tbuckley/cabot-search huggingface dataset:
Guidelines for the management of bullous pemphigoid
Authors: F. Wojnarowska, G. Kirtschig, A.S. Highet, V.A. Venning, N.P. Khumalo
Journal: British Journal of Dermatology (2002)

Summary These guidelines have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence‐based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines and a brief overview of epidemiological aspects, diagnosis and investigation. The guidelines reflect data available from Medline, Embase, the Cochrane library, literature searches and the experience of the authors of managing patients with bullous pemphigoid in special and general clinics for over 10 years. However, caution should be exercised in interpreting the data obtained from the literature because only six randomized controlled trials are available involving small groups of patients.
Isoprenylcysteine Carboxyl Methyltransferase Modulates Endothelial Monolayer Permeability
Authors: Qing Lu, Elizabeth O. Harrington, Chi-Ming Hai, Julie Newton, Megan Garber, Tetsuaki Hirase, Sharon Rounds
Journal: Circulation Research (2003)

RhoA and Rac1 regulate formation of stress fibers and intercellular junctions, thus modulating endothelial monolayer permeability. Posttranslational modifications of RhoA and Rac1 regulate enzyme activity and subcellular localization, resulting in altered cellular function. The role of RhoA and Rac1 carboxyl methylation in modulating endothelial monolayer permeability is not known. In this study, we found that inhibition of isoprenylcysteine- O -carboxyl methyltransferase (ICMT) with adenosine plus homocysteine or N -acetyl- S -geranylgeranyl- l -cysteine decreased RhoA carboxyl methylation, RhoA activity, and endothelial monolayer permeability, suggesting that RhoA carboxyl methylation may play a role in the ICMT-modulated monolayer permeability. Similar studies showed no effect of ICMT inhibition on Rac1 carboxyl methylation or localization. Bovine pulmonary artery endothelial cells (PAECs) stably overexpressing ICMT-GFP cDNA were established to determine if increased ICMT expression could alter RhoA or Rac1 carboxyl methylation, activation, and endothelial monolayer permeability. PAECs stably overexpressing ICMT demonstrated increased RhoA carboxyl methylation, membrane-bound RhoA, and RhoA activity. Additionally, PAECs stably overexpressing ICMT had diminished VE-cadherin and β-catenin at intercellular junctions, with resultant intercellular gap formation, as well as enhanced monolayer permeability. These effects were blunted by adenosine plus homocysteine and by inhibition of RhoA, but not by inhibition of Rac1. These results indicate that ICMT modulates endothelial monolayer permeability by altering RhoA carboxyl methylation and activation, thus changing the organization of intercellular junctions. Therefore, carboxyl methylation of RhoA may modulate endothelial barrier function.
High amino acid variability within the NS5A of hepatitis C virus (HCV) is associated with hepatocellular carcinoma in patients with HCV-1b–related cirrhosis
Authors: Mireia Giménez-Barcons, Sandra Franco, Yanette Suárez, Xavier Forns, Sergi Ampurdanès, Francesc Puig-Basagoiti, Alberto Sánchez-Fueyo, Josep-Maria Barrera, Josep-Maria Llovet, Jordi Bruix, José-María Sánchez-Tapias, Juan Rodés, Juan-Carlos Saiz
Journal: Hepatology (2001)

Interferon therapy may decrease the risk of hepatocellular carcinoma in patients with hepatitis C virus (HCV)–related liver cirrhosis. Interaction of the cellular protein kinase PKR with the PKR–binding domain (PKR–bd) of HCV–NS5A protein may affect cellular growth control and viral resistance to interferon therapy. Mutations within the PKR–bd, which comprises the interferon sensitivity determining region (ISDR), have been associated with interferon sensitivity. To determine whether or not there is an association between HCV heterogeneity and the presence of hepatocellular carcinoma, HCV–1b genomic regions were amplified and directly sequenced from serum samples obtained from 82 patients with liver cirrhosis, 53 with, and 29 without hepatocellular carcinoma. None of them had received antiviral therapy. When compared with the deduced consensus sequence, the median number of amino acid changes in the PKR–bd was higher among samples from patients with (4.22) than from those without hepatocellular carcinoma (1.62; P &lt; .001), and isolates with 3 or more amino acid changes were significantly more common among the former (60%) than among the later (6%, P &lt; .001). No such differences were observed in other viral regions, including Core, E2–HVR–1, E2–PePHD, NS3, and the 5′ and 3′ PKR–bd flanking regions. In addition, amino acid variation in viral regions other than HVR–1 did not accumulate over time in the analyzed sequential serum samples obtained from patients with or without hepatocellular carcinoma. Therefore, a mutated HCV–PKR–bd phenotype is very common in cirrhotic patients with hepatocellular carcinoma.
Acrodermatitis continua of Hallopeau in a patient with myelodysplastic syndrome
Authors: P.C.M. van der KERKHOF, P.M. STEIJLEN, R.A.P. RAYMAKERS
Journal: British Journal of Dermatology (1996)

Acrodermatitis continua of Hallopeau (ACH) is a rare manifestation of pustular psoriasis which may considerably disable affected patients. In this case report we confirm the efficacy of acitretin in the treatment of ACH and, in addition, describe the course of the myelodysplastic syndrome (MDS) from which the patient was suffering. During acitretin treatment, there was a transformation into acute myeloid leukaemia. We discuss the effect of retinoids on the bone marrow of normal subjects, patients with MDS, and patients with acute myeloid leukaemia. Our experience in the present case, and the information from the available literature, lead us to advise against the use of the aromatic retinoids, acitretin and etretinate, in patients with MDS. If such treatment is indicated, intensive haematological supervision is mandatory.
Regional Remodeling as the Cause of Late Stent Malapposition
Authors: Gary S. Mintz, Vivek M. Shah, Neil J. Weissman
Journal: Circulation (2003)

Background— Late stent malapposition (LSM) is only detected if intravascular ultrasound (IVUS) is performed at implantation and follow-up. We used a novel “regional” IVUS analysis to assess the mechanism of LSM. Methods and Results— Corresponding image slices on postimplantation and follow-up IVUS studies of 11 malapposed stents were identified and electronically rotated until they were aligned. The geometric center of the stent was identified, and the angle of late malapposition measured. Radii were drawn from this center through the transition points between complete apposition and LSM. These two circumferences were divided into equal arcs, and radii were drawn to the external elastic membrane (EEM). Measurements included EEM radius and circumference, plaque and media (P&amp;M=EEM minus stent radius) thickness and area, and stent-intima separation. Mean baseline EEM radius and P&amp;M thickness were similar in apposed and malapposed circumferences. At follow-up, mean EEM radius increase within the malapposed circumference (0.57±0.34 mm) was larger than within the apposed circumference (0.16±0.18 mm; P =0.0004). ΔEEM for each malapposed radius was greater than for each apposed radius ( P &lt;0.05 for all comparisons). Stent-intima separation correlated with EEM radius increase within the malapposed circumference ( r =0.83, P =0.0013). At follow-up, the mean P&amp;M thickness decreased in the malapposed circumference (−0.31±0.22 mm; P &lt;0.0001). However, the decrease in P&amp;M thickness in the malapposed circumference occurred because the same P&amp;M area was distributed over a larger circumference (4.1±1.6 mm to 5.4±3.0 mm; P =0.05), the result of positive remodeling. Conclusion— The main cause of LSM is a regional increase in EEM (regional positive remodeling).
The Effect of Hypoxia on the Heart and Pulmonary Arterioles of Mice
Authors: W. R. L. James, A. J. Thomas
Journal: Cardiovascular Research (1968)

Journal Article The Effect of Hypoxia on the Heart and Pulmonary Arterioles of Mice Get access W. R. L. James, W. R. L. James From the Department of Pathology, the Welsh National School of Medicine, and Llandough Hospital (The United Cardiff Hospitals), Penarth, Glamorgan Search for other works by this author on: Oxford Academic PubMed Google Scholar A. J. Thomas A. J. Thomas From the Department of Pathology, the Welsh National School of Medicine, and Llandough Hospital (The United Cardiff Hospitals), Penarth, Glamorgan Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 2, Issue 3, July 1968, Pages 278–283, https://doi.org/10.1093/cvr/2.3.278 Published: 01 July 1968 Article history Received: 07 December 1967 Published: 01 July 1968
Cost/utility ratio in chronic heart failure: comparison between heart failure management program delivered by day-hospital and usual care
Authors: Soccorso Capomolla, Oreste Febo, Monica Ceresa, Angelo Caporotondi, Giampaolo Guazzotti, Maria Teresa La Rovere, Marina Ferrari, Francesca Lenta, Sonia Baldin, Chiara Vaccarini, Marco Gnemmi, GianDomenico Pinna, Roberto Maestri, Paola Abelli, Sandro Verdirosi, Franco Cobelli
Journal: Journal of the American College of Cardiology (2002)
A self-management programme of activity coping and education (SPACE) for COPD: Patients perspective
Authors: Lindsay Apps, Samantha Harrison, Jo Williams, Mick Steiner, Mike Morgan, Sally Singh
Journal: European Respiratory Journal (2012)

Introduction : We have developed a self-management programme 'SPACE for COPD' and as part of it's wider evaluation a nested qualitative study was conducted exploring patient's perspectives of self-management before and after completing the programme.

Method: Semi-structured interviews were carried out with participants randomised to 'SPACE for COPD' prior to starting SPACE and 6 weeks later. Interviews were transcribed verbatim and thematic analysis was performed supported by NVivo(Version 8). A third researcher analysed a sub-group of interviews to ensure agreement over themes.

Results: Four main themes describe patient's beliefs and expectations prior to starting 'SPACE for COPD' - role of self-management, barriers to exercise, facilitators to exercise, role of healthcare professionals. Patients had differing perspectives of self-management and were focussed on maintaining current activity levels. All desired more knowledge about COPD.

Analysis of follow-up interviews identified themes - changing perceptions, the impact of SPACE for COPD, barriers to exercise, facilitators to exercise, the manual as a motivator . The experience of using SPACE was positive and many described the motivating effect of the manual. Education was an important component of the intervention and self-management skills were demonstrated. At baseline patients anticipating positive results had been encouraged to initiate exercise and at follow-up when positive results had been observed, this further reinforced exercise behaviour. Barriers to exercise identified at baseline remained at follow-up.

Conclusion: ' SPACE for COPD' has enabled patients to learn more about their condition and become more active.
pp60c-Src Phosphorylates and Activates Vacuolar Protein Sorting 34 to Mediate Cellular Transformation
Authors: Dianne S. Hirsch, Yi Shen, Milos Dokmanovic, Wen Jin Wu
Journal: Cancer Research (2010)

Vacuolar protein sorting 34 (VPS34) contributes to the regulation of the mammalian target of rapamycin complex 1/S6 kinase 1 pathway downstream of nutrient signaling. However, intracellular mechanisms leading to VPS34 activation remain unclear. Here, we report that Src directly phosphorylates VPS34, and that this phosphorylation activates VPS34 lipid kinase activity, leading to Src-Y527F-mediated cellular transformation. Silencing endogenous VPS34 specifically inhibits Src-Y527F-induced colony formation in soft agar, but not Ras-G12V-induced colony formation. We have identified two novel hVPS34 mutations, which either eliminate lipid kinase activity (kinase-dead mutant) or reduce tyrosine phosphorylation by Src-Y527F. When kinase-dead mutant of hVPS34 is stably expressed in Src-Y527F-transformed cells, transformation activities are blocked, indicating that the lipid kinase activity of hVPS34 is essential for Src-mediated cellular transformation. Furthermore, stable expression of this hVPS34 kinase-dead mutant causes an increased number of binucleate and multinucleate cells, suggesting that the kinase activity of hVPS34 is also required for cytokinesis. Moreover, when the hVPS34 mutant that has reduced tyrosine phosphorylation by Src is stably expressed in Src-Y527F-transformed cells, Src-Y527F-stimulated colony formation is also reduced. Data presented here provide important evidence that VPS34 lipid kinase activity could be positively regulated by Src-mediated tyrosine phosphorylation in mammalian cells. This finding highlights a previously unappreciated relationship between VPS34, a class III phosphatidylinositol-3-kinase, and Src non-receptor tyrosine kinase. Additionally, we find that the levels of VPS34 expression and tyrosine phosphorylation are correlated with the tumorigenic activity of human breast cancer cells, indicating that Src to VPS34 signaling warrants further investigation as a pathway contributing to the development and progression of human cancers.
Sublingual versus oral immunotherapy for peanut-allergic children: A retrospective comparison
Authors: Stacy J. Chin, Brian P. Vickery, Michael D. Kulis, Edwin H. Kim, Pooja Varshney, Pamela Steele, Janet Kamilaris, Anne M. Hiegel, Suzanna K. Carlisle, P. Brian Smith, Amy M. Scurlock, Stacie M. Jones, A. Wesley Burks
Journal: Journal of Allergy and Clinical Immunology (2013)
“Damm Sokkor”: Factors Associated With the Quality of Care of Patients With Diabetes
Authors: Hugh Alberti, Nessiba Boudriga, Mounira Nabli
Journal: Diabetes Care (2007)

To identify the organizational, physician, and patient factors associated with the quality of care of patients with diabetes in a low-/middle-income country.Data from 2,160 randomly selected patients with diabetes were extracted from the manual medical records of a nationwide sample of 48 randomly selected health centers. Physician and organizational characteristics were collected from national reports, questionnaires, interviews, and observation at the centers. Univariate and multivariate regression analyses were undertaken to identify associations with four quality-of-care scores, based on processes and intermediate outcomes of care and 53 potential explanatory factors.The mean age of the study population was 62.4 years, mean duration of diabetes was 8.4 years, 62% were female, and 94% had type 2 diabetes. In the final multivariate models, factors independently and significantly associated with higher process-of-care scores were regional affluence, doctor motivation, and the use of chronic disease clinics (P < 0.05). Health centers with younger patients and increased availability of medication were independently and significantly associated with improved outcome-of-care scores (P < 0.05). The final models of the four quality-of-care scores explained 55-71% of the variations in scores.Use of chronic disease clinics, availability of medication, and possibly doctor motivation appear to be the most strongly related modifiable factors influencing diabetes care. These findings will be used to develop and implement culturally appropriate quality improvement interventions to improve the quality of diabetes care. We recommend our findings be taken into account in other low-/middle-income countries.
Electrophysiological identification of alpha- and beta-intercalated cells and their distribution along the rabbit distal nephron segments.
Authors: S Muto, K Yasoshima, K Yoshitomi, M Imai, Y Asano
Journal: Journal of Clinical Investigation (1990)

By cable analysis and intracellular microelectrode impalement in the in vitro perfused renal tubule, we identified alpha- and beta-intercalated (IC) cells along the rabbit distal nephron segments, including the connecting tubule (CNT), the cortical collecting duct (CCD), and the outer medullary collecting duct in the inner stripe (OMCDi). IC cells were distinguished from collecting duct (CD) cells by a relatively low basolateral membrane potential (VB), a higher fractional apical membrane resistance, and apparent high Cl- conductances of the basolateral membrane. Two functionally different subtypes of IC cells in the CCD were identified based on different responses of VB upon reduction of the perfusate Cl- from 120 to 12 mM: the basolateral membrane of beta-IC cells was hyperpolarized, whereas that of alpha-IC cells was unchanged. This is in accord with the hypothesis that the apical membrane of beta-IC cells contains some Cl(-)-dependent entry processes, possibly a Cl-/HCO3- exchanger. Further characterization of electrical properties of both subtypes of IC cells were performed upon lowering bath or perfusate Cl- from 120 to 12 mM, and raising bath or perfusate K+ from 5 to 50 mM. A 10-fold increase in the perfusate K+ had no effect on VB in both subtypes of IC cells. Upon abrupt changes in Cl- or K+ concentration in the bath, a large or a small depolarization of the basolateral membrane, respectively, was observed in both subtypes of IC cells. The electrical properties of alpha- and beta-IC cells were similar among the distal nephron segments, but their distribution was different: in the CNT, which consists of IC cells and CNT cells, 97.3% (36/37) of IC cells were of the beta type. In the CCD, which consists of IC cells and CD cells, 79.8% (79/99) of IC cells were of the beta-type, whereas in the OMCDi 100% (19/19) were of the alpha type, suggesting that the beta type predominates in the earlier and the alpha type in the later segment.
Diagnosis of coronary artery disease by controlled coronary vasodilation with adenosine and thallium-201 scintigraphy in patients unable to exercise.
Authors: M S Verani, J J Mahmarian, J B Hixson, T M Boyce, R A Staudacher
Journal: Circulation (1990)

Pharmacological coronary vasodilation induced by dipyridamole is often used in association with thallium-201 myocardial scintigraphy to evaluate the presence and prognostic significance of coronary artery disease. Because dipyridamole acts by blocking the cellular uptake of adenosine, we investigated the usefulness of direct intravenous administration of adenosine, a physiological substance with an exceedingly short (less than 2 seconds) plasma half-life, to induce maximal controlled coronary vasodilation in conjunction with 201Tl scintigraphy. We studied 89 patients (44 men and 45 women; mean age, 64 +/- 10 years [SD]) who were unable to perform an exercise test and were referred for evaluation of suspected coronary artery disease. The intravenous infusion of adenosine began at an initial rate of 50 micrograms/kg/min and was increased by stepwise increments every minute to a maximal rate of 140 micrograms/kg/min. 201Tl was injected intravenously after 1 minute at the highest infusion rate, followed by immediate and delayed (4 hour) tomographic imaging. At the highest infusion rate, adenosine induced a significant (p less than 0.001) decrease in systolic (8.7 +/- 19.3 mm Hg) and diastolic (6.7 +/- 9.4 mm Hg) blood pressures as well as a significant (p = 0.0001) increase in heart rate (14.5 +/- 11.0 beats/min). Side effects occurred in 83% of the patients but resolved spontaneously within 1 or 2 minutes after discontinuing the adenosine infusion. Chest, throat, or jaw pain were the most frequent symptoms and occurred in 57% of the patients. Headache (35%) and flush (29%) were also common. Ischemic electrocardiographic changes occurred in 12% of the patients, and transient first-degree atrioventricular block occurred in 10%.(ABSTRACT TRUNCATED AT 250 WORDS)
Type A Aortic Dissection in Marfan Syndrome
Authors: Bartosz Rylski, Joseph E. Bavaria, Friedhelm Beyersdorf, Emanuela Branchetti, Nimesh D. Desai, Rita K. Milewski, Wilson Y. Szeto, Prashanth Vallabhajosyula, Matthias Siepe, Fabian A. Kari
Journal: Circulation (2014)

Background— Data on outcomes after Stanford type A aortic dissection in patients with Marfan syndrome are limited. We investigated the primary surgery and long-term results in patients with Marfan syndrome who suffered aortic dissection. Methods and Results— Among 1324 consecutive patients with aortic dissection type A, 74 with Marfan syndrome (58% men; median age, 37 years [first and third quartiles, 29 and 48 years]) underwent surgical repair (85% acute dissections; 68% DeBakey I; 55% composite valved graft, 30% supracoronary ascending replacement, 15% valve-sparing aortic root replacement; 12% total arch replacement; 3% in-hospital mortality) at 2 tertiary centers in the United States and Europe over the past 25 years. The rate of aortic reintervention with resternotomy was 24% (18 of 74) and of descending aorta (thoracic+abdominal) intervention was 30% (22 of 74) at a median follow-up of 8.4 years (first and third quartiles, 2.2 and 12.7 years). Freedom from need for aortic root reoperation in patients who underwent primarily a composite valved graft or valve-sparing aortic root replacement procedure was 95±3%, 88±5%, and 79±5% and in patients who underwent supracoronary ascending replacement was 83±9%, 60±13%, 20±16% at 5, 10, and 20 years. Secondary aortic arch surgery was necessary only in patients with initial hemi-arch replacement. Conclusions— Emergency surgery for type A dissection in patients with Marfan syndrome is associated with low in-hospital mortality. Failure to extend the primary surgery to aortic root or arch repair leads to a highly complex clinical course. Aortic root replacement or repair is highly recommended because supracoronary ascending replacement is associated with a high need (&gt;40%) for root reintervention.
Seasonal Variation of Fibrinogen in Dipper and Nondipper Hypertensive Patients
Authors: Ramón C. Hermida, Carlos Calvo, Diana E. Ayala, José E. López, José R. Fernández, Artemio Mojón, María J. Domínguez, Manuel Covelo
Journal: Circulation (2003)

A seasonal variation with higher values in winter has been previously reported in plasma fibrinogen, a recognized marker of the potential risk of myocardial infarction and stroke. The lack of nocturnal decline in blood pressure has also been associated with an increase in cardiovascular events. Accordingly, we have compared the yearly variation of plasma fibrinogen in dipper and nondipper hypertensive patients.We studied 1006 stage 1 to 2 hypertensive patients (482 men and 524 women, 53.0+/-13.4 years of age). Blood pressure was measured every 20 minutes during the day and every 30 minutes at night for 48 consecutive hours. Physical activity was simultaneously evaluated at 1-minute intervals with a wrist actigraph. A blood sample was collected on the same day before starting blood pressure monitoring. The circannual variation of fibrinogen was established for all patients as well as for subgroups of dippers and nondippers (n=513; nocturnal blood pressure decline <10%) by multiple-component analysis. For the whole group of patients, fibrinogen was characterized by a highly significant seasonal variation (P<0.001) with a mean value of 318 mg/dL, double circannual amplitude (extent of predictable change along the year) of 40 mg/dL, and time of peak value in February. Throughout the year, the nondippers showed higher plasma fibrinogen levels than did the dippers (P<0.001).The elevated plasma fibrinogen levels in nondipper patients appear to be directly related to their increased risk in vascular events, which are more prominent during the late winter months.