Biomedical subjects

Andrew Lloyd

Publications and source records attributed to Andrew Lloyd.

12 recordsLinked to original sources

PubMed2005

Does genotype mask the relationship between psychological factors and immune function?

This paper examined the interaction between genetic influences of the polymorphic human leukocyte antigens (DRB1 and DQB1) and psychological distress on the development of cellular immunity to the novel antigen, keyhole limpet hemocyanin (KLH). Participants (n = 227) were immunized with KLH and the development of cutaneous delayed-type hypersensitivity (DTH) against KLH was examined 3 weeks later. Distress was assessed using the Profile of Mood States. DNA was typed for the serologically defined DRB1 and DQB1 antigens. There was a significant correlation between distress at immunization and the development of DTH skin test responses to KLH (n = 214, r = .24, p = .003). HLA DQ2 was weakly associated with a decreased likelihood of developing a cutaneous delayed-type hypersensitivity response against KLH (odds ratio [OR] = 1.6; confidence interval [CI] 0.9-2.7). HLA DQ5 was weakly associated with an increased likelihood of responding to the antigen (OR=0.6; CI=0.3-1.0). The correlation between distress and immune function in HLA DQ2 negative individuals was .34 (n = 136, p = .00) and in HLA DQ2 positive individuals it was .06 (n = 74, p =. 64). For HLA DQ5 negative individuals the correlation was .26 (n = 140, p = .00) and for HLA DQ5 positive individuals it was .22 (n = 70, p = .07). These results suggest that the distress/immune relationship in genetically susceptible or protected individuals may be underestimated in psychoneuroimmunology research.

Adjuvants, Immunologic↗

PubMed2005

The health-related quality of life and economic burden of constipation.

Constipation is a prevalent condition that disproportionately affects women and older adults and leads to self-medication and/or medical consultation. It occurs as a result of functional idiopathic causes or secondarily as a result of a variety of factors including dietary and exercise patterns, adverse effects of medication and disease processes. Constipation is often perceived to be a benign, easily treated condition with short-term treatment being relatively straightforward; however, chronic constipation is associated with mild complications that, left untreated, can develop into more serious bowel complaints (faecal impaction, incontinence and bowel perforations) with further implications for healthcare costs and the patient's health-related quality of life (HR-QOL). This review summarises the evidence of the HR-QOL impact and economic burden of constipation on patients. Relatively few studies have systematically explored the HR-QOL and economic impact of constipation; however, the existing evidence suggests that HR-QOL is lower in patients with constipation than in non-constipated individuals, and treatments for constipation improve HR-QOL. Additionally, constipation represents an economic burden for the patient and healthcare provider. Resource utilisation associated with the diagnosis and management of constipation is a significant cost driver, whereas constipation prevention programmes have demonstrated cost savings.

Cathartics↗

PubMed2005

Bipolar disorder and health-related quality of life : review of burden of disease and clinical trials.

Bipolar disorder is a chronic psychiatric disorder with a variable course and significant impact on patients' social, occupational, and general functioning and wellbeing. Although there are effective pharmaceutical and psychosocial interventions for patients with bipolar disorder, many patients receive poor-quality care. Prospective longitudinal studies demonstrate that less than half of bipolar disorder patients have a good long-term response to treatment, long-term outcome is highly variable, and many patients do not fully recover. There is substantial evidence that bipolar disorder is associated with significant impairment to functioning and wellbeing.However, few clinical trials comparing treatments for bipolar disorder have incorporated health-related quality-of-life (HR-QOL) assessments. Existing studies suggest that, while treatment improves HR-QOL, there is limited evidence for differences between the mood stabilisers in terms of HR-QOL outcomes. Additional clinical trials are needed to evaluate patient-reported outcomes associated with the most frequently used pharmacological treatments to determine whether there are meaningful differences between treatments. There are challenges in measuring HR-QOL in patients with acute mania, and future studies should assess the psychometric qualities of HR-QOL instruments in these and other bipolar disorder patients. HR-QOL outcome data may be useful in informing psychiatrists, patients and patient family members of the effects of treatment for bipolar disorder on patients' everyday lives, functioning and wellbeing.

Antimanic Agents↗

PubMed2004

The relationship between distress and the development of a primary immune response to a novel antigen.

Forty-five medical students were recruited to examine the effects of distress on the development of an immune response to the novel antigen, keyhole limpet hemocyanin (KLH). The subjects' level of distress was manipulated by immunizing them either at the time of an important viva voce examination (n=22) or during examination-free term time (n=23). This manipulation increased variance amongst the subjects, but the emphasis in this research was on individual distress as a predictor of immune function. In the group as a whole, the likelihood of developing DTH skin responses to KLH was reduced in the more distressed subjects (r=-.45; p=.002), independently of a number of behavioral (e.g., sleep disturbance) and demographic (e.g., sex) variables. Proliferation of T cells against KLH in vitro and the development of anti-KLH IgG antibodies were not related to levels of distress. Thus, cellular, rather than humoral, immune responses in vivo appear susceptible to the influence of distress. This immunization model provides the opportunity to further dissect the basis of these stress-immune pathways.

Adult↗

PubMed2004

Radiographic hand joint space width assessed by computer is a sensitive measure of change in early rheumatoid arthritis.

OBJECTIVE: To compare changes in the computerized measurement of radiographic hand joint space width (JSW) to changes in modified Sharp scores in a retrospective 2-year study of early rheumatoid arthritis (RA). METHODS: First and last standard clinical hand radiographs of 245 patients with RA were analyzed blind using purpose-written computer software to measure changes in JSW for proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints in the 3 middle fingers of each hand. Before measurement, the radiographs were scored independently by 2 radiologists using a modification of Sharp scoring. RESULTS: The paired changes in JSW (-0.051 +/- 0.005 mm) and Sharp score (+3.81 +/- 0.50) were both significant over the study duration. In measured joints showing an increase in joint space narrowing (JSN) score, 92% had a corresponding reduction in JSW. In patients with an increase in total score, including JSN and erosion scores in fingers and wrists, 84% had a corresponding reduction in mean (PIP + MCP) JSW. Patients with no change in Sharp score (47%) still experienced a significant reduction in measured JSW (-0.027 +/- 0.006 mm). HLA-DR genetic markers of severe disease progression were associated with significantly greater reductions in JSW but not increases in Sharp score. ( VALUES: mean +/- standard error of mean). CONCLUSION: Measured JSW averaged over 6 PIP and 6 MCP joints was a valid and more sensitive measure of change than total Sharp score in this study of early RA.

Adolescent↗

PubMed2003

Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution.

BACKGROUND: Chronic fatigue syndrome (CFS) is defined by symptoms and disability, has no confirmatory physical signs or characteristic laboratory abnormalities, and the etiology and pathophysiology remain unknown. Difficulties with accurate case ascertainment contribute to this ignorance. METHODS: Experienced investigators from around the world who are involved in CFS research met for a series of three day workshops in 2000, 2001 and 2002 intended to identify the problems in application of the current CFS case definition. The investigators were divided into focus groups and each group was charged with a topic. The investigators in each focus group relied on their own clinical and scientific knowledge, brainstorming within each group and with all investigators when focus group summaries were presented. Relevant literature was selected and reviewed independent of the workshops. The relevant literature was circulated via list-serves and resolved as being relevant by group consensus. Focus group reports were analyzed and compiled into the recommendations presented here. RESULTS: Ambiguities in the current CFS research definition that contribute to inconsistent case identification were identified. Recommendations for use of the definition, standardization of classification instruments and study design issues are presented that are intended to improve the precision of case ascertainment. The International CFS Study Group also identified ambiguities associated with exclusionary and comorbid conditions and reviewed the standardized, internationally applicable instruments used to measure symptoms, fatigue intensity and associated disability. CONCLUSION: This paper provides an approach to guide systematic, and hopefully reproducible, application of the current case definition, so that case ascertainment would be more uniform across sites. Ultimately, an operational CFS case definition will need to be based on empirical studies designed to delineate the possibly distinct biological pathways that result in chronic fatigue.

Cognition↗

PubMed2003

Therapeutic immunisation with COPV early genes by epithelial DNA delivery.

Following challenge with COPV (canine oral papillomavirus), DNA plasmids encoding COPV L1, E1 or E2 protein were delivered into oral mucosal and cutaneous sites in beagles using particle-mediated immunotherapeutic delivery (PMID). Two weeks post-challenge, a priming dose of 8 microg DNA was delivered followed by a booster dose after a further two weeks. A group of control dogs were vaccinated using plasmid DNA encoding Hepatitis B virus surface (HBVs) gene. All of the control animals developed warts at the vast majority of sites (94%). All of the animals given wild type L1, E1, or E2 developed warts at most sites (88%, 75%, and 88%, respectively). The animals given codon optimised E2 however, were protected from wart growth with only one tiny lesion seen on a single animal that persisted for only a few days. The E1 codon optimised group was also significantly protected with a far lower number of smaller warts (48%) that persisted for a shorter duration. These data suggest that therapeutic immunisation by PMID with papillomavirus early genes is effective and emphasizes the importance of antigen load in the generation of protective responses to papillomavirus proteins.

Animals↗

PubMed2003

Measurement of EBV-IgG anti-VCA avidity aids the early and reliable diagnosis of primary EBV infection.

Current serological methods for the diagnosis of Epstein-Barr virus (EBV) infection still differentiate poorly between primary infection and reactivation. This is particularly true when IgG and IgM antibodies are present simultaneously and only a single serum sample is provided for analysis. The demonstration of the IgG avidity state has the potential to distinguish recent from past or reactivated infection. An analysis of the kinetics of avidity maturation of anti-VCA antibodies in primary EBV infection was undertaken with longitudinally collected sets of sera from 28 well-characterised EBV cases and in sera from 35 cases with previous EBV infection and recent primary infection due to HIV, CMV, or hepatitis A. Antibodies directed against the viral capsid antigen (VCA) and Epstein-Barr nuclear antigen (EBNA-1) were sought, using a commercial enzyme immunoassay (EIA). In parallel with standard IgG anti-VCA detection, serum was incubated with 8 M urea to disrupt low-avidity complexes to allow calculation of the percentage avidity. In cases with primary EBV infection, the mean avidity rose from 54% at 6 weeks to 82% by 28 weeks after the onset of symptoms, but remained lower than that of the control sera (96%). The addition of the avidity measurement improved the sensitivity of IgG and IgM anti-VCA testing in diagnosis of primary EBV infection from 93% to 100%. The specificity of IgM anti-VCA testing alone was poor, with 14 of 35 cases (49%) demonstrating false-positive results, but it improved to 97% by the demonstration of high-avidity IgG anti-VCA. The combination of negative IgG anti-EBNA and low-avidity IgG anti-VCA had a sensitivity and specificity of 100%. The routine addition of IgG anti-VCA avidity estimation to diagnostic EBV serology is recommended.

Adolescent↗

PubMed2003

Multicentric Castleman's disease treated with antivirals and immunosuppressants.

A patient negative for human immunodeficiency virus (HIV) developed multicentric Castleman's disease (MCD) and Kaposi's sarcoma (KS) associated with active human herpesvirus 8 (HHV-8) infection. He was treated with sequential antiviral therapy, chemotherapy, and corticosteroids. HHV-8 levels were monitored throughout the course of the patient's illness, and were found to rise on relapse. No consistent change in HHV-8 levels was found with antiviral therapy. We demonstrate that in this patient antiviral therapy was clinically ineffective, and did not alter HHV-8 levels, but that corticosteroid and combination chemotherapy led to clinical improvement. Despite the implication of HHV-8 as a cause of MCD, few studies have correlated HHV-8 levels with clinical response.

Aged↗

PubMed2002

Intraepithelial DNA immunisation with a plasmid encoding a codon optimised COPV E1 gene sequence, but not the wild-type gene sequence completely protects against mucosal challenge with infectious COPV in beagles.

DNA plasmids encoding the open reading frames of canine oral papillomavirus (COPV) nonstructural early genes E1, E2, or E7 protein were delivered into both oral mucosal and cutaneous epithelial sites in beagle dogs using particle-mediated immunotherapeutic delivery (PMID) technology. Control dogs were vaccinated with plasmid encoding either hepatitis B virus surface antigen (HBVs) or COPV L1. Using a prophylactic immunisation protocol, a priming dose of plasmid DNA was followed by a booster dose 6 weeks later. Four weeks after boost, all dogs were challenged with infectious COPV particles. Following viral challenge, as shown previously (M. A. Stanley et al., 2001, Vaccine 19, 2783-2792), mucosal papillomas developed in the negative-control HBVs vaccinated dogs, but all animals in the COPV L1 group were fully protected from disease development. In the early gene-vaccinated groups five of six in the E1-vaccinated dogs, two of six in E2-vaccinated dogs, and three of six in the E7-vaccinated beagles developed oral papillomas. Compared to the HBVs negative-control group the oral papillomas that did develop in the early-gene vaccinated beagles were significantly smaller, shorter in duration, and fewer in number. Taken together the disease burden was markedly reduced and this was statistically significant. In a second experiment one group of animals was vaccinated with plasmid encoding the wild-type COPV E1 gene, and a separate group was vaccinated with plasmid encoding a synthetic codon-optimised COPV E1 gene sequence. None of the codon-optimised E1-vaccinated animals developed papillomas at any challenge site. However, all animals vaccinated with wild-type E1 had papillomas. These data suggest that immunisation by PMID with papillomavirus early genes can significantly impact upon subsequent disease development and that full protection can be achieved using improved vectors encoding codon-optimised gene sequences perhaps emphasizing the importance of antigen load in the generation of protective responses to papillomavirus proteins.

Animals↗

PubMed2002

Decision making heuristics and the elicitation of preferences: being fast and frugal about the future.

It has been suggested that individuals employ simple decision heuristics when answering stated preference questions. Evidence from discrete choice experiments of individuals failing to trade may indicate that they employ simple decision making heuristics. However, individuals might not trade because their preferences are not captured by the range of trade-offs they are offered. This is explored by offering a series of choices where the trade-offs implied by subsequent choices depend on the subject's responses to previous choices. The results suggest that individuals answer discrete choices without recourse to simplifying heuristics, and that information is generated on their preferences rather than on how they make such choices.

Consumer Behavior↗

PubMedDate not supplied

The osteo-odonto-keratoprosthesis (OOKP).

The osteo-odonto-keratoprosthesis (OOKP), although described over 40 years ago, remains the keratoprosthesis of choice for end-stage corneal blindness not amenable to penetrating keratoplasty. It is particularly resilient to a hostile environment such as the dry keratinized eye resulting from severe Stevens-Johnson syndrome, ocular cicatricial pemphigoid, trachoma, and chemical injury. Its rigid optical cylinder gives excellent image resolution and quality. The desirable properties of the theoretical ideal keratoprosthesis is described. The indications, contraindications, and patient assessment (eye, tooth, buccal mucosa, psychology) for OOKP surgery are described. The surgical and anaesthetic techniques are described. Follow-up is life-long in order to detect and treat complications, which include oral, oculoplastic, glaucoma, vitreo-retinal complications and extrusion of the device. Resorption of the osteo-odonto-lamina is responsible for extrusion, and this is more pronounced in tooth allografts. Regular imaging with spiral-CT or electron beam tomography can help detect bone and dentine loss. The optical cylinder design is discussed. Preliminary work towards the development of a synthetic OOKP analogue is described. Finally, we describe how to set up an OOKP national referral center.

Alveolar Process↗