No change in hemoglobin mass after 40 days of physical activity in previously untrained adults.

A high hemoglobin mass (Hb(mass)) is associated with a high maximum aerobic power (VO(2max)), however, the extent to which Hb(mass) is influenced by training is currently unclear. Accordingly, this study monitored changes in Hb(mass) and VO(2max) in 12 previously untrained adults (aged 18-25 years) following 40 days of regular physical activity. Hb(mass) and VO(2max) were assessed at the start and end of a 40-day physical activity program, which comprised of approximately 40 min of daily, moderate-intensity physical activity. Relative VO(2max) increased by 11.3%, yet there was no significant change in relative Hb(mass) (1.7%) and body mass (0.2%) during the 40-day period. There was a significant correlation between Hb(mass) and VO(2max) at the start of the study (r=0.58, P=0.05), but not between the change in relative VO(2max) and the change in relative Hb(mass) (r=-0.07, P=0.83). Our results support the concept of relative stability in Hb(mass) with approximately 1 month of moderate-intensity physical activity suggesting that Hb(mass) may be used for talent identification and possibly for anti-doping purposes.

Meta-analysis: deamidated gliadin peptide antibody and tissue transglutaminase antibody compared as screening tests for coeliac disease.

BACKGROUND: Following the appreciation of the importance of gliadin deamidation in the immunopathogenesis of coeliac disease, diagnostic tests based on antibodies to deamidated gliadin peptides have been developed and shown to have high sensitivity and specificity. AIM: To compare the performance of the deamidated gliadin peptides antibody test with the current standard, the tissue transglutaminase antibody test, through a meta-analysis of published studies. METHODS: Databases from 1998 to 2008 were searched for relevant studies. These were assessed for methodological quality and standard statistical tests were applied to compare particularly the sensitivity and specificity of the two tests for the diagnosis of coeliac disease. RESULTS: Most studies had methodological flaws, especially ascertainment bias. The pooled sensitivities for the deamidated gliadin peptides antibody and tissue transglutaminase antibody tests were 87.8% (95% CI, 85.6-89.9) and 93.0% (95% CI, 91.2-94.5) respectively and the pooled specificities were 94.1% (95% CI, 92.5-95.5) and 96.5% (95% CI, 95.2-97.5) respectively. CONCLUSION: Although both tests perform well, the tissue transglutaminase antibody test outperforms the deamidated gliadin peptides antibody test and remains the preferred serological test for the diagnosis and/or exclusion of coeliac disease.

No increase in risk of fracture, malignancy or mortality in dermatitis herpetiformis: a cohort study.

BACKGROUND: Dermatitis herpetiformis forms part of the same spectrum of gluten-sensitive disorders as coeliac disease yet may have different risks of morbidity and mortality. AIMS: To quantify the risks of fracture, malignancy and mortality in people with dermatitis herpetiformis compared with the general population. METHODS: Using the General Practice Research Database, we identified 846 people with dermatitis herpetiformis and 4225 age-, gender- and practice-matched controls. We used Cox regression to estimate hazard ratios. RESULTS: Comparing people with dermatitis herpetiformis to the general population, the overall hazard ratio for any fracture was 1.1 (95% CI: 0.77-1.52). The overall hazard ratio for any malignancy was 1.0 (95% CI: 0.73-1.49); there was no increased risk of gastrointestinal (HR: 1.6; 95% CI: 0.67-3.67) or lymphoproliferative cancers (HR: 1.6; 95% CI: 0.44-6.06). A reduction in risk of breast cancer was not statistically significant (HR: 0.19; 95% CI: 0.03-1.39). The hazard ratio for all-cause mortality was 0.93 (95% CI: 0.70-1.23). CONCLUSIONS: Unlike the fivefold increase in risk seen in coeliac disease, we found no increased risk of lymphoproliferative cancer and no increase in fracture, malignancy or mortality in people with dermatitis herpetiformis compared with the general population. It is not clear whether differences in degree of intestinal inflammation or other reasons account for this. Like coeliac disease, dermatitis herpetiformis may protect against breast cancer.

Systematic review: the use of serology to exclude or diagnose coeliac disease (a comparison of the endomysial and tissue transglutaminase antibody tests).

BACKGROUND: With the appreciation of the high prevalence of coeliac disease there is increasing use of serology in screening asymptomatic people and testing those with suggestive features. AIM: To compare the sensitivities and specificities of the endomysial antibody and the tissue transglutaminase antibody tests. METHODS: Using electronic databases a search was made for relevant papers using the terms tissue transglutaminase and endomysial antibody. RESULTS: Both the endomysial antibody and tissue transglutaminase antibody have very high sensitivities (93% for both) and specificities (>99% and >98% respectively) for the diagnosis of typical coeliac disease with villous atrophy. Human recombinant tissue transglutaminase performs much better than guinea pig tissue transglutaminase. Review of studies comparing endomysial antibody with human recombinant tissue transglutaminase antibody shows that endomysial antibody more often has a higher specificity and human recombinant tissue transglutaminase antibody more often has a higher sensitivity. CONCLUSION: The human recombinant tissue transglutaminase antibody is the preferred test for screening asymptomatic people and for excluding coeliac disease in symptomatic individuals with a low pretest probability (i.e. <25%) for coeliac disease. Furthermore, it has a number of practical and financial advantages. If the pretest probability is >25%, biopsy is preferred as the post-test probability of coeliac disease with a negative test is still >2%.

Under utilisation of the 2-week wait initiative for lung cancer by primary care and its effect on the urgent referral pathway.

The '2-week wait' scheme for referral of patients with cancer to secondary care coincided with the introduction of Department of Health (DoH) Guidelines on referral of patients with suspected lung cancer. The aim of this study was to examine the impact of this process on the urgent referral pathway for lung cancer. Medical records of all patients referred with suspected lung cancer were reviewed for the year prior to introduction of the 2-week wait and DoH guidelines and for the subsequent 24 months. A total of 1044 patients were referred, of which 650 (62%) were found to have malignancy. In the first and second years of the 2-week wait scheme, only 57 and 58% were referred via the scheme. Department of Health guidelines were followed in all but a small number. Median wait time increased from 7 to 9 days. The proportion of all urgent referrals seen within 2 weeks fell from 84 to 71%. The proportion of non-2-week wait urgent referrals being seen within 2 weeks was only 75.5% in the first year of the scheme and fell further to 60.9% in the second year. The absolute number of referrals rose and the proportion having cancer fell from 78% before the scheme to 46% in the second year. During this time, there was no change in stage at presentation. Symptoms were not helpful in discriminating benign from malignant disease and haemoptysis was actually more common in the benign group. However, over 50% of patients in the benign group were appropriate to be seen in secondary care. The 2-week wait scheme has so far failed to reduced waiting times for lung cancer. The findings of this study suggest that this is partly due to continued usage of urgent referral routes outside the 2-week wait scheme and secondly due to a large increase in referrals, probably generated by the introduction of the DoH guidelines. Some adjustment to the guidelines may be appropriate to reflect more emphasis on the early performance of a chest X-ray and the use of direct access to other imaging modalities such as CT. Patients referred outside the 2-week wait are disadvantaged and thus practitioners would be wise to refer all their patients through the 2-week wait system.

Fas receptor-Fas ligand system is independent of both CD34 status and chemosensitivity in acute myeloid leukemia.

OBJECTIVE: To determine whether the Fas receptor-Fas ligand (FasR-FasL) system, which triggers apoptosis in sensitive cells, is an important mechanism of cytotoxicity in acute myeloblastic leukemia (AML). MATERIALS AND METHODS: We investigated FasR expression in primary AML cells and its upregulation by tumor necrosis factor (TNF), as well as the apoptosis induced by anti-Fas antibody and the potential interaction between the FasR-FasL system and the cytotoxic drug daunorubicin (DNR). RESULTS: FasR was expressed on all 25 AML samples and three normal bone marrow harvests. The intensity of expression was variable (range 1. 6-2.1 in normal bone marrow CD34(+) cells and 1.5-5.1 in AML cells, median 2.4) and was related to the morphologic FAB classification, with the highest expression in FAB types M4 and M5 (range 1.6-5.1, median 3.2). No relationship was found between FasR expression and expression of the CD34 antigen. FasR was heterogeneously upregulated in all AML cells on treatment with TNF-alpha. The degree of FasR upregulation induced was found to be related to the FAB subtype, with the greatest response observed in immature FAB types M1, M2, and M6 (range 11.0-207.1%, median 48.7%). Apoptosis could be induced in all AML samples, but not in normal bone marrow CD34(+)ve cells, by the CH11 anti-FasR antibody, although the response was variable (range 4.1-37.6%, median 16.5%). The monocytic differentiated M4 and M5 AML cells exhibited the greatest sensitivity to Fas-mediated apoptosis (range 4.4-37.6, median 20.65%); however, no relationship was found between sensitivity to Fas-mediated apoptosis and FasR expression or CD34 positivity. Apoptosis in response to DNR was observed in all AML cases; however, sensitivity was heterogeneous and found to be unrelated to FasR expression or sensitivity to Fas-mediated apoptosis. The blocking anti-FasR antibody ZB4 blocked anti-FasR-mediated apoptosis but had no inhibitory effect on DNR-induced apoptosis in AML blasts. No cytotoxic synergistic effect was demonstrated when anti-FasR antibody was used in combination with DNR. CONCLUSION: In AML, DNR induces apoptosis through an Fas-independent pathway. However, the induction of apoptosis through the Fas pathway might be a novel and effective approach for leukemia immunotherapy, particularly because Fas-mediated apoptosis was noted in CD34(+) and CD34(-) cases.