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.

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.

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.

Anti-NMDA receptor encephalitis with associated catatonia during pregnancy.

Anti-NMDA-R encephalitis has been described as a cause of acute psychosis in young females. It is rare during pregnancy. We describe a primigravida 32-year-old woman with acute onset psychosis during the first trimester. Eight weeks after becoming pregnant, the patient became psychotic with associated catatonia and autonomic disturbance. Serum anti-NMDA-R antibodies were found. She responded to plasma exchange. At caesarean section, a healthy baby boy was born and a benign mature cystic teratoma was removed from the left ovary. Catatonia associated with psychosis may occur in pregnancy secondary to anti-NMDA-R encephalitis. Prompt and aggressive treatment can lead to a good outcome for both baby and mother.

MRI assessment of changes in liver iron deposition post-venesection.

OBJECTIVE: The aim of this study was to determine if changes in hepatic iron content in patients with hemochromatosis pre- and post-venesection could be detected by changes in liver signal intensity with MRI. MATERIALS AND METHODS: The study was performed with institutional ethics approval and with informed consent. Gradient echo images were performed on 20 patients with hemochromatosis pre- and post-venesection and 10 control subjects: gradient echo T1-weighted in- and out-phases (4.54 (in)/2.27 (out), 167 [TE/TR], Flip 70°) and gradient echo T2* (5/18 [TE/TR], Flip 10°). The liver to muscle signal ratio was compared pre- and post-venesection. RESULTS: All MRI sequences showed significant correlation between the liver to muscle signal intensity ratio and the serum ferritin pre-venesection [r=-0.70, -0.65, -0.74, -0.72, in/out/T2*r/T2*, respectively]. There was a significant increase on all sequences in the liver to muscle signal intensity ratio post-venesection (p<0.001). The control group and patients post-venesection had almost identical liver to muscle signal intensity ratios. CONCLUSION: The reduction in liver signal intensity caused by iron excess in hemochromatosis returns to normal post-venesection. Measurement of liver to muscle signal intensity ratios may be a useful tool in assessing treatment response in iron overload states.

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.

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.

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.

Survey of medical students and junior house doctors on the effects of medical radiation: is medical education deficient?

BACKGROUND: We investigated the knowledge of ionising radiation among medical students and junior doctors in Ireland and assessed whether this knowledge improved with clinical experience. METHODS: A total of 269 subjects completed a questionnaire on the fundamentals of diagnostic imaging and patient doses. RESULTS: Overall knowledge was poor, 99% of subjects underestimated the dose of radiation involved in a barium enema, plain film of abdomen, lumbar spine X-ray and a PET scan. Almost 90% underestimated the dose of a CT abdomen/pelvis. 42% of subjects knew that PET involved ionising radiation while 27% thought that MRI did. There was a significant improvement in understanding after transition to a clinical environment, however, no further development. 1% had attended formal radiation protection courses. CONCLUSION: The knowledge of basic radiological procedures and patient doses was extremely limited. Current undergraduate teaching needs to be expanded and continued post-qualification to improve core understanding and facilitate safe practice.

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.

Percutaneous cholecystostomy--a safe option in the management of acute biliary sepsis in the elderly.

Percutaneous cholecystostomy (PC) has been used in the management of acute cholecystitis and biliary sepsis in patients with severe comorbidities where emergency cholecystectomy or open cholecystostomy are considered to carry prohibitive risks of mortality. We reviewed three consecutive cases of elderly patients with biliary sepsis presenting acutely to our unit who were managed successfully with this approach, and present herein these cases and a review of the literature.

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.

Magnetic resonance portal venography: use of fast-acquisition true FISP imaging in the detection of portal vein thrombosis.

AIM: To determine the accuracy of true fast imaging with steady-state precession (true FISP) in the diagnosis of portal vein thrombosis in patients with cirrhosis and compare it to contrast-enhanced three-dimensional (3D) magnetic resonance (MR) angiography, the reference standard. MATERIALS AND METHODS: Twenty-four consecutive patients with suspected portal venous thrombosis underwent contrast-enhanced 3D MR angiography and true FISP imaging of the portal vein. All patients had undergone at least one other imaging study, either computed tomography, (CT) or ultrasound. Both sets of MR images were evaluated for patency of the portal venous system and for image quality. RESULTS: Portal vein thrombosis was diagnosed in six of the 24 patients. Four patients with portal vein thrombosis were accurately diagnosed on the true FISP sequence. This sequence also accurately diagnosed the patency of the portal vein in 17 patients. However, the results were inconclusive in three patients. The image quality of the true FISP sequence of the three inconclusive patients was graded as either poor or fair. Of these three patients, contrast-enhanced 3D MR angiography confirmed portal vein thrombosis in two patients and portal vein stenosis in one patient. True FISP imaging had a sensitivity of 67% and a specificity of 100% for the diagnosis of portal vein thrombosis. CONCLUSION: The results of the present study show that the true FISP sequence is useful in diagnosing portal vein thrombosis. It could be employed as an adjunct to contrast-enhanced MR angiography in the severely debilitated patient where respiratory motion may degrade the images or in patients where the use of intravenous contrast medium is not possible due to poor venous access.

(18)FDG uptake during induction chemoradiation for oesophageal cancer fails to predict histomorphological tumour response.

To determine whether [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) could predict the pathological response in oesophageal cancer after only the first week of neoadjuvant chemoradiation. Thirty-two patients with localised oesophageal cancer had a pretreatment PET scan and a repeat after the first week of chemoradiation. The change in mean maximum standardised uptake value (SUV) and volume of metabolically active tissue (MTV) was compared with the tumour regression grade (TRG) in the final histology. Those who achieved a TRG of 1 and 2 were deemed responders and 3-5 nonresponders. In the responders (28%), the SUV fell from 12.6 (+/-6.3) to 8.1 (+/-2.9) after 1 week of chemoradiation (P=0.070). In nonresponders (72%), the results were 9.7 (+/-5.4) and 7.1 (+/-3.8), respectively (P=0.003). The MTV in responders fell from 36.6 (+/-22.7) to 22.3 (+/-10.4) cm(3) (P=0.180), while in nonresponders, this fell from 35.9 (+/-36.7) to 31.9 (+/-52.7) cm(3) (P=0.405). There were no significant differences between responders and nonresponders. The hypothesis that early repeat FDG-PET scanning may predict histomorphologic response was not proven. This may reflect an inflammatory effect of radiation that obscures tumour-specific metabolic changes at this time. This assessment may have limited application in predicting response to multimodal regimens for oesophageal cancer.

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.

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.