tbuckley/cabot-search huggingface dataset:
Hodgkin’s lymphoma in remission after first-line therapy: which patients need FDG–PET/CT for follow-up?
Authors: U. Petrausch, P. Samaras, P. Veit-Haibach, A. Tschopp, J.D. Soyka, A. Knuth, T.F. Hany, A. Mischo, C. Renner, N.G. Schaefer
Journal: Annals of Oncology (2009)
Reduction in Carotid Intima-Media Thickness After Pancreatic Islet Transplantation in Patients With Type 1 Diabetes
Authors: Kirstie K. Danielson, Betul Hatipoglu, Katie Kinzer, Bruce Kaplan, Joan Martellotto, Meirigeng Qi, Alessandra Mele, Enrico Benedetti, José Oberholzer
Journal: Diabetes Care (2012)

Determine the impact of islet transplantation on carotid intima-media thickness (CIMT), a marker for atherosclerosis, in type 1 diabetes without kidney disease.
Cell Autonomous Role of PTEN in Regulating Castration-Resistant Prostate Cancer Growth
Authors: David J. Mulholland, Linh M. Tran, Yunfeng Li, Houjian Cai, Ashkan Morim, Shunyou Wang, Seema Plaisier, Isla P. Garraway, Jiaoti Huang, Thomas G. Graeber, Hong Wu
Journal: Cancer Cell (2011)
Ronald ("Ronnie") Shaw
Authors: T. Shaw and Jon Shaw
Journal: BMJ (2003)

Former consultant anaesthetist Warwick and Leamington Spa (b Oldham, Lancashire, 1912; q Cambridge/St Mary's Hospital, London, 1937; MA, DA), d 30 March 2002.

During the second world war he was posted to a maxillofacial unit in Ranikhet, India, and a mobile neurosurgical unit at Dimapur, treating casualties from Kohima and the Burmese theatre of operations. He was noted for his successful improvisations in the field in Burma, where the facilities were entirely dependent on air drops and mule transport. After a period as a general practitioner in Leamington Spa he gained his FFARCS in 1954 and joined the Warwick and Warneford Hospital staff as a consultant anaesthetist until his retirement. A keen water polo player from his time at St Mary's, where Alexander Fleming was the polo secretary, he captained a team in Leamington Spa. He leaves a wife, Margaret; three children; and three grand-children.
OC-027 Fgf19 Levels In Subjects With Primary Bile Acid Diarrhoea And Elevated Triglycerides
Authors: J Nolan, S Pattni, JR Walters, IM Johnston
Journal: Gut (2014)

<h3>Introduction</h3> There is evidence that primary bile acid diarrhoea (PBAD) is caused by disordered bile acid homeostasis. Most patients with severe PBAD have low fasting serum FGF19 which fails to rise above 300 pg/ml postprandially. Different patterns of postprandial FGF19 response have been demonstrated, with some resembling those of healthy individuals. Others have shown that serum triglyceride levels reflect expression of the luminal bile acid transporter ASBT. It is hypothesised that a subset of individuals with hypertriglyceridaemia have different fasting FGF19 levels and postprandial FGF19 response. <h3>Methods</h3> Study 1: 162 patients with chronic diarrhoea were recruited prospectively. All patients underwent routine testing to exclude other causes of diarrhoea and had SeHCAT tests. Patients were classified as having PBAD, or unexplained chronic diarrhoea (CD). Other diagnoses were excluded. Fasting blood samples were taken and processed for triglycerides and FGF19. Subjects with either diagnosis were also analysed within 2 subgroups according to triglyceride level (cut off 2.30 mmol/l). Study 2: 18 subjects took part in a study to examine FGF19 levels over the course of 6 h. After an overnight fast, blood was sampled every 90 min for 6 h. Meals were provided at 9 am and 12 noon. Serum FGF19 was quantified by ELISA using a commercially available kit. Triglycerides were quantified by standard colorimetric technique. Mann-Whitney and Spearman rank correlation tests were used in analyses. <h3>Results</h3> Study 1: Overall subjects with elevated triglycerides (n = 18) have significantly lower SeHCAT retention (median 7.95 vs. 19.5% p = 0.01). Subjects with severe BAD with elevated triglycerides had higher fasting FGF19 levels (241 vs 101 pg/l p = 0.02). Study 2: There was no significant difference in fasting triglycerides between different phenotypes of FGF19 response (previously presented work). The percentage increase in FGF19 from fasting to 90 min after breakfast correlates with fasting serum triglyceride level (R = 0.59, p &lt; 0.005). <h3>Conclusion</h3> We have identified a subset of PBAD subjects with high triglycerides and fasting FGF19 levels comparable to healthy individuals. The post prandial rise in FGF19 suggests no defect in the response of FGF19 synthesis in this subset. It may instead be caused by impaired BA absorption due to reduced ASBT expression which is also manifested as high serum triglycerides. PBAD may be a heterogenous condition with more than one underlying key abnormality. <h3>Disclosure of Interest</h3> None Declared.
OC-034 Outcome Of Patients Considered Unsuitable For Liver Transplantation – A Missed Opportunity For Palliative Care?
Authors: A Phoolchund, S Murray, B Hogan, J O’Beirne
Journal: Gut (2014)

<h3>Introduction</h3> Patients with end stage liver disease (ESLD) and/or hepato-cellular carcinoma (HCC) may be considered unsuitable for liver transplantation (LT) due to disease severity at presentation or de-listed due to disease progression. These patients have complex medical needs and a limited life expectancy and would be expected to benefit from access to palliative care services. <h3>Methods</h3> We performed a retrospective audit of patients assessed for LT between 2010–12 at the Royal Free Hospital. We studied patients who were either not listed at the time of assessment, or listed and subsequently de-listed prior to LT. Sources used included transplant meeting records, hospital notes, local death records and palliative care database. <h3>Results</h3> 106 patients were identified. Median age was 58 years (IQR 51–72) and 67% were male. The median MELD score at the time of assessment was 13 (IQR 11–18.75) with a UKELD score of 52 (IQR 49–57). Aetiology of liver disease was divided into Alcohol related Liver Disease (39), Viral (32), Autoimmune (19), Metabolic (8), Cryptogenic cirrhosis (3), other (5). Reasons for not listing included poor clinical state/co-morbidities (48), tumour outside transplant criteria (25), psychosocial/compliance issues (18) and currently too well for LT (15). Excluding patients who were 'Too Well' for LT, Kaplan-Meier Survival analysis calculated the median survival following delisting as 219 days (IQR 28–540). Specifically for those delisted for 'poor clinical state' median survival was 29 days. Overall, 17 (19%) patients were referred to palliative care a median 4 days before death (IQR 2.5–47.5). <h3>Conclusion</h3> Those patients who are unfit for LT due to poor clinical state should be referred immediately for palliative care due to limited survival. Patients with HCC outside criteria have a significantly longer survival but still appear to have limited access to palliative care. Liver Transplant programs should have access to dedicated liver palliative care services. <h3>Disclosure of Interest</h3> None Declared.
Association of body mass with pulmonary function in the Childhood Asthma Management Program (CAMP)
Authors: K G Tantisira
Journal: Thorax (2003)

<b>Background:</b> While increases in body mass index (BMI) have been associated with the incidence and prevalence of asthma, the mechanisms behind this association are unclear. <b>Methods:</b> We hypothesised that BMI would be independently associated with measures of asthma severity in a population of children with mild to moderate asthma enrolled in the Childhood Asthma Management Program (CAMP). A multivariable baseline cross sectional analysis of BMI with our outcomes of interest was performed. <b>Results:</b> BMI was generally not associated with symptoms, nor was it associated with atopy. While BMI was positively associated with the methacholine concentration that causes a 20% fall in forced expiratory volume in 1 second (PC<sub>20</sub>FEV<sub>1</sub>), this association did not persist after adjustment for FEV<sub>1</sub>. Increasing BMI was associated with increasing FEV<sub>1</sub> (β = 0.006 l, 95% CI (0.001 to 0.01)) and forced vital capacity (FVC) (β = 0.012 l, 95% CI (0.007 to 0.017)). However, decrements in the FEV<sub>1</sub>/FVC ratio were noted with increasing BMI (β = −0.242, 95% CI (−0.118 to −0.366)). Thus, an increase in BMI of 5 units was associated with a decrease in FEV<sub>1</sub>/FVC of over 1%. <b>Conclusions:</b> Although the association of FEV<sub>1</sub> and FVC with BMI did not support our initial hypothesis, the decrease noted in the FEV<sub>1</sub>/FVC ratio has potential relevance in the relationship between BMI and asthma severity.
Shear Stress Inhibits Homocysteine-Induced Stromal Cell–Derived Factor-1 Expression in Endothelial Cells
Authors: Mao-Lin Sung, Chia-Ching Wu, Hsin-I Chang, Chia-Kuang Yen, Heng Jung Chen, Ju-Chien Cheng, Shu Chien, Cheng-Nan Chen
Journal: Circulation Research (2009)

Hyperhomocysteinemia contributes to vascular dysfunction and risks of cardiovascular diseases. Stromal cell-derived factor (SDF)-1, a chemokine expressed by endothelial cells (ECs), is highly expressed in advanced atherosclerotic lesions. The interplays among homocysteine, chemokines, and shear stress in regulating vascular endothelial function are not clearly understood.To investigate the mechanisms for modulations of EC SDF-1 expression by homocysteine and shear stress.Homocysteine stimulation induced dose- and time-dependent SDF-1 expression and phosphorylation of mitogen-activated protein kinases extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. By using specific inhibitors, small interfering (si)RNA, and dominant negative mutants, we demonstrated that activation of JNK pathway is critical for the homocysteine-induced SDF-1 expression. Transcription factor ELISA and chromatin immunoprecipitation assays showed that homocysteine increased Sp1- and AP-1-DNA binding activities in ECs. Inhibition of Sp1 and AP-1 activations by specific siRNA blocked the homocysteine-induced SDF-1 promoter activity and expression. Preshearing of ECs for 1 to 4 hours at 20 dyn/cm2 inhibited the homocysteine-induced JNK phosphorylation, Sp1 and AP-1 activation, and SDF-1 expression. The homocysteine-induced SDF-1 expression was suppressed by NO donor. Inhibitor or siRNA for endothelial NO synthase abolished the shear inhibition of SDF-1 expression.Our findings serve to elucidate the molecular mechanisms underlying the homocysteine induction of SDF-1 expression in ECs and the shear stress protection against this induction.
Role of Organic Anion Transporters in the Tubular Transport of Indoxyl Sulfate and the Induction of its Nephrotoxicity
Authors: Atsushi Enomoto, Michio Takeda, Akihiro Tojo, Takashi Sekine, Seok Ho Cha, Suparat Khamdang, Fumio Takayama, Isao Aoyama, Sakurako Nakamura, Hitoshi Endou, Toshimitsu Niwa
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. In uremic patients, various uremic toxins are accumulated and exert various biologic effects on uremia. Indoxyl sulfate (IS) is one of uremic toxins that is derived from dietary protein, and serum levels of IS are markedly increased in both uremic rats and patients. It has been previously reported that the accumulation of IS promotes the progression of chronic renal failure (CRF). This study demonstrates the role of rat organic anion transporters (rOATs) in the transport of IS and the induction of its nephrotoxicity. The administration of IS to 5/6-nephrectomized rats caused a faster progression of CRF, and immunohistochemistry revealed that IS was detected in the proximal and distal tubules where rOAT1 (proximal tubules) and/or rOAT3 (proximal and distal tubules) were also shown to be localized. In in vitro study, the proximal tubular cells derived from mouse that stably express rOAT1 (S2 rOAT1) and rOAT3 (S2 rOAT3) were established. IS inhibited organic anion uptake by S2 rOAT1 and S2 rOAT3, and the Ki values were 34.2 and 74.4 μM, respectively. Compared with mock, S2 rOAT1 and S2 rOAT3 exhibited higher levels of IS uptake, which was inhibited by probenecid and cilastatin, organic anion transport inhibitors. The addition of IS induced a decrease in the viability of S2 rOAT1 and S2 rOAT3 as compared with the mock, which was rescued by probenecid. These results suggest that rOAT1 and rOAT3 play an important role in the transcellular transport of IS and the induction of its nephrotoxicity.
M<scp>USCLE</scp> T<scp>RIGLYCERIDE AND</scp> I<scp>NSULIN</scp> R<scp>ESISTANCE</scp>
Authors: David E. Kelley, Bret H. Goodpaster, Len Storlien
Journal: Annual Review of Nutrition (2002)

▪ Abstract Skeletal muscle contains the majority of the body's glycogen stores and a similar amount of readily accessible energy as intramyocellular triglyceride (imTG). While a number of factors have been considered to contribute to the pathogenesis of insulin resistance (IR) in obesity and type 2 diabetes mellitus (DM), this review will focus on the potential role of skeletal muscle triglyceride content. In obesity and type 2 DM, there is an increased content of lipid within and around muscle fibers. Changes in muscle in fuel partitioning of lipid, between oxidation and storage of fat calories, almost certainly contribute to accumulation of imTG and to the pathogenesis of both obesity and type 2 DM. In metabolic health, skeletal muscle physiology is characterized by the capacity to utilize either lipid or carbohydrate fuels, and to effectively transition between these fuels. We will review recent findings that indicate that in type 2 DM and obesity, skeletal muscle manifests inflexibility in the transition between lipid and carbohydrate fuels. This inflexibility in fuel selection by skeletal muscle appears to be related to the accumulation of imTG and is an important aspect of IR of skeletal muscle in obesity and type 2 DM.
Tumour response and safety of cetuximab in a window pre-operative study in patients with squamous cell carcinoma of the head and neck
Authors: S. Schmitz, M. Hamoir, H. Reychler, M. Magremanne, B. Weynand, R. Lhommel, F.-X. Hanin, T. Duprez, N. Michoux, D. Rommel, M. Lonneux, N. Cappoen, A. Gillain, J.-P. Machiels
Journal: Annals of Oncology (2013)
Diagnosing pigmented skin lesions in general practice: Objective assessment of skin lesions is possible
Authors: M D. Humzah
Journal: BMJ (2003)

EDITOR—The paper by English et al confirms a view that serial photography does not alter the final diagnosis of a skin lesion1; a suspicious lesion that remains will require a biopsy to confirm the pathological diagnosis.

With serial photography it is difficult to obtain a standard image. The ambient …
Glucose-Modified Proteins Modulate Essential Functions and Apoptosis of Polymorphonuclear Leukocytes
Authors: GERALD COHEN, MICHAEL RUDNICKI, FRANZISKA WALTER, TOSHIMITSU NIWA, WALTER H. HO[Combining Diaeresis]RL
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Any modulation of the activity of polymorphonuclear leukocytes (PMNL) is a potential cause of the altered immune response in uremia. Because the level of glycation products is elevated in uremic sera and peritoneal effluents, the effect of glycated proteins on essential functions and on apoptosis of PMNL was investigated. Proteins from sera of healthy donors were incubated with and without glucose. The extent of early glycation was monitored by boronate chromatography and the fructosamine assay. The formation of late glycation products was assessed by fluorescence spectroscopy and Western blotting that used a specific antibody for imidazolone, a late glycation product. With the addition of aminoguanidine, a compound that inhibits the formation of late but not of early glycation products, protein samples with early glycation only were obtained. Glucose-modified proteins increased chemotaxis and activation of the 2-deoxy-D-glucose uptake of PMNL obtained from healthy donors, compared with those of unmodified proteins. PMNL apoptosis, assessed by morphologic changes, by detecting DNA strand breaks, and by measurement of the caspase 3 activity, was increased in the presence of glucose-modified serum proteins. It was found that the formation of late glycation products is necessary for the effect on PMNL chemotaxis. In contrast, early glycation of proteins is responsible for the increase of glucose uptake and apoptosis. It was concluded that the accumulation of glycated proteins in uremic sera and peritoneal fluid may contribute to the diminished immune function observed in uremia, by modulation of essential PMNL functions and acceleration of PMNL apoptosis.
Functional <b> <i>STK15</i> </b> Phe31Ile Polymorphism Is Associated with the Occurrence and Advanced Disease Status of Esophageal Squamous Cell Carcinoma
Authors: Xiaoping Miao, Tong Sun, Yonggang Wang, Xuemei Zhang, Wen Tan, Dongxin Lin
Journal: Cancer Research (2004)

STK15/BTAK/Aurora-A involved in regulating centrosomes and chromosome segregation is amplified and overexpressed in human cancers. A T91A polymorphism in STK15 causes Phe31Ile substitution, and the 31Ile variant has been shown to be preferentially amplified and associated with degree of aneuploidy in human tumors. We genotyped 656 patients with esophageal squamous cell carcinoma (ESCC) and 656 controls for the polymorphism to examine the hypothesis that the STK15 variation may affect individual susceptibility to the occurrence and aggression of ESCC. It was found that the Ile/Ile genotype was significantly associated with increased risk of ESCC occurrence [odds ratio (OR) = 1.97, 95% confidence interval (CI) = 1.36-2.85] compared with the Phe/Phe genotype. The 31Ile allele frequency significantly increased as ESCC stage increased (trend test, P = 0.006). Patients with the Ile/Ile genotype had an increased risk for invasive disease (stage II-IV; OR = 2.13, 95% CI = 1.04-4.39) or metastatic disease (stage III and IV; OR = 2.31, 95% CI = 1.06-5.05) compared with those with the Phe/Phe genotype. A positive correlation between the Ile/Ile genotype and high ESCC grade was also observed. Our results demonstrate for the first time that the STK15 polymorphism is a genetic susceptibility factor for the occurrence and aggression of ESCC.
Folic Acid Prevents Nitroglycerin-Induced Nitric Oxide Synthase Dysfunction and Nitrate Tolerance
Authors: Tommaso Gori, Jason M. Burstein, Sofia Ahmed, Steve E.S. Miner, Abdul Al-Hesayen, Susan Kelly, John D. Parker
Journal: Circulation (2001)

Background — In healthy humans, continuous treatment with nitroglycerin (GTN) causes nitric oxide synthase dysfunction, probably through the reduced bioavailability of tetrahydrobiopterin. Recent studies proposed that folic acid is involved in the regeneration of tetrahydrobiopterin in different disease states. Therefore, we investigated whether folic acid administration would prevent this phenomenon. We also sought to determine if folic acid supplementation could prevent the development of tolerance to GTN. Methods and Results — On the first visit, 18 healthy male volunteers (aged 19 to 32 years) were randomized to receive either oral folic acid (10 mg once a day) or placebo for 1 week in a double-blind designed study. All subjects also received continuous transdermal GTN (0.6 mg/h). On the second visit, forearm blood flow was measured with venous occlusion strain gauge plethysmography in response to incremental infusions of acetylcholine (7.5, 15, and 30 μg/min), N -monomethyl- l -arginine (1, 2, and 4 μmol/min), and GTN (11 and 22 nmol/min). Folic acid prevented GTN-induced endothelial dysfunction, as assessed by responses to intraarterial acetylcholine and N -monomethyl- l -arginine ( P &lt;0.01). Moreover, in the subjects treated with folic acid plus transdermal GTN, responses to intraarterial GTN were significantly greater than those observed after transdermal GTN plus placebo ( P &lt;0.05). Conclusion — Our data demonstrate that supplemental folic acid prevents both nitric oxide synthase dysfunction induced by continuous GTN and nitrate tolerance in the arterial circulation of healthy volunteers. We hypothesize that the reduced bioavailability of tetrahydrobiopterin is involved in the pathogenesis of both phenomena. Our results confirm the view that oxidative stress contributes to nitrate tolerance.
Retinopathy Is Associated With Cardiovascular and All-Cause Mortality in Both Diabetic and Nondiabetic Subjects
Authors: Manon V. van Hecke, Jacqueline M. Dekker, Giel Nijpels, Annette C. Moll, Hendrik A. van Leiden, Robert J. Heine, Lex M. Bouter, Coen D.A. Stehouwer, Bettine C.P. Polak
Journal: Diabetes Care (2003)

Diabetic retinopathy has been associated with increased cardiovascular and all-cause mortality risks among diabetic populations (1). The exact mechanism of this association, however, still remains unclear (1). Recently, we reported (2) that hypertension, dyslipidemia, and obesity are associated with retinopathy in diabetic and nondiabetic individuals. Conceivably, these associations with cardiovascular risk factors, which explain the occurrence of retinopathy in a nondiabetic population, may also explain the association of retinopathy and mortality. Therefore, the purpose of this population-based, prospective cohort study was to describe the association of …
The first stable variant of erythrocyte glucose‐phosphate isomerase associated with severe hemolytic anemia
Authors: A. Zanella, C. Izzo, P. Rebulla, L. Perroni, M. Mariani, G. Canestri, G. Sansone, G. Sirchia
Journal: American Journal of Hematology (1980)

Abstract A new variant of glucosephosphate isomerase (GPI) associated with hemolytic anemia, mental retardation, and muscular hypotonia is described. The defective enzyme showed increased affinity for fructose‐6‐phosphate (F‐6‐P), decreased affinity for glucose‐6‐phosphate (G‐6‐P), altered electrophoretic and isoelectrofocusing patterns, and shift to the left of the precipitin curve. The enzyme was stable under all the conditions tested (heat, urea, guanidine‐HCl, and storage). Optimum pH, K i for 6‐phosphogluconic acid (6‐PGA) and for erythrose‐4‐phosphate (E‐4‐P), molecular weight, GPI‐related antigen concentration, immunodiffusion pattern, and immunoinactivation were in the normal range. This is the first example of the association of a stable mutant GPI with severe hemolytic anemia. Enzyme instability has been present in all previously reported cases.
A Study of Conversion Symptoms in Psychiatric Outpatients
Authors: SAMUEL B. GUZE, ROBERT A. WOODRUFF, PAULA J. CLAYTON
Journal: American Journal of Psychiatry (1971)

A study of 500 psychiatric clinic patients indicated that no psychiatric disorder was free of conversion symptoms. Significant differences in prevalence between patients with and those without conversion symptoms were found for hysteria, antisocial personality, secondary affective disorder, and primary affective disorder. Race, sex, and age were not significantly associated with conversion symptoms but level of education was. This resulted partly from the lower educational achievement of those with hysteria and antisocial personality but was significant even when these disorders were excluded.