tbuckley/cabot-search huggingface dataset:
VATS Versus Open Surgery for Lung Cancer Resection: Moving Beyond the Incision
Authors: Aaron M. Cheng, Douglas E. Wood
Journal: Journal of the National Comprehensive Cancer Network (2015)

Surgery remains the primary therapy in the treatment of early-stage lung cancer. Traditionally, anatomic resection via open thoracotomy has been the conventional approach, but as experience with minimally invasive lung surgery has increased, video-assisted thoracoscopic surgical (VATS) lobectomy is being performed more commonly for treatment of lung cancer. Proponents of VATS have argued that thoracoscopic resection for lung cancer is not only safe but is also superior to the open approach. VATS enthusiasts even have proposed that this approach should be the standard of care and a metric for quality in lung cancer surgery. Such zeal for promoting a "preferred" technique, however, obscures focus from other time-proven, but perhaps less fashionable, factors that have a tremendous impact on quality and lung cancer outcomes, namely cancer staging and quality of cancer surgery. Rather than debate incisions, thoracic surgeons should advocate for specialty care and surgical quality that assures the best short- and long-term outcomes for patients, regardless of the surgical approach.
The β1 subunit of the Ca2+-sensitive K+ channel protects against hypertension
Authors: Mark T Nelson, Adrian D Bonev
Journal: Journal of Clinical Investigation (2004)

Previous animal studies have demonstrated that the loss of the beta(1) subunit of the large-conductance Ca(2+)-activated K(+) (BK) channel leads to hypertension. A new study demonstrates that a gain in beta(1) subunit function is associated with protection against diastolic hypertension in humans, underscoring the importance of the beta(1) subunit and the BK channel in the regulation of vascular resistance.
Impaired Microvascular Vasodilatory Function in 3-Month-Old Infants of Low Birth Weight
Authors: Kah Lay Goh, Angela C. Shore, Michael Quinn, John E. Tooke
Journal: Diabetes Care (2001)

OBJECTIVE—Low birth weight has been linked to an increased risk of type 2 diabetes and cardiovascular disease in adult life. The fetal insulin hypothesis proposed that a genetic predisposition to insulin resistance may also influence vascular development. Therefore, impaired vascular function may be an intrinsic abnormality in low–birth weight infants that antedates clinical features of the insulin resistance syndrome. RESEARCH DESIGN AND METHODS—Two groups of 3-month-old term infants were included in the study: 17 infants of lowest quartile birth weight (LQBW) and 21 infants of highest quartile birth weight (HQBW). Three aspects of skin microvascular function were examined; response to local heating, response to acetylcholine iontophoresis, and capillary density. RESULTS—Median (interquartile ranges) birth weights of the LQBW and HQBW infants were 3,140 g (2,738–3,254) and 3,920 g (3,750–4,020), respectively. Skin maximal hyperemic response to local heating was 2.14 V (1.68–2.30) in the LQBW group vs. 2.44 V (1.96–2.90) in the HQBW group (P = 0.020), and the endothelium-dependent vasodilatory response was 1.03 V (0.62–1.32) in the LQBW group vs. 0.78 V (0.45–1.32) in the HQBW group (P = 0.297). Capillary density in the LQBW and HQBW groups were 46.3 mm−2 (40.1–53.7) and 44.1 mm−2 (41.7–56.0), respectively (P = 0.736). CONCLUSIONS—Skin maximal hyperemic response was lower in LQBW infants, although no reduction in capillary density or defect in endothelium-dependent vasodilatation was observed. Such a lower maximal hyperemic response in early life in LQBW subjects who are at risk for type 2 diabetes and cardiovascular disease supports the hypothesis that impaired microvascular function is an early antecedent to diabetes in later life.
Uric acid transport and disease
Authors: Alexander So, Bernard Thorens
Journal: Journal of Clinical Investigation (2010)

Uric acid is the metabolic end product of purine metabolism in humans. It has antioxidant properties that may be protective but can also be pro-oxidant, depending on its chemical microenvironment. Hyperuricemia predisposes to disease through the formation of urate crystals that cause gout, but hyperuricemia, independent of crystal formation, has also been linked with hypertension, atherosclerosis, insulin resistance, and diabetes. We discuss here the biology of urate metabolism and its role in disease. We also cover the genetics of urate transport, including URAT1, and recent studies identifying SLC2A9, which encodes the glucose transporter family isoform Glut9, as a major determinant of plasma uric acid levels and of gout development.
Ultrastructural demonstration of T cells in cutaneous tissue sections using specific anti-human T cell antiserum
Authors: D. M. MACDONALD, D. SCHMITT, D. GERMAIN, J. THIVOLET
Journal: British Journal of Dermatology (1978)

The presence of T lymphocytes in the situ in cutaneous infiltrates of contact dermatitis and lichen planus has been demonstrated by an immunoelectronmicroscope technique. A specific anti-human T cell antiserum labelled with peroxidase-conjugated anti-immunoglobulin serum was used to reveal the specific human T lymphocyte antigen (HTLA) which was visualized ultrastructurally. This technique shows that labelling is limited to the surface membrane and allows study of the in situ interrelationship of T cells.
Investigation of the possible association between nosocomial candiduria and candidaemia
Authors: C.A. Binelli, M.L. Moretti, R.S. Assis, N. Sauaia, P.R. Menezes, E. Ribeiro, D.C.P. Geiger, Y. Mikami, M. Miyaji, M.S. Oliveira, A.A. Barone, A.S. Levin
Journal: Clinical Microbiology and Infection (2006)
Preβ1-HDL Concentration Is a Predictor of Carotid Atherosclerosis in Type 2 Diabetic Patients
Authors: Satoshi Hirayama, Takashi Miida, Osamu Miyazaki, Yoshifusa Aizawa
Journal: Diabetes Care (2007)

Pre-β1-HDL is a minor HDL subfraction that stimulates cholesterol efflux from cell membranes (1,2). However, the fasting preβ1-HDL concentration is elevated in patients with coronary artery disease (CAD), hyperlipidemia, and obesity and in hemodialysis patients (3–7). We examined whether the preβ1-HDL concentration is elevated in type 2 diabetic patients and whether elevated preβ1-HDL concentration is a predictor of carotid atherosclerosis.

We measured the preβ1-HDL concentration in 30 patients with type 2 diabetes (mean ± SD age 58.5 ± 12.3 years, 13 men and 17 women) and in 30 age- and sex-matched healthy control subjects. We excluded patients receiving hypolipidemic agents and those with renal dysfunction. The diabetic group had a long duration of disease (9.9 ± 8.6 years), high A1C levels (10.4 ± 2.0%), and high BMI (26.1 ± 6.5 kg/m2). The preβ1-HDL in frozen plasma, pretreated with sucrose solution for stabilization, was measured using an immunoassay (8). In the diabetic group, we evaluated the severity of carotid atherosclerosis using ultrasonography with a 7.5-MHz probe. The greatest intima-media thickness (max IMT) and plaque score were determined as previously reported (9).

The diabetic group had higher triglyceride concentrations than the control subjects (166.9 ± 138.4 vs. 90.9 ± 28.6 mg/dl, P < 0.01), while the two groups did not differ significantly in total cholesterol (215.1 ± 49.9 vs. 201.0 ± 20.9 mg/dl), LDL cholesterol (135.9 ± 37.1 vs. 125.3 ± 17.9 mg/dl), or HDL cholesterol (55.5 ± …
The impact of rheumatoid factor and ACPA on bone erosion in rheumatoid arthritis
Authors: Carolin Hecht, Georg Schett, Stephanie Finzel
Journal: Annals of the Rheumatic Diseases (2014)

The impact of rheumatoid factor and ACPA on bone erosion in rheumatoid arthritisIn their letter, Van Steenbergen and colleagues present data on the radiographic progression in rheumatoid arthritis (RA) patients stratified for anti-citrullinated protein antibody (ACPA) and rheumatoid factors (RFs) in two different patient cohorts. 1 They show that the presence of ACPA is associated with a more pronounced progression of structural damage when scoring conventional radiographs by the standardised Sharp-van der Heijde method. 1 These findings (i) underline previous radiographic findings that ACPAs are associated with radiographic progression in RA, 2 (ii) stay in line with the known pathophysiologic function of ACPA in osteoclast differentiation 3 and (iii) also support our high-resolution CT data showing the relevance of ACPA in bone erosions. 4he authors, however, found no difference in radiographic progression whether RF was present or not.At first sight, this finding seems to contradict our recently published highresolution CT data, where we could dissect the role of ACPA and RF on bone erosion showed that RF also affects bone loss in RA patients in addition to ACPA. 4 However, limitations of conventional radiographs are likely being a simple explanation for the fact that Van Steenbergen and colleagues were not able to detect differences between RF-positive and RF-negative individuals.Based on the 2D nature and its limited resolution, a substantial number of erosions escape their detection by conventional radiography when compared with high-resolution CT. 5 The latter technique with a resolution of slightly more than 100 mm can even detect very small lesions with a volume of less than 1 mm 3 , independent at which anatomical site they are localised.Hence, we believe that the detection threshold with respect to lesion size and localisation for conventional radiography is simply too high to pick up the more subtle differences in erosions; one can accurately pick up by high-resolution CT.This situation creates an 'insufficient' signal-to noise ratio to detect a certain process, which cannot simply be compensated by increasing the sample size or including more joints without changing the method itself.Hence, the intrinsic limitations of the method will be still present even when increasing the number of measurements.Although we think that the aforementioned point sufficiently explains these differences between our approach and the one by Van Steenbergen and colleagues, another important factor may additionally affect the results presented in this letter: RF, in contrast to ACPA, is much more linked to disease activity.Hence, effective treatment of RA, which for sure has been initiated in the patients included in these two cohorts, may have cleared the RF-immune complexes in these patients over time and level out the differences between the two groups of ACPA-positive RA patients.
Diagnosis of human preimplantation embryo viability
Authors: David K. Gardner, Marcos Meseguer, Carmen Rubio, Nathan R. Treff
Journal: Human Reproduction Update (2015)

BACKGROUNDTransfer of more than a single embryo in an IVF cycle comes with the finite possibility of a multiple gestation. Even a twin pregnancy confers significant risk to both mother and babies. The move to single-embryo transfer for all patients will be greatly facilitated by the ability to quantify embryo viability. Developments in time-lapse incubation systems have provided new insights into the developmental kinetics of the human preimplantation embryo. Advances in molecular methods of chromosomal analysis have created platforms for highly effective screening of biopsied embryos, while noninvasive analysis of embryo physiology reveals more about the embryo than can be determined by morphology alone.
The clinical genetics of hidradenitis suppurativa revisited
Authors: J.M. Von Der Werth, H.C. Williams, J.A. Raeburn
Journal: British Journal of Dermatology (2000)

Journal Article The clinical genetics of hidradenitis suppurativa revisited Get access J.M. Von Der Werth, J.M. Von Der Werth Department of Dermatology, Queen’s Medical Centre, Nottingham NG7 2UH, U.K. Dr J.M.von der Werth, Consultant Dermatologist, County Hospital Lincoln, Lincoln LN2 5QY, U.K. Search for other works by this author on: Oxford Academic Google Scholar H.C. Williams, H.C. Williams Department of Dermatology, Queen’s Medical Centre, Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.A. Raeburn J.A. Raeburn Centre for Medical Genetics, City Hospital Nottingham, Nottingham NG5 1PB, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 5, 1 May 2000, Pages 947–953, https://doi.org/10.1046/j.1365-2133.2000.03476.x Published: 01 May 2000
Stabilizing mutation of CTNNB1/beta-catenin and protein accumulation analyzed in a large series of parathyroid tumors of Swedish patients
Authors: Peyman Björklund, Daniel Lindberg, Göran Åkerström, Gunnar Westin
Journal: Molecular Cancer (2008)

Abstract Background Aberrant accumulation of β-catenin plays an important role in a variety of human neoplasms. We recently reported accumulation of β-catenin in parathyroid adenomas from patients with primary hyperparathyroidism (pHPT). In CTNNB1 exon 3, we detected a stabilizing mutation (S37A) in 3 out of 20 analyzed adenomas. The aim of the present study was to determine the frequency and zygosity of mutations in CTNNB1 exon 3, and β-catenin accumulation in a large series of parathyroid adenomas of Swedish patients. Results The mutation S37A (TCT &gt; GCT) was detected by direct DNA sequencing of PCR fragments in 6 out of 104 sporadic parathyroid adenomas (5.8%). Taking our previous study into account, a total of 9 out of 124 (7.3%) adenomas displayed the same mutation. The mutations were homozygous by DNA sequencing, restriction enzyme cleavage, and gene copy number determination using the GeneChip 500 K Mapping Array Set. All tumors analyzed by immunohistochemistry, including those with mutation, displayed aberrant β-catenin accumulation. Western blotting revealed a slightly higher expression level of β-catenin and nonphosphorylated active β-catenin in tumors with mutation compared to those without. Presence of the mutation was not related to distinct clinical characteristics. Conclusion Aberrant accumulation of β-catenin is very common in parathyroid tumors, and is caused by stabilizing homozygous mutation in 7.3% of Swedish pHPT patients.
Acute monocytic or myelomonocytic leukemia with balanced chromosome translocations to band 11q23 after therapy with 4-epi-doxorubicin and cisplatin or cyclophosphamide for breast cancer.
Authors: J Pedersen-Bjergaard, T C Sigsgaard, D Nielsen, S B Gjedde, P Philip, M Hansen, S O Larsen, M Rørth, H Mouridsen, P Dombernowsky
Journal: Journal of Clinical Oncology (1992)

PURPOSE To report five cases of acute monocytic or myelomonocytic leukemia after chemotherapy with 4-epidoxorubicin for breast cancer and to evaluate the risk of leukemia after the use of this drug. PATIENTS AND METHODS One hundred fifty-seven patients with advanced breast cancer were randomized to either 4-epi-doxorubicin plus cisplatin or 4-epi-doxorubicin alone. An additional 203 patients were treated prospectively with 4-epi-doxorubicin alone. All were observed closely for leukemic complications. RESULTS Three patients from the randomized study developed leukemia; all were in the subgroup of 74 patients who received 4-epi-doxorubicin plus cisplatin, whereas no leukemia was observed among the remaining 83 patients in the randomized study or among the additional 203 patients who were treated prospectively with 4-epi-doxorubicin alone (P = .023, log-rank test). In the subgroup of 74 patients who were treated with 4-epi-doxorubicin plus cisplatin, the cumulative risk of leukemia was 16.0% +/- 9.9% (mean +/- SE) 33 months after the start of therapy; the relative risk was 668 (95% confidence interval [Cl], 138 to 1,953). Two other cases of acute monocytic and myelomonocytic leukemia were observed after 4-epi-doxorubicin plus alkylating agents were administered for breast cancer. Three of five cases of leukemia presented balanced translocations to chromosome band 11q23 and two, loss of a whole chromosome no. 7 or its long arm. CONCLUSIONS 4-epi-doxorubicin is leukemogenic, and the leukemias are often acute monocytic or myelomonocytic with balanced chromosome translocations to band 11q23, such as in the leukemias after therapy with the epipodophyllotoxins. Furthermore, our results suggest a synergistic effect in leukemogenesis between 4-epi-doxorubicin targeting DNA-topoisomerase II and directly genotoxic drugs such as cisplatin or alkylating agents.
Rate-dependent changes in intraventricular conduction produced by procainamide in anesthetized dogs. A quantitative analysis based on the relation between phase 0 inward current and conduction velocity.
Authors: S Nattel, W Jing
Journal: Circulation Research (1989)

Antiarrhythmic drug effects on maximal upstroke velocity (Vmax) are frequency dependent, which implies that the effects of these drugs on conduction should also be rate dependent. Previous in vivo studies have been limited by assumptions about unchanging propagation pathway, and by the empirical use of a first-order recovery model. To explore time-dependent antiarrhythmic drug-induced conduction slowing in vivo, we used 56-electrode epicardial mapping in chloralose-anesthetized dogs with formalin-induced atrioventricular block. Interval-dependent changes in conduction time were assessed under control conditions and then after three loading and maintenance infusions of procainamide. Under control conditions, epicardial activation time (86 +/- 26 msec at a basic cycle length of 300 msec) was unchanged (87 +/- 24 msec) by pauses up to 6.6 +/- 2.2 seconds. Procainamide caused conduction slowing that dissipated as a function of recovery interval, with 94 +/- 6% recovery over a maximum pause of 6.7 +/- 1.5 seconds, but did not alter activation pattern. Drug-induced changes in conduction were evaluated by use of a mathematical model assuming phase 0 inward current proportional to conduction velocity squared. Conduction changes were better fitted by this "quadratic model" (least sum of squared deviations 3.9 x 10(-3) by mapping in five dogs, 2.7 x 10(-2) by use of QRS duration in nine dogs) than by a monoexponential model (sum of squared deviations 5.7 x 10(-3) by mapping, 3.4 x 10(-2) with QRS; p less than 0.01 vs. quadratic model for each). As predicted by theoretical analysis, recovery time constants from the quadratic model were similar to time constants for procainamide-induced changes in Vmax in vitro, and significantly longer than values obtained with a monoexponential model. Drug-induced changes in QRS duration were highly correlated with simultaneous changes measured by epicardial mapping (r = 0.95, p less than 0.001), indicating that QRS duration is a valid index of drug effects on ventricular conduction. We concluded that procainamide causes interval-dependent changes in ventricular conduction in vivo that are consistent with a proportional relation between phase 0 inward current and the square of conduction velocity. These observations have important potential implications for the dose-dependent and heart rate-dependent effects of antiarrhythmic drugs.
Relation between a career and family life for English hospital consultants: qualitative, semistructured interview study
Authors: C. Dumelow
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To explore the relation between work and family life among hospital consultants and their attitude towards the choices and constraints that influence this relation. <b>Design:</b> Qualitative study of consultants9 experiences and views based on tape recorded semistructured interviews. <b>Setting:</b> Former South Thames health region in southeast England. <b>Participants:</b> 202 male and female NHS hospital consultants aged between 40 to 50 years representing all hospital medical specialties. <b>Results:</b> Three types of relation between work and family life (career dominant, segregated, and accommodating) were identified among hospital consultants. Most consultants had a segregated relation, although female consultants were more likely than male consultants to have a career dominant or an accommodating relation. Many male consultants and some female consultants expressed considerable dissatisfaction with the balance between their career and family life. A factor influencing this dissatisfaction was the perceived lack of choice to spend time on their personal or family life, because of the working practices and attitudes within hospital culture, if they wanted a successful career. <b>Conclusions:</b> Consultants are currently fitting in with the profession rather than the profession adapting to enable doctors to have fulfilling professional and personal lives. Current government policies to increase the medical workforce and promote family friendly policies in the NHS ought to take account of the need for a fundamental change in hospital culture to enable doctors to be more involved in their personal or family life without detriment to their career progress.
1059-21 Skeletal myoblast transplantation through a catheter-based coronary sinus approach: An effective means of improving function of infarcted myocardium
Authors: Camille Brasselet, Claire Carrion, Miguel Morichetti, Emmanuel Messas, Patrick Bruneval, Jean-Thomas Vilquin, Antoine Lafont, Albert A Hagège, Philippe Menasché, Michel Desnos
Journal: Journal of the American College of Cardiology (2004)
Loss of myocardial LIF receptor in experimental heart failure reduces cardiotrophin-1 cytoprotection. A role for neurohumoral agonists?
Authors: N LOPEZ, N VARO, J DIEZ, M FORTUNO
Journal: Cardiovascular Research (2007)

Cardiomyocyte loss is involved in the transition from compensatory left ventricular hypertrophy (LVH) to heart failure (HF). Our aim was to investigate the status of the leukaemia inhibitory factor receptor (LIFR)/gp130 survival pathway and its cytoprotective activity in intact cardiac tissue and in cardiomyocytes obtained from adult spontaneously hypertensive rats (SHR) with LVH (non-failing SHR) and from aged SHR with overt HF (failing SHR).Cardiac morphometry was assayed by planimetry in an image analysis system. mRNA and protein expression were quantified by real time RT-PCR and Western blotting. Receptors were localized by immunocytochemistry. Trypan blue staining, TUNEL, and MTT cell viability assays were employed to study the cytoprotective activity of cardiotrophin-1 (CT-1) in isolated caridomyocytes.Compared to non-failing SHR, failing SHR exhibited enhanced myocardial cell death (p<0.01) demonstrated by the increase in Bax/Bcl-2 ratio, caspase-3 activation and poly (ADP-ribose) polymerase (PARP) fragmentation. Failing SHR had a 7-fold diminished expression (p<0.01) of LIFR, no changes in gp130, and 1.6-fold increased myocardial expression (p<0.01) of CT-1. In cardiomyocytes isolated from non-failing SHR, recombinant CT-1 inhibited apoptotic and non-apoptotic cell death induced by angiotensin II or hydrogen peroxide. LIFR protein was entirely absent in cardiomyocytes isolated from failing SHR, which were resistant to the cytoprotective effects of CT-1. Finally, stimulation of non-failing SHR cardiomyocytes with angiotensin II, aldosterone, norepinephrine or endothelin-1 significantly decreased (p<0.01) LIFR expression.These data suggest that loss of CT-1-dependent survival mechanisms may contribute to the increase of cell death associated with HF in SHR. Neurohumoral activation may contribute to this alteration via suppression of LIFR.