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Biomedical subjects

J Meller

Publications and source records attributed to J Meller.

At least 19 recordsLinked to original sources

fw2.2: a quantitative trait locus key to the evolution of tomato fruit size.

Domestication of many plants has correlated with dramatic increases in fruit size. In tomato, one quantitative trait locus (QTL), fw2.2, was responsible for a large step in this process. When transformed into large-fruited cultivars, a cosmid derived from the fw2.2 region of a small-fruited wild species reduced fruit size by the predicted amount and had the gene action expected for fw2.2. The cause of the QTL effect is a single gene, ORFX, that is expressed early in floral development, controls carpel cell number, and has a sequence suggesting structural similarity to the human oncogene c-H-ras p21. Alterations in fruit size, imparted by fw2.2 alleles, are most likely due to changes in regulation rather than in the sequence and structure of the encoded protein.

Alleles↗

[Improved detection of gastrointestinal bleeding sites with 99mTc market autologous erythrocytes and continuous dynamic scintigraphy with cine-mode display].

BACKGROUND: Scintigraphic studies of gastrointestinal bleeding are usually performed in static acquisition mode and without continuous imaging over a longer period. The aim of this study was to evaluate the diagnostic accuracy of continuous dynamic 99mTc red blood cell scintigraphy (BQS) and cine-mode display in the assessment of unexplained gastrointestinal bleeding. PATIENTS AND METHODS: We performed BQS in 40 patients (mean age 57 years) with gastrointestinal bleeding from an undetermined source. All these patients had negative findings of previous examinations. Blood transfusions were required in 16 patients. Continuous dynamic scintigraphic acquisition was performed up to 6 h post injection (p.i.). The scintigraphic data were reviewed without knowledge of the patient's final diagnosis. For this purpose we used a cine-mode display. RESULTS: Dynamic 99mTc red blood cell scintigraphy correctly identified the site of active bleeding in 22 of 23 patients with positive scintigraphic findings. The sensitivity of the scan was 95%, the specificity 94%, the positive and negative predictive values 95% and 94%, respectively. Forty-three percent of the scans became positive within 1.5 h and 82% within 5 h. Positive scans were more likely in patients who required blood transfusions than in patients without transfusion requirement (16 vs 7 patients), and the bleeding site was identified earlier in the former group (mean 2.83 vs 5.28 h p.i.). The scintigraphic identification of the bleeding lesions enabled the performance of a more limited surgical approach in the colon as well as in the distal small intestine, while exact scintigraphic localization was not possible if the bleeding site was located in the proximal small intestine. DISCUSSION: Continuous dynamic 99mTc red blood cell scintigraphy interpreted by cine-mode display is highly accurate in the identification of a bleeding site. When performed correctly, scintigraphy enables usually segmental resection of these lesions.

Diagnosis, Differential↗

67Ga-citrate and 99Tcm-MDP for estimating the severity of vertebral osteomyelitis.

The aim of this study was to evaluate the roles of 67Ga-citrate and 99Tcm-methylene diphosphonate (99Tcm-MDP) planar and single photon emission tomographic (SPET) imaging in patients with vertebral osteomyelitis. Thirty patients (22 females, 8 males) aged 62.7 +/- 16.4 years (mean +/- s) were enrolled prospectively between May 1995 and May 1998. The patients had been on antibiotics for 7 +/- 4 weeks prior to the study. Histology was available for all but nine patients with mild infections, who were evaluated by a combination of magnetic resonance imaging (MRI), clinical and laboratory tests. 67Ga-citrate (185 MBq) and three-phase bone (555 MBq 99Tcm-MDP) planar and SPET imaging were performed in all patients, together with MRI as a comparison. In total, 67 infectious foci were detected. Based on histology, there were four cases of severe, 13 cases of moderate and four cases of mild osteomyelitis; nine mild infections were also classified by the combination of MRI, clinical and laboratory results. Combined MRI and 67Ga-citrate SPET correctly classified all patients; MRI detected all 67 infectious foci, whereas 67Ga-citrate SPET identified 54 only. False-negative results were seen with all other modalities, especially in cases of mild and moderate infection. 67Ga-citrate SPET identified unsuspected cases of endocarditis (n = 2), paravertebral abscess (n = 1), subaxillary soft tissue abscess (n = 1) and rib osteomyelitis (n = 1). For 67Ga-citrate SPET, the target-to-background ratio was 2.24 +/- 0.31, 1.76 +/- 0.07 and 1.30 +/- 0.18 for severe, moderate and mild osteomyelitis, respectively. Significant differences were noted between severe and moderate infection (P = 0.0051) and between severe and mild infection (P < 0.0001); that between moderate and mild infection was non-significant. For 99Tcm-MDP planar and SPET imaging, and for planar 67Ga-citrate imaging, there was no correlation with severity. We conclude that 67Ga-citrate SPET is able to identify vertebral osteomyelitis and detect additional sites of infection. It can also aid in determining the severity of infection and, potentially, the response to therapy.

Aged↗

[Clinical implications of a new TSH receptor antibody assay (DYNOtest TRAKhuman) in autoimmune thyroid diseases].

AIM: Conventional radioreceptor-antibody-assays (RAAs) fail in the detection of TSH-receptor antibodies (TRAKs) in 10-30% of patients with Graves' disease (GD). The aim of this study was the evaluation of the diagnostic and clinical impact of a new RRA (DYNOtest TRAKhuman) which uses the human recombinant TSH-Receptor in the diagnosis of autoimmune thyroid disease. METHODS: Sera from 142 consecutive patients (GD: n = 50, autoimmune thyroiditis/AIT: n = 92) and from 55 controls (31 patients without any thyroid disease and 14 with euthyroid goiter) were evaluated both with the DYNOtest TRAKhuman-assay and a conventional RRA (TRAK-Assay). Thyroid in vitro parameters and thyroid sonography were performed in all patients. RESULTS: The DYNOtest TRAK-assay was significantly superior to the conventional RRA in the diagnosis of GD (p < 0.00012), especially in those who were treated by thionamides (p < 0.003) and in the diagnosis of TRAK-positive patients with AIT (p < 0.003). The majority of TRAK-positive AIT-patients suffered from hypothyroidism. One false positive result in patients with euthyroid goiter was found in the TRAK-Assay as well as in the DYNOtest TRAKhuman-Assay. Therefore the specificity of the DYNOtest TRAKhuman was not inferior compared with the conventional assay. CONCLUSION: The DYNOtest TRAK-assay is superior in the diagnostic work up of Graves' disease compared with a conventional TRAK-assay and offers an equal specificity.

Female↗

[Juvenile dermatomyositis--acute recidivism or sepsis?].

A 22-year-old male with juvenile dermatomyositis presented with fever up to 40 degrees C and acute pain in his right thigh accompanied by muscle weakness, a skin rash and a tender swelling. Serum aspartate aminotransferase (AST) and aldolase were mildly elevated. C-reactive protein (CRP) and fibrinogen were markedly increased. The differential white blood cell count revealed relative lymphopenia. Radiography showed diffuse calcifications particularly around the thighs and knees of both legs. Magnetic resonance imaging (MRI) demonstrated inflammatory infiltrates in the right thigh. The lesions were identified as phlegmone by immunoszintigraphy with 99mTc-labelled antigranulocyte antibodies. On the 10th day of treatment Staphylococcus aureus was cultured from blood. Patients with juvenile dermatomyositis and calcinosis may develop bacterial infections of soft tissue which sometimes mimic a disease flare. For differential diagnosis plain radiographs, CT scans and MRI are of limited value. Immunoszintigraphy is able to differentiate between infiltrates caused by granulocytes and lymphocytes.

Adult↗

Scintigraphy with 99mTc-pertechnetate in the evaluation of functional thyroidal autonomy.

Iodine deficiency and iodine deficiency disorders are still present in several parts of Europe. Sonography is neither specific in the diagnosis nor sensitive in the evaluation of the amount of autonomous thyroid tissue. Thyroidal autonomy is defined as a functional state of the thyroid and therefore only functional scintigraphic imaging, preferably performed with 99mTc-pertechnetate (99mTcO4-), will offer both high sensitivity and specificity in its diagnosis. Recently the cloning and characterisation of the Na+/I- symporter (NIS) offered a deeper understanding of iodine and pertechnetate uptake in the thyroid gland. Overexpression of the Na+/I- symporter following activation of the adenylate-cyclase-cAMP-cascade has been demonstrated in hot nodules, which gives for the first time an explanation for the enhanced iodine clearance of autonomous thyroidal tissue on a molecular level. The scintigraphic evaluation of thyroidal autonomy is performed both as a quantitative and qualitative thyroid scintigraphy, using a gamma camera fitted with an on-line computer system. A strong and linear correlation between the global 99mTc-pertechnetate thyroid uptake (TCTU) and 123I clearance has been recognised. Therefore TCTU-values can be used as a reliable equivalent of the iodine clearance in the evaluation of actual thyroid function. The clinical value of the TCTU in the diagnosis of thyroidal autonomy is limited because it represents iodine clearance of both normal and autonomous tissue. As a consequence scintigraphic diagnosis and quantification of autonomy can only be established if the global 99mTc-pertechnetate thyroid uptake under suppression (TCTUs) is determined. This method is sensitive in risk stratification of spontaneous or iodine induced hyperthyroidism, in the estimation of the target volume prior to radioiodine therapy independently of its distribution and in the evaluation of therapeutic success after definitive therapy.

Humans↗

Increased benzodiazepine receptor density in the prefrontal cortex in patients with panic disorder.

There are published studies concerning a regionally changed function of GABA-benzodiazepine-receptor-complexes in anxiety disorder. These studies implicate the limbic lobe, the brainstem and the prefrontal cortex. Using 123I-Iomazenil and single photon emission tomography (SPET) we investigated the benzodiazepine receptor density in twelve patients with panic disorder who had never been treated with benzodiazepines before. Nine age- and sex-matched volunteers who were free of mental illness served as controls. Patients with panic disorder showed a significant increase of benzodiazepine receptor binding in the right supraorbital cortex and a trend to an increased uptake in the right temporal cortex. There was no correlation between receptor density and scores on Spielberger's State Trait Anxiety Inventory in the patient group. Since the findings cannot be explained by benzodiazepine exposure we hypothesize an upregulation due to functional or neuroanatomic changes (at least) in the frontotemporal cortex.

Adult↗

Computer simulations of carbon monoxide photodissociation in myoglobin: structural interpretation of the B states.

The early diffusion processes of a photodissociated ligand (carbon monoxide) in sperm whale myoglobin and its Phe29 mutant are studied computationally. An explicit solvent model is employed in which the protein is embedded in a box of at least 2300 water molecules. Electrostatic interactions are accounted for by using the particle mesh Ewald. Two hundred seventy molecular dynamics trajectories are computed for 10 ps. Different models of solvation and the ligand, and their influence on the diffusion are examined. The two B states of the CO are identified as "docking" sites in the heme pocket. The sites have a similar angle with respect to the heme normal, but differ in the orientation in the plane. The computational detection of the B states is stable under a reasonable variation of simulation conditions. However, in some trajectories only one of the states is observed. It is therefore necessary to use extensive simulation data to probe these states. Comparison to diffraction experiments and spectroscopy is performed. The shape of the experimental infrared spectra is computed. The overall linewidth is in an agreement with experiment. The contributions to the linewidth (van der Waals and electrostatic interactions) are discussed.

Animals↗

Scintigraphic evaluation of functional thyroidal autonomy.

The scintigraphic evaluation of thyroidal autonomy is performed both as a quantitative and qualitative thyroid scintigraphy with 99m-Tc-pertechnetate (99m-TcO4-), using a gamma camera fitted with an on-line computer system. A strong and linear correlation between the global 99m-Tc-pertechnetate thyroid uptake (TCTU) and I-123 clearance has been recognised. Therefore TCTU-values can be used as an reliable equivalent of the iodine clearance in the evaluation of actual thyroid function. The clinical value of the TCTU in the diagnosis of thyroidal autonomy is limited because it represents iodine clearance of both normal and autonomous tissue. As a consequence scintigraphic diagnosis and quantification of autonomy can only be established if the global 99m-Tc-pertechnetate thyroid uptake under suppression (TCTUs) is determined. This method is valuable in risk stratification of spontaneous or iodine induced hyperthyroidism, in the estimation of the target volume prior to radioiodine therapy and in the evaluation of therapeutic success after definitive therapy.

Gamma Cameras↗

Immunoscintigraphy (BW 250/183) in neonates and infants with fever of unknown origin.

Fever of unknown origin is defined as a temperature above 39.0 degrees C together with a white blood cell count > or = 15,000 mm-3, the duration of fever exceeding 2 weeks and a correct diagnosis not being obtained in the first week of hospitalization. In neonates and infants with fever of unknown origin, the localization of the infectious focus is often difficult and unsatisfactory. In this retrospective study, the clinical value of 99Tcm-labelled antigranulocyte antibodies for this group of patients was investigated. Thirty-two immunoscintigrams were performed using 185-259 MBq 99Tcm-labelled antigranulocyte antibodies (BW 250/183) in 30 neonates and infants (21 boys, 9 girls, mean age 29.4 +/- 2 months), who had fever of unknown origin. Immunoscintigraphy was carried out as whole-body images (n = 7) or single planar images (n = 25) 4 h and 24 h post-injection. In children with known cardiac failure, single photon emission tomography of the thorax was performed to diagnose endocarditis (n = 2). For verification, the results of the immunoscintigrams were compared with radiology (conventional radiography = 14, MRI = 5, CT = 3), biopsy (n = 2), blood culture (n = 10) and clinical follow-up after specific therapy. In 11 of 30 children (36%), the diagnosis of an infective focus was possible with immunoscintigraphy. The sensitivity and specificity of diagnosing infective foci was 72% and 95% respectively (n = 11; colitis = 2, infection of the central permanent catheter tip = 2, middle ear infection = 1, spondylitis/discitis = 3, osteomyelitis = 2, umbilical infection = 1). In vertebral body infections, all lesions were photopenic. In 18 children (60%), no infective focus was found on immunoscintigraphy. In this group of children, the main reason (n = 5) for fever of unknown origin was chronic juvenile rheumatoid arthritis. No uptake was seen in two infants with cardiac failure and suspected endocarditis on SPET. In 3 of the 18 patients (17%), localization of an infective focus was not possible with immunoscintigraphy or on other examinations. In these patients, the fever disappeared spontaneously after a few days of antibiotic therapy. In conclusion, we have shown that 99Tcm-anti-NCA-95 scanning is a safe method with a high sensitivity and specificity for detecting infectious foci in neonates and infants with fever of unknown origin. Furthermore, this method is easy to perform, since no withdrawal of blood is necessary.

Antibodies, Monoclonal↗

[123I-scintigraphy and perchlorate depletion test in the diagnosis of congenital hypothyroidism].

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.

Child↗

[Suppressibility of thyroid autonomy in endogenous and additional exogenous TSH suppression in patients with thyroid autonomy].

AIM: The aim of this retrospective study was to examine the effect of an additional exogenous thyroid hormone suppression on the 99m Technetium Thyroid-Uptake (TcTU) in patients with thyroid autonomy and endogenous TSH suppression. METHODS: 21 patients were examined in the years 1992-1996; they had a primary endogenous suppression (end) of the TSH-b and an evaluation of the TcTU. After an additional exogenous suppression (ex) of the thyroid, the first two weeks with 75 micrograms/dl and the following 2 weeks 150 micrograms/d, or depending on the bodyweight 2 micrograms/kg levothyroxin, another evaluation of the TcTU was performed. The whole patients were called group I with a TcTUend of 1.6%-7.4%. The subgroups were selected by thresholds of the TcTUend; group Ia TcTUend > or = 1.6% and < 2.5%, group lb TcTUend > or = 2.5%, group Ic TcTUend > or = 3%. RESULTS: The intraindividual comparison showed a significant decrease of the autonomous "volume" after exogenous suppression with levothyroxin. This is shown by the following values of the TcTU: group I TcTUend = 3.47 +/- 1.65 and TcTUex = 2.91 +/- 1.38, which means a reduction of 20 rel.% (p < or = 0.001); group Ia TcTUend = 2.05 +/- 0.27, TcTUex = 1.85% +/- 0.22, which means 10 rel.% (p < or = 0.001); group Ib TcTUend = 4.18 +/- 1.59, TcTUex = 3.45% +/- 1.34, which means 20 rel.% (p < or = 0.001); group Ic TcTUend = 5.00% +/- 1.43, TcTUex = 4.05% +/- 1.32, which means 20 rel.% (p < or = 0.001). CONCLUSION: Supposing a structural variability of autonomous thyroid tissue with heterogenous TSH receptors our study shows a significant additional exogenous suppression in already endogenous suppressed TSH receptors.

Adult↗

[Effectiveness of goiter treatment with L-thyroxine in patients over 40].

AIM: We examined the effect of levothyroxine on thyroid size in elderly patients (an age > 40 y) with diffuse or nodular goitres. METHODS: 76 patients without relevant autonomy were treated with levothyroxine (2 micrograms/kg BW/d) over a period of 6-12 months. The elderly patients with diffuse goitres (group A, n = 33) and nodular goitres (group B, n = 21) were compared to 18-30 year old respective control groups (group C, n = 13, group D, n = 9). Laboratory parameters and ultrasonic determined goitre volumes were documented before levothyroxine treatment and after 6-12 months, respectively. All measured thyroid volume reductions were referred to the total goitre size. RESULTS: After 6-12 months levothyroxine treatment a significant thyroid reduction was observed in group A (14.8%, p < 0.001), group C (16.0%, p < 0.05) and in group D (19.8%, p < 0.05), whereas in group B thyroid volume was nearly unchanged (4.5%). The result of group B differed from that of group D (p < 0.05). CONCLUSION: These results suggest that levothyroxine can reduce diffuse goitres in elderly patients (group A), whereas in nodular goitres of elderly patients (group B) only a further thyroid growth can be provided.

Adult↗

Clinical value of immunoscintigraphy in patients with fever of unknown origin.

UNLABELLED: The aim of our study was to evaluate the clinical value of immunoscintigraphy with the monoclonal antibody 99mTc-BW 250/183 in patients with fever of unknown origin (FUO). The antibody BW 250/183 is an immunoglobulin G1 subtype that binds to the antigen NCA-95, which is expressed on the cell membrane surface of granulocytes. METHODS: We studied 51 patients who were referred with the diagnosis of FUO. Thirty-five percent of the patients suffered from infection, 17% had autoimmune diseases, 14% had neoplasms and 8% had other diseases. The remaining 28% of the patients did not have a diagnosis. Planar imaging was performed in all patients, and 19 patients underwent SPECT. In our analysis, both cold and hot spots were considered diagnostic. RESULTS: Pyogenic infections were visualized correctly in 13 foci. The diagnosis of endocarditis (n = 4) could be determined only by SPECT. False-negative results were found in 4 patients and false-positive uptake was seen in 2 patients. No false-positive uptake or cold spots in the central bone marrow were found in patients with viral, granulomatous and autoimmune diseases or in those patients in whom no FUO cause was found in a 6-mo follow-up. In these patients, a negative scan did not change their diagnostic work-up. Cold spots in the central bone marrow were correctly interpreted in 5 of 6 patients. Sensitivity in detecting pyogenic foci was 73% and specificity was 97%. Positive and negative predictive values were 93% and 87%, respectively. Including areas of decreased uptake in the analysis, sensitivity for detecting an underlying inflammatory or malignant process for FUO was 81 % and specificity was 87%. Positive and negative predictive values were 81% and 87%, respectively. CONCLUSION: Immunoscintigraphy with 99mTc-BW 250/183 in patients with FUO has clinical potential for the diagnosis and exclusion of pyogenic causes of FUO. Metastatic malignant disease and high-grade spondylodiskitis could be diagnosed early in a diagnostic work-up by a characteristic cold spot pattern in the bone marrow. SPECT is indispensible for scintigraphic imaging of endocarditis.

Adult↗

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.

Child↗