Biomedical subjects

H Stein

Publications and source records attributed to H Stein.

At least 91 records · Page 5Linked to original sources

PubMed2000

The restricted expression pattern of the Hodgkin's lymphoma-associated cytokine receptor CD30 is regulated by a minimal promoter.

One of the most peculiar immunohistological characteristics of the tumour cells of Hodgkin's lymphoma, anaplastic large cell lymphoma (ALCL), and embryonal carcinoma of the testis is the expression of the CD30 antigen. Physiologically, CD30 expression is restricted to a few activated lymphocytes in normal lymphoid tissue and a small population of decidual cells. To clarify the reasons behind this highly restricted expression pattern and to learn about the combination of transcription factors involved in this regulation in Hodgkin's lymphoma and other CD30(+) malignancies, the 5'-flanking regulatory region of the cd30 gene was analysed. The major transcription start site was determined to be 270 bases upstream of the translational start codon in the Hodgkin's lymphoma-derived cell lines L591 and L428. Reporter gene assays revealed that the CD30 promoter (-413 to 84) induces a 50- to 1000-fold higher luciferase expression in CD30(+) human lymphoid cell lines (Co, Jurkat, and the Hodgkin's lymphoma-derived cell line L540) than in CD30(-) human lymphoid cell lines (DG75, SUP-T1, and U698M), CD30(-) human carcinoma cell lines (HeLa and MCF-7), or COS1 cells. Deletion analysis defined a TATA-less, minimal promoter sequence from -164 to 84. The transcription factor Sp1 and members of the Ets family induce CD30 expression, whereas the transcription factor Sp3 diminishes its induction. These data suggest that a high Sp1/Sp3 expression ratio and a peculiar expression pattern of the Ets transcription factors are involved in the overexpression of CD30 and might contribute to the transformation of CD30(+) tumour cells.

Base Sequence↗

PubMed2000

Pathology of intestinal lymphomas.

The advent of immunohistological and molecular techniques has enabled the comprehensive characterization of many lymphoma entities. Furthermore, it has increased the consensus in lymphoma classification among pathologists. In this review we describe the pathological features of primary intestinal lymphomas classified according to the revised European-American classification of lymphoid neoplasms. The majority of primary intestinal lymphomas are of B-cell lineage and most of these are high-grade tumors. By morphology they may be classified as diffuse large B-cell lymphomas of centroblastic, immunoblastic or plasmablastic type and Burkitt lymphomas. The latter occur predominantly in the terminal ileum and affect children or young adults. Low-grade extra-nodal marginal-zone lymphoma of the mucosa-associated lymphoid tissue (MALT) type and, less frequently, follicular center-cell lymphomas are the low-grade B-cell lymphomas most commonly observed in this region. The first mentioned tumor and its specific intestinal variant, alpha-chain disease or immunoproliferative small intestinal disease are well known for their indolent clinical course. Primary intestinal mantle-cell lymphoma often presents as multiple lymphomatous polyposis and similarly to its node-based equivalent is associated with an unfavorable prognosis. Most primary intestinal T-cell lymphomas display a characteristic immunophenotype, particular histological features with prominent epitheliotropism and are often associated with celiac disease indicating that these tumors form a specific lymphoma type. It has been termed intestinal T-cell lymphoma or enteropathy-type T-cell lymphoma. Clinically, these are aggressive diseases with a high mortality rate. In summary, primary intestinal lymphomas consist of several entities which display distinct clinicopathological features thus confirming the relevance of lymphoma typing.

Humans↗

PubMed2000

Esophageal cancer: a European perspective.

A survey was conducted among a group of European surgeons in order to investigate current attitudes and strategies in the management of squamous cell carcinoma of the esophagus. The survey consisted of a questionnaire mailed to surgeons in eight different countries with extensive clinical experience and scientific interest in the field. Eight questionnaires including the data of 6146 operated patients were available for analysis. A consensus emerged among the panelists that protocols of induction therapy should be routinely used in patients with locally advanced disease, especially in supracarinal tumors. Four of the surgeons advocated bilateral neck dissection in these patients. A progressive improvement in survival over the past three decades was noted. After 1990, the postoperative mortality rate was 6.2% after surgery alone and 9.7% after chemoradiation therapy followed by surgery. The 5-year survival rate after a complete resection was 38.5%. In the opinion of the panelists, esophagectomy remains the "gold standard" of therapy and should be regarded as an integral component of the treatment plan for patients with squamous cell carcinoma.

Attitude of Health Personnel↗

PubMed2000

Regression of Epstein-Barr virus-associated lymphoproliferative disorders in patients with acquired immunodeficiency syndrome during therapy with foscarnet.

Epstein-Barr virus (EBV)-associated lymphoproliferative disorders frequently develop in patients with acquired immunodeficiency syndrome (AIDS). The lymphoproliferative disorders are usually treated with a combination of cytotoxic drugs, and virustatic medication is thought to be ineffective. However, we report about two AIDS patients with EBV-associated lymphoproliferative disorders not responding to a standard chemotherapy, who achieved complete tumour regression after virustatic therapy with foscarnet.

Acquired Immunodeficiency Syndrome↗

PubMed2000

[The new WHO classification of malignant lymphoma. After "REAL" a further step on the road to a worldwide consensus].

For decades, rival classification systems for malignant lymphoma that were hardly even comparable have existed side by side: the Kiel Classification has so far been used in the German-speaking parts of Europe and the "Working Formulation" mainly in the USA. At the beginning of the 1990's it became possible to overcome this unsatisfactory situation, when pathologists in the Old and New Worlds joined forces to elaborate a new classification for lymphoma, the Revised European-American Lymphoma (REAL) Classification, based on current scientific data. One new feature is the absence of a malignancy grading that is applicable to more than one entity. The system centres on the definition of distinct lymphomatous diseases that can be diagnosed with a high degree of reproducibility. Morphological and clinical characteristics are used for diagnosis, but so, consistently, are immuno-phenotypical and molecular genetic ones. An international cooperative study has confirmed the high reproducibility and clinical practicability of this tentative classification system. An international panel of pathologists appointed by the World Health Organization has updated the REAL classification, which is expected to be published in the updated version in 2001 under the title New WHO Classification. The articles that follow are based on the new WHO classification.

Europe↗

PubMed2000

[Lymphatic system and differentiation of B and T lymphocytes].

Most malignant tumours are classified according to their cellular origins. With regard to the classification of the malignant lymphomas, however, the application of this concept was not possible for a long period. Attitudes towards this changed rapidly with the discovery and description of the various cellular components of lymphoid tissue, and with the development of methods, which reliably distinguish the cells of the lymphoid system from each other. It has become apparent that the cellular origin of most lymphomatous diseases determines their respective morphological and clinical characteristics and, therefore, represents a sound basis for the classification of most lymphomas. This principle of classifying malignant lymphomas was initially applied by the Kiel Classification. Since itsí publication, further scientific discoveries have enabled us to close the gaps in our knowledge regarding the development of lymphoid tissue and cells. These advances were incorporated in the REAL Classification, and, subsequently, in the new WHO Classification. It is obvious, therefore, that an understanding of the malignant lymphomas and their classification requires a basic understanding of the differentiation of the cells of the lymphoid system. Consequently, a description of the components, the development and of the various developmental stages of the lymphoid cells will be briefly reviewed here, serving as a basis for the following chapters, which will summarise the characteristics of the different lymphomas. As the majority of the malignant lymphomas arise from B- and T-cells, these cell types will be concentrated upon in this review.

B-Lymphocytes↗

PubMed2000

[Hodgkin lymphoma. Classification and pathogenesis].

In the last few years our understanding of Hodgkin's lymphoma (HL) has enormously progressed. Molecular analysis has revealed that almost all cases of this disease are clonal B cell neoplasms, therefore the term Hodgkin's lymphoma instead of Hodgkin's disease is being proposed in the new WHO classification. Lymphocyte predominance HL (LPHL) differs in respect to morphology, immunophenotype and clinical features from the other forms of HL and represents its own distinct entity. In addition to morphologic features (nodularity, presence of L&H cells) the immuno-phenotype of tumor cells is most important in establishing a diagnosis of LPHL, and particularly in differentiating LPHL from the other forms of HL. The remaining forms of HL (nodular sclerosis, mixed cellularity, lymphocyte depletion) display a mostly identical antigen profile and similar clinical characteristics, they are therefore grouped together in the REAL classification under the heading of classical HL. Recent immuno-histological analysis have revealed that one third of HL cases, which formerly were classified as LPHL, display the immuno-phenotype of classical HL. These cases are now considered to represent examples of classical HL and termed nodular lymphocyte rich classical HL. According to retrospective clinico-pathological analysis, the biological behaviour of this newly identified form of classical HL also differs from LPHL. Differences between classical HL and LPHL also occur on the molecular level. Thus LPHL often displays ongoing mutations of the immunoglobulin genes, and the tumor cells express immunoglobulin protein and transcripts, while these characteristics are absent in classical HL. Since peripheral B cells that do not express immunoglobulins die from apoptosis, these findings imply that the regulation of apoptosis is defective in Hodgkin and Sternberg Reed cells. Several laboratories are currently working intensely to clarify the defective apoptosis pathway in HL.

B-Lymphocytes↗

PubMed2000

[The many faces of anaplastic large cell lymphoma].

Fifteen years after their first description by one of the authors (HS) anaplastic large cell lymphoma (ALC-lymphoma, ALCL) now represents a generally accepted group of large cell lymphomas. Essential defining features comprise of a proliferation of large lymphoid cells with strong expression of the cytokine receptor CD30 and a characteristic growth pattern. Using molecular and clinical criteria three entities of ALC-lymphoma have been identified: primary systemic anaplastic lymphoma kinase (ALK)-positive ALC-lymphoma, primary systemic ALK-negative ALC-lymphoma and primary cutaneous ALC-lymphoma. The ALK expression in the primary systemic ALC-lymphoma entity is caused by chromosomal translocations, most commonly t(2;5), and can nowadays be reliably detected by immuno-histology. ALK-positive ALC-lymphoma predominantly affects young male patients and if treated with chemotherapy has a favourable prognosis. They show a broad morphological spectrum, with the "common type", the small cell variant and the lymphohistiocytic variant being most commonly observed. The knowledge of the existence of these variants is essential in establishing the correct diagnosis. ALK-negative ALC-lymphomas occur in older patients, equally affecting both genders and have an unfavorable prognosis. The morphology and the immuno-phenotype of primary cutaneous ALC-lymphoma shows an overlap with that of lymphomatoid papulosis. Both diseases have an excellent prognosis and secondary systemic dissemination is only rarely observed. The ALC-lymphomas described above derive from T cells and are generally accepted as biological entities. In contrast, large B-cell-lymphomas with anaplastic morphology are now believed not to represent an own entity but a morphologic variant of diffuse large B-cell lymphoma. Malignant lymphomas with morphological features of both Hodgkin- and ALC-lymphoma have formerly been classified as ALCL Hodgkin-like. Recent immuno-histological analysis of these cases however suggests that ALCL Hodgkin-like does not represent an own lymphoma entity. Most of these cases are likely to be examples of tumor cell rich classical Hodgkin lymphoma, while a minority of these cases appear to fall either into the category of ALK-positive or ALK-negative ALC-lymphoma.

Biomarkers, Tumor↗

PubMed2000

[Clinico-pathologic forms of peripheral T-and NK-cell lymphomas].

Malignant lymphomas, originating from peripheral T or NK cells, are rare tumours in Europe and account for less than 10% of all malignant lymphomas. In this review, the salient features of the more frequently occurring entities derived from T or NK cells will be presented. Nasal NK/T cell lymphoma is mainly found in the nose and paranasal sinuses and often, but not always, display an angiocentric growth pattern leading to coagulation necrosis. The tumor cells consistently express CD56, CD2 and the EBER molecules encoded by the Epstein-Barr virus. Clonal T cell receptor gene rearrangements are often absent indicating, in the majority of cases, a derivation of these tumors from NK cells. Enteropathy-type intestinal T-cell lymphomas often arise in patients with celiac disease and have a dismal prognosis. The tumour cells express T cell antigens, CD103 and cytotoxic molecules, but are negative for CD4. Approximately 20% of the cases display CD56 mostly in combination with CD8. Recently, an early purely intraepithelial form of this tumour was identified. Histologically these cases resemble celiac disease, however the intraepithelial lymphocytes often exhibit an abnormal immunophenotype with absent CD8 and T-cell-receptor protein expression, and, they are clonal by molecular analysis. Clinically, the patients suffer from refractory sprue or ulcerative jejunitis. The prognosis is bad with the patients often dying from malnutrition or an invasive tumour-forming T-cell lymphoma. Angioimmunoblastic T-cell lymphoma is defined by characteristic morphological findings (atypical lymphoid cells in part with pale cytoplasm, arborizing high endothelial venules and large FDC-meshworks) as well as clinical features (systemic symptoms, signs of a dys-regulated immune response). Peripheral T-cell lymphomas, that do not fit into a distinct entity, are classified in the REAL and the new WHO classifications as peripheral T-cell lymphomas unspecified. These display a broad morphological spectrum (including the T-cell lymphomas of different cell sizes, Lennert's lymphoma and T-zone lymphoma of the Kiel-classification) and in general are clinically aggressive.

Antigens, CD↗

PubMed2000

[Small cell B-cell lymphomas: guidelines for differential diagnosis].

Similar to the R.E.A.L-System, the small cell B-cell lymphomas of the new WHO classification consist of chronic lymphocytic leukaemia of B cell type, mantle cell lymphoma, follicular lymphoma, lymphoplasmocytic lymphoma/immunocytoma, hairy cell leukaemia, as well as plasmacytoma. The only major difference between the WHO- and the REAL-classification is the consideration of prolymphocytic leukaemia as a single disease entity in the former system. All the above-mentioned lymphomas arise from B cells of varying stages of differentiation and, therefore, often demonstrate architectural, cytological and immunophenotypic characteristics of their normal physiological counterparts. Consideration of tumour cell growth pattern, -cytology, -immunophenotype and -growth fraction, together with the presence and consistency of the reactive cell infiltrate, usually leads to categorisation of a lymphoma in the majority of cases. The molecular biological characteristics of follicular lymphoma and mantle cell lymphoma are the best defined of the small cell B-cell lymphomas. Chromosomal translocations involving the immunoglobulin heavy chain genes and the bcl-2 gene or Cyclin D1 gene, respectively, probably belong to the initial changes in a cell, which, together with several subsequent unidentified genetic alterations, lead to the development of these tumours. Although nodal small cell B-cell lymphomas are usually diagnosed at an advanced stage of the disease, the progression of the disease--with the exception of mantle cell lymphomas--is often indolent. As a result, the small cell B-cell lymphomas were previously considered as "low-grade" Non-Hodgkin lymphomas in the Kiel classification. However, since the progress of a lymphoma subtype can be heterogeneous and since mantle cell lymphomas cannot really be considered as "low-grade" tumours, "umbrella grading" of lymphomas has been discarded in the WHO classification, with emphasis being placed on grading within a lymphoma disease entity. In the following pages, the characteristics important for the diagnosis and categorisation of the small cell B-cell lymphomas will be summarised. Further, we present information regarding the molecular biological and clinical characteristics of these lymphomas.

Diagnosis, Differential↗

PubMed2000

[Marginal zone lymphomas: extranodal MALT type, nodal and splenic].

Marginal zone B-cell lymphomas (MCL) of extranodal, nodal and splenic origin appear to be different lymphoma entities with a similar growth pattern in the marginal zone of the B-follicles. Decisive for the detection of MCL as a distinct lymphoma entity was the "MALT concept" for lymphoid infiltrates in the gastric and intestinal mucosa as described by Isaacson et al. in the 1980's. Immunohistological stainings for the immunoglobulin light and heavy chains and molecular pathological studies of the immunoglobulin heavy chain gene configuration have subsequently confirmed the neoplastic nature of the extranodal infiltrates and differentiated marginal zone cells from mantle zone cells. In 1994, the MCL of MALT type as well as of nodal and splenic origin were included in the REAL classification and in 1998 in the new WHO classification for lymphomas. Meanwhile extranodal MCL of MALT-type have been observed in almost every organ and site of the body, by far most frequently in the gastric mucosa. Beside the typical growth pattern, lymphoepithelial lesions are a distinct diagnostic feature of extranodal MCL. Clinically, the small cell extranodal MCL show a very good prognosis with regression after treatment. As for nodal and splenic MCL, we need further studies to evaluate the prognostic aspects and to compare them with other B-cell lymphomas. The same is true for primary extranodal large B-cell lymphomas or blastic transformation to a large cell lymphoma; in these tumors the diagnosis of a MALT type lymphoma should only be made if a small cell component with MALT-specific criteria can be proved.

Humans↗

PubMed2000

[Large B-cell lymphomas: variants and entities].

Large B-cell neoplasms represent one of the most frequent groups of non-Hodgkin-lymphomas (30-40%). They are characterized by an aggressive clinical course. These lymphomas may evolve either de novo or secondary during the course of a less aggressive lymphoma. In addition to primary nodal, a primary extranodal manifestation is rather common. The neoplastic cells, even within one given case, show a broad morphological spectrum. Several findings of the last two decades have revealed that the large B-cell lymphomas represent an inhomogeneous group. This fact has been taken into account by the new WHO classification of malignant lymphomas. There are two groups identified, that of the variants and that of the subtypes. The various variants (centroblastic, immunoblastic, anaplastic, T-cell/histiocyte-rich) correspond to lymphomas without reproducible discriminating criteria lacking characteristic clinical, immuno-phenotypical and genetic findings. In contrast, the primary mediastinal, the intravascular, the primary effusion and primary central nervous system lymphomas represent distinct disease entities. A number of recently described large cell lymphoma types, i.e. plasma-blastic, ALK-positive and primary gastric, are included in the classification, their designation as distinct entities is still under discussion.

Genotype↗

PubMed2000

Chromosomal imbalances in Barrett's adenocarcinoma and the metaplasia-dysplasia-carcinoma sequence.

To characterize cytogenetic alterations found in Barrett's adenocarcinoma (BA) and, more importantly, its premalignant stages, we studied chromosomal imbalances in various lesions in the histologically proposed metaplasia-dysplasia-carcinoma sequence using comparative genomic hybridization (CGH). Using 30 esophageal adenocarcinoma resection specimens, we were able to study 30 areas of Barrett's adenocarcinoma and 8 lymph node metastases (LN). In addition, we investigated 25 premalignant lesions adjacent to BA derived from a subset of 14 resection specimens including 11 areas of high grade dysplasia (HGD), 8 areas of low grade dysplasia (LGD), and 6 areas of intestinal metaplasia (IM), which were laser-microdissected and studied with CGH. To validate the CGH findings, fluorescence in situ hybridization analysis on 13 BA with probes specific for HER-2/neu and 20q13.2 were performed. The chromosomal alterations most often identified in BA were: gains on 8q (80%), 20q (60%), 2p, 7p and 10q (47% each), 6p (37%), 15q (33%) and 17q (30%). Losses were observed predominantly on the Y-chromosome (76%), 4q (50%), 5q and 9p (43% each), 18q (40%), 7q (33%) and 14q (30%). High-level amplifications were observed on 8q23-qter, 8p12-pter, 7p11-p14, 7q21-31, 17q11-q23. Recurrent chromosomal changes were also identified in metaplastic (gains on 8q, 6p, 10q, losses on 13q, Y, 9p) and dysplastic epithelium (gains on 8q, 20q, 2p, 10q, 15q, losses on Y, 5q, 9p, 13q, 18q). Novel amplified chromosomal regions on chromosomes 2p and 10q were detected in both Barrett's adenocarcinoma and premalignant lesions. An increase of the average number of detected chromosomal imbalances from IM (7.0 +/- 1.7), to LGD (10.8 +/- 2.2), HGD (13.4 +/- 1.1), BA (13.3 +/- 1.4), and LN (22 +/- 1.2) was seen. Although the detection of common chromosomal alterations in premalignant lesions and adjacent carcinomas suggest a process of clonal expansion, the occurrence of several chromosomal changes in an apparently random order relative to one another is striking evidence that clonal evolution is more complex than would be predicted by linear models. This is probably a reflection of the existence of many divergent neoplastic subpopulations and highlights one of the main problems associated with surveillance of Barrett's patients, namely sampling error.

Adenocarcinoma↗

PubMed2000

Interleukin-6 modulates trabecular and endochondral bone turnover in the nude mouse by stimulating osteoclast differentiation.

A great deal of evidence has been accumulating that implicates the immune system in normal and pathological bone turnover. The objective of the present study was to examine the possible involvement of cytokines produced by T lymphocytes in bone metabolism. We have chosen the immunologically compromised athymic mouse, which demonstrate sclerotic features in its trabecular bone, as the animal model for assessment of possible modulation effects of interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6) on bone and cartilage metabolism. The cytokines were applied by daily subcutaneous injections for 3 consecutive days. Histomorphometry, measuring epiphyseal trabecular bone volume (ETBV), metaphyseal trabecular bone volume (MTBV), and the width of the growth plate, and tartrate-resistant acid phosphatase (TRAP) histochemistry were used to assess parameters of bone turnover in the proximal tibia. IL-6, but not IL-1alpha, reduced ETBV and MTBV. Both IL-6 and IL-1alpha reduced the width of the growth plate. IL-6, but not IL-1alpha, increased the number of chondroclasts and osteoclasts in the primary spongiosa of the proximal tibia, as well as the number of nuclei. The resultant bone resembled that of the wild-type mouse. The results point to IL-6 as a possible regulator of bone turnover in vivo. It is suggested that the athymic mouse has a deficiency somewhere in the cascade of events leading to the production of IL-6 or, alternatively, that IL-6 replaces other factors that are supplied by T lymphocytes directly or indirectly. As T lymphocytes interact with B lymphocytes it is suggested that the athymic mouse might be appropriate for studying the in vivo effects of the immune system on normal bone metabolism.

Animals↗

PubMed2000

Molecular genetic changes in metastatic primary Barrett's adenocarcinoma and related lymph node metastases: comparison with nonmetastatic Barrett's adenocarcinoma.

Lymph node metastasis is one of the strongest negative prognostic factors for patients with Barrett's adenocarcinoma (BCA). However, despite the importance of the metastatic process in BCA, the molecular basis of it remains poorly understood. To search for cytogenetic events associated with metastasis in regional or distant lymph nodes in BCA, we investigated 8 primary BCA and their lymph node metastases and compared them with 18 nonmetastatic BCA. In metastatic primary BCA, we observed significantly more DNA gains on 3q (P = .013), 17q (P = .019), and 22q (P = .021) compared with nonmetastatic primary BCA. No statistically significant correlation could be observed between DNA copy number changes and the histopathologic stage, grade, or survival (P > .05). The most frequent alteration observed only in lymph node metastases but not in the related primary tumor was loss of 2q (5 of 8). Coamplification of 7p and chromosome 17 was found in 6 of 8 lymph node metastases. A comparison of DNA copy number changes between primary tumors and their corresponding metastases indicated a high degree of genetic heterogeneity. Fluorescence in situ hybridization analysis demonstrated the involvement of the Her-2/neu gene in primary BCA and its related lymph node metastases. Each of the investigated primary tumors and related lymph node metastases also showed striking heterogeneity with respect to Her-2/neu, with several areas displaying different levels of amplification. In summary, our data indicate that DNA copy number changes on 2q, 3q, 7p, 17q, and 22q may be involved in the metastatic process in BCA. Furthermore, the striking genetic heterogeneity that we found between primary BCA and its lymph node metastases may underlie BCA's poor responsiveness to therapy and could help explain why prognostic biomarkers measured exclusively in primary tumors give an incomplete view of the biologic potential of BCA.

Adenocarcinoma↗

PubMed2000

Using the Ilizarov external fixation device for skin expansion.

Addressing war injuries requires tailoring treatment that provides the best functional and aesthetic results within a reasonable period of time. The authors report a young soldier who sustained a gunshot injury that caused an open fracture of the proximal tibia and patella (Gustilo type B-III). A local muscle flap could not be used, and thus the authors decided to use the already applied Ilizarov device for gradual expansion of the wound edge. The expanded skin covered the exposed fracture successfully, and later enabled solid union of the fracture. This reconstructive method seems to be an original solution for the management of open fractures, and additional proof that well-vascularized skin may be equivalent to a muscle flap, and may be considered for selected patients.

Adult↗

PubMed2000

Clinical relevance of immunoglobulin mutation analysis.

The precise diagnosis of malignant B-cell lymphoproliferations is essential for their appropriate clinical management. Histologic and immunophenotypical features alone are often insufficient in discriminating between various lymphoma entities and subtypes. The analysis of clonally rearranged immunoglobulin chain genes of the tumor cells was therefore suggested as an additional parameter. This article reviews current knowledge and describes which conclusions can be drawn for lymphoma diagnosis based on the type of immunoglobulin chain gene rearrangement, as well as on the number and distribution of somatic immunoglobulin mutations. Although there are striking correlations between the clinical outcome and the immunoglobulin mutations in some entities, many additional studies are required in order to draw final conclusions for most types of lymphoma.

B-Lymphocytes↗

PubMed2000

Hybrid external fixation in high-energy elbow fractures: a modular system with a promising future.

BACKGROUND: Severe, high-energy, periarticular elbow injuries producing a "floating joint" are a major surgical challenge. Their reconstruction and rehabilitation are not well documented. Therefore, the following reports our experience with treating such injuries caused by war wounds. METHODS: Seven adults with compound open peri- and intra-articular elbow fractures were treated in hybrid ring tubular fixation frames. After debridement, bone stabilization, and neurovascular reconstructions, early controlled daily movements were started in the affected joint. RESULTS: These seven patients had together seven humeral, five radial, and six ulnar fractures. All fractures united at a median time of 180 days. No deep infection developed. The functional end results assessed by the Khalfayan functional score were excellent in two, good in one, and fair in four of these severely mangled upper extremities. None was amputated. CONCLUSIONS: The Mangled Extremity Severity Score has been shown to be unable to provide a reliable assessment for severe high-energy limb injuries surgically managed with the modular hybrid thin wire tubular external fixation system. This hybrid system is a very useful addition to the surgical armamentarium of orthopedic trauma surgeons. It both allows complex surgical reconstructions and reduces the incidence of deep infections in these heavily contaminated injuries. The hybrid circular (thin wire) external fixation system is very modular and may provide secure skeletal stabilization even in cases of severely comminuted juxta-articular fractures on both sides of the elbow joint (floating elbow) with severe damage to soft tissues. This fixation system allows individual fixation of forearm bone fractures, thus allowing the preservation of pronation-supination movements.

Adult↗