Lolium perenne peptide immunotherapy is well tolerated and elicits a protective B-cell response in seasonal allergic rhinitis patients.

BACKGROUND: Systemic allergic reactions are a risk for allergen immunotherapy that utilizes intact allergen preparations. We evaluated the safety, efficacy and immune mechanisms of short-course treatment with adjuvant-free Lolium perenne peptides (LPP) following a 6-week dose-escalation protocol. METHODS: In a prospective, dose-escalation study, 61 grass pollen-allergic patients received 2 subcutaneous injections of LPP once weekly for 6 weeks. Safety was assessed evaluating local reactions, systemic reactions and adverse events. The clinical effect of LPP was determined by reactivity to the conjunctival provocation test (CPT). Specific IgE, IgG4 and blocking antibodies were measured at baseline (V1), during (V6) and after treatment (V8). RESULTS: No fatality, serious adverse event or epinephrine use was reported. Mean wheal diameters after injections were <0.6 cm and mean redness diameters <2.5 cm, independent of dose. Transient and mostly mild adverse events were reported in 33 patients. Two patients experienced a grade I and 4 patients a grade II reaction (AWMF classification). At V8, 69.8% of patients became nonreactive to CPT. sIgG4 levels were higher at V6 (8.1-fold, P < .001) and V8 (12.2-fold, P < .001) than at V1. The sIgE:sIgG4 ratio decreased at V6 (-54.6%, P < .001) and V8 (-71.6%, P < .001) compared to V1. The absolute decrease in IgE-facilitated allergen binding was 18% (P < .001) at V6 and 25% (P < .001) at V8. CONCLUSION: Increasing doses of subcutaneous LPP appeared safe, substantially diminished reactivity to CPT and induced blocking antibodies as early as 4 weeks after treatment initiation. The benefit/risk balance of LPP immunotherapy remains to be further evaluated in large studies.

Success factors for adherence in hyposensitization.

For the success of an immunotherapy regimen, adherence is a major success factor. The goal of our study was to identify the factors that positively and negatively influence patient compliance, and to create strategies to improve it. Four questionnaires were designed for different patient groups: A - after immunotherapy; B - during immunotherapy; C - before immunotherapy; D - no experience with immunotherapy. From March to October 2008, 790 questionnaires were collected. For the first group, questionnaire A was answered by 272 patients. Of these, 15.8% had dropped out of immunotherapy. Women had higher dropout rates than men (16.8% vs. 12.3%). The following aspects of immunotherapy were viewed by the patients as negative: time consuming (69.5%), adverse reactions (62.5%), insufficient patient information (53.7%), no change in use of symptomatic medication (33.8%) and no change in symptoms (60.7%). Despite the mentioned drawbacks, 74% of all patients would still recommend allergen immunotherapy. Questionnaire B was completed by 281 patients. In this group, 8.7% had already considered dropping out. The following unfavourable aspects were identified: time consuming (66.2%), adverse reactions (61.9%), insufficient patient information (54.8%), no change in symptoms (51.2%) and use of symptomatic medication (47.0%). Despite this, up to 95.4% of all patients would recommend immunotherapy. Questionnaire C was filled-out by 55 patients. The following reasons were rated by the patients as "important" or "very important" for the decision to start hyposensitization: long-lasting symptom alleviation (100%), few adverse reactions (98.2%), comprehensive patient information (96.3%), easy integration into daily routine (89.1%), re-assessment of therapy by doctor (83.3%) and reduced need for symptomatic medication (81.8%). Questionnaire D was filled in by 182 participants. 89% had already heard the term hyposensitization before. Their general knowledge regarding this therapy was average (3.23 on a scale of 1 - 6; where 1 = optimum). Long-lasting symptom alleviation (99.5%), comprehensive patient information (97.8%), easy integration into daily routine (96.1%), reduced symptomatic medication use (92.6%) and re-assessment by doctor (88.8%) were considered "very important" or "important" characters in the desired immunotherapy regime. Adherence to the hyposensitization schedule is essential for its success. The treating doctor should aim at choosing the right therapy and working out an individualized patient treatment plan. Equally important is providing information to the patient throughout the duration of the treatment. The doctor should assist the patient to create an optimized time schedule to help make the therapy less time-consuming.

RCAT reflects symptom control and quality of life in allergic rhinoconjunctivitis patients.

BACKGROUND: The Global Allergy and Asthma European Network (GA2 LEN) Taskforce has requested more data on correlations between various patient-reported outcomes (PROs) in clinical trials on allergy. We compared three tools-the Rhinitis Control Assessment Test (RCAT), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Rhinitis Total Symptom Score (RTSS)-to determine whether the RCAT alone is a sufficient primary outcome parameter in clinical trials on allergic rhinoconjunctivitis. METHODS: In two double-blind, placebo-controlled immunotherapy studies, 33 patients allergic to grass pollen and 94 to birch pollen completed two questionnaires (RCAT and RQLQ) and kept their own symptom diary from which the RTSS was calculated. RESULTS: Upon comparing RCAT and RQLQ results, we found strong correlations of r = -0.871 for grass pollen-allergic patients and r = -0.795 for birch pollen-allergic patients. The comparison between RCAT and RTSS results showed a strong correlation of r = -0.811 (grass pollen-allergic patients) and a moderate correlation of r = -0.539 (birch pollen-allergic patients). In the RCAT, 69.7% of grass pollen-allergic patients and 45.7% of birch pollen-allergic patients receiving guideline-concordant therapy were regarded as having insufficiently controlled symptoms. CONCLUSION: The strong correlations suggest that the RCAT alone is equivalent to the RQLQ with respect to patients' symptom control and quality of life. Patients with uncontrolled symptoms can be identified using the RCAT. Hence, the physician can decide whether symptomatic therapy can be intensified or allergy immunotherapy should be administered.

A randomized, double-blind, placebo-controlled, dose-finding trial with Lolium perenne peptide immunotherapy.

BACKGROUND: A novel subcutaneous allergen immunotherapy formulation (gpASIT+™) containing Lolium perenne peptides (LPP) and having a short up-dosing phase has been developed to treat grass pollen-induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity and safety. METHODS: This prospective, double-blind, placebo-controlled, phase IIb, parallel, four-arm, dose-finding study randomized 198 grass pollen-allergic adults to receive placebo or cumulative doses of 70, 170 or 370 µg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3 and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks and after completion. Grass pollen-specific immunoglobulins were analysed before and after treatment. RESULTS: Conjunctival provocation test (CPT) response thresholds improved from baseline to V7 by at least one concentration step in 51.2% (170 µg; P = .023), 46.3% (370 µg), and 38.6% (70 µg) of patients receiving LPP vs 25.6% of patients receiving placebo (modified per-protocol set). Also, 39% of patients in the 170-µg group became nonreactive to CPT vs 18% in the placebo group. Facilitated allergen-binding assays revealed a highly significant (P < .001) dose-dependent reduction in IgE allergen binding across all treatment groups (70 µg: 17.1%; 170 µg: 18.8%; 370 µg: 26.4%). Specific IgG4 levels increased to 1.6-fold (70 µg), 3.1-fold (170 µg) and 3.9-fold (370 µg) (mPP). CONCLUSION: Three-week immunotherapy with 170 µg LPP reduced CPT reactivity significantly and increased protective specific antibodies.

Ultra-short-course booster is effective in recurrent grass pollen-induced allergic rhinoconjunctivitis.

BACKGROUND: A relevant proportion of allergic rhinoconjunctivitis (ARC) patients experience recurrent symptoms after successfully completing allergen immunotherapy (AIT). This prospective, controlled, noninterventional study used internationally standardized instruments to determine the clinical effects of a preseasonal, ultra-short-course booster AIT on clinical outcome parameters. METHODS: This two-arm study included patients aged ≥12 years with recurrent grass pollen-induced seasonal AR who had completed a successful course of any grass pollen AIT at least 5 years before enrolment. Overall, 56 patients received one preseasonal short-course booster AIT using tyrosine-absorbed grass pollen allergoids containing the adjuvant monophosphoryl lipid A (MPL® ); 51 control patients received symptomatic medication. The combined symptom and medication score (CSMS) was recorded in the (peak) grass pollen season. Furthermore, concomitant (antiallergic) medication use, the patients' state of health, Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) results and safety/tolerability of the treatment were assessed. RESULTS: The CSMS in the peak grass pollen season was significantly lower in the booster AIT group (Δ=38.4%, P<.01). Moreover, significantly more patients in this group used no concomitant antiallergic medication throughout the peak grass pollen season. Twice as many patients in the booster AIT group as in the control group reported having a better state of health than in the preceding season. MiniRQLQ results showed significant differences favouring the booster AIT. The booster AIT was generally well tolerated, with only two patients reporting mild, grade 1 systemic adverse events. CONCLUSION: Booster AIT using tyrosine-absorbed allergoids containing the adjuvant MPL® effectively prevents re-occurrence of symptoms in patients with grass pollen-induced ARC.

On the consistency of seismically imaged lower mantle slabs.

The geoscience community is increasingly utilizing seismic tomography to interpret mantle heterogeneity and its links to past tectonic and geodynamic processes. To assess the robustness and distribution of positive seismic anomalies, inferred as subducted slabs, we create a set of vote maps for the lower mantle with 14 global P-wave or S-wave tomography models. Based on a depth-dependent threshold metric, an average of 20% of any given tomography model depth is identified as a potential slab. However, upon combining the 14 models, the most consistent positive wavespeed features are identified by an increasing vote count. An overall peak in the most robust anomalies is found between 1000-1400 km depth, followed by a decline to a minimum around 2000 km. While this trend could reflect reduced tomographic resolution in the middle mantle, we show that it may alternatively relate to real changes in the time-dependent subduction flux and/or a mid-lower mantle viscosity increase. An apparent secondary peak in agreement below 2500 km depth may reflect the degree-two lower mantle slow seismic structures. Vote maps illustrate the potential shortcomings of using a limited number or type of tomography models and slab threshold criteria.

A 12-week DBPC dose-finding study with sublingual monomeric allergoid tablets in house dust mite-allergic patients.

BACKGROUND: In sublingual immunotherapy, optimal doses are a key factor for therapeutic outcomes. The aim of this study with tablets containing carbamylated monomeric house dust mite allergoids was to determine the most effective and safe dose. METHODS: In this double-blind, placebo-controlled dose-finding study, 131 patients with house dust mite-induced allergic rhinoconjunctivitis were randomized to 12-week treatments with 300 UA/day, 1000 UA/day, 2000 UA/day, 3000 UA/day or placebo. Conjunctival provocation tests (CPT) were performed before, during and after treatment. The change in mean allergic severity (primary endpoint), calculated from the severity of the CPT reaction, and the proportion of patients with an improved CPT threshold (secondary endpoint) determined the treatment effect. RESULTS: The mean allergic severity decreased in all groups, including the placebo group. It was lower in all active treatment groups (300 UA/day: 0.14, 1000 UA/day: 0.15, 2000 UA/day: 0.10, 3000 UA/day: 0.15) than in the placebo group (0.30). However, this difference was not statistically significant (P < 0.1). The percentage of patients with an improved CPT threshold was higher in the active treatment groups (300 UA/day: 73.9%; 1000 UA/day: 76.0%; 2000 UA/day: 88.5%; 3000 UA/day: 76.0%) than in the placebo group (64.3%). The difference between placebo and 2000 UA/day was statistically significant (P = 0.04). In 13 (10%) exposed patients, a total of 20 treatment-related adverse events of mild severity were observed. CONCLUSIONS: The 12-week daily treatment using 2000 UA/day monomeric allergoid sublingual tablets is well tolerated and reduces the CPT reaction in house dust mite-allergic patients.

[Risks acceptability related to obstetrical epidural analgesia]. / Acceptabilité des risques associés à la mise en place d'une analgésie péridurale obstétricale.

OBJECTIVES: Evaluation of the acceptability of complications related to obstetrical epidural analgesia in two populations, parturients and anesthesiologists. STUDY DESIGN: Prospective, transversal, single center study. MATERIALS AND METHODS: Evaluation of the acceptability of complications associated with obstetric epidural analgesia performed using a questionnaire of six clinical scenarii in two populations: parturients cared at the University maternity of Nancy and anesthesiologists of Lorraine. Patients were interviewed by an anesthesiologist, physicians via Internet. Acceptability was assessed using two tools, the absolute acceptability with a visual analog scale and the relative acceptability obtained by classifying clinical scenario against each other, in ascending order of acceptability. RESULTS: One hundred and forty-six parturients and 87 anesthetists assessed the acceptability of the different scenarios. The three less serious scenarios (hypotension, failure, dural tap) were acceptable for both populations. One case (spinal hematoma) was unacceptable for parturients. Three cases of varying severity (failure, dural tap, plexus injury with sequelae) were judged significantly less acceptable by patients than physicians (5.9 vs. 7.9 [P<0.001], 5.75 vs. 8.1 [P<0.01], 4.1 vs. 5.1 [P=0.035]). Multivariate analysis did not show any predictive factor of acceptability in both populations. CONCLUSION: In this study, the overall acceptability of the inherent complications of epidural analgesia was good in the two populations. It was essentially based on the notion of severity and preventability. A large interindividual variability was observed and a better acceptance by the anesthesiologists.

Objectifying the conjunctival provocation test: photography-based rating and digital analysis.

BACKGROUND: Patients with allergic rhinoconjunctivitis are susceptible to both nasal and ocular symptoms. The conjunctival provocation test (CPT) is an established diagnostic procedure used in allergic rhinoconjunctivitis, particularly to document a patient's current reactivity to allergens. To date, there are no international guidelines defining the CPT. No approved evaluation method exists for interpreting CPT results. This paper aims to establish the digital analysis of macroimages as an objective, validated and standardized method for interpreting CPT results. METHODS: In a clinical immunotherapy trial with 155 patients, treatment progress was documented based on the CPT. Local investigators used a symptom score to grade tearing, reddening and the patients' subjective perception of symptoms (mucosal irritation). A central observer rated conjunctival hyperemia via digital photography. Digital image analysis software was utilized to determine conjunctival hyperemia. RESULTS: Spearman's correlation between the local investigators' and the central observer's ratings was r = 0.729 (p < 0.001); the percentage of total agreement was 48% (based on 739 photos). Digital image analysis (based on 48 photos) had a high percentage of total agreement with the central observer's ratings (69%) but a low percentage of total agreement with the investigators' ratings (38%). The corresponding correlations were r = 0.264 and 0.064, respectively. CONCLUSION: Photography-based rating by a central observer may represent a valuable supplement to the local investigator's assessment for making an objective evaluation of CPT results. Digital image analysis possesses the potential of being an objective evaluation method compared to the wide-spread subjective evaluation by the investigators.

Efficacy and tolerability of bromelain in patients with chronic rhinosinusitis--a pilot study.

OBJECTIVES: To evaluate the efficacy, tolerability, and impact on quality of life (QoL) of bromelain tablets (500 FIP) in patients with chronic rhinosinusitis (CRS). METHODS: In this prospective, open-label observational pilot study, 12 patients suffering from CRS with (CRS+NP) or without (CRS-NP) nasal polyps who had undergone prior sinus surgery were treated with bromelain tablets (500 FIP) for three months. Efficacy was evaluated using symptom scores (Total Symptom Scores: TSS); a Total Rhinoscopy Score (TRS) was also determined. QoL was assessed by using the German, adapted version of the Sinonasal Outcome Test 20 (SNOT-20 GAV). RESULTS: Treatment with bromelain tablets (500 FIP) improved TSS, TRS and SNOT-20 GAV on average. This treatment was found to be more effective, however, for CRS-NP than for CRS+NP. The average intake was six tablets, equivalent to a daily dosage of 3000 FIP. No adverse events were observed. CONCLUSION: Preliminary results indicate good tolerability, symptom control, and improvement in QoL for the treatment of CRS using bromelain tablets (500 FIP).

A meta-analysis of the efficacy of quinolone containing otics in comparison to antibiotic-steroid combination drugs in the local treatment of otitis externa.

BACKGROUND: The term otitis externa denotes the inflammation of the external auditory canal and can be treated locally in the form of monotherapy or a combination drug. OBJECTIVE: The aim of the present meta-analysis was to compare the efficacy of an antibiotic-steroid combination drug with that of monotherapy. According to current data, a comparable investigation based on network analysis does not exist. METHODS: After systematically searching the PubMed, Medline, Medpilot, Web of Science and Embase electronic databases, 12 relevant randomized, controlled, clinical studies were identified involving 2682 evaluable patients with regard to the cure rate and seven publications with 1251 microbiologically assessable patients. The collected data were compared directly and indirectly by means of network analysis. RESULTS: The direct comparison showed a trend towards the superiority of the monotherapy containing quinolone. The network analysis verified this tendency and demonstrated that pure quinolone drugs can achieve a significantly higher cure rate (OR: 1.29; 95% CI: 1.06-1.57; p = 0.01) and a significantly superior eradication rate (OR: 1.44; 95% CI: 1.03-2.02; p = 0.03) compared to combination drugs not containing quinolone. We found substantial heterogeneity (with I(2) up to 88.7%) between studies, presumably due to treatments applied in varying frequency, thus bearing on compliance and outcome. CONCLUSION: With a level Ia evidence, this investigation validates the clinical benefit of quinolones as compared to classic combination drugs in the local treatment of acute otitis externa.

Medication persistence with long-term, specific grass pollen immunotherapy measured by prescription renewal rates.

OBJECTIVE: We assessed medication persistence using prescription renewal rates for grass pollen specific immunotherapy (SIT) in a representative population of patients in Germany to evaluate whether the perception of superior persistence for the subcutaneous route compared to the sublingual route could be confirmed in clinical practice. METHODS: Individual prescriptions for allergen immunotherapy were extracted from a national prescription database (INSIGHT Health) and followed over 3 years on a per-patient basis. However, patients' medical history and treatment schedules were not available for analysis. Products were identified by the national drug code (PZN number) and grouped to either subcutaneous immunotherapy (SCIT) with natural extract injections, SCIT with modified allergens (allergoids) or sublingual immunotherapy (SLIT) with natural pollen extract solutions. Persistence was defined as at least one prescription of the individual drug in the respective years. RESULTS: A total of 1409 patients started SIT in 2005 (112, 695, and 602 for natural extract SLIT, natural extract SCIT, and allergoid SCIT, respectively). In 2006, 71%, 55%, and 59% of those patients had at least one renewal prescription of natural extract SLIT, natural extract SCIT, and allergoid SCIT, respectively, as well as 51%, 34%, and 39% in 2007. In both years, persistence with natural extract SLIT was significantly higher than with natural extract SCIT (p = 0.0015 for 2006, p = 0.0003 for 2007) and allergoid SCIT (p = 0.0152 for 2006, p = 0.0111 for 2007). There were no significant differences between the two SCIT groups. CONCLUSION: Medication persistence with grass pollen SIT in a representative sample of patients in Germany was similar to published medication persistence in asthma and COPD patients. The sublingual application route shows significantly better persistency than the subcutaneous route with native allergens or allergoids.

4-Phase-Rhinomanometry (4PR)--basics and practice 2010.

The last comprehensive publications about the theory and practice of rhinomanometry appeared more than 20 years ago. Since the 1980's, the general progress of sensor techniques, fluid physics and data processing was accompanied by the permanent work of the authors to analyze the errors of rhinomanometry and to create a fundament for a contemporary and practical method that can be used in functional diagnostics of the nasal air stream. In this special document, the objectives and measurement principles, as well as the history of rhinomanometry are described in the first three chapters. It is pointed out, that the key parameters are not only intranasal pressure and flow, but also the factor time. The technical requirements as following from the dynamics of breathing are described. The process of averaging of rhinomanometric data lead to a separate and time-dependent analysis of the changes of pressure and flow and implicated the introduction of the 4 breathing phases (ascending and descending curve part in inspiration and expiration) into rhinomanometry and is therefore called 4-Phase-Rhinomanometry (4PR). Chapter 4 is containing a comprehensive analysis of the practical errors, which may follow neglecting the 4 breathing phases. The in chapter 5 described mathematical-physical concept of 4PR is based on the introduction of the terms "steady" and "unsteady" flow, in addition to the up to now used terms of laminarity and turbulence. After the derivation of the HOFFRICHTER-equation as explaining the loops around the intersection point of the x-axis and y-axis, a clinical classification of the rhinomanometric findings is given and confirmed by physical experiments with "artificial noses". Finally, testing the rhinomanometric method by CFD (Computational Fluid Dynamics), lead to the same conclusions as to the importance of 4 phases of the breathing cycle. The precondition for the worldwide introduction of new parameters into the 4PR is a comprehensive statistical analysis. The disadvantages of the present recommended standard values are described in chapter 6. Following previous studies in 5800 cases, the parameters Vertex Resistance (VR), Effective Resistance (Reff) and their logarithmic transformations have been investigated in 1580 rhinograms of different degrees of obstructions, also including the correlations to a VAS. It could be confirmed, that the parameters VR and Reff after logarithmic transformation, have a significant and high correlation to the sensation of obstruction. The new clinical classification of obstruction and conductance of the nose is proposed in Table 1 for Caucasian noses. Table 1. Clinical classification of obstruction and conductance for Causcasian noses. [see text for table]. Chapter 7 is dedicated to the advantages of 4PR in the functional diagnosis of nasal valve problems. Graphical as well as numerical solutions are available by the fact, that the motions of the nasal entrance as caused by the breathing process are now visible from the shape of the 4PR-curve. Discussing practical aspects in chapter 8, the start point of proposals and discussions are the standard recommendations of the ISOANA and the results of its consensus conference in 2003. In particular the calibration processes, hygiene, the correct attachment of the pressure tube at the nostril ("tape method") and the different measurement procedures (AAR, APR), decongestion and provocation tests are extensively described. Both the final chapters are clinical contributions from mainland China, which are of high importance because of the racial differences in nasal respiratory function. In chapter 9, tests of the assessment of normal nasal airway in adult Chinese by 4PR, rhinomanometry and acoustic rhinometry are presented. This investigation lead to the conclusion that 4PR is an important supplement to classic rhinomanometry and acoustic rhinometry, if the classification of obstruction is adapted to the higher basic resistance of the Chinese population. Chapter 10 is dealing with 4PR and acoustic rhinometry in the functional evaluation of septal deviations and concludes, that both methods are valuable objective instruments for the evaluation of nasal obstruction.

Evaluation of the plasma quality after filtration.

BACKGROUND AND THE PURPOSE OF THE STUDY: The quality of some of the human plasma derived drugs such as coagulation factor VIII and coagulation factor IX which can be used for the treatment of hemophilia A and B, depends on their activity which may be affected by filtration. In this study the quality of plasma with respect to coagulation factors FVII, FVIII, FIX, FV, FXI, Fibrinogen, antithrombin III, anti-plasmin and antitrypsin activities obtained after plasma filtration with CPD (citrate-phosphate-dextrose) using integral filter was evaluated. METHODS: Sixty units of plasma were individually separated from whole blood by centrifugation and immediately filtered by integral filter system. Specific plasma filtration was carried out between 4 and 20 hrs after blood donation. Before filtration, 60 units of non filtered fresh plasmas were kept as control. Coagulation factors were determined by one-stage clotting assay in an automated system. Antithrombin III activity was determined by immunochrom assay in an automated system. Activity of anti-plasmin was determined by Berichrom α(2)-antiplasmin and antitrypsin activity was assayed with human neutrophil elastase. RESULTS: The activity of coagulation factors FVIII, FIX, Fibrinogen, FV, and FXI, were not affected by filtration, in all experiments. Filtration only caused negligible change in FVII activity. Antithrombin III, anti-plasmin and antitrypsin activities were not influenced by filtration. Nonfiltrated and filtrated plasma values were not significantly different (P> 0.05). CONCLUSIONS: Plasma filtration dose not result in a measurable impairment of coagulation factors and inhibitors. Although a little changes in FVII activity was observed after filtration, but these filtration-dependent changes apparently have no impact on the therapeutic quality of whole blood- filtered fresh plasma for transfusion.

Expression of reverse cholesterol transport proteins ATP-binding cassette A1 (ABCA1) and scavenger receptor BI (SR-BI) in the retina and retinal pigment epithelium.

AIMS: Excessive lipid accumulation in Bruch's membrane (BrM) is a hallmark of ageing, the major risk factor for age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells may utilise reverse cholesterol transport (RCT) activity to move lipid into BrM, mediated through ATP-binding cassette A1 (ABCA1) and scavenger receptor BI (SR-BI). METHODS: ABCA1 expression was assessed by reverse transcription polymerase chain reaction (RT-PCR) and western blotting of human RPE cell extracts. Lipid transport assays were performed using radiolabelled photoreceptor outer segments (POS). ABCA1 and SR-BI expression was examined in normal mouse eyes by immunofluorescence staining. BrMs of ABCA1 and SR-BI heterozygous mice were examined microscopically. RESULTS: Human RPE cells expressed ABCA1 mRNA and protein. The ABCA1 and SR-BI inhibitor glyburide (also known as glibenclamide) abolished basal transport of POS-derived lipids in RPE cells in the presence of high-density lipoprotein. Mouse retina and RPE expressed ABCA1 and SR-BI. SR-BI was highly expressed in RPE. BrMs were significantly thickened in SR-BI heterozygous mice, but not in ABCA1 heterozygous mice. CONCLUSION: RPE cells express ABCA1 and SR-BI. This implies a significant role for SR-BI and ABCA1 in lipid transport and RCT in the retina and RPE.

Prevalence of left main coronary artery disease among patients with ischemic heart disease: insights from the Tehran Angiography Registry.

AIM: This study was designed to investigate the prevalence of left main coronary artery (LMCA) significant stenosis among patients with stable angina (SA) or acute coronary syndromes (ACSs) and to assess the influence of demographic and clinical profiles on these findings. METHODS: A review of the Angiography Registry demonstrated that 18137 patients had SA or ACSs. The patients' characteristics were compared in subgroups with and without LMCA disease. RESULTS: Significant and minimal LMCA stenoses were found in 659 (3.6%) and 1157 (6.4%) patients, respectively. An unprotected LMCA disease was estimated in 609 (3.4%) subjects. A cumulative Logit Model analysis revealed the male gender (odds ratio [OR]=1.480, 95% confidence interval [CI]=1.287 to 1.703; P<0.001), diabetes mellitus (OR=1.158, 95% CI=1.029 to 1.303; P=0.015), dyslipidemia (OR=1.125, 95% CI=1.001 to 1.265; P=0.048), and aging (OR=1.028, 95% CI=1.022 to 1.034; P<0.001) as the independent predictors of LMCA stenosis with coexistent diseases in the rest of the coronary arteries. In the patients with normal or minimal stenoses of the other coronary arteries, cigarette smoking (OR=3.749, 95% CI=1.698 to 8.070) was found to be the independent risk factor of isolated LMCA disease. Luminal stenosis >50% in the right coronary artery, the left circumflex artery, and the left anterior descending artery was significantly more frequent in association with LMCA disease. CONCLUSIONS: The patients with LMCA disease were more likely to be male, older, and have diabetes mellitus or dyslipidemia, whereas cigarette smoking was found as an independent predictor of isolated LMCA. There was a strong correlation between the severity of LMCA stenosis and coexistent diseases in the rest of the coronary arteries.

Non-invasive monitoring of commonly used intraocular drugs against endophthalmitis by Raman spectroscopy.

PURPOSE: To develop a non-contact and non-invasive method for quantification of the local concentration of certain antibiotic and antifungal drugs in the eye. STUDY DESIGN/MATERIALS AND METHODS: An integrated CCD-based Raman spectroscopic system designed specifically for ophthalmic applications was used to non-invasively detect the presence of ceftazidime and amphotericin B in ocular media. Specific Raman signatures of the above named drugs were determined for various concentrations that were injected through a needle in the aqueous humor of rabbit eyes in vivo. Raman spectra were subsequently acquired by focusing an argon laser beam within the anterior chamber of the eye. RESULTS: Compared to ocular tissue, unique spectral features of ceftazidime appeared near 1,028, 1,506, 1,586, and 1,641 cm(-1). Amphotericin B exhibited its characteristic peaks at 1,156.5 and 1,556 cm(-1). The amplitude of the spectral peak corresponding to these drugs (acquired by 1 second exposure time and 25 mW of laser power) were determined to be linearly dependent on their local concentration in the anterior chamber of the eye. CONCLUSIONS: Raman spectroscopy may offer an effective tool to non-invasively assess the local concentration of the delivered drugs within the ocular media. This technique potentially could be used to investigate the pharmacokinetics of intraocular drugs in vivo either from a releasing implant or a direct injection.

The respiratory and allergic manifestations of human myiasis caused by larvae of the sheep bot fly (Oestrus ovis): a report of 33 pharyngeal cases from southern Iran.

Myiasis--the feeding of fly larvae on living mammals--may have various presentations, depending on the tissues or organs involved. The respiratory and non-respiratory manifestations of human pharyngeal myiasis caused by Oestrus ovis larvae in 33 patients from the Fars province, in southern Iran, are described here. All but one of the 33 cases were male and all lived in rural areas, in close contact with sheep and goats. The myiasis only occurred in spring and summer (April-September). Symptoms always appeared abruptly, all of the cases sensing the presence of foreign bodies in their throats, a burning sensation and itching in the throat being followed by cough and then various other respiratory, nasal, aural, and eye manifestations. Fly larvae were observed directly in the throats of five patients, and recovered in throat washings from all 33 cases. All of the larvae were identified as those of the sheep bot fly (Oestrus ovis). Removal of the larvae, by irrigation of the throat with a large volume of normal saline, provided an effective and fast treatment. In Iran at least, myiasis caused by Oestrus ovis larvae should be considered an occupational disease among farmers who keep sheep and goats.

Noninvasive detection of ganciclovir in ocular tissue by Raman spectroscopy: implication for monitoring of drug release.

UNLABELLED: Treatment of various pathological conditions in ophthalmology, such as cytomegalovirus (CMV) retinopathy and endophthalmitis, requires a local drug intervention rather than a systemic approach. Accurate knowledge of intraocular drug concentration can permit the ophthalmologist to maintain drug levels within the therapeutic levels necessary for an optimal prognosis, while preventing or minimizing toxicity associated with drug overdose. PURPOSE: To develop a noninvasive/noncontact method for quantification of the local concentration of ganciclovir in the ocular media. METHODS: An integrated CCD-based Raman spectroscopic system designed specifically for ophthalmic applications was used to noninvasively detect the presence of ganciclovir in the ocular media. Various known concentrations of ganciclovir were injected into the aqueous humor of rabbit eyes in a pilot study, in vivo. Raman spectra were then acquired by focusing an argon laser beam within the anterior chamber of the eye. The specific Raman signature of ganciclovir was assessed at several concentrations. RESULTS: Spectral features unique to ganciclovir were identified and distinguished from those of ocular tissue. The amplitudes of the spectral peaks corresponding to ganciclovir exhibited a linear dependence on the local concentration of the drug in the anterior chamber of the eye. CONCLUSION: Raman spectroscopy may offer an effective tool for the noninvasive assessment of the local concentration of ganciclovir in the ocular media. This technique offers the potential to determine both the amount and the rate of the drug release from implants designed to deliver antiviral drugs locally within the eye. The availability of such data could enable the ophthalmologist to improve treatment efficacy by avoiding premature or late surgical replacement of the implants.

Malocclusion and the need for orthodontic treatment in 9-year-old immigrant children in Stockholm, Sweden.

In this study the prevalence of malocclusion and the need for orthodontic treatment were studied from objective and subjective aspects in 174 immigrant children (89 boys and 85 girls). At the time of the study the children were 9 years of age. The objective need for orthodontic treatment was judged according to the 5-point scale of the Swedish National Board of Health and Welfare (Medicinalstyrelsen 1966). No need for treatment (grade 0) was observed in 11% of the children and only minor treatment need (grade 1) in 29%. A desirable need for treatment (grade 2) was found in 28% of the children at the time of the examination and an urgent need for treatment (grades 3 and 4) in 32%. Twenty per cent of those with a desirable need for treatment (grade 2; 6% of all the children) will probably develop an urgent need for treatment when the mixed dentition is replaced by the permanent dentition. 56% of the children were not interested in orthodontic treatment, and 63% found the arrangement of their teeth attractive. These results are discussed in relation to earlier Scandinavian epidemiological studies.