tbuckley/cabot-search huggingface dataset:
Increased disease activity in a patient with sarcoidosis after high dose interleukin 2 treatment for metastatic renal cancer
Authors: T F Logan
Journal: Thorax (2005)

Sarcoidosis is a disease of unknown aetiology in which cytokines such as interleukin 2 (IL-2) are thought to play an important role. We present the case history of a 48 year old man with sarcoidosis who received treatment with high dose IL-2 for metastatic renal cell cancer, following which he developed hypercalcaemia characterised by a raised level of 1,25-dihydroxyvitamin D (1,25-(OH)<sub>2</sub>-D<sub>3</sub>), a finding consistent with sarcoidosis associated hypercalcaemia. The increased activity in his sarcoidosis following IL-2 treatment provides direct supportive evidence for the role of IL-2 in the pathogenesis of sarcoidosis.
A Placebo-Controlled Trial of Antimicrobial Treatment for Acute Otitis Media
Authors: Paula A. Tähtinen, Miia K. Laine, Pentti Huovinen, Jari Jalava, Olli Ruuskanen, Aino Ruohola
Journal: New England Journal of Medicine (2011)

The efficacy of antimicrobial treatment in children with acute otitis media remains controversial.In this randomized, double-blind trial, children 6 to 35 months of age with acute otitis media, diagnosed with the use of strict criteria, received amoxicillin-clavulanate (161 children) or placebo (158 children) for 7 days. The primary outcome was the time to treatment failure from the first dose until the end-of-treatment visit on day 8. The definition of treatment failure was based on the overall condition of the child (including adverse events) and otoscopic signs of acute otitis media.Treatment failure occurred in 18.6% of the children who received amoxicillin-clavulanate, as compared with 44.9% of the children who received placebo (P<0.001). The difference between the groups was already apparent at the first scheduled visit (day 3), at which time 13.7% of the children who received amoxicillin-clavulanate, as compared with 25.3% of those who received placebo, had treatment failure. Overall, amoxicillin-clavulanate reduced the progression to treatment failure by 62% (hazard ratio, 0.38; 95% confidence interval [CI], 0.25 to 0.59; P<0.001) and the need for rescue treatment by 81% (6.8% vs. 33.5%; hazard ratio, 0.19; 95% CI, 0.10 to 0.36; P<0.001). Analgesic or antipyretic agents were given to 84.2% and 85.9% of the children in the amoxicillin-clavulanate and placebo groups, respectively. Adverse events were significantly more common in the amoxicillin-clavulanate group than in the placebo group. A total of 47.8% of the children in the amoxicillin-clavulanate group had diarrhea, as compared with 26.6% in the placebo group (P<0.001); 8.7% and 3.2% of the children in the respective groups had eczema (P=0.04).Children with acute otitis media benefit from antimicrobial treatment as compared with placebo, although they have more side effects. Future studies should identify patients who may derive the greatest benefit, in order to minimize unnecessary antimicrobial treatment and the development of bacterial resistance. (Funded by the Foundation for Paediatric Research and others; ClinicalTrials.gov number, NCT00299455.).
Membrane current changes in left ventricular myocytes isolated from guinea pigs after abdominal aortic coarctation
Authors: K O Ryder, S M Bryant, G Hart
Journal: Cardiovascular Research (1993)

Objective: The aim was to look for membrane current changes as a basis for the prolongation of action potential duration in left ventricular myocytes following abdominal aortic coarctation. Methods: Immature female guinea pigs underwent laparotomy and an aortic coarctation was fashioned immediately distal to the renal arteries. After 20 weeks the hearts were removed and single myocytes were isolated from the left ventricles by standard enzymatic techniques. The switch-clamp technique was used. Results: Heart weight:body weight ratio was increased by 7% in the coarctation group (p<0.01). Systolic left ventricular pressure was 59(SEM 4) mm Hg in control and 76(7) mm Hg in coarctation animals (p<0.05). Cell capacity was increased by 21% in the coarctation group (p<0.05), and mean resting potential was 4.6 mV more negative in this group (p<0.001). Action potential duration at 90% repolarisation was 310(17) ms in the control group (n=22) and 358(13) ms in the coarctation group (n=34, p<0.05). Peak density of L-type calcium current was -8.6(0.4) pA·pF−1 in control and −11.1(0.7) pA·pF−1 in coarctation cells (p<0.01). The regression line for calcium current versus cell capacity was shifted to higher calcium currents in the coarctation group. The half inactivation potential for this current was shifted by 11.5 mV (p<0.01). Calcium-activated tail currents were larger and the envelope of tail currents was prolonged in the coarctation cells. No significant differences were found in the amplitude of IK or of IK1. Conclusions: After infrarenal aortic coarctation, action potential duration of left ventricular myocytes is prolonged. This prolongation may be attributed to an increase in calcium current density and a shift of its inactivation variable, together with an increased magnitude and prolonged time course of sodium-calcium exchange current. These current changes are potentially arrhythmogenic. Cardiovascular Research 1993;27:1278-1287
I-test: a 34-year-old female with hip pain and remote trauma
Authors: S B S Wong, C Yong-Hing, T L C Lee, J E Taunton, G T Andrews, B B Forster
Journal: British Journal of Sports Medicine (2011)

A 34-year-old former national gymnast presented to the regional Sports Medicine Centre with a chronic history of intermittent right low back pain, quiescent after physiotherapy. During the appointment, she revealed an ongoing history of right hip discomfort, with clicking and popping, worse during cycling. She had a cycling accident a month earlier, falling onto her right side, with extensive bruising on her right thigh laterally still present during the appointment. She denied any sensory changes and had self-medicated with Naprosyn.

On examination, no pelvic tilt or limb length discrepancy was seen. She had mild soft tissue swelling over the lateral aspect of the right hip joint but no bruising. Lumbar spine range of motion was good, with no slump or pain on straight leg raises and negative bowstring and femoral stretch signs. No sensory abnormality was elicited.

She had weak right hip joint abduction, normal hip flexion power and pain during forced flexion–abduction and internal rotation of the hip. Her right hip was more internally rotated than the left side.

A set of exercises to strengthen her right hip abduction and to maintain her core strength, low back strength and flexibility was prescribed. An MR hip arthrography, to rule out a labral tear, was performed (figures 1–3).



Figure 1 
Coronal T1W fat saturation images from the MR hip arthrography. Note the homogeneous hypointense signal fluid collection in-between the subdermal fat layer and the iliotibial band aponeurosis. Hip joint intra-articular contrast medium is from the arthrography.





Figure 2 
Coronal T2W fat saturation images from the MR hip arthrography show a heterogeneous hyperintense fluid collection with multiple internal septations and a hypointense capsule of variable thickness.





Figure 3 
Coronal T2W fat saturation images from the MR hip arthrography, at a more …
Airway inflammatory response to ozone in subjects with different asthma severity
Authors: B. Vagaggini, S. Carnevali, P. Macchioni, M. Taccola, E. Fornai, E. Bacci, M.l. Bartoli, S. Cianchetti, F.l. Dente, A. Di Franco, D. Giannini, P.l. Paggiaro
Journal: European Respiratory Journal (1999)

The aim of this study was to evaluate whether ozone exposure induces a similar airway inflammatory response in subjects with different degrees of asthma severity. Two groups of asthmatic subjects were studied: seven with intermittent mild asthma not requiring regular treatment (group A); and seven with persistent mild asthma requiring regular treatment with inhaled corticosteroids and long-acting beta2-agonists (group B). All subjects were exposed, in a randomized cross-over design, to air or O3 (0.26 parts per million (ppm) for 2 h with intermittent exercise); subjects in group B withdrew from regular treatment 72 h before each exposure. Before the exposure, and 1 and 2 h after the beginning of the exposure they performed a pulmonary function test, and a questionnaire was completed to obtain a total symptom score (TSS). Six hours after the end of the exposure, hypertonic saline (HS) sputum induction was conducted. Sputum cell percentages, eosinophil cationic protein (ECP) and interleukin (IL)-8 concentrations in the sputum supernatant were measured. TSS significantly increased and forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) significantly decreased after O3 exposure in comparison with air exposure in group A, whereas no changes were observed in group B except for a significant decrement of FEV1 2 h after the beginning of O3 exposure. Sputum neutrophil percentage was significantly higher after O3 exposure than after air exposure in both groups (Group A: 70.2% (28-87) versus 26.6% (8.6-73.2); Group B: 62.1% (25-82.4) versus 27.9% (14.4-54)). IL-8 was higher in sputum supernatant collected 6 h after O3 exposure than after air, only in group A. No change due to O3 has been found in sputum eosinophil percentage and ECP concentration in both groups. In conclusion, the degree of airway response to a short-term exposure to ozone is different in subjects with asthma of different severity. The available data do not allow elucidation of whether this difference depends on the severity of the disease or on the regular anti-inflammatory treatment.
E2F8 as a Novel Therapeutic Target for Lung Cancer
Authors: Sin-Aye Park, James Platt, Jong Woo Lee, Francesc López-Giráldez, Roy S. Herbst, Ja Seok Koo
Journal: JNCI Journal of the National Cancer Institute (2015)

The E2F members have been divided into transcription activators (E2F1-E2F3) and repressors (E2F4-E2F8). E2F8 with E2F7 has been known to play an important physiologic role in embryonic development and cell cycle regulation by repressing E2F1. However, the function of E2F8 in cancer cells is unknown. E2F8 expression was assessed by immunoblotting or immunofluorescence staining in human lung cancer (LC) cells and tissues from LC patients (n = 45). Cell proliferation, colony formation, and invasion analysis were performed to evaluate the role of E2F8 in LC. Microarray analysis was used to determine the target genes of E2F8. The regulation of E2F8 on the expression of ubiquitin-like PHD and RING domain-containing 1 (UHRF1), one of E2F8 target genes, was determined using chromatin immunoprecipitation and promoter activity assays. Human LC xenograft models were used to determine the effects of inhibiting E2F8 by siRNAs (n = 7 per group) or antisense morpholino (n = 8 per group) on tumor growth. Survival was analyzed using the Kaplan-Meier method and group differences by the Student’s t test. All statistical tests were two-sided. LC tumors overexpressed E2F8 compared with normal lung tissues. Depletion of E2F8 inhibited cell proliferation and tumor growth. E2F8 knockdown statistically significantly reduced the expression of UHRF1 (~60%-70%, P < .001), and the direct binding of E2F8 on the promoter of UHRF1 was identified. Kaplan-Meier analysis with a public database showed prognostic significance of aberrant E2F8 expression in LC (HR = 1.91 95% CI = 1.21 to 3.01 in chemo-naïve patients, P = .0047). We demonstrated that E2F8 is overexpressed in LC and is required for the growth of LC cells. These findings implicate E2F8 as a novel therapeutic target for LC treatment.
Similar Genetic Features and Different Islet Cell Autoantibody Pattern of Latent Autoimmune Diabetes in Adults (LADA) Compared With Adult-Onset Type 1 Diabetes With Rapid Progression
Authors: Nóra Hosszúfalusi, Ágnes Vatay, Katalin Rajczy, Zoltán Prohászka, Éva Pozsonyi, Laura Horváth, Andrea Grosz, László Gerõ, László Madácsy, László Romics, István Karádi, George Füst, Pál Pánczél
Journal: Diabetes Care (2003)

OBJECTIVE—To compare the clinical parameters, C-peptide levels, pattern of islet cell-specific autoantibodies, and prevalence of predisposing genotypes in subjects with latent autoimmune diabetes in adults (LADA) and those with adult-onset type 1 diabetes with rapid progression. RESEARCH DESIGN AND METHODS—We evaluated the clinical parameters, C-peptide levels, and islet cell-specific autoantibodies in 54 LADA, 57 adult-onset type 1 diabetic, and 190 type 2 diabetic patients. Islet cell autoantibodies were also compared between subgroups of newly diagnosed patients with LADA and those with newly diagnosed adult-onset and childhood-onset type 1 diabetes. The genetic study was performed in subjects with LADA and those with adult-onset type 1 diabetes in comparison with a control population. RESULTS—There were no differences in the clinical parameters between LADA and adult-onset type 1 diabetes. Patients with LADA had lower BMI (P &amp;lt; 0.0001), waist-to-hip ratio (0.0029), total cholesterol (P = 0.001), and triglycerides (P = 0.001); higher HDL cholesterol levels (P &amp;lt; 0.0001); and lower prevalence of hypertension (P = 0.0028) compared with patients with type 2 diabetes. C-peptide levels were similar at onset (P = 0.403) but decreased less rapidly in LADA than in adult-onset type 1 diabetes (P = 0.0253). Single-autoantibody positivity was more often seen in LADA than in type 1 diabetes (P = 0.0001). The prevalence of predisposing HLA-DQB1*0302, -DR4, -DR3, and -DR3/DR4 genotypes and the DR4-DQB1*0302 haplotype were increased in both LADA and adult-onset type 1 diabetic subjects compared with the control population. There were no differences in the frequencies of these risk alleles and haplotypes between the two patient groups. CONCLUSIONS—Subjects with LADA had clinical characteristics similar to those with adult-onset type 1 diabetes with rapid progression. C-peptide levels did not differ at onset but decreased less rapidly in LADA. Patients with LADA rather had single islet cell-specific autoantibody positivity. The prevalence of HLA-DQB1*0302, -DR4, -DR3, and -DR3/DR4 risk alleles and the DR4-DQB1*0302 high-risk haplotype did not differ in the two forms of autoimmune diabetes.
Role of microRNAs in diabetes and its cardiovascular complications
Authors: S. Shantikumar, A. Caporali, C. Emanueli
Journal: Cardiovascular Research (2011)

Diabetes is the most common metabolic disorder and is recognized as one of the most important health threats of our time.MicroRNAs (miRNAs) are a novel group of non-coding small RNAs that have been implicated in a variety of physiological processes, including glucose homeostasis.Recent research has suggested that miRNAs play a critical role in the pathogenesis of diabetes and its related cardiovascular complications.This review focuses on the aberrant expression of miRNAs in diabetes and examines their role in the pathogenesis of endothelial dysfunction, cardiovascular disease, and diabetic retinopathy.Furthermore, we discuss the potential role of miRNAs as blood biomarkers and examine the potential of therapeutic interventions targeting miRNAs in diabetes.
Single Nucleotide Polymorphism of <i>Pi</i>-Class Glutathione <i>S</i>-Transferase and Susceptibility to Endometrial Carcinoma
Authors: Queeny K.Y. Chan, Ui-Soon Khoo, Hextan Y.S. Ngan, Chong-Qing Yang, Wei-Cheng Xue, Kelvin Y.K. Chan, Pui-Man Chiu, Philip P.C. Ip, Annie N.Y. Cheung
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Endometrial carcinoma is the most common gynecologic cancer in developed countries. Prolonged unopposed estrogen exposure has been identified as the major risk factor. The pi-class glutathione S-transferase (GSTP1) is a phase II metabolic enzyme that is important in the detoxification of a wide range of electrophiles including carcinogenic steroid-hormone intermediates generated through oxidative metabolism. In this study, we aimed at determining the association between the GSTP1 polymorphism and the risk of endometrial carcinoma in a Chinese population. Experimental Design: Genotyping of 180 cases and 200 age-matched controls were assessed by PCR-RFLP approach and confirmed by direct sequencing. Results: Statistical analysis showed that patients of valine allele carriers had 2.03-fold of increased risk of developing endometrial carcinoma (P &amp;lt; 0.01). The allele frequencies for the Ile and Val variants between the cancer cases and controls were also significantly different (P &amp;lt; 0.01; odds ratio, 1.59; 95% confidence interval, 1.13-2.23). Such association was shown in endometrial cancers as a group and in type I endometrioid adenocarcinoma but not the type II nonendometrioid adenocarcinoma. In addition, the Val allele was found significantly associated with high-grade endometrial cancer and/or endometrial cancer of deep myometrial invasion (P &amp;lt; 0.01). Interestingly, the relatively low frequency of Val/Val genotype in both the cancer cases and controls, in parallel with the lower incidence of endometrial cancer in Chinese, was observed when compared with those in Caucasians. Conclusions: Our findings suggested that the GSTP1 Ile105Val polymorphism was associated with an increased risk of endometrial cancer. Further studies may be required to explore the possible significance of these polymorphisms on GSTP1-related metabolism that may affect the susceptibility of Asians to endometrial carcinoma.
Recent Advances in Freeze-Preservation of Red Blood Cells
Authors: C. Robert Valeri
Journal: JAMA (1969)

The methods currently in clinical use for freezing human red blood cells (RBC) require the intracellular additive, glycerol, either in high concentration (approximately 45% W/V) with the slow freeze-thaw technique, or in low concentration (approximately 18% W/V) with the rapid freeze-thaw technique. The major technological problem in the current methods is the removal of the glycerol. Postthaw washing is presently accomplished by serial centrifugation ("batch washing"), continuous centrifugation, or a dilution procedure with recovery of RBC by agglomeration. Recent advances in the use of continuous centrifugation are extremely encouraging. However, for widespread clinical application of this approach disposable washing material Is urgently needed.
Identification and Partial Characterization of A Somatostatin–14 Binding Protein on Rat Liver Plasma Membranes
Authors: Steven E. Raper, Piyush C. Kothary, John Del Valle
Journal: Hepatology (1992)

Binding of somatostatin-14 to rat liver plasma membranes was characterized with 125-labeled[tyr11] somatostatin-14. Binding at 24 degrees C reached a plateau at 50 min and was reversible by synthetic somatostatin-14. Scatchard analysis revealed a single class of binding sites (affinity constant = 2.4 +/- 0.2 nmol/L, binding capacity = 148 +/- 0.02 fmol/mg protein). Specificity for somatostatin-14 was demonstrated by the inhibition of 125I-[tyr11]somatostatin-14 binding by biologically active somatostatin analogs but not by a biologically inactive somatostatin analog or unrelated peptides. The radioiodinated binding site complex could be cross-linked with disuccinimidyl suberate. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel autoradiography revealed a 70,000-Da band. Dithiothreitol, a reducing reagent, did not alter the mobility of the band, and the band could be abolished in the presence of 10 mumol/L synthetic somatostatin-14. Covalently cross-linked, iodinated binding protein complexes could be solubilized by the nonreducing detergents Zwittergent 3-12 and 3-([3-cholamidopropyl] diethylammonio)-1-propanesulfonic acid (CHAPS). Solubilized complex bound to wheat-germ agglutinin-agarose columns and was eluted by N,N',N"-triacetylchitotriose. Binding to wheat-germ agglutinin agarose columns was lost after pretreatment with endo-beta-N-acetylglucosaminidase F. Binding studies with liver plasma membranes, 125I-labeled[tyrosine11]somatostatin-14 and guanine nucleotides showed inhibition of binding in the presence of guanine nucleotides. These results indicate that the purified rat liver plasma membranes contain a specific binding protein for somatostatin-14, the binding protein appears to be glycosylated and somatostatin-14 binding to rat liver plasma membranes may be regulated by G proteins.
Phase III Trial of Concurrent or Sequential Adjuvant Chemoradiotherapy After Conservative Surgery for Early-Stage Breast Cancer: Final Results of the ARCOSEIN Trial
Authors: Alain Toledano, David Azria, Pascal Garaud, Alain Fourquet, Daniel Serin, Jean-François Bosset, Joelle Miny-Buffet, Anne Favre, Olivier Le Floch, Gilles Calais
Journal: Journal of Clinical Oncology (2007)

Purpose In 1996, we initiated the French multicenter phase III randomized trial to compare the effect on disease-free survival (DFS) of concurrent versus sequential chemotherapy (CT) and radiotherapy (RT) after breast-conserving surgery for stages I and II breast cancer. This report presents the clinical results with a median follow-up of 60 months. Patients and Methods Between February 1996 and April 2000, 716 patients were entered onto this trial. Adjuvant treatment began within 6 weeks after surgery. Sequential treatment of CT administered first followed by RT was compared with concurrent treatment of CT administered with RT. The CT regimen consisted of mitoxantrone (12 mg/m 2 ), fluorouracil (500 mg/m 2 ), and cyclophosphamide (500 mg/m 2 ) on day 1, and it was repeated every 21 days for six courses. RT was delivered to the breast and, when indicated, to the regional lymphatics. Results There was no statistically significant difference in treatment in the 5-year DFS (80% in both groups; P = .83), locoregional recurrence-free survival (LRFS; 92% in sequential v 95% in concurrent; P = .76), metastasis-free survival (87% in sequential v 84% in concurrent; P = .55), or overall survival (90% in sequential v 91% in concurrent; P = .76). Nevertheless, in the node-positive subgroup, the 5-year LRFS was statistically better in the concurrent arm (97% in concurrent v 91% in sequential; P = .02), corresponding to a risk of locoregional recurrence decreased by 39% (hazard ratio, 0.61; 95% CI, 0.38 to 0.93). Conclusion This treatment protocol remains an appealing clinical option for many women with operable breast cancer at a high risk of recurrence. Combination treatments with new drugs for breast cancer are warranted.
Chlamydia pneumoniae and asthma
Authors: F. BLASI, L. ALLEGRA, P. TARSIA
Journal: Thorax (1998)

The paper by Cook et al 1 examines the possible association between Chlamydia pneumoniae infection and asthma. The authors conclude that their data do not support this association. However, we feel that the serological tests performed give important information on the prevalence of infection, but are not sufficiently complete to make definitive conclusions on the …