Biomedical subjects

Paul Hutchinson

Publications and source records attributed to Paul Hutchinson.

At least 19 recordsLinked to original sources

PubMed2006

Airway inflammation in asymptomatic children with episodic wheeze.

Airway pathologies have been comprehensively researched in adult asthma, but in children, the extent of airway inflammation associated with episodic wheeze, often diagnosed as asthma, has not been fully characterized. It is not clear whether persistent airway inflammation is present in the absence of wheezing symptoms, and there is controversy regarding the role of age and atopy. This study assessed cellular and cytokine markers of airway inflammation in asymptomatic children with a history of episodic wheeze. Children with a history of episodic wheeze and cough (study group) and nonasthmatic patients requiring elective surgery (control group) were recruited. All subjects in the study group had a history of significant episodic wheezing (>2 episodes per year), and used only as-needed beta-agonist treatment. Bronchoalveolar lavage (BAL) was obtained using bronchoscopic lavage (study group) and nonbronchoscopic lavage (control group). Differential cell counts of BAL and flow cytometry were performed to identify T-lymphocyte phenotypes, and intracellular cytokine profiles were measured after phorbol-12-myristate 13-acetate (PMA) stimulation of BAL fluid T-cells. Twenty-one children with a history of 2-12 episodes of wheeze per year and 21 nonasthmatic subjects without respiratory symptoms were recruited. Study and control subjects were matched for age (median age, 5 years) and demographic characteristics. Study subjects had higher IgE levels, but their measurements were still within normal range. No significant differences in BAL differential cell counts were noted, and in both groups, the majority of T-cells were CD3+ CD8+, with a median CD4:CD8 ratio of 0.6. There was no significant difference in T-cell expression of the activation markers HLA-DR and CD25 (IL-2 receptor), or in PMA-induced production of the intracellular cytokines IFN-gamma, IL-2, IL-4, IL-5, and IL-10. The results of this study suggest that significant T-cell-driven airway inflammation is absent in mild or nonatopic, asymptomatic children of this age group who have episodic wheeze. Our findings support asthma management guidelines that do not recommend long-term treatment of this group of patients with anti-inflammatory medications.

Asthma↗

PubMed2006

The effects of religious affiliation on sexual initiation and condom use in Zambia.

PURPOSE: To determine whether religious affiliation reduces HIV risk among young women in Zambia, and to examine the effects of religious affiliation on sexual initiation and on condom use during first sexual experience. METHODS: Data from a representative probability sample of 5534 women aged 13-20 years was analyzed. The instrument included questions on sexual initiation, condom use during first sex, religious affiliation, and sociodemographic characteristics of respondents. Statistical tests were performed at the bivariate and multivariate levels. Cox proportional hazards and logistic regression were used at the multivariate levels. Standard errors were adjusted for the "clustering" effect found in data from multistage cluster samples. RESULTS: Affiliation with religious groups that excommunicate members for engaging in premarital sex, and that oppose condom use has both positive and negative effects on behaviors that carry the risk of HIV infection; young women affiliated with conservative groups are more likely to delay sexual initiation but less likely to use condoms during first sex. CONCLUSIONS: Denominations that are not only strongly opposed to premarital sex and condom use, but are able to exercise control over adolescents through socialization or the threat of social exclusion, are likely to create conflicting behaviors among adolescents that cancel each other in terms of HIV risk. Overall, these findings suggest that affiliation with conservative religious groups is unlikely to reduce the risk of HIV infection. Additional studies are recommended.

Adolescent↗

PubMed2006

The cost-effectiveness of health communication programs: what do we know?

While a considerable body of evidence has emerged supporting the effectiveness of communication programs in augmenting health, only a very small subset of studies has examined also whether these programs are cost-effective, that is, whether they achieve greater health gains for available financial resources than alternative interventions. In this article, we examine the available literature on the cost-effectiveness of health behavior change communication programs, focusing on communication interventions involving mass media, and, to a lesser extent, community mobilization and interpersonal communication or counseling. Our objective is to identify the state of past and current research efforts of the cost-effectiveness of behavior change communication programs. This review makes three principal conclusions. First, the analysis of the cost-effectiveness of health communication programs commonly has not been performed. Second, the studies reviewed here have utilized a considerable diversity of methods and have reflected varying levels of quality and adherence to standard cost-effectiveness methodologies. This leads to problems of transparency, comparability, and generalizability. Third, while the available studies generally are indicative of the cost-effectiveness of communication interventions relative to alternatives, the evidence base clearly needs to be expanded by additional rigorous cost-effectiveness analyses.

Cost-Benefit Analysis↗

PubMed2006

Cost-effectiveness analysis for health communication programs.

This article describes methods for analyzing the cost-effectiveness of health communication programs, focusing in particular on estimating program effectiveness with econometric methods that address experimental and quasi-experimental designs (and their absence), national or subnational program coverage, and endogenously targeting of programs. Experimental designs provide a gold standard for assessing effectiveness but are seldom feasible for large-scale health communication programs. Even in the absence of such designs, however, fairly simple methods can be used to examine intermediate objectives, such as program reach, which in turn can be linked to program costs to estimate cost effectiveness. When moving beyond program reach to behavioral or other outcome measures, such as contraceptive use or fertility, or when faced with full-coverage national programs, more elaborate data and methods are required. We discuss data requirements and assumptions necessary in each case, focusing on single-equation multiple regression models, structural equations models, and fixed effects estimators for use with longitudinal data, and then describing how cost information can be incorporated into econometric models so as to get measures of the cost-effectiveness of communication interventions.

Cost-Benefit Analysis↗

PubMed2006

Measuring the cost-effectiveness of a national health communication program in rural Bangladesh.

In this article we examine the cost-effectiveness of the Smiling Sun multichannel media campaign, which was undertaken in Bangladesh from 2001 to 2003 and involved a nationally broadcast television serial drama supported by radio, television, newspaper, and billboard advertisements and local promotion activities. The goal was to encourage the use of a package of family health services at NGO (nongovernmental organization) Service Delivery Program (NSDP) providers. This analysis relates the costs of the Smiling Sun campaign at the national and local level to measures of change in the use of health services, namely, antenatal care and childhood immunizations. Effectiveness is measured using data from cross-sectional surveys conducted in 2001 and 2003 in NSDP catchment areas in rural Bangladesh. The statistical approach, bivariate probit estimation, controls for nonrandom exposure to the program's media messages, advertisements, and signs. Using national-level data, we find that the Smiling Sun campaign was both effective and cost-effective, inducing higher levels of service utilization for only $0.05 per additional antenatal care (ANC) user and only $0.30 and $0.36 for each additional child vaccinated for measles and DPT3, respectively. With respect to local promotion activities, the cost per attributable behavior change was considerably higher--nearly $8 per new ANC user, $37 per new DPT3 vaccination, and $32 per new measles vaccination.

Adolescent↗

PubMed2006

Advanced methods for evaluating the impact of family planning communication programs: evidence from Tanzania and Nepal.

Evaluations of national family planning communication campaigns are often complicated by nonrandomized research designs and self-reported measures of exposure to media messages, both of which can bias estimates of campaign effectiveness if suitable analytical methods are not employed. This study uses three methods to address these problems: (1) single-equation multiple regression analysis; (2) propensity score matching (PSM); and (3) maximum-likelihood simultaneous equation models (SEM), namely bivariate probit. We use these methods to evaluate the impact of family planning health-communication campaigns on the use of modern family planning methods, focusing primarily on the radio drama Zinduka! in Tanzania and Ghanti Heri Haad Nilaun in Nepal. We find that these methods led to substantially different estimates of the magnitude of the impact of these communication campaigns. Specifically, we found that self-reported exposure to each radio program was exogenously related to family planning use and that PSM and multiple regression analysis gave similar estimates in those situations. An indicator of exposure to any type of family planning message was found to be endogenous, in which case bivariate probit and PSM gave different estimates of program impact. Researchers should, therefore, pay close attention to the results of tests for endogeneity and identification that guide the appropriate use of the different methods.

Adolescent↗

PubMed2006

Regulation of annexin I in rheumatoid synovial cells by glucocorticoids and interleukin-1.

The glucocorticoid (GC)-induced antiinflammatory molecule annexin I is expressed in leukocytes and has antiinflammatory effects in animal models of arthritis, but the expression of annexin I in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) is unknown. We report the constitutive and dexamethasone (DEX)-inducible expression of annexin I in RA FLS. DEX increased FLS annexin I protein translocation and mRNA expression. Interleukin (IL)-1beta also induced annexin I translocation and mRNA but also increased intracellular protein. DEX and IL-1 had additive effects on annexin I mRNA, but DEX inhibited the inducing effect of IL-1beta on cell surface annexin I. These results indicate that glucocorticoids and IL-1beta upregulate the synthesis and translocation of annexin I in RA FLS, but interdependent signalling pathways are involved.

Annexin A1↗

PubMed2005

Leukocyte phenotype and function predicts infection risk in renal transplant recipients.

BACKGROUND: The degree to which transplant recipients are immunosuppressed influences their risks of rejection, infection and cancer. Current measures of immune suppression are crude (clinical events) or indirect (drug exposure). We assessed a direct measure of immune status, leukocyte phenotype and function (LPF, a composite measure of five aspects of peripheral blood leukocyte phenotype and function), as a predictor of infection. METHODS: A double-blind, prospective, cohort study was conducted, to determine the burden of infection in stable renal transplant recipients with moderate-severe (Group I, n = 34) or minimal (Group II, n = 36) impairment of LPF, a composite score of: (i) CD4 count; (ii) lymphocyte proliferation in response to phytohaemagglutinin A (PHA); (iii) serum Ig concentrations; (iv) neutrophil phagocytic function; and (v) reactive oxygen species generation. Subjects completed a 6 month diary and each recorded infection was scored 1-4: 1, minor undefined infection (e.g. URTI); 2, minor, microbiologically defined infection (e.g. UTI); 3, major defined infection (requiring hospitalization); 4, opportunistic infection (e.g. Herpes zoster). Final infection score was the sum of all infective episodes. Subjects were then followed-up for 5 years for outcome measures. RESULTS: Groups were well matched for age, sex, diabetes, serum creatinine, rejection and trough cyclosporin concentrations. Group I (moderate to severe impairment of LPF) recorded a higher infection score, 2.4+/-2.8 vs 1.2+/-1.2 for Group II, P = 0.02, due to a higher incidence of moderate to severe infection. This relationship was confirmed by multivariate analysis (OR 1.83, CI 1.08, 3.11, P = 0.03 per unit increase in infection score). During the 5 year follow-up period they had significantly more episodes of admission to hospital, and twice as many admissions due to infections, but no difference in malignancy, graft or patient outcome. CONCLUSION: LPF testing prospectively identified a cohort who incurred a higher burden of infection. Further studies are required to determine the predictive value of LPF for acute rejection, infection and cancer, and to determine whether adjustments to therapy on the basis of LPF can lead to improved outcomes.

Adult↗

PubMed2005

The impact of life skills education on adolescent sexual risk behaviors in KwaZulu-Natal, South Africa.

PURPOSE: To assess the impact of exposure to life skills education by youth in KwaZulu-Natal Province (KZN, South Africa) on knowledge and behaviors associated with the spread of HIV/AIDS. METHODS: Data come from a panel study of 2222 youth from several population subgroups in KZN. The youth were aged 14-24 years when interviewed in 1999 and 2001. The intervention was a full coverage life skills education program for all students in middle and secondary schools. Impact was measured as net dose-response relationships between life skills exposure and outcomes. Econometric methods were used to control for nonrandom exposure to life skills education. Outcomes included sexual behavior and condom use indicators. RESULTS: Significant effects, albeit modest in magnitude, were observed on selected areas of sexual-reproductive health knowledge and perceived condom self-efficacy, along with larger effects on condom use at first and last sex. No consistent effects on age at sexual initiation, secondary abstinence, or partnering behaviors were observed among these youth. CONCLUSIONS: School-based life skills education appears capable of communicating key information and helping youth develop skills relevant to reducing HIV risk. However, the South African national program has yet to be fully implemented, and whether this initiative will result in sustained behavior modification among youth on a sufficient scale to affect the HIV/AIDS epidemic is uncertain.

Adolescent↗

PubMed2005

Detection of the p53 regulator murine double-minute protein 2 in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by hyperplasia of synovial lining tissue, which is involved directly in the damage of cartilage and bone. One of the factors thought to contribute to this synovial lining hyperplasia is dysregulation of, or functional abnormality in, the tumor suppressor protein p53. The protein known as murine double-minute protein 2 (MDM2) is the major negative regulator of p53, and in tumors contributes to increased cell proliferation. The detection of MDM2 in rheumatoid synovium has not previously been described. We investigated whether this protein is detectable in cells and tissues derived from patients with RA. METHODS: Expression of MDM2 protein was examined in fibroblast-like synoviocytes (FLS) by methods including permeabilization flow cytometry, immunofluorescence, and Western blotting, and in synovial tissues using immunohistochemistry. The proliferative capacity of these cells was also examined using 3H/thymidine incorporation. Cell cycle analysis was performed by propidium iodide incorporation. RESULTS: MDM2 was detected in RA FLS and synovial tissues. MDM2 protein was identified in CD14-positive and CD14-negative synovial lining cells and CD14-positive sublining cells. RA FLS exhibited faster proliferative rates and higher levels of MDM2 expression than FLS derived from patients with osteoarthritis (OA). Both OA and RA FLS were found to be in similar phases of the cell cycle at the time of MDM2 protein analysis. CONCLUSION: The abundant expression of MDM2 in RA may be a contributing factor to the hypoapoptotic phenotype of lining tissue through its capacity to downregulate p53 levels and effects. Further studies are required to determine the relationship between this cell-cycle protein profile, tissue hyperplasia, and the functional abnormality of p53 in RA.

Animals↗

PubMed2004

Fibroblasts derived from Gpx1 knockout mice display senescent-like features and are susceptible to H2O2-mediated cell death.

The Free Radical Theory of Aging proposes that reactive oxygen species (ROS) contribute to the pathophysiology of aging. Our previous data highlight the importance of antioxidant enzymes, superoxide dismutase 1 (Sod1) and glutathione peroxidase 1 (Gpx1), in regulating this process. Previously, we demonstrated that a perturbation in the Sod1-to-Gpx1 ratio, as a consequence of Sod1 overexpression, leads to senescence-like changes. We proposed that this was mediated via the Sod1 dismutation product H2O2, because H2O2 induced similar changes in control cells. However, it has been suggested that H2O2 production, via Sod1 dismutation, is rate-limited by the availability of the substrate O2*-, and therefore age-related changes may occur as a result of other functions of Sod1. In this study, we test this notion in fibroblasts derived from Gpx1 null mutant mice (Gpx1-/-) that have elevated H2O2 as a consequence of the lack of its removal by Gpx1. We demonstrate senescence-like changes in Gpx1-/- fibroblasts that include (1) reduced proliferative capacity, DNA synthesis, and responsiveness to EGF and serum; (2) elevated levels of Cip1; (3) increased NF-kappaB activation; and (4) morphological features of senescent cells. Gpx1-/- fibroblasts also demonstrate a dose-dependent susceptibility to H2O2-induced apoptosis. Our findings suggest that Gpx1 is protective against both ROS-mediated senescence-like changes and oxidant-mediated cell death.

Animals↗

PubMed2004

Evaluation of a method to reduce over-the-counter medication dosing error.

OBJECTIVES: To introduce a simple method of dosing over-the-counter medication in a home setting using a color-coding concept and to compare dosing deviation from recommended dosage using the color-coded method with dosing deviation using conventional package labeling. DESIGN: Randomized controlled clinical trial. SETTING: Pediatric emergency center at a tertiary care medical center. PARTICIPANTS: A sample of 101 caregivers of children with nonemergent complaints separated into 2 groups. One group used a conventional dosing method and the other group used a color-coded method to determine and measure a dose of acetaminophen for their child. MAIN OUTCOME MEASURES: For both dose determination and dose measuring, percentage of deviation from recommended acetaminophen dosage was calculated and compared between the 2 groups. RESULTS: There was no significant difference in sociodemographic characteristics between the 2 groups. How-ever, for dose determination, the average deviation (25.8% vs 1.7%) and median deviation (1% vs 0%) from recommended dosage were both higher for the group using conventional methods compared with the group using the color-coded method. The Wilcoxon rank sum test indicated that the median deviation was significantly different between the 2 groups (P<.001). Similar results were obtained for dose measuring. The average deviation (29% vs 0.5%) and the median deviation (17.2% vs 0%) from recommended dosage were higher for the group using conventional methods compared with the group using the color-coded method. The median deviation was also significantly different between the 2 groups (P<.001). CONCLUSION: This study suggests a marked improvement in caregivers' ability to correctly determine and measure an over-the-counter medication for their child using a color-coded method compared with conventional methods.

Acetaminophen↗

PubMed2004

Rhinovirus detection: comparison of real-time and conventional PCR.

Rhinoviruses are important human respiratory viruses and the major causative agents of the common cold. Historically, detection of rhinovirus has been by virus culture and this was significantly improved by the use of PCR assays. Recently real-time PCR was developed but to date there have been no reported comparisons of conventional and real-time PCR assays for detection of rhinovirus. In this study, we first compared real-time PCR (SYBR Green I) to conventional PCR for the detection of rhinovirus in serially diluted standard DNA and rhinovirus stock to determine the limits of detection. Next, assays were compared for sensitivity to detect rhinovirus in cell culture with a known number of infected cells. Finally, the assays were compared using clinical samples known to contain rhinovirus. Real-time PCR was 10-fold more sensitive than conventional PCR to detect rhinovirus in standard DNA and in virus stock and >10-fold more sensitive to detect rhinovirus in cultured cells. Real-time PCR was significantly superior for detection of rhinovirus in patients' nasal aspirates (sensitivity 72% versus 39%, P < 0.05). In summary, we found that real-time PCR was more sensitive than conventional PCR and reduced post-PCR processing. Hence, real-time PCR is suitable for both research and clinical purposes.

Common Cold↗

PubMed2004

Reduction in arthritis severity and modulation of immune function in tissue factor cytoplasmic domain mutant mice.

Tissue factor (TF), a transmembrane receptor for plasma factor VII(a), is the main initiator of the coagulation cascade. It has also been implicated in noncoagulant processes, including inflammation. The function of the TF cytoplasmic domain was studied in mice in which 18 of the 20 cytoplasmic amino acids were deleted. This mutation (TF(deltaCT/deltaCT)) is not associated with alterations in blood coagulation. Arthritis was induced by intra-articular injection of methylated bovine serum albumin (mBSA) in mice preimmunized with mBSA. Arthritis severity was significantly reduced in TF(deltaCT/deltaCT) mice compared to wild-type mice, including reductions in synovitis, synovial exudate, cartilage degradation, and bone damage. A marked reduction in synovial interleukin (IL)-1beta and IL-6 mRNA was also observed. Serum anti-mBSA IgG1, but not IgG2a, was increased in mutant mice. Cutaneous delayed-type hypersensitivity and antigen-induced T-cell proliferation were reduced in TF(deltaCT/deltaCT) compared to wild-type mice. A significant down-regulation of lipopolysaccharide-induced IL-1, tumor necrosis factor, IL-6, macrophage migration inhibitory factor, and matrix metalloproteinase-13 mRNA was observed in immunized, but not in naive TF(deltaCT/deltaCT) macrophages ex vivo. These data suggest a significant role for the cytoplasmic domain of TF in the regulation of the immunoinflammatory responses, a murine arthritis model, and macrophage function.

Animals↗

PubMed2004

The role of flow cytometric ANCA detection in screening for acute pauci-immune crescentic glomerulonephritis.

BACKGROUND: Most cases of pauci-immune crescentic glomerulonephritis (PICGN) are associated with serum anti-neutrophil cytoplasmic antibodies (ANCA). This article studied the sensitivity and specificity of serum ANCA, determined by flow cytometry and indirect immunofluorescence (IIF), to identify patients with acute PICGN. METHODS: 577 adults presenting for first biopsy of their native kidneys with serum taken for ANCA (flow cytometry and IIF) determination were studied. A positive ANCA was defined using a flow cytometric ANCA assay as a screening test, followed by a slide-based indirect IIF technique. Pathological confirmation of acute PICGN was used to assess the sensitivity and specificity of this combined approach and its positive predictive value (PPV) and negative predictive value (NPV) in patients presenting for renal biopsy due to abnormal urinary sediment. RESULTS: Forty-nine patients were found to have acute PICGN on renal biopsy. Of these 47 were ANCA positive (sensitivity 95.9%). Overall 93 of the renal biopsy patients were ANCA positive, (specificity 91.3%). A further seven patients (two ANCA positive) had advanced sclerosing disease consistent with PICGN but without evidence of current disease activity. The PPV and NPV of ANCA, assessed by flow cytometry and slide IIF, in predicting that patients presenting with undifferentiated renal disease would have acute PICGN was 50.5 and 99.8%, respectively. CONCLUSIONS: Flow cytometric screening of serum for ANCA in patients undergoing renal biopsy has a high NPV for determining those with acute PICGN. It may provide a rapid, simple screening test for this lesion in laboratories using diagnostic flow cytometry and may complement IIF/ELISA in evaluating ANCA positive patients.

Acute Disease↗

PubMed2004

Nutritional indicators, peripheral blood lymphocyte subsets and survival in an institutionalised elderly population.

The objectives of this study were to determine the percentage and absolute counts of the peripheral blood lymphocyte subsets, and to examine the relationship between lymphocyte subsets and nutritional status, and total mortality in an institutionalised elderly population. Design The study had a cross-sectional and observational design. The sample of 115 permanent elderly residents was drawn from large geriatric institution in Melbourne, Australia. The main outcome measures were as follows: (i) percentages and absolute counts of lymphocyte subsets, (ii) association between biochemical indices of nutritional status (ferritin, iron and zinc) and peripheral blood lymphocyte subsets, (iii) total mortality during a 22-month period in relation to baseline lymphocyte subset counts. Women had higher absolute counts of various lymphocyte subsets than men. Positive correlations of serum ferritin with the number of CD8 (T-suppressor cell) and of serum iron with CD56 (natural killer, NK cells) were observed in men. In women, serum zinc was positively correlated with the absolute counts of CD3 (total T-cells), CD4 (T-helper cell) and CD19 (total B-cell). The analysis of survival data after 22 months showed that the mean number of CD4 cells of non-survivors (524 +/-292 x10(6)cells/L) was significantly lower than that of survivors (759+/-292 x 10(6) cells/L). The biochemical indicators of iron and zinc status partly account for variations in lymphocyte subset counts, consistent with known effects of iron overload and of zinc deficiency on immunocompetence. The number of CD4 T-cells may be useful in the prediction of total mortality in an institutionalised elderly population.

Aged↗

PubMed2003

Regulation of p53 by macrophage migration inhibitory factor in inflammatory arthritis.

OBJECTIVE: To study the capacity of macrophage migration inhibitory factor (MIF) to regulate proliferation, apoptosis, and p53 in an animal model of rheumatoid arthritis (RA) and in fibroblast-like synoviocytes (FLS) from humans with RA. METHODS: Antigen-induced arthritis (AIA) was induced in MIF(-/-) mice and littermate controls. FLS were obtained from patients with RA. Western blotting and immunohistochemistry were used to measure p53 in cells and tissues. Apoptosis was detected in cells by flow cytometry using TUNEL and annexin V/propidium iodide labeling. Apoptosis in tissue was detected using TUNEL. Proliferation was assessed in cultured cells and tissue by (3)H-thymidine incorporation and Ki-67 immunostaining, respectively. RESULTS: MIF inhibited p53 expression in human RA FLS. Levels of p53 were correspondingly increased in MIF(-/-) mouse tissues and cells. Spontaneous and sodium nitroprusside-induced apoptosis were significantly increased in MIF(-/-) cells. In vitro exposure of FLS to MIF reduced apoptosis and significantly induced FLS proliferation. Synoviocyte proliferation in MIF(-/-) mice was correspondingly reduced. A decrease in the severity of AIA in MIF(-/-) mice was associated with an increase in p53 and apoptosis in synovium. Evidence of in situ proliferation was scant in this model, and no difference in in situ proliferation was detectable in MIF(-/-) mice compared with wild-type mice. CONCLUSION: These results indicate a role for MIF in the regulation of p53 expression and p53-mediated events in the inflamed synovium and support the hypothesis that MIF is of critical importance in the pathogenesis of RA.

Animals↗

PubMed2003

Laboratory assessment of immune function in renal transplant patients.

BACKGROUND: Advances in immunosuppression have made renal transplantation an effective therapy for end stage renal failure; with low rejection rates and long graft survival times. However, the major adverse consequences, infection and malignancy have not diminished. To predict this risk a score of immune competence has been developed from the simultaneous laboratory assessment of multiple parameters of immune function. METHODS: The immune status of 152 transplant recipients (138 renal and 14 pancreas/renal) was assessed by measurement of lymphocyte subsets, mitogen-induced T-cell proliferative responses, neutrophil phagocytic capacity and reactive oxygen species (ROS) generation. A scoring system was devised based on the average number of these parameters below 10th percentile of normal. RESULTS: The most common abnormality was B-cell lymphopenia (85%) followed by reduced neutrophil ROS production (63% of patients), NK cell lymphopenia (50%), lymphocyte mitogen response (49%) and CD4 number (23%). The abnormalities were unrelated to the duration of immunosuppression (up to 15 years), and variable combinations of cyclosporine A, azathioprine, prednisolone and mycophenolate mofetil (MMF) (except for a consistent reduction in lymphocyte mitogen response in MMF treated patients). Retrospective comparison of infective episodes showed a significantly greater index of infections in patients with the worst score compared with a normal score. CONCLUSIONS: The data suggests that this quantification of immune function may allow assessment of the level of host immune defence reflecting the level of drug-induced immunosuppression and thus risks of immunosuppressive complications.

Adult↗