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Biomedical subjects

C Mueller

Publications and source records attributed to C Mueller.

At least 55 records · Page 3Linked to original sources

Distribution and patterns of blunt traumatic cervical spine injury.

STUDY OBJECTIVE: Previous studies of cervical spine injury involve individual institutions or special populations. There is currently little reliable information regarding natural cervical spine injury patterns after blunt trauma. This substudy of the National Emergency X-Radiography Utilization Study project was designed to accurately assess the prevalence, spectrum, and distribution of cervical spine injury after blunt trauma. METHODS: We prospectively enrolled all patients with blunt trauma undergoing cervical spine radiography at 21 diverse institutions. Injury status was determined by review of all radiographic studies obtained on each patient. For each individual injury, we recorded which specific films revealed the injury, the level and location of injury on each vertebra, and the age and sex of the patient. RESULTS: Of 34,069 enrolled patients with blunt trauma, 818 (2.4%) individuals had a total of 1,496 distinct cervical spine injuries to 1,285 different cervical spine structures. The second cervical vertebra was the most common level of injury (286 [24.0%] fractures, including 92 odontoid fractures), and 470 (39.3%) fractures occurred in the 2 lowest cervical vertebrae (C6 and C7). The vertebral body, injured in 235 patients, was the most frequent site of fracture. Nearly one third of all injuries (29.3%) were considered clinically insignificant. CONCLUSION: Cervical spine injuries occur in a small minority of patients with blunt trauma who undergo imaging. The atlantoaxial region is the most common site of injury, and the sixth and seventh vertebrae are involved in over one third of all injuries. Other spine levels are much more commonly involved than has previously been appreciated. A substantial minority of radiographically defined cervical spine injuries are of little clinical importance.

Adult↗

Urea as a PCDD/F inhibitor in municipal waste incineration.

Emissions of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from municipal waste incineration have been widely studied because of their extensive toxicity, and many efforts have been made to restrict their emissions. Although a number of chemical compounds have been shown in laboratory-scale tests to inhibit the formation of PCDD/Fs, few have been tested in pilot- or full-scale plants. This work evaluates the effect of urea as a PCDD/F inhibitor in a pilot-scale incinerator that uses refuse-derived fuel (RDF). The decomposition of urea under the test conditions was also studied using detailed kinetic modeling. An aqueous solution of urea was injected into the flue gas stream after the furnace at approximately 730 degrees C, with varied urea concentrations and flue gas residence times used between the furnace and the sampling point. The results demonstrate that urea can successfully inhibit PCDD/F formation in waste incineration if concentrations and injection points are properly adjusted. The kinetic model showed that urea can be rapidly decomposed under appropriate flue gas conditions, indicating that in addition to the urea molecule itself, decomposition products of urea can also be responsible for the reduction of PCDD/F production during incineration.

Benzofurans↗

Chemokines and interleukin-18 are up-regulated in bronchoalveolar lavage fluid but not in serum of septic surgical ICU patients.

Our objective was to investigate the levels of chemokines (MIP1-alpha, MCP-1, and Gro-alpha), Interleukin-18 (IL-18), and Interleukin (IL-6) in bronchoalveolar lavage (BAL) fluid and serum at the onset and ongoing states of sepsis as defined by the American College of Chest Physicians/Society of Critical Care Medicine in septic surgical ICU patients. Our summary background data was to understand the significance of compartmentalized inflammatory mediator production in an immunologically active organ (lung) in comparison with levels in the systemic circulation. The study group consisted of 20 septic patients and 10 non-septic patients on surgical ICU. At the onset of sepsis, both BAL fluid and serum samples were taken and levels of MIP-1alpha, MCP-1, GRO-alpha, IL-18, and IL-6 were measured by ELISA. Furthermore, over a subsequent 8-day period, levels of these mediators were determined in serum. In some experiments, IL-18 mRNA levels were determined in peripheral blood lymphocytes (PBL) of septic and non-septic patients. At the onset of sepsis, MIP-1alpha, MCP-1, GRO-alpha, IL-18, and IL-6 levels were significantly up-regulated in BAL fluid as compared with non-septic controls. In marked contrast, with the exception of IL-18 mRNA and IL-6 peptide, there was no increase in serum levels of inflammatory mediators determined both at the onset and during the ongoing states of sepsis. Based on the present data, monitoring levels of serum chemokines and IL-18 protein as markers of sepsis might be misleading since despite their non-detection in serum, they were highly up-regulated in the lung tissue compartment. These data might underscore the role of MIP-1alpha, MCP-1, GRO-alpha, and IL-18 in the mediation of local tissue damage. Furthermore, these findings raise the notion that mediator measurement in immunologically active organs might serve as pivotal indicators of sepsis prior to the actual fulfillment of specific clinical criteria that defines the patient as being septic.

Bronchoalveolar Lavage Fluid↗

Influence of long-term preservation with endobronchially administered perfluorodecalin on pulmonary graft function.

BACKGROUND: Experimental studies demonstrated a suppression of oxygen-derived free radicals, reduced adhesion of activated neutrophils on the endothelium and an increase of de novo synthesis of surfactant during liquid ventilation with perflurocarbon. The purpose of this study was to assess the pulmonary graft function after preservation with endobronchially administered perfluorocarbon as an alternative to flush perfusion. METHODS: Native bred pigs underwent orthotopic left lung transplantation. Donor lungs were flushed in situ with either a low-potassium dextran solution (LPD, n=6) or a perfluorochemical was administered endobronchially (PFC, n=6) and were then stored after removal for 18 hr at 4 degrees C. Pulmonary graft function was assessed after reperfusion for 5 hr by measuring pulmonary gas exchange and hemodynamics during isolated ventilation and perfusion. Tissue specimens were taken for analysis of morphology and wet/dry ratio. All values were compared to a sham-operated group (n=6). RESULTS: Pulmonary gas exchange of the graft revealed reduced paO2 values and elevated paCO2 values in the PFC group throughout the observation period as compared with the LPD group and sham group. Endothelial alterations and fibrin exudate in the PFC group were significantly more pronounced. Lungs in the LPD group showed functional and morphological recovery close to sham group. CONCLUSIONS: Long-term preservation with endobronchially administered perfuorocarbon is possible. Impaired pulmonary graft function and pronounced morphological alterations indicate an aggravation of the ischemic reperfusion injury after lung transplantation compared to LPD preserved lungs.

Animals↗

A mutagenic PCR identifies isolates of Borrelia garinii responsible for Lyme borreliosis.

Borrelia garinii is one of the three major Borreliae responsible for Lyme borreliosis in Europe. We have characterized a protein of B. garinii (VS102) and a genomic fragment from the gene encoding this protein was cloned. The DNA sequence of the fragment showed high homology with a known gene of B. burgdorferi sensu stricto. The protein encoded by this gene in B. burgdorferi sensu stricto is a phosphocarrier protein (histidine-containing protein). A mutation T to G polymorphism at codon 57 was found to be specific to B. garinii. A PCR-based approach that allows the rapid detection of this mutation made it possible to specifically discriminate B. garinii from other B. burgdorferi genospecies with high sensitivity and specificity.

Animals↗

Inefficient T cell memory in the brain of mice infected with Candida albicans.

We compared the contribution of T cell memory to the clearance of the fungus Candida albicans from the liver, kidneys and brain of Balb/c mice in a model of secondary systemic infection. In secondary infection, the fungi were more rapidly eliminated from the liver and kidneys than during primary infection. This was most pronounced in the liver where the fungi were eliminated at day 14 of infection. In contrast, in the brain, cultivable yeasts were still detectable 35 days after infection. Although both CD4(+) and CD8(+) cells could be detected in the brain with immunohistology, these cells appeared later in infection and in lower numbers than in the liver, and there were no significant differences in the numbers of T cells detected in the brain between primary and secondary infection. In contrast to the liver and the kidneys where an effect of T cells on the fungal load could be demonstrated, depletion of neither CD4(+) nor CD8(+) nor Thy-1.2(+) cells resulted in a significant increase of the amount of fungi in the brain above levels measured in secondarily infected mice treated with irrelevant antibodies. We conclude that the contribution of CD4(+) and CD8(+) cells to the clearance of C. albicans in secondary infection is organ-dependent and that T cell memory is inefficient in the brain.

Animals↗

Intestinal intraepithelial lymphocytes exert potent protective cytotoxic activity during an acute virus infection.

After systemic infection of mice with 104 PFU of lymphocytic choriomeningitis virus (LCMV), infected cells are detected simultaneously in various organs, including spleen and intestinal mucosa. Most notably, virus-infected cells are also present among CD11c+ dendritic cells in the subepithelial area of the small intestinal mucosa. Some of these virus-infected cells are in close spatial association with intestinal intraepithelial lymphocytes (IEL). Therefore, we compared virus-specific cytotoxic activity of CD8 splenocytes with that of IEL subsets. While ex vivo isolated TCRalphabeta+CD8alphaalpha+ IEL exert only minimal virus-specific cytotoxicity, maximum specific killing mediated by TCRalphabeta+CD8alphabeta+ IEL on day 8 postinfection exceeds maximum cytotoxic activity observed with CD8 splenocytes when assessed in vitro. Maximum cytotoxic activity of IEL is preceded by peak perforin and granzyme B mRNA expression in IEL around day 6 postinfection, suggesting a recent activation in situ. The antivirus cytotoxicity of in vivo primed IEL is further demonstrated by the protection from virus production in the spleen of mice infected with LCMV 10 h before adoptive cell transfer. These data indicate a potent priming of LCMV-specific IEL in situ after systemic LCMV infection and suggest that cytotoxic IEL markedly contribute to the elimination of virus-infected cells in the intestinal mucosa.

Acute Disease↗

Differential contribution of Fas- and perforin-mediated mechanisms to the cell-mediated cytotoxic activity of naive and in vivo-primed intestinal intraepithelial lymphocytes.

Intestinal intraepithelial lymphocytes (IELs) are known to exert strong constitutive cytotoxic activity. In the present study we compared the Ag-specific cytotoxic activity and the effector mechanisms involved in non-Ag-primed, naive and in in vivo-primed IELs and splenic CD8 T cells. Ex vivo isolated naive CD8alphaalpha TCRalphabeta IELs, CD8alphabeta IELs, and splenocytes from lymphocytic choriomeningitis virus (LCMV)-specific TCR transgenic mice exert Ag-specific cytotoxic activity in a long-term, but not in a short-term, cytotoxicity assay. This cytotoxic activity is mainly Fas-Fas ligand mediated and is significantly reduced in the presence of 20 microg/ml Fas-Fcgamma1 fusion protein. Both CD8alphabeta IELs and CD8alphabeta splenocytes isolated from LCMV-infected C57BL/6 mice exert potent perforin-dependent cell-mediated cytotoxicity. CD8alphaalpha TCRalphabeta IELs from LCMV-infected animals, however, show only minimal Ag-specific cytotoxicity. The potent cytotoxic activity of in vivo activated CD8alphabeta IELs is not affected by the addition of Fas-Fcgamma1. Nevertheless CD8alphabeta IELs from LCMV-infected perforin-deficient mice exert Ag-specific cytotoxicity in a short-term cytotoxicity assay, and this cytotoxicity is almost completely blocked by the addition of Fas-Fcgamma1. These results demonstrate that naive CD8alphabeta IELs exert Ag-specific, Fas-Fas ligand-mediated, constitutive cytotoxic activity in a long-term cytotoxicity assay, whereas primed CD8alphabeta IELs primarily use the perforin-dependent exocytosis pathway to exert their potent cytotoxic activity. Furthermore, these results clearly illustrate the requirement for Ag-specific determination of IEL-mediated cytotoxicity, because the elevated, but variable, frequencies of memory-type T cells in this compartment may lead to ambiguous results when polyclonal activation or redirected assays are used.

Animals↗

Pulmonary graft function after long-term preservation of non-heart-beating donor lungs.

BACKGROUND: Critical organ shortage in lung transplantation could be attenuated by the use of non-heart-beating donor (NHBD) lungs. In addition, prolonged ischemic tolerance of the organs would contribute to the alleviation of organ shortage. The aim of this study was to investigate pulmonary graft function of NHBD lungs after long-term hypothermic storage. METHODS: Twelve native-bred pigs (bodyweight 20 to 30 kg) underwent left lung allotransplantation. In the heart-beating donor (HBD) group, lungs were harvested immediately after cardiac arrest. In the NHBD group, lungs were subjected to a warm ischemic period of 90 minutes before harvesting. After a total ischemic time of 19 hours, pulmonary grafts in both groups were reperfused and pulmonary graft function was assessed. All values were compared with a sham-operated control group. RESULTS: Pulmonary graft function in the HBD group was excellent. In the NHBD group, pulmonary gas exchange was impaired, but still provided good graft function compared with the excellent graft function in the HBD group. Pulmonary vascular resistance was even lower in the NHBD group. In the NHBD group, calculated intrapulmonary shunt fraction (Qs/Qt) was significantly increased compared with the sham-group. Histologic alteration and wet-to-dry ratio did not differ significantly between the HBD and NHBD group. CONCLUSIONS: We conclude that NHBD lungs (90 minutes of warm ischemic time) have the potential to alleviate organ shortage in lung transplantation even after an extended total ischemic time.

Animals↗

Differential expression of chemokines in normal pancreas and in chronic pancreatitis.

BACKGROUND & AIMS: Cellular infiltrates are present already in early stages of chronic pancreatitis. The mechanisms responsible for their recruitment are unknown. Hence, we determined the differential expression of chemokine genes and their cellular sources in normal and affected pancreatic tissues. METHODS: Pancreatic tissues from 23 patients with chronic pancreatitis and from 4 normal controls were subjected to in situ hybridization for detecting messenger RNA (mRNA) of the chemokine genes interleukin 8, ENA-78, MIG, MCP-1, and I-309. RESULTS: Normal pancreatic tissues lack cells expressing mRNA for IL-8, ENA-78, MIG, and MCP-1. In contrast, pancreatic lobuli with mild to moderate signs of tissue alterations strongly expressed MCP-1 mRNA in centroacinar ducts, endothelia, fibroblasts, macrophages, T cells, and occasionally in nerves. Interleukin 8 and ENA-78 mRNA is preferentially detected in centroacinar ducts of pancreatic lobuli with more advanced alterations. Variable numbers of pancreas-infiltrating T cells express MIG mRNA. I-309 mRNA, however, is consistently observed in normal acini and in tissue with mild to moderate signs of tissue alterations. CONCLUSIONS: The observed differential expression of distinct chemokine genes in pancreatic parenchyma and infiltrates from patients with chronic pancreatitis strongly suggests an involvement of distinct chemokines in the initiation and perpetuation of disease.

Adult↗

O(6)-methylguanine DNA adducts associated with occupational nitrosamine exposure.

Occupational nitrosamine exposures from a rubber vehicle seal (VS) curing operation were compared with the peripheral blood lymphocyte concentrations of two nitrosamine-related DNA adducts, N(7)-methylguanine (N(7)mdG) and O(6)-methylguanine (O(6)mdG), and with the activity of the enzyme that repairs O(6)mdG adducts, O(6)-alkylguanine-DNA alkyltransferase (AGT). The occupational personal breathing zone (PBZ) nitrosamine exposures ranged from 0.4 to 9.3 microg/m(3) in the VS area, from 0.1-2 microg/m(3) in an area remote from the VS and were not detected at a nearby rubber plant. Workers from all three of these locations had detectable concentrations of N(7)mdG adducts, ranging from 0.1 to 133.2 adducts/10(7) deoxyguanosine nucleosides. Although N(7)mdG concentrations were elevated for those who worked in the VS area (median 3.60 compared with 1.44), the difference was not statistically significant after controlling for confounding factors. The O(6)mdG adduct concentrations were much lower than those of N(7)mdG, ranging from non-detectable to 12.7 O(6)mdG adducts/10(7) deoxyguanosine nucleosides and many of the participants (40/78 successfully analyzed) did not have detectable amounts of these adducts (limit of detection 0.03 O(6)mdG adducts/10(7) deoxyguanosine nucleosides). Analysis of the ordinal exposure categories (high, medium/high, medium/low, low and no exposure) yielded a statistically significant association with having detectable O(6)mdG adducts (Kendall's taub = -0.253, asymptotic SE = 0.096). There was no significant association between AGT activity and nitrosamine exposure or exposure category (P > 0.30). Although no association was found between PBZ exposure and either the N(7)mdG adduct concentrations or AGT activity, the significant positive association between working in and near the VS department and the presence of O(6)mdG adducts, which have mutagenic potential, provides evidence to link nitrosamine exposure one step closer to human cancer by demonstrating an association between external nitrosamine exposures and cancer-related biological effects.

DNA Adducts↗

Value-added outcomes: the use of advanced practice nurses in long-term care facilities.

The purpose of this study was to determine the effect on clinical outcomes for newly admitted nursing home residents when advanced practice gerontological nurses (APNs) worked with staff to implement scientifically based protocols for incontinence, pressure ulcers, depression, and aggressive behavior. Use of APNs in this manner differs from the usual way APNs have been used in nursing homes, in which their primary focus has been to augment the physician's role. The APN treatment was randomly assigned to two nursing homes and usual care was assigned to a third. Trajectories from admission to 6 months revealed that residents with APN input into their care (n = 86) experienced significantly greater improvement or less decline in incontinence, pressure ulcers, and aggressive behavior, and they had higher mean composite trajectory scores compared with residents receiving usual care (n = 111). Significantly less deterioration in affect was noted in cognitively impaired residents in the treatment group. Findings suggest that APNs can be effective links between current scientific knowledge about clinical problems and nursing home staff.

Aged↗

The RUG-III case mix classification system for long-term care nursing facilities: is it adequate for nurse staffing?

The purpose of this study was to explore the validity of the nursing time associated with the Resource Utilization Group Version III (RUG-III) case mix classification system by determining its potential usefulness for making nurse staffing decisions in long-term care (LTC) facilities. Experts in LTC nursing administration were asked to determine the amount of nursing time required by nursing home residents. The estimates were significantly higher than the RUG-III nursing time for all case mix groups. This finding suggests that the nursing time associated with the RUG-III system may not meet the needs of nursing home residents if used as a basis for nurse staffing. Further analysis questions the wisdom of mandating minimum staffing standards for LTC facilities without taking into account the individual needs of residents.

Delphi Technique↗

Evaluation of occupational transmission of hepatitis A virus among wastewater workers.

To provide information concerning potential occupational transmission of hepatitis A virus (HAV) among wastewater workers in a large city in the United States, a cross-sectional survey was performed using a saliva test to detect antibodies to HAV (anti-HAV). Fifty-nine (20%) of 302 participants tested positive for anti-HAV. After controlling for the confounding effects of age and race, wastewater work was not significantly associated with an increase in the prevalence of anti-HAV (prevalence ratio = 1.3; 95% confidence interval 0.7 to 2.4). Additionally, when examining only the wastewater workers, no statistically significant occupational risk factors for anti-HAV were identified. The results of this survey are consistent with the position of the Centers for Disease Control and Prevention regarding groups at risk for HAV infection.

Adult↗

A novel system to study the impact of epithelial barriers on cellular metabolism.

Medications introduced into the systematic circulation must be transported across biological barriers such as skin, gastrointestinal, or bronchial epithelia, which can alter their kinetic and metabolic profiles. It is, therefore, important to understand diffusion kinetics across barrier membranes when choosing a dosing regime that will elicit the greatest cellular response. An in vitro system that combines membrane transport studies with a downstream cell culture chamber has been developed. The system has been tested with skin and a small intestine model (Caco-2 cell monolayers) as barriers, the peroxovanadium compound [VO(O2)2 1, 10 phenanthroline] bpV(phen), as the test chemical, Hep-G2 (liver) as the test cells, and glucose consumption as the test assay. Peroxovanadium has insulin mimetic properties and has been previously demonstrated to effectively lower blood glucose levels in diabetic rats when administered transdermally. A dose of 10 mM bpV(phen) placed on the skin epidermis with a continuous iontophoretic current of 0.5 mA/cm2 for 4.5 h led to a net 22% increase in glucose consumption by Hep-G2 cells. The same dose of bpV(phen) passively diffusing across a Caco-2 cell monolayer led to an increase in glucose consumption by Hep-G2 cells of 23%. This system is highly versatile and can be used to study many other processes, involving a variety of biological membranes, cell types, chemicals and assays, making it a valuable research tool.

Animals↗

On the biogeography of yeasts in the Wickerhamiella clade and description of Wickerhamiella lipophila sp. nov., the teleomorph of Candida lipophila.

We describe the new yeast species Wickerhamiella lipophila, the teleomorph of Candida lipophila, a haploid heterothallic yeast previously isolated from insects associated with morning glories in Hawaii. Both mating types were recovered in the eastern region of Maui, and a single strain was found in the Waimea region of Kauai. We reexamined the mating compatibility of the several strains of Candida lipophila previously collected on the island of Hawaii and found them to be fertile mating types that had been overlooked because of the unpredictability of mating and ascus formation. The type culture of Candida lipophila [UWO(PS)91-681.3 = CBS 8458, h+] is transferred to the genus Wickerhamiella, and strain UWO(PS)00-340.1 (CBS 8812, h-) is designated as isotype. Also found on Maui and Kauai were strains of Candida drosophilae that produced a strong extracellular protease. An update on the global distribution of members of the Wickerhamiella clade is given.

Animals↗

Cytochrome P450RAI(CYP26) promoter: a distinct composite retinoic acid response element underlies the complex regulation of retinoic acid metabolism.

The catabolism of retinoic acid (RA) is an essential mechanism for restricting the exposure of specific tissues and cells to RA. We recently reported the identification of a RA-inducible cytochrome P450 [P450RAI(CYP26)], in zebrafish, mouse, and human, which was shown to be responsible for RA catabolism. P450RAI exhibits a complex spatiotemporal pattern of expression during development and is highly inducible by exogenous RA treatment in certain tissues and cell lines. Sequence analysis of the proximal upstream region of the P450RAI promoter revealed a high degree of conservation between zebrafish, mouse, and human. This region of the promoter contains a canonical retinoic acid response element (5'-AGT-TCA-(n)5-AGTTCA-3'), embedded within a 32-bp region (designated R1), which is conserved among all three species. Electrophoretic mobility shift assays using this element demonstrated the specific binding of murine retinoic acid receptor-gamma (RARgamma) and retinoid X receptor-alpha (RXRalpha) proteins. Transient transfection experiments with the mouse P450RAI promoter fused to a luciferase reporter gene showed transcriptional activation in the presence of RA in HeLa, Cos-1, and F9 wild-type cells. This activation, as well as basal promoter activity, was abolished upon mutation of the RARE. Deletion and mutational analyses of the P450RAI promoter, as well as DNase I footprinting studies, revealed potential binding sites for several other proteins in conserved regions of the promoter. Also, two conserved 5'-TAAT-3' sequences flanking the RARE were investigated for their potential importance in P450RAI promoter activity. Moreover, these studies revealed an essential requirement for a G-rich element (designated GGRE), located just upstream of the RARE, for RA inducibility. This element was demonstrated to form complexes with Sp1 and Sp3 using nuclear extracts from either murine F9 or P19 cells. Together, these results indicate that the P450RAI-RARE is atypical in that conserved flanking sequences may play a very important role in regulating RA inducibility and expression of P450RAI(CYP26).

Animals↗