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Biomedical subjects

D M Francis

Publications and source records attributed to D M Francis.

At least 19 recordsLinked to original sources
PubMed2005

Thyroid autoimmunity in chronic urticaria.

BACKGROUND: Chronic urticaria (CU) is an autoimmune process in some patients. An association between CU and autoimmune thyroid disease has also previously been proposed. Our group has identified functionally significant histamine-releasing autoantibodies in one subset of CU patients (subset 1), predicted by positive autologous intradermal serum tests and positive histamine release from donor basophil leucocytes in vitro. Sera from a second subset of patients (subset 2), all of whom had positive autologous intradermal serum tests, failed to release histamine from donor basophils. A final disease subset (subset 3) has no identifiable skin reactivity (negative autologous serum skin test) or in vitro histamine releasing activity. OBJECTIVES: In order to examine further the possible relationships between thyroid autoimmunity, thyroid dysfunction and CU, we have examined thyroid autoantibodies and thyroid-stimulating hormone (TSH) levels (an indirect measure of thyroid dysfunction) in the three CU subsets. PATIENTS/METHODS: We studied 182 patients (69% female), of whom 90 had a positive autologous intradermal serum test. RESULTS: Eighteen skin test-positive and four skin test-negative patients had thyroid microsomal antibodies (TMA). TSH outside the normal range was found in 13 skin test-positive and one skin test-negative patient. These findings represent clustering of TMA positivity [risk ratio (RR) 4.06, 95% confidence interval (CI) 1.56-10.6] and of abnormal thyroid function (RR 15.5, CI 2.07-11.6) among the skin test-positive patients. However, in the overall study group an elevated TSH was present in seven patients (3.8%, CI 1.6-7.8) comparable to the 5% expected prevalence in the community. Thyroglobulin antibodies (TGA) were present in two of 182 patients. CONCLUSIONS: There were significant differences between skin test-positive and skin test-negative patients with regard to autoimmune thyroid disease. Evidence for autoimmune thyroid disease and abnormal thyroid function was largely found among the skin test-positive patients, supporting the theory of an autoimmune aetiology in this group.

Adolescent↗
PubMed2004

Mapping, genetic effects, and epistatic interaction of two bacterial canker resistance QTLs from Lycopersicon hirsutum.

Two quantitative trait loci (QTL) from Lycopersicon hirsutum, Rcm 2.0 and Rcm 5.1, control resistance to Clavibacter michiganensis subsp. michiganensis ( Cmm). To precisely map both loci, we applied interval mapping techniques to 1,056 individuals in three populations exhibiting F(2) segregation. Based on a 1-LOD confidence interval, Rcm 2.0 mapped to a 14.9-cM interval on chromosome 2 and accounted for 25.7-34.0% of the phenotypic variation in disease severity. Rcm 5.1 mapped to a 4.3-cM interval on chromosome 5 and accounted for 25.8-27.9% of the phenotypic variation. Progeny testing of recombinant plants narrowed the QTL location for Rcm 2.0 to a 4.4-cM interval between TG537-TG091 and to a 2.2-cM interval between CT202-TG358 for Rcm 5.1. A population of 750 individuals exhibiting F(2) segregation was used to detect epistasis between both loci using ANOVA and orthogonal contrasts ( P=0.027), suggesting that resistance was determined by additive gene action and an additive-by-additive epistatic interaction. A partial diallel mating design was used to confirm epistasis, advance superior genotypes, randomize genetic backgrounds, and create recombination opportunities. This crossing scheme created a more balanced population ( n=112) containing the nine F(2) genotypic classes. Parents in the diallel were selected from the previous population based on resistance, genotype at the Rcm 2.0 and Rcm 5.1 loci, and horticultural traits. A replicated trial using the diallel population confirmed additive-by-additive epistasis ( P<0.0001). These results validate the gene action, intra -locus interaction, and map position of two loci controlling resistance to Cmm.

Actinomycetales↗
PubMed2003

Blood basophil numbers in chronic ordinary urticaria and healthy controls: diurnal variation, influence of loratadine and prednisolone and relationship to disease activity.

BACKGROUND: The basopenia of chronic urticaria relates to histamine releasing autoantibodies in the serum of patients with autoimmune urticaria. This reduction in circulating basophils may be due to active recruitment into weals. If so, it might be expected that numbers in blood would be reduced when urticaria is active and increased after treatment. The primary aim of this study was to look at diurnal variation of basophil numbers in patients with chronic ordinary urticaria (not physical or vasculitic) in relation to disease activity and the effect of treatment with antihistamines and corticosteroids, and to compare the results with healthy controls. A secondary aim was to compare a standard manual counting method with automated basophil counts and to look at numbers of other circulating leucocytes that might be relevant to urticaria pathogenesis. METHODS: Manual basophil counts using a toluidine blue stain and automated 5-part differentials (Coulter Gen. S) were performed at 4-hourly intervals from 08.00 to 20.00 in 10 healthy controls (six women, age 24 to 63 years) and seven chronic urticaria patients (five women, 24 to 50 years). All chronic urticaria patients had severe daily or almost daily urticaria. Only one of six chronic urticaria sera showed in vitro basophil histamine releasing activity. Counts were performed without treatment, after a week of taking loratadine 10 mg daily and after 3 days of adding prednisolone at 0.6 mg/kg/day (maximum 40 mg). Daily urticarial activity scores (UAS) were derived from weal numbers and itch, maximum 7. RESULTS: There was no significant overall diurnal variation of basophil numbers in healthy controls or chronic urticaria patients. Mean (SE) manually counted basophil were higher in healthy controls than chronic urticaria (43.4/ microL (2.1) vs. 4.4 (0.8), P < 0.001). Basophil counts were reduced in healthy controls on steroids (19.2 (1.9), P < 0.001) but increased in chronic urticaria (8.9 (1.9), P < 0.001). Loratadine did not influence them. UAS fell on treatment (3.3 (0.4) baseline, 1.4 (0.5) on loratadine and 0.5 (0.2) on prednisolone with loratadine, P < 0.001). There was a negative linear correlation between basophil numbers and UAS in untreated chronic urticaria patients (P = 0.001, Spearman rank correlation). Manual and automated basophil counts showed poor agreement. Lymphocyte numbers were lower in chronic urticaria than healthy controls. Neutrophils increased whereas lymphocytes and eosinophils decreased in all subjects on prednisolone. They were unaffected by loratadine. CONCLUSION: The results are consistent with the hypothesis that circulating basophils may be recruited from blood into urticarial weals during disease activity. Automated counts are not suitable for assessing basophil numbers in chronic urticaria. The relevance of reduced lymphocyte numbers in chronic urticaria needs to be explored.

Adult↗
PubMed2000

The safety and efficacy of laparoscopic live donor nephrectomy: a systematic review.

BACKGROUND: The aim of this systematic review was to compare the safety and efficacy of laparoscopic live donor nephrectomy with the "gold" standard of open live donor nephrectomy. METHODS SEARCH STRATEGY: Three search strategies were devised to enable literature retrieval from the Medline, Current Contents, Embase, and Cochrane Library databases up until, and including, February 2000. STUDY SELECTION: Inclusion of a report was determined on the basis of a predetermined protocol, independent assessment by two reviewers, and a final consensus decision. English language reports were selected and acceptable study designs included randomized-controlled trials, controlled clinical trials, case series, or case reports. Each report was required to provide information on at least one of several safety and efficacy outcomes as detailed in the protocol. DATA COLLECTION AND ANALYSIS: Twenty-five reports met the inclusion criteria. They were tabulated and critically appraised in terms of the methodology and design, sample size, outcomes, and the possible influence of bias, confounding, and chance. RESULTS: High level evidence comparing the safety and efficacy of laparoscopic live donor nephrectomy with open donor nephrectomy was not available at the time of this review. Limited low level evidence suggested that the laparoscopic approach might be advantageous regarding the donor's hospital stay, convalescence, pain, and resumption of employment. CONCLUSIONS: The ASERNIP-S Review Group concluded that the evidence-base for laparoscopic live donor nephrectomy was inadequate to make a safety and efficacy recommendation. Clinical and research recommendations were developed regarding the introduction and current practice of this procedure in Australia.

Australia↗
PubMed2000

Renal xenografts from triple-transgenic pigs are not hyperacutely rejected but cause coagulopathy in non-immunosuppressed baboons.

BACKGROUND: The genetic modification of pigs is a powerful strategy that may ultimately enable successful xenotransplantation of porcine organs into humans. METHODS: Transgenic pigs were produced by microinjection of gene constructs for human complement regulatory proteins CD55 and CD59 and the enzyme alpha1,2-fucosyltransferase (H-transferase, HT), which reduces expression of the major xenoepitope galactose-alpha1,3-galactose (alphaGal). Kidneys from CD55/HT and CD55/CD59/HT transgenic pigs were transplanted into nephrectomised, nonimmunosuppressed adult baboons. RESULTS: In several lines of transgenic pigs, CD55 and CD59 were expressed strongly in all tissues examined, whereas HT expression was relatively weak and did not significantly reduce alphaGal. Control nontransgenic kidneys (n=4) grafted into baboons were hyperacutely rejected within 1 hr. In contrast, kidneys from CD55/HT pigs (n=2) were rejected after 30 hr, although kidneys from CD55/CD59/HT pigs (n=6) maintained function for up to 5 days. In the latter grafts, infiltration by macrophages, T cells, and B cells was observed at days 3 and 5 posttransplantation. The recipients developed thrombocytopenia and abnormalities in coagulation, manifested in increased clotting times and an elevation in the plasma level of the fibrin degradation product D-dimer, within 2 days of transplantation. Treatment with low molecular weight heparin prevented profound thrombocytopenia but not the other aspects of coagulopathy. CONCLUSIONS: Strong expression of CD55 and CD59 completely protected porcine kidneys from hyperacute rejection and allowed a detailed analysis of xenograft rejection in the absence of immunosuppression. Coagulopathy appears to be a common feature of pig-to-baboon renal transplantation and represents yet another major barrier to its clinical application.

Animals↗
PubMed2000

Randomized double-blind study of cyclosporin in chronic 'idiopathic' urticaria.

BACKGROUND: Histamine-releasing activity (HRA) is detectable in up to 50% of patients with chronic ordinary urticaria. OBJECTIVES: To determine the effect of cyclosporin on clinical features and HRA in patients with chronic urticaria. METHODS: Thirty patients with severe unremitting disease, responding poorly to antihistamines and showing a positive autologous serum skin test (ASST) as a marker of HRA, were randomized to 4 mg kg-1 daily of cyclosporin (Sandimmun, n = 20) or placebo (n = 10) for 4 weeks. Non-responders were offered open-label cyclosporin for 4 weeks. All were followed for up to 20 weeks or until clinical relapse; all took cetirizine 20 mg daily throughout the study. The primary measure of efficacy was a daily urticaria activity score (UAS) of weal numbers and itch (maximum score 42 per week). A positive response was defined as a reduction to < 25% of baseline weekly UAS and relapse as a return to > 75%. The effect of cyclosporin on serum HRA was assessed by in vitro basophil histamine release assays and ASSTs before and after treatment. RESULTS: Twenty-nine patients (19 active, 10 controls) completed the randomized trial medication. Eight of 19 on active treatment but none on placebo had responded at 4 weeks (P < 0.05). Three others on active drug met the criterion for response at 2 weeks but not at 4 weeks. Mean reduction in UAS between weeks 0 and 4 was 12.7 (95% confidence interval, CI 6.6-18.8) for active and 2.3 (95% CI - 3.3-7.9) for placebo (P = 0.005). Seventeen non-responders (seven randomized to active and 10 to placebo) chose open-label cyclosporin and 11 responded after 4 weeks. Six of the eight randomized active drug responders relapsed within 6 weeks. Of the 19 responders to randomized and open-label cyclosporin, five (26%) had not relapsed by the study end-point. Mean in vitro serum HRA fell from 36% (95% CI 22-49%) to 5% (95% CI 1-8%) after cyclosporin treatment (n = 11, P < 0.0001). The ASST response to post-treatment serum was also reduced (P < 0.05). CONCLUSIONS: This study shows that cyclosporin is effective for chronic urticaria and provides further evidence for a role of histamine-releasing autoantibodies in the pathogenesis of this chronic 'idiopathic' disease.

Adult↗
PubMed1999

Cutaneous inflammatory cell infiltrate in chronic idiopathic urticaria: comparison of patients with and without anti-FcepsilonRI or anti-IgE autoantibodies.

BACKGROUND: Previous studies defining the histopathologic features of patients with chronic idiopathic urticaria (CIU) were performed on wheals of uncertain duration and before the identification of functional autoantibodies against FcepsilonRI and/or IgE, now known to be present in approximately 30% of patients with CIU. OBJECTIVE: We sought to determine the timing of the inflammatory infiltrate in the wheals of patients with CIU and to detect differences between patients with and without autoantibodies. METHODS: Immunohistochemistry was used to identify neutrophils (neutrophil elastase), T lymphocytes (CD3), and activated eosinophils (EG2) in biopsy specimens from uninvolved skin and wheals present for less than 4 hours and greater than 12 hours in 22 patients with CIU, as well as in biopsy specimens from the skin of 12 healthy control subjects. Patients were identified as having functional autoantibodies on the basis of their serum-evoked histamine release in vitro from the basophils of 2 healthy donors. RESULTS: EG2(+), neutrophil elastase+, and, to a lesser extent, CD3(+) cells were found in greater numbers in wheals undergoing biopsy at less than 4 and greater than 12 hours than in uninvolved skin (P <.05). Patients without autoantibodies (n = 12) had significantly more EG2(+) cells in wheals of greater than 12 hours' duration than patients with autoantibodies (n = 10; P =.02). There was no other difference between patients with and without autoantibodies in the cutaneous cellular infiltrate. CONCLUSION: Neutrophil and eosinophil accumulation occurs early in the evolution of a wheal in patients with CIU, but eosinophil activation may occur later or be more persistent in patients without autoantibodies.

Adult↗
PubMed1999

Chronic idiopathic urticaria: comparison of the clinical features of patients with and without anti-FcepsilonRI or anti-IgE autoantibodies.

BACKGROUND: Previous studies defining the clinical features of patients with chronic idiopathic urticaria (CIU) were performed before the identification of functional autoantibodies against FcepsilonRI and/or IgE, now known to be present in approximately 30% of patients with CIU. OBJECTIVE: Our purpose was to determine whether there are differences between patients with and those without autoantibodies in the clinical features or severity of CIU. METHODS: The clinical features of 107 patients with CIU were evaluated prospectively. Patients were identified as having functional autoantibodies on the basis of the serum-evoked histamine release in vitro from the basophils of 2 healthy donors. RESULTS: Patients with autoantibodies (31%) had more wheals (P = .005), a wider distribution of wheals (P = .009), higher itch scores for the most severe episodes of itching (P = .002), more systemic symptoms (P = .03), and lower serum IgE levels (P < .0005) than patients without autoantibodies. CONCLUSION: The presence of autoantibodies indicates a subset of patients with more severe CIU.

Adolescent↗
PubMed1999

The autologous serum skin test: a screening test for autoantibodies in chronic idiopathic urticaria.

One-third of patients with chronic idiopathic urticaria (CIU) have circulating functional autoantibodies against the high affinity IgE receptor FcepsilonRI, or IgE. The intradermal injection of autologous serum causes a weal and flare reaction in many patients with CIU, and this reaction forms the basis of the autologous serum skin test (ASST). We have determined the parameters of the ASST which define the optimal sensitivity and specificity for the identification of patients with autoantibodies. Two physicians (R.A. S. and C.E.H.G.) performed ASSTs in a total of 155 patients with CIU, 40 healthy control subjects, 15 patients with dermographism, nine with cholinergic urticaria and 10 with atopic eczema. Patients were classified as having functional autoantibodies by demonstrating in vitro serum-evoked histamine release from the basophils of two healthy donors. There were significant differences (P < 0.001) in the mean weal diameter, weal volume, weal redness and flare area of the intradermal serum-induced cutaneous responses at 30 min between patients with CIU with autoantibodies and either those without autoantibodies or control subjects. The optimum combined sensitivity and specificity of the ASST was obtained if a positive test was defined as a red serum-induced weal with a diameter of >/= 1.5 mm than the saline-induced response at 30 min. For R.A.S. and C.E.H.G., the ASST sensitivity was 65% and 71% and specificity was 81% and 78%, respectively. Using these criteria, the following subjects had positive ASSTs: none of 15 dermographics, none of 10 atopics, one of nine cholinergics and one of 40 controls.

Autoantibodies↗
PubMed1999

Human leucocyte antigen class II associations in chronic idiopathic urticaria.

The major histocompatibility complex (MHC) acts as a marker for self during T-cell ontogeny and is associated with the pathogenesis of many autoimmune diseases. Recent investigations have shown about 30% of patients with chronic idiopathic urticaria (CIU) have IgG autoantibodies against the high-affinity IgE receptor, FcepsilonRI, or IgE. A link between MHC class II alleles and CIU has not been reported previously. DNA was extracted from blood of 100 Caucasian patients with CIU, and the MHC class II type determined using the polymerase chain reaction with sequence-specific primers, testing for DRB and DQB1 alleles. The frequency of alleles in CIU patients was compared with that found in 603 controls. Further human leucocyte antigen (HLA) typing on patient subsets, classified by the patients' responses to intradermal injection of autologous serum and their serum-induced histamine release from basophil leucocytes of healthy donors, was undertaken. HLA DRB1*04 (DR4) and its associated allele, DQB1*0302 (DQ8), are raised in CIU patients compared with a control population (P = 2 x 10-5 and P = 2 x 10-4, respectively). HLA DRB1*15 (DR15) and its associated allele, DQB1*06 (DQ6), are significantly less frequently associated with CIU. The HLA DRB1*04 association is particularly strong (corrected P = 3.6 x 10-6) for patients whose serum has in vivo and in vitro histamine-releasing activity. HLA class II typing is consistent with the concept that CIU is a heterogeneous disease, and supports an autoimmune pathogenesis in a subset of patients.

Adolescent↗
PubMed1998

Anti-Fc(episilon)RI auto antibodies and basophil histamine releasability in chronic idiopathic urticaria.

BACKGROUND: Circulating functional autoantibodies to the high-affinity IgE receptor (Fc(epsilon)RI) or to IgE have been found in approximately one third of patients with chronic idiopathic urticaria (CIU). OBJECTIVE: We sought to compare basophil histamine release and basophil numbers in patients with CIU with and without autoantibodies. METHODS: Basophil histamine release to the anti-Fc(epsilon)RI mAb 22E7, anti-IgE, and formyl-methionyl-leucyl-phenylalanine (fMLP); basophil numbers; and total cellular histamine were measured in 26 patients with CIU and 18 healthy control subjects. Twelve patients were classified as having functional anti-Fc(epsilon)RI and/or anti-IgE autoantibodies on the basis of their serum-evoked histamine release from the basophils of 2 healthy donors. RESULTS: 22E7 and anti-IgE, but not fMLP, released less histamine from basophils of patients with CIU than from those of control subjects. Mean+/-SEM maximum histamine release to 22E7 from basophils of control subjects and patients with CIU with and without autoantibodies was 38.5%+/-5.0%, 17.9%+/-6.0% (P =.01), and 1.0%+/-0.3% (P <.0001), respectively. Similar results were obtained with anti-IgE, which is dependent on and cross-links cell bound IgE, and 22E7, which directly cross-links the IgE receptor. The mean+/-SEM basophil counts for control subjects and patients with CIU without and with autoantibodies were 52+/-7, 34+/-9 (P =.04), and 5+/-1 (P <.0001) x 10(6) cells/L, respectively, and similar changes were found in measurements of total cellular histamine. CONCLUSION: Patients with autoantibodies have both markedly reduced basophil numbers and basophil histamine release to factors acting through Fc(epsilon)RI, which indicates either a residual pool of functionally distinct basophils or may be a consequence of desensitization of the Fc(epsilon)RI pathway.

Adult↗
PubMed1998

Intravenous immunoglobulin in autoimmune chronic urticaria.

Histamine releasing autoantibodies play a central role in the pathogenesis of chronic urticaria (CU) in approximately 30% of affected patients. We investigated the therapeutic effect of high-dose intravenous immunoglobulin (IVIG) on disease activity in patients with severe CU of autoimmune aetiology. Autoimmune urticaria was diagnosed by the development of a weal-and-flare reaction to the intradermal injection of autologous serum and by serum-induced histamine release from the basophil leucocytes of healthy donors in vitro. Ten patients with severe, autoimmune CU, poorly responsive to conventional treatment, were treated with IVIG 0.4 g/kg per day for 5 days. The outcome on cutaneous wealing and itch was monitored using urticaria activity scores, visual analogue scales and autologous intradermal serum tests. Clinical benefit was noted in nine of 10 patients: three patients continue in prolonged complete remissions (3 years follow-up), two had temporary complete remissions, and symptoms in four patients improved subsequent to treatment. There was significant improvement in the urticaria activity scores and visual analogue scores at 2 (P < 0.01) and 6 weeks (P < 0.01) post-IVIG compared with the baseline values (Wilcoxon matched pairs). The diminution in urticarial activity in the majority of patients corresponded with a reduced weal-and-flare response to the intradermal injection of autologous post-treatment serum compared with the pretreatment serum. Minor side-effects were common, but there were no serious or long-term adverse effects. IVIG represents a novel therapeutic option in selected patients with recalcitrant CU associated with histamine releasing autoantibodies.

Adult↗
PubMed1997

Flow cytometric analysis of basophil numbers in chronic urticaria: basopenia is related to serum histamine releasing activity.

BACKGROUND: Peripheral blood basophils are reduced in some chronic urticaria patients when counted with granule stains. Approximately 30% of patients with severe chronic urticaria have functional autoantibodies which release histamine from healthy donor basophils in vitro but the relationship between basophil numbers in vivo and serum histamine releasing activity has not been studied. OBJECTIVE: To determine the relationship between basophil numbers and serum basophil histamine releasing activity and to assess whether basophils are present, but undetectable, in peripheral blood with granule stains by using a new flow cytometric method based on surface immunophenotype. METHODS: Basophils were counted manually by a chamber method using a granule stain and by flow cytometry using dual staining with anti-IgE and anti-Fc epsilonRI in 25 chronic idiopathic urticaria patients and 25 healthy controls. Serum histamine releasing activity was assessed on healthy donor basophils in vitro and by the weal response to autologous serum skin testing in vivo (patients only). RESULTS: Basophils were significantly reduced in chronic urticaria by manual counting and flow cytometry. A subgroup of seven patients with in vitro histamine releasing activity showed a marked reduction or absence of basophils by both methods. There were no obvious distinguishing clinical characteristics between these patients and the others; six of them showed positive autologous serum skin-test responses. On comparing the two methods, the manual basophil counts were generally lower than flow cytometric counts. Agreement over the full range of values was not strong and therefore counts obtained by the two methods are not directly interchangeable. CONCLUSION: Basopenia in chronic idiopathic urticaria is associated with serum basophil histamine releasing activity in a subgroup of patients. The lack of granule and surface immunophenotype staining suggests a reduction in numbers rather than an inability to detect circulating degranulated cells by conventional counting methods.

Adolescent↗
PubMed1997

Transplantation of adult and paediatric horseshoe kidneys.

BACKGROUND: The incidence of horseshoe kidneys is between 1 in 300 and 1 in 1600. Horseshoe kidneys may be either transplanted into two recipients after division of the kidney, or used for en bloc transplantation into one recipient. METHODS: We report two cases of adult-to-child and child-to-adult transplantation of horseshoe kidneys. Embryology and associated abnormalities are outlined, and previous case reports reviewed. RESULTS: One transplant was successful and one transplant failed due to an unrecognized C peptide deficiency. CONCLUSIONS: Horseshoe kidneys are acceptable as donor organs in renal transplantation.

Adult↗
PubMed1996

Dermal mast cell activation by autoantibodies against the high affinity IgE receptor in chronic urticaria.

Previous studies identified autoantibodies against the IgE high affinity receptor alpha-chain, Fc epsilon RI alpha, in sera of selected patients with severe chronic idiopathic urticaria. We have now determined the incidence of anti-Fc epsilon RI alpha autoantibodies in a group of 163 patients. Intradermal injection of autologous serum caused skin reactions indicative of mast cell degranulation in 98 (60%) patients. Based on histamine release from IgE-sensitized and nonsensitized basophil leukocytes of healthy donors, we detected anti-Fc epsilon RI alpha autoantibodies in sera from 38 (23%) urticaria patients and evidence for anti-IgE antibodies in a further nine patients. The sera that released histamine from basophils induced histamine release (4-34%, n = 12) from mast cells in incubated skin slices. Protein-G affinity chromatography of sera demonstrated that mast cell histamine release was IgG-mediated. Preincubation of sera or the IgG fraction with a recombinant alpha-chain of Fc epsilon RI inhibited histamine release from mast cells and basophils. Further studies with the mouse anti-human Fc epsilon RI alpha antibody 29C6 showed that mast cells and basophils were similarly sensitive to IgG-mediated direct cross-linking of Fc epsilon RI, with 0.01-1.0 micrograms/ml 29C6 evoking histamine release in each case. These studies demonstrate that circulating levels of anti-Fc epsilon RI alpha autoantibodies mediate histamine release from skin mast cells in vitro and, taken together with in vivo evidence of mast cell degranulation following intradermal injection of autologous serum, support the concept that anti-Fc epsilon RI alpha autoantibodies are relevant to the pathogenesis of severe chronic urticaria in about 25% of patients.

Adolescent↗
PubMed1996

Australian multicentre evaluation of a new polyurethane vascular access graft.

BACKGROUND: A new three-layered cast polyurethane vascular access graft (Thoratec VAG) is the most recent addition to the list of materials used in the search for the perfect prosthetic graft material for haemodialysis vascular access. Despite its use in 23 countries, a clinical assessment has not been published. METHODS: An independent retrospective evaluation by questionnaire was obtained for 145 implantation procedures performed by 30 surgeons. RESULTS: Ninety-two per cent of procedures were performed for an acute need for vascular access and 73% had prior failed vascular access surgery. Patients were hospitalized for a median of 4 days and the graft was initially used at a median of 3 days. Median follow-up was 306 days. Thoratec VAG had a problem-free (primary) patency of 44.9% and a functional (secondary) patency 64.5% at 1 year. Major causes of graft loss were thrombosis (17%) and infection (11%). Intra-operative thrombosis was the only significant risk factor for subsequent thrombosis (P = 0.013). Infection was less in patients with antibiotic prophylaxis that included vancomycin (P = 0.02). CONCLUSION: The ability to use the graft soon after surgery is a major advance for patients who urgently need reliable medium to long-term haemodialysis access.

Arteriovenous Fistula↗