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Biomedical subjects

H Walter

Publications and source records attributed to H Walter.

At least 91 records · Page 5Linked to original sources

Reduction of monocyte-platelet interaction and monocyte activation in patients receiving antiplatelet therapy after coronary stent implantation.

BACKGROUND: Monocyte activation induces different procoagulant and proadhesive inflammatory responses and thus may play a role in thrombotic complications after coronary interventions. Monocyte-platelet interaction may trigger these effects inducing monocyte activation. AIMS: To characterize the effect of antiplatelet vs anticoagulation therapy on monocyte-platelet interaction and monocyte function after intracoronary stenting. METHODS AND RESULTS: Immediately before, and during the first 12 days after successful coronary stenting, monocyte-platelet conjugates and monocyte function were assessed by flow cytometric detection of GPIIb/IIIa (CD41) on monocytes and by monocyte surface exposure of Mac-1 (CD11b/CD18) and L-selectin (CD62L). Twenty patients receiving combined antiplatelet therapy (ticlopidine, aspirin) were compared to 20 patients with standard anticoagulation (phenprocoumon, overlapping heparin, aspirin). Before stenting, monocyte-platelet conjugates and Mac-1 surface expression in both groups were significantly increased, while L-selectin was significantly diminished. Anticoagulation did not change these variables significantly during the subsequent 12 days. In contrast, antiplatelet therapy reduced platelet-monocyte conjugates by 46 +/- 9.3% (mean +/- SEM, P = 0.0019) within 4 days, which was associated with a decrease in Mac-1 expression (28 +/- 6.7%, P = 0.0013) and an increase in L-selectin (56 +/- 15.0%, P = 0.0061). CONCLUSION: After intracoronary stenting, combined antiplatelet therapy, but not anticoagulation, causes reduction of monocyte-platelet interaction, which is associated with monocyte deactivation. This may contribute to a decreased risk for thrombotic events.

Adult↗

Genetic studies in Medzev, an isolate in south-eastern Slovakia. 2. Distribution of blood group genetic markers.

Phenotype and gene frequencies of three blood group, four serum protein and seven red cell enzyme polymorphisms were examined in 105 individuals from the population of Medzev, South-Eastern Slovakia. Locus and allele specific tests of homogeneity were calculated in order to obtain the pattern of variation. The results indicate considerable genetic differences between this population and another local population of this region (Chmelnica) as well as between the Medzev population and the total population of Slovakia. The possible reasons of the genetic heterogeneity within Slovakia are discussed.

Analysis of Variance↗

Comparison of acamprosate and placebo in long-term treatment of alcohol dependence.

BACKGROUND: About 50% of alcoholic patients relapse within 3 months of treatment. Previous studies have suggested that acamprosate may help to prevent such relapse. The aim of our study was to assess the efficacy and safety of long-term acamprosate treatment in alcohol dependence. METHODS: In this multicentre, double-blind, placebo-controlled study, we recruited 455 patients, aged 18-65 years, with chronic or episodic alcohol dependence. Patients were randomly allocated treatment with acamprosate (1998 mg daily for bodyweight > 60 kg; 1332 mg daily for < or = kg) or placebo for 360 days. Patients were assessed on the day treatment started and on days 30, 90, 180, 270, and 360 by interview, self-report, questionnaire, and laboratory screening. Patients were classified as abstinent, relapsing, or non-attending. Time to first treatment failure (relapse or non-attendance) was the primary outcome measure. FINDINGS: Seven patients were excluded from the intention-to-treat analysis because they did not attend on the first treatment day and therefore received no medication. The acamprosate (n = 224) and placebo (n = 224) groups were well matched in terms of baseline demographic and alcohol-related variables. 94 acamprosate-treated and 85 placebo-treated patients completed the treatment phase: of those withdrawn, 104 (52 in each group) relapsed, 69 (33 vs 36, respectively) were lost to follow-up, 63 (31 vs 32) refused to continue treatment, 16 (15 vs 11) had concurrent illness, three (two vs one) died, ten (six vs four) had adverse side-effects, one (acamprosate treated) received the wrong medication, and three (placebo treated) were non-compliant. The proportion without treatment failure was higher in the acamprosate than in the placebo group throughout the treatment period (p < 0.001, Mantel-Cox). At the end of treatment, 41 (18.3%) acamprosate-treated and 16 (7.1%) placebo-treated patients had been continuously abstinent (p = 0.007). Mean cumulative abstinence duration was significantly greater in the acamprosate group than in the placebo group (138.8 [SD 137.5] vs 103.8 [119.0] days; p = 0.012). 148 patients (79 acamprosate, 69 placebo) completed 27 months follow-up: 27 (11.9%) acamprosate-treated and 11 (4.9%) placebo-treated patients remained continuously abstinent, and the mean cumulative abstinence duration was 230.8 days (259.1) and 183.0 days (235.2), respectively. Apart from occasional diarrhoea, there was no difference in side-effects between groups. INTERPRETATION: Acamprosate is an effective and well-tolerated pharmacological adjunct to psychosocial and behavioural treatment programmes for treatment of alcohol-dependent patients.

Acamprosate↗

Surface properties of irreversibly sickled cells differ from those of the bulk of sickle cells. Studies by partitioning in aqueous phase systems.

Counter-current distribution (CCD) of red blood cells (RBC) from individuals with homozygous sickle cell (HbSS) disease in a charge-sensitive aqueous dextran-poly(ethylene glycol) phase system, which fractionates cells on the basis of surface properties, indicates that the percentage of irreversibly sickled cells (ISC) increases and the percentage of reticulocytes decreases with increasing cell partition ratios. The high partition ratios of ISC correspond to those of older RBC when RBC from normal individuals are subjected to CCD. Our results thus indicate that ISC differ in surface properties from those of the bulk of sickle RBC (including reticulocytes) in the population and that the difference is, most likely, charge-related. While the question as to whether ISC are indeed old cells has not yet been unequivocally answered, this view finds support in the fact that the independent parameters of ISC surface properties, as reflected by partition ratios, and densities correlate as they do in older RBC from normal individuals.

Cell Separation↗

A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents.

BACKGROUND: The clinical benefit of coronary-artery stenting performed in conjunction with coronary angioplasty is limited by the risk of thrombotic occlusion of the stent as well as hemorrhagic and vascular complications of intensive anticoagulation. We compared antiplatelet therapy with conventional anticoagulant therapy with respect to clinical outcomes 30 days after coronary-artery stenting. METHODS: After successful placement of Palmaz-Schatz coronary-artery stents, 257 patients were randomly assigned to receive antiplatelet therapy (ticlopidine plus aspirin) and 260 to receive anticoagulant therapy (intravenous heparin, phenprocoumon, and aspirin). The primary cardiac end point was a composite measure reflecting death from cardiac causes or the occurrence of myocardial infarction, aortocoronary bypass surgery, or repeat angioplasty. The primary noncardiac end point comprised death from noncardiac causes, cerebrovascular accident, severe hemorrhage, and peripheral vascular events. RESULTS: Of the patients assigned to antiplatelet therapy, 1.6 percent reached a primary cardiac end point, as did 6.2 percent of those assigned to anticoagulant therapy (relative risk, 0.25; 95 percent confidence interval, 0.06 to 0.77). With antiplatelet therapy, there was an 82 percent lower risk of myocardial infarction than in the anticoagulant-therapy group, and a 78 percent lower need for repeat interventions. Occlusion of the stented vessel occurred in 0.8 percent of the antiplatelet-therapy group and in 5.4 percent of the anticoagulant-therapy group (relative risk, 0.14; 95 percent confidence interval, 0.02 to 0.62). A primary noncardiac end point was reached by 1.2 percent of the antiplatelet-therapy group and 12.3 percent of the anticoagulant-therapy group (relative risk, 0.09; 95 percent confidence interval, 0.02 to 0.31). Hemorrhagic complications occurred only in the anticoagulant-therapy group (in 6.5 percent). An 87 percent reduction in the risk of peripheral vascular events was observed with antiplatelet therapy. CONCLUSIONS: As compared with conventional anticoagulant therapy, combined antiplatelet therapy after the placement of coronary-artery stents reduces the incidence of both cardiac events and hemorrhagic and vascular complications.

Aged↗

Pupillary dilatation test and Fourier analysis of pupillary oscillations in patients with multiple sclerosis.

Recently we investigated 29 patients aged between 31 and 60 years with multiple sclerosis by means of two new techniques. The first technique was based on pupillary dilatation response to the topical application of the cholinergic antagonist tropicamide. The second technique was the Fourier analysis of pupillary oscillations for measurement of central activation, carried out without and under the influence of a cognitive task. The multiple sclerosis group had a pupillary dilatation of 31.9% after 40 min. Under the influence of a cognitive task the patient group revealed lower amplitudes of pupillary oscillations reflecting a decreased capacity for cognitive activation.

Adult↗

The inhibitory effect of pentamidine on the production of chemotactic cytokines by in vitro stimulated human blood cells.

Pentamidine is an antiprotozoal drug with additional antiinflammatory activities that are not well understood. We now report that pentamidine inhibited the human whole blood production of the chemotactic cytokines (chemokines) interleukin (IL)-8, growth related gene alpha (GRO alpha) and monocyte chemotactic protein-1 (MCP-1). The title compound dose-dependently suppressed the lipopolysaccharide (LPS)- and phytohemagglutinin (PHA)-stimulated whole blood generation of these chemokines with IC50-values of 2.1 and 2.2 microM (IL-8), 2.4 and 1.8 microM (GRO alpha) and 2.8 and 2.4 microM (MCP-1). The inhibition was specific: when tested at 10 microM, pentamidine had no significant inhibitory effect on the PHA-induced generation of the non-chemotactic cytokines tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, IL-2, IL-4, IL-5, IL-10 and interferon-gamma (IFN-gamma), except for a partial inhibition on IL-6. Time course experiments indicated that pentamidine (10 microM) retained its ability to inhibit PHA-stimulated IL-8 production even when its addition was delayed for up to 24h after mitogen stimulation. Furthermore, reverse transcription PCR studies showed that pentamidine had no effect on IL-8 mRNA expression. These findings indicate that pentamidine is a post-transcription acting inhibitor of human chemokine production. This activity may contribute to the anti-inflammatory action ascribed to the title compound.

Anti-Inflammatory Agents, Non-Steroidal↗

Association between the PI*M3 allele of alpha 1-antitrypsin and Alzheimer's disease? A preliminary report.

The deposition of beta A4-amyloid in senile plaques in the brain and small cerebral vessels is one of the pathological hallmarks of Alzheimer's disease (AD). Serine protease inhibitors (serpins) such as alpha 1-antitrypsin and alpha 1-antichymotrypsin have been found to be associated with beta-amyloid deposits; interest in their role in the pathogenesis of AD has therefore recently increased. We have analyzed alpha 1-antitrypsin phenotypes in a sample of 29 Polish patients with probable Alzheimer's disease. We have found an increased frequency of the PI*M3 allele (0.1897) in patients in comparison with the general population control (0.0563).

Adult↗

Carbohydrate-deficient transferrin as a screening marker for drinking in a general hospital population.

We investigated the usefulness of the laboratory marker of alcohol consumption carbohydrate-deficient transferrin (CDT) in 101 consecutively admitted patients in a surgical and internal medical ward of a hospital in a rural wine-growing area. Four major aspects were considered: the influence of liver disease, the method of expression of CDT values (relative % vs absolute units/1), level and pattern of alcohol consumption and comparison with y-glutamyl transferase (GGT). The results show that %CDT is a more valuable discriminating marker of high alcohol consumption than absolute CDT values and its usefulness in this respect is independent of changes in serum total transferrin levels, as in liver disease. Sensitivity and specificity of % CDT were 70 and 98% respectively, compared with 65 and 83% respectively for GGT.

Adult↗

Alcohol dependence: is carbohydrate-deficient transferrin a marker for alcohol intake?

We investigated %CDT (carbohydrate-deficient transferrin) in 92 ethanol-intoxicated alcohol-dependent patients after consecutive admission to hospital and followed the for 28 days under controlled conditions. At admission, 63% (58 patients) showed elevated CDT (> 2.5%) and 34 patients (37%) had normal CDT levels (< 2.5%). No correlation of the %CDT values to alcohol-related disabilities, severity of the withdrawal syndrome, alcohol-drinking pattern before admission, or several other factors was found. The sensitivity of GGT (gamma-glutamyl transferase) was 58% for the same group of patients. Levels of %CDT decreased during the 28 days following abstinence, whereby we could separate four statistically different groups of "CDT decrease'. In two of these groups, comprising most of the cases studied, normal %CDT levels were reached after 14 days of abstinence. Those patients with %CDT levels exceeding the upper normal level after 14 days of sobriety, showed a decrease during the following 14 days to levels of 2.55-2.61%.

Adult↗

Carbohydrate-deficient transferrin as a marker of alcohol intake: a study with healthy subjects.

This paper reports the results of a 3-week drinking experiment in 51 healthy male subjects, examining the value of %CDT (carbohydrate-deficient transferrin) in the context of different levels of alcohol intake. All healthy persons were urine-tested drug-free and underwent daily breath alcohol tests for the 7 days preceding, and during the whole 3 weeks of, the experiment. Subjects were divided into five groups, consuming different amounts of alcohol daily over a 3-h period in the presence of the investigators. The five groups consisted of 10, 9, 10, 16 and 6 subjects respectively and consumed a daily dose of ethanol of 20, 40, 60, 80 and 80 g respectively for 3 weeks. No significant changes in %CDT were detected in most subjects, even in the 80 g alcohol-consuming groups. The results suggest that CDT is not sensitive for the detection of short-term heavy drinking by healthy subjects.

Adult↗

Coronary Palmaz-Schatz stent implantation in acute myocardial infarction.

OBJECTIVE: To investigate the feasibility of coronary stenting in acute myocardial infarction. DESIGN: Prospective observational study. PATIENTS: 80 patients undergoing direct balloon angioplasty for acute myocardial infarction who had coronary Palmaz-Schatz stents implanted during a 3 year study period. Indications for stenting were abrupt reocclusion, large dissection with threatened reocclusion, and failure to achieve brisk flow of contrast by angioplasty alone. INTERVENTIONS: After stenting, 50 patients were treated by conventional anticoagulation and 30 patients received antiplatelet therapy with aspirin and ticlopidine. MAIN OUTCOME MEASURES: Death and subacute reocclusion within two weeks. RESULTS: Coronary stenting fully restored vessel patency in 79 patients (98.8%). 10 of 14 patients with symptoms of Killip class IV on admission were discharged from hospital alive. Three of the 66 patients with symptoms of Killip classes I-III died in hospital. Repeat angiography in 59 of these patients, showed 3 symptomatic and 2 silent reocclusions (reocclusion rate 8.5%). No stent thromboses were detected in patients treated with ticlopidine. CONCLUSIONS: Coronary stenting is a safe and effective treatment for complicated direct balloon angioplasty in acute myocardial infarction. In patients with symptoms of Killip classes I to III the risk of subacute reocclusion is comparable to that of bail-out stenting after elective balloon angioplasty.

Adult↗

New 'state' markers for the detection of alcoholism.

Specific laboratory tests can be used to identify patients who are alcohol-dependent. The laboratory values of a number of biological 'markers', including carbohydrate-deficient transferrin, are often elevated in cases of chronic and acute alcohol abuse. Trait markers reflect a predisposition for alcoholism; state markers reflect actual alcohol consumption. It has been suggested that state markers can be subdivided into screening and relapse markers, and even further subdivided into pre-relapse markers, i.e. craving markers. We hypothesize that methanol metabolism and the presence of condensation products in the blood may serve as state and pre-relapse markers for alcoholism. Since the sensitivities and specificities of laboratory screening tests vary, and an absolute marker for alcoholism has yet to be identified, research in the area of biological markers for alcoholism should continue.

Alanine Transaminase↗

Subtypes of alcoholism and their role in therapy.

In recent years, the term 'chronic alcoholism' has had a meaning that is more descriptive than diagnostic. Several subtypes of alcoholism have been established and are now a necessary tool for studying therapy outcome. Alcohol-dependent patients can be subtyped based on clearly assigned dimensions (e.g. biological, sociological and psychological disturbances). Craving and the underlying disturbance must be treated. The number of pharmacological agents that may reduce alcohol intake has increased recently. We conducted a prospective long-term study based on four subtypes of alcohol-dependent patients to assess the efficacy of acamprosate. Our findings demonstrate that these patient subtypes are relevant to outcome in trials of pharmacological agents. We strongly recommend subtyping alcohol-dependent subjects in future trials, because the usefulness of effective drugs could be overlooked when they are tested in a heterogeneous population.

Acamprosate↗

Genetic studies in Medzev, an isolate in south-eastern Slovakia. 1. History, demography, marriage patterns.

In Medzev, a village located in South-Eastern Slovakia, the secular variation of two indices of genetic isolation has been studied. It could be seen that this village was highly isolated till the beginning of the 20th century. Both indices show a tendency to increase in the first five decades of this century. For the entire period from 1766-1950 the coefficient of inbreeding estimated by the method of isonymy was found to be F = 0.0074 with different ratios of random (Fr) and non-random (Fn) components in particular periods. The coefficient of inbreeding estimated from the ecclesiastical dispensations for marriages comes to F = 0.0019. The genetic significance of the changes in the population structure of this village will be analyzed in further studies.

Ethnicity↗

Population structure and genetic differentiation among 16 tribal populations of central India.

Genetic polymorphisms for six blood groups, three red cell enzymes, three serum proteins, and hemoglobin were examined in sixteen central Indian tribal populations. Nine of the tribes belonged to Orissa, five to Madhya Pradesh, and two to Maharashtra. Eleven tribes spoke the Dravidian language, three Indo-Ayran, and two the language of the Austro-Asiatic families. The population structure of these tribal populations was analyzed at the inter- and intrastate and linguistic levels, using data for 13 genetic systems (38 alleles or haplotypes). Nine of the 13 loci showed significant heterogeneity in the 16 tribes, and the pattern of heterogeneity was also discernible in the different states and in the Dravidian-speaking tribes. As expected, the extent of genetic differentiation or gene diversity was the highest so far reported from central India. The mean FIS and HS for each locus in the different state, linguistic, and total tribal groups were consistently higher than the FST and GST values, respectively, showing that the genetic structure of each tribe is highly influenced by inbreeding. In a genetic affinity analysis by genetic distance the Indo-Aryan and Austro-Asiatic language groups showed little affinity with each other, although there was some tendency toward geographic affinity. The present analysis indicates that, in addition to genetic drift, gene flow, and selection, the genetic structure of the populations of central India is also highly influenced by sociocultural adaptation and inbreeding.

Ethnicity↗

New 'state' markers for the detection of alcoholism.

Specific laboratory tests can be used to identify patients who are alcohol-dependent. The laboratory values of a number of biological 'markers', including carbohydrate-deficient transferrin, are often elevated in cases of chronic and acute alcohol abuse. Trait markers reflect a predisposition for alcoholism; state markers reflect actual alcohol consumption. It has been suggested that state markers can be subdivided into screening and relapse markers, and even further subdivided into pre-relapse markers, i.e. craving markers. We hypothesize that methanol metabolism and the presence of condensation products in the blood may serve as state and pre-relapse markers for alcoholism. Since the sensitivities and specificities of laboratory screening tests vary, and an absolute marker for alcoholism has yet to be identified, research in the area of biological markers for alcoholism should continue.

Alcohol Drinking↗