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Biomedical subjects

J Willeit

Publications and source records attributed to J Willeit.

At least 73 records · Page 4Linked to original sources
PubMed1995

Lipoprotein(a) and asymptomatic carotid artery disease. Evidence of a prominent role in the evolution of advanced carotid plaques: the Bruneck Study.

BACKGROUND AND PURPOSE: Elevated levels of lipoprotein(a) [Lp(a)] have been reported in association with symptomatic coronary and carotid artery disease. Relevancy of Lp(a) as a risk predictor of presymptomatic atherosclerosis in general populations is not well established. METHODS: Serum Lp(a) distribution and its relation to sonographically assessed carotid atherosclerosis were examined in a random sample of 885 men and women aged 40 to 79 years (Bruneck Study). RESULTS: Logistic regression analysis revealed a binary-type association between Lp(a) and carotid artery disease, with the threshold level of Lp(a) for an enhanced atherosclerosis risk defined at 32 mg/dL. The strength of relation increased with advancing severity of carotid atherosclerosis (odds ratios for Lp(a), 1.8 for nonstenotic and 4.7 for stenotic carotid artery disease; P < .001). Lp(a) was unaffected by environmental factors except for a significant decrease in women taking hormone replacement therapy (P < .05). In a multivariate approach, Lp(a) turned out to be an independently significant predictor of carotid atherosclerosis (P < .001). No differential effect of Lp(a) on atherosclerosis (effect modification) was observed for sex, age, low-density lipoprotein cholesterol, apolipoprotein A-I and B, fasting glucose, diabetes, or hypertension. However, the Lp(a)-atherosclerosis relation was significantly modified by fibrinogen (P < .01) and antithrombin III (P < .05). CONCLUSIONS: The present study demonstrates a strong and independent association between elevated Lp(a) levels and carotid atherosclerosis in a large randomized population and provides evidence of a potential role of Lp(a) in the evolution of carotid stenosis. Apart from atherogenicity of Lp(a) cholesterol, interference with fibrinolysis of atheroma-associated clots and fibrin deposits in the arterial wall may achieve pathophysiological significance.

Adult↗
PubMed1995

Autoantibodies against heat shock protein 60 mediate endothelial cytotoxicity.

Stress or heat shock proteins (hsp) are a family of approximately two dozen proteins with a high degree of amino acid sequence homology between different species, ranging from prokaryotes to humans, and are representative of a generalized response to environmental and metabolic stressors. Our previous studies showed increased expression of human hsp60 on endothelial cells of arterial intima with atherosclerotic lesions, and elevated levels of serum antibodies (Ab) against hsp65/60 in subjects with carotid atherosclerosis. To investigate the possible involvement of anti-hsp65/60 Ab in endothelial injury, specific hsp-Ab were isolated from human high titer sera by affinity chromatography and probed on heat-shock human umbilical vein endothelial cells. Purified human anti-hsp65/60 Ab reacted specifically with mycobacterial hsp65, human hsp60, and a 60-kD protein band of heat-shocked endothelial cells. High levels of hsp60 mRNA expression in endothelial cells were found between 4 and 12 h after 30 min treatment at 42 degrees C. In immunofluorescence tests, positive staining of heat-stressed endothelial cells was observed not only in the cytoplasm but also on the cell surface. Furthermore, only heat-stressed, but not untreated, Cr-labeled endothelial cells were lysed by anti-hsp65/60 Ab in the presence of complement (complement-mediated cytotoxicity) or peripheral blood mononuclear cells (antibody-dependent cellular cytotoxicity). Control Abs, including human anti-hsp65/60 low titer antiserum, human Ig fraction deprived of hsp65/60 Ab, and mAbs to Factor VIII, alpha-actin, hsp70, and CD3 showed no cytotoxic effect. In conclusion, human serum anti-hsp65 antibodies act as autoantibodies reacting with hsp60 on stressed endothelial cells and are able to mediate endothelial cytotoxicity. Thus, a humoral immune reaction to hsp60 may play an important role in the pathogenesis of atherosclerosis.

Aged↗
PubMed1994

Increased concentrations of neopterin in carotid atherosclerosis.

Activation of T-cells and macrophages may play a role in the pathogenesis of atherosclerosis. Therefore, serum concentrations of the immune activation markers neopterin and soluble interleukin-2 receptor were compared with routine laboratory parameters, candidate risk variables and degree of carotid atherosclerosis. Study subjects were 561 individuals (293 men and 268 women) aged between 50 and 79 years who were enrolled in a cross-sectional community based study (Ischemic Heart Disease and Stroke Prevention Study, Bruneck, Italy). Extent of carotid atherosclerosis was quantitated by an ultrasound B-mode procedure based scoring system. Detailed physical examination and quantification of laboratory and candidate risk variables were performed. By univariate as well as multivariate statistical analyses, serum concentrations of neopterin but not soluble interleukin-2 receptor were significantly higher in subjects with carotid atherosclerosis (men, 8.5 +/- 2.7 nmol/l neopterin; women, 9.6 +/- 3.3) than in those without (men, 6.7 +/- 2.3, P < 0.0001; women, 7.5 +/- 2.3, P < 0.0001). The data show that the macrophage-derived immune activation marker neopterin is closely correlated with the extent of carotid atherosclerosis. Chronic activation of immune cells, preferentially of macrophages, may play a key role in atherogenesis and/or progression of atherosclerosis.

Aged↗
PubMed1994

Quantitative assessment of carotid atherosclerosis in a healthy population.

To evaluate the prevalence and extent of carotid atherosclerosis in a general healthy population, duplex ultrasound imaging was performed in 909 men and women aged 40-79 years as part of the prospective Bruneck Ischemic Heart Disease and Stroke Prevention Study. Atherosclerotic lesions were found in 47.8% of men and 36.3% of women. Sex differences in the prevalence rates were most pronounced from age 40 to 60 years with a convergence occurring in the 7th decade. The age range of 60-69 years was found to be the crucial period for the development of advanced carotid artery disease. The frequency of internal carotid artery stenosis (> 50%) in elderly men and women (60-79 years) was 10.5 and 5.5%. In nonstenotic carotid artery disease the lumen diameter turned out to be a useful indirect measure of the vascular status.

Adult↗
PubMed1994

Body iron stores and presence of carotid atherosclerosis. Results from the Bruneck Study.

We hypothesized that the formation of foam cells and fatty streaks requires a postsecretory oxidative modification of lipoproteins that targets them for rapid uptake by macrophages. Lipid peroxidation may in part depend on the concentration of tissue iron, one of the major oxidants in vivo. We analyzed the relation between sonographically assessed carotid atherosclerosis and body iron stores in a population sample of 847 men and women aged 40 to 79 years. In a logistic regression analysis adjusting for age, sex, and all major vascular risk markers, ferritin emerged as one of the strongest indicators of carotid artery disease in both sexes (40 to 59 years; odds ratio, 1.54 per 100 micrograms/L; P < .001). The predictive significance of ferritin was found to be synergistic with that of hypercholesterolemia. Variations in body iron stores between sexes may partly explain evident sex differences in the expression of carotid atherosclerosis. In the elderly (> or = 60 years) the predictive significance of ferritin was found to decrease parallel to that of apolipoprotein B. The current study suggests a possible role of body iron in early atherogenesis.

Adult↗
PubMed1994

Alcohol consumption and carotid atherosclerosis: evidence of dose-dependent atherogenic and antiatherogenic effects. Results from the Bruneck Study.

BACKGROUND AND PURPOSE: Although a variety of epidemiological studies have suggested a U-shaped association between alcohol and cardiovascular disease, controversy still surrounds the role of atherogenesis in the mediation of alcohol effects. METHODS: Carotid atherosclerosis was measured with a sensitive and reproducible B-mode score in a random sample of 460 men drawn from the Bruneck Study (baseline examination in 1990). RESULTS: The age-adjusted relation between alcohol and carotid artery disease was U shaped, with light drinkers facing a lower atherosclerosis risk (odds ratio, 0.44; 95% confidence interval, 0.23 to 0.85; P = .01) than either abstainers (odds ratio, 1.00) or heavy drinkers (odds ratio, 2.78; 95% confidence interval, 1.32 to 5.84; P < .01). The association was not explained by the lifestyle of alcohol consumers (smoking) or inclusion of former (heavy) drinkers in the reference group. The effect of alcohol was modified by drinking behavior (type of beverage). Approximately a quarter of the atherosclerosis risk caused by severe alcohol consumption was mediated by the risk profile associated with drinking, whereas the apparent beneficial effect of low alcohol intake emerged independent of conventional risk attributes. CONCLUSIONS: Our results support the hypothesis that adverse and beneficial effects of alcohol on cerebrovascular disease are mediated in part by analogous atherogenic and antiatherogenic properties.

Adult↗
PubMed1994

[Myoglobinuria and carnitine palmitoyltransferase deficiency. Diagnostic procedure and differential diagnosis].

Carnitine palmitoyltransferase (CPT) deficiency is the most common metabolic cause of recurrent myoglobinuria. We describe five patients with CPT deficiency who were recruited during a 24-months period. Phenotypic expression ranged from mild myalgia without myoglobinuria to severe exercise-induced attacks and a lethal course. The pathophysiological basis of the clinical heterogeneity is discussed. The diagnostic procedure includes a neurological and electromyographical examination as well as an exercise test and extensive biochemical investigations of muscle biopsy specimens. Accurate diagnosis allows an early introduction of preventive measures and clearly improves the outcome.

Adult↗
PubMed1993

Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis.

Arteriosclerotic lesions can be induced in normocholesterolaemic rabbits by immunisation with heat-shock protein (hsp) 65, a stress protein expressed in high concentrations in human atherosclerotic lesions. If an immune reaction to hsp65 also plays a part in human atherogenesis, it should be possible to detect anti-hsp65 antibodies in patients with atherosclerotic lesions. To study the possible relation between immune reaction to hsp65 and atherosclerosis, 867 normal inhabitants of South Tyrol, aged 40-79 years, were selected randomly for determination of serum antibodies against hsp65, simultaneous sonographic assessment of carotid atherosclerotic lesions, and evaluation of established risk factors--ie, blood cholesterol, hypertension, smoking, diabetes mellitus, and obesity. Autoantibodies to nuclear antigens, thyroid antigens, and rheumatoid factors were also measured. Serum anti-hsp65 antibodies were significantly (p < 0.05) increased in subjects aged 60-79 years with carotid atherosclerosis compared with those without lesions, and increased antibody concentration was independent of age, sex, and other established risk factors. On the other hand, the incidence and titres of autoantibodies did not correlate with carotid atherosclerotic lesions. Our data provide the first evidence of a strong correlation between anti-hsp65 antibodies and carotid atherosclerosis, suggesting that hsp65 might be involved in the pathogenesis of atherosclerosis.

Adult↗
PubMed1993

Subarachnoid hemorrhage as presenting feature of isolated neurosarcoidosis.

A 35-year-old man presented with the clinical picture of spontaneous subarachnoid hemorrhage. Four weeks after the first symptoms he noticed blurred vision, and ophthalmological examination detected bitemporal hemianopia. At this time cerebral computed tomography and magnetic resonance imaging showed enlargement of the optic chiasm, and visual evoked potentials revealed delayed latencies. In the cerebrospinal fluid cells and protein content were elevated, and angiotensin-converting enzyme was detectable. Under steroid treatment the patient recovered completely and computed tomography, magnetic resonance imaging, visual evoked potentials, and cerebrospinal fluid findings became normal. Although a great variety of neurological symptoms may occur in neurosarcoidosis, to our knowledge spontaneous subarachnoid hemorrhage as the presenting feature has never been reported before.

Adult↗
PubMed1993

Prevalence and risk factors of asymptomatic extracranial carotid artery atherosclerosis. A population-based study.

To evaluate the prevalence and risk factors of asymptomatic carotid artery disease, we analyzed a sample of 909 men and women (aged 40-79 years) drawn from the community-based Bruneck Ischemic Heart Disease and Stroke Prevention Study. For the four decades of age (40-49, 50-59, 60-69, and 70-79 years), respective prevalence rates as assessed by duplex scanning were found to be 8.2%, 39.7%, 66.4%, and 82.5% in men and 3.3%, 22.3%, 48.7%, and 76.7% in women. High-grade stenosis (> 80%) classified by Doppler criteria was twice as frequent in men (2.4%) as in women (1.1%). Age and sex were found to be particularly strong and independent predictors of asymptomatic carotid artery disease. Accordingly, separate logistic regression models were developed for both men and women in the elderly (65-79 years) and middle-aged (50-64 years) groups. Systolic blood pressure turned out to be the only attribute with independent significance in all subgroups examined. Cigarette smoking, recorded as pack-years, emerged as the leading risk factor of carotid atherosclerosis in men. Serum fibrinogen levels were found to be highly indicative of carotid artery disease in elderly men and women. For apolipoprotein B predictive significance was observed in the middle-aged populations, whereas apolipoprotein A-I had a protective effect in elderly women. Diabetes mellitus completed the risk factor profile for elderly men. In summary, the relation between cardiovascular risk factors and asymptomatic carotid artery disease showed a dynamic dependence on sex and age. These findings may help to improve the efficacy of risk prediction in the general population and facilitate well-directed preventive measures.

Adult↗
PubMed1993

Immunology of atherosclerosis. Demonstration of heat shock protein 60 expression and T lymphocytes bearing alpha/beta or gamma/delta receptor in human atherosclerotic lesions.

Our previous work revealed the presence of a great number of activated T lymphocytes in early human atherosclerotic lesions, and we were able to induce atherosclerosis in normocholesterolemic rabbits by immunization with Mycobacterium tuberculosis heat-shock protein (HSP) 65. We hypothesized this latter phenomenon to arise from cross-reactivity of mycobacterial HSP 65 with the endogenously expressed homologous 60-kd form of this stress protein. To study HSP 60 expression and the phenotype of intima infiltrating T lymphocytes relative to the T cell receptor (TCR) in human atherosclerotic lesions, specimens of aorta, carotid arteries, and internal mammary arteries and veins, as well as saphenous veins and vena cava from 27 subjects, aged 23 to 80 years, were examined using immunohistochemical and immunofluorescence techniques on serial frozen tissue sections. HSP 60 was detected on endothelium, smooth muscle cells, and/or mononuclear cells of all carotid and aortic specimens, whereas vessels of smaller diameter, serving as reference specimens for normal intima without atherosclerotic lesions and mononuclear infiltration, showed no detectable expression of this stress protein. Furthermore, although the majority of CD3+ cells within the mononuclear cell infiltrates of atherosclerotic lesions bear the alpha/beta TCR, a considerable portion also consisted of gamma/delta TCR+ cells. Thus, 9.7% of T cells in the transition zone between normal intima and fatty streaks carry the gamma/delta TCR, a proportion that decreases to 6.6% and 4.3% in fatty streaks and atherosclerotic plaques, respectively. We conclude that the intensity of HSP 60 expression correlates positively with the atherosclerotic severity and that most lymphocytes participating in atherogenesis bear the alpha/beta TCR, although gamma/delta TCR+ cells are also enriched in atherosclerotic lesions. Expression of HSP 60 by intimal cells, caused, eg, by hemodynamic shear forces, may be responsible for recruitment of HSP-sensitized T cells, thus leading to the induction of an initiating inflammatory process in atherosclerosis. Other risk factors, such as high serum cholesterol levels, contribute to the final outcome of the disease.

Adult↗
PubMed1993

[Membranous lipodystrophy (Nasu-Hakola disease)].

We present a case-report and review of the literature on membranous lipodystrophy. This is a rare disease characterized by progressive presenile dementia, multiple bone cysts with pathologic fractures, generalized cerebral seizures with abnormal EEG and bilateral calcifications of the basal ganglia. Neuropathological findings are neuroaxonal dystrophy with neurofilaments in the axons, neuronal cell loss and fibrillary gliosis. The disease is usually inherited as an autosomal recessive. The pathogenesis is unknown but is believed to be an enzyme defect of the glycolipid metabolism.

Adult↗
PubMed1992

Superficial siderosis of the central nervous system: report of three cases and review of the literature.

We present 3 cases and a review of the literature to demonstrate the current state of clinical diagnosis and therapy of superficial siderosis of the central nervous system. Typical symptoms were progressive cerebellar ataxia, spasticity and hearing loss. Repeated subarachnoid hemorrhage was indicated by persistent xanthochromia of the cerebrospinal fluid and confirmed by the presence of erythrophages, siderophages and iron-containing pigments. Deposition of free iron and hemosiderin in pial and subpial structures leads to intoxication of the central nervous system and represents the pathophysiological mechanism of superficial siderosis. Hypointensity of the marginal zones of the central nervous system on T2 weighted MR images indicates an iron-induced susceptibility effect and seems pathognomonic for superficial siderosis. In 39 of the 43 previously described cases superficial siderosis was verified by biopsy or autopsy. Today magnetic resonance imaging enables diagnosis at an early stage of the disease. Therapeutic management requires the elimination of any potential source of bleeding. In patients with unknown etiology no proofed therapy is yet available.

Aged↗
PubMed1992

[Wilson's disease with primary CNS manifestation--current status in diagnosis and therapy].

Five cases studied at our clinic are discussed and the literature reviewed with the aim of assessing the diagnostic value of various examination methods used for Wilson's disease and a modified diagnostic approach is suggested. CT and MRI are compared with regard to sensitivity, specificity and prognostic value. Almost regularly, MRI showed bilateral lesions in the basal ganglia in combination with structural changes in the brain stem. A pattern consisting of symmetrical lesions of the red nuclei, the periaqueductal grey region and, facultatively, the substantia nigra and the dentate nuclei was discovered and appeared almost pathognomonic. Follow-up studies revealed excellent reversibility of MRI changes by both penicillamine and trientine. Auditory evoked potentials showed the highest sensitivity and the best correlation with structural findings. Kayser-Fleischer corneal rings--a diagnostic requirement in the literature--were not found in all patients. The current state of therapy and therapy management is discussed on the basis of pathophysiological considerations. As possible complications of penicillamine administration the deterioration of the clinical condition after initiating therapy, and the risks associated with an abrupt termination of therapy are discussed in detail.

Adolescent↗
PubMed1991

[Orthostatic tremor].

Two men, aged 57 and 77 years old, reported increasing unsteadiness on standing upright for the past 2 and 5 years, respectively. It had become impossible for them to remain standing for more than 10 seconds, as otherwise they might fall down. Walking, sitting and lying were possible without difficulty. Both patients were found to have a fine tremor in both legs on standing only. There were no other neurological signs or symptoms. Electromyography of the leg muscles demonstrated tremor activity at 14-16 Hz. Propranolol, 40 mg three times daily, in the 57-year-old patient brought no improvement. However, on taking primidone, in slowly increasing doses up to 250 and 500 mg daily, respectively, the condition lastingly improved in both patients.

Aged↗
PubMed1991

Cervical herpes zoster and delayed brainstem infarction.

Varicella-zoster (VZ) virus is a rare cause of CNS angiitis, which commonly presents as herpes zoster ophthalmicus with contralateral hemiplegia due to hemispheric infarction. We report the first case of VZ-angiitis with infarction in the ventral pons, following cervical herpes zoster.

Brain Stem↗