A prospective study into the aetiology of lymphocytic duodenosis.

BACKGROUND: Lymphocytic duodenosis is defined by normal villous architecture and intraepithelial lymphocytes (IELs) >25 per 100 enterocytes. Such patients should not be diagnosed with coeliac disease, solely by histology, as previous retrospective studies have suggested other associations with lymphocytic duodenosis. AIM: To study prospectively the aetiology of lymphocytic duodenosis. METHODS: One hundred patients with lymphocytic duodenosis were investigated rigorously for coeliac disease and other known associations for lymphocytic duodenosis by initial investigations of coeliac serology, and exclusion of infection. Of 34 with no explanation for lymphocytic duodenosis, 29 underwent repeat duodenal biopsies following a gluten challenge. RESULTS: Coeliac disease was present in 16% of patients with lymphocytic duodenosis. In the absence of a positive coeliac diagnosis, lymphocytic duodenosis was most commonly associated with drugs (21%), infection (19%), immune dysregulation (4%), inflammatory bowel disease (2%), microscopic colitis (2%), sarcoidosis (1%) and IgA deficiency (1%). Of 34 with no known associations, 18 had symptoms of irritable bowel syndrome (IBS), and in 29 patients investigated with repeat duodenal biopsies, the IEL count returned to normal in 22. CONCLUSIONS: In 66% of cases of lymphocytic duodenosis, a known association can be found by further investigations; importantly, 16% will have coeliac disease. In those with no apparent cause, there may be an association with IBS and the IEL count becomes normal on repeat biopsy in 76%.

Extraction of single-copy nuclear DNA from forensic specimens with a variety of postmortem histories.

Specimens of human bone, teeth and dried blood spots from 3 months to 91 years old, with a variety of postmortem histories, were used in a comparative study of recovery of single-copy nuclear DNA sequences from forensic material. Sequences of the amelogenin and HLA-DPB1 genes were chosen for their value in sexing and identification. Sequences of the mitochondrial non-coding region V were also amplified to compare the recovery of mitochondrial and single-copy nuclear DNA. A variation of the silica method for DNA extraction was refined for application to the forensic specimens in this sample. Single-copy nuclear DNA was amplified from 100% of recent postoperative bone specimens (n = 6), 80% of forensic teeth and bone specimens (n = 10), 78% of recently extracted teeth (n = 18), 78% of exhumed bone up to 91 years old (n = 37) and 69% of 15 year old bone specimens fixed in 10% formalin (n = 20). Amelogenin sexing was correct in 85% of cases (n = 74) in which the sex of the donor had been recorded. There was no correlation between the age of the specimen and the extent of DNA preservation.

Clinical spectrum of familial Hibernian fever: a 14-year follow-up study of the index case and extended family.

OBJECTIVE: To determine the clinical spectrum and natural history of the disease "familial Hibernian fever" (FHF). DESIGN: We ascertained the disease status in all 54 living members and 9 deceased members of the extended family and conducted a detailed study of those affected. MATERIAL AND METHODS: All family members with FHF were clinically assessed and investigated fully, including human leukocyte antigen (HLA) typing. Medical records were studied for relevant clinical features, drug therapy, and complications. All previously obtained histologic specimens were reviewed. Three typical case histories are presented. RESULTS: The updated family tree confirmed an autosomal dominant mode of inheritance in 16 living members with FHF. In addition to the febrile attacks, abdominal pain and localized myalgias were almost invariably present. Episodic erythematous patches, conjunctivitis, and unilateral periorbital edema were also notable features. Of 10 affected male family members, 8 had inguinal hernias (in comparison with 1 of 21 unaffected male family members). No association with HLA status was noted. Secondary amyloidosis was found in one affected member. CONCLUSION: The characteristic clinical features and natural history of FHF distinguish it from other periodic fever syndromes. The discovery of amyloidosis related to FHF alters the prognosis associated with this condition and emphasizes the need to search for effective treatment strategies. The high prevalence of inguinal herniation may provide clues about its pathogenesis.

A simple method for extracting DNA from old skeletal material.

Extraction of DNA from old skeletal material is of great importance in the identification of human remains, but is particularly difficult because the methods currently employed, especially those using phenol/chloroform, are not always satisfactory. A simple technique based on the removal of non-nucleic acid material by salting out (precipitation) with saturated sodium acetate is described; the presence of DNA in the extract being confirmed by amplification of selected sequences of the HLA-DRB1 gene using the polymerase chain reaction (PCR). The method was applied to fresh bone (five femoral heads and six vertebral bodies) and to bone from two forensic cases, 3 and 9 months post-mortem, respectively. Parallel extractions using the phenol/chloroform technique were performed on all samples in order to compare the efficiency of the two methods. Using sodium acetate precipitation, amplifiable DNA was consistently extracted from fresh bone, as well as from the two forensic cases. With the phenol/chloroform method, amplification was successful in only 7 out of 11 instances with the fresh bone samples and failed in both forensic cases. The studies also showed that an effective way of removing PCR inhibitors is to subject the extract to agarose gel electrophoresis, isolate the high molecular weight area and re-extract the DNA from the gel by boiling. It was concluded that the sodium acetate method is a valid alternative to established techniques for extracting DNA from bone and that it offers the advantages of being simple, quick, inexpensive and avoids using hazardous reagents.

Kinetics of the decline phase of the primary response to human serum albumin in the bird.

After the intravenous injection of a wide range of doses of human serum albumin (50 micrograms--10 mg) the biosynthesis of antibody maintained constant kinetics although the peak titre increased with the dose of antigen throughout this range. After the rapid rise to a sharp peak at day 7, the antibody levels in the decline period (7-17 days) manifested exponential decay and a constant half-life of 2.2 days which approximated to that observed with passively administered 131I-labelled 7S chicken Ig. It was concluded that after the antibody peak no further antibody production occurs and the switching-off of this antibody response must begin about 3 days before the time of the peak: counts of antibody-containing plasmacytes in the spleen were maximum at day 4. The rate of antibody catabolism and the timing of switch-off of antibody production appeared to be independent of either the dose of antigen injected or the level of antibody at the peak. The mechanisms of the switch-off are discussed.