tbuckley/cabot-search huggingface dataset:
Mechanisms underlying depressed Na+/Ca2+ exchanger activity in the diabetic heart
Authors: Stephen W. Schaffer, Cherry Ballard-Croft, Scott Boerth, Simon N. Allo
Journal: Cardiovascular Research (1997)

Objectives: Depression in Na+/Ca2+ exchanger activity is an important factor in the development of the diabetic cardiomyopathy. Since the mechanism underlying this depression remains unknown, the aim of this study was to determine the contribution of hyperglycemia and insulinopenia towards the observed impairment in Na+/Ca2+ exchanger activity. Methods: Non-insulin-dependent diabetes was induced in neonatal Wistar rats by injection of 90 mg/kg streptozotocin. Na+/Ca2+ exchange in sarcolemmal vesicles and isolated cardiomyocytes was determined by Na+-dependent 45Ca2+ transport. To assess the role of insulin deficiency and hyperglycemia on Na+/Ca2+ exchanger activity, neonatal cardiomyocytes were incubated for 3 days in media containing either 5 mM glucose and 56 U/l insulin (Control), 30 mM glucose and 56 U/l insulin (High glucose) or 5 mM glucose and 0 insulin (Insulin deficiency). Since hyperglycemia has been shown to affect protein kinase C activity, Ca2+-dependent isoforms of protein kinase C were examined in non-diabetic and diabetic heart using hydroxylapatite chromatography. Also examined was Na+/Ca2+ exchanger mRNA levels in diabetic and non-diabetic hearts using Northern slot blot analysis. Results: Acute insulin produced a dose-dependent increase in Na+/Ca2+ exchanger activity, which was dramatically attenuated in diabetic membrane. Myocytes incubated in media containing 30 mM glucose exhibited a 33% reduction in Na+/Ca2+ exchanger activity, while insulinopenia reduced activity by 63%. Exchanger mRNA levels of the diabetic heart were normal; however, diabetes was associated with major changes in protein kinase C activity. Conclusions: Reduced Na+/Ca2+ exchanger activity resulting from diabetes, hyperglycemia or insulinopenia may be related to changes in protein kinase C activity, but is not caused by altered expression of the transporter.
Inhibition of glutathione synthesis augments lysis of murine tumor cells by sulfhydryl-reactive antineoplastics.
Authors: B A Arrick, C F Nathan, Z A Cohn
Journal: Journal of Clinical Investigation (1983)

GSH plays an important role in cellular defense against a wide variety of toxic electrophiles via the formation of thioether conjugates. We studied the role of GSH in murine tumor cell defense against a novel class of sulfhydryl-reactive antineoplastics, the sesquiterpene lactones (SL). Incubation of P815 mastocytoma cells with any of the four SL tested (vernolepin, helenalin, elephantopin, and eriofertopin) for 1 h resulted in 70-97% depletion of GSH. The importance of GSH resynthesis upon exposure of tumor cells to SL was evaluated with the use of buthionine sulfoximine (BSO), a selective, nontoxic inhibitor of gamma-glutamylcysteine synthetase. Inhibition of GSH synthesis with 0.2 mM BSO markedly enhanced SL-mediated cytolysis of four murine tumor cell lines. A 6- to 34-fold reduction in the amount of SL causing 50% lysis was obtained with BSO. Addition of BSO to P815cells either during or immediately after a 1-h pulse with 10 micrograms/ml of vernolepin increased cytolysis from less than 3% to 78-82%. However, a 1.5-h delay in the addition of BSO to such cells, which allowed for substantial resynthesis of GSH, reduced cytolysis to 30%. Recovery of GSH synthetic capacity after BSO treatment correlated with loss of the synergistic effect of BSO on lysis by vernolepin. BSO did not augment cytolysis by six other antineoplastics (doxorubicin, mitomycin C, vinblastine, cytosine arabinoside, maytansine, and 1,3-bis-[2-chloroethyl]-1-nitrosourea [BCNU]). Of these, only BCNU depleted cellular GSH. Lysis by jatrophone, another GSH-depleting antitumor agent, was increased 21-fold by BSO. Since prolonged incubation with BSO alone results in near-complete GSH depletion without loss of cell viability, SL-mediated cytolysis is probably not a result of GSH depletion. We have demonstrated, however, a critical role for GSH synthetic capacity as a determinant of tumor cell susceptibility to cytolysis by SL. GSH also plays an important role in cellular defense against oxidative injury. Vernolepin, acting as a GSH-depleting agent, markedly sensitized tumor cells to lysis by H2O2 (greater than 6.5-fold increase with 20 micrograms/ml of vernolepin). These findings suggest the possibility that the coordinated deployment of sulfhydryl-reactive antitumor agents, BSO, and oxidative injury might constitute an effective chemotherapeutic strategy.
The Pancreas and Vitamin B<sub>12</sub>Absorption
Authors: Graham H. Jeffries
Journal: New England Journal of Medicine (1971)

The intestinal absorption of physiologic amounts of vitamin B12 — about 1 μg daily — depends on a complex sequence of events in the gastrointestinal tract. Major steps in this sequence are the secretion of intrinsic factor (IF) (a glycoprotein with a molecular weight of 60,000) by gastric parietal cells, the formation of intrinsic-factor-vitamin B12 complex (IF-B12) in the intestinal lumen, the binding of IF-B12 by specific "receptors" on the microvilli of distal small-bowel epithelial cells, and the subsequent transfer of vitamin B12 across the epithelium.1 , 2 Each step in this normal process may be . . .
NHS budget escapes relatively unscathed
Authors: K L Osborne
Journal: BMJ (1981)

diarchy, with the medical staff not under the control of the administrative staff (but he admits that "the Permanent Secretary takes precedence if anyone is ever bothered to ask").Having had considerable administrative experience in different frameworks, including the Army, the MRC, and the NHS, I do not think that Sir George's defence of the status quo of the DHSS is convincing.
Prohibition on assisting a suicide is interference with rights of severely disabled people, UK Supreme Court is told
Authors: C. Dyer
Journal: BMJ (2013)

A builder who was left quadriplegic after a car crash 23 years ago and the widow of a man with locked-in syndrome who died last year after losing his case in the Court of Appeal took their right to die case to the United Kingdom’s highest court this week.

Paul Lamb and Jane Nicklinson, widow of Tony Nicklinson, argued that UK law that prevents doctors helping disabled people who are suffering unbearably to end their lives breaches the European Convention on Human Rights.

A total of nine judges heard the case in the Supreme Court, a measure of the difficulty and sensitivity of the issues confronting the court. Most cases are heard by a panel of only five judges, and more important cases usually by seven.

The issue is whether the right …
Both IgA nephropathy and alcoholic cirrhosis feature abnormally glycosylated IgA1 and soluble CD89–IgA and IgG–IgA complexes: common mechanisms for distinct diseases
Authors: Emilie Tissandié, Willy Morelle, Laureline Berthelot, François Vrtovsnik, Eric Daugas, Francine Walker, Didier Lebrec, Jean-Marie Trawalé, Claire Francoz, François Durand, Ivan C. Moura, Valérie Paradis, Richard Moreau, Renato C. Monteiro
Journal: Kidney International (2011)
Eugenic Sterilization and a Qualified Nazi Analogy: The United States and Germany, 1930-1945
Authors: André N. Sofair, Lauris C. Kaldjian
Journal: Annals of Internal Medicine (2000)

In the United States and Germany before World War II, physicians participated in state-authorized eugenic sterilization programs in an attempt to prevent persons deemed to possess undesirable heritable characteristics from propagating. A comparison of U.S. and German histories reveals similarities that argue against easy dismissal of a Nazi analogy. On the basis of a review of editorials in The New England Journal of Medicine and Journal of the American Medical Association from 1930 to 1945 it is difficult to accept the suggestion that the alliance between the medical profession and the eugenics movement in the United States was short-lived. Comparison of the histories of the eugenic sterilization campaigns in the United States and Nazi Germany reveals important similarities of motivation, intent, and strategy and differences that explain why support for eugenic sterilization in the United States gradually weakened. The eugenics movement in Germany was influenced by economic crisis, radical nationalism, Hitler's totalitarianism, and the medical profession's willing participation and attraction to Nazism for financial and ideological reasons. In the United States, a combination of public unease, Roman Catholic opposition, federal democracy, judicial review, and critical scrutiny by the medical profession reversed the momentum of the eugenics movement and led to the conclusion that eugenic sterilization should be voluntary.
Liver-Spleen Scan of Hepatic Cirrhosis in a Patient with Situs Inversus
Authors: CHARLES A. STEWART, THOMAS J. HAYS
Journal: Clinical Nuclear Medicine (1988)

A 60-year-old woman from Central America was admitted for work-up of left upper quadrant pain and abnormal liver function tests. The patient was known to have situs inversus. Hepatitis-B surface antigen and core antibody were negative. There was no history of alcohol use. A Tc-99m sulfur colloid liver-spleen scan was performed and with careful attention to the anatomy demonstrated a small, mottled liver with colloid shift to an enlarged spleen and the bone marrow documenting cirrhosis. A liver biopsy was performed that showed liver cirrhosis of an uncertain type. The presence of situs inversus and the distortion of the normal liver and spleen anatomy by cirrhosis caused an unusual appearance of the liver-spleen scan.
Why Can't Physicians Examine the Larynx?
Authors: Harold C. Klein
Journal: JAMA (1982)

SOME years ago, attention was focused on the almost total failure of the primary physician to detect promptly tumors of the larynx.<sup>1</sup>This glaring defect was attributed to an inability to cope with the technical demands of the angled laryngeal mirror that, for more than 100 years, had been the only available tool for looking over the top of the tongue down to the glottic bed. As a solution, the article recommended replacing the mirror with the relatively new laryngeal telescopes and then proceeded to elaborate their virtues for the primary physician. They were so simple that they required little training; they afforded a clear view of the larynx in a high percentage of cases; and the examination required only a minute. Now the time has come to look back and see who's gaining on whom. With an effective instrument available, are these tumors being discovered earlier? Has there
Effect of folic or folinic acid supplementation on methotrexate-associated safety and efficacy in inflammatory disease: a systematic review
Authors: S. Prey, C. Paul
Journal: British Journal of Dermatology (2009)

Methotrexate is a folic acid antagonist widely used for the treatment of inflammatory disorders for more than 50 years. Methotrexate is a standard systemic therapy for severe psoriasis and rheumatoid arthritis. Folic acid supplementation has been advocated to limit the toxicity of methotrexate on blood cells, gastrointestinal tract and liver. However, there is still controversy regarding the usefulness of folic acid supplementation.We sought to assess the evidence for the efficacy of folic acid supplementation in patients treated with methotrexate for inflammatory diseases. We also investigated whether folic acid supplementation may decrease the efficacy of methotrexate.Cochrane and MEDLINE databases were systematically searched. Randomized controlled trials in patients treated with methotrexate for rheumatoid arthritis or psoriasis with or without arthritis were included. Study selection, assessment of methodological quality, data extraction and analysis were carried out by two independent researchers. We selected double-blind randomized placebo-controlled trials. Analysis was performed for each subgroup of side-effects: gastrointestinal, mucocutaneous, haematological and hepatic.Six randomized controlled trials met the inclusion criteria, with a total sample of 648 patients. There were 257 patients in the placebo group, 198 patients treated with folic acid, and 193 patients treated with folinic acid. The statistical analysis showed a significant reduction of 35.8% of hepatic side-effects induced by methotrexate for patients with supplementation with folic or folinic acid (95% confidence interval -0.467 to -0.248). There was no statistical difference for mucocutaneous and gastrointestinal side-effects although there was a trend in favour of supplementation. The effect of supplementation on haematological side-effects could not be assessed accurately due to a low incidence of these events in the population studied. We were unable to analyse the effect of supplementation on the effectiveness of methotrexate, as markers of activity used in each study were not comparable.Supplementation with folic acid is an effective measure to reduce hepatic adverse effects associated with methotrexate treatment. There is no difference between folinic acid and folic acid, but the lower cost of the latter promotes its use.
The interaction of monosodium urate with connective tissue components
Authors: Warren A. Katz, Maxwell Schubert
Journal: Journal of Clinical Investigation (1970)

Monosodium urate deposits almost exclusively in the connective tissues of patients with gout. Acetone dried homogenates of bovine nasal cartilage, but not of other tissues, markedly enhances the solubility of urate in buffers having molarities and hydrogen ion concentrations similar to that of most body fluids. The components of cartilage responsible for this effect are the proteinpolysaccharides, compounds of protein and chondroitin sulfate, called PPL. A progressive increase in PPL concentration results in a corresponding increase in urate solubility. If, on the other hand, unbound chondroitin sulfate or PPL digested by trypsin is used, then no significant augmentation of urate solubility occurs indicating that the integrity of the molecule is essential. One subfraction of PPL, PPL(5), causes an even more exaggerated response while another, PPL(3), causes a lesser one. These proteinpolysaccharide macro-molecules also inhibit the crystallization of urate from a supersaturated medium. The mechanism of the solubilizing phenomenon is not known. It is suggested that some type of physical or chemical binding is responsible. When, as a result of normal or accelerated connective tissue turnover, PPL is enzymatically destroyed, urate crystals then precipitate from the saturated tissue fluids.
Ondansetron for Diarrhea Associated with Neuroendocrine Tumors
Authors: Barbara Kiesewetter, Markus Raderer
Journal: New England Journal of Medicine (2013)

Somatostatin analogues are not always effective in controlling diarrhea associated with the products of functional neuroendocrine tumors. Serotonin-3–receptor antagonists such as ondansetron may restore control of this troublesome symptom.
Response to: ‘MBDA: what is it good for?’ by Yazici<i>et al</i>
Authors: Ronald van Vollenhoven, Karen Hambardzumyan, David Chernoff, Rebecca Bolce
Journal: Annals of the Rheumatic Diseases (2014)

We appreciate Drs Yazici and Swearingen's1 interest in our paper.2

The multi-biomarker disease activity (MBDA) blood test has been validated as a quantitative measurement of rheumatoid arthritis (RA) disease activity.3 The research question addressed in our paper …
THE USE OF PLASTER ABOUT THE HAND.
Authors: M. E. PRESTON
Journal: JAMA (1907)

The treatment of fractures of the hand and fingers, as a rule, has been considered of rather minor importance, because of the relatively more serious fractures which have to be dealt with. Yet to the patient with a broken hand there is little to interest him in fractures, except that which concerns the particular lesion from which he is suffering. Attention to details in the treatment of these fractures can not be overestimated, and is just as essential to good results as in the case of more important breaks. The diagnosis is usually easy, but the difficulty arises when one comes to apply a firm and compact dressing. Simple as it may seem, this work is often accomplished in a slipshod manner because of its very simplicity. The usual splints of wood, cardboard, etc., are either too cumbersome or do not hold the parts as firmly as they should, and
Points from letters: Alternative to slow-release potassium
Authors: C N Smyth
Journal: BMJ (1975)

October, p 25) is not alone.At the inception of the NHS in 1948 I was an assistant in general practice and lived above the surgery in a traffic-congested area.At that time I managed my rounds quite easily on a bicycle.Unfortunately both your clientele and your colleagues come to regard you as an outsider, which adds to your emotional burden.The car becomes your
Outcomes following acute nonvariceal upper gastrointestinal bleeding in relation to time to endoscopy: results from a nationwide study
Authors: V. Jairath, B. Kahan, R. Logan, S. Hearnshaw, C. Doré, S. Travis, M. Murphy, K. Palmer
Journal: Endoscopy (2012)

Despite the established efficacy of therapeutic endoscopy, the optimum timeframe for performing endoscopy in patients with nonvariceal upper gastrointestinal bleeding (NVUGIB) remains unclear. The aim of the current audit study was to examine the relationship between time to endoscopy and clinical outcomes in patients presenting with NVUGIB.This study was a prospective national audit performed in 212 UK hospitals. Regression models examined the relationship between time to endoscopy and mortality, rebleeding, need for surgery, and length of hospital stay.In 4478 patients, earlier endoscopy ( < 12 hours) was not associated with a lower mortality or need for surgery compared with later ( > 24 hours) endoscopy (odds ratio [OR] for mortality 0.98, 95 % confidence interval [CI] 0.88 - 1.09 for endoscopy > 24 hours vs. < 12 hours; P = 0.70). In patients receiving therapeutic endoscopy, there was a nonsignificant trend towards an increase in rebleeding associated with later endoscopy (OR 1.13, 95 %CI 0.97 - 1.32 for endoscopy > 24 hours vs. < 12 hours), with the converse seen in patients not requiring therapeutic endoscopy (OR 0.83, 95 %CI 0.73 - 0.95 for endoscopy > 24 hours vs. < 12 hours; interaction P = 0.003). Later endoscopy ( > 24 hours) was associated with an increase in risk-adjusted length of hospital stay (1.7 days longer, 95 %CI 1.39 - 1.99 vs. < 12 hours; P < 0.001).Earlier endoscopy was not associated with a reduction in mortality or need for surgery. However, it was associated with an increased efficiency of care and potentially improved control of hemorrhage in higher risk patients, supporting the routine use of early endoscopy unless specific contraindications exist. These results may help inform the debate about emergency endoscopy service provision.
Plasma Neurotransmitters, Blood Pressure and Heart Rate during Supine Resting, Orthostasis and Moderate Exercise in Severely III Patients: A Model of Failing to Cope with Stress
Authors: Fuad Lechin, Bertha van der Dijs, Beatriz Orozco, Alex E. Lechin, Scarlet Baez, Marcel E. Lechin, Mireya Benaim, Emilio Acosta, Luis Arocha, Vladimir Jimenez, Gladys Leon, Zulay Garcia
Journal: Psychotherapy and Psychosomatics (1996)

Background: Previous clinical research has shown that severely ill (somatic) as well as many psychosomatic patients show raised noradrenaline (NA), adrenaline (AD), cortisol, free serotonin (f5HT) and platelet aggregability. Conversely, they show reduced NA/AD plasma ratio and platelet serotonin (p5HT). They also show adrenal hyperresponsiveness to an oral glucose load. These findings are opposed to those observed in depressed patients who show adrenal gland sympathetic hyporesponsiveness and neural sympathetic hyperactivity. Objective: To investigate adrenal gland and neural sympathetic systems as well as the other parameters in nondrepressed severely ill patients through the orthostasis exercise stress test which in normals triggers NA but no AD rise. Methods: We investigated 35 severely ill patients and their age- and sex-paired controls. Systolic, diastolic pulse pressure (PP), heart rate and neuroendocrine parameters were measured supine (0 min), at orthostasis (1 min) and exercise (5 min). A second test was performed 2 weeks later, after atropine injection. Multivariate analysis of variance, paired t test and Pearson product-moment test were employed. Results: The normal PP orthostasis fall was not observed in patients. At this period, an abnormal AD peak substituted the normal NA peak. The normal p5HT-f5HT orthostasis-exercise peaks were absent in patients. Cortisol and platelet aggregability were raised in patients. Conclusions: Severely ill (somatic) patients responded to the orthostasis-exercise stress test with adrenal and corticosuprarenal but not neural sympathetic activity. They did not show the normal parasympathetic activity at orthostasis. This adrenal gland sympathetic hyperactivity registered in somatic patients is similar to that observed in mammals which fail to cope with stress and contrary to the profile registered in depressed subjects who show NA but not AD rise.
Tachycardia-Aggravated Heart Disease
Authors: TOBY R. ENGEL
Journal: Annals of Internal Medicine (1974)

A woman with chronic sinoatrial tachycardia developed ventricular dysfunction 9 years after the onset of the tachycardia. Her history suggests that the myocardial contractile alterations may be a result rather than a cause of tachycardia. The cause of the tachycardia was not defined despite unique responses to electrophysiologic tests. Despite severely altered ventricular function, beta-adrenergic blockade markedly improved symptoms and hemodynamics.
Nonsteroidal Antiinflammatory-induced Acute Renal Failure Detected on Bone Scintigraphy
Authors: Alan Ting, Judith Freund
Journal: Clinical Nuclear Medicine (2004)

A 49-year-old intravenous drug user with chronic but worsening lower back pain had a bone scan which revealed increased uptake in L5/S1. Incidental diffuse bilateral increased renal uptake of methylene diphosphonate (thereafter Tc-99m MDP) was noted, and renal investigations were suggested. The patient subsequently deteriorated and was admitted 2 days later with staphylococcal endocarditis and vertebral osteomyelitis. His creatinine was found to be elevated at 230 mmol/L compared with 119 mmol/L 2 months previously. The patient had taken significant amounts of diclofenac and ibuprofen. The creatinine normalized over 48 hours after withdrawal of the nonsteroidal antiinflammatory drugs (NSAIDs). He was inadvertently given a dose of ketorolac the next week, resulting in a further but transient rise in the creatinine. A subsequent bone scan revealed resolution of the increased renal uptake.
Effective Psychotherapy for Low-Income and Minority Patients
Authors: Carl C. Bell
Journal: JAMA (1983)

Quality psychotherapy services have traditionally been unavailable to low-income and minority patients. The manner in which these services should be delivered has been poorly conceived, as race, ethnicity, and lowincome status have not been considered as important factors that influence treatment, outcome, and mental health service utilization. As it has been shown that nearly 70% of this country's population is composed of people in the poor and working classes and that mental illness is more prevalent in these income groups, this very interesting little book addresses an important issue. Drawing on their extensive experiences with low-income and minority patients, the authors discuss which psychotherapeutic approaches generally work best while stressing the important concept that all patients should have individualized treatment plans that meet their specific needs. They suggest that therapy with this population be conceptualized in brief segments of time from four to six sessions involving active counseling directed toward