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Biomedical subjects

A J Grau

Publications and source records attributed to A J Grau.

At least 19 recordsLinked to original sources

Helicobacter pylori infection as an independent risk factor for cerebral ischemia of atherothrombotic origin.

Chronic infection may increase the risk for ischemic stroke. Presently, it is insufficiently established whether Helicobacter pylori infection represents a risk factor for ischemic stroke. We analyzed IgG antibodies against H. pylori in 109 patients with acute cerebral ischemia and 82 age- and sex-matched control patients with non-vascular and non-inflammatory neurological diseases. Antibody titers were significantly higher in patients than in control subjects (p=0.007). H. pylori seropositivity tended to be more common in patients (odds ratio (OR) 1.55, 95% confidence interval (ci) 0.87-2.76), but this trend was further attenuated in multivariate analysis (OR 1.42; 95% 0.75-2.67) with hypertension, diabetes mellitus, current or previous smoking, previous cerebral ischemia and low socioeconomic status. H. pylori seropositivity increased the odds for cerebral ischemia of atherothrombotic origin in univariate (OR 3.63; 95% ci 1.37-9.65) and multivariate analysis (OR 3.53; 95% ci 1.09-11.4). H. pylori seropositivity may be an independent risk factor for stroke of atherothrombotic origin.

Aged↗

Assessment of plasma lactoferrin in Parkinson's disease.

Iron may play an important role in the pathogenesis of Parkinson's disease (PD). Recent studies have shown that the iron-transporting glycoprotein lactoferrin (LF) and its receptor are increased in the substantia nigra (SN) in PD. We investigated whether plasma levels of LF are altered in dopa-responsive PD. Plasma LF was not different between patients with PD (n = 23; 306 +/- 116 [mean +/- standard deviation] ng/ml) and age- and sex-matched healthy control subjects (n = 15; 359 +/- 126 ng/ml ). However, LF was inversely correlated with PD severity (r = -0.68, P = 0.002), an association that remained significant after adjustment for treatment with levodopa, monoaminooxidase inhibitors, and dopa agonists (r = -0.53, P = 0.017). Plasma transferrin and ferritin levels were not different between groups and neither correlated with disease severity nor with LF levels. Together with the result of increased nigral lactoferrin, this finding is compatible with the hypothesis of an imbalance between LF levels in blood and SN in progressing PD. Larger and particularly longitudinal studies and measurements of LF in cerebrospinal fluid are warranted to further examine the role of LF in PD.

Dopamine↗

Thrombolytic properties of leukocytes from peripheral blood in healthy subjects and in patients with acute cerebral ischemia.

Polymorphonuclear leukocytes are activated in acute ischemic stroke. Activated polymorphonuclear leukocytes may contribute to thrombolysis by proteolytic degradation of fibrin and by modification of the plasminogen system. We used an in vitro thrombolysis model to investigate (1) thrombolytic properties of leukocytes in young and healthy subjects, (2) to test the hypothesis of increased polymorphonuclear leukocyte-associated thrombolysis in patients with acute cerebral ischemia, and (3) to assess plasminogen-dependent and -independent thrombolytic properties of polymorphonuclear leukocyte elastase. Coincubation of polymorphonuclear leukocytes with fibrin clots led to increased thrombolysis, a process reaching statistical significance after 8 hours [1x10(7) polymorphonuclear leukocytes/mL; 12.8+/-1.9% (mean+/-SEM), spontaneous clot lysis: 7.3+/-0.7%]. Polymorphonuclear leukocytes inside clots caused more efficient thrombolysis than polymorphonuclear leukocytes in the incubation medium. Spontaneous and polymorphonuclear leukocyte-associated lysis tended to be lower in patients with acute cerebral ischemia (n=9, 24 hours, 9.5+/-1.8% and 12.9+/-2.2%) than in age- and sex-matched control subjects (n=8; 12.2+/-2.0% and 17.4+/-1.9%). In the presence of alpha(2)-antiplasmin, thrombolysis tended to be faster with elastase-digested plasminogen (miniplasminogen) than with native plasminogen. Purified polymorphonuclear leukocyte elastase itself had no thrombolytic effect. We conclude that the thrombolytic capacity of polymorphonuclear leukocytes from peripheral blood is small and slow and may have been overestimated in previous reports. Polymorphonuclear leukocyte thrombolytic activity may not be increased in acute cerebral ischemia. Miniplasminogen may be an interesting adjunct to plasminogen activators in acute stroke models.

Aged↗

Evidence for infection with Chlamydia pneumoniae in a subgroup of patients with multiple sclerosis.

In a pilot study, we identified Chlamydia pneumoniae in the cerebrospinal fluid by polymerase chain reaction in 5 of 10 patients with definite multiple sclerosis (MS). In a second series, 2 of 20 patients with definite MS and 3 of 17 patients with possible/probable MS or MS variants, but none of 56 patients with other neurological, diseases were polymerase chain reaction-positive. We confirm that C. pneumoniae can be found in the cerebrospinal fluid of MS patients, but our rate of positive results is lower than in a recent report.

Adolescent↗

Fever and infection early after ischemic stroke.

Previous studies showed that elevated body temperature early after ischemic stroke is associated with severe neurological deficit and a poor outcome. The aim of this study was to analyse the prevalence and putative etiology of febrile body temperature (>/=38.0 degrees C) early after stroke and to investigate the association between body temperature, stroke severity and outcome. We investigated 119 consecutive patients who were admitted within 24 h after ischemic stroke. Patients were examined for infection before ischemia using a standardized questionnaire and received daily clinical examination after stroke. In case of fever, standardized radiological and microbiological examinations were performed. Fever within 48 h after stroke was observed in 30 (25.2%) patients. The probable cause of fever was infective or chemical aspiration pneumonia (n=12), other respiratory tract infection (n=7), urinary tract infection (n=4), viral infections (n=3) or insufficiently defined (n=5). (One patient had two potential causes of fever.) In thirteen of these patients, infection was most probably acquired before stroke. Fever newly developed more often during day 1 to 2 than day 3 to 7 after stroke (P=0.016). Fever was associated with a more severe deficit on admission independent from age, vascular diseases and risk factors (odds ratio 9.6; 95% confidence interval 3.1-29). Fever is a frequent complication early after stroke and in the majority of cases, it can be explained by infection or chemical aspiration pneumonia. In about half of the infected patients, infection was most probably acquired before stroke. Fever was associated with a more severe neurological deficit on admission.

Aged↗

Association of cervical artery dissection with recent infection.

BACKGROUND: Cervical artery dissection (CAD) is an important cause of ischemic stroke in younger patients. However, its cause is insufficiently understood. OBJECTIVE: To test the hypothesis that CAD is frequently associated with recent infection. SUBJECTS AND METHODS: We compared the prevalence of infection during the preceding week in 43 consecutive patients with acute CAD and 58 consecutive patients younger than 50 years with acute cerebral ischemia from other causes (control patients). In subgroups of patients, we correlated infectious status with electron microscopic studies of skin biopsy specimens and investigated pathways potentially linking infection and CAD. RESULTS: Recent infection was more common in patients with CAD (25/43 [58.1%]) than in control patients (19/58 [32.8%]; P=.01). Respiratory tract infection was preponderant in both groups. Recent infection, but not the mechanical factors cough, sneezing, or vomiting, was independently associated with CAD in multivariate analysis. Investigation of serum antibodies against Chlamydia pneumoniae, smooth muscle cells, endothelial cells, collagen types I through IV, and heat shock protein 65 and assessment of serum alpha1-antitrypsin and HLA did not contribute to the understanding of the pathogenesis of CAD. More patients with pathologic findings in skin biopsy specimens tended to have had a recent infection (13/21 [62%]) than patients without pathologic findings (2/9 [22%]; P=.11). CONCLUSION: Our results suggest a significant association between recent infection and CAD that is not explained by mechanical factors occurring during infection.

Acute Disease↗

Stroke from internal carotid artery occlusion during mumps infection.

During the terminal incubation period of severe mumps infection, a 40-year-old patient suffered from large infarction in the right middle cerebral artery territory. The proximal right internal carotid artery (ICA) was occluded on angiography. Computed tomography of the neck detected a hemorrhage located ventromedial to the right common carotid artery. Four months later the right ICA was partly recanalized. Carotid surgery revealed an atherosclerotic plaque and a vessel wall, which was fragile and less compact than usually. A strong inflammatory reaction to mumps infection may have contributed to the pathogenesis of the cervical hemorrhage and to acute thrombosis and occlusion of the ICA.

Adult↗

Recent bacterial and viral infection is a risk factor for cerebrovascular ischemia: clinical and biochemical studies.

We performed a case-control study to investigate the role of recent infection as stroke risk factor and to identify pathogenetic pathways linking infection and stroke. We examined 166 consecutive patients with acute cerebrovascular ischemia and 166 patients hospitalized for nonvascular and noninflammatory neurologic diseases. Control subjects were individually matched to patients for sex, age, and season of admission. We assessed special biochemical parameters in subgroups of stroke patients with and without recent infection (n = 21) who were similar with respect to demographic and clinical parameters. Infection within the preceding week was a risk factor for cerebrovascular ischemia in univariate (odds ratio [OR] 3.1; 95% confidence interval (CI), 1.57 to 6.1) and age-adjusted multiple logistic regression analysis (OR 2.9; 95% CI, 1.31 to 6.4). The OR of recent infection and age were inversely related. Both bacterial and viral infection contributed to increased risk. Infection elevated the risk for cardioembolism and tended to increase the risk for arterioarterial embolism. Stroke patients with and without preceding infection were not different with respect to factor VII and factor VIII activity, fibrin monomer, fibrin D-dimer, von Willebrand factor, C4b-binding protein, protein S, anticardiolipin antibodies, interleukin-1 receptor antagonist, soluble tumor necrosis factor-alpha receptor, interleukin-6, interleukin-8, and neopterin. In conclusion, recent infection is an independent risk factor for acute cerebrovascular ischemia. Its role appears to be more important in younger age groups. The pathogenetic linkage between infection and stroke is still insufficiently understood.

Adult↗

Increased fraction of circulating activated platelets in acute and previous cerebrovascular ischemia.

Determination of circulating activated platelets may be helpful to estimate the prognosis and to stratify therapies in arterial vascular disorders including stroke. We used flow cytometry and phase contrast microscopy to study whether the fraction of platelets expressing p-selectin and CD63 and the fraction of platelets with shape change are increased in patients with acute and previous cerebrovascular ischemia. The proportion of platelets expressing activation dependent antigens was higher in patients with acute (n = 24; p-selectin: 8.23 +/- 4.21%; CD63: 3.53 +/- 2.53%) and with previous cerebrovascular ischemia (n = 46; 3.86 +/- 1.98%; 2.80 +/- 1.79%) as compared to age- and sex-matched control subjects (n = 35; 2.17 +/- 0.96%; 1.79 +/- 0.75%; p < or = 0.005, respectively). In patients with previous ischemia, there was no difference between treatment with aspirin (n = 25) or phenprocoumon (n = 21). Hypertension, diabetes mellitus and smoking were not associated with increased antigen expression (analysis of variance). The fraction of discoid platelets and platelet counts were not significantly different between groups. Our results indicate increased expression of platelet neoantigens in acute and to a less degree in previous cerebrovascular ischemia. Ongoing platelet activation after cerebrovascular ischemia despite therapy with aspirin or phenprocoumon indicates that new anti-platelet drugs may be of benefit for these patients. Flow cytometry appears to be a useful tool to assess platelet function in cerebrovascular ischemia.

Aged↗

Infection-associated cervical artery dissection. Three cases.

BACKGROUND: The pathogenesis of cervical artery dissection remains unknown. Infection-mediated damage of the arterial wall may be one contributing mechanism. We present three male patients with respiratory infection prior to cervical artery dissection. CASE DESCRIPTIONS: Case 1: During an upper respiratory tract infection, a 49-year-old patient developed bilateral carotid and vertebral artery dissection with complete vessel restitution. Case 2: Within 3 years, a 40-year-old patient experienced two episodes of bilateral internal carotid artery dissection, both preceded by febrile upper respiratory tract infection. Case 3: A 52-year-old patient developed right-sided and, 2 years later, left-sided internal carotid artery dissection, each following upper respiratory tract infection. CONCLUSIONS: Infection may be a trigger factor in the pathogenesis of cervical artery dissection.

Adult↗

Association between acute cerebrovascular ischemia and chronic and recurrent infection.

BACKGROUND AND PURPOSE: We performed a case-control study to investigate whether chronic or recurrent respiratory, ear-nose-throat (ENT), and dental infections are risk factors for cerebrovascular ischemia. METHODS: Using a standardized questionnaire we investigated past infectious diseases in 166 consecutive patients with acute cerebrovascular ischemia and in 166 age- and sex-matched nonstroke neurological patient controls. In subgroups, we performed standardized ENT (69 patients, 66 control subjects) and dental examinations including orthopantomography (66 patients, 60 control subjects). Dental status was determined by a total dental index (TDI) that reflects caries, periapical lesions, periodontitis, and other dental lesions and by an orthopantomography index (OPGI) that was assessed blinded. RESULTS: Frequent (> or = 2 episodes in each of the 2 preceding years) or chronic bronchitis was associated with cerebrovascular ischemia in age-adjusted multiple logistic regression analysis (odds ratio, OR, 2.2; 95% confidence interval, CI, 1.04 to 4.6). Groups were not different in ENT examination. Patients tended to have a worse dental status (TDI: P = .070; OPGI: P = .062) and had more severe periodontitis (P = .047) and periapical lesions (P = .027) than control subjects. In age-adjusted multiple logistic regression analysis with social status and established vascular risk factors, poor dental status (TDI) was independently associated with cerebrovascular ischemia (OR, 2.6; 95% CI, 1.18 to 5.7). CONCLUSION: Recurrent or chronic bronchial infection and poor dental status, mainly resulting from chronic dental infection, may be associated with an increased risk for cerebrovascular ischemia.

Acute Disease↗

The association of leukocyte count, fibrinogen and C-reactive protein with vascular risk factors and ischemic vascular diseases.

In 154 subjects (age 63 +/- 11 years; 63 women and 91 men) randomly selected from the population, we tested the hypothesis that inflammatory parameters are associated with vascular risk factors and particularly with a history of ischemic vascular diseases. The subjects were part of the control group (n = 197) in a case-control study investigating recent infection as a risk factor for acute cerebrovascular ischemia and had been matched for sex and age with patients suffering from acute ischemic stroke or transient ischemic attack. Subjects with malignant or inflammatory diseases, with recent trauma, surgery or vascular diseases (n = 43) were excluded from the present analysis. In multivariate analysis, current smoking, diabetes mellitus, age > or = 65 years, and a history of stroke independently increased the leukocyte count. Hypertriglyceridemia, peripheral arterial disease, and diabetes mellitus were positively associated with C -reactive protein (CRP). Age > or = 65 years and diabetes mellitus independently increased fibrinogen. (p < 0.05, respectively) Subjects with a history of cerebrovascular, cardiovascular or peripheral arterial disease had higher leukocyte counts, fibrinogen and CRP than subjects without vascular risk factors and higher leukocytes and fibrinogen than subjects with one or more risk factors. Subjects under the age of 65 with vascular risk factors but without ischemic diseases had higher leukocyte count, fibrinogen and CRP and subjects older than 65 with risk factors had higher CRP than subjects without risk factors or ischemic diseases in the same age group. (p < 0.05, respectively) These results support the hypotheses that low-grade inflammation is associated with vascular risk factors and that inflammatory mechanisms may contribute to the risk of organ ischemia.

Adolescent↗

[Infectious diseases as a cause and risk factor for cerebrovascular ischemia].

Cerebrovascular ischemia can be caused by infectious diseases which involve cerebral arteries or the heart, including infectious endocarditis, bacterial and fungal meningitis, neurosyphilis, neuroborreliosis, herpes zoster, the acquired immunodeficiency syndrome, cat scratch disease and other rare infectious diseases. Presently, there is increasing evidence that infection in general and mainly respiratory infection is a risk factor for ischemic stroke. Case reports and smaller case series reported an association of cerebrovascular ischemia and recent infection in children and younger adults. Two case control studies from Helsinki (54 patients under the age of 50) and from Heidelberg (197 patients aged 80 or less) identified recent infection as an important risk factor for ischemic stroke. Febrile, bacterial and respiratory infections were most important in this respect. In the study from Heidelberg, the neurological deficit was more severe and cardioembolism was more frequent in infection-associated stroke than in stroke without preceding infection. This review summarizes the association of infectious diseases and cerebrovascular ischemia and discusses potential pathogenetic mechanisms linking both diseases.

Adult↗