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Objectives Several plaque and lesion characteristics have been associated with an increased risk for procedural stroke during or shortly after carotid artery stenting (CAS). While technical advancements in stent design and cerebral protection devices (CPD) may help reduce the procedural stroke risk, and anatomy remains important, tailoring stenting procedures according to plaque and lesion characteristics might be a useful strategy in reducing stroke associated with CAS. In this descriptive report of the ongoing Asymptomatic Carotid Surgery Trial-2 (ACST-2), it was assessed whether choice for stent and use or type of CPD was influenced by plaque and lesion characteristics. Materials and methods Trial patients who underwent CAS between 2008 and 2015 were included in this study. Chi-square statistics were used to study the effects of plaque echolucency, ipsilateral preocclusive disease (90–99%), and contralateral high-grade stenosis (>50%) or occlusion of the carotid artery on interventionalists' choice for stent and CPD. Differences in treatment preference between specialties were also analysed. Results In this study, 831 patients from 88 ACST-2 centres were included. Almost all procedures were performed by either interventional radiologists (50%) or vascular surgeons (45%). Plaque echolucency, ipsilateral preocclusive disease (90–99%), and significant contralateral stenosis (>50%) or occlusion did not affect the choice of stent or either the use of cerebral protection and type of CPD employed (i.e., filter/flow reversal). Vascular surgeons used a CPD significantly more often than interventional radiologists (98.6% vs. 76.3%; p < .001), but this choice did not appear to be dependent on patient characteristics. Conclusions In ACST-2, plaque characteristics and severity of stenosis did not primarily determine interventionalists' choice of stent or use or type of CPD, suggesting that other factors, such as vascular anatomy or personal and centre preference, may be more important. Stent and CPD use was highly heterogeneous among participating European centres.

The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.

The study explores the possibility of efficiently codelivering DNA vaccines and protein-based vaccines by formulation with aluminum phosphate (AlPO4). When mixed with aluminum adjuvants, plasmid DNA bound tightly onto aluminum hydroxide [Al(OH)3] but not to AlPO4. Different doses of DNA vaccines formulated with AlPO4 [but not Al(OH)3] induced enhanced humoral responses and supported priming of MHC class I restricted cellular immunity. Different proteins mixed with the plasmid DNA vaccine in the AlPO4 formulation did not impair its immunogenicity. Coinjection of two different vaccine-relevant antigens in the same AlPO4 formulation, one as a DNA vaccine and the other as a recombinant protein, elicited polyvalent, humoral, and cellular immune responses to all antigens delivered. The isotype profiles of the induced humoral responses and the cytokine profiles of the specifically primed T cell responses indicated that the combined vaccines supported copriming of Th1- and Th2-biased as well as balanced responses. These findings indicate that the AlPO4 adjuvant, a widely accepted adjuvant in human vaccination practice, can be used to combine protein- and DNA-based vaccination to prime an enhanced and balanced specific immunity.

This is the report of the thirty-fifth of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). ECVAM's main goal, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures which would enable it to become well informed about the state-of-the-art of non-animal test development and validation, and the potential for the possible incorporation of alternative tests into regulatory procedures. It was decided that this would be best achieved by the organisation of ECVAM workshops on specific topics, at which small groups of invited experts would review the current status of various types of in vitro tests and their potential uses, and make recommendations about the best ways forward (1). This joint ECVAM/FELASA (Federation of European Laboratory Animal Science Associations) workshop on The Immunisation of Laboratory Animals for the Production of Polyclonal Antibodies was held in Utrecht (The Netherlands), on 20-22 March 1998, under the co-chairmanship of Coenraad Hendriksen (RIVM, Bilthoven, The Netherlands) and Wim de Leeuw (Inspectorate for Health Protection, The Netherlands). The participants, all experts in the fields of immunology, laboratory animal science, or regulation, came from universities, industry and regulatory bodies. The aims of the workshop were: a) to discuss and evaluate current immunisation procedures for the production of polyclonal antibodies (including route of injection, animal species and adjuvant ); and b) to draft recommendations and guidelines to improve the immunisation procedures, with regard both to animal welfare and to the optimisation of immunisation protocols. This report summarises the outcome of the discussions and includes a number of recommendations and a set of draft guidelines (included in Appendix 1).

More than 80 years have passed since the initial discovery that aluminum salts, when injected together with an antigen, resulted in highly elevated specific antibody titers. Since then the aluminum adjuvants have achieved an undisputed status as the most commonly used adjuvants in human and veterinary vaccines. The present chapter compiles historical data on aluminum adjuvants from the very early start and data made obtainable thanks to the development of analytical tools for providing general insight into the mechanisms of the immune system. Applying these tools in adjuvant research have helped characterizing the aluminum adjuvants in terms of isotypic profiles, surface marker expression profiles, cytokine profiles and within the latest 5 years with the discovery of the NALP3 inflammasome its importance for the secretion of interleukin (IL)-1β and IL-18 as pro-inflammatory mediators in the early phases of the immune response. For decades very little was known about the mechanisms of action of aluminum adjuvants, and their use in vaccine design was predominantly based on empirical principles. The results from applying such analytical tools are about to take us to the next level of understanding aluminum adjuvants.

The ESAT-6 antigen fromMycobacterium tuberculosisis a dominant target for cell-mediated immunity in the early phase of tuberculosis (TB) in TB patients as well as in various animal models. The purpose of our study was to evaluate the potential of ESAT-6 in an experimental TB vaccine. We started out using dimethyl dioctadecylammonium bromide (DDA), an adjuvant which has been demonstrated to be efficient for the induction of cellular immune responses and has been used successfully before as a delivery system for TB vaccines. Here we demonstrate that, whereas immune responses to both short-term-culture filtrate and Ag85B are efficiently induced with DDA, this adjuvant was inefficient for the induction of immune responses to ESAT-6. Therefore, we investigated the modulatory effect of monophosphoryl lipid A (MPL), an immunomodulator which in different combinations has demonstrated strong adjuvant activity for both cellular and humoral immune responses. We show in the present study that vaccination with ESAT-6 delivered in a combination of MPL and DDA elicited a strong ESAT-6-specific T-cell response and protective immunity comparable to that achieved withMycobacterium bovisBCG.

Aluminium phosphate adjuvant remained amorphous when autoclaved for 30 or 60 min at 121 degrees C. However, deprotonation and dehydration reactions occurred as evidenced by a decrease in the pH. The protein adsorption capacity, rate of acid neutralization at pH 2.5 and point of zero charge also decreased indicating that the deprotonation/dehydration reactions resulted in a decreased surface area. Autoclaving aluminium hydroxide adjuvant increased the degree of crystallinity as measured by the width at half height of the major band in the X-ray diffractogram. The pH decreased during autoclaving suggesting that the same deprotonation/dehydration reactions which reduced the surface area of aluminium phosphate adjuvant were responsible for the increased degree of crystallinity. These reactions also resulted in a reduced surface area as both the protein adsorption capacity and viscosity decreased following autoclaving.

Purpose: To describe a component-based aortomonoiliac stent-graft system and the first clinical results achieved with this device in endovascular abdominal aortic aneurysm (AAA) repair. Methods: From November 1993 to October 1996, 45 patients aged 60 to 86 years underwent endoluminal exclusion of true AAAs (median diameter 60 mm) involving the common iliac arteries (median diameter 16 mm right and 15 mm left) using unilimb stent-grafts deployed with the Ivancev-Malmö system. Results: Six immediate conversions occurred in the beginning of the series due to endografts that were too short. Complications, including 2 inadvertent renal artery occlusions, 7 kinked grafts, 6 iliac artery dissections, and 3 perioccluder leaks, were prominent features in the first 15 patients. Five patients died in the postoperative period, four of whom were nonsurgical candidates. There were five significant stent-graft migrations: one 3 weeks after surgery due to mechanical injury of the proximal stent and four after 1 year owing to continuous dilation of a wide proximal neck, stent-graft placement in a conical, thrombus-lined proximal neck, and two instances of proximal extension separation from the main graft. Translumbar aneurysm perfusion required embolization in 3 patients. Conclusions: Despite early complications associated with a learning curve, exclusion of large AAAs using unilimb stent-grafts is feasible. Strict inclusion criteria are necessary in order to improve mortality among nonsurgical candidates and minimize the risk for late migration.

Risk factors for development of peripheral arterial disease (PAD) are the same as for atherosclerotic coronary or precerebral disease, and patients with PAD have a high prevalence of concomitant atherosclerotic disease in coronary and precerebral arteries. However, these patients are still less likely to receive appropriate pharmacological secondary prevention than patients with coronary artery disease. The aim of this study was to evaluate the treatment of risk factors for patients undergoing open or endovascular surgery for PAD in our vascular department.We evaluated pharmacological treatment, lipid levels, blood pressures (BP), and smoking habits one month postoperatively in 953 patients (age [mean ± SD] 71±11 years, 524 [55%] men) undergoing open or endovascular surgical interventions for PAD.We found that 89% of patients received statins and 98% received either platelet aggregation inhibitors or anticoagulants at the one month follow-up. Four hundred nineteen (70%) patients had achieved target level4.5 mmol/L for s-total cholesterol, and 394 (67%) target level2.5 mmol/L for s-LDL cholesterol. BP (mean ± SD) was 144±22/76±12 mmHg, systolic and diastolic target BPs (140 mmHg and90 mmHg, respectively) were achieved in 482 (51%) and 887 (95%) patients, respectively. The proportion of active smokers had been reduced from 41% preoperatively to 24% at the one month follow-up (P0.0001).Even though our practice has improved, there is still room for better follow-up of pharmacological risk factor treatment in PAD patients.

Iohexol and 99mTc-DTPA were used in 43 patients to determine the relative glomerular filtration rate (GFR), i.e., the GFR of each kidney in percent of total GFR. The amount of any GFR marker accumulating in Bowman's space, tubuli and renal pelvis within a few minutes after i.v. injection, before any marker had left the kidney via the ureter, was defined as proportional to the GFR of that kidney. The renal accumulation of iohexol was determined by CT using 10 slices of 8-mm thickness 1 to 4 minutes after injection. The renal accumulation of 99mTc-DTPA was determined with a gamma camera within 2 minutes after injection. The correlation coefficient between the two methods was 0.98. Due to the higher radiation dose from CT than from 99mTc-DTPA injection, relative GFR determination with CT should be performed when there is also a diagnostic need to reveal morphology.

The etiology of abdominal aortic aneurysm (AAA) includes inflammation, coagulation, and endothelial dysfunction. We have prospectively evaluated relations between these mechanisms and AAA growth. Tumour necrosis factor (TNF)-α, interleukin (IL)-6, endothelin (ET)-1, CD40 ligand and the complex formed between activated protein C (APC) and protein C inhibitor (PCI) were measured annually and related to AAA growth during up to 5 years in 206 patients with conservatively followed AAA.We evaluated 163 patients up to 1 year, 126 patients up to 2 years, 83 patients up to 3 years, 53 patients up to 4 years, and 33 patients up to 5 years. The total number of patient follow-up years was 458.ET-1 remained unchanged except for a tendency to increase in the third and fourth years of follow-up. TNF-α decreased significantly during the first year and thereafter increased back to baseline values. There were no changes in IL-6, CD40 ligand, and APC-PCI complex. When patients in the highest and lowest quartiles of AAA growth up to 5 years follow-up were compared, APC-PCI complex levels tended to be higher (P=0.06) in the highest quartile of growth at three years (0.45 µg/l [i.q.r. 0.40-0.77] versus 0.28 µg/L [i.q.r. 0.14-0.36]). Δ-values of ET-1 and TNF-α did not show any correlation to growth. The 14 AAA patients that ruptured during follow-up did not differ from patients with non-ruptured AAA regarding biomarkers.In conclusion, none of the investigated mediators could be used to predict growth or rupture, or help to prolong intervals between ultrasound examinations in follow-up of AAA patients.

To determine the reliability of the disabled children's quality-of-life measure (DISABKIDS) chronic generic questionnaire and diabetes module in children. The questionnaire is being evaluated for repeated routine health-related quality-of-life (HrQoL) assessment and in association with the Swedish national paediatric diabetes registry (Swediabkids), which is a tool for regular clinical use.Children and parents completed the questionnaire during a routine visit to the diabetes clinic. In total, 120 families completed the test and retest. Split-half reliability correlation and intraclass correlation (ICC) coefficients were calculated. BlandAltman plots were calculated on the generic HRQoL domain.Both child and parent versions showed good internal consistency. Test-retest ICC coefficients for the generic HrQoL module were 0.913 for the children and 0.820 for the parent version. All generic domains independently showed good reliability. The diabetes module had a score of 0.855 for children and 0.823 for parents. Split-half correlation for generic and diabetes modules was 0.930 and 0.848 for children, 0.953 and 0.903 for parents. Bland and Altman plots showed substantial agreement between the two administrations for both children and parents.The DISABKIDS questionnaire is a reliable instrument for the repeated measurements of HrQoL in children with diabetes.

Continuous glucose monitoring system (CGMS) provides detailed information on glucose fluctuations. The aim was to establish whether CGMS could be used during physical exercise and whether it detects more episodes of hypoglycaemia and hyperglycaemia than frequent blood glucose measurements.Adolescents with type 1 diabetes (12 girls and 47 boys) participated in three annual sports camps that lasted for 3-4 days and included different types of exercise: soccer, floorball + cross-country skiing and golf. During the study, blood glucose values, mean 8.7 ± 3.3 per day, were obtained with Hemocue in parallel with the CGMS.Ninety-eight per cent of the participants used the sensor at all times during the camps. Eighty-seven per cent of the sensors gave adequate signals for 24 h and 66% for 48 h. Median durations of hypoglycaemia and hyperglycaemia were 1.7 h per day and 3.8 h per day, respectively. The CGMS identified significantly more episodes of hypoglycaemia (p0.005) and hyperglycaemia (p0.005) during the day and night than frequent blood glucose tests.We demonstrate that, even during days that included episodic strenuous physical exercise, CGMS could provide useful information on glucose fluctuations during day and night, albeit with significant failure rates.

Twenty-one patients undergoing carotid endarterectomy were investigated by simultaneous intra-operative measurements of carotid stump pressure (CSP) and transcranial Doppler (TCD) flow velocity in the middle cerebral artery. The relationship between the two methods was evaluated as well as the potential benefits of the intraoperative transcranial Doppler monitoring technique. Clamping of the carotid artery resulted in a significant decrease in TCD flow velocity in the ipsilateral middle cerebral artery as well as in CSP. There was no correlation between relative change in CSP and the simultaneously obtained relative change in TCD flow velocity during carotid clamping (r = 0.31, p = 0.26). The insertion of an intra-operative shunt was followed by an increase in flow velocity compared to the clamping value. One patient with clear TCD signs of a re-occlusion (a sudden decrease in flow velocity) during closure of the wound, demonstrated a thrombosis at re-exploration. TCD gives information of the collateral cerebral circulation during carotid clamping and is an alternative monitoring technique during carotid endarterectomy. The method is useful intraoperatively for detecting embolic events as well as thrombosis during wound closure. Further studies are necessary to clarify the critical change in flow velocity during clamping when the use of a peroperative shunt is indicated.

Bone formation was studied after intramuscular implantation of demineralized bone matrix. Ash weight determinations were used to verify the bone-forming ability of implants, and confirmed that no bone was formed when non-active implants (stripped of their bone-forming ability) were used. A solution hybridization/RNase protection assay was used for the detection of specific mRNA transcripts in the implants and surrounding tissue. Analysis of insulin-like growth factor I (IGF-I) mRNA showed a transient increase peaking on day 3 following implantation. Radioimmunoassay (RIA) for IGF-I-like immunoreactivity indicated a corresponding increase of IGF-I peptide in extracts from the implants at that time point. IGF-II mRNA and alkaline phosphatase mRNA reached highest levels around day 11 following implantation. Bone formation in old rats, 50 weeks of age, was associated with lower IGF-I mRNA levels 3 days after implantation compared with young animals. IGF-II mRNA levels were also affected and tended to be higher 12 days after implantation compared with young animals. These results indicate that IGFs could be paracrine or autocrine factors in the bone-forming process. During this process, IGF-I mRNA is expressed at an early stage, in correlation with the recruitment and proliferation of surrounding mesenchymal cells, whereas IGF-II mRNA is activated significantly later, correlating to the beginning of the actual calcifying process during endochondral bone formation.

Adjuvants have been used to augment the immune response in experimental immunology as well as in practical vaccination for more than 60 years. The chemical nature of adjuvants, their mode of action and the profile of their side effects are highly variable. Some of the side effects can be ascribed to an unintentional stimulation of different mechanisms of the immune system whereas others may reflect general adverse pharmacological reactions. The most common adjuvants for human use today are still aluminium hydroxide, aluminium phosphate and calcium phosphate although oil emulsions, products from bacteria and their synthetic derivatives as well as liposomes have also been tested or used in humans. In recent years monophosphoryl lipid A, ISCOMs with Quil-A and Syntex adjuvant formulation (SAF) containing the threonyl derivative of muramyl dipeptide have been under consideration for use as adjuvants in humans. At present the choice of adjuvants for human vaccination reflects a compromise between a requirement for adjuvanticity and an acceptable low level of side effects.

Over the last twenty years research has provided an important insight into the mechanisms responsible for the immunotoxicity of both local and systemic adverse reactions following the use of immunostimulating drugs and adjuvants. In this article we provide an update of the present knowledge relating to the various parameters and reactants of the immune system at the cellular as well as molecular level that are believed to play a key role in reactogenicity. We discuss evidence obtained from observations in vitro, in vivo in animal models and from clinical applications, including adjuvants used in large scale vaccination today. The data discussed are mainly taken from animal models following hyperstimulation of the immune system; either by the use of very powerful adjuvants, like Freund's that are too toxic for use in practical vaccination, by deliberate high dose application of adjuvants or by the in vivo application of cytokines. Although such hyperstimulating regimens are unlikely to find their way into practical vaccination of humans, this information is of great value as it may facilitate the understanding of the toxicity mechanisms, aid the design of standardised models for the assessment of adjuvant safety and the possible application of new adjuvants in vaccines for humans.

Important new knowledge about the effect of aluminum adjuvants on the immune response in terms of their impact on cytokine profiles, uptake by antigen-presenting cells (APC), and surface marker expression has been published in recent years. However, although the knowledge about these adjuvants is thus more comprehensive now than ever before, the user is often still confined to a more empirical approach when confronted with practical issues when it comes to the handling and use of these adjuvants. In this chapter we have given focus to the user's perspective, discussing practicalities like dosage, temperature stability, relevant monographs, and preparation with antigen.

This article reviews the problem of bleeding in connection with epidural/spinal anaesthesia, with special emphasis on the use of low molecular weight heparins for thromboprophylaxis. There are methodological difficulties to studying the problem in a scientifically correct way because of the rarity of the complication. However, from the data in the literature there are no indications of an increased risk in using the combination of low molecular weight heparin in prophylactic doses and epidural/spinal anaesthesia. So far, there is only a single case report, of spinal haematoma, although low molecular weight heparins have been used in combination with epidural/spinal anaesthesia in at least 1,000,000 patients. In controlled studies, at least 10,000 patients have been given the combination without complications.

Important new knowledge about the effect of aluminum adjuvants on the immune response in terms of their impact on cytokine profiles, uptake by antigen-presenting cells (APC), and surface marker expression has been published in recent years. However, although the knowledge about these adjuvants is thus more comprehensive now than ever before, the user is often still confined to a more empirical approach when confronted with practical issues when it comes to the handling and use of these adjuvants. In this chapter we have given focus to the user's perspective, discussing practicalities like dosage, temperature stability, relevant monographs, and preparation with antigen.

This retrospective study evaluated long-term effects of percutaneous transluminal renal angioplasty (PTRA) in atherosclerotic renal artery stenosis (ARAS), and predictors of benefit on blood pressure (BP).During 1997-2003, 234 patients (age 69+/-11 years, 138 [59%] males) underwent PTRA for ARAS at Malmö Vascular Centre. Cure was defined as diastolic (D)BP90 mmHg and systolic (S)BP140 mmHg off antihypertensive medication. Improvement was defined as DBP90 mmHg and/or SBP140 mmHg on the same or reduced number of medications, or reduction in DBP ofor=15 mmHg with the same or reduced number of medications. Benefit was defined as cure or improvement.After PTRA, SBP and DBP decreased (P0.001), and remained lower (P0.001) until last follow-up after 4.1+/-3.3 years. Antihypertensive medication decreased (P0.001), and remained lower at one month (P0.001), one year (P0.01), and last follow-up (P0.05). Renal function was unchanged until last follow-up, when it deteriorated (P0.001). Patients showing benefit of PTRA on BP at last follow-up (N.=150 [64%]) used more antihypertensive drugs before PTRA (P=0.012), especially angiotensin converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) (P=0.010), and diuretics (P=0.015). In logistic regression, use of ACEi or ARBs failed to reach significancy (P=0.054). Patients dying during follow up (N.=100 [43%]) showed higher age (P0.0001) and s-creatinine (P0.0001), lower glomerular filtration rate (P0.0001), and higher frequency of diabetes mellitus (P0.005). In logistic regression only age (P=0.009) and diabetes mellitus (P=0.014) predicted mortality.We confirmed beneficial effects on BP with PTRA in ARAS. ACEi, ARB and diuretic treatment before PTRA predict favourable long-term BP-response in univariate analysis.

To investigate health-related quality-of-life (HrQoL) in childhood diabetes and the level of agreement between West Sweden and European reference data for the new multi-cultural European questionnaire - DISABKIDS.Twenty percent of the Swedish paediatric diabetes population was included in the survey. Child-parent pairs completed the DISABKIDS chronic generic (37 questions) and diabetes modules (10 questions) during their routine clinic visit. A one-page results summary, based on positive domains, was used to provide feedback to clinicians.Three hundred and sixty-one child-parent pairs were included in the analysis. In Sweden, diabetes was perceived by the children as having less impact than the European average. Swedish parents rated the HrQoL of their children lower than did the European parents. Swedish girls had a lower HrQoL than boys and greater difficulty accepting their diabetes; adolescents had greater difficulty accepting the diagnosis than younger children. Parents reported greater impact of diabetes on their children than the children themselves but reported no difference between boys and girls. Parents reported better acceptance of treatment in boys. The child's reported quality-of-life (QoL) is related to age and gender.Our results confirm the applicability of DISABKIDS to the Swedish paediatric diabetes population.

Reference values should be produced under standardized conditions. To enable comparison it is desirable to use the same procedure also in other clinical situations. A procedure for the collection of venous blood from children with special reference to production of reference values is recommended. It deals with five items: preparation of the child before specimen collection, preparation of the blood collection site, equipment for specimen collection, the specimen collection itself, and handling and storage of the specimen. Alternative methods are described since no single method is suitable for all paediatric age groups. The problem of adhering to a proposed procedure during routine clinical work is also commented upon. The recommendation has been produced as a joint effort of the Scandinavian Committee on Reference Values and a working group set up by the National Paediatric Societies in the Nordic countries.

In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.

We perform two-dimensional, time dependent, hydrodynamical simulations of the gas flow in a potential representing the barred spiral galaxy NGC 1365 using the FS2 code originally written by G.D. van Albada. We find good agreement between observations and models, both concerning the morphology and the velocity field. Contrary to observations, the pure bar perturbed models cannot drive an inner arm across corotation. Models having both a bar and spiral perturbing potential reduce this problem, thus suggesting the existence of massive spiral arms in NGC 1365.

This observational study was undertaken in order to analyse whether any differences could be detected between diabetic and non-diabetic patients with critical limb ischemia (CLI) concerning the inflammatory response.A total number of 259 consecutive patients with CLI were treated between October 2001 and January 2003.Among the 259 patients, 135 (52%) had diabetes, previously known in 123, and detected during hospitalization in 12. The diabetic patients more often showed gangrene (P0.05) and infra-inguinal atherosclerosis (84% vs 67%, P=0.001). The patients with diabetes showed a better lipid profile (total cholesterol 4.6 vs 5 mmol/L, P=0.006 and lower LDL-cholesterol (2.7 vs 3.1 mmol/L, P=0.010) despite the same frequency of statin treatment. They showed a higher creatinine (149 vs 117 micromol/L, P=0.0003) than the non-diabetic patients. Of the inflammatory markers, C-reactive protein (CRP) was equally elevated in both groups. Tumor necrosis factor-a (TNF-a) was increased among the diabetic patients (2.6 vs 1.8 pg/mL, P0.05), and this difference was most evident in those with gangrene. Neopterin was also higher among the diabetic patients (31 vs 21 mmol/L, P0.01), but CD40L was not different between groups.Diabetes mellitus was very common in CLI patients, and more often combined with renal impairment and infra-inguinal atherosclerosis. The inflammatory markers TNF-a and neopterin were elevated in patients with diabetes as compared to non-diabetic patients, but this difference cannot explain why CLI is 10 times more frequent in diabetic patients.

Publisher Summary Two categories of inorganic mineral compounds are applied as immunological adjuvants in vaccine formulation—aluminum compounds and calcium phosphate. Of the two, the aluminum compounds have the longest history and by far the most comprehensive record of use. When evaluating the profile of an adjuvant for possible new applications, very few adjuvants can match the extremely comprehensive cohorts that are available for aluminum adjuvants in terms of records of efficacy and safety profiles. The aluminum adjuvants have beyond doubt proven their efficiency in a large number of applications as vaccine adjuvants in both human and veterinary immunoprophylaxis with very few problems and they are fairly inexpensive. This is of great importance for establishing effective vaccination programs in developing countries, where funding is limited. More research is needed to clarify a possible difference in the ability of the calcium and aluminum based adjuvants in the stimulation of IgE, especially with respect to the cytokine profiles. Only then it becomes possible to judge whether or not calcium phosphate is to be regarded as a clear-cut Th2 stimulator.

The epidemiology of critical limb ischemia (CLI) is insufficiently studied, and treatment of risk factors for atherosclerosis has received less attention in CLI patients than in patients with coronary or precerebral atherosclerosis. The aim of this study was to establish the incidence of CLI and the quality of risk factor treatment in Swedish CLI patients.During 14 months, 316 consecutive CLI patients were referred to the Malmo Department of Vascular Diseases. Two hundred and fifty-nine (82%) consented to evaluation of intercurrent disease, medication, ankle and arm blood pressures (BP), plasma glucose and lipid levels, p-homocysteine, cardiolipin antibodies and activated protein C (APC)-resistance.The incidence of CLI was 38/100,000 inhabitants/year. Patient age was 75 +/- 10 years, and BP 147 +/- 26/75 +/- 14 mmHg. Systolic or diastolic BP above recommended levels (140/90 mmHg) occurred in 137 (53%) patients. P-cholesterol was 4.8+/-1.2 mMol/L, but cholesterol above recommended level (5 mMol/L) or LDL above recommended level (3 mMol/L) occurred in 125 (48%) patients. Only 24% of patients met national recommendations for both BP and lipid levels. Diabetes mellitus was previously known in 123 (47%) patients, and another 12 (5%) patients showed diabetic fasting glucose levels during the hospital stay. Eighty-four (32%) patients were active, and 72 (28%) were former smokers. Myocardial infarction or angina pectoris had previously been diagnosed in 123 (47%) patients. P-homocysteine was 17 +/- 7 _mol/l, cardiolipin antibodies occurred in 71 (27%) and APC-resistance in 34 (13%) patients.Patients with CLI show high comorbidity in vascular diseases and high prevalence of modifiable risk factors for atherosclerotic vascular disease. The use of evidence-based medical therapy is suboptimal in this high-risk group.

Several authors have explored the field of gas dynamics in barred systems. One of the aims of these investigations was to compare the model gaseous response, due to some assumed underlying stellar gravitational field, with observed gas density distribution and kinematics of barred galaxies. The gas is known to respond in a highly non-linear way, and therefore should give clues to dynamical parameters like the mass distribution, positions and existence of principal resonances and thereby the pattern speed.High resolution HI data now exist for NGC 1365 (Jörsäter & van Moorsel 1995), and the kinematical HI data have been combined with optical long slit measurements to obtain the velocity field (Lindblad et al. 1995) used for extracting the rotation curve, representing the axisymmetric forces in NGC 1365, and for comparisons with models. A mosaic image of NGC 1365 in the J-band was used to compute the perturbing potential used in the models.

Aluminium adjuvants are the most widely used adjuvants in both human and veterinary vaccines. These adjuvants have been used in practical vaccination for more than 60 years and are generally recognized as safe and as stimulators of Th2 immunity. The present review gives a short introduction to the pioneering research at the start of the use of aluminium compounds as adjuvants, including references on the chemistry of these compounds. Analytical methods for identifying the most commonly used aluminium compounds, such as boehmite and aluminium hydroxyphosphate, are mentioned. Emphasis is placed on the important factors for antigen adsorption and on the latest work using gene-deficient mice in the research of the mechanism of aluminium adjuvants in terms of cytokine and T-cell subset stimulation. Key references on the ability of aluminium adjuvants to stimulate IgE and also in vivo clearing of aluminium adjuvants are discussed. Furthermore, the review addresses the issue of local reactions in the context of injection route and local tissue disturbance. Possible new applications of aluminium adjuvants in, for example, combined aluminium-adsorbed protein and DNA oligonucleotide vaccines as well as the possible use of aluminium adjuvants in combination with IL-12 to stimulate Th1-type immune responses are mentioned.

Aluminium compounds have been used as adjuvants in practical vaccination for more than 60 years to induce an early, an efficient and a long lasting protective immunity and are at present the most widely used adjuvants in both veterinary and human vaccines. Although the last two decades of systematic research into the nature of these adjuvants has contributed significantly to understanding their nature and their limitations as Th2 stimulators the more detailed mode of action of these adjuvants is still not completely understood. We have a comprehensive record of their behaviour and performance in practical vaccination, but an empirical approach to optimising their use in new vaccine formulations is still to some extent a necessity. The aim of the present review is to put the recent findings into a broader perspective to facilitate the application of these adjuvants in general and experimental vaccinology.

In order to compute stellar orbits in spiral galaxies the gravitational potential and its pattern speed must be known. Observationally, these parameters are difficult to determine, in particular for strongly barred galaxies. We will briefly review different methods and illustrate in more detail the case where the problem has been approached by numerical gasdynamical simulations.

We report on endovascular repair of a ruptured abdominal aortic aneurysm. A bifurcated stent graft was inserted under local anesthesia. Aortic clamping is rapidly provided by percutaneous placement of an aortic occlusion balloon catheter. Carbon dioxide can usually replace conventional contrast in patients with renal insufficiency. This minimally invasive procedure may reduce perioperative morbidity and mortality in patients with ruptured aortic aneurysms. The advantages and limitations of this novel technique are discussed.

Recent developments in medical care and research involve the increased use of immunochemical assays for hormones, tumour markers, vitamins and drugs. External quality assurance programmes using pooled human sera usually fail to detect analytical interference due to substances (e.g. anti-immunoglobulin or anti-ligand antibodies) present in individual serum specimens. The article reports on experience gained during a three-year period when specimens from individual patients attending a thyroid unit were distributed to hospital laboratories in Sweden for analysis. Specimen selection criteria were based on contradictory findings at the initial clinical or laboratory evaluation. The programme has given rise to the formation of a network of the laboratories involved, under the co-ordination of EQUALIS (External quality assurance in laboratory medicine in Sweden).

A short or otherwise suboptimal neck precludes the use of endovascular repair in 30% to 50% of patients with abdominal aortic aneurysms. Stent-graft fixation in an unsuitable neck carries the risk of technical failure owing to development of a proximal endoleak or stent-graft migration. Furthermore, in some patients, the neck dilates postoperatively. Endovascular healing with tissue incorporation into the graft material seems in and of itself insufficient to fixate the stent-graft adequately or to prevent neck dilation. Therefore, neck dilation is often associated with detachment of the stent-graft from the aortic wall, which is followed by the development of a proximal endoleak or stent-graft migration. Fixation of stent-grafts can be improved by placing the proximal stent above one or both of the renal artery orifices. Current experimental and clinical data suggest that renal function is not impaired by suprarenal aortic stents during the first year; however, this finding may not apply to all types of stents. Fixation of stent-grafts also may be improved by using stents with barbs that pierce the aortic wall. Additionally, the force that is exerted on the anchoring device may well be reduced by fully stented grafts with an associated increase in column strength. In the future, the risk of neck dilation and stent-graft dislodgement might also be limited by novel techniques such as laparoscopic banding of the neck or endoluminal stapling devices.

Chronic mesenteric ischaemia is a rare but serious condition, which if untreated may cause death secondary to starvation or bowel infarction. As the symptoms are sometimes unspecific, its diagnosis may be delayed or missed. Although open surgical revascularisation has been the traditional treatment, a review of published reports suggests it to be associated with operative mortality rates of 6-9 per cent, and major morbidity rates of 22-26 per cent. Reports by others, and our own experience, suggest that endovascular treatment of mesenteric atherosclerotic obstructions with PTA (percutaneous transluminal angioplasty) and stenting may yield patency rates differing little from those associated with surgery, but significantly lower mortality (1.6%) and morbidity (5.6%).

There is a need for prosthetic venous conduits in surgery for trauma, cancer and thrombotic disease. Such conduits in use today have a low patency rate, leaving room for much improvement.This experimental study investigated the dynamics of the early attachment of radiolabelled platelets, leucocytes and fibrinogen to endothelial cell-seeded Dacron venous conduits in sheep. Grafts were placed as jugular vein interposition grafts, seeded on one side, not seeded on the other, and followed for 4 h.No difference could be demonstrated between the two graft types. Platelets showed an increasing attachment during the whole period, leucocytes an immediate attachment followed by an undulating pattern, and fibrinogen an immediate attachment with a tendency to decrease. Measurements on the vein itself showed a high attachment and, for platelets, an extremely high attachment when measured after the graft in the direction of flow.The seeding process did not seem to affect early thrombogenicity. The carefully dissected vein wall showed highly thrombogenic properties, in many ways as high as in the prosthetic graft.