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Biomedical subjects

W Ward

Publications and source records attributed to W Ward.

At least 19 recordsLinked to original sources
PubMed2000

Antitumor polycyclic acridines. 7. Synthesis and biological properties of DNA affinic tetra- and pentacyclic acridines.

New synthetic routes to a series of tetra- and pentacyclic acridines related in structure to marine natural products are reported. The novel water-soluble agent dihydroindolizino[7,6,5-kl]acridinium chloride 14 has inhibitory activity in a panel of non-small-cell lung and breast tumor cell lines exceeding that of m-AMSA. The salt inhibited the release of minicircle products of kDNA confirming that disorganization of topoisomerase II partly underlies the activity of the compound. COMPARE analysis of the NCI mean graph profile of compound 14 at the GI(50) level corroborates this conclusion with Pearson correlation coefficients (>0.6) to clinical agents of the topoisomerase II class: however, this correlation was not seen at the LC(50) level. The inhibitory action of 14 on Saccharomyces cerevisiae transfected with human topoisomerase II isoforms showed a 3-fold selectivity against the IIalpha isoform over the IIbeta isoform. Unlike m-AMSA, 14 is not susceptible to P-glycoprotein-mediated drug efflux and retains activity in lung cells with derived resistance to the topoisomerase II inhibitor etoposide.

Acridines↗
PubMed2000

Comparative response in growth and bone status to three dexamethasone treatment regimens in infant piglets.

The objectives of this study were 1) to determine whether a zenith in bone formation (indicated by circulating osteocalcin) existed at night in early life, and 2) to compare the effects of three different dexamethasone (DEX) treatment regimens on bone turnover, bone mineral content, and growth. Three DEX treatment regimens were tested in 8-d-old piglets (n = 8/group): 1) low evening dose of DEX (0.5 mg/kg/d) as 70% in the morning and 30% in the evening for 10 d; 2) tapering course of DEX (0.5, 0.3, and 0.2 mg/kg/d) as 50% in the morning and 50% in the evening for 14 d; and 3) constant dose of DEX (0.5 mg/kg/d) as 50% in the morning and 50% in the evening for 10 d. Oral water placebo groups were tested with the same time courses. At pretreatment, plasma osteocalcin was significantly higher (p < 0.05) at 0100 than at 0900 and 1700. At necropsy, measures for DEX groups were calculated as Z-scores using values from the placebo groups. The low evening DEX dose led to a significantly lower reduction in plasma osteocalcin compared with the tapered and constant dosing regimens (p < 0.05). The significant weight. reduction in the DEX group occurred at d 9 in the low evening dose regimen but at d 7 in the constant dosing regimen, compared with the placebo group. Bone mineral content Z-score was reduced similarly in all DEX-treated groups across the three dosing regimens. We conclude that a plasma osteocalcin zenith at night exists in early life. A high DEX dose in the morning and low DEX dose in the evening may partially attenuate corticosteroid-induced suppression of bone formation and growth restriction.

Animals↗
PubMed1999

Implementation of condom social marketing in Louisiana, 1993 to 1996.

OBJECTIVES: This article describes the implementation and impact of the first statewide condom social marketing intervention in the United States. METHODS: A statewide social marketing program made condoms freely available in 93 public health clinics, 39 community mental health centers, 29 substance abuse treatment sites, and more than 1000 businesses in neighborhoods with high rates of sexually transmitted diseases (STDs) and HIV. Surveys about condom use were conducted annually. RESULTS: Between 1994 and 1996, more than 33 million condoms were distributed without significant opposition. Over time, self-reported condom use at the last sexual encounter increased among African American women (from 28% in 1994 to 36% in 1996), particularly African American women with 2 or more sex partners (from 30% to 48%). Condom use at the last sexual encounter increased among African American men (from 40% in 1994 to an average of 54% in 1996). The number of reported sex partners did not increase. CONCLUSIONS: Condom social marketing can be successfully implemented in the United States. The widespread availability of free condoms is associated with increased condom use, particularly among persons at high risk for STDs and HIV.

Adolescent↗
PubMed1997

A primitive enzyme for a primitive cell: the protease required for excystation of Giardia.

Protozoan parasites of the genus Giardia are one of the earliest lineages of eukaryotic cells. To initiate infection, trophozoites emerge from a cyst in the host. Excystation is blocked by specific cysteine protease inhibitors. Using a biotinylated inhibitor, the target protease was identified and its corresponding gene cloned. The protease was localized to vesicles that release their contents just prior to excystation. The Giardia protease is the earliest known branch of the cathepsin B family. Its phylogeny confirms that the cathepsin B lineage evolved in primitive eukaryotic cells, prior to the divergence of plant and animal kingdoms, and underscores the diversity of cellular functions that this enzyme family facilitates.

Animals↗
PubMed1997

Microsatellite evolution--a reciprocal study of repeat lengths at homologous loci in cattle and sheep.

The application of microsatellites in evolutionary studies requires an understanding of the patterns governing their evolution in different species. The finding that homologous microsatellite loci are longer, i.e., containing more repeat units, in human and in other primates has been taken as evidence for directional microsatellite evolution and for a difference in the rate of evolution between species. However, it has been argued that this finding is an inevitable consequence of biased selection of longer-than-average microsatellites in human, because cloning procedures are adopted to generate polymorphic and, hence, long markers. As a test of this hypothesis, we conducted a reciprocal comparison of the lengths of microsatellite loci in cattle and sheep using markers derived from the bovine genome as well as the ovine genome. In both cases, amplification products were longer in the focal species, and loci were also more polymorphic in the species from which they were originally cloned. The crossing pattern that we found suggests that interspecific length differences detected at homologous microsatellite loci are the result of biased selection of loci associated with cloning procedures. Hence, comparisons of microsatellite evolution between species are flawed unless they are based on reciprocal analyses or on genuinely random selection of loci with respect to repeat length.

Animals↗
PubMed1997

Amoxycillin as an alternative to dihydrostreptomycin sulphate for treating cattle infected with Leptospira borgpetersenii serovar hardjo.

OBJECTIVE: To assess the effect of amoxycillin treatment on urinary excretion of leptospires from cattle infected with Leptospira borgpetersenii serovar hardjo. DESIGN: A chemotherapy trial with controls. PROCEDURE: Fourteen heifers serologically negative to L hardjo were inoculated with L hardjo via the conjunctival route and assessed for evidence of infection by serological, fluorescent antibody and microbiological tests. Two injections (48 h apart) of amoxycillin at a dose of 15 mg/kg were administered intramuscularly to seven heifers 6.5 weeks after infection; the remaining heifers acted as untreated controls. Later, these seven control group heifers were treated with a single dose of amoxycillin (15 mg/kg). Samples of urine were collected before and after amoxycillin treatments; kidneys were collected at slaughter, and examined by fluorescent antibody test and microbiological culture. RESULTS: Leptospires were isolated from the urine of 11 of 14 heifers inoculated with L hardjo. After treatment of six of these with two injections of amoxycillin, leptospires were not isolated. Of the controls, four of the five initially leptospiruric heifers continued to shed leptospires; after a single injection of amoxycillin, no leptospires were detected in the kidneys of these four. CONCLUSION: Amoxycillin may be an acceptable alternative to dihydrostreptomycin sulphate for the treatment of cattle infected with L hardjo.

Amoxicillin↗
PubMed1997

Experimental Leptospira borgpetersenii serovar hardjo infection of pregnant cattle.

OBJECTIVE: To observe the effect upon the foetus of experimental infection of pregnant cattle with Leptospira borgpetersenii serovar hardjo. DESIGN: A disease transmission study using pregnant cattle. PROCEDURE: Fourteen heifers serologically negative to L hardjo were artificially inseminated and later challenged with a north-Queensland isolate of L hardjo by conjunctival inoculation. The heifers were serologically monitored and their urine examined for the presence of leptospires using culture and fluorescent-antibody tests at appropriate intervals. Elective caesarean sections were performed on pregnant heifers at 6.5 weeks after the challenge. Foetuses were examined using serological, histopathological, microbiological and fluorescent-antibody tests. RESULTS: Ten of the heifers became pregnant, but three subsequently aborted before challenge. After challenge, all 14 heifers seroconverted and L hardjo was isolated from the urine of 6 of the 7 pregnant heifers. No evidence of foetal L hardjo infection was detected. Two of the foetuses had histopatho-logical lesions consistent with Neospora sp infection. CONCLUSION: It is likely that the isolate of L hardjo used in this study does not normally infect the foetus. Neospora sp may be a more significant cause of bovine reproductive wastage.

Animals↗
PubMed1997

Psychiatric morbidity in Australian veterans of the United Nations peacekeeping force in Somalia.

OBJECTIVE: Since World War II, an increasing number of soldiers have been deployed in United Nations (UN) peacekeeping forces. However, little is known about the psychiatric impact of such deployments. The present study investigated the nature, prevalence, aetiology and natural history of psychiatric morbidity in Australian veterans of the United Nations peacekeeping force in Somalia. METHOD: Fifteen months after their return from Somalia, 117 Somalian veterans completed the 28-item version of the General Health Questionnaire (GHQ-28), the Impact of Events Scale (IES), the Combat Exposure Scale (CES), and a checklist of posttraumatic stress disorder symptoms, completed by veterans 12 months previously as part of an evaluation by the Department of Defence. Seventy-seven non-veteran controls also completed the GHQ-28. RESULTS: Veterans scored significantly higher on the GHQ-28 than controls. Twenty-four-point-eight per cent (24.8%) of veterans were GHQ cases (using 4/5 as a cut-off point) compared to 13.0% of controls. Psychiatric morbidity in veterans was associated with combat exposure and a past psychiatric history. Levels of morbidity reduced over time, although they remained substantial at 15 months following soldiers' return to Australia, with posttraumatic stress disorder symptoms being reported by approximately 20% of veterans. CONCLUSIONS: At least one-fifth of Australian soldiers who served in Somalia had significant levels of psychiatric morbidity 15 months following their return. This was almost twice that of their non-veteran peers. Risk factors for the development of psychiatric morbidity included combat exposure and past psychiatric history. Levels of psychiatric morbidity were much higher than those reported in previous studies on UN soldiers.

Adult↗
PubMed1997

The significance of the IgG anti-B-cell crossmatch on renal transplant outcome.

Transplantation in the presence of anti-class I antibodies usually results in allograft hyperacute rejection. Because of the perception of its uncertain clinical significance, B-cell crossmatch which identifies presence of anti-class II antibodies is not universally performed. In a retrospective study, the clinical course of renal transplant recipients with IgG anti-B-cell antibodies was analyzed and compared with case control patients transplanted contemporaneously, matched demographically and immunologically. The incidence of hyperacute, acute, and chronic rejection as well as graft loss were significantly higher in the group with anti-IgG B-cell antibodies compared to the control. We conclude that anti-B-cell IgG antibodies are harmful to allografts with a spectrum of events that include hyperacute, acute, vascular and chronic rejection. While allografts were successful in some patients, our experience suggests caution whenever anti-donor B-cell IgG is present. If transplants are performed, then more potent immunosuppression should be used.

Acute Disease↗
PubMed1995

In vitro T cell function, delayed-type hypersensitivity skin testing, and CD4+ T cell subset phenotyping independently predict survival time in patients infected with human immunodeficiency virus.

Human immunodeficiency virus type 1 (HIV-1)-infected patients (n = 335) in the US Air Force HIV Natural History Program were followed for 3 years (mean) after skin testing, immunophenotyping of CD4+ cell subsets, and measurement of in vitro interleukin-2 production after stimulation by phytohemagglutinin, alloantigens, tetanus toxoid, and influenza A virus. The T cell functional assay predicted survival time (P < .001) and time for progression to AIDS (P = .014). Skin testing for tetanus, mumps, and Candida antigen and the total number of positive tests (P < .001 for each) stratified patients for survival time. In a multivariable proportional hazards model, the T cell functional assay (P = .008), the absolute number of CD4+ T cells (P = .001), the percentage of CD4+ CD29+ cells (P = .06), and the number of reactive skin tests (P < .001) predicted survival time. Thus, cellular immune functional tests have significant predictive value for survival time in HIV-1-infected patients independent of CD4+ cell count.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Elevation of intracellular free calcium levels in HEp-2 cells infected with enteropathogenic Escherichia coli.

Enteropathogenic Escherichia coli (EPEC) are a class of diarrheagenic organisms that induce a characteristic attaching and effacing lesion in enterocytes and various cultured cell lines. Infection of cultured HEp-2 cells by EPEC isolates 2036-80 (serotype O119) and E2348-69 (serotype O127) resulted in significant elevation of intracellular free calcium levels, determined quantitatively with the fluorescent calcium indicator dye 2-([2-bis(carboxymethyl)amino-5-methylphenoxy]methyl)-6-methoxy-8- bis(carboxymethyl)aminoquinoline. This effect, which was not observed on infection with non-lesion-forming E. coli strains, was inhibited by dantrolene, a drug that prevents calcium mobilization from intracellular stores. Moreover, activated protein kinase C in infected cells was dissociated from cell membranes by a process that was inhibited by cyclosporin A, suggesting involvement of the calcium-dependent protease calpain. A qualitative method for observing intracellular calcium fluxes by fluorescence microscopy with the recently described fluorescein-based indicator fluo-3 was used to screen a collection of well-characterized E. coli isolates from patients with infantile enteritis. Increased localized calcium-dependent fluo-3 fluorescence was observed only in HEp-2 cells infected with known lesion-forming EPEC strains. We propose that enhancement of intracellular free calcium levels in enterocytes infected with EPEC would result in formation of the characteristic lesion by calcium-dependent activation of actin-depolymerizing proteins, with eventual loss of absorptive capacity.

Calcium↗
PubMed1991

The use of the Roy Adaptation Model in nursing administration.

In recent years, considerable attention has been paid to the use of a nursing conceptual model for nursing practice. Although many of the theorists and early writers on the subject suggested that a nursing conceptual model could be used to guide nursing administration, there has been little attention given to this in the literature. This article describes the process that one hospital engaged in as they implemented the Roy Adaptation Model for nursing administration. The article discusses the use of the Roy Model in creating a nursing philosophy, mission statements, standards of practice, job descriptions, performance planning and appraisal system and a quality monitoring system. The authors conclude that the use of the Roy Model has contributed to the development of a highly integrated system of nursing administration and practice.

Adaptation, Psychological↗