[Determinants for the Access to Follow-Up Rehabilitation Concerning Cardiological Patients after Surgery]. / Einflussfaktoren des Zugangs in die Anschlussrehabilitation (AHB) von operativ versorgten kardiologischen Patienten.

OBJECTIVE: The aim was to analyze individual and environmental factors influencing the access to follow-up rehabilitation of cardiological patients after surgery. METHODS: An exploratory, cross-sectional study without intervention was conducted. A standardized questionnaire was used for data collection in two acute care clinics at cardiological and cardiosurgical wards. Multivariate logistic regression was used to measure the influence of different factors on the access to follow-up rehabilitation. In 61.0% of the patients a follow-up rehabilitation was granted. RESULTS: 210 patients were included. The average age was 52.1 years, 81.0% were male. There were significant differences between the groups with and without follow-up rehabilitation concerning age (p=0.018), sex (p=0.007), the PAREMO-scales "Änderungsbereitschaft" (p=0.011) and "Skepsis" (p=0.005) and the aim of rehabilitation to learn skills in dealing with the disease (p=0.043). The Barthel-Index was not significant different between the two groups. The chance to get a follow-up rehabilitation was significantly increased by indications corresponding to the "AHB-Indikationskatalog" (p=0.001; OR=5.76) and after request of the patients to get a follow-up rehabilitation (p<0.001; OR=17.91). DISCUSSION: The access to follow-up rehabilitation was predominantly indication-specific and depended on patients' request of cardiological patients after surgery. A follow-up rehabilitation requires an adequate rehabilitation capacity (Barthel-Index). However the effect of the Barthel-Index on the access to follow-up rehabilitation was not significant. CONCLUSION: It is still in question, to what extent the personal patient's wish can be linked to parameters of rehabilitation capacity. Furthermore it is necessary to develop concepts which increase the influence of rehabilitation capacity on the decision of a follow-up rehabilitation.

Rare autosomal copy number variations in early-onset familial Alzheimer's disease.

Over 200 rare and fully penetrant pathogenic mutations in amyloid precursor protein (APP), presenilin 1 and 2 (PSEN1 and PSEN2) cause a subset of early-onset familial Alzheimer's disease (EO-FAD). Of these, 21 cases of EO-FAD families carrying unique APP locus duplications remain the only pathogenic copy number variations (CNVs) identified to date in Alzheimer's disease (AD). Using high-density DNA microarrays, we performed a comprehensive genome-wide analysis for the presence of rare CNVs in 261 EO-FAD and early/mixed-onset pedigrees. Our analysis revealed 10 novel private CNVs in 10 EO-FAD families overlapping a set of genes that includes: A2BP1, ABAT, CDH2, CRMP1, DMRT1, EPHA5, EPHA6, ERMP1, EVC, EVC2, FLJ35024 and VLDLR. In addition, CNVs encompassing two known frontotemporal dementia genes, CHMP2B and MAPT were found. To our knowledge, this is the first study reporting rare gene-rich CNVs in EO-FAD and early/mixed-onset AD that are likely to underlie pathogenicity in familial AD and perhaps related dementias.

Climate information for public health: the role of the IRI climate data library in an integrated knowledge system.

Public health professionals are increasingly concerned about the potential impact of climate variability and change on health outcomes. Protecting public health from the vagaries of climate requires new working relationships between the public health sector and the providers of climate data and information. The Climate Information for Public Health Action initiative at the International Research Institute for Climate and Society (IRI) is designed to increase the public health community's capacity to understand, use and demand appropriate climate data and climate information to mitigate the public health impacts of the climate. Significant challenges to building the capacity of health professionals to use climate information in research and decision-making include the difficulties experienced by many in accessing relevant and timely quality controlled data and information in formats that can be readily incorporated into specific analysis with other data sources. We present here the capacities of the IRI climate data library and show how we have used it to build an integrated knowledge system in the support of the use of climate and environmental information in climate-sensitive decision-making with respect to health. Initiated as an aid facilitating exploratory data analysis for climate scientists, the IRI climate data library has emerged as a powerful tool for interdisciplinary researchers focused on topics related to climate impacts on society, including health.

Serum metalloproteinase leukolysin (MMP-25/MT-6): a potential metabolic marker for atopy-associated inflammation.

BACKGROUND: Leukolysin is a novel matrix metalloproteinase (MMP-25/MT-6) released mainly by granulocytic cells, primarily neutrophils, which are implicated in chronic airways inflammation. OBJECTIVE: To determine if leukolysin might be a serum marker for atopic asthma or chronic obstructive pulmonary disease (COPD). METHODS: Three study populations were evaluated: (1) nuclear families with medical history of atopic asthma (N=337), (2) married-in individuals from an independent study of asthma genetics (N=122) and (3) randomly selected males with diagnosis of COPD (N=100). Each person was screened for asthma or COPD symptoms, respiratory function by standardized spirometry and serum total IgE and leukolysin and anti-IL1 levels by immunoassay. Study groups (1 and 2) were also screened by skin prick test using a battery of 14 common aeroallergens. Heritability estimates for leukolysin and total IgE were made by variance components analysis. RESULTS: For those without asthma or who had asthma defined as having symptoms, a physician's diagnosis and bronchial hyper-reactivity as demonstrated by reversibility in response to albuteral and/or bronchial reactivity as measured by a methacholine challenge, serum leukolysin levels were found to be higher for those with any positive skin test result. This paralleled trends for serum total IgE. In the nuclear families and COPD patients, serum leukolysin levels were significantly elevated for those who also had elevated total IgE levels (log[IgE]>2.0) compared with those with lower IgE (log[IgE]<2.0). Serum IL-1 levels correlated with the leukolycin levels. In contrast to IgE, leukolysin showed no apparent inherited component. CONCLUSION: Among individuals with history of chronic airways inflammation (asthma and COPD) serum leukolysin may be a metabolic marker associated with chronic atopy-associated respiratory inflammation. Common factors may stimulate increased production or release of both leukolysin from myeloid cells and IgE from lymphoid cells.

Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events.

BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.

Web-based climate information resources for malaria control in Africa.

Malaria remains a major public health threat to more than 600 million Africans and its control is recognized as critical to achieving the Millennium Development Goals. The greatest burden of malaria in Africa occurs in the endemic regions where the disease pathogen is continuously present in the community. These regions are characterized by an environment that is conducive to interactions between the Anopheles mosquito, malaria parasites and human hosts, as well as housing of generally poor quality, which offers little protection from mosquito-human contact. Epidemic malaria tends to occur along the geographical margins of endemic regions, when the equilibrium between the human, parasite and mosquito vector populations is occasionally disturbed and a sharp but temporary increase in disease incidence results. When malaria control measures are inadequate, as is the case in much of sub-Saharan Africa, the disease distribution is closely linked with seasonal patterns of the climate and local environment. In the absence of good epidemiological data on malaria distribution in Africa, climate information has long been used to develop malaria risk maps that illustrate the boundaries of 'climatic suitability for endemic transmission.' The best known of these are produced by the Pan-African-based MARA Collaboration. This paper describes the development of additional malaria suitability maps which have been produced in an online, interactive format to enable temporal information (i.e., seasonality of climate conditions) to be queried and displayed along with spatial information. These maps and the seasonal information that they contain should be useful to the malaria control and health service communities for their planning and operational activities.

Random outcomes of allergen-specific responses in atopic families.

BACKGROUND: Allergens are common non-infectious antigens to which people will mount T cell dependent humoral responses. Among genetically susceptible individuals, an antigen-specific response results involving the production of allergen-specific IgE (atopy). OBJECTIVE: Determine if this susceptibility is manifested as an inherited, allergen-specific trait or a random response to allergens among susceptible people. METHODS: We evaluated allergen-specific outcomes in 1099 members of families with positive atopic history (26 multi-generation and 112 nuclear families). Each was tested for sensitivity to 14 common allergens by standardized skin prick test (SPT), a marker of specific IgE production. Over 15,000 individual SPT's were evaluated. Among five randomly selected multi-generation families (N=163), semi-quantitative determinations of Amb a 1-specific IgA1,2 and IgG1-4 were determined in three groups: (A) Amb a SPT(+)/Amb a 1-IgE(+), (B) Amb a SPT(-)/Amb a 1-IgE(+), (C) Amb a SPT(-)/Amb a 1-IgE(-). RESULTS: By rank correlation statistics, there were no discernible 'patterns' of specific SPT outcomes among any of the multi-generation families, suggesting that environmental exposure rather than allergen-specific inheritance determined the responses. This was confirmed among the nuclear families since the conditional SPT outcomes among children were independent of the SPT responses of their parents. Among five randomly selected multi-generation families, the relative proportionate concentrations of the Amb a 1-specific IgA and IgG subclasses were comparable, regardless of atopic sensitization to the ragweed allergen Amb a. CONCLUSION: While the general propensity for atopy may be inherited, an individual's specific atopic outcome is a random variable independent of familial sensitization patterns.

Genome scan for loci linked to mite sensitivity: the Collaborative Study on the Genetics of Asthma (CSGA).

Mite sensitivity has been reported to be a major risk factor for asthma. As part of the Collaborative Study on the Genetics of Asthma (CSGA), a genome scan using mite reactivity (Dermatophagoides Pteronyssinus (Der p) and Dermatophagoides farinae (Der f)) as the phenotype was conducted. In 287 CSGA families, 122 were informative for linkage. Evidence supporting linkage was observed for regions on chromosome 19 (D19S591, lod=2.43, P=0.0008; D19S1037, lod=1.57, P=0.007) and chromosome 20 (D20S473/D20S604, lod=1.41, P=0.01). All three ethnic groups appeared to contribute to the evidence for linkage on chromosome 20. African-American families gave strongest support for linkage on chromosomes 3 (D3S2409, lod=1.33, P=0.01), 12 (D12S373, lod=1.51, P=0.008) and 18 (ATA82B02, lod=1.32, P=0.01). Caucasian families showed strong evidence for linkage on chromosome 19 (D19S591, lod=3.51, P=0.00006). Hispanic families supported linkage on chromosomes 11 (D11S1984, lod=1.56, P=0.007), 13 (D13S787, lod=1.30, P=0.01) and 20 (D20S470, lod=1.71, P=0.005). These results suggest that multiple genes may be involved in controlling skin reactivity to Dermatophoigoies.

Evidence of an affinity threshold for IgE-allergen binding in the percutaneous skin test reaction.

BACKGROUND: Atopy is an aberrant immune response involving allergen-specific IgE production, though serum IgE concentration is not an entirely reliable diagnostic tool, particularly for epidemiological and genetic studies. There is no clear correlation between IgE and other indicators of atopy such as skin prick tests (SPT)s, and physiological associations are difficult to justify in cases with detectable IgE but negative SPT results. OBJECTIVE: IgE reflects the number of molecules available to produce an atopic response, but the degree of the response is determined by the binding strength (affinity) between receptor-bound IgE and the allergen. We sought to determine if there was an association between binding affinity and SPT results in people with histories of atopy. METHODS: Standard SPTs (whole allergen extracts) were administered to people with histories of sensitivities to ragweed and house dust mite. The concentrations and affinities of serum allergen-specific IgEs were determined using the purified allergens Amb a 1 and Der p 1. RESULTS: There was a positive correlation between weal area and allergen-specific IgE among SPT-positive donors. However, for those individuals with detectable amounts of allergen-specific IgE, there was considerable overlap of IgE values between SPT-positive and -negative groups. Among sensitized donors, IgE-allergen interactions were characterized by two or three specific reactions of very high affinity (K(A) range 10(8) -10(11) M). Negative SPT reactions were associated with lowered IgE binding affinities to major allergens. This delimited two groups with atopic disorders: specific IgE(+)/ SPT(+) and specific IgE(+)/SPT(-). CONCLUSION: The product of antibody affinity and concentration, which we define as antibody capacity (CAP = K(A) x IgE), is more informative with regard to describing allergen sensitivity than antibody concentration alone. Antibody binding capacity provides physiological evidence of atopy in some subjects who do not test positively by common methods and suggests an affinity threshold to produce a positive SPT reaction.

Ethnic differences in asthma and associated phenotypes: collaborative study on the genetics of asthma.

BACKGROUND: In the Collaborative Study on the Genetics of Asthma, 314 families with 2584 subjects were characterized for asthma and allergy. OBJECTIVE: The purpose of this investigation was to examine clinical heterogeneity observed in asthma and allergic characteristics among 3 ethnic groups (African American, white, and Hispanic family members). METHODS: Pulmonary function parameters and asthma associated phenotypes were compared among the ethnic groups. RESULTS: In comparison with the other groups, African American sibling pairs had a significantly lower baseline FEV(1) percent of predicted (P =.0001) and a higher rate of skin test reactivity to cockroach allergen (P =.0001); Hispanic sibling pairs had significantly more skin reactivity overall (P =.001); and white sibling pairs had significantly lower total serum IgE (P <.05). In addition, there were significantly more relatives with asthma among the African American families than among the white and the Hispanic families (P =.001). CONCLUSION: Although different environmental backgrounds should be considered, these clinical differences could be due to differences in genetic susceptibility among the ethnic groups, such as those suggested by our previous genome screen.

Corneal endothelial cytotoxicity of diluted povidone--iodine.

PURPOSE: To assess corneal endothelial toxicity of diluted povidone-iodine (PI) in vivo and in vitro. SETTING: Cell Biology Laboratory and the Laboratory for Intraocular Microsurgery and Implants, Goldschleger Eye Research Institute, Sackler School of Medicine, Tel-Aviv University, Chaim Sheba Medical Center, Tel-Hashomer, Israel. METHODS: In an in vitro study, cultured bovine corneal endothelial cells were exposed to diluted PI. The degree of cell damage was determined by staining with trypan blue and by comparing the results to those in a control group. In an in vivo study, a single dose of diluted PI was injected into the anterior chamber of rabbit eyes, completely replacing the aqueous humor. The eyes were evaluated by clinical examination, specular microscopy, pachymetry, pneumotonometry, and histopathology and compared to a control group injected with a balanced salt solution. RESULTS: In vitro, PI concentrations of 0.05% or less did not induce endothelial cell damage. Significant damage was observed with a PI concentration of 0.1%. Calf serum concentrations of 1% and higher in the culture media protected the endothelial cell monolayer from cytotoxic damage by PI. Aqueous humor did not have a similar effect. In vivo, PI concentrations of 0.1% or less did not induce changes in corneal endothelium morphology or function as assessed by specular microscopy and pachymetry. A PI concentration of 1% served as a positive control, causing corneal edema and endothelial cell loss as demonstrated by pachymetry, histopathology, and elevated intraocular pressure. CONCLUSIONS: The concentrations of PI tolerated by animal endothelium in vitro and in vivo were higher than the reported bactericidal levels. These findings justify further investigation of the safety and efficacy of PI for intracameral prophylaxis during surgery.

Genomewide screen and identification of gene-gene interactions for asthma-susceptibility loci in three U.S. populations: collaborative study on the genetics of asthma.

The genomewide screen to search for asthma-susceptibility loci, in the Collaborative Study on the Genetics of Asthma (CSGA), has been conducted in two stages and includes 266 families (199 nuclear and 67 extended pedigrees) from three U.S. populations: African American, European American, and Hispanic. Evidence for linkage with the asthma phenotype was observed for multiple chromosomal regions, through use of several analytical approaches that facilitated the identification of multiple disease loci. Ethnicity-specific analyses, which allowed for different frequencies of asthma-susceptibility genes in each ethnic population, provided the strongest evidence for linkage at 6p21 in the European American population, at 11q21 in the African American population, and at 1p32 in the Hispanic population. Both the conditional analysis and the affected-sib-pair two-locus analysis provided further evidence for linkage, at 5q31, 8p23, 12q22, and 15q13. Several of these regions have been observed in other genomewide screens and linkage or association studies, for asthma and related phenotypes. These results were used to develop a conceptual model to delineate asthma-susceptibility loci and their genetic interactions, which provides a promising basis for initiation of fine-mapping studies and, ultimately, for gene identification.

Experimental studies of capsular equator rings of soft latex.

PURPOSE: To determine the efficacy of wide equatorial rings of various materials in reducing posterior capsule opacification (PCO) and maintaining the circular contour of the capsular equator in a rabbit model. SETTING: Laboratory for Intraocular Microsurgery and Implants, Goldschleger Eye Research Institute, Tel-Aviv University, Sheba Medical Center, Tel-Hashomer, Israel. METHODS: Closed rings made of poly(methyl methacrylate), Teflon(R), polyurethane, and latex were introduced into the capsular bags of rabbit eyes after removal of the lens material. The soft latex rings were deemed the only practical rings for atraumatic implantation through a small incision. Latex rings of 2 dimensions with rectangular edges were implanted in 8 rabbits. One eye served as a control after lens removal and no ring implantation. The eyes were followed for up to 5 months and then evaluated by light microscopy. RESULTS: Posterior capsule opacification was minimal or absent in all animals implanted with the latex rings. Mild to moderate inflammatory reaction was noted in most eyes. It was caused by the ring material or secondary to long-standing pressure on the ciliary tissue. The rings also maintained well the circular contour of the capsular bags. CONCLUSIONS: Equatorial rings of soft latex with sharp rectangular edges were effective in minimizing PCO and maintaining the shape of the capsule after lens removal in rabbits. Soft rings made of a biocompatible material may be effective in humans.

Genome-wide linkage analyses of total serum IgE using variance components analysis in asthmatic families.

Variance components models were used to analyze total IgE levels in families ascertained though the Collaborative Study of the Genetics of Asthma (CSGA) using a genome-wide array of polymorphic markers. While IgE levels are known to be associated with clinical asthma and recognized to be under strong genetic control (here the heritability was estimated at 44-60% in the three racial groups), specific genes influencing this trait are still largely unknown. Multipoint analysis of 323 markers yielded little indication of specific regions containing a trait locus controlling total serum IgE levels (adjusted for age and gender). Although a number of regions showed LOD statistics above 1.5 in Caucasian families (chromosome 4) and in African-American families (chromosomes 2 and 4), none yielded consistent evidence in all three racial groups. Analysis of total IgE adjusted for gender, age and Allergy Index (a quantitative score of skin test sensitivity to 14 common aeroallergens) was conducted on these data. In this analysis, a much stronger signal for a trait locus controlling adjusted log[total IgE] was seen on the telomeric end of chromosome 18, but only in Caucasian families. This region accounted for most of the genetic variation in log[total IgE], and may represent a quantitative trait locus for IgE levels independent of atopic response. Oligogenic analysis accounting simultaneously for the contribution of this locus on chromosome 18 and other chromosomal regions showing some evidence of linkage in these Caucasian families (on chromosomes 2, 4 and 20) failed to yield significant evidence for interaction.

Nedocromil sodium 2% ophthalmic solution for the treatment of ragweed pollen seasonal allergic conjunctivitis.

PURPOSE: To determine the efficacy and safety of nedocromil sodium 2% ophthalmic solution in the treatment of seasonal allergic conjunctivitis. METHODS: A combined analysis of two multicenter, randomized, comparative, double-masked, placebo-controlled clinical trials involving 261 patients diagnosed with seasonal allergic conjunctivitis was used. Patients were randomly assigned to receive either topical 2% nedocromil sodium or placebo twice daily for eight weeks. Diary card scores and clinician assessments of allergic symptoms were recorded throughout the study; efficacy was determined by comparing symptom severity at the peak pollen period with symptom severity at baseline. Clinician and patient evaluations of treatment effectiveness were used as secondary measurements of efficacy. RESULTS: Patients treated with nedocromil sodium experienced improvement in allergy symptoms, with reductions in the summary symptom score, itch, redness, conjunctival injection, and conjunctival edema significantly (p<0.05) greater than those observed in the patients treated with placebo. Clinicians' and patients' opinions of nedocromil sodium treatment effectiveness were significantly (p<0.02) superior to those of placebo treatment effectiveness. CONCLUSION: Nedocromil sodium is effective in the management of seasonal allergic conjunctivitis.

Efficacy and safety of nedocromil sodium 2% ophthalmic solution b.i.d. in the treatment of ragweed seasonal allergic conjunctivitis.

The efficacy and safety of twice-daily nedocromil sodium 2% ophthalmic solution and vehicle were compared in the treatment of ragweed seasonal allergic conjunctivitis. Two separate multicenter, randomized, double-masked, placebo-controlled studies were subjected to a combined analysis. Following a one-week baseline period during the beginning of the ragweed pollen season, 189 patients with seasonal allergic conjunctivitis received either nedocromil sodium or vehicle b.i.d. for eight weeks. Efficacy was evaluated by patient diary cards and clinical eye examinations. Safety was assessed by reports of adverse events. Compared with vehicle, nedocromil sodium produced significantly greater decreases in summary symptom score (p = 0.005), itch (p = 0.005), tearing (p = 0.004), overall eye condition (p = 0.001), and clinician-evaluated conjunctival edema (p = 0.018), and significantly better (p = 0.001), and patient (p = 0.001) opinions of treatment effectiveness at the peak pollen period. Additionally, the superiority of nedocromil sodium compared to vehicle approached statistical significance in redness reduction (p = 0.087) and clinician-evaluated conjunctival injection (p = 0.087). There were no serious treatment-related adverse events in either treatment group. In summary, nedocromil sodium 2% ophthalmic solution b.i.d. was found to be effective and to have a favorable safety profile in the treatment of seasonal allergic conjunctivitis.