tbuckley/cabot-search huggingface dataset:
Vascular endothelial growth factor synthesis in the acute phase of experimental and clinical lung injury
Authors: B. Maitre, S. Boussat, D. Jean, M. Gouge, L. Brochard, B. Housset, S. Adnot, C. Delclaux
Journal: European Respiratory Journal (2001)

Vascular endothelial growth factor (VEGF) is a potent angiogenic and endothelial survival factor, which is abundantly expressed in the normal lung. Conceivably, VEGF may be released by numerous cell types found around the airspaces, including alveolar type 2 cells, alveolar macrophages, and polymorphonuclear neutrophils. Using a bacteria-induced lung injury model in rats, VEGF expression in lung was investigated. Both VEGF protein and VEGF messenger ribonucleic acid (mRNA), 4 and 24 h after bacterial challenge (Pseudomonas aeruginosa), were decreased compared with sham rats. VEGF protein was also investigated in bronchoalveolar lavage (BAL) from patients studied within 7 days of acute respiratory distress syndrome (ARDS) onset and in patients without ARDS. VEGF protein levels in BAL were decreased in patients with ARDS versus those without (14.3 +/- 11.1 pg x mL(-1) versus 76.8 +/- 51.1 pg x mL(-1), p = 0.03). In aggregate, these findings show that the initial phase of acute lung injury is associated with a decrease in vascular endothelial growth factor in the lung. This downregulation may represent a protective mechanism aimed at limiting endothelial permeability, and may participate in the decrease in capillary number that is observed during early acute respiratory distress syndrome.
A Phase I and Pharmacokinetic Study of Pegylated Camptothecin as a 1-Hour Infusion Every 3 Weeks in Patients With Advanced Solid Malignancies
Authors: Eric K. Rowinsky, Jinee Rizzo, Leonel Ochoa, Chris H. Takimoto, Bahram Forouzesh, Garry Schwartz, Lisa A. Hammond, Amita Patnaik, Joseph Kwiatek, Andrew Goetz, Louis Denis, Jeffrey McGuire, Anthony W. Tolcher
Journal: Journal of Clinical Oncology (2002)

To assess the feasibility of administering camptothecin (CPT), the prototypic topoisomerase I inhibitor, as polyethylene glycol (PEG)-CPT, a macromolecule consisting of CPT conjugated to chemically modified PEG. The study also sought to determine the maximum-tolerated dose (MTD) of PEG-CPT, characterize its pharmacokinetic behavior, and seek preliminary evidence of anticancer activity.Patients with advanced solid malignancies were treated with escalating doses of PEG-CPT as a 1-hour intravenous (IV) infusion every 3 weeks. A modified continual reassessment method was used for dose-level assignment to determine the MTD, which was defined as the highest dose level at which the incidence of dose-limiting toxicity did not exceed 20%.Thirty-seven patients were treated with 144 courses of PEG-CPT at seven dose levels ranging from 600 to 8,750 mg/m(2). Severe myelosuppression was consistently experienced by heavily pretreated (HP) and minimally pretreated (MP) patients at the highest dose level evaluated, 8,750 mg/m(2), whereas both HP and MP patients tolerated repetitive treatment at 7,000 mg/m(2). Cystitis, nausea, vomiting, and diarrhea were also observed but were rarely severe. A partial response was noted in a patient with platinum- and etoposide-resistant small-cell lung carcinoma, and minor responses were noted in one patient each with adenocarcinoma of unknown primary type and osteosarcoma. The pharmacokinetics of free CPT were dose proportional. Free CPT accumulated slowly in plasma, with maximal plasma concentrations achieved at 23 +/- 12.3 hours; the harmonic mean half-life (t(1/2)) of free CPT was long (t(1/2), 77.46 +/- 36.77 hours).Clinically relevant doses of CPT can be delivered by administering PEG-CPT. The recommended dose for phase II studies in both MP and HP patients is 7,000 mg/m(2) as 1-hour IV every 3 weeks. The characteristics of the myelosuppressive effects of PEG-CPT, the paucity of severe nonhematologic toxicities with repetitive treatment, the preliminary antitumor activity noted, and the slow clearance of CPT enabling simulation of desirable pharmacokinetic parameters with a convenient single-dosing regimen warrant further disease-directed evaluations.
Involvement of the small intestine in systemic mast cell disease.
Authors: B B Scott, G J Hardy, M S Losowsky
Journal: Gut (1975)

A patient is reported with mast cell infiltration of the small intestine in the absence of the skin involvement characteristic of mast cell disease. She also had subtotal villous atrophy responsive to a gluten-free diet. Criteria for diagnosing mast cell disease of the small intestine are proposed. The literature of small intestinal mast cell disease is reviewed and the relationship to coeliac disease is discussed.
Quantitative analysis of the peripheral blood cytotoxic T lymphocyte response in patients with chronic hepatitis C virus infection.
Authors: B Rehermann, K M Chang, J G McHutchison, R Kokka, M Houghton, F V Chisari
Journal: Journal of Clinical Investigation (1996)

Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTL) are present in the peripheral blood and liver of chronically infected patients. The current study was performed to study the relationship between the strength of the CTL response, liver disease severity, and viral load. The results may be summarized as follows: first, using CTL precursor frequency (CTLpf) analysis to quantitate the peripheral blood CTL response, chronically infected patients were less strongly sensitized to a panel of well-defined HCV epitopes than they were to an epitope within the influenza matrix protein. Second, HCV-specific CTLpf did not correlate with disease activity or viral load in the majority of patients on a cross-sectional basis, although it did increase in three patients concomitant with sharp increases in liver disease. Finally, interferon therapy did not enhance the CTLpf against the HCV epitopes studied in these patients, indicating that its antiviral effect is independent of the CTL response. Since the HCV-specific CTLpf in the blood is actually quite low, the CTL may contribute to ongoing liver disease in these patients while being quantitatively inadequate to destroy all of the infected hepatocytes, thereby facilitating HCV persistence and contributing to chronic liver disease.
Testing the Accelerator Hypothesis: Body Size, β-Cell Function, and Age at Onset of Type 1 (Autoimmune) Diabetes
Authors: Terence J. Wilkin
Journal: Diabetes Care (2006)

The contribution by Dabelea et al. (1) to the growing debate on the accelerator hypothesis is an important one, but I wonder if there is a confounder that has not been accounted for in the reasoning. The report revolves principally around Fig. 2, which shows, after appropriate adjustments, a clear inverse relationship between age at diagnosis and BMI (the acceleration predicted) among those whose fasting C-peptide (FCP) levels lay below the median, but none among those whose FCP lay above. The difference is interpreted to mean that any relationship to insulin resistance applies only to a subset of type 1 diabetic children with low β-cell reserve.

The accelerator hypothesis argues that “type 1 and type 2 diabetes are the …
Training and ventilatory assistance in chronic obstructive pulmonary disease
Authors: L. Bianchi
Journal: European Respiratory Journal (2006)

To the Editors: 

It was with great interest that I read the paper by van't Hul et al . 1, which was recently published in the European Respiratory Journal , regarding the effectiveness of training with inspiratory support in chronic obstructive pulmonary disease (COPD) patients.

In particular, I longed for an answer to the main question on this topic, i.e. which COPD patients should benefit most from the adjunct of assisted ventilation during training.

Despite brilliant results on the acute effects of assisted ventilation on exercise tolerance and dyspnoea in severe COPD based on a …
Thymidine phosphorylase (platelet-derived endothelial cell growth factor), microvessel density and clinical outcome in hepatocellular carcinoma
Authors: Akitaka Yamamoto, Dipok Kumar Dhar, Osama Nazmy El-Assal, Igarashi Masahiko, Tabara Hideki, Nagasue Naofumi
Journal: Journal of Hepatology (1998)
An Integrated Genome-Wide Approach to Discover Tumor-Specific Antigens as Potential Immunologic and Clinical Targets in Cancer
Authors: Qing-Wen Xu, Wei Zhao, Yue Wang, Maureen A. Sartor, Dong-Mei Han, Jixin Deng, Rakesh Ponnala, Jiang-Ying Yang, Qing-Yun Zhang, Guo-Qing Liao, Yi-Mei Qu, Lu Li, Fang-Fang Liu, Hong-Mei Zhao, Yan-Hui Yin, Wei-Feng Chen, Yu Zhang, Xiao-Song Wang
Journal: Cancer Research (2012)

Tumor-specific antigens (TSA) are central elements in the immune control of cancers. To systematically explore the TSA genome, we developed a computational technology called heterogeneous expression profile analysis (HEPA), which can identify genes relatively uniquely expressed in cancer cells in contrast to normal somatic tissues. Rating human genes by their HEPA score enriched for clinically useful TSA genes, nominating candidate targets whose tumor-specific expression was verified by reverse transcription PCR (RT-PCR). Coupled with HEPA, we designed a novel assay termed protein A/G-based reverse serological evaluation (PARSE) for quick detection of serum autoantibodies against an array of putative TSA genes. Remarkably, highly tumor-specific autoantibody responses against seven candidate targets were detected in 4% to 11% of patients, resulting in distinctive autoantibody signatures in lung and stomach cancers. Interrogation of a larger cohort of 149 patients and 123 healthy individuals validated the predictive value of the autoantibody signature for lung cancer. Together, our results establish an integrated technology to uncover a cancer-specific antigen genome offering a reservoir of novel immunologic and clinical targets.
T-cell division in human immunodeficiency virus (HIV)-1 infection is mainly due to immune activation: a longitudinal analysis in patients before and during highly active antiretroviral therapy (HAART)
Authors: Mette D. Hazenberg, James W. T. Cohen Stuart, Sigrid A. Otto, Jan C. C. Borleffs, Charles A. B. Boucher, Rob J. de Boer, Frank Miedema, Dörte Hamann
Journal: Blood (2000)
Use of weaning protocols for reducing duration of mechanical ventilation in critically ill adult patients: Cochrane systematic review and meta-analysis
Authors: B. Blackwood, F. Alderdice, K. Burns, C. Cardwell, G. Lavery, P. O'Halloran
Journal: BMJ (2011)

<b>Objective</b> To investigate the effects of weaning protocols on the total duration of mechanical ventilation, mortality, adverse events, quality of life, weaning duration, and length of stay in the intensive care unit and hospital. <b>Design</b> Systematic review. <b>Data sources</b> Cochrane Central Register of Controlled Trials, Medline, Embase, CINAHL, LILACS, ISI Web of Science, ISI Conference Proceedings, Cambridge Scientific Abstracts, and reference lists of articles. We did not apply language restrictions. <b>Review methods</b> We included randomised and quasi-randomised controlled trials of weaning from mechanical ventilation with and without protocols in critically ill adults. <b>Data selection</b> Three authors independently assessed trial quality and extracted data. A priori subgroup and sensitivity analyses were performed. We contacted study authors for additional information. <b>Results</b> Eleven trials that included 1971 patients met the inclusion criteria. Compared with usual care, the geometric mean duration of mechanical ventilation in the weaning protocol group was reduced by 25% (95% confidence interval 9% to 39%, P=0.006; 10 trials); the duration of weaning was reduced by 78% (31% to 93%, P=0.009; six trials); and stay in the intensive care unit length by 10% (2% to 19%, P=0.02; eight trials). There was significant heterogeneity among studies for total duration of mechanical ventilation (I<sup>2</sup>=76%, P&lt;0.01) and duration of weaning (I<sup>2</sup>=97%, P&lt;0.01), which could not be explained by subgroup analyses based on type of unit or type of approach. <b>Conclusion</b> There is evidence of a reduction in the duration of mechanical ventilation, weaning, and stay in the intensive care unit when standardised weaning protocols are used, but there is significant heterogeneity among studies and an insufficient number of studies to investigate the source of this heterogeneity. Some studies suggest that organisational context could influence outcomes, but this could not be evaluated as it was outside the scope of this review.
Down-Regulation of Phosphatidylinositol 3′-Kinase/AKT/Molecular Target of Rapamycin Metabolic Pathway by Primary Letrozole-Based Therapy in Human Breast Cancer
Authors: Daniele Generali, Stephen B. Fox, Maria Pia Brizzi, Giovanni Allevi, Simone Bonardi, Sergio Aguggini, Manuela Milani, Alessandra Bersiga, Leticia Campo, Rossana Dionisio, Federica Vergoni, Roberto Giardini, Luigi Dogliotti, Alberto Bottini, Adrian L. Harris, Alfredo Berruti
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The phosphatidylinositol 3′-kinase (PI3K)/AKT/molecular target of rapamycin (mTOR) pathway is involved in the development of tumor resistance to endocrine therapy in breast cancer cell lines and represents an attractive target for pharmacologic intervention. However, the effects of endocrine therapy with aromatase inhibitors on in vivo expression of this signaling cascade, and its relation to tumor response and patient outcome, is unknown. Experimental Design: PI3K, phospho-AKT (pAKT) and phospho-mTOR were assessed by immunohistochemistry on tumor specimens collected at baseline and after 6 months of treatment in 113 elderly breast cancer patients consecutively enrolled in a randomized phase II trial of primary letrozole therapy and letrozole associated with metronomic cyclophosphamide. Results: Basal expression of the pathway was not significantly correlated with response or patient outcome. Both letrozole alone and letrozole with cyclophosphamide resulted in a significant reduction of PI3K expression (P = 0.02 and P &amp;lt; 0.005, respectively) and phospho-mTOR expression (P = 0.0001 and P = 0.0001, respectively). pAKT showed no change in the letrozole arm, whereas it was significantly decreased in the letrozole plus cyclophosphamide arm (P &amp;lt; 0.005). pAKT expression reduction was associated with a greater response rate (P = 0.05) and greater reduction in Ki67 expression (P = 0.05). Phospho-mTOR expression reduction was associated with a significantly longer disease-free survival in a multivariate analysis (P = 0.02). Conclusions: Letrozole inhibits key molecules in the PI3K pathway that are important targets of new drugs being developed to overcome resistance. Changes in these molecules may have prognostic significance. These results should be taken into account when planning prospective trials testing up-front aromatase inhibitor with drugs targeting the PI3K/AKT/mTOR signaling pathway.
Transgenic expression of the endothelin-B receptor prevents congenital intestinal aganglionosis in a rat model of Hirschsprung disease.
Authors: C E Gariepy, S C Williams, J A Richardson, R E Hammer, M Yanagisawa
Journal: Journal of Clinical Investigation (1998)

The spotting lethal rat, a naturally occurring rodent model of Hirschsprung disease, carries a deletion in the endothelin-B receptor (EDNRB) gene that abrogates expression of functional EDNRB receptors. Rats homozygous for this mutation (sl) exhibit coat color spotting and congenital intestinal aganglionosis. These deficits result from failure of the neural crest-derived epidermal melanoblasts and enteric nervous system (ENS) precursors to completely colonize the skin and intestine, respectively. We demonstrate that during normal rat development, the EDNRB mRNA expression pattern is consistent with expression by ENS precursors throughout gut colonization. We used the human dopamine-beta-hydroxylase (DbetaH) promoter to direct transgenic expression of EDNRB to colonizing ENS precursors in the sl/sl rat. The DbetaH-EDNRB transgene compensates for deficient endogenous EDNRB in these rats and prevents the intestinal defect. The transgene has no effect on coat color spotting, indicating the critical time for EDNRB expression in enteric nervous system development begins after separation of the melanocyte lineage from the ENS lineage and their common precursor. The transgene dosage affects both the incidence and severity of the congenital intestinal defect, suggesting dosage-dependent events downstream of EDNRB activation in ENS development.
Benefits and risks of using local anaesthetic for pain relief to allow early return to play in professional football
Authors: J W Orchard
Journal: British Journal of Sports Medicine (2002)

To investigate the risks and benefits of the use of local anaesthetic in a descriptive case series from three professional football (rugby league and Australian football) teams.Cases of local anaesthetic use (both injection and topical routes) and complications over a six year period were recorded. Complications were assessed using clinical presentation and also by recording all cases of surgery, incidences of players missing games or leaving the field through injury, and causes of player retirement.There were 268 injuries for which local anaesthetic was used to allow early return to play. There were 11 minor and six major complications, although none of these were catastrophic or career ending. About 10% of players taking the field did so with the assistance of local anaesthetic. This rate should be considered in isolation and not seen to reflect standard practice by team doctors.The use of local anaesthetic in professional football may reduce the rates of players missing matches through injury, but there is the risk of worsening the injury, which should be fully explained to players. A procedure should only be used when both the doctor and player consider that the benefits outweigh the risks.
Delayed DMSO Administration Protects the Kidney from Mercuric Chloride-Induced Injury
Authors: Sang-Kyung Jo, Xuzhen Hu, Peter S.T. Yuen, Amy G. Aslamkhan, John B. Pritchard, James W. Dear, Robert A. Star
Journal: Journal of the American Society of Nephrology (2004)

Reactive oxygen species are implicated as mediators of tissue damage in ischemic and toxic acute renal failure. Whereas many agents can inhibit renal ischemic injury, only hepatocyte growth factor, melatonin, N-acetylcysteine, and DMSO inhibit injury after mercuric chloride administration. Although it has been suggested that DMSO may chelate the mercuric ion, more recent studies suggest that it has anti-inflammatory and antioxidant effects. Acute renal failure was induced by 5 mg/kg subcutaneous injection of mercuric chloride in BALB/c mice. DMSO (3.8 ml/kg, 40% in PBS) or vehicle (PBS) was injected intraperitoneally at 0 and 24 h after mercuric chloride injection, or DMSO treatment was delayed 3 or 5 h. DMSO prevented increases in serum creatinine and tubular damage at 24 and 48 h. When DMSO treatment was delayed by 3 h, it was still beneficial; however, with a 5-h delay, the histology score and serum creatinine were not significantly decreased. DMSO partially prevented a mercuric chloride-induced decrease in glutathione peroxidase activity and completely prevented the transient decrease in superoxide dismutase activity. Neither mercuric chloride nor DMSO affected catalase activity significantly. For investigating possible effects of DMSO on cellular mercuric ion uptake, MDCK cells that were transfected with human organic anion transporter-1 were used. 203Hg uptake was inhibited 90% by N-acetylcysteine but only 5% by DMSO, indicating that the effect of DMSO is not related to chelating mercuric ion or inhibiting its uptake. It is concluded that DMSO acts in part as an antioxidant to inhibit mercuric chloride-induced acute renal injury.
Preoperative motor mapping by navigated transcranial magnetic brain stimulation improves outcome for motor eloquent lesions
Authors: S. M. Krieg, J. Sabih, L. Bulubasova, T. Obermueller, C. Negwer, I. Janssen, E. Shiban, B. Meyer, F. Ringel
Journal: Neuro-Oncology (2014)

Navigated transcranial magnetic stimulation (nTMS) has been proven to influence surgical indication and planning. Yet there is still no clear evidence how these additional preoperative functional data influence the clinical course and outcome. Thus, this study aimed to compare patients with motor eloquently located supratentorial lesions investigated with or without preoperative nTMS in terms of clinical outcome parameters. A prospectively enrolled cohort of 100 patients with supratentorial lesions located in motor eloquent areas was investigated by preoperative nTMS (2010–2013) and matched with a control of 100 patients who were operated on without nTMS data (2006–2010) by a matched pair analysis. Patients in the nTMS group showed a significantly lower rate of residual tumor on postoperative MRI (OR 0.3828; 95% CI 0.2062–0.7107). Twelve percent of patients in the nTMS and 1% of patients in the non-nTMS group improved while 75% and 81% of the nTMS and non-nTMS groups, respectively, remained unchanged and 13% and 18% of patients in the nTMS and non-nTMS groups, respectively, deteriorated in postoperative motor function on long-term follow-up (P = .0057). Moreover, the nTMS group showed smaller craniotomies (nTMS 22.4 ± 8.3 cm2; non-nTMS 26.7 ± 11.3 cm2; P = .0023). This work increases the level of evidence for preoperative motor mapping by nTMS for rolandic lesions in a group comparison study. We therefore strongly advocate nTMS to become increasingly used for these lesions. However, a randomized trial on the comparison with the gold standard of intraoperative mapping seems mandatory.
The clinical implication of cervical interspinous bursitis in the diagnosis of polymyalgia rheumatica
Authors: M. A Gonzalez-Gay
Journal: Annals of the Rheumatic Diseases (2008)

Polymyalgia rheumatica (PMR) is a relatively common inflammatory condition characterised by pain, aching and morning stiffness involving the shoulder and hip girdles and the neck.1 2 Patients are generally older than 50 years and the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are usually elevated.1 PMR may occur as an isolated disease or it may be observed in the setting of giant cell arteritis (GCA).3

Arthroscopic studies have confirmed the presence of synovitis in proximal joints of patients with PMR.4 However, the cause of musculoskeletal symptoms in these patients is not clearly defined because joint synovitis may only partially explain the diffuse discomfort along with involvement of periarticular structures. Interestingly, MRI and ultrasonography (US) studies disclosed bilateral inflammation of subacromial and subdeltoid bursae in association with synovitis of the glenohumeral joints and tenosynovitis of the biceps in patients with PMR.5 6 More recently, using MRI and US, Cantini et al also confirmed the presence of trochanteric bursitis and, less commonly, iliopsoas and ischiogluteal bursitis in PMR patients.7 These studies support the pivotal role of the involvement of extraarticular synovial structures, in particular bursae, in PMR.

Shoulder pain is the most common and the presenting feature in patients with PMR.1 2 By contrast, pelvic and cervical involvement is less commonly observed.2 In this regard, in a population-based study from Northwest Spain, the frequency of shoulder girdle involvement was almost 100% in patients with isolated PMR and PMR associated with GCA.8 However, neck involvement was observed in 74% of individuals with isolated PMR and 67% of those with PMR associated with GCA.8

Population-based studies have confirmed …