Biomedical subjects

A Richter

Publications and source records attributed to A Richter.

At least 127 records · Page 7Linked to original sources

PubMed2000

Effect of a comprehensive infection control program on the incidence of infections in long-term care facilities.

BACKGROUND: Control of infection within the long-term care facility is a daunting problem. Elderly patients are at high risk for contracting infection because of reduced innate immunity, malnutrition, and the presence of chronic medical conditions. This small study tested the effect of developing and implementing a comprehensive preventive infection control program in the long-term care setting and examined the resultant incidence of infections. METHODS: Eight private, freestanding, long-term care facilities in urban and suburban settings were selected for the study. The 4 test sites had a total of 443 beds; there were 447 beds in 4 matched control sites. Data on infection rates were accrued in both preintervention and intervention years. The control homes maintained their existing infection control policies and procedures. The test homes were provided with an infection control educational program and replaced all currently used germicidal products with single-branded products for a 12-month period. A criteria-based standardized infection control surveillance system was used to monitor and report infections in all facilities. RESULTS: In the preintervention year, the test sites experienced 743 infections (incidence density rate, 6.33) and the control homes experienced 614 infections (incidence density rate, 3.39). In the intervention year, the test homes reported 621 infections, a decrease of 122 infections (incidence density rate, 4.15); in the control homes, the number of infections increased slightly, to 626 (incidence density rate, 3.15). The greatest reduction in infections in the test homes was in upper respiratory infections (P =.06). CONCLUSIONS: This study provides additional evidence that a comprehensive infection control program that includes handwashing and environmental cleaning and disinfecting may help reduce infections among the elderly residing in long-term care settings.

Age Distribution↗

PubMed2000

A microdialysis study of striatal dopamine release in the circling rat, a genetic animal model with spontaneous lateralized rotational behavior.

The circling rat is an autosomal recessive mutant (homozygous ci2/ci2) that displays lateralized circling behavior, locomotor hyperactivity, hyperexcitability, ataxia, and stereotypic head-movement. These abnormal behaviors are induced or intensified by stress. Heterozygous (ci2/+) littermates display normal spontaneous behaviors. We have previously found that ci2 rats of both genders have a lower tissue content of dopamine in the striatum ipsilateral to the preferred direction of rotation, indicating that the rats turn away from the brain hemisphere with higher striatal dopaminergic activity. For further evaluation as to whether the spontaneous turning behavior of the mutant rats results from specific disturbances within the nigrostriatal circuitry, we used microdialysis in freely moving mutant rats and their unaffected littermates to measure extracellular levels of dopamine and its metabolites in the striatum of both hemispheres. Rats were habituated to the experimental procedures, so that mutant animals behaved as normal during a first phase of microdialysis ("rest phase"), which was followed by a "stress phase" with induction of lateralized circling by handling-stress. During rest, no significant imbalance in striatal dopamine release was observed in mutant rats, their unaffected littermates, and a second control group consisting of normal, unaffected rats from the same Lewis/Ztm strain. Stress induced a significant increase in dopamine release in the contralateral striatum of mutant rats of both genders, whereas no significant alterations in dopamine release were seen in either the left or right striatum of control groups. When amphetamine (100 or 500 microM) was added to the perfusion medium, the evoked dopamine release in the contralateral striatum of female mutant rats was significantly higher than that in the ipsilateral striatum, whereas no such asymmetry was observed in male mutants or unaffected female and male controls. The data further substantiate that mutant circling rats possess a genetically mediated dysfunction of the central dopaminergic system, but it remains to be determined whether neurochemical disturbances in other regions contribute to the behavioral phenotype of the ci2 rat. The continued study of this mutant may provide important new insights into the anatomical, neurochemical and molecular basis of hyperkinetic motor syndromes and other disorders related to dopaminergic dysfunction.

Amphetamine↗

PubMed2000

Evidence for striatal dopaminergic overactivity in paroxysmal dystonia indicated by microinjections in a genetic rodent model.

Mutant dystonic hamsters (dt(sz)), a model of primary paroxysmal dystonia, display attacks of generalized dystonia in response to mild stress in an age-dependent manner. Recent studies in dystonic hamsters have revealed decreased densities of dopamine D(1) and D(2) in the dorsal striatum. This finding has been interpreted as a down-regulation in response to enhanced dopamine release because systemic treatments with neuroleptics reduced the severity of dystonia while levodopa exerted prodystonic effects. Therefore, in the present study we investigated the effects of amphetamine as well as of selective D(1) or D(2) receptor agonists and antagonists on the severity of dystonia after systemic administrations and after microinjections into the dorsal striatum. Amphetamine and the dopamine D(2) agonist quinpirole increased the severity of dystonia after systemic and striatal injections, while the dopamine D(1) agonist SKF 38393 exerted only moderate prodystonic effects after systemic administration of a high dose but not after striatal injections. These results suggest that a predominant overstimulation of D(2) receptors is pathogenetically involved in the dystonic syndrome. Combined systemic or striatal administrations of the D(1) and D(2) receptor agonists did not reveal synergistic prodystonic effects at the examined doses. The selective D(1) antagonist SCH 23390 as well as the D(2) antagonist raclopride tended to decrease the severity of dystonia after systemic administration but failed to exert significant effects after striatal injection. The coadministration of ineffective doses of the antagonists SCH 23390 and raclopride, however, exerted an enormous antidystonic efficacy after both systemic and striatal injections. Since striatal injections of compounds which enhance dopaminergic activity aggravated dystonia, while coinjections of dopamine D1 and D2 receptor antagonists reduced the severity of dystonia, the present findings clearly support the hypothesis that striatal dopaminergic overactivity plays a crucial role for the manifestation of dystonic attacks in the hamster model of paroxysmal dystonia.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2000

Assessing the Saskatchewan database for outcomes research studies of depression and its treatment.

This study was conducted to evaluate the validity of using the Saskatchewan Health administrative claims databases for conducting depression research. To develop a claims-based definition of depression, we identified a cohort of individuals who began a "new" period of antidepressant use (no use 180 days prior) from which we selected a stratified random sample (n = 600) for medical record abstraction. The medical record diagnosis was used as the gold standard for judging our database definitions of depression. After defining a primary database definition of depression, we tried to refine it using medically probable scenarios and assessed refinement by agreement statistics. Defining depression with ICD9 codes 296 (affective disorders), 309 (adjustment reaction), and 311 (depressive disorders), the sensitivity (Se), specificity (Sp), positive (PV+) and negative predictive (PV-) values were: 71%, 85%, 86%, and 70%, respectively. Algorithms that limited the number of false-negatives resulted in: Se = 84% and PV- = 77% whereas those that limited false-positives resulted in: Sp = 90% and PV+ = 86%. Although our depression definition requires treatment with antidepressants, this definition will allow us to conduct future studies of depression and its treatment using the Saskatchewan Health databases.

Adult↗

PubMed2000

ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS or SACS) is an early onset neurodegenerative disease with high prevalence (carrier frequency 1/22) in the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region of Quebec. We previously mapped the gene responsible for ARSACS to chromosome 13q11 and identified two ancestral haplotypes. Here we report the cloning of this gene, SACS, which encodes the protein sacsin. The ORF of SACS is 11,487 bp and is encoded by a single gigantic exon spanning 12,794 bp. This exon is the largest to be identified in any vertebrate organism. The ORF is conserved in human and mouse. The putative protein contains three large segments with sequence similarity to each other and to the predicted protein of an Arabidopsis thaliana ORF. The presence of heat-shock domains suggests a function for sacsin in chaperone-mediated protein folding. SACS is expressed in a variety of tissues, including the central nervous system. We identified two SACSmutations in ARSACS families that lead to protein truncation, consistent with haplotype analysis.

Amino Acid Sequence↗

PubMed2000

Antidystonic efficacy of nitric oxide synthase inhibitors in a rodent model of primary paroxysmal dystonia.

In a hamster model (genetic symbol dt(sz)) of primary paroxysmal non-kinesiogenic dystonic choreoathetosis, recent studies have shown beneficial effects of glutamate and dopamine receptor antagonists. Nitric oxide (NO), synthesized from L-arginine by NO synthase in response to glutamate receptor activation, elicits cyclic GMP and modulates glutamate-mediated processes and striatal dopamine release. Therefore, the effects of NO synthase inhibitors and of L-arginine on severity of dystonia were investigated in dt(sz) hamsters in which dystonic attacks, characterized by twisting movements and postures, can be induced by stress. The NO synthase inhibitors N(G)-nitro-L-arginine (L-NNA), N(G)-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole significantly reduced the severity of dystonia. At antidystonic effective doses neither L-NNA nor L-NAME caused observable side effects, whereas 7-nitroindazole exerted moderate reduction of locomotor activity. The antidystonic effect of L-NAME was reversed by co-administration of the NO precursor L-arginine. However, L-arginine administered alone did not exert any effect on severity of dystonia. Cerebellar cyclic GMP levels in brains of mutant hamsters in comparison to non-dystonic control hamsters did not significantly differ, but the cerebellar cyclic GMP levels tended to be increased in dt(sz) hamsters during a dystonic attack. L-NAME significantly decreased the cerebellar cyclic GMP levels in both dt(sz) and control hamsters. Although an overproduction of NO is probably not critically involved in the pathogenesis of paroxysmal dystonia, it may contribute to the manifestation of dystonic attacks, as indicated by the antidystonic effects of NO synthase inhibitors. Peripheral side effects may limit the clinical use of NO synthase inhibitors, but more selective inhibitors of the neuronal NO synthase should be considered as interesting candidates for the treatment of paroxysmal dystonia.

Animals↗

PubMed2000

Functional dissociation between medial and lateral prefrontal cortical spatiotemporal activation in negative and positive emotions: a combined fMRI/MEG study.

The orbitofrontal cortex has been cytoarchitectonically and connectionally subdivided into a medial and a lateral part which are assumed to subserve distinct functions in emotional processing. However the exact spatiotemporal mechanisms of negative and positive emotional processing in medial and lateral orbitofrontal cortex remain unclear. We therefore investigated spatiotemporal orbitofrontal and prefrontal cortical activation patterns during emotional stimulation in a combined fMRI/MEG study. We investigated 10 healthy subjects, 5 women and 5 men. Positive and negative pictures from the International Affective Picture system (IAPS) were used for emotional stimulation, whereas neutral and gray pictures were taken as control conditions. fMRI/MEG measurements covered the whole frontal lobe and a time window between -2000 and +200 ms around motor responses (right index finger extension) associated with each picture. Positively and negatively correlated activities were determined in various prefrontal/frontal cortical regions in fMRI. Isocontour maps and single dipoles in MEG were analyzed in 50 ms time windows ranging from -2000 to +200 ms. Dipoles and fMR images were mapped on three-dimensional anatomical MRI so that anatomical localization of single dipoles and regional fMRI activity could be compared. Both negative and positive emotional conditions differed from non-emotional control conditions by strong orbitofrontal and lateral prefrontal activation as well as by the presence of early magnetic fields (-1700 to +1100 ms). Negative emotional processing was characterized by strong medial orbitofrontal activation and earlier (-1700 ms), stronger and more medially oriented orbitofrontal dipoles. In contrast positive emotional processing showed a rather strong activation in lateral prefrontal cortex with later (-1500 ms), weaker and more laterally oriented orbito and prefrontal dipoles. Negative emotional processing can be characterized by strong and early medial orbitofrontal cortical activation, whereas positive emotional processing showed rather later and weaker activation in lateral orbitofrontal/prefrontal cortex. Such a functional dissociation between medial and lateral orbito-frontal/prefrontal cortex during negative and positive emotional processing lends further support to the assumption of a functional subdivision in the orbitofrontal cortex.

Adult↗

PubMed2000

Photosynthetic carbohydrate metabolism in the resurrection plant Craterostigma plantagineum.

The resurrection plant Craterostigma plantagineum (Hochst) is able to survive almost complete tissue dehydration when water is withheld from it, and then can rehydrate rapidly on rewatering. This ability is believed to be the result of the accumulation of sucrose in aerial tissues as a result of metabolism of 2-octulose. In this work the metabolic activity of well-watered Craterostigma plantagineum plants has been investigated. It is shown that Craterostigma makes raffinose series oligosaccharides as a product of photosynthesis and translocates them in the phloem. Evidence is also provided that 2-octulose is a product of photosynthesis and accumulates in the leaves over the light period and is mobilized at night. Thus 2-octulose acts as a temporary storage carbohydrate in leaves during photosynthesis in a similar fashion to starch in most C3 plants. Other potential roles of 2-octulose are discussed. Other than these observations Craterostigma plants are very similar to other C3 plants under these conditions.

Carbohydrate Metabolism↗

PubMed2000

Involvement of the epidermal growth factor receptor in epithelial repair in asthma.

Epithelial damage and airway remodeling are consistent features of bronchial asthma and are correlated with disease chronicity, severity, and bronchial hyperreactivity. To examine the mechanisms that control bronchial epithelial repair, we investigated expression of the epidermal growth factor receptor (c-erbB1, EGFR) in asthmatic bronchial mucosa and studied repair responses in vitro. In biopsies from asthmatic subjects, areas of epithelial damage were frequently observed and exhibited strong EGFR immunostaining. EGFR expression was also high in morphologically intact asthmatic epithelium. Using image analysis, EGFR immunoreactivity (% of total epithelial area, median (range) was found to increase from 9.4 (4.1-20.4) in normal subjects (n=10) to 18.4 (9.3-28.9) in mild asthmatics (P<0.01, n=13) and 25.4 (15.4-31.8) in severe asthmatics (P<0.00, n=5). Epithelial EGFR immunoreactivity remained elevated in patients treated with corticosteroids and was positively correlated with subepithelial reticular membrane thickening. Using 16HBE 14o- bronchial epithelial cells, we found that EGF accelerated repair of scrape-wounded monolayers and that the EGFR-selective inhibitor, tyrphostin AG1478, inhibited both EGF-stimulated and basal wound closure whereas dexamethasone was without effect. Intrinsic activation of the EGFR was confirmed by analysis of tyrosine phosphorylated proteins, which revealed a rapid, damage-induced phosphorylation of the EGFR, irrespective of the presence of exogenous EGF. To assess the relationship between EGFR-mediated repair and tissue remodeling, release of the profibrogenic mediator TGF-beta2 was also measured. Scrape wounding increased release of TGF-beta2 from epithelial monolayers and EGF had no additional stimulatory effect. However, when repair was retarded with AG1478, the amount of TGF-beta2 increased significantly. These data indicate that the EGFR may play an important role in bronchial epithelial repair in asthma and that impairment of this function may augment airway remodeling.

Adult↗

PubMed2000

Frequency and width crossing of two interacting resonances in a microwave cavity

Frequency and width crossing have been observed for two coupled resonances in a microwave cavity. The cavity consisted of two nearly identical rectangular boxes. The boxes were coupled by a slit of variable width. The data are well described by a non-Hermitean S matrix leading to a 2x2 non-Hermitean effective Hamiltonian. The values of the interaction strength |v| for which width crossing and frequency crossing, respectively, were observed, are above and below a critical value |v(c)| for which one expects a joint frequency and width crossing.

Journal Article↗

PubMed2000

Gaussian unitary ensemble statistics in a time-reversal invariant microwave triangular billiard

The spectrum of a chaotic two-dimensional quantum billiard with threefold symmetry has been studied in an experiment with a superconducting microwave cavity. In total 622 eigenvalues were identified experimentally and compared with numerical calculations. The statistical analysis of the data shows that Gaussian unitary ensemble statistics can be observed for a spectrum of a time-reversal invariant system.

Journal Article↗

PubMed2000

Angiogenesis and cathepsin expression are prognostic factors in pancreatic adenocarcinoma after curative resection.

BACKGROUND: Curative resection of pancreatic adenocarcinoma is the only clinical parameter related to a favorable prognosis while other clinicopathological parameters fail. To evaluate whether angiogenesis, vascular endothelial growth factor (VEGF) or certain tumor proteases, e.g., cathepsin B (CTSB) and L (CTSL), are factors of prognostic relevance, we investigated their expression in patients with long- and short-term survival after curative resection (RO) because of pancreatic adenocarcinoma. METHODS: Twenty-nine tissue samples from patients with adenocarcinoma of the pancreas were examined. The patients were selected in a long-term survival group with a survival > or = 24 mo (n = 18) and a shortterm survival group of patients, who died within 8 mo after surgery because of their malignancy (n = 11). The microvessel quantification was performed immunohistochemically using a monoclonal anti-CD34 antibody. VEGF, CTSB, and CTSL expressions was studied using polyclonal antibodies (PAbs). RESULTS: The median microvessel density (MVD) was 75 (range 39-182). MVD correlated significantly with the survival time after surgery (p = 0.0132) but not with clinicopathological parameters. In cancer cells, VEGF was positive in 82.8% and showed significant correlation with the MVD (p = 0.0002) and survival time (p = 0.0395). Positive immunoreactivity could be obtained for 96.5% for CTSB and 84.2% for CTSL. Expression of both proteases correlated significantly with the survival time after surgery (CTSB p = 0.0002, CTSL p = 0.0001). Furthermore, CTSB expression correlated with invasion of the perineural space. Thus, a short postoperative survival correlated with a high MVD, and highly expressed VEGF, CTSB, and CTSL. No significant correlation between MVD, VEGF, as well as CTSL and clinicopathological parameters was found. For routinely assessed markers (e.g., TNM-stage, UICC-stage, and so on) no significant correlation with survival time was found in this small group of patients. CONCLUSION: These findings indicate that the MVD, VEGF, CTSB, and CTSL are prognostic factors after curative resection, whereas other parameters (TNM, UICC, and so on) failed to show prognostic relevance in our group of patients. Furthermore, the correlation between MVD and VEGF underlines the importance of this growth factor for angiogenesis and tumor growth. The correlation between CTSB and perineural invasion demonstrates the involvement of cathepsins in local tumor invasion.

Adenocarcinoma↗

PubMed2000

Potential savings in the cost of caring for Alzheimer's disease. Treatment with rivastigmine.

OBJECTIVE: To estimate savings in the cost of caring for patients with Alzheimer's disease (AD) during 6 months, 1 year and 2 years of treatment with rivastigmine. An intermediate objective was to estimate the relationship between disease progression and institutionalisation. DESIGN AND SETTING: We assessed the relationship between Mini-Mental State Examination (MMSE) score and institutionalisation using a piecewise Cox proportional hazard model. To estimate cost savings from treatments lasting 6 months, 1 year and 2 years, estimates of the probability of institutionalisation were integrated with data from two 6-month phase III clinical trials of rivastigmine and a hazard model of disease progression. MAIN OUTCOME MEASURES AND RESULTS: Our data suggest that savings in the overall cost of caring for patients with mild and moderate AD can be as high as $US4839 per patient after 2 years of treatment. Furthermore, the probability of institutionalisation increases steadily as MMSE score falls. Among our study individuals, age, race, level of education and marital status were significant predictors of institutionalisation, whereas gender had little effect. CONCLUSIONS: Using rivastigmine to treat AD results in a delay in disease progression for patients who begin treatment during the mild or moderate stages of the disease. By delaying the probability that a patient will be institutionalised, the cost of caring for AD patients can be significantly reduced.

Aged↗

PubMed2000

Cost-effectiveness model of cytomegalovirus management strategies in renal transplantation. Comparing valaciclovir prophylaxis with current practice.

BACKGROUND: Cytomegalovirus (CMV) disease may occur following renal transplantation and has been shown to have health and cost consequences in this setting. OBJECTIVE: To compare the cost effectiveness of different CMV management strategies for renal transplant patients: prophylaxis with (i) oral valaciclovir or (ii) intravenous ganciclovir; viral testing for CMV followed by (iii) pre-emptive therapy with intravenous ganciclovir or (iv) adjustment of immunosuppression and intensive monitoring; or (v) waiting to treat when CMV disease develops. METHODS: A decision-tree model was constructed that included the different management strategies for the donor seropositive/recipient seronegative (D+R-) population. Clinical outcomes for the D+R- population came from clinical trials. Treatment algorithms and costs for CMV syndrome and tissue invasive disease were developed from published literature and UK physician interviews. One- and 2-way sensitivity analyses were performed. STUDY PERSPECTIVE: UK National Health Service. RESULTS: Prophylaxis with either oral valaciclovir or intravenous ganciclovir dominated (lower costs and fewer cases of CMV disease) the pre-emptive treatment and wait-and-treat strategies. The cost per patient was from 157 Pounds to 438 Pounds higher with oral valaciclovir prophylaxis compared with intravenous ganciclovir prophylaxis and the incremental cost per case of CMV disease avoided with valaciclovir prophylaxis ranged from 2243 Pounds to 8111 Pounds (1996 values). These results are sensitive to the efficacy of intravenous ganciclovir prophylaxis and CMV management costs. CONCLUSIONS: For D+R- renal transplant patients, prophylaxis is the dominant (more effective and less costly) management strategy compared with pre-emptive and wait-and-treat strategies. The cost per patient with oral valaciclovir prophylaxis compared with intravenous ganciclovir prophylaxis is slightly higher in our base case scenario, but may be lower under reasonable alternative assumptions.

Acyclovir↗

PubMed2000

Roundtable discussion: Part I--Epidemiologic, demographic, and treatment challenges in hypertension.

Hypertension is one of the most pervasive medical disorders in this country. As the nation's population ages, the number of patients with hypertension can be expected to rise substantially. On December 9, 1999, a panel of managed care medical directors, pharmacy directors, clinicians, and health economists convened in Irvine, Texas to discuss aspects of hypertension management and economic analysis. This roundtable is presented in three parts, including (1) a summary of the challenges of hypertension management from the point of view of the clinician, (2) the introduction of a pharmacoeconomic model of hypertension management, and (3) a discussion of how health plans approach this insidious disorder.

Aged↗

PubMed2000

Roundtable discussion: Part II--Development of a pharmacoeconomic model in hypertension.

Antihypertensive medications are targeted by most health plans as a major cost center. However, the efficacy of these medications, their side effects, and their resulting ability to prevent serious long-term complications must be factored into the value equation. To illustrate the possible economic effects of a single antihypertensive agent's inclusion on a health plan's drug formulary, an innovative pharmacoeconomic model was developed. In this portion of the roundtable, the design, results, and caveats of this model are discussed.

Antihypertensive Agents↗

PubMed2000

Roundtable discussion: Part III--Hypertension management in health plans.

In the final section of the roundtable discussion, participants describe how their individual managed care plans approach hypertension from the standpoints of disease management targeting, strategies to combat noncompliance, and how these plans utilize pharmacoeconomic information in drug formulary decision making.

Antihypertensive Agents↗

PubMed1999

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): high-resolution physical and transcript map of the candidate region in chromosome region 13q11.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS or SACS) is a neurodegenerative disease frequent in northeastern Québec. In a previous study, we localized the disease gene to chromosome region 13q11 by identifying excess sharing of a marker allele in patients followed by linkage analysis and haplotyping. To create a detailed physical map of this region, we screened CEPH mega-YACs with 41 chromosome 13 sequence-tagged-sites (STSs) known to map to 13q11-q12. The YAC contig, composed of 27 clones, extends on the genetic map from D13S175 to D13S221, an estimated distance of at least 19.3 cM. A high-resolution BAC and PAC map that includes the ARSACS critical region flanked by D13S1275 and D13S292 was constructed. These YAC and BAC/PAC maps allowed the accurate placement of 29 genes and ESTs previously mapped to the proximal region of chromosome 13q. We confirmed the position of two candidate genes within the critical region and mapped the other 27 genes and ESTs to nearby intervals. Six BAC/PAC clones form a contig between D13S232 and D13S787 for sequencing within the ARSACS critical region.

Bacteriophage P1↗