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Biomedical subjects

I Williams

Publications and source records attributed to I Williams.

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

Colonic epithelial hPepT1 expression occurs in inflammatory bowel disease: transport of bacterial peptides influences expression of MHC class 1 molecules.

BACKGROUND & AIMS: hPepT1 is an intestinal epithelial apical membrane transporter responsible for uptake of di/tripeptides (including bacterial derived proinflammatory n-formyl peptides). hPepT1 expression normally has a strict axial gradient-highest in the proximal small intestine with no expression in the colon. METHODS: Small intestinal-like cells (Caco2-BBE), and colonic-like cells (HT29-Cl.19A), and colonic mucosa from diseased and control patients were used in the present study. RESULTS: hPepT1 expression occurs aberrantly in the colon with chronic ulcerative colitis (6 patients) and Crohn's disease (4 patients), but not in normal colon (4 patients) or colon with microscopic colitis (4 patients). To model expression of hPepT1 by colonic-like cells in inflamed states, we stably transfected HT29-Cl.19A cells with a modified hPepT1 tagged on the N-terminus with green fluorescence protein. Analysis of transfected cells revealed that: GFP-hPepT1 protein, like the natural protein, is targeted to the apical plasma membrane. In addition, the tagged protein retains the capability of di/tripeptide absorption, and the expression of the tagged protein by HT29-Cl.19A cells permits absorption of N-formyl-methionyl-leucyl-phenylalanine (fMLP), as occurs in hPepT1 expressing Caco2-BBE cells. fMLP uptake by colonic cells expressing GFP-hPepT1 specifically enhances major histocompatibility complex class I surface expression. CONCLUSIONS: These data collectively indicate that, in some states of chronic inflammation, hPepT1 may be anomolously expressed in the colon. Further, transport of fMLP by hPepT1 potentially stimulates expression of key accessory immune molecule, MHC-1.

Amino Acid Sequence↗
PubMed2001

Decision aids: are they worth it? A systematic review.

OBJECTIVES: The field of consumer decision support interventions has grown rapidly in the last 20 years, particularly since the increased formalization of evidence-based decision-making in health care. However, little is known as yet about the effect these decision aids have on relevant outcomes. To identify outcomes influenced by consumer decision aids (CDAs) and the particular effects of CDAs on those outcomes. METHOD: Published reports of randomized controlled trials and other designs in English identified from searches of Medline, Cancerlit, CINAHL, PsycINFO, Social Science Abstracts, the Cochrane Library and Current Contents, and from ancestry searches, hand searches and consultation with key informants. Studies were included if consumers were the decision-makers, decisions were real and not hypothetical, the intervention met a strict definition of a CDA and decisions involved treatment or screening. Data on setting, subjects, decision types, decision aid features and outcomes were extracted. The validity of each study included was evaluated by two team members. Summative ratings were calculated and categorized as high, medium and low. RESULTS: Over 500 titles were initially assessed; 96 study reports were obtained and screened for inclusion. Twenty-two reports representing 20 studies met the inclusion criteria. Eight studies with a low rating were excluded. Results were synthesized from the remaining 12 studies. Published studies of CDAs are increasing although still few in number. Outcomes such as knowledge and decision-making processes are influenced by CDAs but effects on treatment preferences, the actual decision or other outcomes have yet to be clearly established. CONCLUSIONS: Improved outcomes result from the use of CDA in some categories of outcome but insufficient evidence exists yet to support improved outcomes in all categories or to evaluate whether, given the considerable costs of many CDAs, funding for extensive ongoing development and testing can be sustained.

Canada↗
PubMed2000

The multiperson use of non-syringe injection equipment and risk of hepatitis c infection in a cohort of young adult injection drug users, chicago 1997-1999.

PURPOSE: The possibility that hepatitis C virus (HCV) is transmitted via the multiperson use of injection paraphernalia other than syringes has been suggested, but epidemiologic studies to examine the association are difficult to design due to saturation levels of infection in most samples of injection drug users (IDUs). This study (1) assembled a sample of young adult IDUs, among whom hepatitis C infection prevalence was still moderate, (2) measured incident HCV infection, and (3) determined the risk for seroconversion associated with specific forms of sharing injection paraphernalia.METHODS: Between 1997 and 1999, 702 IDUs, 18-30 years old, were interviewed and screened for antibodies to HCV at baseline and at 6 and 12 months post-baseline. Participants were recruited through street outreach, advertising and chain-referral from ethnically diverse neighborhoods in metropolitan Chicago. Data were analyzed using standard survival statistical methods.RESULTS: HCV prevalence was 27% at enrollment. During 296.5 person-years of observation, we observed 37 HCV seroconversions (incidence: 12.5/100 person-years). The adjusted relative hazard (RH) of seroconversion, after controlling for demographic and drug use covariates, was highest for sharing cookers (RH, 3.58; 95% CI 1.47-8.70), followed by sharing rinse water (RH, 2.16; 95% CI 1.03-4.52), and cottons (RH, 1.84; 95% CI 0.95-3.56). Risk associated with syringe sharing was marginally significant, and backloading was unassociated with hepatitis C seroconversion. Adjusting for syringe sharing, the independent effects of sharing cookers and cottons remained significant, and a final model that included each sharing practice demonstrated that sharing cookers had at the strongest association with seroconversion (RH, 3.03; 95% CI 1.05-8.72).CONCLUSIONS: This study suggests that sharing non-syringe paraphernalia may be an important cause of hepatitis C virus transmission between IDUs.

Journal Article↗
PubMed2000

Protein phosphatase 1beta is required for the maintenance of muscle attachments.

Type 1 serine/threonine protein phosphatases (PP1) are important regulators of many cellular and developmental processes, including glycogen metabolism, muscle contraction, and the cell cycle [1] [2] [3] [4] [5]. Drosophila and humans both have multiple genes encoding PP1 isoforms [3] [6] [7]; each has one beta and several alpha isoform genes (alpha(1), alpha(2), alpha(3) in flies, alpha and gamma in humans; mammalian PP1beta is also known as PP1delta). The alpha/beta subtype differences are highly conserved between flies and mammals [6]. Though all these proteins are >85% identical to each other and have indistinguishable activities in vitro, we show here that the Drosophila beta isoform has a distinct biological role. We show that PP1beta9C corresponds to flapwing (flw), previously identified mutants of which are viable but flightless because of defects in indirect flight muscles (IFMs) [8]. We have isolated a new, semi-lethal flw allele that shows a range of defects, especially in muscles, which break away from their attachment sites and degenerate.

Alleles↗
PubMed2000

What help do GPs want from specialist services in managing patients with dementia?

The views of GPs about psychiatric services for dementia were obtained by questionnaire survey. Provision of adequate long term care, together with support for both family carers and healthcare workers were strongly stated needs. Other needs were rapid access to care, clear diagnosis, special needs of young patients with Alzheimer's disease, joint guidelines, and an increased role for CPNs. GPs valued the role of voluntary organisations and help given to them by Consultant Psycho-geriatricians.

Adult↗
PubMed2000

Sequence heterogeneity of TT virus and closely related viruses.

TT virus (TTV) is a recently discovered infectious agent originally obtained from transfusion-related hepatitis. However, the causative link between the TTV infection and liver disease remains uncertain. Recent studies demonstrated that genome sequences of different TTV strains are significantly divergent. To assess genetic heterogeneity of the TTV genome in more detail, a sequence analysis of PCR fragments (271 bp) amplified from open reading frame 1 (ORF1) was performed. PCR fragments were amplified from 5 to 40% of serum specimens obtained from patients with different forms of hepatitis who reside in different countries (e.g., China, Egypt, Vietnam, and the United States) and from normal human specimens obtained from U.S. residents. A total of 170 PCR fragments were sequenced and compared to sequences derived from the corresponding TTV genome region deposited in GenBank. Genotypes 2 and 3 were found to be significantly more genetically related than any other TTV genotype. Moreover, three sequences were shown to be almost equally related to both genotypes 2 and 3. These observations suggest a merger of genotypes 2 and 3 into one genotype, 2/3. Additionally, five new groups of TTV sequences were identified. One group represents a new genotype, whereas the other four groups were shown to be more evolutionary distant from all known TTV sequences. The evolutionary distances between these four groups were also shown to be greater than between TTV genotypes. The phylogenetic analysis suggested that these four new genetic groups represent closely related yet different viral species. Thus, TTV exists as a "swarm" of at least five closely related but different viruses. These observations suggest a high degree of genetic complexity within the TTV population. The finding of the additional TTV-related species should be taken into consideration when the association between TTV infections and human diseases of unknown etiology is studied.

Base Sequence↗
PubMed2000

HIV associated culture proved tuberculosis has increased in north central London from 1990 to 1996.

OBJECTIVES: To examine rates of culture proved tuberculosis in HIV infected patients in three specialist centres in north central London. METHODS: Cases of tuberculosis in patients with previously documented HIV infection from 1990 to 1996 were identified retrospectively from microbiological/clinical records at Chelsea and Westminster, St Mary's, and University College London Hospitals. RESULTS: Between 1990 and 1996 202 cases of culture proved tuberculosis were identified at the three centres. Of these, 132/202 (65.3%) occurred in homosexual/bisexual men, 41/202 (20.3%) were in patients with heterosexual contact in sub-Saharan Africa, and 29/202 (14.4%) were in "others." Overall 148/202 (73.3%) had pulmonary tuberculosis. The total number of HIV infected individuals seen at the three centres increased from 4298 in 1990 to 5048 in 1996. Rates of tuberculosis in the three centres increased from 0.46% in 1990 to 0.83% in 1996. Part of this increase was due to an increase in tuberculosis among Africans from 1993 to 1996. CONCLUSIONS: Rates of HIV associated tuberculosis increased in these three centres in north central London between 1990 and 1996. In part this was due to an increase in the number of African patients with HIV infection attending the three centres. In addition, there was circumstantial evidence of recent transmission among homosexual men with HIV infection. Prospective "real time" surveillance of tuberculosis in HIV infected patients is needed in order to detect case clustering and to improve tuberculosis control.

Africa↗
PubMed2000

Assessing effectiveness of treatment of depression in primary care. Partially randomised preference trial.

BACKGROUND: There is a mismatch between the wish of a patient with depression to have counselling and the prescription of antidepressants by the doctor. AIMS: To determine whether counselling is as effective as antidepressants for depression in primary care and whether allowing patients to choose their treatment affects their response. METHOD: A partially randomised preference trial, with patients randomised to either antidepressants or counselling or given their choice of either treatment. The treatment and follow-up were identical in the randomised and patient preference arms. RESULTS: There were 103 randomised and 220 preference patients in the trial. We found: no differences in the baseline characteristics of the randomised and preference groups; that the two treatments were equally effective at 8 weeks, both for the randomised group and when the randomised and patient preference groups for a particular treatment were combined; and that expressing a preference for either treatment conferred no additional benefit on outcome. CONCLUSIONS: These data challenge several assumptions about the most appropriate treatment for depression in a primary care setting.

Adolescent↗
PubMed2000

Relationship between factor VIII mutation type and inhibitor development in a cohort of previously untreated patients treated with recombinant factor VIII (Recombinate). Recombinate PUP Study Group.

A cohort of 79 previously untreated patients (PUPs) with moderate-severe haemophilia A (baseline Factor VIII < or =2%) were enrolled in a study to evaluate the safety, efficacy and immunogenicity of recombinant factor VIII (r-FVIII, Recombinate). Blood samples were obtained retrospectively from a total 55 PUPs who were investigated for the spectrum of FVIII gene mutations responsible for their haemophilia. FVIII gene inversion mutations were found in 27 (49%) patients. Two patients had partial gene deletions. The remaining 26 patients were then screened for mutations in the FVIII gene coding region using conformation sensitive gel electrophoresis. Point mutations were identified in 22 (85%) of the patients and 14 of these mutations were novel. Study subjects were monitored for the development of FVIII inhibitors throughout the study. A total of 23 of the 73 evaluable subjects (including one subject with a low inhibitor titer at baseline) demonstrated an inhibitor on one or more occasions; 11 (15%) were persistent. Inhibitors were detected in patients with partial gene deletions and inversions and in three of eight patients with missense mutations. No inhibitors were found in 11 patients with small insertions or deletions resulting in an alteration of the protein translation reading frame (frameshift mutations). The results corroborate the observation that mutation type is an important determinant of the propensity to develop inhibitory anti-FVIII antibody.

Antibody Formation↗
PubMed1999

Epidemiology of hepatitis C in the United States.

Although hepatitis C virus (HCV) infection is the most common chronic blood-bome infection in the United States, the annual incidence of new infections has decreased by more than 80% since 1989 to approximately 36,000 new infections by 1996. The Third National Health and Nutrition Examination Survey (NHANES III) revealed that an estimated 3.9 million US citizens (1.8%) have been infected with HCV. Of these, approximately 2.7 million persons are chronically infected with HCV. Population-based studies indicate that 40% of chronic liver disease is HCV related. Chronic hepatitis C results in an estimated 8,000 to 10,000 deaths each year. Because the prevalence of HCV infection is approximately threefold higher among persons now between 30 and 49 years of age, the number of deaths resulting from HCV-related liver disease could increase substantially during the next 10 to 20 years, as this cohort reaches the ages at which complications from chronic liver disease typically occur. Most people who develop chronic infection may not even be aware that they have been infected, because acute disease is commonly benign. However, infected persons can transmit the disease to others and are at risk for developing chronic liver disease. HCV is transmitted primarily through direct percutaneous exposures to blood. In the United States, blood transfusion accounted for a substantial proportion of HCV infections before 1990, when routine testing began, but now accounts for only a small percentage. Injection drug use is currently the major risk factor for acute HCV infection. Prevention and control of HCV infection in the United States must focus not only on reduction of transmission in groups at high risk of infection (e.g., injection drug users) but also on the early identification of persons with chronic infection.

Acute Disease↗
PubMed1999

Decreased morbidity and use of hospital services in English HIV-infected individuals with increased uptake of anti-retroviral therapy 1996-1997. National Prospective Monitoring System Steering Group.

OBJECTIVE: To investigate the relationship between changing morbidity patterns, the use of hospital services by HIV-infected patients and the uptake of antiretroviral therapy (ART) in England. DESIGN: Prospective serial cross-sectional analyses based on data collected through the National Prospective Monitoring System (NPMS), a multi-centre prospective monitoring system. SETTING: HIV-infected patients seen in 10 clinics, five London and five non-London, during the three semesters, 1 January 1996 to 30 June 1997. MAIN OUTCOME MEASURES: The mean use of hospital services per patient-year, mean new HIV-related opportunistic illnesses per 1000 patient-years and percentage uptake of ART. RESULTS: The use of inpatient services changed particularly among AIDS patients. The mean number of inpatient days for AIDS patients decreased from 19.7 [95% confidence interval (CI) 13.7-25.7] in 1996 to 11.2 (95% CI 6.1-15.6) per patient-year in 1997. Concurrently the number of new AIDS-defining events decreased significantly from 567 (95% CI 529-607) to 203 (95% CI 183-225) per 1000 patient-years. The overall uptake of ART increased significantly from 33% (95% CI 31-35%) to 50% (95% CI 48-52%), and a switch from mono or dual to triple therapy or quadruple or more therapy was observed. However, by mid-1997 only 29% (95% CI 26-32%) of asymptomatic patients and 51% (95% CI 49-54%) of patients with symptomatic non-AIDS were on ART, compared with 69% (95% CI 66-71%) of AIDS patients. CONCLUSION: The observed reduction in new AIDS-defining events has led to a reduction in the need for inpatient hospital care and has been associated with an increased uptake of ART, including a switch to triple therapy. All of these factors are likely to have contributed to the observed reduction in mortality among English AIDS patients. As the overall uptake of ART remained relatively low in English centres further improvements can be anticipated. However, the medium to long-term effects of these treatment regimens will need to be closely monitored.

Anti-HIV Agents↗
PubMed1999

Patient satisfaction with HIV service provision in NPMS hospitals: the development of a standard satisfaction questionnaire. NPMS Steering Group.

A self-completion satisfaction questionnaire evaluating the standard of care of HIV outpatient services was developed as part of the National Prospective Monitoring System on the Use, Cost and Outcome of HIV Service Provision in English Hospitals (NPMS). The questionnaire was designed in conjunction with service users and health care professionals, and piloted in three London and three non-London HIV clinics. In addition to testing alternative methods of administering the questionnaire, the pilot provided satisfaction scores on a variety of aspects of service provision for participating clinics. The questionnaire was completed by 548 respondents and was most effectively collected using a sealed box in the clinic waiting area. Mean satisfaction scores for the attitude and skills of staff members was 4.7 (95% CI 4.6-4.7) but satisfaction scores were significantly lower for the clinic environment with a mean of 4.1 (95% CI 4.1-4.2). Satisfaction scores did not differ significantly by gender, age, sexual orientation, ethnic group, employment status or severity of symptoms. London respondents were more satisfied with the clinic environment and seeing preferred members of staff than their non-London counterparts, however there were no other differences between clinics. The questionnaire functioned well in practice and provided meaningful and useful information for individual clinics as well as at aggregate level.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Action research: a useful method of promoting change in primary care?

BACKGROUND: Action research has been used successfully to promote change in disciplines other than medicine, but there are few examples of its use in primary care. OBJECTIVE: We aimed to discuss the benefits and difficulties of using action research in primary care using the example of child health surveillance provision in general practice. METHODS: Twenty-eight general practices were randomly allocated into two groups. Action research was used to promote change in 14 practices by facilitating practice meetings and by providing written feedback. The other 14 practices received written feedback alone. The two groups of practices were compared using the following: (i) semi-structured interviews with one health visitor and GP from each practice; (ii) observation of baby clinics; (iii) questionnaires to parents; and (iv) return rates of child health surveillance reviews from the personal child health record. RESULTS: All 14 practices in the action research arm of the study met as individual practice teams and decided to make changes to their provision of child health surveillance. Ten practices audited their child health surveillance as a result. More health visitors in the action research practices than in the comparison practices reported changes to child health surveillance, audit, communication and use of the personal child health record. The majority of health visitors and GPs thought involvement in the action research process was beneficial. However, we were unable to show a statistically significant difference between the two groups of practices in baby clinic provision, parent satisfaction or the return rate of child health surveillance reviews. CONCLUSION: Our study suggests that action research is a successful method of promoting change in primary care. However, measuring the impact of change is difficult.

Adult↗
PubMed1998

Growth stimulation of beetle larvae reared on a transgenic oilseed rape expressing a cysteine proteinase inhibitor.

The resistance of a transgenic line of oilseed rape expressing constitutively the cysteine proteinase inhibitor oryzacystatin I (OCI) was assessed against Psylliodes chrysocephala L. (Coleoptera: Chrysomelidae). The levels of OCI expression in the transformed line averaged 0.2% and 0.05% of total soluble protein in leaves and petioles respectively. In vitro analyses showed that P. chrysocephala larvae use both cysteine and serine proteinases for protein digestion, and that all the cysteine proteolytic activity is OCI-sensitive. However, bioassays showed that adults fed identically on leaf discs from control or transformed plants. When larvae were reared on transgenic plants expressing OCI, they showed an increase in weight gain compared to those reared on control plants. Furthermore, those larvae from transgenic plants exhibited a 2-fold increase in both cysteine and serine proteolytic activity as a reponse to the presence of OCI. The plasticity of insect digestive physiology and feeding behaviour are discussed, as well as the relevance of engineering a genotype expressing both types of proteinase inhibitors.

Journal Article↗
PubMed1998

Evidence of CNS impairment in HIV infection: clinical, neuropsychological, EEG, and MRI/MRS study.

OBJECTIVES: To identify by clinical examination, EEG, MRI, and proton spectroscopy, and neuropsychological assessment the prevalence of signs of CNS involvement in patients infected with HIV, and to relate such findings to the evidence of immunosuppression. METHODS: The design was a cross sectional analysis of a cohort of male patients with infected HIV with an AIDS defining diagnosis or low CD4 count (<350), and seropositive asymptomatic subjects, both groups being followed up in a longitudinal study. Control groups consisted of seronegative subjects from the same genitourinary medicine clinics. RESULTS: This report sets out the cross sectional findings at the seventh visit in the longitudinal study. Patients with AIDS had more signs of neurological dysfunction, poorer performance on a neuropsychological test battery, were more likely to have an abnormal EEG, and to have abnormalities on MRI. They more often had cerebral atrophy, abnormal appearing white matter, and abnormal relaxometry and spectroscopy. There was little evidence of abnormality in seropositive people who had a CD4 count >350 compared with seronegative people from a similar background. CONCLUSIONS: Detailed testing failed to disclose significant CNS impairment without immunosuppression in men infected with HIV. Findings from MRI and magnetic resonance spectroscopy (MRS) correlated with those of the neurological examination and neuropsychological assessment. A combination of such assessments offers a simple surrogate for studies of CNS involvement in HIV disease.

AIDS Dementia Complex↗
PubMed1998

The use and cost of HIV service provision in England in 1996. National Prospective Monitoring System (NPMS) Steering Group and NPMS Working Party on Costs.

OBJECTIVE: The aim of the study was to measure the use and estimate the cost of HIV service provision in England. DESIGN AND SETTING: Standardised activity and case-severity data were collected prospectively in 10 English HIV clinics (5 London and 5 non-London sites) for the periods 1 January 1996 to 30 June 1996 and 1 July 1996 to 31 December 1996 and linked to unit cost data. In total, 5440 patients with HIV infection attended during the first 6 months and 5708 during the second 6 months in 1996. MAIN OUTCOME MEASURES AND RESULTS: The mean number of inpatient days per patient-year for patients with AIDS was 19.7 [95% confidence interval (CI): 13.7 to 25.7] for January to June and 20.8 (95% CI: 15.3 to 26.4) for July to December 1996. The mean number of outpatient visits for asymptomatic patients with HIV infection was 14.8 (95% CI: 11.9 to 17.6) and 13.3 (95% CI: 10.8 to 15.7) for the respective periods and 16.1 (95% CI: 13.21 to 18.97) and 15.7 (95% CI: 11.2 to 20.2), respectively, for patients with symptomatic non-AIDS (i.e. symptomatic patients with HIV infection but without AIDS-defining conditions). Substantial centre-to-centre variation was observed, suggesting that many clinics can continue the shift from an inpatient- to an outpatient-based service. Cost estimates per patient-year for HIV service provision for 1996 varied from 4695 Pounds (95% CI: 3769 Pounds to 5648 Pounds) for asymptomatic patients, to 7605 Pounds (95% CI: 6273 Pounds to 8909 Pounds) for symptomatic non-AIDS patients to 20,358 Pounds (95% CI: 17,681 Pounds to 23,206 Pounds) for patients with AIDS. CONCLUSIONS: Different combinations of antiretroviral therapy affect the cost estimates of HIV service provision differently. Anticipated reduction in inpatient-related activity through the increased use of combination antiretroviral therapy will further shift service provision from an inpatient- to outpatient-based service and reduce costs per patient-year. The extent and duration of such effects are currently unknown. The long term effects of combination treatment on the morbidity and mortality patterns of individuals infected with HIV are also currently unknown, as are their implications on the use and cost of HIV service provision. Multicentre databases like the National Prospective Monitoring System (NPMS) will provide healthcare professionals with information to improve existing services and anticipate the impact of new developments.

Acquired Immunodeficiency Syndrome↗