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Biomedical subjects

J Mehlhorn

Publications and source records attributed to J Mehlhorn.

At least 19 recordsLinked to original sources

[Simultaneous papillary carcinoma in a thyroglossal duct remnant and the thyroid gland].

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.

Aged↗

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.

Antibody Formation↗

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.

Aged↗

[Rupture of the pulmonary artery - fatal complication by pulmonary artery balloon-tipped catheter].

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.

Aged↗

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.

Cause of Death↗

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.

Genes, p53↗

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.

Autoantibodies↗

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.

Aged↗

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.

Adult↗

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.

Alleles↗

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.

Adult↗

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.

Autoantibodies↗

[Frequency and differential diagnosis of cribriform structures of the prostate].

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.

Adenocarcinoma↗

[The diagnostic value of "dysplastic" changes in the prostate].

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)

Adult↗

[The frequency of demonstration of 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.

Adolescent↗

[Quartz crystals in the skin as a cause of progressive systemic scleroderma].

There is a close correlation between the systemic sclerosis and the exposure to crystalline silica in the GDR. The silica content was investigated in the skin of the patients. Silica particles were found using phase-contrast and polarizing microscopy. The size of the crystals varied from 1 to 90 micrometer. Below a silica content of 10% in the dust it is unlikely that systemic sclerosis is developing.

Biopsy↗

[Drug taking behavior of internal medicine inpatients].

There are only few publications about patient compliance in in-patients. The compliance of 134 female patients of a common hospital was detected after prescription of riboflavin tablets. Over a period of 10 days four examinations of the urine for signs of fluorescence were performed. 24% of the in-patients were noncompliant. Patients aged over 70 years or with chronic diseases like diabetes or hypertension were seen to have a good compliance compared with younger ones or patients without these diseases. In-patients with psychiatric or psychosomatic disorders were more incompliant than the other ones. In this group the intake must be controlled. A large number of prescribed tablets negatively influenced the compliance but the frequency of intake did not adversely affect the compliance. The history of individual patient compliance will indicate the future compliance. The results show that compliance should be taken into account in in-patients care especially according to a successful therapy.

Adult↗