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Biomedical subjects

A Trojan

Publications and source records attributed to A Trojan.

At least 19 recordsLinked to original sources

Eosinophilic pneumonia after administration of fludarabine for the treatment of non-Hodgkin's lymphoma.

Fludarabine is a purine analogue which is effective in the treatment of patients with low-grade non-Hodgkin's lymphoma, including chronic lymphocytic leukemia. While pulmonary toxicity due to cytotoxic drugs is increasingly diagnosed, only few cases of interstitial pneumonitis have been described following fludarabine administration. Here we report the first case in the literature of an acute eosinophilic pneumonia associated with peripheral blood eosinophilia after the administration of fludarabine monotherapy for stage IV follicular lymphoma.

Antineoplastic Agents↗

[Adverse chemotherapy effects on skin and mucous membranes].

Mucocutaneous side effects of chemotherapeutic agents are frequent, especially alopecia and stomatitis. The latter can be dose limiting or can endanger the patient in case of secondary infection. Nail changes and hyperpigmentation are cosmetically disturbing. For the diagnosis of the acral erythrodysesthesia syndrome and the neutrophilic eccrine hidradenitis knowledge of the clinical presentation is required. Interaction of chemotherapeutic agents with radiotherapy or UV light can aggravate or cause skin changes like the radiation recall. Despite the completely different mode of action of new substances or immunotherapeutic agents like monoclonal antibodies the same range of side effects can be observed.

Antineoplastic Agents↗

[Work-satisfaction and Health of Hospital Nursing and Medical Personnel].

The implementation of new service demands and increasing rationalisation measures exercise stress and pressure on medical and nursing personnel in German hospitals. However, their satisfaction and health are important quality criteria in the ranking of a hospital. Basing on the introduction of a new tool, an inquiry was conducted among the medical and nursing personnel of two hospitals (A and B) in respect of the quality of their working conditions. The scope of the questionnaires covered the nature and kind of the work, opportunities of professional success, management of co-operation and conflicts, physical and structural obstacles to smooth working as well as the management of quality. Finally, a scale of complaints and a burn-out scale served to assess the personnel's subjective health situation. The questionnaire was submitted in hospital A between November 1999 and February 2000 to a total of 39 doctors (58 % compliance) and 84 nursing personnel (47 % compliance) of the specialist departments concerned with internal medicine, rheumatology, urology, general and accident surgery. In hospital B the questionnaire was completed between March and July 2001 by a total of 40 doctors (54 %) and 91 nursing personnel (68 %) of two departments of internal medicine, surgery, neurosurgery and gynaecology. Comparable to other studies, the nursing personnel in both the hospitals rated the working conditions more negatively than the medical personnel. The differences, however, are more of a quantitative (number of frequency of problems) than of a qualitative nature (type or kind of problems). With both groups, problems connected with structural difficulties in working and with quality management were by far most important while the nursing personnel also underlined physical stress. Individual health condition were also classified more negatively by the nursing personnel than by the doctors, and the overall physical complaints of the nursing personnel were generally greater than with the average population, whereas medical personnel registered fewer complaints. Health promotion measures in hospitals may help to prevent negative developments. Such measures are too rarely translated into reality.

Germany↗

Fusion PET-CT imaging of neurolymphomatosis.

In a patient suffering from peripheral neuropathy due to neurolymphomatosis, fused PET-CT imaging, performed on a novel in-line PET-CT system, showed multiple small nodular lesions extending along the peripheral nerves corresponding to an early relapse of a transformed B-cell non-Hodgkin's lymphoma.

Aged↗

Induction of cytotoxic T-cell responses against immunoglobulin V region-derived peptides modified at human leukocyte antigen-A2 binding residues.

Cytotoxic T-lymphocyte (CTL) responses can be generated against peptides derived from the immunoglobulin (Ig) V region in some but not all patients. The main reason for this appears to be the low peptide-binding affinity of Ig-derived peptides to major histocompatibility complex (MHC) class I molecules and their resulting low immunogenicity. This might be improved by conservative amino acid modifications at the MHC-binding residues of the peptides (heteroclitic peptides). In this study, it was found that in 18 Ig-derived peptides, that heteroclitic peptides from the Ig gene with improved binding to human leukocyte antigen (HLA)-A*0201 can be used to improve CTL responses. Amino acid substitution substantially increased predicted binding affinity, and there was a strong correlation between predicted and actual binding to HLA-A*0201. CTLs generated against the heteroclitic peptide had not only enhanced cytotoxicity against the heteroclitic peptide but also increased killing of antigen-presenting cells pulsed with the native peptide. Surprisingly, no difference was observed in the frequency of T cells detected by MHC class I peptide tetramers after stimulation with the heteroclitic peptide compared with the native peptide. CTLs generated against heteroclitic peptides could kill patients' tumor cells, showing that Ig-derived peptides can be presented by the tumor cell and that the failure to mount an immune response (among other reasons) likely results from the low immunogenicity of the native Ig-derived peptide. These results suggest that heteroclitic Ig-derived peptides can enhance immunogenicity, thereby eliciting immune responses, and that they might be useful tools for enhancing immunotherapy approaches to treating B-cell malignant diseases.

Amino Acid Sequence↗

Generation of cytotoxic T lymphocytes against native and altered peptides of human leukocyte antigen-A*0201 restricted epitopes from the human epithelial cell adhesion molecule.

A growing number of human tumor antigens have been described that can be recognized by CTLs in a MHC class I restricted fashion. The epithelial cell adhesion molecule (Ep-CAM) is expressed in a variety of human tumors and has attracted attention as a therapeutic target for monoclonal antibody serotherapy. We have identified immunogenic peptides derived from Ep-CAM, that bind to human leukocyte antigen-A*0201 and elicit strong peptide-specific human CTL responses, demonstrating that there is an effective T-cell repertoire against these Ep-CAM-derived peptides that can be recruited. Alterations to these peptides were made to increase their binding affinity to MHC class I molecules. The use of such "heteroclitic" peptides allowed generation of cytotoxic T cells that demonstrated increased killing of target cells pulsed not only with the heteroclitic but also with the native peptide. Most important, CTL cell lines that are generated against these peptides specifically lyse epithelial tumor cells expressing Ep-CAM but not normal hematopoietic or bronchial epithelial cells.

Antigens, Neoplasm↗

Human leukocyte antigen G up-regulation in lung cancer associates with high-grade histology, human leukocyte antigen class I loss and interleukin-10 production.

Immune evasion in lung cancer results from both structural and functional alterations of human leukocyte antigen (HLA) class I molecules and the local release of immunosuppressive cytokines. Recent data suggest that HLA-G, a nonclassical class Ib molecule, is involved in immune evasion by tumor cells. We sought to determine whether HLA-G could contribute to immunescape in lung cancer. All of 19 tumor specimens examined demonstrated detectable membrane-bound (HLA-G1), as well as soluble (HLA-G5) isoform transcription. Nine of 34 (26%) tumors were positive by immunohistochemistry using monoclonal antibody (mAb) 4H84, recognizing all denatured HLA-G isoforms, of which six were positive using mAb 16G1, recognizing soluble HLA-G. HLA-G immunoreactivity correlated with high-grade histology, with HLA-G being preferentially expressed on large-cell carcinomas. In these patients, loss of classical HLA class I molecules was observed to associate with HLA-G protein up-regulation. Moreover, we found interleukin-10 expressed in 15 of 34 (44%) tumors, and in most of the HLA-G-positive cases (7 of 9), suggesting up-modulation of HLA-G by interleukin-10. It is conceivable that HLA-G expression in lung cancer might be one of the ways how the tumor down-regulates host immune response, in addition to interleukin-10 production and HLA class I loss.

Aged↗

[Social urban development and poverty control as health promotion].

The Salomon Neumann Medal of the German Society for Social Medicine and Prevention bears the inscription. "Medicine is a Social Science". This provocative statement is most topical. It compels us to actively promote health by healthier living and environmental conditions apart from medical prevention. A core of this sphere of action is the reduction of social inequalities. Several recent congresses and publications have clearly shown that this subject remains one of the biggest challenges facing health promotion. German law has set the signs for reducing socially rooted inequalities for chances of health. This article postulates the thesis that health promotion can find allies for a healthy public policy in programmes planning for healthy urban development and for combatting poverty. The specific approaches for combatting social inequalities in the health sphere are reported and examples are given how such a health promotion policy may be translated into reality on a communal level. Finally, spotlight is on the dilemma of combatting inequality of chance due to differences in social status.

Germany↗

Inflammatory myofibroblastic tumor with CNS involvement.

BACKGROUND: Inflammatory myofibroblastic tumors (IMT) represent a spectrum of neoplasms that occur in the mesentery and retroperitoneum and less frequently in the mediastinum of children and young adults. Transformation into inflammatory fibrosarcoma and metastases are rare. CASE REPORT: We report the case of a 16-year-old patient with an inflammatory myofibroblastic tumor of the mesentery with mediastinal metastases. Partial remission was obtained by chemotherapy with ifosfamide, dactinomycine, and vincristine. Two months later, relapse with infiltration of the meninges developed, and the patient died. CONCLUSION: This case demonstrates unusual features of an IMT: presentation with metastases, excellent response to chemotherapy, dissemination to the CNS.

Adolescent↗

Real-Time polymerase chain reaction of immunoglobulin rearrangements for quantitative evaluation of minimal residual disease in multiple myeloma.

The majority of patients with multiple myeloma (MM) have persistence of minimal residual disease (MRD), as determined by polymerase chain reaction (PCR) detection of clonal immunoglobulin H (IgH) gene rearrangements. As a result, PCR analysis has not provided clinically useful prognostic information in myeloma patients. Instead, quantitative PCR approaches are required to predict patient outcomes and assess response to novel treatment strategies. We adapted real-time PCR technology to quantify myeloma cells using the IgH rearrangement and then assessed the utility of this approach in 29 patients with myeloma who had undergone autologous stem cell transplantation. Because of the high cost of producing a specific reporting probe for each patient, H-chain V-region family-specific consensus probes were used in association with allele-specific oligonucleotides for PCR amplification. Because of the high frequency with which somatic hypermutation at the immunoglobulin locus occurs in MM, a number of mismatches occurred between the patient sequences and the consensus probe. However, construction of a limited number of probes allowed real-time PCR with a sensitivity of 10(-4) to 10(-5). To validate this method, we extensively evaluated assay accuracy and reproducibility. Results indicate that real-time PCR using consensus probes provides a feasible, accurate, and reproducible method for evaluating MRD in M M and possibly in other differentiated B-cell malignancies, and one that is less expensive than the use of patient-specific probes. This technique is being used to assess tumor depletion after immunologic purging and changes in tumor burden in patients undergoing stem cell transplantation and novel treatment approaches.

Gene Rearrangement, B-Lymphocyte, Heavy Chain↗

Immunoglobulin framework-derived peptides function as cytotoxic T-cell epitopes commonly expressed in B-cell malignancies.

Although the idiotypic structures of immunoglobulin from malignant B cells were the first tumor-specific determinants recognized, and clinical vaccination trials have demonstrated induction of tumor-specific immunity, the function of immunoglobulin-specific CD8+ cytotoxic T lymphocytes in tumor rejection remains elusive. Here, we combined bioinformatics and a T cell-expansion system to identify human immunoglobulin-derived peptides capable of inducing cytotoxic T-lymphocyte responses. Immunogenic peptides were derived from framework regions of the variable regions of the immunoglobulin that were shared among patients. Human-leukocyte-antigen-matched and autologous cytotoxic T lymphocytes specific for these peptides killed primary malignant B cells, demonstrating that malignant B cells are capable of processing and presenting such peptides. Targeting shared peptides to induce T-cell responses might further improve current vaccination strategies in B-cell malignancies.

B-Lymphocytes↗

[Liver changes in AIDS. Retrospective analysis of 227 autopsies of HIV-positive patients].

In a retrospective study of a 12-year period (1981-1992) liver histology was analyzed in 227 autopsied patients infected with the human immunodeficiency virus. Normal histology could only be documented in 29 patients (13%). In the majority of cases (56%) uncharacteristic changes were seen such as steatosis (34%), hemosiderosis (10%) or non-specific reactive hepatitis (7%). The finding of hepatic peliosis obtained in 4 patients was not associated with inflammatory liver changes, especially infections from Rochalimaea. Within a wide range of opportunistic infections recorded in 50 patients (22%), hepatitis caused by Cytomegalovirus (8%), Toxoplasma gondii (5%), Leishmania donovani (1%), Cryptococcus neoformans and Pneumocystis carinii (each 0.5%) was diagnosed. Among 16 cases (7%) of mycobacterial liver infections typical mycobacteria were found in two patients and atypical mycobacteria in 14 patients, respectively. In 23 patients (10%) chronic viral hepatitis, caused by HBV (7%) or HCV infections (3%), respectively, was observed. Hepatitis was typed as mild only in each 5 patients with HBV or HCV infection, whereas the remaining cases showed a transition towards cirrhosis. Two patients with HBV-associated cirrhosis developed hepatocellular carcinoma. The remaining 32 malignant liver tumors represented secondary neoplasms, including 13 cases of non-Hodgkin's lymphomas.

AIDS-Related Opportunistic Infections↗

CT appearances of hepatic involvement in systemic varicella-zoster.

In a patient suffering from T-cell non-Hodgkin's lymphoma and systemic varicella-zoster, contrast enhanced CT showed multiple hypodense nodular lesions in the liver which corresponded to areas of focal liver necrosis. This appearance on CT may be characteristic of varicella-zoster involvement of the liver.

Female↗