New sonographic method for fetuses with small abdominal circumference improves fetal weight estimation.

PURPOSE: Accurate estimation of fetal weight is a valuable tool for determining further obstetric management. Commonly used weight formulas lack accuracy, even though some equations appear to be favorable within defined weight ranges. However, due to the fact that fetal weight is not known in advance, it is not always clear which formula is suitable. In most of the commonly used equations, the fetal abdominal circumference (AC) is not only included but also has the greatest impact on weight estimation. The aim of our study was to develop and evaluate a new formula specifically designed for a small fetal AC in order to improve weight estimation. MATERIALS AND METHODS: The study included 323 pregnancies. The inclusion criteria were singleton pregnancy, ultrasound examination with complete biometric parameters and an AC ≤ 29.0 cm within 7 days of delivery, and an absence of structural or chromosomal malformations. Two "best-fit" formulas were derived by forward regression analysis. Finally, the accuracy of the new formulas was compared to commonly used weight equations by using the percentage error, absolute percentage error (APE), limits of agreement (LOA) and cumulative distribution. RESULTS: Contrary to the routine methods, which significantly underestimated fetal weight, the new formulas did not have a systematic error. The medians of the APE were the lowest (7.13 and 7.16) when compared to other equations. Moreover, the new formulas demonstrated the narrowest LOA. At all discrepancy levels (5%, 10%, 15%, and 20%), the new formulas included significantly more cases than the commonly used methods. CONCLUSION: The specifically designed equations help to improve fetal weight estimation for fetuses with an AC ≤ 29.0 cm. For optimal weight estimation, we recommend using the new formula II.

New sonographic method for fetuses with a large abdominal circumference improves fetal weight estimation.

PURPOSE: Birth weight (BW) is an important prognostic parameter for neonatal morbidity and mortality. Commonly used weight formulas lack accuracy, especially at the lower and upper end of the fetal weight range. Fetal abdominal circumference (AC) as part of most of the commonly used equations has the greatest impact on weight estimation. It has been shown that formulas specifically designed for a small fetal AC can improve weight estimation. The aim was to find out whether a new formula specifically designed for fetuses with a large AC may also improve weight determination. MATERIALS AND METHODS: The study included 830 singleton pregnancies. The inclusion criteria were ultrasound examination with complete biometric parameters and an AC ≥ 36.0 cm within 7 days of delivery, and an absence of structural or chromosomal malformations. Two "best-fit" formulas were derived by forward regression analysis. The accuracy of the new formulas was compared with commonly used weight equations using percentage error (PE), absolute percentage error (APE), limits of agreement (LOA) and cumulative distribution. RESULTS: New formula I had no systematic error while new formula II and the routine methods significantly overestimated fetal weight. The medians of the APE were the lowest among the new equations (5.77 and 7.25). The new formulas also demonstrated the narrowest LOA. Importantly, at all discrepancy levels (5 %, 10 %, 15 %, and 20 %), new formula I included significantly more cases than the commonly used methods. CONCLUSION: These specifically designed equations help to improve fetal weight estimation for fetuses with an AC ≥ 36.0 cm. For optimal weight estimation, we recommend using new formula I.

Nature of the band gap of In2O3 revealed by first-principles calculations and x-ray spectroscopy.

Bulk and surface sensitive x-ray spectroscopic techniques are applied in tandem to show that the valence band edge for In2O3 is found significantly closer to the bottom of the conduction band than expected on the basis of the widely quoted bulk band gap of 3.75 eV. First-principles theory shows that the upper valence bands of In2O3 exhibit a small dispersion and the conduction band minimum is positioned at Gamma. However, direct optical transitions give a minimal dipole intensity until 0.8 eV below the valence band maximum. The results set an upper limit on the fundamental band gap of 2.9 eV.

Clinical impact of retinoids in redifferentiation therapy of advanced thyroid cancer: final results of a pilot study.

Differentiated thyroid cancer is a malignant tumour that has a fairly good prognosis, with patients surviving for many years. Multimodal therapy with surgery, radioiodine therapy and TSH suppressive medication is of proven efficacy. However, loss of differentiation is observed in up to one-third of patients with differentiated thyroid cancer, paralleled by an increase in tumour grading and loss of thyroid-specific functions (thyrotropin receptor, iodine accumulation). Such tumours may no longer be amenable to standard treatment protocols, including TSH suppression and radioiodide therapy. Retinoic acids have been shown to exert re-differentiating effects on thyrocytes in various experimental studies and case reports, and it was on this basis that this pilot study was initiated. Patients with advanced thyroid cancer and without the therapeutic options of operation or radioiodide therapy were treated with 13- cis-retinoic acid at a dosage of 1.5 mg/kg body weight daily over 5 weeks. Parameters for assessment of the therapeutic effect were serum thyroglobulin (TG) levels, radioiodine uptake, and tumour size prior to and after retinoid treatment. Fifty patients were evaluated for response, classified as reduction in tumour size and TG levels, stable disease or disease progression. Thirteen patients showed a clear increase in radioiodine uptake, and eight a mild increase. TG levels were unchanged or decreased in 20 patients. Tumour size was assessable in 37 patients; tumour regression was observed in six, and there was no change in 22. In total, a response was seen in 19 patients (38%). Response to retinoid therapy did not always correlate with increased radioiodine uptake, so other direct antiproliferative effects have to be assumed. The encouraging results of the study and the low rate of side-effects with good tolerability of retinoids warrant further studies with altered inclusion criteria and employment of other redifferentiating drugs or combinations of agents.

[Multivariate analysis of factors influencing the effect of radiosynovectomy]. / Multivariate Analyse der Einflussfaktoren auf die Wirkung der Radiosynoviorthese bei entzündlichen Gelenkerkrankungen.

OBJECTIVE: In this prospective study, the time to remission after Radiosynovectomy (RSV) was analyzed and the influence of age, sex, underlying disease, type of joint, and duration of illness on the success rate of RSV was determined. METHODS: A total number of 57 patients with rheumatoid arthritis (n = 33) and arthrosis (n = 21) with a total number of 130 treated joints (36 knee, 66 small and 28 medium-size joints) were monitored using visual analogue scales (VAS) from one week before RSV up to four to six months after RSV. The patients had to answer 3 times daily for pain intensity of the treated joint. The time until remission was determined according to the Kaplan-Meier survivorship function. The influence of the prognosis parameters on outcome of RSV was determined by multivariate discriminant analysis. RESULTS: After six months, the probability of pain relief of more than 20% amounted to 78% and was significantly dependent on the age of the patient (p = 0.02) and the duration of illness (p = 0.05), however not on sex (p = 0.17), underlying disease (p = 0.23), and type of joint (p = 0.69). CONCLUSION: Irrespective of sex, type of joint and underlying disease, a measurable pain relief can be achieved with RSV in 78% of the patients with synovitis, whereby effectiveness is decreasing with increasing age and progress of illness.

Does an individual estimation of halflife improve the results of radioiodine therapy of Graves' disease?

AIM: The impact of our dosimetry concept on radioiodine therapy success in Graves' disease (GD) was analysed. Three questions arised: Did individual estimation of pretherapeutic halflife improve therapeutic success? Did individual dosimetry result in accurate dose calculation? Did antithyroid medication have a measurable influence on therapeutic success under the prevailing conditions? METHODS: 126 consecutive patients were treated with 200 Gy I-131 in our therapy ward for GD and followed-up six to nine months after therapy. Success quote was assessed using a standardized protocol and treatment was classified as successful when the patient was eu- or hypothyroid, or unsuccessful when he or she presented with a suppressed TSH-level or in hyperthyroid condition after antithyroid medication withdrawal. Antithyroid medication, activity I-131, dose, concentration of fT3 and fT4, specific delivered dose and halflife were put into a multiple regression model to assess their influence on therapeutic success. In order to assess possible factors disturbing the therapeutic outcome, relevant parameters were analyzed using Logit transformation. RESULTS: Out of 126 patients 84 were classified as successfully treated and 42 (33.3%) as failures. A significant influence on the outcome only was found for thyroid mass. However, therapeutic success appeared to be more distinctly determined by the specific delivered dose using an estimated halflife of 5.5 days (Odds: 10.0, p < 0.001). Accurate intratherapeutic dosimetry did not play a significant role to enhance therapeutic success. Neither did antithyroid medication during radioiodine therapy exert any significant impact. CONCLUSIONS: Measurement of individual intratherapeutic halflife as opposed to an estimate using a standard halflife did not provide improved results concerning the target dose. Retrospectively, the therapeutic outcome on the basis of a measured halflife as compared to a standard halflife did not significantly improve. In addition, no influence of antithyroid medication on therapy success was found.

Fluorine-18 fluorodeoxyglucose positron emission tomography in medullary thyroid cancer: results of a multicentre study.

The aim of this study was to evaluate the clinical use of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in medullary thyroid cancer (MTC) on the basis of comparison with findings obtained using indium-111 pentetreotide (SMS), pentavalent technetium-99m dimercaptosuccinic acid (DMSA), technetium-99m sestamibi (MIBI), computed tomography (CT) and magnetic resonance imaging (MRI). One hundred FDG-PET examinations in 85 patients (40 males, 45 females) with elevated tumour marker levels and/or pathological findings on other imaging methods were evaluated retrospectively. Eighty-two patients were examined after total thyroidectomy, and the remaining three patients prior to surgery. Overall, 181 lesions could be identified with at least one of the imaging techniques. Fifty-five lesions were confirmed histologically. FDG-PET detected 123 of 181 sites, which is a lesion detection probability of 68%. In the 55 cases with histological confirmation, we found 32 true positive, 3 false positive, 11 true negative and 9 false negative lesions using FDG-PET, resulting in a sensitivity of 78% and a specificity of 79%. Sensitivity and specificity were, respectively, 25% and 92% for SMS, 33% and 78% for DMSA, 25% and 100% for MIBI, 50% and 20% for CT and 82% and 67% for MRI. Compared with morphological techniques and functional imaging methods with single-photon emitters, FDG-PET showed the highest lesion detection probability for MTC tissue, with a high sensitivity and specificity. It is concluded that FDG-PET is a useful method in the staging and follow-up of MTC.

Antithyroid drugs as a factor influencing the outcome of radioiodine therapy in Graves' disease and toxic nodular goitre?

There is controversy over the factors that may influence the outcome of radioiodine therapy for benign thyroid diseases. Antithyroid medication has been claimed to negatively influence the effectiveness of radioiodine therapy in Graves' disease. In a longitudinal study, we assessed the influence of sex, age, antithyroid drugs, target radiation dose, target mass, applied activity, delivered dose, interval between last meal and application, and TSH, FT3 and FT4 levels on the outcome of radioiodine therapy. One hundred and forty-four patients (111 female, 33 male) suffering from Graves' disease (GD) and 563 patients (434 female, 129 male) with toxic nodular goitre (TNG) were entered in the study and followed up until 8 months after therapy. Treatment was defined as successful when the TSH level was found to be normal or elevated. Ninety-eight GD patients and 418 TNG patients were successfully treated. Forward stepwise multiple regression analysis models retained only the target mass in GD and the applied activity in TNG as significantly associated with the outcome of therapy. The predictive value of all variables involved was extremely low in both disease groups. Whereas concomitant antithyroid medication had no influence in GD, it adversely influenced radioiodine therapy of TNG. This effect may be attributed to a radioiodine "steal phenomenon" induced by TSH-stimulated normal thyroid tissue, which causes overestimation of the uptake in toxic nodules.

[Severe Vitamin D(dihydrotachysterol)-intoxication with temporary anemia and hypercalcemia responsive to bisphosphonates]

Severe Vitamin D(dihydrotachysterol)-intoxication with temporary anemia and hypercalcemia responsive to bisphosphonates. HISTORY AND FINDINGS: A 31-year old female patient presented with pain of her skeletal system. 6 months prior to her presentation, she underwent thyroid surgery for Graves disease. She also suffered from endocrine orbitopathy. Afterwards, she expirienced surgical hypoparathyroidism and received dihydrotachy-sterol (A.T.10 (R)) in a dose of up to 4 mg per day. The physical examination was unremarkable except for the presence of Graves' ophthalmopathy and a swelling at the left ancle. INVESTIGATIONS: Upon admittance, she had severe hypercalcemia (serum calcium: 4.1 mmol/l) with plasma intact PTH levels below the limit of detection, renal failure (serum creatinine: 5.5 mg/dl) and normocytic anemia (initial hemoglobin: 8.3 g/dl, upon rehydration: 6.6 g/dl). TREATMENT AND COURSE: Upon rehydration and induced diuresis, the renal function improved and the serum calcium came down rapidly in the early treatment phase. However, serum calcium remained elevated at around 3.0 mmol/l after 4 weeks. Only after the use of the bisphosphonate pamidronate (15 mg), serum calcium returned into the normal range and remained there. Treatment for hypoparathyroidism had to be reinstituted only 20 weeks after dihydrotachysterol had been discontinued. The anemia had resolved without any treatment at that time. CONCLUSIONS: Treatment with dihydrotachysterol and other long-acting Vitamin D preparations has to be monitored closely because of the risk of severe hypercalcemia, which may be difficult to treat. In our case, dihydrotachysterol was still active until week 20 after the drug was discontinued. Anemia should be considered as a side effect of dihydrotachysterol intoxication and does not warrant elaborate differential diagnosis in this context. A single administration of a bisphosphonate turned out to be of major therapeutic benefit and resulted in a lasting correction of hypercalcemia. Therefore, bisphosphonates should become part of the treatment regimen for vitamin D intoxication.

The use of recombinant human TSH in a patient with metastatic follicular carcinoma and insufficient endogenous TSH production.

We present a case of a patient suffering from metastatic differentiated thyroid carcinoma (DTC) and insufficient endogenous TSH production suspicious of secondary hypothyroidism. The use of recombinant human TSH (rhTSH) enabled us to administer a therapeutic activity of radioactive iodine (RAI) under maximal TSH-stimulation, achieving a marked decrease in thyroglobulin accompanied by a clinical improvement.

Fe(II)-catalyzed imidation of allyl sulfides and subsequent

Allyl aryl sulfides 1 and 5 were shown to undergo an imidation/[2,3]-sigmatropic rearrangement reaction upon treatment with N-tert-butyloxycarbonyl azide (BocN3) and catalytic amounts of FeCl2 in CH2Cl2. The N-Boc-protected N-allyl sulfenamides 3 and 21 were obtained in yields between 48 and 75% (12 examples). Whereas the reaction is well suited for the transformation of alpha-unbranched sulfides to alpha-branched sulfenamides, the enantiomerically pure alpha-branched sulfides 10 and 13 reacted sluggishly. The corresponding sulfenamides 22 and 23 were obtained in only moderate enantiomeric excess (36-39% ee). A reaction mechanism is proposed that postulates the intermediacy of an N-Boc-substituted Fe(IV)-nitrene complex 14 acting as the imidation reagent in the catalytic cycle. Possible side reactions are discussed. The benzenesulfenamides 3 were further converted into N-Boc-N-allylamines 4 by removal of the phenylsulfanyl group. Bu3SnH in benzene was found to be the reagent of choice for the deprotection of alpha-branched amines that bear a secondary allyl substituent (five examples, 71-93% yield). This method failed for the alpha-branched amines 3i-k with a tertiary allyl substituent. The phenylsulfanyl group was finally removed with P(OEt)3/NEt3 in CH2Cl2 (three examples, 43-62% yield).

[Is the post-therapeutic dosimetry of patients with short-term hospitalization after 131I therapy sufficiently reliable?]. / Ist die posttherapeutische Dosimetrie bei verkürzter stationärer Verweildauer der Patienten nach 131-I-Therapie ausreichend zuverlässig?

AIM: According to the new recommendations of the Federal German Radiation Protection Committee (SSK) for patient discharge, that were published in April 1997, patients can be discharged after radioiodine therapy with a radiation exposure of less than 1 mSv per year in 2 m distance. The aim of this study was to evaluate whether the measurement of the achieved dose was different 48 hours after application of I-131 and after an interval of one week. The study was planned in order to ensure quality management in the follow-up of the patients. METHOD: In a prospective study 115 patients were followed, that were treated for a benign thyroid disease. The patients were discharged 48 hours after the intake of I-131 after falling short of the exposure limit. All patients were measured at discharge and about 8 days later with the same uptake facility. RESULTS: Because of similar results focal and disseminated forms of benign thyroid diseases could be analysed together. The calculated doses 8 days after the discharge were higher than the values at the time of discharge. The doses were underestimated about 4% with an standard error of 15%. CONCLUSION: The error in early dosimetric measurements is small in comparison to the overall uncertainty in therapy and uptake dosimetry. A valid dosimetry and sufficient quality management can be guaranteed even for an early discharge.

[Incidence of familial non-medullary thyroid carcinoma in the patient register of the Clinic and Polyclinic of Nuclear Medicine, University of Würzburg]. / Häufigkeit des familiären nicht-medullären Schilddrüsenkarzinoms im Krankengut der Klinik und Poliklinik für Nuklearmedizin der Universität Würzburg.

AIM: In this study the incidence rate of familial non-medullary thyroid carcinoma was investigated in the first and second grade relatives of patients registered at the Clinic and Polyclinic for Nuclear Medicine, University of Würzburg. PATIENTS AND METHODS: In this study 596 patients with differentiated thyroid carcinoma were enclosed, who were treated between 01.01.81 and 31.12.95. The data concerning a familial occurrence were studied by a retrospective survey-based analysis. These data were compared to a literature analysis for familial non-medullary thyroid carcinoma. RESULTS: 14 patients of the 596 patients treated showed a familial occurrence (2.3%). All these patients suffered from papillary thyroid carcinoma. According to the prognostic factors (tumor state, lymph node involvement, metastatic disease) no differences could be evaluated in the different groups (sporadic versus familial non-medullary thyroid disease). CONCLUSION: A familial occurrence of differentiated thyroid carcinomas is not frequently observed, but should be considered due to further genetic diseases.

[Measurement of incorporation in family members of radioiodine therapy patients after therapy of benign thyroid diseases]. / Inkorporationsmessungen bei Angehörigen von Radioiodtherapiepatienten nach Therapie benigner Erkrankungen der Schilddrüse.

AIM: Patients exhale I-131 after radioiodine therapy. In this study we quantify the amount of radioactivity and resulting thyroid doses found in people living in close contact to patients treated with I-131 after their release from a therapy ward. METHODS: For 31 relatives of 25 patients treated with I-131 the incorporation was monitored using the thyroid probe of a whole body counter. These values are used for a determination of thyroid doses. RESULTS: 11 of the 31 monitored persons had a thyroid activity of less than the minimal detectable activity of 13 Bq. The mean value of the remaining 20 people was 104 Bq in the thyroid resulting in a mean thyroid dose of 0.2 mSv (Maximum: 2 mSv). CONCLUSION: The intake of I-131 for persons in close contact to patients after dismissal from a therapy ward is low. In no case an effective dose exceeding 1 mSv was observed.

Micronuclei induced by modulators of methylation: analogs of 5-azacytidine.

Jones and coworkers demonstrated a qualitative correlation between 5-azacytidine and some of its analogs in inducing changes in cell morphology and their ability in preventing DNA methylation. Previously, we evaluated the same compounds to determine their ability to induce trifluorothymidine (TFT) resistance in L5178Y mouse cells and found that their mutagenic potency also correlated with their reported ability to induce morphological changes in C3H10T1/2 cells. Here, we examine four of the same analogs, 5-fluoro-2'-deoxycytidine, 5-azacytidine, 5,6-dihydro-5-azacytidine and 6-azacytidine, to find out if micronuclei induced by these compounds correlated with these effects. The most cytotoxic analog was 5-fluoro-2'-deoxycytidine, followed by 5-azacytidine. 5,6-Dihydro-5-azacytidine and 6-azacytidine were substantially less cytotoxic. All four compounds induced micronuclei. The lowest dose ranges at which responses were observed for micronucleus induction were -0.04 microM for 5-fluoro-2'-deoxycytidine, 0.2 microM for 5-azacytidine and 10-20 microM for 5,6-dihydro-5-azacytidine and 6-azacytidine. Lack of kinetochore staining in most of the micronuclei indicated that all four compounds were clastogenic. We note a general trend in the biological activity of these analogs: compounds that are specifically blocked at the 5 position such as 5-azacytidine and 5-fluoro-2'-deoxycytidine effect changes in cell morphology, cytotoxicity, TFT resistance and the induction of micronuclei at very low doses. 5-Azacytidine analogs that possess more chemically accessible 5 positions such as 5,6-dihydro-5-azacytidine and 6-azacytidine either require doses that are orders of magnitude greater to induce these effects or are unable to induce changes in cell morphology and TFT resistance at doses below which the compound is lethal to the cells.

Encapsulation of human erythrocytes by growing ice crystals.

In this study the interaction of human erythrocytes in suspension with a planar ice-liquid interface is investigated. Due to a repulsive van der Waals force repelling the cells from the crystal and an attractive force resulting from the viscous drag of melt flow around the cell a velocity was determined below which the cell is pushed by the growing crystal and above which it is entrapped by the solid phase. The critical velocity for erythrocytes suspended in 0.85 wt% NaCl-D2O solution can be derived from measuring the time periods of pushing and is calculated to be 1.1 microns/s at a temperature gradient of 15.3 K/mm.

An investigation of micronucleus and mutation induction by oxazepam in mammalian cells.

The benzodiazepines are a class of drugs that are widely used in the treatment of various psychiatric disorders. One member of this class, oxazepam, is also a common metabolite of several other benzodiazepines. Since the evidence for the genetic toxicity and carcinogenic properties of these compounds is inconsistent, we investigated the oxazepam-induced formation of micronuclei in Syrian Hamster embryo fibroblast (SHE) cells, human amniotic fluid fibroblast-like (AFFL) cells and L5178Y mouse cells. A dose-dependent increase in micronucleus fractions was found in all three cell lines. The time course of micronucleus induction in L5178Y cells showed a maximum at 5 h after treatment, suggesting that the micronuclei were formed in the first mitosis after treatment. Kinetochore staining (CREST-antiserum) revealed the presence of kinetochores in approximately 50% of the micronuclei in all three cell types. This result was further confirmed by in situ hybridization in L5178Y cells and indicates the presence of whole chromosomes or centric fragments as well as acentric fragments in the oxazepam-induced micronuclei. The L5178Y cells did not show a mutagenic response to oxazepam at any of the doses or expression times used.

Cell-cycle dependent micronucleus formation and mitotic disturbances induced by 5-azacytidine in mammalian cells.

5-Azacytidine was originally developed to treat human myelogenous leukemia. However, interest in this compound has expanded because of reports of its ability to affect cell differentiation and to alter eukaryotic gene expression. In an ongoing attempt to understand the biochemical effects of this compound, we examined the effects of 5-azacytidine on mitosis and on micronucleus formation in mammalian cells. In L5178Y mouse cells, 5-azacytidine induced micronuclei at concentrations at which we and others have already reported its mutagenicity at the tk locus. Using CREST staining and C-banding studies, we showed that the induced micronuclei contained mostly chromosomal fragments although some may have contained whole chromosomes. By incorporating BrdU into the DNA of SHE cells, we determined that micronuclei were induced only when the compound was added while the cells were in S phase. Microscopically visible effects due to 5-azacytidine treatment were not observed until anaphase of the mitosis following treatment or thereafter. 5-Azacytidine did not induce micronuclei via interference with formation of the metaphase chromosome arrangement in mitosis, a common mechanism leading to aneuploidy. Supravital UV microscopy revealed that chromatid bridges were observed in anaphase and, in some cases, were sustained into interphase. In the first mitosis after 5-azacytidine treatment we observed that many cells were unable to perform anaphase separation. All of these observations indicate that 5-azacytidine is predominantly a clastogen through its incorporation into DNA.