tbuckley/cabot-search huggingface dataset:
Thrombopoietin-Receptor Agonists for Primary Immune Thrombocytopenia
Authors: Paul Imbach, Mark Crowther
Journal: New England Journal of Medicine (2011)

A young woman with immune thrombocytopenia (ITP) who has been treated with a thrombopoietin-receptor agonist presents for advice regarding long-term treatment. The agents in this therapeutic class, romiplostim and eltrombopag, are effective in increasing platelet counts.
Molecular Heterogeneity in Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency Causing Pediatric Cardiomyopathy and Sudden Death
Authors: Amit Mathur, Harold F. Sims, Deepika Gopalakrishnan, Beverly Gibson, Piero Rinaldo, Jerry Vockley, George Hug, Arnold W. Strauss
Journal: Circulation (1999)

Background —Genetic defects are being increasingly recognized in the etiology of primary cardiomyopathy (CM). Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the first step in the β-oxidation spiral of fatty acid metabolism, the crucial pathway for cardiac energy production. Methods and Results —We studied 37 patients with CM, nonketotic hypoglycemia and hepatic dysfunction, skeletal myopathy, or sudden death in infancy with hepatic steatosis, features suggestive of fatty acid oxidation disorders. Single-stranded conformational variance was used to screen genomic DNA. DNA sequencing and mutational analysis revealed 21 different mutations on the VLCAD gene in 18 patients. Of the mutations, 80% were associated with CM. Severe CM in infancy was recognized in most patients (67%) at presentation. Hepatic dysfunction was common (33%). RNA blot analysis and VLCAD enzyme assays showed a severe reduction in VLCAD mRNA in patients with frame-shift or splice-site mutations and absent or severe reduction in enzyme activity in all. Conclusions —Infantile CM is the most common clinical phenotype of VLCAD deficiency. Mutations in the human VLCAD gene are heterogeneous. Although mortality at presentation is high, both the metabolic disorder and cardiomyopathy are reversible.
Altered purine nucleotide degradation during exercise in patients with essential hypertension
Authors: Toru Kinugawa, Kazuhide Ogino, Shuichi Osaki, Masahiko Kato, Akihiro Endo, Toshihiro Hamada, Yukimasa Honami, Osamu Igawa, Ichiro Hisatome, Chiaki Shigemasa
Journal: Metabolism (2001)
Limited B cell repertoire in severe combined immunodeficient mice engrafted with peripheral blood mononuclear cells derived from immunodeficient or normal humans.
Authors: A Saxon, E Macy, K Denis, M Tary-Lehmann, O Witte, J Braun
Journal: Journal of Clinical Investigation (1991)

The ability to engraft human PBMC or fetal tissue immune cells in the severe combined immunodeficient (SCID) mouse has created a need for characterization of these systems and their application to disease models. We demonstrate that SCID mice reconstituted with PBMC support the growth and differentiation of a restricted set of B cells. Human IgG levels of 1-2 mg/ml (10-20% of normal human serum levels) were routinely achieved in spite of a serum half life of only 12 d. Ig levels peaked around 50 d and Ig production was maintained for greater than 100 d. The Ig was greater than 85% IgG though some IgM, IgA, IgD, and even IgE could be detected. However, the human IgG produced in hu-PBL-SCID mice was pauci-clonal when analyzed by isoelectric focusing and by kappa/lambda light chain usage. Using a new polymerase chain reaction based analysis capable of monitoring individual VH family utilization, we found that the engrafted B cells showed skewed and restricted human VH subfamily utilization. These parameters were markedly variable among hu-PBL-SCID mice reconstituted from the same donor cell population at both early (21-50 d) and late stages (greater than 100 d). Hu-PBL/CVI-SCID mice constructed with cells from patients with common variable immunodeficiency with an in vitro block in terminal B cell differentiation produced human Ig responses that were quantitatively the same as those produced by hu-PBL-SCID mice from normal donors. The hu-PBL-SCID system using PBMC appears to lead to growth and Ig production by a small number of B cells and results in a restricted B cell repertoire.
THERAPEUTIC INDICATIONS SUGGESTED BY THE CONDITION OF THE BLOOD.
Authors: O. T. OSBORNE
Journal: JAMA (1901)

We are in the age when a better understanding of pathology and bacteriology has shown the absurdity of many pseudospecifics and of symptomatic treatment. We realize more and more the "phusis" of Hippocrates, the "archeus" of Paracelsus, the "pneuma" of Hoffmann, the "anima" of Stahl, and the "vis medicatrix naturæ" of later writers, which power Hahnemann so well demonstrated with his multiple dilutions of nothing, allowing disease to recover without interference. Also, we recognize the uselessness of attempting to cure or even to stay organic disintegration or obliteration. While acknowledging the above, I think we have become too pessimistic therapeutically, and while we are directing our energies and remedial agents to the etiology and pathology of disease, we have forgotten to better, or correct, or aid the normal metabolism of the body. Too many books on practice and too many teachers instruct carefully in the etiology, pathology, symptomatology, diagnosis, and
Systemic Arterial Blood Pressure during Exercise in Patients with Atherosclerosis Obliterans of the Lower Limbs
Authors: EINAR LORENTSEN
Journal: Circulation (1972)

Systemic intraarterial blood pressure and heart rate have been measured during exercise on a foot ergometer in 13 patients suffering from unilateral intermittent claudication. Each limb was exercised separately for 5 min. Both systolic and diastolic blood pressure increased to significantly higher levels during exercise with the diseased limbs than during exercise with the nondiseased limbs. No significant difference was found in heart rate. After cessation of exercise the blood pressure and heart rate dropped abruptly. For the first 2 min of recovery the systolic blood pressure in the diseased limbs stayed higher than the pressure measured at rest immediately before exercise. Ten patients were also exercised for 2 or 3 min with arrested circulation. During this period no significant differences between the diseased and nondiseased limbs were found in relation to blood pressure or heart rate.
Educational resource pack exists to help staff listen to what concerns children
Authors: U. M MacFadyen
Journal: BMJ (1998)

EDITOR—Hart and Chesson emphasise the importance and feasibility of soliciting the views of children and young people on their healthcare experiences and needs.1Staff must raise awareness that children and young people may have different concerns from those of adults and that recognising children's anxieties is important but not always easy. This can leave clinicians and managers unsure how to start improving their …
Maintenance haemodialysis and renal transplantation.
Authors: C. Ogg
Journal: BMJ (1970)

During the last decade it has become apparent that a diagnosis of terminal renal failure is not necessarily a death sen- tence and that there are now techniques which can frequently prolong life indefinitely.Unfortunately these techniques are cumbersome and expensive in terms of staff and equipment and it is impossible to offer renal substitution to all the patients who could reasonably benefit.Perhaps half the 7,000 patients who die annually in the United Kingdom from chronic renal failure are unsuitable because of their extreme age or youth or because of the presence of other serious disease.The remainder are all more or less suitable for treat- ment, but at present only about one in five can be taken on.Selection policies vary widely but most units can usually accept only patients between the age of 15 and 50 years.Pref- erence is given to the happily married patient with young children and particular emphasis is placed on the qualities of reliability, common sense, and stoicism.Many units, however, take patients as they present, accepting that psychiatric assess- ment of a uraemic patient may be impossible.It is important to start dialysis at the correct time.If it is too early the patient will suffer the burdens and dangers without benefit, and if it is too late he may die or experience an unnecessary and dangerous illness.In practice it is reason- able to start when life on conservative management becomes dangerous or more unpleasant than it is on dialysis.This cor- responds to a creatinine clearance below 3 ml./min. in a nor- motensive patient or below 6 ml./min. in one with hyperten- sion.The inability to excrete more than 6 g. of urea in 24 hours must also be regarded as an indication.The two techniques of maintenance haemodialysis and renal transplantation are complementary and most patients can be treated by either.Transplantation must be preceded by a period of dialysis and, if the graft fails, it should be possible to re-establish the patient on a machine. Maintenance Haemodialysis PrincipleSubstances of low molecular weight pass down a concentra- tion gradient through a semipermeable membrane which retains larger particles.Heparinized blood flows over a cellulose-based membrane which separates it from dialysate containing sodium, calcium, magnesium, and chloride in roughly the' same concentrations as in normal blood.Acetate is used as a buffer, and the fluid also contains potassium and glucose.Urea, creatinine, uric acid, phosphate, and other metabolites pass from the blood into the dialysate.Water is removed by ultrafiltration.
Prediction of response to pegylated interferon plus ribavirin in HIV/hepatitis C virus (HCV)-coinfected patients using HCV genotype, IL28B variations, and HCV-RNA load
Authors: Karin Neukam, Angela Camacho, Antonio Caruz, Norma Rallón, Almudena Torres-Cornejo, Jürgen K. Rockstroh, Juan Macías, Antonio Rivero, José M. Benito, Luis F. López-Cortés, Jacob Nattermann, Jesús Gómez-Mateos, Vicente Soriano, Juan A. Pineda
Journal: Journal of Hepatology (2011)
Interactions of chrysotile asbestos with erythrocyte membranes.
Authors: A R Brody, L H Hill
Journal: Environmental Health Perspectives (1983)

Chrysotile asbestos causes lysis of red blood cells. It has been proposed that the mechanism of hemolysis is mediated through interactions between asbestos and cell membrane glycoproteins. Our studies support this concept and the following results are reported. Electron microscopy shows that asbestos fibers distort red blood cells and bind to cell membranes which may become wrapped around the fibers. This reaction is prevented by pretreatment of the cells with neuraminidase. The distribution of lectins which bind to membrane glycoproteins is altered by treating the cells with asbestos. Cell distortion and membrane deformation consequent to asbestos treatment correlate with a clear increase in the ratio of intracellular Na+:K+ ions.
James Antony Garrod
Authors: Tim Garrod
Journal: BMJ (2005)

Rheumatologist who bridged the gaps between cardiology, rheumatology, and herbal medicine John Cosh had many interests in clinical medicine but his main contributions were his long term studies of the effects of rheumatoid arthritis, co-discovery of the genes associated with rheumatoid arthritis, and his work on the benefits of herbal medicines.In 1973, with R K Jacoby and M I Jayson, he published an 11 year follow-up of 100 patients newly diagnosed as having rheumatoid arthritis (BMJ 1973;2(5858): 96-100) and followed them for a further 30 years, showing that rheumatoid arthritis is a progressive disease impairing function for decades after onset.By 2004 eight of the sample were severely disabled with rheumatoid arthritis, three were less disabled, and only five had normal functioning.Of the 84 who died, median survival was reduced by 10 to 11 years, and the leading cause of death was heart disease.In 1986 he published, with other rheumatologists, a study that showed the association of rheumatoid arthritis with several human lymphocyte antigens; the associations were stronger in patients with more advanced disease.John Cosh had originally wanted to be a heart surgeon, but his interests shifted towards cardiology and then to the cardiological aspects of rheumatology.He was born in Bristol, the son of a pharmacist.From Bristol Grammar School he won a
Abnormal left ventricular wall rotation in patients with complete left bundle branch block: analysis using magnetic resonance imaging tagging images
Authors: S. Hirasaki, H. Sugihara, H. Matsui, A. Matsuo, T. Shima, Y. Harada, T. Nakamura, A. Azuma, T. Kuribayashi, M. Nakagawa
Journal: Journal of the American College of Cardiology (1998)
Hepatitis B virus and polymyalgia rheumatica: a search for HBsAg, HBsAb, HBcAb, HBeAg, and HBeAb.
Authors: H Elling, P Skinhoj, P Elling
Journal: Annals of the Rheumatic Diseases (1980)

Forty-three consecutive patients with polymyalgia rheumatica were studied for serological markers of actual or previous hepatitis B virus infection. Signs of active virus replication, which include HBsAg supported by the presence of HBeAg and anti-HBc in high titres, were not found in any cases. Anti-HBs, a serological sign of previous hepatitis B virus exposure, was present in 16.8%. The prevalence of anti-HBs is strongly age-dependent in the normal population, and its prevalence in polymyalgia rheumatica was not significantly different from the incidence found in other hospital patients. No significantly raised incidence was found in any subgroups, including patients without liver dysfunction. These results do not support the concept that current or previous hepatitis B virus infection plays any role in the pathogenesis of the majority of cases of polymyalgia rheumatica.
Too posh to infect?
Authors: T. Dalrymple
Journal: BMJ (2008)

In John Buchan’s last book, Sick Heart River , published posthumously in 1941, the protagonist, Sir Edward Leithen, has been given a year to live by an eminent London specialist, Acton Croke. A gas attack in the first world war has awakened tuberculosis as a delayed effect, and it is now galloping through his lungs. Although occurring only a handful of years before the discovery of streptomycin, Sir Edward’s tuberculosis is a death sentence.

Buchan finished the book just a few days before his own death from cerebral thrombosis. Then governor general of Canada, he had been a martyr to peptic ulcer for decades, and he eked out his …
Prevalence of Poliovirus Neutralizing Antibodies in Young Adult Women
Authors: Thomas R. Mayer
Journal: JAMA (1981)

One hundred nulliparous women, aged 21 to 29 years, were screened for antibody to poliovirus. One subject lacked detectable poliovirus neutralizing antibody to type 1 and another to poliovirus type 2, while four women lacked antibody to poliovirus type 3. None of the subjects was negative for more than one poliovirus serotype. Another oral polio vaccine booster should be considered after the primary series to improve protection for these young adults who will be significantly exposed in the future to vaccine strain virus when their children are immunized. (<i>JAMA</i>1981;246:1207-1209)
Comment on Balkau et al. Factors Associated With Weight Gain in People With Type 2 Diabetes Starting on Insulin. Diabetes Care 2014;37:2108–2113
Authors: Nick Finer
Journal: Diabetes Care (2014)

The study by Balkau et al. (1) finds that people who are thinner and have more poorly controlled diabetes gain the most weight when started on insulin. While weight gain is a legitimate concern for patients and clinicians, we should take care not to immediately equate weight gain in this setting with harm, as it is changes in body composition that are …
Medicines Control Agency must be more open
Authors: Z. Kmietowicz
Journal: BMJ (2003)

The UK Medicines Control Agency needs to communicate better with the public about the safety of medicines and to become more transparent about the way it operates, says an independent review.

In its report, the National Audit Office has praised the agency for tackling financial pressures, human resources, and technology issues in a changing marketplace. The agency has seen a sharp downturn in the number of applications for …
Effect of idiotype-specific suppressor T cells on primary and secondary responses.
Authors: F L Owen, A Nisonoff
Journal: The Journal of Experimental Medicine (1978)

Previous reports have shown that suppression of idiotype can be adoptively transferred by T cells, or by rosettes containing T cells with anti-idiotypic receptors, from an idiotypically suppressed, syngeneic mouse. The present data indicate that secondary B cells are highly resistant to such suppression. Priming recipients to the relevant hapten, p-azophenylarsonate, 6 days or 4 mo before the adoptive transfer prevented suppression. This was independent of the carrier used for the hapten group during priming or subsequent immunization, suggesting that resistance to suppression is attributable to secondary cells with specificity for the hapten. The effect of suppressor T cells could also be overcome by mixing them with specifically purified B cells having receptors for the hapten group before the adoptive transfer. Adoptive transfer of the suppressed state by specifically purified B cells from suppressed, hyperimmunized animals confirmed our previous finding that the suppression of idiotype can also be caused by B cells lacking idiotypic receptors, evidently through a mechanism involving clonal dominance. Possible mechanisms of idiotypic suppression by T cells are discussed.
Effect of a neuromuscular warm-up programme on muscle power, balance, speed and agility: a randomised controlled study
Authors: K Pasanen, J Parkkari, M Pasanen, P Kannus
Journal: British Journal of Sports Medicine (2009)

Objective: To investigate whether a 6-month neuromuscular warm-up programme could improve muscle power, balance, speed and agility. Design: Cluster randomised controlled study. Setting: 27 top level female floorball teams in Finland. Participants: 222 players (mean age 24 years); 119 in the intervention group and 103 in the control group were followed-up for one league season (6 months). Intervention: A neuromuscular warm-up programme included sports-specific running technique, balance, jumping and strengthening exercises. The teams were advised to use the programme 1–3 times per week through the league season. One training session took ∼25 min. Main outcome measures: Performance tests were assessed before and after the 6-month intervention and included static jump, countermovement jump, jumping over a bar, standing on a bar and figure-of-eight running. Results: At 6 months, significant between-group differences were found in two outcome measures: jumping over a bar (number of jumps in 15 s) and standing on a bar (number of balance losses in 60 s). These differences were 2.3 jumps (95% CI 0.8 to 3.8, p = 0.003), favouring the intervention group, and −0.4 balance losses (95% CI −0.8 to 0.0, p = 0.050), again in favour of the intervention group. Conclusion: A neuromuscular warm-up programme improved the floorball players’ sideways jumping speed and static balance. The exercises were also safe to perform and can thus be recommended for weekly training of floorball players. Trial registration number: ISRCTN26550281.
Tissue Oxygen and Carbon Dioxide Tensions During Hyperbaric Oxygenation
Authors: Edward H. Bergofsky, Michael C. H. Wang, Takashi Yamaki, Julius H. Jacobson
Journal: JAMA (1964)

BREATHING AIR enriched with O<sub>2</sub>in chambers where the ambient pressure has been artificially elevated (hyperbaric oxygenation) leads to vast increases in the amount of O<sub>2</sub>carried in physical solution in the arterial blood. In principle, the requirements of the organism may be met entirely by the O<sub>2</sub>dissolved in plasma without recourse to oxyhemoglobin; as a result, the O<sub>2</sub>pressure gradient between blood and tissues remains high even while blood is traversing the capillary, and tissue areas deprived by disease states of an adequate blood supply may be nourished with O<sub>2</sub>by this large pressure gradient. Even though hyperbaric chambers for therapeutic purposes in man are increasing,<sup>1-3</sup>two potential physiological consequences of hyperbaric oxygenation, which may limit its clinical usefulness, have been difficult to study.<sup>4,5</sup>These are (1) vasoconstriction, either in toto or in individual organs,<sup>6</sup>which may reduce blood flow
Vascular Smooth Muscle Overexpression of G Protein–Coupled Receptor Kinase 5 Elevates Blood Pressure, Which Segregates With Sex and Is Dependent on G <sub>i</sub> -Mediated Signaling
Authors: Janelle R. Keys, Rui-Hai Zhou, David M. Harris, Charles A. Druckman, Andrea D. Eckhart
Journal: Circulation (2005)

Essential hypertension involves an increase in sympathetic nervous system activity and an associated decrease in beta-adrenergic receptor (AR)-mediated dilation. In addition, increased levels of G protein-coupled receptor (GPCR) kinases (GRKs), which regulate GPCR signaling, are associated with increased blood pressure (BP).We generated transgenic mice with approximately 2-fold vascular smooth muscle (VSM)-specific overexpression of GRK5 to recapitulate a selective aspect of hypertension and understand the impact on GPCR regulation of BP. VSM-GRK5 mice were hypertensive, with a 25% to 35% increase in BP, whereas there was no concomitant cardiac or VSM hypertrophy. BP elevations were segregated with sex, with male mice having higher levels than female mice, and ovariectomy did not alter this phenotype. BP was restored to control values with pertussis toxin Gi-signaling inhibition or chronic beta1AR inhibition after 7 days of CGP20712A, whereas the beta2AR antagonist ICI 118,551 was ineffective. Alpha1AR response was not altered, nor was betaAR-mediated dilation in male blood vessels, whereas norepinephrine sensitivity was increased. In contrast, female VSM-GRK5 blood vessels have diminished betaAR-mediated dilation and enhanced sensitivity to angiotensin II (Ang II).Our data suggest that in both male and female mice, VSM-specific overexpression of GRK5 elevates BP mediated by Gi and, at least in part, by beta1AR in males and Ang II receptors in females. Understanding mechanisms underlying an increase in VSM-GRK5 may have a profound influence on the use and development of antihypertensive therapeutics.
Thallium-201 Uptake in Keloid Tissue Masquerading as a Pulmonary Neoplasm
Authors: SHUNG C. CHAE, BONG R. LEE, SEUNG W. KANG, JAETAE LEE, JAE E. JUN, WEE H. PARK, KYUBO LEE, JAEKYEONG HEO
Journal: Clinical Nuclear Medicine (1994)

TI-201 imaging is useful in the diagnostic work-up of tumors. However, TI-201 uptake is not specific for tumor and is also noted in other conditions. A case is described in which TI-201 was taken up by a keloid.
Myocardial fascicle and fiber disarray in 25 mu-thick sections.
Authors: H Fujiwara, C Kawai, Y Hamashima
Journal: Circulation (1979)

We compared the histologic picture of myocardial fiber disarray in thin (4 mu) and thick (25 mu) sections of tissues obtained at autopsy from 18 adults and eight infants with clinically normal hearts, from 10 hearts with concentric hypertrophy (hypertensive patients), nine with myocardial infarction and four with hypertrophic cardiomyopathy (HCM). In the thick sections, so-called bizarre myocardial fiber disarray in thin sections was seen as a bizarre fascicle disarray. Therefore, the usual fiber disarray reported in cases of HCM is actually a fascicle disarray with a three-dimensional complex network. There was no marked difference in distribution and frequency of fascicle disarray among normal adult and infant hearts, and diseased hearts with hypertension and myocardial infarction. In the four hearts with HCM, diffuse bizarre fascicle disarray in the thick section was detected in the septum and anterior and posterior walls of the left ventricles in all cases, and in the lateral walls in one case. In the portions without the diffuse fascicle disarray, the distribution of disarray was the same as that in hearts with no HCM. Such fascicle disarray, including that of HCM, is probably congenital.