Low Altitude Solar Magnetic Reconnection, Type III Solar Radio Bursts, and X-ray Emissions.

Type III solar radio bursts are the Sun's most intense and frequent nonthermal radio emissions. They involve two critical problems in astrophysics, plasma physics, and space physics: how collective processes produce nonthermal radiation and how magnetic reconnection occurs and changes magnetic energy into kinetic energy. Here magnetic reconnection events are identified definitively in Solar Dynamics Observatory UV-EUV data, with strong upward and downward pairs of jets, current sheets, and cusp-like geometries on top of time-varying magnetic loops, and strong outflows along pairs of open magnetic field lines. Type III bursts imaged by the Murchison Widefield Array and detected by the Learmonth radiospectrograph and STEREO B spacecraft are demonstrated to be in very good temporal and spatial coincidence with specific reconnection events and with bursts of X-rays detected by the RHESSI spacecraft. The reconnection sites are low, near heights of 5-10 Mm. These images and event timings provide the long-desired direct evidence that semi-relativistic electrons energized in magnetic reconnection regions produce type III radio bursts. Not all the observed reconnection events produce X-ray events or coronal or interplanetary type III bursts; thus different special conditions exist for electrons leaving reconnection regions to produce observable radio, EUV, UV, and X-ray bursts.

[Aortic thrombosis in a calf]. / Aortenthrombus bei einem Kalb.

A two month-old female Simmental calf was presented with sensomotoric dysfunction and recumbency. Neurologic examination revealed dysfunction of the cerebral cortex and paralysis of both hind limbs. Examination of the skeletal system revealed a marked reduction of the skin temperature of both hind limbs and the absence of femoral pulse. Examination of cerebrospinal fluid yielded physiological parameters. The radiographic examination of the vertebral column, hip and femur on both sides revealed no evidence of alteration of the bone structures. Thiamine pyrophosphate test indicated thiamine deficiency. Based on these findings a tentative diagnosis of cerebrocortical necrosis and aortic thrombosis were made and the animal was euthanised. Post mortem examination yielded thrombosis of the abdominal aorta cranial to the branching of the iliac arteries and consecutive necrosis of the skeletal muscle of the hind limbs. Possible causes of pathogenesis are discussed.

Sequential targeting of CFTR by BAC vectors generates a novel pig model of cystic fibrosis.

Cystic fibrosis (CF) is the most common lethal inherited disease in Caucasians and is caused by mutations in the CFTR gene. The disease is incurable and medical treatment is limited to the amelioration of symptoms or secondary complications. A comprehensive understanding of the disease mechanisms and the development of novel treatment options require appropriate animal models. Existing CF mouse models fail to reflect important aspects of human CF. We thus generated a CF pig model by inactivating the CFTR gene in primary porcine cells by sequential targeting using modified bacterial artificial chromosome vectors. These cells were then used to generate homozygous CFTR mutant piglets by somatic cell nuclear transfer. The homozygous CFTR mutants lack CFTR protein expression and display severe malformations in the intestine, respiratory tract, pancreas, liver, gallbladder, and male reproductive tract. These phenotypic abnormalities closely resemble both the human CF pathology as well as alterations observed in a recently published CF pig model which was generated by a different gene targeting strategy. Our new CF pig model underlines the value of the CFTR-deficient pig for gaining new insight into the disease mechanisms of CF and for the development and evaluation of new therapeutic strategies. This model will furthermore increase the availability of CF pigs to the scientific community.

Fasciated nerve-muscle explants for in vitro comparison of magnetic and electrical neuromuscular stimulation.

Neuromuscular stimulation has become a central technique for research and clinical efforts in rehabilitation, but available devices still do not show the needed performance in strength and selectivity for this approach. However, the knowledge about the exact intramuscular structure formed by the axons, muscle fibers with their different metabolism types and properties as well as the motoric endplates in between is still too rough for purely theoretical optimization. In this text, we present an experimental setup for parametrized studies of the spatial and temporal degrees of freedom (DOF) in electrical as well as magnetic stimulation. For clarification of the physiologic background, nerve-muscle explants are dissected and kept on life support in a nutrient system with glucose and oxygen supply. The setup provides two-channel EMG signals and a dynamic force signal. The design was adapted to meet the conditions for physical compatibility with magnetic stimulation and allows coil position sweeps with four (three translational and one rotational) DOF. The setup provides access to essential boundary conditions and means to simulate lesions as well as the influence of drugs. Besides with the presented setup, comparisons and even combined application of magnetic and electrical stimulation become possible on the level of the neuromuscular system. Finally, this approach shall help to improve rehabilitation by peripheral stimulation after nerve lesions. The focus of this text lies on the setup and the nutrition which will entail particular studies in the sequel.

[Euthyroid goiter with and without functional autonomy in the euthyroid phase: a comparison]. / Jodmangelstruma mit und ohne funktionelle Autonomie in der euthyreoten Phase: Ein Vergleich.

AIM: Analysis of functional autonomy in euthyroid goitre. METHODS: In an area of moderate iodine deficiency 163 goitrous patients without and 179 with functional autonomy all clinically euthyroid were compared by sex, age, signs and symptoms, sonographic results, qualitative and quantitative scintigraphy without and with suppression, TRH test, hormone concentrations and iodine excretion in the urine. RESULTS: Age, signs and symptoms, thyroid volume and structure did not contribute sufficiently to diagnosis. To detect functional autonomy quantitative scintigraphy under suppression was superior to the TRH test. Increased hormone concentrations were observed in 15% of patients with functional autonomy. A global 99mTc thyroid uptake of > or = 3% under suppression indicates a higher risk of spontaneous hyperthyroidism. It was present in 20% of patients with functional autonomy. CONCLUSION: To diagnose and treat adaequately functional autonomy in euthyroid goitre quantitative scintigraphy, determination of TSH and hormone concentrations are inevitable.

[123I-scintigraphy and perchlorate depletion test in the diagnosis of congenital hypothyroidism]. / 123I-Szintigraphie und Perchlorat-Depletionstest bei der Diagnostik der kongenitalen Hypothyreose.

AIM: Thirty eight children suffering from congenital primary permanent hypothyroidism were studied to determine the diagnostic impact of 123I scintigraphy in comparison to laboratory findings and ultrasonography. METHODS: In all patients 123I scintigraphy was performed after intravenous administration of 3.7 MBq 123I. If accumulation of the radiotracer in thyroid tissue occurred a perchlorate discharge test was performed subsequently. RESULTS: Scintigraphy revealed athyrosis in 7 children. In 9 children a lingual thyroid was observed. Deficiency in iodine organification was diagnosed by a significant discharge of 123I in 15 patients. In four of these children the diagnosis of Pendred's syndrome could be established. Ectopic thyroid tissue could be demonstrated only by scintigraphy where clinical examination and sonography failed in the diagnosis in all cases. Hypoplasia of the thyroid gland as it was diagnosed in 2 cases by ultrasonography appeared to be unlikely because a normal 123I uptake was seen in these patients. In 2 patients with scintigraphic proven athyrosis an orthotopic gland had been falsely considered by ultrasound. In 44% of our patients the final diagnosis could only be established if 123I scintigraphy and perchlorate discharge test were performed. CONCLUSION: This findings suggest that scintigraphy is indispensible in the correct diagnostic work up of congenital hypothyroidism.

Somatostatin receptor scintigraphy in the staging of lymphomas.

In this prospective study we evaluated the somatostatin receptor scintigraphy in the initial staging of 19 patients suffering from Hodgkin's (HD) and non-Hodgkin's lymphomas (NHL) and in the restaging of 16 patients. Scintigraphy was compared to the results of the methods applied for adequate staging of lymphoma patients in the large multicentre trials. Planar imaging and SPECT was performed after intravenous injection of 110 or 220 MBq of 111In-pentetreotide. The patient-based analysis yielded an overall sensitivity of 88%, contrasting lesion-based sensitivities of 57%, 35%, and 43% in HD, low-grade NHL and high-grade NHL, respectively. The best results were obtained in the head-and-neck region and the worst in the abdomen (sensitivities of 61% and 24%, respectively). Bone marrow infiltration was visible in 1/12 cases only. There was no significant difference between the outcomes of patients in the initial staging and restaging and no influence of the amount of injected radiopharmaceutical on the results. In terms of the Ann-Arbor classification, 10/35 patients were concordant whereas 22 were understaged and 3 overstaged scintigraphically. In conclusion, somatostatin receptor scintigraphy is not useful in the initial staging or restaging of malignant lymphomas, especially NHL, due to low lesion detection rates most probably because of low receptor densities. In addition, intraindividual heterogeneity of somatostatin receptor expression has to be considered.

Diagnostic value of 123iodine scintigraphy and perchlorate discharge test in the diagnosis of congenital hypothyroidism.

AIM: Forty children suffering from congenital primary permanent hypothyroidism were studied to determine the diagnostic impact of 123I scintigraphy in comparison to laboratory findings and ultrasonography. METHODS: In all patients 123I scintigraphy was performed after intravenous administration of 3.7 MBq 123I. If accumulation of the radiotracer in thyroid tissue occurred a perchlorate discharge test was performed subsequently. RESULTS: Scintigraphy revealed athyrosis in 7 children. In 11 children a lingual thyroid was observed. Deficiency in iodine organification was diagnosed by a significant discharge of 123I in 15 patients. In four of these children the diagnosis of Pendred's syndrome could be established. Ectopic thyroid tissue could be demonstrated only by scintigraphy where clinical examination and sonography failed in the diagnosis in all cases. Hypoplasia of the thyroid gland as it was diagnosed in 2 cases by ultrasonography appeared to be unlikely because a normal 123I uptake was seen in these patients. In 2 patients with scintigraphic proven athyrosis an orthotopic gland had been considered by ultrasound. In 50% of our patients the final diagnosis could only be established if 123I scintigraphy and perchlorate discharge test were performed. CONCLUSION: This findings suggest that scintigraphy is indispensible in the correct diagnostic work up of congenital hypothyroidism.

Assessment of myocardial viability in persistent defects on thallium-201 SPECT after reinjection using gradient-echo MRI.

This prospective study assessed myocardial viability in 30 patients with coronary heart disease and persistent defects despite reinjection on TI-201 single-photon computed tomography (SPECT). In each patient, three observers graded TI-201 uptake in 7 left ventricular wall segments. Gradient-echo magnetic resonance imaging in the region of the persistent defect generated 12 to 16 short axis views representing a cardiac cycle. A total of 120 segments were analyzed. Mean end-diastolic wall thickness and systolic wall thickening (+/-SD) was 11.5 +/- 2.7 mm and 5.8 +/- 3.9 mm in 48 segments with normal TI-201 uptake, 10.1 +/- 3.4 mm and 3.7 +/- 3.1 mm in 31 with reversible lesions, 11.3 +/- 2.8 mm and 3.3 +/- 1.9 mm in 10 with mild persistent defects, 9.2 +/- 2.9 mm and 3.2 +/- 2.2 mm in 15 with moderate persistent defects, 5.8 +/- 1.7 mm and 1.3 +/- 1.4 mm in 16 with severe persistent defects, respectively. Significant differences in mean end-diastolic wall thickness (p < 0.0005) and systolic wall thickening (p < 0.005) were found only between segments with severe persistent defects and all other groups, but not among the other groups. On follow-up in 11 patients after revascularization, 6 segments with mild-to-moderate persistent defects showed improvement in mean systolic wall thickening that was not seen in 6 other segments with severe persistent defects. These data indicate that most myocardial segments with mild and moderate persistent TI-201 defects after reinjection still contain viable tissue. Segments with severe persistent defects, however, represent predominantly nonviable myocardium without contractile function.

Quantification of the negative feedback mechanism between pituitary and thyroid in subjects with normal thyroid function.

Using sufficiently sensitive and precise assays, we systematically investigated the correlation between thyrotropin, thyroglobulin, index of free thyroxine and index of free triiodothyronine after different doses of thyroxine (25, 50, 100, 150 micrograms), which were administered daily for 10 days to individuals with normal thyroid function and in a control group. Analysis of the data using relative median values expressing changes to basal values before administration of thyroxine yielded the following results: (i) thyrotropin and thyroglobulin decreased monoexponentially, depending on the doses of thyroxine administered; (ii) the extent of their decrease showed a linear correlation with the dose of thyroxine administered and was greater for thyrotropin than for thyroglobulin; (iii) the relative velocity of their decrease increased monoexponentially with the dose of thyroxine and did not differ between thyrotropin and thyroglobulin. These results provide strong evidence for a clear quantitative reaction of the feedback mechanism and confirm that the secretion of thyroglobulin is a physiological process dependent on thyrotropin. The high intra-individual variations obtained for thyrotropin were probably due to its pulsatile secretion.

[Simultaneous double nucleotide scintigraphy with indium 111 antimyosin Fab and technetium sestamibi for evaluation of myocardial viability after experimental and clinical infarct]. / Simultane Doppelnuklid-Szintigraphie mit Indium-111-Antimyosin-Fab und Technetium-99m-Sestamibi zur Beurteilung der Myokardvitalität nach experimentellem und klinischem Infarkt.

This study combined In-111 antimyosin Fab (AM) with Tc-99m sestamibi (MIBI) to assess myocardial viability in the subacute stage of infarction. In 9 pigs, the LAD was occluded for 45 min. Seventy-four MBq of AM were injected after 48 h of reperfusion and 740 MBq of MIBI 24 h later. In myocardial specimens, activity relative to normal myocardium (n = 35) in the region of necrosis (n = 35) was found to be 3.96 +/- 2.48 for AM and 0.30 +/- 0.20 for MIBI, in the intermediate zone of macrohistochemically reversibly damaged myocardium (n = 35) 2.79 +/- 1.29 and 0.83 +/- 0.28, respectively. Discriminant analysis classified all 105 specimens with a sensitivity of 83% and specificity of 96%. On the scans, the intermediate zone presented as overlap between both tracers. Twelve patients aged 40 to 76 years with invasively documented acute myocardial infarction (4 x anterior, 8 x inferior) were injected also with 74 MBq of AM 27 to 110 h after the onset of chest pain and with 740 MBq of MIBI 21 to 26 h later. In 8 patients, the infarct vessel was open not later than 5 h after the onset of chest pain. MIBI markedly supported reconstruction of the sections and localization of the lesions with AM on simultaneous double-nuclide single-photon emission computed tomography (SPECT). In 7 patients both tracers overlapped. Four patients showed only faint AM uptake. This demonstrates that in experimental infarction AM overestimates the region of necrosis while the combination with MIBI allows the delineation towards the intermediate zone and normal myocardium. In patients, SPECT shows similar patterns of tracer distribution. MIBI facilitates AM SPECT.

Leakage measurement during selective limb perfusion using a gamma probe.

The objective of this study was to establish a probe system for intraoperative quantitative leakage measurement during selective limb perfusion for adjuvant high-dose chemotherapy in patients with malignant melanomas. We used a portable gamma probe with digital display and investigated the physical properties in a phantom study simulating blood pool activity at different angles of the probe to the surface and different distances. In 20 patients the limb circulation was surgically separated from the systemic blood circulation, and the limb was then selectively perfused (cytostatics added) for 60 min. Initially, 15 MBq technetium-99m labelled autologous red blood cells was injected into the limb circulation, and an equal amount was kept as a standard. Every 10 min, blood samples were drawn from the body circulation and count rates were simultaneously measured by the probe system at the lower end of the sternal body. At the end of perfusion, the circulation of the limb was reconnected, the standard injected into the systemic circulation, and a blood sample drawn after 10 min. All blood samples were counted for calculation of leakage in terms of percent of the injected dose, and the results compared with the intraoperative count rates of the probe system. In the range of leakage observed in this study (0%-86%), the count rate of the probe system (corrected for blood volume, i.e. for body surface) correlated with the results of conventional measurement (r=0.92) according to the equation: %leakage=counts per sx[1.2xbody surface (m2)-1.19]. In conclusion, the use of the described probe system is a feasible approach for leakage quantification which continuously yields data during selective limb perfusion.

Immunoscintigraphy for the detection of brain abscesses.

The aim of this prospective study was to assess the diagnostic usefulness of a 99Tcm-anti-granulocyte antibody in the early differentiation of the aetiology of a ring-enhancing structure on computed tomography (CT) scans following neurosurgical intervention. In 26 patients (15 males, 11 females) aged 20-82 years with suspected intracranial infection, 29 SPET scans of the head were obtained 4-6 h following the intravenous injection of 555 MBq 99Tcm-anti-granulocyte antibody. The patients had antibiotic, antimycotic or corticosteroid therapy. The diagnosis was confirmed by surgery (19 cases) or subsequent CT/MRI (magnetic resonance imaging) scans and clinical follow-up (10 cases). The immunoscan was true-positive (abscess) in 6 (sensitivity = 100%), true-negative in 19 and false-positive in 4 (specificity 83%) cases. There was no obvious detrimental effect on the results due to the antibiotic, antimycotic or corticosteroid therapy. In conclusion, despite false-positive results, the 99Tcm-anti-granulocyte antibody is a useful tool in the early detection and exclusion of intracranial abscess after neurosurgical interventions.

Prophylactic application of thyrostatic drugs during excessive iodine exposure in euthyroid patients with thyroid autonomy: a randomized study.

In a prospective, randomized study we examined the influence of prophylactic short-term thyrostatic therapy on thyroid iodine metabolism in patients with euthyroid autonomy undergoing elective coronary angiography. From a total of 1177 patients, 51 fulfilled the criteria of euthyroid autonomy before coronary angiography (negative thyrotropin-releasing hormone test, 10-min uptake of at least 1.2%, 99mTc and no elevation of free thyroxine and free triiodothyronine indices) and were randomized into three groups: group 1 (N = 17) received 20mg/day of thiamazole and group 2 (N = 17) received 900 mg/day of sodium perchlorate; thyrostatic therapy was begun on the day before angiography and continued for 14 days; group 3 (N = 17) served as controls without treatment. Parameters of thyroid function-free thyroxine (FT4) index and free triiodothyronine (FT3) index, thyrotropin (TSH) and delta-TSH urine iodine excretion and 99mTc uptake were determined before and 30 days after coronary angiography. At the end of the study the mean FT4 index and FT3 index were elevated significantly in the control group compared with baseline values, but were still within the normal range. In contrast, the mean FT4 index and FT3 index remained unchanged in the treated groups. Four mild cases of hyperthyroidism were observed at the end of the study: two cases in the control group and one case in each of the treated groups. Thyrotropin suppression, urine iodine excretion and 99mTc uptake differed significantly between the treated groups and the control group. In the treated groups TSH suppression, urine iodine excretion and 99mTC uptake remained unchanged 30 days after coronary angiography compared with baseline values. In the control group the degree of TSH suppression and the level of urine iodine excretion increased (about twofold) significantly after coronary angiography, whereas 99mTc uptake decreased significantly (ca. 50%). In conclusion, short-term prophylactic thyrostatic therapy seems to have a protective effect against iodine excess in patients with euthyroid autonomy. However, mild hyperthyroidism could not be prevented in some cases. Probably a combination therapy of thiamazole and perchlorate would be more effective.

[123I]IBZM SPET analysis of dopamine D2 receptor occupancy in narcoleptic patients in the course of treatment.

Elevated levels of central D2 dopamine receptors were found on postmortem examination in cases of human narcolepsy. In vivo investigations using positron emission tomography (PET) and single photon emission tomography (SPET) found no changes of D2 binding in the striatal structures. To investigate whether the elevated D2 receptors in postmortem investigations are due to long-term treatment effects, we applied 123I-labeled (S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide (IBZM) ([123I]IBZM, a highly selective CNS D2 dopamine receptor ligand) and SPET in narcoleptic patients in the course of treatment with stimulants and/or antidepressants. Before treatment we found no changes in D2 binding in 10 patients (in comparison to 10 normal controls). After treatment (performed in five patients for 3 months) we found changes in D2 binding in four of them, indicating that the results of the postmortem studies could have been influenced by long-term medications. Human narcolepsy seems not to be related to a striatal D2 dopaminergic disturbance.

Falsely negative 99mTc-antigranulocyte immunoscintigraphy and positive 99mTc-HMPAO-labelled leukocyte scan in active Crohn's disease. Possible effects of immunosuppressive therapy?

A 19-year-old woman with active Crohn's disease under immunosuppressive therapy underwent scintigraphy with 99mTc-anti-NCA-95 antigranulocyte antibodies in order to determine the extent of inflammation. It turned out to be falsely negative whereas a 99mTc-HMPAO-labelled leukocyte scan revealed a marked terminal ileitis and pancolitis. It is assumed that immunosuppressive therapy was the main reason for the falsely negative antibody scan, possibly affecting the red bone marrow where most of the antibodies bind to granulocytes. Peripheral leukocytes labelled in vitro do not seem to be subject to these hypothetical effects on red bone marrow.

[Radioiodine therapy of funcitonal autonomy using the functional autonomous volume]. / Radiojodtherapie der funktionellen Autonomie unter Verwendung des funktionellen autonomen Volumens.

In order to determine the effective radiation dose to be delivered by 131I in functional autonomy we have used the functional autonomous volume calculated from the global 99mTc thyroid uptake under exogenous or endogenous suppression before and 3 to 7 months after treatment. The radiation dose to the autonomous volume was calculated retrospectively in 131 patients with unifocal, multifocal and disseminated autonomy (75 hyperthyroid, 56 euthyroid) who received 131I treatment of 200-300 Gy to the total volume of the gland. It could be shown that at least 350 Gy to the autonomous volume are required to reach the desired effect of treatment which was dependent only on the radiation dose delivered to the functional autonomous volume.