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Biomedical subjects

Barbara Murphy

Publications and source records attributed to Barbara Murphy.

At least 37 records · Page 2Linked to original sources
PubMed2003

Fecal incontinence after high-risk delivery.

OBJECTIVE: To investigate the prevalence of and factors associated with fecal incontinence and its precursors among high-risk women at 12 months postpartum. METHODS: A survey of women in the immediate and later postpartum was conducted. Participants were 568 women at higher risk of anal sphincter damage, namely those who had an instrumental delivery and/or delivered a high birth weight infant (4000 g or more) at tertiary teaching hospitals in Australia. Women participated in a baseline hospital-based interview and a 12-month follow-up telephone interview. The main outcome measures were frank fecal incontinence (solid and/or liquid stool) and precursor symptoms (flatal incontinence, soiling, and/or fecal urgency) at 12 months postpartum. RESULTS: Prevalence rates were 2.6% for solid stool incontinence and 4.9% for liquid stool incontinence. Overall, 6.9% women had either one or both of these symptoms of frank fecal incontinence. Prevalence rates were 24.4% for flatal incontinence, 10.9% for soiling, and 14.8% for fecal urgency. Overall, 32.4% women had at least one of these precurser symptoms. Concurrent urinary incontinence and postpartum constipation were significantly associated with both frank fecal incontinence and precursor symptoms. In addition, joint hypermobility and older maternal age were associated with frank fecal incontinence, whereas inability to stop the urine flow and multiparity was associated with precursor symptoms. CONCLUSION: The present findings suggest that older and multiparous women, and women with joint hypermobility are at increased risk of postpartum anal incontinence symptoms after a high-risk delivery. Concurrent urinary incontinence, flow-stopping inability, and constipation are also associated with postpartum anal incontinence symptoms after high-risk deliveries.

Adolescent↗
PubMed2003

The prevention and treatment of radiotherapy - induced xerostomia.

Efforts to reduce the severity of postradiotherapy xerostomia include the use of salivary substitutes to gain symptomatic relief, salivary gland stimulants, agents delivered to protect the glands during radiotherapy (RT), and physical means to partially spare the major salivary glands from RT while adequately irradiating tumor targets. These means include advanced RT treatment planning and salivary tissue transfer to nonirradiated areas. The relative potential gain from each of these strategies is discussed in this article. The combination of partial salivary gland sparing and radiation protectors/stimulants may provide additive or synergistic gains in reducing the severity of xerostomia.

Head and Neck Neoplasms↗
PubMed2003

CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment.

Multiple systems have been developed for grading the adverse effects (AEs) of cancer treatment. The National Cancer Institute Common Toxicity Criteria (CTC) system has substantially evolved since its inception in 1983. The most recent version, CTCAE v3.0 (Common Terminology Criteria for Adverse Events version 3.0) represents the first comprehensive, multimodality grading system for reporting the acute and late effects of cancer treatment. The new CTC requires changes in the application of AE criteria including new guidelines regarding late effects, surgical and pediatric effects, multimodality issues, and for reporting the duration of an effect. It builds on the strengths of previous systems, represents a considerable effort among hundreds of participants, and signifies an international collaboration and consensus of the oncology research community. This article updates recent progress in the evolution of adverse effects grading systems and reviews the development of CTCAE v3.0.

Academies and Institutes↗
PubMed2003

How should we measure and report radiotherapy-induced xerostomia?

Xerostomia is commonly measured and graded using objective measures of major salivary gland output and observer-rated toxicity grading. The separation between the different grades is somewhat ambiguous in the current toxicity grading systems. We propose a new grading system based primarily on the functional deficits associated with xerostomia. Salivary flow rates have been added as a criterion to the grading system, notwithstanding the weak correlation reported in most studies between the symptoms and objective functional measures. In addition to the observer-rated toxicity grading, recording of patient-reported quality of life, using validated instruments, is encouraged.

Head and Neck Neoplasms↗
PubMed2003

Factors associated with non-attendance at a secondary prevention clinic for cardiac patients.

BACKGROUND: A randomised controlled trial was undertaken to test the effectiveness of a secondary prevention clinic. Secondary prevention programs can improve prognosis after an acute cardiac illness. It is therefore important to encourage high participation rates. AIM: The present study was a post-hoc analysis to identify factors associated with patients' non-attendance at the clinic. METHODS: We compared the baseline socio-demographic and clinical characteristics of 83 (73.5% male) non-attending patients and a random sample of 96 (85.4% male) attending patients. Self-reported data were gathered during interviews conducted on an average of 30 months after hospital admission to investigate long-term outcomes of the clinic. RESULTS: Using logistic regression analysis, we found that non-attendance was significantly and independently associated with being female, being under 60 years of age, having no history of high cholesterol and having no angina prior to the event. In bivariate analyses, non-attendance was also associated with being born overseas and not having private health insurance. CONCLUSIONS: Likely non-attending patients should be identified early and more effective strategies should be devised to facilitate their participation in secondary prevention programs.

Adult↗
PubMed2003

The impact of costimulatory molecule gene polymorphisms on clinical outcomes in liver transplantation.

CTLA-4 and CD28 deliver opposing signals for T-cell proliferation. We examined single nucleotide polymorphisms (SNPs) CTLA-4 -318C/T and CD28 IVS3 +17T/C for associations with acute rejection in liver transplant recipients. These and two other polymorphisms in CTLA-4 [microsatellite polymorphism +642(AT)n and SNP +49 A/G] were also analyzed for influence on graft survival. Two hundred and eleven liver transplant recipient genotypes were determined by direct sequencing or restriction fragment length polymorphism analysis of PCR-amplified genomic DNA. Mean graft survival for patients with the GG genotype of CTLA-4 +49 A/G was 58.5 +/- 6.0 months compared with 70.3 +/- 4.0 months and 73.8 +/- 2.8 months for the AA and AG genotypes, respectively (p = 0.0055). This is in support of previous studies suggesting decreased CTLA-4 function and increased incidence of autoimmune disease for this genotype. The 92-, 94-, and 100-bp alleles of CTLA-4 +642(AT)n occurred more often in African-American transplant recipients and were associated with decreased graft survival (p = 0.0001 and 0.007, respectively) but the independence of these variables could not be established. No associations with acute rejection or graft survival were found for CTLA-4 -318C/T or CD28 IVS3 +17T/C. The described associations between CTLA-4 gene polymorphisms and transplant outcomes provide the foundation for further investigations leading to genetic risk stratification for transplant recipients.

Alleles↗
PubMed2003

Genetic variability and transplantation.

PURPOSE OF REVIEW: The purpose of this review is to summarize recent advances within the area of genetic polymorphisms with a specific emphasis on renal transplantation, and to discuss the potential clinical applications. RECENT FINDINGS: Due to recent advances in molecular techniques, there has been an abundance of publications describing genetic variability in molecules relevant to transplant outcome. Many studies are now demonstrating associations between polymorphisms in these candidate genes and outcomes in organ transplantation. SUMMARY: These studies emphasize the potential role of genetic variability in transplantation, and provide the rationale for large prospective studies to clearly define the potential benefits of genotyping in the risk stratification of transplant recipients.

Animals↗
PubMed2003

A novel mechanism for the immunomodulatory functions of class II MHC-derived peptides.

There is now extensive evidence that synthetic peptides corresponding to linear sequences of MHC molecules are effective immunoregulators, targeting the immune response at many different sites. It has been previously shown that peptides derived from a highly conserved region of MHC class II inhibit proliferation to autoantigen and to both the direct and indirect pathways of allorecognition. This study demonstrates that inhibition of lymphocyte proliferation by nonpolymorphic MHC class II peptides, specifically HLA-DQA1, is sequence-specific and that the inhibitory effect is mediated through the induction of apoptosis in antigen-presenting cells via a caspase-independent mechanism. In addition, T lymphocytes stimulated in the presence of HLA-DQA1 are rendered hyporesponsive to subsequent stimuli. Immunomodulation by HLA-DQA1 is effective in vivo because it prevents both the priming and the effector function of primed allogeneic T cells in a murine DTH model. These observations have important implications for the development of a novel therapy for immune-mediated diseases.

Adjuvants, Immunologic↗
PubMed2003

Acceptability of a urinary continence promotion programme to women in postpartum.

OBJECTIVE: To assess the acceptability to postpartum women of a physiotherapist-delivered urinary continence promotion programme. DESIGN: A survey of women participating in a randomised controlled trial where women received the intervention (which involved training in pelvic floor exercises and incorporated adherence-enhancing strategies) or usual postpartum care. SETTING: Postpartum wards of three tertiary teaching hospitals in the Hunter Region, NSW, Australia. SAMPLE: Women were eligible to participate in the trial if they had a forceps/ventouse assisted delivery and/or delivered a higher birthweight baby (> or =4000 g). This study is based primarily on data obtained for 348 women in the intervention group. METHODS: Baseline hospital-based interview; eight-week follow up appointment with physiotherapist; three-month follow up telephone interview. MAIN OUTCOME MEASURES: Comparative dropout rates for intervention and control groups; reasons for non-participation; attendance at hospital follow up; self-reported acceptability of and embarrassment about per vaginum examination; utilisation and perceived usefulness of intervention components; self-reported adherence with recommended pelvic floor exercise regime. RESULTS: There was no significant difference in dropouts between intervention (5.9%) and control groups (6.3%). Only 14% of women gave not wanting the per vaginum assessments as their main reason for not participating in the study. Eighty-eight percent of women participated in the eight-week postpartum follow up visit with the physiotherapist, with two-thirds of these women attending the hospital for this; 72.2% of women reported no embarrassment, and 22.5% just a little embarrassment about per vaginum assessment. The information components of the intervention were well received. At the eight-week follow up visit, 83.9% reported performing pelvic floor exercises at adequate frequency. CONCLUSIONS: The postpartum period provides an ideal opportunity for pelvic floor muscle testing and the delivery of continence promotion advice.

Adolescent↗
PubMed2002

Analysis of gene polymorphisms in the regulatory region of MCP-1, RANTES, and CCR5 in liver transplant recipients.

Chemokines and their receptors play a major role in the inflammatory and immune responses that mediate allograft outcome. The production of some chemokines varies among individuals and these variations may be determined by genetic polymorphisms, most commonly within the regulatory region of the gene. We investigated whether the functional polymorphisms of the chemokines RANTES, MCP-1 and chemokine receptor CCR5 are associated with the incidence of acute rejection and long-term liver graft survival. Two hundred nine liver transplant recipients were genotyped using polymerase chain reaction sequence-specific primers for the following polymorphisms: RANTES-28, MCP-1 -2518, and CCR5-59029. There was no association with any of the three genotypes and the incidence of acute rejection episodes. In addition, no association of RANTES-28, MCP-1 -2518, or CCR5 -59029 variants with long-term liver graft survival was found. In conclusion, variants of RANTES-28, MCP-1 -2518, and CCR5-59029 neither influenced the incidence of acute rejection nor affected long-term allograft survival upon liver transplantation in the context of this analysis.

Adult↗
PubMed2002

The impact of polymorphisms in chemokine and chemokine receptors on outcomes in liver transplantation.

Chemokines and their corresponding receptors likely play a central role in directing mononuclear cells to the graft sites during rejection. Genes for the chemokine stromal derived factor-1 (SDF1) and CC chemokine receptors CCR2 and CCR5 are characterized by polymorphisms which alter their function. We genotyped DNA of 207 liver transplant recipients by PCR or PCR-RFLP for CCR2-641, CCR5delta32, and SDF1-3'A polymorphisms, and examined their association on outcomes in liver allograft recipients. Due to the low number of patients homozygous for CCR2-641 and CCR5delta32, only the effects of their heterozygous variants were addressed in this study. None of the investigated polymorphisms showed a significant shift in gene frequency in acute rejection and rejection-free groups, or for graft survival. The gene frequency of the SDF1-3'A allele was significantly (p = 0.034) higher in patients who died (29.0%, n = 31) compared to recipients still alive (17.1%, n = 172). The mean patient survival time post transplant was 134 months in patients with SDF1 wild-type, significantly (log rank p = 0.014) longer than 98 months in patients with at least one SDF1-3'A allele. The CCR2 and CCR5 polymorphisms were not associated with significant differences in mortality rate. In conclusion, CCR2-641, CCR5delta32, and SDF1-3'A genotypes did not influence the risk for acute rejection or graft survival. However, in liver allograft recipients SDF1-3'A is significantly associated with higher mortality.

Chemokine CXCL12↗
PubMed2002

A Monocyte chemoattractant protein-1 (MCP-1) polymorphism and outcome after renal transplantation.

Among the factors modulating transplant rejection and cardiovascular disease, chemokines and their respective receptors deserve special attention. In this respect, increased expression of MCP-1 and the corresponding receptor CCR2 have been demonstrated in renal transplant rejection and coronary artery disease. The impact of the MCP-1-2518G and CCR2-64I genotypes on renal allograft function was investigated in 232 patients who underwent transplantation over an 11-yr period. Genomic DNA was genotyped using PCR with sequence-specific primers followed by restriction fragment length polymorphism analysis. Eighteen (7.8%) patients were homozygous for the MCP-1-2518G mutation. The G/G allele of MCP-1 -2518 behaved as a determinant for long-term allograft survival and resulted in reduction of the mean graft survival, as compared with the heterozygous (A/G) or wild-type (A/A) allele (67 +/- 14 versus 95 +/- 4 mo; Log rank P = 0.0052). The 64I mutation of CCR2 had no effect on kidney graft failure (93 +/- 6 and 91 +/- 5 mo, respectively; P = 0.81). None of the investigated polymorphisms showed a significant shift in gene frequency in acute rejection and rejection-free groups. In conjunction with these findings, peripheral blood mononuclear cells from kidney transplant recipients carrying the G-allele were characterized by a 2.5-fold higher MCP-1 secretion (P < 0.05). In conclusion, recipients of renal transplants homozygous for the -2518 G mutation of the MCP-1 gene are at risk for premature kidney graft failure. This variant of MCP-1 may be a future predictor for long-term kidney graft failure.

Acute Disease↗
PubMed2001

Indirect allorecognition of donor class I and II major histocompatibility complex peptides promotes the development of transplant vasculopathy.

Recent clinical and experimental evidence suggests that indirect allorecognition may promote the development of chronic rejection, but definitive experimental studies are lacking. To study the contribution of indirect allorecognition to chronic rejection, naïve Lewis (RT1(1)) rats were immunized with synthetic Wistar Furth (WF) class II-RT1(u).D (HLA-DR-like) or -RT1(u).B (HLA-DQ-like) or class I-RT1(u).A (HLA-A-like) peptides emulsified in complete Freund's adjuvant 7 d before transplantation (n = 5 to 7/group). Experimental and control animals then acted as recipients of fully mismatched WF vascularized cardiac allografts. Recipients received immunosuppression in the form of cyclosporine at a tapering dose that allows for long-term allograft survival. Animals were sacrificed at either 3 or 6 mo, with allograft arterial luminal occlusion scored on elastin stains by a blinded observer. At 3 mo, mean vessel scores were significantly higher in the RT1(u).A-immunized versus class II-immunized and control groups (P < 0.05). By 6 mo, there was progression of chronic allograft vasculopathy and a significantly higher mean vessel score in the RT1(u).A- and RT1(u).D-immunized versus RT1(u).B and control groups (P < 0.05). In vitro studies show evidence of shifting MHC allopeptide immunogenicity. It was concluded that T cells primed by specific donor class I and II MHC allopeptides promote the development of chronic vascularized allograft rejection. These novel observations provide definitive evidence of a link between indirect allorecognition and the development and progression of chronic rejection.

Animals↗
PubMedDate not supplied

Long-term behavioral outcomes after attendance at a secondary prevention clinic for cardiac patients.

PURPOSE: Secondary prevention interventions, including hospital clinics, can help patients improve their risk factors and lifestyles after an acute cardiac event. This study aimed to investigate the long-term behavioral outcomes of attending and nonattending patients consecutively enrolled in a trial of a family-based clinic providing screening, advice, and support 3 months after hospital admission. The study also aimed to identify predictors of long-term smoking status, dietary habit, and physical activity. METHODS: Semistructured interviews were conducted an average of 30 months after the acute cardiac event with 83 of the 103 nonattending patients and a random sample of 96 patients who had attended the clinic. Behavioral outcomes were investigated, and self-reported risk factors at the time of the acute illness were documented. RESULTS: The patients who had attended the clinic were significantly more likely than nonattenders to report positive dietary changes and, among former smokers, successful cessation of smoking. Furthermore, they reported being more physically active than nonattenders. Using logistic regression, clinic attendance was identified as a significant and independent predictor of all three outcomes. CONCLUSIONS: The results of this observational study suggest that attendance at a secondary prevention clinic facilitates maintenance of improved long-term health behaviors, although this finding is based on self-report. Factors possibly responsible for favorable outcomes include strong physician advice and support from a multidisciplinary team of health professionals. Furthermore, the timing of the intervention may have been appropriate for enrollment in a secondary prevention clinic.

Adult↗
PubMedDate not supplied

Causal attributions for coronary heart disease among female cardiac patients.

PURPOSE: Beliefs about the etiology of coronary heart disease (CHD) can influence patient outcomes following an acute cardiac event. However, past research has focused predominantly on male patients. The present study investigated causal attributions and their associations with actual risk profiles in female cardiac patients. METHODS: Female cardiac patients consecutively admitted to hospital after an acute myocardial infarction (AMI) or for coronary artery bypass graft surgery (CAGS) were interviewed in hospital at 2, 4, and 12 months postdischarge. RESULTS: Among 260 women (mean age = 68.6, SD = 10.4), there was little correspondence between actual and perceived risk factors. Hypertension was least recognized: only 5% of the 180 women who had hypertension acknowledged it as a cause of their CHD. High cholesterol, obesity, and high-fat diet were also underacknowledged, with only 14%, 15%, and 17% of women with these risk factors implicating them in their CHD. A higher percentage, 44%, of smokers and 40% of women with a positive family history acknowledged these risk factors as a cause of their CHD. Women who had no idea about the cause of their CHD constituted 20%. There was little change in causal attributions over the 12-month study period and little apparent impact of cardiac rehabilitation (CR) program attendance on causal beliefs. CONCLUSIONS: Women were more likely to attribute their CHD to smoking or positive family history than to other major modifiable risk factors. The lack of correspondence between actual and perceived risk factors and the lack of impact of CR attendance on causal attributions highlight the need for personalized advice and support regarding risk factor modification.

Acute Disease↗
PubMedDate not supplied

Peptide-mediated immunosuppression.

There is now a substantial body of data demonstrating the abilities of synthetic peptides and peptide analogues to inhibit the auto- and alloimmune response in vitro and in vivo. We have studied the immunomodulatory role of synthetic peptides derived from highly conserved regions of the class II MHC alpha chain. These MHC-derived peptides inhibit the rat, human, and mouse mixed lymphocyte response (MLR), proliferation to autoantigen, cytokine production, and cytolytic T lymphocyte (CTL) generation. Our studies demonstrated that the inhibitory effect of the MHC class II nonpolymorphic peptides is mediated through the induction of apoptosis in APCs via a nonclassic caspase-independent pathway. In addition, T lymphocytes initially stimulated in the presence of HLA-DQA1 are rendered hyporesponsive to subsequent stimuli. Immunomodulation by HLA-DQA1 was effective in vivo because it prevented both the priming and the effector function of primed allogeneic T cells in a murine DTH model. Our data demonstrate that peptides derived from highly conserved regions of the class II MHC alpha chain can alter T-lymphocyte immune responses both in vitro and in vivo. These results have important implications for the development of a novel therapy for immune mediated diseases.

Animals↗
PubMedDate not supplied

Kidney transplantation in HIV-infected patients.

Human immunodeficiency virus (HIV) infection has traditionally been considered an absolute contraindication to solid organ transplantation. With improvements in survival and increases in the prevalence of end-stage liver and kidney disease in HIV-positive patients treated with highly active antiretroviral therapy, many transplant centers have begun to reconsider the role of transplantation in patients with well-controlled HIV infection. This article reviews the literature on transplantation in HIV-infected patients, with a focus on kidney transplantation in the era of highly active antiretroviral therapy.

Antiretroviral Therapy, Highly Active↗