tbuckley/cabot-search huggingface dataset:
Features of systemic lupus erythematosus in mice injected with bacterial lipopolysaccharides: identificantion of circulating DNA and renal localization of DNA-anti-DNA complexes.
Authors: S Izui, P H Lambert, G J Fournié, H Türler, P A Miescher
Journal: The Journal of Experimental Medicine (1977)

After injection of lipopolysaccharides (LPS) in mice, there is first a release of DNA into plasma and secondly an induction of anti-DNA antibodies. The circulating DNA was purified from plasma and physico-immunochemically characterized. This DNA has a similar density to mammalian cellular DNA,is 4--6S insize, and probably represents a mixture of single-stranded DNA (SSDNA) and double-stranded DNA (DSDNA) or DSDNA with some single-stranded regions. This purified DNA was shown to react with anti-DNA antibodies which appeared as early as 3 days after a single injection of LPS in mice. In serum, DNA-anti-DNA complexes were not detected, although unidentified circulating immune complex-like material was demonstrated 5-8 days after the injection of LPS. In tissues, particularly in renal glomeruli, fine granular immune complex-type immunoglobulin deposits appeared along the glomerular capillary walls and in the mesangium 3 days after the injection of LPS. There is a direct correlation between the level of anti-DNA antibodies and the intensity of glomerular deposits and about 40% of immunoglobulins eluted from kidneys are anti-DNA antibodies, indicating that some of the immune complexes localized in kidneys are DNA-anti-DNA complexes. Based on these observations, the following hypothetical mechanism for the glomerular localization of DNA-anti-DNA complexes after the injection of LPS in mice is proposed. First, DNA, which has been released in circulating blood after injection of LPS, might bind to renal glomeruli, probably on glomerular basement membranes (GBM) through a high affinity of GBM for DNA; secondly, circulating anti-DNA antibodies, which appear later, might react with the glomerular-bound DNA and form immune complexes independently of circulating immune complexes. However, the possibility of direct deposition of immune complexes is not ruled out.
Clinical Genetics: A Source Book for Physicians
Authors: Joe Leigh Simpson
Journal: JAMA (1980)

Many clinicians are uncomfortable with disorders that are genetic in etiology. This is certainly not surprising, given both the recent genetic advances and the relative inattention to the discipline in the typical medical curriculum. In view of the above, it is surprising that no single book heretofore could be recommended as an initial source for inquiry into the genetic status of a given disorder. By contrast, innumerable books about genetic principles exist, and there is no shortage of clinical works limited to particular subsets of clinical genetics (eg, chromosome disorders). Edited by two eminent medical geneticists,<i>Clinical Genetics</i>fills the void. Following a succinct review of genetic principles, various contributors first consider multisystem genetic disorders—cytogenetic, neoplastic, immunologic, and metabolic. Thereafter, disorders are considered by organ system—cardiovascular, endocrine, gastrointestinal, hematological, muscular, neurologic, ophthalmologic, auditory, renal, respiratory, skeletal, dermatologic, and even dental. A few brief comments on genetic counseling and prenatal diagnosis
Worse patient VAS occurs at weeks 7 and 8 after infliximab infusions
Authors: N Shenker
Journal: Annals of the Rheumatic Diseases (2004)

The new tumour necrosis factor α (TNFα) blockers are revolutionising the treatment of patients with resistant rheumatoid arthritis. Generally good response rates are seen and the treatments are well tolerated. These agents, however, are costly and questions about their long term side effects remain. In the UK, the administration of infliximab and etanercept has been reviewed by NICE, and guidelines were published in March, 2002.1 They recommend that “non-responders” discontinue treatment after 3 months. Non-responders are defined by a Disease Activity Score using a 28 joint count (DAS28) that remains greater than 3.2 or has not reduced by at least 1.2 from the score before treatment.

Anecdotal evidence suggests that patients become increasingly symptomatic towards the end of the 8 weeks between infusions. …
Molecular basis of erythroenzymopathies associated with hereditary hemolytic anemia: Tabulation of mutant enzymes
Authors: Shiro Miwa, Hisaichi Fujii
Journal: American Journal of Hematology (1996)

Molecular abnormalities of erythroenzymopathies associated with hereditary hemolytic anemia have been determined by means of molecular biology. Pyruvate kinase (PK) deficiency is the most common and well-characterized enzyme deficiency in the glycolytic pathway, and it causes hereditary hemolytic anemia. To date, 47 gene mutations have been identified. We identified one base deletion, one splicing mutation, and six distinct missense mutations in 12 unrelated families with a homozygous PK deficiency. Mutations located near the substrate or fructose-1,6- diphosphate binding site may change the conformation of the active site, resulting in a drastic loss of activity and severe clinical symptoms. Glucose-6-phosphate dehydrogenase (G6PD)deficiency is the most common metabolic disorder, and it is associated with chronic hemolytic anemia and/or drug- or infection-induced acute hemolytic attack. An estimated 400 million people are affected worldwide. The mutations responsible for about 78 variants have been determined. Some have polymorphic frequencies in different populations. Most variants are produced by one or two nucleotide substitutions. Molecular studies have disclosed that most of the class 1 G6PD variants associated with chronic hemolysis have the mutations surrounding either the substrate or the NADP binding site. Among rare enzymopathies, missense mutations have been determined in deficiencies of glucosephosphate isomerase, (TPI), phosphoglycerate kinase, and adenylate kinase. Compound heterozygosity with missense mutation and base deletion has been determined in deficiencies of hexokinase and diphosphoglyceromutase. Compound heterozygosity with missense and nonsense mutations has been identified in TPI deficiency. One base junction mutations resulting in abnormally spliced PFK-M mRNA have been identified in homozygous PFK deficiency. An exception is hemolytic anemia due to increased adenosine deaminase activity. The basic abnormality appears to result from the overproduction of a structurally normal enzyme.
Characteristics of stimulation of H+ transport by aldosterone in turtle urinary bladder.
Authors: Q Al-Awqati, L H Norby, A Mueller, P R Steinmetz
Journal: Journal of Clinical Investigation (1976)

Aldosterone stimulates not only Na+ absorption but also urinary acidification. In this investigation the effects of aldosterone on H+ transport are examined in vitro in turtle bladder, a urinary membrane in which several of the factors controlling H+ transport have been defined. H+ transport was increased in bladder halves exposed to aldosterone compared to control halves. Stimulation of H+ secretion was observed as early as 1 h after addition of aldosterone and occurred before that of Na+ transport. In bladders depleted of endogenous substrate addition of glucose increased H+ transport more in aldosterone-treated halves (10.0+/-1.3 nmol/min) than in control halves (6.8+/-2.3). Addition of pyruvate failed to increase H+ transport (--0.3+/-0.7) in control halves but caused significant increments (2.4+/-0.5) in aldosterone-treated halves. In aldosterone-treated bladders glucose caused larger increments (16.5+/-2.7) in H+ transport than pyruvate (9.3+/-2.0) when halves of the same bladders were compared. Na+ transport, however, was equally increased by the two substrates. Despite the differences in time course and substrate requirements between the stimulation of H+ and Na+ transport, both increases were abolished by actinomycin-D. To examine the effect of aldosterone on the force of the H+ pump, protonmotive force, the pH gradient that would nullify the transport rate was determined with and without aldosterone. Aldosterone did not alter protonmotive force but significantly increased the slope of the H+ transport rate on the applied pH gradient. It is concluded that aldosterone stimulates H+ transport independently of Na+ transport. It increases the responsiveness of the transport rate to glucose and to a lesser extent pyruvate, an effect probably secondary to the increased transport rate. Equivalent circuit analysis indicates that aldosterone facilitates the flow of protons through the active transport pathway but does not increase the force of the pump.
Evidence for an intrinsic mechanism regulating heart rate variability in the transplanted and the intact heart during submaximal dynamic exercise?
Authors: L. Bernardi, F. Salvucci, R. Suardi, P. L. Solda, A. Calciati, S. Perlini, C. Falcone, L. Ricciardi
Journal: Cardiovascular Research (1990)

Journal Article Evidence for an intrinsic mechanism regulating heart rate variability in the transplanted and the intact heart during submaximal dynamic exercise? Get access Luciano Bernardi, Luciano Bernardi Correspondence to: Dr Bernardi Search for other works by this author on: Oxford Academic PubMed Google Scholar Fabrizio Salvucci, Fabrizio Salvucci Search for other works by this author on: Oxford Academic PubMed Google Scholar Roberto Suardi, Roberto Suardi Search for other works by this author on: Oxford Academic PubMed Google Scholar Pier Luigi Soldá, Pier Luigi Soldá Search for other works by this author on: Oxford Academic PubMed Google Scholar Alessandro Calciati, Alessandro Calciati Search for other works by this author on: Oxford Academic PubMed Google Scholar Stefano Perlini, Stefano Perlini Search for other works by this author on: Oxford Academic PubMed Google Scholar Colomba Falcone, Colomba Falcone Search for other works by this author on: Oxford Academic PubMed Google Scholar Lucio Ricciardi Lucio Ricciardi Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 24, Issue 12, December 1990, Pages 969–981, https://doi.org/10.1093/cvr/24.12.969 Published: 01 December 1990 Article history Received: 30 January 1990 Accepted: 22 June 1990 Published: 01 December 1990
Myocardial lactate release during ischemia in swine. Relation to regional blood flow.
Authors: B D Guth, J A Wisneski, R A Neese, F C White, G Heusch, C D Mazer, E W Gertz
Journal: Circulation (1990)

To determine the relation between regional myocardial blood flow, contractile function, and myocardial lactate release during mild-to-moderate regional myocardial ischemia, nine open-chest swine were instrumented for measurement of regional myocardial blood flow (microsphere method), contractile function (sonomicrometry), and hemodynamics. L-[1-14C]Lactate or L-[U-13C]lactate was infused intravenously using a primed continuous infusion technique to quantify regional myocardial lactate release. D-[U-13C]glucose or D-[6-14C]glucose was simultaneously infused to determine the contribution of exogenous glucose to lactate release. Graded coronary ischemia (two to three levels) was created in the left anterior descending coronary arterial distribution by mechanically constricting the artery in five animals or by decreasing flow through a cannulated left anterior descending artery in four animals. In all nine animals, subendocardial blood flow was 0.99 +/- 0.21 (ml/min)/g during control and 0.34 +/- 0.14 (ml/min)/g during the most severe grade of underperfusion (p less than 0.001) in the left anterior descending coronary arterial distribution. Regional myocardial lactate release was 0.15 +/- 0.09 and 1.19 +/- 0.75 mumols/ml, respectively (p less than 0.003). A highly significant inverse correlation was observed between subendocardial blood flow and myocardial lactate release during the graded reductions in blood flow (r = -0.71, p less than 0.001). Results from sonomicrometry showed a significant reduction in contractile ventricular function in the anterior wall during the graded reductions in blood flow. The regional arterial-venous glucose difference increased significantly with underperfusion in the left anterior descending coronary arterial distribution, from 0.14 +/- 0.15 to 0.56 +/- 0.37 mumols/ml (p less than 0.003). The contribution of exogenous glucose to lactate release also increased significantly; 0.04 +/- 0.03 mumols/ml of the lactate came from exogenous glucose during control compared with 0.64 +/- 0.59 mumols/ml during the most severe underperfusion (p less than 0.02). A significant positive correlation exists between lactate release and lactate from exogenous glucose during graded underperfusion (r = 0.96, p less than 0.001). In summary, these data demonstrate a close inverse relation between regional myocardial lactate release and regional subendocardial blood flow during graded ischemia.
Five Patients: The Hospital Explained
Authors: Thomas P. Kugelman
Journal: JAMA (1970)

Five clinical situations, each illustrating a different aspect of contemporary health care, serve as the vehicle for Crichton, then a fourthyear medical student, to analyze the structure and function of the monolithic Massachusetts General Hospital. He includes a cardiac arrest, requiring the resources, speed, skill, and impersonality of the modern emergency room; a fever of unknown origin with its seemingly limitless battery of tests, consultations, and expense; a virtually severed arm meticulously repaired with ultrasophisticated surgical techniques; a space-age history and physical examination performed via closed-circuit TV on a traveler at Logan Airport; and, finally, a "diagnostic problem" (lupoid hepatitis) emphasizing the complex interpersonal relationships between patients and doctors at a teaching hospital. Together they create a vivid and representative image of the ultimate potential of modern medicine. The author achieves historical perspective by tracing the origin, growth, and development of the MGH as a university teaching hospital and community
Personality Characteristics and Dysthymic States in Bronchial Asthma
Authors: G.C. Lyketsos, A. Karabetsos, J. Jordanoglou, T. Liokis, A. Armagianidis, C.G. Lyketsos
Journal: Psychotherapy and Psychosomatics (1984)

Patients with bronchial asthma were compared with physically ill patients as to personality traits and dysthymic states. Asthmatics were less dominant and more intropunitive, more anxious and more depressed than the control group. Low dominance or dependent social attitude and inhibited hostility was correlated with low vital capacity (FVC).
Prognosis in lung cancer: physicians' opinions compared with outcome and a predictive model.
Authors: M. F. Muers, P. Shevlin, J. Brown
Journal: Thorax (1996)

BACKGROUND: Although the study of prognostic factors in small cell lung cancer has reached the stage where they are used to guide treatment, fewer data are available for non-small cell lung cancer. Although correct management decisions in non-small cell lung cancer depend upon a prognostic assessment by the supervising doctor, there has never been any measurement of the accuracy of physicians9 assessments. METHODS: A group of consecutive patients with non-small cell lung cancer was studied and the predictions of their physicians as to how long they would survive (in months) was compared with their actual survival. A prognostic index was also developed using features recorded at the patients9 initial presentation. RESULTS: Two hundred and seven consecutive patients diagnosed and managed as non-small cell lung cancer, who did not receive curative treatment for their condition, were studied. Of the 196 patients whose date of death was known, physicians correctly predicted, to within one month, the survival of only 19 patients (10%). However, almost 59% of patients (115/196) had their survival predicted to within three months and 71% (139/196) to within four months of their actual survival. Using Cox9s regression model, the sex of the patient, the activity score, the presence of malaise, hoarseness and distant metastases at presentation, and lymphocyte count, serum albumin, sodium and alkaline phosphatase levels were all identified as useful prognostic factors. Three groups of patients, distinct in terms of their survival, were identified by the use of these items. When the prediction of survival made by the physician was included as a prognostic factor in the original model, it was shown to differentiate further between the group with a poor prognosis and the other two groups in terms of survival. CONCLUSIONS: Physicians were highly specific in identifying patients who would live less than three months. However, they had a tendency to overestimate survival in these patients, failing to identify almost half the patients who actually died within this time. Both the physicians and the prognostic factor model gave similar performances in that they were more successful in identifying patients who had a short time to survive than those who had a moderate or good prognosis. Physicians appear to use information not identified in the prognostic factor analysis to reach their conclusions.
High dose NSAIDs may double the risk of heart attacks and heart failure, says new study
Authors: K. Chinthapalli
Journal: BMJ (2013)

High doses of commonly used non-steroidal anti-inflammatory drugs (NSAIDs) could double the risk of myocardial infarction and heart failure, according to a new study published in the Lancet .1

Daily treatment with cyclo-oxygenase 2 (COX 2) inhibitors, such as celecoxib and etoricoxib, or high dose daily regimens of ibuprofen (2400 mg), diclofenac (150 mg), and naproxen (1000 mg) were analysed for cardiovascular and gastrointestinal side effects. 

In a series of meta-analyses of over 600 randomised trials with over 350 000 participants (mean age 61 years), the authors found that all NSAIDs doubled the risk of heart failure (rate ratio 1.85-2.28). Compared with placebo, a COX 2 inhibitor or diclofenac caused three additional major vascular events per 1000 participants per year (from a baseline risk of eight events per 1000 participants per year), with one such event causing death. A major vascular event was defined …
Sympathetic outflow to the hand in patients with Raynaud's phenomenon
Authors: J. FAGIUS, H. BLUMBERG
Journal: Cardiovascular Research (1985)

Microelectrode recordings of skin nerve sympathetic activity were made in the median nerve supplying the right hand of nine patients with Raynaud's phenomenon and 10 control subjects. With subjects warmed up (finger temperature 33 to 34°C) different manoeuvres were used to evoke strong, single sympathetic bursts, giving rise to vasoconstriction of the same magnitude in patients and control subjects. Immersion of the contralateral hand in ice water for 1 min elicited an increase in sympathetic outflow without any difference between patients and control subjects. It is concluded that neither hypersensitivity of the vessels to strong sympaihetic bursts, nor abnormal increase of sympathetic outflow following shortlasting, local cold exposure, was present in the patients. A possible change of the functional relationship between nerve and vessel, the importance of which is uncertain, was observed in the patient group. The study provides direct evidence against a primary sympathetic hyperfunction and indirect support for a local fault mechanism in Raynaud's phenomenon.
Expanded access programmes: patient interests versus clinical trial integrity
Authors: Paul Lorigan, Paolo A Ascierto, Reinhard Dummer, Alexander M Eggermont, Keith T Flaherty, Claus Garbe, Helen Gogas, Axel Hauschild, Richard F Kefford, John M Kirkwood, James Larkin, Georgina V Long, Michele Maio, Grant A McArthur, Antoni Ribas, Caroline Robert, Dirk Schadendorf, Vernon K Sondak, Jedd D Wolchok, Andrew M Hudson
Journal: The Lancet Oncology (2014)
A Controlled Trial of Buprenorphine Treatment for Opioid Dependence
Authors: Rolley E. Johnson, Jerome H. Jaffe, Paul J. Fudala
Journal: JAMA (1992)

<h3>Objective.</h3> —To assess the efficacy of buprenorphine for short-term maintenance/detoxification. <h3>Design.</h3> —A randomized, double-blind, parallel group study comparing buprenorphine, 8 mg/d, methadone, 60 mg/d, and methadone, 20 mg/d, in a 17-week maintenance phase followed by an 8-week detoxification phase. <h3>Setting.</h3> —Outpatient facilities at the Addiction Research Center, Baltimore, Md. <h3>Patients.</h3> —One hundred sixty-two volunteers seeking treatment for opioid dependence. <h3>Intervention.</h3> —In addition to the medication, counseling using a relapse prevention model was offered but not required. <h3>Primary Outcome Measures.</h3> —Retention time in treatment, urine samples negative for opioids, and failure to maintain abstinence. <h3>Results.</h3> —Throughout the maintenance phase, retention rates were significantly greater for buprenorphine (42%) than for methadone, 20 mg/d (20%,<i>P</i>&lt;.04); the percentage of urine samples negative for opioids was significantly greater for buprenorphine (53%,<i>P</i>&lt;.001) and methadone, 60 mg/d (44%,<i>P</i>&lt;.04), than for methadone, 20 mg/d (29%). Failure to maintain abstinence during the manintenance phase was significantly greater for methadone, 20 mg/d, than for buprenorphine (<i>P</i>&lt;.03). During the detoxification phase, no differences were observed between groups with respect to urine samples negative for opioids. For the entire 25 weeks, retention rates for buprenorphine (30%,<i>P</i>&lt;.01) and methadone, 60 mg/d (20%,<i>P</i>&lt;.05), were significantly greater than for methadone, 20 mg/d (6%). All treatments were well tolerated, with similar profiles of self-reported adverse effects. The percentages of patients who received counseling did not differ between groups. <h3>Conclusions.</h3> —Buprenorphine was as effective as methadone, 60 mg/d, and both were superior to methadone, 20 mg/d, in reducing illicit opioid use and maintaining patients in treatment for 25 weeks. (<i>JAMA</i>. 1992;267:2750-2755)
JAUNDICE IN CHILDHOOD
Authors: A. C. Hampson
Journal: BMJ (1931)

CHILDHOODTH TIE B1TCLJOM EDCLJOURNAlL 4. The clinico-pathological features of endometrioma are described, and stress is laid on the multiple character of the lesions resulting from endometriosis.5. Surgical treatment is discussed, and radical measures are advocated for all but the earliest cases.6. Statistics are quoted from a personal series of 137 cases operated on during the last five years, and individual cases referred to where necessary.
Endoscopic ultrasound (EUS)-guided coil embolization therapy in gastric varices
Authors: R. Romero-Castro, F. Pellicer-Bautista, M. Giovannini, F. Marcos-Sánchez, C. Caparros-Escudero, M. Jiménez-Sáenz, M. Gomez-Parra, A. Arenzana-Seisdedos, V. Leria-Yebenes, J. Herrerias-Gutiérrez
Journal: Endoscopy (2010)

Bleeding from gastric varices is a life-threatening event, however, there is no global consensus on its optimum treatment. Recently, the use of therapeutic endoscopic ultrasound (EUS) in vascular disorders has been reported [1] [2] [3] [4] [5]. Here we report on four patients with severe gastric varices (two patients with Child–Pugh class A, and one each with class B and C; two patients with bleeding) treated with EUS-guided coil embolization.