Screening for asymptomatic celiac disease among patients referred for bone densitometry measurement.

Celiac disease (CD) is a relatively common gastrointestinal disorder that can be asymptomatic. An increased prevalence of subclinical CD has been reported in many populations. Even among asymptomatic patients a reduction in bone mineral density (BMD) has been observed. The aim of this study was to evaluate the prevalence of silent CD in a cohort of consecutive individuals referred for bone densitometry measurement. Serum samples were taken from 454 women attending for bone densitometry (mean age: 56 +/- 11 years). Of the individuals evaluated, 89 had normal BMD and 365 had low BMD (T score < -1.0). Subjects were screened for the presence of serum IgA anti-endomysial antibodies (EMA) and IgA tissue transglutaminase (tTG) antibodies by indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA), respectively. BMD was measured by dual X-ray absorptiometry (DEXA) at the lumbar spine and femoral neck. Eight EMA tTG-positive individuals were identified in this population (1.8% or 1:57). Serologically positive women had a lower mean Z score at both the lumbar spine and femoral neck than EMA tTG-negative women. But this did not approach significance. There was no significant difference in the incidence of CD between the normal- and low-BMD groups in this dataset (P = 0.365). In conclusion, our study indicates that the prevalence of CD in our dataset is high. However, the frequency of asymptomatic CD among low-BMD individuals is similar to that among normal-BMD individuals in our population. These observations do not support the hypothesis that serological testing for CD may be a good accompaniment to DEXA scanning.

Coeliac disease and autoimmune Addison's disease: a clinical pitfall.

BACKGROUND: Coeliac disease has an increased prevalence in a number of autoimmune endocrine conditions. An association between coeliac disease and Addison's disease has been proposed in isolated case reports, but has not been formally studied. AIM: To investigate the extent of this association. DESIGN: Prospective screening of patients with confirmed Addison's disease. METHODS: From central computerized records, we identified all living patients with a diagnosis of autoimmune Addison's disease in the past 30 years and presently attending our affiliated hospitals. After exclusions, 44 were invited to attend for screening. RESULTS: Of 41 patients screened, five (12.2%) had coeliac disease: Three were previously diagnosed coeliacs and this was confirmed on review, including examination of biopsy material. A further two had positive IgA-endomysial antibodies. Histological confirmation was obtained in both cases. Neither had laboratory or clinical evidence of malabsorption. DISCUSSION: In this series of patients with Addison's disease, a higher co-morbidity with coeliac disease was observed than in any previously studied endocrine condition. We recommend that coeliac serology (anti-endomysial and tissue transglutaminase antibody) testing be incorporated routinely into the autoimmune screen for other conditions in patients with Addison's disease.

Fate of (14)C-labeled carbonyl sulfide on grains and grain fractions.

14C-Labeled carbonyl sulfide (COS) was used to measure the amount of sorbed fumigant and alteration products on grains. Wheat, paddy rice, polished rice, mungbean, and safflower were exposed to a 60 mg L(-)(1) of (14)COS for 7 days and then aired for 5 days. Carbonyl sulfide and/or alteration products in sugars, protein, starch, amino acids, protopectines, and hemicelluloses were undetectable. The total uptakes of radioactivity determined after fractionation and also by extraction were in the range of 36-53 ng g(-)(1) COS equiv. The total radioactivity determined by autoradiography was below the detection limit of 70 ng g(-)(1) COS equiv. Radioactivity in the commodities was less than 0.003% of all the radioactivity applied. The amount of retained radiolabel was measured in three ways. First, biochemical fractions such as lipids and amino acids were separated by chromatography, and the activity was determined in each component. Second, commodities were crushed and extracted in aqueous acetone until the maximum amount of radiolabel was extracted. Third, autoradiography was carried out on commodity kernels.

Evaluation of a high-throughput second antibody radiobinding assay for measuring IgA antibodies to human tissue transglutaminase.

We describe a novel high-throughput radiobinding assay for IgA antibodies to tissue transglutaminase (TG) which uses second antibody precipitation to isolate immune complexes. Using this assay, 24 of 25 patients with untreated coeliac disease (96%) and nine of 526 healthy blood donors (2%) had TG antibody levels above a threshold defined by the 97.5th centile of 347 schoolchildren. All patients and five of the nine blood donors with transglutaminase antibodies above this threshold were endomysial antibody (EMA) positive. Using this threshold, 410/445 (92%) routine clinical samples were concordant for TG antibodies and EMA, including 72 of 75 with EMA. TG antibodies above the 97.5th centile were found in 32 of 370 EMA negative samples, 15 of whom had anti-gliadin antibodies (AGA), histologically proven coeliac disease or partial villous atrophy. We conclude that this assay achieves a sensitivity and a specificity at least equivalent to those of EMA. It is technically simple and suitable for coeliac disease screening.

Paradoxical response to heparin in 10 patients with ulcerative colitis.

OBJECTIVES: A patient with ulcerative colitis refractory to standard therapy was treated with heparin for a deep vein thrombosis. Paradoxically, rectal bleeding did not increase; instead, his colitis rapidly went into remission. The same effect occurred when this patient was later treated for a pulmonary embolism. On the basis of these observations and reports of a hypercoagulable state in ulcerative colitis, heparin was tested as a therapeutic agent in nine additional patients. METHODS: Nine of the 10 patients had ulcerative colitis poorly controlled on sulfasalazine and prednisolone. Two had associated thromboembolic disease, and one was on no medication. Patients were started on heparin in hospital, taught to self-inject subcutaneously, and discharged to continue on 10,000 U of unfractionated heparin twice daily. Current doses of sulfasalazine were maintained; prednisolone was tapered and stopped. Patients were carefully monitored for adverse side-effects. Sections of colonic mucosa from nine patients were examined for intravascular thrombosis of the mucosal blood vessels. RESULTS: Nine patients became asymptomatic (normal stool frequency, no rectal bleeding) on combined heparin and sulfasalazine therapy; one patient had a partial improvement in symptoms. Highly significant statistical differences between pre- and posttreatment mean scores were found for all disease parameters. Intravascular fibrin thrombi were identified in sections from six of nine patients. No serious complications were associated with this use of heparin. CONCLUSIONS: The heparin-linked remission of ulcerative colitis, observed by chance in our first patient, was followed by similar responses in eight of nine further patients. This suggests that, used as described, heparin may have a role in treating refractory ulcerative colitis.

Epstein-Barr virus in normal, pre-malignant, and malignant lesions of the uterine cervix.

AIM--To detect the presence or absence of Epstein-Barr virus (EBV) in cervical lesions ranging from normality to invasive malignancy. METHODS--Eighteen randomly selected cases of invasive squamous cell carcinomas of the uterine cervix were examined as well as 25 cases each of normal cervices and those showing cervical intra-epithelial neoplasia (CIN) I, II, and III. DNA-DNA in situ hybridisation, using a biotinylated probe to the Bam H1 "W" fragment of EBV, was carried out in addition to the polymerase chain reaction using specific primer sequences that flank a 153 base pair segment of the Bam H1 "W" region of the EBV genome and which do not cross-amplify other DNA herpes viruses. Positive control material included paraffin wax embedded P3 HR1 lymphoblastoid cells (containing high copy numbers of EBV) and two nasopharyngeal carcinomas positive for EBV. RESULTS--Neither normal nor CIN I tissue was positive. Eight per cent of CIN II tissue was positive; 8% of CIN III, and 43% of carcinomas were positive for EBV. CONCLUSION--The study shows that the virus is present in some cases of cervical carcinoma and to a lesser degree in some premalignant lesions of the cervix, but the exact association between it and cervical oncogenesis, be it causative or incidental, remains to be determined.

Adenoacanthoma of the endometrium: morphological changes induced by human papillomavirus.

The observation of koilocyte-like features in the squamous epithelium of some endometrial adenoacanthomas prompted an investigation into a possible viral aetiology. These changes closely resemble those that occur in the ectocervical mucosa which are accepted as morphological evidence of human papillomavirus (HPV) infection. Sections of 87 hysterectomy specimens removed for endometrial carcinoma over 12 years, together with preoperative curettings, were reviewed for the presence of acanthomatous change and for appearances suggestive of HPV infection. The ages of the women ranged from 36 to 84 years, average age 62.6. Light microscopical examination showed koilocytosis, papillary formations, and intranuclear eosinophilic inclusions of both squamous and glandular epithelium in some tumours. Immunocytochemistry and DNA in situ hybridisation indicated the presence of HPV antigen in squamous and glandular cells, and perinuclear virus particles characteristic of HPV were seen on electron microscopical examination in those cells with nuclear inclusions. HPV probably infects endometrial adenocarcinomas directly from the cervix but it is unlikely that it has an aetiological role. It is possible, however, that in addition to being a "passenger," the virus may stimulate squamous metaplasia in some adenocarcinomas of the endometrium and may also exert some influence on their behaviour.