A comparison of antibodies to tissue transglutaminase with conventional serological tests in the diagnosis of coeliac disease

BACKGROUND: Tissue transglutaminase is now recognized as the autoantigen for antiendomysial antibodies. Antibodies to tissue transglutaminase have been proposed as a valuable test for coeliac disease. OBJECTIVE: To determine the value of antibodies to tissue transglutaminase in the diagnosis of coeliac disease in our outpatient population. METHODS: Patients who underwent serological tests for coeliac disease during the first 18 months of the tissue transglutaminase antibody assay were retrospectively identified from the regional serology laboratory database. Patients' symptoms were noted, along with serological results and duodenal histology in those patients who underwent duodenal biopsy.RESULTS In total, 586 patients were identified as having been serologically tested for coeliac disease, of whom 92 patients (33 men; mean age 51.7 years) had been followed up with duodenal biopsies. Of these 92 patients, 29 (31%; 14 men; mean age 52.5 years) had histological features of coeliac disease. The 63 patients with normal histology (19 men; mean age 51.8 years) acted as controls. Weight loss was more frequent in coeliac disease patients compared to controls (7 vs 5; P = 0.04) whereas the frequency of anaemia (P = 0.85) and diarrhoea (P = 0.74) did not differ significantly between the two groups. The sensitivity and specificity of tissue transglutaminase antibodies (86%; 84%) were compared to those for antiendomysial antibodies (90%; 98%) and antigliadin antibodies (76%; 79%). CONCLUSIONS: The diagnostic value of tissue transglutaminase antibodies was intermediate between that of antiendomysial antibodies and antigliadin antibodies. However, duodenal biopsy remains the gold standard diagnostic test for coeliac disease.     

Updated model of group A Streptococcus M proteins based on a comprehensive worldwide study

Group A Streptococcus (GAS) M protein is an important virulence factor and potential vaccine antigen, and constitutes the basis for strain typing (emm-typing). Although >200 emm-types are characterized, structural data were obtained from only a limited number of emm-types. We aim to evaluate the sequence diversity of near-full-length M proteins from worldwide sources and analyse their structure, sequence conservation and classification. GAS isolates recovered from throughout the world during the last two decades underwent emm-typing and complete emm gene sequencing. Predicted amino acid sequence analyses, secondary structure predictions and vaccine epitope mapping were performed using MUSCLE and Geneious software. A total of 1086 isolates from 31 countries were analysed, representing 175 emm-types. emm-type is predictive of the whole protein structure, independent of geographical origin or clinical association. Findings of an emm-type paired with multiple, highly divergent central regions were not observed. M protein sequence length, the presence or absence of sequence repeats and predicted secondary structure were assessed in the context of the latest vaccine developments. Based on these global data, the M6 protein model is updated to a three representative M protein (M5, M80 and M77) model, to aid in epidemiological analysis, vaccine development and M protein-related pathogenesis studies.     

Magnitude and time course of changes in maximal oxygen uptake in response to distinct regimens of chronic interval training in sedentary women

Purpose

This study aimed to compare changes in maximal oxygen uptake (VO_2max) in response to two regimens of chronic interval training.

Methods

Twenty healthy sedentary women (mean ± SD age and VO_2max = 23.0 ± 5.7 years and 30.1 ± 4.4 mL kg^?1 min^?1, respectively) were randomized to complete 12 weeks of one of two interval training regimes, while an additional seven women served as controls. Training was performed 3 days week^?1 on a cycle ergometer and consisted of 6–10 bouts of 1 min duration at lower (60–80 % W _max = LO, n = 10) or more intense (80–90 % W _max = HI, n = 10) workloads separated by a brief recovery. Every 3 weeks, measures of VO_2max and W _max were repeated to assign new training intensities. Changes in blood pressure and body composition were also examined.

Results

Data revealed significant (p < 0.001) improvements in VO_2max in LO (22.3 ± 6.9 %) and HI (21.9 ± 11.6 %) that were similar (p > 0.05) between groups. Approximately 60 % of the increase in VO_2max in HI was observed in the initial 3 weeks, compared to only 20 % in LO. No change (p > 0.05) in body weight or body composition was revealed in response to training. Results demonstrate that a relatively prolonged regimen of moderate or more intense interval training induces similar improvements in cardiorespiratory fitness, although HI induced greater increases in VO_2max early on in training than LO. Completion of more intense interval training may be an effective means to expedite increases in VO₂max soon after initiation of exercise training.     

The relationship between lymphovascular invasion and angiogenesis,hormone receptors,cell proliferation and survival in patients with primary operable invasive ductal breast cancer

Background

Several well-established tumour prognostic factors are used to guide the clinical management of patients with breast cancer. Lymphovascular invasion and angiogenesis have also been reported to have some promise as prognostic factors. The aim of the present study was to examine the prognostic value of tumour lymphovascular invasion and microvessel density compared with that of established prognostic factors in invasive ductal breast cancer.

Methods

In addition to hormone receptor status and Ki-67 proliferative activity, lymphovascular invasion and microvessel density and their relationship with survival were examined in patients with invasive ductal breast cancer. Full sections and tissue microarrays (n?=?384 patients) were utilised to assess these factors and were scored by appropriate methods.

Results

On univariate analysis tumour size (P?<?0.05), lymph node involvement (P?<?0.01), lymphovascular invasion (P?<?0.05), microvessel density (P?<?0.05) and local- regional treatment (P?<?0.01) were associated with poorer survival in ER negative tumours. On multivariate analysis in ER negative tumours lymph node involvement (P?<?0.01) and local- regional treatment (P?<?0.05) were independently associated with poorer cancer-specific survival. On univariate analysis tumour grade (P?<?0.05), lymph node involvement (P?<?0.001), HER-2 (P?<?0.05), Ki-67 (P?<?0.01) and lymphovascular invasion (P?<?0.001) were associated with poorer survival in ER positive tumours. On multivariate analysis lymph node involvement (P?<?0.001), Ki-67 (P?<?0.001) and lymphovascular invasion (P?<?0.05) were independently associated with poorer cancer-specific survival in ER positive tumours.

Conclusion

Lymphovascular invasion but not microvessel density was independently associated with poorer survival in patients with ER positive but not ER negative invasive ductal breast cancer.

     

Systematic review of enhanced recovery after gastro-oesophageal cancer surgery

Introduction

Fast track methodology or enhanced recovery schemes have gained increasing popularity in perioperative care. While evidence is strong for colorectal surgery, its importance in gastric and oesophageal surgery has yet to be established. This article reviews the evidence of enhanced recovery schemes on outcome for this type of surgery.

Methods

A systematic literature search was conducted up to March 2014. Studies were retrieved and analysed using predetermined criteria.

Results

From 34 articles reviewed, 18 eligible studies were identified: 7 on gastric and 11 on oesophageal resection. Three randomised controlled trials, five case-controlled studies and ten case series were identified. The reported protocols included changes to each stage of the patient journey from pre to postoperative care. The specific focus following oesophageal resections was on early mobilisation, a reduction in intensive care unit stay, early drain removal and early (or no) contrast swallow studies. Following gastric resections, the emphasis was on reducing epidural anaesthesia along with re-establishing oral intake in the first three postoperative days and early removal of nasogastric tubes.In the papers reviewed, mortality rates following fast track surgery were 0.8% (9/1,075) for oesophageal resection and 0% (0/329) for gastric resection. The reported morbidity rate was 16.5% (54/329) following gastric resection and 38.6% (396/1,075) following oesophageal resection. Length of stay was reduced in both groups compared with conventional recovery groups in comparative studies.

Conclusions

The evidence for enhanced recovery schemes following gastric and oesophageal resection is weak, with only three (low volume) published randomised controlled trials. However, the enhanced recovery approach appears safe and may be associated with a reduction in length of stay.     

Types and Number of Traumas Associated With Suicidal Ideation and Suicide Attempts in PTSD: Findings From a U.S. Nationally Representative Sample

Posttraumatic stress disorder (PTSD) is associated with suicidal ideation and suicide attempt; however, research has largely focused on specific samples and a limited range of traumas. We examined suicidal ideation and suicide attempt relating to 27 traumas within a nationally representative U.S. sample of individuals with PTSD. Data were from the National Epidemiologic Survey of Alcohol and Related Conditions (N = 34,653). Participants were assessed for lifetime PTSD and trauma history, suicidal ideation, and suicide attempt. We calculated the proportion of individuals reporting suicidal ideation or suicide attempt for each trauma and for the number of unique traumas experienced. Most traumas were associated with greater suicidal ideation and suicide attempt in individuals with PTSD compared to individuals with no lifetime trauma or with lifetime trauma but no PTSD. Childhood maltreatment, assaultive violence, and peacekeeping traumas had the highest rates of suicidal ideation (49.1% to 51.9%) and suicide attempt (22.8% to 36.9%). There was substantial variation in rates of suicidal ideation and suicide attempt for war and terrorism‐related traumas. Multiple traumas increased suicidality, such that each additional trauma was associated with an increase of 20.1% in rate of suicidal ideation and 38.9% in rate of suicide attempts. Rates of suicidal ideation and suicide attempts varied markedly by trauma type and number of traumas, and these factors may be important in assessing and managing suicidality in individuals with PTSD.     

The role of antiplatelet autoantibody assays in the diagnosis of immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is a disorder almost always manifested by antibody-induced thrombocytopenia. In 1987, two clinically useful antigen-specific assays were reported, the immunobead assay and the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay. These two assays and their variations give similar results and can measure both platelet-associated and plasma antibodies. Three prospective studies have reported assay results with sensitivities ranging from 49% to 66% and specificities ranging from 78% to 93%. Most antibodies react with either platelet glycoprotein (GP) IIb/IIIa or GPIb/IX. Recent evidence suggests that antiplatelet antibody assays may also be useful in predicting disease prognosis. Rare ITP patients have bleeding with normal or near-normal platelet counts, a prolonged bleeding time, and aggregation abnormalities due to autoantibodies that affect platelet function. Incubation of patient plasma, IgG or eluate with normal platelet-rich plasma reproduces the patient's aggregation abnormalities.     

Extracellular matrix of cultured bovine aortic endothelial cells contains functionally active type 1 plasminogen activator inhibitor

The extracellular matrix (ECM) of cultured bovine aortic endothelial cells (BAEs) was analyzed by immunoblotting and reverse fibrin autography and shown to contain type 1 plasminogen activator inhibitor (PAI-1). Most PAI-1 in the ECM formed complexes with exogenously added tissue-type plasminogen activator (tPA), demonstrating that this PAI-1 was functionally active. The resulting tPA/PAI-1 complexes were recovered in the reaction solution, indicating that the PAI-1 in such complexes no longer bound to ECM. The PAI-1 could not be removed by incubating ECM in high salt (2 mol/L NaCl), sugars (1 mol/L galactose, 1 mol/L mannose), glycosaminoglycans (10 mmol/L heparin, 10 mmol/L dermatan sulfate), or epsilon-aminocaproic acid (0.1 mol/L). However, PAI-1 could be extracted from ECM by treatment with either arginine (0.5 mol/L) or potassium thiocyanate (2 mol/L), or by incubation under acidic conditions (pH 2.5). ECM depleted of PAI-1 by acid extraction was able to bind both the active and latent forms of PAI-1. In this instance, most of the bound PAI-1 did not form complexes with tPA, indicating that the latent form was not activated as a consequence of binding to ECM. Although the PAI-1 activity in conditioned medium decayed with a half-life (t 1/2) of less than 3 hours, the t 1/2 of ECM- associated PAI-1 was greater than 24 hours. These data suggest that PAI- 1 is produced by cultured BAEs in an active form and is then either released into the medium where it is rapidly inactivated or into the subendothelium where it binds to ECM. The specific binding of PAI-1 to ECM protects it from this inactivation.     

Effectiveness of methyl-GAG (methylglyoxal-bis[guanylhydrazone]) in patients with advanced malignant lymphoma

We treated 51 patients with advanced malignant lymphoma refractory to conventional therapy with methyl-glyoxal-bis(guanylhydrazone) (methyl- GAG) at doses ranging from 400 to 800 mg/sq m. Therapy was started on a weekly schedule and was switched to every other week in responding patients at the onset of toxicity. Partial responses were observed in 6 of 13 evaluable patients with Hodgkin's disease (46%), 5 of 10 patients with diffuse poorly differentiated lymphocytic lymphoma (50%), 2 of 4 patients with nodular poorly differentiated lymphocytic lymphoma (50%), and 3 of 13 patients with diffuse histiocytic lymphoma (23%). Two of six patients with mycosis fungoides showed objective improvement in cutaneous disease. Toxicity was generally mild and included muscular weakness, myalgia, mucositis, and diarrhea; two patients developed bronchospasm following drug infusions. We conclude that methyl-GAG has major antitumor activity when administered on this schedule to patients with advanced malignant lymphoma. The low degree of toxicity, unique mechanism of action, and minimal myelosuppressive effects suggest that methyl-GAG will prove useful in future trials of combination chemotherapy regimens for the treatment of lymphoma.