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Biomedical subjects

D Carr

Publications and source records attributed to D Carr.

At least 19 recordsLinked to original sources
PubMed2003

Urban traffic and pollutant exposure related to respiratory outcomes and atopy in a large sample of children.

Conflicting results have been reported for the relationship between traffic exposure and inception of atopy. The effect of traffic on the prevalence of asthma and atopy at school age was investigated in a representative population. Random samples of schoolchildren (n=7,509, response rate 83.7%) were studied using the International Study of Asthma and Allergies in Childhood phase-II protocol with skin-prick tests, measurements of specific immunoglobulin E and lung function. Traffic exposure was assessed via traffic counts and by an emission model which predicted soot, benzene and nitrogen dioxide (NO2). Traffic counts were associated with current asthma, wheeze and cough. In children with tobacco-smoke exposure, traffic volume was additionally associated with a positive skin-prick test. Cough was associated with soot, benzene and NO2, current asthma with soot and benzene, and current wheeze with benzene and NO2. No pollutant was associated with allergic sensitisation. High vehicle traffic was associated with asthma, cough and wheeze, and in children additionally exposed to environmental tobacco smoke, with allergic sensitisation. However, effects of socioeconomic factors associated with living close to busy roads cannot be ruled out.

Asthma↗
PubMed2002

Why study pain? A qualitative analysis of medical and nursing faculty and students' knowledge of and attitudes to cancer pain management.

Although effective means for pain management have long been available, cancer pain remains widely undertreated. Surveys of medical personnel have revealed knowledge deficits and attitudinal barriers to pain management, but have not determined why such attitudes persist and how they may be addressed in medical and nursing curricula. This paper presents findings from a qualitative study of the beliefs and attitudes toward pain and cancer pain management held by medical and nursing students and faculty who participated in the Cancer Education Module for the Management of Pain (CEMMP) project. Analysis centered on informants' prioritization and knowledge of pain and cancer pain management and on the meanings informants assigned to pain in a clinical context. Themes in prioritization included the importance of learning about pain versus cancer pain and the responsibility of primary care providers versus specialists for pain and cancer pain management. Themes in informants' knowledge of pain included knowledge deficits about medications and adjunct therapies and the presence of pain management in the curriculum, and the role of knowledgeable faculty members and mentors in the dissemination of information about pain management. Themes in the meanings informants' assigned to pain included opioidphobia, and the (inter-)subjectivity of pain. The discussion focuses in particular on tensions within the prioritization, knowledge and meanings of pain that must be resolved before students can be appropriately educated for optimal pain management.

Attitude of Health Personnel↗
PubMed2002

Lung function of school children with low levels of alpha1-antitrypsin and tobacco smoke exposure.

Exposure to environmental tobacco smoke (ETS) and other air pollutants has been associated with small decrements in lung function. The susceptibility to pollution exposure may, however, vary substantially between individuals. Children with an impaired protease-antiprotease balance may be particularly vulnerable. Therefore this study aimed to investigate the effects of ETS exposure on children with reduced levels of alpha1-antitrypsin (alpha1-AT). Random samples of school children (aged 9-11 yrs) (n=3,526) were studied according to the International Study of Asthma and Allergies in Childhood (ISAAC) phase II protocol, including parental questionnaires, pulmonary function and allergy testing. Blood samples were obtained to measure plasma levels of alpha1-AT and to genotype for pleomorphic protein inhibitor (Pi)Z and PiS alleles. Children with low levels of alpha1-AT (< or = 116 mg x dL(-1)) showed significant, albeit small decrements in baseline lung function. When exposed to ETS, pronounced decrements of pulmonary function, particularly in measures of mid- to end-expiratory flow rates, were seen in these children as compared to exposed children with normal levels of alpha1-AT. The mean levels of % predicted+/-SE in both groups were: maximum expiratory flow at 50% of vital capacity 79.4+/-7.2 versus 99.0+/-1.5, maximum expiratory flow at 25% of vital capacity 67.4+/-10.0 versus 100.3+/-2.1, maximal midexpiratory flow 73.7+/-8.6 versus 99.9+/-1.7. These findings suggest that school children with low levels of alpha1-antitrypsin are at risk of developing pronounced decrements in pulmonary function, particularly if they are exposed to environmental tobacco smoke. Parents of children with heterozygous alpha1-antitrypsin deficiency resulting in significantly reduced blood concentrations should be advised to prevent their children from being exposed to environmental tobacco smoke and dissuade them from taking up smoking.

Child↗
PubMed2001

Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey.

BACKGROUND: A farming environment protects against development of asthma, hay fever, and atopic sensitisation in children. We aimed to establish whether increased exposure to microbial compounds has to occur early in life to affect maturation of the immune system and thereby reduces risk for development of allergic diseases. METHODS: We did a cross-sectional survey in rural areas of Austria, Germany, and Switzerland. 2618 (75%) of 3504 parents of 6-13-year-old children completed a standardised questionnaire on asthma, hay fever, and atopic eczema. Children from farming families, and a random sample of non-farmers' children, who gave consent for blood samples to be obtained for measurements of specific serum IgE antibodies to common allergens were invited to participate (n=901). FINDINGS: Exposure of children younger than 1 year, compared with those aged 1-5 years, to stables and consumption of farm milk was associated with lower frequencies of asthma (1% [3/218] vs 11% [15/138]), hay fever (3% [7] vs 13% [18]), and atopic sensitisation (12% [27] vs 29% [40]). Protection against development of asthma was independent from effect on atopic sensitisation. Continual long-term exposure to stables until age 5 years was associated with the lowest frequencies of asthma (0.8% [1/122]), hay fever (0.8% [1]), and atopic sensitisation (8.2% [10]). INTERPRETATION: Long-term and early-life exposure to stables and farm milk induces a strong protective effect against development of asthma, hay fever, and atopic sensitisation.

Adolescent↗
PubMed2001

The farnesyl transferase inhibitor SCH 66336 induces a G(2) --> M or G(1) pause in sensitive human tumor cell lines.

SCH 66336 is a potent farnesyl transferase inhibitor (FTI) in clinical development. It efficiently prevents the membrane association of H-ras, but not K- or N-ras. Yet, in soft agar, it reverts the anchorage-independent growth of human tumor cell lines (hTCLs) harboring H-ras, K-ras, and N-ras mutations, implying that blocking farnesylation of proteins besides ras may be responsible for this effect. Experiments show that SCH 66336 altered the cell cycle distribution of sensitive human tumor cells in two distinct ways. Most sensitive hTCLs accumulated in the G(2)-->M phase after the FTI treatment, but those with an activated H-ras accumulated in G(1) phase, suggesting that the biological effects induced by FTIs in cells with an activated H-ras are distinct from other sensitive cells. A careful genotypic comparison of the hTCLs revealed that those cells with wild-type p53 are especially sensitive to the FTIs. In these cells p53 and its downstream target gene p21(Cip1) are induced after treatment with SCH 66336 for 24 h. These data suggest that cell cycle effects, either G(1) or G(2)-->M accumulation, and p53 status are important for mediating the effects of FTIs on tumor cells.

3T3 Cells↗
PubMed2001

Psychological adjustment to sudden and anticipated spousal loss among older widowed persons.

OBJECTIVES: This study examined if older adults' psychological adjustment to widowhood varies based on whether the death was sudden or anticipated and if these effects are mediated by death context characteristics (e.g., predeath caregiving, nursing home use, spouse's age at death, and couple's communication about the death). METHODS: The effects of forewarning on multiple indicators of mental health and grief were examined in a sample of 210 widowed persons who participated in the Changing Lives of Older Couples (CLOC) study. The CLOC is a probability sample of 1,532 married individuals aged 65 and older for whom baseline information was collected in 1987-88, with widowed persons reinterviewed 6, 18, and 48 months after spousal loss. RESULTS: Forewarning did not affect depression, anger, shock, or overall grief 6 or 18 months after the loss. Prolonged forewarning was associated with elevated anxiety both 6 and 18 months after the death. Sudden spousal death elevated survivors' intrusive thoughts at the 6-month follow-up only. Sudden death was associated with slightly higher levels of yearning among women but significantly lower yearning among men both 6 and 18 months after the loss. DISCUSSION: The findings call into question the widespread belief that grief is more severe if death is sudden and suggest a more complex relationship between bereavement and circumstances of spousal death.

Adaptation, Psychological↗
PubMed2001

Relations among equivalence, naming, and conflicting baseline control.

Three studies were conducted with different groups of 6 students each to explore the effects of training class-inconsistent relations and naming on demonstrations of emergent arbitrary stimulus relations. In all studies, two three-member equivalence classes of Greek symbols (A1B1C1 and A2B2C2) emerged as a result of training in conditional discriminations. Two new symbols were introduced (X and Y), and additional conditional discriminations were trained, whereby X was designated as the positive discriminative stimulus (S+) and Y was designated as the negative discriminative stimulus (S-) for A1 and B2. Conversely, Y was designated as the S+ and X as the S- for B1 and A2. This introduced conflicting sources of control within and between classes. In Study 1, subjects were not provided with names for the stimuli. In Study 2, the experimenter provided common names for the stimuli within each class. In Study 3, the subjects were required to use the common names during conditional discrimination training and test-trial blocks. In all experiments, equivalence responding with respect to the original classes was disrupted for some subjects subsequent to learning the new relations. Furthermore, in Studies 2 and 3, there were frequent examples of noncorrespondence between observed (listener or speaker) naming patterns and derived relations. These results support the view that demonstrations of equivalence are subject to control from a variety of sources rather than being fundamentally dependent on naming.

Adult↗
PubMed2000

Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules.

Human tumor cell lines that are sensitive to the effects of farnesyl transferase inhibitors accumulate in G(2) --> M (except for cells with an activated Ha-ras that accumulate in G(1)). A search for CAAX box proteins from Swiss-Prot revealed more than 300 peptides. Of these, the centromeric proteins CENP-E and CENP-F are preferentially expressed during mitosis and are implicated as mediators of the G(2) --> M checkpoint. Experiments performed here show that peptides from the COOH-terminal CAAX box of CENP-E and CENP-F are substrates for farnesyl transferase but not geranylgeranyl transferase-I. Although both proteins are prenylated in the human tumor cell line DLD-1, their prenylation is completely inhibited by the farnesyl transferase inhibitor, SCH 66336. Immunohistochemical data with the lung carcinoma cell line, A549, showed that preventing the farnesylation of CENP-E and CENP-F by treatment with the farnesyl transferase inhibitor SCH 66336 does not affect their localization to the kinetochores. However, the presence of farnesyl transferase inhibitors alters the association between CENP-E and the microtubules. Our results imply that the inhibition of CENP-E farnesylation results in the alteration of the microtubule-centromere interaction during mitosis and results in the accumulation of cells prior to metaphase.

Alkyl and Aryl Transferases↗
PubMed2000

Evidence for a new Graves disease susceptibility locus at chromosome 18q21.

Graves disease (GD) is a common autoimmune thyroid disorder that is inherited as a complex multigenic trait. By using a single microsatellite marker at each locus, we screened the type 1 diabetes loci IDDM4, IDDM5, IDDM6, IDDM8, and IDDM10 and the fucosyltransferase-2 locus for linkage in sib pairs with GD. This showed a two-point nonparametric linkage (NPL) score of 1.57 (P=.06) at the IDDM6 marker D18S41, but NPL scores were <1.0 at the other five loci. Thus, the investigation of the IDDM6 locus was extended by genotyping 11 microsatellite markers spanning 48 cM across chromosome 18q12-q22 in 81 sib pairs affected with autoimmune thyroid disease (AITD). Multipoint analysis, designating all AITD sib pairs as affected, showed a peak NPL score of 3.46 (P=.0003), at the marker D18S487. Designation of only GD cases as affected (74 sib pairs) showed a peak NPL score of 3.09 (P=.001). Linkage to this region has been demonstrated in type 1 diabetes (IDDM6), rheumatoid arthritis, and systemic lupus erythematosus, which suggests that this locus may have a role in several forms of autoimmunity.

Alleles↗
PubMed2000

Assessment of health-related quality-of-life in patients after heart transplantation under therapy with tacrolimus or cyclosporine.

Reduction of allograft rejections remains a primary goal for patients after orthotopic heart transplantation. In an open, multicentre, prospectively randomised, parallel group study, patients with primary orthotopic heart transplantation under oral immunosuppressive treatments with tacrolimus (FK506) or cyclosporine (sandimmun) were compared with respect to medical outcome data. As health-related quality-of-life (HRQOL) is also supposed to be an important outcome parameter, it was assessed as a secondary variable in these two patient groups. Patients' self-rated generic HRQOL was assessed 6 weeks, 3 months, 6 months and 12 months after surgery with the SF-36 questionnaire, a generic HRQOL instrument. For 70 patients (46 under tacrolimus, 24 under cyclosporine), intent-to-treat analyses were carried out. The tacrolimus group showed improvements in the different HRQOL subscales of the SF-36 compared to the cyclosporine group. Especially the SF-36 subscales 'vitality' and 'mental health' showed statistically higher scores for the tacrolimus group. Aggregating psychological and cognitive subscales in the 'mental component score', patients treated with tacrolimus showed a statistically significant improvement compared to the cyclosporine group. The assessment of HRQOL variables in the evaluation of treatment effects proved to be an outcome parameter in this study. The results demonstrate the benefit of tacrolimus with respect to the HRQOL of patients, especially in the psychological dimension.

Analysis of Variance↗
PubMed2000

Nissen-type fundoplication and its effects on the emetic reflex and gastric motility in the ferret.

Recurrent vomiting with failure to thrive is a common problem in neurologically impaired children. Many undergo fundoplication to control the underlying gastro-oesophageal reflux. The results of surgery are not always satisfactory and post-operative retching may be a major problem - a symptom indicative of activation of the emetic reflex. An animal model of antireflux surgery has been developed and used to investigate the effects of such surgery upon the emetic reflex and vagal influences on gastric motility. Following surgery, animals responded to a previously subemetic dose of a centrally acting opiate receptor agonist (loperamide), suggesting that fundoplication may sensitize the emetic reflex. A gastric vago-vagal reflex (tonic inhibition of corpus tone) and responses to direct stimulation of vagal motor efferents (both cholinergic and nonadrenergic noncholinergic responses) were not significantly affected by antireflux surgery. Mechanisms by which neural damage may sensitize the emetic reflex are discussed, together with the possible clinical implications for the management of post-operative symptoms in neurologically impaired children.

Animals↗
PubMed2000

Marital quality and psychological adjustment to widowhood among older adults: a longitudinal analysis.

OBJECTIVES: This study examined whether psychological adjustment to widowhood is affected by three aspects of marital quality--warmth, conflict, and instrumental dependence-assessed prior to the loss. METHODS: The Changing Lives of Older Couples (CLOC) is a prospective study of a two-stage area probability sample of 1,532 married individuals aged 65 and older. The CLOC includes baseline data on marital quality and mental health and data on grief, anxiety, and depression collected 6, 18, and 48 months after spousal loss. RESULTS: Widowhood was associated with elevated anxiety among those who were highly dependent on their spouses and lower levels of anxiety among those who were not dependent on their spouses. Levels of yearning were lower for widowed persons whose relationships were conflicted at baseline and higher for those reporting high levels of marital closeness and dependence on their spouses. Women who relied on their husbands for instrumental support had significantly higher levels of yearning than men who depended on their wives. DISCUSSION: The findings contradict the widespread belief that grief is more severe if the marriage was conflicted and suggest a more complex relationship between bereavement and characteristics of the marriage.

Adaptation, Psychological↗
PubMed2000

Impact of fluconazole prophylaxis on fungal colonization and infection rates in neutropenic patients. The Canadian Fluconazole Study.

Fungal colonization profiles from four different anatomical sites were evaluated in 266 neutropenic cancer patients receiving intensive cytotoxic therapy for acute leukaemia or for autologous marrow transplantation. At the beginning of chemotherapy patients were allocated randomly to receive oral fluconazole 400 mg daily or an identical placebo until prophylaxis failure or marrow recovery. Candida albicans colonization was reduced from 30 to 10% in the fluconazole recipients while it increased from 32 to 57% in the placebo patients (P<0.001). By the end of prophylaxis, colonization with non-albicans Candida species increased from 7 to 21% and 8 to 18% in the fluconazole and placebo patients, respectively (P = 0.396). Although Candida glabrata was isolated more frequently at the end of the prophylactic period in the fluconazole patients than in the placebo patients (16 versus 7%), only one definite invasive C. glabrata infection was noted. Overall, definite invasive fungal infections were documented in 26 patients [four fluconazole versus 22 placebo patients (P< or =0.001)]. In 23 (92%) patients the infections were caused by persistently colonizing or newly acquired organisms. While probable invasive fungal infections were noted in five fluconazole patients, 10 placebo patients were also affected (P = 0.19). An end-of-prophylaxis colonization index >0.25 was 76% sensitive but only 69% specific for invasive fungal infection. However, a colonization index < or =0.25 at baseline had a negative predictive value of 88% for development of invasive fungal infection. Fluconazole prophylaxis decreased colonization by fungi and subsequent invasive fungal infections in neutropenic cancer patients.

Adolescent↗
PubMed2000

Association analysis of the cytotoxic T lymphocyte antigen-4 (CTLA-4) and autoimmune regulator-1 (AIRE-1) genes in sporadic autoimmune Addison's disease.

Although autoimmune Addison's disease (AAD) may occur as a component of the monogenic autoimmune polyendocrinopathy type 1 syndrome (APS1), it is most commonly found as an isolated disorder or associated with the autoimmune polyendocrinopathy type 2 syndrome (APS2). It is likely that sporadic (non-APS1) AAD is inherited as a complex trait; however, apart from the major histocompatibility complex, the susceptibility genes remain unknown. We have examined polymorphisms at two non-major histocompatibility complex candidate susceptibility loci in sporadic (non-APS1) AAD: the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene and the autoimmune regulator (AIRE-1) gene. DNA samples from AAD subjects (n = 90) and local controls (n = 144 for CTLA-4; n = 576 for AIRE-1) were analyzed for the CTLA-4A/G polymorphism in exon 1 of the CTLA-4 gene and for the common mutant AIRE-1 allele (964de113) in United Kingdom subjects with APS1, by using the restriction enzymes Bst7II and BsrBI, respectively. There was an association of the G allele at CTLA-4A/G in AAD subjects (P = 0.008 vs. controls), which was stronger in subjects with AAD as a component of APS2 than in subjects with isolated AAD. In contrast, the mutant AIRE-1 964del13 allele was carried in one each of the 576 (0.2%) control subjects and the 90 (1.1%) AAD subjects as a heterozygote (P = 0.254, not significant), suggesting that this common AIRE-1 gene abnormality does not have a major role in sporadic (non-APS1) AAD.

Abatacept↗
PubMed2000

Equivalence classes in individuals with minimal verbal repertoires.

Studies from two different laboratories tested for equivalence classes in individuals with severe mental retardation and minimal verbal repertoires. In the first study, 3 individuals learned several matching-to-sample performances: matching picture comparison stimuli to dictated-word sample stimuli (AB), matching those same pictures to printed letter samples (CB), and also matching the pictures to nonrepresentative forms (DB). On subsequent tests, all individuals immediately displayed Emergent Relations AC, AD, BC, BD, CD, and DC, together constituting a positive demonstration of equivalence (as defined by Sidman). The second study obtained a positive equivalence test outcome in 1 of 2 individuals with similarly minimal verbal repertoires. Taken together, these studies call into question previous assertions that equivalence classes are demonstrable only in individuals with well-developed language repertoires.

Adolescent↗