[Ectopic thyroid tissue after total thyroidectomy]. / Ektopes Schilddrüsengewebe nach erfolgter Thyreoidektomie.

Ectopic thyroid gland tissue can occur either as the only detectable thyroid gland tissue or in addition to a normotopic thyroid gland. After a total thyroidectomy thyroid-stimulating hormone (TSH) can induce a compensatory volume increase of previously asymptomatic ectopic tissue. This hyperplastic ectopic tissue can occur as an unclear cervical space-occupying lesion. Prior to surgical exploration of an unclear cervical mass the possibility of ectopic thyroid tissue should be included in the differential diagnostic considerations.

Low medical morbidity and mortality after acute courses of electroconvulsive therapy in a population-based sample.

BACKGROUND: To determine event rates for specific medical events and mortality among individuals receiving electroconvulsive therapy (ECT). METHOD: Population-based cohort study using health administrative data of acute ECT treatments delivered in Ontario, Canada, from 2003 to 2011. We measured the following medical event rates, per 10 000 ECT treatments, up to 7 and 30 days post-treatment: stroke, seizure, acute myocardial infarction, arrhythmia, pneumonia, pulmonary embolus, deep vein thrombosis, gastrointestinal bleeding, falls, hip fracture, and mortality. RESULTS: A total of 135 831 ECT treatments were delivered to 8810 unique patients. Overall medical event rates were 9.1 and 16.8 per 10 000 ECT treatments respectively. The most common medical events were falls (2.7 and 5.5 per 10 000 ECT treatments) and pneumonia (1.8 and 3.8 per 10 000 ECT treatments). Fewer than six deaths occurred on the day of an ECT treatment. This corresponded to a mortality rate of less than 0.4 per 10 000 treatments. Deaths within 7 and 30 days of an ECT treatment, excluding deaths due to external causes (e.g., accidental and intentional causes of death), were 1.0 and 2.4 per 10 000 ECT treatments respectively. CONCLUSION: Morbidity and mortality events after ECT treatments were relatively low, supporting ECT as a low-risk medical procedure.

The development and validation of a health-related quality of life questionnaire for pre-school children with a chronic heart disease.

PURPOSE: Heart diseases are often associated with residual injuries, persisting functional restrictions, and long-term sequelae for psychosocial development. Currently, there are no disease-specific instruments to assess the health-related quality of life (HrQoL) of pre-school children. The aims of this study were to develop a parent proxy instrument to measure the HrQoL of children aged 3-7 years with a heart disease and to confirm its validity and reliability. METHODS: Items from the Preschool Pediatric Cardiac Quality of Life Inventory (P-PCQLI) were generated through focus groups of caregivers. In a pilot study, comprehensibility and feasibility were tested. Five subdimensions were defined theoretically. Psychometric properties were analysed within a multicentre study with 167 parental caregivers. RESULTS: The final 52-item instrument contains a total score covering five moderately inter-correlated dimensions. The total score of the questionnaire showed a very high internal consistency (Cronbachs' α = 0.95). Test-retest correlation was at r tt = 0.96. External validity was indicated by higher correlations (r = 0.24-0.68) with a generic paediatric quality of life questionnaire (KINDL) compared to the Strengths and Difficulties Questionnaire (r = 0.17 to 0.59). Low P-PCQLI total scores were significantly associated with inpatient as opposed to outpatient treatment (t = 6.04, p < .001), with at least moderate disease severity ((t = 5.05, p < .001) NYHA classification) and with poorer prognosis (t = 5.53, p < .001) as estimated by the physician. CONCLUSIONS: The P-PCQLI is reliable and valid for pre-school children with a heart disease. It could be used as a screening instrument in routine care, and for evaluation of HrQoL outcomes in clinical trials and intervention research.

Utilization of psychosocial care and oncological follow-up assessments among German long-term survivors of cancer with onset during adolescence.

BACKGROUND: Survivors of pediatric cancer are at increased risk for medical and psychosocial late effects. This study retrospectively investigated the utilization of oncological and psychosocial care by former adolescent cancer patients (≥ 5 years since cancer diagnosis) in Germany. PATIENTS: Based on data of the German Childhood Cancer Registry (N=1 876 survivors of cancer with an age at diagnosis between 15 and 18 years), the study cohort comprised 820 survivors of adolescent cancer (time since diagnosis: M=13.7, SD=6.0, age at follow-up: M=30.4, SD=6.0 years). METHOD: Survivors of adolescent cancer completed standardized questionnaires measuring symptoms of posttraumatic stress, depression and anxiety as well as items on their utilization of medical and psychosocial care. RESULTS: More than a quarter (26.2%) of the survivors was no longer attending regular oncological follow-up assessments. Less than half of the survivors (44.4%) had received psychosocial care, mostly during their in-patient cancer treatment and their post-acute rehabilitation phase. Out of 184 survivors showing clinically relevant symptoms of posttraumatic stress, anxiety and/or depression at time of the study, 12.0% received psychosocial care and 13.6% took psychotropic medication. CONCLUSION: It should be studied further why only a small proportion of the survivors showing clinically relevant symptoms received psychosocial or psychopharmacological treatment. Systematic oncological follow-up assessments should take psychological late effects into greater account.

Search for axions with the CDMS experiment.

We report on the first axion search results from the Cryogenic Dark Matter Search (CDMS) experiment at the Soudan Underground Laboratory. An energy threshold of 2 keV for electron-recoil events allows a search for possible solar axion conversion into photons or local galactic axion conversion into electrons in the germanium crystal detectors. The solar axion search sets an upper limit on the Primakov coupling g(agammagamma) of 2.4x10(-9) GeV-1 at the 95% confidence level for an axion mass less than 0.1 keV/c2. This limit benefits from the first precise measurement of the absolute crystal plane orientations in this type of experiment. The galactic axion search analysis sets a world-leading experimental upper limit on the axioelectric coupling g(aee) of 1.4x10(-12) at the 90% confidence level for an axion mass of 2.5 keV/c2.

Detection and possible role of proteasomes in the bronchoalveolar space of the injured lung.

Recent observations suggest the presence of 20S proteasomes (20S) in the lung epithelial lining fluid. However, the physiological relevance of 20S in the alveolar space and possible contribution to disease processes are unknown. Thus, we evaluated whether extracellular proteasomes could have a pathophysiological role in the injured lung using a rat model of lung contusion (LC). Bronchoalveolar lavage fluids (BALF) were obtained at various time points for up to 168 h after LC or sham procedure. Enzyme activities, ELISA and Western blots indicated enzymatically active 20S, the 19S subunit Rpt5 and ubiquitin in BALF. 20S and ubiquitin increased significantly after LC, peaked at 24 h and normalized within 168 h. Mg(2+)/ATP-dependent peptidase activities were detectable 6-24 h after LC. BALF after LC also contained ubiquitin-protein-ligase activity. Addition of Mg(2+)/ATP to BALF after LC led to significant proteolysis and could be prevented with epoxomicin and EDTA. These data suggest for the first time that the Mg(2+)/ATP-dependent 26S proteasome complex exists outside the cell, is released into the lung epithelial lining fluid after LC and contributes to the proteolysis of the bulk of protein in the alveolar space of the injured lung. We infer that proteasome complexes may have a pathophysiological role during lung edema clearance.

Glutaraldehyde and oxidised dextran as crosslinker reagents for chitosan-based scaffolds for cartilage tissue engineering.

Chitosan crosslinked with glutaraldehyde or oxidised dextran was studied as a potential scaffold material in tissue engineering for cartilage regeneration. By mixing two solutions of both components it became a gel, which was frozen. After lyophilization a scaffold was generated with interconnected pores with diameters ranging between 120-350 microm. The mechanical properties (yielding point, elastic and viscous moduli), absolute porosity, pore morphology were determined depending on the ratio of chitosan to crosslinker. ATDC5 (murine cell line) and bovine articular chondrocytes (primary cells) were cultured for 14 days on the scaffolds. Cultivation with ATDC5 cells and bovine chondrocytes showed no negative influence of glutaraldehyde on cell vitality and growth.

Antitumor activity and clinical pharmacology of sulofenur in ovarian cancer.

BACKGROUND: Sulofenur is a diarylsulfonylurea with demonstrated antitumor activity in patients with advanced epithelial ovarian cancer refractory to standard chemotherapy. The dose-limiting toxic effects observed in phase I clinical trials have been anemia and methemoglobinemia, resulting in cyanosis. PURPOSE: The purposes of this study were to further define the response rate, toxic effects, and pharmacokinetics and pharmacodynamics of sulofenur in patients with advanced ovarian cancer. METHODS: We conducted a phase II trial of sulofenur at a dose of 800 mg/m2 per day in 35 patients with stage III or IV ovarian cancer refractory to standard chemotherapy. Pharmacokinetics and pharmacodynamics were analyzed by comparing sulofenur parent and metabolite plasma levels with methemoglobin levels. RESULTS: Partial responses lasting 6.5-18 weeks occurred in four (15%; 95% confidence interval = 4%-35%) of the 26 patients assessable for response. In addition, 42% (11) of the assessable patients had prolonged stable disease (median, 20 weeks). The first nine patients received sulofenur as a daily oral dose for 14 days, with a 21-day treatment cycle. However, they developed substantial anemia and methemoglobinemia. As a result, the next 26 patients received sulofenur daily for 5 days followed by 2 days of rest for 3 consecutive weeks, with a 28-day treatment cycle (5/2-day schedule). Preclinical models predicted that 2 days of rest would decrease toxicity while maintaining antitumor activity. Patients treated with the 5/2-day schedule had relatively less severe anemia and methemoglobinemia and needed fewer red blood cell transfusions (31% versus 78% of patients), but 31% still required dose reductions because of these toxic effects. The hydroxy and keto metabolites of sulofenur had prolonged plasma half-lives relative to the parent compound, and the difference was statistically significant. In addition, the correlations of metabolite concentrations with methemoglobin levels were higher than the correlation of sulofenur concentrations with methemoglobin levels, and those differences were statistically significant. CONCLUSION: We conclude that sulofenur has modest clinical activity in heavily pretreated patients with ovarian cancer. IMPLICATIONS: The toxic effects of anemia and methemoglobinemia may limit the ultimate clinical utility of diarylsulfonylureas until less toxic derivatives with alternate metabolic pathways can be identified.

Thermodynamic analysis of the reaction of phosphoramide mustard with protector thiols.

The systemic use of thiol-containing uroepithelial protecting agents, e.g., N-acetylcysteine (NAC) or mesna, in conjunction with the alkylating agent cyclophosphamide is predicated on the assumption that the toxic metabolic by-products will be consumed by thiol without diminishing the cytotoxicity of the active alkylating intermediate, phosphoramide mustard. Studies in murine tumor systems have been with either a single dose or two equally divided doses of thiol, administered within 30 min of the addition of cyclophosphamide, without an observed adverse effect on antitumor activity; however, the relatively short serum half-life of thiol relative to alkylating agent in humans weakens the clinical relevance of these results. This study presents a thermodynamic model for the chemical reaction of phosphoramide mustard with either NAC or mesna. The gas phase thermodynamic parameters for these reactions, enthalpy (H) and entropy (S), were calculated using the semiempirical quantum mechanical method AM1 and were used to predict the free energy (delta G) for these processes. For the reaction of phosphoramide mustard with NAC or mesna, delta G = +3.82 and 2.29 kcal/mol, respectively. In the absence of enzyme catalysis, these results suggest that such reactions are not favored. In order to assess the validity of this gas phase thermodynamic model, the cellular cytotoxicity of phosphoramide mustard in the presence or absence of either NAC or mesna was studied using CCRF-CEM cells in culture. In these experiments the 50% effective dose of phosphoramide mustard was 1.7 micrograms/ml; this result was unchanged in the presence of 10 micrograms/ml concentration of either thiol. This study supports the conclusion that phosphoramide mustard and protector thiols are compatible.

Cellular pharmacology of MTA: a correlation of MTA-induced cellular toxicity and in vitro enzyme inhibition with its effect on intracellular folate and nucleoside triphosphate pools in CCRF-CEM cells.

The mechanism of action of an antifolate may be investigated using a variety of experimental methods. These include experiments in a cell culture setting to observe possible protection against drug effects afforded by the end products of metabolic pathways, assessing the activity of purified target enzymes in the presence of the antifolate, and, finally, the measurement of drug effects on intracellular folate and nucleoside triphosphate pools. The current discussion is focused on studies using CCRF-CEM leukemia cells that were designed to compare and contrast mechanisms of action of the antifolates methotrexate, which is primarily a dihydrofolate reductase inhibitor, raltitrexed, a thymidylate synthase inhibitor, LY309887, a glycinamide ribonucleotide formyltransferase inhibitor, and MTA (multitargeted antifolate), which is a novel antifolate antimetabolite. The results of these studies support the hypothesis that MTA affects multiple enzymatic targets and has a distinct mechanism of action from methotrexate, raltitrexed, and LY309887.

E-17 alpha[125I]iodovinylestradiol: an estrogen-receptor-seeking radiopharmaceutical.

Through the use of radioiododestannylation, the specifically labeled E-17 alpha-[125I]iodovinylestradiol [(I-125)VE2] was synthesized rapidly and in high yield from the stable precursor E-17 alpha-tributylstannylvinylestradiol (SnVE2), and its biodistribution was determined in immature female rats. The agent accumulated in the uterus, achieving a peak uptake of 0.465% ID-kg/g at 2 hr. Uterus-to-blood ratios of 19 and 16 occurred at 1 and 2 hr, respectively, declining to 7 by 4 hr after injection. The uptake of (I-125)VE2 by the uterus at 2 hr was reduced 58--65% by pretreatment of the immature rats with estradiol (5 micrograms) or tamoxifen (100 micrograms), and compared with 16 alpha-[125I]iodoestradiol, (I-125)VE2 showed greater uterine uptake and similar uterus-to-blood ratios. The ease of preparation of the radioligand represents an advantage over the synthetic procedures for other estrogen-receptor-seeking agents.

Magnetic resonance bone densitometry. Comparison of different methods based on susceptibility.

RATIONALE AND OBJECTIVES: Three different magnetic resonance techniques for the assessment of the density of trabecular bone are presented and compared. METHODS: All methods are based on the susceptibility difference between marrow and bony components. Localized spectroscopic (PRESS single voxel spectroscopy) and two different imaging approaches (FLASH gradient echo imaging and MAGSUS imaging) are demonstrated to be sensitive to the trabecular structures on application to the distal femur of a healthy volunteer. This region was chosen because a continuous rarefication of the trabecular density from the epiphysis to the metaphysis occurs physiologically. In addition, results from the heel-bones of five young healthy volunteers were compared with data from three patients with severe osteoporosis. RESULTS: All methods allowed differentiation between the two groups. Advantages and disadvantages of the methods concerning spatial resolution, preparation and measuring time, necessity of postprocessing, problems with shim adjustment, and occurrence of several chemical shift components are reported. The MAGSUS technique combines simple application and avoidance of postprocessing for at least qualitative assessment of bone density with sufficient spatial resolution. CONCLUSIONS: A reliable assessment of osteoporosis by magnetic resonance is possible in peripheral marrow regions of adults. Further studies are needed to establish standard measuring protocols.

Rotational movement (circling) in normal humans: sex difference and relationship to hand, foot and eye preference.

An endogenous asymmetry in striatal dopaminergic function has been identified in rats, and related to spontaneous and drug-induced circling (rotation, turning). We have developed an electronic device for measuring in humans the same kinds of rotational movements observed in rats. Our data indicate that, without being aware of the type of information being obtained, normal men and women rotate preferentially to the left or to the right during a routine day. Women had higher average rates of rotation than men. Males that were consistently right-sided (left-hemisphere dominant) for hand, foot and eye dominance rotated more to the right than to the left, whereas left-hemisphere dominant females rotated more to the left than to the right. Subjects tested on two occasions, 6 weeks apart, exhibited consistent (significantly correlated) rotational preferences--this was much more evident in left-hemisphere dominant than in mixed dominance individuals. In view of similar animal data, the device used in this study may become a useful and objective means for obtaining quantitative information regarding the status of basal ganglia function in humans.

MR imaging and localized proton MR spectroscopy in late infantile neuronal ceroid lipofuscinosis.

PURPOSE: Late juvenile neuronal ceroid lipofuscinosis (NCL) is a lysosomal neurodegenerative disorder caused by the accumulation of lipopigment in neurons. Our purpose was to characterize the MR imaging and spectroscopic findings in three children with late infantile NCL. METHODS: Three children with late infantile NCL and three age-matched control subjects were examined by MR imaging and by localized MR spectroscopy using echo times of 135 and 5. Normalized peak integral values were calculated for N-acetylaspartate (NAA), choline, creatine, myo-inositol, and glutamate/glutamine. RESULTS: MR imaging revealed volume loss of the CNS, most prominently in the cerebellum. The T2-weighted images showed a hypointense thalamus and hyperintense periventricular white matter. Proton MR spectra revealed progressive changes, with a reduction of NAA and an increase of myo-inositol and glutamate/glutamine. In long-standing late infantile NCL, myo-inositol became the most prominent resonance. Lactate was not detectable. CONCLUSION: MR imaging in combination with proton MR spectroscopy can facilitate the diagnosis of late infantile NCL and help to differentiate NCL from other neurometabolic disorders, such as mitochondrial or peroxisomal encephalopathies.

Proton spectroscopy of human brain with very short echo time using high gradient amplitudes.

In localized proton magnetic resonance spectroscopy very short echo times (TE) are achieved to diminish signal loss due to T2 relaxation and to avoid phase distortions due to J-coupling. A sequence for single volume spectroscopy in human brain is described with a TE as low as 5 ms. Examinations were performed on a 1.5 T whole-body imager with actively shielded gradients. A self-designed stimulated echo acquisition mode (STEAM) sequence with very high amplitude spoiling gradients of 24 mT/m was used to take advantage of the whole potential of the gradient system. Optimization of TE was carried out by controlling spectral quality and localization in both phantom and volunteer measurements. Proton spectra of human brain were acquired in 21 healthy volunteers. Spectra of occipital white matter, parieto-occipital grey/white matter, and cerebellum revealed none or only small eddy current distortions at a TE of 5 ms. The volume of interest was 8-12 ml, repetition time was 1.5 s, and mixing time was 5 ms. Peak ratios of major metabolites referring to creatine were estimated and the relative standard deviations were calculated to determine interindividual reproducibility. The relative standard deviation of myo-inositol ranged from 6% to 11% within these brain regions whereas for glutamine and glutamate 7% to 16% were found.

[Myelomalacia following vertebral angiography with a femoral catheter (author's transl)]. / Myelomalazie infolge Vertebralisangiographie mittels Femoraliskatheters

Cerebral angiography with femoral catheters in two patients was followed by an incomplete cervical transverse myelitis. The complications were thought to be due to high contrast concentration in the cervical spinal vessels because of hypoplasia of one vertebral artery, and to contrast injection into the thyro-cervical trunk.

[Echo contrast agents for the color Doppler sonographic diagnosis of deep femoral venous thrombosis]. / Echokontrastmittel für die farbdopplersonographische Diagnostik der tiefen Oberschenkelvenenthrombose.

PURPOSE: Evaluation of an echo contrast medium (Echovist) for color-coded duplex sonography of deep venous thrombosis of the thigh. MATERIAL AND METHODS: In 19 patients with deep vein thrombosis of the thigh, diagnosed by contrast phlebography, 22 color-coded duplex sonography studies were performed for flow analysis at the top of the thrombus. During the studies 8.5 ml echo contrast medium were injected in an ipsilateral vein at the back of the foot. The flow signals of the non-enhanced color coded duplex sonography were compared with those of the echo enhanced study for differentiation between floating thrombi from those adherent to the vein wall. RESULTS: The echo-enhanced color-coded duplex sonography showed a significant increase in detection of perfusion at the top of the thrombus in comparison with non-enhanced color-coded duplex sonography (p < 0.01). 9 thrombi were regarded as wall adherent after the native study, 7 of these could be identified as floating thrombi by echo-enhanced color-coded duplex sonography. CONCLUSION: Echo-enhanced color-coded duplex sonography yields a significant increase of diagnostic information in certain findings of the non-enhanced color-coded duplex sonography differentiating between floating thrombi and wall adherent thrombi in the deep venous system of the thigh.

[MR proton spectroscopy to monitor the concentration changes in cerebral metabolites following a TIPS placement]. / MR-Protonenspektroskopie zur Verlaufsbeurteilung von Konzentrationsänderungen zerebraler Metaboliten nach TIPS-Anlage.

BACKGROUND AND AIMS: In chronic liver dysfunction with portal hypertension the risk of variceal bleeding can be lowered by intrahepatic portosystemic shunting (TIPS). Although less pronounced than in surgical shunting, hepatic encephalopathy (HE) is a well-known undesired side effect. In cerebral proton MR spectroscopy (MRS), HE can be detected by a specific pattern of brain metabolite changes (increase of glutamine/glutamate (Glx) and decrease of myo-inositol (ml) and choline (Cho)). The aim of this study was to examine whether, after TIPS implantation, there is a correlation of the reduction of the portosystemic pressure gradient (PSPG) and the cerebral metabolite changes and their correspondence to the clinical status. METHODS: We examined 10 cirrhotic patients (Child B, C) before and 3-20 days after TIPS implantation. Clinical examination was performed by a senior hepatologist. Localized MR spectra were acquired in parieto-occipital gray/white matter using a short echo time (TE = 5 ms) STEAM sequence. RESULTS: After TIPS we found an increase of Glx/(Cr + PCr) of 13%-40% and a decrease of ml(Cr + PCr) of 6%-46% with a positive (Glx: r = 0.71) respectively negative (ml: r = -0.59) correlation to the reduction of the PSPG. 7/10 patients with a reduction of the PSPG of more than 9 mmHg (9-17 mmHg) showed a clinical impairment of their HE. CONCLUSIONS: Short echo time cerebral MRS allows detection of finest HE specific metabolite changes and can therefore contribute positively to an individually optimized reduction of the PSPG during TIPS implantation.

[Examination of trabecular bone structures of the foot skeleton with MRI imaging]. / Untersuchung spongiöser Knochenanteile im Fussskelett mit bildgebenden MR-Verfahren.

AIMS: To assess trabecular density and structures at various cancellous bone sites in the foot using MR imaging. To compare the MRI findings with the bone mineral density (BMD) values obtained by quantitative computed tomography (QCT) in the lumbar vertebrae. MATERIALS AND METHODS: Bone mineral densities were measured by QCT in lumbar vertebrae 1 to 3 in ten patients with suspected osteoporosis. Sagittal images of the feet were obtained from these patients and also from seven healthy volunteers applying spin-echo and gradient-echo MR techniques. RESULTS: MR imaging revealed differences between patients with osteoporosis and individuals with healthy bones. Comparison of MR and BMD data revealed a significant dependence of MR data on the bone density measured by QCT (alpha < 0.05). In addition, a good correlation (r = 0.73) was found between the results of the different MRI techniques. CONCLUSIONS: The MR imaging techniques investigated offer an interesting tool for the non-invasive assessment of bony structures, at least at peripheral locations with yellow bone marrow. To enable reliable application in the clinical routine setting, additional studies are required to identify suitable standardized methods and establish normal ranges.