tbuckley/cabot-search huggingface dataset:
Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections
Authors: Ravi Retnakaran, Jackie Hochman, J. Hans DeVries, Helene Hanaire-Broutin, Robert J. Heine, Vincent Melki, Bernard Zinman
Journal: Diabetes Care (2004)

OBJECTIVE—Rapid-acting insulin analogs (insulin lispro and insulin aspart) have emerged as the meal insulin of choice in both multiple daily insulin injection (MDII) therapy and continuous subcutaneous insulin infusion (CSII) for type 1 diabetes. Thus, a comparison of efficacy between CSII and MDII should be undertaken only in studies that used rapid-acting analogs for both intensive regimens. RESEARCH DESIGN AND METHODS—We performed a pooled analysis of the randomized controlled trials that compared CSII and optimized MDII therapy using rapid-acting analogs in adults with type 1 diabetes. RESULTS—The three studies that met inclusion criteria provided data on 139 patients, representing 596 patient-months for CSII and 529 patient-months for MDII. Mean age was 38.5 years, with duration of diabetes of 18.0 years. The studies differed significantly in mean baseline A1c (7.95, 8.20, and 9.27%). The pooled estimate of treatment effect comparing the percentage reduction in A1c by CSII with that by MDII (CSII − MDII) was 0.35% (95% CI −0.10 to 0.80, P = 0.08) using a random effect to account for heterogeneity between studies. Importantly, the interaction between baseline A1c and treatment modality emerged as an independent predictor of treatment effect (CSII − MDII) (P = 0.002). The relative benefit of CSII over MDII was found to increase with higher baseline A1c. A model derived from these data predicts that in a patient with a baseline A1c of 10%, CSII would reduce the A1c by an additional 0.65% compared with MDII. Conversely, there would be no A1c benefit of CSII compared with MDII if baseline A1c were 6.5%. There was no significant difference between CSII and MDII in the rate of hypoglycemic events. CONCLUSIONS—When using rapid-acting insulin analogs in CSII and MDII regimens in adult patients with type 1 diabetes, insulin pump therapy is associated with better glycemic control, particularly in those individuals with higher baseline A1c. Thus, CSII emerges as an important modality for implementing intensive therapy and may be uniquely advantageous in patients with poor glycemic control.
Detection and identification of bacterial DNA in serum from patients with acute pancreatitis
Authors: E de Madaria
Journal: Gut (2005)

Bacterial infections are common complications in patients with acute pancreatitis, and translocation of bacteria from the intestinal lumen is probably the first step in the pathogenesis of these infections. As blood cultures in afebrile patients are usually negative, more sensitive methods to investigate this hypothesis in patients are needed. Our group has recently developed a method to detect the presence of bacterial DNA in biological fluids, and we aimed to detect bacterial DNA in patients with acute pancreatitis, as molecular evidences of bacterial translocation.Samples of blood were obtained on three consecutive days within the first six days after admission. Bacterial DNA was detected using a polymerase chain reaction based method, and an automated DNA nucleotide sequencing process allowed identification of bacteria species.Thirty one consecutively admitted patients with acute pancreatitis were studied. Bacterial DNA was detected in six patients (19.3%), and the sequencing process allowed identification of Citrobacter freundii and Pseudomonas aeruginosa. In two patients the same bacteria detected at admission was detected 24 hours later (above 99.9% homology of nucleotide sequence). Basic clinical and biochemical characteristics were similar among patients with or without the presence of bacterial DNA.Detection of gram negative bacteria derived bacterial DNA in our series supports the contention that bacterial translocation is a systemic process in approximately 20% of patients with acute pancreatitis that does not seem to be related to the severity of the episode or immediate development of infection.
Periodontitis is related to lung volumes and airflow limitation: a cross-sectional study
Authors: Birte Holtfreter, Stefanie Richter, Thomas Kocher, Marcus Dörr, Henry Völzke, Till Ittermann, Anne Obst, Christoph Schäper, Ulrich John, Peter Meisel, Anne Grotevendt, Stephan B. Felix, Ralf Ewert, Sven Gläser
Journal: European Respiratory Journal (2012)

This study aimed to assess the potential association of periodontal diseases with lung volumes and airflow limitation in a general adult population. Based on a representative population sample of the Study of Health in Pomerania (SHIP), 1463 subjects aged 25-86 years were included. Periodontal status was assessed by clinical attachment loss (CAL), probing depth and number of missing teeth. Lung function was measured using spirometry, body plethysmography and diffusing capacity of the lung for carbon monoxide. Linear regression models using fractional polynomials were used to assess associations between periodontal disease and lung function. Fibrinogen and high-sensitivity C-reactive protein (hs-CRP) were evaluated as potential intermediate factors. After full adjustment for potential confounders mean CAL was significantly associated with variables of mobile dynamic and static lung volumes, airflow limitation and hyperinflation (p<0.05). Including fibrinogen and hs-CRP did not change coefficients of mean CAL; associations remained statistically significant. Mean CAL was not associated with total lung capacity and diffusing capacity of the lung for carbon monoxide. Associations were confirmed for mean probing depth, extent measures of CAL/probing depth and number of missing teeth. Periodontal disease was significantly associated with reduced lung volumes and airflow limitation in this general adult population sample. Systemic inflammation did not provide a mechanism linking both diseases.
Is Adjuvant Chemotherapy Useful for Women With Luminal A Breast Cancer?
Authors: Alan S. Coates, Marco Colleoni, Aron Goldhirsch
Journal: Journal of Clinical Oncology (2012)

Alan S. Coates, International Breast Cancer Study Group and University of Sydney, Sydney, New South Wales, Australia Marco Colleoni, International Breast Cancer Study Group and European Institute of Oncology, Milan, Italy Aron Goldhirsch, International Breast Cancer Study Group and European Institute of Oncology, Milan, Italy; and Swiss Center for Breast Health, St Anna Clinic, Lugano, Switzerland
Influence of and Optimal Insulin Therapy for a Low–Glycemic Index Meal in Children With Type 1 Diabetes Receiving Intensive Insulin Therapy
Authors: Rochelle L. Ryan, Bruce R. King, Donald G. Anderson, John R. Attia, Clare E. Collins, Carmel E. Smart
Journal: Diabetes Care (2008)

OBJECTIVE—The purpose of this study was to quantify the effects of glycemic index on postprandial glucose excursion (PPGE) in children with type 1 diabetes receiving multiple daily injections and to determine optimal insulin therapy for a low–glycemic index meal. RESEARCH DESIGN AND METHODS—Twenty subjects consumed test breakfasts with equal macronutrient contents on 4 consecutive days; high–and low–glycemic index meals (glycemic index 84 vs. 48) were consumed with preprandial ultra-short-acting insulin, and the low–glycemic index meal was also consumed with preprandial regular insulin and postprandial ultra-short-acting insulin. Each child's insulin dose was standardized. Continuous glucose monitoring was used. RESULTS—The PPGE was significantly lower for the low–glycemic index meal compared with the high–glycemic index meal at 30–180 min (P &amp;lt; 0.02) when preprandial ultra-short-acting insulin was administered. The maximum difference occurred at 60 min (4.2 mmol/l, P &amp;lt; 0.0001). Regular insulin produced a 1.1 mmol/l higher PPGE at 30 min compared with ultra-short-acting insulin (P = 0.015) when the low–glycemic index meal was consumed. Postprandial ultra-short-acting insulin produced a higher PPGE at 30 and 60 min compared with preprandial administration when the low–glycemic index meal was consumed. The maximum difference was 2.5 mmol/l at 60 min (P &amp;lt; 0.0001). CONCLUSIONS—Low–glycemic index meals produce a lower PPGE than high–glycemic index meals. Preprandial ultra-short-acting insulin is the optimal therapy for a low–glycemic index meal.
Length-dependent activation: its effect on the length-tension relation in cat ventricular muscle.
Authors: E G Lakatta, B R Jewell
Journal: Circulation Research (1977)

In cat papillary muscles at 30 degrees C, bathed with Tyrode's solution containing 2.25 mM Ca2+, the effect of various inotropic interventions (varying the stimulus frequency and continual paired stimulation) on the shape of the steady state length-tension relation was examined at lengths from Lmax, where tension production is maximal, to 0.87 Lmax. The relative steepness of the length-tension curves for peak tension developed (DT) and for maximum rate of tension development (dT/dT) varied inversely with the degree of potentiation. Thus, during paired pulse stimulation the relative decline in DT and dT/dT for a given change in muscle length was significantly less than the decline observed during stimulation at 5 min-1. When a muscle was stretched DT did not reach its final steady level for several minutes, and this slow increase in DT contributed significantly to the steepness of the steady state length-tension relation. The half-time of the slow increase in DT exhibited beat-dependency, and conditions that reduce the transsarcolemmal influx of calcium (reduction in bathing [Ca2+] or the presence of verapamil) significantly prolonged the time course of the slow increase and reduced its magnitude. These results support the hypothesis (1) that there is length-dependence of the excitation-contraction coupling process, such that an increase in muscle length is accompanied by greater activation of the contractile system; and (2) that this is due at least in part to an increased influx of calcium into the muscle cells. The implication of this hypothesis is that the influence of muscle length on myocardial performance (the Frank-Starling relation) should not be regarded as fundamentally different in character from other inotropic interventions.
Overexpression of CIP2A is an independent prognostic indicator in nasopharyngeal carcinoma and its depletion suppresses cell proliferation and tumor growth
Authors: Na Liu, Qing-Mei He, Jie-Wei Chen, Ying-Qin Li, Ya-Fei Xu, Xian-Yue Ren, Ying Sun, Hai-Qiang Mai, Jian-Yong Shao, Wei-Hua Jia, Tie-Bang Kang, Mu-Sheng Zeng, Jun Ma
Journal: Molecular Cancer (2014)

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that acts as a prognostic marker for several human malignancies. In this study, we investigated the clinical significance of CIP2A and its function in nasopharyngeal carcinoma (NPC). Quantitative RT-PCR, western blot, and immunohistochemistry analyses were used to quantify CIP2A expression in NPC cell lines and clinical samples. Kaplan-Meier curves were used to estimate the association between CIP2A expression and patient survival. The functional role of CIP2A in NPC cell lines was evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation and xenograft growth. CIP2A levels were upregulated in NPC cell lines and clinical samples at both the mRNA and protein levels (P < 0.01). Patients with high CIP2A expression had poorer overall survival (HR, 1.98; 95% CI, 1.16-3.34; P = 0.01) and poorer disease-free survival (HR, 1.68; 95% CI, 1.07-2.62; P = 0.02) rates than patients with low CIP2A expression. In addition, CIP2A expression status was an independent prognostic indicator for NPC patients. The depletion of CIP2A expression inhibited c-Myc protein expression in NPC cell lines, suppressed cell viability, colony formation, and anchorage-independent growth in vitro, and inhibited xenograft tumor growth in vivo. Our data demonstrate that high CIP2A expression in patients was associated with poor survival in NPC, and depletion of CIP2A expression inhibited NPC cell proliferation and tumor growth. Thus, these results warrant further investigation of CIP2A as a novel therapeutic target for the treatment of NPC.
Surveillance for Recurrent Bladder Cancer Using a Point-of-Care Proteomic Assay
Authors: H. Barton Grossman
Journal: JAMA (2006)

At least 50% of patients with a history of bladder cancer have recurrences, so rigorous surveillance is necessary. Cystoscopy is standard but can fail to detect some bladder cancers, so a urine test is frequently part of the evaluation.To investigate whether a point-of-care proteomic test that measures the nuclear matrix protein NMP22 in voided urine could improve detection of recurrence during monitoring of patients with a history of bladder cancer.From September 2001 to February 2002, 23 academic, private practice, and hospital facilities in 9 US states prospectively enrolled 668 consecutive patients with a history of bladder cancer in this cross-sectional study. Patients provided a voided urine sample for analysis of NMP22 protein and cytology prior to cystoscopy.Diagnosis of bladder cancer recurrence, based on cystoscopy with biopsy, was accepted as the reference standard. The performance of the NMP22 test was compared with voided urine cytology as an aid to detection. Testing for the NMP22 tumor marker was conducted in a blinded manner.Bladder cancer was diagnosed in 103 patients. Cystoscopy alone identified 91.3% of the cancers (94/103; 95% confidence interval [CI], 84.1%-95.9%). The combination of cystoscopy with the NMP22 assay detected 99.0% of the malignancies (102/103; 95% CI, 94.7%-100%; P = .005). The NMP22 assay detected 8 of 9 cancers that were not visualized during initial cystoscopy, including 7 that were high-grade. The sensitivity and specificity of the NMP22 test alone were 49.5% (51/103; 95% CI, 39.5%-59.5%) and 87.3% (493/565; 95% CI, 84.2%-89.9%), respectively. Voided cytology detected only 3 of the malignancies missed during initial cystoscopy and did not significantly increase the sensitivity of cystoscopy (94.2%; 95% CI, 87.7%-97.8%; P = .08).The noninvasive point-of-care assay for elevated urinary NMP22 protein can increase the ability to detect recurrent bladder cancer, with test results available during the patient visit.
FDG-PET predicts survival in recurrent high-grade gliomas treated with bevacizumab and irinotecan
Authors: C. Colavolpe, O. Chinot, P. Metellus, J. Mancini, M. Barrie, C. Bequet-Boucard, E. Tabouret, O. Mundler, D. Figarella-Branger, E. Guedj
Journal: Neuro-Oncology (2012)

Prognosis of recurrent high-grade glioma (HGG) is poor, although bevacizumab has been documented in that context. This study aimed to determine the independent prognostic value of fluorodeoxyglucose (FDG)-PET on progression-free survival (PFS) and overall survival (OS) of recurrent HGG after combined treatment with bevacizumab and irinotecan, compared with other documented prognostic variables. Twenty-five adult patients with histologically proven HGG were included at recurrence. Brain FDG-PET imaging was performed within 6 weeks of starting chemotherapy with bevacizumab and irinotecan. Response based on MRI was assessed every 2 months according to revised assessment in Neuro-Oncology (RANO) criteria. Median PFS and OS were 4 months (range, 0.9-10.4 months) and 7.2 months (range, 1.2-41.7 months), respectively. At 6 months, PFS and OS rate were 16.0% and 72.0%. FDG uptake was the most powerful predictor of both PFS and OS, using either univariate or multivariate analysis, among all variables tested: histological grade, Karnofsky performance status, steroid intake, and number of previous treatments. Moreover, FDG uptake was also prognostic of response to bevacizumab-based therapy. This study provides the first evidence that pretreatment FDG-PET can serve as an imaging biomarker in recurrent HGG for predicting survival following anti-angiogenic therapy with bevacizumab.
Viral evolution in chronic hepatitis B: a branched way to HBeAg seroconversion and disease progression?
Authors: Boris A Ratsch, C-Thomas Bock
Journal: Gut (2012)

Evolution is a natural event that enables the animal and plant kingdoms to adapt and survive to changing environmental effects. The same evolutionary pressures also help to shape micro-organisms, including viruses. The evolutionary significance of virus infections has been a subject of discussion for decades1; however, modern genomic analysis became an important focus of research when it became apparent that genetic variants of viruses could be linked to pathogenesis and disease progression. The first questions relating virus diversity to disease progression were provided by Pierre Lepine in 1938 who reported on the evolution of different strains of rabies viruses and a link between different characteristics of infectivity and virulence.2 Recent reports have also revealed the importance of viral evolution and genetic diversity in the pathogenesis of viral diseases, in particular, of RNA (influenza virus, HCV)3 ,4 and retrovirus infections (HIV).5 Hepatitis B virus (HBV) utilises a reverse transcription strategy that, together with an error-prone viral polymerase, has the potential to generate a large number of genetic variants. Chronic HBV (CHB) infection follows four complex dynamic phases, namely immune tolerance, immune clearance, immune control/inactive state and immune escape/reactivation that evolve over several decades. This scenario is usually accompanied by HBeAg seroconversion. The frequency and severity of hepatitis flares can predict disease progression, while early HBeAg seroconversion confers a favourable outcome, and late or absent HBeAg seroconversion results in progression to severe liver disease, such as cirrhosis. …
Microtentacles Tip the Balance of Cytoskeletal Forces in Circulating Tumor Cells
Authors: Michael A. Matrone, Rebecca A. Whipple, Eric M. Balzer, Stuart S. Martin
Journal: Cancer Research (2010)

Abstract Detection of circulating tumor cells (CTC) is advancing as an effective predictor of patient outcome and therapeutic response. Unfortunately, our knowledge of CTC biology remains limited, and the impact of drug treatments on CTC metastatic potential is currently unclear. Improved CTC imaging in vivo and analysis of free-floating tumor cells now show that cytoskeletal regulation in CTCs contrasts starkly with tumor cells attached to extracellular matrix. In this review, we examine how persistent microtubule stabilization promotes the formation of microtentacles on the surface of detached breast tumor cells and enhances metastatic potential. Cancer Res; 70(20); 7737–41. ©2010 AACR.
Systematic review of efficacy of cognitive behaviour therapies in childhood and adolescent depressive disorder
Authors: R. Harrington, J. Whittaker, P. Shoebridge, F. Campbell
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To determine whether cognitive behaviour therapy is an effective treatment for childhood and adolescent depressive disorder. <b>Design:</b> Systematic review of six randomised trials comparing the efficacy of cognitive behaviour therapy with inactive interventions in subjects aged 8 to 19 years with depressive disorder. <b>Main outcome measure:</b> Remission from depressive disorder. <b>Results:</b> The rate of remission from depressive disorder was higher in the therapy group (129/208; 62%) than in the comparison group (61/168; 36%). The pooled odds ratio was 3.2 (95% confidence interval 1.9 to 5.2), suggesting a significant benefit of active treatment. Most studies, however, were based on relatively mild cases of depression and were of only moderate quality. <b>Conclusions:</b> Cognitive behaviour therapy may be of benefit for depressive disorder of moderate severity in children and adolescents. It cannot, however, yet be recommended for severe depression. Definitive large trials will be required to determine whether the results of this systematic review are reliable. <h3>Key messages</h3> Depressive disorders are a common problem in child psychiatric clinics, but a recent systematic review found that tricyclic medication was of unproved benefit This systematic review identified six randomised trials of a psychological treatment—cognitive behaviour therapy—in subjects aged 8 to 19 years with depressive disorder The results seemed to show that cognitive behaviour therapy is an effective treatment for depressive disorder of moderate severity Because of the small number of trials available for this quantitative analysis definitive large trials will be required to determine whether the present results are reliable
Collagen Signaling Enhances Tumor Progression after Anti-VEGF Therapy in a Murine Model of Pancreatic Ductal Adenocarcinoma
Authors: Kristina Y. Aguilera, Lee B. Rivera, Hoon Hur, Juliet G. Carbon, Jason E. Toombs, Courtney D. Goldstein, Michael T. Dellinger, Diego H. Castrillon, Rolf A. Brekken
Journal: Cancer Research (2013)

Abstract There is growing evidence that antiangiogenic therapy stimulates cancer cell invasion and metastasis. However, the underlying molecular mechanisms responsible for these changes have not been fully defined. Here, we report that anti-VEGF therapy promotes local invasion and metastasis by inducing collagen signaling in cancer cells. We show that chronic VEGF inhibition in a genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDA) induces hypoxia, a less differentiated mesenchymal-like tumor cell phenotype, TGF-β expression, and collagen deposition and signaling. In addition, we show that collagen signaling is critical for protumorigenic activity of TGF-β in vitro. To further model the impact of collagen signaling in tumors, we evaluated PDA in mice lacking Sparc, a protein that reduces collagen binding to cell surface receptors. Importantly, we show that loss of Sparc increases collagen signaling and tumor progression. Together, these findings suggest that collagen actively promotes PDA spread and that enhanced disease progression associated with anti-VEGF therapy can arise from elevated extracellular matrix–mediated signaling. Cancer Res; 74(4); 1032–44. ©2013 AACR.
Cyclophosphamide eliminates suppressor T cells in age-associated central regulation of delayed hypersensitivity in mice.
Authors: A Mitsuoka, S Morikawa, M Baba, T Harada
Journal: The Journal of Experimental Medicine (1979)

Effect of treatment of mice with cyclophosphamide (CY) on the delayed hypersensitivity (DH) response was investigated in C57BL/6 mice. DH to methylated human serum albumin (MHSA) could be enhanced with CY in young mice but not in aged ones. DH enhancement with CY appeared to be due to elimination of suppressor T cells involved in DH. Effector T cells were also sensitive to CY, the damaging effect of CY on these latter cells was, however, transient suggesting the rapid recovery of effector T cells. The overshooting recovery of the effector T cells required the presence of the thymus. It is more probably that there are at least two distinct subpopulations of T cells in DH, effector T cells, and suppressor T cells. The distinction is already apparent in the thymus stage. The suppressor T cells, categorized as a central regulator, seem to be antigen nonspecific and regulate the more effectively the DH in young mice, thus physiological role of these cells in age-associated immune alterations is implicated.
Guidelines for the management of adult lower respiratory tract infections
Authors: M. Woodhead
Journal: European Respiratory Journal (2005)

No risk factors for P. aeruginosa (see table 12) Nonantipseudomonal cephalosporin III+macrolide # or Nonantipseudomonal cephalosporin III+(moxifloxacin or levofloxacin) Risk factors for P. aeruginosa (see table 12) Anti-pseudomonal cephalosporin " or Acylureidopenicillin/b-lactamase inhibitor or Carbapenem + ciprofloxacin P. aeruginosa: Pseudomonas aeruginosa.# : new macrolides preferred to erythromycin