Temperature-controlled Laminar Airflow (TLA) in symptomatic severe asthma - a post hoc analysis of severe exacerbations, quality of life and health economics.

PURPOSE: Uncontrolled severe asthma constitutes a major economic burden to society. Add-ons to standard inhaled treatments include inexpensive oral corticosteroids and expensive biologics. Nocturnal treatment with Temperature-controlled Laminar Airflow (TLA; Airsonett®) could be an effective, safe and cheaper alternative. The potential of TLA in reducing severe asthma exacerbations was addressed in a recent randomised placebo-controlled trial (RCT) in patients with severe asthma (Global Initiative for Asthma (GINA) step 4/5), but the results were inconclusive. We re-analysed the RCT with severe exacerbations stratified by the level of baseline asthma symptoms and Quality of Life. METHODS: More uncontrolled patients, defined by Asthma Control Questionnaire 7 (ACQ7) > 3, EuroQoL 5-Dimension Questionnaire Visual Analogue Scale (EQ5D-VAS) ≤ 65 and Asthma Quality of Life Questionnaire (AQLQ) ≤ 4 were selected for re-analysis. The rates of severe asthma exacerbations, changes in QoL and health-economics were analysed and compared between TLA and placebo. RESULTS: The study population included 226 patients (113 TLA / 113 placebo.) The rates of severe asthma exacerbations were reduced by 33, 31 and 25% (p = 0.083, 0.073, 0.180) for TLA compared to placebo, dependent on selected control measures (ACQ7, EQ5D-VAS, AQLQ, respectively). For patients with less control defined by AQLQ≤4, the difference in mean AQLQ0-12M between TLA and placebo was 0.31, 0.33, 0.26 (p = 0.085, 0.034, 0.150), dependent on selected covariate (AQLQ, EQ5D-VAS, ACQ7, respectively). For patients with poor control defined by ACQ7 > 3, the difference in EQ5D-5 L utility scores between TLA and placebo was significant at 9 and 12 months with a cost-effective ICER. The results from the original study did not demonstrate these differences. CONCLUSION: This post hoc analysis demonstrated an effect of TLA over placebo on severe exacerbations, asthma control and health economics in a subgroup of patients with more symptomatic severe allergic asthma. The results are consistent with the present recommendations for TLA. However, these differences were not demonstrated in the full study. Several explanations for the different outcomes have been outlined, which should be addressed in future studies. FUNDING: NIHR Health Technology Assessment Programme and Portsmouth Hospitals NHS Trust.

Effect of nocturnal Temperature-controlled Laminar Airflow on the reduction of severe exacerbations in patients with severe allergic asthma: a meta-analysis.

Background: Allergen avoidance is important in allergic asthma management. Nocturnal treatment with Temperature-controlled Laminar Airflow (TLA) has been shown to provide a significant reduction in the exposure to allergens in the breathing zone, leading to a long-term reduction in airway inflammation and improvement in Quality of life (QoL). Allergic asthma patients symptomatic on Global Initiative for Asthma (GINA) step 4/5 were found to benefit the most as measured by Asthma Quality of Life Questionnaire (AQLQ). However, the effect of TLA on severe asthma exacerbations is uncertain and therefore a meta-analysis was performed. Methods: Patients with severe allergic asthma (GINA 4/5) were extracted from two 1-year randomised, double-blind, placebo-controlled trials conducted with TLA. A meta-analysis of the effect on severe exacerbations was performed by negative binomial regression in a sequential manner, defined by baseline markers of asthma control (symptoms and QoL scores). Results: The pooled dataset included 364patients. Patients with more symptoms at baseline (ACT<18 or ACQ7>3; N=179), had a significant mean 41% reduction in severe exacerbations (RR=0.59 (0.38-0.90); p=0.015) in favour of TLA. Higher ACQ7 cut-points of 3.5-4.5 resulted in significant reductions of 48-59%.More uncontrolled patients based on AQLQ total and symptom domains ≤3.0 at baseline also showed a significant reduction in severe exacerbations for TLA vs. placebo ((47% (p=0.037) and 53% (p=0.011), respectively). The meta-analysis also confirmed a significant difference in AQLQ-responders ((Minimal Clinically Important Difference)≥0.5; 74% vs. 43%, p=0.04). Conclusion: This meta-analysis of individual patient data shows a beneficial effect on severe exacerbations and quality of life for TLA over placebo in more symptomatic patients with severe allergic asthma. These outcomes support the national management recommendations for patients with symptomatic severe allergic asthma. The actual effect of TLA on severe exacerbations should be confirmed in a prospective study with larger numbers of patients.

Living with consequences of stroke and risk factors for unhealthy diet- experiences among stroke survivors and caregivers in Nairobi, Kenya.

BACKGROUND: Stroke prevalence is increasing in sub-Saharan Africa and has been partly attributed to the rapid economic and population growth that have contributed to changes in lifestyle and increased the prevalence of modifiable risk factors for stroke. Healthy diet is important in stroke management and secondary stroke prevention. The aim was to explore the clinical characteristics and functioning after stroke and the experiences of nutritional aspects among stroke survivors and caregivers in Nairobi, Kenya. METHODS: A cross-sectional study with qualitative and quantitative methods involving two rounds of data collection was utilised. In the first round, data on demographics and clinical characteristics were collected for 30 people poststroke during a seminar organized by the Kenya Stroke Association. In the second round, nine participants then agreed to be interviewed together with their caregivers and asked to describe their own experiences and their household eating patterns after suffering a stroke. The food frequency questionnaire and anthropometric measurements of weight, height and waist measurements were used. The self-reported data were analyzed using descriptive statistics and the transcribed interview texts used a constructivist-based theory. RESULTS: The results give an insight in the life situation for people living with consequences after stroke and their caregivers in Nairobi. The participants were aware that they were overweight and that this indicated an increased risk for the development of cardiovascular diseases. A core category emerged: The caregiver as the main definer of health and enabler of healthy diet among persons who have had a stroke. Healthy diets and provided information on eating healthy were lacking from the healthcare professionals, whereupon the responsibility for managing a healthy diet had shifted to the caregivers. CONCLUSIONS: Support needs to be given to people with stroke and their caregivers to achieve a healthy diet. The importance of healthy eating as a way of reducing the risk of suffering a stroke needs to be communicated by health care. The Kenyan food-based dietary guidelines need to be more implemented and accessible as well as an overall secondary stroke prevention program.

Time to onset of improvements in Quality of Life from Temperature-controlled Laminar Airflow (TLA) in severe allergic asthma.

BACKGROUND: Allergen avoidance is important in allergic asthma management. Nocturnal treatment with Temperature-controlled Laminar Airflow (TLA; Airsonett®) has been shown to provide significant reduction of exposure to allergens in the breathing zone, leading to long-term reduction in airway inflammation and improvement in quality of life. Allergic asthma patients uncontrolled on GINA step 4 were found to benefit the most. A frequently asked question from clinicians and funders is related to time to onset (TTO) of improvements for patients using TLA. METHODS: Asthma Quality of Life Questionnaire (AQLQ) scores were collected in a previous study. TTO of improvements in Quality of Life was analysed for difference (TLA-placebo) in Area-under-Curve using backwards deletion from 12, 9, 6, 3 down to 1 month for the AQLQ total score, the four individual domains and specifically the sleep question. RESULTS: Patients with uncontrolled asthma on GINA step 4 (n = 87)) reported a statistically significant and clinically relevant (≥0.5 point) improvement in total AQLQ score (0.57; p = 0.009) after 3 months treatment for TLA over placebo. The shortest TTO was within 1 month for the environmental domain (0.68; p = 0.016) and the sleep question (0.771; p = 0.037). TTO for the emotional and symptom domains was 3 months (0.66; p = 0.020 and 0.64; p = 0.014 respectively) and for the activity domain 6 months (0.47; p = 0.036). CONCLUSION: Nocturnal avoidance of allergens using TLA provided a statistically significant and clinically relevant improvement in total AQLQ score within 3 months in patients in the GINA 4 + ACT<18 group. Questions related to sleep quality may provide the first signal of response already within a month after commencing treatment.

Intra- and inter-tooth variation in strontium isotope ratios from prehistoric seals by laser ablation multi-collector inductively coupled plasma mass spectrometry.

RATIONALE: Strontium isotope ratios (87 Sr/86 Sr) in modern-day marine environments are considered to be homogeneous (~0.7092). However, in the Baltic Sea, the Sr ratios are controlled by mixing seawater and continental drainage from major rivers discharging into the Baltic. This pilot study explores if variations in Sr can be detected in marine mammals from archaeological sites in the Baltic Sea. METHODS: 87 Sr/86 Sr ratios were measured in tooth enamel from three seal species by laser ablation multi-collector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS). The method enables micro-sampling of solid materials. This is the first time that the method has been applied to marine samples from archaeological collections. RESULTS: The analyses showed inter-tooth 87 Sr/86 Sr variation suggesting that different ratios can be detected in different regions of the Baltic Sea. Furthermore, the intra-tooth variation suggests possible different geographic origin or seasonal movement of seals within different regions in the Baltic Sea through their lifetime. CONCLUSIONS: The method was successfully applied to archaeological marine samples showing that: (1) the 87 Sr/86 Sr ratio in marine environments is not uniform, (2) 87 Sr/86 Sr differences might reflect differences in ecology and life history of different seal species, and (3) archaeological mobility studies based on 87 Sr/86 Sr ratios in humans should therefore be evaluated together with diet reconstruction.

Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease.

BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls. RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10-15 , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex. CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.

Effect of different asthma treatments on risk of cold-related exacerbations.

Common colds often trigger asthma exacerbations. The present study compared cold-related severe exacerbations during budesonide/formoterol maintenance and reliever therapy, and different regimens of maintenance inhaled corticosteroids (ICS), with or without long-acting ß(2)-agonists (LABA), and with as-needed short-acting ß(2)-agonists (SABA) or LABA. Reported colds and severe exacerbations (defined by oral corticosteroid use and/or hospitalisation/emergency room visit) were assessed for 12,507 patients during 6-12 months of double-blind treatment. Exacerbations occurring ≤14 days after onset of reported colds were analysed by a Poisson model. The incidence of colds was similar across treatments. Asthma symptoms and reliever use increased during colds. Budesonide/formoterol maintenance and reliever therapy reduced severe cold-related exacerbations by 36% versus pooled comparators plus SABA (rate ratio (RR) 0.64; p=0.002), and for individual treatment comparisons, by 52% versus the same maintenance dose of ICS/LABA (RR 0.48; p<0.001); there were nonsignificant reductions versus higher maintenance doses of ICS or ICS/LABA (RR 0.83 and 0.72, respectively). As-needed LABA did not reduce cold-related exacerbations versus as-needed SABA (RR 0.96). Severe cold-related exacerbations were reduced by budesonide/formoterol maintenance and reliever therapy compared with ICS with or without LABA and with as-needed SABA. Subanalyses suggested the importance of the ICS component in reducing cold-related exacerbations. Future studies should document the cause of exacerbations, in order to allow identification of different treatment effects.

Measuring asthma control: a comparison of three classification systems.

There are various ways to classify asthma control; however, no classification is universally accepted. This retrospective analysis compared asthma control as assessed by the Asthma Control Questionnaire (5-item version; ACQ-5), Global Initiative for Asthma (GINA) or Gaining Optimal Asthma Control (GOAL) study criteria. Pooled data at the final study week (n = 8,188) from three budesonide/formoterol maintenance and reliever therapy studies which measured ACQ-5 were stratified according to GINA or GOAL criteria and ACQ-5 score distribution. The percentages of patients with a controlled/partly controlled week (GINA), totally/well-controlled week (GOAL) and range of ACQ-5 cut-off points were compared. Patients with GINA controlled, partly controlled and uncontrolled asthma had mean ACQ-5 scores of 0.43, 0.75 and 1.62, respectively. Patients with GOAL totally controlled, well-controlled and uncontrolled asthma had ACQ-5 scores of 0.39, 0.78 and 1.63. The kappa measure of agreement was 0.80 for GINA and GOAL criteria, and 0.63 for GINA controlled/partly controlled and ACQ-5 <1.00. ACQ-5 detected clinically important improvements in 49% of patients who, according to GINA criteria, remained uncontrolled at the end of the study. Asthma control measured by GINA or GOAL criteria provides similar results. GINA Controlled/Partly Controlled and GOAL Totally Controlled/Well-Controlled correspond to ACQ-5 <1.00. The ACQ-5 is more responsive to change in a clinical trial setting than a categorical scale.

Genetic variation in carbon isotope discrimination in six European populations of Castanea sativa Mill. originating from contrasting localities.

The objective of this study was to evaluate the variability of physiological performances of Castanea sativa Mill. in relation to drought tolerance, among and within European populations coming from contrasting environmental conditions. Forty-eight open-pollinated families from a stratified sample (temperature/precipitation) of six naturalized populations from Spain, Italy and Greece were grown for one growth period under two temperature regimes (25 and 32 degrees C), in combination with two watering regimes in growth chambers. Complementary to growth traits analysed in a previous study, carbon isotope discrimination (Delta), a complex physiological trait involved in acclimation and adaptive processes, was studied. anova indicated significant Delta variability for C. sativa populations across Europe and, thereby, variation in adaptedness to drought. The European pattern of Delta variability matches the previously reported one for the centre of origin of C. sativa (Ponto-Caucasian region). This suggests that common mechanisms of drought adaptedness, involving both genetic and physiological determinants, give C. sativa the capacity to colonize a wide range of site conditions. The highest Delta values, indicating the lowest water-use efficiency (WUE), were found within each treatment for populations originating from Mediterranean drought-prone sites. These populations also had the highest phenotypic plasticity of Delta. Significant among-family genetic variation in Delta was found. The heritability based on the joint anova was estimated at 0.31 +/- 0.07. The estimates of the coefficients for the additive variance varied in the range 2.6-4.0%, suggesting possibilities for selection on WUE and adaptedness to drought. The genetic correlations between Delta and growth traits were generally strong and negative, especially in the two high temperature treatments.

Clinical factors and clinical variation influencing the reproducibility of interocclusal recording methods.

OBJECTIVE: The reproducibility of clinical records of the occlusion was assessed in three dimensions using mounted casts. Three distinct areas were examined: 1) mandibular positions (intercuspal position (IP) or retruded contact position (RCP)), 2) materials used in recording the occlusion, 3) clinical variation. DESIGN: Interocclusal records were made in a random order of three patients: one fixed prosthodontics case, one removable partial denture case and one complete denture case, with two different types of waxes, record rims, two different brands of vinyl polysiloxanes and one irreversible hydrocolloid. SETTING: Private practice and Karolinska Institute, Huddinge, Sweden. SUBJECTS: One general dental practitioner and three voluntary patients. RESULTS: Point estimation of variance components indicate that 70-93% of the variation of the positions of the mounted casts are caused by: 1) clinical variation for all three cases and in three directions, 2) the influence of recording materials 0-29%, and 3) mandibular positions (IP/RCP) 0-11%. The ranges of the positions of the mounted casts were lower for the dentate case (0.04-1.39 mm) than for the partially dentate case (0.17-2.65 mm), which in turn was lower than those for the edentulous case (1.42-5.59 mm). CONCLUSION: Clinical variation seems to dominate the variation in positions of mounting casts when making interocclusal records, rather than mandibular position or the recording materials used. Therefore a dentist who makes one single interocclusal record cannot presume that it will reproduce the interocclusal relationship intended, which in the present study was most obvious for the edentulous case. The results showed that impression materials stabilised by a tray did not differ significantly from waxes and record rims concerning the reproducibility. Therefore the stabilised impression materials are an alternative, which also give additional advantages like reduction of appointments as well as superior accuracy.

Interference of transferrin isoform types with carbohydrate-deficient transferrin quantification in the identification of alcohol abuse.

BACKGROUND: Isoforms of transferrin interfere with measurement of carbohydrate-deficient transferrin (CDT) as a marker of heavy alcohol consumption. We evaluated the rate of inaccurate CDT results by immunoassays. METHODS: We studied 2360 consecutive sera (1614 individuals) submitted for CDT assay without clinical information as well as samples from 1 patient with a congenital disorder of glycosylation (CDG Ia) and from 6 healthy carriers of CDG Ia. The CDTect, %CDT-TIA, and new %CDT immunoassays were compared with HPLC (%CDT-HPLC). Transferrin isoform pattern were evaluated by isoelectric focusing (IEF). RESULTS: Transferrin BC and CD heterozygotes were found at frequencies of approximately 0.7% and approximately 0.2%, respectively. Another transferrin C subtype, where di- and trisialotransferrin partly coeluted (tentatively identified as C2C3), was observed in approximately 0.6%. Compared with the %CDT-HPLC method, the immunoassays often produced low results for transferrin BC and high results for transferrin CD and "C2C3". A very high trisialotransferrin value (frequency approximately 1%) often produced high CDT immunoassay results. In four of six healthy carriers of CDG Ia, a- and disialotransferrin were highly increased and the HPLC and IEF isoform patterns were indistinguishable from those in alcohol abuse. CONCLUSIONS: Rare transferrin isoform types and abnormal amounts of trisialotransferrin (total frequency approximately 2-3%) may cause incorrect determination of CDT with immunoassays. The observed variants were readily identified by HPLC and IEF, which can be recommended for verification of CDT immunoassay results in doubtful cases. In healthy carriers of CDG Ia, CDT is high by all assays.

Alcohol biomarkers: clinical significance and biochemical basis.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Raj Lakshman and Mikihiro Tsutsumi. The presentations were (1) Sialic acid index of apolipoprotein J: A new marker for chronic alcohol consumption, by P. Ghosh and M. R. Lakshman; (2) Microheterogeneity of serum glycoproteins in alcoholics, by M. Tsutsumi and S. Takase; (3) Probing protein-ethanol adducts with combinatorial peptide libraries displayed by filamentous phage, by H. Anni, O. Nikolaeva, and Y. Israel Y; (4) Carbohydrate-deficient transferrin as a marker for heavy alcohol use: What have we learned; Where do we go from here, by R. F. Anton; (5) Sensitivity and specificity of carbohydrate-deficient transferrin in drinking experiments and different patient groups, by O. M. Lesch; (6), Transferrin variants interfere with the measurement of carbohydrate-deficient transferrin, by A. Helender, G. Eriksson, and J-O. Jeppson; and (7) Chronic ethanol on protein trafficking in liver, by P. Marmillot, M. N. Rao, and M. R. Lakshman.

Thermodynamic modeling of PCDD/Fs formation in thermal processes.

Three thermodynamic databases of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), derived using the Group Additivity approach and two computational molecular modeling methods, Modified Neglect of Diatomic Overlap (MNDO) and Parametrized Model 3 (PM3), respectively, combined with the Scientific Group Thermodata Europe (SGTE) database have been used to model the formation of PCDD/Fs in thermal processes, such as iron ore sintering process. The predictions using the three different databases are compared, and similar thermodynamic conditions of PCDD/Fs formation are found. The comparison of the calculated values with measured results obtained from industrial iron ore sinter plant indicates that the PCDDs and PCDFs found in practice are not in equilibrium with each other. While within each dioxin and furan homologue equilibrium between the isomers appears to be established in industrial processes, reactions between dioxins and furans seem to be kinetically inhibited. This view has been supported by assuming no reaction at all between PCDFs and PCDDs in the simulation. With this assumption, both PCDFs and PCDDs reached partial pressures between 600 and 800 K in the order of magnitude actually found in practice. Taking this restriction into account, the conditions for PCDD/Fs formation were calculated as a function of oxygen partial pressure; temperature; concentrations of carbon, hydrogen, and chlorine; and C/H ratio.

Comparison of the corneal effects of latanoprost, fixed combination latanoprost-timolol, and timolol: A double-masked, randomized, one-year study.

OBJECTIVE: To compare the long-term effects on corneal endothelial cell density and corneal thickness of latanoprost and the fixed combination latanoprost-timolol to timolol. DESIGN: Double-masked, randomized, prospective, multicenter clinical trial. PARTICIPANTS: Three hundred sixty-nine subjects with bilateral ocular hypertension or open-angle glaucoma who had a baseline central corneal endothelial cell density of at least 1500 cells/mm(2), central corneal thickness of less than 0.68 mm, no corneal pathologic condition on slit-lamp examination, and intraocular pressure of less than 22 mmHg after a 3-week run-in on timolol, 0.5%, once daily were included. INTERVENTION: Subjects were randomly assigned to treatment with latanoprost 0.005% (n = 127), fixed-combination latanoprost 0.005%-timolol 0.5% (FC, n = 116), or timolol 0.5% (n = 126) one drop, once daily in the morning for 1 year. All subjects were treated in both eyes. Specular microscopy and ultrasonic pachymetry were performed before treatment, and after 6 and 12 months of treatment. MAIN OUTCOME MEASURES: Mean percent change in central endothelial cell density and central corneal thickness after 1 year of treatment. RESULTS: For both corneal endothelial cell density and corneal thickness, the mean percent changes from baseline were similar in all three treatment groups. Mean percent endothelial cell change at 1 year from baseline for latanoprost, FC, and timolol was 0.3 +/- 2.2%, 0.1 +/- 1.8%, 0.0 +/- 2.5% (mean +/- standard deviation; 95% confidence interval: latanoprost vs timolol -0.2-1.0; FC vs timolol -0.4-0.7) and mean percent change in corneal thickness was -1.1 +/- 2.5%, -1.0 +/- 2.0%, 0.2 +/- 3.1%, respectively. CONCLUSIONS: Latanoprost and FC are equivalent to timolol regarding long-term corneal effects after 1 year of treatment.

Increased gene expression of interleukin-1alpha and interleukin-6 in rat primary glial cells induced by beta-amyloid fragment.

One of the pathological hallmarks of Alzheimer's disease (AD) is the presence of amyloid plaques. The main constituent of the amyloid plaques is the amyloid beta-peptide (A beta) shown to activate glial cells in vitro. A growing body of evidence suggests that these cells contribute to neurotoxicity through production of inflammatory cytokines, chemokines, and neurotoxic substances, such as reactive oxygen species (ROS). In this study, mRNA levels of the inflammatory cytokines interleukin (IL)-1alpha and beta, and IL-6 were analysed by reverse transcriptase-polymerase chain reaction (RT-PCR) in rat primary mixed glial cells after treatment with A beta(25-35), a biologically active fragment of A beta peptide with neurotoxic properties. Clear morphological changes of the astrocytes, as well as proliferation and clustering of microglial cells were observed by light and immunofluorescence microscopy after 24 h treatment. Significant increases in IL-1alpha and IL-6 mRNA levels were detected after 24 and 72 h, whereas significantly increased levels of IL-1beta mRNA could only be detected after 4 h treatment. The most pronounced effect was seen on IL-6 mRNA expression, which increased approx two- to threefold after treatment. In addition, increased secretion of IL-6 was detected after 96 h exposure. Recently, association of IL-1alpha and IL-6 gene polymorphism with AD was reported, suggesting that these cytokines may play an important role in the development of the disease. The increased mRNA levels of IL-1alpha and IL-6 in parallel with the morphological changes in the mixed glial-cell cultures support that these cytokines may be involved in A beta-induced gliosis and in the pathogenesis of AD.

[Risky alcohol drinking surveyed at a GP unit. Secondary prevention of alcohol problems in primary care patients]. / Riskbruk av alkohol kartlagt på vårdcentral. Sekundärprevention av alkoholproblem hos primärvårdspatienter.

This article describes an implementation of secondary prevention of alcohol abuse at a GP unit in southern Gothenburg, Sweden. During several periods between 1994 and 1996, screening for alcohol problems was performed using either AUDIT or a 4-item instrument called SWAG. In one part of the study, screening was simultaneously carried out using gamma-GT and MCV. The main object of screening efforts was to stimulate interest for alcohol-related conditions, and this goal was reached. The staff was trained in treatment techniques such as motivational interviewing (MI), bio-feedback using gamma-GT and delivery of concise information. Simple methods to determine level of motivation were used for treatment stratification. Some doctors reported that they had insufficient time for adequate MI treatment, and therefore a condensed model was sometimes used. A nurse-staffed treatment unit was started and successfully promoted work with alcohol problem. Attempts were made to spread these methods to other GP units in the region and this was partially successful, although support from the central primary care administration was not secured.

Materials for interocclusal records and their ability to reproduce a 3-dimensional jaw relationship.

PURPOSE: The purpose of this study was to determine if accuracy and dimensional stability of vinyl polysiloxanes and irreversible hydrocolloids stabilized by a tray used for fixed prosthodontics, removable partial, and complete denture cases are comparable to those of waxes and record rims and if storage time (24 hours or 6 days) affects dimensional stability of the tested materials. MATERIALS AND METHODS: Two waxes, two record rims, three vinyl polysiloxanes, and one irreversible hydrocolloid (alginate) were examined. Three pairs of master casts with measuring steel rods were mounted on an articulator (initial position). Five records were made of each material, and the upper cast was remounted after 24 hours or 6 days so that deviations from the initial position could be measured. RESULTS: Vinyl polysiloxanes reinforced by a stabilization tray were the most accurate materials able to reproduce a settled interocclusal position. Mounting casts (fixed prosthodontics cases) without records gave accuracy similar to wax records. Record rims used for removable partial and complete denture cases produced lesser accuracy than vinyl polysiloxanes and irreversible hydrocolloid stabilized by a tray. Accuracy was not significantly affected by storage time. CONCLUSION: The results show that accuracy of vinyl polysiloxanes and irreversible hydrocolloids reinforced by a tray is superior to that of record rims with regard to the complete denture case and is among the most accurate with regard to the removable partial denture case. For fixed prosthodontics, however, reinforcement is unnecessary.

On demand therapy with omeprazole for the long-term management of patients with heartburn without oesophagitis--a placebo-controlled randomized trial.

AIM: To observe the natural course of gastro-oesophageal reflux disease (GERD) in patients without oesophagitis following effective symptom relief, and to determine the place of acid pump inhibitor therapy in the long-term management of these patients. METHODS: We investigated the efficacy of on-demand therapy with omeprazole 20 mg or 10 mg, or placebo in a double-blind, randomized multicentre trial. It involved 424 patients with troublesome heartburn without endoscopic evidence of oesophagitis in whom heartburn had been resolved with short-term treatment. Patients were told to take study medication on demand once daily on recurrence of symptoms until symptoms resolved over a 6-month period. They also had access to antacids. The primary efficacy variable was time to discontinuation of treatment, due to unwillingness to continue. RESULTS: According to life-table analysis, after 6 months the remission rates were 83% (95% CI: 77-89%) with omeprazole 20 mg, 69% (61-77%) with omeprazole 10 mg, and 56% (46-64%) with placebo (P < 0.01 for all intergroup differences). The mean (s.d.) number of study medications used per day in these groups was 0.43 (0.27), 0.41 (0.27) and 0.47 (0.27), respectively. The use of antacids was highest in the placebo group and lowest in the omeprazole 20 mg group. Treatment failure was associated with more than a doubling of antacid use, and a deterioration in patient quality of life. CONCLUSIONS: Approximately 50% of patients with heartburn who do not have oesophagitis need acid inhibitory therapy in addition to antacid medication to maintain a normal quality of life. On-demand therapy with omeprazole 20 mg, is an effective treatment strategy in these patients.

Hypersensitive cytokine response to beta-amyloid 25-35 in astroglial cells from IL-1 receptor type I-deficient mice.

betaA25-35, a neurotoxic fragment of the Alzheimer beta-amyloid peptide (betaA), acts as a strong inducer of pro-inflammatory cytokines, such as interleukin (IL)-1 and IL-6, in glial cells. Since IL-1 is known to induce expression of both IL-1 and IL-6, we have investigated to what extent the induction of IL-1alpha and IL-6 by betaA25-35, is dependent on the IL-1 receptor type I (IL-1RI), the only known signalling IL-1 receptor. Primary astroglial cell cultures prepared from wild-type and IL-1RI-deficient mice were incubated in the presence of betaA25-35 (100 microM) for 19 h, followed by analysis of mRNA levels of IL-1alpha and IL-6. Cell cultures treated with betaA25-35 showed a significant increase in mRNA levels for IL-1alpha and IL-6 and in addition increased levels of IL-1alpha immunoreactivity. A supersensitive IL-1alpha response was observed in astroglial cell cultures lacking the IL-1 RI as compared to betaA25-35 treated cell cultures from wild-type mice. In contrast the betaA25-35-induced increase of IL-6 was lower in the absence of IL-1RI. In conclusion, these results suggest that a functional IL-1 signal transduction is not necessary for induction of mRNA levels of IL-1alpha and IL-6 in astroglial cell cultures treated with betaA25-35, but that induction of IL-6 involves at least two distinct mechanisms, one of which occurs via activation of the IL-1RI.