tbuckley/cabot-search huggingface dataset:
Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis
Authors: Robert K. Semple, Alison Sleigh, Peter R. Murgatroyd, Claire A. Adams, Les Bluck, Sarah Jackson, Alessandra Vottero, Dipak Kanabar, Valentine Charlton-Menys, Paul Durrington, Maria A. Soos, T. Adrian Carpenter, David J. Lomas, Elaine K. Cochran, Phillip Gorden, Stephen O’Rahilly, David B. Savage
Journal: Journal of Clinical Investigation (2009)

Metabolic dyslipidemia is characterized by high circulating triglyceride (TG) and low HDL cholesterol levels and is frequently accompanied by hepatic steatosis. Increased hepatic lipogenesis contributes to both of these problems. Because insulin fails to suppress gluconeogenesis but continues to stimulate lipogenesis in both obese and lipodystrophic insulin-resistant mice, it has been proposed that a selective postreceptor defect in hepatic insulin action is central to the pathogenesis of fatty liver and hypertriglyceridemia in these mice. Here we show that humans with generalized insulin resistance caused by either mutations in the insulin receptor gene or inhibitory antibodies specific for the insulin receptor uniformly exhibited low serum TG and normal HDL cholesterol levels. This was due at least in part to surprisingly low rates of de novo lipogenesis and was associated with low liver fat content and the production of TG-depleted VLDL cholesterol particles. In contrast, humans with a selective postreceptor defect in AKT2 manifest increased lipogenesis, elevated liver fat content, TG-enriched VLDL, hypertriglyceridemia, and low HDL cholesterol levels. People with lipodystrophy, a disorder characterized by particularly severe insulin resistance and dyslipidemia, demonstrated similar abnormalities. Collectively these data from humans with molecularly characterized forms of insulin resistance suggest that partial postreceptor hepatic insulin resistance is a key element in the development of metabolic dyslipidemia and hepatic steatosis.
Home and workplace smoking bans in Italy, Ireland, Sweden, France and the Czech Republic
Authors: J. E. Heck, I. Stucker, S. Allwright, E. R. Gritz, M. Haglund, C. G. Healton, E. Kralikova, S. Sanchez Del Mazo, E. Tamang, C. M. Dresler, M. Hashibe
Journal: European Respiratory Journal (2009)

The purpose of this study was to report predictors and prevalence of home and workplace smoking bans in five European countries. We conducted a population-based telephone survey of 4,977 females, ascertaining factors associated with smoking bans. Odds ratios and 95% confidence intervals were derived using unconditional logistic regression. A complete home smoking ban was reported by 59.5% of French, 63.5% of Irish, 61.3% of Italian, 74.4% of Czech and 87.0% of Swedish females. Home smoking bans were associated with younger age and being bothered by secondhand smoke, and among smokers, inversely associated with greater tobacco dependence. Among nonsmokers, bans were also related to believing smoking is harmful (OR 1.20, 95% CI 1.11–1.30) and having parents who smoke (OR 0.62, 95% CI 0.52–0.73). Workplace bans were reported by 92.6% of French, 96.5% of Irish, 77.9% of Italian, 79.1% of Czech and 88.1% of Swedish females. Workplace smoking bans were reported less often among those in technical positions (OR 0.64, 95% CI 0.50–0.82) and among skilled workers (OR 0.53, 95% CI 0.32–0.88) than among professional workers. Workplace smoking bans are in place for most workers in these countries. Having a home smoking ban was based on smoking behaviour, demographics, beliefs and personal preference.
Mental Disorders Across the Adult Life Course and Future Coronary Heart Disease
Authors: Catharine R. Gale, G. David Batty, David P. J. Osborn, Per Tynelius, Finn Rasmussen
Journal: Circulation (2013)

Depression, anxiety, and psychotic disorders have been associated with an increased risk of coronary heart disease (CHD). It is unclear whether this association between mental health and CHD is present across a wider range of mental disorders.Participants were 1 107 524 Swedish men conscripted at a mean age of 18.3 years. Mental disorders were assessed by psychiatric interview on conscription, and data on hospital admissions for mental disorder and CHD were obtained from national registers during 22.6 years of follow-up. An increased risk of incident CHD was evident across a range of mental disorders whether diagnosed at conscription or on later hospital admission. Age-adjusted hazard ratios (95% confidence intervals) according to diagnoses at conscription ranged from 1.30 (1.05, 1.62) (depressive disorders) to 1.90 (1.58, 2.38) (alcohol-related disorders). [corrected]. The equivalent figures according to diagnoses during hospital admission ranged from 1.49 (1.24-1.80) (schizophrenia) to 2.82 (2.53-3.13) (other substance use disorders). Associations were little changed by adjustment for parental socioeconomic status, or body mass index, diabetes mellitus, and blood pressure measured at conscription, but they were partially attenuated by the adjustment for smoking, alcohol intake, and intelligence measured at conscription, and for education and own socioeconomic position.Increased risk of incident CHD is present across a range of mental disorders and is observable when the disorders are diagnosed at a young age.
Targets for Intervention in Dyslipidemia in Diabetes
Authors: Gerald H. Tomkin
Journal: Diabetes Care (2008)

Treatment for dyslipidemia in diabetes reduces cardiovascular events. Diabetes is associated with major abnormalities in fatty acid metabolism. The resulting disturbance results in an abnormal lipoprotein cascade from the large chylomicron through to the small HDL particle. This suggests that drugs that alter formation of the chylomicron particle might have a very important role in diabetic dyslipidemia. Achieving normal glycemia will reverse the abnormalities in fatty acid metabolism, but this is difficult, particularly as the disease progresses. Genes that regulate cholesterol absorption and excretion have been described (Niemann Pick C1-like 1 [NPC1-L1] and ATP binding cassette proteins [ABC] G5 and G8). An effective NPC1-L1 inhibitor (ezetimibe) improves the reduction in cholesterol caused by statins. Agonists of ABCG5 and G8 may become important in the treatment of dyslipidemia. Microsomal triglyceride transfer protein (MTP) is responsible for the assembly of the chylomicron and VLDL particles. New MTP inhibitors, acting only on the intestine, are exciting possible treatments. The advisability of sitosterol-enriched foods to lower cholesterol may have to be reassessed for patients with diabetes, since these products may lead to an increase in chylomicron sitosterol in diabetic patients. More successful treatment of diabetic dyslipidemia is essential if we are to reduce the burden of cardiovascular disease so commonly found in diabetes.
Fresh onions and blood fibrinolysis.
Authors: I. S. Menon
Journal: BMJ (1969)

MEDICALJOUR 845 drapes;(2) high relative humidity in the room;(3) preoperative dehydration; (4) atropine and other anticholinergic drugs.Heatstroke is a highly fatal disease unless promptly treated.But it is also a prevent- able disease.Surgeons and anaesthetists should consider what can be done to alter the conditions in the operating-room and the condition of the patient.As a single impor- tant way to prevent fatal heatstroke in the operating-room, I suggest monitoring of body temperature during operation.This is easily done, and, because the patient is unconscious, can provide the only clue to diagnosis in time.-I am, etc.,
Continuous intravenous epoprostenol for chronic thromboembolic pulmonary hypertension
Authors: P. Bresser, P.F. Fedullo, W.R. Auger, R.N. Channick, I.M. Robbins, K.M. Kerr, S.W. Jamieson, L.J. Rubin
Journal: European Respiratory Journal (2004)

Pathophysiological findings in chronic thromboembolic pulmonary hypertension (CTEPH) have suggested that a secondary small vessel arteriopathy may contribute to the haemodynamic impairment observed in these patients. It was hypothesised that this element of the elevated vascular resistance may be responsive to continuous intravenous epoprostenol therapy. Retrospectively, the clinical and haemodynamic responses to continuous intravenous epoprostenol were evaluated in nine CTEPH patients who subsequently underwent pulmonary thromboendarterectomy (PTE). Cardiopulmonary haemodynamics were determined prior to the initiation of epoprostenol, while on epoprostenol, prior to PTE, and after PTE. Six patients, treated for 2–26 months prior to PTE, experienced either clinical stability or improvement that was associated with a mean reduction in pulmonary vascular resistance (PVR) of 28% (median 33%, range 0–46%). Three patients, treated for 3–9 months, experienced clinical deterioration during epoprostenol administration, with a significant increase in PVR in two patients. Subsequent PTE resulted in a highly significant improvement of cardiac index, mean pulmonary artery pressure and total pulmonary resistance. To conclude, selected patients with chronic thromboembolic pulmonary hypertension may benefit clinically and haemodynamically from continuous intravenous epoprostenol treatment prior to pulmonary thromboendarterectomy. Factors predictive of a beneficial response, and whether this intervention influences either morbidity or mortality associated with pulmonary thromboendarterectomy, remain to be established.
Changes in regional ventilation and perfusion of the lung after endoscopic laser treatment.
Authors: P J George, G Clarke, S Tolfree, C P Garrett, M R Hetzel
Journal: Thorax (1990)

To determine whether endoscopic laser treatment improves both ventilation and perfusion in patients with advanced lung cancer, krypton-81m ventilation and technetium-99m labelled macro-aggregate perfusion scanning was performed immediately before and two or four days after treatment in a consecutive series of 28 patients. Twelve patients had not received any other treatment before laser therapy and 16 had undergone previous treatments that included radiotherapy. Ventilation and perfusion were quantified by expressing the number of counts in the affected lung as a percentage of the total counts. Ventilation and perfusion improved after laser treatment in 23 patients (82%). The mean ventilation score in the affected lung rose by 50% (p less than 0.001) and the mean perfusion score rose by 24% (p less than 0.001). Incremental changes in ventilation and perfusion scores were positively correlated (r = 0.80). Mean spirometric values, six minute walking distance, the Karnofsky performance index, and breathlessness and wellbeing scores also improved significantly. Patients with main bronchial obstruction who had had no radiotherapy showed the most striking improvements. It is concluded that the removal of intraluminal tumour from the bronchial tree leads to matched improvements in ventilation and perfusion in most patients and that this is associated with valuable improvement in symptoms.
Phase II Study on the Addition of ASA404 (Vadimezan; 5,6-Dimethylxanthenone-4-Acetic Acid) to Docetaxel in CRMPC
Authors: Roberto Pili, Mark A. Rosenthal, Paul N. Mainwaring, Guy Van Hazel, Sandy Srinivas, Robert Dreicer, Sanjay Goel, Joseph Leach, Shirley Wong, Peter Clingan
Journal: Clinical Cancer Research (2010)

This randomized phase II study evaluated ASA404 (vadimezan; 5,6-dimethylxanthenone-4-acetic acid) in combination with docetaxel in castration-refractory metastatic prostate cancer (CRMPC).Seventy-four patients with histopathologically confirmed CRMPC previously untreated with chemotherapy were randomized to receive either<or=10 cycles of docetaxel 75 mg/m2 alone (D; n=39) or docetaxel plus ASA404 1,200 mg/m2 (A-D; n=35). Study endpoints included prostate-specific antigen response, tumor response, median time to tumor progression, median survival, and toxicity.The overall pattern of adverse events was similar in the two groups; however, there was a higher incidence of cardiac adverse events and neutropenia in the A-D group. Coadministration of ASA404 with docetaxel did not affect total systemic exposure of either drug. A higher prostate-specific antigen response rate was reported with A-D versus D (59.4% versus 36.8%), together with a larger median percentage reduction in prostate-specific antigen (84.0% versus 61.9%) and a shorter median time to prostate-specific antigen nadir (105 versus 119 d). Tumor response rate was 23.1% with A-D and 9.1% with D. Time to tumor progression and median survival were similar in the groups (time to tumor progression, 8.7 mo for A-D and 8.4 mo for D; survival, 17.0 mo for A-D and 17.2 mo for D). Hazard ratios for time to tumor progression and survival were 0.81 and 0.80, respectively, favoring A-D; 2-year survival was 33.3% with A-D and 22.8% with D.The study met some endpoints (prostate-specific antigen response, tumor response) but not others (i.e., time to tumor progression). The results indicate that the combination of ASA404 with docetaxel has acceptable toxicity, lacks adverse pharmacokinetic interaction, and, overall, has activity in CRMPC.
224 PREDICTION OF OESOPHAGEAL VARICES (OV) IN HEPATIC CIRRHOSIS BY SERUM NON-INVASIVE MARKERS: RESULTS OF A MULTICENTER, INTERNATIONAL STUDY
Authors: G. Sebastiani, A. Alberti, L. Castera, G. Fattovich, P. Halfon, M. Bourliere, A. Saggioro, D. Tempesta
Journal: Journal of Hepatology (2009)
Functional Characterization of an scFv-Fc Antibody that Immunotherapeutically Targets the Common Cancer Cell Surface Proteoglycan CSPG4
Authors: Xinhui Wang, Akihiro Katayama, Yangyang Wang, Ling Yu, Elvira Favoino, Koichi Sakakura, Alessandra Favole, Takahiro Tsuchikawa, Susan Silver, Simon C. Watkins, Toshiro Kageshita, Soldano Ferrone
Journal: Cancer Research (2011)

Cell surface chondroitin sulfate proteoglycan 4 (CSPG4) is an attractive target for antibody-based cancer immunotherapy because of its role in tumor cell biology, its high expression on malignant cells including cancer-initiating cells, and its restricted distribution in normal tissues. The clinical use of CSPG4 has been hampered by the lack of a CSPG4-specific chimeric, humanized, or fully human monoclonal antibody. To overcome this limitation, we generated a CSPG4-specific fully human single-chain antibody termed scFv-FcC21 and characterized its specificity and antitumor activity. Viable CSPG4(+) melanoma cells were used in a screen of a human scFv phage display library that included CDR3 engineered to optimize antibody binding sites. The scFv antibody isolated was then recombinantly engineered with a human immunoglobulin G1 Fc region to construct the fully human antibody scFv-FcC21, which recognized tumors of neuroectodermal origin, various types of carcinomas, mesotheliomas, and sarcomas as well as myeloid leukemias. scFv-FcC21 inhibited in vitro growth and migration of tumor cells and in vivo growth of human tumor xenografts. These effects were mediated by inhibition of the activation of extracellular signal-regulated kinase and focal adhesion kinase signaling pathways that are critical for tumor cell growth and migration, respectively. Our findings define the CSPG4-specific fully human scFv-FcC21 antibody as a candidate therapeutic agent to target the many types of tumors that express CSPG4.
Repeatability and responsiveness of exercise tests in pulmonary arterial hypertension
Authors: Vincent Mainguy, Simon Malenfant, Anne-Sophie Neyron, Sébastien Bonnet, François Maltais, Didier Saey, Steeve Provencher
Journal: European Respiratory Journal (2012)

Exercise tolerance in pulmonary arterial hypertension (PAH) is most commonly assessed by the 6-min walk test (6MWT). Whether endurance exercise tests are more responsive than the 6MWT remains unknown. 20 stable PAH patients (mean±sd age 53±15 years and mean pulmonary arterial pressure 44±16 mmHg) already on PAH monotherapy completed the 6MWT, the endurance shuttle walk test (ESWT) and the cycle endurance test (CET) before and after the addition of sildenafil citrate 20 mg three times daily or placebo for 28 days in a randomised double-blind crossover setting. Pre- or post-placebo tests were used to assess repeatability of each exercise test, whereas pre- or post-sildenafil citrate tests were used to assess their responsiveness. Sildenafil citrate led to placebo-corrected changes in exercise capacity of 18±25 m (p = 0.02), 58±235 s (p = 0.58) and 29±77 s (p = 0.09) for the 6MWT, the ESWT and the CET, respectively. The 6MWT was associated with a lower coefficient of variation between repeated measures (3% <i>versus</i> 18% <i>versus</i> 13%), resulting in a higher standardised response mean compared with endurance tests (0.72, 0.25 and 0.38 for the 6MWT, the ESWT and the CET, respectively). The 6MWT had the best ability to capture changes in exercise capacity when sildenafil citrate was combined with patients' baseline monotherapy, supporting its use as an outcome measure in PAH.
The influence of female sex hormones on skin thickness: evaluation using 20 MHz sonography
Authors: None Eisenbeiss, None Welzel, None Schmeller
Journal: British Journal of Dermatology (1998)

Changes in skin thickness and echodensity during the spontaneous menstrual cycle, in women taking hormonal contraceptives and pregnant women were investigated by high-frequency (20 MHz) ultrasound. Women with a spontaneous ovulatory menstrual cycle (group I), women taking one-phase contraceptives (group II), women taking three-phase contraceptives (group III) and pregnant women (group IV) were measured at the following locations: proximal and distal forearm and lower leg on both sides. The skin was investigated during three phases of the menstrual cycle: days 2–4 (phase A), days 12–14 (phase B) and days 20–22 (phase C). Oestradiol and progesterone levels were determined at each phase. The pregnant women were investigated 2 weeks prepartal and 6 weeks after delivery. Group I showed a statistically significant increase in the skin thickness from phase A to phase B, but not from phase B to phase C. Group II showed no significant changes in skin thickness, whereas the skin thickness increased from phase A to phase B in group III. In group IV, the skin was significantly thicker prepartal than after delivery. The measured echodensity showed a negative correlation with skin thickness in group III and in pregnant women. We were able to demonstrate that the status of female sex hormones influences the thickness of the skin. These results can be explained by hormone-induced water retention in the skin. Sonography at 20 MHz is able to quantify these effects, which should be considered when performing ultrasound measurement in women.
Evidence of cardiac functional reserve upon exhaustion during incremental exercise to determine VO<sub>2max</sub>
Authors: Adrian D Elliott, Justin Skowno, Mahesh Prabhu, Timothy David Noakes, Les Ansley
Journal: British Journal of Sports Medicine (2013)

There remains considerable debate regarding the limiting factor(s) for maximal oxygen uptake (VO2max). Previous studies have shown that the central circulation may be the primary limiting factor for VO2max and that cardiac work increases beyond VO2max.We sought to evaluate whether the work of the heart limits VO2max during upright incremental cycle exercise to exhaustion.Eight trained men completed two incremental exercise trials, each terminating with exercise at two different rates of work eliciting VO2max (MAX and SUPRAMAX). During each exercise trial we continuously recorded cardiac output using pulse-contour analysis calibrated with a lithium dilution method. Intra-arterial pressure was recorded from the radial artery while pulmonary gas exchange was measured continuously for an assessment of oxygen uptake.The workload during SUPRAMAX (mean±SD: 346.5±43.2 W) was 10% greater than that achieved during MAX (315±39.3 W). There was no significant difference between MAX and SUPRAMAX for Q (28.7 vs 29.4 L/min) or VO2 (4.3 vs 4.3 L/min). Mean arterial pressure was significantly higher during SUPRAMAX, corresponding to a higher cardiac power output (8.1 vs 8.5 W; p<0.06).Despite similar VO2 and Q, the greater cardiac work during SUPRAMAX supports the view that the heart is working submaximally at exhaustion during an incremental exercise test (MAX).
SEQUENTIAL CHANGES IN THE RELATIVE AFFINITY OF ANTIBODIES SYNTHESIZED DURING THE IMMUNE RESPONSE
Authors: Lisa A. Steiner, Herman N. Eisen
Journal: The Journal of Experimental Medicine (1967)

The anti-2,4-dinitrophenyl (DNP) antibodies synthesized by suspensions of lymph node cells obtained at various intervals from rabbits that had been immunized with DNP-bovine gamma-globulin increased progressively in their affinity for the dinitrophenyl determinant. This change accompanied and was apparently responsible for a similar change in the binding properties of anti-DNP antibodies isolated from the serum. The rate of change in affinity was related to the dose of immunogen: increasing the dose delayed the change. The antibodies formed during a brief (5 hr) incubation in vitro were heterogeneous in their binding properties. Therefore, the mixing in the circulation of molecules synthesized at different times may contribute to, but is not alone responsible for, the heterogeneity in the serum antibodies. Variability in binding did not appear to be related to heterogeneity in immunoglobulin class. Indeed, the variations in relative affinity occurred entirely within the gammaG-immunoglobulins.
Zosteriform cutaneous metastases from Hodgkin's lymphoma in a patient with scrofuloderma and nodal tuberculosis
Authors: I. Garcia-Morales, A. Herrera-Saval, J.J. Rios, F. Camacho
Journal: British Journal of Dermatology (2004)

Journal Article Zosteriform cutaneous metastases from Hodgkin's lymphoma in a patient with scrofuloderma and nodal tuberculosis Get access I. García‐Morales, I. García‐Morales Departments of Dermatology and Pathology, Virgen Macarena Hospital, Seville, Spain E‐mail: camachodp@medynet.com Search for other works by this author on: Oxford Academic Google Scholar A. Herrera‐Saval, A. Herrera‐Saval Departments of Dermatology and Pathology, Virgen Macarena Hospital, Seville, Spain E‐mail: camachodp@medynet.com Search for other works by this author on: Oxford Academic Google Scholar J.J. Ríos, J.J. Ríos Departments of Dermatology and Pathology, Virgen Macarena Hospital, Seville, Spain E‐mail: camachodp@medynet.com Search for other works by this author on: Oxford Academic Google Scholar F. Camacho F. Camacho Departments of Dermatology and Pathology, Virgen Macarena Hospital, Seville, Spain E‐mail: camachodp@medynet.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 151, Issue 3, 1 September 2004, Pages 722–724, https://doi.org/10.1111/j.1365-2133.2004.06160.x Published: 01 September 2004