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Michael Beck

Publications and source records attributed to Michael Beck.

At least 37 records · Page 2Linked to original sources
PubMed2006

Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease.

CONTEXT: Fabry disease is an X-linked multisystem disorder. Enzyme-replacement therapy in adults has limited efficacy in treating major sequelae of advanced Fabry disease, such as kidney failure or stroke. This prompted a study of the safety and efficacy of enzyme replacement at an earlier stage of Fabry disease. OBJECTIVES: Our purpose with this work was to evaluate safety and to explore efficacy of enzyme treatment with agalsidase alfa in pediatric patients with Fabry disease. METHODS: We conducted a 6-month open-label study at 3 tertiary care centers with 24 children (19 boys and 5 girls) with a mean age of 11.8 (range: 6.5-18) years, to examine safety parameters, including infusion reactions and antiagalsidase alfa antibodies. RESULTS: Agalsidase alfa was well tolerated, and all of the patients completed the study. Six boys and 1 girl had mild-to-moderate infusion reactions. One boy developed transient immunoglobulin G antibodies against agalsidase alfa. The boys showed a significant reduction in plasma globotriaosylceramide on treatment. Mean estimated glomerular filtration rate, cardiac structure, and function were normal and did not change over 26 weeks. Heart rate variability, as determined by 2-hour ambulatory monitoring, was decreased in the boys compared with the girls at baseline. All indices of heart rate variability improved significantly in the boys. Three patients with anhidrosis, as determined by quantitative sudomotor axon reflex testing, developed sweating. Six of 11 patients could reduce or cease their use of antineuropathic analgesics. CONCLUSIONS: Enzyme replacement with agalsidase alfa was safe in this study. The exploratory efficacy analysis documented increased clearance of globotriaosylceramide and improvement of autonomic function. Prospective long-term studies are needed to assess whether enzyme replacement initiated early in patients with Fabry disease is able to prevent major organ failure in adulthood.

Adolescent↗
PubMed2005

Threshold effect of urinary glycosaminoglycans and the walk test as indicators of disease progression in a survey of subjects with Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome).

A cross-sectional survey in individuals affected with the lysosomal storage disease Mucopolysaccharidosis VI (MPS VI) was conducted to establish demographics, urinary glycosaminoglycan (GAG) levels, and clinical progression of the disease. The survey evaluated 121 bona fide MPS VI-affected individuals over the age of 4 years from 15 countries across the Americas, Europe, and Australasia representing greater than 10% of the estimated world prevalence of the disease. A medical history, complete physical exam, urinary GAG determination, and assessment of several clinical measures related to physical endurance, pulmonary function, joint range of motion, strength, and quality of life were completed for each participant. Although a wide variation in clinical presentation was observed, several general findings were obtained reflecting progression of the disease. Impaired physical endurance, as measured by the distance achieved in a 6-min walk, could be demonstrated across all age groups of MPS VI-affected individuals. High urinary GAG values (>200 mug/mg creatinine) were associated with an accelerated clinical course comprised of age-adjusted short stature and low body weight, impaired endurance, compromised pulmonary function, and reduced joint range of motion. An unexpected result was the predominance of urinary GAG values <100 mug/mg creatinine for those participants over the age of 20 years. Pending the collection of longitudinal data, these results suggest that urinary GAG levels predict clinical morbidity, and longer-term survival is associated with urinary GAG levels below a threshold of 100 mug/mg creatinine.

Adolescent↗
PubMed2005

Thirty-four novel mutations of the GLA gene in 121 patients with Fabry disease.

Fabry disease (FD) is an X-chromosomal disorder caused by mutations in the GLA gene encoding the lysosomal enzyme alpha-galactosidase A. We performed mutation screening on a cohort of 121 patients including 84 male and 37 female index cases and identified a total of 90 different mutations, 34 of which are reported for the first time here. Both point mutations (74.4%) and 'short length' rearrangements (25.6%) were found, including missense (54.4%), nonsense (14.4%), and splice site point mutations (5.6%), deletions (17.8%) or insertions/duplications (5.6%) of a few nucleotides, and complex rearrangements including larger deletions (2.2%). GLA mutations were identified in 82 (97.6%) of the 84 unrelated male patients.

Adolescent↗
PubMed2005

[Is there a connection between right-wing extremism and social distancing from mentally ill people? Results from a representative survey among the adult German population].

OBJECTIVE: There are indications of a link between right-wing extremist orientation and attitudes towards people with mental illnesses. Social distance is used to investigate this. METHOD: In 2002, a representative survey was conducted among the German adult population (n = 2089). Social distance was measured using a question from the European values surveys. Right-wing extremist attitudes were measured with a scale developed by Niedermayer and Faller. RESULTS: Only a marginal link between right-wing extremism and social distance towards people with mental illnesses was found which, moreover, showed an inconsistent pattern. DISCUSSION: It would be premature to conclude from this "negative" finding that a right-wing extremist orientation has no influence on the attitude towards people with mental illnesses, especially in the light of only one form of discrimination being investigated here.

Adolescent↗
PubMed2005

Anemia is a new complication in Fabry disease: data from the Fabry Outcome Survey.

BACKGROUND: The prevalence and causes of anemia among patients with Fabry disease are unknown. METHODS: In a cross-sectional study we examined hemoglobin concentrations of patients with Fabry disease using a large international database, the Fabry Outcome Survey (FOS), and analyzed the association of renal function, heart failure, gastrointestinal symptoms, and inflammation, with anemia (hemoglobin <12 g/dL in females and <13 g/dL in males). RESULTS: Anemia was present in 34% of 345 patients with Fabry disease. Median hemoglobin in 158 females was 12.9 g/dL and the median hemoglobin of 187 male patients was 13.2 g/dL. The prevalence of anemia among females was 20%, and among males 47%. Among patients with normal renal function [estimated glomerular filtration rate (GFR) >90 mL/min/1.73 m(2)] and anemia, heart failure [New York Heart Association (NYHA) class II to IV] and/or elevated C-reactive protein (CRP) levels were documented in 82% of patients. Up to 67% of patients with decreased estimated GFR presented with anemia. There was also a trend for lower hemoglobin levels among patients with signs of inflammation (defined by an elevated CRP level). We observed no association of the presence of gastrointestinal symptoms with anemia. Analyses in 53 patients receiving enzyme replacement therapy for up to 2 years, suggest no effect on anemia. CONCLUSION: The results of this study point to a high prevalence of anemia among patients with Fabry disease that is in most instances related to impaired renal function, heart failure, and inflammation. This finding may be of clinical relevance, because anemia is a major risk factor for patients with kidney disease, heart failure, or stroke, which are important manifestations of Fabry disease.

Adult↗
PubMed2004

Development and testing of new screening method for keratan sulfate in mucopolysaccharidosis IVA.

Mucopolysaccharidosis IVA (MPS IVA), a progressive lysosomal storage disease, causes skeletal dysplasia through excessive storage of keratan sulfate (KS). We developed an ELISA-sandwich assay that used a MAb specific to KS. Forty-five blood and 59 urine specimens from MPS IVA patients (ages 1-65 y) were analyzed to determine whether KS concentration is a suitable marker for early diagnosis and longitudinal assessment of disease severity. Blood specimens were obtained from patients categorized as phenotypically severe (n = 36) and milder (n = 9). Urine specimens were also analyzed from patients categorized as severe (n = 56) and milder (n = 12), respectively. Blood KS levels (101-1525 ng/mL) in MPS IVA patients were two to eight times higher than those in age-matched controls (15-323 ng/mL). It was found that blood KS level varied with age and clinical severity. Blood KS levels in both MPS IVA and controls peaked between 5 and 10 y of age (mean, 776 versus 234 ng/mL, respectively). Blood levels in severe MPS IVA were 1.5 times higher than in the milder form. In contrast to blood, urine KS levels in both MPS IVA and controls peaked between 1 and 5 y (15.3 versus 0.26 mg/g creatinine), and thereafter declined with age. Urine KS level also varied with age and clinical severity, and the severe MPS IVA phenotype was associated with 6.7 times greater urine KS excretion than the milder one. These findings indicate that the new assay for blood or urine KS may be suitable for early diagnosis and longitudinal assessment of disease severity in MPS IVA.

Adolescent↗
PubMed2004

Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase).

OBJECTIVE: To confirm the efficacy and safety of recombinant human alpha-L-iduronidase (laronidase) in patients with mucopolysaccharidosis I (MPS I). STUDY DESIGN: This was a randomized, double-blinded, multinational study of 45 patients with MPS I administered 100 U/kg (0.58 mg/kg) laronidase, or placebo intravenously weekly for 26 weeks. The coprimary efficacy end points compared the median change from baseline to week 26 between groups in percentage of predicted normal forced vital capacity (FVC) and in 6-minute walk test (6MWT) distance through the use of the Wilcoxon rank sum test. RESULTS: The laronidase (n=22) and placebo (n=23) groups had similar baseline characteristics. After 26 weeks, patients receiving laronidase compared with placebo showed mean improvements of 5.6 percentage points in percent of predicted normal FVC (median, 3.0; P=.009) and 38.1 meters in 6MWT distance (median, 38.5; P=.066; P=.039, analysis of covariance). Laronidase also significantly reduced hepatomegaly and urinary glycosaminoglycans, and, in more severely affected patients, improved sleep apnea/hypopnea and shoulder flexion. Laronidase was well-tolerated. Nearly all patients receiving enzyme had development of IgG antibodies, without apparent clinical effects. CONCLUSIONS: In patients with MPS I, laronidase significantly improves respiratory function and physical capacity, reduces glycosaminoglycan storage, and has a favorable safety profile.

Adolescent↗
PubMed2004

[Opinions on psychiatric diseases of the citizens of Novosibirsk: results of a representative study].

BACKGROUND: Citizens of Novosibirsk were questioned regarding their ideas about schizophrenia and depressive disorders, with one of the main concerns being a comparison with the ideas and attitudes of the German population. METHOD: In 2002, a representative survey (N = 745) was conducted among the adult population of Novosibirsk, using a fully structured interview that has been used in previous surveys in Germany. RESULTS: Symptoms of schizophrenia were more frequently identified as an indication of mental disorder than were depressive symptoms. Psychosocial stress and biological influences were similarly frequently seen as the cause of schizophrenia, with the former prevailing among the respondents in the case of depressive symptoms. Psychotherapy was most frequently recommended as a treatment measure, also for schizophrenia. Supposing that no treatment measures will be taken, respondents assessed the prognosis for both mental disorders negatively. Conversely, interviewees gave a positive treatment prognosis. DISCUSSION: Respondents from Germany and Novosibirsk showed similar beliefs, especially as regards the importance of biological influences and psychosocial stress and the assessment of psychotherapy as compared to psychopharmacology. However, German and Russian respondents also held differing views: a comparatively strong tendency of the Russian population to consider mental disorders as self-inflicted - an important finding that could shape future anti-stigma programs.

Adult↗
PubMed2004

The relationship between public causal beliefs and social distance toward mentally ill people.

OBJECTIVE: The aim of this study is to investigate the nature of the relationship between public causal beliefs and social distance toward people with mental disorders, particularly schizophrenia and depression. METHOD: In total, three representative surveys were carried out in Germany, Russia and Mongolia using personal, fully structured interviews. RESULTS: Despite the subjects' different cultural backgrounds, their responses show similar trends with regard to attributing depression and schizophrenia to psychosocial causes: 'acute stress' (life event) was most frequently endorsed as the cause for these two disorders. The biological causes ('brain disease' and 'heredity') were less frequently selected for depression than for schizophrenia. Irrespective of place and type of mental disorder, endorsing biological factors as the cause of schizophrenia was associated with a greater desire for social distance, the same relationship applies to depression in half the instances. CONCLUSIONS: It would be premature to draw conclusions with regard to interventions aimed at reducing discrimination based on stigma. However, our study provides stimulus for re-considering the assumptions underlying antistigma interventions: that promulgating biological concepts among the public might not contribute to a desired reduction in social distance toward people with mental disorders.

Adolescent↗
PubMed2004

The stigma of mental illness: patients' anticipations and experiences.

BACKGROUND: There are studies that either deal with the stigmatization patients anticipate or with patients' concrete stigmatization experiences. Up until now, however, research is short of studies that investigate both aspects of subjective stigmatization simultaneously. AIMS: This study aims at investigating to what extent patients with schizophrenia or depression anticipate and experience stigmatization and how this is influenced by the type of mental disorder and the social environment. METHOD: A total of 210 patients with schizophrenia or a depressive episode were interviewed, one half living in a city and the other in a small town. RESULTS: Most of the patients expect negative reactions from the environment, particularly as concerns the access to work. Concrete stigmatization experiences were most frequently reported in the domain of interpersonal interaction. Even though schizophrenia patients and patients with depression anticipated stigmatization similarly frequently, the former reported concrete stigmatization experiences more frequently than the latter. Conversely, patients living in a small town anticipated stigmatization more frequently than patients from the city, even though both had actually experienced stigmatization at a similar rate. CONCLUSION: The results underline the necessity to differentiate between anticipated and experienced stigmatization. This is highly relevant for planning interventions aimed at reducing the stigma of mental disorder.

Adult↗
PubMed2003

The early clinical phenotype of Fabry disease: a study on 35 European children and adolescents.

UNLABELLED: Fabry disease (FD) is a debilitating progressive multisystem X-linked lysosomal storage disorder. It was generally believed that the disease affects only adult males. Through systematic pedigree analysis, we identified 35 paediatric FD patients (age 1 to 21 years, mean 12.6 years) in 25 families. Predominant signs in this cohort were: acroparesthesia, hypohidrosis, and cornea verticillata. Neurological and psychological changes, such as tinnitus, recurrent vertigo, headache, diminished level of activity, fatigue, and depression were often observed. Angiokeratoma and gastrointestinal symptoms were frequent. Some patients also showed cardiac abnormalities. Six children and adolescents (three males and three females) over 14 years of age had renal involvement (all with proteinuria, one male had a decreased creatinine clearance of 62 ml/min). No males, but three females (1.5, 4 and 9 years of age), were free of signs and symptoms. Males (n=15, age 1 to 21 years, mean 12.4 years) and females (n=20, age 1.5 to 20 years, mean 12.7 years) showed comparable disease severity. However, the clinical courses demonstrated a wide intra- and interfamilial variability and tended to be more heterogeneous in the girls. Female patients are frequently affected at an early age, not much differently than males. They should be carefully examined because most carriers are symptomatic. CONCLUSION: Fabry disease usually becomes clinically manifest in childhood. Renal involvement can begin in adolescence. The diagnosis is made following a high level of suspicion or systematic pedigree analysis. It is crucial for paediatric Fabry disease patients to have early access to optimal supportive symptomatic management. Enzyme replacement therapy has shown promising effectiveness in adults. Considering its widespread therapeutic and potential preventive benefits, enzyme replacement therapy should be initiated at an early stage, prior to the onset of irreversible complications.

Adolescent↗
PubMed2003

Social representations of major depression in West and East Germany--do differences still persist 11 years after reunification?

BACKGROUND: In a population survey that was carried out in 1990, differences between the former Federal Republic of Germany and the German Democratic Republic were observed with regard to the social representation of depression. Back then, we predicted that in a few years these differences would have reduced. To test this hypothesis, a second survey was conducted in 2001. METHOD: In 1990, a representative survey was carried out in both parts of Germany. A total of 3,098 personal, fully structured interviews were completed, 2,118 in West Germany and 980 in East Germany. The survey was repeated in 2001 using the same measures. This time, 5,025 interviews were conducted, 4,005 in West Germany and 1,020 in East Germany. RESULTS: While in 1990 there had been numerous differences between the two parts of Germany with regard to the social representation of depression, in 2001 most of these differences had disappeared. Lay concepts of depression held by interviewees from East Germany have assimilated to those held by interviewees from West Germany. In both parts of Germany, a marked change in favor of biological conceptualizations of depression was observable, with heredity and brain disease more frequently being seen as a cause in 2001. CONCLUSION: The hypothesis that the differences between lay concepts of depression that were prevalent in West and East Germany in 1990 would have reduced by 2001 was supported by our results. Our study shows that cultural processes, such as the process of acculturation that took place in Germany between 1990 and 2001, have an effect on the social representation of mental disorders.

Acculturation↗
PubMed2003

[Stigma as perceived by schizophrenics and depressives].

QUESTION: The goal of this study is to investigate the stigma of mental illness from the perspective of the persons directly affected by it. METHOD: 210 patients with schizophrenia or major depression were questioned about anticipated and concrete stigmatization experiences, using a questionnaire especially developed for this study. RESULTS: Most of the patients expected negative reactions from the environment. Three quarters were convinced that their job application would be rejected when it became known that they are mentally ill. Almost two thirds felt apprehensive that others would avoid them due to their illness. There is hardly any difference between schizophrenia and depressive patients' assessment of stigmatization of mentally ill people. Concrete stigmatization experiences were most frequently reported in the domain of interpersonal interaction. Second comes the distorted picture of mentally ill people that is depicted in the media and experienced as hurtful by the patients. The obstacles to access social roles (partnership, work, etc.) perceived by the patients come third. Participants least frequently mentioned structural discrimination, i. e. disadvantages regarding psychiatric treatment or rehabilitation measures. Contrary to anticipated stigmatization, there are differences between the two diagnostic groups when it comes to concrete stigmatization experiences. Schizophrenia patients more frequently report that others would avoid contact with them and that the access to social roles was especially complicated for them. They also seemed to be more exposed to structural discrimination than depressive patients. CONCLUSION: Based on the results of this study, ways are discussed of how stigmatization and discrimination of mentally ill people can be reduced.

Adaptation, Psychological↗
PubMed2003

Determinants of the public's preference for social distance from people with schizophrenia.

OBJECTIVE: To examine the extent to which the public's desire for social distance from people with schizophrenia is influenced by beliefs about the disorder and stereotypes about those suffering from it. METHODS: In spring 2001, we carried out a representative survey of individuals of German nationality aged 18 years and over (n = 5025). Each subject was given a fully structured interview that began with the presentation of a vignette. RESULTS: Both labelling and beliefs about the disorder's causes and prognosis, as well as the perception that those suffering from it are unpredictable and dangerous, had an impact on the public's desire for social distance. However, the latter proved to be more important. As expected, respondents who identified the disorder depicted in the vignette as mental illness, those who blamed the individual for its development, and those who anticipated a poor prognosis expressed a stronger desire for social distance. Endorsing biological factors as a cause was also associated with increased social distance. CONCLUSIONS: Our findings have important implications for interventions aimed at reducing stigma and discrimination related to schizophrenia. Targeting the stereotype of unpredictability and dangerousness appears to be particularly important.

Adolescent↗
PubMed2002

Cardiac manifestations of Anderson-Fabry disease in heterozygous females.

OBJECTIVES: We sought to define the prevalence of cardiac involvement in female patients with Anderson-Fabry disease (AFD). BACKGROUND: Anderson-Fabry disease is a rare inborn X-linked lysosomal storage disorder. Globotriaosylceramide (Gb(3)), the major substrate of the deficient alpha-galactosidase A enzyme, accumulates progressively in vulnerable cells, including the cardiovascular system. It has been believed that heterozygous females have less cardiac involvement than hemizygous males with AFD. METHODS: We performed two-dimensional echocardiographic examinations of female patients heterozygous for AFD. RESULTS: Since 1997, a total of 55 female patients (mean age, 39.6 years; range, 6.1 to 70.8 years) with proven AFD have been investigated prospectively at our hospital. Of these, 13 (23.6%) had normal left ventricular (LV) geometry and LV mass (LVM). Seven patients (12.7%) had concentric remodeling, 29 patients (52.7%) concentric LV hypertrophy (LVH), and 6 patients (10.9%) eccentric LVH (2 with subaortic pressure gradients). There was a strong correlation between age and the severity of LVH (r(2) = 0.905; p < 0.0001), and all patients older than 45 years had LVH. With increasing LVM, there was a significant age-independent decrease in systolic and diastolic LV function. Mild thickening of the aortic valve leaflets was present in 25.5% of patients, with the same percentage demonstrating mild thickening of the mitral valve leaflets. Mild mitral valve prolapse was documented in 10.9% of patients. CONCLUSIONS: Cardiac involvement, with LVH and structural valve abnormalities, is very common and worsens with age in females who are heterozygous for AFD, and they should therefore be considered candidates for enzyme replacement therapy.

Adolescent↗
PubMed2002

Fabry disease: focus on cardiac manifestations and molecular mechanisms.

PATHOGENESIS: Fabry disease is an inherited lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A. The enzyme deficiency results in accumulation of glycosphingolipids in the lysosomes n nearly all cell types and tissues leading to a multisystem disease. MANIFESTATIONS include painful crisis, angiokeratomas, corneal dystrophy, and hypohydrosis. The severe renal, cerebrovascular, and cardiac involvement is predominantly responsible for premature mortality in Fabry patients. The disease is X-linked and manifests primarily in hemizygous males but also heterozygous females can be affected. CARDIAC INVOLVEMENT is frequent in Fabry disease. Patients develop hypertrophic cardiomyopathy, arrhythmias, conduction abnormalities, and valvular abnormalities. Although Fabry disease leads to a complex clinical syndrome, there are studies indicating that manifestations can be limited to the heart. The isolated cardiac variant of Fabry disease seems to be more common than previously thought: around 3-6% of male patients with left ventricular hypertrophy seem to suffer from this disease variant. ENZYME REPLACEMENT THERAPY: Recent advances in molecular biology and genetic engineering have enabled the development of enzyme replacement therapy in Fabry disease. Results from two independent therapy studies are indeed promising: Infusion of the enzyme preparation seems to be well tolerated and effective in catabolizing the lipid deposits. This enzyme replacement therapy could be one of the first examples for causal treatment of left ventricular hypertrophy. Therefore, early diagnosis of hypertrophy patients with the cardiac variant of Fabry disease is important.

Adolescent↗