tbuckley/cabot-search huggingface dataset:
Metabolism of meso-2,3-dimercaptosuccinic acid in lead-poisoned children and normal adults.
Authors: P Asiedu, T Moulton, C B Blum, E Roldan, N J Lolacono, J H Graziano
Journal: Environmental Health Perspectives (1995)

Meso-2,3-dimercaptosuccinic acid (DMSA, or succimer) is an oral chelating agent for heavy-metal poisoning. While studying the urinary elimination of unaltered DMSA, altered DMSA (i.e., its mixed disulfides), and lead in children with lead poisoning, we observed a pattern of urinary drug elimination after meals suggestive of enterohepatic circulation. The excretion of lead in urine patterned the elimination of altered DMSA rather than the parent molecule. In addition, the half-life of elimination of DMSA via the kidney was positively associated with blood lead concentration. Two additional crossover studies of DMSA kinetics were conducted in normal adults to confirm the presence of enterohepatic circulation of DMSA after meals. In one, increases in plasma total DMSA concentration were observed after meals in all six subjects; these increases were prevented by cholestyramine administration 4, 8, and 12 hr after DMSA. In the second, the administration of neomycin also prevented increases in DMSA after meals. These studies indicate that 1) a metabolite(s) of DMSA undergoes enterohepatic circulation and that microflora are required for DMSA reentry; 2) in children, moderate lead exposure impairs renal tubular drug elimination; and 3) a metabolite of DMSA appears to be an active chelator.
Tc-99m HMDP Accumulation in Primary Peritoneal Mesothelioma
Authors: E GONZALEZ-REIMERS, M A GOMEZ, F SANTOLARIA-FERNANDEZ, M CRUZ-DIAZ, H ALVAREZ-ANG??ELLES
Journal: Clinical Nuclear Medicine (1992)

Tc-99m phosphate compounds are widely used to detect bone metastases and may also accumulate in pleural and pericardial effusions as well as in ascites, although this is unusual. The authors describe a patient with histologically proven malignant rnesothelioma in whom Tc-99m HMDP was found to accumulate in the abdomen.
FDA officials argue over safety of new arthritis drug
Authors: R. Moynihan
Journal: BMJ (2003)

An external advisory panel to the US Food and Drug Administration last week rejected calls from FDA safety experts to withdraw a drug for rheumatoid arthritis from the market.

The Arthritis Advisory Committee found that the benefits of the Aventis drug leflunomide (Arava) outweighed its rare side effects, despite an internal FDA report that said that one in 200 users may …
Decision making for routine measles/MMR and whooping cough immunisation: Author's reply
Authors: D. Jenkinson
Journal: BMJ (1988)

due to various compounds such as barbiturates, organophosphates, and antihistamines'.Like Dr D G Menezies and his colleagues, we had to face the problem of pulmonary aspiration of the charcoal (13 August, p 459); three of our patients developed this complication and died, despite the prior administration of parenteral metoclopramide and ranitidine.To overcome this problem in the next six patients with reduced consciousness we passed a cuffed endotracheal tube before starting treatment with charcoal.The endotracheal tube was retained for the next 48 hours, and since then we have not encountered a problem with aspiration.
Oriented fibrin crystallization: a phenomenon of hypersensitivity to bacteria in psoriasis, vasculitis and other dermatoses
Authors: LENNART JUHLIN, WALTER B. SHELLEY
Journal: British Journal of Dermatology (1977)

Heparinized blood from patients with a variety of dermatological problems was incubated with killed bacteria, bacterial extracts or Gram-negative bacterial endotoxin. Within 18-24 h asteroid bodies consisting of an amorphous centre with fine radiating needle crystals were seen. These bodies, not found in the blood of healthy volunteers, were most consistently observed in blood from patients with psoriasis, vasculitis and bacterial infections. Immunofluorescent studies disclosed the asteroid formations to be crystals of fibrin radiating presumably from a central platelet aggregate. The failure to demonstrate IgG, A, M or D suggests that the phenomenon results from the bacterial activation of complement by a non-immune yet specific pathway which in turn involves white cells, platelet aggregation and release of procoagulants.
Synergistic effect of defined artificial extracellular matrices and pulsed electric fields on osteogenic differentiation of human MSCs
Authors: Ricarda Hess, Anna Jaeschke, Holger Neubert, Vera Hintze, Stephanie Moeller, Matthias Schnabelrauch, Hans-Peter Wiesmann, David A. Hart, Dieter Scharnweber
Journal: Biomaterials (2012)
Differential and Integral Corticosteroid Feedback Effects on ACTH Secretion in Hypoadrenocorticism
Authors: H. L. Fehm, K. H. Voigt, G. Kummer, R. Lang, E. F. Pfeiffer
Journal: Journal of Clinical Investigation (1979)

Recent work suggests the existence of a dual corticosteroid feedback mechanism of stress-induced ACTH secretion in the rat. This possibility led us to study the kinetics of suppression of ACTH levels by corticosteroid administration in patients with nonstress ACTH hypersecretion secondary to hypoadrenocorticism. Cortisol was administered according to different protocols, which were chosen to provide extreme variations of the input signal. By this means, two phases of suppression of ACTH levels could be differentiated. A first decrease occurred without latency whenever, and as long as, plasma cortisol levels were rising. There was a linear regression between the logarithm of the increments in cortisol concentrations and the decrease in ACTH levels per minute (r = 0.951) (differential or rate-sensitive feedback mechanism). Neither the absolute doses of cortisol, nor plasma cortisol concentrations were closely correlated with the degree of suppression of ACTH by this rapid mechanism. A second decrease in ACTH levels began congruent with30 min after corticosteroid administration. In this case there was a significant linear regression between the degree of inhibition of ACTH levels and the cortisol doses (r = 0.997) (integral or dose-sensitive feedback mechanism). The dose-sensitive feedback effects of dexamethasone were less than might have been predicted from its relative anti-inflammatory potency. No rate-sensitive effects were seen with dexamethasone doses of 1.0 or 1.25 mg.
1165 IL-28B GENE POLYMORPHISM INFLUENCES HISTOLOGICAL AND BIOCHEMICAL SEVERITY OF GRAFT HEPATITIS AFTER LIVER TRANSPLANTATION FOR HCV-INDUCED LIVER DISEASE
Authors: D. Eurich, S. Boas-Knoop, M. Ruehl, M. Schulz, E.D. Carrillo, M. Bahra, R. Neuhaus, P. Neuhaus, U.P. Neumann
Journal: Journal of Hepatology (2010)
Ischaemic preconditioning is not mediated by oxygen derived free radicals in rats
Authors: V. Richard, C. Tron, C. Thuillez
Journal: Cardiovascular Research (1993)

Objective: Although several studies have shown that ischaemic preconditioning greatly limits myocardial infarct size in the rat, the mechanisms of the beneficial effect of preconditioning in this species are not known. Experiments in dogs and rabbits have suggested that this effect could be related in part to the production of oxygen derived free radicals, as free radical scavengers partially prevent the limitation of infarct size induced by preconditioning. This study was designed to assess the contribution of oxygen derived free radicals in the infarct size limiting effects of preconditioning in rats, using the cell diffusible free radical scavenger N-2-mercaptopropionyl glycine (MPG). Methods: Open chest rats underwent 20 minutes of coronary occlusion followed by one hour of reperfusion. Preconditioning was elicited by three cycles of five minutes ischaemia and five minutes reperfusion. MPG (20 mg·kg−1) was infused for 60 minutes starting 30 minutes before preconditioning. Control hearts (with or without MPG) were treated identically but without ischaemic preconditioning. Area at risk and infarct size were determined by India ink injection and triphenyltetrazolium chloride stain, with computerised analysis of enlarged sections after colour video acquisition. Results: During preconditioning, reperfusion after the first episode of ischaemia was associated with a high occurrence of severe ventricular arrhythmias, and this was reduced by MPG. Preconditioning, however, reduced arrhythmias and mortality during subsequent episodes of ischaemia and reperfusion. In the absence of MPG, preconditioning greatly limited Infarct size (from (mean (SEM)) 59.8(3.9)% to 1.2(0.6)% of the area at risk; p < 0.01). MPG alone did not affect infarct size (60.5(6.1)%), and did not modify the infarct size limiting effect of preconditioning (infarct size: preconditioning 1.2(0.6)%; preconditioning + MPG 2.9(1.2)%. Conclusions: Preconditioning greatly reduced infarct size, and this was not affected by MPG. These experiments suggest that production of oxygen derived free radicals does not contribute to preconditioning in the rat heart. Cardiovascular Research 1993;27:2016-2021
A novel biomarker assay for cancer immunotherapy development based on myeloid derived supressor cells (MDSCs)
Authors: Henry Hepburne-Scott
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts It has long been known that myeloid derived suppressor cells (MDSCs) inhibit the anti-tumor immune response. And recently a relationship between MDSC levels and patient outcomes to cancer immunotherapy was discovered. Studies conducted at the Memorial Sloan Kettering Cancer Center
SPONTANEOUS HYPOGLYCEMIA IN "SMOKE" DRINKERS
Authors: THOMAS McP. BROWN
Journal: JAMA (1941)

During the past few years we have had an opportunity to observe an unusual form of spontaneous hypoglycemia which, as far as we are aware, has not been previously reported. The patients concerned have all been chronically addicted to alcohol and have been drinkers of denatured alcohol in a form known locally as "smoke." This so-called smoke has been prepared by the addition of a variety of denatured alcohols (varnish and paint removers, antifreeze, "canned heat") to water; the milky or "smoky" appearance of the resultant mixture has been the basis for its name. Samples of typical denatured alcohols used have always given strongly positive tests for methyl alcohol. Not one of the patients, however, has complained of diminution of vision. Although we have gathered little information concerning the exact nature and cause of this hypoglycemic reaction, we are reporting our clinical observations on 6 patients in the hope that
How to think like an ethicist
Authors: D. K. Sokol
Journal: BMJ (2010)

A search for method in the madness of medical ethics

Structure. That is the key. Structure. Did John steal the stethoscope? Go through each of the five components of theft: appropriation, of property, belonging to another, dishonestly, with the intention to permanently deprive. If a single element is missing, there is no theft. Was Tracy negligent when she failed to intubate the young child? Go through the elements of negligence: loss, duty of care, standard of care, breach, causation, and remoteness. Throughout the last year at law school we were told to “think like lawyers.” We had to lose the deep rooted instinct to judge the morality of a person’s act and replace it with a dispassionate legal dissection of the facts at hand.

When training in medical ethics I was never told to “think like an ethicist.” There is no universally accepted way to do ethics, and at times the words from a Dilbert comic strip posted on the notice board of a bioethics department ring worryingly true. Having received the advice he wanted to hear, Dilbert muses that “90% of happiness is finding the right ethicist.” …
Alcoholic beverages produced by alcoholic fermentation but not by distillation are powerful stimulants of gastric acid secretion in humans.
Authors: S Teyssen, T Lenzing, G Gonzalez-Calero, A Korn, R L Riepl, M V Singer
Journal: Gut (1997)

BACKGROUND: The effect of commonly ingested alcoholic beverages on gastric acid output and release of gastrin in humans is unknown. AIM AND METHODS: In 16 healthy humans the effect of some commonly ingested alcoholic beverages produced by fermentation plus distillation (for example, whisky, cognac, calvados, armagnac, and rum) or by alcoholic fermentation (beer, wine, champagne, martini, and sherry) on gastric acid output and release of gastrin was studied. Gastric acid output was determined by the method of intragastric titration. Plasma gastrin was measured using a specific radioimmunoassay. RESULTS: None of the alcoholic beverages produced by fermentation plus distillation had any significant effect on gastric acid output and release of gastrin compared with control (isotonic glucose and distilled water). Alcoholic beverages produced only by fermentation significantly (p &lt; 0.05) increased the gastric acid output by 57% to 95% of maximal acid output (MAO) and release of gastrin up to 5.1-fold compared with control. If beer, wine, and sherry were distilled, only their remaining parts increased gastric acid output by 53% to 76% of MAO and increased release of gastrin up to 4.3-fold compared with control. CONCLUSIONS: (1) Alcoholic beverages produced by fermentation but not by distillation are powerful stimulants of gastric acid output and release of gastrin; (2) the alcoholic beverage constituents that stimulate gastric acid output and release of gastrin are most probably produced during the process of fermentation and removed during the following process of distillation.
Metabolic syndrome is common among middle-to-older aged Mediterranean patients with rheumatoid arthritis and correlates with disease activity: a retrospective, cross-sectional, controlled, study
Authors: S A Karvounaris, P I Sidiropoulos, J A Papadakis, E K Spanakis, G K Bertsias, H D Kritikos, E S Ganotakis, D T Boumpas
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objectives:</b> Patients with rheumatoid arthritis have an increased risk for cardiovascular disease (CVD). The prevalence of metabolic syndrome (MetS)—a major contributor to CVD—in a cohort of patients with rheumatoid arthritis and its relationship with rheumatoid arthritis related factors is investigated here. <b>Methods:</b> 200 outpatients with rheumatoid arthritis (147 women and 53 men), with a mean (standard deviation (SD)) age of 63 (11) years, and 400 age and sex-matched controls were studied. MetS was assessed according to the adult treatment panel III criteria and rheumatoid arthritis disease activity by the disease activity score of 28 joints (DAS28). A standard clinical evaluation was carried out, and a health and lifestyle questionnaire was completed. <b>Results:</b> The overall prevalence of MetS was 44% in patients with rheumatoid arthritis and 41% in controls (p = 0.5). Patients with rheumatoid arthritis were more likely to have low high-density lipoprotein cholesterol compared with controls (p = 0.02), whereas controls were more likely to have increased waist circumference or raised blood pressure (p = 0.001 and 0.003, respectively). In multivariate logistic regression analysis adjusting for demographics and rheumatoid arthritis treatment modalities, the risk of having moderate-to-high disease activity (DAS28&gt;3.2) was significantly higher in patients with MetS compared with those with no MetS components (OR 9.24, 95% CI 1.49 to 57.2, p = 0.016). <b>Conclusion:</b> A high, albeit comparable to the control population, prevalence of MetS was found in middle-to-older aged patients with rheumatoid arthritis. The correlation of rheumatoid arthritis disease activity with MetS suggests that the increased prevalence of coronary heart disease in patients with rheumatoid arthritis may, at least in part, be attributed to the inflammatory burden of the disease.
Reversible posterior leukoencephalopathy syndrome complicating cytotoxic chemotherapy for hematologic malignancies
Authors: C.S. Tam, J. Galanos, J.F. Seymour, A.G. Pitman, R.J. Stark, H.M. Prince
Journal: American Journal of Hematology (2004)

Abstract Reversible posterior leukoencephalopathy syndrome (RPLS) is an uncommon but distinctive clinicoradiological entity comprising of headache, seizures, visual disturbance, and altered mental function, in association with posterior cerebral white matter edema. With appropriate management, RPLS is reversible in the majority of cases. Previous reported associations of RPLS include hypertension, eclampsia, renal failure, and use of immunosuppressive drugs; reports in the adult hematology setting are rare. We report two cases of adults undergoing treatment for hematological malignancies who developed RPLS, and we emphasize the importance of early recognition and institution of appropriate management in reducing the risk of development of permanent neurological disability. Am. J. Hematol. 77:72–76, 2004. © 2004 Wiley‐Liss, Inc.
Biallelic inactivation of protoporphyrinogen oxidase and hydroxymethylbilane synthase is associated with liver cancer in acute porphyrias
Authors: Xiaoye Schneider-Yin, Anne-Moon van Tuyll van Serooskerken, Marko Siegesmund, Philip Went, Jasmin Barman-Aksözen, Reno S. Bladergroen, Paul Komminoth, Roy H.E. Cloots, Véronique J. Winnepenninckx, Axel zur Hausen, Markus Weber, Ann Driessen, Pamela Poblete-Gutiérrez, Peter Bauer, Christopher Schroeder, Michel van Geel, Elisabeth I. Minder, Jorge Frank
Journal: Journal of Hepatology (2014)
Benzene hexachloride poisonong.
Authors: B G Macnamara
Journal: BMJ (1970)

I have a vivid recollection of one of my teachers whose habit was as I was about to divide the second cranial nerve in an enucleation to say, "it was the right eye, wasn't it, Payne?"One knew very well that he would say this, but it never failed to send a shiver down the spine, and I have always felt compelled to verify the laterality by all possible means in the theatre imme- diately before operations of this sort.-Iam, etc., I.
Low Fractional Calcium Absorption Increases the Risk for Hip Fracture in Women with Low Calcium Intake
Authors: Kristine E. Ensrud, Tu Duong, Jane A. Cauley, Robert P. Heaney, Randi L. Wolf, Emily Harris, Steven R. Cummings
Journal: Annals of Internal Medicine (2000)

Background: Decreased ability to absorb calcium with age limits adaptation to low calcium intake and is thought to lead to secondary hyperparathyroidism and increased risk for hip and other fractures. However, the associations between fractional calcium absorption, dietary calcium intake, and risk for fracture have never been studied. Objective: To determine whether low fractional calcium absorption in women with low calcium intake increases the risk for subsequent hip and other nonspine fractures. Design: Prospective cohort study. Setting: Four clinical centers in Baltimore County, Maryland; Portland, Oregon; Minneapolis, Minnesota; and the Monongahela Valley, Pennsylvania. Participants: 5452 nonblack women 69 years of age or older participating in the fourth examination of the Study of Osteoporotic Fractures. Measurements: Fractional calcium absorption was measured by using a 3-hour single isotope (45Ca) technique. Incident fractures were identified prospectively and were confirmed by radiographic report. Results: During an average of 4.8 years, 729 women (13%) experienced at least one nonspine fracture; 153 of these women had hip fractures. After adjustment for age, women with lower fractional calcium absorption were at increased risk for hip fracture (relative risk per 1-SD [7.7%] decrease in fractional calcium absorption, 1.24 [95% CI, 1.05 to 1.48]). Women with low fractional calcium absorption and low calcium intake were at greatest risk for subsequent hip fracture; among women whose dietary calcium intake was less than 400 mg/d, those who had fractional calcium absorption at or below the median value of 32.3% had a 2.5-fold (CI, 1.29-fold to 4.69-fold) increase in risk for hip fracture compared with those who had greater absorption efficiency. Fractional calcium absorption was not related to risk for other nonspine fractures (relative risk per 1-SD [7.7%] decrease in fractional calcium absorption, 1.05 [CI, 0.96 to 1.14]). Conclusions: In elderly women, low fractional calcium absorption in the setting of low calcium intake increases the risk for hip fracture. Our findings support the hypothesis of type II osteoporosis, which postulates that decreased calcium absorption is an important risk factor for hip fracture in older persons. *For members of the Study of Osteoporotic Fractures Research Group, see Appendix.
Indoor nitrous acid and respiratory symptoms and lung function in adults
Authors: Deborah Jarvis, B P Leaderer, Susan Chinn, Peter Burney
Journal: Thorax (2005)

<b>Background:</b> Nitrogen dioxide (NO<sub>2</sub>) is an important pollutant of indoor and outdoor air, but epidemiological studies show inconsistent health effects. These inconsistencies may be due to failure to account for the health effects of nitrous acid (HONO) which is generated directly from gas combustion and indirectly from NO<sub>2</sub>. <b>Methods:</b> Two hundred and seventy six adults provided information on respiratory symptoms and lung function and had home levels of NO<sub>2</sub> and HONO measured as well as outdoor levels of NO<sub>2</sub>. The association of indoor HONO levels with symptoms and lung function was examined. <b>Results:</b> The median indoor HONO level was 3.10 ppb (IQR 2.05–5.09), with higher levels in homes with gas hobs, gas ovens, and in those measured during the winter months. Non-significant increases in respiratory symptoms were observed in those living in homes with higher HONO levels. An increase of 1 ppb in indoor HONO was associated with a decrease in forced expiratory volume in 1 second (FEV<sub>1</sub>) percentage predicted (−0.96%; 95% CI −0.09 to −1.82) and a decrease in percentage FEV<sub>1</sub>/forced vital capacity (FVC) (−0.45%; 95% CI −0.06 to −0.83) after adjustment for relevant confounders. Measures of indoor NO<sub>2</sub> were correlated with HONO (<i>r</i> = 0.77), but no significant association of indoor NO<sub>2</sub> with symptoms or lung function was observed. After adjustment for NO<sub>2</sub> measures, the association of HONO with low lung function persisted. <b>Conclusion:</b> Indoor HONO levels are associated with decrements in lung function and possibly with more respiratory symptoms. Inconsistencies between studies examining health effects of NO<sub>2</sub> and use of gas appliances may be related to failure to account for this association.
What do we want to die from?
Authors: I. Heath
Journal: BMJ (2010)

Continuing to fight all causes of mortality offers no hope of success



Successive governments have been committed to reducing mortality, and the recent white paper shows that the current coalition government is no exception ( BMJ 2010;341:c3796, doi:10.1136/bmj.c3796). The problem with such a commitment begins with the word: mortality means both the number of deaths in any given context but also the condition of being mortal and subject to death. We must all die, and so we must all die from something. The mortality rate for the population as a whole will always be 100%; so to what profile of causes of death should we aspire? If we continue to fight all causes of mortality, particularly in extreme old age, we have no hope of success, and we will consume an ever increasing proportion of healthcare resources for ever diminishing returns.

The World Health Organization’s 2008-2013 action plan for the prevention and control of non-communicable diseases states that these diseases, mainly cardiovascular diseases, cancers, chronic respiratory diseases, and diabetes, “represent a leading threat …