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H Lerch

Publications and source records attributed to H Lerch.

At least 19 recordsLinked to original sources

[Molecular imaging and molecular guided therapy].

AIM AND METHOD: Scientific publications in the journal of Nuklearmedizin Molecular Imaging and Therapy during 2004/2005 were retrospectively examined for their potential classification to molecular imaging or molecular guided therapy, functional imaging and therapy, and were compared to earlier analyses. RESULTS: Of the 57 original papers examined, 36 (63%) were assigned to the category of molecular imaging/molecular guided therapy. Within this category, the number of original papers on molecular guided therapy increased by 19% compared to preceding periods. There was a general overall increase in the proportion of experimental papers and more frequent inclusion of basic background subjects. CONCLUSION: The development of molecular imaging as a direct instrument in therapy planning leads to further promotion of molecular guided therapy. The structural advantage of nuclear medicine, uniting method-lead diagnosis and therapy within one specialist subject, predestines it to advance molecular imaging and molecular guided therapy.

Humans↗

[Nuclear medicine: medical technology research].

UNLABELLED: AIM, METHOD: The scientific publications in the 2003 and 2004 issues of the journal Nuklearmedizin were analyzed retrospectively with regard to the proportion of medical technology research. RESULTS: Out of a total of 73 articles examined, 9 (12%) were classified as medical technology research, that is, 8/15 of the original papers (16%) and one of the case reports (5%). Of these 9 articles, 44% (4/9) focused on the combination of molecular and morphological imaging with direct technical appliance or information technology solutions. CONCLUSION: Medical technology research is limited in the journal's catchment area. The reason for this is related to the interdependency between divergent development dynamics in the medical technology industry's locations, the many years that the area of scintigraphic technology has been underrepresented, research policy particularly in discrepancies in the promotion of molecular imaging and a policy in which health is not perceived as a predominantly good and positive economic factor, but more as a curb to economic development.

Germany↗

[Information technology and nuclear medicine. Primary digitalized data--and then?].

UNLABELLED: AIM, METHOD: The scientific publications in the 2002 and 2003 issues of the journal Nuklearmedizin. Journal of Functional and Molecular Imaging were analyzed retrospectively with regard to the development of information technology methods. RESULTS: Out of a total of 72 original papers and case reports 9 (11%) were classified having information technology as their subject, 5 (56%) of them the fusion of molecular and morphological imaging. Researchers from medical specialities other than nuclear medicine were co-authors in 7 (78%) of the 9 articles, out of the 8 original papers 4 (50%) were prospective studies. Of the 59 original papers, 28 (47%) were predominantly dedicated to methodological development; 46/59 (78%) of them were clinical studies and 2 (3%) experimental research. CONCLUSION: Although a high proportion of the papers were dedicated to methodological development, the proportion dedicated to development of information technology methods was relatively low.

Information Systems↗

[The journal Nuklearmedizin: does the subtitle Journal of Functional and Molecular Imaging describe the current practice of publishing?].

AIM AND METHOD: The scientific publications in the 2001 and 2002 issues of the journal Nuklearmedizin. Journal of Functional and Molecular Imaging were analyzed retrospectively with regard to molecular imaging/therapy content criteria. RESULTS: Out of a total of 82 original papers and case reports 83% were based on molecular or functional methods, 91% of them using commercially available tracers, 57% were categorized as molecular imaging, 11% as molecular therapy, 12% as functional imaging and 2% as functional therapy. 3% of the studies were categorized as experimental research. Researchers from medical specialties other than nuclear medicine were co-authors in 71% of the articles, they were rooted in basic medical sciences in 16%. Of the 65 original papers 51% were predominantly dedicated to methodological development; 49% of them were prospective studies. CONCLUSION: The subtitle Journal of Functional and Molecular Imaging describes the current practice of publishing in Nuklearmedizin. The number of authors from other specialties shows that multidisciplinary integration within the field of molecular imaging is performed. Nevertheless, more integration of basic medical sciences is needed. Nuklearmedizin contributes to the insight of molecular imaging and to its clinical application in humans.

Language↗

[Scientific publishing in the journal Nuclear Medicine].

AIM: The paper reviews current scientific publishing practice in the journal Nuklearmedizin. METHOD: The scientific publications in the 2000 and 2001 issues of the journal were analyzed retrospectively with regard to their authors, formal content criteria and citation practice. RESULTS: 102 articles (69 original papers, 29 case reports, 4 review articles) were published. Of a total of 561 authors, 80 first authors came from Germany, 9 from Austria, 3 from Switzerland, and 10 from other countries. In 58 out of the 102 publications, researchers from other medical specialties were co-authors. The first authors were based at university hospitals or research centers in the case of 88 out of 102 publications. The author of one article had his own practice. Of the 102 first authors, 24 were female with a statistically significantly (p = 0.04) higher proportion in case reports compared to original papers. A total of 88/98 original papers and case reports were categorized as clinical research, 2 out of 69 original papers as experimental research, and 8 as management, health policy and radiation protection. 36 out of 102 articles were in English. The 69 original papers included a median of 48 investigated patients (range 4-991). A total of 2555 other papers with a median of 19 (range 3-230) was cited, comprising 212 citations of the journal Nuklearmedizin, i.e. 8.3% (range 0-56%). CONCLUSION: The number of authors per paper documents the tendency to team work with a major participation of other specialties; university hospitals and research centers are represented more often. There is a predominance of clinical research with a high average number of patients per study. The percentage of first female authors are proportionate to their percentage membership in the learned societies. The relatively high percentage of papers in English raises the potential to increase the scientific response to publication of the content.

Authorship↗

Pulmonary beta adrenoceptor density in arrhythmogenic right ventricular cardiomyopathy and idiopathic tachycardia.

OBJECTIVE: In recent in vivo studies using positron emission tomography (PET) our group demonstrated that the myocardial beta adrenoceptor (betaAR) density is reduced in arrhythmogenic right ventricular cardiomyopathy (ARVC) and idiopathic right ventricular outflow tract tachycardia (RVO-VT) associated with an increased presynaptic catecholamine washout. It was hypothesised that the reduction of myocardial betaAR density is secondary to an increase of local catecholamines in the myocardium resulting from the presynaptic dysfunction since circulating plasma catecholamines were demonstrated to be unchanged in these conditions. To further prove this hypothesis of an organ-limited adrenergic nervous dysfunction of the heart, this study aimed to investigate betaAR density in another thoracic organ, the lung. METHODS: Pulmonary and myocardial betaAR density was measured in 7 ARVC patients, 8 RVO-VT patients and in a group of healthy controls (n = 13) using the non-selective beta-blocker [11C]-CGP 12177 and PET. RESULTS: Pulmonary betaAR density was similar in controls (12.4 +/- 1.7 pmol/g tissue), ARVC (11.6 +/- 1.7 pmol/g tissue, p = ns) and RVO-VT (12.8 +/- 2.0 pmol/g tissue, p = ns), whereas myocardial betaAR density was significantly reduced in ARVC (6.3 +/- 1.1 pmol/g tissue, p = 0.006) and RVO-VT (6.8 +/- 1.2 pmol/g tissue, p=0.02) as compared to controls (8.8+/-1.5 pmol/g tissue). CONCLUSION: The unchanged pulmonary betaAR density in the presence of a previously described significant reduction in myocardial betaAR density in the same patient principally supports our pathophysiological hypothesis that the myocardial betaAR density may be reduced in ARVC and RVO-VT because of an increase in local synaptic catecholamine levels due to an organ-limited presynaptic adrenergic dysfunction of the heart. Since in the present study only pulmonary betaAR density was measured, future functional studies excluding pulmonary betaAR desensitisation are required to finally prove the unchanged pulmonary sympathetic innervation in ARVC and RVO-VT.

Adult↗

Abnormalities of cardiac sympathetic innervation in arrhythmogenic right ventricular cardiomyopathy : quantitative assessment of presynaptic norepinephrine reuptake and postsynaptic beta-adrenergic receptor density with positron emission tomography.

BACKGROUND: The frequent provocation of ventricular tachycardia by stress or catecholamines and the efficacy of antiarrhythmic drugs with antiadrenergic properties suggest an involvement of the cardiac adrenergic system in arrhythmogenesis in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Previous studies demonstrated abnormalities of the presynaptic uptake-1 assessed by (123)I-MIBG-single-photon emission computed tomography. METHODS AND RESULTS: This study investigated neuronal reuptake of norepinephrine (uptake-1) and beta-adrenergic receptor density in 8 patients with ARVC and 29 age-matched control subjects. All subjects underwent positron emission tomography with the volume of distribution (V(d)) of [(11)C]hydroxyephedrine ((11)C-HED) used to assess presynaptic norepinephrine reuptake, the maximum binding capacity (B(max)) of [(11)C]CGP-12177 ((11)C-CGP-12177) to assess postsynaptic beta-adrenergic receptor density, and [(15)O]H(2)O for quantification of myocardial blood flow. Patients with ARVC demonstrated a highly significant global reduction in postsynaptic beta-adrenergic receptor density compared with that in control subjects (B(max) of (11)C-CGP-12177: 5.9+/-1.3 vs 10.2+/-2.9 pmol/g tissue, P<0.0007), whereas the presynaptic uptake-1 tended toward reduction only (V(d) of (11)C-HED: 59.1+/-25.2 vs 71.0+/-18.8 mL/g tissue, NS). There were no differences in myocardial blood flow between the groups, and plasma norepinephrine was within normal limits in patients and control subjects. CONCLUSIONS: The findings demonstrate a significant reduction of myocardial beta-adrenergic receptor density in patients with ARVC. This may result from a secondary downregulation after increased local synaptic norepinephrine levels caused by increased firing rates of the efferent neurons or as the result of impaired presynaptic catecholamine reuptake. These findings give new insights into the pathophysiology of arrhythmogenesis in ARVC, with potential impact on diagnostic evaluation and therapeutic management.

Adult↗

Restricted VH3 gene usage in phage-displayed Fab that are selected by intravenous immunoglobulin.

OBJECTIVE: To perform a comparative analysis of 1) intravenous Ig (IVIG)-bound Fab fragments from a patient with autoimmune thrombocytopenia that had progressed to systemic lupus erythematosus (SLE) and 2) IVIG-selected Fabs from an SLE patient without thrombocytopenia. METHODS: IVIG preparations have been successfully used to treat certain cases of autoimmune thrombocytopenia and SLE. Specific interactions of IVIG with the components of the immune system are not well characterized. To investigate these, we had previously cloned a large number of phage-displayed IgG Fab fragments, derived from 3 patients with autoimmune thrombocytopenia, that were specifically bound by IVIG molecules during panning. Many of these Fabs reacted with platelets. Sequencing revealed that the most frequently used VH germline gene segments of all IVIG-bound Fabs were 3-23 and 3-30/3-30.5. One patient's autoimmune thrombocytopenia had progressed to SLE. Using the same cloning and panning procedures, we performed a comparative analysis of this patient's IVIG-bound Fab fragments and the IVIG-selected Fabs from an SLE patient without thrombocytopenia. RESULTS: We observed an exclusive selection of antibodies derived from 3-23 and 3-30/3-30.5 germline segments. In contrast to the Fab fragments from the autoimmune thrombocytopenia patient who developed SLE, none of the IVIG-selected Fabs from the SLE patient without thrombocytopenia bound to thrombocytes. CONCLUSION: Our results suggest a preferential interaction of a subfraction of IVIG-representative of normal Ig repertoires-with antibodies and B cell receptors derived from these 2 gene segments. Importantly, these are the most frequently rearranged VH germline genes among human B cells. This kind of interaction is characteristic of a B cell superantigen, since light chains, antigen specificity, and the high variation in the third complementarity-determining region 3 showed little influence on the selection of 3-23- or 3-30/3-30.5-derived Fabs by IVIG. However, at least some of the contact residues on Fabs for IVIG appear to be different from those for staphylococcal protein A and human immunodeficiency virus gp 120. The IVIG-selected Fabs may now be used to clone antibodies representative of this IVIG subfraction to study their possible regulatory influence on the B cell repertoire during normal development and disease.

Antigens, Bacterial↗

IVIG-bound IgG and IgM cloned by phage display from a healthy individual reveal the same restricted germ-line gene origin as in autoimmune thrombocytopenia.

Intravenous immunoglobulin preparations (IVIG) have shown positive effects in the treatment of immune defects and autoimmune diseases. It is not clear how IVIG interacts with the components of the immune system. To investigate this, we cloned previously a large number of phage displayed IgG Fab fragments derived from three patients with autoimmune thrombocytopenia (AITP) that were specifically bound by IVIG molecules. Many of these Fabs reacted with platelets. Sequencing revealed that the most frequently used germ-line gene segments of all IVIG-bound Fabs were identical to those observed for many other autoantibodies. Particularly, the loci 3-30 or 3-30/3-30. 5, 3-23 and 3r, 3l, and 2a2 represented the most abundant genes used for the heavy (VH) and light chain V region (VL), respectively. This suggested a specific interaction of IVIG molecules with B cells that present B cell receptors derived from these germ-line genes. In the current study we determined the genetic origin of IVIG-reactive IgG and IgM cloned from a healthy person. A favoured selection of antibodies derived from the same germ-line origins as in AITP was observed. Because 3-30 and 3-23 are the most frequently rearranged VH germ-line gene segments among human B cells, our results suggest that this favoured anti-idiotypic interaction may have an important role for the development and control of the normal B cell repertoire.

Adult↗

Regulation of Drosophila wing vein patterning: net encodes a bHLH protein repressing rhomboid and is repressed by rhomboid-dependent Egfr signalling.

The stereotyped pattern of veins in the Drosophila wing is generated in response to local EGF signalling. Mutations in the rhomboid (rho) gene, which encodes a sevenpass membrane protein required to enhance signalling transmitted by the EGF receptor (Egfr), inhibit vein development and disrupt the vein pattern. By contrast, net mutations produce ectopic veins in intervein regions. We have cloned the net gene and show that it encodes a basic HLH protein that probably acts as a transcriptional repressor. net and rho are expressed in mutually exclusive patterns during the development of the wing imaginal disc. Lack of net activity causes rho expression to expand, and vice versa. Furthermore, ectopic expression of net or rho results in their mutual repression and thus suppresses vein formation or generates tube-like wings composed of vein-like tissue. Egfr signalling and net exert mutually antagonising activities during the specification of vein versus intervein fate. While Egfr signalling represses net transcription, net exhibits a two-tiered control by repressing rho transcription and interfering with Egfr signalling downstream of Rho. Our results further suggest that net is required to maintain intervein development by restricting Egfr signalling, which promotes vein development, to the Net-free vein regions of the wing disc.

Amino Acid Sequence↗

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

The aim of this multicentre study was to evaluate the clinical significance of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in differentiated thyroid carcinoma and to compare the results with both iodine-131 whole-body scintigraphy (WBS) and technetium-99m 2-methoxyisobutylisonitrile (MIBI) or thallium-201 chloride (Tl) scintigraphy. Whole-body PET imaging using FDG was performed in 222 patients: 134 with papillary tumours, 80 with follicular tumours and 8 with mixed-cell type tumours. Finally, for each case an overall clinical evaluation was done including histology, cytology, thyroglobulin level, ultrasonography, computed tomography and subsequent clinical course, to allow a comparison with functional imaging results. Sensitivity of FDG-PET was 75% and 85% for the whole patient group (n = 222) and the group with negative radioiodine scan (n = 166), respectively. Specificity was 90% in the whole patient group. Sensitivity and specificity of WBS were 50% and 99%, respectively. When the results of FDG-PET and WBS were considered in combination, tumour tissue was missed in only 7%. Sensitivity and specificity of MIBI/Tl were 53% and 92%, respectively (n = 117). We conclude that FDG-PET is a sensitive method in the follow-up of thyroid cancer which should be considered in all patients suffering from differentiated thyroid cancer with suspected recurrence and/or metastases, and particularly in those with elevated thyroglobulin values and negative WBS.

Female↗

Platelet-reactive IgG antibodies cloned by phage display and panning with IVIG from three patients with autoimmune thrombocytopenia.

Autoimmune thrombocytopenic purpura (AITP) is a severe disease in children with a still unknown aetiology. It is not known why AITP can either be transient and self limiting or become chronic. The beneficial use of intravenous immunoglobulins (IVIG) in certain groups of AITP patients has been proven. It is, however, not clear how IVIG functions. To analyse patient-derived monoclonal IgG platelet autoantibodies that interact with IVIG in an anti-idiotypic manner, the combinatorial antibody phage display system was applied. From three different patients a large number of clones specifically reacting with IVIG molecules were derived. Many of these IVIG binders also reacted strongly with platelets in ELISA and FACS, in contrast to IVIG binders derived from a healthy individual. The heavy and light chain variable regions were sequenced and compared with each other and with databases. In all three AITP patients clones with a striking complementarity-determining region (CDR) sequence homology to each other and to many of the known anti-platelet antibodies were observed. Selected Fab-phages representing the characteristic variable regions that occurred in the investigated patients with AITP may now be used to clone potentially regulatory anti-idiotypes from healthy donors by phage display.

Adolescent↗

Cardiac 123I-MIBG uptake in idiopathic ventricular tachycardia and fibrillation.

UNLABELLED: Patients with idiopathic ventricular tachycardia or fibrillation have no additional structural or functional myocardial abnormalities. However, the inducibility of typical tachyarrhythmias by physical or mental stress or by catecholamine infusion suggests the involvement of the adrenergic system in the pathogenesis of these potentially life-threatening diseases. METHODS: 45 patients with idiopathic right ventricular outflow tract tachycardia (RVO-VT), 25 patients with idiopathic left ventricular tachycardia (ILVT), 15 patients with idiopathic ventricular fibrillation (IVF) and 10 age-matched control patients were investigated in this study. Diagnoses were made on the basis of detailed evaluation of the results of two-dimensional echocardiography, left and right ventricular angiography, coronary angiography and endomyocardial biopsy. Local presynaptic norepinephrine re-uptake was assessed using the norepinephrine analog 1231-metaiodobenzylguanidine (MIBG), SPECT and semiquantitative 33-segment bull's-eye analysis. RESULTS: Locally reduced 123I-MIBG uptake was found in 27 of 45 RVO-VT patients (60%), 5 of 15 ILVT patients (33%) and 17 of 25 IVF patients (68%). Unlike ILVT patients, RVO-VT and IVF patients had significantly reduced segmental 123I-MIBG uptake of the posterior wall compared with control patients. CONCLUSION: Patients with idiopathic tachycardia and fibrillation show abnormal 1231-MIBG uptake, which indicates presynaptic sympathetic dysfunction. RVO-VT and IVF patients exhibit significantly reduced 123I-MIBG uptake in the posterior left ventricular wall, whereas ILVT patients do not.

3-Iodobenzylguanidine↗

Genetic origin of IgG antibodies cloned by phage display and anti-idiotypic panning from three patients with autoimmune thrombocytopenia.

The beneficial use of intravenous immunoglobulins (IVIG) in certain groups of patients with autoimmune thrombocytopenic purpura (AITP) has been proven. AITP is a severe disease in children with a still unknown etiology. It is not clear how IVIG functions in this and other autoimmune diseases. To analyze and compare patient-derived monoclonal IgG antibodies that are bound by IVIG in an anti-idiotypic manner, the combinatorial antibody phage display system was applied. From three different patients with AITP, a large number of clones specifically reacting with IVIG molecules were enriched. The heavy and light chain variable regions were sequenced and compared with each other and with databases. Many variable regions showed extensive replacement mutations within the complementarity-determining regions, while two were identical to germ-line genes. Our data show that the most frequently used germ-line gene loci of these IVIG binders are identical to those observed for many other autoantibodies. This implicates a specific interaction of IVIG particularly with autoantibodies and B cell receptors derived from germ-line genes that are often used for the generation of autoantibodies.

Adolescent↗

High amino acid uptake in a low-grade desmoplastic infantile ganglioglioma in a 14-year-old patient.

Amino acid uptake is higher in high-grade than in low-grade gliomas; this is the rationale for using radioactively labelled amino acids for the non-invasive grading of brain neoplasms. We present a 14-year-old boy with a low-grade desmoplastic infantile ganglioglioma (DIG) that exhibited marked contrast enhancement on magnetic resonance imaging (MRI), but no signs of infiltration and only minimal surrounding edema. In this benign neoplasm the relative uptake of the radioactively labelled amino acid I-123-alpha-methyl tyrosine (IMT), determined using single-photon emission computed tomography (SPECT), was 3.24; it was considerably higher than that of eleven other pretherapeutic low-grade gliomas where it ranged from 1.06 to 1.94 and also markedly above that average value of 2.37 found in 20 high-grade gliomas. This case report illustrates that results from emission tomography with radioactively labelled amino acids must be interpreted with caution, particularly when rare tumor entities are considered in view of uncommon clinical or radiological findings.

Adolescent↗

Positron emission tomography with F-18-deoxyglucose in patients with differentiated thyroid carcinoma, elevated thyroglobulin levels, and negative iodine scans.

INTRODUCTION: In patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin (hTg) may occur in spite of otherwise negative diagnostic procedures and in particular in spite of a negative iodine-131 scan. Positron emission tomography with F-18-deoxyglucose (FDG-PET) is a potentially useful method for the detection of metastatic lesions or the recurrence of thyroid cancer. We aimed to investigate whether FDG-PET is capable of detecting metastatic lesions or recurrence in patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin, and otherwise negative diagnostic procedures, including the iodine-131 scan. METHODS: From a group of 500 patients with differentiated thyroid carcinoma, a subgroup of 32 patients had elevated serum hTg-levels, negative iodine- 131 scans, negative cervical and abdominal ultrasound, and negative X-ray of the chest. In 12 of these patients (hTg 77.8+/-94.3 ng/ml, range 1.5-277 ng/ml, median 20 ng/ml), FDG-PET was performed. All but one FDG-PET study was performed in a state of hypothyroidism (TSH 75.8+/-32.2 microIU/ml, range 31-116 microIU/ml, median 74.6 microIU/ml). RESULTS: In 6 of the 12 patients investigated, the FDG-PET was positive. In three of the patients, the diagnosis was confirmed by computed tomography or magnetic resonance imaging. In patients with a positive FDG-PET finding, the hTg level was 146.7+/-90.1 ng/ml (23-277 ng/ml, median 144.5 ng/ml). In contrast, in patients with a negative finding the hTg level was only 9.0+/-7.6 ng/ml (range 1.5-17 ng/ml, median 8.1 ng/ml), P=0.01. CONCLUSION: These preliminary results show that in patients with differentiated thyroid carcinoma, elevated hTg levels, and otherwise negative "conventional" diagnostic procedures, FDG-PET is helpful in detecting metastatic lesions.

Adenocarcinoma, Follicular↗