tbuckley/cabot-search huggingface dataset:
Angiotensin-converting enzyme inhibition improves defective angiogenesis in the ischemic limb of spontaneously hypertensive rats
Authors: S Takeshita
Journal: Cardiovascular Research (2001)

Objectives: Natural angiogenesis has been shown to be impaired in spontaneously hypertensive rats (SHR). The purpose of this study was to determine whether pathological angiogenesis in the setting of tissue ischemia is also impaired in SHR, and to what extent it is modified by angiotensin-converting enzyme (ACE) inhibition. Methods: Ischemia was induced in the hindlimb of SHR by excision of the femoral artery, after which the animals were randomly assigned to receive low-dose perindopril (sub-antihypertensive, 0.2 mg/kg/day), high-dose perindopril (antihypertensive, 2.0 mg/kg/day), or vehicle for 3 weeks. Wistar–Kyoto rats (WKY) with femoral artery excision served as a control group. Results: Tissue ACE activity in SHR was significantly increased compared to WKY (49.4±6.2 vs. 34.0±14.2 IU/mg, P<0.01). Administration of perindopril significantly reduced ACE activity in SHR (low dose: 12.4±2.3; high dose: 11.0±2.1 IU/mg, P<0.005). Angiogenesis of the ischemic limb muscles was significantly impaired at 4 weeks in SHR versus WKY as indicated by the lower capillary density in the former (364.5±43.0 vs. 463.8±63.0/mm2, P<0.05) as well as the reduced hindlimb perfusion assessed by laser Doppler imaging (0.86±0.08 vs. 1.03±0.09, P<0.05). Administration of perindopril significantly augmented both the capillary density (low dose: 494.3±69.8; high dose: 543.9±76.9/mm2, P<0.005) and the limb perfusion (low dose: 1.06±0.15; high dose: 1.05±0.12, P<0.05) of the ischemic limb in SHR. Conclusions: These findings indicate that pathological angiogenesis in the setting of tissue ischemia is impaired in SHR compared with WKY, and that this impairment can be reversed by ACE inhibition. The angiogenic properties of an ACE inhibitor may benefit patients with essential hypertension presenting with lower limb vascular insufficiency.
Systemic sarcoidosis and cutaneous lymphoma: is the association fortuitous?
Authors: M Schmuth, C Prior, B Illersperger, G Topar, P Fritsch, N Sepp
Journal: British Journal of Dermatology (1999)

The association of systemic sarcoidosis and malignant lymphoma is known as the 'sarcoidosis-lymphoma syndrome'. Cutaneous involvement is rare in this syndrome. We report a 52-year-old woman who was diagnosed as having tumour-stage mycosis fungoides. Complete remission was achieved by combination therapy consisting of isotretinoin, interferon (IFN) alpha, electron beam irradiation, photochemotherapy and topical corticosteroids. Three years later, the patient developed systemic sarcoidosis characterized by yellowish papules on the abdominal wall and the eyelids that histologically revealed non-caseating granulomas, multiple fine-nodular interstitial pulmonary infiltrates on chest X-ray, hilar lymphadenopathy, decreased vital capacity and increased lymphocyte count in bronchoalveloar lavage fluid. As opposed to most of the reported cases, in our patient the manifestation of cutaneous lymphoma preceded the diagnosis of systemic sarcoidosis. We review the cases reported in the literature and discuss a possible causal and temporal relationship as well as the role of IFN alpha in the development of sarcoidosis.
Explosion fractures of heels.
Authors: P. O'Connor
Journal: BMJ (1968)

position and appearance are precisely as in the St. Catherine's Thorpe specimen, and it is almost certain that we need look no further for a diagnosis.After the onset of the condition increased stresses are thrown on the medial and lateral extensions of the quadriceps tendon of insertion, with roughening of the bone, as found here.No osteoarthritis, which might suggest a chronic functional disturbance, is present in the hips, knees, or feet of this man, so it seems likely that he suffered little interference with locomotion.The frequency of Osgood-Schlatter disease in the Saxon period is unknown.In the course of examining about 2,000 tibiae this is the first case I have seen that looks at all convincing.
Complement factor H–related hybrid protein deregulates complement in dense deposit disease
Authors: Qian Chen, Michael Wiesener, Hannes U. Eberhardt, Andrea Hartmann, Barbara Uzonyi, Michael Kirschfink, Kerstin Amann, Maike Buettner, Tim Goodship, Christian Hugo, Christine Skerka, Peter F. Zipfel
Journal: Journal of Clinical Investigation (2013)

The renal disorder C3 glomerulopathy with dense deposit disease (C3G-DDD) pattern results from complement dysfunction and primarily affects children and young adults. There is no effective treatment, and patients often progress to end-stage renal failure. A small fraction of C3G-DDD cases linked to factor H or C3 gene mutations as well as autoantibodies have been reported. Here, we examined an index family with 2 patients with C3G-DDD and identified a chromosomal deletion in the complement factor H–related (CFHR) gene cluster. This deletion resulted in expression of a hybrid CFHR2-CFHR5 plasma protein. The recombinant hybrid protein stabilized the C3 convertase and reduced factor H–mediated convertase decay. One patient was refractory to plasma replacement and exchange therapy, as evidenced by the hybrid protein quickly returning to pretreatment plasma levels. Subsequently, complement inhibitors were tested on serum from the patient for their ability to block activity of CFHR2-CFHR5. Soluble CR1 restored defective C3 convertase regulation; however, neither eculizumab nor tagged compstatin had any effect. Our findings provide insight into the importance of CFHR proteins for C3 convertase regulation and identify a genetic variation in the CFHR gene cluster that promotes C3G-DDD. Monitoring copy number and sequence variations in the CFHR gene cluster in C3G-DDD and kidney patients with C3G-DDD variations will help guide treatment strategies.
Measuring and quantifying acute exacerbations of COPD: pitfalls and practicalities
Authors: Shawn D. Aaron
Journal: European Respiratory Journal (2014)

Pity the poor clinical researcher who is charged with identifying and quantifying chronic obstructive pulmonary disease (COPD) exacerbation events in clinical trials. An exacerbation of COPD is a clinical event that: 1) has no standard, consensus definition [1]; 2) often goes unreported and undetected if patients choose to stay at home instead of presenting to a healthcare provider [2]; 3) often occurs suddenly with little or no warning [3]; and 4) is subject to diagnostic uncertainty and is easily confused with pulmonary embolism, congestive heart failure or pneumonia [4–6].

Given these inherent difficulties, much-needed efforts have been made towards developing better measurement tools for quantifying COPD exacerbation events [7]. One such new measurement tool is the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), a 14-item, patient-reported daily symptom diary that attempts to accurately capture the frequency, severity, and duration of exacerbations, and which is meant to be used in clinical trials and cohort studies of COPD patients [8]. A tool such as EXACT is desperately needed by COPD clinical researchers [9], assuming that it works.

In this issue of the European Respiratory Journal , Mackay et al. [10] have attempted to test EXACT to see if it fulfils its expected functions. The investigators prospectively administered EXACT as well as their previously validated London COPD Cohort …
Updated analysis of a phase III study of surgical resection and chemotherapy (paclitaxel/carboplatin) (CT) with or without adjuvant radiation therapy (RT) for resected stage III non-small cell lung cancer (NSCLC) CALGB 9734
Authors: M. C. Perry, L. Kohman, J. Bonner, L. Gu, X. Wang, E. Vokes, M. R. Green
Journal: Journal of Clinical Oncology (2005)

7145 Surgical therapy for selected stage IIIA NSCLC patients yields 5-year survival of 15–30%. Post-operative RT may decrease local recurrence but has not been shown to improve survival. We gave CT X 4 cycles and then randomized non progressing patients to RT (5,000 cGy in 25 FX/5wks) or observation (OBS). Primary endpoint was overall survival. Eligibility: stage IIIA (N2) NSCLC, RO resection, surgical staging per protocol, PS 0–1, no prior CT/RT, and compliant laboratory values. Two to 4 weeks after CT and non-invasive restaging, non-progressors were randomized to RT or OBS. Initial accrual goal was 480 (to allow 400 randomized). The study closed after two years due to slow accrual. 44 pts entered study. Efficacy analysis involved 37 randomized patients. Failure free and overall survival were 14.0 and 30.5 months (OBS) and 31.0 and 38.8 months (RT) arm. 16 pts remain in remission, 5 (29%) on the OBS arm and 11 (58%) RT (p = 0.11) Sites of failure: OBS arm 6/17 local; 7/17 distant; 4/17 CNS; RT arm 4/19 local; 6/19 distant; 1/19 CNS. The final sample size of this phase III trial is far too small. However, the study findings are provocative enough to suggest that another attempt to mount a well powered phase III trial of consolidative TRT is indicated, especially now that there are data to support the survival benefit of adjuvant CT in completely resected NSCLC patients. No significant financial relationships to disclose.
Association of Cigarette Smoking With Diabetic Retinopathy
Authors: Scot E Moss, Ronald Klein, Barbara EK Klein
Journal: Diabetes Care (1991)

To determine whether cigarette smoking is associated with the incidence and progression of diabetic retinopathy.Younger-onset diabetic subjects who had been diagnosed at less than 30 yr of age and taking insulin (n = 1210) and a random sample of older-onset diabetic subjects diagnosed at greater than or equal to 30 yr of age (n = 1780) were selected. Baseline examinations were conducted on 996 younger- and 1370 older-onset subjects. Incidence of retinopathy was based on 138 younger-onset and 154 older-onset insulin-taking subjects and 321 older-onset non-insulin-taking subjects who were free of retinopathy at baseline. Progression of retinopathy was based on 530 younger-onset and 418 older-onset insulin-taking subjects and 486 older-onset non-insulin-taking subjects with less than proliferative diabetic retinopathy at baseline.Baseline smoking history was categorized by status (nonsmoker, ex-smoker, current smoker) and pack-years smoked while diabetic. Retinopathy was documented by stereoscopic fundus photography. In univariate analyses, the only significant association was between pack-years and progression to proliferative diabetic retinopathy in older-onset insulin-taking subjects (P less than 0.01). After controlling for known risk factors for the incidence and progression of retinopathy, pack-years smoked was borderline significant (P = 0.052) in predicting incidence of retinopathy in younger-onset subjects. Smoking was not associated with incidence in older-onset subjects or with progression or progression to proliferative diabetic retinopathy in any of the groups.Smoking is not likely to be an important risk factor for diabetic retinopathy.
Automatic detection of sleep-disordered breathing from a single-channel airflow record
Authors: H. Nakano, T. Tanigawa, T. Furukawa, S. Nishima
Journal: European Respiratory Journal (2007)

Single-channel airflow monitors developed for screening of sleep-disordered breathing (SDB) have conflicting results for accuracy. It was hypothesised that the analytical algorithm is crucial for the performance and the present authors tried to develop a novel computer algorithm. A total of 399 polysomnography (PSG) records were employed, including a thermal sensor signal. The first 100 records were used in the development of the algorithm and the remainder for validation. In addition, 119 PSG records, including a thermocouple signal and a nasal pressure signal, were used for the validation. The algorithm was designed to obtain a time series (flow-power) using power spectral analysis, which expresses fluctuation in the airflow signal amplitude. From the time series the algorithm detects transient falls of the flow-power and calculates flow-respiratory disturbance index (RDI), defined as the number of falls per hour. In the validation group, the areas under receiver operating characteristic curves for diagnosis of SDB (apnoea/hypopnoea index > or =5) were 0.96, 0.95 and 0.95, for the records of the thermal sensor, thermocouple and nasal pressure system, respectively. The diagnostic sensitivity/specificity ratios of the flow-RDI were 96/76, 88/80 and 97%/77%, respectively. The present results suggest that a single-channel airflow monitor can be used to detect sleep-disordered breathing automatically if the analytic algorithm is optimised.
ERK3 signals through SRC-3 coactivator to promote human lung cancer cell invasion
Authors: Weiwen Long, Charles E. Foulds, Jun Qin, Jian Liu, Chen Ding, David M. Lonard, Luisa M. Solis, Ignacio I. Wistuba, Jun Qin, Sophia Y. Tsai, Ming-Jer Tsai, Bert W. O’Malley
Journal: Journal of Clinical Investigation (2012)

In contrast to the well-studied classic MAPKs, such as ERK1/2, little is known concerning the regulation and substrates of the atypical MAPK ERK3 signaling cascade and its function in cancer progression. Here, we report that ERK3 interacted with and phosphorylated steroid receptor coactivator 3 (SRC-3), an oncogenic protein overexpressed in multiple human cancers at serine 857 (S857). This ERK3-mediated phosphorylation at S857 was essential for interaction of SRC-3 with the ETS transcription factor PEA3, which promotes upregulation of MMP gene expression and proinvasive activity in lung cancer cells. Importantly, knockdown of ERK3 or SRC-3 inhibited the ability of lung cancer cells to invade and form tumors in the lung in a xenograft mouse model. In addition, ERK3 was found to be highly upregulated in human lung carcinomas. Our study identifies a previously unknown role for ERK3 in promoting lung cancer cell invasiveness by phosphorylating SRC-3 and regulating SRC-3 proinvasive activity by site-specific phosphorylation. As such, ERK3 protein kinase may be an attractive target for therapeutic treatment of invasive lung cancer.
Reduction of Perlecan Synthesis and Induction of TGF-β1 in Human Peritoneal Mesothelial Cells Due to High Dialysate Glucose Concentration
Authors: Susan Yung, Xiao-Rui Chen, Ryan CW Tsang, Qing Zhang, Tak Mao Chan
Journal: Journal of the American Society of Nephrology (2004)

Prolonged exposure of the peritoneal mesothelium to high dialysate glucose concentrations reduces anionic sites that are critical to its selective permeability, thereby impairing the peritoneal transport properties in patients on long-term peritoneal dialysis (PD). Perlecan, an anionic heparan sulfate proteoglycan, is pivotal to the selective permeability of basement membranes, and high glucose concentrations modulate its synthesis in mesangial cells. The effect of glucose on perlecan expression in the peritoneal mesothelium has not been established. We investigated perlecan expression in peritoneal biopsies from patients on PD, and the effect of high glucose concentrations on perlecan synthesis in cultured human peritoneal mesothelial cells (HPMC). Peritoneal biopsies from PD patients showed reduced perlecan expression compared with controls. Exposure of HPMC to high glucose concentrations resulted in a dose-dependent reduction in the synthesis of perlecan polypeptide and its deposition into the extracellular matrix. These effects were mediated in part through the induction of TGF-beta1. Characterization studies showed that perlecan synthesized by HPMC contained solely heparan sulfate glycosaminoglycan (HS GAG) chains, and [(35)S]-incorporation studies demonstrated progressive reduction of their de novo synthesis with increasing glucose concentrations (68142 +/- 3658, 48147 +/- 2517, 31468 +/- 5781, and 25575 +/- 3621 cpm/ micro g cellular protein for 5 mM, 30 mM, 75 mM, and 120 mM D-glucose, respectively; P < 0.001 for 5 mM versus 30 mM D-glucose, and P < 0.0001 for 5 mM versus 75 mM or 120 mM D-glucose). Both the length and the charge density of the HS GAG chains remained unchanged. Reduction of peritoneal perlecan expression in long-term PD was attributed to high dialysate glucose concentrations, which induced TGF-beta1 and reduced perlecan synthesis in HPMC. Since perlecan can sequester growth factors, thereby modulating cell migration and differentiation perturbation of peritoneal perlecan expression contributes to the structural and functional changes of the peritoneum in long-term PD.
Transient Atrioventricular Standstill
Authors: Prem K. Gupta
Journal: JAMA (1975)

Four patients with different clinical conditions had transient cardiac standstill for periods of up to 22.5 seconds. All patients showed signs of cerebral ischemia and required cardiac resuscitation. In one patient, the standstill was thought to be the result of a transient increase in the vagal tone, and no long-term therapy was required. In the second patient, cardiac standstill occurred during hospitalization for impending myocardial infarction. Coronary arteriography followed by coronary artery surgery was performed, and there were no further episodes of standstill. In the third patient, standstill was probably related to long-term ingestion of propranolol hydrochloride, and was not observed after this medication was discontinued. In the fourth patient, standstill was the result of the sick sinus syndrome, and a permanent pacemaker was inserted. Standstill of both atria and ventricles may occur under different clinical settings, and management of arrhythmia should be guided by the etiology of the arrhythmia. (<i>JAMA</i>234:1038-1042, 1975)
451 TELAPREVIR IN COMBINATION WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN: ANALYSES OF PRE-DEFINED SUBPOPULATIONS IN THE PHASE 3 ADVANCE TRIAL
Authors: P. Marcellin, I.M. Jacobson, S. Zeuzem, N. Bzowej, A.J. Muir, G. Dusheiko, R. Reddy, N. Adda, L. Bengtsson, R.S. Kauffman, S. George, A.M. Di Bisceglie
Journal: Journal of Hepatology (2011)
The Epidemiology and Control of Open Angle Glaucoma: A Population-Based Perspective
Authors: James M. Tielsch
Journal: Annual Review of Public Health (1996)

Chronic open angle glaucoma is an etiologically heterogeneous group of diseases characterized by damage to the optic nerve, resulting in peripheral visual loss that can progress to involve the fovea and central vision. Open angle glaucoma can be divided into primary conditions and conditions which are secondary to another ocular or systemic disease. Causes of secondary glaucoma include uveitis, cataract, trauma, and disorders affecting the development structure of the angle. This review focuses on primary open angle glaucoma (POAG), since it accounts for the vast majority of the disease burden in the US population and its etiology remains unknown.
G‐CSF‐mobilized haploidentical peripheral blood stem cell transplantation in children with poor prognostic nonmalignant disorders
Authors: Fikret Arpacı, İlhan Tezcan, Okan Kuzhan, Nevin Yalman, Duygu Uçkan, Ahmet Emin Kürekçi, Aydan İkincioğulları, Ahmet Özet, Atilla Tanyeli
Journal: American Journal of Hematology (2007)

Haploidentical hematopoietic stem cell transplantation (HSCT) is currently one of the alternative curative treatment options for some nonmalignant but also for malignant diseases. However, concerns regarding its safety cause delays in time and a successful outcome. Between 2000 and 2005, twenty-one children with poor prognostic nonmalignant disorders, 13 boys and 8 girls, with a median age of 12 months, underwent 28 haploidentical peripheral HSCT. Immunomagnetic bead depletion device (CliniMACS) was used for indirect T-cell depletion. Indications for transplant were severe combined immunodeficiency (n=16), osteopetrosis (n=2), MDS (n=1), amegakaryocytic thrombocytopenia (n=1), and aplastic anemia (n=1). Five patients (24%) had lung infection at the time of transplantation. The patients received a median of 25.67 x 10(6) G-CSF-mobilized peripheral CD34(+) progenitor cells and a median of 4.19 x 10(4) T-lymphocytes per kilogram of body weight with a T-cell depletion rate of median 4.59 logs. The rate of total engraftment was 66.6%. Median times for leukocyte and platelet engraftment were 14 and 16 days, respectively. The 6-year projected survival was 32% for all patients and 29.76% for patients with severe combined immunodeficiency (SCID). The rates of transplant-related mortality, graft failure, and severe GvHD were 14.2, 33.4%, and 8.3%, respectively. Infection was the main cause of death. The poor outcome may be explained with the poor prognostic factors of our patients such as the type of SCID in most cases (T-B- SCID), the median age over 6 months and the presence of lung infection in some children at the time of transplantation.
Regression of Metastatic Carcinoma of the Skin Appendages after Intralesional Granulocyte-Macrophage Colony-Stimulating Factor
Authors: Hakan Goker
Journal: Annals of Internal Medicine (1998)

Letters15 September 1998Regression of Metastatic Carcinoma of the Skin Appendages after Intralesional Granulocyte-Macrophage Colony-Stimulating FactorHakan Goker, MD and Jacob D. Bitran, MDHakan Goker, MDLutheran General Cancer Care Center; Park Ridge, IL 60068Search for more papers by this author and Jacob D. Bitran, MDLutheran General Cancer Care Center; Park Ridge, IL 60068Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-6-199809150-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that causes the differentiation and proliferation of granulocytes and macrophages [1]. It may be involved in the functional activity of dendritic cells, antigen-presenting cells that are important in host defense mechanisms [2]. Alone or with other cytokines (interleukin-2, interleukin-4), GM-CSF induced antitumor responses in murine models [3] and in humans [4]. We report the regression of metastatic adnexal skin cancer achieved by use of intralesional GM-CSF.A 76-year-old man presented in December 1990 with a 1-cm × 1.5-cm indurated nodule underneath the skin of the right infraorbital area. A biopsy ...References1. Groopman JE, Molina JM, Scadden DT. Hematopoietic growth factors: biology and clinical application. N Engl J Med. 1989; 321:1449-59. Google Scholar2. Mayordomo JI, Zorina T, Storkus JW, Zitvogel L, Celluzzi C, Falo LD, et al. Bone marrow-derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity. Nat Med. 1995; 1:1297-302. Google Scholar3. Wakimoto H, Abe J, Tsunoda R, Aoyagi M, Hirakawa K, Hamada H. Intensified antitumor immunity by a cancer vaccine that produces granulocyte-macrophage colony-stimulating factor plus interleukin 4. Cancer Res. 1996; 56:1827-33. Google Scholar4. Si Z, Hersey P, Coates AS. Clinical responses and lymphoid infiltrates in metastatic melanoma following treatment with intralesional GM-CSF. Melanoma Res. 1996; 6:247-55. Google Scholar Author, Article, and Disclosure InformationAffiliations: Lutheran General Cancer Care Center; Park Ridge, IL 60068 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 September 1998Volume 129, Issue 6Page: 509KeywordsAdenocarcinomaBiopsyCellsCytokinesGranulocyte macrophage colony stimulating factorLesionsRadiation therapyStainingSweat glandsUlcers Issue Published: 15 September 1998 CopyrightCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
My most unfortunate mistake: Not thinking of things
Authors: T P. Snell
Journal: BMJ (2000)

I was fortunate enough to practise medicine for several years in the Himalayas, and many of my patients were Tibetan refugees, employed by the Indian government on road building and repair. One of my first patients was a man with swollen gums and tender thighs, the latter showing a diffuse dusky discoloration. I was puzzled by this combination, and more with …