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Biomedical subjects

E Wright

Publications and source records attributed to E Wright.

At least 37 records · Page 2Linked to original sources

The effect of humidification and smoking habit on the incidence of adverse airway events during deepening of anaesthesia with desflurane.

The effect of two levels of humidification on the incidence of adverse airway events was studied in 58 adult female patients during deepening of anaesthesia using up to 12% desflurane. Humidification was provided by a breathing system filter with either low moisture-conserving performance (17.2 mg x l(-1) at 0.5 1 tidal volume, Group L) or high moisture-conserving performance (33.5 mg x l(-1) at 0.5 1 tidal volume, Group H). Forty-eight per cent of patients smoked and there were more smokers in Group L than in Group H. Adverse airway events consisted of coughing and laryngospasm. For coughing, the dominant explanator was smoking. When both humidity and age were included in the analysis, there was a significant smoking-humidity interaction (p < 0.05), such that high humidity decreased the incidence of coughing in nonsmokers but not in smokers. The incidence of laryngospasm was significantly lower in Group H than in Group L (p < 0.05). We conclude that when patients inspire high concentrations of desflurane during induction of anaesthesia, increasing humidification to the levels achieved in this study decreases the incidence of coughing among nonsmokers and of laryngospasm in both smokers and nonsmokers.

Adult↗

In vivo expression of signal transducer and activator of transcription factor 6 (STAT6) in nasal mucosa from atopic allergic rhinitis: effect of topical corticosteroids.

BACKGROUND: The allergen-induced late nasal response is associated with a high local expression of interleukin (IL) -4, a TH2-type cytokine implicated in immunoglobulin (Ig) E production, tissue eosinophilia and other events considered to be relevant to allergic inflammation. Interaction of IL-4 with its receptor activates at least two distinct signalling pathways that culminate in the transcription of specific target genes. One pathway involves the activation of a transcription factor termed signal transducer and activator of transcription factor 6 (STAT6). OBJECTIVE: To investigate the expression of STAT6 in the allergen-induced late nasal response and to examine the effect of local steroid treatment on STAT6 expression. METHODS: Inferior turbinate biopsies were obtained from subjects with allergic rhinitis out of the allergen season. Subjects were then randomized into topical steroid- (n = 6) and placebo-treated (n = 6) groups in a double-blind fashion. After a 6-week treatment period, a second nasal biopsy was performed 24 h after local challenge with allergen. STAT6 immunoreactivity was examined in biopsy specimens by immunocytochemistry using a specific monoclonal antibody. Numbers of inflammatory cells (CD3+ T cells and MBP+ eosinophils) and IL-4 mRNA+ cells were investigated by immunocytochemistry and in situ hybridization, respectively. RESULTS: STAT6 immunoreactivity was detected in all biopsies studied and localized predominantly to inflammatory tissue of the nasal mucosa. After allergen challenge, expression of STAT6 was markedly increased in placebo-treated patients (P < 0.01). By confocal microscopy, STAT6 was localized to the cytoplasm and the nucleus of positively-staining cells. The allergen-induced increase in STAT6 immunoreactive cells was not observed in the steroid-treated patients. The change in STAT6 immunoreactivity after allergen challenge correlated significantly with the change in numbers IL-4 mRNA+ cells (r = 0.74, P = 0.006) and CD3+ T cells (r = 0.76, P = 0. 004), but not MBP+ eosinophils. CONCLUSION: This study provides the first evidence of increased STAT6 expression in vivo in human allergic inflammation. The results support a role for STAT6 and IL-4 in the pathogenesis of late nasal response and show that decreases in STAT6 expression parallel the reduction in IL-4 expression that occurs with topical steroid treatment.

Administration, Intranasal↗

The experiences of patients and nurses with a nurse-led peripherally inserted central venous catheter line service.

Nurse-led Peripherally Inserted Central Venous Catheter (PICC) services are becoming commonplace in cancer centres across the UK. Research has shown that these services are cost-effective and are associated with fewer catheter-related complications, including infection and thrombosis, than skin-tunnelled catheters. This exploratory study aimed to explore patients' and nurses' experiences of a nurse-led PICC line service. Recorded interviews were conducted with 10 cancer patients with PICC lines inserted, five hospital-based nurses and five community-based nurses experienced in caring for patients with these lines. Respondents' recorded accounts were transcribed, coded and analysed to determine patients' and nurses' perceptions of the service and the extent to which collaborative practice was promoted. Findings were synthesized into five themes: Education, Formation of Expectations, Confidence, Sensory Experience and Adaptation. All respondent groups were positive about the PICC line service and the specialist oncology nurses working within it. The findings did identify some aspects of the service which could be improved, including the timing of information given to patients and the use of more innovative educational approaches. This study has informed the development of a potential flexible service structure which may be incorporated into established and differing care settings using existing resources.

Journal Article↗

Upregulation of the transcription factor GATA-3 in upper airway mucosa after in vivo and in vitro allergen challenge.

BACKGROUND: Allergic rhinitis is a complex upper airways disorder characterized by the infiltration of eosinophils and T(H2)-type T lymphocytes. GATA-3 is a novel transcription factor recently shown to regulate IL-5 and, possibly, IL-4 gene expression. We previously reported that GATA-3 is increased within the bronchial mucosa of allergic asthmatic subjects compared with control subjects. OBJECTIVE: In the present study we set out to determine whether there is also an increased number of cells expressing GATA-3 messenger (m)RNA within the nasal mucosa of patients with allergic rhinitis. METHODS: Inferior turbinate biopsy specimens were obtained from patients with allergic rhinitis and nonatopic control subjects before and after local allergen provocation in vivo. To assess the contribution of resident cells expressing GATA-3 mRNA, we also performed isolated explant studies in which nasal mucosal tissue from subjects with allergic rhinitis and nonatopic control subjects was cultured in allergen-treated medium. The presence of mRNA coding for GATA-3, IL-5, IL-4, IL-13, and GM-CSF was assessed by using in situ hybridization. RESULTS: The number of GATA-3 mRNA(+) cells was increased after local allergen provocation in vivo (increase in GATA-3 mRNA(+) cells [mean +/- SEM]: subjects with allergic rhinitis, 11.3 +/- 8.7; control subjects, 1.2 +/- 4.1; P <.05) and in explanted nasal mucosa in vitro (subjects with allergic rhinitis, 10. 2 +/- 3.8; control subjects, 2.7 +/- 4.4; P <.05). The gene expression of GATA-3 was significantly correlated to the numbers of IL-5 (r = 0.87) and GM-CSF (r = 0.79) mRNA(+) cells but not with IL-4 or IL-13 mRNA(+) cells. CONCLUSION: In summary, the expression of the transcription factor GATA-3 was increased after allergen challenge, and this was evident in the absence of de novo inflammatory cell recruitment. GATA-3 may be a potential target in the treatment of allergic diseases, such as rhinitis.

Allergens↗

Local synthesis of epsilon germline gene transcripts, IL-4, and IL-13 in allergic nasal mucosa after ex vivo allergen exposure.

BACKGROUND: The production of epsilon germline gene transcripts (Iepsilon(+)/Cepsilon(+) RNA) precedes class switch recombination to IgE and is induced by IL-4 and/or IL-13. Although Iepsilon and Cepsilon RNA(+) B cells have been identified within nasal tissue after in vivo allergen exposure, suggesting local germline transcription, whether these were resident or infiltrating B lymphocytes was not clear. OBJECTIVE: We sought to examine whether B cells resident to the nasal mucosa undergo epsilon germline transcription. METHODS: Nasal mucosal biopsy specimens were obtained from asymptomatic patients with seasonal allergic rhinitis and exposed to allergen ex vivo. Using immunocytochemistry, B lymphocytes were enumerated; with in situ hybridization, the number of cells expressing Iepsilon, Cepsilon, IL-4, and IL-13 messenger (m)RNA(+) cells was examined. RESULTS: Tissue cultured in medium containing specific allergen exhibited significantly more Iepsilon and Cepsilon RNA(+) cells compared with medium alone (P <.05). IL-4 and IL-13 mRNA synthesis also resulted from ex vivo allergen exposure; there were significantly more cells expressing transcripts for these cytokines within allergic nasal mucosal tissue cultured with allergen than medium alone (P <.05). Within allergen-stimulated tissue obtained from allergic patients, 30% of total B cells were Iepsilon RNA(+), and the majority of IL-4 and IL-13 mRNA(+) cells were T cells (68% and 44%, respectively) and mast cells (32% and 19%, respectively). CONCLUSION: These results demonstrate that the nasal mucosa is a site of epsilon germline gene transcription and suggest that local T cell and mast cell production of IL-4 and IL-13 may regulate this event.

Allergens↗

Service use patterns of youth with, and at high risk for, HIV: a care typology.

This paper uses confirmatory structural equation models to develop and test a theoretical model for understanding the service utilization history of 4679 youth who received services from 10 national HIV/AIDS demonstration models of youth-appropriate and youth-attractive services funded by the Special Projects of National Significance (SPNS) Program, HIV/AIDS Bureau, Health Resources and Services Administration. Although the projects differ from one another in the areas of emphasis in their service models, each is targeted to youth at high risk for HIV, or those youth who have already contracted HIV. Collectively, the projects represent a comprehensive adolescent HIV service model. This paper examines the characteristics of the services provided to young people ranging from outreach to intensive participation in medical treatment. Major typologies of service utilization are derived empirically through exploratory factor and cluster analysis methods. Confirmatory structural equation modeling methods are used to refine the exploratory results using a derivation and replication strategy and methods of statistical estimation appropriate for non-normally distributed service utilization indicators. The model hypothesizes that youth enter the service system through a general construct of connectedness to a comprehensive service model and through service-specific methods, primarily of outreach or emergency services. Estimates are made of the degree to which a comprehensive service model drives the services as opposed to specific service entry points.

Adolescent↗

Portal venous and enteric exocrine drainage versus systemic venous and bladder exocrine drainage of pancreas grafts: clinical outcome of 40 consecutive transplant recipients.

OBJECTIVE: To test the hypothesis that pancreas transplantation using the more physiologic method of portal venous-enteric (PE) drainage could be performed without compromising patient and graft outcome, compared with the standard method of systemic venous-bladder (SB) drainage. METHODS: Between November 1995 and November 1998, the authors prospectively followed up 20 consecutive patients with SB drainage followed by 20 consecutive patients with PE drainage. All patients underwent simultaneous pancreas-kidney transplantation, and all were immunosuppressed with antilymphocyte serum, cyclosporin, azathioprine, and steroids. RESULTS: The actuarial patient survival rate at 1 year was 95% in the SB group and 100% in the PE group. Death-censored kidney graft survival was 100% in both groups; pancreas graft survival was 95% in the SB group and 100% in the PE group. The mean initial hospital stay was 15 days for both groups. However, during the first 6 months after transplantation, the SB group required more medical day-unit visits, mostly for treatment of metabolic acidosis and dehydration. The incidence of urinary tract infections was similar in both groups. The incidence of cytomegalovirus infections was significantly less in the PE group. The incidence of acute rejection was 37% in the SB group and 15% in the PE group. Mean serum creatinine levels 6 months after transplantation were significantly lower in the PE group than in the SB group. Glycemic control was excellent in both groups, but fasting serum insulin levels were significantly lower in the PE group. CONCLUSIONS: The PE method of pancreas transplantation can be performed with excellent patient and graft outcomes.

Adolescent↗

Norfloxacin dihydrate.

The antibiotic norfloxacin recrystallizes from acetonitrile as a dihydrate with the norfloxacin molecule in a zwitterionic form, i.e. 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazin-4-io)-3-quinolinecarboxylate dihydrate, C(16)H(18)FN(3)O(3).2H(2)O.

Journal Article↗

Risk factors and characteristics of youth living with, or at high risk for, HIV.

Over 8,000 adolescents and young adults (4,111 males; 4,085 females) reported on several HIV-related risk behaviors during enrollment into 10 service demonstration projects targeted to youth living with, or at risk for, HIV. Distinct risk patterns emerged by gender when predicting HIV serostatus (versus unknown serostatus/negative serostatus). Males who had injection drug risk histories, had sex with an HIV positive partner, had sexually transmitted diseases, had sex with males, and/or were homeless had an inflated risk of being HIV positive. Females who engaged in sex with an HIV partner, had sex with an injection drug user, and/or had sexually transmitted diseases, were at the highest HIV risk. For both samples, engaging in sex with women reduced the likelihood of HIV positive status. Very basic information about risk factors obtained at service intake offers important information about HIV status of "high risk" youth presenting for care in community programs, as well as suggests clear risk factors for targeted preventive efforts.

Adolescent↗

Sustained induction of fetal hemoglobin by pulse butyrate therapy in sickle cell disease.

High levels of fetal hemoglobin (Hb F) protect from many of the complications of sickle cell disease and lead to improved survival. Butyrate and other short chain fatty acids were previously shown to increase Hb F production in erythroid cells in vitro and in animal models in vivo. However, butyrates are also known to inhibit the proliferation of many cell types, including erythroid cells. Experience with the use of butyrate in animal models and in early clinical trials demonstrated that the Hb F response may be lost after prolonged administration of high doses of butyrate. We hypothesized that this loss of response may be a result of the antiproliferative effects of butyrate. We designed a regimen consisting of intermittent or pulse therapy in which butyrate was administered for 4 days followed by 10 to 24 days with no drug exposure. This pulse regimen induced fetal globin gene expression in 9 of 11 patients. The mean Hb F in this group increased from 7.2% to 21.0% (P <.002) after intermittent butyrate therapy for a mean duration of 29.9 weeks. This was associated with a parallel increase in the number of F cells and F reticulocytes. The total hemoglobin levels also increased from a mean of 7.8 g/dL to a mean of 8.8 g/dL (P <.006). The increased levels of Hb F were sustained in all responders, including 1 patient who has been on pulse butyrate therapy for more than 28 months. This regimen, which resulted in a marked and sustained increase in Hb F levels in more than two thirds of the adult sickle cell patients enrolled in this study, was well tolerated without adverse side effects. These encouraging results require confirmation along with an appropriate evaluation of clinical outcomes in a larger number of patients with sickle cell disease.

Adolescent↗

The natural history of exercise-induced anaphylaxis: survey results from a 10-year follow-up study.

BACKGROUND: Exercise-induced anaphylaxis (EIA) is a unique physical allergy that is triggered by exertion, the clinical spectrum and modifying factors of which have been previously studied. At the time of initial description, it was postulated that other factors contributed to this disorder. OBJECTIVE: We sought to determine the clinical course and potential modifying factors in EIA. METHODS: In 1993, we conducted a cross-sectional analysis of 671 individuals with exercise-associated symptoms for more than a decade using a validated 75-item questionnaire. Subjects met criteria for EIA if they had anaphylactic symptoms, including hypotension or upper airway obstruction, urticaria, or angioedema with physical exertion but without a passive increase in core body temperature. RESULTS: Of 365 (54%) questionnaire respondents, 279 (87%) met criteria for EIA (199 females and 80 males). At the time of study entry, subjects with EIA (mean age, 37.5 years; range, 13 to 77 years) had an average of 10.6 years of symptoms, which were most frequently triggered by aerobic activities such as jogging or brisk walking (78% and 42%, respectively). On average, subjects reported that the frequency of attacks had decreased (47% of subjects) or stabilized (46% of subjects) since onset. One hundred (41%) subjects reported being completely free of attacks in the past year. Subjects reduced their attacks by avoiding exercise during extremely hot or cold weather (44%), avoiding ingestion of certain foods before exercise (37%), and restricting exercise during their allergy season (36%) or humid weather (33%). The most common pharmacologic agents used to manage symptoms were H1 antagonists (56%) and/or epinephrine (31%). However, 28% used no treatment at all. CONCLUSION: EIA is an episodic condition in which the frequency of attacks tends to stabilize or decrease over time. Improvement appears to result from individual modification of exercise and avoidance of known environmental and ingestible precipitants.

Adolescent↗

Monocyte chemotactic proteins in allergen-induced inflammation in the nasal mucosa: effect of topical corticosteroids.

BACKGROUND: Human allergen-induced rhinitis is associated with the recruitment and activation of inflammatory cells, particularly eosinophils and CD4(+) T cells, in the nasal mucosa. Chemokines are inflammatory mediators capable of attracting specific inflammatory cell populations. Monocyte chemotactic proteins (MCPs), a subfamily of CC chemokines, have been shown to induce chemotactic activity particularly in eosinophils, T cells, and monocytes under in vitro assay conditions. OBJECTIVE: To assess the contribution of MCPs in the recruitment of inflammatory cells in vivo, we investigated the allergen-induced late response in subjects with allergic rhinitis. METHODS: Patients were randomized to receive a 6-week treatment with either topical corticosteroid (n = 6) or a matched placebo (n = 6). Nasal inferior turbinate biopsy specimens were obtained from all subjects before and during allergen-induced late responses. By using immunocytochemistry, tissue sections were examined for the presence of MCP-1, MCP-3, and MCP-4 and for the phenotype of infiltrating cells within the nasal mucosa. In addition, double sequential immunocytochemistry was used to confirm the phenotype of MCP-immunoreactive positive cells. Furthermore, the effect of topical corticosteroids on the expression of MCPs and on the cellular infiltrate was also examined. RESULTS: MCP-1, MCP-3, and MCP-4 were expressed in all the baseline samples, with prominent staining observed within the nasal epithelium. Biopsy specimens taken after challenge exhibited significant upregulation in the expression of MCP-3 and MCP-4 (P <.001). On the other hand, this increase in response to allergen was reduced in patients pretreated with topical corticosteroids. Colocalization experiments revealed that the majority of MCP+ cells in the subepithelium were macrophages, followed by T cells and eosinophils. CONCLUSION: Our results demonstrate that allergen-induced rhinitis is associated with an increased expression of MCP-3 and MCP-4, which may be closely related to the influx of inflammatory cells and may thus contribute to the pathogenesis of allergic rhinitis.

Administration, Topical↗

Specificity of loss of heterozygosity in radiation-induced mouse myeloid and lymphoid leukaemias.

PURPOSE: To determine whether loss of heterozygosity (LOH) at specific chromosomal loci in radiation-induced leukaemias, arising in a similar genetic background, is leukaemia-type specific (myeloid versus lymphoid) or common to both. MATERIALS AND METHODS: Leukaemias that arose in 3 Gy X-irradiated (CBA/H x C57BL/6)F1 intercross and backcross mice were diagnosed as acute myeloid leukaemia (AML) or thymic lymphoma (TL). LOH was determined using 28 polymorphic microsatellite markers distributed over seven chromosomes using control and leukaemic DNA from individual mice. RESULTS: LOH incidences of 0-20% were observed at most loci in both leukaemia types. Specific LOH incidences of 38-76% were observed for myeloid (chromosome 2) and lymphoid (chromosomes 11 and 14) leukaemias. Chromosome 4 LOH was frequently (38-50%) observed in both types, although the commonly deleted regions differed. LOH was detected at either chromosome 2 or 4 in AML and either chromosome 4 or 11 in TL. CONCLUSIONS: LOH incidences of 38-76% suggest a causal role of particular loci which is mainly, but not exclusively, dependent on leukaemia type. LOH incidences of 0-20% at other loci in both leukaemias suggest that many genetic deletions are non-causal and incidental in radiation-leukaemogenesis.

Animals↗

Family functioning, neurocognitive functioning, and behavior problems in children with sickle cell disease.

OBJECTIVE: To investigate the independent and combined contributions of neurocognitive and family functioning to mother-reported behavior problems in children with sickle cell disease (SCD) and evaluate the factor structure of the Family Environment Scale (FES) with African American families. METHOD: The study sample included 289 children enrolled in the multisite Cooperative Study of Sickle Cell Disease. The study protocol included neuropsychological evaluation and brain magnetic resonance imaging (MRI) of the children, and mothers completed the Child Behavior Checklist and Family Environment Scale. RESULTS: With child and maternal demographic parameters controlled, conflicted family functioning, but not neurocognitive functioning, accounted for a significant portion of the variance in mother-reported behavior problems. The factor structure of the FES for families of children with SCD was found to be similar to that for other families. CONCLUSIONS: Family functioning may be a salient target for fostering adaptation to chronic childhood illness.

Adaptation, Psychological↗

Hospital outcome measures following assertive community treatment in Edmonton, Alberta.

OBJECTIVE: To examine hospital outcome measures for individuals with chronic and severe mental illnesses before and after their registration in an assertive community treatment (ACT) program in Edmonton, Alberta. METHODS: Data were collected from Alberta Health on individuals who were registered in ACT from April 1993 to April 1995. For each individual, hospital outcome measures were calculated for the 365 days prior to and 365 days after registration for ACT (thus covering April 1, 1992-March 31, 1996). RESULTS: Data were collected from 295 individuals. Compared with 1 year prior to beginning ACT, there was a 34% reduction in hospital separations for patients with psychiatric diagnoses. The average length of stay (LOS) for each separated patient decreased by 56%, and the hospitalization days for each patient separated also decreased by 39%. The number of emergency visits for psychiatric reasons was reduced by 32%, and the number of clients visiting emergency departments for psychiatric reasons declined by 30%. CONCLUSIONS: In the 1-year period after registration in an ACT program, hospital outcome measures were improved in this cohort of 295 individuals with severe and chronic mental illnesses.

Adult↗