Measurement of Serum Immunoglobulins: A National Survey of Practice.

Aim To survey how serum immunoglobulins (IgG, IgA, IgM) are measured and reported across public hospitals in Ireland. Methods We developed a seven-point questionnaire to elicit the methodology, reporting and reference intervals of serum immunoglobulins. It was distributed electronically by email to sixteen laboratory managers of Irish public hospitals. Results A total of twelve questionnaires were completed. The test method was the same in each laboratory, whilst the analyser and source of the reference intervals varied. In some institutions, the reference interval differed within the adult age population and for sex. The IgG parameter contained the highest spread of results. The lower reference limit ranged 5.4-8.0 g/L, with a standard deviation of 0.81, and the upper reference limit ranged 14.9-18.2 g/L (SD 1.04). Conclusion Considerable variation exists in the reference intervals of serum immunoglobulins within different Irish public hospitals. This has important implications for users of the test, patients and referral patterns.

Linear IgA disease associated with ulcerative colitis: the role of surgery.

The association of linear IgA disease (LAD) with ulcerative colitis (UC) is well documented. One hypothesis for the association proposes immune exposure to autoantigens present in the colon, and subsequent targeting of these autoantigens in the skin. There are variable reports on the effect of bowel surgery on skin disease in such patients. We report a patient with LAD and UC who required colectomy to control her UC, but whose skin disease failed to resolve following surgery. A literature review revealed that in reported cases of this association, proctocolectomy has resulted in remission of skin disease in all cases where it has been performed, in contrast to variable results seen in cases where colectomy alone was performed.

Long-term activation of the pro-coagulant response after neoadjuvant chemoradiation and major cancer surgery.

BACKGROUND: The association between cancer, major surgery and venous thromboembolism (VTE) is well established. Multimodal therapy is increasingly being used as standard treatment for localised gastrointestinal cancer. The aim of this study was to examine the markers of pro-coagulation response and VTE risk in an exemplar multimodal model of pre-operative combination chemotherapy and radiation therapy, followed by complex cancer surgery. METHODS: Consecutive patients (n=36) with localised oesophageal cancer were studied at baseline after the first and second cycles of chemoradiation, and on post-operative days 1-28, and at 3, 6 and 9 months. Factors regulating the pro- and anti-coagulant response, as well as pro-inflammatory markers including NFkappaB activation in peripheral blood mononuclear cells, were examined. All patients received enoxaparin 40 mg s.c. postoperatively up to discharge, and underwent pulmonary CT-pulmonary angiography and venography on day 10 postoperatively. RESULTS: Four (11%) non-fatal thromboembolic events were documented, all after hospital discharge. Neoadjuvant therapy before surgery activated factor VIII (FVIII) and pro-inflammatory NFkappaB, and increased D-dimers, pro-thrombin fragment 1+2 (F1+2) and the thrombin-anti-thrombin complex (TAT). Surgery significantly (P<0.05) increased pro-thrombin time (PT), activated partial thromboplastin time, fibrinogen, D-dimers, TAT, F1+2 and FVIII up to 6 months. CONCLUSION: These data highlight the linked pro-coagulant and immunoinflammatory pathways in the multimodal management of oesophageal cancer, and suggest that the duration of current standard thromboprophylaxis regimens warrants further study.

Associations between leptin and adiponectin receptor upregulation, visceral obesity and tumour stage in oesophageal and junctional adenocarcinoma.

BACKGROUND: Obesity is associated with oesophageal adenocarcinoma, but mechanisms linking fat and carcinogenesis remain poorly understood. Altered circulating adipocytokines may be important. This study aimed to identify pathways through which visceral fat impacts on tumour biology. METHODS: Seventy-five patients with oesophageal adenocarcinoma underwent anthropometric and radiological assessment of obesity. Expression of leptin receptor (ObR) and adiponectin receptors 1 and 2 (AdipR1, AdipR2) was quantified by real-time reverse transcriptase-polymerase chain reaction. The human oesophageal adenocarcinoma cell line OE33 was used as the calibrator sample. RESULTS: Ninety-one per cent of tumours expressed ObR, 95 per cent expressed AdipR1 and 100 per cent expressed AdipR2. Relative expression of ObR was upregulated in 67 per cent, and AdipR1 and AdipR2 were downregulated in 55 and 68 per cent respectively, relative to the calibrator sample. Upregulated ObR and AdipR2 expression was significantly associated with anthropometric and radiological measures of obesity. Upregulated ObR was associated with advanced tumour and node category (P = 0.036 and P = 0.025 respectively), and upregulated AdipR2 with nodal involvement (P = 0.037). CONCLUSION: Obesity is associated with upregulated ObR and AdipR2 expression in oesophageal adenocarcinoma. The association of ObR and AdipR2 with tumour stage suggest that pathways involving adipocytokines affect tumour biology.

Association of visceral adiposity with oesophageal and junctional adenocarcinomas.

BACKGROUND: Obesity is associated with an increased incidence of oesophageal and oesophagogastric junction adenocarcinoma, in particular Siewert types I and II. This study compared abdominal fat composition in patients with oesophageal/junctional adenocarcinoma with that in patients with oesophageal squamous cell carcinoma and gastric adenocarcinoma, and in controls. METHOD: In total, 194 patients (110 with oesophageal/junctional adenocarcinoma, 38 with gastric adenocarcinoma and 46 with oesophageal squamous cell carcinoma) and 90 matched control subjects were recruited. The abdominal fat area was assessed using computed tomography (CT), and the total fat area (TFA), visceral fat area (VFA) and subcutaneous fat area (SFA) were calculated. RESULTS: Patients with oesophageal/junctional adenocarcinoma had significantly higher TFA and VFA values compared with controls (both P < 0.001), patients with gastric adenocarcinoma (P = 0.013 and P = 0.006 respectively) and patients with oesophageal squamous cell carcinoma (both P < 0.001). For junctional tumours, the highest TFA and VFA values were seen in patients with Siewert type I tumours (respectively P = 0.041 and P = 0.033 versus type III; P = 0.332 and P = 0.152 versus type II). CONCLUSION: Patients with oesophageal/junctional adenocarcinoma, in particular oesophageal and Siewert type I junctional tumours, have greater CT-defined visceral adiposity than patients with gastric adenocarcinoma or oesophageal squamous cell carcinoma, or controls.

Analysis of waiting times on Irish renal transplant list.

INTRODUCTION: A number of recipient variables have been identified which influence waiting list times for a renal allograft. The aim of this study was to evaluate these factors in the Irish population. METHODS: We examined patients accepted onto the transplant list from January 1, 2000 until December 31, 2005. Inclusion criteria were adults listed for kidney only, deceased donor transplants. We included patients previously transplanted. Patients were censored, but still included in the analysis, if they died while on the list, permanently withdrew from the list or if they were not transplanted at the time of the study. RESULTS: There were a total of 984 patients accepted onto the waiting list during the study period, of which 745 of these were transplanted. Factors significantly associated with longer waiting times included age above 50 yr, blood group O and high peak panel reactive antibodies level. Gender and patient body mass index were not associated with longer waiting times. CONCLUSION: We have identified factors associated with a longer waiting time on the Irish cadaveric renal transplant list. This information can help our patients make informed decisions regarding likely waiting times and the merits of living related transplantation.

Clinical Immunology Review Series: an approach to the patient with recurrent orogenital ulceration, including Behçet's syndrome.

Patients presenting with recurrent orogenital ulcers may have complex aphthosis, Behçet's disease, secondary complex aphthosis (e.g. Reiter's syndrome, Crohn's disease, cyclical neutropenia) or non-aphthous disease (including bullous disorders, erythema multiforme, erosive lichen planus). Behçet's syndrome is a multi-system vasculitis of unknown aetiology for which there is no diagnostic test. Diagnosis is based on agreed clinical criteria that require recurrent oral ulcers and two of the following: recurrent genital ulcers, ocular inflammation, defined skin lesions and pathergy. The condition can present with a variety of symptoms, hence a high index of suspicion is necessary. The most common presentation is with recurrent mouth ulcers, often with genital ulcers; however, it may take some years before diagnostic criteria are met. All patients with idiopathic orogenital ulcers should be kept under review, with periodic focused assessment to detect evolution into Behçet's disease. There is often a delay of several years between patients fulfilling diagnostic criteria and a diagnosis being made, which may contribute to the morbidity of this condition. Despite considerable research effort, the aetiology and pathogenesis of this condition remains enigmatic.

Sweet's syndrome in association with common variable immunodeficiency.

Sweet's syndrome (SS), a rare reactive neutrophilic dermatosis, has been reported to occur in association with a variety of systemic disorders, categorized by von den Diesch into idiopathic, paraneoplastic, pregnancy and parainflammatory subgroups. The parainflammatory group has been well defined, and includes a wide spectrum of infectious triggers and disorders of immune dysregulation. To date, however, no cases of SS have been described in the context of common variable immunodeficiency (CVID). We report a case of paediatric-onset SS, previously reported as idiopathic, with a subsequent diagnosis of CVID.

FDG-PET scanning in the management of cancer of the oesophagus and oesophagogastric junction: early experience with 100 consecutive cases.

BACKGROUND: The aim was to evaluate the impact of FDG-PET scan on tumour staging and management decisions in oesophageal cancer. METHODS: One-hundred consecutive patients referred for consideration of surgery underwent a whole body FDG-PET scan in addition to CT imaging. RESULTS: Based on CT scan, a curative approach could be considered in 62 patients. The PET scan altered regional nodal (N) staging in 16 patients overall, but did not alter management decisions. Metastatic status (M) was increased in 14 patients, with altered management in 10/62 (16%). Nine were downstaged, with management changed in 3/38 (8%). Seventeen patients underwent 19 additional tests to clarify findings on PET, in 15 patients (88%) the tests revealed no pathology. CONCLUSION: FDG-PET alters M stage in 23% of patients and may impact on surgical decision-making. The spurious investigations and cost of the high false-positive rate of further tests is of concern.

The prevalence of antiphospholipid antibody syndrome among systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by excess autoantibody production. It typically affects women of childbearing age. Antiphospholipid antibody syndrome (APLAs) is associated with serious co-morbidity to mother and child characterized by recurrent vascular thrombosis and/or pregnancy associated morbidity. We reviewed SLE patients attending a specialist connective tissue disease clinic both to assess the occurrence of APLAs and its clinical presentations and to audit the effectiveness of screening for APL antibodies in a specialist clinic. 204 patients attended the newly established connective tissue disease outpatient clinic over a twenty-seven month period; 42 (34 female, 8 male) with a diagnosis of SLE. Ten patients (24%), eight female and 2 male with a median age of 38.5 years (range 20 to 64 years) fulfilled the ACR criteria for secondary APLAs (Table 2). The commonest clinical presentation was pulmonary embolus (five patients). Overall 37 patients (88%) with SLE were screened for APLAs during the study period: 94% of females and 62.5% of males were screened (for anticardiolipin antibodies, lupus anticoagulant or both), 27% had evidence of APLAs, 24% had positive antibodies but were asymptomatic. There is a significant occurrence of APLAs among SLE patients. Given the important clinical implications of this disorder including substantial risk of fetal loss and patient morbidity or mortality, routine screening of all SLE patients for APL antibodies is recommended.

Identification of the novel B*27:144 allele in an Irish Individual.

The sequence of HLA-B*27:144 differs from HLA-B*27:05:02 by one nucleotide change at position 506.

Human leukocyte antigen compatibility in heart transplantation: evidence for a differential role of HLA matching on short- and medium-term patient survival.

BACKGROUND: Studies of the influence of human leukocyte antigen (HLA) matching on cardiac transplant outcome have proved inconclusive, mainly due to the lack of well-matched grafts. However, a growing number of studies report improved clinical course and patient survival in cases with increased HLA compatibility. Opelz et al. believe these benefits justify the introduction of prospective HLA-matching strategies. METHODS: We performed univariate and multivariate analyses to examine the short- and medium-term influence of HLA matching on 556 consecutive primary heart transplants performed at a single center between 1983 and 1994. Overall graft survival at 1, 3, and 5 years was 80%, 74%, and 67% respectively. Sixteen (2.9%) grafts failed within 5 days and were not considered in the analysis of the HLA matching and graft survival data. RESULTS: Complete HLA-A, -B, and -DR typing data were available on 477 transplant pairs. The results demonstrate a 12% 1-year survival advantage for 31 patients with zero to two HLA antigen mismatches compared with three to six mismatches. The influence of each individual locus was 6.1%, 8.4%, and 5.4% for zero HLA-A, -B, and -DR mismatches, respectively, compared with two mismatches. However, when outcome from 1 to 5 years was considered, analysis of the role of each locus revealed marked differences. HLAA-matched grafts (n=45) had a 24% lower survival rate compared with two-antigen-mismatched grafts (n=148; 88% [SE 3.1] vs. 64% [SE 8.2], respectively; P=0.009). Furthermore, 34% of HLA-A-matched grafts failed between 1 and 5 years, compared with only 5% of HLA-B-matched grafts (P=0.013). CONCLUSIONS: These data suggest that although HLA matching is effective at reducing acute graft loss, in the longer term, HLA-A matching may impair survival. HLA-A may serve as a restriction element for indirect presentation of allopeptides or tissue-specific minor histocompatibility antigens, facilitating chronic graft loss. Therefore, we advocate a differential role for HLA matching over two epochs. A blanket approach to prospective matching for heart transplants may be premature for optimal long-term survival.

Effects of single dose compared with three days' prednisolone treatment of healthy volunteers: contrasting effects on circulating lymphocyte subsets.

AIMS: To investigate the effects of longer term corticosteroid treatment on circulating lymphocyte subsets. METHODS: Prednisolone (20 mg daily) was given to 12 healthy volunteers in a single morning dose for three days. Circulating lymphocyte subsets were measured by flow cytometry after whole blood lysis. RESULTS: Seven hours after the first dose of prednisolone there was a significant fall in absolute numbers of lymphocytes, T cells, CD4+ and CD8+ cells, and B cells. The percentage of T cells fell significantly, due to a fall in percentage of CD4+ cells. In contrast to the seven hour findings, at 72 hours there was a significant rise in absolute numbers of lymphocytes, T cells, CD4+, CD8+, and B cells. This trend was already apparent by 24 hours. The percentage of CD4+ cells was significantly raised at 72 hours, while that of CD8+ cells had fallen significantly. The percentage of natural killer cells had fallen at 72 hours; that of B cells remained increased at 72 hours. CONCLUSIONS: These findings show that corticosteroid treatment causes significant changes in lymphocyte subsets, and that such changes must be considered when designing studies of lymphocyte subsets during illness.

Staging of pancreatic cancer before and after neoadjuvant chemoradiation.

Neoadjuvant chemoradiation therapy is used at many institutions for treatment of localized adenocarcinoma of the pancreas. Accurate staging before neoadjuvant therapy identifies patients with distant metastatic disease, and restaging after neoadjuvant therapy selects patients for laparotomy and attempted resection. The aims of this study were to (1) determine the utility of staging laparoscopy in candidates for neoadjuvant therapy and (2) evaluate the accuracy of restaging CT following chemoradiation. Staging laparoscopy was performed in 98 patients with radiographically potentially resectable (no evidence of arterial abutment or venous occlusion) or locally advanced (arterial abutment or venous occlusion) adenocarcinoma of the pancreas. Unsuspected distant metastasis was identified in 8 (18%) of 45 patients with potentially resectable tumors and 13 (24%) of 55 patients with locally advanced tumors by CT. Neoadjuvant chemoradiation therapy and restaging CT were completed in a total of 103 patients. Thirty-three patients with potentially resectable tumors by restaging CT underwent surgical exploration and resections were performed in 27 (82%). Eleven (22%) of 49 patients with locally advanced tumors by restaging CT were resected, with negative margins in 55%; the tumors in these 11 patients had been considered locally advanced because of arterial involvement on restaging CT. Staging laparoscopy is useful for the exclusion of patients with unsuspected metastatic disease from aggressive neoadjuvant chemoradiation protocols. Following neoadjuvant chemoradiation, restaging CT guides the selection of patients for laparotomy but may overestimate unresectability to a greater extent than does prechemoradiation CT.

An unusual case of Behçet's syndrome: triggered by typhoid vaccination?

A case of Behçet's syndrome in a 32-year-old woman occurring shortly after her third vaccination against typhoid fever is described. Scleritis and pyoderma gangrenosum were unusual manifestations of BS that occurred in this case. Treatment benefit was provided by mycophenolate mofetil and etanercept. As bacterial antigens have been proposed as potential triggers for the onset of BS, it is possible that the syndrome was precipitated by typhoid vaccination in this patient.

Skin reactivity to atypical mycobacteria in cystic fibrosis.

Atypical mycobacterial disease has been described in a small number of patients with cystic fibrosis. Apart from one uncontrolled study, there is little information regarding atypical mycobacterial skin reactivity in this group of patients. We evaluated delayed cutaneous hypersensitivity to purified extracts of Mycobacterium avium, Mycobacterium intracellular, Mycobacterium kansasii and Mycobacterium bovis in 23 healthy controls and 43 adult and adolescent patients with cystic fibrosis. Fifteen of the cystic fibrosis group were receiving regular corticosteroids. Additionally, direct smear examination and Lowenstein Jensen culture were performed on sputum from the cystic fibrosis group. The prevalence of positive skin reactions was similar in the group with cystic fibrosis (30%) and in the control group (57%). Subgroup analysis showed that those cystic fibrosis patients receiving corticosteroids had a markedly lower prevalence of positive reactions (7%) compared to controls (P less than 0.01). When this subgroup was excluded from analysis, the prevalence of positive skin reactions among patients with cystic fibrosis was 43%. In the prospective sputum bacteriology study, one of the 43 cases grew Mycobacterium avium-intracellulare and had clinical and radiological evidence of this disease. Of note, this patient showed positive skin tests to all four mycobacterial species tested. Our data show no difference in the prevalence rate of positive skin reactions to atypical mycobacterial antigens between a control population and an adult cystic fibrosis population. In addition, the predictive value of skin testing is low in cystic fibrosis due to the high prevalence of cross-reactivity between different mycobacterial species and the high prevalence of anergy among those patients with advanced disease receiving treatment with corticosteroids.

Computed tomography and magnetic resonance imaging in the assessment of pancreatic disease.

Significant technical advances have occurred in both computed tomography (CT) and magnetic resonance (MR) imaging that have resulted in improved visualization of the pancreas by both techniques. In this article we will consider the advances in both modalities and consider the relative roles of each in imaging the spectrum of pancreatic pathology.

Use of time during body computed tomography scanning in a tertiary care teaching hospital: focus on patient throughput.

RATIONALE AND OBJECTIVES: To control costs, it is increasingly important to make efficient use of imaging technology. We sought to determine and analyze the time required to complete each step of a body computed tomography (CT) scan, focusing on factors that influence patient throughput. METHODS: Over 4 weeks, we prospectively monitored the time required for each step of a body CT scan (i.e., image time, check time, and clear time). Covariate data were collected by patient status: outpatient, inpatient, emergency department (ED), and intensive care unit (ICU); work shift; and radiologist training level (junior resident, senior resident, fellow, and attending). Technologists also predicted whether repeat images would be requested by the radiologist. RESULTS: Three hundred eighty CT examinations were studied: 277 for outpatients, 90 for inpatients, 9 for ED patients, and 4 for ICU patients. The mean total examination time was 44.7 min (mean image time = 33.1 min, mean review time = 8.2 min, and mean clear time = 3.4 min), which did not differ significantly with patient status. A second opinion was sought from a consultant radiologist on the scans of 44 patients. Consultation was requested significantly more frequently (1) by junior residents than by senior residents or fellows and (2) for ED and ICU patients (22% and 50%, respectively) than in outpatients and inpatients (10% and 14%, respectively). Repeat images were obtained from 75 patients, and this was not significantly related to patient status, scan type, or radiologist training level. When the technologist predicted that no repeat images were needed, this prediction agreed with the radiologist in 86% of the cases. When the technologist predicted that repeat images were necessary, this prediction agreed with the radiologist in 56% of the cases. CONCLUSION: Reviewing scans before the patient leaves the CT suite adds considerably to the total time required to complete a scan, particularly if junior residents review scans. If technologists obtain repeat images at their discretion, time would be saved.

Vaccines for preventing infection with Pseudomonas aeruginosa in people with cystic fibrosis.

OBJECTIVES: To assess the effectiveness of vaccination against Pseudomonas aeruginosa in patients with cystic fibrosis. SEARCH STRATEGY: The Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All randomised or pseudorandomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: We planned to assess the following outcomes: time to infection with Pseudomonas aeruginosa, pulmonary function, body mass index, Schwachman score, frequency of pulmonary infective exacerbations, days of antibiotic usage, days unable to carry out normal daily activities, adverse events, mortality, antibody levels to Pseudomonas aeruginosa and T cell proliferation and cytokine production in response to Pseudomonas aeruginosa. MAIN RESULTS: One trial which included 17 vaccinated patients, with follow up reported to 10 years met the inclusion criteria. Finding only a single trial, and the lack of information on our predefined outcomes limited analysis. REVIEWER'S CONCLUSIONS: There is a paucity of randomised controlled trials assessing the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. Increased understanding of modulation of the immune response by vaccination has led to the development of alternative vaccines. We suggest that there is an urgent need for newer vaccines to be evaluated in adequately-powered, multicentre randomised controlled trials examining clinically relevant end-points in addition to immunological variables. Such a trial should assess effectiveness over several years, and include follow-up of vaccinees who become colonised with Pseudomonas aeruginosa.