Harri Sievänen

Celiac Disease Without Villous Atrophy

Current diagnostic criteria of celiac disease require small bowel villous atrophy, although the damage develops gradually. We therefore searched for evidence of disease in 10 adults suspected to have celiac disease, but evincing only minor mucosal inflammation and increase in γδ+ cells without villous atrophy. Twenty untreated celiac and 27 nonceliac patients served as biopsy controls. CD3+, αβ+, and γδ+ cells were increased in patients with only minor mucosal lesions, but less than in celiac patients. The inflammation resolved on gluten-free diet, and abdominal symptoms were alleviated. Eight of 10 had positive endomysial, seven gliadin, and nine tissue transglutaminase antibodies; all normalized on diet. Eight patients had osteopenia; HLA DQ2 was found in all. Minor mucosal lesions with an increase in γδ+ intraepithelial lymphocytes were suggestive of celiac disease. Our patients showed a clinical, histological, and serological recovery on diet; risk of osteopenia speaks in favor of dietary treatment.

Persistent small bowel mucosal villous atrophy without symptoms in coeliac disease

Background  Refractory sprue with malabsorption carries a risk of lymphoma.

Bone isoenzyme of serum alkaline phosphatase and serum inorganic phosphate in metabolic bone disease of prematurity.

We wanted to improve detection of low bone mineral density in preterm infants by combining serum measurements of total alkaline phosphatase, its bone‐type isoenzyme and serum inorganic phosphate in a prospective design. The subjects were 43 preterm infants. Total and bone isoenzyme activity of alkaline phosphatase was determined at 3 wk chronological age and at 3 and 6 mo corrected age. The main outcome measure, apparent bone mineral density (BMAD) at the distal forearm and forearm shaft, was assessed by dual energy X‐ray absorptiometry at 3 and 6 mo corrected age. An apparent density below 95 mg/cm3 at 3 mo corrected age was considered to indicate bone disease, based on the distribution of BMAD values of children with non‐complicated courses of prematurity. At 3 mo corrected age, total alkaline phosphatase activities exceeding 900 IU/l revealed low bone mineral density with 88% sensitivity and 71% specificity. Measurements of bone isoenzyme activity did not improve diagnostic performance. Serum inorganic phosphate levels below 1.8 mmol/l reflected low bone density with high specificity (96%), but the sensitivity was only 50%.

The effects of vibration loading on adipose stem cell number, viability and differentiation towards bone-forming cells

Mechanical stimulation is an essential factor affecting the metabolism of bone cells and their precursors. We hypothesized that vibration loading would stimulate differentiation of human adipose stem cells (hASCs) towards bone-forming cells and simultaneously inhibit differentiation towards fat tissue. We developed a vibration-loading device that produces 3g peak acceleration at frequencies of 50 and 100 Hz to cells cultured on well plates. hASCs were cultured using either basal medium (BM), osteogenic medium (OM) or adipogenic medium (AM), and subjected to vibration loading for 3 h d–1 for 1, 7 and 14 day. Osteogenesis, i.e. differentiation of hASCs towards bone-forming cells, was analysed using markers such as alkaline phosphatase (ALP) activity, collagen production and mineralization. Both 50 and 100 Hz vibration frequencies induced significantly increased ALP activity and collagen production of hASCs compared with the static control at 14 day in OM. A similar trend was detected for mineralization, but the increase was not statistically significant. Furthermore, vibration loading inhibited adipocyte differentiation of hASCs. Vibration did not affect cell number or viability. These findings suggest that osteogenic culture conditions amplify the stimulatory effect of vibration loading on differentiation of hASCs towards bone-forming cells.

Obesity and metabolic changes are common in young childhood brain tumor survivors

A population based cross‐sectional study was used to examine the prevalence of metabolic syndrome and its components in childhood brain tumor survivors.

Gastrointestinal symptoms, quality of life and bone mineral density in mild enteropathic coeliac disease: a prospective clinical trial.

Abstract Objective. The diagnosis of coeliac disease requires small-bowel mucosal villous atrophy with crypt hyperplasia. However, patients with endomysial antibodies but structurally normal villi may suffer from a disorder similar to those with villous atrophy. The aim of this study was to evaluate gastrointestinal symptoms, quality of life and bone mineral density in patients with mild enteropathy, and the effect of a gluten-free diet. Material and methods. A prospective trial was carried out in 73 adults having endomysial antibodies with normal villous morphology (Marsh I–II; mild enteropathy) or villous atrophy (Marsh III). Gastrointestinal symptoms and quality of life were surveyed by means of structured questionnaires and bone mineral density by means of X-ray absorptiometry. Altogether, 110 subjects served as non-coeliac controls. Results. At baseline, patients with mild enteropathy evinced more gastrointestinal symptoms than non-coeliac controls, but there were no significant differences in quality of life between the groups. After 1 year on a gluten-free diet, indigestion and depression were significantly alleviated in the mild enteropathy group. Osteoporosis or osteopenia was detected in 58% of subjects in the mild enteropathy group and there was a trend towards improved bone mineral density after the treatment. Conclusions. Endomysial antibody-positive patients with normal villous structure may suffer from gastrointestinal symptoms and have poor bone health. Furthermore, they benefit from a gluten-free diet similar to those with overt villous atrophy.

Degree of Damage to the Small Bowel and Serum Antibody Titers Correlate With Clinical Presentation of Patients With Celiac Disease

BACKGROUND & AIMS In patients with celiac disease, gluten-induced lesions of the small-bowel mucosa develop gradually. However, it is not clear whether clinical presentation correlates with the degree of mucosal damage based on histology analysis. We investigated whether the degree of mucosal damage to the small bowel correlates with clinical presentation and serum markers of celiac disease. METHODS We collected results from serology tests and mucosal biopsy samples from 638 consecutive patients with celiac disease and compared them with reported gastrointestinal symptoms, health-related quality-of-life scores, results from laboratory tests, and bone mineral densities of patients. We assessed mucosal injury based on the ratio of villous height to crypt depth, numbers of intraepithelial CD3(+) cells, and semiquantitative Marsh classification criteria. Correlations were established based on the Pearson or Spearman coefficients. RESULTS The ratio of the villous height to crypt depth correlated with the severity of gastrointestinal symptoms, quality-of-life scores, laboratory test results, numbers of intraepithelial CD3(+) cells, and serum levels of antibodies associated with celiac disease. There was no correlation between the ratio of villous height to crypt depth and bone mineral density. The number of intraepithelial CD3(+) cells was not associated with symptoms, whereas the Marsh classification and serum levels of antibodies associated with celiac disease correlated with gastrointestinal symptoms, laboratory test results, and numbers of intraepithelial CD3(+) cells. CONCLUSIONS The ratio of small-bowel villous height to crypt depth and results from serology tests correlate with reported symptoms and quality of life of patients with celiac disease. Patient-reported outcomes are therefore of value, in addition to histology findings, in assessing patients with celiac disease.

Bone mineral density is reduced in brain tumour patients treated in childhood

Aim: To determine the prevalence of low bone mineral density among children surviving brain tumours and to identify possible factors underlying impaired bone health. Methods: Cross‐sectional study; total body bone mineral density (TBBMD), fat mass (FM) and lean body mass (LBM) were measured by dual‐energy X‐ray absorptiometry (DXA) in 46 brain tumour patients aged from 3.8 to 28.7 y (mean 14.9 y) treated in childhood 1.4–14.8 y (mean 6.4 y) after end of treatment for brain tumour. Low bone mineral density was defined as TBBMD z score<−2.0. Results: Fifteen patients had TBBMD z scores<−2.0, indicating a 33% prevalence of low bone density. The TBBMD z score ranged from −5.7 to 0.6 (mean −1.7). Out of several potential factors, only combined craniospinal irradiation was significantly associated with low z score (p=0.034, according to multiple regression analysis), while exclusive cranial irradiation showed a borderline statistical association (p=0.100, according to multiple regression analysis).

Clinical Characteristics and the Dietary Response in Celiac Disease Patients Presenting With or Without Anemia.

Background and Aims: It remains unclear as to what are the clinical characteristics associated with the presence of anemia at celiac disease diagnosis, and how these are affected by a gluten-free diet. We investigated these issues in a prospective study. Methods: Clinical and demographic data, small-bowel mucosal histology, serology, and laboratory parameters, body mass index (BMI), and bone mineral density (BMD) both at diagnosis and after 1 year on a gluten-free diet were investigated in 163 adults with celiac disease. Gastrointestinal symptoms and psychological well-being were evaluated by validated Gastrointestinal Symptom Rating Scale and Psychological General Well-Being questionnaires. All study variables were compared between participants with and without anemia at celiac disease diagnosis. Results: Altogether, 23% of the patients had anemia at diagnosis. Anemic patients were more often women (P=0.001) and had more gastrointestinal symptoms (P=0.004) and were less often screen detected (P=0.009). Further, they had higher celiac antibody values (P=0.007) and a lower total iron (P<0.001), BMI (P=0.003), and density of mucosal &ggr;&dgr;+ intraepithelial lymphocytes (P=0.033). After 1 year on a gluten-free diet, the anemia group had a lower mucosal villous height-crypt depth ratio (P=0.008) and BMI (P=0.050), and higher antibody values (P=0.012) and densities of CD3+ (P=0.008) and &agr;&bgr;+ intraepithelial lymphocytes (P=0.022). There was no significant difference between the groups in their bone mineral density, Gastrointestinal Symptom Rating Scale and Psychological General Well-Being. Conclusions: Celiac patients with anemia had more severe disease than nonanemic patients in terms of the serology and a lower BMI. Further, they evinced a slower histologic response to the dietary treatment. An early diagnosis and careful follow-up are important in these patients.

Serum transglutaminase 3 antibodies correlate with age at celiac disease diagnosis

BACKGROUND Transglutaminase (TG)2 is the autoantigen in celiac disease, but also TG3 antibodies have been detected in the serum of celiac disease patients. AIMS To investigate the correlations between serum TG3 antibodies and clinical and histological manifestations of celiac disease and to assess gluten-dependency of TG3 antibodies. METHODS Correlations between serum TG3 antibody levels measured from 119 adults and children with untreated coeliac disease and the demographic data, clinical symptoms, celiac antibodies, histological data and results of laboratory tests and bone mineral densities were tested. TG3 antibodies were reinvestigated in 97 celiac disease patients after 12 months on a gluten-free diet (GFD). RESULTS TG3 antibody titers were shown to correlate with the age at celiac disease diagnosis. Further, negative correlation with TG3 antibodies and intestinal γδ+ cells at diagnosis and on GFD was detected. Correlations were not detected with the clinical manifestation of celiac disease, TG2 or endomysial autoantibodies, laboratory values, severity of mucosal villous atrophy, associated diseases or complications. TG3 antibody titers decreased on GFD in 56% of the TG3 antibody positive patients. CONCLUSION Serum TG3 antibody positivity in celiac disease increases as the diagnostic age rises. TG3 antibodies did not show similar gluten-dependency as TG2 antibodies.