tbuckley/cabot-search huggingface dataset:
Potassium Depletion Exacerbates Essential Hypertension
Authors: G. Gopal Krishna, Shiv C. Kapoor
Journal: Annals of Internal Medicine (1991)

Objective: To determine the effect of potassium depletion on blood pressure in patients with essential hypertension. Design: Double-blind, randomized, crossover study, with each patient serving as his or her own control. Setting: Clinical research center at a university hospital. Patients: Twelve patients with hypertension. Interventions: Patients were placed on 10-day isocaloric diets providing a daily potassium intake of either 16 mmol or 96 mmol. The intake of sodium (120 mmol/d) and other minerals was kept constant. On day 11 each patient received a 2-litre isotonic saline infusion over 4 hours. Measurements: Blood pressure; urinary excretion rates for sodium, potassium, calcium, and phosphorous; glomerular filtration rate; renal plasma flow; and plasma levels of vasoactive hormones. Main Results: With low potassium intake, systolic blood pressure increased (P = 0.01) by 7 mm Hg (95% Cl, 3 mm Hg to 11 mm Hg) and diastolic pressure increased (P = 0.04) by 6 mm Hg (Cl, 1 mm Hg to 11 mm Hg), whereas plasma potassium concentration decreased (P < 0.001) by 0.8 mmol/L (Cl, 0.4 to 1.0 mmol/L). In response to a 2-litre isotonic saline infusion, the mean arterial pressure increased similarly on both diets but reached higher levels on low potassium intake (115 ± 2 mm Hg compared with 109 ± 2 mm Hg, P = 0.03). Potassium depletion was associated with a decrease in sodium excretion (83 ± 6 mmol/d compared with 110 ± 5 mmol/d, P < 0.001). Plasma renin activity and plasma aldosterone concentrations also decreased in patients during low potassium intake, but concentrations of arginine vasopressin and atrial natriuretic peptide, glomerular filtration rate, and renal plasma flow were unchanged. Further, low potassium intake increased urinary excretion of calcium and phosphorus and of plasma immunoreactive parathyroid hormone levels. Conclusion: Dietary potassium restriction increases blood pressure in patients with essential hypertension. Both sodium retention and calcium depletion may contribute to the increase in blood pressure during potassium depletion.
Ethics on Call: A Medical Ethicist Shows How to Take Charge of Life-and-Death Choices
Authors: Steven Miles
Journal: JAMA (1992)

When families and patients want or need to learn about the bioethics of lifeand-death decisions in American hospitals,<i>Ethics on Call</i>is the book to refer them to. Nancy Dubler is a lawyer and nationally recognized expert in health law, bioethics, and geriatric care from the Montefiore Medical Center and the Albert Einstein College of Medicine in New York. The book begins with a general orientation to hospital wards and services. Potential players are identified: ethicists, ethics committees, hospital lawyers, utilization review, social workers, interloping outside advocates, and media. Advice is given on how to recruit or detect the involvement of such parties. There are practical discussions of the basics of life-and-death decisions: informed consent, decision making, definitions of death, the right to take risks, competence, and advance treatment planning. The care of older persons, newborns, children, and teens is separately treated. There is an up-to-date discussion of the anguishing
Crusading for change
Authors: Sophie Arie
Journal: BMJ (2005)

As 115 cardinals began voting for a new pope on Monday, some Catholic organisations and priests working in AIDS ravaged areas called for the church to change its stance on condoms. Sophie Arie reports

For Luyanda Ngonyama, like the rest of his generation of South Africans, AIDS is part of every-day life. But condoms are not. One in five South Africans is living with HIV or AIDS, more people than in any other country.

For years, working for the South African Catholic Bishops Council AIDS programme, Mr Ngonyama,aged 32, saw fellow Catholics grapple with the moral dilemma over whether to use all available methods of protection. “What about my religion?” they would ask. “If I have sex [outside marriage]and use a condom, I'll be committing a double sin.”

Mr Ngonyama became so uncomfortable with the Catholic church's official line on condoms—that they “promote immoral behaviour” and don't help protect from AIDS—that he gave up his job as HIV coordinator in the council programme. He now works for Treatment Action Campaign, the country's most influential AIDS activist group and a prominent pro-condom voice.

“I don't ever push Catholics to use condoms. But they must be free to choose. Any interventionon AIDS that doesn't include condoms is meaning-less,” Mr Ngonyama says. Mr Ngonyama is just one of count-less …
Epigenetic Reactivation of Tumor Suppressor Genes by a Novel Small-Molecule Inhibitor of Human DNA Methyltransferases
Authors: Bodo Brueckner, Regine Garcia Boy, Pawel Siedlecki, Tanja Musch, H. Christian Kliem, Piotr Zielenkiewicz, Sandor Suhai, Manfred Wiessler, Frank Lyko
Journal: Cancer Research (2005)

Abstract DNA methylation regulates gene expression in normal and malignant cells. The possibility to reactivate epigenetically silenced genes has generated considerable interest in the development of DNA methyltransferase inhibitors. Here, we provide a detailed characterization of RG108, a novel small molecule that effectively blocked DNA methyltransferases in vitro and did not cause covalent enzyme trapping in human cell lines. Incubation of cells with low micromolar concentrations of the compound resulted in significant demethylation of genomic DNA without any detectable toxicity. Intriguingly, RG108 caused demethylation and reactivation of tumor suppressor genes, but it did not affect the methylation of centromeric satellite sequences. These results establish RG108 as a DNA methyltransferase inhibitor with fundamentally novel characteristics that will be particularly useful for the experimental modulation of epigenetic gene regulation.
Determining the Clinical Course and Outcome in Chronic Lymphocytic Leukemia
Authors: Kanti R. Rai, Nicholas Chiorazzi
Journal: New England Journal of Medicine (2003)

The typical patient with chronic lymphocytic leukemia (CLL) presents to his physician at the time of a routine physical examination as an asymptomatic man who has reached the time in his life when he can enjoy the fruits of his working years. He learns from his physician that he has a somewhat enigmatic type of leukemia, the clinical course and outcome of which vary considerably from patient to patient, and therefore that his outlook is unpredictable. He may be told that some patients live with the disease for decades and die with (and not because of) the disease. He may . . .
All-Cause Mortality Rate in Patients with Idiopathic Pulmonary Fibrosis. Implications for the Design and Execution of Clinical Trials
Authors: Talmadge E. King, Carlo Albera, Williamson Z. Bradford, Ulrich Costabel, Roland M. du Bois, Jonathan A. Leff, Steven D. Nathan, Steven A. Sahn, Dominique Valeyre, Paul W. Noble
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: FVC has emerged as a standard primary endpoint in clinical trials evaluating novel therapies for patients with idiopathic pulmonary fibrosis (IPF). However, it has recently been proposed that all-cause mortality or a composite comprised of all-cause mortality and all-cause nonelective hospitalization be adopted as the standard primary endpoint for IPF clinical trials.Objectives: To conduct a comprehensive evaluation of mortality in three phase 3 clinical trials and evaluate the feasibility of mortality trials in patients with IPF.Methods: The study population included 622 patients randomized to placebo in the CAPACITY studies evaluating pirfenidone (n = 347) or the INSPIRE study evaluating interferon-γ1b (n = 275). The Kaplan-Meier estimate of 2-year survival was fit to the exponential distribution and used to calculate sample size requirements for a mortality study with 90% power to detect a 25% reduction in all-cause mortality with a two-sided α of 0.05. Modeling analyses were used to assess the effects of selected variables on sample size and study design.Measurements and Main Results: A total of 73 deaths occurred during the period of observation (mean duration of follow-up, 80.1 wk). The all-cause mortality rate was 6.6% at 1 year and 13.7% at 2 years. Based on the observed 2-year mortality rate, a total of 508 events would be required to detect a significant treatment benefit in a two-arm trial with 90% power to detect a 25% reduction in all-cause mortality. The estimated sample size for a trial enrolled over 3 years with a maximum follow-up period of 5 years is 2,582 patients.Conclusions: The all-cause mortality rate is relatively low in patients with IPF with mild to moderate impairment in lung function. Accordingly, the necessary size, duration, and cost of all-cause mortality trials in this population are substantial and likely prohibitive.
ANAPHYLACTIC REACTIONS IN THE SKIN OF THE GUINEA PIG WITH HIGH AND LOW MOLECULAR WEIGHT ANTIBODIES AND GAMMA GLOBULINS
Authors: Zoltan Ovary, Hugh Fudenberg, Henry G. Kunkel
Journal: The Journal of Experimental Medicine (1960)

High molecular weight (19S) γ-globulin produces passive cutaneous anaphylaxis (PCA) reactions with its specific antiserum only when it is used as intravenous antigen. Reversed PCA reactions cannot be produced when the 19S protein is injected intradermally in contradistinction to the results with 7S γ-globulin. Antibodies of the high molecular weight class, when injected intradermally, also failed to give PCA reactions following antigen injection. Heterophile antibodies from the sera of patients with infectious mononucleosis, demonstrated to be entirely of the 19S type, gave negative reactions, while 7S heterophile antibodies from guinea pig did give reactions following intravenous injection of sheep cells. Anti-B isoagglutinins of the 19S class failed to react, while those of the 7S class of similar titer gave clear reactions following the injection of B substance. Evidence was obtained that 19S antibodies were capable of inhibiting the PCA reactions obtained with the 7S type, indicating that interaction with antigen occurred. The failure to elicit PCA reactions appeared to be due to an inability to fix to guinea pig tissues in a manner similar to that known for 7S antibodies and γ-globulin.
Anti-IgE Antibody Therapy for Asthma
Authors: Peter J. Barnes
Journal: New England Journal of Medicine (1999)

Over the past 10 years there have been striking improvements in the treatment of asthma, largely as a result of the earlier and more widespread use of inhaled corticosteroids. The development of new treatments for asthma has proved difficult, although several immunologic approaches are undergoing preclinical and clinical assessment.1 Antileukotrienes are the only new class of drugs to treat asthma that have been introduced in the past 25 years, but their efficacy is somewhat limited and unpredictable, as compared with that of inhaled corticosteroids.Mild asthma can be controlled in most patients by relatively low doses of inhaled corticosteroids, and . . .
Electrical alternans and cardiac electrical instability.
Authors: J M Smith, E A Clancy, C R Valeri, J N Ruskin, R J Cohen
Journal: Circulation (1988)

We investigated the relationship between electrical alternans and cardiac electrical stability in a series of 20 dog experiments and in a pilot clinical study. Electrical alternans was detected in both the QRS complex and the ST-T wave by use of a novel multidimensional spectral technique. The magnitude of the alteration was expressed as the alternating electrocardiographic morphology index (AEMI), expressed as parts per million of waveform energy. Electrical stability in the dog preparations was assessed via the ventricular fibrillation threshold measurement, and in the clinical studies via programmed stimulation. In 10 dog experiments, systemic hypothermia resulted in a 60% decrease in ventricular fibrillation threshold (VFT) (p less than .0001) and a significant increase in both AEMI(QRS) form 3.7 +/- 3.0 to 1448 +/- 548 (p less than .0001) and AEMI(ST-T) from 43.9 +/- 18.4 to 19,178 +/- 5579 (p less than .0001). In 10 dog experiments, transient coronary artery ligation also resulted in a 60% decrease in VFT (p less than .0001), an increase from 76.3 +/- 46.5 to 245 +/- 11 in AEMI(QRS) (p less than .05), and an increase from 842 +/- 505 to 1365 +/- 392 in AEMI(ST-T) (p less than .002). In 119 observations in 20 animal experiments, the rank correlation between VFT and AEMI(QRS) was -.30 (p less than .001), with that between VFT and AEMI(ST-T) being -.55 (p less than .0001). In a double-blind pilot clinical trial consisting of 23 studies in 19 patients, the result of electrophysiologic testing was used as an independent measure of cardiac electrical stability. Alternation in waveform morphology identified the inducible patient population with a sensitivity of 92%, a positive predictivity of 70%, and a specificity of 50% (p less than .05). We conclude that analysis of subtle beat-to-beat variability in electrocardiographic morphology may provide a noninvasive measure of cardiac electrical stability.
Increased risk of glomerulonephritis and chronic kidney disease in relation to the severity of psoriasis, concomitant medication, and comorbidity: a nationwide population-based cohort study
Authors: H.-Y. Chiu, H.-L. Huang, C.-H. Li, Y.-J. Yin, H.-A. Chen, S.-T. Hsu, S.-J. Lin, T.-F. Tsai, S.-Y. Ho
Journal: British Journal of Dermatology (2014)

Few studies have examined the association between psoriasis and glomerulonephritis (GN) as well as chronic kidney disease (CKD).To determine the risk of CKD in patients with psoriasis and evaluate the impact of the severity of psoriasis, comorbidities and concomitant drugs on the risk of GN and CKD in patients with psoriasis.We identified 4344 patients with psoriasis for the study cohort and randomly selected 13,032 subjects as a control cohort. Each subject was individually followed for up for 5 years to identify those who subsequently developed GN and CKD.After adjustment for traditional CKD risk factors, psoriasis was found to be independently associated with an increased risk of CKD during the follow-up period [hazard ratio (HR) 1.28; 95% confidence interval (CI) 1.14-1.44]. The increased incidence of GN in patients with psoriasis (HR 1.50, 95% CI 1.24-1.81) may contribute to the positive association between psoriasis and CKD. Patients with mild and severe psoriasis had an increased risk of CKD and GN compared with the control cohort; the risk increased with severity. Patients with psoriasis and arthritis exhibited a higher risk of CKD than patients without arthritis (HR 1.62 vs. 1.26). Among drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) have the strongest association with CKD in patients with psoriasis (adjusted odds ratio 1.69, 95% CI 1.14-2.49).Psoriasis was associated with a higher risk of developing CKD and GN. High severity, psoriatic arthritis involvement and concomitant NSAIDs use further increased the risk of CKD in patients with psoriasis.
The Significance of Eosinophilia in Abdominal Complaints of American Soldiers
Authors: Eric Denhoff
Journal: New England Journal of Medicine (1947)

IN THE Southwest Pacific the characteristics of many tropical diseases acquired by American soldiers differed from those described in textbooks. Medical officers suspected new syndromes, but laboratory personnel were frequently unable to confirm these impressions with routine methods. The lack of specific diagnostic evidence often forced a diagnosis of psychoneurosis. In the course of time, it was possible to evaluate certain criteria and to devise practical technics that were helpful in differentiating the neurotic patients from those with unusual manifestations of the usual tropical diseases. Some of these methods have been described in previous publications. For example, the proper interpretation . . .
An epidemiological comparison between hand eczema and non-hand eczema
Authors: C.L. GOH
Journal: British Journal of Dermatology (1988)

Thirty four per cent of 2110 patients with eczema attending a contact dermatitis clinic presented with hand eczema. An epidemiological comparison was made of patients with hand eczema and non-hand eczema (defined as eczema on parts of the body other than the hands). Occupational eczema was significantly more common in the hand eczema than the non-hand eczema group (P = o.ooII). The prevalence of atopy was the same in both groups (13%). The prevalence of irritant contact dermatitis was higher in the hand eczema group (32%) than the non-hand eczema group (13%) (P < 0.0001). The rate of allergic contact dermatitis was lower in the hand eczema group (23%) than the non-hand eczema group (39%) (P < 0.0001). The rate of positive patch test reactions was lower in the hand eczema group (41 %) than the non-hand eczema group (56%) (P < 0.0001). Nickel sulphate (8%), cobalt chloride (3%), potassium dichromate (3%), and fragrance mix (4%) were common allergens encountered in hand eczema group. None of these allergens was specifically more prevalent in the hand eczema than the non-hand eczema group. However, the prevalence of allergy to nickel, colophony, epoxy resin and medicaments was significantly higher in the non-hand eczema group.
1,25-Dihydroxyvitamin D3 and retinoid X receptor expression in human colorectal neoplasms.
Authors: K F Kane, M J Langman, G R Williams
Journal: Gut (1995)

Epidemiological studies suggest that 1,25-dihydroxyvitamin D3 (D3) protects against colorectal carcinogenesis. Animal and in vitro studies show an antiproliferative effect of D3 in a variety of tumours including those of large bowel origin. D3 actions are mediated by D3 receptors (VDR) alone or by VDR in conjunction with retinoid X receptors (RXRs) in all D3 responsive tissues. The expression of mRNAs encoding VDR and RXRs in normal and malignant human colorectum was determined. Full length VDR (4.6 kB), RXR alpha (5.5 kB), and RXR gamma (3.5 and 7 kB) mRNAs were expressed in all tissues, but RXR beta mRNA was not expressed in any. VDR expression was reduced in 12 carcinomas relative to paired normal mucosa, and RXR alpha expression was reduced in nine. There was no correlation between VDR or RXR alpha expression and the site, grade of differentiation, or Dukes9s staging of the tumour. The finding of persistent VDR and RXR coexpression in all colorectal tumours provides a rational basis for exploring a role for D3 in the treatment of colorectal malignancy.
Nephrotic Syndrome as an Unusual Paraneoplastic Syndrome of Hodgkinʼs Disease Demonstrated on Gallium-67 Scan
Authors: MALIK JUWEID, CHUN K. KIM, SYDNEY HEYMAN
Journal: Clinical Nuclear Medicine (1994)

Nephrotic syndrome, although rare, is recognized as one of the paraneoplastic syndromes. A patient with documented Hodgkin's disease showed increased uptake of Ga-67 in the cortex of both kidneys in addition to multiple sites of lymphomatous involvement. The patient was not receiving chemotherapy or any nephrotoxic drugs, and no other reasons that may account for renal uptake of gallium could be identified. The final clinical diagnosis was nephrotic syndrome as an unusual paraneoplastic syndrome of Hodgkin's disease. Gallium imaging was able to detect multiple sites of lymphoma and the renal uptake due to the associated nephrotic syndrome.
Serial quantitative analysis of serum hepatitis C virus RNA level in patients with acute and chronic hepatitis C
Authors: Masafumi Naito, Norio Hayashi, Hideki Hagiwara, Kazuhiro Katayama, Akinori Kasahara, Hideyuki Fusamoto, Michio Kato, Manabu Masuzawa, Takenobu Kamada
Journal: Journal of Hepatology (1994)
A Call About Erythropoietin: Conflict of Interest or Investment Opportunity?
Authors: Daniel J. Morris
Journal: JAMA (1990)

<h3>To the Editor.—</h3> Much has been written about the ethics of marketing practices and trends of the pharmaceutical industry. Another event related to this subject that I would like to call to my colleagues' attention is a strategy recently practiced by the brokerage industry. A stockbroker called and indicated to my secretary that he was calling about erythropoietin. He, of course, did not tell my secretary that he was a broker, and she, of course, quite naturally thought he was providing prescribing and pharmaceutical information rather than soliciting a stock account with me. The stockbroker, from the Tampa, Fla, office of Shearson Lehman Hutton, admitted that his strategy was to solicit accounts specifically by calling physicians' offices to discuss the stock market profit potential of biotechnology stocks. I advised the stockbroker that, as an oncologist who prescribes the products he was discussing, I could not actively participate in specific issues,
A Thousand Frightening Fantasies: Understanding and Healing Scrupulosity and Obsessive Compulsive Disorder
Authors: Sara C. Charles
Journal: JAMA (1997)

William Van Ornum, a professor of psychology at Marist College in New York, has written this book for persons who suffer from scrupulosity, a spectrum of symptoms expressive of obsessive-compulsive disorder (OCD) that tends to affect individuals with religious affiliations, especially, but not exclusively, Roman Catholics and Orthodox Jews. The focus of their obsessions—recurrent, anxietyprovoking, intrusive, and inappropriate thoughts—and their compulsions—driven, repetitive behaviors to counteract the obsessions—are usually the beliefs, rituals, and behaviors that reinforce or express the tenets of the religion.  Until the mid 1980s, OCD was generally perceived as rare and poorly responsive to treatment. With the advent of large-scale epidemiological studies and more precise diagnostic criteria, a far greater number of the population have been identified as suffering from OCD, with perhaps a lifetime prevalence of 2% to 3%. Many individuals with symptoms may not recognize it as a known disorder or seek professional evaluation or
Sterilizing Activity of R207910 (TMC207)-containing Regimens in the Murine Model of Tuberculosis
Authors: Murad Ibrahim, Chantal Truffot-Pernot, Koen Andries, Vincent Jarlier, Nicolas Veziris
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

The diarylquinoline R207910 (TMC207) has potent bactericidal activity in a murine model of tuberculosis (TB), but its sterilizing activity has not been determined.To evaluate the sterilizing activity of R207910-containing combinations in the murine model of TB.Swiss mice were intravenously inoculated with 6 log(10) of Mycobacterium tuberculosis strain H37Rv, treated with R207910-containing regimens, and followed for 3 months to determine relapse rates (modified Cornell model).Quantitative lung and spleen colony-forming unit counts and bacteriological relapse rates 3 months after the end of therapy were compared for the following regimens: 2, 3, or 4 months of R207910 (J) and pyrazinamide (Z) combined with rifampin (R) or isoniazid (H) or both and 3 or 4 months of a moxifloxacin (M)-containing regimen and 6 months of the standard WHO regimen RHZ. All J-treated mice were culture negative after 4 months of therapy. The relapse rate in the group treated with 4 months of JHRZ was similar to that of mice treated for 6 months with the RHZ regimen (6 vs. 17%; P = 0.54) and lower than that of RMZ (6 vs. 42%; P = 0,03), a moxifloxacin-containing regimen that was the most active in mice on once-daily basis.Four months of treatment with some J-containing regimens was as effective as the 6-month standard regimen and more effective than 4 months of treatment with M-containing regimens. Supplementation of standard regimen (RHZ) with J or substitution of J for H may shorten the treatment duration needed to cure TB in patients.