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Patricia Price

Publications and source records attributed to Patricia Price.

At least 55 records · Page 3Linked to original sources
PubMed2003

Interferon-gamma response by peripheral blood mononuclear cells to hepatitis C virus core antigen is reduced in patients with liver fibrosis.

Liver fibrosis was correlated with immunological parameters. Peripheral blood mononuclear cells (PBMCs) from patients with low fibrosis scores had more [corrected] interferon (IFN)-gamma-producing cells than did patients with higher fibrosis scores, when stimulated with hepatitis C virus (HCV) core antigen. Irrespective of liver fibrosis score, cells from all cytomegalovirus (CMV)-seropositive patients had similar IFN-gamma responses, when stimulated by CMV antigen, so patients with fibrosis did not have a broad-spectrum immunodeficiency. IFN-gamma response by PBMCs to HCV core antigen may provide a useful marker of the severity of liver disease in patients with hepatitis C.

Adult↗
PubMed2003

Does the occurrence of certain rare cancers indicate an inherited cancer susceptibility?

We sought to determine whether rare cancers indicate an increased risk of inherited cancer susceptibility. We ascertained 77 individuals with rare cancers which occur with increased relative risk in carriers of germline BRCA1/BRCA2 (fallopian, young-onset pancreatic) or HNPCC (biliary, small intestinal, urothelial, gallbladder, young-onset pancreatic) mutations. Individuals with two primary neoplasms (7), or with a first- or two second-degree relatives with breast/ovarian cancer were tested for BRCA1/BRCA2 mutations (18); those with two primary HNPCC cancers or one first degree relative with an HNPCC-related cancer were tested for mutations in MLH1/MSH2 (19). Of these 77 individuals with cancer (19 fallopian, 8 gallbladder, 17 biliary, 17 pancreatic, 11 urothelial, 5 small intestinal), 39 (50.6%) had at least one first degree relative with cancer (excluding lung and skin); two conformed to Bethesda HNPCC criteria. No definitely pathogenic germline MLH1 and MSH2 mutations were found in 19 individuals, although 2 MSH2 variants were detected. A family history of breast/ovarian, HNPCC or colon cancer in a first degree relative was found in 40% of fallopian, 20% of biliary, 35% of pancreatic, 27% of urothelial and 20% of small bowel cancer patients. A BRCA1 frameshift mutation was detected in a woman with fallopian (54 y) and breast (39 y) cancers, and a BRCA2 nonsense mutation in a woman with biliary (48 y) and breast (45 y) cancers. This study supports the premise that the occurrence of rare (especially double primary) cancers does indicate an increased cancer susceptibility, although the numbers of cases ascertained were too small to draw firm conclusions.

Adult↗
PubMed2003

Alleles of the proximal promoter of BAT1, a putative anti-inflammatory gene adjacent to the TNF cluster, reduce transcription on a disease-associated MHC haplotype.

BACKGROUND: BAT1 belongs to the DEAD-box family of proteins, and is encoded in the central region of the MHC, a region containing genes affecting immunopathological disorders including Type 1 diabetes. We showed that BAT1 can reduce inflammatory cytokine production, supporting its candidacy as a disease gene. Here we examined the proximal promoter region of BAT1. RESULTS: Ten single nucleotide polymorphisms were identified in approximately 1.4 kb of sequence, defining at least seven alleles. Sections of the BAT1 promoter region were amplified from cells homozygous for the MHC haplotypes associated with susceptibility (HLA-A1, B8, DR3; 8.1 haplotype) and resistance (HLA-A3, B7, DR15; 7.1 haplotype) to diabetes and cloned into a promoter-less luciferase-encoding plasmid. Jurkat cells transiently transfected with fragments from the 8.1 haplotype exhibited a lower luciferase activity than those transfected with fragments from the 7.1 haplotype, indicating reduced transcription. The effect was clearest with the 520 bp immediately upstream of the transcriptional start site. Electrophoretic mobility shift assays using oligonucleotides spanning polymorphic sites within the 520 bp (proximal) promoter fragment showed haplotype-specific binding of nuclear proteins. CONCLUSIONS: In view of the anti-inflammatory role of BAT1, reduced production on a disease-associated haplotype constitutes a novel and self-consistent model for the effect of central MHC genes on disease.

Alleles↗
PubMed2003

Knowledge of epilepsy and familiarity with this disorder in the U.S. population: results from the 2002 HealthStyles Survey.

PURPOSE: To assess perceptions of knowledge and experience with epilepsy and seizures in the U.S. population to develop communication campaigns to improve the public's understanding of epilepsy. In a national survey, focal points included the public's knowledge of the disorder, whether people know someone who has it, exposure to epilepsy-related information, and knowledge about how to respond to a person having a seizure. METHODS: The Epilepsy Program of the Centers for Disease Control and Prevention included nine items on an annual mail survey that targeted a representative sample of the U.S. population. Data were weighted to be representative of the U.S. population. chi2 analyses were performed, and standardized residuals were used to examine the associations between responses and demographic variables. RESULTS: Responses were obtained from 4,397 persons. Despite the low prevalence of epilepsy, results indicate that about half of all persons have witnessed an epileptic seizure either in person or on television; about one third of all persons know someone with epilepsy, but relatively few are familiar with epilepsy, how to respond to a seizure, or with the Epilepsy Foundation. CONCLUSIONS: In general, the public has relatively little knowledge about epilepsy. Educational campaigns that inform the public about this disorder and about seizures should work through community settings to improve the general public's understanding of epilepsy.

Adolescent↗
PubMed2002

Immune activation in patients infected with HIV type 1 and maintaining suppression of viral replication by highly active antiretroviral therapy.

Immune activation associated with HIV infection declines after highly active antiretroviral therapy (HAART), but may persist or recur in some patients. It is not clear whether this reflects a resurgence of HIV replication or another cause of immune activation, such as inflammatory reactions to opportunistic pathogens (immune restoration disease [IRD]). Here, we studied plasma and cellular immune activation markers in adult HIV-1 patients who had received HAART for >12 months and maintained plasma HIV RNA levels of <400 copies/ml for >6 months. Plasma interleukin 1 receptor antagonist and tumor necrosis factor receptor I levels were similar in patients and HIV-negative control subjects, but the highest levels occurred mainly in patients with a history of IRD. In contrast, expression of HLA-DR and CD38 on monocytes and of HLA-DR on CD8(+) T cells was higher in patients than in control subjects. Thus, cellular markers of immune activation are abnormal in some patients with a good virological response to HAART, and abnormalities of plasma immune activation markers correlate with a history of IRD.

ADP-ribosyl Cyclase↗
PubMed2002

Association of increased hepatitis C virus (HCV)-specific IgG and soluble CD26 dipeptidyl peptidase IV enzyme activity with hepatotoxicity after highly active antiretroviral therapy in human immunodeficiency virus-HCV-coinfected patients.

Hepatotoxicity was investigated, using plasma collected before and during treatment, in 16 human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients who responded to highly active antiretroviral therapy (HAART), during a retrospective longitudinal study. Eleven patients experienced hepatotoxicity (i.e., a >3-fold increase in alanine aminotransferase level) while receiving HAART, including 4 patients with clinical hepatitis. Control subjects were 5 patients without hepatotoxicity. Markers of HCV-specific immune responses (HCV core-specific immunoglobulin G [IgG] antibody), T cell activation (soluble [s] CD26 dipeptidyl peptidase IV [DPP IV] enzyme activity), and inflammation (nitrate/nitrite and soluble tumor necrosis factor receptor I [sTNFRI] levels) were correlated with liver damage and immune reconstitution. All patients with hepatotoxicity had increased HCV core-specific IgG antibody and sCD26 (DPP IV) activity but did not have increased nitrate/nitrite or sTNFRI levels. Hepatotoxicity without clinical hepatitis was associated with increased CD8 T cell counts. Thus, hepatotoxicity in HIV-HCV-coinfected patients who respond to HAART is associated with increased HCV-specific immune responses and T cell activation.

Adult↗
PubMed2002

Polymorphisms in cytokine genes define subpopulations of HIV-1 patients who experienced immune restoration diseases.

OBJECTIVE: To further elucidate the immunopathogenesis of immune restoration diseases (IRD) in HIV patients responding to antiretroviral therapy and determine whether IRD associated with different opportunistic pathogens involve distinct immunopathological mechanisms. DESIGN: DNA samples from patients with a range of IRD were typed for polymorphic loci in genes encoding immune-mediators. METHODS: PCR-restriction fragment length polymorphism assays were used to type loci in the and genes. Alleles of a microsatellite in the CD30 promoter were determined by capillary electrophoresis. RESULTS: Only 8% of patients with IRD associated with a herpesvirus infection carried IL12B-3'UTR*2, compared with 42-54% of patients with other or no IRD. Patients with IRD arising from mycobacterial infection rarely carried IL6-174*C (36% versus 61-71%) and never carried TNFA-308*2 (0% versus 23-52%). TNFA-308*2 was carried by 52% of patients who experienced IRD associated with a herpesvirus infection, as several patients with exacerbations of cytomegalovirus retinitis carried this as part of a HLA-A2,B44 haplotype. Polymorphisms in and showed no distinct patterns. CONCLUSIONS: Distinct cytokine-mediated mechanisms contribute to IRD initiated by herpesvirus and mycobacterial infections.

AIDS-Related Opportunistic Infections↗
PubMed2002

Cytomegalovirus (CMV) retinitis immune restoration disease occurs during highly active antiretroviral therapy-induced restoration of CMV-specific immune responses within a predominant Th2 cytokine environment.

Plasma levels of cytomegalovirus (CMV)-specific immunoglobulin G (IgG), soluble (s) CD30, sCD26 (dipeptidyl peptidase IV [DPP IV]) enzyme activity, and tumor necrosis factor receptor-I (TNFR-I) were assessed in human immunodeficiency virus (HIV)-infected patients who experienced CMV retinitis (CMVR) as an immune restoration disease (IRD) during their first 6 months of highly active antiretroviral therapy (HAART) and in CMV-seropositive, HIV-infected patients with similar baseline CD4(+) T cell counts who had uneventful immune reconstitution. Patients who experienced CMVR IRD had a significant increase in CMV-specific IgG during their first 12 months of HAART, indicating restored CMV-specific immune responses. They also had significantly higher levels of sCD30 both before HAART and for up to 12 months after start of treatment. sCD30 levels remained elevated during 48 months of HAART, suggesting persistence of a predominant Th2 cytokine environment. Levels of sCD26 (DPP IV) enzyme activity and TNFR-I did not differ significantly between the 2 groups at any time point.

Adult↗
PubMed2002

Central MHC genes affect IgA levels in the human: reciprocal effects in IgA deficiency and IgA nephropathy.

This study investigates the hypothesis that alternative alleles of one or more genes in the central major histocompatibility complex (MHC) predispose carriers to IgA deficiency (IgAD) or IgA Nephropathy (IgAN). Australian caucasian IgAD, IgAN patients, and controls were typed at HLA loci, single nucleotide polymorphisms, and microsatellites in the MHC. Alleles of the D6S273 microsatellite exhibited strong associations with IgAD and IgAN. D6S273*129 and *139 were more frequent in IgAD and less frequent in IgAN patients than controls. The reverse was true for D6S273*133 and *131. Alleles of other microsatellites exhibited weak associations with IgAD or IgAN. D6S273*129 is found on the 65.1 ancestral haplotype [HLA-B14(65),DR1], which has been reported to be increased in IgAD, but the majority of IgAD patients with D6S273*129 did not have other alleles of the haplotype. D6S273*139 is characteristic of the 8.1 ancestral haplotype (HLA-A1,B8,DR3), which was common in IgAD and rare in IgAN patients. Further studies of the 8.1 haplotype in Australian, German and Spanish caucasian subjects revealed that HLA-DR3, in the absence of -B8, is not associated with IgAD. However -B8 is associated with IgAD in the absence of -DR3, consistent with a susceptibility locus in the central MHC. Provisional mapping within this region is discussed.

Australia↗
PubMed2002

Do interleukin-1 polymorphisms predict the development of periodontitis or the success of dental implants?

Factors which increase the risk of severe adult periodontitis (AP) may also contribute to the success of dental implants. To determine which cytokines may be relevant, levels of interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) mRNA were quantitated in gingival tissue from periodontitis patients and healthy controls. Periodontitis significantly increased levels of IL-1alpha, IL-1beta, IL-6 and IFN-gamma mRNA relative to healthy tissues. IL-1 was selected for further study, as it has inflammatory and bone resorbing properties. We examined IL-1A(-889) and IL-1B(+3953) alleles in Caucasian patients with AP and early-onset periodontitis (EOP), patients with dental implants and healthy individuals. The IL-1B(+3953) polymorphism was associated with AP. This was evident from an increased homozygosity for allele 2 in patients with AP and a decreased heterozygosity in advanced AP patients. IL-1A(-889) and a composite genotype [IL-1A(-889)2 plus IL-1B(+3953)2] showed no association with the incidence of periodontitis, disease onset or disease severity. IL-1A(-889), IL-1B(+3953) and the composite genotype also showed no association with failure of dental implants.

Adult↗
PubMed2002

Immunological markers predicting outcome in patients with hepatitis C treated with interferon-alpha and ribavirin.

Type 1 (T1) cytokine responses are required for the clearance of hepatitis C virus by cytotoxic T lymphocytes, but can promote liver damage. Interferon-alpha (IFN alpha) can be expected to promote T1 cytokine responses, so treatment outcome may depend on the T1/T2 cytokine environment and levels of immune activation at baseline. This model was tested by monitoring immunological markers in a pilot study of treatment naïve patients given IFN alpha 2b and ribavirin, with the aim of finding markers that predict virological outcome. Soluble (s) CD26/dipeptidyl peptidase IV enzyme activity and levels of sCD30, bioavailable IL-6, sTNF-RI, IL-1ra and nitrite/nitrate (NO(2)(-)/NO(3)(-)) were measured. Levels of IL-1ra and bioavailable IL-6 were lower in patients than controls and did not change with therapy. Treatment decreased sCD26/dipeptidyl peptidase IV enzyme activities and sCD30 levels and increased NO(2)(-)/NO(3)(-) levels. High baseline sCD30 levels predicted an early (P = 0.008) and sustained (P = 0.03) virological response to therapy, suggesting treatment may be more effective in patients with a predominant T2 profile.

Adult↗
PubMed2002

Food handlers' beliefs and self-reported practices.

Despite an increase in the number of food handlers receiving food hygiene training, a high proportion of food poisoning outbreaks still occur as a result of poor food handling practices. This paper uses elements of social cognitive theory to examine the beliefs of food handlers towards food safety and to determine food handlers' self-reported practices. Questionnaires were completed by 137 food handlers from 52 small to medium-sized food businesses in Wales. Generally, food handlers were aware of the food safety actions they should be carrying out but identified a number of barriers which would prevent them from implementing these practices. These barriers included lack of time, lack of staff and a lack of resources. Despite 95% of respondents receiving food hygiene training, 63% admitted to sometimes not carrying out food safety behaviours. All the food handlers also perceived their business to be of relatively low risk and yet all businesses prepared high risk foods. This research highlights the need for training to be based around a risk-based approach and demonstrates that behavioural change will not occur merely as a result of training. Food safety practices will only be implemented given adequate resources and an appropriate management culture.

Attitude to Health↗
PubMed2002

Immune restoration disease in HIV patients: aberrant immune responses after antiretroviral therapy.

Suppression of HIV replication by antiretroviral therapy has various effects on the immune system of HIV-infected patients. Whereas protective pathogen-specific immune responses are restored in some patients, others have persistent immunodeficiency or produce immunopathological responses against opportunistic pathogens that cause immune restoration disease (IRD). Significant morbidity and even mortality may result from IRDs associated with infections by mycobacteria, herpesviruses, hepatitis viruses or the JC virus. Preliminary evidence from our studies suggests that immune responses in patients with IRD may be dysregulated and affected by immunogenetic factors. Thus, herpesvirus IRDs were associated with increased plasma levels of bioavailable interleukin-6 and soluble CD30, while mycobacterial and herpesvirus IRDs were associated with a major histocompatibility complex gene haplotype and/or alleles of particular cytokine genes. A greater understanding of pathogenic mechanisms and the immunogenetics of IRDs may lead to improved preventive and management strategies.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Wound healing and treatments for people with diabetic foot ulcers.

The factors that delay wound healing are multiple and relate both to diabetes and to the effect of its complications. Diabetic foot ulcers readily become chronic, and chronic ulcers have biological properties that differ substantially from acute ones. Much of the available information on the biology of wound healing relates to acute and experimental wounds and may not be directly relevant. It follows that there is limited evidence currently available to underpin protocols for the management of diabetic foot ulcers, or to guide choice of applications and dressings 1. Nevertheless, it is possible to define certain principles.GLYCAEMIC CONTROL: The first relates to glycaemic control. While chronic complications of diabetes such as peripheral vascular disease and neuropathy may be largely irreversible, aspects of structure and function of connective tissue and cells may be impaired by hyperglycaemia, and their function should be improved if normoglycaemia is achieved. PROMOTION OF HEALING: The second principle concerns attempts at active promotion of wound healing by (1) surgical revascularization, and (2) specific attempts to correct defined biological abnormalities thought to be hindering the healing process. These include the use of a variety of applications, dressings and technologies, which may stimulate healing by applying, or stimulating the release of, growth factors and cytokines. While this approach holds the greatest promise for the future, it will be dependent on defining defects which need correction in specific individuals, and having technologies available to address them. This field is in its infancy. WOUND CARE: The third broad principle concerns the management of the wound and its surrounding tissue in order to promote healing. This includes regular inspection, cleansing and removal of surface debris, elimination of pathogenic bacteria and creation of an appropriate environment to facilitate endogenous tissue regeneration. There are many applications and dressings that may be chosen to promote healing, but, whichever is selected, wound management has to be integrated into an effective programme of multidisciplinary care.

Debridement↗
PubMedDate not supplied

Effect of sharp debridement using curette on recalcitrant nonhealing venous leg ulcers: a concurrently controlled, prospective cohort study.

The objective of this study was to evaluate the effect of sharp debridement on the progression of recalcitrant chronic venous leg ulcers (CVLU) and to assess the feasibility of performing this procedure in an outpatient setting. We performed a prospective study of 55 CVLU (53 patients) over a 12-month period. The study group, which underwent debridement, contained 28 CVLU whose wound beds had slough, nonviable tissue, and no granulation tissue. The control group was 27 CVLU with minimal (15-20%) granulation tissue, but no slough or nonviable tissue. Treatments were otherwise similar. Age, body mass index, mean ulcer surface area (MSA) and mean ulcer duration were comparable in both groups. Ulcer measurements were taken at 4 weeks before debridement, at the time of debridement, and 4 and 20 weeks post-debridement. There was no change in the MSA from 4 weeks before to the time of debridement in either group. At 4 weeks post-debridement, the study ulcers showed a 6 cm(2) reduction in the MSA vs. a 1 cm(2) reduction in controls (P = 0.02). By week 20 post-debridement, the study ulcers achieved a 7.4 cm(2) reduction in the MSA vs. an increase of 1.3 cm(2) in controls (P = 0.008). Between weeks 8 and 20 post-debridement, 16% of study ulcers vs. 4.3% of control ulcers achieved complete healing. Infection rates and antimicrobial usage were similar. We conclude that sharp debridement is effective in stimulating healing of recalcitrant CVLU. It is safe, well tolerated, and can be performed in an outpatient setting.

Aged↗
PubMedDate not supplied

Plantar pressure in off-loading devices used in diabetic ulcer treatment.

Four off-loading devices used for the treatment of diabetic forefoot ulcers were compared: a custom-molded insole shoe, a cast MABAL shoe, a prefabricated pneumatic walking brace, and a bivalved total contact cast (BTCC). It was anticipated that all devices would significantly reduce forefoot plantar pressure compared with a control shoe. Sixteen healthy volunteers participated. Plantar pressures were evaluated using the Pedar system, while walking speed was determined using an optoelectric timer. Peak pressure (PP) of ten plantar areas and pressure-time integral for the first metatarsal area were analyzed statistically using a repeated measures analysis of variance. Forefoot pressures were significantly reduced compared with the control shoe for all devices (p<0.001). PP was most reduced (by 65.8%) for the BTCC, and pressure-time integral was most reduced for the BTCC and cast MABAL shoe. Small but significant differences between devices in walking speed (p<0.05) could not explain the substantial PP differences between the different devices. Although all off-loading devices resulted in a significant reduction of forefoot plantar pressure, devices differed significantly in the magnitude of pressure reduction. Further research will have to reveal the level of off-loading sufficient for effective treatment of diabetic ulcers.

Adult↗