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1.
Oper Orthop Traumatol ; 32(2): 171-178, 2020 Apr.
Article in German | MEDLINE | ID: mdl-31690973

ABSTRACT

OBJECTIVE: Treatment of a persistently painful snapping triceps and possibly snapping ulnar nerve. INDICATION: Snapping triceps. CONTRAINDICATIONS: General surgical risks. SURGICAL TECHNIQUE: Following the anterior transposition of the ulnar nerve (subcutaneously or submuscular), the snapping portion of the triceps tendon is transsected and reinforced, and transposition of the medial triceps margin into the central triceps portion is carried out. POSTOPERATIVE MANAGEMENT: Cast for 5-7 days; for a total of 6 weeks functional exercise without maximum flexion and resistance exercise of the triceps. Weight loading after 3 months. RESULTS: In the case presented, complaints were absent after 3 months. Full load exercise, e.g., push-ups, was achieved 4 months after surgery. There was no recurrent snapping within the first year. The results of this case are in agreement with the 25 patients previously reported in the PubMed literature. Recurrence, gross restrictions of movement, and complications were not observed in patients who underwent surgery.


Subject(s)
Muscle, Skeletal , Humans , Range of Motion, Articular , Tendons , Treatment Outcome , Ulnar Nerve
2.
Orthopade ; 46(3): 222-226, 2017 Mar.
Article in German | MEDLINE | ID: mdl-27904932

ABSTRACT

BACKGROUND: Reverse shoulder arthroplasty (RSA) has become a frequently used and established treatment for patients with cuff tear arthropathy, increasingly also for patients with fracture sequelae (FS), failed rotator cuff reconstruction and omarthrosis with cuff insufficiency. Since 2007 new generation prostheses, for example Delta Xtend (Depuy, Warsaw, USA), have been used, but few mid-term results have been published. OBJECTIVES: The aim of this study is to report on the outcome after RSA after a mean follow-up of 68 months (range 63-75), to verify the already published, encouraging early results and to learn about the function and pain situation after RSA in the mid-term period. METHODS: 60 patients underwent RSA with the Depuy Delta Xtend prosthesis in the years 2007 and 2008, performed by the senior author of this study. 39 of these patients were available for follow up and were asked to complete a questionnaire (msCS, modified subjective Constant Score). In addition, 28 patients agreed to a clinical examination. With these patients, in addition, the constant score, age and gender-adjusted constant score and range of motion were evaluated. RESULTS: The mean msCS of preoperative 39.15 points (range 12-69) improved to 71.74 points (range 44-100) after 5 years. The mean CS at 5 years was 65.79 points (range 21-93) and the mean age and gender-adjusted constant score was 92%. The mean active anterior elevation was 139° (range 70-180°), the mean abduction was 135° (range 50-170°) and the mean active external rotation was 17° (range -20-40°). CONCLUSION: This study confirms good early results after RSA after more than 5 years. We see very good outcomes in patients with CTA and omarthrosis, whilst the rate of complication is low.


Subject(s)
Arthroplasty, Replacement, Shoulder/instrumentation , Arthroplasty, Replacement, Shoulder/methods , Patient Satisfaction , Range of Motion, Articular , Rotator Cuff Injuries/diagnosis , Rotator Cuff Injuries/therapy , Shoulder Prosthesis , Aged , Aged, 80 and over , Equipment Failure Analysis , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Middle Aged , Prosthesis Design , Treatment Outcome
3.
Oper Orthop Traumatol ; 28(1): 78-89, 2016 Feb.
Article in German | MEDLINE | ID: mdl-25900829

ABSTRACT

OBJECTIVE: Safe and cost-effective rotator-cuff repair. INDICATION: All types of rotator cuff lesions. CONTRAINDICATIONS: Frozen shoulder, rotator cuff mass defect, defect arthropathy. SURGICAL TECHNIQUE: Extensive four-point fixation on the bony footprint is performed using the double-row lateral augmentation screw anchor (LASA-DR) with high biomechanical stability. Following mobilization of the tendons, these are refixed in the desired configuration first medially and then laterally. To this end, two drilling channels (footprint and lateral tubercle) are created for each screw. Using the shuttle technique, a suture anchor screw is reinforced with up to four pairs of threads. The medial row is then pierced and tied, and the sutures that have been left long are tied laterally around the screw heads (double row). POSTOPERATIVE MANAGEMENT: 4 Weeks abduction pillow, resulting in passive physiotherapy, followed by initiation of active assisted physiotherapy. Full weight-bearing after 4-6 months. RESULTS: Prospective analysis of 35 consecutive Bateman-III lesions with excellent results and low rerupture rate (6%).


Subject(s)
Bone Screws , Plastic Surgery Procedures/instrumentation , Plastic Surgery Procedures/methods , Rotator Cuff Injuries/surgery , Suture Anchors , Suture Techniques , Adult , Aged , Equipment Failure Analysis , Humans , Middle Aged , Prosthesis Design , Rotator Cuff Injuries/diagnosis , Treatment Outcome
4.
Z Orthop Unfall ; 153(4): 399-407, 2015 Aug.
Article in German | MEDLINE | ID: mdl-26274558

ABSTRACT

BACKGROUND: The double-row rotator cuff repair is discussed controversially. Despite improved biomechanical properties, reduced re-tear rates and higher costs, no significant difference compared to single-row fixation in the clinical results is found. Mid-term results of an open double-row fixation with titanium anchor screws are presented. MATERIAL AND METHODS: 237 patients (m = 142, f = 95, median age: 56.3 years) were operated in 2007 with this technique by the senior author (M. G.). Preoperatively, 2 years and 4,5 years postoperatively a subjective shoulder score (SSG) with follow-up rates of 86, 87 and 83 %, was evaluated. 5.1 years postoperatively an objective evaluation of 131 patients using the Constant-Murley scores (CS), the simple shoulder tests (SST), Gerber's shoulder value and the evaluation with school grades followed. The integrity of the cuff was checked with ultrasound. The absolute (re-tears and partial re-tears) and the relative (re-tears, partial re-tears, thinning and thickening of the cuff) re-tear rates were evaluated. RESULTS: In SSG a highly significant improvement from 51 to 83 points was found (p < 0.001). In CS 80 points (min.: 18; max.: 100), and in SST 11 points (min.: 2; max.: 12) were achieved. The shoulder value of Gerber increased significantly from preoperative 28.1 to 84.5 % 5.1 years postoperative (p < 0.001).The absolute re-tear rate, evaluated in ultrasound was 7.6 %, the relative re-tear rate 17.6 %. For primary rotator cuff reconstructions a higher CS with 82 points and a lower relative re-tear rate with 10.5 % were found. The patient's age had no significant influence on the clinical outcome. The rupture size showed a significant impact on the re-tear rate and the scores (p < 0.05). Between the operated and healthy shoulder neither strength nor mobility were found to be significantly different. Men reached a highly significant better strength than women (p < 0.001) which also resulted in a significantly better outcome in the CS (p < 0.01). The costs for open titanium transfixation technique with 330 € per case are markedly less than for arthroscopic suture bridge technique with 600 to 1000 € per case. CONCLUSION: Open double-row cuff repair with titanium screws is a safe and cost effective technique with a low re-tear rate with comparable clinical results regarding open and arthroscopic procedures.


Subject(s)
Bone Screws , Plastic Surgery Procedures/instrumentation , Rotator Cuff Injuries , Rotator Cuff/surgery , Suture Anchors , Titanium/chemistry , Equipment Failure Analysis , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Middle Aged , Prosthesis Design , Plastic Surgery Procedures/methods , Retrospective Studies , Rotator Cuff/diagnostic imaging , Treatment Outcome , Ultrasonography
5.
Z Orthop Unfall ; 152(1): 36-40, 2014 Feb.
Article in German | MEDLINE | ID: mdl-24578112

ABSTRACT

Proximal hamstring origin avulsions are rare injuries. A common cause for this kind of injury is a trauma with the hamstring in overextension and simultaneously forced hip flexion and knee extension. We report on 6 cases, 5 with an acute rupture of the hamstring origin and one case with a delayed presentation in our emergency room. In 3 cases the injury was related to sport activity, the other 3 are related to accidents during work. None of these patients took part in competitive sports. One case was reported 8 weeks after trauma with an MRI performed one week before. Due to the low functional deficits conservative treatment was preferred. In all of the acute injuries open refixation was done within the first two weeks after trauma using 2-3 suture anchors. Postoperative mobilisation was done with partial weight bearing. Active knee flexion against gravity was not started until six weeks postoperative. All patients who had surgery achieved good results 3-28 months after surgery. They suffered from only little pain (VAS1-2) and had good movement ability. Sport activities were reduced in 3 cases, 2 patients returned to pre-injury sport levels. All patients were able to perform one-legged squats. In the evaluated LEFS (Lower Extremity Functional Scale) 75.6/80 points were achieved (72-79). There were no severe complications within this case study. It is important to distinguish proximal hamstring origin avulsions from the majority of hamstring muscle injuries. If the avulsion is treated with surgery, refixation should be performed within the first weeks to prevent the sciatic nerve from being bound in scar tissue with a consecutive high risk of injury during mobilisation of the tendon.


Subject(s)
Exercise Therapy/methods , Hip Injuries/therapy , Suture Anchors , Tendon Injuries/therapy , Tenotomy/methods , Tenotomy/rehabilitation , Adult , Aged , Combined Modality Therapy/instrumentation , Combined Modality Therapy/methods , Female , Hip Injuries/diagnostic imaging , Humans , Male , Middle Aged , Radiography , Plastic Surgery Procedures/instrumentation , Plastic Surgery Procedures/methods , Plastic Surgery Procedures/rehabilitation , Rupture/diagnosis , Rupture/therapy , Tendon Injuries/diagnosis , Tenotomy/instrumentation , Treatment Outcome
6.
Persoonia ; 22: 129-38, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19915689

ABSTRACT

Featuring a high level of taxon sampling across Ascomycota, we evaluate a multi-gene phylogeny and propose a novel order and class in Ascomycota. We describe two new taxa, Geoglossomycetes and Geoglossales, to host three earth tongue genera: Geoglossum, Trichoglossum and Sarcoleotia as a lineage of 'Leotiomyceta'. Correspondingly, we confirm that these genera are not closely related to the genera Neolecta, Mitrula, Cudonia, Microglossum, Thuemenidum, Spathularia and Bryoglossum, all of which have been previously placed within the Geoglossaceae. We also propose a non-hierarchical system for naming well-resolved nodes, such as 'Saccharomyceta', 'Dothideomyceta', and 'Sordariomyceta' for supraordinal nodes, within the current phylogeny, acting as rankless taxa. As part of this revision, the continued use of 'Leotiomyceta', now as a rankless taxon, is proposed.

7.
Stud Mycol ; 64: 17-47S7, 2009.
Article in English | MEDLINE | ID: mdl-20169022

ABSTRACT

The Capnodiales incorporates plant and human pathogens, endophytes, saprobes and epiphytes, with a wide range of nutritional modes. Several species are lichenised, or occur as parasites on fungi, or animals. The aim of the present study was to use DNA sequence data of the nuclear ribosomal small and large subunit RNA genes to test the monophyly of the Capnodiales, and resolve families within the order. We designed primers to allow the amplification and sequencing of almost the complete nuclear ribosomal small and large subunit RNA genes. Other than the Capnodiaceae (sooty moulds), and the Davidiellaceae, which contains saprobes and plant pathogens, the order presently incorporates families of major plant pathological importance such as the Mycosphaerellaceae, Teratosphaeriaceae and Schizothyriaceae. The Piedraiaceae was not supported, but resolves in the Teratosphaeriaceae. The Dissoconiaceae is introduced as a new family to accommodate Dissoconium and Ramichloridium. Lichenisation, as well as the ability to be saprobic or plant pathogenic evolved more than once in several families, though the taxa in the upper clades of the tree lead us to conclude that the strictly plant pathogenic, nectrotrophic families evolved from saprobic ancestors (Capnodiaceae), which is the more primitive state.

8.
Stud Mycol ; 64: 49-83S3, 2009.
Article in English | MEDLINE | ID: mdl-20169023

ABSTRACT

A reappraisal of the phylogenetic integrity of bitunicate ascomycete fungi belonging to or previously affiliated with the Hysteriaceae, Mytilinidiaceae, Gloniaceae and Patellariaceae is presented, based on an analysis of 121 isolates and four nuclear genes, the ribosomal large and small subunits, transcription elongation factor 1 and the second largest RNA polymerase II subunit. A geographically diverse and high density taxon sampling strategy was employed, including multiple isolates/species from the following genera: Anteaglonium (6/4), Encephalographa (1/1), Farlowiella (3/1), Gloniopsis (8/4), Glonium (4/2), Hysterium (12/5), Hysterobrevium (14/3), Hysterographium (2/1), Hysteropatella (2/2), Lophium (4/2), Mytilinidion (13/10), Oedohysterium (5/3), Ostreichnion (2/2), Patellaria (1/1), Psiloglonium (11/3), Quasiconcha (1/1), Rhytidhysteron (8/3), and 24 outgroup taxa. Sequence data indicate that although the Hysteriales are closely related to the Pleosporales, sufficient branch support exists for their separation into separate orders within the Pleosporomycetidae. The Mytilinidiales are more distantly related within the subclass and show a close association with the Gloniaceae. Although there are examples of concordance between morphological and molecular data, these are few. Molecular data instead support the premise of a large number of convergent evolutionary lineages, which do not correspond to previously held assumptions of synapomorphy relating to spore morphology. Thus, within the Hysteriaceae, the genera Gloniopsis, Glonium, Hysterium and Hysterographium are highly polyphyletic. This necessitated the transfer of two species of Hysterium to Oedohysteriumgen. nov. (Od. insidenscomb. nov. and Od. sinense comb. nov.), the description of a new species, Hysterium barrianumsp. nov., and the transfer of two species of Gloniopsis to Hysterobreviumgen. nov. (Hb. smilaciscomb. nov. and Hb. constrictumcomb. nov.). While Hysterographium, with the type Hg. fraxini, is removed from the Hysteriaceae, some of its species remain within the family, transferred here to Oedohysterium (Od. pulchrumcomb. nov.), Hysterobrevium (Hb. moricomb. nov.) and Gloniopsis (Gp. subrugosacomb. nov.); the latter genus, in addition to the type, Gp. praelonga, with two new species, Gp. arciformissp. nov. and Gp. kenyensis sp. nov. The genus Glonium is now divided into Anteaglonium (Pleosporales), Glonium (Gloniaceae), and Psiloglonium (Hysteriaceae). The hysterothecium has evolved convergently no less than five times within the Pleosporomycetidae (e.g., Anteaglonium, Farlowiella, Glonium, Hysterographium and the Hysteriaceae). Similarly, thin-walled mytilinidioid (e.g., Ostreichnion) and patellarioid (e.g., Rhytidhysteron) genera, previously in the Mytilinidiaceae and Patellariaceae, respectively, transferred here to the Hysteriaceae, have also evolved at least twice within the subclass. As such, character states traditionally considered to represent synapomorphies among these fungi, whether they relate to spore septation or the ascomata, in fact, represent symplesiomorphies, and most likely have arisen multiple times through convergent evolutionary processes in response to common selective pressures.

9.
Stud Mycol ; 64: 85-102S5, 2009.
Article in English | MEDLINE | ID: mdl-20169024

ABSTRACT

Five loci, nucSSU, nucLSU rDNA, TEF1, RPB1 and RPB2, are used for analysing 129 pleosporalean taxa representing 59 genera and 15 families in the current classification of Pleosporales. The suborder Pleosporineae is emended to include four families, viz.Didymellaceae, Leptosphaeriaceae, Phaeosphaeriaceae and Pleosporaceae. In addition, two new families are introduced, i.e. Amniculicolaceae and Lentitheciaceae. Pleomassariaceae is treated as a synonym of Melanommataceae, and new circumscriptions of Lophiostomataceaes. str., Massarinaceae and Lophiotrema are proposed. Familial positions of Entodesmium and Setomelanomma in Phaeosphaeriaceae, Neophaeosphaeria in Leptosphaeriaceae, Leptosphaerulina, Macroventuria and Platychora in Didymellaceae, Pleomassaria in Melanommataceae and Bimuria, Didymocrea, Karstenula and Paraphaeosphaeria in Montagnulaceae are clarified. Both ecological and morphological characters show varying degrees of phylogenetic significance. Pleosporales is most likely derived from a saprobic ancestor with fissitunicate asci containing conspicuous ocular chambers and apical rings. Nutritional shifts in Pleosporales likely occured from saprotrophic to hemibiotrophic or biotrophic.

10.
Stud Mycol ; 64: 1-15S10, 2009.
Article in English | MEDLINE | ID: mdl-20169021

ABSTRACT

We present a comprehensive phylogeny derived from 5 genes, nucSSU, nucLSU rDNA, TEF1, RPB1 and RPB2, for 356 isolates and 41 families (six newly described in this volume) in Dothideomycetes. All currently accepted orders in the class are represented for the first time in addition to numerous previously unplaced lineages. Subclass Pleosporomycetidae is expanded to include the aquatic order Jahnulales. An ancestral reconstruction of basic nutritional modes supports numerous transitions from saprobic life histories to plant associated and lichenised modes and a transition from terrestrial to aquatic habitats are confirmed. Finally, a genomic comparison of 6 dothideomycete genomes with other fungi finds a high level of unique protein associated with the class, supporting its delineation as a separate taxon.

11.
Stud Mycol ; 64: 123-133S7, 2009.
Article in English | MEDLINE | ID: mdl-20169026

ABSTRACT

The class Dothideomycetes (along with Eurotiomycetes) includes numerous rock-inhabiting fungi (RIF), a group of ascomycetes that tolerates surprisingly well harsh conditions prevailing on rock surfaces. Despite their convergent morphology and physiology, RIF are phylogenetically highly diverse in Dothideomycetes. However, the positions of main groups of RIF in this class remain unclear due to the lack of a strong phylogenetic framework. Moreover, connections between rock-dwelling habit and other lifestyles found in Dothideomycetes such as plant pathogens, saprobes and lichen-forming fungi are still unexplored. Based on multigene phylogenetic analyses, we report that RIF belong to Capnodiales (particularly to the family Teratosphaeriaceae s.l.), Dothideales, Pleosporales, and Myriangiales, as well as some uncharacterised groups with affinities to Dothideomycetes. Moreover, one lineage consisting exclusively of RIF proved to be closely related to Arthoniomycetes, the sister class of Dothideomycetes. The broad phylogenetic amplitude of RIF in Dothideomycetes suggests that total species richness in this class remains underestimated. Composition of some RIF-rich lineages suggests that rock surfaces are reservoirs for plant-associated fungi or saprobes, although other data also agree with rocks as a primary substrate for ancient fungal lineages. According to the current sampling, long distance dispersal seems to be common for RIF. Dothideomycetes lineages comprising lichens also include RIF, suggesting a possible link between rock-dwelling habit and lichenisation.

12.
Stud Mycol ; 64: 155-173S6, 2009.
Article in English | MEDLINE | ID: mdl-20169029

ABSTRACT

Phylogenetic analyses of four nuclear genes, namely the large and small subunits of the nuclear ribosomal RNA, transcription elongation factor 1-alpha and the second largest RNA polymerase II subunit, established that the ecological group of marine bitunicate ascomycetes has representatives in the orders Capnodiales, Hysteriales, Jahnulales, Mytilinidiales, Patellariales and Pleosporales. Most of the fungi sequenced were intertidal mangrove taxa and belong to members of 12 families in the Pleosporales: Aigialaceae, Didymellaceae,Leptosphaeriaceae, Lenthitheciaceae, Lophiostomataceae, Massarinaceae,Montagnulaceae, Morosphaeriaceae, Phaeosphaeriaceae, Pleosporaceae, Testudinaceae and Trematosphaeriaceae. Two new families are described: Aigialaceae and Morosphaeriaceae, and three new genera proposed: Halomassarina, Morosphaeria and Rimora. Few marine species are reported from the Dothideomycetidae (e.g. Mycosphaerellaceae, Capnodiales), a group poorly studied at the molecular level. New marine lineages include the Testudinaceae and Manglicolaguatemalensis in the Jahnulales. Significantly, most marine Dothideomycetes are intertidal tropical species with only a few from temperate regions on salt marsh plants (Spartina species and Juncus roemerianus), and rarely totally submerged (e.g. Halotthia posidoniae and Pontoporeia biturbinata on the seagrasses Posidonia oceanica and Cymodocea nodosum). Specific attention is given to the adaptation of the Dothideomycetes to the marine milieu, new lineages of marine fungi and their host specificity.

13.
Leuk Lymphoma ; 48(1): 80-8, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17325851

ABSTRACT

Application of five-color staining may improve quantification of minimal residual disease by multiparameter flow cytometry in acute myeloid leukemia. We analysed bone marrow samples in 139 cases using a comprehensive antibody panel with five-color combinations. Sensitivity was estimated by quantification of leukemia-associated aberrant immunophenotype (LAIP)-positive cells for each LAIP in 18 normal bone marrow (BM) samples. The logarithmic difference (LD) in LAIP-positive cells between leukemic and normal BM amounted to a median of 3.32 (range 1.76 - 4.89). Skipping one color resulted in an increase of LAIP-positive normal bone marrow cells while percentages of LAIP-positive leukemic cells changed only marginally (median gain in LD = 0.54; maximum gain = 3.30). Because regenerating bone marrow has not been used as control data are most important to post-therapy checkpoints. In 32 patients with clinical follow-up, a LD higher than the median (3.25) at the follow-up checkpoint corresponded to a longer event-free survival. These data suggest that the application of five-color staining significantly improves the sensitivity and accuracy of the method.


Subject(s)
Flow Cytometry/methods , Leukemia, Myeloid/diagnosis , Neoplasm, Residual/diagnosis , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Bone Marrow Cells/pathology , Disease-Free Survival , Female , Follow-Up Studies , Humans , Immunophenotyping , Leukemia, Myeloid/therapy , Male , Middle Aged , Neoplasm, Residual/pathology , Sensitivity and Specificity
14.
Br J Haematol ; 134(6): 616-9, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16938118

ABSTRACT

AML1-ETO collaborates with further genetic abnormalities to induce acute myeloid leukaemia (AML). We analysed 99 patients with an AML1-ETO rearrangement for additional aberrations. Frequent genetic abnormalities were, loss of a sex chromosome (56/99, 56.5%) and del(9)(q22) (24/99, 24.2%). The most frequent molecular aberrations were mutations of KITD816 (3/23, 13%) and NRAS (8/89, 8.9%). Further molecular abnormalities were FLT3 mutations (3/87, 3.4%), AML1 (1/26, 3.8%) and PU1 (1/14, 7.1%). MLL-PTD, KRAS and CEBPA mutations were not found. These clinical findings support the model that AML1-ETO collaborates with other genetic alterations, such as mutations of receptor tyrosine kinases, to induce AML.


Subject(s)
Chromosomes, Human, Pair 21 , Chromosomes, Human, Pair 8 , Core Binding Factor Alpha 2 Subunit/genetics , Oncogene Proteins, Fusion/genetics , Translocation, Genetic , Acute Disease , Adolescent , Adult , Aged , Cytogenetics , Female , Humans , In Situ Hybridization, Fluorescence , Leukemia, Myeloid , Male , Middle Aged , RUNX1 Translocation Partner 1 Protein
16.
Leukemia ; 20(5): 777-84, 2006 May.
Article in English | MEDLINE | ID: mdl-16511515

ABSTRACT

Chromosomal rearrangements of the human MLL gene are a hallmark for aggressive (high-risk) pediatric, adult and therapy-associated acute leukemias. These patients need to be identified in order to subject these patients to appropriate therapy regimen. A recently developed long-distance inverse PCR method was applied to genomic DNA isolated from individual acute leukemia patients in order to identify chromosomal rearrangements of the human MLL gene. We present data of the molecular characterization of 414 samples obtained from 272 pediatric and 142 adult leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) was determined and several new TPGs were identified. The combined data of our study and published data revealed a total of 87 different MLL rearrangements of which 51 TPGs are now characterized at the molecular level. Interestingly, the four most frequently found TPGs (AF4, AF9, ENL and AF10) encode nuclear proteins that are part of a protein network involved in histone H3K79 methylation. Thus, translocations of the MLL gene, by itself coding for a histone H3K4 methyltransferase, are presumably not randomly chosen, rather functionally selected.


Subject(s)
Leukemia/genetics , Myeloid-Lymphoid Leukemia Protein/genetics , Oncogene Proteins, Fusion/genetics , Translocation, Genetic/genetics , Acute Disease , Adult , Child , Chromosome Aberrations , Chromosome Mapping , DNA/genetics , DNA/isolation & purification , Histone-Lysine N-Methyltransferase , Histones/metabolism , Humans , Methylation
19.
Crit Rev Oncol Hematol ; 56(2): 235-45, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16207531

ABSTRACT

Genetic and molecular techniques have provided increasing insights into the biology of acute myeloid leukemia (AML). These investigations showed that AML is not a homogeneous disease but a heterogeneous group of biologically different subentities. These subentities are currently primarily defined by cytogenetics by which three main subgroups can be discriminated: AML with balanced translocations, AML with unbalanced aberrations and AML without cytogenetically detectable aberrations. Within the latter group molecular alterations are identified in more than half of cases such as NPM mutations, FLT3 mutations, MLL duplications and mutations of CEBP-alpha. The clinical meaning of these findings is illustrated by substantial differences in response to therapy and long-term outcome. As demonstrated by the recent multicenter trial of the German AML Cooperative Group (AMLCG) and other studies intensification of induction therapy may improve the results in distinct subtypes but fails to do so in others. Therefore, new strategies need to be explored which incorporate the knowledge about the biology of AML to develop biology adapted treatment strategies. This process has just begun and is predominantly determined by the availability of new agents and their evaluation in clinical phase I and II studies. A variety of targets are currently explored and some trials have yielded promising results already. The step towards a biology adapted treatment of AML is long and requires the combined efforts of researchers, clinicians and the pharmaceutical industry. The first steps towards this goal have been taken and give rise to the hope for more effective and more specific therapies of AML.


Subject(s)
Leukemia, Myeloid, Acute/therapy , Combined Modality Therapy/methods , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Neoplasm Proteins/genetics , Translocation, Genetic/genetics
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