[Simultaneous papillary carcinoma in a thyroglossal duct remnant and the thyroid gland]. / Simultanes papilläres Schilddrüsenkarzinom in einer medianen Halszyste und Zweitkarzinom der Schilddrüse.

BACKGROUND: In 1 % of the thyroglossal duct cysts malignant transformation is found with predomination of the papillary carcinoma (80 %). CASE REPORT: We present the case of a 51 year old man with a synchronic papillary carcinoma in a thyroglossal duct remnant and a microcarcinoma of the thyroid gland. After exstirpation of a thyroglossal duct cyst histological examination identified a papillary carcinoma. Postoperative staging uncovered enlarged lymph nodes but no abnormalities in the thyroid gland. Cervical lymphadenectomy and total thyroidectomie was performed. On histological examination a synchronic microcarcinoma of the thyroid was shown. CONCLUSION: Only 7 similar cases have been published in literature before. Because of the rare incidence no therapeutic standard could be established so far. We discuss our therapeutic approach as well as the relevant literature.

Diagnostic and prognostic relevance of autoantibodies in uranium miners.

Uranium miners exposed to silica dust have a higher risk of developing systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). Sera of 1976 former uranium miners were analysed for autoantibodies typical of connective tissue disease. The frequency of some of these antibodies (anti-centromere, -topoisomerase I, -nucleolar, -dsDNA, -Ro/SSA, -La-SSB and U1-RNP antibodies) was significantly higher compared to a gender- and age-matched control group and was associated with the intensity of exposure as well as with clinical symptoms of SSc or SLE. It was also shown that SSc-associated autoantibodies may serve as an early indicator of disease development. Some differences in the autoantibody production between silica-dust-associated and idiopathic SLE/SSc were observed that might be caused by environmental factors in the population of uranium miners.

Antibody response to the tumor-associated inhibitor of apoptosis protein survivin in cancer patients.

Antibody reactivity against survivin, a recently identified tumor-associated protein, was determined in sera from patients with lung (n = 51) or colorectal cancer (n = 49). The same collection of sera was tested for the presence of antibodies against p53. Eleven sera from lung cancer patients and four sera from colorectal cancer patients reacted with purified recombinant survivin in an ELISA (21.6% and 8.2%, respectively), whereas four sera from lung cancer patients and nine sera from colorectal cancer patients contained anti-p53 antibodies (7.8% and 18.4%, respectively). The increase in prevalence when anti-survivin and anti-p53 antibodies were determined in parallel was statistically significant (29.4% versus 7.8%, P = 0.005 in lung cancer population; 26.6% versus 8.2%, P = 0.015 in colorectal cancer population). The high prevalence of anti-survivin antibodies makes these antibodies an attractive novel marker for the diagnosis of lung and colorectal cancer, particularly in patients lacking anti-p53 antibodies.

German uranium miner study--historical background and available histopathological material.

Mining activities in the former German Democratic Republic were documented as early as 1168 in the ore mountains (Erzgebirge) of Saxony. Silver, bismuth, cobalt, nickel and tungsten were mined from then up to the end of the 19th century. After the Second World War, the Soviet Occupation Authorities reopened the old silver mines in Saxony to mine uranium for the Soviet nuclear industry. About 400, 000 workers produced a total of 220,000 tons of uranium during the years 1946 to 1990. After the reunification of Germany, the archive of the Institute of Pathology of the mining area was opened for research. It contains protocols of 28,975 autopsy cases and about 400,000 slides collected from 1957 to 1992, about 66,000 tissue blocks, and 238 whole lungs. From the autopsy cases, 17,466 could be identified as workers of the uranium mining company. The remainder of the cases were in the population of the mining area. A comparison of the frequencies of malignancies of male workers older than 15 years with those of the population of the mining area for the years 1957 to 1989 demonstrates a significantly higher percentage of lung cancer among the uranium miners. There was no significant difference for other solid cancers and leukemias.

German uranium miner study--pathological and molecular genetic findings. German Uranium Miner Study, Research Group Pathology.

Uranium miners of the former Wismut company in Germany form the largest cohort of workers exposed to (222)Rn and dust in the world. The German Uranium Miner Study, Research Group Pathology, is evaluating the central pathology archive of the Wismut company. The main tasks of our study are pathological-anatomical and molecular genetic investigations of 28,975 autopsy cases and the evaluation of mining pollutants in the lungs by neutron activation analysis. As part of an observer agreement study, lung tumors are classified according to the WHO/IASLC classification and nontumorigenic lung disorders are registered. Lung tumors were analyzed for the presence of a proposed radon-specific mutation in the TP53 gene (formerly known as p53). Interim results are: (a) In the years 1957 to 1965, a high rate (69%) of small cell carcinomas was found which had declined to 34% by 1990. (b) The percentage of the deceased who suffered from silicosis is not higher in the group of lung tumors than in other tumor groups or the nontumor group. (c) The hypothesis of a radon-characteristic hotspot mutation in the TP53 tumor suppressor gene is not supported by our investigations. (d) Neutron activation analysis demonstrates that uranium, arsenic, chromium, cobalt and antimony can be found in tissue samples from the miners even when they had stopped working more than 20 years before death.

[Rupture of the pulmonary artery - fatal complication by pulmonary artery balloon-tipped catheter]. / Pulmonalarterienruptur - letale Komplikation einer Einschwemmkatheteruntersuchung (Thermodilutionskatheter).

The flow directed balloon-tipped pulmonary artery catheter introduced by Swann and Ganz 1970 has made possible the measurement of filling pressures in the heart and is extensively used in operating rooms, in catheterization laboratories and in intensive care units. The rupture of the pulmonary artery is an uncommon complication associated with a high mortality rate exceeding 50 percent. Main symptoms are cough, hemoptysis, dyspnea and cardiac shock. Complications occur if guidelines for the safe use of the balloon-tipped catheters are not strictly followed: Excessive catheter manipulation, advancing the catheter tip too far peripherally and leaving the inflated balloon in the wedge position for long periods should be avoided. Patients with pulmonary hypertension as well as elderly and anticoagulated patients are at greater risk.

Different distribution of HLA class II and tumor necrosis factor alleles (TNF-308.2, TNFa2 microsatellite) in anti-topoisomerase I responders among scleroderma patients with and without exposure to quartz/metal dust.

OBJECTIVE: To investigate the influence of quartz/ metal dust exposure on the pathogenesis of systemic sclerosis (SSc; scleroderma), by an immunogenetic comparison of HLA class II and tumor necrosis factor (TNF) alleles in patients with and without exposure. METHODS: A retrospective study of 30 SSc patients exposed to quartz/metal dust (qSSc) and 50 patients with idiopathic SSc (iSSc) was conducted by DNA-based typing of HLA, TNF-308, and TNFa/b microsatellite alleles. RESULTS: A neutral or protective haplotype in iSSc anti-topoisomerase I (anti-topo I) responders was found to be a susceptibility haplotype in qSSc patients. HLA-DRB1*0301 (DR3), a component of the extended haplotype HLA-DQA1*0501;B1*0201;DRB1*0301; TNF-308.2;TNFa2/b3, had a decreased frequency in iSSc anti-topo I responders compared with non-responders (P = 0.03, odds ratio [OR] 0.11, 95% confidence interval [95% CI] 0.00-0.95), but a significantly increased frequency in qSSc anti-topo I responders compared with controls and with iSSc anti-topo I responders (P = 0.00004, Pcorr = 0.006, OR 11.38, 95% CI 3.17-44.35 and P = 0.0002, Pcorr = 0.02, OR 30.0, 95% CI 2.05-986, respectively). In contrast, DRB1*1104 (DR5) and DRB1*11/15 (DR5/DR2) with no TNF-308.2 and TNFa2 alleles were prevalent in only the iSSc anti-topo I responders compared with controls (P = 0.0005, Pcorr = 0.04, OR 11.0; 95% CI 2.68-45.93 and P = 0.0002, Pcorr = 0.02, OR 12.43, 95% CI 3.65-40.04, respectively). CONCLUSION: The mechanisms that lead to the development of anti-topo I in qSSc and iSSc patients are suggested to be distinct, although it is not clear that the two diseases themselves are different.

The pathogenic 16/6 idiotype in patients with silica associated systemic lupus erythematosus (SLE) and uranium miners with increased risk for development of SLE.

OBJECTIVE: To investigate the prevalence of the 16/6 idiotype (16/6 Id), a major cross reactive idiotype of anti-DNA antibodies involved in the pathogenesis of experimental lupus, in subjects with an exogenous risk for the development of systemic lupus erythematosus (SLE). METHODS: The titer of 16/6 Id was determined by ELISA in sera of uranium miners exposed to heavy quartz dust: 15 developed definite and 12 probable SLE, 34 had clinical symptoms, and 27 had only serological signs (medium to high titer anti-dsDNA antibodies) of possible connective tissue disease (CTD) development. RESULTS: The prevalence of 16/6 Id was higher in all groups compared to healthy blood donors. It was 18.5% in miners with SLE (definite and probable) and 22.2-26.5% in miners with clinical and/or serological signs for developing CTD. All 16/6 Id positive miners were positive for anti-dsDNA antibodies and other autoantibodies associated with CTD. The prevalence of 16/6 Id in anti-dsDNA positive miners correlated slightly with CTD/SLE symptoms: 55.6% in patients with SLE, 47.4% in miners with possible CTD/SLE, and 22.2% in miners without CTD symptoms. Further, at short term followup, disease progressed in 2 miners of the 16/6 Id positive, but not in 16/6 Id negative miners. CONCLUSION: The detection of 16/6 Id in miners exposed to quartz dust may indicate a higher risk for development of SLE, warranting further studies of the role of 16/6 Id in the development of SLE in a cohort with the same sex, ethnicity, geographic region, and occupation.

Molecular analysis of HLA-DPB1 alleles in idiopathic systemic sclerosis patients and uranium miners with systemic sclerosis.

According to clinical mainifestation and autoantibody pattern [anti-Scl-70, anti-centromere antibodies (ACAs)], systemic sclerosis is a connective tissue disease with heterogenous subgroups. PCR-sequence-specific-oligonucleotide typing was used to study the genetic association of HLA-DPB1 alleles in 54 patients with idiopathic systemic sclerosis, 26 uranium miners with systemic sclerosis and 70 unrelated healthy control subjects. Systemic sclerosis patients with and without former employment in mines were divided into two subgroups according to their scleroderma-typical autoantibody specificities--anti-Scl-70 positive and ACA positive--and third subgroup comprising the rest. Statistical analysis revealed a significantly increased frequency of DPB1*1301(p=0.0001, corrected p=0.011) in idiopathic anti-Scl-70-positive systemic sclerosis cases when compared with unexposed controls. In the same group, we observed an enhanced frequency of DPB1*0601 and *1701 alleles. Since these three alleles carry the information for a glutamic acid residue in position 69 of DPB1, we tested the association of this residue with anti-Scl-70 expression. A strong association between anti-Scl-70 positivity in idiopathic systemic sclerosis patients and amino acid residue 69 of DPB1 was observed when compared with anti-Scl-70-negative idiopathic systemic sclerosis patients (p=0.0009) or unrelated controls (p=0.0007). ACA expression was not associated with the presence of any DPB1 allele tested. The data show that anti-Scl-70 expression in idiopathic systemic sclerosis patients is linked with DPB1*1301 whereas anti-Scl-70-positive miners do not show such a DPB1 association. Futhermore, the data indicate that glutamate 69 of DPB1 might be involved in the susceptibility to idiopathic anti-Scl-70 expression.

Systemic lupus erythematosus after heavy exposure to quartz dust in uranium mines: clinical and serological characteristics.

Epidemiological, clinical and serological data of uranium miners with symptoms of connective tissue diseases (CTD) were collected during the control examinations for occupational lung diseases since 1975. Twenty eight definite (four or more ARA criteria) and 15 probable (2-3 ARA criteria) SLE were diagnosed. The estimated prevalence among heavily silica exposed uranium miners was up to 93 in 100,000. The only significant differences to nonexposed SLE patients were decreased frequency of arthritis and photosensitivity and the absence of anti-Sm and anti-U1-RNP antibodies. ANA were found in all definite SLE patients examined with the following specificities: anti-dsDNA (in 44.4%), & anti-Ro/SSA (in 55.6%, four cases together with anti-dsDNA) and anti-La/SSB (in 22.2%). The autoantibody profiles of patients with probable SLE were similar, but with a lower frequency of ANA, anti-dsDNA and anti-Ro/SSA. Middle to high-titred autoantibodies to dsDNA, Ro/SSA and La/SSB were detected in 3.2% uranium miners with no (N = 1229) and in 20.6% with some symptoms (one ARA criterion and/or two or more of other CTD typical symptoms, N = 68) of CTD development. We conclude, that the strong exposure to dust with a high content of silica may predispose to or initiate the development of SLE. The detection of SLE-typical antibodies in quartz dust-exposed miners may indicate a higher risk for the development of systemic autoimmune disease.

Systemic sclerosis in German uranium miners under special consideration of autoantibody subsets and HLA class II alleles.

Systemic sclerosis (scleroderma) is a connective tissue disease with a wide range of clinical manifestations, with high or low degrees of skin and internal organ involvement together with different antinuclear antibody (ANA) specificities. Several studies provide evidence that males, who are rarely affected by systemic sclerosis, have an increased risk when working in mines. Therefore we reinvestigated 21 male subjects and 6 cases of deceased male patients who had been engaged in East German uranium mines and had shown evidence of this disease in medical examinations. Dermatological investigations, evaluation of chest X-rays and autoantibody estimation were performed. PCR-sequence-specific oligonucleotide typing was used to study the genetic association of HLA-D alleles with autoantibodies typical for scleroderma in these uranium miners suffering from systemic sclerosis and in patients with idiopathic systemic sclerosis. The determined HLA phenotype frequencies and the following statistical analysis (Fisher's exact test (2-sided)) revealed that in comparison with randomly selected controls, alleles DRB1*0300 (DR3) and DQB1*0201 (DQ2) were distinctly increased in the group of affected uranium miners, especially in those with anti-Scl-70 positivity. In contrast, we did not observe significant differences between affected and unaffected miners. Comparing anti-Scl-70-positive affected uranium miners with anti-Scl-70-positive idiopathic systemic sclerosis cases. DRB1*0300 as well as DQB1*0201 were also significantly enhanced in the former group. ACA-positive systemic sclerosis miners had significantly elevated frequencies in DRB1*0100 (DR1) and DRB1*0800 (DR8) only in comparison with unaffected miners and unexposed controls. Our genetic and immunological data lead to the assumption that a different set of HLA-D alleles in combination with exogenous factors is involved in the induction of anti-Scl-70 antibodies in uranium miners that might influence their susceptibility to the disease, whereas the same occupational exposure seems to have no influence on the induction of ACA antibodies.

Anti-CENP-B response in sera of uranium miners exposed to quartz dust and patients with possible development of systemic sclerosis (scleroderma).

OBJECTIVE: To look for anti-CENP-B antibodies and their diagnostic relevance in patients negative and positive for anticentromere antibodies (ACA) with different risk for the development of systemic sclerosis (SSc), including uranium miners exposed to quartz dust. METHODS: We studied sera of 107 patients with SSc, 121 patients with possible SSc, 202 uranium miners heavily exposed to quartz dust, 14 patients with vibration induced white fingers, and 240 control patients. Subjects were screened for ACA by indirect immunofluorescence on HEp-2 cells (IIF-ACA) and then for anti-CENP-B autoantibodies by an ELISA using eukaryotically expressed human full length recombinant CENP-B protein. RESULTS: All IIF-ACA positive sera of "idiopathic" SSc (N = 19), "idiopathic possible" SSc (N = 6) and other patients (N = 11), and 17 of 19 IIF-ACA positive sera of miners exposed to silica with (N = 13) and without (N = 6) symptoms of SSc reacted with CENP-B in this assay. Of the 622 IIF-ACA negative sera, 28 were found positive for anti-CENP-B. There was a significant increase of the prevalence of anti-CENP-B antibodies in IIF-ACA negative patients with possible SSc (11 of 109) and in miners exposed to silica (11 of 196) compared to a group of men older than 60 years with diseases or symptoms not related to SSc (1 of 138). CONCLUSION: (1) CENP-B is also the major target of the IIF-ACA response in diseases other than scleroderma and in the risk group of miners exposed to quartz dust. (2) Anti-CENP-B antibodies can be found in IIF-ACA-negative sera, particularly in those at risk for SSc. (3) The detection of anti-CENP-B antibodies in miners exposed to quartz dust may indicate a high risk group for developing SSc and reveals possibilities for the study of early pathogenetic changes as well as exogenic and endogenic factors involved in the development of this disease.

[The diagnostic value of "dysplastic" changes in the prostate]. / Zur diagnostischen Wertigkeit "dysplastischer" Veränderungen der Prostata.

The technique of serial section was used in systematic investigations of prostates obtained from 450 individuals who had died at the age of 40 to over 80 years. This was done, with a view to clearing up the precancerous potential of so-called dysplastic lesions (intraductal dysplasia, prostatic intraepithelial neoplasia). All accompanying pathomorphological findings were recorded, at the same time, with the totality of data being jointly evaluated and statistically processed by computerised methods. So-called dysplastic alterations were recordable from 57% of all cases (26% to 80%), with incidence rates growing along with advancing age and statistical security depending on age at large. Slight dysplasia was recorded from 41% of all cases, with an average of 2.6 foci (10 foci maximum) to one prostate. Severe dysplasia was recorded from 42% of all cases, with an average of 3.8 foci (24 maximum) to one prostate. The area of 90% of all foci was up to 4 mm2 (16 mm2 maximum in cases of slight dysplasia and 60 mm2 in severe cases). Dysplasia was localised in the posterior region of the organ in 60% of all cases and was detected in the central region in 8% maximum. Carcinoma was identified in 133 cases, with 114 of them (86%) being associated with dysplasia. Dysplasia was also detected in 45% of cases without carcinoma. Severe dysplasia was present in 79% of all carcinoma cases and in 26% of no-carcinoma cases. Slight dysplasia, on the other hand, was recordable form 7% of carcinoma cases and 19% of no-carcinoma cases.(ABSTRACT TRUNCATED AT 250 WORDS)

[Frequency and differential diagnosis of cribriform structures of the prostate]. / Häufigkeit und Differentialdiagnose kribriformer Strukturen der Prostata.

Systematic investigations of the prostate in 450 autopsies of individuals who had lived to the age of 40 to 80 years as well as in 500 prostate biopsies and 480 so-called adenomectomies of the prostate led to detection of cribriform hyperplasia in 30 postmortems (7%), 6 biopsies (1.2%), and 5 adenomectomies (1%). The average age of all hyperplasia cases amounted to 69 years. Cribriform hyperplasia was recordable with and without cellular atypia. Most of the foci, single and multiple up to 4, were not larger than 25 mm2. Statistical calculations revealed good correlations with adenomatous and microglandular hyperplasia as well as with dysplasia of the prostate. A significant relationship was found to exist between cribriform hyperplasia and cellular atypia as well as with prostate carcinoma. Concomitantly recorded were 315 carcinomas, with 81 of these being of the pluriform type and with 68 of the latter (84%) exhibiting cribriform structures. Problems relating to differential diagnosis were found to result from the presence of both benign and malignant structures and are discussed in some detail.

Silica-associated systemic sclerosis is clinically, serologically and immunologically indistinguishable from idiopathic systemic sclerosis.

To determine whether the clinical, immunological and serological features of patients with silica-associated systemic sclerosis are different from patients with the 'idiopathic' form of systemic sclerosis (SS) we studied 22 underground coal miners who were exposed to silica dust (SD), 30 mine workers who later developed silicosis (S) and 17 mine workers exposed to silica dust who subsequently developed a systemic sclerosis-like disease (SA-SS). The patients with SA-SS had features clinically indistinguishable from individual patients with SS. They all had Raynaud's phenomenon, 14 had cutaneous sclerosis identical to that seen in acrosclerosis and three had a generalized cutaneous sclerosis. Sixteen patients had bibasilar pulmonary fibrosis, 10 had necrosis of the fingertip pulps, nine had oesophageal involvement and only one patient had renal involvement. Antinuclear antibodies and circulating immune complexes were detected in three and eight patients with SD, 14 and five patients with S and in 16 and nine patients with SA-SS, respectively. Anti-Scl-70 antibody was detected in eight of the 17 patients with SA-SS. Evidence for in vivo endothelial cell damage, as determined by elevated levels of von Willebrand factor, was found in nine patients with SD, 14 patients with S and in 10 patients with SA-SS. Following incubation of the patient's serum with confluent cultures of human umbilical vein endothelial cells there was only a significant reduction in calcium ionophore-induced release of prostacyclin with the serum from SA-SS patients compared to that with control serum (NC). The mean +/- SEM release of 6-keto-PGF1 alpha (the stable metabolite of prostacyclin expressed as ng/10(4) cells) decreased from 2.90 +/- 0.27 to 2.01 +/- 0.33 (SD), 3.34 +/- 0.42 to 1.76 +/- 0.31 (S), 1.98 +/- 0.12 to 0.64 +/- 0.07 (SA-SS) and 2.28 +/- 0.33 to 1.36 +/- 0.21 (NC) with 1 and 20% serum, respectively. This study demonstrates that immune complex and antinuclear antibody formation and in vivo endothelial cell damage occurs following occupational exposure to silica. The patients who subsequently develop a systemic sclerosis-like disease have clinical, immunological and serological features which are indistinguishable from the idiopathic form of the disease although as a group the SA-SS patients have a higher prevalence of pulmonary involvement and the anti-Scl-70 antibody.

[Occupational progressive systemic sclerodermia caused by a quartz-containing scouring agent]. / Berufsbedingte progressive systemische Sklerodermie durch ein quarzhaltiges Scheuermittel.

We present the case of a 65-year-old woman with progressive systemic sclerosis. For 14 years, she had been occupationally exposed to scouring powder containing crystalline silica. In the skin of the finger of the patient, silica crystals were detected by polarizing microscopy. By means of a special dust measurement at the former working places where scouring powder was used, a silica exposition could be found exceeding the maximum allowable concentrations. Legal recognition of an occupational disease could be achieved in a special procedure by the top expert commission for occupational diseases.

[Reduced mastication as a cause of chronic gastritis]. / Die reduzierte Mastikation als ätiologischer Faktor der chronischen Gastritis.

The influence of reduced mastication on the pathogenesis of chronic gastritis was examined in rats. In spite of reducing experimentally the masticatory effect to a third no inflammation of the gastric mucosa was to provoke. Nevertheless, the attended group showed a significant smaller increase of weight during the experiment.

[The frequency of demonstration of Campylobacter pylori]. / Zur Häufigkeit des Nachweises von Campylobacter pylori.

In 376 patients who underwent gastroscopy the presence of Campylobacter pylori by microscopy, bacterial culture and urea test was studied. Additionally, the histological examination of the antral mucosa was performed. The organisms were detected in 47.9% of the biopsy specimens (37.2% in normal endoscopic findings and 70% in duodenal ulcers). Dependence on sex was not found and also no significant difference of Campylobacter pylori detection in patients younger than 45 years compared with those who are older. However there was a strong correlation between the presence of Campylobacter pylori and the histological results (p less than 0.05). In comparison with international literature we found a distinctly lower percentage of positive Campylobacter pylori rate in patients with peptic ulcer; the association between the presence of Campylobacter pylori and the degree of gastritis was confirmed.

Type III collagen aminopropeptide and laminin P1 levels in serum of patients with silicosis-associated and idiopathic systemic scleroderma.

A group of 191 patients with systemic scleroderma and 12 patients with silicosis-associated scleroderma were investigated for connective tissue turnover. The serum levels of type III collagen aminopropeptide (P-III-P), the laminin PI (Lam PI) fragment and the acid lysosomal beta-galactosidase (beta-Gal) were determined by specific radioimmunoassays and spectrofluorometry, respectively. Increased levels of type III collagen aminopropeptide strongly correlated with enhanced activity of beta-galactosidase. Both parameters correlated with the clinical course in idiopathic systemic scleroderma and in silicosis-associated scleroderma. Serum levels of Lam PI were also found to be elevated in both groups, although there was no correlation with the severity of the disease. Autoantibodies directed against the DNA topoisomerase Scl-70 and against centromeric proteins were found in a similar range in patients with idiopathic systemic and silicosis-associated scleroderma. These results suggest that P-III-P, Lam PI and beta-Gal are useful serological markers of fibrotic activity and demonstrate similarities between idiopathic systemic scleroderma and scleroderma associated with silica-dust exposure.