Performing routine follow-up biopsy 1 year after diagnosis does not affect long-term outcomes in coeliac disease.

BACKGROUND: A repeat biopsy is recommended, but often omitted in coeliac disease patients on a gluten-free diet. The effect of performing or not performing repeat biopsies is currently unknown. AIM: To identify factors associated with and the significance of lacking biopsy for long-term outcome. Predictors and the importance of incomplete histological recovery after 1 year was investigated in re-biopsied patients. METHODS: A total of 760 patients participated in a nationwide follow-up study. Medical data were gathered via interviews and patient records, and blood samples were drawn for serology. Current symptoms and well-being were assessed by validated PGWB, SF-36 and GSRS questionnaires. RESULTS: Malabsorption was more common among those with a repeat biopsy (46%) than those without repeat biopsy (33%), P < 0.001, as were severe symptoms at diagnosis (24% vs. 16%, P = 0.05) and concomitant gastrointestinal (40% vs. 32%, P = 0.049) or musculoskeletal (35% vs. 27%, P = 0.023) diseases such as arthritis, osteoporosis and back pain. Repeat biopsy was more rare in subjects diagnosed in private care (11% vs. 23%, P < 0.001) or by screening (10% vs. 16%, P = 0.010). The groups were comparable as to current symptoms and dietary adherence, but those without re-biopsy were less confident of their diet (89% vs. 94%, P = 0.002) and more often seropositive on diet (14% vs. 9%, P = 0.012). They reported better SF-36 physical functioning (P = 0.043) and less pain and indigestion (P = 0.013 and P = 0.046 respectively) and total GSRS (P = 0.052) score. Incomplete mucosal recovery was predicted by more advanced histological (P < 0.001) and serological (P = 0.001) disease at diagnosis, whereas the groups did not differ in long-term adherence, symptoms, seropositivity, questionnaire scores, frequency of fractures or malignancies. CONCLUSIONS: Severe disease at diagnosis predicted the record of a repeat biopsy and incomplete mucosal recovery. Neither lacking biopsy nor incomplete recovery in a relative short time span of 1 year was associated with poorer long-term outcome, although survival bias cannot be excluded.

Refractory coeliac disease in a country with a high prevalence of clinically-diagnosed coeliac disease.

BACKGROUND: Refractory coeliac disease (RCD) is thought to be a rare disorder, but the accurate prevalence is unknown. AIM: We aimed to identify the prevalence of and the risk factors for developing RCD in a Finnish population where the clinical detection rate of coeliac disease is high. METHODS: The study involved 11 hospital districts in Finland where the number of treated RCD patients (n = 44), clinically diagnosed coeliac disease patients (n = 12 243) and adult inhabitants (n = 1.7 million) was known. Clinical characteristics at diagnosis of coeliac disease between the RCD patients and patients with uncomplicated disease were compared. RESULTS: The prevalence of RCD was 0.31% among diagnosed coeliac disease patients and 0.002% in the general population. Of the enrolled 44 RCD patients, 68% had type I and 23% type II; in 9% the type was undetermined. Comparing 886 patients with uncomplicated coeliac disease with these 44 patients that developed RCD later in life, the latter were significantly older (median 56 vs 44 years, P < 0.001), more often males (41% vs. 24%, P = 0.012) and seronegative (30% vs. 5%, P < 0.001) at the diagnosis of coeliac disease. Patients with evolving RCD had more severe symptoms at the diagnosis of coeliac disease, including weight loss in 36% (vs. 16%, P = 0.001) and diarrhoea in 54% (vs. 38%, P = 0.050). CONCLUSIONS: Refractory coeliac disease is very rare in the general population. Patients of male gender, older age, severe symptoms or seronegativity at the diagnosis of coeliac disease are at risk of future refractory coeliac disease and should be followed up carefully.

Radiation exposure to the population of Europe following the Chernobyl accident.

On the occasion of the 20th anniversary of the Chernobyl accident an attempt has been made to evaluate the impact of the Chernobyl accident on the global burden of human cancer in Europe. This required the estimation of radiation doses in each of the 40 European countries. Dose estimation was based on the analysis and compilation of data either published in the scientific literature or provided by local experts. Considerable variability has been observed in exposure levels among the European populations. The average individual doses to the thyroid from the intake of (131)I for children aged 1 y were found to vary from approximately 0.01 mGy in Portugal up to 750 mGy in Gomel Oblast (Belarus). Thyroid doses to adults were consistently lower than the doses received by young children. The average individual effective doses from external exposure and ingestion of long-lived radiocaesium accrued in the period 1986-2005 varied from approximately 0 in Portugal to approximately 10 mSv in Gomel Oblast (Belarus) and Bryansk Oblast (Russia). The uncertainties in the dose estimates were subjectively estimated on the basis of the availability and reliability of the radiation data that were used for dose reconstruction in each country.

Three patients with 9p deletions including DMRT1 and DMRT2: a girl with XY complement, bilateral ovotestes, and extreme growth retardation, and two XX females with normal pubertal development.

It is well documented that distal 9p monosomy can be associated with XY sex reversal. Recently, the possibility of DMRT1 and/or DMRT2 (the genes for doublesex and mab-3 related transcription factor 1 and 2) being the sex determining genes(s) at 9p has been raised. DMRT1 and DMRT2 map near the 9p telomere, distal of marker D9S1779. We describe here three unrelated females with distal 9p monosomy, one with XY complement and two with XX complements. In each individual, fluorescent in situ hybridization predicted the loss of the DMRT genes. Patient 1, an XY individual with monosomy 9pter --> p24.1 approximately 24.2 and trisomy 7q32 --> qter had normal female external genitalia, a blind ending vagina, no uterus, a Fallopian tube on the right, and bilateral ovotestes with primitive ovarian tissue. She also had extreme growth retardation. Around 80 cases of distal 9p monosomy have been reported previously, but there has been no report of ovotestes or gonads comprising ovarian tissue in a XY patient with 9p deletion. Findings in Patient 1 suggest that the phenotypic spectrum of the heterozygous DMRT deletion may include true hermaphroditism. Patients 2 and 3 were 12- and 14-year-old females with XX complements, normal external genitalia, and normal pubertal development. Patient 2 had pure monosomy 9pter --> p23 and Patient 3 had monosomy 9pter --> p22.3 approximately 23 combined with trisomy 3pter --> p23 approximately 24. To date, detailed reports on the gonadal status of XX 9p-females have been limited to prepubertal girls. Patients 2 and 3 are the first females reported to have distal 9p monosomy and a normal puberty.

Boy with celiac disease, malformations, and ring chromosome 13 with deletion 13q32-->qter.

We describe a 2(1/2)-year-old boy with a ring chromosome 13 with distal deletion of 13q32-->qter and celiac disease.

Persistence of translocations after accidental exposure to ionizing radiation.

PURPOSE: To assess the validity of translocations for retrospective biodosimetry using FISH chromosome painting of peripheral lymphocytes in repeated samples of people accidentally exposed to radiation. MATERIALS AND METHODS: Blood samples from five people exposed to mainly whole-body irradiation of gamma-rays from a radiation accident in Estonia in 1994 were taken at 2-4 month intervals. A total of eight samplings were carried out, including one directly after the accident. Fluorescence in situ hybridization with probes for chromosomes 1, 2 and 4 was performed on metaphase preparations from 48 h whole blood cultures; 1500 cells were scored from each individual per time point. RESULTS: Translocations remained relatively stable during 2 years after exposure in all subjects. A noticeable decrease in complete translocation yields and a significant decrease in incomplete translocations were observed in one person. In addition to whole-body exposure, he had also been exposed to partial-body irradiation. Due to the overall persistence of translocations, dose estimates were very similar throughout the 2 year period. A rapid decline in dicentric frequencies was noted during the first year after exposure. CONCLUSIONS: The results suggest that during 2 years the yield of translocations in peripheral lymphocytes remained at a constant level after whole-body exposure. This finding supports the use of translocations for retrospective dosimetry, at least within this relatively short period of follow-up. In the case of partial-body irradiation, however, the elimination of co-existing unstable aberrations reduced the translocation yield over time. Follow-up will be continued in order to determine the stability of translocations over longer times.

Comparison of dose-response curves for chromosomal aberrations established by chromosome painting and conventional analysis.

PURPOSE: To establish 60Co gamma-ray dose-response curves for dicentrics and translocations visualized by chromosome painting and for dicentrics analysed after conventional solid staining. MATERIALS AND METHODS: Analysis of chromosomal aberrations was performed on peripheral blood lymphocytes obtained from 48 h old cultures of irradiated whole blood. Dicentrics were scored from Giemsa-stained preparations, and bi-coloured dicentrics and translocations after FISH painting of chromosomes 1, 2 and 4. RESULTS: Equal frequencies of complete dicentrics and translocations, where both members of the exchanges were seen, were observed in the chromosome painting analysis at all doses, resulting in similar calibration curves. Due to differences in scoring criteria, dicentrics scored in conventionally Giemsa-stained slides agreed better with data for total than for complete exchanges. Donor differences for translocations at the control level and at low doses were seen and large uncertainty surrounds the linear component of the dose-response for total translocations. CONCLUSIONS: Dose reconstruction of past exposures in cases of low doses is very dependent on the linear coefficient of the curve. Results indicate that total translocations would give less reliable dose estimates and therefore complete translocations are preferred.

Biodosimetry after accidental radiation exposure by conventional chromosome analysis and FISH.

A 137Cs source was stolen from a radioactive waste depository in Estonia on 21 October 1994 and kept in a private house for 4 weeks. This resulted in the death of one person, acute radiation injuries to four people and exposure of several other people to lower doses of radiation. Analysis of chromosomal aberrations in peripheral blood lymphocytes was used in the assessment of radiation exposure of 18 people involved in the accident. Dose estimation assessment based on the frequencies of dicentric chromosomes was performed both by the standard method and by considering possible dose protraction and non-uniform exposure. Considerable differences in dose estimates were obtained depending on the approach used, ranging from about 1 Gy to almost 3 Gy in the patients most heavily exposed. In view of the deterministic health effects observed in some of the subjects, it was concluded that the dose estimates involving information on dose protraction were more realistic than those obtained by comparison with the standard high dose-rate calibration curve. Chromosome painting analyses using fluorescence in situ hybridization, with a probe cocktail for chromosomes 1, 2 and 4 and centromere detection, were performed in parallel. Good agreement on dicentric chromosome frequencies was observed between the conventional and painting analyses. The frequencies of complete translocations were comparable with the frequencies of dicentric chromosomes. In addition to the complete translocations, a pronounced increase in the frequency of incomplete translocations was observed. Dose estimates performed on the basis of FISH translocation frequencies were consistent with the dicentric analysis.

"Pure" partial trisomy 4q25-qter owing to a de novo 4;22 translocation.

A girl with a new de novo translocation of 4q onto the short arm of acrocentric 22 is reported as a case of "pure" partial trisomy 4q. Her karyotype was 46, XX,-22, +mar, t(4;22)(q25-->qter;p11) identified by Giemsa staining and FISH. Comparison of the proband with previously reported cases of "pure" partial trisomy 4q showed the main clinical features to be growth retardation, psychomotor retardation, microcephaly, large, low set, malformed ears, prominent nasal bridge, ptosis and epicanthus.

Populational polymorphisms in silver staining of nucleolus organizer regions (NORs) in human acrocentric chromosomes.

The Ag stainability of the nucleolus organizer region (NOR) was studied in the acrocentric chromosomes identified by Q banding of cultured lymphocytes in 41 karyotypically normal persons (33 males and 8 females) originating from southeast Estonia. The data obtained are compared with those established earlier for a combined Vienna-Ulm population of 51 karyotypically normal persons (see Mikelsaar et al., 1977a). Significant differences between the two populations in the frequency and patterns of Ag-positive NORs were found. The following findings were most striking: the frequency of Ag-positive NORs in chromosome 14 and in the totals was significantly lower in the Estonian population than in the Vienna-Ulm population (P less than 0.01). The average modal number of Ag-positive NORs per individual was 7.8 in the Estonian population and 8.7 in the Vienna-Ulm sample (P less than 0.01). If the data of the two populations were combined the frequency of positive NORs was significantly (P less than 0.05) lower in chromosome 22 than in 13, 15, and 21, but not 14.

Variant chromosome 3 (inv3) in normal newborns and their parents, and in children with mental retardation.

The chromosomes of 102 normal newborn babies (51 boys and 51 girls) born at term, their parents, and 45 nonrelated children with mental retardation at the level of imbecility were investigated by fluorescence microscopy using propyl quinacrine mustard. In each of the 11 families, one of the parents had a variant chromosome 3 that was interpreted as resulting from a pericentric inversion of the brilliant band (or C band) only (inv3). In four cases inv3 was transmitted to the child. The frequency of inv3 in newborn boys and girls was 2 and 6% respectively, and in adult men and women 5 and 6% respectively. In children with mental retardation of unknown etiology the inv3 was detected in five cases (11.1%). This difference from normal persons was not significant.