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M Hummel

Publications and source records attributed to M Hummel.

At least 19 recordsLinked to original sources
PubMed2007

[Burkitt's and Burkitt-like lymphoma. Molecular definition and value of the World Health Organisation's diagnostic criteria].

Among aggressive mature B-cell lymphomas, a reproducible morphological and immunohistological distinction between Burkitt's lymphoma and diffuse large B-cell lymphoma (centroblastic variant) is impossible in a substantial number of cases. The German reference centres for hematopathology collected 220 retrospective cases of aggressive mature B-cell lymphoma whose classification according to the current World Health Organisation criteria was reviewed. Gene expression analysis (Affymetrix) was performed in all cases and chromosomal translocations were determined using fluorescence in situ hybridization. Chromosomal losses and gains were analysed by matrix comparative genomic hybridisation and clinical data were successfully collected for most patients. The application of a novel bioinformatics method led to the identification of a stable and reproducible gene expression signature specific for Burkitt's lymphoma. A total of 44 cases were identified by this molecular signature [designated molecular Burkitt's lymphoma (mBL)]. These molecular Burkitt's lymphomas showed the morphology and immunohistology of classical or atypical Burkitt's lymphoma cases in 29 instances. However, 15 of the molecular Burkitt's lymphoma cases had the morphology of diffuse large B-cell lymphoma or could not be further specified. All molecular Burkitt's lymphomas showed an expression of BCL-6 and CD10, but a MYC translocation was not demonstrable in more than 10% of cases. Of significance is that more than 20% of the molecular Burkitt's lymphomas expressed BCL-2, although weakly in most instances. Our data demonstrate that: (1) the morphological, immunophenotypical and genetic spectrum of Burkitt's lymphoma is broader than previously expected, and (2) our molecular Burkitt's lymphoma signature enables a more precise and extended definition this lymphoma.

Burkitt Lymphoma↗
PubMed2006

Development of autoimmunity to transglutaminase C in children of patients with type 1 diabetes: relationship to islet autoantibodies and infant feeding.

AIMS/HYPOTHESIS: Coeliac disease and transglutaminase antibodies are common in patients with type 1 diabetes and their relatives. We investigated the development of transglutaminase antibodies and analysed potential risk factors for coeliac disease autoimmunity in first-degree relatives of patients with type 1 diabetes. METHODS: The study was conducted by prospective observational follow-up from birth of 1,511 children at increased risk of type 1 diabetes or coeliac disease born in Germany between 1989 and 2000. Mean follow-up was to age 7.6 years. Children were tested for transglutaminase and islet autoantibodies. Children were classified as transglutaminase antibody-positive if antibodies were detected by both ELISA and radiobinding assays. RESULTS: The risk of developing transglutaminase antibodies was 4.9% by age 8 years (n=63; 95% CI, 3.7-6.1%). Transglutaminase antibodies developed at an older age than islet autoantibodies (median age, 4.9 vs 2.3 years; p<0.005), and only three children developed both transglutaminase antibodies and islet autoantibodies. Multivariate analysis indicated an increased risk of transglutaminase antibodies in children with the HLA-DRB1*03 allele (hazard ratio for heterozygous DR3, 5.5; 95% CI, 2.9-10.2; hazard ratio for homozygous DR3, 16.2; 95% CI, 6.7-39; p<0.0001) and in children with impaired uterine growth (birth weight < or = 1st percentile, hazard ratio, 3.1; 95% CI, 1.1-7.8, p=0.03). Neither breast-feeding or its duration nor the age of first exposure to gluten was associated with the risk of developing transglutaminase antibodies. CONCLUSIONS/INTERPRETATION: Coeliac disease autoimmunity is initiated later than islet autoimmunity in children who are at risk. An influence of infant nutrition on the development of coeliac disease autoimmunity could not be confirmed in this prospective study.

Autoantibodies↗
PubMed2006

Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98-3936.

The diagnosis of malignant lymphoma is a recognized difficult area in histopathology. Therefore, detection of clonality in a suspected lymphoproliferation is a valuable diagnostic criterion. We have developed primer sets for the detection of rearrangements in the B- and T-cell receptor genes as reliable tools for clonality assessment in lymphoproliferations suspected for lymphoma. In this issue of Leukemia, the participants of the BIOMED-2 Concerted Action CT98-3936 report on the validation of the newly developed clonality assays in various disease entities. Clonality was detected in 99% of all B-cell malignancies and in 94% of all T-cell malignancies, whereas the great majority of reactive lesions showed polyclonality. The combined BIOMED-2 results are summarized in a guideline, which can now be implemented in routine lymphoma diagnostics. The use of this standardized approach in patients with a suspect lymphoproliferation will result in improved diagnosis of malignant lymphoma.

False Negative Reactions↗
PubMed2006

Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936.

Polymerase chain reaction (PCR) assessment of clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements is an important diagnostic tool in mature B-cell neoplasms. However, lack of standardized PCR protocols resulting in a high level of false negativity has hampered comparability of data in previous clonality studies. In order to address these problems, 22 European laboratories investigated the Ig/TCR rearrangement patterns as well as t(14;18) and t(11;14) translocations of 369 B-cell malignancies belonging to five WHO-defined entities using the standardized BIOMED-2 multiplex PCR tubes accompanied by international pathology panel review. B-cell clonality was detected by combined use of the IGH and IGK multiplex PCR assays in all 260 definitive cases of B-cell chronic lymphocytic leukemia (n=56), mantle cell lymphoma (n=54), marginal zone lymphoma (n=41) and follicular lymphoma (n=109). Two of 109 cases of diffuse large B-cell lymphoma showed no detectable clonal marker. The use of these techniques to assign cell lineage should be treated with caution as additional clonal TCR gene rearrangements were frequently detected in all disease categories. Our study indicates that the BIOMED-2 multiplex PCR assays provide a powerful strategy for clonality assessment in B-cell malignancies resulting in high Ig clonality detection rates particularly when IGH and IGK strategies are combined.

Chromosomes, Human, Pair 11↗
PubMed2006

Powerful strategy for polymerase chain reaction-based clonality assessment in T-cell malignancies Report of the BIOMED-2 Concerted Action BHM4 CT98-3936.

Polymerase chain reaction (PCR) assessment of clonal T-cell receptor (TCR) and immunoglobulin (Ig) gene rearrangements is an important diagnostic tool in mature T-cell neoplasms. However, lack of standardized primers and PCR protocols has hampered comparability of data in previous clonality studies. To obtain reference values for Ig/TCR rearrangement patterns, 19 European laboratories investigated 188 T-cell malignancies belonging to five World Health Organization-defined entities. The TCR/Ig spectrum of each sample was analyzed in duplicate in two different laboratories using the standardized BIOMED-2 PCR multiplex tubes accompanied by international pathology panel review. TCR clonality was detected in 99% (143/145) of all definite cases of T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, peripheral T-cell lymphoma (unspecified) and angioimmunoblastic T-cell lymphoma (AILT), whereas nine of 43 anaplastic large cell lymphomas did not show clonal TCR rearrangements. Combined use of TCRB and TCRG genes revealed two or more clonal signals in 95% of all TCR clonal cases. Ig clonality was mostly restricted to AILT. Our study indicates that the BIOMED-2 multiplex PCR tubes provide a powerful strategy for clonality assessment in T-cell malignancies assisting the firm diagnosis of T-cell neoplasms. The detected TCR gene rearrangements can also be used as PCR targets for monitoring of minimal residual disease.

Gene Amplification↗
PubMed2006

[Prolonged remission after immunotherapy of a previously refractory peripheral T-cell non-Hodgkin lymphoma].

HISTORY AND ADMISSION FINDINGS: A 54-year-old woman in good condition was admitted because of a rapidly growing tumor in the right groin with skin infiltration. There were no B-symptoms and no increased susceptibility to infections. INVESTIGATIONS: Histology revealed a peripheral T cell non-Hodgkin lymphoma (NHL). Laboratory tests showed borderline elevation of lactate dehydrogenase. Staging computed tomography (CT) revealed widespread moderately enlarged lymph nodes and the main lesion in right groin measuring 5 x 6 cm which was classified as stage IIIAE. TREATMENT AND COURSE: According to the phase-II-trial DSHNHL-2003 - 1 (German study group for high grade NHL) the patient was scheduled for cycles of CHOEP at 14-day intervals plus granulocyte colony stimulating factor. During the first cycle she developed a worsening wound infection and an infection of her port catheter. Because response to treatment was only minimal a biopsy was performed which showed persisting malignant lymphoma. As a result she was not given the 4-weekly addition of alemtuzumab, as provides in the study protocol. Instead she received alemtuzumab subcutaneously for eight weeks at a dose of 3 x 30 mg/week plus prophylactic antibiotics. A good partial response was obtained, followed by radiotherapy with 36 Gy to the main lesion in the right groin. The follow up CT-scans one year after treatment showed a stable remission. CONCLUSION: In T-NHL with primary non-response it is especially difficult to induce a stable remission. Despite a course which was complicated by infections and a failing response to increased chemotherapy a remission was achieved in this patient with a monotherapy of alemtuzumab for eight weeks without complications, followed by radiotherapy.

Alemtuzumab↗
PubMed2006

Detection of Aspergillus DNA in cerebrospinal fluid from patients with cerebral aspergillosis by a nested PCR assay.

Invasive aspergillosis (IA), a complication with high mortality rates, especially in disseminated IA with cerebral involvement, is difficult to diagnose. Biopsy of cerebral lesions is often not feasible, and culture of Aspergillus spp. from cerebrospinal fluid (CSF) is frequently negative. New molecular methods have emerged for diagnosing IA. So far, there are only few reports of Aspergillus DNA detection in CSF. After modifying the DNA extraction protocol, we detected Aspergillus DNA in CSF samples by a previously described nested PCR assay. In six patients with hematologic malignancy and cerebral aspergillosis, CSF samples were investigated for Aspergillus DNA. IA was classified according to the EORTC/MSG 2002 criteria. Two patients each had proven, probable, and possible IA. Thirty-five CSF samples were investigated for Aspergillus DNA by nested PCR. Samples with positive results in the nested PCR assay were quantified by LightCycler PCR assay. Fourteen CSF samples showed positive results in the nested PCR assay. Of these, six samples gave positive results in real-time PCR. The range of CFU per ml was 2,154 to 63,100,000. The highest number of CFU per ml was found in a CSF sample of a patient with acute lymphocytic leukemia and probable cerebral aspergillosis. Detection of Aspergillus DNA in CSF samples is thus possible and has the potential to improve diagnosis of cerebral aspergillosis. Further prospective studies with larger numbers of patients must be performed to evaluate the clinical significance of Aspergillus PCR with CSF samples.

Adolescent↗
PubMed2006

An antisense oligodeoxynucleotide to the mu opioid receptor attenuates cocaine-induced behavioral sensitization and reward in mice.

Numerous studies support a role for the endogenous opioid system in cocaine-influenced behavior. Few of these studies, however, selectively delineate a role for the mu opioid receptor (MOR) in this regard. This investigation examined if the MOR modulates cocaine-induced behavior in mice using a 17-base antisense oligodeoxynucleotide (AS ODN) directed against the MOR coding sequence 16-32. Specifically, cocaine-induced behavioral sensitization and conditioned reward were investigated. For the sensitization study, C57BL/6J mice received eight intermittent i.c.v. infusions of saline, mismatch oligodeoxynucleotide (ODN) (20 microg/4 microl) or AS ODN (20 microg/4 microl) over 20 days. Mice also received concomitant once daily i.p. injections of saline (4 ml/kg) or cocaine (15 mg/kg) for 10 days. There was a 7-day withdrawal period, after which all mice were challenged with cocaine (15 mg/kg) to test for behavioral sensitization. For the conditioned place preference (CPP) study, mice received five i.c.v. infusions of mismatch ODN or MOR AS ODN (days 1-5). An unbiased counterbalanced conditioning procedure was used where mice were conditioned with saline (4 ml/kg, i.p.) and cocaine (15 mg/kg, i.p.) on alternate days for four sessions (days 3-6). Mice were tested on day 7 for CPP. Immediately following testing, [3H]DAMGO (D-Ala2, N-Me-Phe4, Gly-ol5-enkephalin) receptor binding to brain homogenates was conducted. MOR AS attenuated cocaine-induced behavioral sensitization and conditioned reward. MOR AS ODN also reduced [3H]DAMGO binding. Collectively, these findings implicate the MOR as playing an important neuromodulatory role in the behavioral effects of cocaine in mice.

Analysis of Variance↗
PubMed2006

[Diabetes mellitus--differential diagnosis].

Differentiation of the various forms of diabetes is necessary for therapeutic reasons. Typical signs of type 2 diabetes are age over 40, obesity, and other markers for metabolic syndrome, a positive famitory, gradual development of the classical symptoms, and no evidence of ketosis. It is important to distinguish this from LADA (latent autoimmune diabetes of adulthood), a form of type 1 diabetes mellitus. To establish this differential diagnosis antibody testing is employed. Antibody tests in patients with newly manifest diabetes make good sense when the clinical diagnosis is not unequivocal, that is, to distinguish it from type 2 diabetes, MODY diabetes, hereditary and secondary forms. At present, immunodiagnosis is used too often in unambiguous cases of type 1 diabetes, but too rarely in supposed type 2 diabetes. As a rule, LADA patients are GADA-positive. If MODY diabetes is suspected, a genetic examination is indicated. In patients with GDM, antibody testing with GADA makes sense, in particular in slim patients receiving insulin treatment, since these patients have a high risk for developing a postpartum diabetes already in the first years.

Adolescent↗
PubMed2006

Wotherspoon criteria combined with B cell clonality analysis by advanced polymerase chain reaction technology discriminates covert gastric marginal zone lymphoma from chronic gastritis.

BACKGROUND AND AIMS: Gastric mucosa associated lymphoid tissue lymphoma is a well defined B cell lymphoma yet often impossible to distinguish from severe chronic gastritis on morphological grounds alone. Therefore, it was suggested to use the clonality of the immunoglobulin (Ig) heavy chain (H) genes, as detected by polymerase chain reaction (PCR), as a decisive criterion. However, there is controversy as to whether B cell clonality also exists in chronic gastritis, hence rendering this approach futile at present. METHODS: An expert panel re-examined the histology and immunohistochemistry of a total of 97 cases of gastric biopsies, including clearcut marginal zone lymphoma, chronic gastritis, and ambiguous cases, applying the Wotherspoon criteria on the basis of haematoxylin-eosin and CD20 immunostainings. In addition, a new and advanced PCR system for detection of clonal IgH gene rearrangements was independently applied in two institutions in each case. RESULTS: The overall IgH clonality assessments of both institutions were in total agreement. Overt lymphoma (Wotherspoon score 5) was clonal in 24/26 cases. Chronic gastritis (Wotherspoon scores 1 and 2) was not clonal in 52/53 cases; the clonal case being Wotherspoon score 2. Of 18 cases with ambiguous histology (Wotherspoon scores 3 and 4) four were clonal. CONCLUSIONS: Using advanced PCR technology, clonal gastritis is extremely rare, if it exists at all. Thus B cell clonality in Wotherspoon 3 and 4 cases is regarded as suitable for definitively diagnosing gastric marginal zone lymphoma.

Algorithms↗
PubMed2006

[62 year-old patient with rapid progressive edema, low potassium and hypertension].

A 62 year-old patient was admitted to hospital with rapid progressive edema, low potassium and hypertension. This symptoms are caused by Cushing's syndrome through ectopic paraneoplastic ACTH-production. Primary neoplasm is a small cell cancer. A Sertoli-cell-tumor of the testis was diagnosed as an additional carcinoma. Palliative chemotherapy and adrenostatic agents did not improve the clinical findings and the patient died eight weeks after admission.

Cushing Syndrome↗
PubMed2006

Histopathology in the light of molecular profiling.

The 2001 WHO classification distinguishes five variants (centroblastic, immunoblastic, plasmablastic, anaplastic and T-cell rich) and three subtypes (primary mediastinal, intravascular and primary effusion large B-cell lymphoma) of diffuse large B-cell lymphomas (DLBCLs).The recognition of the three subtypes as distinct disease entities can be considered as an advance in our understanding of these tumours. However, the variants of DLBCLs, which significantly outnumber the subtypes in frequency, represent an unresolved area. Gene expression profiling (GEP) of the variants led to a discrepancy in results and produced more questions than answers. The authors, therefore, initiated a multi-institutional collaborative research project in Germany aimed at a subtle morphologic, genomic and transcriptional characterisation of DLBCLs and Burkitt lymphoma (BL). We included BL in our study for two reasons: (1) it belongs to aggressive B-NHLs; and (2) at present, there are no reliable criteria that can be applied to distinguish BL from DLBCL. The GEPs derived from 200 patient samples were correlated with reviewed histology, the degree of genetic imbalances and clinical features. The results of this approach show that: (i) the DLBCL can be divided into more than four molecular groups; and (ii) the BL cases, identified by the consensus of five out of six lymphoma expert pathologists, displayed a genomic and gene expression profile that was clearly distinct from those of most DLBCLs. The group of DLBCLs that resembled BL in their GEP had a remarkably good prognosis, whereas those that differed in their GEP from the consensus BLs had unfavourable survival rates. In conclusion, combined application of genomic and gene expression profiling in conjunction with consensus reviewed histology and clinical features, appears to be a reliable approach that enables a reproducible and clinically meaningful characterisation of mature aggressive B-NHLs.

Gene Expression Profiling↗
PubMed2006

Three coexisting lymphomas in one patient: genetically related or only a coincidence?

The simultaneous manifestation of different lymphomas in the same patient or even in the same tissue, defined as composite lymphoma, is very rare. The exceptional case of a patient who, presented with simultaneous manifestation of three different lymphomas after 30 years of successful treatment of a nodal T cell lymphoma is reported here. The three lymphomas were: (1) primary cutaneous marginal zone B cell lymphoma (MZBL); (2) nodal Epstein-Barr virus (EBV)-associated classic Hodgkin's lymphoma (cHL) of the B cell type; and (3) peripheral T cell lymphoma coexisting in the skin and cervical lymph node. Immunohistochemical and molecular analyses showed different clonal origins of EBV-negative cutaneous MZBL and EBV-positive B cell cHL and, in addition, the presence of the same clonal T cell population in the skin and lymph node. The simultaneous occurrence of three different, clonally unrelated lymphomas in one patient at the same time has not been reported yet.

Aged↗
PubMed2006

Progression of sealed initial bovine enamel lesions under demineralizing conditions in vitro.

The use of sealants for the infiltration of proximal enamel lesions could be a promising alternative to the common strategies of remineralization and operative treatment. The aim of the present study was to compare the progression of sealed initial enamel lesions after exposure to a demineralizing solution in vitro. In each of 54 bovine enamel specimens three subsurface lesions were created. Two of the lesions were etched with phosphoric acid and sealed with either a fissure sealant or with various adhesives (1-5) for 15 s or 30 s, respectively, whereas one lesion remained as the untreated control. Subsequently, half of each specimen was covered with nail varnish (baseline) and the other half was reexposed to a demineralizing solution for 14 days (experimental). The specimens were cut perpendicularly to the surface, infiltrated with a low-viscosity fluorescent resin and observed with a confocal laser scanning microscope (CLSM). For lesions sealed with the fissure sealant and adhesives 1-3, the progression of lesion depth (0-31 microm) was significantly decreased (p<0.01; paired t test) compared with the untreated control (57 microm). For the fissure sealant and adhesives 1 and 3 extended penetration times (30 s) resulted in significantly reduced lesion progression compared to 15 s. It can be concluded that filling of the pores in initial enamel lesions with the fissure sealant and adhesives 1-3 can inhibit further demineralization in vitro.

Acrylates↗
PubMed2006

Dermatopathic lymphadenopathy: a differential diagnosis of enlarged lymph nodes in uremic pruritus.

BACKGROUND: In end-stage renal disease patients, the incidence of both infections and malignancies is increased leading to a higher incidence of peripheral lymphadenopathy. In the present work we describe a rare but probably underdiagnosed cause for enlarged lymph nodes in uremic patients. PATIENT: A 43-year-old male patient was admitted to our hospital with inguinal lymphadenopathy and pruritus. He turned out to be uremic due to focal segmental glomerulosclerosis (creatinine 4.5 mg/dl, MDRD creatinine clearance 12 ml/min). FINDINGS: Sonography revealed enlarged lymph nodes (up to 4 cm) with intact corticohilar border differentiation. After extirpation of an inguinal lymph node, histological examination established the diagnosis of dermatopathic lymphadenopathy. T cell lymphoma was excluded by PCR for T cell receptor-gamma rearrangements and subsequent GeneScan analysis. Intravenous fluid supplementation with subsequent decline of creatinine, UVB treatment, clemastine, and topical use of emollients led to a relief of the uremic pruritus and the lymph nodes' size normalized within 8 weeks. CONCLUSION: Dermatopathic lymphadenopathy refers to the reactive condition seen in lymph nodes that drain areas with disruption of the skin integrity, e.g. due to scratch marks. The present case report describes dermatopathic lymphadenopathy as a harmless cause of enlarged lymph nodes in uremic pruritus for the first time. This entity should be considered in the differential diagnosis of peripheral lymphadenopathy of unknown origin in patients with renal failure.

Adult↗
PubMed2005

[The pediatrician's waiting room: a place for health education?].

OBJECTIVES: To assess the presence and impact of health education messages in pediatricians' waiting rooms. METHODS: In September 2001, 81 pediatricians completed a questionnaire about the furnishings and equipment in their waiting rooms. They also distributed a questionnaire about waiting room health education messages to parents, to be completed at home. RESULTS: The analysis considered 1830 questionnaires. Health education messages were posted in 91% of the waiting rooms and most frequently concerned children's accidents, vaccines, hygiene and nutrition. The best topics that the parents remembered involved child neglect, antibiotic therapy, AIDS and other sexually transmitted diseases, and nutrition. Although memorization of the messages was not influenced by duration of the wait, it was higher among parents who had previously visited the pediatrician. These messages led 14% of the parents to discuss them spontaneously with their pediatrician. CONCLUSION: Health education messages are posted in nearly all the waiting rooms studied; parents remember them in a variable and rather inexplicable order. Posting these messages demonstrates the pediatricians' willingness to be involved - beyond the simple consultation - in the health education of children and families. Identifying the real impact of these messages would require further study.

Humans↗
PubMed2005

Aspergillus polymerase chain reaction (PCR) diagnosis.

In recent years novel molecular methods, notably polymerase chain reaction (PCR) assays, have been developed to improve the diagnosis of life-threatening invasive aspergillosis in patients at high risk, especially patients with malignant hematological disease. Early diagnosis and treatment are essential for adequate therapeutic management. Management, however, often remains difficult since most of the diagnostic tools used clinically at present either lack specificity or acceptable sensitivity. The clinical value, advantages and remaining problems of PCR approaches to detect the emerging fungal pathogen are reviewed.

Aspergillosis↗