tbuckley/cabot-search huggingface dataset:
Informed Consent, Cultural Sensitivity, and Respect for Persons
Authors: Lawrence O. Gostin
Journal: JAMA (1995)

The doctrine of informed consent to medical treatment or research is grounded in the ethical principle of respect for persons that regards individuals as autonomous agents "capable of deliberation about personal goals and of acting under the direction of such deliberation."<sup>1</sup>International ethical codes and human rights law appear to accept informed consent as a universal expression of respect for persons. The Nuremberg Code, Helsinki IV, and the Council of International Organizations of Medical Sciences' ethical guidelines focus on the need for full disclosure to enable individuals to make free and informed decisions. Informed consent is also thought to be incorporated into the right to security of the person recognized in the International Bill of Human Rights. The right to autonomy or self-determination, then, is broadly perceived to be a morally necessary method of demonstrating genuine respect for human integrity. See also pp 820 and 826. But is the
Cost-analysis of high-dose chemotherapy and peripheral blood stem-cell support in patients with solid tumors
Authors: M.P. Astier, J.I. Mayordomo, J.M. Abad, L.I. Gómez, A. Tres
Journal: Annals of Oncology (2000)

The use of High-dose chemotherapy (HDC) with peripheral blood stem cells (PBSC) rescue in the treatment of solid tumors is controversial, and may be an important determinant of HDC and PBSC use in the future. Until the use of these procedures is proven through disease-free survival and overall survival compared with standard-dose chemotherapy, the associated cost is also under discussion.We evaluate 27 consecutive patients with solid tumors who underwent HDC and PBSC rescue, through an accurate review of medical records and cost estimate for each patient.Median age was 45 years. Fifteen had breast cancer, six non-Hodgkin's lymphoma and six other solid tumors. The mean hospital length of stay was 21 days and mean cost was 21,445 US dollars (21,232 euro). Mean cost was clearly lower for the 9 patients treated within phase III trials, 17,571 US dollars (17,747 euro) than for the remaining 18 patients, treated in phase I-II trials, 22,747 US dollars (22,975 euro) (P < 0.001). The distribution of costs shows that wages and pharmacy account for 72% of total cost. The distribution of pharmacy costs per patient shows that chemotherapy (56% of pharmacy costs) and antibiotics (26%) account for most of the cost of medication.Our cost estimates agree with those of most countries with national health insurance programs, and are lower than those from the USA. As wages and pharmacy account for more than 70% of the costs, the great different among the costs estimates compared are due essentialy to doctors fees or salary and drugs utilization. Anyway, taking HDC with PBSC rescue as a model for a therapy that is more aggressive than standard, and that is associated to a possible survival improvement in indications such as relapsed high-grade non-Hodgkin's lymphoma, an adequate cost analysis is crucial both to measure cost-effectiveness and to establish payment to health care providers.
Further Observations on the Electrolytic Dispersion of Tumours
Authors: J. Althaus
Journal: BMJ (1875)

To pursue the reflections which the facts and considerations I have so imperfectly stated suggest, into all their bearings and applications, would be a task beyond my present power, and beyond your patience.I must be content with indicating a few general conclusions.x.There exists in pregnancy a peculiar state of the blood, an in- creased arterial tension, and a disposition to phlebectasis, general or affecting particular vascular regions or systems, which may, under cer- tain circumstances, lead to hzemorrhagic effusions.2. These hremorrhagic effusions may be salutary or conservative.llemorrhages from the mucous membranes, by relieving excess of ten- sion, may avert internal hoemorrhages or abortions, or that oppression of the kidneys which results in albuminuria and eclampsia.3. Iemni)rrhages from the uterus inducingr abortion may, in the sIme way, avert more serious mischief, especially albuminuria and CO.ampsia.4. I'ut these hzemorrhages, although we may recognise in them a c nservative purpose, easily exceed physiological or useful limits, and n-ay themselves induce danger by anremia.5. Hxmorrhages, from whatever part, occurring in women within the period of sexual life, should suggest the probability of pregnancy, or of menstrual-disorder.6.The haemorrhages described should be taken as indications to -edluce vascular tension.This may be done in some cases by bleed- ing, general or topical; by purgatives; by salines ; by abstinence from
Increased ocular levels of IGF-1 in transgenic mice lead to diabetes-like eye disease
Authors: Jesús Ruberte, Eduard Ayuso, Marc Navarro, Ana Carretero, Víctor Nacher, Virginia Haurigot, Mónica George, Cristina Llombart, Alba Casellas, Cristina Costa, Assumpció Bosch, Fatima Bosch
Journal: Journal of Clinical Investigation (2004)

IGF-1 has been associated with the pathogenesis of diabetic retinopathy, although its role is not fully understood. Here we show that normoglycemic/normoinsulinemic transgenic mice overexpressing IGF-1 in the retina developed most alterations seen in human diabetic eye disease. A paracrine effect of IGF-1 in the retina initiated vascular alterations that progressed from nonproliferative to proliferative retinopathy and retinal detachment. Eyes from 2-month-old transgenic mice showed loss of pericytes and thickening of basement membrane of retinal capillaries. In mice 6 months and older, venule dilatation, intraretinal microvascular abnormalities, and neovascularization of the retina and vitreous cavity were observed. Neovascularization was consistent with increased IGF-1 induction of VEGF expression in retinal glial cells. In addition, IGF-1 accumulated in aqueous humor, which may have caused rubeosis iridis and subsequently adhesions between the cornea and iris that hampered aqueous humor drainage and led to neovascular glaucoma. Furthermore, all transgenic mice developed cataracts. These findings suggest a role of IGF-1 in the development of ocular complications in long-term diabetes. Thus, these transgenic mice may be used to study the mechanisms that lead to diabetes eye disease and constitute an appropriate model in which to assay new therapies.
A Low–Glycemic Index Meal and Bedtime Snack Prevents Postprandial Hyperglycemia and Associated Rises in Inflammatory Markers, Providing Protection From Early but Not Late Nocturnal Hypoglycemia Following Evening Exercise in Type 1 Diabetes
Authors: Matthew D. Campbell, Mark Walker, Michael I. Trenell, Emma J. Stevenson, Daniel Turner, Richard M. Bracken, James A. Shaw, Daniel J. West
Journal: Diabetes Care (2014)

To examine the influence of the glycemic index (GI) of foods consumed after evening exercise on postprandial glycemia, metabolic and inflammatory markers, and nocturnal glycemic control in type 1 diabetes.On two evenings (∼1700 h), 10 male patients (27 ± 5 years of age, HbA1c 6.7 ± 0.7% [49.9 ± 8.1 mmol/mol]) were administered a 25% rapid-acting insulin dose with a carbohydrate bolus 60 min before 45 min of treadmill running. At 60 min postexercise, patients were administered a 50% rapid-acting insulin dose with one of two isoenergetic meals (1.0 g carbohdyrate/kg body mass [BM]) matched for macronutrient content but of either low GI (LGI) or high GI (HGI). At 180 min postmeal, the LGI group ingested an LGI snack and the HGI group an HGI snack (0.4 g carbohdyrate/kg BM) before returning home (∼2300 h). Interval samples were analyzed for blood glucose and lactate; plasma glucagon, epinephrine, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α); and serum insulin, cortisol, nonesterified fatty acid, and β-hydroxybutyrate concentrations. Interstitial glucose was recorded for 20 h postlaboratory attendance through continuous glucose monitoring.Following the postexercise meal, an HGI snack induced hyperglycemia in all patients (mean ± SD glucose 13.5 ± 3.3 mmol/L) and marked increases in TNF-α and IL-6, whereas relative euglycemia was maintained with an LGI snack (7.7 ± 2.5 mmol/L, P < 0.001) without inflammatory cytokine elevation. Both meal types protected all patients from early hypoglycemia. Overnight glycemia was comparable, with a similar incidence of nocturnal hypoglycemia (n = 5 for both HGI and LGI).Consuming LGI food with a reduced rapid-acting insulin dose following evening exercise prevents postprandial hyperglycemia and inflammation and provides hypoglycemia protection for ∼8 h postexercise; however, the risk of late nocturnal hypoglycemia remains.
Vitamin C in the human stomach: relation to gastric pH, gastroduodenal disease, and possible sources.
Authors: H J O'Connor, C J Schorah, N Habibzedah, A T Axon, R Cockel
Journal: Gut (1989)

Fasting gastric juice pH and concentrations of vitamin C in gastric aspirate and plasma were measured in 73 patients undergoing endoscopy. Vitamin C concentrations were significantly lower in those with hypochlorhydria (pH greater than 4; n = 23) compared with those with pH less than or equal to 4 (p less than 0.005) and there was a significant correlation between gastric juice and plasma concentrations (p = 0.002). Patients with normal endoscopic findings had significantly higher intragastric concentrations of vitamin C than those with gastric cancer (p less than 0.001), pernicious anaemia (p less than 0.005), gastric ulcer (p less than 0.01), duodenal ulcer (p less than 0.05), or after gastric surgery (p less than 0.01). There was a strong trend (0.05 less than p less than 0.1) towards lower intragastric concentrations of vitamin C in patients with chronic atrophic gastritis. In vitro, vitamin C concentrations remained stable in acidic but fell significantly over 24 hours in alkaline gastric aspirate. Gastric secretory studies in five volunteers showed that vitamin C concentrations increased significantly after intramuscular pentagastrin. These findings suggest that the low fasting levels of vitamin C in hypochlorhydric gastric juice may be caused by chemical instability and that vitamin C may be secreted by the human stomach.
Cause of Complete Atrioventricular Block After Percutaneous Aortic Valve Implantation
Authors: Raul Moreno, David Dobarro, Esteban López de Sá, Mario Prieto, Carmen Morales, Luis Calvo Orbe, Isidro Moreno-Gomez, David Filgueiras, Angel Sanchez-Recalde, Guillermo Galeote, Santiago Jiménez-Valero, José-Luis Lopez-Sendon
Journal: Circulation (2009)
Flexible endoscopy of paediatric airways
Authors: F. Midulla, J. de Blic, A. Barbato, A. Bush, E Eber, S Kotecha, E Haxby, C Moretti, P Pohunek, F Ratjen
Journal: European Respiratory Journal (2003)

Paediatric fibreoptic bronchoscopy is used for ever wider indications, and increasingly used in many contexts, including paediatric and neonatal intensive care. The report of this Task Force contains an overview on the current applications of paediatric bronchoscopy. The report discusses the facilities and equipment needed for the procedure, including the newly developed bronchoscopes which are allowing intervention even in very small children. The indications of both flexible and rigid bronchoscopes in the context of newer and smaller flexible endoscopic equipment are also considered. The care of the instruments, including disinfection and sterilisation, is fully documented. Patient management is described, including the relative merits of conscious sedation and general anaesthesia, as well as special settings for the procedure, including the needs in intensive care. Special procedures, increasingly performed bronchoscopically are described. These include bronchoalveolar lavage, endobronchial and transbronchial biopsy, laser therapy, bronchography, and endoscopic intubation and drug therapy. Finally, neonatal bronchoscopy is discussed, and the ethics of bronchoscopic procedures, including bronchoscopic research in children. Advances in instrumentation, and also improved anaesthetic techniques, allow fibreoptic bronchoscopy to be safely performed in even very small, sick infants, provided proper precautions are taken.
Functional Diversification During Evolution of the Murine α1-Proteinase Inhibitor Family: Role of the Hypervariable Reactive Center Loop
Authors: Karen W Barbour, Richard L Goodwin, François Guillonneau, Yanping Wang, Heinz Baumann, Franklin G Berger
Journal: Molecular Biology and Evolution (2002)

α1-Proteinase inhibitor (α1-PI) is a member of the serpin superfamily of serine proteinase inhibitors that are involved in the regulation of a number of proteolytic processes. α1-PI, like most serpins, functions by covalent binding to, and inhibition of, target proteinases. The interaction between α1-PI and its target is directed by the so-called reactive center loop (RCL), an ∼20 residue domain that extends out from the body of the α1-PI polypeptide and determines the inhibitor's specificity. Mice express at least seven closely related α1-PI isoforms, encoded by a family of genes clustered at the Spi1 locus on chromosome 12. The amino acid sequence of the RCL region is hypervariable among α1-PIs, a phenomenon that has been attributed to high rates of evolution driven by positive Darwinian selection. This suggests that the various isoforms are functionally diverse. To test this notion, we have compared the proteinase specificities of individual α1-PIs from each of the two mouse species. As predicted from the positive Darwinian selection hypothesis, the various α1-PIs differ in their ability to form covalent complexes with serine proteinases, such as elastase, trypsin, chymotrypsin, and cathepsin G. In addition, they differ in their binding ability to proteinases in crude snake venoms. Importantly, the RCL region of the α1-PI polypeptide is the primary determinant of isoform-specific differences in proteinase recognition, indicating that hypervariability within this region drives the functional diversification of α1-PIs during evolution. The possible physiological benefits of α1-PI diversity are discussed.
Gene Genealogies, Cryptic Species, and Molecular Evolution in the Human Pathogen Coccidioides immitis and Relatives (Ascomycota, Onygenales)
Authors: Vassiliki Koufopanou, Austin Burt, Timothy Szaro, John W. Taylor
Journal: Molecular Biology and Evolution (2001)

Previous genealogical analyses of population structure in Coccidioides immitis revealed the presence of two cryptic and sexual species in this pathogenic fungus but did not clarify their origin and relationships with respect to other taxa. By combining the C. immitis data with those of two of its closest relatives, the free-living saprophytes Auxarthron zuffianum and Uncinocarpus reesii, we show that the C. immitis species complex is monophyletic, indicating a single origin of pathogenicity. Cryptic species also were found in both A. zuffianum and U. reesii, indicating that they can be found in both pathogenic and free-living fungi. Our study, together with a few others, indicates that the current list of known fungal species might be augmented by a factor of at least two. However, at least in the C. immitis, A. zuffianum, and U. reesii complexes, cryptic species represent subdivisions at the tips of deep monophyletic clades and thus well within the existing framework of generic classification. An analysis of silent and expressed divergence and polymorphism values between and within the taxa identified by genealogical concordance did not reveal faster evolution in C. immitis as a consequence of adaptation to the pathogenic habit, nor did it show positive Darwinian evolution in a region of a dioxygenase gene (tcrP gene coding for 4-HPPD) known to cause antigenic responses in humans. Instead, the data suggested relative stasis, indicative of purifying selection against mostly deleterious mutations. Two introns in the same gene fragment were considerably more divergent than exons and were unalignable between species complexes but had very low polymorphism within taxa.
3D contrast-enhanced lung perfusion MRI is an effective screening tool for chronic thromboembolic pulmonary hypertension: results from the ASPIRE Registry
Authors: Smitha Rajaram, Andrew J Swift, Adam Telfer, Judith Hurdman, Helen Marshall, Eleanor Lorenz, David Capener, Christine Davies, Catherine Hill, Charlie Elliot, Robin Condliffe, Jim M Wild, David G Kiely
Journal: Thorax (2013)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism potentially curable by surgery. Perfusion scintigraphy is currently advocated as the imaging modality of choice to exclude CTEPH due to its high sensitivity. We have evaluated the diagnostic utility of lung perfusion MRI.Consecutive patients attending a pulmonary hypertension referral centre undergoing lung perfusion MRI, perfusion scintigraphy, CT pulmonary angiography (CTPA) and right heart catheterisation within 14 days were identified.Of 132 patients, 78 were diagnosed as having CTEPH. Lung perfusion MRI correctly identified 76 patients as having CTEPH with an overall sensitivity of 97%, specificity 92%, positive predictive value 95% and negative predictive value 96% compared with perfusion scintigraphy (sensitivity 96%, specificity 90%) and CTPA (sensitivity 94%, specificity 98%). No cases of surgically accessible CTEPH were missed with either modality.Lung perfusion MRI has high sensitivity equivalent to perfusion scintigraphy in diagnosing CTEPH but does not require ionising radiation, making it an attractive initial imaging modality to assess patients with suspected CTEPH.
Extensive fixed drug eruption due to lamotrigine
Authors: C-J. Hsiao, J.Y-Y. Lee, T-W. Wong, H-M. Sheu
Journal: British Journal of Dermatology (2001)

Sir, Numerous drugs are known to provoke fixed drug eruption (FDE). To the best of our knowledge, this is the first report of FDE due to lamotrigine (Lamictal®), confirmed by patch testing. Lamotrigine is a novel antiepileptic drug not chemically related to other anticonvulsants in current use.1 It is a triazine derivative1 that blocks voltage‐dependent sodium channels, thereby preventing excitatory neurotransmitter release.2 Lamotrigine is indicated for adjunctive therapy in the treatment of complex and simple seizures that are refractory to other antiepileptic drugs.1 A 54‐year‐old man with a 30‐year history of schizophrenia and a 1‐year history of spinocerebellar degeneration was admitted for sudden onset of a rash that had been widespread for 2 days. He had been given sodium valproate (Depakine®) 200 mg twice daily for one and a half months for complex partial seizures. Because of poor control of the seizures, lamotrigine 50 mg twice daily was added 3 days prior to admission. Ten hours after the first dose, he developed extensive, 2–5 cm, red to violaceous, round patches and plaques with central erosions or vesicular changes. These started at the periorbital area and spread to the trunk and extremities (Fig. 1a). Extensive FDE due to lamotrigine was suspected. Three years previously, he had had one episode of a generalized eruption and erosion of the glans penis after taking carbamazepine (Tegretol®) 200 mg three times daily for 8 days. There was no specific diagnosis of Stevens–Johnson syndrome (SJS) or FDE made regarding the eruption at that time. After that episode, he had not been given carbamazepine. According to his medical records, for schizophrenia and constipation he had been taking haloperidol 1 mg or 5 mg as required, baclofen 10 mg three times daily, trihexyphenidyl hydrochloride 5 mg three times daily and bisacodyl 10 mg before sleep.
Function of the p55 tumor necrosis factor receptor "death domain" mediated by phosphatidylcholine-specific phospholipase C.
Authors: T Machleidt, B Krämer, D Adam, B Neumann, S Schütze, K Wiegmann, M Krönke
Journal: The Journal of Experimental Medicine (1996)

Tumor necrosis factor (TNF) is a pleiotropic mediator of inflammation that has been implicated in the pathogenesis of devastating clinical syndromes including septic shock. We have investigated the role of a TNF-responsive phosphatidylcholine-specific phospholipase C (PC-PLC) for the cytotoxic and proinflammatory activity of TNF. We show here that the cytotoxicity signaled for by the so-called "death domain" of the p55 TNF receptor is associated with the activation of PC-PLC. The xanthogenate tricyclodecan-9-yl (D609), a specific and selective inhibitor of PC-PLC, blocked the cytotoxic action of TNF on L929 and Wehi164 cells. In vivo, D609 prevented both adhesion molecule expression in the pulmonary vasculature and the accompanying leukocyte infiltration in TNF-treated mice. More strikingly, D609 protects BALB/c mice from lethal shock induced either by TNF, lipopolysaccharide, or staphylococcal enterotoxin B. Together these findings imply PC-PLC as an important mediator of the pathogenic action of TNF, suggesting that PC-PLC may serve as a novel target for anti-inflammatory TNF antagonists.
Protective immune responses against West Nile virus are primed by distinct complement activation pathways
Authors: Erin Mehlhop, Michael S. Diamond
Journal: The Journal of Experimental Medicine (2006)

West Nile virus (WNV) causes a severe infection of the central nervous system in several vertebrate animals including humans. Prior studies have shown that complement plays a critical role in controlling WNV infection in complement (C) 3−/− and complement receptor 1/2−/− mice. Here, we dissect the contributions of the individual complement activation pathways to the protection from WNV disease. Genetic deficiencies in C1q, C4, factor B, or factor D all resulted in increased mortality in mice, suggesting that all activation pathways function together to limit WNV spread. In the absence of alternative pathway complement activation, WNV disseminated into the central nervous system at earlier times and was associated with reduced CD8+ T cell responses yet near normal anti-WNV antibody profiles. Animals lacking the classical and lectin pathways had deficits in both B and T cell responses to WNV. Finally, and somewhat surprisingly, C1q was required for productive infection in the spleen but not for development of adaptive immune responses after WNV infection. Our results suggest that individual pathways of complement activation control WNV infection by priming adaptive immune responses through distinct mechanisms.
Loss of Programmed cell death 4 (Pdcd4) associates with the progression of ovarian cancer
Authors: Na Wei, Stephanie S Liu, Thomas HY Leung, Kar F Tam, Xiao Y Liao, Annie NY Cheung, Karen KL Chan, Hextan YS Ngan
Journal: Molecular Cancer (2009)

Abstract Background Programmed cell death 4 (Pdcd4) is a novel tumour suppressor and originally identified as a neoplastic transformation inhibitor. The aim of this study was to investigate the expression, prognostic significance and potential function of Pdcd4 in ovarian cancer. Results The expression of Pdcd4 was examined in 30 normal ovarian tissues, 16 borderline and 93 malignant ovarian tissues. A continuous down regulation of Pdcd4 expression in the sequence of normal, borderline and malignant tissues was observed. The expressions of Pdcd4 in both ovarian borderline tissues and carcinomas were significantly lower than the expression in normal ovarian tissues (p &lt; 0.001). Furthermore, patients with lower Pdcd4 expressions were found to have shorter disease-free survival (p = 0.037). The expression of Pdcd4 was also assessed by immunohistochemical analysis in 13 ovarian normal tissues and 44 carcinomas. Different subcellular localization of Pdcd4 was observed in normal compared to malignant cells. Predominant nuclear localization of Pdcd4 was found in normal ovarian tissues while ovarian carcinomas showed mainly cytoplasmic localization of Pdcd4. Conclusion Our study demonstrated that the loss of Pdcd4 was a common abnormality at molecular level in ovarian cancer and it might be a potential prognostic factor in ovarian cancer patients.