tbuckley/cabot-search huggingface dataset:
Permissive Hypercapnia in Acute Respiratory Failure
Authors: Akhil Bidani
Journal: JAMA (1994)

To evaluate the potential efficacy of pressure limitation with permissive hypercapnia in the treatment of acute respiratory failure/adult respiratory distress syndrome on the basis of current theories of ventilator-induced lung injury, potential complications of systemic hypercarbia, and available human outcome studies.Articles were identified through MEDLINE, reference citations of published data, and consultation with authorities in their respective fields.Animal model experimentation and human clinical trials were selected on the basis of whether they addressed the questions of pressure limitation with or without hypercapnia, the pathophysiologic effects of hypercapnia, or the concept of ventilator-induced parenchymal lung injury. Frequently cited references were preferentially included.Data were analyzed with particular emphasis on obtaining the following variables from the clinical studies: peak inspiratory pressures, tidal volumes, minute ventilation, and PCO2. Quantitative aspects of respiratory physiology were used to analyze the theoretical effects of permissive hypercapnia on ventilatory requirements in normal and injured lungs.Extensive animal model data support the hypothesis that ventilator-driven alveolar overdistention can induce significant parenchymal lung injury. The heterogeneous nature of lung injury in adult respiratory distress syndrome, with its small physiologic lung volume, may render the lung susceptible to this type of injury through the use of conventional tidal volumes (10 to 15 mL/kg). Permissive hypercapnia is an approach whereby alveolar overdistention is minimized through either pressure or volume limitation, and the potential deleterious consequences of respiratory acidosis are accepted. Uncontrolled human trials of explicit or implicit permissive hypercapnia have demonstrated improved survival in comparison with models of predictive mortality.Avoidance of alveolar overdistention through pressure or volume limitation has significant support based on animal models and computer simulation. Deleterious effects of the associated hypercarbia in severe lung injury do not appear to be a significant limiting factor in preliminary human clinical trials. Although current uncontrolled studies suggest benefit, controlled trials are urgently needed to confirm these findings before adoption of the treatment can be endorsed.
In vivo murine model of acquired resistance in myeloma reveals differential mechanisms for lenalidomide and pomalidomide in combination with dexamethasone
Authors: E M Ocio, D Fernández-Lázaro, L San-Segundo, L López-Corral, L A Corchete, N C Gutiérrez, M Garayoa, T Paíno, A García-Gómez, M Delgado, J C Montero, E Díaz-Rodríguez, M V Mateos, A Pandiella, S Couto, M Wang, C C Bjorklund, J F San-Miguel
Journal: Leukemia (2014)
Abstract 5187: The membrane traffic regulator PACS-1 mediates genome stability at S-phase of the cell cycle.
Authors: Mysore S. Veena, Saroj K. Basak, Natarajan Venkatesan, Alborz Zinabadi, Laurel Thomas, Gary Thomas, Eri S. Srivatsan
Journal: Cancer Research (2013)

Abstract We previously mapped a 5.5 kb homozygous deletion in cervical cancer cell lines and primary tumors to chromosome 11q13 within the 1st intron of PACS-1 gene, which encodes a membrane traffic regulator. This deletion correlates with elevated expression of 120 kDa PACS-1 in primary cervical tumors compared to normal tissues as well as the expression of a 140 kDa immunoreactive isoform in the nucleus specifically in cervical cancer cell lines. Inspection of the PACS-1 mRNA sequence revealed a target site for miR449a, which mediates cell fate. Northern blot analysis showed miRNA 449a expression was reduced in cervical cancer cell lines and primary tumors suggesting that dysregulation of miRNA449a or the intronic deletion contributed to aberrant PACS-1 expression and that the increased expression of PACS-1 may mediate cell viability and cell cycle progression. Consistent with this possibility, siRNA knockdown of PACS-1 or increased expression of miR449a caused cells to accumulate in S phase and induced expression of γH2AX. By contrast, overexpression of PACS-1 or expression of antimiR 449a reduced γH2AX expression. Whereas PACS-1 mediates secretory pathway trafficking, the effect of PACS-1 expression on genome stability suggested PACS-1 might shuttle between the cytoplasm and the nucleus to mediate genome stability. Consistent with this possibility, the PACS-1 sequence contains canonical NLS and NES motifs. Indeed, confocal microscopy studies revealed GFP-tagged PACS-1 accumulated in the nucleus in a leptomycin B-dependent manner. We hypothesize that aberrant expression of PACS-1 in cervical cancer cells results in the stabilization and replication of rearranged DNA sequences leading to tumor development. Citation Format: Mysore S. Veena, Saroj K. Basak, Natarajan Venkatesan, Alborz Zinabadi, Laurel Thomas, Gary Thomas, Eri S. Srivatsan. The membrane traffic regulator PACS-1 mediates genome stability at S-phase of the cell cycle. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5187. doi:10.1158/1538-7445.AM2013-5187
Reversal of liver fibrosis in aryl hydrocarbon receptornull mice by dietary vitamin A depletion
Authors: Fausto Andreola, Diego F. Calvisi, Guillermo Elizondo, Sonia B. Jakowlew, Jennifer Mariano, Frank J. Gonzalez, Luigi M. De Luca
Journal: Hepatology (2004)

Aryl hydrocarbon receptor (AHR)-null mice display a liver fibrosis phenotype that is associated with a concomitant increase in liver retinoid concentration, tissue transglutaminase type II (TGaseII) activity, transforming growth factor beta (TGF beta) overexpression, and accumulation of collagen. To test the hypothesis that this phenotype might be triggered by the observed increase in liver retinoid content, we induced the condition of retinoid depletion by feeding AHR-null mice a vitamin A- deficient diet with the purpose to reverse the phenotype. Liver retinoid content decreased sharply within the first few weeks on the retinoid-deficient diet. Analysis of TGF beta 1, TGF beta 2, and TGF beta 3 expression revealed a reduction to control levels in the AHR -/- mice accompanied by parallel changes in TGaseII protein levels. In addition, we observed an increase in the TGF beta receptors, TGF beta RI and TGF beta RII, as well as in Smad4, and their reduction to wild-type mouse liver levels in AHR -/- mice fed the retinoid-deficient diet. Reduction of peroxisomal proliferator-activated receptor gamma (PPAR gamma) messenger RNA (mRNA) and protein levels in AHR -/- mice was consistent with the presence of hepatic stellate cell (HSC) activation and liver fibrosis. Vitamin A deficiency normalized PPAR gamma expression in AHR -/- mice. In conclusion, livers from AHR -/- mice fed the vitamin A-deficient diet showed a decrease in collagen deposition, consistent with the absence of liver fibrosis.
Letter: Glucagon therapy in acute pancreatitis.
Authors: R B Welbourn, A G Cox
Journal: BMJ (1974)

Lastly, we must point out that when hyperthermia is given together with cytotoxic drugs, as is current practice in Edinburgh, the combined treatment is associated with a definite mortality.It therefore appears to us that further controlled studies and consid_rably more data are required before hyperthermia can be accepted as having a significant role to play in cancer management.-We are, etc.,
A short case prolonged
Authors: R. Schiff
Journal: BMJ (2001)

As a senior house officer who had worked only at district general hospitals, I made my first attempt at the MRCP clinical examination at a prestigious London teaching hospital in a state of nervous dread. The “short cases”—when you are taken by two examiners and a nurse to a succession of patients—are seen as the most challenging part of the exam. Half way through my short cases, I was taken to see a frail elderly man and asked to examine his …
Quality of web based information on treatment of depression: cross sectional survey
Authors: K. M Griffiths
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objectives:</b> To evaluate quality of web based information on treatment of depression, to identify potential indicators of content quality, and to establish if accountability criteria are indicators of quality. <b>Design:</b> Cross sectional survey. <b>Data sources:</b> 21 frequently accessed websites about depression. <b>Main outcome measures:</b> (i) Site characteristics; (ii) quality of content—concordance with evidence based depression guidelines (guideline score), appropriateness of other relevant site information (issues score), and subjective rating of site quality (global score); and (iii) accountability—conformity with core accountability standards (Silberg score) and quality of evidence cited in support of conclusions (level of evidence score). <b>Results:</b> Although the sites contained useful information, their overall quality was poor: the mean guideline, issues, and global scores were only 4.7 (range 0-13) out of 43, 9.8 (6-14) out of 17, and 3 (0.5-7.5) out of 10 respectively. Sites typically did not cite scientific evidence in support of their conclusions. The guideline score correlated with the two other quality of content measures, but none of the content measures correlated with the Silberg accountability score. Content quality was superior for sites owned by organisations and sites with an editorial board. <b>Conclusions:</b> There is a need for better evidence based information about depression on the web, and a need to reconsider the role of accountability criteria as indicators of site quality and to develop simple valid indicators of quality. Ownership by an organisation and the involvement of a professional editorial board may be useful indicators. The study methodology may be useful for exploring these issues in other health related subjects.
Health-care information: access or implementation?
Authors: Haris Riaz, Muhammad Bilal Munir, Irbaz Bin Riaz
Journal: The Lancet Global Health (2013)

We read with great interest the Comment by Soumyadeep Bhaumik and colleagues (Sept, p e129) advocating universal access to healthcare information. The communication is important and timely; however, we believe that Bhaumik and colleagues have extrapolated their arguments and made disproportionate and dubious claims to support their viewpoint. For instance, on the basis of the study by Jafar and colleagues, the authors say that a quarter of Pakistani physicians are unaware of the hypertension guidelines “because they do not have adequate information about medicines” and thereby prescribe sedatives. Bhaumik and colleagues then reiterate that governments are legally obliged to ensure adequate access to health-care information. However, the gaps in the practices of Pakistani physicians appear to be because of lack of continued medical education sessions and a subdued tutorial system in medical schools (as elaborated by Jafar and colleagues) rather than inadequate access to health-care information. The National Family Health Survey of India emphasises the need to hydrate children who have diarrhoea, but there is no evidence to show that such an intervention in the home setting improves mortality. The eight out of ten practitioners who are unaware of childhood pneumonia symptoms in the developing world represent a similar example, whereby medical education seminars and rigorous tutorials can improve the situation. Thus, the major dilemma seems to be in the implementation of rather than access to health-care information. Although we strongly believe that health information should be available to all, several fundamental questions need to be answered. To ensure such a provision, funding needs to be made available. Where would this funding come from? These funds would be redirected from the health budget and research allocations. For example, in 2012, the research council in the UK spent US$161 million to provide gold open access in the UK. Whether cutting down on medical research (with a proven potential to save human lives) to ensure healthcare access to all is justifi ed poses great ethical considerations.
Patient-specific decisions about hormone replacement therapy in postmenopausal women
Authors: N. F. Col
Journal: JAMA (1997)

Objective.-To examine the effect of hormone replacement therapy on life expectancy in postmenopausal women with different risk profiles for heart disease, breast cancer, and hip fracture. Design.-Decision analysis using a Markov model. Published regression models were used to link risk factors to disease incidence and to estimate the lifetime risks of developing coronary heart disease (CHD), breast cancer, hip fracture, and endometrial cancer. The impact of hormone therapy on disease incidence was estimated from published epidemiologic studies. Setting.-Mathematical model applicable to primary care. Interventions.-Treatment with hormone replacement therapy or no hormone replacement therapy. Main Outcome Measure.-Life expectancy. Results.-Hormone replacement therapy should increase life expectancy for nearly all postmenopausal women, with some gains exceeding 3 years, depending mainly on an individual's risk factors for CHD and breast cancer. For women with at least 1 risk factor for CHD, hormone therapy should extend life expectancy, even for women having first-degree relatives with breast cancer. Women without any risk factors for CHD or hip fracture, but who have 2 first-degree relatives with breast cancer, however, should not receive hormone therapy. Conclusions.-The benefit of hormone replacement therapy in reducing the likelihood of developing CHD appears to outweigh the risk of breast cancer for nearly all women in whom this treatment might be considered. Our analysis supports the broader use of hormone replacement therapy.
Association between primary biliary cirrhosis and coeliac disease
Authors: W DICKEY, S A MCMILLAN
Journal: Gut (1998)

Editor,—We were interested to read the paper by Kingham and Parker ( Gut 1998; 42 :120–2) as we have recently reported a study exploring the association between primary biliary cirrhosis (PBC) and coeliac disease.1 

We tested serum samples from 57 patients with biopsy proved PBC for IgA class endomysial antibody. Six (11%) had endomysial antibody though only four agreed to undergo small bowel biopsy, which confirmed coeliac disease in all cases. As we have found endomysial antibody to have 100% specificity for coeliac disease,2 11% is likely to be the true prevalence of coeliac disease among our patients with PBC, which is over 15 times that of the general population in Northern Ireland.3 None of the four patients with biopsy proved coeliac disease showed improvement in liver biochemistry after exclusion of dietary gluten.

Our experience of screening patients with coeliac disease for PBC was less productive.4 Of the 129 patients with coeliac disease screened prospectively for liver disease at the time …
Annexin V is localized in association with Z-line of rat cardiac myocytes
Authors: L. Wang, Md.M. Rahman, H. Iida, T. Inai, S.-i. Kawabata, S. Iwanaga, Y. Shibata
Journal: Cardiovascular Research (1995)

Objective: The aim of this study was to characterize a 33-kDa protein (p33) isolated from bovine liver and to determine the subcellular localization of the protein in rat cardiocytes as well as in non-cardiac tissues. Methods: Cycles of calcium-induced precipitation coupled with EGTA-resolubilization were used to isolate crude annexins from bovine and rat tissues. Column chromatography was performed to purify the p33 from the crude annexins. The protein was identified as annexin V by partial amino acid sequence determination. Specificity of anti-annexin V antibody was examined by using Western blotting after one- or two-dimensional electrophoresis. For characterization of the protein, immunofluorescence microscopy and actin-binding assays were carried out. Results: Immunofluorescence microscopy showed that annexin V was stained as a striated pattern along myofibrils on frozen sections of both atria and ventricles of adult rats. The striations were seen more clearly in cultured rat atrial myocytes. Examination of doubly stained cardiocytes with anti-annexin V and anti-α-actinin by a confocal laser scanning microscope suggests that annexin V is localized in association with the Z-line of rat cardiac myocytes. We also found that annexin V was stained intensely in actin-rich regions of non-cardiac tissues such as bile canaliculi of rat liver and brush border-terminal web region in the epithelial cells of both small intestine and kidney proximal tubular cells. F-actin binding experiments revealed that annexin V failed to bind to F-actin directly in vitro. Conclusion: Our results suggest that annexin V is a new component of the Z-line in rat cardiocytes and might be involved in regulation of its organization.
Comparison of Intramuscular and Intravenous Recombinant Alpha-2 Interferon in Melanoma and Other Cancers
Authors: JOHN M. KIRKWOOD
Journal: Annals of Internal Medicine (1985)

In two phase I-II trials, 33 patients were given recombinant interferon alpha-2 daily at dosages of 3, 10, 30, 50, or 100 MU/d for up to 4 weeks by intramuscular or intravenous routes. Dose-limiting toxicities, including neutropenia, elevated hepatocellular enzyme levels, fatigue, and disturbed mentation, correlated with differing serum pharmacokinetics of interferon in the two trials. In the intramuscular study, dose-limiting toxicity occurred at all dosages greater than 10 MU/d, at a median of 6 to 9 days of treatment. In the intravenous dose-study, limiting toxicity was seen only at dosages of 100 MU/d, at a median of day 8. Twenty-three patients had metastatic melanoma and 4 had objective partial or complete responses at dosages of 10 to 50 MU/d in the first month. Two patients with complete responses are free of tumor after 2.5 years of follow-up. A fifth patient had delayed complete regression, requiring 1 year to achieve maximum response, but remains free of disease at 26 months since entry to the trial. Interferon had antitumor activity against melanoma by both routes tested, at dosages of 10 to 50 MU/d.
Effects of nitroprusside and dopamine on pulmonary arterial vasculature in children after cardiac surgery.
Authors: L W Stephenson, L H Edmunds, R Raphaely, D F Morrison, W S Hoffman, L J Rubis
Journal: Circulation (1979)

The hemodynamic effects of nitroprusside and dopamine were studied in 28 children early after intracardiac repair. Children were placed in six groups, five according to their anatomic lesion and one made up of those who had postoperative pulmonary artery hypertension, to evaluate the possible differences in response of the pulmonary arterial vasculature to the drugs. Seven children had repair of an atrial septal defect; six, repair of tetralogy of Fallot; four, repair of ventricular septal defect; five, surgery for pulmonary stenosis; one, closure of a left ventricular to right atrial tunnel; and five, postoperative pulmonary artery hypertension. Dopamine was infused at 8 microgram/kg/min, and nitroprusside at 3 microgram/kg/min. With dopamine, the heart rate increased an average of 10% and the cardiac index 11%; both increases were statistically significant. Changes in systemic and pulmonary vascular resistance, however, were not. With nitroprusside, the heart rate increased an average of 9% and the cardiac index 5%, while there was a significant decrease in both systemic (-20%) and pulmonary (-27%) vascular resistance. With the combination of dopamine and nitroprusside, both the cardiac index (+13%) and heart rate (+20%) increased significantly while systemic vascular resistance fell an average of 23% from control, and the pulmonary vascular resistance decreased 21%. Drug response among all five anatomic subgroups tended to be similar. We conclude that an afterload-reducing agent, such as nitroprusside and an inotropic drug such as dopamine, may have potential clinical advantages when used together in children providing heart rate does not become excessive.
Renin-Angiotensin System Gene Polymorphisms and Retinopathy in Chinese Patients With Type 2 Diabetes
Authors: G. Neil Thomas, Julian A.J.H. Critchley, Brian Tomlinson, Vincent T.F. Yeung, Dennis Lam, Clive S. Cockram, Juliana C.N. Chan
Journal: Diabetes Care (2003)

Diabetic eye disease is the leading cause of new cases of blindness in many developed countries, for which macular edema and proliferative retinopathy are major causes of loss of vision (1). Genetic studies have previously suggested that diabetic retinopathy is partly determined by genetic factors (2). Angiotensin II, produced locally within the retina, has potent hemodynamic and growth-promoting effects and stimulates ocular neovascularization (3,4). The presence of retinopathy is associated with an activated renin-angiotensin system (RAS) (5), and inhibition of the RAS significantly reduced the progression of retinopathy in nonhypertensive patients with type 1 diabetes (6). The ACE gene insertion/deletion (I/D) polymorphism has been reported to be associated with retinopathy in type 1 diabetic subjects, but the findings are heterogeneous …
Successful Treatment of Metachromatic Leukodystrophy Using Bone Marrow Transplantation of HoxB4 Overexpressing Cells
Authors: Noriko Miyake, Koichi Miyake, Stefan Karlsson, Takashi Shimada
Journal: Molecular Therapy (2010)

To evaluate the contribution of bone marrow (BM) cells to treat neurological disorders, we examined the effectiveness of BM cells expressing the homeobox B4 (HoxB4) gene to cure mice with metachromatic leukodystrophy (MLD) through transplantation. Increased number of donor cells was observed in brains of the MLD mice transplanted with HoxB4-transduced BM cells (B4MLD) in contrast to those transplanted with control green fluorescent protein (GFP)-transduced BM cells (MIGMLD). Immunohistochemical staining showed that most of the GFP(+) cells were Iba1(+) microglia. In addition, O4(+) oligodendrocytes were identified only in the B4MLD brains but not in the MIGMLD brain. Alcian blue staining showed that accumulation of sulfatide was dramatically reduced in brain tissue from B4MLD mice, and there was a corresponding improvement in the animals' ability to walk a balance beam 8 months after transplantation. Thus transplantation of BM cells overexpressing HoxB4 appears to effectively prevent the progression of MLD in this mouse model. These findings support the idea that hematopoietic stem cells (HSCs) transduced with a HoxB4 expression vector could be the useful carriers of therapeutic proteins into the brain for regeneration of oligodendrocytes to treat such demyelinating disorders as MLD, Krabbe disease, and multiple sclerosis.
Cytotoxic T lymphocytes directed to the preferentially expressed antigen of melanoma (PRAME) target chronic myeloid leukemia
Authors: Concetta Quintarelli, Gianpietro Dotti, Biagio De Angelis, Valentina Hoyos, Martha Mims, Luigia Luciano, Helen E. Heslop, Cliona M. Rooney, Fabrizio Pane, Barbara Savoldo
Journal: Blood (2008)
Number of breast cancer cases detected by screening has doubled in a decade in England
Authors: S. Mayor
Journal: BMJ (2009)

The routine breast screening programme in England is detecting twice as many cases of breast cancer each year as it did 10 years ago, the latest figures show.

A report from the NHS Information Centre says that the programme detected 14 110 cases of breast cancer in 2007-8, twice the number found in 1997-8, 6914 cases. More than three quarters (79%) of the cancers detected last year were invasive, and just over half of these (52%) were less than 15 mm …