tbuckley/cabot-search huggingface dataset:
Cure or cocoa?
Authors: Nick Ross
Journal: Journal of the Royal Society of Medicine (2009)

Surgeons and safetySo surgeons are looking to the airline industry now for guidance on safety. 1 What a pity they don't glance over the screen at the top of the operating table to the anaesthetist.We have been doing 'Cockpit Drills' for 30 years or more.The parallels between the processes of flying and anaesthesia are closer than with surgery.Over the years I have observed that anaesthetists in general spend far more time than the surgeon in undertaking pre-assessment, both of the patient and of the work environment.How long have I waited in theatre for the X-rays or a favoured surgical tool to be found, which a little forethought would have made available when needed.Learn about preparation by all means but don't bother to go to the hangar, ask on the other side of the screen.
ARDSnet Ventilatory Protocol and Alveolar Hyperinflation
Authors: Salvatore Grasso, Tania Stripoli, Michele De Michele, Francesco Bruno, Marco Moschetta, Giuseppe Angelelli, Irene Munno, Vincenzo Ruggiero, Roberto Anaclerio, Aldo Cafarelli, Bernd Driessen, Tommaso Fiore
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: In patients with acute respiratory distress syndrome (ARDS), a focal distribution of loss of aeration in lung computed tomography predicts low potential for alveolar recruitment and susceptibility to alveolar hyperinflation with high levels of positive end-expiratory pressure (PEEP).Objectives: We tested the hypothesis that, in this cohort of patients, the table-based PEEP setting criteria of the National Heart, Lung, and Blood Institute's ARDS Network (ARDSnet) low tidal volume ventilatory protocol could induce tidal alveolar hyperinflation.Methods: In 15 patients, physiologic parameters and plasma inflammatory mediators were measured during two ventilatory strategies, applied randomly: the ARDSnet and the stress index strategy. The latter used the same ARDSnet ventilatory pattern except for the PEEP level, which was adjusted based on the stress index, a monitoring tool intended to quantify tidal alveolar hyperinflation and/or recruiting/derecruiting that occurs during constant-flow ventilation, on a breath-by-breath basis.Measurements and Main Results: In all patients, the stress index revealed alveolar hyperinflation during application of the ARDSnet strategy, and consequently, PEEP was significantly decreased (P < 0.01) to normalize the stress index value. Static lung elastance (P = 0.01), plasma concentrations of interleukin-6 (P < 0.01), interleukin-8 (P = 0.031), and soluble tumor necrosis factor receptor I (P = 0.013) were significantly lower during the stress index as compared with the ARDSnet strategy–guided ventilation.Conclusions: Alveolar hyperinflation in patients with focal ARDS ventilated with the ARDSnet protocol is attenuated by a physiologic approach to PEEP setting based on the stress index measurement.
Cancer-Associated Cachexia and Underlying Biological Mechanisms
Authors: Vickie E. Baracos
Journal: Annual Review of Nutrition (2006)

Cancer metastases (spread to distant organs from the primary tumor site) signify systemic, progressive, and essentially incurable malignant disease. Anorexia and wasting develop continuously throughout the course of incurable cancer. Overall, in Westernized countries nearly exactly half of current cancer diagnoses end in cure and the other half end in death; thus, cancer-associated cachexia has a high prevalence. The pathophysiology of cancer-associated cachexia has two principal components: a failure of food intake and a systemic hypermetabolism/hypercatabolism syndrome. The superimposed metabolic changes result in a rate of depletion of physiological reserves of energy and protein that is greater than would be expected based on the prevailing level of food intake. These features indicate a need for nutritional support, metabolic management, and a clear appreciation of the context of life-limiting illness.
Role of hepatic autoregulation in defense against hypoglycemia in humans.
Authors: G Bolli, P De Feo, G Perriello, S De Cosmo, M Ventura, P Campbell, P Brunetti, J E Gerich
Journal: Journal of Clinical Investigation (1985)

To assess the role of hepatic autoregulation in defense against hypoglycemia, we compared the effects of complete blockade of glucose counterregulation with those of blockade of only neurohumoral counterregulation during moderate (approximately 50 mg/dl) and severe (approximately 30 mg/dl) hypoglycemia induced by physiologic hyperinsulinemia during subcutaneous infusion of insulin in normal volunteers. Compared with observations in control experiments, neurohumoral counterregulatory blockade (somatostatin, propranolol, phentolamine, and metyrapone), during which identical moderate hypoglycemia was achieved using the glucose clamp technique, resulted in suppressed glucose production (0.62 +/- 0.08 vs. 1.56 +/- 0.07 mg/kg per min at 12 h, P less than 0.01) and augmented glucose utilization (2.17 +/- 0.18 vs. 1.57 +/- 0.07 mg/kg per min at 12 h, P less than 0.01). Complete blockade of counterregulation (neurohumoral blockade plus prevention of hypoglycemia) did not further enhance the suppressive effects of insulin on glucose production. However, when severe hypoglycemia was induced during neurohumoral counterregulatory blockade, glucose production was nearly two times greater (1.05 +/- 0.05 mg/kg per min at 9 h) than that observed during complete counterregulatory blockade (0.58 +/- 0.08 mg/kg per min at 9 h, P less than 0.01) and that observed during mere neurohumoral blockade with moderate hypoglycemia (0.59 +/- 0.06 mg/kg per min at 9 h, P less than 0.01). These results demonstrate that glucose counterregulation involves both neurohumoral and hepatic autoregulatory components: neurohumoral factors, which require only moderate hypoglycemia for their activation, augment glucose production and reduce glucose utilization; hepatic autoregulation requires severe hypoglycemia for its activation and may thus serve as an emergency system to protect the brain when other counterregulatory factors fail to prevent threatening hypoglycemia.
Human endogenous retroviruses in health and disease
Authors: John M Grange, Bernd Krone, Klaus Kölmel
Journal: Journal of the Royal Society of Medicine (2005)

In his excellent and comprehensive review on human endogenous retroviruses (HERVs), Frank Ryan (December 2004, JRSM1) introduces a subject that could well become of central importance in 21st century medicine. To take one example, HERVs could provide the key to understanding how environmental changes associated with improved hygiene in the industrialized nations appear to be associated with the upsurge of certain diseases, notably autoimmunity, allergy and cancer.

In this context, the risk of childhood leukaemia has been linked to hygiene-related factors,2 and an extensive multicentre study showed that the risk of melanoma is reduced by certain vaccinations—BCG and vaccinia—as well as some uncommon but serious infectious diseases early in life.3,4 Furthermore, the prognosis of melanoma patients who had previously received BCG and/or vaccinia was significantly better than that of unvaccinated patients.5 There is evidence that many cases of melanoma are associated with the expression of HERV-encoded proteins that induce malignant change by altering the intracellular redox potential. The 'Achilles' heel' of this process is that a HERV-derived nonapeptide or decapeptide epitope, HERV-K-MEL, is expressed on the surface of the cell undergoing malignant transformation, in principle enabling it to be recognized by the immune system.6 We have shown that BCG, vaccinia and the agents causing the infectious diseases that afford protection against melanoma have analogues of the HERV-K-MEL epitope and we have therefore postulated that these vaccinations or infections generate populations of cross-reactive T cells able to engage in immunosurveillance and effect repair or destruction of melanocytes expressing this antigen.7

Accordingly, improvements in hygiene in the industrially developed countries resulting in less infectious diseases, together with the abandonment of vaccinia vaccination in all such countries and BCG in many, could be having a deleterious effect on the development of effective immunosurveillance against at least one type of cancer.

Further epidemiological studies to determine whether malignant disease other than melanoma and leukaemia are affected by hygiene-related factors, as well as laboratory studies to confirm the molecular basis of carcinogenesis and immunosurveillance, are required. Such studies could lead to the rational development of effective preventive and immunotherapeutic agents based on the relevant HERV-encoded epitopes or on micro-organisms, including some currently available vaccines, which induce cross-reacting immune responses to such epitopes.
Detection of arterial dilatation in the distal aorta-- lower limb arteries using continuous wave Doppler ultrasound
Authors: K N HUMPHRIES, T K HAMES, A D B CHANT
Journal: Cardiovascular Research (1982)

Continuous wave Doppler ultrasound techniques were used to obtain signals from the common femoral, popliteal, posterior tibial and dorsalis pedis arterial sites and the ankle systolic pressure indices in 54 patients with arteriographic, ultrasound "B"-Scan or surgical confirmation of arterial dilatation. The Doppler-shifted signals were spectrum-analysed and processed using a maximum frequency detector. The maximum frequency envelopes were examined retrospectively to determine whether there were any characteristics of the signals which could be used as diagnostic indicators of arterial dilatation. Ankle systolic pressure indices (ASPI), pulsatility index (PI), and delta, derived from the Laplacian transform method, were used in an attempt to quantify any changes produced by dilatation. The results indicate that characteristic and distinctive maximum frequency envelope signatures can be identified with arterial dilatation but that parameters such as ASPI and PI cannot distinguish these changes from the normal state and the Laplacian transform parameter "delta" places the dilatation cases in the minor stenosis category. However, generalised dilatation can be detected with a sensitivity of 85% if pattern recognition techniques are used.
What is the Best Standard for the Standard of Care in Clinical Research?
Authors: Rieke van der Graaf, Johannes J. M. van Delden
Journal: The American Journal of Bioethics (2009)

During the past decennium, one of the main issues discussed in research ethics has been focused on the care that should be provided to the control group in a clinical trial. This discussion is also called the standard of care debate. Current international research ethics guidelines contain a wide variety of standards for the standard of care--including the provision of the highest attainable, the best available, the best current, a proven, and an established effective treatment. In this article, we systematically review the currently used standards and argue that none of the current standards is adequate to serve as a universal standard for the standard of care. Alex London has made a substantial proposal for a universal standard, but universally adopting his standard is problematic. In this article, we propose a revised version of London's standard.
Ability of antigen-specific helper cells to effect a class-restricted increase in total Ig-secreting cells in spleens after immunization with the antigen.
Authors: Y J Rosenberg, J M Chiller
Journal: The Journal of Experimental Medicine (1979)

Immunization with antigens stimulates not only B lymphocytes secreting specific antibody but, in addition, results in the generation of very large numbers of splenic Ig-secreting cells which lack specificity for that antigen. The present report examined the nature of the antigens capable of eliciting this effect and the mechanisms whereby B cells could be nonspecifically activated. It is shown that the ability of T-dependent, but not T-independent antigens, to induce such increases requires the participation of T helper cells specific for the antigen so that any one antigen results in the activation of only a proportion of total B cells. Analysis of this nonspecific plaque-forming-cell response reveals that B cell activation is not random but occurs in a class-restricted manner. The magnitude of the increase and the isotype produced are shown to be characteristic of the immunizing antigen. Based on the data presented, the apparent nonspecific T-B collaboration can best be explained by invoking a second Ig-specific helper mechanism in which helper cells capable of recognizing determinants on Ig molecules, e.g. isotype or idiotype, cause the stimulation of B cells of any specificity providing they express that determinant.
THE FIRST IN HUMAN CLINICAL USE OF A COMBINED NEAR INFRARED SPECTROSCOPY AND INTRAVASCULAR ULTRASOUND CATHETER TO IDENTIFY AND CHARACTERISE INTRACORONARY PLAQUE (SAVOIR STUDY)
Authors: Evelyn Regar, Scot Garg, Martin van der Ent, Carl Schultz, Frits Mastik, Gijs van Soest, Jolanda J. Wentzel, Patrick W. Serruys, Mark A. Wilder, James E. Muller, Antonius FW van der Steen
Journal: Journal of the American College of Cardiology (2010)
Dutch experience of monitoring euthanasia
Authors: Bregje D Onwuteaka-Philipsen, Agnes van der Heide, Martien T Muller, Mette Rurup, Judith A C Rietjens, Jean-Jacques Georges, Astrid M Vrakking, Jacqueline M Cuperus-Bosma, Gerrit van der Wal, Paul J van der Maas
Journal: BMJ (2005)

<i>Doctors in the United Kingdom can accompany their patients every step of the way, up until the last. The law stops them helping their patients take the final step, even if that is the patient9s fervent wish. Next month9s debate in the House of Lords could begin the process of changing the law. To help doctors decide where they stand we publish a range of opinions</i>
THE NERVOUS AND CHEMICAL CONTROL OF SWEATING*
Authors: T. M. CHALMERS, C. A. KEELE
Journal: British Journal of Dermatology (1952)

Journal Article THE NERVOUS AND CHEMICAL CONTROL OF SWEATING Get access T. M. CHALMERS, T. M. CHALMERS Departments of Medicine and Pharmacology, Middlesex Hospital Medical School Search for other works by this author on: Oxford Academic Google Scholar C. A. KEELE C. A. KEELE Departments of Medicine and Pharmacology, Middlesex Hospital Medical School Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 64, Issue 2, 1 February 1952, Pages 43–54, https://doi.org/10.1111/j.1365-2133.1952.tb16160.x Published: 01 February 1952
Multicenter evaluation of mycobacteria growth indicator tube (MGIT) compared with the BACTEC radiometric method, BBL biphasic growth medium and Löwenstein—Jensen medium
Authors: Enrico Tortoli, Ferruccio Mandler, Mirella Tronci, Valeria Penati, Giovanni Sbaraglia, Danila Costa, Giuseppe Montini, Massimo Predominato, Renato Riva, Cristiana Passerini Tosi, Claudio Piersimoni, Pasquale Urbano
Journal: Clinical Microbiology and Infection (1997)
Phenotypic diversity and molecular mechanisms of airway smooth muscle proliferation in asthma
Authors: S.J. Hirst, T.R. Walker, E.r Chilvers
Journal: European Respiratory Journal (2000)

Chronic persistent asthma is characterized by poorly reversible airflow obstruction and airways inflammation and remodelling. Histopathological studies of airways removed at post mortem from patients with severe asthma reveal marked inflammatory and architectural changes associated with airway wall thickening. Increased airway smooth muscle content, occurring as a result of hyperplastic and/or hypertrophic growth, is believed to be one of the principal contributors to airway wall thickening. In recent years, significant advances have been made in elucidating the mediators and the intracellular pathways that regulate proliferation of airway smooth muscle. The contribution that smooth muscle makes to persistent airflow obstruction may not, however, be limited simply to its increased bulk within the airway wall. Interest is growing in the possibility that reversible phenotypic modulation and increased heterogeneity of airway smooth muscle function may also be a feature of the asthmatic airway. This review focuses on possible mechanisms controlling smooth muscle phenotype heterogeneity as well as on the mediators and intracellular pathways implicated in its cellular proliferation. Particular attention is paid to mechanisms involving activation of the extracellular signal regulated kinase-, protein kinase C- and phosphoinositide 3-kinase-dependent pathways, since these appear to be the major candidate second messenger pathways for G protein- and tyrosine kinase-coupled receptor-stimulated proliferation.
Maternal vitamin D intake and mineral metabolism in mothers and their newborn infants.
Authors: F Cockburn, N R Belton, R J Purvis, M M Giles, J K Brown, T L Turner, E M Wilkinson, J O Forfar, W J Barrie, G S McKay, S J Pocock
Journal: BMJ (1980)

Pregnant women receiving daily supplements of 400 IU (10 microgram) of vitamin D2 from the 12th week of pregnancy had plasma calcium concentrations higher at 24 weeks but similar at delivery to those in control pregnant women who did not receive the supplements. Infants of the women receiving the supplements had higher calcium, lower phosphorus, and similar magnesium concentrations on the sixth day of life and a lower incidence of hypocalcaemia than infants of the control women. Plasma concentrations of 25-hydroxycholecalciferol, which showed a seasonal variation, were higher in mothers and infants in the treated group. Cord-blood calcium, magnesium, phosphorus, and 25-hydroxycholecalciferol concentrations correlated with maternal values at delivery. Breast-fed infants had higher calcium and magnesium and lower phosphorus and 25-hydroxycholecalciferol concentrations than artificially fed infants. A defect of dental enamel was found in a high proportion of infants (many of whom had suffered from hypocalcaemia) born to the control women. These results suggest that vitamin D supplementation during pregnancy would be beneficial for mothers, whose intake from diet and skin synthesis is appreciably less than 500 IU of vitamin D daily.
Sleep apnoea, sleepiness, inflammation and insulin resistance in middle-aged males and females
Authors: Ilia Kritikou, Maria Basta, Alexandros N. Vgontzas, Slobodanka Pejovic, Duanping Liao, Marina Tsaoussoglou, Edward O. Bixler, Zacharias Stefanakis, George P. Chrousos
Journal: European Respiratory Journal (2013)

In obese males obstructive sleep apnoea (OSA) is associated with inflammation and insulin resistance; however, findings are confounded by adipose tissue, a hormone- and cytokine-secreting organ. Our goal was to examine whether in a relatively nonobese population, OSA is associated with sleepiness and inflammation/insulin resistance, and to assess the effects of a 2-month placebo-controlled continuous positive airway pressure (CPAP) use. 77 subjects, 38 middle-aged males and post-menopausal females with OSA and 39 male and female controls, were studied in the sleep laboratory for 4 nights. Measures of sleepiness (objective and subjective), performance, serial 24-h blood samples for interleukin (IL)-6, tumour necrosis factor receptor (TNFR)-1, leptin and adiponectin, and single samples for high-sensitivity C-reactive protein (hsCRP), fasting glucose and insulin levels were obtained. Apnoeic males were significantly sleepier and had significantly higher hsCRP, IL-6, leptin and insulin resistance than controls. Apnoeic females had significantly higher hsCRP; however, objective sleepiness, IL-6, TNFR-1, insulin resistance (Homeostatic Model Assessment index), leptin and adiponectin were similar to controls. CPAP improved subjective sleepiness, but no changes were observed in any of the biomarkers. In conclusion, OSA is associated with sleepiness, inflammation and insulin resistance, even in nonobese males, and this association is stronger in males than in females. Short-term CPAP does not improve the inflammatory/metabolic aberrations in OSA.
Ultrasound and Doppler-guided mini-surgery to treat midportion Achilles tendinosis: results of a large material and a randomised study comparing two scraping techniques
Authors: Håkan Alfredson
Journal: British Journal of Sports Medicine (2011)

Background Treatment based on ultrasound (US) and colour Doppler (CD) findings in midportion Achilles tendinosis has shown promising results. In a randomised study on a small patient material, similar short-term clinical results were demonstrated with surgery outside the tendon and sclerosing polidocanol injections, but surgical treatment led to a faster return to activity. Objective To evaluate the clinical results of US and CD-guided mini-surgery (scraping) outside the ventral tendon in a larger patient material and, in a randomised study, compare two different techniques for surgical scraping. Material and methods 103 patients (66 men, 37 women), mean age 43 years (range 24–77), with midportion tendinosis in 125 Achilles tendons were included. Patients from a large group (88 tendons), and a randomised study (37 tendons), were in local anaesthesia treated with a US and CD-guided new surgical approach outside the ventral tendon. All patients in the large group, and one arm of the randomised study, were treated open with a scalpel, while the other arm of the randomised study were treated percutaneously. Pain during Achilles tendon loading activity (Visual Analogue Scale (VAS)), and satisfaction with treatment, were evaluated. Results Before surgery, the mean VAS was 73. After surgery (follow-up mean 18 months, range 6–33), the mean VAS was 3 in 111 tendons (89%) from satisfied patients back in full Achilles tendon loading activity. In the randomised study, there were no significant differences in the results between open treatment with a scalpel and percutaneous treatment with a needle. Conclusions US and CD-guided scraping show good short-term results in midportion Achilles tendinosis.
Comparative Dynamics and Distribution of Influenza Drug Resistance Acquisition to Protein M2 and Neuraminidase Inhibitors
Authors: Vanessa Garcia, Stéphane Aris-Brosou
Journal: Molecular Biology and Evolution (2013)

Although efficient influenza vaccines are designed on a regular basis, the only protection of human populations against an unforeseen virus such as during the H1N1 pandemic in 2009 might be antiviral drugs. Adamantanes and neuraminidase inhibitors (Oseltamivir) represent two classes of such drugs that target the viral matrix protein 2 and neuraminidase, respectively. Although the emergence of resistance to both drugs has been described, the timing and spread of the acquisition of either single or dual resistances by different hosts is still unclear. Using a multilayered phylogenetic approach based on relaxed molecular clocks and large-scale maximum likelihood approaches, we show that Adamantane resistance evolved multiple times in various subtypes and hosts, possibly in breeding contexts (swine); and Oseltamivir resistance was also found in different subtypes and hosts, but its transmission is only sustained in humans. Furthermore, the dynamics of the emergence of antiviral resistance were examined for each drug. This showed that although the first mutations conferring resistance to Adamantanes precede US Food and Drug Administration (FDA) approval, general resistance emerged 15–38 years post-drug approval. This is in contrast to Oseltamivir resistance mutations that emerged at most 7 years after FDA approval of the drug. This study demonstrates the power of large-scale analyses to uncover and monitor the emergence dynamics of drug resistance.