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Biomedical subjects

B Lindahl

Publications and source records attributed to B Lindahl.

At least 73 records · Page 4Linked to original sources
PubMed1997

Proinflammatory cytokines, measured in a mixed population on arrival in the emergency department, are related to mortality and severity of disease.

OBJECTIVES: To investigate whether serum levels of tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) are related to mortality and severity of disease in patients admitted to the Emergency Department (ED). DESIGN: Prospective cohort study. SETTING: Emergency Department of a tertiary university hospital. SUBJECTS: A total of 140 patients admitted to the ED, representing common acute medical diseases, such as stroke, obstructive lung disease, heart failure, myocardial infarction, angina pectoris, infectious diseases and acute abdominal disorders. MAIN OUTCOME MEASURES: APACHE II score at admission, hospital mortality and length of stay in hospital (LOS). RESULTS: A moderate rise in cytokine levels (IL-6; 50-300 ng L(-1), TNF-alpha; 10-70 ng L[-1]) was found in all diagnosis-groups, with the most pronounced elevation seen in patients with acute abdominal disorders (up to 6900 ng L[-1]). IL-6 on arrival to the ED was significantly correlated to the APACHE II score (r = 0.48, P < 0.0001), LOS (r = 0.36, P < 0.0001) and was elevated in nonsurvivors (n = 9) compared to those who did survive. TNF-alpha on arrival showed a significant correlation to LOS (r = 0.36, P < 0.0001) and APACHE II (r = 0.41, P < 0.0001), but was not associated to later mortality. CONCLUSIONS: Serum levels of proinflammatory cytokines collected at admission to the ED were related to the severity of disease and hospital mortality.

APACHE↗
PubMed1997

Risk stratification in unstable coronary artery disease. Additive value of troponin T determinations and pre-discharge exercise tests. FRISK Study Group.

In 963 patients, participating in a randomized study of low molecular weight heparin in unstable coronary artery disease and followed for 5 months, troponin T was determined. In the 766 patients with a pre-discharge exercise test both troponin T level and exercise test response were independent predictors of prognosis. Cardiac death or myocardial infarction occurred in 5, 9 and 13% of the patients with a maximal troponin T level of < 0.06 (n = 154), 0.06-0.2 (n = 175) and > or = 0.2 microgram.l-1 (n = 437), respectively. Based on exercise tolerance and occurrence of ST depression, patients with a low (n = 361), intermediate (n = 325) and high risk (n = 80) exercise test response were identified. In these, death or myocardial infarction occurred in 5, 13 and 29%, respectively. The combination of troponin T and the exercise test response allowed an even better categorization into low (n = 84), intermediate (n = 406) and high (n = 276) risk groups with 1, 7 and 20% death or myocardial infarction, respectively. Among those 197 patients unable to perform an exercise test the incidence was 3, 16 and 27% in patients with troponin T < 0.06, 0.06-0.2 and > or = 0.2 microgram.l-1, respectively. Thus, troponin T determinations and pre-discharge exercise tests alone and combined are valuable for risk assessment in unstable coronary artery disease.

Aged↗
PubMed1997

Proinsulin, intact insulin, and fibrinolytic variables and fibrinogen in healthy subjects. A population study.

OBJECTIVE: As high serum insulin predicts impaired fibrinolysis and proinsulin reacts in most conventional insulin assays, we hypothesized that proinsulin could link low fibrinolytic activity and hyperinsulinemic conditions. RESEARCH DESIGN AND METHODS: We explored the relationship between fibrinolysis and plasma fibrinogen on the one hand and specific insulin and proinsulin on the other, in a healthy population sample of 165 men and women, 25-74 years of age, from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Study. Specific insulin and proinsulin were measured by enzyme-linked immunosorbent assay. Partial correlation coefficients, adjusted for age and sex, were calculated. RESULTS: Plasma fibrinogen levels were related to insulin (r = 0.25, P < 0.01) and proinsulin (r = 0.29, P < 0.001), as was plasminogen activator inhibitor (PAI)-1 activity (r = 0.36 and r = 0.29, respectively; P < 0.001). Tissue Plasminogen activator (tPA) activity correlated inversely to insulin (r = 0.35, P < 0.001) and proinsulin (r = - 0.36, P < 0.001). In a multivariate analysis taking also smoking and anthropometric and metabolic measurements into account, fasting proinsulin was a significant predictor of high plasma fibrinogen level. Insulin and proinsulin levels were not related to tPA activity. High levels of postload insulin, triglycerides, and diastolic blood pressure, but not proinsulin, predicted high PAI-l activity. CONCLUSIONS: In a healthy population, the relationship previously described between high insulin levels and impaired fibrinolysis is not attributable to confounding from proinsulin. Elevated proinsulin levels are associated with high fibrinogen levels.

Adult↗
PubMed1997

Neural network analysis of biochemical markers for early assessment of acute myocardial infarction.

Neural network analysis was applied for early diagnosis/exclusion of acute myocardial infarction and prediction of infarct size. Eighty-eight patients admitted with onset of chest pain within 8 hours were included. Frequent blood samples for measurement of myoglobin, CK-MB and troponin-T were obtained and used in the development of a set of neural network components of a decision support system. The results indicate that this approach could provide useful support for assessment of patients with suspected AMI.

Biomarkers↗
PubMed1997

Early assessment of patients with suspected acute myocardial infarction by biochemical monitoring and neural network analysis.

Neural network analysis was applied for early diagnosis/exclusion of acute myocardial infarction (AMI), prediction of infarct size, and estimation of "time from onset of infarction." Eighty-eight patients admitted within 8 h after onset of chest pain were included. Blood samples for measurement of myoglobin, creatine kinase isoform MB, and troponin T were obtained every 30 min during the first 3 h and then after successively longer intervals. Data from 50 patients were used to train a set of neural network components of a decision support system. The performance of the system was evaluated and compared with experienced clinicians for the remaining 38 patients. The computer system detected myocardial infarction and predicted infarct size earlier than the clinicians, but did not differ significantly in terms of diagnostic sensitivity, specificity, and predictive values when disregarding time for diagnosis. With a cross-validation procedure the cumulated sensitivities of the computer system for the first five measurements were estimated to be (mean +/- 2SEM, n = 100): 0.77 +/- 0.03, 0.89 +/- 0.02, 0.94 +/- 0.02, 0.97 +/- 0.01, and 0.99 +/- 0.01, respectively, with corresponding cumulated specificities between 0.93 +/- 0.01 and 0.91 +/- 0.01. We concluded that neural network analysis of serial measurements of biochemical markers might provide useful support for the early assessment of patients with suspected AMI.

Aged↗
PubMed1996

Tamoxifen-induced DNA adducts in endometrial samples from breast cancer patients.

Tamoxifen-induced DNA adducts were analyzed with the (32)P-postlabeling method using high-performance liquid chromatography (HPLC)-radioactivity detection from endometrial tissue of breast cancer patients and controls. Liver DNA from tamoxifen-treated rats was used as a positive standard. In blind analysis, five of the seven samples from tamoxifen-treated patients showed DNA adducts; none of the five controls were positive. The identity of the tamoxifen adduct was confirmed by using different chromatographic systems, isolating the HPLC fractions and running them on TLC, with or without spiked rat liver samples. The level of adducts in the treated patients was 2.7 adducts/10(9) nucleotides in the HPLC analysis.

Aged↗
PubMed1996

Selective loss of cerebral keratan sulfate in Alzheimer's disease.

Proteoglycans, especially heparan sulfate-substituted species, are known to be associated with the deposition of amyloid in Alzheimer's disease. We previously found that heparan sulfate from afflicted brains, and from control subjects, differed minimally in quantity and structure (Lindahl, B., Eriksson, L., and Lindahl, U.(1995) Biochem. J. 306, 177-184). In the present study, a glycosaminoglycan fraction, shown to contain heparan sulfate and keratan sulfate, was radiolabeled by partial N-deacetylation (hydrazinolysis) followed by re-N-acetylation using [3H]acetic anhydride. Quantitation of the 3H-labeled polysaccharides, based on digestion with heparitinase I from Flavobacterium heparinum and keratanase from Pseudomonas sp., revealed that the amounts of keratan sulfate in Alzheimer cerebral cortex are reduced to less than half of control values. Moreover, a monoclonal antibody against a highly sulfated keratan sulfate epitope bound to the majority of the neurons in normal cortex but not in the diseased tissue. The lack of highly sulfated keratan sulfate structures may reflect a specific functional defect of the cells.

Acetic Anhydrides↗
PubMed1996

Relation between troponin T and the risk of subsequent cardiac events in unstable coronary artery disease. The FRISC study group.

BACKGROUND: Early risk assessment is important in patients with unstable coronary artery disease, ie, unstable angina or non-Q-wave myocardial infarction. Some previous small studies have indicated that patients with unstable angina and elevation of troponin T (tn-T) have worse short-term and long-term prognoses. In this study, the prognostic value of tn-T was evaluated and compared with other early available risk indicators. METHODS AND RESULTS: Nine hundred seventy-six patients participating in a randomized study of low-molecular-weight heparin in unstable coronary artery disease were followed for 5 months after the index episode. The risk of cardiac events increased with increasing maximal levels of tn-T obtained in the initial 24 hours. The lowest quintile (<0.06 microgram/L) constituted a low-risk group, the second quintile (0.06 to 0.18 microgram/L) an intermediate-risk group, and the three highest quintiles (> or =0.18 microgram/L) a high-risk group, with 4.3%, 10.5%, and 16.1% risk of either myocardial infarction or cardiac death, respectively. Troponin T level was identified together with age, hypertension, number of antianginal drugs, and ECG changes at rest as independent prognostic variables for myocardial infarction or cardiac death in a multivariate analysis. The prognostic value of tn-T was independent of the classification of index event into unstable angina or myocardial infarction. CONCLUSIONS: Troponin T determination is an inexpensive and widely applicable method for early risk assessment in patients with unstable coronary artery disease. The maximum tn-T value obtained during the first 24 hours provides independent and important prognostic information.

Aged↗
PubMed1996

Insulin resistance syndrome and fibrinolytic activity: the northern Sweden MONICA study.

BACKGROUND: Many studies have, in small and highly selected study populations, described how cardiovascular risk factors tend to cluster in subjects with insulin resistance. Recently, interest has focused on possible relationships between this insulin resistance syndrome and fibrinolysis, and the role of triglycerides in this association. The present study addresses these issues in a general population. METHODS: A subsample of participants in the population-based Northern Sweden MONICA (MONItoring of trends and determinants in CArdiovascular diseases) Study, consisting of 353 men and 403 women in the 25-64 year age range, was investigated. Insulin resistance was estimated indirectly from the fasting levels of insulin and glucose. Fibrinolytic activity was measured both as plasminogen activator inhibitor type 1 (PAI-1) activity and tissue plasminogen activator ((t)PA) activity. RESULTS: Insulin resistance was highly correlated with those cardiovascular risk factors that have been associated with the insulin resistance syndrome, and to the measures of fibrinolytic activity. Subjects in the upper tertile of insulin resistance had a PAI-1 activity that was three times higher than that of the lower third men and twice as high in women. There was a strong interaction between insulin resistance and serum triglycerides. Low versus high levels of both variables together were associated with a fivefold difference in PAI-1 activity in men and a threefold difference in women. The (t)PA activity was inversely correlated to both insulin resistance and serum triglycerides. CONCLUSIONS: In a general population, the 'insulin resistance syndrome' is closely associated with low fibrinolytic activity. Serum triglyceride levels interact with insulin resistance to predict fibrinolytic activity.

Adult↗
PubMed1996

Dynamic vectorcardiography for early diagnosis of acute myocardial infarction compared with 12-lead electrocardiogram. BIOMACS Study Group.

BACKGROUND: The aim of the study was to assess the diagnostic accuracy of multilead continuous vectorcardiography (VCG) for early diagnosis of acute myocardial infarction (AMI) in patients admitted to hospital because of suspicion of AMI. VCG was compared with resting 12-lead electrocardiogram (ECG) on admission. METHODS: In a multicentre study, 107 patients with chest pain (< or = 12 h) were included. The diagnosis of AMI was on the basis of World Health Organization criteria. Continuous VCG was recorded for 12-24 h and the data were evaluated blindly at 2 and 6 h of recording and after the completion of recording (12-24 h). RESULTS: AMI was diagnosed in 74 patients. The VCG recording had a diagnostic accuracy of 71% after 2 h and 86% after both the 6 h and the completed VCG recording. Compared with ECG on admission, the VCG recording after 6 h showed a significantly greater sensitivity: 86% compared with 62% (P < 0.01). In patients with non-diagnostic ECG on arrival (n = 55), VCG after 6 h had a diagnostic accuracy of 85%, a sensitivity of 82% and a specificity of 89%. CONCLUSIONS: VCG might be useful for early diagnosis of AMI, especially in patients with non-diagnostic ECG.

Electrocardiography↗
PubMed1996

Biochemical markers of myocardial damage for early diagnosis and prognosis in patients with acute coronary syndromes. Minireview based on a doctorial thesis.

In patients with suspected AMI. Monitoring of a combination of myoglobin and CK-MB or tn-T allowed ruling-in AMI within 2-3 hours and ruling-out AMI within 3-6 hours in almost all patients admitted with chest pain and a nondiagnostic ECG. This might have a large impact on the early handling and treatment of these patients. The neural network methodology, with monitoring of myoglobin, CK-MB and tn-T allowed, within the first three hours, reliable diagnosis/exclusion of AMI/MMD and prediction of infarct size in patients admitted with suspicion of AMI. The computer system was faster than clinicians. Thus, neural network methodology might be a useful support for the early assessment of patients with suspected myocardial infarction. In patients with unstable CAD. The risk of subsequent cardiac events is increased by increasing maximal levels of tn-T obtained during the initial 24 hours. Thereby a normal, a slightly elevated and a clearly elevated tn-T level identified a low, intermediate and high risk group, respectively, for MI or death. The tn-T level was an independent prognostic variable for MI or death in a multivariate analysis comparing other early available risk indicators. Furthermore, tn-T seemed to be superior to CK-MB (mass) for risk stratification. In patients able to perform a predischarge ET both the tn-T level and the ET response were independent prognostic indicators for MI or death. The combination of tn-T and the ET response allowed a further improved risk stratification. In patients with tn-T elevation at inclusion, prolonged dalteparin treatment was beneficial. However, in patients without tn-T elevation, long term dalteparin treatment had no protective effect. Thus, tn-T determination provides independent and important prognostic information in unstable CAD. In the selection of treatment strategy for the individual patient, this simple, inexpensive and early available biochemical test might be useful.

Aged↗
PubMed1995

Structure of heparan sulphate from human brain, with special regard to Alzheimer's disease.

Heparan sulphate (HS) was isolated after proteolytic digestion of cerebral cortex, obtained at autopsy, of patients with Alzheimer's disease (AD) and of control subjects. Deaminative cleavage in combination with selective radiolabelling procedures showed that the N-acetylated regions in the intact polysaccharides ranged from isolated residues to approximately 10 consecutive N-acetylated disaccharide units, without any apparent difference between AD and control HS. The yield of disaccharide deamination products was slightly higher with AD than with control HS, suggesting a differential distribution of N-sulphate groups. Separation of the disaccharides by anion-exchange h.p.l.c. yielded four mono-O-sulphated and one di-O-sulphated disaccharide; these components occurred in strikingly similar proportions in all cerebral HS preparations (except polysaccharide from neonatal brain) irrespective of the age of the individual and the histopathology of the cortex specimen. No significant difference was noted between HS obtained from control and from AD tissue. By contrast, the composition of HS isolated from brain differed significantly from that of HS preparations derived from other human organs.

Acetylation↗
PubMed1995

Identification of O-sulphate substituents on D-glucuronic acid units in heparin-related glycosaminoglycans using novel synthetic disaccharide standards.

The two disaccharides, methyl 4-O-(2-O-sulpho-beta-D-glucopyranosyl-uronic acid)-2-deoxy-2-amino-alpha-D-glucopyranoside and methyl 4-O-(3-O-sulpho-beta-D-glucopyranosyluronic acid)-2-deoxy-2-amino-alpha-D-glucopyranoside, were prepared by de novo synthesis, and converted to the corresponding 2,5-anhydro-D-[1-3H]mannitol derivatives by deamination with nitrous acid followed by reduction with NaB3H4. The resultant labelled products were used as standards in the identification, by anion-exchange high-performance liquid chromatography (HPLC), of disaccharides generated by HNO2/NaB3H4 treatment of heparan sulphate isolated from human brain. The two standards, containing 2-O- and 3-O-sulphated glucuronic acid, respectively, were clearly separated by the HPLC procedure. Comparison with the deamination products derived from heparan sulphate showed that the mono-O-sulphated disaccharide species containing a sulphated glucuronic acid unit co-eluted with the 2-O-sulphated standard. The corresponding component isolated from other heparan sulphate preparations, or from heparin, also eluted at the same position. No disaccharide derived from heparin or heparan sulphate appeared at the elution position of the 3-O-sulphated standard. It is concluded that D-glucuronic acid units in heparin-related glycosaminoglycans may be sulphated at C2, whereas no evidence has been found for sulphation at C3. By contrast, analysis of mono-O-sulphated disaccharides derived from a chemically sulphated, bacterial capsular polysaccharide (generated by Escherichia coli K5) clearly demonstrated the occurrence of O-sulphate groups at C-3 of D-glucuronic acid units.

Carbohydrate Sequence↗
PubMed1995

Early diagnosis and exclusion of acute myocardial infarction using biochemical monitoring. The BIOMACS Study Group. Biochemicals Markers of Acute Coronary Syndromes.

BACKGROUND: The aim was to evaluate whether frequent analysis of creatine kinase MB (CK-MB), myoglobin and troponin T alone or in combination could either confirm or exclude acute myocardial infraction (AMI) within the first few hours after patients were admitted to hospital with chest pain and a non-diagnostic ECG. METHODS: One hundred and forty-two patients with chest pain (< or = 12 h) and a non-diagnostic ECG were included in the study. Blood samples were obtained every 30 min during the first 3 h and thereafter at longer intervals. Different discriminatory levels and combinations of markers were tested for their ability to detect (n = 59) or exclude (n = 83) AMI during the first 6 h after admission. RESULTS: No single marker adequately combined high early sensitivity and specificity. However, a combination of myoglobin and CK-MB analyses had a sensitivity at entry of 59%, which increased by 5-10% every 30 min and reached 92% after 2 h and 98% after 6 h with a specificity of 93%. A combination of myoglobin and troponin T analyses showed identical sensitivity but a slightly inferior specificity. In the patients with no AMI it was possible to exclude AMI in 64% within 3 h by using myoglobin and within 6 h in approximately 70% by using CK-MB or troponin T. CONCLUSIONS: Monitoring of a combination of myoglobin and CK-MB or troponin T will allow confirmation or exclusion of AMI within 3-6 h in almost all patients. This method will have a large impact on the handling of patients with suspected AMI without a diagnostic ECG.

Aged↗
PubMed1994

Hyperinsulinemia predicts low tissue plasminogen activator activity in a healthy population: the Northern Sweden MONICA Study.

Fibrinogen levels predict atherothrombotic disease, and impaired fibrinolysis has been proposed as a risk factor for myocardial infarction. Fibrinolysis is mainly dependent on the activity of tissue plasminogen activator (tPA) and its inhibitor plasminogen activator inhibitor type-1 (PAI-1). Oral glucose tolerance tests were performed in 318 randomly selected healthy men and 324 women aged 25 to 64 years. tPA activity was strongly predicted by fasting insulin in both univariate analysis (r = -.37 and -.34 in men and women, respectively) and multivariate analysis with age, anthropometric measurements, lipids, and blood pressure included. Fasting insulin was the strongest predictor of PAI-1 activity (r = .49 and .51). In women, the influence of fasting insulin level on tPA and PAI-1 activity was consistently stronger after than before menopause, and a threshold effect was seen with distinctly lower fibrinolytic activity in the highest quartile of insulin (> 7.0 mU/L). In men, the relation between insulin and fibrinolytic variables was linear. Fibrinogen levels were not related to insulin or glucose levels after adjustment for age and other risk factors in a multiple regression. Subjects with previously unknown diabetes or impaired glucose tolerance tended to have elevated fibrinogen and PAI-1 activity and decreased tPA activity. Our data support previous findings of a strong correlation between insulin and PAI-1 activity in small highly selected groups, and extend them to randomly selected population samples. The strong inverse relation between endogenous insulin levels and tPA activity has not previously been demonstrated in a healthy population.

Adult↗
PubMed1994

Five year survival rate in endometrial carcinoma stages I--II: influence of degree of tumour differentiation, age, myometrial invasion and DNA content.

OBJECTIVE: To compare the prognostic capability of clinical stage, tumour differentiation, myometrial invasion, age and DNA content in endometrial carcinoma. Then to use the results to identify a small, high risk group suitable for more intensive adjuvant therapy. DESIGN: A prospective five year follow up between June 1980 and June 1987. SETTING: Department of Oncology, gynaecological section, University Hospital, Lund, Sweden. Endometrial tissue was obtained immediately prior to treatment for flow cytometric DNA analysis. SUBJECTS: Two hundred and fifty-one patients referred for treatment. INTERVENTIONS: None. RESULTS: Age, myometrial invasion of greater than 50%, and number of DNA populations (ploidy) were the only significant parameters related to survival. By combining myometrial invasion and number of DNA populations, we divided the patients into four groups. A very small high risk group was identified (7%) with a low survival rate (61%). Two intermediate groups with either myometrial invasion exceeding 50% or with more than one DNA population present constituted 34% of the patients and these had an overall survival rate of 75% and a relatively large low risk group of 59% of the patients (with a survival rate of 95%) was constructed out of those without deep myometrial invasion and demonstrating only one DNA population. CONCLUSIONS: These data suggest that number of DNA populations and depth of myometrial invasion could be combined to identify a small high risk group (7%) with a low survival rate (61%) suitable for adjuvant therapy.

Adult↗