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Biomedical subjects

L Moss

Publications and source records attributed to L Moss.

At least 19 recordsLinked to original sources
PubMed2001

Quinolone use as a risk factor for nosocomial Clostridium difficile-associated diarrhea.

OBJECTIVE: To determine modifiable risk factors for nosocomial Clostridium difficile-associated diarrhea (CDAD). DESIGN: Case-control study. SETTING: 300-bed tertiary-care hospital. PARTICIPANTS: Hospital inpatients present during the 3-month study period. METHODS: Case-patients identified with nosocomial CDAD over the study period were compared to two sets of control patients: inpatients matched by age, gender, and date of admission; and inpatients matched by duration of hospital stay. Variables including demographic data, comorbid illnesses, antibiotic exposure, and use of gastrointestinal medications were assessed for case- and control-patients. Conditional logistic regression was performed to identify risk factors for nosocomial CDAD. RESULTS: 27 case-patients were identified and were compared to the two sets of controls (1:1 match for each comparison set). For the first set of controls, use of ciprofloxacin (odds ratio [OR], 5.5; 95% confidence interval [CI 95], 1.2-24.8; P=.03) was the only variable that remained significant in the multivariable model. For the second set of controls, prior exposure to cephalosporins (OR, 6.7; CI 95, 1.3-33.7; P=.02) and to ciprofloxacin (OR, 9.5; CI 95, 1.01-88.4; P=.05) were kept in the final model. CONCLUSIONS: Along with cephalosporins, prior quinolone use predisposed hospitalized patients to nosocomial CDAD. Quinolones should be used judiciously in acute-care hospitals, particularly in those where CDAD is endemic.

4-Quinolones↗
PubMed2001

Moving to evidence-based practice for pain management in the critical care setting.

Widespread application of EBPM by bedside providers is needed to demonstrate the success of pain management strategies on patient outcomes. This goal is not easy to attain and generally requires time, patience, and a multidisciplinary team approach. Implementation and evaluation of pain interventions increase awareness and knowledge of pain management strategies and can result in an overall improvement in pain management. The literature and guidelines recommend the use of specific strategies to ensure practice change. Studies suggest that a more intensive or "active" effort to alter practice is generally most successful. The pain management program should be marketed so that both the health care providers and patients are aware of the goal and resources available. It may take 3 to 5 years to infuse the change and see the improvement. Reinfusion over time also needs to be planned. Bedside practitioners need to have knowledge of the current best evidence in pain management of the critically ill patient. Barriers to implementation must be eliminated so that practitioners can conscientiously and judiciously implement strategies to relieve pain. Opinion leaders and change agents need to be available to continually champion EBPM, and prompts to ask about pain should be provided to practitioners and patients.

Diffusion of Innovation↗
PubMed1996

Deliberate self harm and the Probation Service; an overlooked public health problem?

Reducing the suicide rate is one of chief targets of Health of the nation, although consideration scepticism has been expressed about whether or not this can be achieved. We have reported that nearly a third of those supervised by the West Yorkshire Probation Service had a history of deliberate self harm (DSH). Comparing the known risk factors for DSH and suicide with the composition of those supervised by the Probation Service suggests this is a high-risk group that has not traditionally been well served by mental health services.

Attitude to Health↗
PubMed1995

Gene therapy for diabetes mellitus in rats by hepatic expression of insulin.

Type 1 diabetes mellitus is caused by severe insulin deficiency secondary to the autoimmune destruction of pancreatic beta cells. Patients need to be controlled by periodic insulin injections to prevent the development of ketoacidosis, which can be fatal. Sustained, low-level expression of the rat insulin 1 gene from the liver of severely diabetic rats was achieved by in vivo administration of a recombinant retroviral vector. Ketoacidosis was prevented and the treated animals exhibited normoglycemia during a 24-hr fast, with no evidence of hypoglycemia. Histopathological examination of the liver in the treated animals showed no apparent abnormalities. Thus, the liver is an excellent target organ for ectopic expression of the insulin gene as a potential treatment modality for type 1 diabetes mellitus by gene therapy.

Animals↗
PubMed1995

Accuracy and clinical utility of transtelephonic pacemaker follow-up.

The diagnostic accuracy of transtelephonic pacemaker monitoring (TTM) has been quantified in a retrospective study involving 369 patients in three U.S. cardiac centers. Using existing medical records, TTM findings in a total of 413 reports were judged for equivalence to the findings of subsequent physical examinations in pacemaker clinics. This study found TTM follow-up testing to have a sensitivity of 94.6%, specificity of 98.5%, positive predictive value of 93.3%, and negative predictive value of 98.8%. The study also documents the clinical utility of TTM in identifying various modes of pacemaker malfunctions and instances of significant arrhythmia.

Arrhythmias, Cardiac↗
PubMed1994

Glycosylation of human trophoblast integrins is stage and cell-type specific.

Cytotrophoblasts are the specialized epithelial cells of the placenta. During the first trimester, a subpopulation of chorionic villus cytotrophoblasts differentiates along an invasive pathway and penetrates the maternal endometrium, decidua and spiral arterioles. Cytotrophoblast invasiveness declines rapidly during the second half of gestation. Isolated cytotrophoblasts of different gestational ages retain this differential invasiveness in culture. To determine whether the properties of integrin receptors for extracellular matrix molecules differ between invasive and non-invasive cytotrophoblasts, detergent extracts of isolated cytotrophoblasts of different gestational ages, and of first-trimester villous fibroblasts, were immunoprecipitated with subunit-specific anti-beta 1 integrin antibodies. Striking alterations in electrophoretic mobility were observed in beta 1 integrins from first-trimester cytotrophoblasts, as compared with those from term cytotrophoblasts or first-trimester villous fibroblasts, suggesting a cell-type-specific, temporally regulated alteration in glycosylation. Treatment of total first-trimester cytotrophoblast beta 1 integrins or the isolated alpha 5/beta 1 fibronectin receptor with endo-beta-galactosidase restored electrophoretic mobility to control levels, suggesting the presence of polylactosamine-bearing oligosaccharides. Further analysis by enzyme digestion and lectin-affinity chromatography suggested that they consisted of at least three antennae and short, sialylated lactosamine units. These oligosaccharides did not affect the affinity of the first-trimester cytotrophoblast fibronectin receptor for fibronectin. However, this receptor bound more strongly to wheat germ agglutinin than control fibronectin receptor and resisted elution by high concentrations of sugar hapten, requiring ionic detergent for removal. These results suggested that the altered glycosylation affected the conformation of the fibronectin receptor.

Amino Acid Sequence↗
PubMed1994

Improved mammographic imaging using tissue expanders for breast augmentation.

Several studies indicate that mammographic evaluation of the breast is inhibited by both submammary and submuscular implants, regardless of implant composition. Two hundred radiographs were evaluated following subpectoral placement of 25 combination gel/saline and 25 saline-filled tissue expanders. Within 3 months after augmentation, mammograms were performed using the standard and displacement techniques; patients with inflated implants were followed by a repeat displacement study (with the expander deflated). After completion of the mammogram, expanders were reinflated. Our experience demonstrates that better visualization of breast tissue may be accomplished by implant-deflated views in patients with small amounts of breast tissue, tight skin envelopes, or capsular contraction. In each of these circumstances, the displaced view failed to adequately demonstrate glandular tissue. The presence of the inflated implant impairs mammographic visualization in a number of ways, including implant opacity, impaired automatic exposure control, interference with breast compressibility, and implant displacement. These effects are consistently present in small breasts (< an estimated 300 g), in breasts with grade III or IV capsular contracture, and in breasts with minimal skin laxity (i.e., nonptotic breasts). Breast compression was compromised to a greater degree in the presence of grade III and IV capsular contracture; however, deflation of an adjustable implant optimized radiographic interpretation to a high degree. The deflatable saline implant yields a less obscured evaluation of the augmented breast. We suggest that an extended-use deflatable device (i.e., tissue expander) be considered as an option in our search for a safe and reliable implant for augmentation mammoplasty, particularly in patients with small breasts, tight skin envelopes, or a propensity for capsular contracture.

Breast Implants↗
PubMed1994

Research utilization in critical care: an exemplar.

The authors describe the process and outcome of implementing a research-based pain management protocol in four adult critical care units at a large, Midwestern tertiary care center. The project was initiated and directed by members of the divisional research committee. Strategies used to change practice included determining if pain management was a problem via quality assessment monitors, surveying nurses regarding their knowledge and attitude toward pain management, educating staff members about the research base for the practice change, using change champions in each unit, and developing a core group of nurses in each unit to facilitate the change. Outcomes of this research utilization project include a 41% decline in the number of patients in pain, a 44% decline in pain intensity, and improvement in nurses knowledge about pain.

Clinical Nursing Research↗
PubMed1993

Sch 39304, a new antifungal agent: oral and topical treatment of vaginal and superficial infections.

Sch 39304 is a new broad spectrum triazole antifungal agent that is active, orally and topically, against superficial Trichophyton mentagrophytes and vaginal Candida albicans infections. Sch 39304 was compared to fluconazole (FLZ) in a T. mentagrophytes infection model in guinea pigs. Following topical administration, Sch 39304 (0.125%, twice daily, 10 days), was 5-8-fold more effective than FLZ, based on culture and lesion score results. Following oral administration, Sch 39304 (2.5 mg kg-1, once daily, 10 days) produced a dramatic reduction in lesion scores and was 20-fold more active than FLZ; however, due to the length of time it takes for the drugs to reach the infected area of the skin and eradicate the infections, most animals remained culture positive with both drugs. Sch 39304 was also compared with FLZ in a vaginal C. albicans infection in hamsters. Following oral administration (4 days), Sch 39304 (1.6 mg kg-1), cured all hamsters and was 4-fold more active than FLZ. In addition, Sch 39304 as a single oral dose (10 mg kg-1) also cured all hamsters. When treatment was intravaginal (8 days), Sch 39304 was again more active than FLZ (2-fold), and also micronazole (8-fold), with 100% of the hamsters cured at concentrations as low at 0.025%.

Administration, Oral↗
PubMed1992

Myelin turnover in hyperphenylalaninaemia. A re-evaluation with the HPH-5 mouse.

Myelin turnover has been studied in the 25-day-old HPH-5 mouse, a phenylalanine hydroxylase-deficient mouse mutant. The half-life of the fast component of myelin decreased from 15 days in control mice to 4.5 days at blood phenylalanine levels of 2.5 mmol/L. The slow component of myelin seems also to be affected by the high phenylalanine level. These observations confirm similar observations obtained with chemically induced models of hyperphenylalaninaemia and are therefore due to the hyperphenylalaninaemia per se, independently of the inhibitors of phenylalanine hydroxylase. An intermediate blood level of phenylalanine (0.7 mmol/L) likewise seems to interfere with myelin metabolism, although to a lesser degree.

Aging↗
PubMed1991

Sulfonylurea signal transduction.

In the pancreatic beta cells the proximal step in sulfonylurea signal transduction is the binding of these clinically important drugs to high-affinity receptors in the beta cell membrane. Using HIT cells as a model system, we have established an extremely close correlation between the affinity of binding of glyburide and its analog, iodoglyburide, and the activation of various steps in stimulus-secretion coupling--inhibition of 86Rb+ efflux, increase in [Ca2+]i resulting from gating of voltage-gated calcium channels by cell depolarization, and the exocytosis of insulin. Two different L-type channel cDNAs have been identified in an HIT cell library, one neuroendocrine in type and one more cardiac-like. A HIT cell membrane protein of Mr 140,000, which we believe to be the high-affinity sulfonylurea receptor, can be covalently linked to 5(125)-iodo-2-hydroxyglyburide by ultraviolet irradiation. The receptor has been solubilized and retains binding activity and the same rank order of displacement of the 5(125)-iodo-2-hydroxyglyburide as observed with the native receptor. The Mr 140,000 protein has been partially purified and the amino acid sequences of three proteolytic fragments have been used to design oligonucleotides to screen HIT cell cDNA libraries. Since the binding constant of glyburide or iodoglyburide is closely correlated with the ability of these compounds to inhibit the ATP-sensitive K+ channel, increase [Ca2+]i, and elicit insulin secretion, we have identified the Mr 140,000 protein as the sulfonylurea receptor. Expression of the cloned cDNA should allow us to test this hypothesis directly.

ATP-Binding Cassette Transporters↗
PubMed1990

Determination of apical membrane polarity in mammary epithelial cell cultures: the role of cell-cell, cell-substratum, and membrane-cytoskeleton interactions.

The membrane glycoprotein, PAS-O, is a major differentiation antigen on mammary epithelial cells and is located exclusively in the apical domain of the plasma membrane. We have used 734B cultured human mammary carcinoma cells as a model system to study the role of tight junctions, cell-substratum contacts, and submembraneous cytoskeletal elements in restricting PAS-O to the apical membrane. Immunofluorescence and immunoelectronmicroscopy experiments demonstrated that while tight junctions demarcate PAS-O distribution in confluent cultures, apical polarity could be established at low culture densities when cells could not form tight junctions with neighboring cells. In such cultures the boundary between apical and basal domains was observed at the point of cell contact with the substratum. Immunocytochemical analysis of these cell-substratum contacts revealed the absence of a characteristic basement membrane containing laminin, collagen (IV), and heparan sulfate proteoglycan. However, serum-derived vitronectin was associated with the basal cell surface and the cells were shown to express the vitronectin receptor on their basolateral membranes. Additionally, treatment of cultures with antibodies against the vitronectin receptor caused cell detachment. We suggest, then, that interactions between vitronectin and its receptor, are responsible for establishment of membrane domains in the absence of tight junctions. The role of cytoskeletal elements in restricting PAS-O distribution was examined by treating cultures with cytochalasin D, colchicine, or acrylamide. Cytochalasin D led to a redistribution of PAS-O while colchicine and acrylamide did not. We hypothesize that PAS-O is restricted to the apical membrane by interactions with a microfilament network and that the cytoskeletal organization is dependent upon cell-cell and cell-substratum interactions.

Actin Cytoskeleton↗
PubMed1988

Cell-to-cell heterogeneity in the expression of carbohydrate-based epitopes of a mucin-type glycoprotein on the surface of human mammary carcinoma cells.

A large, O-linked glycoprotein, termed PAS-O, is a major differentiation antigen on the surface of normal lactating breast epithelia and is also found on the surface of many mammary tumors and mammary carcinoma cell lines. A characteristic feature of populations of tumor cells that express PAS-O is the cell-to-cell heterogeneity with respect to the presence or absence of the molecule. In this study, we used the human mammary carcinoma line 734B and a set of six monoclonal antibodies reactive with PAS-O to study the basis of this heterogeneity. Extensive Western blot analysis of antibody binding to PAS-O in milk fat globule membranes and in skim milk revealed that the antibodies all recognized different epitopes of PAS-O. Moreover, the epitopes were destroyed by periodic acid oxidation, demonstrating their oligosaccharide basis. All six monoclonal antibodies stained the 734B cells heterogeneously. In addition, five clones derived from the parent 734B population also exhibited heterogeneity in the expression of each of the epitopes. An analysis of staining of the 734B clones revealed that, in some cases, certain cells within the cloned population stained with one monoclonal antibody but not with another antibody. Significantly, though, when the 734B cells were treated with neuraminidase prior to antibody staining, most of the heterogeneity was eliminated, and all but one of the monoclonal antibodies stained 90-100% of the cells. This increase in cell staining was matched by an increase in PAS-O staining on Western blots. We conclude that heterogeneity in PAS-O expression on 734B cells is due partly to masking of epitopes by sialic acid and a variation (on a cell-to-cell basis) in the extent of PAS-O sialylation.

Antibodies, Monoclonal↗
PubMed1987

Purification and some properties of liver adenylylsulfate kinase.

Adenylylsulfate kinase (ATP:adenylylsulfate 3'-phosphotransferase, EC 2.7.1.25) has been purified over 1300-fold from rat liver in 10% yield. The enzyme has a molecular weight of 58,000 and is composed of four subunits of equal molecular weight. ATP is an allosteric activator of adenylylsulfate kinase, with a Hill coefficient of 2.2 and a K0.5 of 2.5 mM. Adenosine phosphosulfate is a potent inhibitor of adenylylsulfate kinase, but the adenosine phosphosulfate concentration for maximal reaction is dependent on the ATP concentration. At the physiological levels of ATP the inhibition by adenosine phosphosulfate is not likely to play a role, while the allosteric regulation of adenylylsulfate kinase by ATP may be operative.

Adenosine Phosphosulfate↗
PubMed1987

Properties of the 3'-phosphoadenosine-5'-phosphosulfate (PAPS) synthesizing systems of brain and liver.

Chromatography of brain and liver 100,000 g supernatants over HPLC molecular sieve columns revealed striking differences in the molecular weight distribution of ATP-sulfurylase and APS-kinase of the two tissues, pointing to different enzymic species for both enzymes in brain and liver. This was further substantiated by kinetic characterization of the two enzymes of both tissues. APS-kinase of liver is allosterically activated by ATP, while the brain enzyme is not. ATP-sulfurylase of brain is activated at high, but still physiological concentrations of ATP. Brain ATP-sulfurylase is inhibited by phenylalanine.

Adenine Nucleotides↗
PubMed1987

Regulation of differentiation and polarized secretion in mammary epithelial cells maintained in culture: extracellular matrix and membrane polarity influences.

Several previous studies have demonstrated that mammary epithelial cells from pregnant mice retain their differentiated characteristics and their secretory potential in culture only when maintained on stromal collagen gels floated in the culture medium. The cellular basis for these culture requirements was investigated by the monitoring of milk protein synthesis and polarized secretion from the mouse mammary epithelial cell line, COMMA-1-D. Experiments were directed towards gaining an understanding of the possible roles of cell-extracellular matrix interactions and the requirements for meeting polarity needs of the epithelium. When cells are cultured on floating collagen gels they assemble a basal lamina-like structure composed of laminin, collagen (IV), and heparan sulfate proteoglycan at the interface of the cells with the stromal collagen. To assess the role of these components, an exogenous basement membrane containing these molecules was generated using the mouse endodermal cell line, PFHR-9. This matrix was isolated as a thin sheet attached to the culture dish, and mammary cells were then plated onto it. It was found that cultures on attached PFHR-9 matrices expressed slightly higher levels of beta-casein than did cells on plastic tissue culture dishes, and also accumulated a large number of fat droplets. However, the level of beta-casein was approximately fourfold lower than that in cultures on floating collagen gels. Moreover, the beta-casein made in cells on attached matrices was not secreted but was instead rapidly degraded intracellularly. If, however, the PFHR-9 matrices with attached cells were floated in the culture medium, beta-casein expression became equivalent to that in cells cultured on floating stromal collagen gels, and the casein was also secreted into the medium. The possibility that floatation of the cultures was necessary to allow access to the basolateral surface of cells was tested by culturing cells on nitrocellulose filters in Millicell (Millipore Corp., Bedford, MA) chambers. These chambers permit the monolayers to interact with the medium and its complement of hormones and growth factors through the basal cell surface. Significantly, under these conditions alpha 1-, alpha 2-, and beta-casein synthesis was equivalent to that in cells on floating gels and matrices, and, additionally, the caseins were actively secreted. Similar results were obtained independently of whether or not the filters were coated with matrices.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗