bluuebunny/crossref_metadata_2025 huggingface dataset:
Initial management of suspected transient cerebral ischaemia and stroke in primary care: implications of recent research
Authors: Lasserson D S
Published: July 2009

Strategies are required to reduce the personal, societal and healthcare burden caused by cerebrovascular disease. Urgent medical intervention after transient ischaemic attack (TIA) can prevent recurrent stroke, and modern healthcare has to respond rapidly to the patient with TIA. The primary care practitioner contributes to stroke prevention by rapidly and accurately diagnosing TIA and arranging urgent specialist assessment. Diagnosis of TIA in primary care is difficult, as transient symptoms are common. Stroke-screening tools are available, but there is no evidence base for diagnostic support tools for TIA in primary care. The ABCD2 scoring system identifies patients after TIA at high early risk, and secondary care assessment within 24 h is reserved for patients with a high predicted risk. General practitioners are advised to give aspirin at the time of diagnosis, although prescribing a full range of vascular risk-reducing therapies may be appropriate. Specialist assessment confirms the diagnosis, usually with cerebral imaging (preferably MRI to detect cerebral injury), and carotid ultrasound will detect patients suitable for endarterectomy. Patients with suspected stroke should be urgently transferred to the nearest stroke centre, for assessment and investigation before potential thrombolysis, which may be effective within a longer timeframe than current practice. Primary care follow-up is essential to ensure adherence to evidence-based therapies. Dual combinations of antiplatelet agents (aspirin and dipyridamole) and antihypertensive agents (ACE inhibitors and thiazides) as well as high-dose statins have proven benefit. For patients in atrial fibrillation, even if very elderly, anticoagulation has a net benefit in preventing stroke.
Potential benefits of statins on morbidity and mortality in chronic obstructive pulmonary disease: a review of the evidence
Authors: Young R P , Hopkins R , Eaton T E
Published: July 2009

Studies show reduced forced expiratory volume in 1 s (FEV1) in patients with chronic obstructive pulmonary disease (COPD) is an important independent predictor of cardiovascular death and is characterised by both pulmonary and systemic inflammation. Evidence shows statins have important anti-inflammatory effects in both the lungs and arteries. Although randomised control trials are yet to be reported, non-randomised studies have consistently shown benefit in COPD patients taking statins compared with those not. These include reductions in both cardiovascular and respiratory morbidity/mortality. Other potential benefits include a reduced decline in FEV1 and reduced risk of lung cancer. It is argued that confounding by a “healthy user effect” is unlikely to explain the observed benefit. Given the undisputed benefit of statins in high risk populations and the growing body of data suggesting statins may benefit patients with COPD, the question arises “Should statins be considered more often in patients with COPD?”.
Point of sale tobacco displays and smoking among 14–15 year olds in New Zealand: a cross-sectional study
Authors: Paynter J , Edwards R , Schluter P J , McDuff I
Published: July 2009

Objective:

To examine the association between exposure to tobacco displays at the point of sale and teenage smoking and susceptibility to the uptake of smoking.

Design:

The sample comprised a national cross-section of 14–15 year olds with two measures of exposure to tobacco displays at the point of sale and three outcome measures. The outcome measures were susceptibility to smoking initiation, experimenting with smoking or current smoking.

Results:

Compared with visiting stores less often than weekly, a greater frequency of store visits was related to increased odds of being susceptible to smoking (daily visits, adjusted OR 1.8, 95% CI 1.6 to 2.2) and experimenting with smoking (daily visits, adjusted OR 2.7, 95% CI 2.4 to 3.1). The likelihood of being a current smoker increased with a greater frequency of store visits among students of medium and high socioeconomic status, but not among those of low socioeconomic status.

Conclusion:

Although these findings are cross-sectional in nature, they are consistent with the notion that greater exposure to tobacco displays at the point of sale increases youth smoking, and suggest display bans are needed.
The tobacco industry’s thwarting of marketing restrictions and health warnings in Lebanon
Authors: Nakkash R , Lee K
Published: July 2009

Aims:

This article outlines how the tobacco industry has undermined tobacco control efforts in Lebanon since the early 1970s.

Methods:

An analysis of online and on-site tobacco industry documents, reviews of newspapers, policy and other documents, and interviews with key policy makers were conducted.

Results:

Findings reveal how the weakness of tobacco control legislation in Lebanon has been the product of an effective tobacco industry strategy to weaken the content and scope of regulation, and delay adoption and implementation.

Conclusions:

The tobacco industry has built and maintained strong alliances that were and are regularly mobilised to effectively oppose regulation. Despite ratification of the World Health Organization Framework Convention on Tobacco Control in 2005, Lebanon's tobacco control track remains weak. Public health professionals and the government should work hard to oppose such tobacco industry tactics.
REALIZATION OF A TWO-ION SWAP GATE IN THE ION-TRAP SYSTEM
Authors: QIU DA-RONG , YE LIU
Published: July 2009

We propose an experimentally feasible scheme for implementing a two-ion swap gate in the context of the ion-trap system. In this scheme, we drive the ion with one laser beam and we map the states of one ion and the motional mode to each other. The scheme is based on resonant sideband excitation, and thus it may be realized with current ion-trap techniques.
INDEXING FUZZY NUMERICAL DATA WITH A B+ TREE FOR FAST RETRIEVAL USING NECESSITY-MEASURED FLEXIBLE CONDITIONS
Authors: BARRANCO CARLOS D. , CAMPAÑA JESÚS R. , MEDINA JUAN M.
Published: July 2009

This paper proposes an indexing procedure for improving the performance of query processing on a fuzzy database. It focuses on the case when a necessity-measured atomic flexible condition is imposed on the values of a fuzzy numerical attribute. The proposal is to apply a classical indexing structure for numerical crisp data, a B +-tree combined with a Hilbert curve. The use of such a common indexing technique makes its incorporation into current systems straightforward. The efficiency of the proposal is compared with that of another indexing procedure for similar fuzzy data and flexible query types. Experimental results reveal that the performance of the proposed method is similar and more stable than that of its competitor.
ON AN INTERPRETATION OF KEYWORDS WEIGHTS IN INFORMATION RETRIEVAL: SOME FUZZY LOGIC BASED APPROACHES
Authors: ZADROŻNY SŁAWOMIR , KACPRZYK JANUSZ
Published: July 2009

Relevant contributions of fuzzy logic to the logical models in information retrieval is studied. It makes it possible to grasp the graduality of some relevant concepts and to model both imprecision and uncertainty inherent to the retrieval process, still in the framework of the broadly meant logical approach. In this perspective we discuss various extensions to the basic Boolean model which are needed to attain such a greater expressivity. In particular, we show how the well-known semantics of keywords weights may be recovered in various fuzzy logic based information retrieval models.
A FUZZY CONCEPTUAL MODEL FOR MULTIMEDIA DATA WITH A TEXT-BASED AUTOMATIC ANNOTATION SCHEME
Authors: KÜÇÜK DİLEK , BURCUÖZGÜR N. , YAZICI ADNAN , KOYUNCU MURAT
Published: July 2009

The size of multimedia data is increasing fast due to the abundance of multimedia applications. Modeling the semantics of the data effectively is crucial for proper management of it. In this paper, we present a fuzzy conceptual data model for multimedia data which is also generic in the sense that it can be adapted to all multimedia domains. The model takes an object-oriented approach and it handles fuzziness at different representation levels where fuzziness is inherent in multimedia applications and should be properly modeled. The proposed model also has the nice feature of representing the structural hierarchy of multimedia data as well as the spatial and temporal relations of the data. The model is applied to the news video domain and implemented as a fuzzy multimedia database system where it turns out to be effective in representing the domain and thereby provides an evidence for the general applicability of the model. The model is accompanied by an automatic multimedia annotation scheme which makes use of information extraction techniques on the corresponding multimedia texts.
FUZZY INTERVALS TO REPRESENT FUZZY VALID TIME IN A TEMPORAL RELATIONAL DATABASE
Authors: GARRIDO CARMEN , MARÍN NICOLÁS , PONS OLGA
Published: July 2009

Temporal databases offer a common framework to those database applications that need to store or handle different types of temporal data from a variety of sources. They allow the concept of time to be handled from the point of view of meaning, representation, and manipulation. Although at first sight the incorporation of time into a database might appear to be a direct and simple task, it is, however, quite complex: not only must new structures and specific operators be included, but the semantics of conventional DML sentences (insert, update, or delete) and queries must be appropriately changed. In addition, temporal information is not always as precise as desired since it might be affected by imprecision due to the use of natural language or to the nature of the information source. In this paper, we deal with the problem of the update (and, implicitly, insert and delete) and query operations when time is expressed by means of a fuzzy interval of dates.
EnteropathogenicEscherichia coliinhibits intestinal vitamin B1 (thiamin) uptake: studies with human-derived intestinal epithelial Caco-2 cells
Authors: Ashokkumar Balasubramaniem , Kumar Jeyan S. , Hecht Gail A. , Said Hamid M.
Published: July 2009

Infection with the gram-negative enteropathogenic Escherichia coli (EPEC), a food-borne pathogen, represents a significant risk to human health. Whereas diarrhea is a major consequence of this infection, malnutrition also occurs especially in severe and prolonged cases, which may aggravate the health status of the infected hosts. Here we examined the effect of EPEC infection on the intestinal uptake of the water-soluble vitamin B1 (thiamin) using an established human intestinal epithelial Caco-2 cell model. The results showed that infecting Caco-2 cells with wild-type EPEC (but not with nonpathogenic E. coli, killed EPEC, or filtered supernatant) leads to a significant ( P < 0.01) inhibition in thiamin uptake. Kinetic parameters of both the nanomolar (mediated by THTR-2) and the micromolar (mediated by THTR-1) saturable thiamin uptake processes were affected by EPEC infection. Cell surface expression of hTHTR-1 and -2 proteins, (determined by the biotinylation method) showed a significantly ( P < 0.01) lower expression in EPEC-treated cells compared with controls. EPEC infection also affected the steady-state mRNA levels as well as promoter activity of the SLC19A2 and SLC19A3 genes. Infecting Caco-2 cells with EPEC mutants that harbor mutations in the escN gene (which encodes a putative ATPase for the EPEC type III secretion system, TTSS) or the espA, espB, or espD genes (which encode structural components of the TTSS) did not affect thiamin uptake. On the other hand, mutations in espF and espH genes (which encode effector proteins) exhibited partial inhibition in thiamin uptake. These results demonstrate for the first time that EPEC infection of human intestinal epithelial cells leads to inhibition in thiamin uptake via effects on physiological and molecular parameters of hTHTR-1 and -2. Furthermore, the inhibition appears to be dependent on a functional TTSS of EPEC.
El papel de la microbiota en la enfermedad inflamatoria intestinal
Authors: Chermesh Irit , Shamir Raanan
Published: July 2009

La enfermedad de Crohn y la colitis ulcerosa son enfermedades inflamatorias del tubo digestivo que conjuntamente abarcan un espectro patológico denominado enfermedad inflamatoria intestinal (EII). El intestino humano es colonizado con una microbiota comensal a concentraciones que superan el número de células del cuerpo humano. En condiciones fisiológicas normales se produce una interacción entre estas bacterias y el hospedador humano en un proceso que mantiene la integridad del sistema inmunitario en la salud y la enfermedad. La microbiota intestinal desempeña un importante papel en la EII. Las bacterias comensales y las bacterias patógenas abarcan una parte de la etiología de la EII y la microbiota intestinal en pacientes con EII difiere de la correspondiente a controles sanos. Su influencia se origina probablemente en el inicio de la enfermedad, así como en reactivaciones y es lógico suponer que la manipulación de la microbiota intestinal podría ser una medida preventiva en la evolución de la EII, así como posiblemente desempeñar un papel terapéutico en la exacerbación de la enfermedad. En esta revisión comentaremos brevemente cuestiones relacionadas con el estudio de la microbiota intestinal, y la interacción de esta microbiota con el sistema inmunológico en la EII centrándonos en el papel de la microbiota en la etiología, las reactivaciones y el tratamiento de la EII.
In vivo Analysis of Tissue Response to Plasma-Treated Collagen-I-Coated Titanium Alloys
Authors: Hauser J. , Ring A. , Schaffran A. , Henrich L. , Esenwein S.A. , Steinau H.U. , Stricker I. , Langer S.
Published: July 2009

Purpose: The aim of this study was to evaluate the in vivo tissue response to low-pressure plasma-pretreated collagen-I-coated titanium implant in a middle-term mouse model. Methods: Plasma-treated collagen-coated titanium implants were transplanted into the dorsal skinfold chambers of BALB/c mice. Untreated, regular titanium implant material served as control. The neovascularization (functional vessel density) of the implant border zone and of the surrounding muscle tissue was analysed by intravital fluorescence microscopy. Additional histological analysis was performed to observe the inflammatory reaction. Results: Statistical analysis revealed that the vessel density in the border zone of the implants was significantly enhanced in the plasma-treated collagen-I-coated group compared to controls. The histological examination of the two groups confirmed that the inflammatory response to the collagen-coated titanium implants was reduced compared to controls. Conclusion: Plasma pretreatment and collagen I coating of titanium implant material leads to an enhanced tissue vascularization and a reduced inflammatory response.
Propolis Prevents the Effects of Chronic Alcohol Intake on Ocular Tissues
Authors: Emre Sinan , Yılmaz Zümrüt , Öztürk Feral , Emre M. Hanifi
Published: July 2009

Aim: This study is designed to investigate the protective effects of propolis in ocular tissues against chronic alcohol exposure. Material and Method: Wistar albino rats were used in this study. Rats were divided into 4 groups, and each group was fed a special liquid diet which contained an equal amount of calories. The control group was fed the liquid special diet without alcohol and propolis. We added propolis (150 mg/kg) to the diet of the second group. The diet of the third group contained alcohol, the concentration of which was increased progressively. The fourth group was fed a diet including propolis and alcohol. To counterbalance caloric intake, we decreased the amount of glucose in the special liquid diet for groups 3 and 4. At the end of 30 days, the animals were sacrificed and samples were kept at –80°C until evaluation. Specimens were investigated by light microscopy for morphology and morphometry. Results: In the histological investigation of ocular tissues, alcohol caused an increase in thickness of the cornea and corneal epithelium compared to the control group (p < 0.05). This incremental tendency was significantly reduced by propolis, and values were very close to those of the control group (p > 0.05). Alcohol did not cause any significant alteration of rat retinal thickness. Conclusion: This study showed that propolis is highly effective against corneal edema secondary to chronic alcohol intake.
Comparison of Transobturator Vaginal Tape and Retropubic Tension-Free Vaginal Tape: Clinical Outcome and Sonographic Results of a Case-Control Study
Authors: Reich Andreas , Wiesner Kathrin , Kohorst Frauke , Kreienberg Rolf , Flock Felix
Published: July 2009

Objectives: To compare the results and ultrasonographic characteristics of the transobturator vaginal tape (TVT-O) and retropubic (TVT) methods. Methods: 120 patients were treated with TVT-O. These were paired with similar patients treated with TVT. The patients were matched according to age, low-pressure urethra, preexisting mixed incontinence, and additional prolapse repair. The follow-up time was 3 months. Assessment variables included a standardized questionnaire, medical history, voiding diary, urinary stress test, 24-hour pad test, and introital ultrasound. The position of the tape was defined by its location in relation to urethral length (%) and the narrowness by its distance to the hypoechoic center of the urethra (mm). Results: The rates of postoperative complications including bladder perforation, urinary retention, and erosion through the vagina were similar. The number of hematomas occurring after TVT was insignificantly higher than after TVT-O (5 cases vs. 1 case). The rates for cure or improvement of stress incontinence were 77 and 17% after TVT-O and 85 and 14% after TVT (not significant). The sonographic characteristics were identical. Conclusion: In terms of clinical outcome, TVT and TVT-O appear to be equally effective. Complications and sonographic characteristics of the tapes were similar after both procedures.
Telestroke 10 Years Later – ‘Telestroke 2.0’
Authors: Switzer Jeffrey A. , Levine Steven R. , Hess David C.
Published: July 2009

Background: The lack of physicians with specialty stroke training represents a significant challenge to the future of stroke. This deficit limits both quality stroke care and clinical research initiatives. Methods: The use of telemedicine for stroke (‘telestroke’) has been an attempt to overcome this shortage and extend stroke expertise to locations which lack coverage. However, the initial telestroke systems required a point-to-point connection for transmission and only provided videoconferencing which limited their generalizability and usefulness. ‘Telestroke 2.0’ is the authors’ vision of an integrative web-based telestroke system combining high-quality audiovideo transmission, the ability of consults and teleradiology to be carried out from any desktop or laptop computer with web-access, decision and technical support, creation of billable physician documentation and electronic medical record connectivity. Results: These features will facilitate the development of statewide and regional telestroke call networks with an opportunity for physician supply companies to fill in coverage gaps. In addition, telestroke 2.0 may improve acute stroke research by increasing trial efficiency via the addition of non-academic recruitment sites, enhancing trial validity by centralizing neurologic examinations via recorded encounters, and generalizing clinical trial results to community hospital settings. Conclusions: Greater diffusion and long-term sustainability of telestroke systems will be dependent upon improvements in patient and hospital reimbursement for acute stroke and telestroke care.
Recovery after Ischemic Stroke: Criteria for Good Outcome by Level of Disability at Day 7
Authors: Hallevi Hen , Albright Karen C. , Martin-Schild Sheryl B. , Barreto Andrew D. , Morales Miriam M. , Bornstein Natan , Ifejika Nneka L. , Shuaib Ashfaq , Grotta James C. , Savitz Sean I.
Published: July 2009

Background: Ischemic stroke is a leading cause of morbidity. Assessing the chances of recovery is critical to optimize poststroke care. Methods: We used a cohort of patients from the Virtual International Stroke Trial Archive that participated in acute stroke trials (control arm) and were followed for 90 days. The cohort was grouped by day 7 (D7) modified Rankin scale (mRS) scores. Variables that were associated with good outcome (mRS 0–2 at 90 days) in the univariate analysis were entered into a logistic regression model to determine the independent good outcome criteria for each D7 mRS tier. Results: We analyzed 1,798 patients. The independent good outcome criteria identified for different mRS tiers were: D7 mRS of 3: age ≤70, 0–2 vascular risk factors, D7 NIH Stroke Scale (NIHSS) arm strength ≤1, D7 NIHSS language score = 0; D7 mRS of 4: age ≤70, male, D7 NIHSS facial palsy ≤1, D7 NIHSS visual = 0, D7 NIHSS leg strength ≤1, D7 NIHSS dysarthria = 0; D7 mRS of 5: age ≤70, IV tPA treatment, D7 NIHSS dysarthria = 0, D7 NIHSS leg strength ≤2. For each mRS tier, we observed a graded increase in the percentage of the primary and secondary end points with increase in the number of criteria. Conclusions: We identified clinical variables that predict good outcome, are specific to each day 7 mRS tier, and enable easy and informative assessment of the patient’s likelihood of achieving varying degrees of recovery at day 90. These results may be useful in both clinical practice and research but require validation in an independent patient cohort.
Risk of High-Grade Skin Rash in Cancer Patients Treated with Cetuximab – an Antibody against Epidermal Growth Factor Receptor: Systemic Review and Meta-Analysis
Authors: Su Xiao , Lacouture Mario E. , Jia Yuxia , Wu Shenhong
Published: July 2009

Background: Cetuximab, a chimeric antibody against epidermal growth factor receptor has emerged as an effective therapy for advanced colorectal cancer (CRC) and head-neck cancer. However, severe skin toxicity may limit its use. Its efficacy in the treatment of other cancers is also undergoing extensive investigation. We performed a systemic review and meta-analysis of published clinical trials to quantify the overall incidence and risk of severe skin rash. Methods: Databases Medline (OVID 1998 to July 2008), Web of Science, and abstracts presented at the American Society of Clinical Oncology conferences from 2004 through July 2008 were searched to identify relevant studies. Eligible studies include phase II and III clinical trials in which patients were treated with a single agent, i.e. cetuximab at 400 mg/m2 as initial dose followed by 250 mg/m2 weekly. Incidence, relative risk (RR), and 95% confidence intervals (CI) were calculated using a fixed-effects or random-effects model based on the heterogeneity of included studies. Results: A total of 2,037 patients with a variety of solid tumors from 16 trials were included for analysis. The overall incidence of all-grade skin rash was 88.2% (95% CI: 84.8–91.0%), with11.3% (95% CI: 8.8–14.3%) being high-grade (grade 3 or above). The overall incidence of all-grade acne-like skin rash was 81.6% (95% CI: 75.4–86.6%) with 6.5% (95% CI: 4.1–10.0%) being high-grade. Notably, patients with CRC exhibited a significantly higher incidence of high-grade skin rash (12.6%, 95% CI: 9.7–16.4%) than those with non-CRC (6.6%, 95% CI: 3.6–11.8%) with a risk ratio of 1.9 (95% CI: 1.0–3.6, p = 0.049). From randomized controlled studies, patients who received cetuximab had a significantly increased risk of developing high-grade skin rash in comparison with controls (RR 21.8, 95% CI: 6.9–68.8, p < 0.001). Conclusion: Cancer patients who received cetuximab have a substantial risk of developing high-grade skin rash. The risk may be particularly increased in patients with CRC. Further studies are strongly recommended for the prevention and treatment of high-grade skin rash.
Limited Value of CA 19-9 in Predicting Early Treatment Failure in Patients with Advanced Pancreatic Cancer
Authors: Vormittag Laurenz , Gleiss Andreas , Scheithauer Werner , Lang Fritz , Laengle Friedrich , Kornek Gabriela V.
Published: July 2009

Objective: The role of CA 19-9 in monitoring treatment response in advanced pancreatic cancer remains uncertain. We assessed its value in predicting early failure of first-line chemotherapy. Methods: Data of 84 patients with advanced pancreatic cancer who had received first-line chemotherapy were analyzed with regard to changes in CA 19-9 during the first 2 months of treatment. Results: Median time to progression and overall survival in patients with a transient increase in CA 19-9 during month 1 (n = 15; 5.5 and 13 months) and in those with no increase during the 2 months (n = 52; 6.5 and 12 months) were comparable and slightly above the median values of the entire study population. The hazard ratios for disease progression for a 20% increase in CA 19-9 during the first and second month of therapy were 1.065 and 1.339 in the univariate- and 1.092 and 1.298 in the multiple Cox regression model, respectively. CA 19-9 did not influence survival. Conclusion: Our results suggest that early CA 19-9 measurements are weakly associated with disease progression rather than survival in patients with advanced pancreatic cancer receiving palliative chemotherapy. In view of a possible tumor marker flare, values after the first month of therapy must be interpreted with caution.
Population-Based Epidemiological Study of Neurological Diseases in Taiwan: I. Creutzfeldt-Jakob Disease and Multiple Sclerosis
Authors: Lai Chien-Hsu , Tseng Hung-Fu
Published: July 2009

Background: The purpose of the study is to investigate the epidemiology of Creutzfeldt-Jakob disease (CJD) and multiple sclerosis (MS) in Taiwan. Methods: Cases of CJD and MS were identified from the National Health Insurance Research Database from January 2000 to December 2005. Age- and sex-specific incidences of these diseases were estimated by dividing the incidence number by population data obtained from the Department of Statistics, Ministry of the Interior. Results: During the study period, 79 cases of CJD, 41 women and 38 men, were identified. The average annual incidence rate was 0.63/million. Most cases were older than 60 years. There were 1,262 cases of MS. The male-to-female ratio was 0.4. The average annual incidence rate was 0.79/100,000. The incidence reached a peak at the age group of 40–60 years for females and at the age group of over 55 years for males. The prevalence of MS was 2.96/100,000 in 2005, which is higher than those of previous studies in Taiwan. Conclusions: The annual incidence rate of CJD in Taiwan is lower than in western countries. The annual incidence rate and prevalence of MS in Taiwan are low. The prevalence of MS in Taiwan increased in recent decades.
Phase IV Study of Bevacizumab in Combination with Infusional Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in First-Line Metastatic Colorectal Cancer
Authors: Sobrero Alberto , Ackland Stephen , Clarke Stephen , Perez-Carrión Ramón , Chiara Silvia , Gapski John , Mainwaring Paul , Langer Bernd , Young Scott
Published: July 2009

Background: Bevacizumab (Avastin®) significantly improves overall survival (OS) and progression-free survival (PFS) when combined with first-line irinotecan (IFL) plus bolus 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic colorectal cancer (CRC). This open-label, phase IV trial evaluated the efficacy and safety of first-line bevacizumab in combination with IFL and infusional 5-FU/LV (FOLFIRI). Methods: Two-hundred and nine treatment-naïve metastatic CRC patients were enrolled and received bevacizumab and FOLFIRI every 2 weeks. Treatment was continued until disease progression. The primary objective was PFS, with additional determinations of OS, response and toxicity. Results: Median PFS was 11.1 months and is comparable to that observed in published phase III and community-based trials using first-line bevacizumab plus FOLFIRI, and to phase III trials using bevacizumab in combination with bolus 5-FU/LV plus IFL. Median OS was 22.2 months. Overall response rate was 53.1% and the disease control rate 85.6%. Most adverse events were grade 1/2 and were manageable. The most common grade 3/4 adverse events (≥10%) were neutropenia, venous thromboembolic events, diarrhea, and fatigue. Conclusion: Bevacizumab combined with first-line FOLFIRI is an effective and well-tolerated therapy option for patients with metastatic CRC.
Antibody Response in Rabbits Following Intranasal and Parenteral Administration of Birch Pollen
Authors: Belin L. , Strannegård Ö.
Published: July 2009

Rabbits given birch pollen intranasally responded by forming serum and nasal antibody and also by developing immediate skin reactivity. The components of birch pollen which were mainly responsible for the development of immediate skin reactivity were identical with the components which are allergenic in man. In contrast, parenterally immunized rabbits, developed skin reactivity against allergenic as well as non-allergenic pollen components. These results suggest that allergenicity of a substance is not solely determined by its ability to induce reagin formation. The serum antibody response of the rabbits was characterized by an early appearance of antibodies against heat-labile, non-allergenic antigens whereas antibodies against heat-stable components usually appeared only after repeated antigenic stimulations. In contrast, antibodies in the nasal secretions seemed to be directed against heat-stable antigens, mainly. These results are discussed with regard to hyposensitization therapy and the function of ‘blocking’ antibodies.
Hapten Inhibition of Passive Antidextran Dextran Anaphylaxis in Guinea Pigs
Authors: Richter W.
Published: July 2009

High titred antidextran antisera have been raised in rabbits by prolonged immunization with soluble conjugates between isomaltose oligosaccharides or dextran mw 4,400 and bovine serum albumin in complete Freund’s adjuvant. Guinea pigs sensitized with such antisera exhibited anaphylactic shock on i.v. challenge with fractions of hydrolyzed B512 dextran. The severity of anaphylaxis depended on the amount of sensitizing antibody and the dose and molecular size of the challenging dextran fraction. In maximally sensitized animals, fractions of mw 3,600 or larger were anaphylactogenic and smaller molecular size fractions were nonanaphylactogenic. In submaximally sensitized animals, dextran fractions of mw 10,500 or less were foundnonanaphylactogenic. In addition, nonanaphylactogenic dextran fractions produced desensitization, i.e. protection from anaphylaxis due to subsequent or simultaneous injection of more high molecular and anaphylactogenic dextran fractions. When the molar ratio in a mixture of nonanaphylactogenic/anaphylactogenic fractions was about 7.6, protection was complete with reduction of mortality from 100 to 0%. A molar ratio of 1.9, corresponding to a 13-percent by weight admixture of nonanaphylactogenic dextran, still significantly reduced mortality from 100 to 50%. From the ability to form precipitates with antidextrans and to elicit anaphylaxis in sensitized guinea pigs, and from the absence of these properties, the approximate molecular size range of bivalent and monovalent dextran B512 fractions was found to correspond to mw 3,600 and mw 1,430, respectively. The practical applicability of hapten inhibition is discussed.
Release of Histamine from Skin during in vitro Anaphylaxis
Authors: Greaves M.W. , Fairley V.M. , Yamamoto S.
Published: July 2009

An in vitro system for the study of type I anaphylactic reactions in skin is described. Thin skin slices from sensitised rats are incubated with specific antigen and release of histamine is measured. Some simple characteristics of this system are defined. In further experiments histamine release is shown to be temperature-dependent and inhibition of release by disodium cromoglycate (Intal) is demonstrated.
Demonstration of Reagin-Allergen Complexes Formed on Elution of Reagins from Immunosorbent with Allergens
Authors: Kisil F.T. , Centeno E.R. , Attallah N.A. , Sehon A.H.
Published: July 2009

Elution of human reagins to ragweed pollen from an immunosorbent, synthesized by coupling the non-dialyzable components of the aqueous extract of the pollen to ethylene maleic anhydride copolymer, with low molecular weight components of the dialysate or of the ultrafiltrate of this extract resulted in the formation of allergen-reagin (A-R) complexes. Evidence for these complexes was inferred from the following observations: (a) intradermal injection of A-R eluates into the skin of normal volunteers produced immediate wheal and flare reactions; (b) when normal skin sites sensitized with allergic sera were challenged with A-R eluates, in dilutions which did not elicit any reactions in non-sensitized sites or in sites sensitized with normal human serum, wheal and flare reactions were obtained; (c) sensitization of normal skin sites with A-R eluates prevented further fixation of additional reagins.
Interaction Between ‘Sensitized Lymphocytes’ and Antigen in vitro
Authors: Maillard J.L. , Pick E. , Turk J.L.
Published: July 2009

The skin-reactive factor (SRF) synthesized by immunized guinea pig lymphocytes cultured in the presence of antigen or mitogen has been further investigated taking advantage of the vascular permeability induced by culture supernatant in the skin of the same species. The extravasation of Evans blue between the 20th minute and the 4th hour following the intradermal injection of culture supernatants reflects SRF activity, with precision. By means of this test lymph node lymphocytes in living condition are shown to produce a purer form of SRF than lymphocytes from other sources. Pharmacological studies disclosed that certain plasma fractions had an enhancing effect. Certain inhibitors of the kinins and of the coagulation systems had a depressing effect on SRF activity. The substance, with a suggested molecular weight of 39,000, could not be identified with any of the common mediators of inflammation. Several other properties of lymphocyte culture supernatants have been studied for their relationship on vascular permeability.
Studies of Non-Migrating, Long-Lived Lymphocytes in Rats and Mice
Authors: Miller III J.J. , Cole L.J.
Published: July 2009

Lymphocytes in mouse and rat popliteal lymph nodes were labeled with tritiated thymidine after an immunologic stimulus. Thirty days later the animals were given one or a series of injections of heterologous anti-lymph node or anti-thymus serum. The proportion of persistently labeled lymphocytes in the popliteal nodes was determined one or two days later. The proportion of long-lived lymphocytes in the nodes did not change even when a significant lymphopenia was produced. Since the nodes were depleted of small lymphocytes, labeled cells must have emigrated. These data support the hypothesis that non-migrating lymphocytes are not qualitatively different from the circulating lymphocyte pool.
Partial Immunologic Tolerance to the Human B but not to the A Antigen
Authors: Grundbacher F.J. , Shreffler D.C.
Published: July 2009

Quantitation of anti-A and anti-B isoantibodies in 472 selected children of the Tecumseh population has provided strong evidence that the A antigen of the mother does not induce any immunologic tolerance in her group-O children. Mean levels of hemolytic and saline anti-B, on the other hand, were lower in children of mothers with the B antigen than in children of mothers who lacked B, thus, indicating that the B antigen of the mother induces partial immunologic tolerance in her children.
Studies on Heart Anaphylaxis
Authors: Bernauer W. , Hahn F. , Nimptsch P. , Wissler J.
Published: July 2009

The effect of antigen (ovalbumin) on the sensitised papillary muscle and of anaphylatoxin (AT) and compound 48/80 on the sensitised and non-sensitised papillary muscle of guinea-pigs was studied. Two AT preparations were used: crude rat serum AT and a highly purified crystallised AT formed from hog serum. Each agent increased the contractile force of the papillary muscle leaving a state of ‘desensitisation’ or ‘tachyphylaxis’ against the same agent but not against the two others. Cross-desensitisation was observed between the crude and the crystallised AT only. AT or ovalbumin did not change the sensitivity of the papillary muscle to histamine. Pre-treatment with antigen, AT (crude preparation) or compound 48/80 markedly reduced the number of undamaged mast cells and in most experiments also reduced the total number of mast cells in the papillary muscle. It is concluded from these data that all three agents act on the papillary muscle of guinea-pigs mainly by histamine-independent mechanisms which are subject to tachyphylaxis. AT, histamine and compound 48/80 had no stimulating effect on the papillary muscle of rats. Dextran and serotonin were weakly effective whereas adrenaline and noradrenaline were potent stimulants. The mast cell count of the papillary muscle of rats is very low.
Enzyme-Potentiated Hyposensitisation
Authors: McEwen L.M. , Starr M.S.
Published: July 2009

The ability of preparations of hyaluronidase and β-glucuronidase to potentiate the hyposensitising effect of small doses of antigen injected subcutaneously into previously sensitised animals has been investigated in three different models of experimental anaphylaxis. Guinea-pigs were sensitised by egg albumen and repeatedly challenged by exposure to an aerosol of the antigen at weekly intervals. A small dose of antigen by injection increased their pre-convulsion times on subsequent challenge, and this was potentiated by the addition of hyaluronidase and β-glucuronidase. Rats were sensitised by horse serum and challenged 18 days later with intravenous antigen, deaths being noted within 24 h. Ten days after sensitisation, subcutaneous injections of antigen and β-glucuronidase greatly reduced the mortality on subsequent challenge although antigen injected alone had no effect. In mice sensitised by horse serum and challenged by pinnal anaphylaxis, the anamnestic increase in sensitivity produced by a subcutaneous dose of antigen was prevented by β-glucuronidase. Using this model, tolerance was induced by the intravenous injection of antigen and this was prevented by the addition of hyaluronidase.
Primary and Secondary Immune Response Kinetics in the Syrian Hamster
Authors: Erb P. , Lazàry S. , Loeffler H.
Published: July 2009

Numbers of direct and indirect plaque-forming cells (pfc) per 106 spleen cells, total and mercaptoethanol-resistant hemolysin and hemagglutinin activity have been determined in adult male Syrian hamsters at different times after primary and secondary intraperitoneal injection of 1×1010 sheep red blood cells (SRBC). Only a high antigen dose was sufficient for stimulating a uniform immune response. The kinetics of the primary response at the cellular and serum level corresponds in general to that of the mouse and other laboratory animals. In the secondary response the direct pfc/106 spleen cells and total serum hemolysin and hemagglutinin concentrations were higher than in the primary response and the pfc and serum antibody curves declined rapidly again after reaching their peaks.
Characterization of Allergen Extracts by Polyacrylamide Gel Isoelectrofocusing and Radioimmunosorbent Allergen Assay
Authors: Ceska M. , Eriksson R. , Varga J.M.
Published: July 2009

Commercial extracts of birch pollen and birch allergen extracts prepared from the pollen of five different Betula species were characterized by gel isoelectrofocusing and paper-disk radioimmunosorbent allergen assay, as described in earlier communications. No correlation between the distribution of total protein and allergenic activity in the fractions could be demonstrated. The major common allergen components appeared to have pI values between 4.5 and 5.5 in both the commercial and our own extracts. Additional minor components with both lower and higher pI could be demonstrated in extracts obtained from some Betula species.
Effect of Prednisone Treatment on the Human Immune Response to Keyhole Limpet Hemocyanin
Authors: Tuchinda M. , Newcomb R.W. , DeVald B.L.
Published: July 2009

The immune responses to KLH injections were investigated in 12 children with asthma, 6 of whom received prednisone for control of asthma. Two injections of 320 μgN KLH were given 14 days apart. Antibodies were investigated by hemagglutination titration, radioactive antigen-binding techniques and skin testing. The results suggested that therapeutic doses of prednisone, given on alternate days, may have enhanced the primary γG- and γM-antibody responses, but had no effect on antibody levels formed after the booster dose of KLH. However, positive wheal and flare skin reactions were somewhat more frequent in the non-steroid treated subjects 4 weeks after the second immunizing KLH dose than in the steroid-treated children. No unequivocal delayed type skin reactions were found in either group.
Investigation of the Responsiveness of BCG-Vaccinated Children with Whooping-Cough to Tuberculin
Authors: Pieroni R.E. , Stevens D.L. , Stojanović A. , Levine L.
Published: July 2009

Of 29 BCG-vaccinated children with a clinical diagnosis of pertussis, only 4 (14%) were found to be tuberculin positive. This is in marked contrast to the high rate of reactivity reported for normal BCG-vaccinated children of similar age. The 4 positive reactors did not differ significantly from the 25 negatives with respect to age, interval between onset of pertussis and tuberculin test, nor to lymphocyte count taken either as the absolute number or as the percentage of leukocytes. Possible mechanisms to account for this anergic state are discussed.
Influence of Species of Origin of Red Blood Cells on in vitro Inhibition of Streptolysin O by Serum Lipoproteins
Authors: Hamnström B. , Winblad S.
Published: July 2009

High non-specific anti-streptolysin·titres (lipoprotein-dependent) showed different values in the same sera when tested with various kinds of erythrocytes. With rabbit erythrocytes, low non-specific titres were obtained, in contrast to red blood cells from sheep, man, ox, horse, pig and rat. In contrast, high specific anti-streptolysin·titres did not vary much with the kind of red blood cells used.
The Detection of Autoantibody-Forming Cells
Authors: Lennon Vanda , Feldmann Marc
Published: July 2009

A haemolytic plaque assay method is described for the detection of lymphoid cells forming autoantibody in vitro. Sheep red blood cells coated with the basic protein of myelin as antigen were lysed specifically by antibody produced by lymph node cells from guinea-pigs immunized with this basic protein, an organ-specific antigen of brain. The background number of plaque-forming lymphoid cells, using uncoated or coated sheep red cells, was very low, less than 6 per million, in non-immunized guinea-pigs. From day 7 after intradermal immunization with basic protein, plaque-forming cells were found in the regional lymph nodes, but the majority were detectable only after the addition of ‘enhancing’ anti-guinea-pig immunoglobulin serum. Haemolysis of cells coated with basic protein was due to the release of specific anti-basic protein antibody because lysis was inhibited by excess free basic protein, and red cells coated with an unrelated antigen were not lysed. Red cells coated with basic protein were also used in a haemolytic titration assay for serum antibody to basic protein: this proved almost as sensitive as radioimmunoassay and so is a useful alternative to it. The particular value in studying autoantibody-forming cells in vitro by the haemolytic plaque technique may be in the detection of those autoantibodies not hitherto demonstrable in serum by reason of absorption in vivo to target autoantigens in tissues.
Experience with Lymphocyte Transformation Tests in Evaluating Allergy to Aminosalicylic Acid, Isoniazid and Streptomycin
Authors: Mathews K.P. , Pan Pauline M. , Wells J.H.
Published: July 2009

Patients with possible allergic reactions to aminosalicylic acid, isoniazid or streptomycin were systematically evaluated to ascertain circumstances under which in vitro transformation of their lymphocytes cultured with the suspected drug would and would not be observed. Leukocytes were cultured for 6 days with 1,000, 100 and 10 µg of drug/ml and tritiated thymidine uptake determined. Stimulation was observed in 13 of 53 cultures from 39 patients and in only 1 of 45 control cultures of lymphocytes from persons who had taken these drugs without evident adverse effects. Optimal drug concentration was variable. In correlating lymphocyte culture results with clinical information, it was found that individuals experiencing predominantly febrile drug reactions usually had negative cultures. In general, lymphocyte transformation does not necessarily indicate immunologic responsiveness of a deleterious type, but in this study there was a significant empiric correlation with clinical drug allergy.
Salivary Immunoglobulins in Sjögren's Syndrome
Authors: Bluestone R. , Gumpel J.M. , Goldberg L.S. , Holborow E.J.
Published: July 2009

Using a new electro-immunodiffusion assay, serum and salivary immunoglobulin levels were measured in patients with SjÖgren’s syndrome (SS) and in normal control subjects. Salivary IgG levels were generally higher in the patients (mean 17.3 mg%, SEM 1.7) compared to normals (mean 12.1 mg%, SEM 1.3), the higher values usually correlating with elevated serum IgG levels. Salivary IgA levels were similar in both groups – a mean of 10.3 mg%, SEM 2.5 in normals and 8.9 mg%, SEM 2.0 in the patients. In the latter group much of the salivary IgA was secretory IgA; absolute levels of secretory IgA ranged from 2.5 to 6.4 mg% (mean 4.4). No measurable levels of IgM were detected in the salivas of patients or normal subjects, although IgM was demonstrated by immunofluorescence in labial gland biopsies from two patients. Four patients had serum anti-salivary duct antibodies, but none had this autoantibody in their saliva. Thus, patients with SS retain competence of the salivary immune system even in the advanced stages of their disease.