tbuckley/cabot-search huggingface dataset:
The cellular electrophysiologic mechanism of the dual actions of disopyramide on rabbit sinus node function.
Authors: T Katoh, H S Karagueuzian, J Jordan, W J Mandel
Journal: Circulation (1982)

To determine the contribution of disopyramide's suggested opposing direct depressant and indirect acceleratory actions on sinus node function, we studied the effects of disopyramide, 1 x 10(-7) to 1 x 10(-4) M, on isolated rabbit sinus node preparations using standard microelectrode techniques. Transmembrane potentials were recorded simultaneously from the sinus node and adjoining crista terminalis area. Disopyramide, as much as 1 x 10(-5) M, had no effects on the sinus cycle length. At a concentration of 1 x 10(-4) M, sinus cycle length was significantly prolonged due to prolongation of the sinus nodal action potential duration. During cholinergic blockade with atropine, 1 x 10(-6) M, disopyramide, 1 x 10(-7) to 1 x 10(-4) M, significantly prolonged sinus cycle length as a result of a prolongation of the sinus nodal action potential duration and a decrease of the slope of phase 4 depolarization. During cholinergic stimulation with carbamyl choline, 1 x 10(-9) M, disopyramide, 1 x 10(-7) to 1 x 10(-6) M, tended to reverse carbamyl choline-induced prolongation of the sinus cycle length (NS). This acceleratory action of disopyramide was caused by a significant increase of the slope of phase 4 depolarization. Disopyramide, 1 x 10(-7) to 1 x 10(-4) M, had no significant effects on corrected sinus node recovery time or on sinoatrial conduction time under any conditions studied. We conclude that disopyramide has a direct depressant action on normal sinus node cells at the upper therapeutic and toxic levels, which is enhanced during cholinergic blockade, and that disopyramide's acceleratory action appears only at much lower concentrations and only during cholinergic stimulation.
INTERNATIONAL COLLEGE OF SURGEONS
Authors: Arnold Jackson
Journal: JAMA (1952)

<h3>To the Editor:—</h3> In order to clarify certain misconceptions based on unfounded rumors concerning the Qualification Board of the International College of Surgeons, it is our desire to reemphasize the functions of our examining body. The qualifying examinations we established in 1946, are in no way intended to invade the province of the American Boards of Surgery or any other national board. These rigid examinations have been created for the specific purpose of establishing the qualifications of those applying for membership in the International College of Surgeons exclusively. At no time has the International College of Surgeons been in competition with any surgical organization. As a matter of fact, the vast majority of our fellows are also members of other existing boards and organizations approved by the American Medical Association and the Advisory Board for Medical Specialties.
Chromosomal abnormalities in ascitic fluid from patients with alcoholic cirrhosis.
Authors: A To, H T Boyo-Ekwueme, M C Posnansky, D V Coleman
Journal: BMJ (1981)

Cytology and cytogenetics were used to study ascitic fluid obtained from five patients with alcoholic cirrhosis. Cytological examination showed that all fluids contained numerous mesothelial cells and some leucocytes. Cytogenetic analysis showed abnormal karyotypes in cultured cells from all five patients and in uncultured cells from three. A consistent abnormality was the presence of spreads with over 70 chromosomes. Clones of abnormal cells, with marker chromosomes, pseudodiploidy, or aneuploidy, in an effusion are characteristic of malignancy; the abnormal karyotypes fulfilled these criteria. This finding of abnormal karyotypes indicates that transformation of the mesothelium can occur in vivo, and such a reaction may be a reflection of the mutagenic effect of alcohol.
217 CD40L-CO-STIMULATION IMPROVES IMMUNOTHERAPY WITH a-FETOPROTEIN PULSED DENDRITIC CELLS TOWARDS ESTABLISHED ORTHOTOPIC HEPATOCELLULAR CARCINOMA IN VIVO
Authors: M.A. Gonzalez-Carmona, A. Vogt, T.H. Ayub, G. Decker, Y. Yildiz, T. Sauerbruch, W.H. Caselmann
Journal: Journal of Hepatology (2011)
M Mujibur Rahaman
Authors: W. B. Greenough, J. Sack
Journal: BMJ (2015)

<b>Aims and objectives:</b> Effect of systemic inflammation and comorbidities on treatment and outcome of adult-onset asthma remains unknown and is the objective of this study. <b>Methods:</b> As part of Seinäjoki Adult Asthma Study (SAAS) with 12-year follow-up of patients with new-onset adult asthma, serum interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP) and lung function were measured and clinical information on comorbidities and medication collected. After excluding patients with co-existing COPD 170 patients remained in the cohort. <b>Results:</b> At follow-up visit, 54 % of the patients had systemic inflammation as indicated by elevated IL-6 or hsCRP, 58 % had at least one comorbidity and 30 % at least two comorbidities (other than asthma-related). Patients with systemic inflammation were treated with higher dose of inhaled corticosteroid (ICS) and they had lower lung function and higher blood neutrophils when compared to patients without systemic inflammation. Patients having ≥ 2 comorbidities had lower asthma control test (ACT) score and this association remained significant when adjusted for age, BMI, gender and pack-years. Patients with both systemic inflammation and comorbidities showed poorest outcome of asthma. In multivariate regression analysis, high ICS dose was predicted by elevated IL-6 (&gt;1.55 pg/ml), elevated blood neutrophils (&gt;3.9x10<sup>9</sup>/l) and eosinophils (&gt;0.2x10<sup>9</sup>/l) at follow-up and poorer lung function at baseline (FEV<sub>1</sub>&lt;80 % predicted) and at follow-up (FEV<sub>1</sub>/FVC post&lt;0,75). <b>Conclusions:</b> Altogether, in patients with adult-onset asthma, elevated IL-6 was associated with use of high dose ICS while multi-morbidity was linked to worse symptoms of asthma.
Predominance of Early Endometrial Cancers After Long-term Estrogen Use
Authors: Barbara S. Hulka, David G. Kaufman, Wesley C. Fowler, Roger C. Grimson, Bernard G. Greenberg
Journal: JAMA (1980)

Clinical stage and pathological characteristics of endometrial cancer cases were related to several aspects of estrogen prescribing. In comparing 256 cases with 321 community control subjects, estrogen use of less than 3 1/2 years' duration did not increase the risk of endometrial cancer for any stage, grade, histological type, or extent of ivasion. With long-term estrogen use (3 1/2 years or more), relative risks were significantly increased (5.2 to 7.6) for the early cancers--those clinically stage IA, histologically grade 1, and invading the endometrium only. These increases were seen with both high-dose (greater than 0.625 mg) and low-dose (less than or equal to 0.625 mg) preparations. Risks were only minimally increased for the more advanced cancers. However, long-duration estrogen use did produce an increased risk of advanced cancer when administration was continuous rather than cyclic.
Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity
Authors: Juan Manuel Torres, Rubén Martinez-Barricarte, Sonia García-Gómez, Marina S. Mazariegos, Yuval Itan, Bertrand Boisson, Rita ρlvarez, Anaïs Jiménez-Reinoso, Lucia del Pino, Rebeca Rodríguez-Pena, Antonio Ferreira, Enrique Hernández-Jiménez, Victor Toledano, Carolina Cubillos-Zapata, Mariana Díaz-Almirón, Eduardo López-Collazo, José L. Unzueta-Roch, Silvia Sánchez-Ramón, Jose R. Regueiro, Eduardo López-Granados, Jean-Laurent Casanova, Rebeca Pérez de Diego
Journal: Journal of Clinical Investigation (2014)

Heterotrimers composed of B cell CLL/lymphoma 10 (BCL10), mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), and caspase recruitment domain-containing (CARD) family adaptors play a role in NF-κB activation and have been shown to be involved in both the innate and the adaptive arms of immunity in murine models. Moreover, individuals with inherited defects of MALT1, CARD9, and CARD11 present with immunological and clinical phenotypes. Here, we characterized a case of autosomal-recessive, complete BCL10 deficiency in a child with a broad immunodeficiency, including defects of both hematopoietic and nonhematopoietic immunity. The patient died at 3 years of age and was homozygous for a loss-of-expression, loss-of-function BCL10 mutation. The effect of BCL10 deficiency was dependent on the signaling pathway, and, for some pathways, the cell type affected. Despite the noted similarities to BCL10 deficiency in mice, including a deficient adaptive immune response, human BCL10 deficiency in this patient resulted in a number of specific features within cell populations. Treatment of the patient's myeloid cells with a variety of pathogen-associated molecular pattern molecules (PAMPs) elicited a normal response; however, NF-κB-mediated fibroblast functions were dramatically impaired. The results of this study indicate that inherited BCL10 deficiency should be considered in patients with combined immunodeficiency with B cell, T cell, and fibroblast defects.
The Profit Motive and Patient Care: The Changing Accountability of Doctors and Hospitals
Authors: David H. Mark
Journal: JAMA (1991)

Profit-making is not a new phenomenon in medical care. Physicians' incomes are essentially the profits of private medical practice. Pharmaceutical and medical equipment manufacturers have long been flourishing profit-oriented industries. For services such as medical care, though, the market sometimes doesn't distribute services in ways that are acceptable to society. In the United States, one of the few industrial nations without national health insurance, we have relied heavily on two forces to attempt to ensure a reasonable distribution of health care services: (1) the service orientation and charity mission of nonprofit hospitals and (2) a highly developed fiduciary ethic of the medical profession. It is not really known how well society has been served by reliance on these forces. However, combined with the growth of third-party payments by employers and government, these forces are inherently expansionary and are at least partially responsible for our current cost problems. The Profit Motive
Relevance of Traditional CEA and CA15-3 and Bone Turnover Markers in Predicting Bone Relapse in Breast Cancer Patients.
Authors: T. Ibrahim, E. Sacanna, L. Mercatali, E. Scarpi, M. Ricci, R. Ricci, P. Serra, C. Tison, D. Amadori
Journal: Cancer Research (2009)

Abstract Background: Over 50% of breast cancer patients who relapse systemically develop bone metastases. The RANK/RANKL/OPG axis governs osteoclastogenesis and bone reabsorption. In particular, osteoprotegerin (OPG) is a decoy receptor of RANK-L (receptor activator of nuclear factor kappa B ligand) and seems to prevent bone destruction by blocking the binding of RANKL with its receptor. We studied the efficacy of circulating OPG compared to the traditional markers CEA and CA15-3 for the early detection of bone lesions.Methods: The study was carried out on peripheral blood from 72 patients with breast cancer, of whom 33 were disease-free and 39 had bone metastases. The OPG transcript was determined using quantitative PCR analysis, and the traditional markers were quantified by immunoenzymatic assays.Results: The OPG median value was higher in disease-free patients (median = 1.7, 0.4-8.9) than in bone-relapse patients (median = 0.6, 0.1-5.2) (p&amp;lt;0.001). CEA and CA15-3 median values were 1.3 (0.0-8.3) ng/ml and 10.6 (0-45.7) U/ml, respectively, in disease-free patients and 4.8 (0.0-90.6) ng/ml and 69.8 (7-1538) U/ml, respectively, in patients with bone metastases (p&amp;lt; 0.0001 for both markers). Considering 0.9 as cut off of OPG relative expression, our analyses revealed a specificity of 88% with respect to 97% for CEA and 94% for CA15-3. OPG sensitivity was 73% compared to only 49% for CEA and 67% for CA15-3. When OPG was considered in combination with the traditional markers, sensitivity increased from 49% to 83% for CEA and from 67% to 88% for CA15.3.Conclusions: Our results on a preliminary series of breast cancer patients indicate that the bone turnover marker OPG greatly increases CEA and CA15-3 sensitivity in predicting bone metastases. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3027.
Immunisation of adults against diphtheria.
Authors: J Wallace
Journal: BMJ (1978)

Biochemically, norethisterone reduces nuclear oestrogen and soluble progesterone receptor formation and induces the formation of oestradiol 173-dehydrogenase.3We have evidence that in oestrogen-treated climacteric women the principal intranuclear oestrogen is oestradiol8-in spite of the plasma excess of oestrone.9The dehydrogenase is likely to be of paramount importance in protecting against endometrial hyperstimulation as it converts oestradiol to the less potent oestrone, thereby reducing the biological effectiveness of the oestrogenic stimulus.We believe that sequential oestrogen/ progestogen therapy is to be preferred to unopposed oestrogen therapy.However, the type and dosage of progestin and the duration of administration most effective in depressing cell proliferation still need to be determined.We believe a better understanding of intra- cellular steroid interactions, and of their fine- structural and biochemical sequelae, will enable rapid development of a highly efficacious regimen which does not hyperstimulate the endometrium.
The Diabetic Pancreas
Authors: George F. Cahill
Journal: New England Journal of Medicine (1978)

Central in the constellation of anatomic and physiologic abnormalities that make up the syndrome of diabetes mellitus in man is an absolute or relative deficiency in pancreatic beta-cell function. For over 100 years anatomists have studied the histology of these cells, which in higher vertebrates are scattered in clusters throughout the exocrine pancreas, forming the islets of Langerhans. The relevant literature is voluminous and frequently contradictory, and the student trying to correlate the pathologic findings with the symptoms and natural history of diabetes faces a most difficult and confusing task.Two advances have helped to shed some light. The first . . .
Hemolytic Anemia Secondary to Stibophen Therapy
Authors: Mercedes V. Vda. de Torregrosa
Journal: JAMA (1963)

STIBOPHEN (Fuadin) (sodium antimony III biscatechol-2-4 disulfonate heptahydrate), is an anthelmintic which since 1929 has been used extensively in the treatment of schistosomiasis. The manufacturers claim that toxicity is low and that severe side effects have not been observed. Transient nausea, vomiting, headache, diarrhea, and muscular and joint pains have been the most frequently observed side effects. Thrombocytopenia has been the most common hematological complication.1  In 1956 Harris2,3described the occurrence of hemolytic anemia in a patient who was receiving stibophen therapy. Furthermore, he found that when stibophen was added to the patient's serum, antibodies active against cells from the patient and compatible red blood cells could be demonstrated. The patient had a positive direct and indirect Coombs' test.  In 1960, a similar case occurred but the antibodies appeared to be of the saline agglutinating type. During 1961, two cases of stibophen-induced hemolytic anemia came to our attention.
External pH modifies sodium channel block by mexiletine in guinea pig ventricular myocytes
Authors: M. Ono, A. Sunami, T. Sawanobori, M. Hiraoka
Journal: Cardiovascular Research (1994)

Objective: The aim was to examine the kinetics and the degree of Na+ channel block by mexiletine under different values of external pH to produce a fractional variation of charged and uncharged forms of mexiletine. Methods: The Na+ current (INa) was recorded using the patch clamp technique of whole cell configuration in guinea pig ventricular myocytes. Results: In the presence of 20 μM mexiletine, INa block developed with a single exponential when depolarising pulse trains of 5 ms were applied to −30 mV from a holding potential of −100 mV at a diastolic interval of 500 ms. At the 30th pulse, the degree of use dependent block of INa was 12.3(SEM 0.41)% (n = 4) of the 1st pulse. When the duration of pulses was prolonged to 200 ms, the degree of use dependent block was increased to 25.6(4.7)%, which had the block development of two exponentials with fast and slow rate constants. The slow component at the 200 ms pulses was comparable to the single exponential component at the 5 ms pulses. Drug binding to the inactivated channel was increased by external alkalinisation, which increased the uncharged form of mexiletine, whereas the block at the 5 ms pulses was not affected by the change of external pH. Conclusions: Uncharged mexiletine caused use dependent block with a fast rate constant having affinity for the inactivated state of the Na+ channel, while the charged form produced a slow component of the block having affinity for the activated state. Therefore the fraction of the uncharged to the charged form of mexiletine could be one of the important determinants in the development and mechanism of INa block. Cardiovascular Research 1994;28:973-979
Using Routine Surveillance Data to Estimate the Epidemic Potential of Emerging Zoonoses: Application to the Emergence of US Swine Origin Influenza A H3N2v Virus
Authors: Simon Cauchemez, Scott Epperson, Matthew Biggerstaff, David Swerdlow, Lyn Finelli, Neil M. Ferguson
Journal: PLoS Medicine (2013)

Using a novel method to assess the risks of outbreaks and epidemics, Simon Cauchemez and colleagues provide insight into a simple tool that allows for more robust monitoring of the epidemic potential of zoonoses.
Bile Acid Metabolism in Cirrhosis. VIII. Quantitative Evaluation of Bile Acid Synthesis From [7β-3H]7α-Hydroxycholesterol and [G-3H]26-Hydroxycholesterol
Authors: Marc Goldman, Z. Reno Vlahcevic, Charles C. Schwartz, Jan Gustafsson, Leon Swell
Journal: Hepatology (2007)

In order to evaluate more definitively the observed aberrations in the synthesis of cholic and chenodeoxycholic acids in patients with advanced cirrhosis, two bile acid biosynthesis pathways were examined by determining the efficiency of conversion of [3H]7α-hydroxycholesterol and [3H] 26-hydroxycholesterol to primary bile acids. Bile acid kinetics were determined by administration of [14C]cholic and [14C]chenodeoxycholic acids. Cholic acid synthesis in cirrhotic patients was markedly depressed (170 vs. 927 μmoles per day) while chenodeoxycholic acid synthesis was reduced to a much lesser degree (227 vs. 550 μmoles per day). The administration of [3H]7α-hydroxycholes-terol allowed for an evaluation of the major pathway of bile acid synthesis via the 7α-hydroxylation of cholesterol. This compound was efficiently incorporated into primary bile acids by the two normal subjects (88 and 100%) and two cirrhotic patients (77 and 91%). However, the recovery of the label in cholic acid was slightly less in cirrhotic patients than in normal subjects. [3H]26-hydroxycholesterol was administered to ascertain the contribution of the 26-hydroxylation pathway to bile acid synthesis. All study subjects showed poor conversion (9 to 22%) of this intermediate into bile acids. The results of this study suggest that a major block in the bile acid synthesis pathway in cirrhosis is at the level of 7α-hydroxylation of cholesterol (impairment of 7α-hydroxylase) and/or in the feedback triggering mechanism regulating bile acid synthesis. The data also suggest that the 26-hydroxylation pathway in normal subjects and patients with cirrhosis is a minor contributor to synthesis of the primary bile acids. Therefore, the relative sparing of chenodeoxycholic acid synthesis observed in cirrhotic patients is not due to preferential synthesis of this bile acid via the 26-hydroxylation pathway.
Relationship of Age at First Live Birth, Parity and Duration of Breast Feeding with Non Familial Breast Cancer in Pakistani Women. A Study of the Cancer Research Group Pakistan.
Authors: S. Ahmad, H. Mahmood, S. Kanwal, A. Mahmood, K. Ahmad, M. Masood, M. Faheem, N. Akbar, M. Hafeez
Journal: Cancer Research (2009)

Abstract Background and objectives; This multicenter case control study is being conducted at seven different centers in Pakistan in order to find out the association and relationship of different hormonal and reproductive factors with breast cancer. These factors have been identified either as risk factors or protective factors for breast cancer in other communities but not in Pakistani women. Preliminary results from four centers are being reported here.Method; Patients attending these cancer treatment centers were interviewed by the trained medical personals and the findings were recorded in a proforma. Age and area matched unrelated controls were randomly selected and interviewed with same questions and findings were recorded in a corresponding proforma. SPSS version 11.5 was used for statistical analysis.Results; From June, 2008 to May, 2009 six hundred eighty eight cases were compared with an equal number of controls. Median age of cases was 47 years (26-70 years) and controls 47.5 years (25-71 years). One hundred ninety eight of cases (28.78%) and 208 of controls (30.23 %) gave first full term live birth before the age of 20. Sixty two cases (09.01%) and 38 controls (5.52%) gave first full term live birth after the age of 30. Seventy one cases and 65 controls were nulliparous.Fifty cases (07.27%) and 51 controls (07.41%) had only one child whereas 104 (15.12%) cases and 118 controls (17.15%) had more then 7 children.Breast feeding duration was more then 24 months in 410 (72.31%) of all women who had more then 1 child. Duration of breast feeding in cases Vs. control in women with 2-4 children, 5-7 children and more then 7 children was similar. Statistical analysis reveals that first live birth below the age of 20 and duration of breast feeding of greater then 24 months duration are not associated as protective factors in this patient population. Odds ratio of 1.35, 95% CI; 1.01-1.70 and 1.014, 95% CI; 0.80-1.22 respectively. Age at first live birth after 30 years of age seems to be positively associated with breast cancer. Odds ratio of 1.75, 95% CI; 1.15-2.65. These results do not support the young age at first full term pregnancy and prolonged duration of breast feeding as protective factors against the breast cancer.Key Words: Breast Cancer, Breast feeding, Parity, Risk Factor Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2071.
Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3)
Authors: Aleena Syed, Marco A Garcia, Shu-Chen Lyu, Robert Bucayu, Arunima Kohli, Satoru Ishida, Jelena P Berglund, Mindy Tsai, Holden Maecker, Gerri O'Riordan, Stephen J Galli, Kari C Nadeau
Journal: Journal of Allergy and Clinical Immunology (2014)
Perfecting the World: The Life and Times of Dr Thomas Hodgkin 1798-1866
Authors: W. F. Bynum
Journal: JAMA (1989)

An eponym can confer a kind of immortality on its subject, although men like Alois Alzheimer and Moric Kaposi might be surprised at the familiarity their names invoke today. Thomas Hodgkin (1798-1866) was not "awarded" his eponym until after his death, but the name has stuck. The fact that Hodgkin's disease is relatively common, and that Hodgkin, with Richard Bright and Thomas Addison, is one of the trio of eponymic "Great Men of Guy's," ensures that we know his name. The Kasses' magnificent new biography means there is no excuse not to know a good deal more. Hodgkin lived through a dramatic time in medicine, during which the hospital assumed center stage in medical education. This "hospital medicine" was most highly developed in Paris, where the work of men like Xavier Bichat, Jean Corvisart, and R. T. H. Laennec gave a new precision to physical diagnosis and championed the idea