Paracoccidioidomycosis: characterization of subpopulations of macrophages and cytokines in human mucosal lesions.

Mucosal lesions of paracoccidioidomycosis (PCM) are frequently described and clinically important. Macrophages are classified as M1 or M2. M1 are proinflammatory and M2 are related to chronicity. Dectin-1 recognizes ß-glucan and plays an important role against fungal cells. The objective was to verify the presence of M1, M2, and dectin-1 and a possible correlation with Th1/Th2 cytokines in mucosal PCM lesions. In sum, 33 biopsies of oral PCM were submitted to histological and immunohistochemistry analysis, and positive cells were quantified. Eleven biopsies were characterized by compact granulomas (G1), 12 with loose granulomas (G2), and 10 with both kind of granulomas (G3). pSTAT-1 was equally increased in the three groups. G1 was characterized by an increased number of CD163+ macrophages. G2 presented similar number of arginase 1, iNOS, and CD163 expressing cells. G3 presented an increased number of cells expressing arginase 1 and CD163 over iNOS. G1 and G3 presented high number of cells expressing interferon (IFN)-γ; interleukin (IL) 5 was increased in G2 and G3; the expression of IL10 was similar among the three groups, and the expression of tumor necrosis factor (TNF)-α was higher in G3. G1 correlates to Th1 cytokines and pSTAT-1 and G2 correlates to Th2 cytokines. G3 presents both kinds of cytokines. We could not associate the expression of arginase-1, CD163, iNOS, and dectin-1 with the pattern of cytokines or kind of granuloma.

Complexity vs. unity in unilateral spatial neglect.

Unilateral spatial neglect constitutes a heterogeneous syndrome characterized by two main entangled components: a contralesional bias of spatial attention orientation; and impaired building and/or exploration of mental representations of space. These two components are present in different subtypes of unilateral spatial neglect (visual, auditory, somatosensory, motor, allocentric, egocentric, personal, representational and productive manifestations). Detailed anatomical and clinical analyses of these conditions and their underlying disorders show the complexity of spatial cognitive deficits and the difficulty of proposing just one explanation. This complexity is in contrast, however, to the widely acknowledged effectiveness of rehabilitation of the various symptoms and subtypes of unilateral spatial neglect, exemplified in the case of prism adaptation. These common effects are reflections of the unity of the physiotherapeutic mechanisms behind the higher brain functions related to multisensory integration and spatial representations, whereas the paradoxical aspects of unilateral spatial neglect emphasize the need for a greater understanding of spatial cognitive disorders.

Mobile health for cancer in low to middle income countries: priorities for research and development.

Many current global health opportunities have less to do with new biomedical knowledge than with the coordination and delivery of care. While basic research remains vital, the growing cancer epidemic in countries of low and middle income warrants urgent action - focusing on both research and service delivery innovation. Mobile technology can reduce costs, improve access to health services, and strengthen health systems to meet the interrelated challenges of cancer and other noncommunicable diseases. Experience has shown that even very poor and remote communities that only have basic primary health care can benefit from mobile health (or 'mHealth') interventions. We argue that cancer researchers and practitioners have an opportunity to leverage mHealth technologies that have successfully targeted other health conditions, rather than reinventing these tools. We call for particular attention to human centred design approaches for adapting existing technologies to suit distinctive aspects of cancer care and to align delivery with local context - and we make a number of recommendations for integrating mHealth delivery research with the work of designers, engineers and implementers in large-scale delivery programmes.

Dermal dendrocytes FXIIIA+ phagocytizing extruded mast cell granules in drug-induced acute urticaria.

BACKGROUND: Few authors have been attempting between mast cells and dermal dendrocytes interactions on urticaria. OBJECTIVE: To describe the extruded mast cell granules and dermal dendrocytes in drug-induced acute urticaria. METHODS: Seven patients with drug-induced acute urticaria were enrolled in the study. We token skin biopsies of urticaria lesion and perilesional skin. The 14 fragments collected were processed to immunogold electron microscopy using single stains to tryptase and FXIIIa, besides double immunogold labeling with both. RESULTS: Some sections demonstrated mast cells in degranulation process, both in anaphylactic and piecemeal degranulation types. After double immunogold staining, 10 nm (FXIIIa) and 15 nm (Tryptase) gold particles were present together over the granules in mast cells indicating that tryptase and FXIIIa are each localized within the granules of these cells. Interestingly, we found a strong evidence of than the exocytosed mast cell granules contents both FXIIIa and tryptase immunolabeled are phagocytized by dermal dendrocytes. CONCLUSIONS: The current observations provide morphological evidence that the exocytosis-phagocytosis mechanisms of mast cell granules represents one pathophysiological example of mast cells-dermal dendrocytes interactions in urticaria.

Leprosy in transplant recipients: report of a case after liver transplantation and review of the literature.

Leprosy still is an important public health problem in several parts of the world including Brazil. Unlike the diseases caused by other mycobacteria, the incidence and clinical presentation of leprosy seems little affected in immunosuppressed patients. We report the first case, to our knowledge, of a liver transplant patient who developed multi-bacillary leprosy. The patient presented with papules and infiltrated plaques with loss of sensation suggestive of leprosy 3.5 years after living-related liver transplantation for autoimmune hepatitis. A skin biopsy showing non-caseating macrophagic granulomas, neuritis, and intact acid-fast bacilli on Fite-Faraco stain, confirmed the diagnosis of borderline lepromatous leprosy. The donor of the liver did not show any evidence of leprosy. During follow-up, the patient presented 2 episodes of upgrading leprosy type I reactions, 1 mild before leprosy treatment, and 1 moderate 3 months after receiving standard multi-drug treatment (rifampicin, clofazimine, and dapsone). These reactions were accompanied by increase in liver function tests, especially of canalicular enzymes. This reaction occurred despite the patient's triple immunosuppression regimen. The moderate reaction was successfully treated with further immunosuppression (prednisone, 0.5 mg/kg). Currently, the patient is asymptomatic, off leprosy medication, with routine liver transplant follow-up. The dilemmas in diagnosis and management of such a case are discussed and the literature on leprosy in transplant recipients is reviewed.

The expression of TLR9 in human cutaneous leishmaniasis is associated with granuloma.

The Toll-like receptor (TLR) signalling pathway is the first system that defends against Leishmania. After recognising Leishmania as nonself, TLRs trigger NF-κB expression.NF-κB proceeds to the nucleus and promotes the transcription of pro-inflammatory cytokines. TLR9 is thus an important factor in the induction of an effective immune response against Leishmania. We examined the pattern of TLR9 expression in 12 patients with cutaneous leishmaniasis caused by Leishmania braziliensis detected by polymerase chain reaction. Normal skin was analysed as a negative control. TLR9 expression was examined in the dermis and epidermis by immunohistochemical analysis of paraffin-embedded biopsy tissue. TLR9 expression was primarily observed in the granuloma. The protein was detected in a few cells in the dermis. A lower expression level was detected in the epidermis of patients with leishmaniasis when compared with normal skin. The presence of TLR9 in the skin of patients with cutaneous leishmaniasis is associated with granuloma and expressed by macrophages.

Tissue and serum immune response in chronic hepatitis C with mild histological lesions.

The immunopathogenesis of chronic hepatitis C virus (HCV) infection is a matter of great controversy and has been suggested to involve a complex balance between cytokines with pro and anti-inflammatory activity. We investigated the expression of inflammatory cells and cytokines in the liver and serum of 51 chronically HCV infected patients and compared them to data from two sets of normal controls: 51 healthy blood donors and 33 liver biopsies of healthy liver donors. We also assessed the relationship between selected cytokines and cell populations in hepatic compartments and the disease stage. Compared with controls, hepatitis C patients had a greater expression of portal TNF-alpha, TGF-beta and CD4(+) and acinar IFN-gamma, TNF-alpha, IL-1beta and IL-4, as well as a higher serum concentration of IL-2, IL-10 and TGF-beta. Significant positive correlations were found between portal CD4+ and TNF-alpha, portal CD8(+) and TGF-beta, portal CD45(+)RO and TNF-alpha, acinar CD45(+)RO and IFN-gamma and acinar CD57(+) and TGF-beta. In conclusion, we have shown that (i) in this sample of predominantly mild disease, the immune response was associated with a pro-inflammatory response pattern, (ii) CD4(+) T-lymphocytes played a major role in orchestrating the immune response and (iii) these events primarily took place in the portal space.

In situ immune responses to interstitial pneumonitis in human visceral leishmaniasis.

Lung disease during active human visceral leishmaniasis is frequently reported. As such, studies have associated pulmonary symptoms to interstitial pneumonitis with a mononuclear infiltrate. However, the immune response in this condition has never been described before. The aim of this study was to determine the immunophenotypic pattern and cytokine profile of lung involvement (IPL) in human visceral leishmaniasis. Quantitative methods of analysis were performed using immunohistochemistry, and were compared with a control group of normal lung. Interstitial macrophages and cd8 cells were increased in IPL, and IL-4 as well as TNF-alpha displayed increased expression when compared to the control group. This inflammatory process with a Th2 pattern, as suggested by increased IL-4 and low IFN-gamma expression, is consistent with the immune response in other organs of visceral leishmaniasis. The microenvironment of the immune response in this condition is associated with lung disease in patients with interstitial pneumonitis related to visceral leishmaniasis, increasing the chance of bacterial infection.

The effects of human herpesvirus 8 infection and interferon-gamma response in cutaneous lesions of Kaposi sarcoma differ among human immunodeficiency virus-infected and uninfected individuals.

BACKGROUND: Kaposi sarcoma (KS) is associated with human herpesvirus 8 (HHV-8). The cutaneous immune response in this tumour is not well established and a better understanding is necessary. OBJECTIVES: To evaluate the HHV-8 expression and immune response in cutaneous lesions of classic KS (CKS) and AIDS-associated KS (AIDS-KS). METHODS: We performed a quantitative immunohistochemical study of cells expressing HHV-8 latency-associated nuclear antigen (LANA), CD4, CD8 and interferon (IFN)-gamma in skin lesions from patients with CKS and AIDS-KS (with or without highly active antiretroviral therapy, HAART). RESULTS: CKS showed higher LANA expression compared with AIDS-KS, regardless of HAART. We also found higher LANA expression in nodules compared with patch/plaque lesions. The tissue CD4+ cell proportion was lower in AIDS-KS patients without HAART than in patients with CKS. In CKS lesions, CD4+ and CD8+ cells expressed IFN-gamma, as shown by double immunostaining. AIDS-KS presented low numbers of IFN-gamma-expressing cells. CD8+ cell numbers were similar in all groups, which appeared unrelated to the clinical or epidemiological type of KS. CONCLUSIONS: Our quantitative data on the pattern of KS lesions in selected groups of patients, as shown by in situ immune response, demonstrated a CD4+ T-cell involvement associated with IFN-gamma, an environment of immune response-modified human immunodeficiency virus (HIV) infection. In our sample, the promotion of KS in patients without HIV appears to be related to higher HHV-8 load or virulence than in those with AIDS. This higher resistance may be explained by a sustained immune response against this herpesvirus, that is only partially restored but effective after HAART.

Paradoxical effects of vitamin C in Chagas disease.

Trypanosoma cruzi infection stimulates inflammatory mediators which cause oxidative stress, and the use of antioxidants can minimize the sequelae of Chagas disease. In order to evaluate the efficacy of vitamin C in minimizing oxidative damage in Chagas disease, we orally administered ascorbic acid to Swiss mice infected with 5.0 × 104 trypomastigote forms of T. cruzi QM2 strain. These animals were treated for 60 days to investigate the acute phase and 180 days for the chronic phase. During the acute phase, the animals in the infected and treated groups demonstrated lower parasitemia and inflammatory processes were seen in more mice in these groups, probably due to the higher concentration of nitric oxide, which led to the formation of peroxynitrite. The decrease in reduced glutathione concentration in this group showed a circulating oxidant state, and this antioxidant was used to regenerate vitamin C. During the chronic phase, the animals in the infected and treated group showed a decrease in ferric reducing ability of plasma and uric acid concentrations as well as mobilization of bilirubin (which had higher plasma concentration), demonstrating cooperation between endogenous non-enzymatic antioxidants to combat increased oxidative stress. However, lower ferrous oxidation in xylenol orange concentrations was found in the infected and treated group, suggesting that vitamin C provided biological protection by clearing the peroxynitrite, attenuating the chronic inflammatory process in the tissues and favoring greater survival in these animals. Complex interactions were observed between the antioxidant systems of the host and parasite, with paradoxical actions of vitamin C.

Semiology of neglect: An update.

Hemispatial neglect is a common disabling condition following brain damage to the right hemisphere. Generally, it involves behavioral bias directed ipsilaterally to the damaged hemisphere and loss of spatial awareness for the contralesional side. In this syndrome, several clinical subtypes were identified. The objective of this article is to provide a nosological analysis of the recent data from the literature on the different subtypes of neglect (visual, auditory, somatosensory, motor, egocentric, allocentric and representational neglect), associated ipsilesional and contralesional productive manifestations and their anatomical lesion correlates. These different anatomical-clinical subtypes can be associated or dissociated. They reflect the heterogeneity of this unilateral neglect syndrome that cannot be approached or interpreted in a single manner. We propose that these subtypes result from different underlying deficits: exogenous attentional deficit (visual, auditory neglect); representational deficit (personal neglect, representational neglect, hyperschematia); shift of the egocentric reference frame (egocentric neglect); attentional deficit between objects and within objects (allocentric neglect), endogenous attentional deficit (representational neglect) and transsaccadic working memory or spatial remapping deficit (ipsilesional productive manifestations). Taking into account the different facets of the unilateral neglect syndrome should promote the development of more targeted cognitive rehabilitation protocols.

The Digital Heart Manual: A pilot study of an innovative cardiac rehabilitation programme developed for and with users.

OBJECTIVE: Patients are seeking greater choice and flexibility in how they engage with self-management programmes. While digital innovations offer opportunities to deliver supportive interventions to patients undergoing cardiac rehabilitation little is known about how accessible, useful and acceptable they are for this group. This project developed a digital version of a leading evidenced cardiac rehabilitation programme, the Heart Manual (HM). The prototype was developed and evaluated iteratively in collaboration with end users. METHODS: Using a mixed methods design 28 participants provided feedback using semi-structured questionnaires and telephone interviews. RESULTS: Rich data revealed the perceived user-friendliness of the HM digital format and its effectiveness at communicating the programme's key messages. It flagged areas requiring development, such as more flexible and intuitive navigation pathways. These suggestions informed the refinement of the resource. CONCLUSION: This evaluation offers support for the new Digital Heart Manual and confirms the value of employing a user-centred approach when developing and improving online interventions. The system is now in use and recommendations from the evaluation are being translated into quality improvements. PRACTICE IMPLICATIONS: The Digital Heart Manual is user friendly and accessible to patients and health professionals, regardless of age, presenting a suitable alternative to the paper version.

Immunopathology of the duodenal mucosa of HIV-positive patients during combined antiretroviral therapy.

The objective of the present study was to evaluate the duodenal mucosa of HIV-infected patients during antiretroviral therapy. This was an observational study conducted on HIV-positive patients and a control group. Group 1 comprised 22 HIV-negative individuals while 38 HIV-positive individuals were classified according to the CDC 1993 classification into group 2 (A1 or A2) or group 3 (B2, A3, B3, C2, C3). All subjects were submitted to upper gastrointestinal endoscopy with duodenal biopsies. Qualitative, semi-quantitative and quantitative histological analyses were performed. Results were considered significant when P < 0.05. A higher prevalence of inflammatory infiltrate and eosinophilia was observed in the HIV group, together with a reduction in mucosal CD4+ lymphocyte (L) counts [median (lower-upper quartiles), 12.82 (8.30-20.33), 6.36 (1.75-11.66) and 1.75 (0.87-3.14) in groups 1, 2 and 3, respectively] which was not correlated with disease stage. The extent of CD4+L count reduction was similar in blood and duodenal mucosa. Normal CD8+L and CD45RO+L counts, and normal numbers of macrophages and antigen-presenting cells were also found in the HIV patients. The cytokine pattern did not differ among groups. Tissue HIV, assessed by p24 antigen, correlated with a higher CD45RO+L count (77.0 (61-79.8) and 43.6 (31.7-62.8) in p24+ and p24-, respectively, P = 0.003), and IL-4 positivity (100 and 48.2% in p24+ and p24-, respectively, P = 0.005). The duodenal mucosa of HIV+ patients showed a relatively preserved histological architecture. This finding may be characteristic of a population without opportunistic infections and treated with potent antiretroviral therapy, with a better preservation of the immune status.

Differential actigraphy for monitoring asymmetry in upper limb motor activities.

Most applications of accelerometry-based actigraphy require a single sensor, properly located onto the body, to estimate, for example, the level of activity or the energy expenditure. Some approaches adopt a multi-sensor setup to improve those analyses or to classify different types of activity. The specific case of two symmetrically placed actigraphs allowing, by some kind of differential analysis, for the assessment of asymmetric motor behaviors, has been considered in relatively few studies. This article presents a novel method for differential actigraphy, which requires the synchronized measurements of two triaxial accelerometers (programmable eZ430-Chronos, Texas Instruments, USA) placed symmetrically on both wrists. The method involved the definition of a robust epoch-related activity index and its implementation on-board the adopted programmable platform. Finally, the activity recordings from both sensors allowed us to define a novel asymmetry index AR24 h ranging from -100% (only the left arm moves) to +100% (only the right arm moves) with null value marking a perfect symmetrical behavior. The accuracy of the AR24 h index was 1.3%. Round-the-clock monitoring on 31 healthy participants (20-79 years old, 10 left handed) provided for the AR24 h reference data (range -5% to 21%) and a fairly good correlation to the clinical handedness index (r = 0.66, p < 0.001). A subset of 20 participants repeated the monitoring one week apart evidencing an excellent test-retest reliability (r = 0.70, p < 0.001). Such figures support future applications of the methodology for the study of pathologies involving motor asymmetries, such as in patients with motor hemisyndromes and, in general, for those subjects for whom a quantification of the asymmetry in daily motor performances is required to complement laboratory tests.

Patient perspectives on multiple medications versus combined pills: a qualitative study.

BACKGROUND: A growing number of patients are taking multiple medications. Unfortunately, adherence may fall as drug numbers and procedural complexity increase. While there are plausible theoretical reasons why combining pills might improve non-adherence, patients' attitudes are unknown. AIM: To explore attitudes and practices to medication regimens among patients already in receipt of multiple medications, and to assess whether a combined tablet would be perceived as advantageous. DESIGN: Qualitative study. METHODS: Ninety-two men and women aged >40 years currently receiving both antihypertensive and cholesterol-lowering medications took part in 14 focus groups. RESULTS: Drugs were seen as unwelcome but necessary. Some took drugs flexibly by changing dose timing, thereby increasing the complexity of their regimen. A routine was seen as the key to coping with multiple medications, although it was sometimes threatened by changes in prescriptions and life circumstances. While some participants welcomed a combined pill, there was uncertainty about whether a combination that mirrored their current doses would be available. There were also concerns about tablet size, allergies, the attribution of side-effects, timing of tablets throughout the day, and the ability to alter dose levels. CONCLUSION: While some patients would be willing to try a combined pill and would appreciate the associated convenience, they are likely to have a number of concerns that prescribers should address. Willingness to move to combined therapy may be hindered if drug combinations that mirror personalized and trusted regimens are not available.

Increased glucose-dependent insulinotropic polypeptide (GIP) secretion in acromegaly.

OBJECTIVE: Acromegaly is often associated with fasting and postprandial hyperinsulinemia, and the mechanisms involved are only partly understood. Hypersecretion of incretins such as glucose-dependent insulinotropic polypeptide (GIP) could play a role in determining hyperinsulinemia in acromegaly, but the available data are inconsistent. The aim of this study was to characterize the fasting and postprandial pattern of plasma GIP and insulin in a group of acromegalic patients. DESIGN AND METHODS: Eleven non-diabetic patients with newly diagnosed acromegaly and 11 sex- and age-matched healthy subjects were studied. Blood samples were taken at regular intervals in fasting conditions and for 3 h after a standard solid-liquid meal for growth hormone (GH), GIP and insulin measurements. RESULTS: Not only insulin, but also fasting and postprandial GIP levels were significantly higher in the patients with acromegaly than the healthy subjects (P<0.01). In the former group fasting GIP levels and the integrated GIP response to the meal correlated significantly with GH basal levels (r=0.83, P<0.01 and r=0.65, P<0.05, respectively). Moreover, multivariate linear regression analysis showed that the presence of acromegalic status was associated with higher fasting and postprandial GIP levels independently of sex, age, fasting and postprandial plasma glucose and insulin levels, and the occurrence of normal or impaired glucose tolerance. CONCLUSION: This study provides evidence that in patients with acromegaly fasting and postprandial GIP levels are abnormally high. GIP hypersecretion in turn might play a role in the pathogenesis of hyperinsulinemia that characterizes acromegaly.

The patient's role in the spread and control of bacterial resistance to antibiotics.

As the ultimate consumers, patients play an important role in the emergence, spread and control of bacterial resistance to antibiotics. Improved knowledge of antibiotics and the problem of resistance, as well as a better understanding of beliefs, pressures/concerns, and expectations, from both the patient's and physician's perspectives, are fundamental for controlling antibiotic use. There is growing evidence to suggest that empowering patients through implementation of patient-centered health-care strategies, such as shared decision-making, in conjunction with educational initiatives help to change attitudes and behavior, and improve access to and completion of appropriate antimicrobial therapy. This, in turn, may help to control the development and spread of resistance to antibiotics.

Searching for coeliac disease in patients with non-alcoholic fatty liver disease.

BACKGROUND: A non-negligible percentage of patients with non-alcoholic fatty liver disease, a leading cause of hepatic progressive disorder related to insulin resistance, have no metabolic risk factors, and abnormal intestinal permeability has been suggested to be involved in the pathogenesis of the liver damage. Coeliac disease, a curable disorder characterised by inflammatory mucosal damage, may show hepatic histological features similar to steatohepatitis. Conflicting data have been reported on the prevalence of coeliac disease in non-alcoholic steatohepatitis. AIM: To search for coeliac disease in a series of patients with non-alcoholic fatty liver disease by screening with anti-tissue transglutaminase and anti-endomysium antibodies. PATIENTS AND METHODS: Fifty-nine consecutive patients with hypertransaminasemia and non-alcoholic fatty liver disease, 38 (64%) with steatohepatitis. Anti-endomysium antibodies were assayed by indirect immunofluorescence, IgA anti-tissue transglutaminase by ELISA. Patients who tested positive underwent HLA DQ typing and endoscopy. RESULTS: Tissue transglutaminase antibodies were positive in six (10%) patients and anti-endomysium in two (3.4%); only two (3.4%), positive for both anti-endomysium positive and anti-transglutaminase, resulted to have coeliac disease based on histological findings. After 6 months of gluten-free diet, liver enzymes normalised. CONCLUSIONS: The prevalence of silent coeliac disease is 3.4% in patients with non-alcoholic fatty liver. The inclusion of anti-endomysium antibodies test in studying patients with non-alcoholic fatty liver and persistent biochemical abnormalities has to be taken into account, since positivity for tissue transglutaminase antibodies, in the absence of confirmatory anti-endomysium antibodies, is not sufficient to perform diagnostic endoscopy.

Serological markers for coeliac disease: is it time to change?

BACKGROUND: Anti-gliadin and anti-endomysium antibodies are useful markers in the screening and follow-up of coeliac disease. The recent finding that tissue transglutaminase is the main auto-antigen of anti-endomysium has led to the discovery of anti-tissue transglutaminase antibodies. AIM: To compare, in a prospective study, the diagnostic accuracy of anti-tissue transglutaminase, anti-gliadin and anti-endomysium antibodies in a large series of adult patients. METHODS: The study involved 80 consecutive subjects undergoing upper gastrointestinal tract endoscopy for suspected coeliac disease (subsequently confirmed in 40 cases), 195 coeliac patients on a gluten-free diet, and 70 patients with different gastrointestinal disor ders and normal duodenal histology. Anti-gliadin, anti-endomysium and anti-tissue transglutaminase antibodies levels were measured using commercial kits. RESULTS: The diagnostic sensitivity and specificity of anti-gliadin, anti-endomysium and anti-tissue transglutaminase antibodies were, respectively, 95% and 89.1%, 100% and 97.3%, and 100% and 98.2%: the agreement between the markers was substantial or almost perfect. In terms of follow-up, the positivity of the markers varied according to the strict adherence to, and duration of the gluten-free diet; the agreement between antiendomysium and anti-tissue transglutaminase antibodies was almost perfect. CONCLUSIONS: Anti-endomysium and anti-tissue transglutaminase antibodies are both highly efficient for routine laboratory screening: the choice of one or the other will depend on the available facilities. However, neither can replace intestinal biopsy for general population screening because, in this case, their respective positive predictive values are only 15.7% and 21.8%. During follow-up, anti-gliadin retain their value as an early predictor of gluten ingestion.