tbuckley/cabot-search huggingface dataset:
General Practitioner Referrals to an Eye Hospital: A Standard Referral Form
Authors: N P Jones, I C Lloyd, J Kwartz
Journal: Journal of the Royal Society of Medicine (1990)

To assess general practitioner (GP) referrals to an eye hospital, 500 consecutive referral letters were analysed for content, diagnosis, ocular examination, and medical and drug history. Inadequate information was provided. Visual acuity was measured by general practitioners in only 3.7% of referrals. The standard of ocular examination compared unfavourably with that of ophthalmic opticians. A standard ophthalmic referral form is proposed, and referral protocols are desirable. Undergraduate education in ophthalmology is inadequate and requires more curricular time.
A Novel Collagen Matricryptin Reduces Left Ventricular Dilation Post-Myocardial Infarction by Promoting Scar Formation and Angiogenesis
Authors: Merry L. Lindsey, Rugmani Padmanabhan Iyer, Rogelio Zamilpa, Andriy Yabluchanskiy, Kristine Y. DeLeon-Pennell, Michael E. Hall, Abdullah Kaplan, Fouad A. Zouein, Dustin Bratton, Elizabeth R. Flynn, Presley L. Cannon, Yuan Tian, Yu-Fang Jin, Richard A. Lange, Dorota Tokmina-Roszyk, Gregg B. Fields, Lisandra E. de Castro Brás
Journal: Journal of the American College of Cardiology (2015)
Abstract 3363: Quantitative In Vivo T2 Measurements Differentiate Both Infarcted and Peri-Infarct from Normal Myocardium
Authors: Anthony H Aletras, Peter Kellman, Bibhu D Mohanty, Robert F Hoyt, Andrew E Arai
Journal: Circulation (2007)

Introduction: T2-weighted MRI, which reflects water content and mobility, has been recently shown to delineate the area at risk (AAR). However, in-vivo T2 measurements within the viable and infarcted regions of the AAR have not been presented to date. We hypothesized that state-of-the-art T2 methods could discriminate different T2 relaxation constants not only between the AAR and remote myocardium but also between viable and infarcted tissue within the AAR. Methods: Acute myocardial infarction was created by coronary occlusion (90 min N = 9, 180 min N = 5) followed by reperfusion in canines. In-vivo imaging was performed 3 days post-infarction at 1.5T. T2-prepared steady-state free-precession (T2P-SSFP) was used to measure T2 prior to Gd-DTPA infusion. Infarct size was determined by delayed contrast enhancement. Results: T2 Bright regions within the left anterior descending coronary artery were detected in all experiments and were larger and generally of greater transmural extent than the regions of delayed enhancement. Using regions of interest determined by the delayed enhancement, T2 showed step-wise abnormalities from normal to peri-infarct and infarcted myocardium (45 +/−4 vs 60 +/−5 vs 67 +/−5 ms; all pairwise comparisons significant). A threshold T2 of 54 ms distinguished normal from abnormal in all but one region. Conclusions: The degree of edema or mobility of water varies between infarcted myocardium and the peri-infarct zone and both are significantly different from normal. Due to the subtlety of T2 abnormalities in the heart, parametric maps can display T2 in an objective manner and could improve the diagnostic value of T2 weighted MRI of infarction and myocarditis.
Efficacy and clinical cross-resistance of a new combination therapy (AMSA/VP16) in previously treated patients with acute nonlymphocytic leukemia.
Authors: L Tschopp, V E von Fliedner, C Sauter, P Maurice, A Gratwohl, M Fopp, F Cavalli
Journal: Journal of Clinical Oncology (1986)

We investigated the tolerance, efficacy, and clinical cross-resistance of a new combination chemotherapy in 38 patients with previously treated acute myeloblastic leukemia (AML). It consisted of 120 mg2/d 4'(9-acridinylamino) methanesulfon-m-Anisidide (m-AMSA) in a one-hour infusion and 80 mg/m2/d etoposide (VP-16) in a 24-hour infusion, both administered for 5 days. The first 27 patients also received vinblastine, 6 mg/m2 on day 8, but this therapy was discontinued because of intestinal complications. Thirteen of 23 patients (56%) at first or subsequent relapse and five of 15 patients (33%) who were primarily resistant to an anthracycline/cytarabine combination achieved a complete response (CR) (hemoglobin level not taken into account) with a median CR duration of 5 months and 2 months, respectively. The response rate was as high as 63% for patients at first or second relapse whether the remission was maintained or not. The median times to recovery of normal bone marrow cellularity, of blood granulocyte counts greater than 500/microL, and of platelets greater than 20,000/microL were 34, 27, and 22 days, respectively. Marked but reversible gastrointestinal toxicity was observed in 24% of the patients, and two patients died of infection during induction. The one-hour AMSA/continuous VP-16 combination is effective for patients with relapsing AML and shows no cross-resistance in a proportion of patients refractory to the standard anthracycline-cytarabine combination.
Serum periostin in obstructive airways disease: Range, relationships and response to corticosteroid
Authors: James Fingleton, Justin Travers, Darren Bowles, Rianne Strik, Rob Siebers, Cecile Holweg, John Matthews, Mark Weatherall, Richard Beasley
Journal: European Respiratory Journal (2014)

Introduction: 

Serum periostin is a potential biomarker of response to therapies which target a T-helper 2 (Th2) pattern of inflammation in asthma.

Aims: 

To determine serum periostin levels in a random sample of adults with symptoms of airflow obstruction, its relationship with other variables, including other biomarkers of a Th2 pattern of disease, and the change in serum periostin levels with inhaled corticosteroid (ICS) treatment.

Methods: 

Serum periostin levels were determined as part of the New Zealand Respiratory Health Survey, a cross-sectional study designed to explore phenotypes and biomarkers in individuals aged 40 to 75 who reported wheeze and breathlessness in the last 12 months (n=386). 49 steroid naive subjects had repeat periostin testing after 12 weeks open label ICS (budesonide 800 mcg/day).

Results: 

Serum periostin values ranged from 15.0ng/ml to 164.7ng/ml, with a right skewed distribution. Mean (SD) periostin was 57.3 (18.6), median (IQR) 54.0 (45.1 to 65.6). Periostin was positively correlated with exhaled nitric oxide (r=0.22, p<0.001), blood eosinophils (r=0.21, p<0.001), and total IgE (r=0.14, p=0.007). Atopy was associated with a higher mean periostin level (59.4 v 53.9, p=0.002; median 55.9 v 51.0). Gastro-oesophageal reflux was associated with a lower mean periostin (54.6 v 59.6, p=0.002; median 51.5 v 55.9).

Twelve weeks of ICS therapy in steroid naive participants was associated with a 10% reduction in mean periostin, from 52.9 to 47.6, median periostin reduced from 49.8 to 47.3.

Conclusion: Serum periostin is a marker of a Th2 pattern of airways disease, and a course of ICS therapy leads to a mean reduction in serum periostin levels of 10%.
Abstract 1662: Heparin Cofactor II Deficiency Causes Accelerated Thrombosis and Atherosclerosis in Mice
Authors: Ken-ichi Aihara, Hiroyuki Azuma, Masashi Akaike, Yasumasa Ikeda, Shusuke Yagi, Takashi Iwase, Yuka Sumitomo, Masataka Sata, Shigeaki Kato, Toshio Matsumoto
Journal: Circulation (2006)

(Background) Enhanced thrombin generation has been recognized as one of major risk factors in the development of thrombosis and atherosclerosis. Heparin cofactor II (HCII) is a serine protease inhibitor that specifically inhibits thrombin action at the site of injured vascular wall. We previously reported that a high level of plasma HCII activity reduces incidences of in-stent restenosis after percutaneous coronary intervention and carotid plaque ( Circulation 2004 ; 109 : 461 –5, 2761–5 ). However, it is not clear what role HCII plays in the development of thrombosis and atherosclerosis. (Methods and Results) HCII homozygous mutant mice we generated were embryonic lethal. Therefore, we employed HCII heterozygous mutant (HCII+/−) mice in this study. No structural differences in the femoral artery and aortic root between HCII+/+ mice and HCII+/− mice were observed, whereas prominent neointimal hyperplasia (2.2+/−0.3 mm2 in HCII+/+ mice vs 3.4+/−0.4 mm2 in HCII+/− mice, p&lt;0.05) and higher incidence of arterial occlusion due to thrombosis (20% in HCII+/+ mice vs 40% in HCII+/−mice, p&lt;0.05) were noted in HCII+/− mice after femoral artery wire denudation injury. Whole blood aggregation was enhanced in HCII+/− mice compared to that in HCII+/+ mice. Next, we generated HCII+/− ApoE−/− mice and found that the double-mutant mice manifested lower plasma total cholesterol level than that in HCII+/+ ApoE−/ − mice (298+/−18 mg/dl in HCII+/+ ApoE−/ − mice vs 257+/−18 mg/dl in HCII+/− ApoE−/ − mice, p&lt;0.05). However, atherosclerotic plaque area (1.1+/−0.3 mm2 in HCII+/+ ApoE−/ − mice vs 2.1+/−0.4 mm2 in HCII+/− ApoE−/ −mice, p&lt;0.05), protease activated receptor 1, a major thrombin receptor, and F4/80, a marker of macrophage-positive cells, were significantly increased in the aortic root of HCII+/− ApoE−/ −mice compared to those in HCII+/+ ApoE−/ − mice. (Conclusions) HCII has protective roles against the formation of thrombosis and atherosclerosis induced by mechanical and metabolic vascular stresses. Therefore, HCII may be a novel therapeutic target for atherothrombosis.
Editor's Note: Inhibition of Platelet-derived Growth Factor–mediated Proliferation of Osteosarcoma Cells by the Novel Tyrosine Kinase Inhibitor STI571
Authors: Eric C. McGary, Kristy Weber, Lisa Mills, Michelle Doucet, Valerie Lewis, Dina Chelouche Lev, Isaiah J. Fidler, Menashe Bar-Eli
Journal: Clinical Cancer Research (2019)

The editors are publishing this note to alert readers to a concern about this article (1): Figure 2 is missing a splice line in the lanes between PDGF-BB 50 and 10, and the original data are not available for review.
Changes in the nail unit in patients with secondary lymphoedema identified using clinical, dermoscopic and ultrasound examination
Authors: E. Le Fourn, E. Duhard, V. Tauveron, A. Maruani, M. Samimi, G. Lorette, L. Vaillant, L. Machet
Journal: British Journal of Dermatology (2010)

Secondary lymphoedema is characterized by lymphatic stasis that is often the result of a lymph node lesion. At advanced stages it may cause trophic changes in the skin. However, the presence of changes in the nail unit has not been reported to date.The aim of this study was to determine the presence of nail abnormalities in cases of secondary lymphoedema.This was a prospective study, conducted on patients with unilateral secondary lymphoedema. A comparative clinical and dermoscopic examination and 20-MHz high-resolution ultrasound imaging of the affected limb and the contralateral limb were performed.Thirty-three patients were included. On physical examination, hyperkeratosis of the lateral nail folds, friability of the nail surface, 'ragged' proximal nail folds and cuticle and apparent leuconychia were observed more frequently on the lymphoedematous limb. The ultrasound study of the nails of the thumb and the big toe did not reveal any differences in thickness of the different structures of the nail between the lymphoedema side and the opposite side. The nail matrix was longer on the lymphoedema side.Our study showed mild changes in the nail unit compatible with the xerosis often associated with severe lymphoedema. However, the study also showed frequent evidence of 'ragged' cuticles, which in these patients at high risk of erysipelas are entry points for bacteria. This should be taken into account when counselling patients with limb lymphoedema in order to prevent erysipelas.
Risks of Exposure to Occupational Asthmogens in Atopic and Nonatopic Asthma
Authors: Tsu-Nai Wang, Meng-Chih Lin, Chao-Chien Wu, Sum-Yee Leung, Ming-Shyan Huang, Hung-Yi Chuang, Chien-Hung Lee, Deng-Chyang Wu, Pei-Shan Ho, Albert Min-Shan Ko, Po-Ya Chang, Ying-Chin Ko
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Asthma is often work-related and can be classified as atopic or nonatopic on the basis of its pathogenesis. Few studies have reported an association between exposure to occupational asthmogens and asthma with and without atopy.Objectives: We investigated, in adults with asthma, whether occupational exposure to asthmogens influenced the risk of having atopic or nonatopic asthma, and their level of lung function.Methods: We recruited 504 hospital-based adults with current asthma, 504 community-based control subjects, and 504 hospital-based control subjects in southern Taiwan. Asthma with atopy was defined as having asthma in combination with an increase in total IgE (≥100 U/ml) or a positive Phadiatop test (≥0.35 Pharmacia arbitrary unit/L) (Pharmacia ImmunoCAP; Pharmacia, Uppsala, Sweden). Occupational exposure to asthmogens was assessed with an asthma-specific job exposure matrix.Measurements and Main Results: We found a significant association between atopic asthma and exposure to high molecular weight asthmogens (adjusted odds ratio [AOR], 4.0; 95% confidence interval [CI], 1.8–8.9). Nonatopic asthma was significantly associated with exposure to low molecular weight asthmogens (AOR, 2.6; 95% CI, 1.6–4.3), including industrial cleaning agents and metal sensitizers. Agriculture was associated with both atopic and nonatopic asthma (AOR, 7.8; 95% CI, 2.8–21.8; and AOR, 4.1; 95% CI, 1.3–13.0, respectively). The ratio of FEV1 to FVC in the high-risk group was significantly lower than in the no-risk group (P = 0.026) in currently employed patients with asthma.Conclusions: In adults with asthma, occupational exposure to high and low molecular weight asthmogens appears to produce differential risks for atopic and nonatopic asthma.
Abstract 4839: Colocalization of Regional MEF2 Activity With Myocardial Scarring in Hypertrophic Cardiomyopathy
Authors: Tetsuo Konno, Dan Chen, Libin Wang, Hiroko Wakimoto, Polakit Teekakirikul, Christine Seidman, Jonathan Seidman
Journal: Circulation (2008)

Background- The molecular triggers activated by a sarcomere gene mutation that remodel the heart and produce histopathologic manifestations of hypertrophic cardiomyopathy (HCM) are incompletely known. Myocyte enhancer factor 2 (MEF2) has emerged as a critical regulator of gene expression in the heart. Objective- To examine whether MEF2 is essential for HCM pathogenesis, we assessed in vivo MEF2 expression versus myocyte hypertrophy, disarray and interstitial fibrosis, the prototypic histopathology of HCM. Methods and Results- Wild-type or heterozygous mice harboring an Arg403Gln missense mutation in the alpha-myosin heavy chain gene (MHC403/+ mice) were crossed with transgenic mice harboring a MEF2-dependent reporter gene. Mouse hearts at 30 weeks of the age were evaluated by beta-galactosidase staining to detect transcriptional activity of MEF2 in vivo. Activity of MEF2 was heterogeneously increased in the left ventricle of MHC403/+ mouse hearts compared with wild-type mouse hearts. Gomori’s trichrome staining for collagen revealed that regional activation of MEF2 uniquely colocalized with myocardial scarring in MHC403/+ mouse hearts whereas only baseline activity of MEF2 was detected in the area without myocardial scarring. von Kossa staining revealed myocardial necrosis near to MEF2 staining. To further explore whether MEF2 activity is involved in the pathogenesis of myocardial necrosis, mice carrying a homozygous Arg403Gln mutation (MHC403/403) and the MEF2-dependent reporter gene were analyzed. MEF2 was regionally activated in 3-days old MHC403/403 mouse hearts, in advance of the myocardial necrosis that occurs in homozygous mutant hearts. At 6-days, greater MEF2 activity was observed compared with 3-days old MHC403/403 hearts, and massive necrosis was present where MEF2 was activated. Conclusions- These findings provide the first evidence for regional activation of the MEF2-pathway is involved in evolution of myocardial fibrosis and necrosis in HCM. Because myocyte loss and myocardial scarring is implicated in the progression of ventricular dysfunction, these data indicate that strategies to prevent MEF2 activation may attenuate remodeling and heart failure development.
Cutaneous Vasculopathy as an Adverse Effect of the Anti–Vascular Endothelial Growth Factor Agent Axitinib
Authors: Veronica J. Shi, Anjela Galan, Ian D. Odell, Jennifer N. Choi
Journal: JAMA Dermatology (2015)

AxitinibAxitinib is a targeted chemotherapeutic agent against the vascular endothelial growth factor (VEGF) receptor pathway.Cutaneous toxic effects of these newer targeted therapies are increasingly being recognized.Herein we present a case of cutaneous vasculopathy associated with axitinib.
Outpatient Biochemotherapy With Interleukin-2 and Interferon Alfa-2b in Patients With Metastatic Malignant Melanoma: Results of Two Phase II Cytokine Working Group Trials
Authors: L. E. Flaherty, M. Atkins, J. Sosman, G. Weiss, J. I. Clark, K. Margolin, J. Dutcher, M. S. Gordon, M. Lotze, J. Mier, P. Sorokin, R. I. Fisher, C. Appel, W. Du
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The Cytokine Working Group performed a randomized phase II trial of two outpatient biochemotherapy regimens to identify an outpatient regimen with high antitumor activity and less toxicity than inpatient regimens which might be compared with chemotherapy or inpatient biochemotherapy regimens in future phase III trials. PATIENTS AND METHODS: Eighty-one patients with metastatic malignant melanoma received dacarbazine 250 mg/m 2 /d intravenously (IV) and cisplatin 25 mg/m 2 /d IV on days 1, 2, and 3, plus interferon (IFN) alfa-2b 5 mU/m 2 subcutaneously (SC) on days 6, 8, 10, 13, and 15, given every 28 days. Interleukin-2 (IL-2) was given daily on days 6 to 10 and 13 to 15. In group 1, IV IL-2 was given at 18.0 MU/m 2 , and in group 2, SC IL-2 was given at 5.0 mU/m 2 . RESULTS: In group 1 (IV IL-2), there were five complete responses (CRs) and 11 partial responses (PRs) among 44 patients (objective response rate [ORR], 36%; 95% confidence interval [CI], 22% to 51%). In group 2 (SC IL-2), there was one CR and five PRs among the 36 patients (ORR, 17%; 95% CI, 4% to 29%). The median survival was 10.7 months in group 1 and 7.3 months in group 2. Eleven patients in group 1 and four patients in group 2 remain alive as of the last follow-up. Toxicities in both groups were similar. No patient required hospitalization for neutropenic fever. CONCLUSION: Biochemotherapy has activity in these outpatient regimens with acceptable toxicity. The antitumor activity observed with the IV IL-2 regimen seems similar to that of inpatient biochemotherapy regimens. If inpatient biochemotherapy regimens develop an established role in the management of melanoma, future phase III trial comparisons with this outpatient IV IL-2 regimen would be appropriate.
Heterozygote Expression in Propionyl Coenzyme A Carboxylase Deficiency
Authors: Barry Wolf, Leon E. Rosenberg
Journal: Journal of Clinical Investigation (1978)

We measured propionyl coenzyme A carboxylase (PCC) activity in extracts of skin fibroblasts and peripheral blood leukocytes from controls and obligate heterozygotes for PCC deficiency. 6 heterozygotes were from the pcc A complementation group; 12 were from the other major complementation group, designated pcc C. Mean PCC activity in fibroblast extracts from pcc A heterozygotes was 52% of that in controls, whereas mean PCC activity in pcc C heterozygotes was indistinguishable from that of controls. Similar results were obtained with extracts of peripheral blood leukocytes. In none of eight families (three pcc A and five pcc C) in which PCC activity was studied in both parents of an affected child were significant intrafamilial differences observed. The activities of two other mitochondrial enzymes (β-methyl-crotonyl CoA carboxylase and glutamate dehydrogenase) were comparable in controls and both groups of heterozygotes. Whereas the data from pcc A heterozygotes are consistent with expected gene dosage effects, those from pcc C heterozygotes are not. Inasmuch as mammalian PCC is a large molecular weight tetramer, each protomer of which is probably composed of two nonidentical subunits, the latter results are most consistent with unbalanced rates of synthesis and(or) degradation of the two subunits in normal cells with compensatory balancing in pcc C heterozygotes.
Effects of water aerosol on pediatric allergic asthma
Authors: Martin Gaisberger, Renata Sanovic, Heidemarie Dobias, Predrag Kolarz, Angelika Moder, Josef Thalhamer, Amina Selimovic, Isidor Huttegger, Markus Ritter, Arnulf Hartl
Journal: European Respiratory Journal (2012)

Objective:  Ionized water aerosols have been suggested to exert beneficial health effects on pediatric allergic asthma. Their effectwas evaluated in a controlled randomized clinical trial as part of a summer asthma camp.   Methods:  Asthmatic allergic children (n=54) spent three weeks in an alpine asthma camp; half of the group was exposed to water aerosol for one hour per day, whereas the other half spent the same time at a “control site”. Immunological analysis, lung function and FeNO testing was performed during the stay, and sustaining effects were evaluated after 2 months. Symptom score testing was done over a period of 140 days.   Results: The water aerosol group showed a significant improvement in all lung function parameters whereas the control group only in peek expiratory flow. All patients showed significant improvement in symptom score and significant decrease of FeNO after the camp. Only the water aerosol group exhibited a long lasting effect on asthma symptoms, lung function and inflammation in the follow-up examination. Induction of IL-10 and regulatory (Treg) cells was measured in both groups, with a pronounced increase in the water aerosol group. IL-13 was significantly decreased in both groups, whereas IL-5 and eosinophil cationic protein were decreased only in the water aerosol group.   Conclusion:  Our findings confirm the induction of Treg cells and reduction of inflammation by climate therapy. They indicate a synergistic effect of water aerosols resulting in a long lasting beneficial effect on asthma symptoms, lung function and airway inflammation.
The danger of underlying<i>Chlamydia trachomatis</i>infection in treating urinary tract infection with over-the-counter antibiotics
Authors: S-J Winceslaus, Sivaraj Venkateshwaran
Journal: BMJ (2015)

Knox makes a compelling case for women with acute uncomplicated urinary tract infections (UTIs) to access nitrofurantoin without prescription but fails to mention an important drawback to this practice.1 Both UTIs and genital sexually transmitted infections (STIs) are common in sexually active young women, so women with lower UTI …
Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria
Authors: Maria Rescigno, Matteo Urbano, Barbara Valzasina, Maura Francolini, Gianluca Rotta, Roberto Bonasio, Francesca Granucci, Jean-Pierre Kraehenbuhl, Paola Ricciardi-Castagnoli
Journal: Nature Immunology (2001)