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Biomedical subjects

W Strauss

Publications and source records attributed to W Strauss.

At least 19 recordsLinked to original sources
PubMed2002

Out-patient behaviour therapy in alcoholism: treatment outcome after 2 years.

OBJECTIVE: The main aim of the study was the evaluation of out-patient behavioural approaches in alcohol dependence. Additionally, the persistence of treatment effects and the impact of psychiatric comorbidity in long-term follow-up was examined. METHOD: A total of 120 patients were randomly assigned to non-specific supportive therapy or to two different behavioural therapy programmes (coping skills training and cognitive therapy) each comprising 26 weekly sessions; the follow-up period lasted 2 years. RESULTS: Patients undergoing behavioural therapy showed a consistent trend towards higher abstinence rates; significant differences between the two behavioural strategies could not be established. Moreover, the results indicate a reduced ability of cognitive impaired patients to cope with short-time abstinence violations and at a reduced benefit from behavioural techniques for patients with severe personality disorders. CONCLUSION: Behavioural treatment yielded long-lasting effects and met high acceptance; yet, still in need of improvement is the development of specific programmes for high-risk patients.

Adult↗
PubMed2002

Quantitative radionuclide lymphoscintigraphy predicts outcome of manual lymphatic therapy in breast cancer-related lymphedema of the upper extremity.

Secondary lymphedema is a localized, acquired lymphatic microcirculatory disturbance that affects large numbers of patients after breast cancer therapy. There is a paucity of objective methods to quantitate lymphatic function and to anticipate the response to therapeutic interventions. We applied radionuclide lymphoscintigraphy to evaluate lymphatic transport and axillary lymph node visualization in women following breast cancer therapy to determine the utility of these data in these patients. Lymphoscintigraphy was performed after subcutaneous injection of 0.25 mCi of Tc-filtered sulfur colloid. Subcutaneous accumulation of radiotracer ('dermal backflow') and the visualization of axillary lymph nodes were graded using our own scoring system. The ratio of radioactivity within the affected to normal axillae (ARR) was also quantified. Nineteen patients with lymphedema after breast cancer therapy were evaluated. The disease severity was documented by serial measurements of the limb volume using the truncated cone formula. Responses to therapy were quantified after completion of the therapy. There was a correlation between the ARR and the percentage reduction in edema volume. The lymphoscintigraphic score correlated with the initial arm volume excess and with the durationof lymphedema. It can be concluded that quantitative and semi-quantitative assessment by radionuclide lymphoscintigraphy represents a potentially useful tool for the clinical assessment of upper extremity lymphedema.

Aged↗
PubMed2001

Increased production of apolipoprotein B-containing lipoproteins in the absence of hyperlipidemia in transgenic mice expressing cholesterol 7alpha-hydroxylase.

The finding that expression of a cholesterol 7alpha-hydroxylase (CYP7A1) transgene in cultured rat hepatoma cells caused a coordinate increase in lipogenesis and secretion of apoB-containing lipoproteins led to the hypothesis that hepatic production of apoB-containing lipoproteins may be linked to the expression of CYP7A1 (Wang, S.-L., Du, E., Martin, T. D., and Davis, R. A. (1997) J. Biol. Chem. 272, 19351-19358). To examine this hypothesis in vivo, a transgene encoding CYP7A1 driven by the constitutive liver-specific enhancer of the human apoE gene was expressed in C56BL/6 mice. The expression of CYP7A1 mRNA (20-fold), protein ( approximately 10-fold), and enzyme activity (5-fold) was markedly increased in transgenic mice compared with non-transgenic littermates. The bile acid pool of CYP7A1 transgenic mice was doubled mainly due to increased hydrophobic dihydroxy bile acids. In CYP7A1 transgenic mice, livers contained approximately 3-fold more sterol response element-binding protein-2 mRNA. Hepatic expression of mRNAs encoding lipogenic enzymes (i.e. fatty-acid synthase, acetyl-CoA carboxylase, stearoyl-CoA desaturase, squalene synthase, farnesyl-pyrophosphate synthase, 3-hydroxy-3-methylglutaryl-CoA reductase, and low density lipoprotein receptor) as well as microsomal triglyceride transfer protein were elevated approximately 3-5-fold in transgenic mice. CYP7A1 transgenic mice also displayed a >2-fold increase in hepatic production and secretion of triglyceride-rich apoB-containing lipoproteins. Despite the increased hepatic secretion of apoB-containing lipoproteins in CYP7A1 mice, plasma levels of triglycerides and cholesterol were not significantly increased. These data suggest that the 5-fold increased expression of the low density lipoprotein receptor displayed by the livers of CYP7A1 transgenic mice was sufficient to compensate for the 2-fold increase production of apoB-containing lipoproteins. These findings emphasize the important homeostatic role that CYP7A1 plays in balancing the anabolic lipoprotein assembly/secretion pathway with the cholesterol catabolic bile acid synthetic pathway.

Animals↗
PubMed2001

Out-patient behaviour therapy in alcoholism: relapse rates after 6 months.

OBJECTIVE: In spite of the increasing interest in out-patient treatment programmes for alcoholics, there still exist only a few experimental studies on this issue. In this still ongoing study the efficacy of different behaviour therapy strategies is to be examined. METHOD: One hundred and twenty patients were assigned randomly to non-specific supportive therapy or to two forms of behavioural therapy (coping skills training and cognitive therapy). Behavioural treatment comprised 26 weekly sessions; follow-up examinations will take place every 6 months over 2 years. RESULTS: Patients undergoing behavioural therapy showed less drop-outs and significantly higher rates of abstinence compared with supportive treatment. Nevertheless, statistically significant differences between the two behavioural therapy strategies could not be established so far. CONCLUSION: Preliminary results demonstrate the feasibility and efficacy of behaviour therapy programmes in the out-patient treatment of alcoholism. Furthermore, they stress the importance of professional psychiatric and psychotherapeutic engagement in the field of addiction.

Adult↗
PubMed2000

Tissue factor pathway inhibitor levels in patients with homocystinuria.

Thrombotic events are a well-recognized complication of homocystinuria. However, the mechanisms involved in the atherogenic and thrombotic effects of homocyst(e)ine remain incompletely understood. The objective of this study was to determine the role of endothelial cell activation/damage as indicated by levels of thrombomodulin, tissue factor and tissue factor pathway inhibitor, and factor VII activity in patients with homocystinuria. Six patients with homocystinuria, nonresponsive to pyridoxine, treated only with trimethylglycine (betaine) were injected with a bolus of 20 IU/kg body weight of unfractionated commercial heparin to induce the release of tissue factor pathway inhibitor from the vascular endothelium. Tissue factor, thrombomodulin, and factor VII activity were measured by enzyme-linked immunosorbent assay and clotting assay before heparin administration. Tissue factor pathway inhibitor antigen and activity were measured before and 5 minutes after the bolus of heparin. Levels of homocyst(e)ine were elevated (patients: 144.2+/-19.2 micromol/L; controls: 10.2+/-0.9 micromol/L); however, levels of thrombomodulin, tissue factor, and tissue factor pathway inhibitor antigen were not statistically different from the control group. In contrast, tissue factor pathway inhibitor activity showed a significantly increased level (patients: 2.09+/-0.34 U/L; controls: 1.14+/-0.20 U/L; p<0.05) that was correlated with homocyst(e)ine. Factor VII activity was significantly decreased (patients: 64.7+/-5.1%; controls: 91.4+/-4.7%; p<0.05) and inversely correlated with homocyst(e)ine. After heparin the patients released higher amounts of tissue factor pathway inhibitor antigen and activity compared with the control group; however, the difference was not statistically significant. Although not treated with antithrombotic drugs, none of the patients had any thromboembolic complications after starting betaine. In addition to betaine treatment, the enhanced factor pathway inhibitor antigen activity observed in this small series of patients suggests that factor pathway inhibitor antigen may play an additional, as yet unexplained, role in this genetic disorder.

Adult↗
PubMed2000

Regulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosine kinase.

BACKGROUND: Telomeres consist of repetitive (TTAGGG) DNA sequences that are maintained by the multisubunit telomerase ribonucleoprotein. Telomerase consists of an RNA, which serves as template for the sequence tracts, and a catalytic subunit that functions in reverse transcription of the RNA template. Cloning and characterization of the human catalytic subunit of telomerase (hTERT) has supported a role in cell transformation. How telomerase activity is regulated, however, is largely unknown. RESULTS: We show here that hTERT associates directly with the c-Abl protein tyrosine kinase. We also found that c-Abl phosphorylates hTERT and inhibits hTERT activity. Moreover, our findings demonstrate that exposure of cells to ionizing radiation induces tyrosine phosphorylation of hTERT by a c-Abl-dependent mechanism. The functional significance of the c-Abl-hTERT interaction is supported by the demonstration that cells deficient in c-Abl show telomere lengthening. CONCLUSIONS: The ubiquitously expressed c-Abl tyrosine kinase is activated by DNA double-strand breaks. Our finding of telomere lengthening in c-Abl-deficient cells and the functional interactions between c-Abl and hTERT support a role for c-Abl in the regulation of telomerase function.

Catalytic Domain↗
PubMed1999

Two-dimensional proton echo-planar spectroscopic imaging of brain metabolic changes during lactate-induced panic.

BACKGROUND: A fast, proton echo-planar spectroscopic imaging (PEPSI) technique, capable of simultaneously measuring metabolites from multiple brain regions, was used to investigate the anatomical distribution and magnitude of brain lactate responses to intravenous lactate infusion among subjects with panic disorder and control subjects. METHODS: Fifteen subjects with panic disorder and 10 control subjects were studied. All subjects were medication free and met DSM-IV criteria for panic disorder, or, for controls, no Axis I psychiatric disorder. Two-dimensional axial metabolite images having 1-cm3 spatial resolution were acquired at 61/2-minute intervals during 3 conditions: a 20-minute baseline, 20-minute 0.5-mol/L sodium lactate infusion, and 15-minute postinfusion period. RESULTS: Intravenous lactate infusion increased brain lactate levels throughout the axial brain section studied in all subjects. Panic-disordered subjects had significantly greater global brain lactate increases in response to lactate infusion. Lateralization of brain lactate response did not occur, nor were discrete regional loci of elevated lactate observed. Cerebrospinal fluid lactate changes corresponded to lactate changes in brain tissue. Severity of symptoms provoked by lactate infusion did not directly correlate with brain lactate response. CONCLUSIONS: Greater overall rises in brain lactate among subjects with panic disorder compared with controls occurred in response to lactate infusion. We were unable to detect a distinct regional pattern for magnitude differences in brain lactate rise by which to identify a specific neuroanatomical substrate underlying a lactate-induced panic response. The wide anatomical distribution of these brain lactate increases suggest metabolic and/or neurovascular mechanisms for the abnormal rise in subjects with panic disorder.

Adult↗
PubMed1999

The Northern Bolivian Altiplano: a region highly endemic for human fascioliasis.

The worldwide importance of human infection by Fasciola hepatica has been recognized in recent years. The endemic region between Lake Titicaca and the valley of La Paz, Bolivia, at 3800-4100 m altitude, presents the highest prevalences and intensities recorded. Large geographical studies involving Lymnaea truncatula snails (malacological, physico-chemical, and botanic studies of 59, 28 and 30 water bodies, respectively, inhabited by lymnaeids; environmental mean temperature studies covering a 40-year period), livestock (5491 cattle) and human coprological surveys (2723 subjects, 2521 of whom were school children) were conducted during 1991-97 to establish the boundaries and distributional characteristics of this endemic Northern Altiplano region. The endemic area covers part of the Los Andes, Ingavi, Omasuyos and Murillo provinces of the La Paz Department. The human endemic zone is stable, isolated and apparently fixed in its present outline, the boundaries being marked by geographical, climatic and soil-water chemical characteristics. The parasite distribution is irregular in the endemic area, the transmission foci being patchily distributed and linked to the presence of appropriate water bodies. Prevalences in school children are related to snail population distribution and extent. Altiplanic lymnaeids mainly inhabit permanent water bodies, which enables parasite transmission during the whole year. A confluence of several factors mitigates the negative effects of the high altitude.

Adolescent↗
PubMed1999

Human brain metabolic response to caffeine and the effects of tolerance.

OBJECTIVE: Since there is limited information concerning caffeine's metabolic effects on the human brain, the authors applied a rapid proton echo-planar spectroscopic imaging technique to dynamically measure regional brain metabolic responses to caffeine ingestion. They specifically measured changes in brain lactate due to the combined effects of caffeine's stimulation of glycolysis and reduction of cerebral blood flow. METHOD: Nine heavy caffeine users and nine caffeine-intolerant individuals, who had previously discontinued or substantially curtailed use of caffeinated products because of associated anxiety and discomforting physiological arousal, were studied at baseline and then during 1 hour following ingestion of caffeine citrate (10 mg/kg). To assess state-trait contributions and the effects of caffeine tolerance, five of the caffeine users were restudied after a 1- to 2-month caffeine holiday. RESULTS: The caffeine-intolerant individuals, but not the regular caffeine users, experienced substantial psychological and physiological distress in response to caffeine ingestion. Significant increases in global and regionally specific brain lactate were observed only among the caffeine-intolerant subjects. Reexposure of the regular caffeine users to caffeine after a caffeine holiday resulted in little or no adverse clinical reaction but significant rises in brain lactate which were of a magnitude similar to that observed for the caffeine-intolerant group. CONCLUSIONS: These results provide direct evidence for the loss of caffeine tolerance in the human brain subsequent to caffeine discontinuation and suggest mechanisms for the phenomenon of caffeine intolerance other than its metabolic effects on elevating brain lactate.

Adult↗
PubMed1999

Short report: Diagnosis of human fascioliasis: detection of anti-cathepsin L antibodies in blood samples collected on filter paper.

We have developed an ELISA for the diagnosis of human fascioliasis based on the detection of IgG4 antibodies to Fasciola hepatica cathepsin LI cysteine protease. Use of this assay in the Bolivian Altiplano, a region with a high prevalence of the disease, was hampered by the reluctance of the indigenous population to provide blood. To overcome this problem, we have investigated the method of collecting small quantities of blood from the finger onto filter paper, followed by the elution of antibodies for use in the diagnostic assay. Serum samples and blood samples collected onto filter paper were obtained from 57 individuals living in the village of Cutusuma in 1987 and from 11 individuals in Chijipata in 1996. Analysis of the IgG4-ELISA results revealed that there is highly significant linear relationship (P < 0.001) between the two methods of sampling. Most importantly, a reliable diagnosis was made with the blood-filter samples from Cutusuma, which had been stored for 10 years at 40 degrees C. While some deterioration of the blood-filter samples from Cutusuma had occurred over the 10-year storage period, no deterioration occurred with the Chijipata samples, which were stored for one year. Therefore, the method of collecting blood onto filter paper should prove useful for large-scale epidemiologic studies on human fascioliasis in the Bolivian Altiplano and in other regions where this disease is prevalent.

Animals↗
PubMed1999

Short report: Immunodiagnosis of human fascioliasis using recombinant Fasciola hepatica cathepsin L1 cysteine proteinase.

Our laboratory recently developed a diagnostic test (ELISA) for human fascioliasis based on the detection of serum IgG4 antibodies reactive with Fasciola hepatica cathepsin L1 (CL1). In the present study, we have used recombinant CL1, generated by functional expression of the cDNA in Saccharomyces cerevisiae, in this immunodiagnostic test and compared its performance with native CL1. Sera obtained from 64 individuals living in Cutusuma village in the northern Altiplano of Bolivia, a region with a high prevalence of human fascioliasis, were analyzed by the IgG4-ELISA. A highly statistically significant correlation (r2 = 0.751, P < 0.001) was demonstrated between the absorbances obtained using the recombinant and native proteins. These assays showed that 38 (59%) of the individuals tested were seropositive for fascioliasis, whereas only 26 of them were coprologically positive for F. hepatica eggs. All seronegative patients were also coprologically negative. Serum from individuals infected with schistosomiasis mansoni, cysticercosis, hydatidosis, and Chagas disease did not contain antibodies reactive with the recombinant or native CL1. Therefore, recombinant CL1 shows excellent potential for the development of the first standardized assay for the sensitive and specific diagnosis of human fascioliasis. Finally, our data supports earlier reports on the high prevalence of human fascioliasis in the Bolivian Altiplano, which collectively suggest that the disease has been endemic there for more than a decade.

Adolescent↗
PubMed1999

Dyslexic children have abnormal brain lactate response to reading-related language tasks.

BACKGROUND AND PURPOSE: Children with dyslexia have difficulty learning to recognize written words owing to subtle deficits in oral language related to processing sounds and accessing words automatically. The purpose of this study was to compare regional changes in brain lactate between dyslexic children and control subjects during oral language activation. METHODS: Brain lactate metabolism was measured during four different cognitive tasks (three language tasks and one nonlanguage task) in six dyslexic boys and in seven control subjects (age- and IQ-matched right-handed boys who are good readers) using a fast MR spectroscopic imaging technique called proton echo-planar spectroscopic imaging (1-cm3 voxel resolution). The area under the N-acetylaspartate (NAA) and lactate peaks was measured to calculate the lactate/NAA ratio in each voxel. RESULTS: Dyslexic boys showed a greater area of brain lactate elevation (2.33+/-SE 0.843 voxels) as compared with the control group (0.57+/-SE 0.30 voxels) during a phonological task in the left anterior quadrant. No significant differences were observed in the nonlanguage tasks. CONCLUSION: Dyslexic and control children differ in brain lactate metabolism when performing language tasks, but do not differ in nonlanguage auditory tasks.

Aspartic Acid↗
PubMed1998

Immunodiagnosis of Fasciola hepatica infection (fascioliasis) in a human population in the Bolivian Altiplano using purified cathepsin L cysteine proteinase.

Cathepsin L1 (CL1), an immunogenic cysteine proteinase secreted by juvenile and adult Fasciola hepatica, was assessed for its potential as a diagnostic agent for the serologic detection of human fascioliasis. Using ELISAs, we compared the ability of liver fluke homogenates (LFH), excretory/secretory (ES) products, and CL1 to discriminate between seropositive (infected) and seronegative (noninfected) individuals within a population of 95 patients from the Bolivian Altiplano. A high prevalence of human fascioliasis has been reported in this region. The division between the seropositive and seronegative individuals was poorly defined when LFH was used as the antigen. A greater discrimination between these populations was achieved with both ES and CL1. A K-means cluster analysis using the combined ES and CL1 ELISA data identified a cluster of seropositive individuals. Cathepsin L1 detected a subset (20) of these seropositive individuals while ES detected all 26; however, ES detected nine additional individuals that were in the seronegative cluster. The ratio of the mean absorbance readings between seropositive and seronegative individuals was markedly improved by using conjugated second antibodies to IgG4, the predominant isotype elicited by infection. In these IgG4-ELISAs, CL1 again identified fewer individuals as seropositive than did ES, but improved the discrimination between the seropositive and seronegative individuals and thus provided a more conclusive diagnosis. Sera obtained from patients infected with schistosomiasis mansoni, cysticercosis, hydatidosis, and Chagas' disease were negative in these assays, which demonstrated the specificity of the IgG4-ELISA for detecting fascioliasis. Twenty of the 95 patients (21%) were seropositive for fascioliasis by the CL1 IgG4-ELISA, confirming the earlier reports of the high prevalence of disease in this region. A standardized diagnostic test for human fascioliasis, based on an ELISA that detects IgG4 responses to CL1, could be available to all diagnostic centers if sufficient quantities of recombinant CL1 can be produced.

Adolescent↗
PubMed1998

High Cryptosporidium prevalences in healthy Aymara children from the northern Bolivian Altiplano.

The prevalence of Cryptosporidium infection was determined in four Aymara communities in the Bolivian Altiplano, between the city of La Paz and Lake Titicaca, at an altitude of 3,800-4,200 meters. Single stool specimens were randomly collected from 377 5-19-year-old students, all apparently asymptomatic. The total prevalence (31.6%) is possibly the highest reported among healthy humans (a maximum of 9.8% and 2.0% in coprologic surveys in underdeveloped and developed countries, respectively) and one of the highest even in symptomatic subjects. No significant age and sex differences were observed. Such an infection prevalence is probably related to the poor sanitation conditions, contaminated water supplies, overcrowding, and close contact with domestic animals. Continuous exposure to the parasite could be associated with protection against parasite-related symptoms in the children examined.

Adolescent↗
PubMed1997

Single-voxel 1H-MRS investigation of brain metabolic changes during lactate-induced panic.

Intravenous sodium lactate infusion is a robust laboratory technique for eliciting panic in susceptible individuals. The objective for this study was to replicate previous work which found differential brain lactate rises among lactate-sensitive panic subjects relative to control subjects using single-voxel 1H-magnetic resonance spectroscopy (MRS). Single-voxel 1H-MRS was used to measure brain lactate changes in the insular cortex region among 13 panic disorder subjects and 10 healthy control subjects during the infusion. One panic subject prematurely terminated the study due to a panic response during lactate infusion. Data from two additional control subjects and one panic subject were lost due to technical problems. Four panic subjects were reinfused with lactate while panic-free under treatment with fluoxetine (20 mg/day). At the time of initial infusion, all subjects were medication-free for at least 1 month. Ten panic subjects, but no control subjects, panicked during lactate infusion. In comparison to control subjects, panic subjects demonstrated significantly greater and prolonged brain lactate rises in the insular cortex region. Three of four medicated panic subjects experienced blockage of panic symptoms during lactate reinfusion but all exhibited persistent excesses in brain lactate rise. Consistent with our prior observations, greater and prolonged lactate rises in the insular brain region occur during and following lactate infusion among panic subjects compared to control subjects. This differential brain metabolic response did not appear to normalize when a small subset of panic patients were reinfused following resolution of panic symptoms during treatment over 3-4 months with fluoxetine.

Adult↗
PubMed1997

Presence of very high prevalence and intensity of infection with Fasciola hepatica among Aymara children from the Northern Bolivian Altiplano.

Coprological studies of school children from four communities in the Northern Bolivian Altiplano were carried out in order to estimate the prevalences and intensities of Fasciola hepatica infection. Single stool specimens were collected at random from 558 school children (308 boys and 250 girls) aged 5-19 years old. Nineteen different parasite species (13 protozoan and six helminths) were detected. Of the children examined, 98.7% (96.5-100%) presented infection with at least one parasite species. The mean prevalence of 27.6% by Fasciola hepatica (range, 5.9-38.2%) was the highest not only with respect to the helminth species found in the Northern Bolivian Altiplano but also among the fasciolosis prevalences reported in children in other parts of the world to date. Prevalences were significantly different among the communities surveyed and was significantly higher in the 9-12 years age group. There were, however, no significant differences between sexes. Among the 154 children presenting F. hepatica eggs in stools, intensities ranged from 24-5064 eggs per gram of faeces (epg), with arithmetic and geometric means of 474 and 201 epg, respectively. Significant differences in mean egg output were detected between communities, sexes and age groups. Individual fasciolosis infections coexisting with other pathogenic parasite species (Entamoeba histolytica and/or E. dispar, Giardia intestinalis, Balantidium coli, Dientamoeba fragilis, Cryptosporidium sp., Hymenolepis nana, Taenia spp., Trichuris trichiura, Ascaris lumbricoides and Enterobius vermicularis) were detected. A significant positive association with F. hepatica was only found in the case of G. intestinalis. This coprological study not only verifies the existence of high prevalences of F. hepatica among humans in the Northern Bolivian Altiplano, but also demonstrates the need to expand the Southern boundaries of this high endemic zone to include the Southeastern region of Lake Titicaca.

Adolescent↗