tbuckley/cabot-search huggingface dataset:
Investigation of a hemodynamic basis for syncope in hypertrophic cardiomyopathy. Use of a head-up tilt test.
Authors: D M Gilligan, P Nihoyannopoulos, W L Chan, C M Oakley
Journal: Circulation (1992)

BACKGROUND Syncope and sudden death in hypertrophic cardiomyopathy may have a hemodynamic basis. The presence of a small ventricular cavity with high intracavity pressures may activate left ventricular baroreceptors and cause reflex hypotension as described in other populations with syncope. METHODS AND RESULTS To investigate this potential mechanism of syncope in hypertrophic cardiomyopathy, we studied 17 patients with a history of syncope (syncopal), 19 without syncope (nonsyncopal), and nine normal control subjects by using a head-up tilt test. Head-up tilt at 60 degrees for 45 minutes was followed by 10-minute tilts during incremental doses of isoprenaline. Heart rate, blood pressure, and two-dimensional and Doppler echocardiography were monitored throughout. On tilting, hypertrophic cardiomyopathy patients showed a decline in mean arterial pressure of -5 +/- 6 mm Hg (p less than 0.001) compared with no change in control subjects (0.2 +/- 6 mm Hg, p = 0.9). Left ventricular outflow tract velocity decreased on tilting in control subjects (-8 +/- 6 cm/sec, p = 0.004) but increased in the syncopal and nonsyncopal patients (20 +/- 50 cm/sec, p = 0.05). Reflex hypotension with or without bradycardia, associated with syncope or presyncope, was induced in seven syncopal patients, two nonsyncopal patients, and two control subjects (p = 0.05). The early response to tilt in these subjects was characterized by maintenance of blood pressure but a greater increase in left ventricular fractional shortening than in the other subjects (10 +/- 8% versus 1 +/- 1%, p = 0.002). The onset of hypotension was associated with a trend toward further decreases in left ventricular diameters, outflow tract velocity, and transmitral flow velocities. In the remaining patients who had a negative test, transient hypotension (systolic pressure less than 100 mm Hg) occurred in seven syncopal patients and three nonsyncopal patients compared with none of the control subjects (p = 0.01). In total, hypotension was demonstrated in 82% of syncopal patients compared with 26% of nonsyncopal patients and 22% of control subjects (p = 0.001). CONCLUSIONS Patients with hypertrophic cardiomyopathy and a history of syncope frequently display hypotension during head-up tilt. In some cases, sudden hypotension occurs and is usually associated with bradycardia and a reduced cavity size, findings compatible with activation of a ventricular baroreflex. In other cases, transient hypotension occurs and could be explained by an impairment of baroreceptor function. These mechanisms may contribute to the occurrence of syncope in daily life.
Clinical symptoms associated with seroconversion for HIV-1 among misusers of intravenous drugs: comparison with homosexual seroconverters and infected and non-infected intravenous drug misusers.
Authors: G H Mientjes, E J van Ameijden, H M Weigel, J A van den Hoek, R A Coutinho
Journal: BMJ (1993)

OBJECTIVE--To study the clinical symptoms associated with seroconversion for HIV-1 among misusers of intravenous drugs. DESIGN--Case-control study in cohorts of drug misusers and homosexual men. SETTING--Outpatient clinic, Municipal Health Service, Amsterdam. SUBJECTS--Misusers of intravenous drugs from our prospective cohort who seroconverted for HIV. Controls were drug users positive for HIV, drug users negative for HIV, and homosexual men who had seroconverted. RESULTS--Five out of 18 (28%) drug users were admitted to hospital with bacterial pneumonia in the four to six months between their last visit at which they were HIV negative and their first visit when they were HIV positive. For comparison none of the 27 homosexual men who seroconverted for HIV, three out of 177 (2%) drug users negative for HIV, and 10 out of 112 (9%) drug users positive for HIV reported bacterial pneumonia. One out of the 18 drug users who seroconverted suffered from oesophageal candidiasis at the time of seroconversion. Other clinical symptoms did not differ between drug users who seroconverted and those who remained negative for HIV, probably due to the high background morbidity among the drug users. CONCLUSIONS--Seroconversion to HIV-1 among intravenous drug misusers is associated with bacterial pneumonia. Those drug users with previously negative test results for HIV who are admitted to hospital for bacterial pneumonia should be tested to detect primary infection with HIV-1.
Dose-Related Effects of Smallpox Vaccine
Authors: Sharon E. Frey, Frances K. Newman, John Cruz, W. Brian Shelton, Janice M. Tennant, Tamara Polach, Alan L. Rothman, Jeffrey S. Kennedy, Mark Wolff, Robert B. Belshe, Francis A. Ennis
Journal: New England Journal of Medicine (2002)

We conducted a double-blind, randomized trial of three dilutions of vaccinia virus vaccine in previously unimmunized adults in order to assess the clinical success rates, humoral responses, and virus-specific activity of cytotoxic T cells and interferon-γ–producing T cells.
SUPPRESSION OF PANCREATIC ENDOCRINE TUMOUR SECRETION BY LONG-ACTING SOMATOSTATIN ANALOGUE
Authors: R.G. Long, T.E. Adrian, M.R. Brown, J.E. Rivier, A.J. Barnes, C.N. Mallinson, W. Vale, N.D. Christofides, S.R. Bloom
Journal: The Lancet (1979)
Use of Diuretics in Hypertension
Authors: Ray W. Gifford
Journal: JAMA (1961)

THE INTRODUCTION of potent oral diuretics is one of the most significant advances in antihypertensive therapy of the past decade—a decade which saw the birth and rapid development of effective medical treatment for hypertension.  For reasons that are not yet entirely elucidated, benzothiadiazine (thiazide) derivatives (Table 1) as well as other diuretics1exert a modest hypotensive action in their own right when administeredto hypertensive patients, even though edema is not present. Furthermore, they enhance the potency of other antihypertensive agents, such as reserpine (Serpasil), hydralazine (Apresoline), ganglionblocking agents and the newer sympathetic-inhibiting drugs, bretylium tosylate (Darenthin) and guanethidine sulfate (Ismelin). Since the thiazide diuretics produce few unpleasant symptomatic side effects and since they frequently make possible a reduction in dosage or elimination of more potent agents that do cause unpleasant side effects, the net result of their use is better and easier control of hypertension with greater
Reducing harm from alcohol
Authors: M. McKee, P. Belcher, T. Hervey
Journal: BMJ (2009)

The UK must tackle the problem of cheap alcoholThe United Kingdom has a drink problem.Whether measured as alcohol related deaths, hospital admissions, or crimes, its condition has been deteriorating markedly.And the problem is not confined to a small number of people going on a binge each weekend.Mortality from cirrhosis, a marker of more insidious harm, is now one of the highest rates in Europe, at a time when it is falling in many other European countries.1
Coal Workers' Pneumoconiosis
Authors: John A. Kibelstis
Journal: JAMA (1972)

To the Editor.—  The article entitled  Workers'  (220:223, 1972) was a tremendous disappointment. In this article, Drs. Naeye and Dellinger repeat their unfounded supposition that Coal Workers' Pneumoconiosis includes such diseases as chronic bronchitis, silicosis, emphysema, tuberculosis and occasionally other disease processes. Once again, they fail to prove their point.  The authors have diligently collected anatomic data on 77 men who were miners, had been autopsied, and had had a technically acceptable x-ray film of the chest within a year of death. They present no evidence to indicate that this is a truly representative sample of all dying coal miners. Although they did note that 32 had complained of dyspnea at some time prior to death, the authors neglect to mention such descriptive data as smoking history, previous pulmonary disease, and cause of death. Without these data, it is impossible to know whether dyspnea represents more cardiac illness
Government ruling would protect US healthcare workers who object to abortion
Authors: J. H. Tanne
Journal: BMJ (2008)

The US Department of Health and Human Services has issued a draft proposal to protect healthcare workers from discrimination if they object to abortion.

The regulation would apply to 584 000 employers in the healthcare sector that receive federal funding from programmes such as Medicare (which provides health insurance for elderly and some disabled people), Medicaid (which provides insurance for poor people), those that offer reproductive health services to poor people, and biomedical research projects. It applies to doctors and nurses and workers in “any activity with a reasonable connection” to the particular service. 

Hospitals, doctors’ offices, nursing homes, and other facilities would have to certify in writing that they do not discriminate against employees who have religious or moral objections to abortion. Facilities could lose federal funding, …
P17.75 * UTILITY OF 3D SURGICAL PLANNING FOR RESECTION OF HIGH-GRADE GLIOMAS
Authors: A. V. Rozumenko, V. D. Rozumenko
Journal: Neuro-Oncology (2014)

OBJECTIVES: Surgical resection of gliomas involving eloquent brain areas carries a high risk of postoperative neurological deterioration. METHODS: Total of 129 patients (75 males, 54 females, mean age 45.5 years, range 20-70 years) underwent preoperative MRI with Gd-enhancement (3D-T1W, T2W, FLAIR, DTI-FT, fMRI). Brain tumors located in eloquent areas (Sawaya grade III) in 93 (72.1%) patients and close to eloquent areas (Sawaya grade II) in 36 (27.9%) patients. The surgical planning and tumor microsurgery resection were carried out using StealthStation navigation system (Medtronic Inc., USA). The surgical planning was performed with a 3D volumetric reconstruction of cerebral hemispheres' surface, tumor, corticospinal tracts, motor areas, ventricles, cerebral arteries, dural sinuses and cortical surface veins. The surgical trajectory and volume of safe tumor resection were defined and calculated preoperative. RESULTS: A gross total tumor resection was achieved in 54 (41.9%) patients, subtotal resection in 61 (47.3%), partial resection in 14 (10.8%). Glioblastomas (WHO Grade IV) were found in 61 (47.3%) cases, anaplastic gliomas (WHO Grade III) _ in 68 (52.7%). Median KPS score increased from 68.4 to 84.8 after surgery (p < 0.05). The neuronavigation system supports the ability of multimodal data sets integration and preoperative planning with using of 3D models presenting anatomical and functional structures. The 3D modeling reveals anatomical relations of tumor with the surrounding eloquent areas and vessels that creates conditions for determination of the optimal surgical tactics. The use of multimodal neuronavigation provided intraoperative orientation by comparing position of virtual structures from preoperative planning data with the anatomical structures in the operative field. CONCLUSION: The 3D surgical planning allows evaluating the risk of injury of eloquent structures, facilitates the orientation in operative field, and reduces the level of neurological disorders in operated patients.
Antimicrobial peptides in lung transplant recipients with bronchiolitis obliterans syndrome
Authors: R. L. Anderson, P. S. Hiemstra, C. Ward, I. A. Forrest, D. Murphy, D. Proud, J. Lordan, P. A. Corris, A. J. Fisher
Journal: European Respiratory Journal (2008)

Mechanisms other than classical alloimmunity are implicated in the pathogenesis of bronchiolitis obliterans syndrome (BOS). It was hypothesised that antimicrobial peptides (AMPs), elements of the innate immune response, have a role in BOS pathogenesis. Pulmonary expression of the neutrophil-derived AMPs human cathelicidin (hCAP)-18/LL-37 and α-defensins (human neutrophil peptides (HNP) 1–3), and the epithelial cell-derived AMPs human β-defensin (hBD)-2, elafin and secretory leukoprotease inhibitor (SLPI) were measured in stable lung transplant recipients and those with BOS. The relationship between airway pathogens and AMP levels was examined. Bronchoalveolar lavage (BAL) was performed on 44 lung transplant recipients (30 stable, 14 with BOS). BAL was cultured for pathogens and ELISA for AMPs was performed. The presence of airway pathogens was associated with significantly increased levels of neutrophil-derived and epithelial-derived AMPs. When patients without pathogens in BAL fluid were analysed, eight recipients with BOS had elevated hCAP-18/LL-37 and HNP 1–3 compared with 25 stable recipients. hBD-2 and elafin levels were comparable in BOS and stable recipients, but SLPI levels were reduced in BOS. Bronchiolitis obliterans syndrome is associated with elevated airway human cathelicidin 18/LL-37 and human neutrophil peptides 1–3 from activated neutrophils, even in the absence of pathogens. Together with reduced airway secretory leukoprotease inhibitor this may favour nonalloimmune airway injury with reduced antiprotease defence and increased neutrophil degranulation.
Adiponectin Prevents Cerebral Ischemic Injury Through Endothelial Nitric Oxide Synthase–Dependent Mechanisms
Authors: Masaki Nishimura, Yasuhiro Izumiya, Akiko Higuchi, Rei Shibata, Jianhua Qiu, Chiho Kudo, Hwa Kyoung Shin, Michael A. Moskowitz, Noriyuki Ouchi
Journal: Circulation (2007)

Adiponectin is a fat-derived plasma protein that has beneficial actions on cardiovascular disorders. A low level of plasma adiponectin is associated with increased mortality after ischemic stroke; however, the causal role of adiponectin in ischemic stroke is unknown.To explore the role of adiponectin in the development of acute cerebral injury, we subjected adiponectin-deficient (APN-KO) and wild-type (WT) mice to 1 hour of middle cerebral artery occlusion followed by 23 hours of reperfusion. APN-KO mice exhibited enlarged brain infarction and increased neurological deficits after ischemia-reperfusion compared with WT mice. Conversely, adenovirus-mediated supplementation of adiponectin significantly reduced cerebral infarct size in WT and APN-KO mice. APN-KO mice showed decreased cerebral blood flow during ischemia by laser speckle flowmetry methods. Adiponectin colocalized within the cerebral vascular endothelium under transient ischemic conditions by immunohistochemical analysis. Phosphorylation of endothelial nitric oxide synthase in ischemic brain tissues and the production of nitric oxide metabolites in plasma were attenuated in APN-KO mice compared with WT mice. Adenovirus-mediated administration of adiponectin stimulated endothelial nitric oxide synthase phosphorylation and nitric oxide metabolites during cerebral ischemia in both WT and APN-KO mice. Neuronal nitric oxide synthase expression during ischemia did not differ between WT and APN-KO mice. Adenovirus-mediated delivery of adiponectin did not affect brain infarction in mice deficient in endothelial nitric oxide synthase.These data provide causal evidence that adiponectin exerts a cerebroprotective action through an endothelial nitric oxide synthase-dependent mechanism. Adiponectin could represent a molecular target for the prevention of ischemic stroke.
COMPLETE VERSUS CULPRIT ONLY REVASCULARIZATION IS NOT BENEFICIAL IN ACUTE ST ELEVATION MYOCARDIAL INFARCTION: A META-ANALYSIS
Authors: Ankur Sethi, Amol Bahekar, Rohit Bhuriya, Sarabjeet Singh, Aziz Ahmed, Sandeep Khosla
Journal: Journal of the American College of Cardiology (2010)
Unreliability of reports of hypoglycaemia by diabetic patients
Authors: S. Heller, J. Chapman, J. McCloud, J. Ward
Journal: BMJ (1995)

In those with diabetes the importance of hypoglycaemia as a cause of considerable illness and occasionally death has been increasingly recognised as patients have struggled to maintain tight control of their blood glucose concentration to prevent long term diabetic complications.1 Whether human insulin decreases the awareness of hypoglycaemia and increases severe hypoglycaemic episodes is debatable.2 The evidence has largely depended on patient recall, which may be uncertain when cerebral function is impaired during hypoglycaemia. We therefore measured the reliability of retrospective questionnaires by asking patients and their partners about hypoglycaemia.

We questioned consecutive patients attending diabetic clinics in two hospitals over four weeks, including in the study only those with a partner or close relative at home. Patients completed a questionnaire in the …
Trichomoniasis in Males-Reply
Authors: H. Close Hesseltine
Journal: JAMA (1963)

Dr. Hesseltine replies in the letter which follows. Dr. Kean's letter has points worthy of consideration. He agreed both with our article and with the editorial inThe Journal(<b>184</b>:1036) that treatment should be given only to those shown to have trichomoniasis. His second point deals with infection of husbands. Regardless of one's views about the suspected incidence in males, the demonstration of trichomonal infections remains controversial. The actual demonstration of trichomonads in males is said by some to be infrequent. Promiscuity may be related to increased incidence. Over the years, the urologists working with us have found infrequently any relationship of the husband's genital-tract infections with chronicity of vaginal trichomoniasis. The incidence of vaginal trichomoniasis varies greatly. Studies of women of "easy virtue" and in penal institutions reveal a greater number of infections or carrier states than in the general population. On the other hand, the incidence is
Contribution of atenolol, bendrofluazide, and hydrallazine to management of severe hypertension.
Authors: R G Wilcox, J R Mitchell
Journal: BMJ (1977)

The efficacy of various combinations of atenolol, bendrofluazide, and hydraliazine given twice daily was assessed in a double-blind trial on 39 patients with moderate to severe essential hypertension. Concurrent treatment with all three drugs proved most effective and produced a mean reduction in blood pressure of 43/31 mm Hg. In the dosage used, hydrallazine affected only the diastolic blood pressure, and when added to either bendrofluazide or bendrofluazide plus atenolol it produced a further mean reduction in pressure of 6 mm Hg. Once-daily treatment with atenolol and bendrofluazide was as effective in reducing blood pressure as the same combination given twice daily, and the hypotensive effect was still present at least 24 hours after the last dose of tablets. A combined tablet of atenolol and bendrofluazide taken once daily would be a simple regimen to follow and would provide almost as much hypotensive effect as a twice-daily regimen incorporating a modest dose of hydrallazine. The hypotensive effect of atenolol was equal to that of bendrofluazide on systolic pressure but significantly better than that of bendrofluazide on diastolic pressure. Atenolol reduced plasma renin and urate concentrations but increased plasma potassium levels. The biochemical effects of atenolol, therefore, may be an advantage over those of bendrofluazide when deciding on first-line treatment for essential hypertension.
Extracellular Signal–Regulated Kinase (Erk) Activation by the Pre-T Cell Receptor in Developing Thymocytes in Vivo
Authors: Alison M. Michie, Sébastien Trop, David L. Wiest, Juan Carlos Zúñiga-Pflücker
Journal: The Journal of Experimental Medicine (1999)

The first checkpoint in T cell development occurs between the CD4−CD8− and CD4+CD8+ stages and is associated with formation of the pre-T cell receptor (TCR). The signaling mechanisms that drive this progression remain largely unknown. Here, we show that extracellular signal–regulated kinases (ERKs)-1/2 are activated upon engagement of the pre-TCR. Using a novel experimental system, we demonstrate that expression of the pre-TCR by developing thymocytes induces ERK-1/2 activation within the thymus. In addition, the activation of this pre-TCR signaling cascade is mediated through Lck. These findings directly link pre-TCR complex formation with specific downstream signaling components in vivo.
Neural Stem Cell-based Cell Carriers Enhance Therapeutic Efficacy of an Oncolytic Adenovirus in an Orthotopic Mouse Model of Human Glioblastoma
Authors: Atique U Ahmed, Bart Thaci, Nikita G Alexiades, Yu Han, Shuo Qian, Feifei Liu, Irina V Balyasnikova, Ilya Y Ulasov, Karen S Aboody, Maciej S Lesniak
Journal: Molecular Therapy (2011)

The potential utility of oncolytic adenoviruses as anticancer agents is significantly hampered by the inability of the currently available viral vectors to effectively target micrometastatic tumor burden. Neural stem cells (NSCs) have the ability to function as cell carriers for targeted delivery of an oncolytic adenovirus because of their inherent tumor-tropic migratory ability. We have previously reported that in vivo delivery of CRAd-S-pk7, a glioma-restricted oncolytic adenovirus, can enhance the survival of animals with experimental glioma. In this study, we show that intratumoral delivery of NSCs loaded with the CRAD-S-pk7 in an orthotopic xenograft model of human glioma is able to not only inhibit tumor growth but more importantly to increase median survival by ~50% versus animals treated with CRAd-S-pk7 alone (P = 0.0007). We also report that oncolytic virus infection upregulates different chemoattractant receptors and significantly enhances migratory capacity of NSCs both in vitro and in vivo. Our data further suggest that NSC-based carriers have the potential to improve the clinical efficacy of antiglioma virotherapy by not only protecting therapeutic virus from the host immune system, but also amplifying the therapeutic payload selectively at tumor sites. The potential utility of oncolytic adenoviruses as anticancer agents is significantly hampered by the inability of the currently available viral vectors to effectively target micrometastatic tumor burden. Neural stem cells (NSCs) have the ability to function as cell carriers for targeted delivery of an oncolytic adenovirus because of their inherent tumor-tropic migratory ability. We have previously reported that in vivo delivery of CRAd-S-pk7, a glioma-restricted oncolytic adenovirus, can enhance the survival of animals with experimental glioma. In this study, we show that intratumoral delivery of NSCs loaded with the CRAD-S-pk7 in an orthotopic xenograft model of human glioma is able to not only inhibit tumor growth but more importantly to increase median survival by ~50% versus animals treated with CRAd-S-pk7 alone (P = 0.0007). We also report that oncolytic virus infection upregulates different chemoattractant receptors and significantly enhances migratory capacity of NSCs both in vitro and in vivo. Our data further suggest that NSC-based carriers have the potential to improve the clinical efficacy of antiglioma virotherapy by not only protecting therapeutic virus from the host immune system, but also amplifying the therapeutic payload selectively at tumor sites.
Book: Publishing Your Medical Research Paper: What They Don't Teach You in Medical School
Authors: T. Greenhalgh
Journal: BMJ (1999)

Daniel W Byrne Lippincott Williams and Wilkins, £16.95, pp 288 ISBN 0683 300 74 Rating: ![Graphic][1]</img> Nothing makes my toes curl more than books that promise “200 expert tips” on a subject which your professors foolishly and inexplicably omitted from the curriculum when you were at university. Such books are almost invariably published in north America, written in a slack, simplistic, anti-academic style, and slip unconsciously into jargon when anything complex has to be explained. They tend to be replete with numbered or bulleted lists, clip … [1]: /embed/inline-graphic-1.gif