tbuckley/cabot-search huggingface dataset:
THERAPEUTIC RESULTS AND CLINICAL MANIFESTATIONS FOLLOWING THE USE OF TETRAETHYLTHIURAM DISULFIDE (ANTABUSE)
Authors: GEORGE P. CHILD, WALTER OSINSKI, ROBERT E. BENNETT, EUGENE DAVIDOFF
Journal: American Journal of Psychiatry (1951)

The observations made during the treatment of 120 chronic alcoholics with Antabuse are reported. Certain animal experiments are also described. 1. In large doses Antabuse is toxic to animals. Death by respiratory arrest is preceded by an ascending paralysis. The Antabuse in these large doses produces liver, spleen, kidney, and C.N.S. damage. 2. In human subjects, large doses produce gastro-intestinal and nervous symptoms. In therapeutic amounts there are no apparent effects on liver, kidney, blood, heart, or brain. Patients should not be given Antabuse until at least 4 days have elapsed since their last alcoholic debauch. 3. In rats a moderate dose of Antabuse markedly increases the toxicity of ethyl alcohol. 4. In patients on Antabuse therapy a definite pattern of reaction may be seen after a test dose of alcohol. This syndrome, subjectively and objectively, is much like that observed after the ingestion of a large quantity of alcohol at one time. Cardiovascular collapse may result. Supportive therapy and intravenous ascorbic acid may abort the syndrome. There is an increased blood acetaldehyde during the reaction. 5. The selection of patients for therapy must be on an individual basis. The patient must be willing to take the drug. He should have no organic disease that might endanger his life if he should imbibe a small amount of alcohol. 6. A test dose of alcohol is given each patient to determine the effectiveness of the Antabuse, and to give him the startling experience of becoming violently intoxicated on a very small amount of alcohol. 7. Intensive psychotherapy must be employed in the management of the alcoholic on Antabuse. The patient's family and friends and the A. A., social agencies, and others should be called upon for the rehabilitation of the patient. 8. Each Antabuse patient should carry a clinic card indicating that he is on Antabuse therapy, SO that if he should drink and have a reaction, emergency therapy may be started if required. Some experiences with such "slips" are described. 9. Of the 120 patients reported in this paper, 74 are improved. The initial "cure" rate was much higher. Most slips occurred at 3 months. The question is raised whether a test dose should be given every 3 months. 10. It is most important that the drug be administered under careful medical psychiatric supervision. Indiscriminate use of Antabuse by the private practitioner without the aid of a therapeutic regime, hospital or clinic, and without psychiatric consultation is to be condemned.
Influence of Hypoxia on Nitric Oxide Synthase Activity and Gene Expression in Children With Congenital Heart Disease
Authors: Carlos Regenga Ferreiro, Antonio Carlos Palandri Chagas, Maria Helena Catelli Carvalho, Ana Paula Dantas, Marcelo Biscegli Jatene, Luiz Carlos Bento de Souza, Protásio Lemos da Luz
Journal: Circulation (2001)

Background —Chronic hypoxia has been shown to modulate nitric oxide (NO) responses in different cell models, but the relationship between hypoxia and NO synthase (NOS) regulation in humans was not studied. We studied the relationship between endothelial and inducible NOS (eNOS and iNOS) activities and expression and chronic hypoxia in children with cyanotic and acyanotic congenital heart defects. Methods and Results —Right atrial tissue was excised from 18 patients during cardiac surgery. eNOS and iNOS activities were measured by conversion of l -[H 3 ]arginine to l -[H 3 ]citrulline. Gene expression of eNOS and iNOS was quantified by competitive reverse transcription–polymerase chain reaction. The eNOS activity and expression were significantly reduced in cyanotic hearts compared with acyanotic hearts: 0.38±0.14 versus 1.06±0.11 pmol · mg −1 · min −1 ( P &lt;0.0001) and 0.54±0.08 versus 0.80±0.10 relative optical density (ROD) of cDNA ( P &lt;0.0001), respectively. In contrast, iNOS activity and expression were significantly higher in cyanotic than in acyanotic children: 7.04±1.20 versus 4.17±1.10 pmol · mg −1 · min −1 ( P &lt;0.0001) and 2.55±0.11 versus 1.91±0.18 ROD of cDNA ( P &lt;0.0001), respectively. Conclusions —Hypoxia downregulates eNOS activity and gene expression in cardiac tissue from patients with cyanotic congenital heart defects. By contrast, iNOS activity and expression are increased in cyanotic children and may represent an alternative mechanism to counteract the effects of hypoxia in the cardiovascular system. Therefore, a novel adaptive mechanism during hypoxia is suggested.
When the Treatment Goal Is Not Cure: Are Cancer Patients Equipped to Make Informed Decisions?
Authors: Melina Gattellari, Katie J. Voigt, Phyllis N. Butow, Martin H.N. Tattersall
Journal: Journal of Clinical Oncology (2002)

Informed decision making now is considered the underpinning of ethical medical practice. We aimed to determine the extent to which patients with incurable cancer are adequately informed of their prognosis and treatment options and encouraged to participate in treatment decisions.One hundred eighteen cancer patients with incurable disease presenting for an initial consultation with one of nine oncologists at two Sydney tertiary referral hospitals participated in the study. Consultations were recorded on audiotape to permit a content analysis of doctor-patient interactions. We devised a coding system to assess disclosure of information and to evaluate doctor encouragement of patient participation in treatment decision making. Patient recall, satisfaction, anxiety, and perceptions of the decision-making process were assessed to determine the effects of informed decision making on patient outcomes.Most patients were informed about the aim of anticancer treatment (84.7%), that their disease was incurable (74.6%), and about life expectancy (57.6%). An alternative to anticancer treatments was presented to 44.1%, 36.4% were informed about how anticancer treatment would affect quality of life, and 29.7% were offered a management choice. Oncologists checked patient understanding in only 10.2% of consultations. Although greater information disclosure did not seem to elevate anxiety levels, greater patient participation in the decision-making process was associated with increased anxiety levels (P =.0005), which persisted over a 2-week time span.Most patients were well informed, but important gaps remain, especially concerning information about prognosis and alternatives to anticancer treatment. These gaps invite the question concerning whether patients are led toward anticancer treatment.
Propranolol-induced depression.
Authors: H. J. Waal
Journal: BMJ (1967)

Propranolol-induced Depression SIR,-Therapeutic indications for the beta- receptor adrenergic blocking agent propranolol, of which we have experience, include angina, cardiac arrythmias, and hypertension' ; and there are reports of its value in phaeochromocytoma not amenable to surgery,' hypertrophic obstructive cardio- myopathy,3 even Parkinsonian tremor,4 anxiety,' the sympathetic side-effects of thyrotoxicosis, and cyanotic attacks in Fallot's tetralogy.'It is likely, therefore, that
Activity of cAMP-dependent protein kinase and Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human hearts
Authors: U Kirchhefer
Journal: Cardiovascular Research (1999)

Objectives: A hallmark of human heart failure is prolonged myocardial relaxation. Although the intrinsic mechanism of phospholamban coupling to the Ca2+-ATPase is unaltered in normal and failed human hearts, it remains possible that regulation of phospholamban phosphorylation by cAMP-dependent mechanisms or other second messenger pathways could be perturbed, which may account partially for the observed dysfunctions of the sarcoplasmic reticulum (SR) associated with this disease. Methods: cAMP-dependent protein kinase (PKA) and Ca2+/calmodulin-dependent protein kinase II (CaM kinase) were characterized initially by DEAE-Sepharose chromatography in hearts from patients with end-stage dilated cardiomyopathy. We measured the activity of PKA and CaM kinase in left ventricular tissue of failing (idiopathic dilated cardiomyopathy; ischemic heart disease) and nonfailing human hearts. Results: Basal PKA activity was not changed between failing and nonfailing hearts. One major peak of CaM kinase activity was detected by DEAE-Sepharose chromatography. CaM kinase activity was increased almost 3-fold in idiopathic dilated cardiomyopathy. In addition, hemodynamical data (left ventricular ejection fraction, cardiac index) from patients suffering from IDC positively correlate with CaM kinase activity. Conclusions: Increased CaM kinase activity in hearts from patients with dilated cardiomyopathy could play a role in the abnormal Ca2+ handling of the SR and heart muscle cell.
Acute treatment of duodenal ulcer: a multicentre study to compare ranitidine 150 mg twice daily with ranitidine 300 mg once at night.
Authors: F I Lee, P I Reed, J P Crowe, R L McIsaac, J R Wood
Journal: Gut (1986)

A randomised double blind clinical trial was undertaken in the UK and Ireland to compare ranitidine 300 mg given as a single bed time tablet with ranitidine 150 mg twice daily in the acute treatment of duodenal ulcers. Of the 594 patients with endoscopically diagnosed duodenal ulcer entered into the trial, 424 patients had complete endoscopic findings on which healing rates at four weeks were determined. By this time 156 of 201 (78%) patients healed with ranitidine 300 mg nocte compared with 186 of 223 (83%) receiving ranitidine 150 mg twice daily (p = 0.28). After eight weeks of treatment 97% of the patients in each group were healed. The healing rates for smokers and non-smokers did not differ significantly at either four or eight weeks. Each regimen was equally effective in reducing day and night-time pain. Adverse events were reported in 23 patients overall; 12 were withdrawn from the trial. Minor abnormalities in liver function tests were noted in three patients. The trial confirmed that a single dose of ranitidine 300 mg given at night is a safe, effective alternative treatment to ranitidine 150 mg bd for the acute treatment of duodenal ulcer.
Effects of Pretransplantation Treatment With Rituximab on Outcomes of Autologous Stem-Cell Transplantation for Non-Hodgkin's Lymphoma
Authors: Amy L. Hoerr, Feng Gao, Josephine Hidalgo, Divya Tiwari, Kristie A. Blum, Vikram Mathews, Douglas R. Adkins, William Blum, Steven Devine, Ravi Vij, Lawrence T. Goodnough, John F. Dipersio, Hanna J. Khoury
Journal: Journal of Clinical Oncology (2004)

To analyze the effects of preautografting treatment with rituximab (R) on stem-cell mobilization, post-transplantation complications, engraftment, disease-free survival, and overall survival in patients with non-Hodgkin's lymphoma (NHL).Single-institution retrospective comparative outcome analysis in a cohort of 273 relapsed chemosensitive NHL patients of whom 127 (47%) received R pretransplantation.R was administered a median of 3 months before autologous transplantation. When compared to the nonrituximab group, R patients were older (56 v 50 years; P < .001), and had delays in post-transplantation platelets recovery (39 v 27 days; P = .001). Pretransplantation R did not affect stem-cell mobilization, post-transplantation early complications, duration of hospitalization, or mortality rates at days 30 and 100. In contrast to patients with low-grade NHL, both disease-free and overall survival rates were significantly better when R was included in the pretransplantation salvage therapy for patients with intermediate-grade NHL.In this large, single-center retrospective analysis, pretransplantation treatment with R was associated with improved survival in patients with intermediate-grade NHL, at the price, however, of a delay in platelet engraftment.
Family incidence of carcinoma of the colon and rectum in north-east Scotland.
Authors: J L Duncan, J Kyle
Journal: Gut (1982)

Family histories were obtained from 50 patients with adenocarcinoma of the colon or rectum in north-east Scotland. A comparable control group was similarly interviewed and in each group the case notes of the first degree relatives were studied where possible. Eight (16%) of the patients with cancer of the colon or rectum had a close relative with intestinal cancer compared with one (2%) of the control group. The patients with a positive family history of cancer of the large intestine did not have a higher proportion with adenomatous polyps nor were they younger than those patients with no such family history.
Ragweed antigen E and anti-IgE in human central versus peripheral isolated bronchi.
Authors: J L Ellis, W C Hubbard, S Meeker, B J Undem
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The ability of antigen to contract passively sensitized tissues was examined in human central (5 to 12 mm) and peripheral (0.5 to 2 mm) bronchi. Both central and peripheral bronchi contracted to ragweed antigen E (RW AgE), and these contractions were virtually abolished by a combination of indomethacin, cysteinyl-leukotriene, and histamine antagonists. There were, however, quantitative differences in contractile responses and in mediator release to RW AgE between central and peripheral bronchi. RW AgE was approximately 20-fold more potent in contracting peripheral bronchi compared with central bronchi. On a per weight of tissue basis, RW AgE released six-fold more histamine, 15- to 20-fold more immunoreactive leukotriene D4 (i-LTD4) and two- to 10-fold more prostanoids in the peripheral bronchi compared with central bronchi. Anti-IgE mimicked the effect of RW AgE with respect to inflammatory mediator release and with respect to the magnitude of the contractile response in peripheral and central bronchi. Anti-IgE, however, was more potent in contracting central than peripheral bronchi. Moreover, in peripheral bronchi, contractile responses to anti-IgE were only partially inhibited by a combination of indomethacin, cysteinyl-leukotriene, and histamine antagonists. These results indicate that the qualitative characteristics of antigen-induced mediator release and muscle contraction are similar in central versus peripheral bronchi. However, RW AgE is much more potent in causing smooth muscle constriction, and is capable of releasing a greater quantity of inflammatory mediators in peripheral bronchi/bronchioles than in the more central bronchi.
Opposite effects of allergy prevention depending on CD14 rs2569190 genotype in 3 intervention studies
Authors: Marjan Kerkhof, Denise Daley, Dirkje S. Postma, Julie E. Park, Moira Chan Yeung, Alet H. Wijga, Ulrike Gehring, Johan C. de Jongste, Henriëtte A. Smit, Bert Brunekreef, Onno C.P. van Schayck, Allan Becker, Gerard H. Koppelman
Journal: Journal of Allergy and Clinical Immunology (2011)
The dermatopathology of Cowden's syndrome*
Authors: MARTIN H. BROWNSTEIN, AMIR H. MEHREGAN, JOSEPH B. BIKOWSKI, AUREL LUPULESCU, JARROLD C. PATTERSON
Journal: British Journal of Dermatology (1979)

During the past 2 years we have studied eighty‐nine biopsy specimens from nineteen patients with Cowden's syndrome. Among fifty‐three facial lesions, twenty‐nine were trichilemmomas. Twenty‐ three of the others were consistent with trichilemmoma, showed a non‐specific benign verrucous acanthoma, or were not diagnostic; one was a bluenaevus. All fourteen oral mucosal biopsy specimens were benign fibromas. Nineteen of twenty‐two biopsy specimens from the hands and feet showed the pattern of benign keratosis. Multiple trichilemmomas were found in all patients with Cowden's syndrome, but at times several biopsy specimens were required before a diagnostic picture was un‐ covered. All patients with multiple facial trichilemmomas were found to have Cowden's syndrome. The combination of multiple facial trichilemmomas, oral fibromas, and benign acral keratoses enables one to diagnose Cowden's syndrome at a stage before serious internal complications develop.
Filling in the Pieces of the Sleep Apnea–Hypertension Puzzle
Authors: Vishesh K. Kapur, Edward M. Weaver
Journal: JAMA (2012)

BSTRUCTIVESLEEPAPNEA(OSA)ISACOMMONBUT underdiagnosed disorder that is associated with excessive sleepiness, poor quality of life, neurocognitivedeficits,metabolicdysfunction,cardiovascular disease, and early mortality. Continuous positive airway pressure (CPAP) therapy efficaciously ameliorates obstructed breathing events. 1 Randomized controlled trials (RCTs) show that CPAP therapy reduces sleepiness and improvesqualityoflifeinpatientswithmoderateandsevereOSA. 2 A number of difficulties have complicated the assessment of thecausallinkbetweenOSAandhypertension,includingmultiplesharedriskfactors,differentialsusceptibilityofsubgroups to the deleterious effects of OSA, and the challenges of conducting definitive RCTs. Despite these barriers, a significant evidencebasehasdevelopedtosupporttheidentificationand treatment of OSA in patients with hypertension. Multiple hypertensionguidelinesrecognizeOSAasasecondarycause ofhypertensionandspecificallyadviseassessmentandtreatment of OSA in patients with refractory hypertension. 3-5 DatalargelysupportacausallinkbetweenOSAandhypertension, with causation supported by the Bradford-Hill criteriaof(1)biologicalplausibility;(2)associationstrength,consistency,temporality,anddoseresponse;and(3)reversibility. It is biologically plausible that OSA may cause hypertension, becauseintermittenthypoxiaandsleepdisruption(asinOSA) stimulatesympatheticexcitationandhypertensionacutely,and alter vascular resistance, increase blood pressure, and produce endothelial dysfunction chronically. 6 Evidence of association from longitudinal epidemiologic studies complementsthebiologicaldata.TheWisconsinSleepCohortStudy of middle-aged adults found a strong dose-response relationship between baseline OSA severity and incident hypertension 4 years later. 7 The Sleep Heart Health Study analysis of older adults without hypertension also found a doseresponse relationship between baseline OSA severity and incident hypertension, but the association was not statistically significantinthefullyadjustedanalysis 8 ;however,morethan 50% of the original cohort was excluded because of baseline hypertension. Together, these findings are consistent with a modest association between OSA and incident hypertension
Ethical Issues in Health Care System Reform
Authors: John Glasson
Journal: JAMA (1994)

AS AMERICAN Medical Association (AMA) policy states, society should afford every citizen access to adequate health care: "The patient has a basic right to have available adequate health care."<sup>1</sup>In this report, the Council discusses the ethical foundations of society's obligation to ensure that none of its members is denied access to adequate health care because of an inability to pay for it. This obligation rests primarily on the belief that a just society affords its members reasonable protection from illness and disability to ensure that they have a fair opportunity to pursue their goals in life.<sup>2,3</sup> The Council also discusses the definition of "adequate health care" in this report, because determining an adequate level of health care is an essential step in guaranteeing meaningful universal access. The Council believes that the definition should follow sound ethical principles and fair procedures and take the form of a basic
Knockout of Secretin Receptor Reduces Large Cholangiocyte Hyperplasia in Mice With Extrahepatic Cholestasis Induced by Bile Duct Ligation
Authors: Shannon Glaser, Ian P. Lam, Antonio Franchitto, Eugenio Gaudio, Paolo Onori, Billy K. Chow, Candace Wise, Shelley Kopriva, Julie Venter, Mellanie White, Yoshiyuki Ueno, David Dostal, Guido Carpino, Romina Mancinelli, Wendy Butler, Valorie Chiasson, Sharon DeMorrow, Heather Francis, Gianfranco Alpini
Journal: Hepatology (2010)

During bile duct ligation (BDL), the growth of large cholangiocytes is regulated by the cyclic adenosine monophosphate (cAMP)/extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and is closely associated with increased secretin receptor (SR) expression. Although it has been suggested that SR modulates cholangiocyte growth, direct evidence for secretin-dependent proliferation is lacking. SR wild-type (WT) (SR+/+) or SR knockout (SR−/−) mice underwent sham surgery or BDL for 3 or 7 days. We evaluated SR expression, cholangiocyte proliferation, and apoptosis in liver sections and proliferating cell nuclear antigen (PCNA) protein expression and ERK1/2 phosphorylation in purified large cholangiocytes from WT and SR−/− BDL mice. Normal WT mice were treated with secretin (2.5 nmoles/kg/day by way of osmotic minipumps for 1 week), and biliary mass was evaluated. Small and large cholangiocytes were used to evaluate the in vitro effect of secretin (100 nM) on proliferation, protein kinase A (PKA) activity, and ERK1/2 phosphorylation. SR expression was also stably knocked down by short hairpin RNA, and basal and secretin-stimulated cAMP levels (a functional index of biliary growth) and proliferation were determined. SR was expressed by large cholangiocytes. Knockout of SR significantly decreased large cholangiocyte growth induced by BDL, which was associated with enhanced apoptosis. PCNA expression and ERK1/2 phosphorylation were decreased in large cholangiocytes from SR−/− BDL compared with WT BDL mice. In vivo administration of secretin to normal WT mice increased ductal mass. In vitro , secretin increased proliferation, PKA activity, and ERK1/2 phosphorylation of large cholangiocytes that was blocked by PKA and mitogen-activated protein kinase kinase inhibitors. Stable knockdown of SR expression reduced basal cholangiocyte proliferation. SR is an important trophic regulator sustaining biliary growth. Conclusion: The current study provides strong support for the potential use of secretin as a therapy for ductopenic liver diseases. Hepatology 2010
Quality-of-life assessment in children and adolescents with asthma
Authors: C Rutishauser, SM Sawyer, G Bowes
Journal: European Respiratory Journal (1998)

Health-related quality of life has become an essential part of health outcome measurement in chronic disorders. However, it is only recently that health professionals have focused on quality-of-life assessment in children and adolescents. Several generic, as well as the asthma-specific quality-of-life instruments specifically designed for use in children and adolescents are reviewed in this article with particular regard to the conceptual and methodological features of the measures and their applicability in clinical studies. The recently published Child Health Questionnaire is a useful generic instrument to comprehensively assess quality of life, in particular when comparing young people with different chronic disorders. The Pediatric Asthma Quality-of-life Questionnaire has shown responsiveness to change over time, but it lacks age-specificity with regard to psychosocial issues and comprehensiveness of quality-of-life assessment. In contrast, the Childhood Asthma Questionnaire provides three different versions for different target ages. However, its generic part is not reflective of the respondent's health status. The other asthma-specific instruments have major conceptual deficiencies when used as a single measure for quality-of-life assessment. In the absence of a single ideal instrument, the use of batteries of quality-of-life instruments is therefore recommended and further research is required to identify the impact that age and developmental status have on quality-of-life assessment.