tbuckley/cabot-search huggingface dataset:
STUDIES ON DIGITALIS. I. DIRECT EFFECTS ON PERIPHERAL VASCULAR RESISTANCE
Authors: John Ross, John A. Waldhausen, Eugene Braunwald, Robert Lewis
Journal: Journal of Clinical Investigation (1960)

There is a substantial body of evidence which supports the view that the action of digitalis preparations is not limited to the heart.It had been suggested that the primary action of digitalis is extracardiac (1-3) and that the direct effects on the vascular bed may be responsible, in part, for its therapeutic action (4).However, in most studies, attention has been directed to the power- ful positive inotropic action of this drug (5-10).The direct effects of digitalis on the peripheral circulation alone have not been clearly defined be- cause of alterations in the cardiac output which usually accompany digitalization.The present study was designed to characterize the direct effects of several digitalis glycosides on vascular resistance in the dog.Two types of preparations were employed in which the circulatory effects resulting from the inotropic action of these drugs could be completely eliminated. METHODSFifty-three mongrel dogs, ranging from 10.5 to 24.0 kg in weight, and averaging 15.4, were studied.Fifty- one dogs were premedicated with 2 mg per kg morphine and received chloralose and urethan intravenously (11); in two dogs, pentobarbital (30 mg per kg) was used instead of morphine.Two basic preparations were em-
The duration of pretreatment with ticlopidine prior to stenting is associated with the risk of procedure-related non–Q-wave myocardial infarctions
Authors: Steven R Steinhubl, Michael S Lauer, Debabrata P Mukherjee, David J Moliterno, A. Michael Lincoff, Stephen G Ellis, Eric J Topol
Journal: Journal of the American College of Cardiology (1998)
Modeling Mesothelioma Risk Associated with Environmental Asbestos Exposure
Authors: Milena Maria Maule, Corrado Magnani, Paola Dalmasso, Dario Mirabelli, Franco Merletti, Annibale Biggeri
Journal: Environmental Health Perspectives (2007)

BackgroundEnvironmental asbestos pollution can cause malignant mesothelioma, but few studies have involved dose–response analyses with detailed information on occupational, domestic, and environmental exposures.ObjectivesIn the present study, we examined the spatial variation of mesothelioma risk in an area with high levels of asbestos pollution from an industrial plant, adjusting for occupational and domestic exposures.MethodsThis population-based case–control study included 103 incident cases of mesothelioma and 272 controls in 1987–1993 in the area around Casale Monferrato, Italy, where an important asbestos cement plant had been active for decades. Information collected included lifelong occupational and residential histories. Mesothelioma risk was estimated through logistic regression and a mixed additive–multiplicative model in which an additive scale was assumed for the risk associated with both residential distance from the plant and occupational exposures. The adjusted excess risk gradient by residential distance was modeled as an exponential decay with a threshold.ResultsResidents at the location of the asbestos cement factory had a relative risk for mesothelioma of 10.5 [95% confidence interval (CI), 3.8–50.1), adjusted for occupational and domestic exposures. Risk decreased rapidly with increasing distance from the factory, but at 10-km the risk was still 60% of its value at the source. The relative risk for occupational exposure was 6.0 (95% CI, 2.9–13.0), but this increased to 27.5 (95% CI, 7.8–153.4) when adjusted for residential distance.ConclusionsThis study provides strong evidence that asbestos pollution from an industrial source greatly increases mesothelioma risk. Furthermore, relative risks from occupational exposure were underestimated and were markedly increased when adjusted for residential distance.
Evidence not ideology
Authors: Julian Tudor Hart
Journal: BMJ (2005)

Editor—Godlee asks for evidence without ideology, as though it were possible either to discover or use evidence without ideology of some kind.1 Scientific evidence is derived from hypotheses conceived within an ideology—that is, a set of prior assumptions about the real world, established by previous evidence, by faith, or by both. New evidence can then be produced by testing hypotheses derived from those assumptions against reality. The validity of competing hypotheses, including those macro-hypotheses about the world or society we call ideologies, depends on their explanatory and predictive power in the real world.

About the private finance initiative and the Blair government's disintegration of the NHS into a competitive market led by consumer wants rather than by national health needs, nobody has published more evidence than Pollock. For the editor of the BMJ to dismiss this as led by ideology is an impertinence. Without exception, every paper published by the BMJ starts from ideological assumptions of some kind. That the editor's assumptions apparently coincide with those of currently fashionable and conventional opinion does not change their ideological nature. Readers can make their own judgments as to which ideology has most explanatory and predictive power, either experimentally or in the more chaotic real world of practice, which in the absence of pilot projects is all we have to go on in assessing the consequences of marketisation.

This is a deadly serious business. Asked to describe the nature of the corporate state in the 1920s, before the full consequences of fascism were understood by comfortable people outside Italy, Mussolini answered that in his state the worlds of government and business would become one and indivisible. Godlee should consider how far we have already travelled along that road, and then reconsider the ethics of neutrality in such a situation. At the birth of the NHS, the BMJ had a role of which its later editors were frankly ashamed. Today, when the NHS is being buried alive, has it lost the power of speech?
Early Versus Delayed Angiotensin-Converting Enzyme Inhibition in Experimental Chronic Heart Failure
Authors: Paul Mulder, Bruno Devaux, Vincent Richard, Jean-Paul Henry, Marie-Catherine Wimart, Emmanuel Thibout, Bertrand Mace´, Christian Thuillez
Journal: Circulation (1997)

Background The efficacy of ACE inhibitors in congestive heart failure (CHF) might be affected by the pathophysiological status present at the onset of treatment. We compared in a rat model the effects of ACE inhibition (lisinopril, 10 mg·kg −1 ·d −1 ) initiated early (1 week) or late (3 months) after myocardial infarction (ie, at time points corresponding to moderate or severe CHF without or with established cardiac remodeling). Methods and Results Survival was improved by early treatment at 3 months (from 76% to 95%) and by both early and delayed treatment at 9 months (placebo, 28%; early, 90%; delayed, 61%). Delayed treatment was initiated in a more severe pathophysiological context of CHF than early treatment, illustrated in untreated rats by higher left ventricular (LV) end-diastolic and central venous pressures and by increased LV weight and LV cavity circumference. After 9 months, early and delayed treatments reduced systolic, LV end-diastolic, and central venous pressures. Both treatments also similarly decreased LV weight, LV cavity circumference, and LV collagen density. Conclusions In this rat model of CHF, early and delayed ACE inhibitor treatments both increase survival and exert similar beneficial effects on cardiac hemodynamics and remodeling. Although early treatment prevents the development of ventricular dysfunction and remodeling, delayed treatment is capable of reversing cardiac hypertrophy and remodeling, as well as ventricular dysfunction. Thus, ACE inhibitors exert marked beneficial effects even when treatment is initiated late into the evolution of heart failure (ie, at a time of established ventricular dysfunction and remodeling).
Identification of a Genetic Signature of Activated Signal Transducer and Activator of Transcription 3 in Human Tumors
Authors: James V. Alvarez, Phillip G. Febbo, Sridhar Ramaswamy, Massimo Loda, Andrea Richardson, David A. Frank
Journal: Cancer Research (2005)

Abstract Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated in diverse human tumors and may play a direct role in malignant transformation. However, the full complement of target genes that STAT3 regulates to promote oncogenesis is not known. We created a system to express a constitutively active form of STAT3, STAT3-C, in mouse fibroblasts and used it to identify STAT3 targets. We showed that a subset of these targets, which include transcription factors regulating cell growth, survival, and differentiation, are coexpressed in a range of human tumors. Using immunohistochemical staining of tissue microarrays, we showed that these targets are enriched in breast and prostate tumors harboring activated STAT3. Finally, we showed that STAT3 is required for the expression of these genes in a breast cancer cell line. Taken together, these results identify a cohort of STAT3 targets that may mediate its role in oncogenesis.
White rice and risk of type 2 diabetes
Authors: B. Neal
Journal: BMJ (2012)

New study highlights old challenges of nutritional epidemiology

A marked rise in the incidence of type 2 diabetes is a characteristic feature of populations that have undergone nutritional transition.1 First seen in the developed Western world, the same pattern is now being replicated in low income and middle income countries, where most new cases of diabetes now occur.2 The role of poor diet in the diabetes epidemic is undisputed, but the details have long been debated.3 Although overconsumption of energy and accumulation of excess body fat is a common cause of type 2 diabetes,4 diet almost certainly has other unknown effects, and specific foods with particular adverse effects may have a direct role in the development of type 2 diabetes.

The linked paper by Hu and colleagues (doi:10.1136/bmj.e1454) sheds new light on the relation between diet and diabetes, and the authors bring a new level of rigour to efforts to answer the question of the possible effect of higher consumption of white rice.5 They systematically searched for …
Incidence and risk factors of major opportunistic infections after initiation of antiretroviral therapy among advanced HIV-infected patients in a resource-limited setting
Authors: Weerawat Manosuthi, Achara Chaovavanich, Somsit Tansuphaswadikul, Wisit Prasithsirikul, Yoawarat Inthong, Suthat Chottanapund, Chayanan Sittibusaya, Visal Moolasart, Patamavadee Termvises, Somnuek Sungkanuparph
Journal: Journal of Infection (2007)
Medical journals don't publish trials on major global diseases
Authors: David Spurgeon
Journal: BMJ (2004)

Few randomised controlled trials published in leading general medical journals address the major health problems that affect most of the world's poor people.

An analysis of trials published in six leading general medical journals in 1999 shows that only 14 of 90 trials (16%) that looked at at least one of the top 10 causes of the global burden of disease were highly relevant to international health, as assessed by World Health Organization criteria ( CMAJ 2004;170:1673-7). Seven of the 35 most deadly and debilitating diseases were not studied in …
Abstract 3705: Multicenter phase II clinical trial of gemcitabine and liposomal paclitaxel combination chemotherapy in patients with advanced biliary cancer
Authors: Keon Uk Park, Jin Young Kim, Young Rok Do, Hong Suk Song, Hun-Mo Ryoo
Journal: Cancer Research (2012)

Abstract OBJECTIVE: Advanced biliary tract cancer is associated with a poor prognosis due to wide resistance to chemotherapeutic agents. This phase II clinical trial was conducted to determine the safety and efficacy of weekly gemcitabine and liposomal paclitaxel (Genexol-PM®) in patients with unrectable or metastatic biliary cancer. METHODS: The eligibility criteria were patients 1) with pathologically proven unresectable or metastatic biliary cancer, 2) with an ECOG performance status 0 to 2, 3) aged more than 18, 4) with measurable lesions, 5) with adequate hematologic, renal and liver functions, and 6) who provided written informed consent. Each treatment cycle was consisted of gemcitabine 1000 mg/m*2 and liposomal paclitaxel 100 mg/m*2 on days 1, 8 followed by rest perioid of 14 days. It was repeated until the appearance of disease progression or unacceptable toxicity up to maximal 9 cycles. The primary end point of this study was reponse rate, and secondary end points included toxicity, progression free survival and overall survival. RESULTS: Thirty five patients were enrolled; median age was 63 years; male (n=30) and female (n-10). The median number of cycles administered was 3.5 (range, 1-10). Thirty patients were assessable for efficacy. Nine partial responses and 16 stable diseases were confirmed. Giving an overall response rate was 35.6% and disease control rate was 55.6% in per-protocol population. Median overall survival was 12.3 months (95% CI: 5.79-18.74) and median progression free survival was 4.07 months(95% CI: 3.12-5.01). The most frequent adverse events (AE) of all grades were anemia and neutropenia (n=17) followed by leucopenia (13). Grade 3/4 hematologic AEs: anemia (n=6), neutropenia (n=11), thrombocytopenia (n=1). Grade 3/4 non-hematologic AEs: elevated liver function tests (n=3), hyperbilirubinemia (n=1) hyponatremia (n=1). CONCLUSION: Weekly gemcitabine combined with liposomal paclitaxel appears to be effective against advanced biliary cancers. Further randomized trials are needed to confirm this finding. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3705. doi:1538-7445.AM2012-3705
Medicine in the age of global interdependence
Authors: R. Smith
Journal: BMJ (2002)

> “The great question of this new century is whether the age of interdependence is going to be good or bad for humanity. The answer depends upon whether we in the wealthy nations spread the benefits and reduce the burdens of the modern world, on whether the poor nations enact the changes necessary to make progress possible, and on whether we all can develop a level of consciousness high enough to understand our obligations and responsibilities to each other.”
> 
> Bill Clinton, 26 January 20021
> 
> “A century of destruction unlike any other befalls and blights the human race — scores of millions of ordinary people condemned to suffer deprivation upon deprivation, atrocity upon atrocity, evil upon evil, half the world or more subjected to pathological sadism as social policy, whole societies organised and fettered by the fear of violent persecution, the degradation of individual life engineered on a scale unknown throughout history, nations broken and enslaved by ideological criminals who rob them of everything, entire populations so demoralised as to be unable to get out of bed in the morning with the minutest desire to face the day … all the terrible touchstones presented by the century, and here they are up in arms about … Monica Lewinsky! … This, in 1998, is the wickedness they have to put up with. This, in 1998, is their torture, their torment, and their spiritual death.”
> 
> Philip Roth, The Human Stain 2

Can we make sense of what is happening in …
Intravital detection of skin capillary aneurysms by videomicroscopy with indocyanine green in patients with progressive systemic sclerosis and related disorders.
Authors: A Bollinger, B Saesseli, U Hoffmann, U K Franzeck
Journal: Circulation (1991)

Conventional capillaroscopy and infrared fluorescence videomicroscopy with indocyanine green were performed at the nailfold in 12 healthy controls and 38 patients with microangiopathy due to systemic sclerosis or related disorders. Saccular aneurysms featuring head and neck (type 1) and aneurysmatic enlargements (type 2) were defined. Microaneurysms were located at the apex or near the apex of capillary loops and were significantly more common in patients than in controls (p less than 0.02 for type 1 and p less than 0.001 for type 2). Combination of the two lesions was found only in patients and appears to be a valuable new diagnostic sign for the presence of microangiopathy. In comparison with conventional capillaroscopy, about twice as many microaneurysms were detected by videomicroscopy with indocyanine green coupling almost completely to plasma proteins. The new technique allows visualization of capillary aneurysms even when filled only by plasma.
Breast-feeding protects against respiratory syncytial virus infections.
Authors: M A Downham, R Scott, D G Sims, J K Webb, P S Gardner
Journal: BMJ (1976)

Eight out of 115 infants admitted to hospital with respiratory syncytial (RS) virus infection had been breast-fed compared with 46 out of 167 controls; this difference was statistically significant. Twenty-one specimens of human colostrum were examined, and all contained RS virus neutralising activity. Specific IgA and IgG were detected in 18 specimens, whereas IgM was detected in none. The titre of IgA antibody was usually higher and correlated more closely to the titre of neutralising activity than that of IgG. Infants inhale milk feeds and regurgitate them through the nose, and the IgA collecting in the respiratory tract might protect against severe respiratory infection. Alternatively, if severe RS virus illness is a sign of hypersensitivity to the virus breast-feeding might protect the infant from an early sensitising infection.
Patients with small duct primary sclerosing cholangitis have a favourable long term prognosis
Authors: E Bjornsson
Journal: Gut (2002)

Patients with cholestatic liver function tests and histological features of primary sclerosing cholangitis (PSC) but a normal cholangiogram are considered to have small duct PSC. The natural history of this condition is unknown.Thirty three patients with small duct PSC were identified among patients admitted for diagnostic workup of cholestatic liver function tests in one centre in the UK (Oxford) and one centre in Norway (Oslo). A total of 260 patients with large duct PSC were compared, and prognosis in terms of death, cholangiocarcinoma, biochemical features, histological features, and symptoms analysed.Mean age at diagnosis was 38 years and 39 years in small duct and large duct PSC, respectively. Mean follow up was 106 months in small duct and 105 months in large duct patients. Four patients originally considered to have small duct developed large duct PSC. Two of these underwent liver transplantation during follow up. Of the remainder who did not develop large duct PSC, two patients died during follow up: one of liver failure and the other of cardiac death unrelated to her liver disease. A total of 122 (47%) large duct patients either required liver transplantation (34 patients) or died (88 patients). Small duct patients had a significantly better survival compared with large duct patients. Among small duct patients, none developed cholangiocarcinoma compared with 28 of 260 (11%) large duct patients.Patients with small duct PSC seem to have a good prognosis in terms of survival and development of cholangiocarcinoma. Small duct PSC progresses to large duct PSC in a small proportion of patients.
Blockade of ATP-sensitive potassium channels increases infarct size but does not prevent preconditioning in rabbit hearts.
Authors: J D Thornton, C S Thornton, D L Sterling, J M Downey
Journal: Circulation Research (1993)

Ischemic preconditioning renders the heart resistant to infarction by an unknown mechanism. This study tests whether preconditioning may be working through activation of ATP-sensitive potassium channels. If that were the case, then blockade of the channels should eliminate preconditioning's protection, and activation of these channels should mimic it. Thirty minutes of regional coronary ischemia followed by 3 hours of reperfusion caused 38.0 +/- 3.7% of the risk zone to become infarcted in control rabbits. Preconditioning with 5-minute ischemia followed by a 10-minute reperfusion before the 30-minute insult caused only 8.8 +/- 2.1% infarction, which was a reduction of 29.2% in infarct size by preconditioning (p < 0.01 versus control value). Pretreatment with the potassium channel blocker glibenclamide at three different concentrations significantly elevated infarct size in the nonpreconditioned hearts at all doses. Preconditioning, however, continued to limit infarct size by an amount not different from that seen in the control group at all doses of glibenclamide. Pinacidil, a potassium channel agonist, given before a 30-minute ischemic insult resulted in infarct sizes no different from that seen in nonpreconditioned control rabbits. We conclude that ATP-sensitive potassium channels are not involved in preconditioning in the rabbit heart; however, blocking those channels does exacerbate ischemia.
Biguanides and lactic acidosis.
Authors: P J Phillips, D W Thomas, P E Harding
Journal: BMJ (1977)

Background: Incidence of cancer is still increasing. Chemotherapy is often unsuccessful; moreover, anticancer drugs cause serious side-effects. It is necessary to develop effective agents for combination therapies that would increase antitumor effects of treatment and reduce its side-effects. Materials and Methods: Anticancer activity of oxicam derivatives (PR17 and PR18) alone and in combination with simvastatin on doxorubicin-resistant colon cancer cells was studied. Apoptosis was investigated via caspase-3 activation assay as well as via western blot analysis of expression of apoptotic components, B-cell lymphoma 2 protein (BCL2) and BCL2-associated X protein (BAX). Expression and activity of cyclo-oxygenase-2 (COX2) was also assessed. Results: Oxicam derivatives induced apoptosis through a caspase-3-dependent pathway, up-regulated BAX expression, and down-regulated BCL2 expression. Additionally, oxicam derivatives reduced expression and activity of COX2. Effect of oxicam derivatives on these processes was strongly potentiated by simvastatin. Conclusion: Oxicam derivatives at low concentrations effectively inhibit growth of cancer cells after co-administration with simvastatin.