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Biomedical subjects

J R Westphal

Publications and source records attributed to J R Westphal.

At least 37 records · Page 2Linked to original sources

The Louisiana Medicare Electro-Convulsive Therapy Quality Improvement Project.

The first collaborative statewide psychiatric quality improvement project, initiated by Louisiana Health Care Review, Inc, focused on the practice of inpatient electro-convulsive therapy (ECT) among Medicare patients. Data from the project indicated that the majority of Medicare patients receiving ECT were white females living at home, in good physical health, in their seventies, and with a diagnosis of major depression or major depression with psychotic features. The quality indicators for the project included: (documentation of) monitoring of cognitive side effects, monitoring of depressive target symptoms, ECT appropriateness, electrode placement, anesthesia evaluation, and dental examination. An additional indicator (administration of possibly detrimental medication during ECT) was developed based on the recommendation by the study group. At project conclusion, significant improvement occurred in all project indicators. ECT as practiced in the participating hospitals was effective and appropriate. Appropriateness was determined as depression refractory to two medication trails or an emergency due to severe suicidal ideation or physical deterioration secondary to malnutrition. Transient hypertension (13%) and cardiac dysrhythmia (3.5%) which resolved in the recovery period were the most frequent complications.

Aged↗

An improved procedure to quantify tumour vascularity using true colour image analysis. Comparison with the manual hot-spot procedure in a human melanoma xenograft model.

In a number of recent papers, the degree of tumour vascularization has been described as a promising new prognostic factor. Methods for the assessment of vascular density involve immunohistochemical staining of the vasculature, followed by counting the number of vessel profiles in the angiogenic hot spot. One of the problems of this procedure is the selection of the angiogenic hot spot, which has been described as being subject to inter-observer variation. In this study, the value of true colour image analysis in reducing inter-observer variation has been assessed. Highly (MV3) and poorly (M14) vascularized human melanoma xenografts were used to evaluate the image analysis procedure, and the image analysis results were compared with results from the conventional manual hot-spot procedure. Assessment by image analysis was performed on measurement fields covering the entire tumour tissue specimens rather than on a single hot-spot field. Also, by selecting the most densely vascularized area from all fields assessed by the semi-automatic procedure, it was possible to objectify the hot spot selection (automated hot-spot procedure). Manual assessment showed a good correlation between two independent observers for MV3 xenografts (r = 0.74, P = 0.014), but a poor correlation for M14 xenographs (r = 0.4, P > 0.05). Automated assessment by different operators showed good correlations for both MV3 xenografts (r = 0.99, P < 0.001) and M14 xenografts (r = 0.80, P = 0.006). It is concluded that although both manual vessel counting and semi-automated image analysis can differentiate between the level of vascularization in the two types of xenograft (P < 0.001 for both methods), the automated method is favourable in that it showed no significant inter-observer effects. In M14 xenografts, the manual hot-spot vessel densities did not correlate well with the automated hot-spot densities (r = 0.27, P > 0.05), indicating that selection of angiogenic hot spots in this tumour type is indeed subject to observer bias. The automated hot-spot vessel densities were a reliable indicator of overall tumour vessel density in both tumour types. Image analysis allows analysis of vessel subclasses based on morphological criteria such as vessel profile area or diameter. In the model system used, the discrimination between MV3 and M14 xenografts was further enhanced by selectively examining vessels with diameters between 6 and 9 microns (P < 0.0005). In conclusion, image analysis appears to offer an objective and more reproducible method to quantify tumour vascularity than manual counting of vessel profiles in the hot spot. Analysis of subclasses of vessels may further enhance the value of vessel density measurements in discriminating between tumour types differing in biological behaviour.

Animals↗

Expression of macrophage-derived chemokine (MDC) mRNA in macrophages is enhanced by interleukin-1beta, tumor necrosis factor alpha, and lipopolysaccharide.

A cDNA encoding the C-C chemokine MDC was isolated from a human macrophage cDNA library by differential hybridization using monocyte- and macrophage-specific cDNA probes. During monocyte to macrophage differentiation in vitro, MDC expression is first detected after 1 day of culturing and reaches maximum levels after 6 days when macrophages have fully matured, as judged from the expression of known macrophage marker genes. Exposure of macrophages to lipopolysaccharide (LPS) results in a dose-dependent increase in MDC mRNA levels, with maximum induction occurring after 6-8 h, whereas expression levels of macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-2, interleukin-1beta (IL-1beta), and tumor necrosis factor alpha (TNF-alpha) respond much faster to LPS. Furthermore, MDC expression in macrophages is enhanced by the inflammatory mediators TNF-alpha and IL-1beta. Similar to other TNF-alpha/IL-1beta-inducible genes, costimulation of macrophages with both cytokines leads to higher MDC expression levels than stimulation with a single cytokine. By contrast, both resting and activated monocytes do not express MDC mRNA.

Chemokine CCL22↗

Gambling behavior of adolescents in residential placement in northwest Louisiana.

BACKGROUND: The rapid expansion of legalized gambling in the United States necessitates evaluation of its impact on vulnerable populations, especially adolescents. METHODS: Gambling behavior in 135 adolescents in residential placement in northwestern Louisiana was measured using the South Oaks Gambling Screen-Revised for Adolescents. RESULTS: During the past year, 41% of these adolescents reported minimal problems with gambling, 21% reported level 2 or problem gambling, and 38% reported level 3 or pathologic gambling. In this population, the first drink of alcohol, the first cigarette, and the first experience with gambling began on average at 11 years of age, with the first use of marijuana and the first episode of alcohol intoxication occurring a year later. CONCLUSION: The level 2 rate of gambling exceeded the upper extreme of the adolescent community sample range, and the level 3 rate was approximately six times the reported level 3 community prevalence rate for adolescents. Residential placements sites should be considered when developing prevention programs for gambling disorders.

Adolescent↗

New approach to administrative medical decision-making: evidence-based medicine using high dose chemotherapy/bone marrow transplant for breast cancer.

BACKGROUND: Payment for experimental treatments using medical necessity criteria has been controversial. The process of obtaining a decision on coverage of an experimental treatment can be distressful for the treating physician, the patient, and family members. METHOD: The techniques of evidence-based medicine were used to assist with treatment/coverage decisions concerning high dose chemotherapy with autologous bone marrow transplants (HDC/ABMT) for invasive breast cancer. RESULTS: We reviewed the literature, finding minimal evidence for effectiveness of HDC/ABMT for invasive breast cancer; therefore, it is our opinion that it remains an experimental therapy. Its cost utility is likely to be low (approximately $100,000 per additional quality year gained). Numerous patients have been treated with HDC/ABMT outside of clinical trials, impeding scientific analysis of the treatment's effectiveness. CONCLUSION: Data-based policies and procedures for funding experimental medical treatments need to be developed to eventually replace the medical necessity criteria.

Antineoplastic Agents↗

Endothelial P-selectin expression is reduced in advanced primary melanoma and melanoma metastasis.

Some malignant tumors induce a cellular immune response that results in the formation of an inflammatory infiltrate and subsequent tumor regression. The infiltrating leukocytes extravasate from the bloodstream after binding to adhesion receptors on the surface of the endothelium. One of these receptors is the P-selectin molecule (CD62P) that is constitutively present on normal capillaries. We observed that P-selectin expression is absent from the microvasculature in advanced primary melanoma and in melanoma metastasis in contrast to benign melanocytic lesions where P-selectin expression was identical to that in normal skin. We suggest that one of the mechanisms by which advanced melanoma lesions evade inflammatory regression operates via a decrease of endothelial P-selectin expression.

Antigens, Surface↗

Trichotillomania resulting in a trichobezoar: a case report.

This paper presents a case of a 19-year-old, 10 1/2-week-pregnant woman with trichotillomania that resulted in a trichobezoar. The case illustrates typical presentation, patient behavior, symptomatology, and physical findings of patients with trichobezoars. The hypothesized methods for trichobezoar formation, complications, and treatment are discussed. The diagnostic criteria, epidemiology, and treatment of trichotillomania are also discussed.

Adult↗

Vascular density in melanoma xenografts correlates with vascular permeability factor expression but not with metastatic potential.

We studied the relation between tumour vascular density and tumour growth rate, metastatic incidence and vascular permeability factor (VPF) mRNA levels in a human xenograft model described previously. Vascular density was determined by automated image analysis. Xenografts derived from cell lines BLM and MV3 showed the highest mean vascular density (MVD), the highest in vivo growth rate, high VPF mRNA levels and rapid development of lung metastases. Xenografts of cell lines M14, Mel57 and MV1 showed a significantly lower degree of vascularization, lower in vivo growth rates and lower levels of VPF mRNA, but formed lung metastases with a similar incidence as those of BLM and MV3. Xenografts from cell line 1F6 did not form lung metastases, whereas tumours derived from a spontaneous mutant of 1F6, designated 1F6m, gave rise to lung metastases to the same extent as Mel57, M14 and MV1 tumours. MVD values in 1F6 and 1F6m xenografts, VPF mRNA levels and in vivo growth rates of 1F6 and 1 F6m xenografts, however, were similar. In conclusion, in the melanoma xenograft model vascular density is correlated with in vivo growth rate and with in vitro VPF mRNA levels, but not with the ability to metastasize.

Animals↗

Quantifying utilization and practice variation of electroconvulsive therapy.

The objective of this study was to quantify inpatient electroconvulsive therapy (ECT) utilization and its practice variation within the State of Louisiana using Medicare data for beneficiaries age 65 years and older. The Louisiana Medicare claims (MedPar) history and the Medicare beneficiary denominator files for fiscal years 1993 and 1994 were used for analysis. Statistical techniques used were: chi 2 to determine significance of the proposed null hypothesis, and the modified systemic component of variance (SCV) to determine the magnitude of variation between the individual parish utilization rates for ECT. The ECT utilization rate for the Louisiana Medicare population was found to be 2.38 per 10,000 person-years, falling well within the range of previous ECT utilization studies in the United States. The chi 2 value was 0.0003 when comparing parishes, indicating the presence of significant nonrandom variation. The SCVs of inpatient treatment for major depression and impatient ECT were 0.47 and 1.34, respectively. Inpatient ECT in this population demonstrates high geographic variability. Further research is required to determine and quantitate the factors responsible for the geographic variation in inpatient ECT utilization within the Louisiana Medicare population.

Aged↗

Pathological gambling in Louisiana: an epidemiological perspective.

A review of telephone interview data using the South Oaks Gambling Screen on a random sample of 1,818 Louisiana residents > 18 years indicated that 4.8% of adults > 21 years (approximately 122,500) have gambling disorders, compared to 14.4% of 18 to 21 year olds (approximately 21,000). Geographic distribution of gambling disorders shows equal statewide penetrance. Pathological gamblers are demographically distinct, more likely to be male, < 30 years, non-Caucasian, unmarried, and less likely to have graduated from high school than nonproblem gamblers. Two demographic clusters, males < 21 who primarily wager on video poker and those > 30 who primarily wager on horse racing, were noted. Data is needed on adolescent incidence and prevalence to plan prevention and early intervention programs in Louisiana.

Adolescent↗

T lymphocyte adhesion to human brain pericytes is mediated via very late antigen-4/vascular cell adhesion molecule-1 interactions.

T cell adhesion to the brain microvascular endothelium and subsequent migration into the brain parenchyma is one of the major events in the development of multiple sclerosis (MS). Interactions of the T cell integrin very late antigen-4 (VLA-4) with its receptor, vascular cell adhesion molecule-1 (VCAM-1) have been described to be of crucial importance for the development of MS. We investigated the expression of these adhesion molecules in MS brain tissue by immunohistochemical analysis, and studied their functional involvement in an in vitro T cell adhesion assay. A number of other adhesion molecules were studied for comparison. In cryosections of several MS brains, expression of VCAM-1 was demonstrated not only on the endothelium of vessels surrounding MS plaques, but also in perivascular positions, suggesting expression by pericytes. T cells adhered to both cell types in vitro. Both LFA-1/intercellular adhesion molecule-1 and VLA-4/VCAM-1 interactions were equally involved in the adhesion of T cells to TNF-alpha-stimulated endothelial cells. However, adhesion of T cells to TNF-alpha-stimulated pericytes was clearly dominated by VLA-4/VCAM-1 interactions. These results indicate that pericytes, next to endothelial cells, may play an important role in regulating T cell infiltration into the central nervous system.

Brain↗

Expression of endoglin in psoriatic involved and uninvolved skin.

Endoglin is a glycoprotein with TGF-beta binding capacity and is predominantly expressed on endothelial cells. In psoriasis, TGF-beta has appeared to play a role in the extravasation of peripheral blood mononuclear cells via the endothelium. In order to find out more about the role of endoglin in psoriasis, immunohistochemical staining with PN-E2, a novel anti-endoglin, and of PAL-E, recognizing vascular endothelium, was carried out in psoriatic involved, psoriatic uninvolved and normal skin. The expression of the antigens was assessed semi-quantitatively using a five-point scale. In psoriatic involved skin, a high endoglin expression was found. In psoriatic uninvolved skin, however, we found that endoglin expression was significantly decreased compared with normal skin. The relevance of these findings to the pathogenesis of psoriasis is discussed.

Adolescent↗

Developing a system for automated monitoring of psychiatric outpatients: a first step to improve quality.

OBJECTIVE: To evaluate an automated system of quality monitoring for psychiatric outpatients. DESIGN: Cross-sectional study. SETTING: Large outpatient psychiatry clinic in Kaiser Permanente--Northern California. PARTICIPANTS: Approximately 1500 new psychiatric patients and 20 clinicians. INTERVENTIONS: This system gave clinicians data on new patients from validated instruments before their intake interviews, measured outcomes for the depressed and panic-disordered patients, and monitored the clinic's case-mix. MAIN OUTCOME MEASURES: Clinic case-mix: Axis II disorders (Personality Disorder Questionnaire--Revised); emotional, social and physical functioning (Health Status Questionnaire 2.0); Axis I symptoms (Symptom Checklist-90); depression and panic disorder (Health Outcomes Institute Modules). Clinician reaction to system (telephone interview). RESULTS: The study population was 62.4% female; 73.9% Caucasian; 70% employed; 15.9% had evidence of personality disorder; 63% reduced daily activities because of emotional problems; 18% had depression; 7% had panic disorder. Over 75% of clinicians used the data reports and found them helpful; criticism focused on questionnaire length, inadequate training, numerous false-positives, and insufficient administrative support. CONCLUSION: An automated patient monitoring system can be implemented; clinician involvement needs to be significant; more research is needed to establish the usefulness of standardized data and outcomes management.

Adult↗

Adenovirus infection induces loss of HLA class I and CD3 antigens, but does not induce cell surface presentation of the La (SS-B) autoantigen.

Antibodies to the RNA polymerase III transcription termination factor La are frequently found in the serum of patients with various autoimmune diseases. The mechanisms by which autoimmune responses are evoked remain largely obscure, but the presentation of autoantigens on the cell surface during stress conditions has been reported as a possible factor. In this study we analysed the effects of adenovirus infection on the binding of anti-La antibodies to the surface of several human cell lines and on the levels of the membrane-expressed glycoproteins HLA class I, CD44 and the CD3 complex. In addition, we studied the relative amount and the intracellular distribution of the La protein as well as its association with the major species of non-coding virus-associated (VAI) RNA. While immunofluorescence patterns revealed a redistribution and possibly cell surface expression of the La protein during infection, this could not be confirmed by other techniques. In contrast, surface levels of HLA class I proteins and CD3 complex were severely affected. The data suggest that the subcellular distribution of the La protein is not detectably influenced by adenovirus infection.

Adenovirus Infections, Human↗

Anti-endothelial cell antibodies in sera of patients with autoimmune diseases: comparison between ELISA and FACS analysis.

In some patients suffering from rheumatoid arthritis (RA), vasculitis is a clear clinical manifestation, mentioned as rheumatoid vasculitis (RV). Autoantibodies directed against endothelial cells (AEA) have been implicated in the pathogenesis of this disorder, and it has been suggested in a number of studies that testing for AEA should be included in diagnosing RV. To test this hypothesis, we have evaluated the presence of AEA in sera of patients suffering from various autoimmune diseases, employing an ELISA with fixed cultured endothelial cells (EC). In all the groups of patients ELISA-positive sera were present. A significant difference in percentage of positivity was found between the RA and RV group (P < 0.05). In addition, our results indicated that not only antibodies directed against antigens on the EC membrane were detected, but also antibodies directed against intracellular components like DNA, histones and cytoskeletal components. Therefore, we also tested all these patient sera on unfixed intact EC using indirect immunofluorescence followed by FACS analysis. Whereas in the total patient population 34 out of 65 patients were AEA-positive as determined in the ELISA, only seven patients were weakly positive when examined by flow cytometry. We conclude that: (i) an ELISA on fixed EC does not specifically detect AEA. A positive test result is, however, to some extent correlated with the occurrence of vasculitis, and may therefore be helpful in diagnosing this disease; (ii) FACS analysis is a more suitable method than ELISA to measure the presence of membrane-specific AEA in patient sera; (iii) specific IgG-AEA are less common in patients suffering from autoimmune disorders than was assumed previously.

Adult↗

Accumulation of intercellular adhesion molecule-1 in senile plaques in brain tissue of patients with Alzheimer's disease.

The still unsolved pathogenesis of Alzheimer's disease (AD) has been the subject of extensive speculation. Some years ago, a local acute phase reaction involving production of interleukin-1 (IL-1) and IL-6 was proposed as the triggering event in AD. Since it has been reported that these cytokines induce expression of intercellular adhesion molecule-1 (ICAM-1), we analyzed AD brain tissue cryosections for the presence of ICAM-1 by immunostaining and for ICAM-2 expression as a control. In senile plaques a marked diffuse or granular staining for the ICAM-1 domains 1, 4, and 5 was observed, whereas ICAM-2 expression was observed in microglial cells. Immunoprecipitation analysis demonstrated the presence of a 85 kd ICAM-1 molecule in AD frontal cortex. Our findings indicate that ICAM-1 accumulates in senile plaques as a complete 5-domain molecule at a relatively early stage of senile plaque formation. Our results are in support of a cytokine-mediated pathogenesis of senile plaque formation.

Adolescent↗