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Biomedical subjects

E Rambusch

Publications and source records attributed to E Rambusch.

8 recordsLinked to original sources

Complete response of a gastric primary after a short but toxic course of 'S-1' EORTC Early Clinical Studies Group.

We report the case of an unresected, metastatic gastric cancer, which was treated with a very short course of the oral 5-fluorouracil (5-FU) prodrug S-1. The patient had to discontinue chemotherapy during the first treatment cycle due to severe toxicity, but achieved a pathologically confirmed, long-term complete response of her primary tumour, a diffuse-type poorly differentiated adenocarcinoma.

Adenocarcinoma↗

Malabsorption with progressive weight loss and multiple intestinal ulcers in a patient with T-cell lymphoma.

We describe a 52-year-old woman who presented with severe diarrhea, nausea, intermittent abdominal pain and weight loss of 18 kg within ten months. Jejunal and duodenal ulcers were detected by endoscopy and multiple biopsies revealed villous atrophy of the jejunum. However, neither gliadin nor endomysium antibodies were detected and no clinical and histological improvement was achieved after gluten withdrawal. Despite strong clinical suspicion for intestinal lymphoma many unrevealing biopsies were done. The patient developed intermittent septic fever and diagnostic laparotomy revealed jejunal perforation. Partial jejunal resection was performed and histology confirmed the diagnosis of an intestinal T-cell lymphoma without celiac disease. Malabsorption and all intestinal ulcers disappeared during the course of chemotherapy (six cycles CHOP) and the patient recovered remarkably.

Biopsy↗

Caries experience, dental health behaviour and social status--three comparative surveys among Danish military recruits in 1972, 1982 and 1993.

OBJECTIVE: To compare caries experience among young Danish men in 1972, 1982 and 1993; and on the same occasions to describe relationship between their utilisation of regular dental care and social status, as well as the relationship between their caries experience, utilisation of dental services and social status. DESIGN: During their routine health examinations in 1972, 1982 and 1993 all recruits enlisted in the Danish Air Force were subjected to an additional oral examination combined with a structured socio-dental questionnaire. Identical methods were applied in each of the three surveys. SETTING: Dental clinics at air bases in Denmark. SUBJECTS: 4,103 male military recruits, aged 18 to 25 years. OUTCOME MEASURES: Caries was registered in accordance with the WHO Basic Methods 1971. The questionnaire provided information on age, place of residence during childhood, social origin, and patterns of utilisation of dental services. RESULTS: The findings indicated a considerable decrease in average caries experience from 16.6 DMFT in 1972 to 11.8 in 1982 and 6.2 in 1993. The results further documented markedly increased availability of public school dental health services, the coverage rising from 33% in 1972 to 65% in 1982 and 100% in 1993, as well as moderately increased utilisation of regular dental care with private practitioners, rising from 71% in 1972 to 86% in 1982 and 84% in 1993. In 1993 as in 1982 and 1972, recruits who used the public school dental health services and also received regular dental care after their school leaving age showed the lowest average caries experience. CONCLUSIONS: The findings indicate a marked decrease in average caries experience and an increased utilisation of dental services among Danish young men from 1972 to 1993. However, in 1993 the least privileged social group continued to maintain the highest average caries experience and the lowest rate of utilisation of regular dental care.

Adolescent↗

Patients treated with interferon-alpha, interferon-beta, and interleukin-2 have a different thyroid autoantibody pattern than patients suffering from endogenous autoimmune thyroid disease.

Cytokines are believed to mediate the induction and perpetuation of autoimmune thyroid disease (ATD) in humans. However, this concept is mainly based on in vitro findings and to date, concrete in vivo evidence is still lacking. This prompted us to compare serum thyroid parameters of patients treated with cytokines with patients suffering from ATD. The cytokine group (n = 61) consisted of patients suffering from chronic hepatitis (n = 27) and from hemato-oncological diseases (n = 34). Patients were treated with interferon-alpha (IFN-alpha) or IFN-beta, either alone (n = 31) or in combination with interleukin-2 (IL-2) (n = 15) or with antineoplastic agents (n = 15). The ATD group (n = 105) consisted of 51 patients with Graves' disease, 26 with euthyroid ATD, 18 with Hashimoto's disease, and 10 with atrophic thyroiditis. Only 6 of 61 patients (10%) from the cytokine-treated group had thyroid peroxidase antibody (TPOAb) titers equal to or greater than 100 U/mL, whereas 82 of 87 patients (94%) suffering from ATD had TPOAb titers equal to or greater than 100 U/mL (p = 0.0001). In contrast, the percentage of patients who had thyroglobulin antibody (TgAb) serum titers equal to or greater than 100 U/mL were identical in both groups: 25 of 61 patients (41%) treated with cytokines versus 40 of 87 patients (46%) suffering from ATD (p = 0.789). Thus, patients with ATD had significantly higher TPOAb titers (p = 0.0001) whereas TgAb titers were not significantly different compared with patients from the cytokine group. The substantial difference in autoantibody response raises the possibility that thyroid abnormalities associated with ATD reflect genetic susceptibility and/or an independent stimulus or incident aside from cytokine dysfunction and that cytokines may play a secondary, rather than primary role in disease expression.

Adult↗

TSH-receptor expression and human thyroid disease: relation to clinical, endocrine, and molecular thyroid parameters.

Thyrotropin receptor (TSH-R) gene expression can be positively or negatively regulated by TSH and stimulating TSH-R antibodies (TSAbs) in immortalized thyroid cell lines such as rat FRTL-5 cells. However, regulation is less clear in other mammalian cells including cultures of human thyroid cells. Additionally, it has been suggested, based on FRTL-5 cell data, that TSH-R gene negative regulation by TSH or TSAbs might be lost in Graves' disease. The present study evaluated TSH-R gene transcript levels in thyroids from patients with Graves' disease to correlate in vivo data with in vitro observations or hypotheses. TSH-R mRNA levels were characterized in a total of 66 human thyroid glands with particular concern to levels in Graves' patients. Results were related to clinical parameters, transcript levels of thyroglobulin (TG), and thyroid peroxidase (TPO), as well as transcript levels of thyroid transcription factor 1 (TTF-1) which regulates the expression of all three genes and paired box-gene 8 (Pax-8) which regulates TG and TPO gene expression. Northern blot analyses showed that TSH-R expression was significantly increased, 2.2-fold, in Graves' thyroids (p = 0.0098, n = 35) by comparison to normals (n = 6). TSH-R mRNA levels were decreased to 30% and 7% of normal levels in Hashimoto's thyroids (p = 0.0281, n = 5) and anaplastic carcinomas (p = 0.0033, n = 6), respectively. No significant changes were seen in endemic goiters (n = 8) and in thyroid autonomy (n = 6). TSH-R RNA levels were higher, 3.6-fold, in thyroids of a subgroup of Graves' patients that had not been pretreated with iodide before surgery (n = 10) by comparison to thyroids from those that had been treated before surgery, 1.7-fold (n = 25). TSH-R antibodies exhibited a nonsignificant tendency toward a negative correlation. All other clinical or endocrine parameters showed no clear relation to TSH-R mRNA levels. Pax-8 and TTF-1 transcripts were detectable in normal thyroids; however, Pax-8 expression was increased in Graves' thyroids (3.8-fold), whereas TTF-1 expression was only minimally changed in all thyroids investigated. Changes of the two did not correlate. Pax-8 expression correlated with TG and TPO expression (in all cases, p = 0.0001); TTF-1, despite its minimal change, still correlated with TG (p = 0.0471) but not with TPO expression (p = 0.0984). TTF-1, again despite its minimal changes, correlated positively with TSH-R gene expression (p = 0.0251); however, surprisingly, Pax-8, which does not regulate TSH-R gene expression, correlated even better with TSH-R transcript levels (p = 0.0001). We conclude that augmentation of TSH-R expression levels, and thus potential ligand binding sites, may indicate an important regulatory principle in the pathogenesis of autoimmune hyperthyroidism in vivo: the responsiveness of the TSH-R to TSH and TSAb induced negative regulation is lost. This increase of TSH-R expression levels is not due to an ongoing transcriptional activation of the TTF-1 gene. Pax-8, though positively correlated with TSH-R RNA levels, cannot be the factor either, because Pax-8 does not upregulate TSH-R expression. This predicts that other factors involved in TSH-R induced negative regulation are abnormal and must be searched for and evaluated.

Adolescent↗