Correlation of clinical characteristics and small bowel histopathology in celiac disease

The reversible hearing loss in the nonoperated ear noted by patients after ear surgery remains unexplained. This study proposes that this hearing loss is caused by drill noise conducted to the nonoperated ear by vibrations of the intact skull. This noise exposure results in dysfunction of the outer hair cells, which may produce a temporary hearing loss. Estimations of outer hair cell function in the nonoperated ear were made by recording the change in amplitude of the distortion-product otoacoustic emissions before and during ear surgery. Reversible drill-related outer hair cell dysfunction was seen in 2 of 12 cases. The changes in outer hair cell function and their clinical implications are discussed.     

Genome search in celiac disease

Celiac disease (CD), a malabsorption disorder of the small intestine, results from ingestion of gluten. The HLA risk factors involved in CD are well known but do not explain the entire genetic susceptibility. To determine the localization of other genetic risk factors, a systematic screening of the genome has been undertaken. The typing information of 281 markers on 110 affected sib pairs and their parents was used to test linkage. Systematic linkage analysis was first performed on 39 pairs in which both sibs had a symptomatic form of CD. Replication of the regions of interest was then carried out on 71 pairs in which one sib had a symptomatic form and the other a silent form of CD. In addition to the HLA loci, our study suggests that a risk factor in 5qter is involved in both forms of CD (symptomatic and silent). Furthermore, a factor on 11qter possibly differentiates the two forms. In contrast, none of the regions recently published was confirmed by the present screening.     

Demonstration of celiac disease in Cuba

A study performed in 50 children carriers of celiac disease with ages between 8 months and 14 years of age, is presented; diagnosis was proved based on clinical picture, histological changes of jejunal mucosa, intestinal absorption tests and response to the suppression of gluten from the diet, with clinical, histological and biochemical control according to international criteria. It has been insisted on the familial study and the gluten overload test and its incidency in the black race. The development of public health has made it possible to demostrate the existence of this disease in our country.     

Low serum somatomedin activity in celiac disease. A misleading aspect in growth failure from asymptomatic celiac disease

In 4 children with celiac disease, aged 7 months to 11 years, serum somatomedin activities (SMA) were consistently low: less than 0.40 U/ml (N greater than 0.50 U/ml). Basal plasma growth hormone (GH) levels were not elevated and increased normally under arginine-insulin stimulation in 3 patients. Human GH administration at a dosage which usually determines an increase of serum SMA in children with GH deficiency (4 mg/day/2 days) did not modify significantly the low serum SMA. However, in 1 child a clear-cut increase of serum SMA (0.22-0.82 U/ml) was noted under a higher dosage of human GH (8 mg/day/2 days). In 3 patients serum SMA was studied 3 weeks to 4 months after starting the gluten-free diet and was found to be normal. A limitation of the somatomedin generation unrelated to a deficit in GH secretion and probably resistant to GH appears therefore to be present in celiac disease. The rapid normalization of serum SMA under gluten-free diet suggests that the low serum SMA is induced through some unknown hormonal or metabolic signal by the protein malabsorption and/or the nutritional deficiency present in celiac disease.     

Superior mesenteric artery blood flow in celiac disease

Measurements of the hemodynamic parameters of the superior mesenteric artery were performed in 18 patients with celiac disease. Ten were studied at the time of diagnosis, when a small bowel biopsy showed a flat mucosa. The remaining eight patients were studied after complete clinical and histological recovery induced by a gluten-free diet. Doppler ultrasound flowmetry was used to measure blood flow in physiological and fasting conditions and after a mixed liquid test meal (Ensure-Plus). The results were compared with those of healthy subjects (N = 7). Mean basal flow was 50% higher in untreated celiac disease patients than in healthy controls and patients with chronic pancreatitis (P = NS). Postprandial mesenteric blood flow was significantly increased (P < 0.002) and delayed in time (P < 0.005) in celiac disease as compared to controls. Successful treatment reduced the mesenteric blood flow in celiac disease to normal values. Our study demonstrates that pathophysiological changes in the small bowel mucosa during the active clinical phase of celiac disease induce an abnormal splanchnic circulation.     

Adherence issues in clinical practice

The reproducibility of short tandem repeat (STR) amplification of aDNA extracts is limited by means of formation of artifacts during PCR. One of these artifacts, the so called allelic-dropout (failure of the amplification of alleles), may result in false-homozygote typing of a sample, if genotyping is based on the analysis of a single amplification product. 30 tooth- and bone samples collected from 17 individuals of three burial sites were investigated in a blind test. Using the polymerase chain reaction (PCR) the two independent segregating STR-loci HUMVWA and HUMTH01 were amplified. Corresponding to a mathematical estimation, multiple amplifications of each sample and genelocus were carried out. The results of this genotyping were compared intraindividually.     

Activated T cells and genetic restriction in celiac disease

Studies in the last decade demonstrated that in children tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR) is identical to TP/GFR; TP indicating tubular phosphate reabsorption under basal conditions, without phosphate load. TP/GFR is calculated from the formula TP/GFR = SP-UP x SCr:UCr, based on simultaneous urine and blood creatinine and phosphate concentrations, and is applicable in both the fasting and non-fasting child. These studies also demonstrated that the use of Walton and Bijvoet nomogram in children may result in overestimation of TmP/GFR compared with TP/GFR calculated from the above formula. When using the formula, one should bear in mind that creatinine is used to express GFR and as a result a significant deviation from true GFR may occur in patients with renal failure. Therefore when employing TP/GFR for the investigation of the renal handling of phosphate in children, three factors should be taken into consideration: (1) the formula in reality expresses TP/CCr; (2) only data obtained by exactly the same methodology can be used as reference values; data obtained from studies in which the nomogram was utilized or in which methods other than CCr were used to measure GFR should not be used for reference; (3) in patients with renal failure, TP/CCr will significantly overestimate TP/Cinulin.     

Evaluation of the endomysial antibody for celiac disease: operating properties and associated cost implications in clinical practice

OBJECTIVE: To evaluate the operating properties of endomysial antibodies (EMAs) in the diagnosis of celiac disease and to examine, using a cost minimization model, different strategies used in the diagnosis of celiac disease. METHODS: A total of 248 EMA results were reviewed and compared with small bowel biopsy results in 66 patients who had undergone both tests. Regression analysis was used to look for predictors of positive EMA results and positive biopsy results. A cost minimization model from a societal perspective was used to evaluate the cost differences among three different strategies. RESULTS: EMAs had a sensitivity of 95% and specificity of 64%. The only predictor of a positive biopsy result that reached statistical significance was a positive EMA. The strategy of EMA as a diagnostic test for celiac disease was the most expensive strategy, with a cost of $3,174 per patient assessed. The strategy of small bowel biopsy for all patients had a cost of $997, and a strategy of EMA followed by small bowel biopsy for positive patients had a cost of $866 per patient. The results were sensitive to cost of a gluten-free diet, the specificity of the EMA and the cost of a small bowel biopsy. CONCLUSION: The EMA is best used as a screening test from both a clinical and cost perspective.     

Validity issues in clinical assessment.

The data investigators should provide to support the validity of inferences they make based on scores from a measure depend on (a) whether the measure is assumed to assess a hypothetical construct or behavior and (b) the purposes for which the measure is intended. The authors distinguish between the representational phase of validity assessment, which establishes that a measure produces scores that reflect the construct or behavior it purports to assess, and the elaborative validity phase, in which the meaning and utility of scores are examined. Key issues relevant to convergent, discriminant, and criterion-related validity are examined for measures of latent traits or constructs and then for measures of behaviors or response classes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contemporary issues in clinical training.

66 directors of clinical training and 118 randomly selected clinicians responded to a questionnaire concerning issues in clinical training. Directors of training were more favorably inclined toward the scientist–professional model than were random clinicians. Random clinicians were more favorably inclined toward alternative, professional models of training than were directors of training. A factor analysis revealed that endorsement of either a scientist–professional model or a professional model and a rejection of the alternative model accounted for 45% of the variance of responses to the questionnaire. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sucrosemia in untreated celiac disease: a potential screening test

During studies to develop serum tests of small intestinal permeability, we detected an unidentified disaccharide in HPLC traces of sera from untreated celiacs. This present study aimed to identify the disaccharide and determine whether the presence of the disaccharide in the serum after an oral challenge had potential as a simple screening test for celiac disease. The disaccharide was identified as sucrose by incubation studies of sera with disaccharidases. Twenty untreated celiacs, 15 treated celiacs, and 20 normal or dyspeptic controls were studied for the presence of sucrose in their serum after an oral load (8 g). The results in celiacs were compared with the presence of serum IgA endomysial antibodies. The 10 normal controls were also given a larger sucrose challenge (50 g). Ten of the untreated celiacs and 10 controls had their brush border disaccharidase activities measured. Sucrose eluted in the same position as the unidentified disaccharide in the HPLC trace and the latter could be removed by incubation with sucrase. All untreated celiacs but none of the treated celiacs had sucrose in their serum after the 8-g oral challenge. None of the controls had sucrose in their serum after the 8-g or 50-g challenges. Three untreated celiacs were IgA endomysial antibody negative as were all the treated cases. Brush border sucrase activity was low in untreated celiac disease. The presence of sucrose in the serum after an oral load shows promise as a noninvasive test for celiac disease.     

Antibody diagnosis iin sprue/celiac disease]

The clinical appearance of celiac disease is diverse, often times uncharacteristic and may therefore be very difficult to diagnose. Furthermore, severe inflammation of the small bowel can be present without gastrointestinal symptoms. It is estimated that most subjects with celiac disease are not diagnosed. Yet, early diagnose is desirable, since celiac disease causes growth retardation in untreated children and is potentially cancer disposing. Thus, all patients should adhere to a strict gluten-free diet. The role of antibody testing and small bowel biopsy in celiac disease will be discussed. In the future, the development of new tests may allow screening of large populations.     

Bone mineral affection in asymptomatic adult patients with celiac disease

OBJECTIVES: Osteopenia is a well-known complication of overt celiac disease, but whether such defective bone mineralization is present among asymptomatic or silent patients is not known. Our objectives were: 1) to examine bone mineralization of a group of asymptomatic celiac patients; 2) to compare these results with those of symptomatic patients. METHODS: Bone mineral density of the spine and total skeleton by dual energy x-ray absorptiometry and serum parameters of mineral metabolism of eight recently diagnosed asymptomatic patients with celiac disease were studied. Results were compared with those obtained in 20 untreated symptomatic celiacs, 14 patients treated with gluten-free diet for a mean time of 15 yr, and 153 healthy adult subjects, matched by sex and age. RESULTS: Four and five out of eight asymptomatic patients presented with reduced mineralization of the spine and the total skeleton, respectively (> 1 SD below normal values for sex and age). Two patients presented with severe osteopenia of the spine, and the other three presented with severe osteopenia of the whole skeleton (> 2 SD below mean normal values). Osteopenia at plane bone level (total skeleton) was significantly lower when compared to healthy controls (p < 0.02). Symptomatic untreated patients had significantly more severe deterioration of bone mineralization than did asymptomatics (p < 0.05) and treated patients (p < 0.05). No difference in bone mineral density was observed between treated patients and asymptomatic celiacs. Serum levels of calcium, alkaline phosphatase, 25-OH vitamin D, and parathormone did not show conclusive abnormalities. CONCLUSIONS: Our findings provide direct evidence that reduced bone mineralization occurs in asymptomatic celiac patients before any other symptom becomes evident. Only early diagnosis and treatment of celiac disease can avoid the deterioration of the bone structure observed in all clinical status of celiac disease.     

Blockage of T-cell costimulation inhibits T-cell action in celiac disease

Alteromonas haloplanctis is a bacterium that flourishes in Antarctic sea-water and it is considered as an extreme psychrophile. We have determined the crystal structures of the alpha-amylase (AHA) secreted by this bacterium, in its native state to 2.0 angstroms resolution as well as in complex with Tris to 1.85 angstroms resolution. The structure of AHA, which is the first experimentally determined three-dimensional structure of a psychrophilic enzyme, resembles those of other known alpha-amylases of various origins with a surprisingly greatest similarity to mammalian alpha-amylases. AHA contains a chloride ion which activates the hydrolytic cleavage of substrate alpha-1,4-glycosidic bonds. The chloride binding site is situated approximately 5 angstroms from the active site which is characterized by a triad of acid residues (Asp 174, Glu 200, Asp 264). These are all involved in firm binding of the Tris moiety. A reaction mechanism for substrate hydrolysis is proposed on the basis of the Tris inhibitor binding and the chloride activation. A trio of residues (Ser 303, His 337, Glu 19) having a striking spatial resemblance with serine-protease like catalytic triads was found approximately 22 angstroms from the active site. We found that this triad is equally present in other chloride dependent alpha-amylases, and suggest that it could be responsible for autoproteolytic events observed in solution for this cold adapted alpha-amylase.     

Proposed criteria for diagnosis of celiac disease in children]

At a seminar arranged in September 1997 by the Swedish Paediatric Working Group for Coeliac Disease, a diagnostic protocol proposed by the working group was approved by a majority of the paediatricians present, representing almost all paediatric units in Sweden. Briefly, a small bowel biopsy is called for in all children, both at presentation and as a control during gluten-free dieting. Subsequent gluten challenge and biopsy are mandatory only in cases of atypical presentation or if the diagnosis is questioned at some future date. Serum antigliadin and anti-endomysial antibody tests are complementary tools. Agreement was also reached regarding the institution of a national coeliac disease registry.