AHC--community partnerships for interdisciplinary education.
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Community-Institutional Relations↗
Biomedical subjects
C Mueller
Publications and source records attributed to C Mueller.
Exposure of casino employees to environmental tobacco smoke.
Environmental and medical evaluations were performed to evaluate occupational exposure to environmental tobacco smoke (ETS) among casino employees. Air concentrations of both nicotine and respirable dust were similar to those published in the literature for other non-industrial indoor environments. The geometric mean serum cotinine level of the 27 participants who provided serum samples was 1.34 nanograms per milliliter (ng/mL) (pre-shift) and 1.85 ng/mL (post-shift). Both measurements greatly exceeded the geometric mean value of 0.65 ng/mL for participants in the Third National Health and Nutrition Examination Survey (NHANES III) who reported exposure to ETS at work. This evaluation demonstrates that a sample of employees working in a casino gaming area were exposed to ETS at levels greater than those observed in a representative sample of the US population, and that the serum and urine cotinine of these employees increased during the workshift.
Adult↗
Evaluation of Murex CMV DNA hybrid capture assay for detection and quantitation of cytomegalovirus infection in patients following allogeneic stem cell transplantation.
Murex hybrid capture DNA assay (HCS) is a solution hybridization antibody capture assay for detection and quantitation of cytomegalovirus (CMV) DNA in leukocytes. To determine whether CMV HCS is sensitive enough to initiate and monitor antiviral therapy after allogeneic stem cell transplantation (SCT), 51 consecutive SCT recipients were prospectively screened for the appearance of CMV infection by HCS, PCR, and culture assays from blood samples. Preemptive antiviral therapy was initiated after the second positive PCR result in all patients, as previously reported, and HCS was not considered for clinical decision making. A total of 417 samples were analyzed. Of these, 21 samples were found to be positive by PCR and HCS, 88 samples were PCR positive but HCS negative, and 308 were negative by both assays. Concordance of results between PCR and HCS and between HCS and blood culture was observed in 78.9 and 95.9% of the samples assayed, respectively. PCR was found to be more sensitive than HCS, and HCS was more sensitive than the blood culture assay (P < 0.0001). Four patients with symptomatic CMV infection were PCR positive prior to the onset of CMV-related symptoms, whereas HCS detected CMV DNA in three patients prior to and one at onset of CMV disease. The numbers of genomes per milliliter of blood were higher in patients with symptomatic CMV infection than in those with asymptomatic CMV infection (P = 0.06). None of the HCS-negative patients developed CMV disease. Thus, all patients with CMV disease were correctly identified by HCS; however, the lower sensitivity limit of the HCS assay may still be insufficient to allow diagnosis of CMV infection early enough to prevent CMV disease in patients following allogeneic SCT.
Adolescent↗
Activated CD4+ and CD8+ cytotoxic cells are present in increased numbers in the intestinal mucosa from patients with active inflammatory bowel disease.
The contribution of cell-mediated cytotoxicity to the pathogenesis of inflammatory bowel disease (IBD) is controversial, and results of in vitro assays vary according to experimental procedures. Therefore, we compared the frequency of cytotoxic effector cells in situ. On tissue sections of controls (n = 11), low frequencies of granzyme A and perforin mRNA-expressing cells are found in the lamina propria (1.77 +/- 0.15% and 1.46 +/- 0.12%, respectively) and in the epithelial cell layer (0.76 +/- 0.12% and 0.66 +/- 0.10%, respectively). In patients with IBD (n = 33), corresponding values were significantly (P < 0.02) higher, 6.1 +/- 0.40% and 5.92 +/- 0.57% for granzyme A and perforin expression in the lamina propria and 2.50 +/- 0.19% and 2.59 +/- 0.28%, respectively, in the epithelial compartment. Differences between ulcerative colitis and Crohn's disease are statistically not significant (P > 0.33). Activated cytotoxic cells are preferentially found at sites facing the intestinal lumen. Perforin mRNA-expressing cells are mainly CD8+ T cells. CD4+ T cells expressing perforin mRNA are mainly isolated from affected areas of patients with Crohn's disease. Immunostaining for perforin protein generally coincides with perforin mRNA in situ. These data demonstrate that cytotoxic cells are vigorously activated in situ in the intestinal mucosa of patients with active IBD.
Adult↗
A new polyoxometalate complex inhibits retrovirus encoded reverse transcriptase activity in vitro and in vivo.
We examined the recently synthesized and characterized polyoxometalate compound (NH4)10[Co2Sb2W20 O70(H2O)6] (POM1). The inhibitory potency of POM1 was studied in tissue culture experiments with uninfected and Rous sarcoma virus (RSV)-infected chicken embryo fibroblasts (CEF) in vivo. We measured a considerable decrease in total cellular phosphotyrosine content in treated infected cells in vivo. POM1 treatment of SR-RSV-A infected CEF in vivo resulted in decreased pp60v-src activity, possibly due to a reduced rate of v-src translation caused by the inhibitory effect of POM1 on the RSV encoded reverse transcriptase activity (RT) activity. In further studies we were able to demonstrate the inhibitory effect of this complex on the RT activity of RSV in vitro and in vivo.
Animals↗
A primer on lower extremity outcome measurement instruments.
Tracing the roots of lower extremity outcome scales is an interesting and somewhat bemusing journey. A large number of different grading methods can be found with limited reliability and/or validity testing. The usefulness of these instruments in the assessment of patient outcomes after lower extremity interventions is worrisome. This article focuses on the most commonly used scales and demonstrates an alarming and incestuous pattern of cross-validation with moderate to weak associations between potentially unreliable and crudely validated original instruments.
Activities of Daily Living↗
Bulimic adolescents benefit from massage therapy.
Twenty-four female adolescent bulimic inpatients were randomly assigned to a massage therapy or a standard treatment (control) group. Results indicated that the massaged patients showed immediate reductions (both self-report and behavior observation) in anxiety and depression. In addition, by the last day of the therapy, they had lower depression scores, lower cortisol (stress) levels, higher dopamine levels, and showed improvement on several other psychological and behavioral measures. These findings suggest that massage therapy is effective as an adjunct treatment for bulimia.
Adolescent↗
Prevention of autoimmune diabetes mellitus in NOD mice by transgenic expression of soluble tumor necrosis factor receptor p55.
The non-obese diabetic (NOD) mouse represents a relevant animal model of autoimmunity for insulin-dependent diabetes mellitus. The pathogenic role of tumor necrosis factor (TNF) in insulitis and beta cell destruction observed in these mice remains controversial, since injections of TNF or of anti-TNF antibodies have been reported to exert protection or acceleration of diabetes, depending on the timing of administration. In this study, we demonstrate that, in contrast to the non-transgenic littermates, NOD mice with permanent neutralization of TNF by high blood levels of soluble TNF receptor p55-human FcIgG3-fusion molecules resulting from the expression of a transgene are protected from spontaneous diabetes. They are also protected from accelerated forms of disease caused by transfer of NOD spleen cells or cyclophosphamide injections. This protection is associated with a marked decrease in the severity and incidence of insulitis and in the expression of the adhesion molecules MAdCAM-1 and ICAM-1 on the venules of pancreatic islets. These data suggest a central role for TNF-alpha in the mediation of insulitis and of the subsequent destruction of insulin-secreting beta-cells observed in NOD mice. They may be relevant to cell-mediated autoimmune diseases in general, in which treatment with soluble TNF receptors might be beneficial.
Animals↗
CD5- CD8 alpha beta intestinal intraepithelial lymphocytes (IEL) are induced to express CD5 upon antigen-specific activation: CD5- and CD5+ CD8 alpha beta IEL do not represent separate T cell lineages.
We followed alpha beta T cell receptor (TCR) usage in subsets of gut intraepithelial lymphocytes (IEL) in major histocompatibility complex class I-restricted alpha beta TCR-transgenic (tg) mice. The proportion of tg alpha beta TCR+ CD8 alpha beta IEL is reduced compared with CD8+ splenocytes of the same animal, particularly under conventional conditions of maintenance. Further fractionation of CD8 alpha beta IEL according to the expression level of surface CD5 revealed that in conventionally housed animals tg TCR+ CD5- CD8 alpha beta IEL are as frequent as in specific pathogen-free (SPF) mice, whereas tg TCR+ CD5int or, even more pronounced, tg TCR+ CD5hi CD8 alpha beta IEL are greatly diminished when compared with mice kept under SPF conditions. Upon antigen-specific stimulation of CD5- CD8 alpha beta IEL in vitro, CD5 surface expression is up-regulated on a large fraction of cells within 48 h. Up-regulation of CD5 surface expression is further enhanced by the presence of the anti-alpha IEL monoclonal antibody 2E7. This clearly demonstrates that CD5-, and CD5+ CD8 alpha beta IEL cannot be considered as separate T cell lineages.
Animals↗
Regulation and function of the CXC chemokine ENA-78 in monocytes and its role in disease.
Epithelial neutrophil-activating protein 78 (ENA-78) is a member of the CXC chemokines and acts as a potent chemoattractant and activator of neutrophil function. On stimulation in vitro, ENA-78 is highly expressed in many cell types. ENA-78 protein levels are strongly elevated in synovial fluid and blood of patients with rheumatoid arthritis. By in situ hybridization and immunofluorescence staining, ENA-78 has been recognized as a major CXC chemokine expressed in epithelial cells of the intestinal mucosa of patients with Crohn's disease, ulcerative colitis, and acute appendicitis. A high expression of ENA-78 and interleukin-8 (IL-8) was also observed in the exocrine tissue of patients with chronic pancreatitis (CP). It is interesting to note that expression of IP-10, MIP-1alpha, and MCP-1 is high in healthy pancreatic tissue but low in tissue of patients with CP, suggesting a mutually exclusive expression of the ELR-CXC vs. non-ELR-CXC/CC chemokines. High-resolution studies of intracellular chemokines has revealed specific immunoreactivity for ENA-78 associated with the endoplasmic reticulum of many cell types. In contrast, GROalpha immunoreactivity was exclusively localized in the nucleus. Despite their common effects on neutrophil functions, the differential intracellular localization of ENA-78 and GROalpha suggests additional roles for these two chemokines in normal cell biology.
Arthritis, Rheumatoid↗
Aminopeptidase N-mediated signal transduction and inhibition of proliferation of human myeloid cells.
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Antibodies, Monoclonal↗
Ocular flutter and truncal ataxia may be associated with enterovirus infection.
We report on three patients who presented a rare, uniform clinical syndrome consisting of ocular flutter and truncal ataxia. In all patients the symptoms followed an upper respiratory infection and resolved without sequelae within a few weeks. Previous reports have emphasized the apparent relationship of this entity to infectious disease, but the infectious agent remained uncertain. In one patient we could find a significant rise in antibody titres to enterovirus. We are not aware of any other similar documented case.
Adult↗
Cytotoxic cells are activated in cellular infiltrates of alcoholic chronic pancreatitis.
BACKGROUND & AIMS: Perforin messenger RNA (mRNA) expression has been shown to be a specific in vivo activation marker for cytotoxic cells. In this study, the contribution of cell-mediated cytotoxicity in the pathogenesis of alcoholic chronic pancreatitis is assessed. METHODS: Tissue sections of patients with alcoholic chronic pancreatitis were analyzed for perforin mRNA expression by in situ hybridization. In a further step, the phenotype and the relative frequency of perforin mRNA-expressing cells were determined. RESULTS: In the normal pancreas, perforin mRNA-expressing cells are rarely present (mean, 0.3 cells/mm2). In contrast, the frequency of perforin mRNA-expressing cells is increased severalfold in diseased tissue specimens (mean, 6.6 cells/mm2). The frequency of perforin mRNA-expressing cells is high in the CD56+ (18%) and CD8+ cell population (12%) but low in the CD4+ cell population (1%). CONCLUSIONS: The significantly elevated frequencies of perforin mRNA-expressing cells in the pancreas of patients with alcoholic chronic pancreatitis suggest an involvement of cell-mediated cytotoxicity in the pathogenesis of this disease. The preferential localization of these activated cells close to areas with parenchyma provides circumstantial evidence that autoreactive cytotoxic cells may contribute to tissue destruction in alcoholic chronic pancreatitis.
Cell Separation↗
The C-X-C chemokine ENA-78 is preferentially expressed in intestinal epithelium in inflammatory bowel disease.
BACKGROUND & AIMS: Secretion of chemokines by epithelial cells may represent a crucial event in the pathogenesis of inflammatory bowel disease (IBD). Expression of the chemokine epithelial neutrophil-activating peptide 78 (ENA-78) was monitored in patients with IBD and normal controls. METHODS: In situ hybridizations were performed on 41 tissue specimens from 15 patients with IBD and 10 controls to detect ENA-78 messenger RNA (mRNA). Immunofluorescence stainings were used to localize ENA-78 protein. RESULTS: Intestinal epithelial cells expressing ENA-78 mRNA at detectable levels are found at comparable frequencies in patients with Crohn's disease and ulcerative colitis. Tissue specimens with mild to moderate histological signs of disease activity show slightly higher frequencies of ENA-78 mRNA-expressing epithelial cells than areas with signs of severe disease activity (P = 0.14). Immunofluorescence stainings showed presence of the ENA-78 protein in > 90% of preserved epithelial cells in IBD, in control tissues, ENA-78 mRNA was not detectable, and ENA-78 protein was detectable in 0%-30% of epithelial cells. CONCLUSIONS: The observations are in agreement with a role of the C-X-C chemokine ENA-78 in the pathogenesis of IBD.
Acute Disease↗
The failure of 'adult' interventions with adolescent depression: what does it mean for theory, research and practice?
The literature on the biological and phenomenologic presentation of major depressive disorder (MDD) in adolescents is reviewed and compared with that of depressed adults. Biological and psychosocial treatment approaches with adults and adolescents are then contrasted and the applicability of adult interventions to adolescents is examined. Some biological, cognitive, and experiential differences between adult and adolescent MDD may have treatment implications which have not yet been adequately addressed in the field. No effective treatments for adolescent MDD have, as yet, been developed or empirically tested. Based upon the results of this review, suggestions are made for the direction of future research.
Adolescent↗
Fluconazole versus nystatin in the prevention of candida infections in children and adolescents undergoing remission induction or consolidation chemotherapy for cancer.
An open, prospective, randomized pilot study was performed to assess the efficacy and safety of oral fluconazole 3 mg/kg once daily compared with oral nystatin 50,000 units/kg/day in four divided doses in preventing candida infections in 50 children undergoing remission induction or consolidation therapy for cancer. In 21 of 25 fluconazole-treated and 20 of 25 nystatin-treated patients the overall outcome of prophylaxis was clearly successful. Mild and transient oropharyngeal candidosis was observed in two and three patients in the fluconazole and nystatin groups respectively. One patient randomized to fluconazole and two patients randomized to nystatin required empirical treatment with amphotericin B and one patient assigned to fluconazole developed tissue-proven candida colitis. Initially non-colonized patients remained yeast-free throughout treatment with no differences between the two study arms. Initially colonized patients stayed colonized throughout treatment although at the end of the study, more patients randomized to nystatin were still harbouring yeasts (P = 0.05). Almost exclusively, Candida albicans (95%) was isolated. A change in species was observed in one patient in each arm of the study. Candida krusei or Candida glabrata were not encountered. Transient elevations of hepatic transaminases were more common in the fluconazole group, although not statistically significant (28% vs 12%, P = 0.15). Reversible grade I gastrointestinal and skin symptoms were observed in four patients randomized to fluconazole (16 vs 0%, P < 0.05). Fluconazole was as safe and effective as nystatin in controlling yeast colonization and in preventing superficial and invasive candida infections and the empirical use of amphotericin B in children and adolescents undergoing intensive chemotherapy for cancer.
Adolescent↗
Detection of perforin and tumour necrosis factor alpha mRNA expressing cells in sclerosing lymphocytic lobulitis of the breast.
The contribution of a cellular immune response to tissue destruction in sclerosing lymphocytic lobulitis of the breast is not well understood. In this study, comparison of one case with two age matched control cases showed an increased frequency of activated perforin mRNA expressing cells at the site of tissue destruction in lobulitis. Along with the detection of tumour necrosis factor alpha (TNF alpha) mRNA expressing cells in the infiltrates, the striking association of perforin expressing activated cytotoxic cells with remaining gland parenchyma and the high level of perforin mRNA suggests activation of cytotoxic cells in situ. These findings are evidence that cell mediated cytotoxicity plays a significant role in the destruction of mammary gland tissue in sclerosing lymphocytic lobulitis.
Adult↗
Are aluminium potroom workers at increased risk of neurological disorders?
OBJECTIVE: To determine whether long term potroom workers in an aluminium smelter are at increased risk of neurological disorders. METHODS: Cross sectional study of 63 current and former aluminium potroom workers first employed before 1970 and with at least 10 years of service. A group of 37 cast house and carbon plant workers with similar durations of employment and starting dates in the same smelter were used as controls. The prevalence of neurological symptoms was ascertained by questionnaire. Objective tests of tremor in both upper and lower limbs, postural stability, reaction time, and vocabulary were conducted. All subjects were examined by a neurologist. RESULTS: No significant differences in age, race, or education were found between the two groups. Although the potroom group had higher prevalences for all but one of the neurological symptoms, only three odds ratios (ORs) were significantly increased; for incoordination (OR 10.6), difficulty buttoning (OR 6.2), and depression (OR 6.2). Tests of arm or hand and leg tremor in both the visible and non-visible frequencies did not show any significant differences between the two groups. Testing of postural stability showed no definitive pattern of neurologically meaningful differences between the groups. There were no significant differences between the two groups in reaction time, vocabulary score, or clinical neurological assessment. CONCLUSIONS: The objective measures of neurological function provided little support for the finding of increased neurological symptom prevalences in the potroom workers, although increased symptoms may be an indicator of early, subtle neurological changes. The results provide no firm basis for concluding that neurological effects among long term potroom workers are related to the working environment, in particular aluminium exposure, in potrooms. These findings should be treated with caution due to the low participation of former workers and the possibility of information bias in the potroom group.
Adult↗