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Biomedical subjects

W G Franke

Publications and source records attributed to W G Franke.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Changes in regional cerebral perfusion in depression.SPECT monitoring of response to treatment].

The objective of this study was to investigate the relationship between the effect of sleep deprivation, recovery and regional brain perfusion in patients with major depression. Regional cerebral blood flow was assessed by 99mTc-HMPAO-SPECT before and after sleep deprivation in fourteen medicated patients. Three of the patients underwent a follow-up measurement after clinical recovery and with an unchanged antidepressant medication. Before sleep deprivation the responding patients had a significantly higher anterior cingulate perfusion than the nonresponding patients, that normalized after sleep deprivation. Cingulate perfusion uniquely differentiated eventual treatment response from non-responders, as perfusion in no other region under study discriminated the two groups. At baseline all patients revealed hypoperfusion in the left prefrontal cortex when compared to the right side, which was not affected by sleep deprivation, whereas prefrontal hypoperfusion was reversible upon remission. These findings are in agreement with previous PET investigations and provide evidence for cingulate and prefrontal dysfunction associated with depression, that are reversible by successful treatment and may represent state markers.

Brain↗
PubMed1999

Multicenter study on TGPO autoantibody prevalence in various thyroid and non-thyroid diseases; relationships with thyroglobulin and thyroperoxidase autoantibody parameters.

OBJECTIVE: TGPO autoantibodies (aAbs) that bind simultaneously to thyroglobulin (Tg) and thyroperoxidase (TPO) are present in the serum of patients with autoimmune thyroid diseases (AITD) and have been found to differ from monospecific Tg and TPO aAbs. To obtain further insights on the prevalence defined as the rate of occurrence and significance of TGPO aAbs in a large population, we carried out a collaborative study involving 15 European teams. METHODS: Serum samples from 3122 patients with various thyroid and non-thyroid diseases and normal subjects were assayed using a novel TGPO aAb detection kit. This test was designed so that TGPO aAbs are trapped between the Tg-coated solid phase and the soluble TPO labeled with a radioiodinated monoclonal antibody. RESULTS: Only three out of the 220 normal subjects (prevalence of 1.4%) were found to have positive TGPO aAb levels, which were mainly observed in the patients with AITD: the group of patients suffering from Hashimoto's thyroiditis had a TGPO aAb prevalence of 40.5% (n=437 patients), those with Graves' disease, a prevalence of 34.6% (n=645) and those with post-partum thyroiditis, 16.0% (n=243). Among the non-AITD patients with positive TGPO aAb levels, the TGPO aAb prevalence ranged from 20.7% among those with thyroid cancer (n=246) to 0% among those with toxic thyroid nodules (n=47). Among the patients with non-thyroid diseases, the TGPO aAb prevalence ranged from 9.8% in the case of Biermer's pernicious anemia (n=78) to 0% in that of premature ovarian failure (n=44). It is worth noting that the groups showing the highest TGPO aAb prevalence also contained the patients with the highest TGPO aAb titers. Statistical comparisons between the TGPO aAb prevalences in the various groups showed that TGPO aAb could be used as a parameter to distinguish between the groups of Hashimoto's and Graves' patients and between the women with post-partum thyroiditis and the post-partum women with only Tg and/or TPO aAb established during early pregnancy. Unexpectedly, the correlations between TGPO aAbs and Tg and TPO aAbs were found to depend mainly on the assay kit used. CONCLUSION: High TGPO aAb titers are consistently associated with AITD but the reverse was not found to be true. TGPO aAbs are a potentially useful tool, however, for establishing Hashimoto's diagnosis, and would be worth testing in this respect with a view to using them for routine AITD investigations.

Autoantibodies↗
PubMed1999

Clinical value of a bispecific antibody binding to thyroglobulin and thyroperoxidase (TGPO-aAb) in various thyroid diseases.

TGPO-aAb is a bispecific antibody which binds to thyroglobulin as well as thyroid peroxidase. It is supposed to be raised in some patients with autoimmune thyroid disease. We investigated 205 patients suffering from Graves' disease (n = 81), Hashimoto's thyroiditis (n = 36), toxic nodular goitre (n = 50), differentiated carcinoma of the thyroid (n = 10), and autoimmune thyropathy of unknown origin (n = 28). An immunoradiometric assay was used to measure serum TGPO-aAb. Eighty-nine of 205 patients had elevated titres of TGPO-aAb. If TGPO-aAb were raised then autoantibodies against thyroglobulin and thyroid peroxidase were always raised, too. This was, however, not true vice versa. We found TGPO-aAb in 61% of patients with Hashimoto's, 49% of patients with Graves', 64% of patients with autoimmune thyropathy, but only in 12% of patients with toxic nodular goitre. In patients with thyroid carcinoma TGPO-aAb was found only if there was evidence of paraneoplastic autoimmune thyroiditis. We re-examined 16 of 36 patients with Hashimoto's thyroiditis after 1 year: 8 patients had retained their raised TGPO-aAb, 4 patients showed no TGPO-aAb on both occasions, and 4 patients had 'lost' their previously raised TGPO-aAb on follow-up. We conclude that TGPO-aAb may provide additional information in Hashimoto's thyroiditis. Determination of TGPO-aAb does not allow to distinguish between various forms of autoimmune thyroid disease. Nevertheless, the presence of TGPO-aAb and its variation during the natural course of autoimmune thyroid disease remains to be understood which would give a better insight into its clinical significance.

Adult↗
PubMed1999

[Can immunoradiometric measurement of thyrotropin (TSH) in human serum compete with a luminometric assay?].

UNLABELLED: The development of highly sensitive, nonradioimmunometric assays for the measurement of thyrotropin (TSH) during the last few years have improved the measurement of low TSH values and thus benefit the diagnosis of thyroid function disorders. These third or fourth generation assays are especially popular in laboratories not accustomed to the use of radioactive tracers and can be easily automatized. AIM: This study investigates whether these new assays provide an advantage in routine diagnosis of thyroid disorders. METHODS: TSH was measured in 150 patients with various thyroid pathology using an immunoradiometric assay (IRMA) as well as a highly sensitive luminometric assay (LUMI), both by B.R.A.H.M.S. Diagnostica. We used the current modern IRMA (available since 1997) TSH was below 0.4 mU/l, between 0.4 and 4.0 mU/l, and above 4.0 mU/l in a third of the patients in each group, respectively. RESULTS: As expected the results obtained with LUMI and IRMA correlated well for TSH values above 0.1 mU/l and less well between 0.1 and 0.01 mU/l. There was no correlation between the two types of assay at TSH concentrations below 0.01 mU/l. This shows that measurements using both types of assay become increasingly less precise below 0.1 mU/l. CONCLUSION: Both types of assay gave an identical estimate of thyroid function in every single patient. Use of the LUMI did not give additional information leading to a change in patient management. Therefore, TSH measurement using IRMA does still meet today's routine clinical requirements.

Automation↗
PubMed1999

Pharmacokinetics and metabolism of the methyl-branched fatty acid (BMIPP) in animals and humans.

UNLABELLED: The aim of this study was to further characterize the major metabolite of 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP). METHODS: Radioactive components of 131I-BMIPP were evaluated in Langendorff-perfused rat hearts, as well as in blood samples from 20 patients after injection of 123I-BMIPP. Rat hearts were perfused with pH 7.4 Krebs-Henseleit buffer with or without 0.4 mmol/L bovine serum albumin (BSA) or 0.4 mmol/L palmitate. Lipids were Folch extracted and hydrolyzed from samples of the outflow, as well as from homogenized hearts. Radioactive components were determined by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) analyses. The major metabolite of BMIPP was then further characterized by electrospray mass spectrometry. RESULTS: The rat heart perfusate showed one major polar metabolite observed by TLC (Rf = 0.35; solvent = benzene-dioxane-acetic acid 80:18:2). The addition of BSA/palmitate to the perfusate buffer significantly increased backdiffusion of BMIPP (Rf = 0.55), as well as reduced BMIPP uptake and metabolism. The major metabolite was identified by mass spectral analysis as 2-(p-iodophenyl)acetic acid (IPC2). From TLC and HPLC analyses of the serum lipids obtained from patients, the same metabolite could be identified with levels increasing over time (0%, 5.2% and 11.8% of the injected dose; 3 min, 20 min and 3 h postinjection, respectively). In addition to the identification of unmetabolized BMIPP (53.9%), the rat heart lipid hydrolysate also contained alpha-methyl-14-(p-iodophenyl)tetradecanoic acid (20.8%), 12-(p-iodophenyl)-substituted-dodecanoic (17.1%), -hexanoic acid (5.2%) and IPC2 (1.1%). CONCLUSION: The animal results show the complexity of uptake, metabolism and release of BMIPP from which a part is metabolized through alpha- and subsequent beta-oxidation to the final IPC2 metabolite as confirmed by mass spectral analysis. The results from patient studies suggest that the slow myocardial washout observed in vivo after intravenous administration of BMIPP may represent a similar process, because both unmetabolized BMIPP and the final metabolite were also identified in serum samples.

Animals↗
PubMed1997

Thyreoglobulin and violent asphyxia.

The concentration of thyreoglobulin (tg) was determined for death caused by hanging, strangulation by ligature, and throttling. Cases of sudden death (traumatic aortic rupture, penetrating wounds of the heart) were used for comparison. The mean values in cases of hanging (149.9 +/- 202.3 ng/ml), strangulation by ligature (193.1 +/- 173.3), manual strangulation (561.6 +/- 173.9) are distinguishable from violent acute deaths (23.3 +/- 27.6) and living healthy individuals (17.3 +/- 16.1). By means of statistical comparisons, significant differences were found between throttling and strangulation by ligature and between throttling and hanging (adjusted P < 0.001). In connection with examination of the bodies high tg values can be regarded as a vital reaction in obstructive asphyxia.

Asphyxia↗
PubMed1997

Uptake of 169Yb complexes in normal and tumour cells: influence of ligand and metabolic cell activity and stability of cellular association.

For better understanding of the accumulation of trivalent radiometal tracers in tumours, studies of uptake of different 169Yb complexes into cultured normal (V79/4) and tumour (KTCTL-2) cells were performed. Cellular uptake of 169Yb3+ is dependent on both the metabolic activity of the cells and the nature of the ligand used. Uptake of 169Yb3+ from the citrate complex is an active cellular transport process but not tumour-specific. The 169Yb-aminopolycarboxylic acid complexes are taken up via a different, unknown mechanism, and in higher amounts by the tumour cells than by the V79/4 cell line, but the general features of uptake were principally the same with the normal and the tumour cells. Uptake of the complexes studied leads to a stable association of cellular components, which is a good premise for the therapeutic use of trivalent radiometals.

Animals↗
PubMed1997

[Influence on extratumoral organ activities of tumor-affinity samarium-153 preparations].

AIM: Possibilities to exercise an influence on the biodistribution of a tumor-affine 153Sm-preparation, samarium-153-nitrilotriacetate (NTA), were tested. METHODS: Animals experiments on tumor-bearing mice after additional application of EDTMP (ethylenediamine tetramethylene phosphonate) for the reduction of extratumorale liver-radioactivity and yttrium chloride for the reduction of unwanted underground radioactivity in bone were carried out. Furthermore, the combination of both measurements was tested. RESULTS: The biodistribution of 153Sm-NTA showed a rather low tumor-radioactivity of app. 0.72%/g. The additional EDTMP-application caused a dose-dependent decrease of the underground-radioactivity in liver especially if given 2 h in advance or simultaneously. The additional application of the stable yttrium salt reduced the bone radioactivity on simultaneous increase of liver- and spleen-radioactivity and practically unchanged tumor-radioactivity. The combined use of EDTMP together with the bone-affine metal salt led to a reduction of liver radioactivity on simultaneous reduction of bone radioactivity. CONCLUSIONS: The background radioactivity can be reduced on unchanged tumor-radioactivity by combined Na-EDTMP/YCl3-application. The present results do not allow a therapeutic exploitation because of the low tumor accumulation.

Animals↗
PubMed1995

[Biokinetics of tumor-affinity yttrium preparations--2].

After demonstrating that the application form 87Y-NTA-EDTMP-Ca is superior to the so far used citrate form of yttrium especially regarding the tumour/liver and tumour/bone ratios, the relationships between the concentrations of the components in the 87Y-NTA-EDTMP-Ca mixture and the 87Y biokinetics were investigated in tumour-bearing mice. The increase of the EDTMP and Ca2+ concentrations by several orders of magnitude caused no significant changes of tumour radioactivity but a clear radioactivity decrease in the liver, spleen and bone, respectively. The increase of the NTA concentration led also to a radioactivity decrease in all organs and tissues investigated. A significant radioactivity reduction in the tumour could be observed only after administration of rather high NTA amounts. Considerations of the tumour/background ratios depending on different compositions of the injection mixture showed the possibility of optimizing radionuclide biodistribution.

Animals↗
PubMed1995

[Biokinetics of tumor-affinity yttrium preparations--Part 1].

Differences of yttrium biokinetics after application to male tumor-bearing mice of 87Y-citrate were studied in comparison to a 87Y-NTA-EDTMP-Ca mixture after variation of both the manner of application (intraperitoneal vs. intratumoral) and the tumor type (mamma carcinoma vs. melanoma). The application of 87Y as NTA-EDTMP-Ca preparation led--in comparison to the citrate form applied so far--to a similar radionuclide tumor accumulation and distinctly lower extratumoral radioactivities in liver, spleen and skeleton with clearly more favorable tumor/background ratios. Melanomas showed a significantly higher radioactivity accumulation (factor 2-3) after injection of 87Y-NTA-EDTMP-Ca than mamma carcinomas. Intratumoral application led to high initial radioactivities in the tumors. Radioactivity concentrations which are comparable with those after intraperitoneal application were achieved within 4 h after intratumoral application. The application of the EDTMP-containing mixture promises in comparison to the traditional citrate form higher radiation doses in the tumor related to the whole-body radiation exposure. The consequences for a possible tumor therapy will be further investigated.

Animals↗
PubMed1994

A new method for site-specific labelling of the oligosaccharide chain of antibodies: preliminary results.

There are various approaches for improving endoradiotherapy and diagnosis with monoclonal antibodies in nuclear medicine. The known methods of site-specific labelling of biomolecules based either on reactions with sulfhydryl groups or on reactions with aldehyde groups of the oligosaccharide chains effect unwanted alterations of the biomolecules. We present a new method to introduce radioactive halogens into the oligosaccharide chains of an antibody, based on the enzymatic transfer of the labelled synthetic sialic acid derivative CMP-9-deoxy-9-salizoyl-NeuAc. It was first labelled by the iodogen-method (iodine) in yields of more than 90%. Under selected conditions it was possible to obtain di- and trihalogenated products. Then the radioactive sialic acid derivatives were transferred during 90 minutes at room temperature with 2.6-sialyltransferase from rat liver into the oligosaccharide chains of antibodies. It is necessary to use neuraminidase pretreated antibodies with an increased number of binding sites for sialic acid derivatives. Yields of about 55% were obtained for the monoiodinated sialic acid derivative. With this method we present a reasonable alternative reaction of labelled compounds with biomolecules. Studies of the immunoreactivity are now in progress.

Animals↗
PubMed1994

Radioiodine therapy during an unknown remained pregnancy and radiation exposure of the fetus. A case report.

PURPOSE: A papillary thyroid cancer staged as p T2N3M0 was treated in a 28-year-old woman by surgery, percutaneous radiation and radioiodine therapy (10 single applications ranging from 3300 to 3840 MBq with an average radioactivity of 3350 MBq). In the course of radioiodine therapy an attended gynaecologist found the woman pregnant in the 24th week of gravidity. Because the pregnancy remained unknown until this time radioiodine was administered during the 2nd and the 22nd week of pregnancy, each time 3700 MBq. Because of the risk of malformations this pregnancy was interrupted after consultation and taking the recommendations of the so-called Danish rule as a basis for the decision. METHODS: Ovarian and fetal doses as well as the fetal thyroid exposure has been estimated as exactly as possible using data at hand. The fetus was studied with regard to possible consequences of radiation exposure by pathologico-anatomical, cytogenetic and radiobiological methods. RESULTS: The accumulated ovarian doses resulting from the radioiodine administrations before pregnancy was estimated to 2200 mGy, the fetal doses resulting from the two administrations during pregnancy to 250 mGy in each case, and the fetal thyroid dose to between 90 Gy and 900 Gy for the 2nd therapy during pregnancy. In the fetus the most important changes were found within the thyroid gland (atrophy, sclerosis, subcapsular interstitial fibrosis, necrobiosis of follicular epithelial cells). On the other hand, analysing the karyotype using dermal fibroblastic cell cultures, no radiation induced chromosomal aberrations were seen. CONCLUSION: Despite of all precautionary measures it seems to be conceivable that in extremely rare cases--in our 35-year experience with more than 20,000 radioiodine therapies only the present case--an early pregnancy may remain undetected. The results of these studies give useful information on effects to be expected as a result of radioiodine application during certain periods of pregnancy. They may help to extend the radiobiological knowledge with regard to the fetal period.

Abortion, Therapeutic↗
PubMed1993

[Initial results in tumor diagnosis with radioactive lanthanide complexes].

Clinical investigations have been made in 70 patients to determine whether 169Yb-labelled metal ligand complexes accumulate in various tumors as was shown by previous animal experiments. The time course of these radiopharmaceuticals in tumors, the skeleton and the liver permitted a good to excellent tumor imaging in 61/70 cases. Even 2-5 h after intravenous injection of the radioactive compound, a meaningful diagnosis could be made in the majority of cases. A number of lesions were found for which no equivalent findings were available with other methods. They were therefore interpreted as metastases.

Colorectal Neoplasms↗
PubMed1993

[The effect of ethylenediaminetetramethylenephosphonate on the biodistribution of tumor-seeking radionuclides].

It is well known that after application of radioactive complexes for tumour diagnosis or therapy, such as 67Ga-citrate or radiolanthanide complexes (167Tm- or 169Yb-nitrilotriacetate, -citrate, -alpha-hydroxyisobutyrate, 90Y-citrate, etc.) activity is accumulated not only in the tumour but also in other organs, above all liver and bone. This is the main obstacle to their medical use. Recently published results encouraged us to use ethylenediaminetetramethylene phosphonate (EDTMP) for the reduction of extratumoural liver activity. The results show that even small amounts of EDTMP (1-2 mg/kg BW) reduce the activity deposition in the liver by about one order of magnitude. EDTMP provoked elimination of activity from tumour, skeleton and other tissues but not to the same extent as from the liver. Tumor/liver activity ratios > 5 are achievable in this manner.

Animals↗