tbuckley/cabot-search huggingface dataset:
TRANCE (Tumor Necrosis Factor [TNF]-related Activation-induced Cytokine), a New TNF Family Member Predominantly Expressed in T cells, Is a Dendritic Cell–specific Survival Factor
Authors: Brian R. Wong, Régis Josien, Soo Young Lee, Birthe Sauter, Hong-Li Li, Ralph M. Steinman, Yongwon Choi
Journal: The Journal of Experimental Medicine (1997)

TRANCE (tumor necrosis factor [TNF]–related activation-induced cytokine) is a new member of the TNF family that is induced upon T cell receptor engagement and activates c-Jun N-terminal kinase (JNK) after interaction with its putative receptor (TRANCE-R). In addition, TRANCE expression is restricted to lymphoid organs and T cells. Here, we show that high levels of TRANCE-R are detected on mature dendritic cells (DCs) but not on freshly isolated B cells, T cells, or macrophages. Signaling by TRANCE-R appears to be dependent on TNF receptor–associated factor 2 (TRAF2), since JNK induction is impaired in cells from transgenic mice overexpressing a dominant negative TRAF2 protein. TRANCE inhibits apoptosis of mouse bone marrow–derived DCs and human monocyte-derived DCs in vitro. The resulting increase in DC survival is accompanied by a proportional increase in DC-mediated T cell proliferation in a mixed leukocyte reaction. TRANCE upregulates Bcl-xL expression, suggesting a potential mechanism for enhanced DC survival. TRANCE does not induce the proliferation of or increase the survival of T or B cells. Therefore, TRANCE is a new DC-restricted survival factor that mediates T cell–DC communication and may provide a tool to selectively enhance DC activity.
Treatment of first episodes of acute anal fissure: prospective randomised study of lignocaine ointment versus hydrocortisone ointment or warm sitz baths plus bran.
Authors: S L Jensen
Journal: BMJ (1986)

One hundred and three patients with an acute first episode of posterior anal fissure were randomised to receive a three week trial of lignocaine ointment (n = 33) versus hydrocortisone ointment (n = 35) or warm sitz baths combined with an intake of unprocessed bran (n =35). Seven patients were withdrawn owing to failure to adhere to the trial protocol. After one and two weeks of treatment symptomatic relief was significantly better among patients treated with sitz baths and bran than among patients treated with lignocaine ointment or hydrocortisone ointment. After three weeks there was no difference in symptomatic relief among the three groups. Patients treated with lignocaine, however, had significantly fewer healed fissures (60%) than patients treated with hydrocortisone (82.4%) or warm sitz baths and bran (87%). In this study warm sitz baths plus an intake of unprocessed bran came out as the treatment of choice for an acute first episode of posterior anal fissure. This treatment is cheap, has no potential serious side effects, and brings the best and quickest relief of symptoms.
Allergy to Penicillin
Authors: A. I. Suchett-Kaye
Journal: BMJ (1947)

From a limited experience of the operation the impression is gaining ground that the presence of pre-morbid obsessional traits is of good prognostic significance when considering candidates for leucotomy.This appears not only to explain the good results claimed in obsessional neurosis and depression but appears to be at the.back of the improvement obtained in this case.Before accepting the operation as the treatment of choice in any case of psychoneurosis a thorough exploration and evaluation of the psychodynamic factors are indicated, and only if these are considered unmodifiable by any other practicable means should the operation be recommended.-I am, etc.,
Comparative-Effectiveness Research — Implications of the Federal Coordinating Council's Report
Authors: Patrick H. Conway, Carolyn Clancy
Journal: New England Journal of Medicine (2009)

Despite a plethora of diagnostic and treatment options, practical information that can guide health care choices for an individual patient are often elusive, and the resultant clinical uncertainty is an important factor driving regional variations in clinical practice. Clinicians and patients need to know not only that a treatment works on average but also which interventions work best for specific types of patients. Comparative patient-centered information is essential to translating new discoveries into better health outcomes, accelerating the application of beneficial innovations, and delivering the right treatment to the right patient at the right time.1 The American Recovery and Reinvestment . . .
Transverse Myelitis Associated With Heroin Addiction
Authors: Ralph W. Richter, Roger N. Rosenberg
Journal: JAMA (1968)

Acute transverse myelitis involving thoracic segments was observed as a new complication of heroin addiction in four Negro men. Three of the four patients had not taken heroin for periods of one to six months either while in prison or the hospital. The acute myelitis developed shortly after heroin was taken again intravenously. At onset, three patients suddenly became paraplegic, and moderate paraparesis developed in one. All four demonstrated thoracic sensory levels. Myelograms were normal for the three patients on whom they were performed. One patient died five weeks after taking heroin again. Extensive necrosis of the spinal cord in the lower thoracic region was found at necropsy. Another patient died, but no autopsy was performed. Mild paraparesis with sensory loss remains in one man, and severe paraparesis with sensory loss persists in the other survivor.
Production of Hypertension and Vascular Disease by Kidney Extracts
Authors: GEORGES M. C. MASSON, CHUJIRO KASHII, JEAN-CLAUDE PANISSET, SHIGERU YOGI, IRVINE H. PAGE
Journal: Circulation Research (1964)

Hypertension was induced in rats by constricting the aorta between the origins of the renal arteries. The left kidney, which became ischemic and atrophic ("endocrine kidney"), caused a malignant type of hypertension associated with weight loss, cardiac hypertrophy, hypertension, cardiac necrosis, nephrosclerosis of the right kidney, and arteritis. Amounts of pressor substances were increased in the left kidney and decreased in the right as compared with those in kidneys of normal rats. Aqueous extracts of ischemic kidneys, of kidneys contralateral to ischemic kidneys and of normal kidneys were prepared and the supernatant solutions were injected subcutaneously into test rats which had been uninephrectomized a few hours previously. Extracts of ischemic kidneys caused hypertension, cardiac hypertrophy, weight loss, and renal and vascular lesions mimicking the signs which result from renal ischemia. The extracts from the other kidneys were inactive. Administration of renin in doses roughly equivalent in pressor activity to the extracts of ischemic kidneys caused a rise in pressure, diuresis, and proteinuria but no lesions when given subcutaneously. It is proposed as a working hypothesis that renal hypertensive disease results not only from increased secretion of renin and formation of angiotensin but from simultaneous release from kidneys with reduced perfusion pressure of a substance which augments the enzymatic formation of angiotensin. This substance is presumably absent from normal kidneys and from semipurified renin preparations.
α<sub>4</sub>β<sub>7</sub>integrin: beyond T cell trafficking
Authors: Sarah L Kempster, Arthur Kaser
Journal: Gut (2013)

Integrins and chemokines are critical for immune cell recruitment to tissue under homeostatic and pathological conditions.1 The heterodimeric integrin α4β7, expressed on T cells, specifies the recruitment of T cells to the intestinal mucosa upon its interaction with its ligand MAdCAM-1.1 Intestinal specificity is imprinted in T cells via upregulation of α4β7 integrin upon their interaction with CD103 dendritic cells (DCs) in the mesenteric lymph node when their cognate antigen is being presented by the major histocompatibility complex.2 The vitamin A metabolite retinoic acid (RA), produced by CD103 DCs via the enzyme retinaldehyde dehydrogenase 2 (encoded by Aldh1a2 gene), acting on T cells plays a critical role in this intestinal imprinting,3 and DCs with this capacity can be identified by an assay that detects this enzymatic activity (ALDE+).4 

Pharmacological intervention in tissue-specific recruitment of T cells has the potential advantage of very precise therapeutic intervention at the site of inflammation.5 This theoretical promise that stemmed from fundamental work and preclinical model systems was indeed upheld. Blockade of the brain-specific localisation signal α4β1 via the anti-α4 antibody Natalizumab is among the most potent therapeutics currently available for multiple sclerosis, while the same antibody that similarly blocks the intestinal-specific α4β7 integrin also demonstrated efficacy in active Crohn's disease.6 However, due to its uncommon, but detrimental adverse effect of reactivating infection with JC virus which may lead to progressive multifocal leukoencephalopathy (PML),7 Natalizumab received only limited marketing approval for Crohn's disease in specific jurisdictions. However, more precise approaches, which are indeed specific for the intestinal tract but should leave leucocyte recruitment to the brain and other organs intact, have been developed and are at different stages of clinical development …
Mechanical Increase of Vascular Resistance in Experimental Myocardial Infarction with Shock
Authors: LESLIE A. KUHN, HOWARD J. KLINE, ANTHONY J. MARANO, ROBERT I. HAMBY, JORGE CESTERO, LAWRENCE J. COHN, HARRY WEINRAUCH, MARVIN BERGER
Journal: Circulation Research (1966)

The hemodynamic and cardiac metabolic effects of increasing central aortic pressure by obstructing the abdominal aorta with a balloon catheter introduced via a femoral artery were determined in 28 anesthetized dogs with acute myocardial infarction and shock produced by coronary embolization with plastic spheres. Following coronary embolization, aortic pressure, cardiac output, and left ventricular mechanical efficiency declined in all animals; left ventricular "excess lactate" appeared in about one-half. With abdominal aortic obstruction for 1 hour, there were significant elevations of postembolic aortic pressure, coronary flow, cardiac output, left ventricular oxygen consumption and mechanical efficiency. Left atrial pressure rose slightly but not beyond normal limits. Arterial-coronary sinus oxygen difference diminished, and left ventricular excess lactate diminished or disappeared in 60% of the animals in which it was noted in the postembolic state. After 1 hour of abdominal aortic obstruction, cardiac output, central aortic pressure, and coronary flow diminished moderately. It is concluded that mechanical increase of vascular resistance for periods up to 1 hour may improve myocardial performance in acute myocardial infarction with shock. The increased left ventricular oxygen needs are met adequately by the increase of coronary flow associated with the increase of perfusion pressure.
Elevated levels of eotaxin and interleukin-5 in blister fluid of bullous pemphigoid: correlation with tissue eosinophilia
Authors: M. Wakugawa, K. Nakamura, H. Hino, K. Toyama, N. Hattori, H. Okochi, H. Yamada, K. Hirai, K. Tamaki, M. Furue
Journal: British Journal of Dermatology (2000)

Bullous pemphigoid (BP) often provokes blood and tissue eosinophilia, which suggests that some chemoattractants modulate the eosinophil infiltration in BP. Eotaxin, a CC chemokine, strongly attracts eosinophils, and interleukin (IL)-5 induces eosinophil differentiation, proliferation and colony formation in vitro.To examine the correlation between levels of eotaxin and IL-5 and the number of lesional eosinophils, and the expression of eotaxin in BP lesions.In this study we measured eotaxin and IL-5 levels in blister fluid of BP by enzyme-linked immunosorbent assay. We also examined the expression of eotaxin in BP lesions by immunohistochemistry.Both eotaxin and IL-5 were detected at high levels in BP blister fluid. Blister fluid eotaxin, but not IL-5 levels, correlated significantly with the number of dermal infiltrating eosinophils. By immunohistochemistry, eotaxin was strongly expressed in epidermal keratinocytes around BP blisters.These findings suggest that eotaxin and IL-5 are strongly associated with the tissue eosinophilia of BP. Therapies which aim to inhibit production of eotaxin and IL-5 may improve the inflammation and blister formation in BP.
ABC of sleep disorders. Practical management of insomnia: behavioural and cognitive techniques.
Authors: C A Espie
Journal: BMJ (1993)

iting characteristics of ic insomnia i sleep onsetInsomnia is something to do with "not getting enough proper sleep."The ient sleep time essence of the definition is subjective dissatisfaction.Such concern may it or prolonged awakenings reflect a poor sleep pattern, poor quality of sleep, daytime effects, or a night variability in pattern combination of these.uality Effective practical management of insomnia must respond to the s or agitated before and during sleep presenting characteristics of the complaint, otherwise they may persist.unrefreshed and unrested after sleep This article deals with the psychological strategies that have been xperiences negative and not systematically evaluated as potentially useful treatments of insomnia.They fle may be effective alternatives to hypnotic drugs, particularly in people with e correlates long term insomnia. Non-specific treatmentBasic education about sleep-Giving accurate information is a form of treatment.Although patients with insomnia are probably no less informed about sleep than good sleepers, there is benefit in discussing some simple facts and relating them to the problem.This will help the patient to place the sleep problem in its context.Sleep hygiene-this term refers to general advice that may help to promote a good sleep pattern, though the elements themselves are unlikely to be sufficient treatment for long term insomnia.
Quinidine-Digoxin Interaction
Authors: Gary R. Matzke
Journal: JAMA (1979)

To the Editor.—  We read the report by Leahey et al (240:533,1978) of a possible interference with serum digoxin concentrations by quinidine. Indeed, we as well as others have made similar observations. 1 However, based on the data presented, we have some reservations regarding the incidence of this interaction.  Many of the serum digoxin concentrations reported as steady-state values before quinidine therapy were considerably lower than would have been expected based on the dose of digoxin supposedly being administered. We estimated the steady-state serum digoxin concentrations for hypothetical patients with creatinine clearances of 50, 75, and 100 mL/min to be 1.9, 1.5, and 1.2 ng/mL, respectively. 2 (To make these calculations, we assumed a lean body weight of 70 kg and daily administration of 0.25 mg of digoxin with 80% absorption.) Since these calculated serum digoxin concentration values are considerably higher than many of those reported by the authors, we question
The perplexing case of the geranylgeranyl transferase–deficient mouse
Authors: Mark R. Philips
Journal: Journal of Clinical Investigation (2011)

Proteins that end with a CAAX sequence are targeted to cellular membranes by a series of posttranslational modifications that include prenylation, proteolysis, and carboxyl methylation. Two prenyltransferases modify CAAX proteins: farnesyltransferase and geranylgeranyltransferase type I (GGTase-I). Rho family GTPases that control the actin cytoskeleton and are therefore critical to inflammatory cell function are substrates for GGTase-I. In this issue of the JCI, Khan et al. examined mice in which GGTase-I was conditionally deleted in macrophages. Rather than obtunded cells, the authors found activated Rho proteins in fully functional macrophages that hypersecreted inflammatory cytokines and induced an erosive, inflammatory arthritis. This surprising result calls into question the role of protein geranylgeranylation in inflammatory cell signaling.
Alexithymia and Psychopathology in Patients with Psychiatric and Functional Gastrointestinal Disorders
Authors: Piero Porcelli, Valeria Affatati, Antonello Bellomo, Massimo De Carne, Orlando Todarello, Graeme J. Taylor
Journal: Psychotherapy and Psychosomatics (2004)

Alexithymia and psychopathology may influence the way individuals experience psychological distress and somatic symptoms. This study evaluated patients referred to psychiatric and gastroenterologic outpatient settings in order to investigate the levels of alexithymia and psychopathology, and the possible role of alexithymia in symptom perception and health care utilization. The association between psychiatric disorders and functional gastrointestinal disorders (FGIDs) was also assessed.Psychopathology (by the Revised 90-item Symptom Checklist), alexithymia (by the 20-item Toronto Alexithymia Scale), and gastrointestinal symptoms (by the Gastrointestinal Symptom Rating Scale) were evaluated in 52 psychiatric outpatients and 58 medical outpatients with FGIDs. Two comorbid subgroups of 25 psychiatric patients with FGIDs and 38 FGID patients with psychiatric disorders were formed and compared.Forty-eight percent of the psychiatric patients had associated FGIDs, and 65.5% of the FGID patients had associated psychiatric disorders. The FGID patients had significantly less psychopathology, but significantly higher alexithymia and more severe gastrointestinal symptoms, than the psychiatric patients. In the comparison of the two subgroups with comorbidity, FGID patients with psychiatric disorders were still more alexithymic and had less psychopathology than psychiatric patients with FGIDs, but gastrointestinal symptoms were not significantly different.Patients with 'functional' gastrointestinal symptoms attending a medical care service are likely to be highly alexithymic, whereas those attending a psychiatric care service are likely to show severe psychopathology. Alexithymia seems to influence the presentation of 'functional' somatic symptoms and the type of health care utilization.
Risk Stratification in Patients With Inferior Acute Myocardial Infarction Treated by Percutaneous Coronary Interventions
Authors: Evangelos Giannitsis, Stephanie Lehrke, Uwe K. H. Wiegand, Volkhard Kurowski, Margit Müller-Bardorff, Britta Weidtmann, Gert Richardt, Hugo A. Katus
Journal: Circulation (2000)

Background —Cardiac troponin T (cTnT) elevations on admission indicate a high-risk subgroup of patients with ST-segment elevation acute myocardial infarction (AMI). This finding has been attributed to less effective reperfusion after thrombolytic therapy. The aim of this study was to determine the role of admission cTnT on the efficacy of percutaneous coronary interventions (PCIs) in inferior AMI. Methods and Results —One hundred fifty-nine consecutive patients with inferior ST-segment AMI were enrolled and followed up for a mean of 448 days. Patients were stratified by cTnT on admission. A cTnT ≥0.1 μg/L was found in 58% of patients. These patients had longer time intervals from onset of symptoms to therapy ( P &lt;0.001) and higher 30-day (10.8% versus 1.5%, P =0.027) and long-term (17.2% versus 4.5%, P =0.023) cardiac mortalities. Rates of the combined end point of death, nonfatal reinfarction, and need for repeated target vessel revascularization procedures were not different in cTnT groups (log rank, 0.69; P =0.41). PCI was attempted in 93.3% of cTnT-positive and 98.5% cTnT-negative patients ( P =0.24) but was less frequently successful in patients with cTnT ≥0.1 μg/L (77.9% versus 96.9%, P &lt;0.001). Coronary stenting reduced 30-day and long-term cardiac mortality, particularly among cTnT-positive patients. In a multivariate analysis, cTnT indicated an ≈5-fold-higher risk (adjusted OR, 4.6; 95% CI, 0.79 to 27.11; P =0.089) and was a strong albeit not independent risk predictor. Conclusions —In inferior AMI, a positive admission cTnT is associated with lower success rates of direct PCI and higher rates of cardiac events over the short and long term. These patients benefit from coronary stenting.
Reserve may be just another word for cowardice
Authors: R G Choa
Journal: BMJ (1998)

EDITOR—I was appointed as the second urologist in Plymouth at the age of 36. When I was 38 I became ill, and Parkinson's disease was diagnosed.

I carried on working for nearly three years and kept my diagnosis a secret from everyone except my fellow urologist and some close friends, because I thought I would have no credibility as a surgeon if it were made public. Apart from thinking, somewhat altruistically, that I would be able to continue to be of some help to my patients, I also thought that as long as I was able to maintain my standards I did not need to …
Making the transition to action
Authors: Eva Kralikova, Erzsebet Podmaniczky, Hanna Stypulkowska-Misiurewicz, Elena Kavcova, Aurelijus Veryga, Tanith Muller
Journal: BMJ (2005)

The news on smoking from the European Union's eastern frontiers is better than expected, with no evidence of a future gulf in lung cancer mortality between old and new member states.1 However, the special challenges faced by the eastern transitional economies—such as aggressive tobacco marketing, rapid liberalisation of the tobacco trade, and the political influence of the leading tobacco companies2—remain. And a closer look at the study by Didkowska et al1 shows just how much work is still needed throughout the EU to reduce deaths from lung cancer and from other tobacco related disease.

The tobacco epidemic cannot be …
Genetic variability in the regulation of gene expression in ten regions of the human brain
Authors: Adaikalavan Ramasamy, Daniah Trabzuni, Sebastian Guelfi, Vibin Varghese, Colin Smith, Robert Walker, Tisham De, Lachlan Coin, Rohan de Silva, Mark R Cookson, Andrew B Singleton, John Hardy, Mina Ryten, Michael E Weale
Journal: Nature Neuroscience (2014)
Impaired coronary flow and ventricular function in hearts of hypertensive rats
Authors: A. ALFARO, T. F SCHAIBLE, A. MALHOTRA, T. YIPINTSOI, J. SCHEUER
Journal: Cardiovascular Research (1983)

Hearts of rats made hypertensive (BP greater than 150 mmHg) by left renal artery clipping and sham operated controls were studied in two series of experiments. In series I, cardiac function was studied in an isolated working heart apparatus at weeks 4, 9 to 10 and 16 to 17 post-surgery. In series II, coronary flow was studied during normoxic and anoxic retrograde perfusions at days 6 to 9 and at weeks 4 and 10 post-surgery. In series I, when compared with controls, hypertensives had lower body weights at weeks 4 and 9 to 10, and higher left ventricular weights at each period. Heart function was depressed for hypertensives when compared with controls as measured by lower stroke volume, peak left ventricular systolic pressure, stroke work, ejection fraction, positive dP/dt, peak aortic flow, and maximal flow acceleration. Relaxation rate as measured by negative dP/dt was also depressed. Hearts from hypertensives had significantly lower coronary flows and MVO2, and increased percent oxygen extraction and effluent lactate/pyruvate ratios. LVEDP was significantly elevated for hypertensives, when LVEDV (ml) was similar for hypertensives and controls. Myocardial actomyosin ATPase activity was depressed for hypertensives at weeks 9 to 10 and 16 to 17 post-surgery. In series II, when hearts were perfused retrogradely, coronary flow was lower for hypertensives than for controls during normoxia at days 6 to 9 and at week 4, and during anoxia at all time periods. The findings demonstrate that impaired coronary vascular reserve develops within days of the development of hypertension in rats, and this can be associated with impaired ventricular function.
Primary Anorectal Actinomycosis
Authors: Nelson S. Brewer
Journal: JAMA (1974)

Nine cases of actinomycosis primarily involving the anorectal region have been seen at the Mayo Clinic since 1950. Complete healing may be expected once the correct diagnosis is made, on the basis of the characteristic clinical manifestations and laboratory identification of the organism, and proper antimicrobial and surgical therapy is administered.  ( JAMA 228:1397-1400, 1974)