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Biomedical subjects

T Dowell

Publications and source records attributed to T Dowell.

18 recordsLinked to original sources
PubMed2001

Māori women and menopause.

Māori are the indigenous people of New Zealand who in total make up 14.5% of the population. Although this group has a significantly lower life expectancy than non-Māori, coupled with increased rates of mortality and morbidity, very little is known about the menopausal health needs of older Māori women. As the first step in addressing the health needs of this group, older Māori women's definitions, attitudes, symptoms, expectations and health needs at menopause need to be identified and described. The study Ngā Ruahine or "Māori in Menopause" is the foundation study of the Aotearoa Women's Health Initiative (AWHI). AWHI is a women's health programme being developed by the Wellington School of Medicine, which involves a suite of studies. The objective is to describe the journey of older Māori women through menopause and beyond and to compare and contrast the experience of Māori women from both traditional and contemporary upbringings, with reference to the Pākehā (European) population. It is hoped that this work could lead to further studies such as, for example, a longitudinal observational study looking at older New Zealand women. The potential significance of this approach is discussed.

Age Factors↗
PubMed1998

Early detection of differences in surgical outcome for cleft lip and palate.

This study examined the dento-alveolar relationships of 5-year-old children born with a unilateral cleft lip and palate with primary surgical repair performed in one of two centres (Bristol or Oslo). The Bristol sample comprised 46 sets of study models and the Oslo CLP Growth Archive provided 54 cases with a very similar sex distribution. We used a recently developed 5-year-old index to measure differences in outcome between the two centres. The Oslo sample were assessed as having up to 57 per cent in the ideal groupings (1 and 2), in the Bristol group this was only 35 per cent. Bristol had up to 46 per cent of cases assessed in the worst groups (4 and 5). The comparative figure from the Oslo group was 15 per cent. These results suggest that it is possible to detect differences in surgical outcome at 5 years of age.

Age Factors↗
PubMed1997

Psychological outcomes amongst cleft patients and their families.

Our aims were to determine the psychological status of a sample of cleft lip and palate patients and their parents using standardised interviews and to assess subjects' satisfaction with cleft treatment. In all, 242 interviews of 112 patients and 130 parents were carried out in nine base hospitals used for cleft treatment. 73% (n = 38) of 15- and 20-year-old subjects felt their self-confidence had been very much affected as a result of their cleft. 60% of all 112 interviewed patients were teased about speech or cleft related features. A significant minority of 15-year-old subjects (23%, n = 7) felt excluded from treatment planning decisions. Despite high levels of overall satisfaction with cleft care, 60% (n = 78) of parents and 37% (n = 41) of interviewed patients made suggestions for improvements. No agreement between parent/child pairs for their satisfaction with clinical outcome of cleft related features was found using the weighted kappa statistic to determine the level of agreement. Differences between parents' and their child's satisfaction ratings for cleft related features were not statistically significant except for the ratings for 'lip' (P < 0.005) and 'teeth' (P < 0.05) for 15-year-old subjects (Wilcoxon signed rank sum test). Patients' views on planned treatment should therefore be independently sought from their parents' views, as no agreement was found within the groups for perceived satisfaction with clinical outcome. This study demonstrates the importance of identifying 'psychological outcome' as well as 'clinical outcome' in order to improve rehabilitation for cleft lip and palate patients. Seven families were referred for counselling for cleft-associated emotional problems as a result of this survey.

Adolescent↗
PubMed1997

Satisfaction with facial appearance among subjects affected by a cleft.

OBJECTIVE: This study examined the satisfaction of patients with clefting and their parents with facial appearance and how this alters with age. The relationship between satisfaction with appearance and psychosocial functioning was also examined. DESIGN: Prospective SETTING: Subjects were recruited for the study from nine hospital-based clinics. PARENTS, PARTICIPANTS: All subjects has some type of cleft and were 10, 15 or 20 years of age. In all, 111 subjects with clefting and 62 parents were included. MAIN OUTCOME MEASURES: Facial appearance was rated on a subjective ordinal scale of 1 to 7; psychosocial adjustment was measured with the Childhood Experience Questionnaire. RESULTS: Self-satisfaction with appearance among the 10- and 15-year-old subjects correlated with their psychosocial adjustment (p = .027). The 20-year-old subjects were, on average, significantly more satisfied with their appearance than the 10- and 15-year-olds (p = .009 and p = .012, respectively). However, some 20-year-old subjects remained greatly dissatisfied with aspects of their facial appearance. Subjects with visible anomalies were significantly more dissatisfied with their appearance than subjects with invisible anomalies (p = .035). The 15-year-old subjects were identified as being significantly more dissatisfied with appearance than their parents (p = .005). CONCLUSIONS: Subjects affected by a cleft with visible impairments are more dissatisfied with their facial appearance than are subjects with invisible impairments. Satisfaction with facial appearance among 10- and 15-year-old subjects with a cleft may be associated with their self-reported levels of psychosocial functioning. Measuring self-satisfaction with appearance may help to identify subjects at risk from adjustment problems.

Adaptation, Psychological↗
PubMed1997

A new index for assessing surgical outcome in unilateral cleft lip and palate subjects aged five: reproducibility and validity.

OBJECTIVE: This study assessed the reproducibility, reliability, and predictive validity of a previously developed index by the authors for assessing surgical outcome in unilateral cleft lip and palate (UCLP) children aged 5. METHODS: Sixty randomly selected study models of 5- to 6-year-old complete UCLP subjects were obtained and the index was used to assess their surgical outcomes. RESULTS: Assessment of these study models using the new index demonstrated excellent intra-examiner agreement. The inter-examiner agreement was shown to be good. The corresponding longitudinal models at 16 to 18 years of 54 of the initial 5- to 6-year-old sample were also acquired. These subjects had undergone orthodontic treatment but not orthognathic surgery. The need for osteotomy amongst these models was assessed. Between 13% and 18% (depending on examiner) of 5-year-olds' models were scored in the groups likely to require orthognathic surgery. In the corresponding 16- to 18-year-olds' models, 9% were assessed as likely to benefit from an osteotomy. However, on an individual basis, it was not possible to predict future growth from study models at age 5. CONCLUSIONS: This study has provided a reliable and reproducible index for assessing the outcome of surgery in UCLP subjects earlier than indices already available. True validation of the index was not possible but it appears that it relies on face validity.

Adolescent↗
PubMed1996

The use of oral dehydroepiandrosterone sulfate as an adjuvant in tetanus and influenza vaccination of the elderly.

Elderly individuals often exhibit a poorer immune response and shorter duration of immunity to vaccines than younger persons. Improvement in vaccine response has been demonstrated when administering the hormone dehydroepiandrosterone sulfate (DHEAS) as an adjuvant in animal trials. Two separate, randomized double-blinded vaccine trials were therefore conducted using DHEAS as an oral adjuvant in individuals age 65 or older. Sixty-six individuals were randomized to DHEAS, 50 mg po bid for 4 days, or a placebo capsule. Tetanus vaccination was given immediately before the fifth dose. At entry the level of protective antibody was age-dependent (P = 0.009), and by 28 days post-vaccination most individuals had protective levels of antibody, with no difference noted between treatment groups. In the second study, 67 individuals received placebo capsules or DHEAS immediately before and 24 h after influenza vaccination. The number of individuals who developed protective titers (> or = 1:40) was not different in the two groups. The mean log increase in HAI response was greater in the DHEAS group to all three vaccine components, although this did not achieve significance. Minimal side-effects of DHEAS administration were noted. Given the trend toward improved response in the elderly to influenza, larger trials using DHEA as an adjuvant in vaccines that are neoantigens may be indicated.

Adjuvants, Immunologic↗
PubMed1995

DHEAS as an effective vaccine adjuvant in elderly humans. Proof-of-principle studies.

We have demonstrated that in aged mice, the titer of serum antibody induced against tetanus toxoid correlates with resistance to local paralysis caused by injection of tetanus toxin. Only mice immunized shortly after oral dosing with DHEAS demonstrated high serum antibody titers and complete protection from paralysis. These results became the basis for initiating proof-of-principle studies in human volunteers above age 65 using a licensed influenza vaccine and tetanus toxoid in two independent studies. The use of an oral delivery form of DHEAS before influenza vaccination was associated with a demonstrable increase in the number of individuals with a fourfold increase in HAI titers following vaccination. The overall mean increase in HAI titers was highest in the DHEAS-treated group. The use of DHEAS in the immunization of elderly subjects against tetanus toxoid, while unable to enhance the responses, was not a detriment to antibody response. We conclude that further studies will justify the use of DHEAS as an adjuvant for antigens that represent primary responses in the elderly.

Adjuvants, Immunologic↗
PubMed1991

Platelet-derived growth factor is a potent biologic response modifier of T cells.

Freshly isolated lymph node (LN) cells cultured in serum-containing medium were restricted to produce primarily interleukin 2 (IL-2) subsequent to T cell activation. Only minimal amounts of IL-4, IL-5, or interferon gamma (IFN-gamma) were produced under these conditions. Similar populations of LN cells cultured in serum-free medium were able to produce a variety of lymphokines after T cell activation, with the relative quantities of each species being dependent upon the lymphoid organ source of the lymphocytes. A similar relationship in the patterns of lymphokines produced by activated T cell hybridomas maintained under serum-free conditions was also observed, whereas activation in serum-supplemented media resulted in a predominant restriction to the secretion of IL-2. Additional studies determined that the entity in serum responsible for restricting T cell function in vitro was platelet-derived growth factor (PDGF). The PDGF-BB isoform was established to be the most active in the regulation of T cell function, enhancing IL-2 while depressing the production of IL-4, IL-5, and IFN-gamma at concentrations below 1 ng/ml. PDGF-AB was also found to be quite active, however, this isoform of PDGF was incapable of influencing IFN-gamma production at the concentrations tested. PDGF-AA was very weakly active. It therefore appears that PDGF, acting primarily through a beta receptor subunit (either alpha/beta- or beta/beta-type receptors) is able to influence profoundly the behavior of T cells, with some of its modulatory effects exhibiting isoform specificity. This is reflected by an enhancement in the production of IL-2, while simultaneously depressing the secretion of IL-4, IL-5, and IFN-gamma (PDGF-BB only) after T cell activation. Kinetic studies, where cell supernatants were analyzed both 24 and 48 h after T cell activation, suggested that "desensitization" to PDGF influences can occur naturally in vitro. Those species of lymphokines that were inhibited by PDGF over the first 24 h after activation could be produced at normal levels over the subsequent 24-h period. Finally, lymphokines maintained in the presence of PDGF-BB for greater than 24 h before their activation lost sensitivity to this growth factor. These cells regained responsiveness to PDGF after an additional incubation period in PDGF-free medium. Collectively, our data imply that the pattern of T cell lymphokines produced, plus the kinetics of their production after activation, are being controlled by the potent serum growth factor PDGF.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Dihydrotestosterone exerts a depressive influence on the production of interleukin-4 (IL-4), IL-5, and gamma-interferon, but not IL-2 by activated murine T cells.

The present study examined the effects of the androgen steroid, dihydrotestosterone (DHT), on murine T-cell production of a number of lymphokines. Direct exposure of murine T cells to DHT in vitro was found to reduce the amount of interleukin-4 (IL-4), IL-5, and gamma-interferon (gamma IFN) produced after activation with anti-CD3 without affecting the production of IL-2. Exposure of T cells to either androstenedione or testosterone (the metabolic precursors of DHT) affected no change in the biosynthesis of either of these lymphokines. We have determined that macrophages possess 5 alpha-reductase, and are thus competent to metabolize testosterone to DHT. This physicochemical information is complemented by a functional analysis of macrophage metabolism of testosterone. By incubating bone marrow macrophages with testosterone, before their use as accessory cells, the IL-4 and IL-5 producing potential of the activated T cells cocultured with them was depressed. That the observed effect was mediated by the conversion of testosterone to DHT was further corroborated by illustrating that the inhibition of IL-4 production was abrogated if 4MA, a specific 5 alpha-reductase inhibitor, was added to macrophage cultures containing testosterone. The biologic role of DHT in lymphokine and immune response regulation in vivo was addressed using several lines of investigation. First, transdermal delivery of DHT to groups of mice altered the capacity of T cells residing in the draining lymph nodes, only, to produce lymphokines. Second, treatment of either aged mice or the T cells isolated from them with a combination of dehydroepiandrosterone and DHT restored the capacity of their T cells to produce IL-2, IL-4, and gamma IFN to levels equivalent to that of younger mice. Finally, we observed a difference between males and females of a given age to produce IL-2, IL-4, and gamma IFN, with both IL-4 and gamma IFN production being elevated in females. Collectively, our findings indicate that DHT, similar to other steroid hormones, may play an important role in lymphokine regulation in vivo.

Androstenedione↗
PubMed1989

Regulation of murine lymphokine production in vivo. Ultraviolet radiation exposure depresses IL-2 and enhances IL-4 production by T cells through an IL-1-dependent mechanism.

The exposure of experimental animals to the inflammatory effects of ultraviolet radiation (UVR) is known to cause depressions in their ability to initiate and effectuate various types of cellular immune responses. Contact-type and delayed-type hypersensitivity, plus the ability to generate protective forms of anti-viral and anti-tumor immunity, are all affected by the prior exposure of normal animals to the effects of this physical agent. Presently, the cellular and molecular mechanism(s) responsible for mediating the changes in immune function observed in UVR-exposed animals is not fully understood. Herein we report that one reproducible consequence of exposing normal mice to low doses of UVR is a dramatic change in the pattern of lymphokines secreted by their activated T cells. Lymphocytes isolated from UVR-exposed donors produce/secrete greatly reduced levels of the T cell lymphokines IL-2 and IFN-gamma activation in vitro with protein Ag of the polyclonal T cell stimulant anti-CD3. The secretion of IL-4 by these lymphocyte cultures, however, is consistently elevated in comparison to normal controls. Further studies determined that a similar change in lymphokine production was induced when mice were treated with either bacterial LPS or rIL-1 beta, a cytokine known to be elevated in vivo after UVR or LPS exposure. The ability of IL-1 to facilitate a change in the capacity of T lymphocytes to produce/secrete lymphokines after in vitro activation does not appear to represent a direct effect of this cytokine on lymphocyte or accessory cell targets because addition of IL-1 beta to cultures of Ag-primed lymphocytes obtained from normal donors was incapable of altering the pattern of lymphokine production. Collectively, our present results add further support to the hypothesis that UVR-induced elevations in endogenous IL-1 are, in part, responsible for the immunomodulatory effects of UVR. These findings provide compelling evidence that UVR, plus other agents capable of endogenously stimulating the production of IL-1, may function to alter the expression of different effector mechanisms in vivo. This could be facilitated through selective reductions in lymphokines produced by Th-1-type cells (IL-2 and IFN-gamma) and a simultaneous augmentation in a lymphokine produced by Th-2-type cells (IL-4).

Animals↗
PubMed1988

An adjunct trait of HEL/I-Ab-specific T helper cell is sensitivity to antigen-specific immunosuppression.

The present study tests whether the specific inhibition of helper T (Th) cell (and T hybridomas) by suppressor T (Ts) cells is a phenotypic trait of Th cells correlating with their acquired specificity for antigen/major histocompatibility complex or a genotypic trait not related to selection of the T cell repertoire for antigen. To do this we took advantage of the fact that H-2d parental strains of mice commonly restrict recognition of chicken egg-white lysozyme to the L3 peptide (a.a. 105-129) and H-2b parental mice to the L2 peptide (a.a. 13-105). F1 hybrids of these strains display two subsets of lysozyme-reactive T cells, one for each parental phenotype. Using (B10 X B10.D2)F1 mice reconstituted with B10.D2 bone marrow, we were able to develop genetic H-2d T cell clones that could express an atypical specificity, that is L2/I-Ab. Clones of this type, like genetic H-2b, are also sensitive to the inhibiting effects of HEL-activated Ts cells. To overcome some of the drawbacks of using heterogeneous populations of T, B and accessory cells in our assays, we constructed T hybridomas from HEL-immune, chimeric lymph node T cell blasts which respond to a unique antigen/major histocompatibility complex with production of the lymphokine interleukin 2. Our results indicate that all HEL/I-Ab-specific T cells (helper and hybridomas) are inhibited by suppression regardless of the T cell's haplotype at the H-2 locus: H-2b (B10), H-2d (D2) or H-2b,d (BDF1). Furthermore, there is a strict correlation between the antigen and I-A specificity: I-Ab-restricted T cells recognize non-L3 determinants even though some are derived from H-2d mice.

Animals↗
PubMedDate not supplied

The effect of patient ethnicity on prescribing rates.

The issuing of a prescription is central to any doctor-patient interaction. Prescribing variation exists and remains largely unexplained. There is little documented evidence of the effect of patient ethnicity on prescribing patterns. We carried out a secondary analysis of data from the General Household Surveys to examine the association between being given a prescription and patient ethnicity. After modelling, we found that Pakistanis and Indians were significantly more likely to receive a prescription from their general practitioner at a consultation compared to white and West Indian ethnic groups. In addition, consultation rate explained the different prescribing rates among women and men in the white group only. This study raises further questions of the underlying reasons causing these differences which need answering.

Adolescent↗