tbuckley/cabot-search huggingface dataset:
Investigating young adults with chronic diarrhoea in primary care
Authors: Thomas P Chapman, Lucia Y Chen, Laurence Leaver
Journal: BMJ (2015)

#### The bottom line

A previously well 25 year old man presents to his general practitioner with a six month history of crampy abdominal pain, bloating, and diarrhoea, with passage of loose stools up to six times a day. There is urgency but no incontinence. On clinical examination he has mild lower abdominal tenderness, but digital rectal examination is normal.

Chronic diarrhoea can be defined pragmatically as the passage of loose stools more than three times a day for at least four weeks.1 A patient’s own perception of diarrhoea may be markedly different, and it is essential to clarify—for example, faecal incontinence is commonly misconstrued as diarrhoea.1

Irritable bowel syndrome (IBS), a functional disorder, is the most prevalent cause of chronic diarrhoea.2 Other important causes include inflammation (inflammatory bowel disease (IBD), microscopic colitis, and more rarely infection), bile acid diarrhoea, malabsorption (coeliac disease, lactose intolerance, and pancreatic insufficiency), drugs, food additives, and endocrine conditions (thyrotoxicosis and diabetes). Clinicians should always be mindful of an underlying cancer, particularly in patients over 45 years, and …
The Medical Association of Georgia's Impaired Physicians Program
Authors: G. Douglas Talbott
Journal: JAMA (1987)

Risk factors for the disease of chemical dependence, or addiction to alcohol and/ or drugs, for physicians have not been clearly defined. Yet chemical dependence is believed to be a leading occupational hazard for physicians. This study compares the specialties of a population of physicians assessed for the presence of impairment (study group, N =1000) with the distribution of specialties for all US physicians. Only 21 of the total were found to be free of impairment from chemical dependence or psychiatric disease, while 920 physicians (92.0%) had a primary diagnosis of chemical dependence, and 59 (5.9%) had a major psychiatric illness. Anesthesia and family and general practice were found to be overrepresented in the population under study, as compared with all US physicians. There were significant differences between the study group and all US physicians with respect to age, sex, and practice activity status. The authors urge these apparent high-risk specialties, as well as the medical profession itself, to develop control or prevention strategies that will reduce risk for chemical dependence through education, early identification, intervention, and treatment of those individuals with the disease. (<i>JAMA</i>1987;257:2927-2930)
The Hemodynamic Response to Chronic Anemia
Authors: MARTIN DUKE, WALTER H. ABELMANN
Journal: Circulation (1969)

To determine whether the hyperkinetic circulatory response to chronic anemia is obligatory and to assess its strength and potential reversibility, the hemodynamic state at rest was assessed (indicator-dilution method) in 24 patients with chronic anemia before and after certain interventions. A comparison of cardiac output measured before and after treatment established the consistency of the hyperdynamic response to anemia. In the absence of convalescent data, this response might have been overlooked in some anemic patients whose cardiac output fell within the normal range. In the anemic state, cardiac output correlated negatively and significantly with age (r=-0.752). This relationship may account for the apparent absence of the hyperkinetic circulation in elderly, anemic patients. In only the most anemic (hemoglobin, 3.8 g/100 ml) of six patients did inhalation of 100% oxygen lower cardiac output significantly. In four patients, studied in both the supine and sitting posture, orthostatic stress was consistently accompanied by a decrease in central blood volume (7%) and an increase in total systemic resistance (64%), resulting in a reduction of both stroke index (28%) and cardiac index (23%). Administration of methoxamine to seven anemic patients resulted in increases in mean arterial blood pressure (24%) and total systemic resistance (40%) in all and a decrease in cardiac output in all but one patient (mean, 20%). Peripheral vasoconstriction induced by means of orthostatic stress or by a pressor amine thus effected an acute reversal of the high output state in chronic anemia. These observations suggest that redistribution of blood volume and vasodilatation play a dominant role in the hyperkinetic circulatory response to chronic anemia and indicate that this state is labile rather than fixed.
Neonatal rabbit juxtamedullary proximal convoluted tubule acidification.
Authors: M Baum
Journal: Journal of Clinical Investigation (1990)

The present in vitro microperfusion study examined apical membrane Na+/H+ antiporter and basolateral membrane Na(HCO3)3 symporter activity in newborn and adult juxtamedullary proximal convoluted tubules. Proton fluxes were determined from the initial rate of change of intracellular pH after a change in the luminal or bathing solution, buffer capacity, and tubular volume of newborn and adult tubules. Intracellular pH (pHi) was measured fluorometrically using the pH-sensitive dye (2',7')-bis (carboxyethyl)-(5,6)-carboxyfluorescein (BCECF). Apical Na+/H+ antiporter proton flux, assayed by the effect of sodium removal (147----0 meq/liter) on pHi, was one-third the adult level for the first 2 wk and doubled in the 3rd wk of life. Adult levels were achieved by 6 wk of age. Na+/H+ antiporter activity was not detected on the basolateral membrane of 1-wk-old newborns, indicating that polarity of this transporter was already present. Basolateral membrane Na(HCO3)3 proton flux, assayed by the effect of a bath bicarbonate change (25----5 meq/liter) and by a bath sodium change (147----0 meq/liter) on pHi, was 50-60% of adult values in 1-wk-old newborns. Basolateral membrane Na(HCO3)3 proton flux assayed by a bath bicarbonate change (25----5 meq/liter) remained at 50-60% of adult values for the 1st mo of life and increased to adult levels by 6 wk of age. This transporter not only plays a role in net acidification, but is an important determinant of cell pH in newborn juxtamedullary proximal convoluted tubules.
Associations of Matrix Metalloproteinase-9 Protein Polymorphisms with Lymph Node Metastasis but not Invasion of Gastric Cancer
Authors: Yang Tang, Jinwei Zhu, Ling Chen, Linyin Chen, Sheng Zhang, Jianyin Lin
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Like most cancers, gastric cancer has a complex multistep etiology that involves both environmental and genetic factors. Matrix metalloproteinase-9 (MMP-9) is frequently overexpressed in gastric cancer. We investigated the effect of the genetic differences in MMP-9 coding region on the occurrence and progression of gastric cancer. Experimental Design: A case-control study was conducted in a population of 74 patients and 100 healthy people in southeast China. Individuals were genotyped for two single nucleotide polymorphisms (SNP) in MMP-9: R279Q and P574R. Genotypic distributions between patient and control groups were compared for correlations with cancer occurrence. Associations between genotypic distributions and several clinicopathologic features were also analyzed using univariate tests, multivariate logistic regression modeling, and stratified analyses. Results: Significant associations were revealed between both SNPs and lymph node metastasis [P = 0.012 and 0.025; odds ratio (OR), 3.4 and 2.8, respectively]. After adjustment using logistic regression for the potential confounding effects of gender, age, and location of the tumors, homozygous MMP-9 279RR and 574PP are more evidently associated with lymph node metastasis with ORadjusted of 5.7 [95% confidence interval (95% CI), 1.80-18.34] and 4.2 (95% CI, 1.37-12.69). The homozygous 279R-574P haplotype showed a stronger association by an ORadjusted of 6.1 (95% CI, 1.92-12.29) and was also associated with the 1-year postoperative mortality (ORadjusted, 6.5; 95% CI, 1.18-35.74). Interestingly, our data also suggested that the MMP-9 polymorphisms seem to result in higher risk of lymph node metastasis through a pathway independent of cancer invasion because no positive associations were found between these polymorphisms and cancer invasion (OR, 0.59 &amp;lt; 1). The stratified analyses indicated a synergistic interaction between the MMP-9 polymorphisms and the type of diffuse in affecting lymph node metastasis (OR, 13.4; Pbetween strata = 0.04). Significant association between both SNPs and the overall occurrence of gastric cancer was not observed. Conclusion: The present study has shown significant associations between the two nonsynonymous MMP-9 polymorphisms with lymph node metastasis in gastric cancer, especially with the diffuse type. The relatively large values of ORs and disassociation with cancer invasion suggest that the genetic differences of MMP-9 protein play an important and specific role in lymph node metastases, and therefore, further investigation of the underlying molecular mechanism is warranted.
Incorporating a gender dimension in food allergy research: a review
Authors: A. DunnGalvin, J. O'B. Hourihane, L. Frewer, R. C. Knibb, J. N. G. Oude Elberink, I. Klinge
Journal: Allergy (2006)

Sex and gender are the major determinants of health and disease in both men and women. The aim of this review paper was to examine differences in gender and sex in relation to the prevalence and effects of food allergy. There are still major gaps in our knowledge about the kinds of processes which shape men's and women's perceptions and experiences of food allergy. The expression and experience of health and illness may be moderated by variables such as biological vulnerability, exposure to health risks, perception of symptoms, evaluation of risk, information processing and role expectations. This review highlights the complex links between biological sex, gender, and health in general and offers a synthesis of how these may interact to produce sex and gender differences in biopsychosocial manifestations of food allergy. Implications for research and public health practice are discussed.
Efficacy of rituximab in the treatment of pulmonary rheumatoid nodules: findings in 10 patients from the French AutoImmunity and Rituximab/Rheumatoid Arthritis registry (AIR/PR registry)
Authors: Baptiste Glace, Jacques-Eric Gottenberg, Xavier Mariette, Ravaud Philippe, Bruno Pereira, Thierry Lequerré, Jean-Marie Berthelot, Maxime Dougados, Eric Toussirot, Thao Pham, Yannick Allanore, Damien Loeuille, Liana Euller-Ziegler, Martin Soubrier
Journal: Annals of the Rheumatic Diseases (2012)

Pulmonary rheumatoid nodules (PRN) occur in 20%−25% of rheumatoid arthritis (RA) patients and can lead to complications.1 Disease-modifying antirheumatic drugs (leflunomide, methotrexate) and antitumour necrosis factor α (anti-TNFα) have been implicated in their development.2,–,4 The immunopathological characteristics of PRN are quite distinct from those of subcutaneous nodules with the presence of B lymphocytes expressing CD20 in the periphery.5 We therefore decided to assess the efficacy of rituximab (RTX) in patients with PRN using data from the French AutoImmunity and Rituximab/Rheumatoid Arthritis registry.6 Of the 10 patients studied, all but one (n 8) were positive for rheumatoid factors and anticitrullinated protein antibodies (anti-CCP). Five patients had a history of smoking: two were active smokers (n 2, 3), and three past smokers (n 5, 7, 9). All patients had previously received anti-TNF …
Development and assessment of tyrosinase inhibitory activity of liposomes of Asparagus racemosus extracts
Authors: Narin Therdphapiyanak, Montree Jaturanpinyo, Neti Waranuch, Lalana Kongkaneramit, Narong Sarisuta
Journal: Asian Journal of Pharmaceutical Sciences (2013)

The purpose of this study was to develop liposomal formulations of Asparagus racemosus root extract (AR1-6) as well as evaluate the physicochemical properties and in vitro tyrosinase inhibitory activity. Liposomes composed of AR1-6 to lipid weight ratio of 1:10 and lecithin (LEC) or Phospholipon® 90G (PC90G) as structural phospholipid at 7:3 molar ratio to CHOL were prepared by various methods, i.e. chloroform-film (CF), reverse-phase evaporation (REV), polyol dilution (PD), and freeze-drying of monophase solution (MFD) methods. The results revealed that vesicles prepared by CF and MFD were multilamellar whereas those prepared by REV and PD were oligolamellar in nature with particle sizes ranging from 0.26 to 13.83 μm. The zeta potentials were in the range of −1.5 to −39.3 mV. AR1-6 liposomes with LEC possessed significantly higher entrapment than those with PC90G. The highest entrapment efficiency and in vitro tyrosinase inhibitory activity of 69.08% and 25%, respectively, were obtained from liposomes having LEC and prepared by PD method. The tyrosinase inhibitory activity were in the rank order of LEC > PC90G, and PD > CF > REV > MFD. It could be concluded that the mechanism of vesicle forming in each method of preparation was the key factor influencing physicochemical properties, particularly vesicle type, size, surface charge, and entrapment, which were well correlated with the biological activity.
Atrial Arrhythmias
Authors: Michael J. Landzberg, Frank Cecchin
Journal: Circulation (2009)

acknowledges the multitude of physical and nonphysical determinants of life's richness.His narrator sees these influences as interwoven and spanning the ages from youth through adulthood in timeless fashion.In this week's issue of Circulation, Bouchardy and colleagues 2 determine the prevalence of atrial (tachy)arrhythmias (AA) in adults with congenital heart disease (ACHD) and then analyze the prognostic implications of such.The authors' findings carry far-reaching implications that, in a fashion that Browning's narrator would have advocated, extend to principles, design, and application of medical care that begin at the earliest pediatric years and continue throughout the entire development and aging of the ACHD population.
IgE against ethylene oxide-altered human serum albumin in patients with anaphylactic reactions to dialysis
Authors: Leslie C. Grammer, Bruce F. Paterson, David Roxe, John T. Daugirdas, Todd S. Ing, Peter T. Ivanovich, Colin B. Brown, Anthony J. Nicholls, Roy Patterson
Journal: Journal of Allergy and Clinical Immunology (1985)
Surgery and radiotherapy for early breast cancer
Authors: J M. Dixon
Journal: BMJ (1995)

Better local control not yet translated into improved survival

Although prospective randomised trials have shown that treating early breast cancer by conservative surgery and radiotherapy is as effective as mastectomy, revelations of scientific misconduct in the largest of these trials last year caused widespread public concern.1 Media reports that one contributor to the United States national surgical adjuvant breast and bowel project had altered some of his data suggested that patients could no longer trust the trial's conclusions, and it left many patients angry and frightened that they had not been treated appropriately. Three articles in last week's New England Journal of Medicine provide reassurance about the efficacy of breast conserving treatment.2 3 4

The first article is an audit of the trial from the United States National Cancer Institute. It reports that 97.5% of the data were entered correctly.2 The second article is a reanalysis of the audited data after 12 years of follow up. The trial compared the outcome in women with early breast cancer after total mastectomy alone or after lumpectomy with or without radiotherapy. The reanalysis shows no significant difference in survival between the three groups, although the incidence of ipsilateral tumour recurrence was 35% in the group treated by lumpectomy alone compared with 10% in the group treated with lumpectomy and radiotherapy.3 …
In vitro acetylcholine biosynthesis in normal and failing guinea pig hearts.
Authors: R Roskoski, P G Schmid, H E Mayer, F M Abboud
Journal: Circulation Research (1975)

Choline acetyltransferase activity, which is rate limiting in acetylcholine biosynthesis, was measured in the four heart chambers of guinea pigs subjected to (1) sham surgery, (2) constriction of the ascending aorta, (3) constriction of the descending thoracic aorta, and (4) constriction of the pulmonary artery. After 30 days when hypertrophy and heart failure were fully established, choline acetyltransferase was quantified in vitro by a radiochemical assay. In the sham-operated group, enzyme activity expressed in terms of unit weight of cardiac tissue was greatest in the right atrium and the right ventricle and lower in th left atrium and the left ventricle (3.62 plus or minus 0.30, 2.96 plus or minus 0.52, 1.64 plus or minus 0.15, and 1.67 plus or minus 0.22 nmoles/min g-1, respectively). Enzyme activity was reduced (P less than 0.05) in the right atria and the right ventricles of guinea pigs with constriction of the pulmonary artery (1.68 plus or minus 0.37 and 1.31 plus or minus 0.29 nmoles/min g-1, respectively). Enzyme activity also tended to be reduced in the left atria and the left ventricles of guinea pigs with constriction of the aorta. These changes represented a relative dilution of enzyme activity per unit weight but not an absolute depletion, since choline acetyltransferase activity per ventricle was not reduced. The absence of significant changes in the total amount of the neuronal enzyme, choline acetyltransferase, per ventricle contrasted with the observed increases in the myocardial enzyme, carnitine acetyltransferase. These results confirm the presence of significant parasympathetic innervation of the ventricles as well as the atria but do not demonstrate alterations in parasympathetic neurotransmitter biosynthesis in hypertrphied and failing myocardium. The absence of absolute reductions in choline acetyltransferase activity in hypertrophied and failing ventricle contrasts strikingly with the previously reported reductions in tyrosine hydroxylase, which is rate limiting in sympathetic neurotransmitter biosynthesis.
Phase II, open-label study of PTK787/ZK222584 for the treatment of metastatic gastrointestinal stromal tumors resistant to imatinib mesylate
Authors: H. Joensuu, F. De Braud, P. Coco, T. De Pas, C. Putzu, C. Spreafico, P. Bono, S. Bosselli, T. Jalava, D. Laurent, P.G. Casali
Journal: Annals of Oncology (2007)
Isotype distribution of anticardiolipin antibodies in systemic lupus erythematosus: prospective analysis of a series of 100 patients.
Authors: R Cervera, J Font, A Lopez-Soto, F Casals, L Pallares, A Bove, M Ingelmo, A Urbano-Marquez
Journal: Annals of the Rheumatic Diseases (1990)

Genetic alterations in Ca<sup>2+</sup> channel subunits can be used to study the interaction among channel subunits and their roles in channel function. P/Q- and N-type Ca<sup>2+</sup> channels reside at the presynaptic terminal and control the release of neurotransmitter at mammalian central synapses. We used fluorescence imaging techniques to investigate presynaptic Ca<sup>2+</sup>currents and neurotransmitter release at hippocampal Schaffer collateral synapses in both <i>tottering</i>(<i>tg</i>, α<sub>1A</sub> subunit) and<i>lethargic</i> (<i>lh</i>, β<sub>4</sub> subunit) mutant mice. Application of selective toxins revealed a large reduction in presynaptic P/Q-type Ca<sup>2+</sup> transients, from 39% of total in +/+ mice to 6% in <i>tg/tg</i> mice, whereas the proportion of N-type increased from 35 to 68%, respectively. Neurotransmitter release in the <i>tg/tg</i> mutant relied almost exclusively on N-type channels, as shown by the complete blockade of synaptic transmission with ω-conotoxin GVIA. Remarkably, loss of β4, a subunit predicted to regulate the subcellular targeting and modulation of both P/Q- and N-type channels, resulted in no significant difference in the ratio of Ca<sup>2+</sup> channel subtypes or Ca<sup>2+</sup>dependence of neurotransmitter release in lethargic mice. G-protein-mediated inhibition of Ca<sup>2+</sup> channels was also unaltered. These results indicate that a profound decrease in presynaptic P/Q-type currents leads to dependence of neurotransmitter release on N-type channels. In contrast, absence of β<sub>4</sub>appears not to compromise either P/Q- or N-type channel function at this hippocampal synapse, implicating rescue of presynaptic Ca<sup>2+</sup> currents by other available β subunits. The present study reveals compensatory molecular mechanisms in the regulation of presynaptic Ca<sup>2+</sup> entry and neurotransmitter release.
Criterion Validity of Medicare Chemotherapy Claims in Cancer and Leukemia Group B Breast and Lung Cancer Trial Participants
Authors: Elizabeth B. Lamont, James E. Herndon, Jane C. Weeks, I. Craig Henderson, Rogerio Lilenbaum, Richard L. Schilsky, Nicholas A. Christakis
Journal: JNCI Journal of the National Cancer Institute (2005)

To determine the accuracy with which Medicare claims data measure chemotherapy use in elderly Medicare beneficiaries with cancer, we performed a criterion validation study. We compared gold-standard clinical trial data for 175 elderly cancer patients treated in two Cancer and Leukemia Group B (CALGB) breast and lung cancer trials (i.e., 45 from trial 9344 and 130 from trial 9730) with contemporaneous ambulatory and in-patient Medicare health insurance claims data from Centers for Medicare and Medicaid Services (CMS). The breast trial participants studied were those elderly enrolled between 1995 and 1997 and treated with doxorubicin and cyclophosphamide or this combination with paclitaxel. The lung trial participants studied were those elderly enrolled between 1998 and 2000 and treated with paclitaxel and carboplatin or paclitaxel alone. Comparing CALGB data with Medicare claims, we found the crude sensitivity for chemotherapy administration was 93% (95% confidence interval [CI] = 88% to 96%). Individual chemotherapy agents had similarly high sensitivities, ranging from 81% (95% CI = 70% to 89%) for carboplatin to 91% (95% CI = 79% to 98%) for cyclophosphamide. Agent-specific specificities were 100%. CMS data reliably captured repeat administration of chemotherapy to within one cycle. Administrative Medicare claims data appear to be a valid source of information for chemotherapy administered to elderly Medicare beneficiaries with cancer.