[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.

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.

Genetic mapping of Ir locus in man: linkage to second locus of HL-A.

Fifty-seven members of a family that spanned three generations were studied for antigen E and ragweed skin sensitivity and HL-A antigens. There was significant association between the haplotype HL-A 2-12 and antigen E skin hypersensitivity (F = .22 to .26) in this family. The map order is first locus of HL-A, second locus of HL-A, and IrE. These determinants are considered to be part of the linkage group HL-1.

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.

Measuring depressive symptomatology in a general population.

Three hundred twenty respondents in selected geographic areas were interviewed with a structured questionnaire that included the Zung Self-Rating Depression Scale. Dimensional analysis indicates that some items are not pure measures of the constructs they were originally intended to assess. Moreover, some of the dimensions within the scale apparently convey different meanings to different segments in the population. In addition, different dimensions within the scale have varying demographic correlates. The analysis suggests that in order for the scale to be a truly useful device for assessing depressive symptomatology in a general population, additional items need to be added and some questions need to be followed by probes to clarify the exact frame of reference of the respondents.

Depressive symptomatology and role function in a general population.

Depressive symptomatology, marital satisfaction and functioning, job satisfaction, and social relationships were investigated in 320 respondents comprising 160 married couples. Responses to the Zung Self-Rating Depression Scale indicated that 13% of the respondents had scores similar to those obtained by patients with diagnosed depressions and an additional 27% had scores comparable to those of persons with other psychiatric problems. Responses to a variety of questions about the respondents' social life, job satisfaction, and marital function indicate that increased depressive symptomatology in this general population is associated with a decline in satisfaction and functioning in these areas. The data suggest that this association is not solely due to response bias but is associated with a real decline in function, particularly in the area of child rearing.

A model of risk of falling for psychogeriatric patients.

One hundred community-dwelling psychiatric outpatients, 60 years and older, were evaluated for factors associated with symptoms of dizziness, falling, and orthostatic hypotension. Thirty-nine percent complained of dizziness or falling, and 34% had systolic orthostatic hypotension. Together, systolic and diastolic blood pressure drop, type of somatic illness, type and number of drugs, and psychiatric diagnosis accounted for 50% of the variance in dizziness and falling. Type of illness, drug category, and psychiatric diagnosis accounted for only 19% of the variance in orthostatic hypotension. Statistical analysis showed that systolic orthostatic hypotension, disease classification, and type and number of drugs taken contribute independently to dizziness and falling. In geriatric psychiatric patients, careful attention to orthostatic hypotension, concurrent somatic illness, and number and type of medication is essential to the prevention of dizziness, falling, and their consequences.

The affinity of allergen specific IgE and the competition between IgE and IgG for the allergen in Amb a V sensitive individuals.

We have calibrated a solid state RAST assay with affinity purified allergen-specific IgE. We then utilized the calibrated assay to measure the average affinity of individual IgE-containing sera in terms of the average association constant < K > for purified allergen Amb a V. The binding data yielded linear reciprocal plots indicating that the range of affinities of the responding clones was narrow. The range of the average association constant for the IgE-Amb a V complex was 0.9-26 x 10(10) M-1. The average affinity of the corresponding IgG response in the same individual, estimated by inhibition studies of IgE binding, was 10(7) M-1 in one case and lower than 10(6) M-1 in all the other cases.

Characterization of polyclonal allergen-specific IgE responses by affinity distributions.

Polyclonal IgE responses have been previously characterized by allergen-specific antibody levels and by identification of amino acid sequences related to immunodominant epitopes. However, the binding affinities related to these antibody families are not well known. Using sera from donors with known sensitivities to ragweed or house dust mite allergens, we studied the binding reactions between the purified allergens Amb a 1 and Der p 1 and allergen-specific IgE's by determining affinity distribution functions. The distributions of binding affinities only exhibited a few dominant reactions indicated by peaks in an affinity distribution display. In all the donors tested, there were two dominant peaks and in 2/3 of the cases there was a third peak for both Amb a 1 and Der p 1. We further characterized the polyclonal interactions between IgE and Der p 1 by inhibiting the specific binding of IgE using peptide fragments known to be constituents of Der p 1 epitopes. Each peptide inhibited only a single peak in the affinity distributions. It would appear that the peaks in the affinity distribution represent antibodies directed to single epitopes. These results suggest that in our atopic population the response is surprisingly uniform. The bulk of the IgE response (70-80%) is of high affinity (10(8)-10(11) M(-1)) and directed towards a few epitopes. The relative affinities towards epitopes seem to be determined by the structure of the epitope and not variations of individuals' immune responses.

Expression of IgH chain genes in antibody response to ragweed and purified Amb a 1: evidence for differential regulation of isotype production.

A survey of the work with Ig response to allergens carried out previously reveals an allergen-specific response both by IgE and all of IgG subclasses. Response of non-sensitive people is characterized by the appearance of a variety of the IgG subclasses. We have reexamined ragweed and Amb a 1 specific Ig response in 54 nonsensitive and 147 atopic or atopic-allergic people using a new inverse sandwich immunoassay allowing discrimination based on antibody affinity. We show that non-sensitive people present no, 0 out of 54, Ig response with affinities higher than Ka 10(7) M(-1). The subpopulation of 66 atopics who never have experienced desensitization responds vigorously and solely (56 out of 66) with genes of the sequence gamma2-alpha2. Only ten showed an additional weak response from gamma1-alpha1. This suggests a possible association between the atopic state and selective activation of part of the gene sequence.

Dizziness and falling in elderly psychiatric outpatients.

The authors examined 100 psychiatric patients who were 60 years old and older for orthostatic hypotension and symptoms of dizziness and falling. Almost 40% of the patients complained of dizziness and falling, although only 27% had systolic orthostatic hypotension. Drug treatment, particularly the combination of tricyclics with other orthostatic hypotension-inducing drugs, was the most important factor accounting for the dizziness and falling. Underlying medical illness, particularly heart disease, also correlated significantly with the patients' symptoms.

Developing a curriculum in psychogeriatrics.

Psychiatric problems are rampant among the aged, yet the psychiatric profession has not developed sufficient resources for training the necessary number of practitioners able and willing to treat elderly psychiatric patients. The management of psychiatric problems in old age differs substantially from that in younger age groups. The elderly patient is likely to have multiple needs and to require diverse services. Fundamental goals in training geriatric psychiatrists should focus on differential diagnosis and treatment, pharmacologic issues, consultation, community resources, and psychiatric, medical, and psychosocial aspects of care. The authors describe a curriculum tailored to meet these goals.

Role of phospholipase D in laminin-induced production of gelatinase A (MMP-2) in metastatic cells.

Metastatic spread depends critically upon the invasiveness of tumor cells, i.e. their ability to breach basement membranes by elaborating and secreting specific proteolytic enzymes such as gelatinase A (MMP-2). Laminin is a major constituent of the extracellular matrix that can trigger production of MMP-2 in metastatic cells, but not in non-metastatic cells. The present study was designed to examine the role of phospholipase D (PLD) and its product, phosphatidic acid, in the intracellular signal transduction mechanisms that mediate induction of MMP-2 by laminin. Here we show that stimulation of tumor cells with laminin results in a time- and dose-dependent activation of PLD. Laminin-induced production of MMP-2 is attenuated by 1-butanol, a competitive substrate of PLD that reduces PLD-catalyzed production of PA. Moreover, phosphatidic acid itself can induce production of MMP-2 in metastatic tumor cells. MMP-2 can also be induced by exposing the cells to exogenous bacterial PLD. Elevated cellular phosphatidic acid induces MMP-2 in metastatic ras-transformed 3T3 fibroblasts but, like laminin, fails to do so in normal cells. These data indicate that laminin-induced activation of PLD and consequent generation of phosphatidic acid are involved in a signal propagation pathway leading to induction of MMP-2 and enhanced invasiveness of metastatic tumor cells.

An automated method for determination of antibody affinity distribution functions with nanogram quantities.

We have developed a method to determine the binding affinity distribution functions (the probability density function for affinity constants will be referred to as affinity distribution throughout the text) for human serum antigen specific IgE for their respective allergens. This fully automated method, based on the Access technology of Sanofi Diagnostics Pasteur, is a highly sensitive two-step sandwich immunoassay requiring only nanogram quantities of antibodies. Allergen-antibody binding isotherms can be determined covering a range of 5 magnitudes of ligand (allergen) concentration. An affinity distribution function, describing the polyclonal nature of the antibody response, can be calculated from the binding isotherm. The validity of the method is assessed using mAbs against the purified allergen Der p 1. The resolving power and sensitivity of the method are demonstrated using selected sera from donors with high and low levels of specific IgE for these allergens. We are able to show that heterogeneous IgE populations can be determined using 100 microl of sera containing 150 pg of specific IgE per ml. Overall, the range of affinities that can be determined by this method is 1 x 10(6)-1 x 10(11) M(-1).

The effect of continuous strenuous exercise on intraocular pressure.

The effect of a continuous 110-km march with a 20-kg backpack load on intraocular pressure (IOP), plasma osmolarity, blood lactate, pH, and other related laboratory parameters was studied in 22 healthy young volunteers. Intraocular pressure decreased significantly at all marching intervals and returned to baseline level 3 hr after the completion of marching. The maximal average reduction during marching was 4.1 mmHg, 26.5% below the baseline level. The IOP decreased again 48 hr after the march and returned to baseline level 48 hr later. There were two peaks of increased plasma osmolarity (one during the march and the other 48 hr after the march). There was no correlation between IOP changes and levels of pH, blood lactate, serum proteins, and electrolytes or hematologic parameters. These findings suggest that IOP reduction is related inversely to plasma osmolarity during and after strenuous exercise.

The penetration of gentamicin into the vitreous humor in man.

Twenty-two patients received gentamicin intramuscularly or subconjunctivally 35-220 min prior to undergoing ocular surgery. There were no detectable gentamicin levels in the vitreous humor of patients who received the drug systemically. Of the patients who received gentamicin subconjunctivally, three quarters had no detectable gentamicin levels, only three of these patients had therapeutic concentrations in their vitreous humor. These results confirm kinetic drug studies performed in animals in which low or absent vitreal gentamicin levels were observed following systemic and subconjunctival administrations. It is suggested that intravitreal injection of aminoglycosides is required in the treatment of bacterial endophthalmitis.

Experimental coronary arterial occlusion and release. Effects on enzymes, electrocardiograms, myocardial contractility and reactive hyperemia.

After less than 1 hour of coronary arterial occlusion, the myocardium suffers irreversible changes as revealed by electron microscopy. Yet, the earliest clinical laboratory indexes of myocardial infarction--elevated serum enzyme levels and significant Q waves on the electrocardiogram--are not detected until at least 6 hours after coronary occlusion. To study the early period after coronary occlusion in the dog, occlusion of the left anterior descending coronary artery for 1 to 3 hours was followed by release, and coronary sinus and venous enzyme levels, the electrocardiogram and myocardial contractility from the infarcted area, and reactive hyperemia were monitored. Coronary sinus enzyme levels rose within 15 minutes after release of occlusion in half of the experiments with 1 to 1 1/2 hours and in all of those with 2 to 3 hours of occlusion, and this rise preceded the rise in venous levels by only 10 to 20 minutes. Significant Q waves appeared 15 to 30 minutes after release of occlusion as the serum enzymes were increasing. Thus, clinically, the delayed appearance of increased serum enzymes and significant electrocardiographic Q waves is probably largely due to a lack of circulation in the infarcted area rather than to prolonged survival time. Also, the venous enzyme level reflects the coronary sinus level minutes later. The presence of viable myocardium in the infarcted area was suggested by elevation of the S-T segment upon reclamping, and by residual myocardial contractility and retained capacity for reactive hyperemia. These findings occurred in some experiments even in the presence of a significant Q wave.

Effects of fosinopril on exercise tolerance and clinical deterioration in patients with chronic congestive heart failure not taking digitalis. Fosinopril Heart Failure Study Group.

A total of 241 men and women with mild to moderately severe chronic heart failure (New York Heart Association functional class II [90%] or III) and a mean (+/- SD) left ventricular ejection fraction of 25 +/- 7%, entered a 24-week, prospective, double-blind, placebo-controlled trial of 10 or 20 mg/day of fosinopril, a phosphinic acid angiotensin-converting enzyme inhibitor. Patients received concomitant diuretic therapy but not digitalis. Primary end points were mean change in maximal treadmill exercise time and occurrence of prospectively defined clinical events indicative of worsening heart failure (most to least severe): death, withdrawal for worsening heart failure, hospitalization for worsening heart failure, need for supplemental diuretic or emergency room visit for worsening heart failure, and no event. At study end point, treadmill exercise time had improved in the fosinopril versus the placebo group (+28.4 vs -13.5 seconds, p = 0.047). New York Heart Association functional class had improved at end point more frequently (24% vs 13%) and deteriorated less frequently (18% vs 32%) in the fosinopril group (p = 0.003). More patients treated with fosinopril (66% vs 50%) remained free of clinical events indicative of worsening heart failure, and fosinopril-treated patients had less severe clinical events (p = 0.004). Dyspnea, fatigue, and paroxysmal nocturnal dyspnea improved more often and worsened less often in this group (p < or = 0.002), and edema showed a trend toward improvement (p = 0.088). These clinical benefits did not require concomitant digitalis therapy. Fosinopril was associated with an acceptable safety profile.