PubMed Health⌕ Search

Biomedical subjects

S Kiechl

Publications and source records attributed to S Kiechl.

At least 19 recordsLinked to original sources
PubMed2002

Screening for carnitine palmitoyltransferase II deficiency by tandem mass spectrometry.

Mitochondrial carnitine palmitoyltransferase II (CPT II) deficiency is the most common inherited disorder of lipid metabolism in adults. Currently the routine diagnosis is based on the determination of CPT enzyme activity in muscle tissue. We have analysed the tandem mass spectra of serum acylcarnitines of nine CPT II-deficient patients. These spectra were compared to those of a cohort of 99 patients with other neuromuscular disorders and metabolic conditions supposed to cause alterations of the long-chain acylcarnitines. The spectra in CPT II deficiency showed characteristic elevations of C16:0 and C18:1 acylcarnitines while acetylcarnitine C2 was not elevated. In the present study, the ratio (C16:0+C18:1)/C2 has detected all CPT II deficiencies and discriminated them from unspecific alterations of serum acylcarnitines. The ratios of CPT II-deficient patients showed virtually no overlap with those observed in patients with other neuromuscular disorders. We suggest mass spectrometry of serum acylcarnitines as a rapid screening test that should be included early in the diagnostic work-up of patients with recurrent myoglobinuria, recurrent muscular weakness and myalgia.

Adolescent↗
PubMed2001

Chronic infections and the risk of carotid atherosclerosis: prospective results from a large population study.

BACKGROUND: Chronic infections have been implicated in the pathogenesis of atherosclerosis, yet from an epidemiological perspective, this concept remains controversial. METHODS AND RESULTS: The Bruneck Study is a prospective population-based survey on the pathogenesis of atherosclerosis. In 826 men and women 40 to 79 years old (1990 baseline), 5-year changes in carotid atherosclerosis were thoroughly assessed by high-resolution duplex scanning. The presence of chronic respiratory, urinary tract, dental, and other infections was ascertained by standard diagnostic criteria. Chronic infections amplified the risk of atherosclerosis development in the carotid arteries. The association was most pronounced in subjects free of carotid atherosclerosis at baseline (age-/sex-adjusted odds ratio [95% CI] for any chronic infection versus none, 4.08 [2.42 to 6.85]; P:<0.0001) and applied to all types of chronic (bacterial) infections. It remained independently significant after adjustment for classic vascular risk attributes and extended to low-risk individuals free of conventional risk factors. Among subjects with chronic infections, atherosclerosis risk was highest in those with a prominent inflammatory response. Markers of systemic inflammation, such as soluble adhesion molecules and circulating bacterial endotoxin, and levels of soluble human heat-shock protein 60 and antibodies to mycobacterial heat-shock protein 65 were elevated in subjects with chronic infections and predictive of an increased risk of atherosclerosis. CONCLUSIONS: The present study provides solid evidence for a role of common chronic infections in human atherogenesis. Induction of systemic inflammation and autoimmunity may be potential pathophysiological links.

Adult↗
PubMed2001

Epidemiology of sudden infant death syndrome (SIDS) in the Tyrol before and after an intervention campaign.

OBJECTIVE: We investigated the epidemiology of sudden infant death syndrome (SIDS) in the Tyrol before and after an intervention campaign. PATIENTS AND METHODS: Descriptive characteristics and risk factors of SIDS before the campaign were assessed in a retrospective case-control study (1984 to 1994). In April 1994 a country-wide information campaign on modifiable risk behaviours was initiated. Thereafter we prospectively collected data on child care practices four to six weeks after birth for all infants born in the Tyrol (participation rate 72%; n = 28,361) and evaluated new SIDS cases (1994 to 1998). For this purpose two questionnaires were used, one with 96 items for the evaluation of all SIDS cases and assessment of child care practices before 1994, and the other with 24 items for prospective data collection. RESULTS: The incidence of SIDS decreased from 1.83 (mean incidence, 1984-1994) to 0.4/1000 live births immediately after the campaign and remained low until 1998. The frequency of maternal smoking during pregnancy declined (22.9% vs. 14.5%, p < 0.01), as did the prevalence of the prone sleeping position (53.7% vs. 5.4%, p < 0.001) and of non-breastfeeding (21.3% vs. 6.7%, p < 0.001). All these variables were prominent risk factors for SIDS before the campaign and remained significant thereafter. On account of the markedly reduced prevalence of the prone sleeping position, smoking became the most common SIDS risk factor. The prevalence of sleeping on the side significantly increased (5.1% vs. 36.4%, p < 0.001) and the social status of mothers of SIDS infants tended to be lower than that before the campaign. The clear winter preponderance of SIDS which was evident before the campaign disappeared, or was even reversed. CONCLUSIONS: Our study documents the long-term efficacy of a low-cost intervention campaign by way of health education. Further efforts must be directed toward lower social classes, thereby focusing on maternal smoking and avoidance of the side sleeping position.

Adult↗
PubMed2001

Juvenile asymmetric segmental spinal muscular atrophy (Hirayama's disease): three cases without evidence of "flexion myelopathy".

Compression of the cervical spinal cord during neck movements ("flexion myelopathy") was proposed to be the main pathomechanism of juvenile asymmetric spinal muscular atrophy (JASSMA). We present 3 patients with the clinical appearance of JASSMA and typical high-intensity signals in the anterior horn cell region of the lower cervical spinal cord (T2-weighted magnetic resonance images) but without evidence of dynamic spinal cord compression. In all these patients pathomechanism distinct from mechanical damage must be assumed.

Adolescent↗
PubMed2001

The role of immune activation in endotoxin-induced atherogenesis.

Some infectious agents may contribute to atherosclerosis by maintaining a heightened state of inflammatory response. Although the risk for atherosclerosis was associated with elevated plasma levels of endotoxin, it is difficult to firmly establish what place endotoxin assumes in the etiology of this disease. As the ability for endotoxin to promote disease may depend on its ability to initiate an inflammatory response, it may be controlled by additional regulatory factors. We measured plasma levels of endotoxin and serum levels of neopterin and soluble interleukin-2 receptor in a random population of 402 men and women, 50-79 years old at the 1990 baseline evaluation (Bruneck Study). End point of the prospective survey was incident (early) atherosclerosis in the carotid arteries as assessed with duplex ultrasound. Subjects with high endotoxin levels (90th percentile) in combination with low neopterin or soluble interleukin-2 receptor levels (below median) did not differ from those with low endotoxin in their risk of incident atherosclerosis. The risk associated with high endotoxin, however, was markedly elevated in subjects with high (above median) neopterin or soluble interleukin-2 receptor levels. The study provides epidemiological evidence that the atherogenic potential of endotoxemia is affected by concomitant immune activation.

Aged↗
PubMed2000

Infections, immunity, and atherosclerosis: associations of antibodies to Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus with immune reactions to heat-shock protein 60 and carotid or femoral atherosclerosis.

BACKGROUND: Atherogenesis involves inflammatory processes in which infections are incriminated as possible contributors. METHODS AND RESULTS: We evaluated cardiovascular risk factors as well as seropositivity to Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus in a population-based study. A significant association between prevalence and severity of atherosclerosis in carotid and femoral arteries and IgA antibodies to C pneumoniae was demonstrated that was not substantially altered after adjustment for established risk factors. For anti-H pylori IgG antibodies, significant correlations to vascular disease were restricted to low social status and lesions in carotid arteries. In addition, the study design allowed us to monitor lesion progression over time. In this prospective analysis, C pneumoniae seropositivity emerged as a significant risk predictor. Antibody titers against cytomegalovirus were not a marker for prevalence or incidence of atherosclerosis in this population. Further infection parameters added to the predictive value of chlamydial serology in risk assessment: Mean odds ratios for the prevalence of carotid atherosclerosis were 4.2 and 6.3 for seropositive subjects with elevated C-reactive protein levels and clinical evidence for chronic respiratory infection, respectively. For subjects with all 3 infection parameters, the odds ratio of carotid atherosclerosis reached 10.3 (P<0.0001). Concomitantly, serum antibodies to mycobacterial heat-shock protein 65 (mHSP65) correlated with seropositivity to C pneumoniae and H pylori but not to cytomegalovirus. CONCLUSIONS: This prospective population-based study provides strong evidence for a potential atherogenic role of persistent bacterial infection, especially C pneumoniae, as indicated by serological and clinical data and demonstrates a correlation between immune reactions to mHSP65 and bacterial infections in atherogenesis.

Aged↗
PubMed2000

Serum soluble heat shock protein 60 is elevated in subjects with atherosclerosis in a general population.

BACKGROUND: Work from our laboratory has proven that increased titers of anti-heat shock protein 60 (HSP60) antibodies are associated with atherosclerosis and that HSP60-reactive T-cells are present in atherosclerotic lesions. Recent studies from others demonstrated that HSP60 directly activates endothelial cells and macrophages. METHODS AND RESULTS: To explore the possibility that HSP60 exists in the circulation, where it could exert its functions, we performed a population-based study with 826 subjects aged 40 to 79 years. The following items were measured in all participants: serum soluble HSP60 (sHSP60); anti-Escherichia coli lipopolysaccharide; anti-HSP65, anti-Chlamydia and anti-Helicobacter pylori antibodies; and a variety of acute phase reactants (C-reactive protein, alpha(1)-antitrypsin, and ceruloplasmin) and markers of systemic inflammation. Carotid atherosclerosis was assessed twice (1990 and 1995), and 15 other risk factors were evaluated. Our data show that levels of sHSP60 were significantly elevated in subjects with prevalent/incident carotid atherosclerosis and that these levels were correlated with common carotid artery intima/media thickness. Multiple logistic regression analysis documented these associations as independent of age, sex, and other risk factors. Interestingly, sHSP60 was also correlated with anti-lipopolysaccharide, anti-Chlamydia and anti-HSP60 antibodies, various markers of inflammation, and the presence of chronic infections. The risk of atherosclerosis associated with high sHSP60 levels was amplified when subjects had clinical and/or laboratory evidence of chronic infections. CONCLUSIONS: Our data provide the first evidence of a strong correlation between sHSP60 and atherosclerosis, suggesting that sHSP60 may play important roles in activating vascular cells and the immune system during the development of atherosclerosis.

Adult↗
PubMed2000

Vascular endothelial growth factor in CSF: a biological marker for carcinomatous meningitis.

OBJECTIVE: To determine the value of vascular endothelial growth factor (VEGF) in CSF as a marker for carcinomatous meningitis (CM). METHODS: The concentration of VEGF was measured by ELISA in matched samples of CSF and serum collected from 162 patients. These included patients with solid tumors with CM (n = 11) or brain metastases without concomitant CM (n = 12), paraneoplastic neurologic syndromes (n = 4), viral (n = 15) and bacterial (n = 20) meningitis, and a variety of non-neoplastic and noninfectious neurologic diseases (n = 100). Using CSF/serum albumin ratios, the VEGF index was calculated to estimate the proportion of intrathecally produced VEGF. Immunohistochemical staining for VEGF was performed in a brain metastasis from a mammary carcinoma associated with CM. RESULTS: High VEGF levels (median 6,794.8 pg/mL) were found in CSF of all patients with CM, whereas VEGF levels in matched sera were comparable to other disease groups. In patients with CM, the concentration of VEGF in CSF decreased significantly following antineoplastic treatment. In CSF samples from patients with brain metastases without concomitant CM, VEGF was not detectable. Median VEGF concentration in CSF from patients with acute bacterial meningitis was 38.6 pg/mL, with only 9 of these 17 patients showing detectable VEGF levels in CSF. The VEGF indices in patients with bacterial meningitis were significantly lower than in tumor patients with CM (<22.8 versus >62.3), suggesting that the proportion of intrathecally produced VEGF is much higher in patients with CM as compared with patients with bacterial meningitis. Patients without neoplastic or infectious neurologic disorders consistently showed VEGF levels in CSF below the assay detection limit of 25 pg/mL. Immunohistochemistry revealed strong cytoplasmic staining for VEGF in a metastatic lesion from breast cancer infiltrating the meninges. CONCLUSION: In patients with carcinomatous meningitis, significant amounts of VEGF are released into CSF. This study yields preliminary evidence that VEGF in CSF may be a useful biologic marker for both the diagnosis and evaluation of treatment response in carcinomatous meningitis.

Adolescent↗
PubMed2000

[SIDS prevention program in Tyrol].

In April 1994, an intervention campaign to reduce the incidence of sudden infant death syndrome (SIDS) was established in the Tyrol. The campaign was intended to increase knowledge concerning risk factors for SIDS in the general community and to improve individual care for infants at risk. In contrast to interventional programmes in other federal states of Austria (i.e. Vorarlberg, Styria), this programme did not utilise polysomnography for identifying infants at risk. A part of the intervention programme was the "Styrian risk questionnaire", a standardised questionnaire concerning risk factors for SIDS. Individual instructions for health care of children at risk (risk score > or = 7) were provided and, if necessary, subscription of home monitoring was performed at the out-patient department (SIDS out-patient service) of the Department of Paediatrics in Innsbruck and other paediatric departments throughout the Tyrol. The educational programme also included information concerning basic life support. Psychological support was offered to parents of SIDS infants. Risk factors for SIDS in the Tyrol before the campaign were assessed in a retrospective case-control study (time period 1984-1994; 99 SIDS infants, 136 controls). The risk of SIDS was markedly reduced when parents had detailed knowledge of the risk factors of SIDS (odds ratio (OR) 0.03; p < 0.001), which emphasises the importance of information and educational programmes. The incidence of SIDS declined after the beginning of the intervention campaign from 1.83/1000 live births (average incidence from 1984-1994) to 0.4/1000 live births and remained at this level thereafter. Post-neonatal mortality also declined from 3.9 to 1.3/1000 live births. The prevalence of the prone sleeping position declined immediately after the campaign (53.7% vs. 5.4%, p < 0.001), as did the frequency of maternal smoking during pregnancy (22.9% vs. 14.5%, p < 0.01). Breast feeding became more popular. In all, the low-cost intervention programme in the Tyrol proved to be highly efficient in reducing the risk of SIDS and in maintaining this effect for several years.

Adult↗
PubMed2000

Impaired glucose tolerance, Type II diabetes mellitus and carotid atherosclerosis: prospective results from the Bruneck Study.

AIMS/HYPOTHESIS: Cardiovascular disease is a well-known severe complication of impaired glucose tolerance and Type II (non-insulin-dependent) diabetes mellitus. The independent contribution of glucose intolerance to cardiovascular disease and the underlying pathogenic mechanisms are still, however, not clear. METHODS: In this prospective population-based study, 826 subjects aged 40-79 years underwent high resolution duplex ultrasound examinations of carotid arteries and extensive clinical and laboratory screenings for potential vascular risk factors at baseline and 5 years later. The ultrasound protocol involved measurements of maximum axial diameter of atherosclerotic plaques, if any, in common and internal carotid arteries on both sides and enable differentiation of two main stages in carotid artery disease, termed early non-stenotic and advanced stenotic atherosclerosis. Intima-media thickness was assessed at the follow-up examination. RESULTS: Type II diabetes and, to a lesser extent, impaired glucose tolerance were found to be statistically significant risk predictors of 5-year changes in carotid atherosclerosis. These associations were in part independent of other vascular risk factors typically clustering with glucose intolerance. Both impaired glucose tolerance and Type II diabetes mellitus were not independently related to early non-stenotic atherosclerosis. In contrast, Type II diabetes mellitus was the strongest single risk predictor of advanced stenotic atherosclerosis [odds ratio 5.0 (95% confidence intervals 2.3-11.1)] and impaired glucose tolerance was of relevance as well [odds ratio 2.8 (1.2-6.4)] (p < 0.001). CONCLUSION/INTERPRETATION: Impaired glucose tolerance and, to a greater extent, Type II diabetes were strong independent predictors of advanced carotid atherosclerosis in our prospective population-based study.

Adult↗
PubMed2000

High plasma levels of alpha- and beta-carotene are associated with a lower risk of atherosclerosis: results from the Bruneck study.

BACKGROUND AND PURPOSE: A large number of studies have contributed to the hypothesis that carotenoids, vitamins A and E are protective against atherosclerosis by acting as antioxidants. The aim of this study was to assess the relationship between plasma levels of carotenoids (alpha- and beta- carotene, lutein, lycopene, zeaxanthin, beta-cryptoxanthin), vitamins A and E, and atherosclerosis in the carotid and femoral arteries. METHODS: This prospective and cross sectional study involved a randomly selected population sample of 392 men and women aged 45-65 years. Carotid and femoral artery atherosclerosis was assessed by high-resolution duplex ultrasound. RESULTS: alpha- and beta- carotene plasma levels were inversely associated with the prevalence of atherosclerosis in the carotid and femoral arteries (P=0.004) and with the 5-year incidence of atherosclerotic lesions in the carotid arteries (P=0.04). These findings were obtained after adjustment for other cardiovascular risk factors (sex, age, LDL (low density lipoproteins), ferritin, systolic blood pressure, smoking, categories of alcohol consumption, social status, C-reactive protein). Atherosclerosis risk gradually decreased with increasing plasma alpha- and beta-carotene concentrations (P=0.004). No associations were found between vitamin A and E plasma levels and atherosclerosis. CONCLUSIONS: This study provides further epidemiological evidence of a protective role of high alpha- and beta- carotene in early atherogenesis.

Adult↗
PubMed2000

Biology of arterial atheroma.

Endothelial dysfunction and changes in arterial wall morphology including thickening of the tunica intima, excess synthesis of collagenous matrix (fibroblastic intimal thickening) and permanent or dynamic deposition of lipids (fatty streaks) already occur in childhood or adolescence. Definite atherosclerotic plaques in the carotid arteries usually do not manifest themselves before menopause in women or age 40 in men. Obviously, cumulative (long-term) and excessive exposure of the vessel wall to risk factors is required to overcome highly effective defense mechanisms which have not yet been fully investigated. Initiation and early progression of atherosclerosis rely on conventional vascular risk factors such as hyperlipidemia, hypertension, smoking, severe alcohol consumption and chronic infections. Plaque extension is effectively compensated by a focal widening of the vessel, thereby preventing the development of lumen obstruction (vascular remodeling). For stenosis to emerge conventional plaques must convert to complicated plaques characterized by plaque rupture and consecutive atherothrombosis. This process usually starts with small- to medium-sized plaques. Potential determinants of plaque rupture are the composition of the lesion (large lipid-rich core), damage of the fibrous cap (destabilization by chronic inflammation) and hemodynamic stress. According to pathological observations, fissuring of atherosclerotic lesions is a frequent event, while the formation of overlying large thrombi (with progression of stenosis or vessel occlusion) is definitely rare. This conjecture emphasizes the significance of local and systemic thrombus-promoting factors. Actually, the risk profile of advanced atherogenesis in the Bruneck Study was primarily composed of markers of enhanced prothrombotic capacity, attenuated fibrinolysis and clinical conditions known to interfere with coagulation. Almost all subjects with > or =3 procoagulant risk conditions developed carotid stenosis or showed progression of preexisting stenosis during a 5-year period. Increasing insights into the complex biology of arterial atheroma and awareness of the etiologic peculiarities of advanced complicated plaques may serve as a basis for identifying high-risk subjects and for novel vascular prevention strategies with focus on plaque stabilization and antithrombotic/anticoagulant measures.

Arteries↗
PubMed2000

Distinct risk profiles of early and advanced atherosclerosis: prospective results from the Bruneck Study.

Most epidemiological surveys on risk factors of atherosclerosis were cross-sectional in design and did not consider the existence of pathologically distinct processes. The Bruneck Study is a prospective survey in the general community (age range, 40 to 79 years). The baseline examination and first reevaluation were performed in the summers of 1990 and 1995 (participation, 92%; follow-up, 96%). Carotid atherosclerosis was monitored with high-resolution duplex ultrasound. Early (incidence and/or extension of nonstenotic lesions) and advanced (incidence and/or progression of stenosis >40%) stages of atherogenesis were differentiated. The risk profile of early atherogenesis consists of traditional risk factors, such as hypertension, hyperlipidemia, and cigarette smoking (pack-years), supplemented by a variety of less well-established risk conditions, including high body iron stores, hypothyroidism, microalbuminuria, and high alcohol consumption. In contrast, the risk profile of advanced atherogenesis includes markers of enhanced prothrombotic capacity, attenuated fibrinolysis, and clinical conditions known to interfere with coagulation: high fibrinogen, low antithrombin, factor V Leiden mutation, lipoprotein(a) >0.32 g/L, high platelet count, cigarette smoking, and diabetes. Hyperlipidemia and hypertension were of only minor relevance. These findings, along with the epidemiological features of advanced atherogenesis and emergence of an elevated fibrin turnover, suggest atherothrombosis to be a key mechanism in the development of advanced stenotic atherosclerosis. Supplementary 6-category logistic regression models illustrate the changing association between major risk predictors and atherosclerosis of increasing severity and substantiate appropriateness of the 40% threshold applied for the definition of advanced stenotic atherosclerosis. Atherosclerosis is a heterogeneous process that subsumes etiologically and epidemiologically distinct disease entities. The multifactorial etiology of atherosclerosis, which goes far beyond the traditional risk factors, has not yet achieved adequate attention in clinical practice and disease prevention.

Adult↗