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Biomedical subjects

H Walter

Publications and source records attributed to H Walter.

At least 37 records · Page 2Linked to original sources

Frequency of genotypic and phenotypic drug-resistant HIV-1 among therapy-naive patients of the German Seroconverter Study.

Genotypic and phenotypic resistance of viral reverse transcriptase (RT) and protease (PR) was determined for 64 therapy-naive, HIV-1-infected seroconverters of the German Seroconverter Study coordinated by the Robert Koch-Institut, Berlin. The date of seroconversion of patients and the laboratory, clinical, and therapeutic follow-up data were documented. Samples were collected between 1996 and 1999. Phenotypic resistant HIV-1 were found in 8 (13%) seroconverters; in most cases resistance was weak and mainly directed against RT inhibitors (4 nucleoside reverse transcriptase inhibitors [NRTIs], 2 nonnucleoside reverse transcriptase inhibitors [NNRTIs], 1 combination NRTI/NNRTI). Only one infection with a weak PR inhibitor resistance was identified. Transmission of multidrug-resistant HIV-1 has not yet been observed. Frequently at least one or more amino acid mutations associated with antiretroviral drug resistance were detected by genotypic analysis. The mean number of resistance-associated mutations in the RT of the transmitted virus has increased significantly since 1996. Studies have shown the improved benefit of initial antiretroviral therapy if based on genotypic resistance data. In view of the considerably high level of transmission of resistant HIV-1 in Germany, which is also seen in other studies in Europe and the United States, we suggest determining the genotypic resistance pattern before starting therapy of newly HIV-1-infected patients.

Anti-HIV Agents↗

Enantio-selective cognitive and brain activation effects of N-ethyl-3,4-methylenedioxyamphetamine in humans.

In a randomised double-blind trial the subjective, neuropsychological and brain activation effects of the two enantiomers of the MDMA (ecstasy-) like drug N-ethyl-3,4-methylenedioxyamphetamine (MDE) were studied in five normal subjects using functional magnetic resonance imaging (fMRI). (S)-MDE produced elevated mood, impairments in conceptually driven cognition and marked right frontal activation. In contrast, (R)-MDE produced increased depression, enhanced visual feature processing, and activation of visual cortical and left frontal areas. Plasma concentrations were higher for the (R)-enantiomer. The so-called entactogenic effects of MDE are likely to be caused by the (S)-enantiomer, whereas (R)-MDE appears to be responsible for neurotoxic effects.

3,4-Methylenedioxyamphetamine↗

Sensitivity and specificity of carbohydrate-deficient transferrin in drinking experiments and different patients.

Information provided by patients about the amounts of alcohol they drink may often be too subjective and therefore unreliable. Because of the possible serious consequences of interactions between alcohol and medication, reliable laboratory test markers for alcohol consumption are needed. Carbohydrate-deficient transferrin (CDT) is at present the best available objective measure of drinking behavior. During a withdrawal trial, 92 alcohol-dependent patients who had been admitted to a hospital in an ethanol-intoxicated state were monitored over the following 28 days by using the percent carbohydrate-deficient transferrin (%CDT of total transferrin) (%CDT) method. At the time of admission, 63% showed elevated %CDT levels. After a subsequent period of abstinence, a decrease in %CDT levels was apparent in four different groups of patients, whereas in two groups, comprising the greatest number of patients, normal %CDT levels were evident after 14 days of abstinence. In patients whose CDT levels were very high at study initiation, it took at least 21 to 28 days--and sometimes longer--for CDT to decrease to the radioimmunoassay (RIA) %CDT test cutoff point of 2.5. In a further study of 56 male alcohol-dependent patients, we measured liver enzyme concentrations, mean corpuscular volume (MCV), and four CDT variants on the first day of evidence of withdrawal syndrome. We found a significant correlation between results on the Munich Alcoholism Test (MALT) and MCV levels; among gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels; and among all four CDT variants. A cluster analysis yielded three clusters: (1) GGT, AST, and ALT levels; (2) MCV levels and MALT results; and (3) all CDT measurement variants. We conclude that these three clusters measure different detriments to the patient and that all available CDT variants are commensurate.

Alcohol Drinking↗

Delusions in first-admitted patients: gender, themes and diagnoses.

Whether there is a specific link between certain delusional symptoms and particular etiologies has not yet been completely clarified. In this study, 639 first ever admitted deluded patients were investigated in order to find out whether age and gender are associated with certain delusional contents, whether age at first admission may be linked to certain etiologies and whether it is possible to detect indicators particularly related to basic dysfunctions. At first admission, delusional female patients were older than men with a significant predomination of delusions of persecution, while men presented significantly more frequently delusions of jealousy and grandiosity. Within delusions of persecution, of religious or metaphysical content and of grandiosity, women were even significantly older than men. Religious or metaphysical and grandiosity contents occurred significantly more frequently in ICD-8 schizophrenia, indicating that these themes seem to be particularly linked to ICD-8 schizophrenia. Additionally, some target symptoms not included in the delusional symptomatology were investigated to test the relationship between delusions and schizophrenia. Overall, the results of the present investigation indicate that delusions are not specific for schizophrenia, and therefore, other symptomatological criteria should be applied for the nosographic attribution.

Adolescent↗

[Management of hallucinating patients].

Hallucinations are perceptions lacking any extern or physical stimulus. They can affect all senses and may occur in the course of different physical or psychiatric diseases. Patients experiencing hallucinations may derive the conviction that the contents of their hallucinations and the consequent interpretations are real, therefore they may try to convince their relatives and friends. Thus it has proved helpful to follow certain rules in the treatment of these patients. It is important not only to diagnose the basic disorder or illness but also to deal with the patient's anxiety, respect his/her perceptions and to try to establish alternative models of explanation. Apart from therapy of the underlying disorder it is wise to recommend psychotherapy and the attendance of self-help groups.

Antipsychotic Agents↗

[Diagnosis and differential diagnosis of consciousness disorders from the psychiatric viewpoint].

Diagnosis and differential diagnosis of disturbance of consciousness are often difficult, especially when occurring in the course of psychiatric diseases. Apart from discord in defining the term of consciousness it is not always easy to distinguish between qualitative and quantitative alterations of the disorders. The performance of an exact interview and a thorough clinical examination allows an estimation of the degree of dimming of consciousness as well as the possible causes. Disorder of Consciousness is often found in patients carrying out substance abuse but also in the course of other psychiatric diseases such as depression, schizophrenia, personality disorders and dissociative disorders. This article is dealing with the clinical approach towards patients experiencing alterations or disturbances of consciousness and is also trying to communicate innovations in the field of psychiatric diagnostics.

Alcoholic Intoxication↗

[Allele sequences and population genetics of pentanucleotide tandem repeat D6S957].

OBJECTIVE: Pentanucleotide tandem repeat loci are useful markers of short tandem repeat (STR) for genetic analysis. We focused on the analysis of the DNA sequence for each allele at the pentanucleotide STR locus D6S957 in order to understand their structures in the human genome and to construct human allelic ladder, which is necessary for forensic DNA typing. In order to evaluate the forensic applicability of D6S957, we investigated the genotype distributions and allele frequencies in major ethnic groups. METHODS: A total of 230 samples from unrelated individuals were analyzed by PCR. Allele determination was carried out by comparison with a sequenced human allelic ladder made in-house. An example of each allele was sequenced on an ABI 377 automated sequencer. RESULTS: This pentanucleotide STR exhibited a minimal amount of stutter and provided easily interpretable results. Eight alleles were found in these populations. No evidence of deviation from Hardy-Weinberg equilibrium was observed. In 64 confirmed father/mother/child triplets no mutation events were observed. The mutation rate was indirectly estimated at 2.5 x 10(-5) using a maximum likelihood method. CONCLUSION: D6S957 is a useful marker for forensic casework and paternity analysis.

Alleles↗

[Results of an intensive training program for hypertension at the Institute for Preventive Medicine].

BACKGROUND AND OBJECTIVE: The burden of insufficiently treated arterial hypertension is still underestimated. During 1998 to 1999 we conducted an intensive training program in cooperation with regional practitioners. The aim of this program was to educate the patients about their disease and motivate them to comply with therapy. The effectivity of this program yet needs to be evaluated. PATIENTS AND METHODS: 146 patients (mean age 62 years; 57 male, 89 female) with arterial hypertension were trained. They received 8 training units of 90 min each. Before training and 6 months after training data concerning health status and life style risk factors were assessed with questionnaires. RESULTS: There was a marked reduction in blood pressure after 6 months (152/89 mmHg vs 145/85 mmHg, p < 0.001). The mean body weight also declined on the average by 0.9 kg (p < 0.001). Physical exercise spent per week increased from mean 2.0 to 2.8 hours (p < 0.01). Moreover, knowledge about hypertension increased (p < 0.001). The established questionnaire SF-36 revealed a better score for vitality (p < 0.05) six months after therapy than before. CONCLUSION: Our intensive training program of patients with arterial hypertension has profound effects on their systolic and diastolic blood pressure. It also motivates patients to change life style. Our data suggest that intensive training programs should be developed on a widespread basis.

Adult↗

Simple algorithm derived from a geno-/phenotypic database to predict HIV-1 protease inhibitor resistance.

BACKGROUND: Resistance against protease inhibitors (PI) can either be analysed genotypically or phenotypically. However, the interpretation of genotypic data is difficult, particularly for PI, because of the unknown contributions of several mutations to resistance and cross-resistance. OBJECTIVE: Development of an algorithm to predict PI phenotype from genotypic data. METHODS: Recombinant viruses containing patient-derived protease genes were analysed for sensitivity to indinavir, saquinavir, ritonavir and nelfinavir. Drug resistance-associated mutations were determined by direct sequencing. geno- and phenotypic data were compared for 119 samples from 97 HIV-1 infected patients. RESULTS: Samples with one or two mutations in the gene for the protease were phenotypically sensitive in 74.3%, whereas 83.6% of samples with five or more mutations were resistant against all PI tested. Some mutations (361, 63P, 71V/T, 771) were frequent both in sensitive and resistant samples, whereas others (241, 30N, 461/L, 48V, 54V, 82A/F/T/S, 84V, 90M) were predominantly present in resistant samples. Therefore, the presence or absence of a single drug resistance-associated mutation predicted phenotypic PI resistance with high sensitivity (96.5-100%) but low specificity (13.3-57.4%). A more specific algorithm was obtained by taking into account the total number of drug resistance-associated mutations in the gene for the protease and restricting these to certain key positions for the PI. The algorithm was subsequently validated by analysis of 72 independent samples. CONCLUSION: With an optimized algorithm, phenotypic PI resistance can be predicted by viral genotype with good sensitivity (89.1-93.0%) and specificity (82.6-93.3%). The reliability and relevance of this algorithm should be further evaluated in clinical practice.

Acquired Immunodeficiency Syndrome↗

Partitioning and concentrating biomaterials in aqueous phase systems.

Aqueous phase separation is a general phenomenon which occurs when structurally distinct water-soluble macromolecules are dissolved, above certain concentrations, in water. The number of aqueous phases obtained depends on the number of such distinct macromolecular species used. Aqueous two-phase systems, primarily those containing poly(ethylene glycol) and dextran, have been widely used for the separation of biomaterials (macromolecules, membranes, organelles, cells) by partitioning. The polymer and salt compositions and concentrations chosen greatly affect the physical properties of the phases. These, in turn, interact with the physical properties of biomaterials included in the phases and affect their partitioning. Specific extractions of biomaterials can be effected by including affinity ligands in the systems. The phase systems can also be used to obtain information on the surface properties of materials partitioned in them; to study interactions between biomaterials; and to concentrate such materials.

Animals↗

Consequences of phase separation in cytoplasm.

Solutions of structurally different macromolecules, when mixed, above certain concentrations, tend to phase separate. The high concentration and diversity of proteins present in the liquid phase of cytoplasm, together with the phenomena which accompany macromolecular crowding, appear to meet the requirements for multiphase separation. The resulting cytoplasmic phase compartments, bounded by interfaces and/or other intracellular surfaces, would provide a dynamic, three-dimensional organizational structure. Based on the known physicochemical properties of aqueous phase systems and the partitioning behavior of biomaterials in them, such an organization could account for numerous phenomena observed in cytoplasm, such as its microcompartmentation. Aqueous phase separation is an attractive model for the liquid phase of cytoplasm because it comprises not only a structure (phase compartments, interfaces) for constraining biomaterials but also a mechanism (partitioning) for translocating them to other sites.

Animals↗

Primary intracoronary stenting in acute myocardial infarction: long-term clinical and angiographic follow-up and risk factor analysis.

BACKGROUND: Coronary stent placement may be an effective primary intervention in acute myocardial infarction. Recently published or reported data indicate that primary stenting may be superior to primary plain balloon angioplasty in this setting. The aim of this study was to analyze the long-term clinical and angiographic follow-up of patients treated with primary intracoronary stenting and to identify the predictive factors of an adverse outcome. METHODS: The study population was composed of 519 consecutive patients with acute myocardial infarction (43 in cardiogenic shock) and attempted primary stent implantation. Adverse clinical events such as death, recurrent infarction, and target vessel revascularization were recorded. Six-month follow-up angiography was performed in 78.2% of the eligible patients, and coronary dimensions were assessed with an automated quantitative system. RESULTS: Procedural success was achieved in 500 patients (96.3%). The incidence of reocclusion was 3.2%. Thirty-day mortality rate was 5. 4% (2.5% in patients without shock); adverse clinical events were encountered in 10.4% of the patients. Independent risk factors for an adverse outcome were longer time to treatment, Killip class, reduced left ventricular function, overlapping stents, and residual dissection. The incidence of angiographic restenosis was 30.6%. One-year survival rate was 89.0%; 86.5% of the patients did not have a myocardial infarction and 71.7% did not have any major adverse event. CONCLUSIONS: Primary intracoronary stenting in patients with acute myocardial infarction is associated with a favorable early and long-term outcome. This is the result of low reocclusion and restenosis rates achieved by stenting.

Aged↗

Low level of cross-resistance to amprenavir (141W94) in samples from patients pretreated with other protease inhibitors.

The therapeutic success of an antiretroviral salvage regimen containing protease inhibitors (PI) is limited by PI-resistant viral strains exhibiting various degrees of resistance and cross-resistance. To evaluate the extent of cross-resistance to the new PI amprenavir, 155 samples from 132 human immunodeficiency virus type 1-infected patients were analyzed for viral genotype by direct sequencing of the protease gene. Concomitantly, drug sensitivity to indinavir, saquinavir, ritonavir, nelfinavir, and amprenavir was analyzed by a recombinant virus assay. A total of 111 patients had been pretreated with 1-4 PI, but all were naive to amprenavir. A total of 105 samples (67.7%) were sensitive to amprenavir; 25 samples (16.1%) were intermediately resistant, and another 25 samples were highly resistant (4- to 8-fold- and >8-fold-reduced sensitivity, respectively). The mutations 46I/L, 54L/V, 84V, and 90M showed the strongest association with amprenavir resistance (P < 0. 0001). The scoring system using 84V and/or any two of a number of mutations (10I/R/V/F, 46I/L, 54L/V, and 90M) predicted amprenavir resistance with a sensitivity of 86.0% and a specificity of 81.0% within the analyzed group of samples. Of 62 samples with resistance against 4 PI, 23 (37.1%) were still sensitive to amprenavir. In comparison, only 2 of 23 samples (8.7%) from nelfinavir-naive patients with resistance against indinavir, saquinavir, and ritonavir were still sensitive to nelfinavir. Amprenavir thus appears to be an interesting alternative for PI salvage therapy.

Carbamates↗