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H Dralle

Publications and source records attributed to H Dralle.

At least 145 records · Page 8Linked to original sources
PubMed1997

Ectopic intrathyroidal thymus diagnosed as a solid thyroid lesion: case report and review of the literature.

The authors report a case of a 6-year-old boy in whom aberrant thymic tissue was misdiagnosed as an intrathyroidal solid lesion. The patient underwent hemithyroidectomy and did well. Because cervical ectopic thymus rarely produces symptoms, the true incidence in children is unclear. Surgeons need to consider this rare entity, not to mistake it as a thyroid neoplasm, and not to perform extensive thyroid resection.

Child↗
PubMed1997

Reoperation in metastasizing medullary thyroid carcinoma: is a tumor stage-oriented approach justified?

BACKGROUND: Lymph node metastases (LNM) are very often found in medullary thyroid carcinoma. After primary therapy, elevated levels of calcitonin are measurable in many patients. Because of the low sensitivity and specificity of diagnostic tools to detect micrometastases, the question remains whether an extended lymphadenectomy improves the chance of cure and whether this approach should be tumor stage oriented. METHODS: We analyzed the results of 36 patients with medullary thyroid carcinoma consecutively reoperated from 1988 to 1996, performing microdissection of all four locoregional lymph node compartments. RESULTS: Pathologic tumor stage (pT) category was classified as pT1, n = 3; pT2 n = 22; pT3, n = 6; and pT4, n = 5. LNM were found in 34 patients (94%). The cervicocentral compartment contained LNM in 85%, the cervicolateral compartments in 41% to 54%, and the upper mediastinum in 36%. Patients with different pT category did not differ in the rate of LNM. Ipsilateral cervicolateral LNM were found in 50% to 71% and contralateral cervicolateral LNM in 14% to 40%. Nine (35%) of 26 patients without distant metastases were biochemically cured. In 10 patients (38%) calcitonin level decreased more than 50%. CONCLUSIONS: LNM were almost always (94%) found in patients who have elevated calcitonin levels after primary therapy. In patients without distant metastases, four-compartment lymphadenectomy gives a chance of cure in 35%. A tumor stage-oriented approach does not seem to be justified.

Adolescent↗
PubMed1997

Cardiological effects of catecholamine-secreting tumours.

Correlations between endocrine and cardiological findings were investigated in 106 patients with catecholamine-secreting tumours during the florid phase of their illness. Endocrine data showed an elevation of urinary catecholamine or vanillylmandelic acid excretion in all but one subject. Hypertension was found in 78%, symptoms of coronary heart disease in 26% and arrhythmias in 20% of the patients. Twelve per cent of the patients came to the hospital with heart attacks, 7% with acute left heart failure and 6% with myocardial infarction. At admission electrocardiograph (ECG) analysis showed a sinus rhythm in 98%, tachycardia > 100 min-1 in 14% and bradycardia < 60 min-1 in 10%. In 16% of the ECGs cQT was increased, in 17% the ST segment was lowered and in 37% abnormal T waves occurred. Indices of myocardial hypertrophy such as the Sokolow index, the modified Romhilt-Estes score and the Murphy score were raised in 29%, 19% and 38% respectively. In 23 of 51 (45%) patients echocardiography showed left ventricular hypertrophy, in 16% mitral valve insufficiency and in 24% disturbances of contractility. Comparison of cardiac and endocrine parameters confirm in vitro and animal studies indicating that, in particular, the alpha-mimetic noradrenaline (NA) has deleterious effects on the cardiovascular system. Urinary NA, but not adrenaline or dopamine, excretion was significantly higher in constantly hypertensive than in normotensive patients and associated with an elevation of the Sokolow index and the Romhilt-Estes score. Both indices and plasma NA were higher in patients with myocardial hypertrophy and we found a significant correlation between the Romhilt-Estes score and NA excretion.

Adult↗
PubMed1997

Congenital hyperthyroidism.

Congenital hyperthyroidism is a very rare disease. But, for each affected child it has to be considered as a serious condition because of the negative impact of hyperthyroidism on fetal and postnatal development. If the manifestation occurs during fetal life tachycardia, cardiac arrhythmia, growth retardation and, most significant, prematurity are the consequences. Postnatal signs of hyperthyroidism are irritability, tachycardia, hypertension, poor weight gain and thyroid enlargement. Even cardiac failure may occur if hyperthyroidism is severe and treatment not adequate which explains the high early mortality rate of 16%. The main complication of persistent hyperthyroidism in the neonatal period and during infancy is craniosynostosis. Severe developmental delay or even mental retardation can be the consequence of inadequate high T4-levels during fetal and neonatal life. Congenital hyperthyroidism was first recognized in infants born to mothers with Graves' disease. The description of transplacental passage of the maternal thyroid stimulating antibodies elucidated the molecular mechanism in this major group of patients with "autoimmune congenital hyperthyroidism". In contrast to this transient, self-limited character of "autoimmune congenital hyperthyroidism", due to the clearance of maternal antibodies from the infant's circulation, some cases of persistent congenital hyperthyroidism without signs of thyroid autoimmunity have been recognized. Activating mutations in the thyroid-stimulating hormone receptor were described recently as the underlying molecular pathogenesis in this group of "non-immune congenital hyperthyroidism". Therefore the possibility of a molecular differential diagnosis of both groups of congenital hyperthyroidism now exists and opens the opportunity of optimal treatment for each patient.

Autoimmune Diseases↗
PubMed1997

Protection of mice by an attenuated variant against the wild-type lymphocytic choriomeningitis virus.

L cells persistently infected with strain Armstrong lymphocytic choriomeningitis virus generated a variant which failed to develop the lethal neurologic disease after application to the brain. This virus was able to protect mice from the fatal consequences when inoculated intracerebrally prior to challenge with wild-type (wt) virus. After infection of mice with the attenuated variant and thereafter with the wt virus, production of the latter was extraordinarily reduced. As expected, virus elimination was finally achieved by cytotoxic T lymphocytes, whose activation was accelerated. Furthermore, two events seem to play an important part in this enhanced virus reduction. First, from the beginning of the infection with wt virus, neutralizing antibodies could be noticed. The second observation was an excessive production of interferon-alpha 1 day after the challenge infection.

Animals↗
PubMed1997

Detection of p53 autoantibodies in sera of gastric cancer patients and their prognostic relevance.

BACKGROUND: Changes in the p53 gene product can be immunogenic and enable the formation of p53 serum antibodies (p53ab), detectable in patients with different cancer types. So far, there have been no reports describing the detectability of p53ab in gastric cancer patients. METHODS: We investigated the presence of p53ab and their clinical relevance in a cohort of 74 gastric cancer patients, using an enzyme-linked immunosorbent assay system. RESULTS: In our investigation 20.3% of all patients (15 of 74) and 46.9% of the patients with immunohistochemically (IHC) p53-positive tumors (15 of 32) showed detectable p53ab in serum. All p53ab-positive patients had IHC p53-positive tumors. We have found a significant correlation of p53ab with a higher tumor stage (P = 0.002) and also with a poor prognosis of survival (P = 0.04). CONCLUSION: We have shown that in gastric cancer patients p53ab are also detectable and that p53ab positivity is a predictor of an unfavorable prognosis.

Adult↗
PubMed1996

[Lymph node excision in thyroid carcinoma].

The prognostic value of lymph node metastases in thyroid cancer has been a matter of controversy for many years. However, during the past decade most multivariate analyses have shown a prognostic influence of lymph node metastases in papillary as well as medullary thyroid carcinoma constituting the basis for a standardized concept of lymphadenectomy oriented to the lymph node classification of the UICC (1993). Due to the frequency of lymph node metastases in the ipsilateral cervicocentral compartment (42-86%), in the ipsilateral cervicolateral compartment (32-68%), in the contralateral cervicolateral compartment (12-24%), and in the mediastinal compartment (3-20%), these compartments can be defined as the lymph node regions of the first, second, third and fourth order, respectively. Cervicocentral systematic lymphadenectomy should be part of the en bloc resection of the thyroid gland and the first lymph node region in any thyroid cancer. Cervicolateral as well as mediastinal lymphadenectomy should be performed according to the extent of lymph node involvement, i.e. systematically when multiple lymph node metastases are present, otherwise selectively. One exception is in medullary thyroid carcinoma, where a four-compartment lymphadenectomy is recommended in any patient with positive lymph nodes. Performing a gentle technique using magnifying glasses and bipolar coagulation forceps, systematic lymphadenectomy does not increase the rate of complications, can decrease the recurrence rate and improve survival.

Adenocarcinoma↗
PubMed1996

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↗
PubMed1996

In vivo and in vitro evidence for iodide regulation of major histocompatibility complex class I and class II expression in Graves' disease.

Increases in thyroid cell major histocompatibility complex (MHC) class I and class II expression have been suggested to be an important factor in the development or perpetuation of Graves' disease. It is hypothesized that elevations result in abnormal presentation of thyroid antigens to immune cells, and that iodide and/or methimazole (MMI) are effective therapeutic agents because, at least in part, of their suppression of MHC expression. In this report, we show that Graves' patients pretreated with iodide only 4 days before surgery have lower levels of MHC class I and class II RNA levels in their thyroid tissue than do patients with no iodide pretreatment (P < 0.001 and 0.03, respectively). Because patients in both groups are treated with MMI and because the change is independent of the amounts of MMI used to treat patients, the class I and class II changes cannot be ascribed to MMI. The iodide action to decrease MHC class I and class II RNA levels was duplicated using cultured human thyroid cells in vitro; the iodide effect was dependent on the iodide concentration, was not duplicated by chloride, was not associated with an alteration in cAMP levels or with a change in thyrotropin receptor RNA levels, and was evident in gamma-interferon-treated cells. The data suggest, therefore, that the therapeutic action of iodide in Graves' patients is associated with decreased MHC gene expression, that this action is a direct effect of high concentrations of iodide on the thyroid cells, and that altered MHC gene expression in the target tissue may well be associated with the development or perpetuation of Graves' disease.

Adolescent↗
PubMed1996

Mutations of the ret protooncogene in German multiple endocrine neoplasia families: relation between genotype and phenotype. German Medullary Thyroid Carcinoma Study Group.

It has been suggested that not only the position but also the nature of the mutations of the ret protooncogene strongly correlate with the clinical manifestation of the multiple endocrine neoplasm type 2 (MEN 2) syndrome. In particular, individuals with a Cys634-Arg substitution should have a greater risk of developing parathyroid disease. We, therefore, analyzed 94 unrelated families from Germany with inherited medullary thyroid carcinoma (MTC) for mutation of the ret protooncogene. In all but 1 of 59 families with MEN 2A, germline mutations in the extracellular domain of the ret protein were found. Some 81% of the MEN 2A mutations affected codon 634. Phenotype-genotype correlations suggested that the prevalence of pheochromocytoma and hyperparathyroidism is significantly higher in families with codon 634 mutations, but there was no correlation with the nature of the mutation. In all but 1 of 27 familial MTC (FMTC) families, mutations were detected in 1 of 4 cysteines in the extracellular domain of the ret protooncogene. Half of the FMTC mutations affected codon 634. Mutations outside of codon 634 occurred more often in FMTC families than in MEN 2A families. In all but 1 of 8 MEN 2B patients, de novo mutations in codon 918 were found. These data confirm the preferential localization of MEN 2-associated mutations and the correlation between disease phenotype and the position of the ret mutation, but there was no correlation between the occurrence of hyperparathyroidism or pheochromocytoma and the nature of the mutation.

Amino Acid Sequence↗
PubMed1996

Completion thyroidectomy in 131 patients with differentiated thyroid carcinoma.

OBJECTIVE: To evaluate the prognostic factors that influence survival and recurrence after "completion" thyroidectomy (removal of the total thyroid remnant after diagnosis of carcinoma has been made in a specimen that was incompletely excised for a benign condition). DESIGN: Open study. SETTING: Teaching hospital, Germany. SUBJECTS: 131 Patients (65 with papillary and 66 with follicular thyroid cancer) who underwent completion thyroidectomy after primary subtotal resection. INTERVENTIONS: Indications for further operation were: tumour stage worse than pT1 ( n = 116), tumour stage pT1 and the suspicion of persistence of the tumour (n = 13), and incompletely resected tumour (n = 2). Multivariate analysis by Cox's proportional hazards model. MAIN OUTCOME MEASURES: Recurrence, development of metastases, and length of survival. RESULTS: Patients who underwent their completion thyroidectomies within six months of the primary operation had significantly fewer recurrences, fewer lymph node metastases, fewer haematogenous metastases and survived significantly longer than those in whom the second operation was delayed for longer than six months. The age at the time of diagnosis and the stage of the tumour influenced survival, whereas sex and type of tumour did not. CONCLUSION: Completion thyroidectomy as soon as possible after incomplete resection of the tumour may improve prognosis in differentiated thyroid cancers the stage of which is worse than pT1 or in patients whose recurrent tumour is diagnosed at follow-up.

Adenocarcinoma, Follicular↗
PubMed1995

Presymptomatic DNA screening in families with multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma.

BACKGROUND: Missense mutations of the ret proto-oncogene on chromosome 10q11.2 are the underlying cause of hereditary medullary thyroid carcinoma (MTC), either as familial MTC only (FMTC) or as a part of multiple endocrine neoplasia type 2 syndrome (MEN 2). This study presents our experience with direct presymptomatic DNA screening in MEN 2 and FMTC kindreds. METHODS: Twenty one families with MEN 2 or FMTC were considered in the study. One hundred three individuals had been analyzed; 56 were at risk. The ret mutations were detected by DNA analysis of exons 10, 11, and 16 by using nonradioactive labeling method based on digoxigenin DNA sequencing technique. Serum calcitonin evaluation was carried out in all individuals at risk. Thyroidectomy was performed in those who had to undergo surgery. RESULTS: The ret mutations were identified in all 21 families. In MEN 2A and FMTC families mutations occurred in exons 10 and 11. MEN 2B families had mutations in exon 16. The most frequent mutation in MEN 2A and FMTC affected codon 634. Twenty one gene carriers were identified in unaffected individuals at risk. Ten of 21 gene carriers had elevated calcitonin levels, and 11 had normal levels. MTC or C-cell hyperplasia was found in six gene carriers with pathologic calcitonin values who underwent operation. In a 5-year-old gene carrier with normal calcitonin values C-cell hyperplasia was evident. CONCLUSIONS: Direct predictive DNA analysis allows us to identify MEN 2 or FMTC gene carriers and offer them prophylactic treatment.

Base Sequence↗
PubMed1995

The value of lymph node dissection in hereditary medullary thyroid carcinoma: a retrospective, European, multicentre study.

Clinical data of 139 patients with hereditary medullary thyroid carcinoma (HMTC) from nine european centres surgically treated from 1980 to 1991 were reviewed retrospectively to analyse the value of systematic versus selective lymphadenectomy (LA). Biochemical cure rate was significantly higher in patients who underwent LA compared to patients who did not. In nodal-positive HMTC, systematic LA compared to selective LA improved biochemical cure in small but not large tumours. In nodal-negative HMTC, systematic LA compared to selective LA could not improve biochemical cure in either small or large primary tumours. To prevent local recurrences with the risk of increased surgical and tumour-related morbidity, systematic LA should be performed in all HMTC patients regardless of the primary tumour stage. However, an improvement of biochemical cure by systematic LA seems to be possible only in nodal-positive small primary tumours without distant metastases.

Adult↗
PubMed1995

Pheochromocytoma in multiple endocrine neoplasia type 2: European study. The Euromen Study Group.

OBJECTIVES: Pheochromocytoma (pheo) is the second component of the multiple endocrine neoplasia type 2 (MEN 2) syndrome. Clinical expression is sometimes poor, and chronology between medullary thyroid carcinoma (MTC) and pheo is not well evaluated. Therefore, a retrospective study was done in eight European countries in order to precise the main characteristics of pheo in MEN 2. SUBJECTS: Data from 300 MEN 2 patients with pheo (274 MEN 2 A and 26 MEN 2 B) were obtained from cases registered by the EuroMen study group, and collected by a medical standardized questionnaire. These cases occurred between 1969 and 1992. RESULTS: Mean age at diagnosis of pheo was 39.5 years (range 14-68 years) in MEN 2A and 32.4 years (range 15-41 years) in MEN 2B patients. Pheo occurred first in 25.1% of the cases (2-15 years before diagnosis of MTC) and after MTC in 40.2% (2-11 years). In other cases (34.7%), MTC and pheo were diagnosed at the same time. Involvement was bilateral in 67.8% of cases. Malignancy was only 4%. Thirty-nine deaths occurred in these 300 patients, 64.1% were linked in pheo, 23.1% to MTC and 12.8% to other causes. Surgery was unilateral in 39.7% of the cases and bilateral adrenalectomy was the first procedure in 48.4%. A bilateral adrenalectomy in two steps had to be done in 11.9% of cases. In conclusion, these results justify systematic and prolonged biochemical screening of pheo during follow-up of MTC and address some questions about the best mode of surgery.

Adolescent↗
PubMed1995

Primary hyperparathyroidism in multiple endocrine neoplasia type 2A.

The rarity of primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia type 2A (MEN 2A) led us to study clinical findings, surgical therapy and outcome in 67 patients in order to evaluate our therapeutic strategy. The retrospective study was based on cases registered by the EUROMEN study group (nine participating centres) from 1972 to 1993. Characteristics of PHPT in 67 patients (41 females, 26 males) with MEN 2A were reviewed. All patients underwent exploratory neck surgery; PHPT was confirmed histologically and/or biochemically. The median age at diagnosis of PHPT was 38 years. In 75% of the patients, PHPT and medullary thyroid carcinoma were diagnosed synchronously, while in 4%. PHT was diagnosed earlier. In 18% of the patients, PHPT was diagnosed after thyroidectomy, and in 3%, after discovery of pheochromocytoma. Primary hyperparathyroidism was asymptomatic in 84% of the patients; 15% suffered from renal stones. Serum calcium was slightly elevated in 69% (2.9 +/- 0.2 mmol-1) and normal in 16% of subjects. A single adenomectomy was performed in 42% of the patients, subtotal parathyroidectomy in 31% and total parathyroidectomy with autotransplantation in 16%. Independent from the extent of resection, cure was achieved in 94% of the patients, including 13% with hypoparathyroidism; hypercalcaemia persisted in 3% and no information was available in 3%. In an 8-year follow-up, hypercalcaemia recurred in 12% of the patients, although half had undergone parathyroidectomy totally or subtotally. CONCLUSION. MEN 2A-related PHPT is characterized by a mild hypercalcemia which is mostly asymptomatic and can be cured by simple resection of an enlarged parathyroid gland in most cases.

Adolescent↗
PubMed1995

Antiviral protective immunity induced by major histocompatibility complex class I molecule-restricted viral T-lymphocyte epitopes inserted in various positions in immunologically self and nonself proteins.

Injection into mice of chimeric proteins consisting of a portion of either the simian virus 40 large tumor antigen or nonstructural protein 1 of influenza A virus or of the murine tumor suppressor p53 on one hand and T-cell epitopes of lymphocytic choriomeningitis virus on the other resulted in antiviral protective immunity, which was independent of the epitopes' position in the protein and the same whether the latter was immunologically nonself or self. Mice of different haplotypes were protected when the corresponding class I molecule-restricted epitopes had been inserted close to each other in one carrier protein.

Amino Acid Sequence↗