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Biomedical subjects

P M Schumm-Draeger

Publications and source records attributed to P M Schumm-Draeger.

At least 19 recordsLinked to original sources

[Controversial therapeutic strategies in the treatment of type 2 diabetes mellitus].

At the time of the diagnosis insulin resistance is present in the majority of type 2 diabetics. Only in those type 2 diabetics who are of normal weight at diagnosis must a disturbance of insulin secretion be assumed. These pathophysiological facts, discovered in recent years, mandate a differentiated treatment of type 2 diabetics. The primary aim must be the treatment of the insulin resistance. Insulinotropic drugs are indicated only during the further course of the disease. The use of glitazones makes possible a largely causal treatment of insulin resistance. Over the long term better glycemic control is achieved with glitazones rather than sulfonylureas. As a secondary effect, the insulin-producing beta cells are protected, and such cardiovascular risk factors as diabetic dyslipoproteinemia, hypertension or microalbuminuria are favorably influenced.

Cardiovascular Diseases↗

[Endocrinological transition clinic].

Patients with chronic endocrinological diseases, whether congenital or manifesting in childhood, have to date been the domain of the pediatric clinic long beyond puberty into adulthood. The reason for this is the complete lack of adequate communication between pediatricians and internists specialized in endocrinology. However, intensive and constant cooperation between the two specialties is a prerequisite for the successful transition of adolescent to adult patients. The transition clinic is of central importance for the appropriate management and a stable status of the patient. Nevertheless, only very few university centers so far established such a clinic. Only by overcoming sectoral boundaries, and the creation of a network structure between university policlinic, non-university outpatient department, specialty practice and the family doctor can the intensity and quality of management be improved. The requirement fortransition clinics urgently needs to be met, also in the form of model projects.

Adolescent↗

[Diagnosis and treatment of benign goiter].

Although the German population is now appreciably better supplied with iodine, this is still not adequate in all regions and in all situations, e.g. during pregnancy and breast feeding. As a result, more than 20 million Germans have an iodine-deficiency goiter that requires treatment. Investigation of a goiter is effected with sonography and the determination of serum TSH. If the results indicate euthyroid diffuse goiter, medical treatment should be initiated. In recent years, the combination of thyroid hormone and iodine has proved particularly effective. In contrast to monotherapy with levothyroxine goiter recurrence after discontinuation of treatment is less common, and the combination is usually tolerated better.

Adolescent↗

[How to treat benign thyroid gland nodules].

Investigations within the framework of the thyroid gland initiative "Papillon" turned up an unexpectedly high level of pathogenic findings. Determination of TSH and sonography are considered the pillars of the diagnostic evaluation of the thyroid gland. Useful further investigations aimed at excluding functional disorders are, for example, the determination of FT3 and FT4 or a search for autoantibodies. To investigate suspicious nodules and to exclude malignant processes, additional scintigraphy and, were indicated, fine-needle puncture can be applied. Depending on the individual situation of the patient, the therapeutic option of choice is surgical operation or treatment with iodine-31 therapy. Medical treatment of nodular goiter is currently still controversial.

Biopsy, Fine-Needle↗

Lymphocyte homing in xenotransplanted human thyroid tissue can be inhibited by LFA-1 and ICAM-1 antibodies.

OBJECTIVES: Homing of lymphocytes is an important factor with respect to the initiation of the autoimmune process in Graves' disease (GD). As previously shown, human lymphocytes, particularly of intrathyroidal origin, derived from patients with GD, are able to migrate into normal xenotransplanted thyroid tissue and induce functional and histological changes. The aim of this study was to investigate the effect of LFA-1 and ICAM-1 antibodies on the homing of lymphocytes of different origin into xenografted human thyroid tissue. METHODS: Eighty-five nude mice bearing 8-week-old xenografts of normal human thyroid tissue were treated twice with anti-CD 54 (anti-ICAM-1), anti-CD 11a (anti-LFA-1), a combination of both, or, serving as controls, iso-antibodies without specific binding capacity or saline. Thereafter, intrathyroidal (ITL) or peripheral blood lymphocytes (PBL) obtained from 4 patients with GD or saline were injected into the animals (i.v., 0.2 mL, 10(6) cells). After 48 hours the mice were sacrificed and transplants as well as mice thyroids were examined by immunohistochemical staining with Ki67, CD3, HLA-II (DAKO, Hamburg), IgG, CD44, ICAM-1, and VCAM-1 (Immunotech, Hamburg). RESULTS: Pretreatment with anti-ICAM-1 and anti-LFA-1 decreased lymphocyte homing (CD3-staining), and expression of HLA-II, IgG, CD44, and VCAM-1 in the transplants. CONCLUSION: Our data show that [ICAM-1/LFA-1 stimulated (induced)] lymphocyte homing and subsequently thyrocyte proliferation are inhibited by ICAM-1 and LFA-1 antibodies in xenotransplanted thyroid tissue. This suggests that ICAM1 and LFA-1 play an important role in the early steps of autoimmune thyroid disease. The inhibition/suppression of ICAM-1 and LFA-1 interaction by respective antibodies, as demonstrated in the present study, may provide a new concept for prophylaxis and therapy.

Animals↗

[Autoimmune thyroiditis. Treatment with thyroid gland hormones in subclinical hypothyroidism or already in euthyroid state?].

In patients with subclinical hypothyroidism thyroid hormone therapy should be recommended more often with respect to analysis of effectiveness and risks. There is no cost-difference between treated patients and those who undergo thyroid hormone controls only, but thyroid hormone therapy probably induces improvement of clinical and laboratory parameters and reduction of cardiovascular risk factors. These therapeutic effects have to be elucidated in clinical prospective studies. Thyroid hormone therapy of patients with autoimmune thyroiditis and still euthyroid function obviously inhibits the autoimmune process and development of hypothyroidism. A final recommendation, however, can be given after the data of clinical studies with larger populations are available.

Adult↗

[Optimal recurrence prevention of iodine deficiency related goiter after thyroid gland operation. A prospective clinical study].

In summary the data of our study show: (1) Sonographically determined thyroid volume of patients with euthyroidism after surgery is found to be significantly lower with a combination therapy (iodide 150 microgram +Levothyroxine 75 microgram) compared to patients with iodide monotherapy (200 microgram). (2) Thyroid volume of patients with hypothyroidism after surgery is found to be significantly lower during a combination therapy (150 microgram iodide + 75 microgram L-thyroxine) compared to patients with a Levothyroxine monotherapy. (3) Patients with hypothyroidism and Levothyroxine monotherapy, however present with a significant increase of thyroid volume after surgery. (4) Urinary iodide excretion in the treatment groups with iodide or combination therapy increases significantly during therapy, however, patients with Levothyroxine monotherapy do not show changes. (5) Thyroid function is well stabilized in all treatment groups with adequate controls and adjustment of Levothyoxine dosage. There data clearly demonstrate that the combination therapy with Levothyoxine and iodide significantly improves prophylaxis of goiter recurrence.

Adult↗

[Thyroid gland ultrasound screening (Papillon Initiative). Report of 15 incidentally detected thyroid cancers].

In the framework of the Thyroid initiative Papillon 2001 - 2002 thyroid nodules and sonographically detectable focal lesions with a diameter more than 5 mm were verified in 23.1% of 64.123 persons without a history of thyroid disease. The frequency of such findings was with 33.0% in 46-65 years old persons three times higher then in persons aged 18-30 years (9.6%). In the diagnostic workup thyroid cancer was detected in 15 patients operated on up to now (6 women and 9 men; papillary cancers in 12 cases, follicular cancers in 3 cases) The smallest tumor had a diameter of 1.3 cm, the mean diameter was 2.3 +/- 91 cm. In 3 patients the tumor had invaded the tissue beyond the thyroid capsule, in 4 cases multicentric growth was detected. Lymph node metastases were found in 7/15 cases and distant metastases in 2/15 cases. These result reveal, that thyroid cancer detected by chance may be relatively aggressive. In daily routine, sonographically detectable lesions with poor echogenicity, irregular margins or internal calcifications with a diameter of more than 1 cm should be clarified by fine needle aspiration biopsy.

Adolescent↗

Detection of thyroid peroxidase mRNA in peripheral blood of patients with malignant and benign thyroid diseases.

The aim of this study was to evaluate thyroid peroxidase (TPO) mRNA expression in peripheral blood of patients with benign and malignant thyroid disease. Included were 120 thyroid cancer patients, 85 patients with goitre or Graves' disease (GD) and 54 healthy volunteers. TPO mRNA expression was analysed in peripheral blood by nested RT-PCR. In cancer patients, RT-PCR results were compared with staging, grading and serum thyroglobulin (TG) measurement. TPO transcripts were detected in 7/10 (70%) patients with known metastases of thyroid cancer and in 39 of 110 (36%) patients without metastases (P<0.05), in 15/44 (34%) patients with goitre, in 17/41 (41%) cases with GD and in 4/54 (7.4%) subjects in the control group (P<0.05, controls vs all patients with thyroid disease). Among cancer patients without metastatic disease, RT-PCR results correlated positively with lymph node status (P=0.05), grading (P=0.01) and elevated serum thyroglobulin levels (P=0.03). This is the largest study investigating the use of the TPO-RT-PCR assay. Positivity in TPO-RT-PCR correlates significantly with metastatic disease in cancer patients and with the presence of thyroid disease in general. To date, TPO-RT-PCR cannot substitute for standard techniques in the diagnosis of local recurrence or metastatic spread in thyroid cancer patients. However, as results of TPO-RT-PCR correlate significantly with lymph node status, grading and serum TG measurements in patients with non-metastatic disease, TPO seems to be an interesting molecular marker to look at in follow-up studies.

Adult↗

Circulating calcitonin and carcinoembryonic antigen m-RNA detected by RT-PCR as tumour markers in medullary thyroid carcinoma.

Detection of local relapse or metastasis in medullary thyroid carcinoma (MTC) continue to pose a major diagnostic challenge. Besides established diagnostic studies such as serum calcitonin (CT) and carcinoembryonic antigen (CEA), molecular detection of circulating tumour cells may be an additional diagnostic tool for the early detection of disease recurrence. We performed reverse transcription-polymerase chain reaction (RT-PCR) on blood samples from patients diagnosed with MTC disease using primers specific for CT and CEA, respectively. CT mRNA was not detectable in peripheral blood of all patients with MTC (n = 11) and all controls (n = 32). CEA mRNA was significantly more often detected patients with MTC (72.7%) than in controls (34.4%; p = 0.038; Fisher exact test). With an example of a patient with MTC and massive tumour mass in the neck we demonstrate the failure of detection of CT mRNA over a period of 6 months, whereas CEA mRNA could be detected in peripheral blood of this patient. As a consequence, CT mRNA detected by RT-PCR in the peripheral blood can not be recommended as a tumour marker in MTC. However, the use of carcinoembryonic mRNA may provide a significant improvement in diagnosis of recurrent disease in MTC.

Biomarkers, Tumor↗

Sodium/iodide symporter (NIS) and cytokines.

It has been shown that TSH upregulates rat NIS gene expression in vitro, and this induction can be modulated by cytokines. Analysis of the distribution of rat NIS mRNA ex vivo demonstrated variable levels of NIS transcription in different tissue samples. - IL-1beta and IL-6 have been found to decrease NIS mRNA expression in TSH-stimulated FRTL-5-cells. IL-6 has no effect on NIS functional activity, whereas IL-1beta suppresses iodide accumulation. The NIS is expressed in thyroid tissue of patients with autoimmune thyroid diseases, and its expression is increased in Graves' disease. With respect to other thyroidal autoantigens such as TPO and Tg, NIS obviously shows a very similar pattern to the well-described antigenic targets and may participate as an autoantigen in these diseases. Up to now only data of in vitro studies are available which started to evaluate the effects of different cytokines on NIS expression. The mechanisms of NIS regulation with respect to cytokine modulation in thyroid autoimmune disease remain still unproven and data of experimental in vivo studies and clinical trials in patients with thyroid autoimmune disease have to further elucidate these open questions in the future.

Animals↗

Expression of intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 and homing factor CD44 after engraftment of Graves' lymphocytes in xenotransplanted human thyroid tissue in athymic nude mice.

The expression of adhesion molecules on thyrocytes and endothelium cells plays an important role in the pathogenesis of Graves' disease (GD). The intercellular adhesion molecule-1 (ICAM-1), the vascular cell adhesion molecule-1 (VCAM-1), and the homing receptor CD44 are responsible for the specific migration of lymphocytes in autoimmune thyroid diseases (AITD) (homing). Eight weeks after transplantation of thyroid tissue from 26 patients with nonautoimmune thyroid disease (nontoxic nodular goiter [NTG]) into nude mice, peripheral (PBL) and intrathyroidal lymphocytes (ITL) from 14 patients with NTG and 12 patients with GD were grafted into the animals. Two days after lymphocyte engraftment, the thyroid transplants were examined histologically (HE) and immunohistologically stained with monoclonal antibodies directed against ICAM-1, VCAM-1, and CD44. After injection of GD lymphocytes, thyroid transplants expressed significantly more ICAM-1, VCAM-1, and CD44 than after injection of NTG lymphocytes. This expression was even more pronounced after grafting of GD intrathyroidal lymphocytes. Our data demonstrate that only GD lymphocytes induce the expression of adhesion molecules and homing factor CD44, both of which play an important role in the migration of lymphocytes and induction of the autoimmune process.

Animals↗

One-year prophylactic treatment of euthyroid Hashimoto's thyroiditis patients with levothyroxine: is there a benefit?

Studies in animal models of spontaneous Hashimoto's autoimmune thyroiditis (HT) show that prophylactic treatment with levothyroxine (LT4) can reduce incidence and degree of lymphocytic infiltration in HT. The aim of the present study was to clarify whether there is a benefit of prophylactic treatment with LT4 in patients with euthyroid HT with respect to the progression of the autoimmune process. Twenty-one patients with euthyroid HT were checked for thyroid function (thyrotropin [TSH], free triiodothyronine [FT3], free thyroxine [FT4]), thyroid volume, antibodies (thyroglobulin [Tg-Ab], thyroid peroxidase [TPO-Ab]), and lymphocyte subsets. Peripheral (PBL) and thyroid-derived lymphocytes (TL) were analyzed by triple color flow cytometry. One-half of the patients with euthyroid HT were treated with LT4 for 1 year (n = 10). The other half (n = 11) were never treated with LT4. TL were obtained by fine-needle aspiration biopsy (FNAB). Thirteen healthy subjects (C) without medical history of thyroid disease served as controls concerning PBL, and patients with non-toxic nodular goiter (NG; n = 10) served as controls concerning TL. Thyroid-derived T-helper cells were found more frequently in euthyroid patients with HT compared to patients with NG (p < 0.01). After 1 year of therapy with LT4, TPO-Abs and B lymphocytes decreased significantly only in the treated group of euthyroid patients with HT (p < 0.05). In contrast, TPO-Abs levels did not change or even increased in untreated euthyroid patients with HT. Thyroid volume did not differ before and after therapy. Prophylactic treatment of euthyroid patients with HT reduced both serological and cellular markers of autoimmune thyroiditis. Therefore, prophylactic LT4 treatment might be useful to stop the progression or even manifestation of the disease. However, the long-term clinical benefit of prophylactic LT4 therapy in euthyroid patients with HT is yet to be established.

Adult↗

Molecular detection of thyroglobulin mRNA transcripts in peripheral blood of patients with thyroid disease by RT-PCR.

The sensitive detection of circulating tumour cells in patients with differentiated thyroid cancer may precede the detection of relapse by other diagnostic studies--such as serum thyroglobulin-and thus may have important therapeutic and prognostic implications. We performed reverse transcription-polymerase chain reaction (RT-PCR) on blood samples from patients diagnosed with thyroid disease using two different RT-PCR sensitivities. Additionally, tissue specificity of TG mRNA-expression was determined using RNA extracts from 27 different human tissues. The lower limit of detection was 50-100 TG mRNA producing cells/ml blood using a 'normal' RT-PCR sensitivity and 10-20 cells/ml blood using a 'high' sensitivity. With the normal sensitivity TG mRNA was detected in 9/13 patients with thyroid cancer and metastasis, 63/137 patients with a history of thyroid cancer and no metastasis, 21/85 with non-malignant thyroid disease and 9/50 controls. With the high sensitivity TG mRNA was detected in 11/13 patients with thyroid cancer and metastasis, 111/137 patients with a history of thyroid cancer and no metastasis, 61/85 with non-malignant thyroid disease and 41/50 controls. Interestingly, using the normal RT-PCR sensitivity TG mRNA transcripts are specific for thyroid tissue and detectable in the peripheral blood of controls and patients with thyroid disease, which correlates with a diagnosis of metastasized thyroid cancer. However, with a high RT-PCR sensitivity, TG mRNA expression was found not to be specific for thyroid tissue and was not correlated with a diagnosis of thyroid cancer in patients. As a consequence, to date TG mRNA detected by RT-PCR in the peripheral blood cannot be recommended as a tumour marker superior to TG serum-level.

Case-Control Studies↗

[The significance of A1 and A2 antibodies against beta-casein in type-1 diabetes mellitus].

BACKGROUND AND OBJECTIVE: The hypothesis that cow's milk components may constitute environmental factors in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) is increasingly gaining in importance. This study for the first time determined, in a family study, antibodies against the most common variants of the beta-casein (A1 and A2). PATIENTS AND METHODS: A total of 1,257 sera--from 287 patients with IDDM, 386 siblings, 477 individual parents and 107 healthy controls--were tested by enzyme-linked immunosorbent assay (ELISA) for anti-beta casein A1- and A2-IgG antibodies. RESULTS: Antibodies against casein were present in all four groups, highest titres being found in diabetics. In all four groups there was an inverse correlation between A1 and A2 antibodies and age (p < 0.001). Increased amounts of anti-casein A1 antibodies were found among patients with IDDM and their siblings. On the other hand, the serum samples from parents and control persons contained antibodies against the A2 variant. The preferential binding of sera to the one or other casein variant was in all four groups statistically significant (p < 0.001). CONCLUSION: Because the A1 variant of beta-casein correlates with the onset of IDDM, but can also occur in normal controls, this may confirm the hypothesis of a defective oral immunotolerance to cow's milk antigens in IDDM.

Adolescent↗