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Biomedical subjects

R Pitman

Publications and source records attributed to R Pitman.

12 recordsLinked to original sources
PubMed2006

Tuberculosis screening in migrants in selected European countries shows wide disparities.

Well-established tuberculosis screening units in Western Europe were selectively sampled. Three screening units in Norway, two in the UK, one in the Netherlands and one in Switzerland were evaluated. The aim of this study was to describe a range of service models used at a number of individual tuberculosis units for the screening of new entrants into Europe. Semi-structured interviews were conducted with clinicians, nurses and administrators from a selected sample of European tuberculosis screening units. An outline of key themes to be addressed was forwarded to units ahead of scheduled interviews. Themes included the history of the unit, structure, processes and outputs involved in screening new entrants for tuberculosis. Considerable variation in screening services exists in the approaches studied. Units are sited in transit camps or as units within hospital facilities. Staff capacity and administration varies from one clinic per week with few dedicated staff to fully dedicated units. Only one site recorded symptoms; tuberculin testing was universal in children, but varied in adults; chest radiograph screening was universal except at one site where a positive tuberculin skin test or symptoms were required in those <35 yrs of age before ordering a radiograph. Few output data are routinely and systematically collected, which hinders comparison and determination of effectiveness and efficiency. Service models for screening new immigrants for tuberculosis appear to vary in Western Europe. The systematic collection of data would make international comparisons between units easier and help draw conclusions that might usefully inform service development.

Adult↗
PubMed2004

Screening programmes for tuberculosis in new entrants across Europe.

Screening foreign-born groups with high rates of tuberculosis may help to ensure that they can benefit from early treatment and minimise onward transmission. In January 2003, we surveyed new entrant screening programmes in Europe. Of the 26 countries from whom a response was received, 13 (50%) conducted no specific tuberculosis screening. Of 13 countries with programmes, none conducted pre-entry screening, three conducted screening at ports of entry, and nine screened in other centres. All 13 principally screened refugees. All programmes used chest X-rays as a screening tool, but no two countries took the same specific clinical approach.

Europe↗
PubMed2002

Molecular epidemiology of tuberculosis in London 1995-7 showing low rate of active transmission.

BACKGROUND: Tuberculosis notification rates for London have risen dramatically in recent years. Molecular typing of Mycobacterium tuberculosis has contributed to our understanding of the epidemiology of tuberculosis throughout the world. This study aimed to assess the degree of recent transmission of M tuberculosis in London and subpopulations of the community with high rates of recent transmission. METHODS: M tuberculosis isolates from all persons from Greater London diagnosed with culture positive tuberculosis between 1 July 1995 and 31 December 1997 were genetically fingerprinted using IS6110 restriction fragment length polymorphism (RFLP) typing. A structured proforma was used during record review of cases of culture confirmed tuberculosis. Cluster analysis was performed and risk factors for clustering were examined in a univariate analysis followed by a logistic regression analysis with membership of a cluster as the outcome variable. RESULTS: RFLP patterns were obtained for 2042 isolates with more than four copies of IS6110; 463 (22.7%) belonged to 169 molecular clusters, which ranged in size from two (65% of clusters) to 12 persons. The estimated rate of recent transmission was 14.4%. Young age (0-19 years) (odds ratio (OR) 2.65, 95% confidence interval (CI) 1.59 to 4.44), birth in the UK (OR 1.55, 95% CI 1.04 to 2.03), black Caribbean ethnic group (OR 2.19, 95% CI 1.15 to 4.16), alcohol dependence (OR 2.33, 95% CI 1.46 to 3.72), and streptomycin resistance (OR 1.82, 95% CI 1.15 to 2.88) were independently associated with an increased risk of clustering. CONCLUSIONS: Tuberculosis in London is largely caused by reactivation or importation of infection by recent immigrants. Newly acquired infection is also common among people with recognised risk factors. Preventative interventions and early diagnosis of immigrants from areas with a high incidence of tuberculosis, together with thorough contact tracing and monitoring of treatment outcome among all cases of tuberculosis (especially in groups at higher risk of recent infection), remains most important.

Adolescent↗
PubMed2002

Tuberculosis transmission and the impact of intervention on the incidence of infection.

SETTING: England and Wales. OBJECTIVE: To quantify the relative contribution of vaccination, chemotherapy and preventive therapy to the reduction in tuberculosis incidence in England and Wales between 1953 and 1990. DESIGN: A compartmental model of tuberculosis transmission was fitted to notification data between 1913 and 1939 to estimate pre-vaccination parameters. Best-fit estimates of the rates of chemotherapy and preventive therapy were derived by fitting the model to notification data between 1953 and 1990. Published vaccination rates were used. MAIN OUTCOME MEASURE: Number of cases of pulmonary tuberculosis averted. RESULTS: The numbers of respiratory tuberculosis cases averted between 1953 and 1990 by the use of preventive therapy, vaccination and chemotherapy were 288318, 57085 and 206996, respectively. CONCLUSIONS: Of those interventions considered, preventive therapy has the greatest impact on transmission. The duration of infectiousness is long, with an onset that is likely to pre-date sputum positivity.

Antibiotic Prophylaxis↗
PubMed2001

The multiple roles of major histocompatibility complex class-I-like molecules in mucosal immune function.

The human major histocompatibility complex (MHC) on chromosome 6 encodes three classical class-I genes: human leukocyte antigens (HLA) A, B, and C. These polymorphic genes encode a 43- to 45-kDa cell surface glycoprotein that, in association with the 12-kDa beta2-microglobulin molecule, functions in the presentation of nine amino acid peptides to the T-cell receptor of CD8-bearing T lymphocytes and killer inhibitory receptors on natural killer cells. In addition to these ubiquitously expressed, polymorphic proteins, the human genome also encodes several nonclassical MHC class-I-like, or class Ib, genes that, in general, encode nonpolymorphic molecules involved in various specific immunological functions. Many of these genes, including CD1, the neonatal Fc receptor for IgG, HLA-G, HLA-E, the MHC class-I chain-related gene A, and Hfe, are prominently displayed on epithelial cells, suggesting an important role in epithelial cell biology.

CD8 Antigens↗
PubMed2001

A study of the variation in tuberculosis incidence and possible influential variables in Manchester, Liverpool, Birmingham and Cardiff in 1991-1995.

SETTING AND OBJECTIVE: The reversal of the decline in United Kingdom tuberculosis rates has sparked a resurgence of interest in the epidemiology and prevention of tuberculosis in the UK. In this paper we quantify the primary factors explaining the variability in the electoral ward level relative risk of tuberculosis in Manchester, Liverpool, Birmingham and Cardiff. DESIGN: Ecological analysis of the incidence of tuberculosis in 397 wards using hospital admissions data as a proxy for tuberculosis incidence. Admissions were evaluated from the financial years 1991/1992 to 1994/1995. Ward level covariates included measures of country of birth, ethnicity and various socio-economic measures. RESULTS: Separate analyses were carried out for pulmonary and non-pulmonary tuberculosis. For pulmonary tuberculosis the final model included measures of the ward population born in India and Pakistan, overcrowded housing and not-owner-occupied housing. For non-pulmonary tuberculosis the covariates were ward population born in India and Pakistan, overcrowded housing and the proportion of households with no car. CONCLUSIONS: The country of birth of the ward population is the single most influential explanatory factor in the variability of the ward rates for both pulmonary and non-pulmonary tuberculosis in these four cities. Measures of poverty are of secondary importance.

Adolescent↗
PubMed2000

Human CD1d associates with prolyl-4-hydroxylase during its biosynthesis.

Recent studies have shown that the CD1 family of proteins present various glycolipid antigens to subsets of T cells. CD1d is expressed on human intestinal epithelial cells (IEC) and exists in two biochemical forms: 37-kDa, beta2-microglobulin (beta2m) independent, nonglycosylated, and 47-kDa, beta2m dependent, glycosylated forms. The biosynthetic pathways and the mechanisms of generation of these two biochemically distinct forms of CD1d in human IEC are unknown. Using a human colonic cell line, T84, transfected with CD1d, the biosynthesis of CD1d was investigated. Pulse-chase metabolic labeling studies of T84 transfected with wild type CD1d demonstrated that CD1d was a stable protein over a 4-day chase period. During the first 24 h of the chase, a novel 65-kDa glycoprotein was co-immunoprecipitated with CD1d. Microsequencing of this protein identified the glycoprotein as the alpha and beta subunits of the resident endoplasmic reticulum protein, prolyl-4-hydroxylase (P4H), an enzyme responsible for hydroxyl modification of proline residues. To study if either one or both biochemical forms of CD1d contained hydroxyproline residues, amino acid composition analysis of the 37 and 48 kDa was performed, and demonstrated that only the 37-kDa, but not the 48-kDa form of CD1d, contained hydroxyproline residues. These studies demonstrate that CD1d exhibits a prolonged association with P4H and that the 37-kDa form contains hydroxyproline residues. This suggests that P4H association with CD1d during its biosynthesis results in a novel post-translational modification of CD1d.

Antigens, CD1↗
PubMed1999

Molecular investigations implicate human endogenous retroviruses as mediators of anti-retroviral antibodies in autoimmune rheumatic disease.

Polymerase chain reaction using specific primers, failed to detect HTLV-I amplicons in patients with rheumatic diseases previously shown to possess antibodies to retroviral products. However, by employing broad spectrum oligonucleotide primers, 135 bp amplicons were generated from peripheral blood mononuclear cells and synovial fluid cells. Subsequent cloning and DNA sequencing revealed homology to a number of exogenous and human endogenous retroviruses (HERVs). Furthermore, in combining the presence of type B and C related endogenous retroviruses, a significant association (p=0.014) was apparent for chronic autoimmune rheumatic diseases as compared to controls. Reverse transcription polymerase chain reaction of RNA derived from patients, healthy controls and cell lines (U937, BJAB, human endothelial lung fibroblasts) demonstrated ubiquitous expression of HERV-K10 and RTVL-H2. Furthermore messenger RNA expression of HERV-K10 was enhanced in fibroblasts infected with human cytomegalovirus. It is plausible that subsequent production of HERV peptides could explain the presence of anti-retroviral antibodies in cohorts of patients with autoimmune rheumatic diseases.

Antibodies, Viral↗
PubMed1995

A comparative study of higher primate foamy viruses, including a new virus from a gorilla.

Few foamy (spuma) retroviruses have been investigated in molecular detail, despite their previous isolation from several mamalian species, including ten neutralization serotypes from various primates. Here, we have studied a new gorilla foamy virus (SFV-Gg) and investigated its functional and phylogenetic relationship to the human (HFV) and other primate foamy viruses, including that recently described in orangutans (SFV-11). Nucleotide sequencing of PCR products obtained from the R/U5 region of the LTR, gag, and pol genes revealed a close relationship between HFV and three chimpanzee isolates (SFV-6, SFV-7, and SFV-cpz). The SFV-Gg, SFV-11, rhesus macaque (SFV-1), and African green monkey (SFV-3) isolates were more divergent. To explore functional relationships, primate foamy virus transactivation of HFV LTR driven beta-galactosidase expression in a newly constructed cell line, BHLL, was investigated. HFV, SFV-6, and SFV-7 potently transactivated HFV LTR driven lacZ gene expression, SFV-Gg induced expression approximately 10-fold less efficiently, and SFV types 1, 2, 3, and 11 did not significantly transactivate the HFV LTR. It was, thus, possible to assay serum neutralizing activity in SFV-infected primates against HFV, SFV-6, and SFV-7 by reduction of beta-galactosidase activity following infection of the indicator cell line. Sera from infected chimpanzees and gorillas neutralized, to varying degrees, each of these three viruses, whereas orangutan sera did not. Our results, based on DNA sequences and functional assays, support the conclusion that HFV is closely related to foamy viruses of chimpanzee origin.

Animals↗
PubMed1994

Molecular epidemiology of HIV-1 in the former Soviet Union: analysis of env V3 sequences and their correlation with epidemiologic data.

OBJECTIVE: To investigate the HIV-1 V3 sequence diversity in the former Soviet Union in 30 subjects infected with HIV-1 via different modes of transmission. PATIENTS: A cohort of children infected after exposure to nonsterile needles during the epidemic in 1988-1989 in southern Russia (Elista, n = 12 and Rostov-on-Don, n = 10), and eight HIV-seropositive subjects from Belarus (Minsk), infected via sexual (n = 7) and parenteral (n = 1) infection. METHODS: The HIV-1 V3 encoding region was amplified by nested polymerase chain reaction on DNA of primary peripheral blood mononuclear cells collected from the study subjects and then cloned and sequenced. RESULTS: The alignment of 127 V3 sequences from 22 patients in the cohort group demonstrated common consensus sequences in both the Elista and Rostov samples. The average means of interperson variation were 5.9 and 6.6% in Elista and Rostov subjects, respectively, and comparable to the mean intraperson variation. The average mean interperson variation between nucleotide sequences of HIV patients infected through sexual transmission was considerably higher (14.9%). CONCLUSION: V3 sequence analysis confirms the epidemiologic data which support the transmission of HIV-1 in children from a single source, and suggests the infection of a mother from her parenterally infected child. Furthermore, the genetic variability of HIV-1 V3 in the noncohort group was particularly divergent indicating the heterogeneity of the virus circulating in the former Soviet Union.

Adolescent↗
PubMed1987

An elderly man with bilateral lung disease.

A 60-year-old man with a past history of sprue was admitted with cough and dyspnea and was found to have diffuse, bilateral interstitial lung disease with Kerley-B lines and pleural effusions. An open lung biopsy revealed a diffuse lymphatic infiltration of the interstitium with lymphocytes which were judged to be neoplastic rather than inflammatory. Thus non-Hodgkin's lymphoma was diagnosed. A good response to therapy was obtained.

Humans↗