Persistent small bowel mucosal villous atrophy without symptoms in coeliac disease.

BACKGROUND: Refractory sprue with malabsorption carries a risk of lymphoma. AIM: To examine whether a good clinical but poor histological response during a strict gluten-free diet predicts a poor outcome. METHODS: The study involved all coeliac patients who showed no histological recovery within 2 years on a strict gluten-free diet. Small intestinal biopsy and bone mineral density were investigated in 2001 and clinical features were followed up until 2005. The results were compared to those in 18 coeliac patients with a good histological recovery. RESULTS: Thirteen coeliac patients had persistent small intestinal villous atrophy despite maintaining gluten-free diet. All had demonstrated a good clinical response. Osteoporosis was found in 58% and 22% of the non-responders and responders, respectively (P = 0.04). In 2005, two of the non-responders had developed symptomatic refractory sprue, one died of lymphoma and one of carcinoid tumour, and one gastric adenocarcinoma was operated. None of the 18 controls had developed refractory sprue or malignancy. The frequency of histological non-responsive disease was 1.9%. CONCLUSIONS: Persistent villous atrophy in adult coeliac disease, even in the absence of symptoms, carries a risk of subsequent severe complications. The follow-up biopsy is important in detecting these individuals.

Diagnostic significance of HLA-DQ typing in patients with previous coeliac disease diagnosis based on histology alone.

BACKGROUND: Coeliac disease is strongly associated with human leukocyte antigen (HLA)-DQ2 or DQ8 genotypes. The diagnosis is based on demonstrating crypt-hyperplastic villous atrophy, endomysial or transglutaminase antibodies and correlation of disease activity with gluten intake. AIM: To evaluate the clinical utility of HLA-DQ typing, when coeliac disease diagnosis had previously been established solely by histology. METHODS: HLA-DQ alleles, endomysial and transglutaminase antibodies were investigated and histology slides reviewed in 70 patients diagnosed 2-25 years earlier by small-intestinal biopsy but without measuring endomysial or transglutaminase antibodies. Patients without DQ2 or DQ8 or without unequivocal villous atrophy were followed-up on free diet by using serology and biopsies. RESULTS: All 40 endomysial/transglutaminase antibodies positive patients carried DQ2 or DQ8, and 39 of them had severe villous atrophy. Only 56% of patients without endomysial or transglutaminase antibodies positivity had DQ2 or DQ8 (P < 0.001). Seropositivity and relapse developed in 4 of 11 DQ2 positive but in none of 15 DQ2 and DQ8 negative patients on long-term gluten exposure. CONCLUSIONS: Coeliac disease diagnosis based solely on histology is not always reliable. HLA-DQ typing is important in identifying DQ2 and DQ8 negative subjects who need revision of their diagnosis, but it does not have additive diagnostic value if endomysial positivity is already known.

Cytokine gene polymorphisms and genetic association with coeliac disease in the Finnish population.

Coeliac disease (CD) is an intestinal disorder caused by intolerance to dietary gluten in susceptible individuals. The HLA-DQ genes are major risk factors for CD, but other genes also play an important role in the disease susceptibility. Immune-mediated mechanisms are known to underlie the pathogenesis of CD. We studied single-nucleotide polymorphisms in transforming growth factor (TGF)-beta1, interleukin (IL)-10, IL-6, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha genes in the Finnish population using family-based association approach. In addition, we genotyped a trinucleotide repeat polymorphism in the major histocompatibility complex (MHC) class I chain-related protein A (MICA) gene, located in the human leucocyte antigen (HLA) region in the vicinity of TNF-alpha. To control the effect of linkage disequilibrium between HLA-DQ genes and MICA and TNF-alpha, an HLA-stratified association analysis was performed. We did not find evidence of association between TGF-beta1, IL-10, IL-6 and IFN-gamma polymorphisms and CD susceptibility. No association was found for any of the MICA alleles independently of DQ genes, whereas TNF-alpha-308 A allele was slightly overrepresented on chromosomes carried by CD patients compared with control chromosomes, indicating that either TNF-alpha, or another gene in linkage disequilibrium with it, could confer increased susceptibility to CD. This result supports the earlier findings that the HLA region harbours a novel susceptibility factor in addition to HLA-DQ.

Elevation of IgG antibodies against tissue transglutaminase as a diagnostic tool for coeliac disease in selective IgA deficiency.

BACKGROUND: IgA serum autoantibodies against tissue transglutaminase (tTG) have an established diagnostic value in coeliac disease, and high efficacy tests are widely available for their detection. However, serological evaluation of IgA deficient subjects is still difficult. AIMS: To evaluate the diagnostic potential of IgG class anti-tTG autoantibodies measured quantitatively using an enzyme linked immunosorbent assay (ELISA) compared with immunofluorescent detection of coeliac autoantibodies. PATIENTS: We tested serum samples from 325 IgA deficient subjects, including 78 patients with coeliac disease, 73 disease controls, and 174 blood donors. METHODS: IgG antibodies against human recombinant tTG were measured with an ELISA. IgG antiendomysium antibodies (EMA) were assayed by indirect immunofluorescence on human jejunum and appendix sections. RESULTS: The IgG anti-tTG ELISA had a sensitivity of 98.7% and a specificity of 98.6%, and the correlation with IgG EMA titres was high (r(s)=0.91). One coeliac patient, initially negative in all autoantibody tests, displayed both IgG anti-tTG antibodies and IgG EMA during later gluten exposure. IgG anti-tTG antibodies and EMA titres showed significant decreases (p<0.001) in treated patients. The frequency of IgG anti-tTG autoantibody positivity was 9.8% among IgA deficient blood donors and 11 of the 12 positive subjects with known HLA-DQ haplotypes carried DQ2 or DQ8 alleles. CONCLUSIONS: IgG anti-tTG and IgG EMA autoantibody tests are highly efficient in detecting coeliac disease in IgA deficient patients. The high prevalence of coeliac antibodies among symptom free IgA deficient blood donors who also carry coeliac-type HLA-DQ genes indicates that all IgA deficient persons should be evaluated for coeliac disease.

CD80 (B7-1) and CD86 (B7-2) genes and genetic susceptibility to coeliac disease.

The role of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) in T-cell activation makes them good candidates for coeliac disease susceptibility genes. We conducted a genetic linkage study of the CD80/86 gene region in the general Finnish population and in a local subisolate. No linkage was found in either population.

Adjuncts to the nurse's skills? Advantages and disadvantages of expert systems.

Expert systems can, if properly devised, help nurses make clinical decisions. This, the final article in the series, looks at the advantages and disadvantages to their use.

A computerised assessment for clinical care. An expert system for pressure sore management.

Computer technology can be used to provide practical guidance in the clinical setting. This article describes how an expert system was devised to assist nurses in the decision making process required in pressure sore management.

An expert to help you give the right care. Expert systems in clinical decision-making.

Expert systems provide nurses with a computerised assessment of the nursing care applicable to their specialty. Rather than representing a threat to the profession, they enable specialist knowledge to be made more widely available.

Crisis theory: a paradigm of effective intervention with families of critically ill people.

Admission to a critical care unit often causes a great deal of distress and anguish, not only for the patient but also his or her family. If one believes in the holistic approach to care, then it is essential that the critical care nurse is able to identify the specific needs of family members, and demonstrate appropriate intervention techniques with those in need of support. It is suggested that crisis theory can provide an effective tripartite framework on which to base such nursing care. Following a brief description of its development and basic principles, application of its approach will be demonstrated in relation to the specific needs and concerns which have been identified from responses of family members themselves. Suggestions are offered which may assist the nurse in further developing basic communication skills which can assist the intervention process at this difficult time. Awareness of such principles is of value to all workers in critical care areas.

Nursing diagnosis: exploring the factors which may influence the reasoning process.

Nursing diagnosis is defined and discussed in relation to nursing's metaparadigm, the cognitive processes involved in problem-solving, and nursing's theoretical knowledge base. It is argued that each of these distinct yet related domains must be addressed by the clinician when applying the reasoning process. Factors are identified which can hinder and dramatically influence this diagnostic process, even to the detriment of the patient's welfare. Suggestions are offered throughout the discussion which may assist the nurse in developing more effective and accurate clinical decision-making strategies.