast-like MG-63 cell line. Cells were propagated on the surface of: reaction-bonded silicon nitride discs, sintered after reaction-bonded silicon nitride discs or control polystyrene surface for 48 h. Compared to cells propagated on polystyrene surface, cells grown on the surface of unpolished silicon nitride discs had significantly lower cell yield and decreased osteocalcin production. In contrast, cells on the surface of polished silicon nitride discs showed similar proliferative capacity to control cells propagated on polystyrene surface. Cells propagated on polished discs also produced higher levels of osteocalcin than cells on unpolished discs. SEM analysis showed cells with well-delineated morphology and cytoplasmic extensions when propagated on polished sintered after reaction-bonded discs. Cells appeared more spherical, when grown on polished reaction-bonded discs. The results of this study suggest that silicon nitride is a non-toxic, biocompatible ceramic surface for the propagation of functional human bone cells in vitro. Its high wear resistance and ability to support bone cell growth and metabolism make silicone nitride an attractive candidate for clinical application. Further studies are needed to explore the feasibility of using silicon nitride clinically as an orthopedic biomaterial.
Effect of sulfinpyrazone on ventricular fibrillation during acute myocardial ischemia.
Authors: C B Moschos, A J Escobinas, O B Jorgensen, T J Regan
Journal: Circulation (1981)

In patients treated with sulfinpyrazone, an apparent reduction in the incidence of sudden death and presumed ventricular fibrillation has been reported. Using an intact animal model without microcirculatory thrombosis, we studied the effects of sulfinpyrazone on ischemic myocardium in 58 anesthetized dogs divided into three groups: control untreated (n =24), group 1 (n = 16), treated daily with 300 mg of sulfinpyrazone for 7 days, and group 2 (n = 18), treated daily with 300 mg of sulfinpyrazone for 7 days but omitting treatment on day 8. Although consistent hemodynamic differences were not apparent, the degree of injury determined by ECG mapping was significantly lower in group 1. The incidence of fibrillation was 54% for control and 0% in group 1. Group 2 had a 44% incidence, suggesting a limited duration of action. The apparent absence of microcirculatory thrombosis in this model suggests other mechanisms of action. A significantly smaller increase in tissue water and Na+ and smaller loss of K+ in group 1 may have contributed to the lower incidence of fibrillation, perhaps through selective prostaglandin inhibition.
Multimodality Imaging in Characterizing the Metastases of Multiple Endocrine Neoplasia Type 2a
Authors: Myles Webb, Adil Al-Alnahhas
Journal: Clinical Nuclear Medicine (2004)

A 40-year-old man, known to be an index case of multiple endocrine neoplasia type 2a (MEN2a), presented with back pain. He had locally recurrent medullary thyroid carcinoma (MTC) and a history of right adrenalectomy for pheochromocytoma. Plain films of the thoracolumbar spine and a Tc-99m methylene diphosphonate (MDP) bone scan showed multiple skeletal metastases. Two questions were raised: 1) were the metastases the result of MTC or pheochromocytoma, and 2) could the nuclear medicine department offer a therapy option? I-123 metaiodobenzylguanidine (MIBG), In-111 octreotide, and Tc-99m pentavalent dimercaptosuccinic acid (V-DMSA) scans were subsequently performed.
(-)-Adrenaline-induced, calcium-dependent phosphorylation of proteins in human platelets.
Authors: L H Block, H Jaksche, P Erne, P Bolli, F R Bühler
Journal: Journal of Clinical Investigation (1985)

In human platelets, adrenaline stimulated, approximately four-fold, as compared with controls, the phosphorylation of primarily two proteins of apparent molecular weights of 20,000 and 40,000, respectively. Maximum phosphorylation occurred after incubation for 1 min and was inhibited by the addition of either yohimbine, prostaglandin E1, or EGTA. Phosphorylation of the two proteins was accompanied by diacylglycerol formation. The (-)-adrenaline-induced phosphorylation of proteins corresponds to the activation of a calcium-dependent protein kinase partially purified by DEAE-cellulose and Sephadex G150 column chromatography. The enzymatic activity was modulated by addition of (-)-adrenaline and CaCl2, by diolein, and in the presence of membranes or phosphatidylinositol but not phosphatidylethanolamine and phosphatidylcholine. A phospholipid-dependent reaction appears to be involved in the molecular mechanism of action of adrenaline.
Post-Transfusion Hepatitis — Effect of Modified Gamma Globulin Added to Blood in Vitro
Authors: Ricardo Katz, Julio Rodriguez, Robert Ward
Journal: New England Journal of Medicine (1971)

Abstract A significant reduction in the incidence of post-transfusion hepatitis with jaundice was observed in patients receiving modified gamma globulin added to blood before transfusion as compared with controls receiving blood alone. Standard gamma globulin was modified by the Swiss method (hydrolysis); 10 ml of a 6 per cent solution were added to each unit of blood before transfusion. Five of 1970 patients receiving gamma globulin and 18 of 2019 controls receiving blood without added gamma globulin acquired icteric hepatitis (p equal to 0.014). No severe cases were observed in those receiving gamma globulin. Six severe cases with two deaths occurred in the controls. The incidence of anicteric hepatitis in the two groups was not significantly different. No untoward reactions were related to the intravenous use of modified gamma globulin.
Oral decitabine reactivates expression of the methylated γ‐globin gene in <i>Papio anubis</i>
Authors: Donald Lavelle, Janet Chin, Kestis Vaitkus, Sanjeev Redkar, Pasit Phiasivongsa, Chunlin Tang, Roselle Will, Maria Hankewych, Bryan Roxas, Mahipal Singh, Yogen Saunthararajah, Joseph DeSimone
Journal: American Journal of Hematology (2007)

Abstract The silencing of tumor suppressor genes associated with increased DNA methylation of the promoter regions is a frequent observation in many forms of cancer. Reactivation of these genes using pharmacological inhibitors of DNA methyltransferase such as 5‐aza‐2′‐deoxycytidine (decitabine) is a worthwhile therapeutic goal. The effectiveness and tolerability of low‐dose intravenous and subcutaneous decitabine regimens to demethylate and reactivate expression of the methylated γ‐globin gene in baboons and in patients with sickle cell disease led to successful trials of low‐dose regimens of this drug in patients with myelodysplastic syndrome. Since these low‐dose regimens are well‐tolerated with minimal toxicity, they are suitable for chronic dosing to maintain promoter hypomethylation and expression of target genes. The development of an orally administered therapy using DNA methyltransferase inhibitors would facilitate such chronic approaches to therapy. We tested the ability of decitabine and a new salt derivative, decitabine mesylate, to reactivate the methylated γ‐globin gene in baboons when administered orally. Our results demonstrate that oral administration of these drugs at doses 17–34 times optimal subcutaneous doses of decitabine reactivates fetal hemoglobin, demethylates the ϵ‐ and γ‐globin gene promoters, and increases histone acetylation of these promoters in baboons ( Papio anubis ). Am. J. Hematol., 2007. Published 2007 Wiley‐Liss, Inc.
Mechanism of action of insulin in diabetic patients: a dose-related effect on glucose production and utilisation
Authors: P M Brown, C V Tompkins, S Juul, P H Sonksen
Journal: BMJ (1978)

Six insulin-requiring diabetics were studied after insulin had been withheld for 24 hours. On three separate occasions each received a two-hour infusion of insulin at a low dose (2·6 U/h) and a high dose (10·6 U/h) and an infusion of saline as control. The rates of production and utilisation of glucose were measured isotopically. The rate of fall of plasma glucose concentration was faster on the high-dose infusion of insulin than on the low, whereas the fall in plasma free fatty acids, glycerol, and keton bodies was the same on both insulin infusions. The mechanism whereby the two rates of insulin administration lowered plasma glucose concentration differed: during the low-dose infusion the decrease in the glucose concentration was produced entirely by a fall of hepatic glucose output, whereas during the high-dose insulin infusion the glucose concentration fell because both the rate of glucose production fell and the rate of glucose utilisation rose. In all experiments there was a direct relation between a fall in serum potassium concentration and the fall in plasma glucose concentration irrespective of the mechanism that reduced the glucose concentration. These results indicate that in uncontrolled diabetics low-dose insulin infusions lower the blood glucose concentration entirely by reducing glucose production from the liver and that the effect of insulin on potassium transport is independent of its effect on glucose uptake.
Risk of adverse gastrointestinal outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis
Authors: Julia Hippisley-Cox, Carol Coupland, Richard Logan
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To determine the risk of an adverse upper gastrointestinal event in patients taking different cyclo-oxygenase-2 inhibitors compared with non-selective non-steroidal anti-inflammatory drugs. <b>Design</b> Nested case-control study. <b>Setting</b> 367 general practices contributing to the UK QRESEARCH database, spread throughout every strategic health authority and each health board in England, Wales, and Scotland. <b>Participants</b> Patients aged 25 or more with a first ever diagnosis of an adverse upper gastrointestinal event (peptic ulcer or haematemesis) between 1 August 2000 and 31 July 2004 and up to 10 controls per case matched for age, sex, calendar time, and practice. <b>Main outcome measures</b> Unadjusted and adjusted odds ratios for adverse upper gastrointestinal events associated with celecoxib, rofecoxib, ibuprofen, diclofenac, naproxen, other selective and non-selective non-steroidal anti-inflammatory drugs, and aspirin. <b>Results</b> The incidence of adverse upper gastrointestinal events was 1.36 per 1000 person years (95% confidence interval 1.34 to 1.39). We identified 9407 incident cases and 88 867 matched controls. Increased risks of adverse gastrointestinal events were associated with current use of cyclo-oxygenase-2 inhibitors and with conventional non-steroidal anti-inflammatory drugs. Risks were reduced after adjustment for confounders but remained significantly increased for naproxen (adjusted odds ratio 2.12, 95% confidence interval 1.73 to 2.58), diclofenac (1.96, 1.78 to 2.15), and rofecoxib (1.56, 1.30 to 1.87) but not for current use of celecoxib (1.11, 0.87 to 1.41). We found clinically important interactions with current use of ulcer healing drugs that removed the increased risks for adverse gastrointestinal events for all groups of non-steroidal anti-inflammatory drugs except diclofenac, which still had an increased odds ratio (1.49, 1.26 to 1.76). <b>Conclusion</b> No consistent evidence was found of enhanced safety against gastrointestinal events with any of the new cyclo-oxygenase-2 inhibitors compared with non-selective non-steroidal anti-inflammatory drugs. The use of ulcer healing drugs reduced the increased risk of adverse gastrointestinal outcomes with all groups of non-steroidal anti-inflammatory drugs, but for diclofenac the increased risk remained significant.
Employee ownership in the NHS
Authors: C. Ham, J. Ellins
Journal: BMJ (2010)

Mutual models may help to deliver higher levels of performance

Although the coalition government’s plans to put general practices in charge of commissioning have attracted widespread interest and comment, its proposals for provider reform are equally radical. By 2013 it is expected that all NHS trusts will have become foundation trusts, and that providers from the independent sector will play a bigger part in delivering services to NHS patients. The government also wants to encourage employee owned healthcare providers, with the aim of creating “the largest and most vibrant social enterprise sector in the world.”1

These plans are part of a broader programme of public service reform, at the heart of which is a concern to move away from state ownership to greater diversity in how public services are run in pursuit of the “big society.”2 Cabinet Office Minister, Francis Maude, announced recently that the government will take this programme forward by putting in place a right for public sector workers to take over the running of their services.3 This builds on the previous government’s interest in mutualism in the public sector, and it signals a renewed commitment to explore …