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Biomedical subjects

J Donovan

Publications and source records attributed to J Donovan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Australian adolescents' attitudes and beliefs concerning pregnancy, childbirth and parenthood: the development, psychometric testing and results of a new scale.

Recent research suggests that many adolescents hold unrealistic and idealised beliefs about the likely consequences of pregnancy and parenthood. Such attitudes potentially play an important role in the aetiology of adolescent pregnancy. Disillusionment with reality may also contribute to postnatal depression, domestic violence and child abuse. This paper reports on the development of a scale to measure the prevalence of such beliefs. The scale was administered to a sample of 1546 Australian adolescents. Between one-quarter and one-third of the sample exhibited idealised beliefs, with males having higher levels of idealization. On factor analysis, the idealization construct comprised an overestimation of positive aspects and an underestimation of negative ones. Subjects reported that very few of their beliefs derived from formal educational input.

Adolescent↗
PubMed2001

Pressure rinsing of coronary stents immediately before implantation reduces inflammation and neointimal hyperplasia.

OBJECTIVES: This study evaluates whether rinsing stents with high pressure immediately before implantation minimizes stent-induced inflammation and neointimal formation. BACKGROUND: Several reports indicate that manual stent manipulation before implantation results in foreign body contamination and increased neointimal hyperplasia. METHODS: A stent-cleaning chamber was developed to rinse stents at a sustained hydrodynamic pressure of 4 atm for 10 s. Commercial pre-mounted stents were examined with different levels of manipulation: 1) untouched stents: no stent manipulation before implantation; 2) handled stents: manual stent re-crimping on the balloon; 3) rinsed stents: pressure-rinsed with the stent-cleaning chamber. In vitro surface analysis was evaluated by scanning electron microscopy. Neointimal hyperplasia and inflammation around stent struts were also assessed in the pig in-stent restenosis model. RESULTS: In vitro analysis revealed fewer contaminants on rinsed stents compared with untouched (p = 0.01) and handled stents (p < 0.001). In vivo, neointimal thickness, neointimal area and vessel percent stenosis were significantly reduced in rinsed, compared with not-rinsed, stents (p = 0.002, p = 0.007, p = 0.008 respectively). In addition, a significant reduction in the inflammatory infiltrate around struts was observed in untouched, compared with handled, stents (p = 0.04) and in rinsed, compared with not-rinsed, stents (p < 0.001). Regression analysis accounting for injury and neointimal thickness showed significant differences in slopes between "handled + not-rinsed" and "handled + rinsed" stents (p = 0.004), and between "untouched + not-rinsed" and "untouched + rinsed stents" (p = 0.037). CONCLUSIONS: Rinsing stents under high pressure immediately before coronary implantation results in less inflammation around struts and thinner neointima at 28 days in this pig model.

Animals↗
PubMed2001

Cisplatin chemotherapy plus adenoviral p53 gene therapy in EBV-positive and -negative nasopharyngeal carcinoma.

We have previously shown that the introduction of human recombinant wild-type p53 mediated by an adenoviral vector (Ad5CMV-p53), either alone or delivered in combination with ionizing radiation, was cytotoxic to two nasopharyngeal carcinoma (NPC) cell lines. To further explore the potential therapeutic role for gene therapy, the combination of Ad5CMV-p53 and cisplatin was examined in two NPC cell lines, CNE-1 and C666-1. The C666-1 cells are particularly relevant because they express Epstein-Barr virus latent gene products analogous to human NPC in situ. Cells were infected with 5 pfu/cell of Ad5CMV-p53 or Ad5CMV-beta-gal, followed by exposure to increasing doses of cisplatin. Clonogenic and MTT assays were used to assess the sensitivity of cells to these treatments, and apoptosis was also quantified. The combination of Ad5CMV-p53 and cisplatin resulted in approximately 25% greater cytotoxicity compared to that observed with cisplatin alone in either cell line. Apoptosis was induced in approximately 50% of cells following administration of both Ad5CMV-p53 and cisplatin, but was induced in considerably fewer cells following either treatment alone. The two modalities appeared to interact in an additive manner. Ad5CMV-p53 gene therapy resulted in the expression of biologically active p53 protein, shown by induction of p21(WAF1/CIP1). Cisplatin treatment showed little effect on either p53 or p21(WAF1/CIP1) expression. Therefore, both p53 gene therapy and cisplatin chemotherapy demonstrated cytotoxicity mediated by apoptosis despite the presence of EBV gene products in the C666-1 cells, but it appears that the two modalities induce cytotoxicity by independent pathways.

Adenoviridae↗
PubMed2001

A randomized trial comparing the effectiveness and preference of a touch-screen computer system with a leaflet for providing women with information on urinary symptoms suggestive of detrusor instability.

OBJECTIVES: To evaluate how well women learned and retained information given to them by either a leaflet or a computer-generated information system, and which system they preferred to use for obtaining information about urinary symptoms. SUBJECTS AND METHODS: Forty women answered 11 questions on the aetiology, investigation and treatment of lower urinary tract symptoms. They were then randomized to use one of the information systems for 20 min, after which they answered the same urological questions. The women then crossed over to use the other information system for 20 min and afterwards completed a preference questionnaire. RESULTS: The mean baseline scores from a possible total of 11 were 3.9 and 4.3 for the computer and leaflet groups, respectively. The mean improvements in scores were 3.6 (P < 0.001) and 2.8 (P < 0.001) for the computer and leaflet groups, respectively. Both information systems were well liked by all of the women and 26 (65%) said they would prefer to use a computer-generated system in the future if given a choice. CONCLUSIONS: Women significantly increased their knowledge of urinary problems after using a computer-generated information system or a leaflet. Although there were few subjects, there appeared to be a trend for the computer system to be both better liked and slightly more effective.

Adult↗
PubMed2001

The relationship between active renin concentration and plasma renin activity in Type 1 diabetes.

AIMS: Circulating activity of the renin-angiotensin-aldosterone system (RAAS) can be assessed by measuring plasma active renin concentration (ARE), as well as by measuring plasma renin activity (PRA). We aimed to assess the relationships between ARE and PRA in Type 1 diabetic compared with non-diabetic control subjects. We also assessed concentrations of the active renin precursor, prorenin. PATIENTS AND METHODS: Thirty-five Type 1 diabetic subjects and 34 non-diabetic control subjects were assessed. Groups had similar ages, sex distributions, body mass indices, systolic and diastolic blood pressures. PRA was measured by radioimmunoassay of angiotensin I generation from endogenous substrate. ARE and total renin concentration (TRE) were measured by immunoradiometric assay (Nichols Institute Diagnostics, USA). Prorenin concentration was calculated as the difference between ARE and TRE. RESULTS: PRA was significantly lower in Type 1 diabetic than in control subjects (0.8 (0.4-1.1) vs. 1.1 (0.9-1.9) pmol/ml per h; P < 0.005), while ARE was similar (17 (9-33) vs. 18 (15-25) mU/l; P = 0.548). PRA (loge transformed) correlated strongly with ARE in diabetic (r = 0.49; P = 0.003) and control subjects (r = 0.59; P = 0.0002), but there was significant vertical separation of the regression lines for the two groups (P < 0.0001). Prorenin concentrations were significantly higher in Type 1 diabetic subjects (249 (170-339) vs. 171 (153-219) mU/l; P = 0.005). Diabetic subjects with high prorenin concentrations (> 400 mU/l (control mean + 3 SD)) were more likely to have microalbuminuria (P = 0.027) and peripheral neuropathy (P = 0.049). CONCLUSIONS: Type 1 diabetes is associated with an altered relationship between ARE and PRA, such that ARE is higher for a given PRA compared with non-diabetic control subjects. Both ARE and PRA are used to assess circulating RAAS activity. The altered relationship between the two in Type 1 diabetic subjects suggests that neither parameter alone is necessarily an adequate and reliable index of such activity. Higher prorenin concentrations, particularly in association with microvascular complications, were confirmed in the Type 1 diabetic subjects. Diabet. Med. 18, 451-458 (2001)

Adult↗
PubMed2001

Urinary incontinence in older people in the community: a neglected problem?

BACKGROUND: The prevalence and impact of urinary incontinence has been investigated much less in older men than in older women. It is suggested that those who perceive that their daily lives are affected should have priority for services. However, many people do not seek medical help, even though they may be severely affected. AIM: To investigate unmet need in relation to the prevalence and impact on everyday life of urinary incontinence in men and women over the age of 65 years. DESIGN OF STUDY: Cross-sectional survey to measure prevalence of urinary incontinence, the impact on people's lives, use of protection, and health services. SETTING: Stratified random sample of 2000 community-living elderly (equal numbers of men and women, aged 65 to 74 years and over 75 years) in 11 general practices in a British city. RESULTS: The response rate was 79%. The overall prevalence of incontinence in the previous month was 31% for women and 23% for men. Women generally had more severe frequency of incontinence and a greater degree of wetness than men. Protection use was greater in women than in men. Only 40% of men and 45% of women with incontinence had accessed health services. Significant predictors of the use of health services were: incontinence reported as a problem, increased frequency of incontinence, and greater degree of wetness. About one-third of people who leaked with severe frequency or who reported that it was a problem had not accessed NHS services for incontinence. CONCLUSIONS: Urinary incontinence is a common problem for older men and women living in the community and can have a deleterious effect on their lives. There is the opportunity to improve the lives of many older people with urinary incontinence, probably by a combination of increased public, patient, and professional awareness that should lead to earlier presentation and initiation of effective care.

Age Factors↗
PubMed2000

Reduction of Cdc25A contributes to cyclin E1-Cdk2 inhibition at senescence in human mammary epithelial cells.

Replicative senescence may be an important tumor suppressive mechanism for human cells. We investigated the mechanism of cell cycle arrest at senescence in human mammary epithelial cells (HMECs) that have undergone a period of 'self-selection', and as a consequence exhibit diminished p16INK4A levels. As HMECs approached senescence, the proportion of cells with a 2N DNA content increased and that in S phase decreased progressively. Cyclin D1-cdk4, cyclin E-cdk2 and cyclin A-cdk2 activities were not abruptly inhibited, but rather diminished steadily with increasing population age. In contrast to observations in fibroblast, p21Cip1 was not increased at senescence in HMECs. There was no increase in p27Kip1 levels nor in KIP association with targets cdks. While p15INK4B and its binding to both cdk4 and cdk6 increased with increasing passage, some cyclin D1-bound cdk4 and cdk6 persisted in senescent cells, whose inhibition could not be attributed to p15INK4B. The inhibition of cyclin E-cdk2 in senescent HMECs was accompanied by increased inhibitory phosphorylation of cdk2, in association with a progressive loss of Cdc25A. Recombinant Cdc25A strongly reactivated cyclin E-cdk2 from senescent HMECs suggesting that reduction of Cdc25A contributes to cyclin E-cdk2 inhibition and G1 arrest at senescence. Although ectopic expression of Cdc25A failed to extend the lifespan of HMECs, the exogenous Cdc25A appeared to lack activity in these cells, since it neither shortened the G1-to-S phase interval nor activated cyclin E-cdk2. In contrast, in the breast cancer-derived MCF-7 line, Cdc25A overexpression increased both cyclin E-cdk2 activity and the S phase fraction. Thus, mechanisms leading to HMEC immortalization may involve not only the re-induction of Cdc25A expression, but also activation of this phosphatase.

Adult↗
PubMed2000

A prospective longitudinal study examining the quality of life of patients with esophageal carcinoma.

BACKGROUND: Quality of life (QL) measurement provides detailed information about outcome from the patient's perspective. This study assessed the impact on short and long term QL of esophagectomy and palliative treatment in patients with esophageal carcinoma. METHODS: Consecutive patients undergoing potentially curative esophagectomy or purely palliative treatment completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the dysphagia scale from the EORTC QLQ-OES24 before treatment and at regular intervals until death or for 3 postoperative years. Median scores were calculated for patients surviving more than 2 years after surgery (n = 17), for patients surviving less than 2 years after esophagectomy (n = 38), and for patients undergoing palliative treatment (n = 37). RESULTS: Baseline functional and symptom QL scores were similar in both groups of patients undergoing esophagectomy, and these were better than scores from patients selected for palliative treatment. Six weeks after esophagectomy, patients reported worse functional, symptom, and global QL scores than before treatment. In patients who survived at least 2 years, QL scores returned to preoperative levels within 9 months, but patients who died within 2 years of surgery never regained their former QL. In both groups, dysphagia improved after surgery and the improvement was maintained until death or for the duration of the study. Patients undergoing palliative treatment reported gradual deterioration in most aspects of QL until death. CONCLUSIONS: Esophagectomy has a negative impact on QL; this effect is transient for patients who survive for 2 or more years. This finding should be considered when selecting patients for surgery.

Aged↗
PubMed2000

Comparative organization of cattle chromosome 5 revealed by comparative mapping by annotation and sequence similarity and radiation hybrid mapping.

A whole genome cattle-hamster radiation hybrid cell panel was used to construct a map of 54 markers located on bovine chromosome 5 (BTA5). Of the 54 markers, 34 are microsatellites selected from the cattle linkage map and 20 are genes. Among the 20 mapped genes, 10 are new assignments that were made by using the comparative mapping by annotation and sequence similarity strategy. A LOD-3 radiation hybrid framework map consisting of 21 markers was constructed. The relatively low retention frequency of markers on this chromosome (19%) prevented unambiguous ordering of the other 33 markers. The length of the map is 398.7 cR, corresponding to a ratio of approximately 2.8 cR(5,000)/cM. Type I genes were binned for comparison of gene order among cattle, humans, and mice. Multiple internal rearrangements within conserved syntenic groups were apparent upon comparison of gene order on BTA5 and HSA12 and HSA22. A similarly high number of rearrangements were observed between BTA5 and MMU6, MMU10, and MMU15. The detailed comparative map of BTA5 should facilitate identification of genes affecting economically important traits that have been mapped to this chromosome and should contribute to our understanding of mammalian chromosome evolution.

Animals↗
PubMed2000

Transforming growth factor-beta and breast cancer: Cell cycle arrest by transforming growth factor-beta and its disruption in cancer.

Altered responsiveness to extracellular signals and cell cycle dysregulation are hallmarks of cancer. The cell cycle is governed by cyclin-dependent kinases (cdks) that integrate mitogenic and growth inhibitory signals. Transforming growth factor (TGF)-beta mediates G1 cell cycle arrest by inducing or activating cdk inhibitors, and by inhibiting factors required for cdk activation. Mechanisms that lead to cell cycle arrest by TGF-beta are reviewed. Loss of growth inhibition by TGF-beta occurs early in breast cell transformation, and may contribute to breast cancer progression. Dysregulation of cell cycle effectors at many different levels may contribute to loss of G1 arrest by TGF-beta. Elucidation of these pathways in breast cancer may ultimately lead to novel and more effective treatments for this disease.

Breast Neoplasms↗
PubMed2000

CD34 selection as a stem cell purging strategy for neuroblastoma: preclinical and clinical studies.

BACKGROUND: The suitability of CD34 selection for purging peripheral blood progenitor cells (PBPC) collected from patients with neuroblastoma (NB) has been called into question, largely because of reports of detection of low levels of CD34 on the surface of some NB cell lines and tumors. PROCEDURE: We used three approaches to address the issue of purging of NB from stem cell specimens and possible labeling of NB: 1) Flow cytometric detection of CD34 on NB cell lines. We assessed CD34 expression using a panel of anti-CD34 monoclonal antibodies (MoAbs) including 9C5, 12.8, and QBend10 and showed no increase in labeling over secondary-only control. 2) Spiking experiments with the Isolex 50 system. NB cell lines were used to contaminate aliquots of PBPC collections, after which the products were purified using the Isolex 50. Purging of NB was assessed by quantitative multiplex RT-PCR (TaqMan system) using a tumor-specific transcript, GAGE. We demonstrated >2 logs of tumor cell depletion from these specimens. 3) Analysis of clinical specimens. PBPC pre- and post-CD34 selection were analyzed from patients treated on the CHP-594 transplant trial. RESULTS: In nine specimens selected using the Ceprate LC CD34 selection system where tumor was detectable by immunocytochemistry preselection, we observed >2.4 to >4.6 logs of NB purging after selection. We then analyzed 23 aliquots of PBPC infused into patients post-CD34 selection and compared them to the product preselection; 20/23 specimens showed depletion of NB, although some level of GAGE message was observed in most post-CD34 selection specimens. CONCLUSION: These data show that purging of NB from PBPC specimens using CD34 selection is feasible, yielding infused products that are negative at the level of ICC but often positive at the level of RT-PCR.

Antigens, CD34↗
PubMed2000

The development and validation of a quality-of-life measure to assess partner morbidity in benign prostatic enlargement.

OBJECTIVE: To investigate morbidity in the partners of patients with benign prostatic enlargement (BPE) by developing and validating a disease-specific questionnaire. PATIENTS AND METHODS: Phase 1 of the study comprised preliminary interviews with 15 patients who had newly diagnosed BPE, and with their partners, to determine the relevant issues for the partners. In phase 2, using these issues, a questionnaire was produced and tested on the 15 partners. In phase 3 the questionnaire was completed by 90 further partners, 50 at interview and the next 40 by post. As part of the validation process, the partners were also asked to complete the Short-Form-36 questionnaire, and the patients the Internation Prostate Symptom Score (IPSS) and the ICSmale questionnaires. RESULTS: In phase 1 all 15 of the partners were affected by the patients' disease and nine issues were identified. In phase 2, of the 90 partners, only one had no morbidity from the patient's symptoms; 71% were worried that the patient may have cancer and 69% concerned that the patient may require an operation. Only six partners were present at the patients' urological consultation. The partners' questionnaire scores were related significantly to the Mental Health and Vitality domains of the SF36 and with the patients' IPSS. CONCLUSIONS: The study confirmed the presence of significant morbidity in the partners of patients with BPE. The degree of partner morbidity was related to the severity of the patients' symptoms. Many of the questionnaire issues can be addressed in the consulting room by open discussion with patient and partner.

Female↗
PubMed2000

Teenage pregnancy: whose problem is it?

BACKGROUND: The UK has the highest rates of teenage conception in Europe. Teenage conception has been identified in medical literature as a problem for society and teenagers. However, little attempt has been made to see it from the perspective of the teenagers themselves. OBJECTIVE: To explore teenage women's attitudes to sexual health, contraception and pregnancy. METHODS: Ethnographic qualitative study based on in-depth interviews and participant observation. The study took place in young mothers' groups, young persons' clinics and general practices in Bristol. Subjects were 34 young women between the ages of 16 and 20, sampled purposefully in two groups to include young mothers and never-pregnant young women from advantaged and disadvantaged socioeconomic backgrounds. RESULTS: The two groups did not differ in their use of contraception at first intercourse. Young women from more socioeconomically advantaged backgrounds felt that motherhood would not be acceptable to them, but were more tolerant to others who became young mothers. The pregnant/ young mothers revealed more difficulties getting access to reliable contraceptive services, and dissatisfaction with sex education in schools. The pregnant/young mothers found abortion to be less acceptable than the more socially advantaged group. Both groups reported sexual behaviour that involved risks of becoming pregnant, but the more socially advantaged group were more likely to use emergency contraception. CONCLUSIONS: The study demonstrates the importance of taking the views of young people into account when planning both sex education and the provision of contraceptive services.

Abortion, Induced↗