Remission of pure red cell aplasia in T-cell receptor gammadelta-large granular lymphocyte leukemia after therapy with low-dose alemtuzumab.
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Publications and source records attributed to M Vesely.
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BACKGROUND: Malignant effusion in invasive breast cancer, either pleural or pericardial, is associated with a poor survival rate. We investigated the role of the location of invasive breast cancer in developing malignant pleural or pericardial effusion. METHODS: Three thousand eight hundred and fifty six women with a history of invasive breast cancer between 1960 and 1994 were analyzed in a retrospective study. Two hundred and six patients (5.34%; group A) developed malignant pleural and/or pericardial fluid as the first visible clinical sign of distant metastasis. A control group of 206 patients (group B) without malignant effusions were matched in terms of clinical and pathological characteristics. The two groups were compared in respect of the location of the primary tumor. Fifty patients in group A (n = 50; 24.2%) had tumors in the inner quadrants, 83 patients (n = 83; 40.3%) in the outer quadrants, and 13 patients (n = 13; 6.3%) in a central location. No data were available for 60 patients (n = 60; 29.1%). In group B, 12 patients (n = 12; 5.9%) had tumors in the inner quadrants, 140 patients (n = 140; 68.0%) in the outer quadrants, 14 patients (n = 14; 6.8%) had centrally located tumors, while no data were available for 40 patients (n = 40; 19.4%). Invasive ductal carcinomas (IDC) located in the inner quadrants were highly significantly associated with increased pleural or pericardial effusion as the first site of distant metastasis (p <or= 0.0001; chi-square tests). CONCLUSION: IDC in the inner quadrants were associated with a 4-fold higher rate of malignant pleural or pericardial effusions. Further studies will have to determine whether tumor location is a criterion for more aggressive adjuvant therapy.
This study investigates the ability of desert ants to adapt their path integration system to an "open-jaw" training paradigm, in which the point of arrival (from the nest) does not coincide with the point of departure (to the nest). Upon departure the ants first run off their home vector and then start a systematic search for the nest. Even if they are subjected to this training-around-a-circuit procedure for more than 50 times in succession, they never adopt straight homeward courses towards the nest. Their path integration vector gets slightly recalibrated (pointing a bit closer to the nest), and their search pattern gets asymmetric (with its search density peak shifted towards the nest), but the bipartite structure of the inbound trajectory invariably remains. These results suggest (1). that the ants cannot learn separate inbound and outbound vectors (i.e. vectors that are not 180 degrees reversals of each other), (2). that the recalibrated vector is dominated by the ant's outbound course, (3). that the recalibration of the vector and the modification of the search geometry are fast and flexible processes occurring whenever the ant experiences a mismatch between the stored and actual states of its path integrator.
Adventitial stripping of the palmar arch, the palmar common digital arteries, or the proper digital arteries is a last resort in the treatment of refractory primary or secondary Raynaud's phenomenon. Seven patients who had adventitial stripping of the ulnar and radial arteries proximal to the wrist and resection of the nerve of Henle, if identifiable, are presented. All of them were evaluated by telethermography, acral rheography, and a questionnaire before and after surgery. All were asymptomatic after surgery with satisfactory healing of the ulcers at the fingertips. None of them relapsed during the follow-up time of 1.5 years.
PURPOSE: Assessment of the post-operative results of peripheral sympathectomy in Raynaud's phenomenon. METHODS: Six patients with therapy refractory Raynaud's phenomenon underwent a 4 cm long adventitial stripping of the radial and ulnar arteries proximal to the wrist. The nerve of Henle was followed up to the surface of the palmar arch and resected. The pre- and postoperative examinations were performed using the help of a questionnaire, telethermography and infra-red laser reflexion rheography. RESULTS: All but two patients (two hands) were free of complaints (four patients, six hands), the three ulcers on the finger tips healed well. According to the questionnaire there was a dramatic improvement in the quality of life of the patients. CONCLUSION: In the follow-up period of two years, there was no recurrence. Adventitial stripping of the radial and ulnar arteries and resection of the nerve of Henle proximal to the wrist have demonstrated favourable results in the treatment of therapy-resistant complaints in Raynaud's phenomenon.
PURPOSE: In the hand surgery literature, more and more studies seem to indicate that the number of sympathetic fibers in the median and the ulnar nerves varies. However, there are no studies that confirm this suspicion. METHOD AND MATERIAL: Six hours post mortem samples were taken from the median and ulnar nerves, the superficial branch of the radial nerve, and from all digital nerves (each five females and males, average age 78 years). 13 samples were taken from one hand. To make sympathetic fibers visible, the immunohistochemical staining technique with tyrosinhydroxylase (TH) antibodies was used. Quantitative assessment of the sympathetic axons was made in whole cross-sections of the nerve. Statistical evaluation was performed with Wilcoxon rank-sum tests. RESULTS: The TH-positive axons are arranged in groups and are located in the endoneurium. No isolated sympathetic fibers were found in the peri- and epineurium. TH-positive axons were present on the arterial walls including the smallest arterioles. Proximal to the wrist, the median nerve has more sympathetic fibers than the ulnar nerve. The number, however, of the fibers was the same in each fascicle. A comparison of the digital nerves shows significant differences only between the radial nerve of the thumb and the ulnar nerve of the ring finger and between the radial nerve of the index finger and the ulnar nerve of the little finger. CONCLUSION: Although the median nerve proximal to the wrist has on average 20 fascicles and the ulnar nerve only 14, the number of fibres in each fascicle is the same. Therefore, based on the present study we conclude that there is no significant difference in the sympathetic fiber distribution of the two nerves.
Primary breast lymphoma generally is a rare disease. We present a case of a low-grade mucosa-associated (MALT) lymphoma of the breast in a 32-year-old woman, a distinctive type of localized non-Hodgkin's lymphoma (NHL), which is very seldom located in the breast. We performed differential diagnosis and radiological-pathological correlation with regard to typical microscopic criteria and clinical relevance that apply for that special entity.
We aimed to evaluate whether the histopathologic variability of fibroadenomas accounts for their varied appearance in contrast enhanced power Doppler (PD). Forty patients with fibroadenomas (aged 19 to 61 years) underwent power Doppler ultrasound (US) prior to and following IV bolus injection of a microbubble contrast agent. A 3-min computer-assisted assessment of the color pixel density (CPD) was used for objective evaluation of the increase in color Doppler signals. Enhancement characteristics were correlated to histopathologic features of microvessel density and epithelial hyperplasia, patient's age, tumor size, use of exogenous hormones and menopausal status. Epithelial hyperplasia was diagnosed in 19 patients. Compared to baseline values, patients with epithelial hyperplasia showed a significant increase in mean CPD following contrast media administration (p < 0.01). There was a significant correlation to patient's age (p < 0.0001) and tumor size (p < 0.0001), but not to the use of exogenous hormones and menopausal status. Microvessel counts did not show a significant correlation to CPD at baseline (p = 0.07) or with CPD on contrast enhanced PD (p = 0.13), or with patient age (p = 0.43) or tumor size (p = 0.34). Intratumoral epithelial hyperplasia, primarily occurring in young patients, may contribute to the differential diagnostic overlap in some fibroadenomas and thus limit the ability of PD to distinguish between benign and malignant masses on the basis of enhancement characteristics.
The monoclonal antibodies L26 (CD20) and CD79a are very useful reagents for the immunohistochemical assessment of B-cell lineage in lymphoproliferative disorders. Although very few CD20-positive peripheral T-cell lymphomas (PTL) have been reported, comprehensive analyses of CD79a reactivity in extranodal PTL and NK/T-cell lymphomas have not been performed previously. This study investigated CD79a (clone JCB117) and CD20 reactivity in 94 extranodal non-B-cell lymphomas (enteropathy-type intestinal T-cell lymphoma [n = 52], nasal NK/T-cell lymphoma [n = 11], and primary cutaneous PTL [n = 31]) and in 17 cases of nodal PTL, unspecified. In four cases (enteropathy-type intestinal T-cell lymphoma [n = 3] and nasal NK/T-cell lymphoma [n = 1]), the majority of tumor cells stained for CD79a (all CD20 negative) and one cutaneous PTL, unspecified, was CD20 positive (CD79a negative). Extensive immunophenotyping and polymerase chain reaction-based molecular analyses revealed that all five B-cell marker-positive extranodal lymphomas had a cytotoxic phenotype and did indeed represent monoclonal peripheral T-cell proliferations. To minimize the risk of misinterpretation of lymphoma cell lineage, especially in cases of extranodal, lymphoproliferative disease, we suggest the use of both CD79a and CD20 in combination with a panel of antibodies reactive to T cells, such as betaF1 and CD5, and to T cells and NK cells, such as CD3, CD2, CD56, and TIA-1.
A program of computer-assisted texture analysis was applied to evaluate its usefulness for objective description of changes in tumor architecture due to primary medical treatment in patients with locally advanced breast cancer. Changes in values of parameters of the statistical pattern recognition technique were compared to ultrasonographically depictable, subjectively recorded changes in echogenicity and echotexture (brightness, homogeneity) and reviewed with regard to histopathologic evaluation of tumor regression. Characteristic trends of defined quantitative texture parameters (mean gradient, mean gray value, contrast from the co-occurrence matrix) corresponded to visually depictable changes of the B-mode image and underlying histopathologic changes. The results indicate that quantitative texture analysis may aid in noninvasive monitoring of tumor response to neoadjuvant chemotherapy.
So far, reproducible histomorphologic and immunological criteria to distinguish clinicopathologic subtypes of blastic peripheral B-cell non-Hodgkin's lymphoma (BBCL), especially centroblastic (cb) and immunoblastic (ib) lymphomas, for daily diagnostic use are still lacking. Therefore, we correlated the cytogenetic findings in 126 patients with BBCL with histopathologic diagnoses. Subclassification of cb and ib lymphomas relied on the criteria defined in the updated Kiel classification; these subtypes are also listed in the Revised European-American Lymphoma (REAL) classification and in a preliminary report on the newly established World Health Organization classification, to investigate their clinical significance. Moreover, we performed a multivariate analysis to compare the prognostic significance of cytogenetic findings with the International Index. There were significant differences in the frequency of chromosome aberrations between different BBCL subtypes: t(8;14) was predominantly present in Burkitt's lymphomas, t(14;18) in centroblastic lymphomas, deletions in 8q and 14q, changes of 4q and losses of chromosome 10 in immunoblastic lymphomas; t(11;14) was restricted to blastoid mantle cell lymphomas and associated with a poor prognosis. In cb lymphomas, deletions in 1q42-qter, duplications in 1q23-32, trisomy 5, and changes of 15q were identified as independent prognostic factors. In ib lymphomas, changes of 7q and 8q had stronger impact on survival than the International Index. These findings underline that Burkitt's, cb, ib, and blastoid mantle-cell lymphoma are biologically distinct and clinically relevant entities and that cytogenetic findings can be helpful to subtype BBCL.
Mucosa-associated lymphoid tissue (MALT) lymphomas most frequently involve the gastrointestinal tract and are the most common subset of extranodal non-Hodgkin lymphoma (NHL). Here we describe overexpression of BCL10, a novel apoptotic signalling gene that encodes an amino-terminal caspase recruitment domain (CARD), in MALT lymphomas due to the recurrent t(1;14)(p22;q32). BCL10 cDNAs from t(1;14)-positive MALT tumours contained a variety of mutations, most resulting in truncations either in or carboxy terminal to the CARD. Wild-type BCL10 activated NF-kappaB but induced apoptosis of MCF7 and 293 cells. CARD-truncation mutants were unable to induce cell death or activate NF-kappaB, whereas mutants with C-terminal truncations retained NF-kappaB activation but did not induce apoptosis. Mutant BCL10 overexpression might have a twofold lymphomagenic effect: loss of BCL10 pro-apoptosis may confer a survival advantage to MALT B-cells, and constitutive NF-kappaB activation may provide both anti-apoptotic and proliferative signals mediated via its transcriptional targets.
The topography of the nerve of Henle was reviewed. Fifty-two human cadaveric upper extremities were studied. In 30 (58%) the nerve was well defined; in 22 (42%) its origin from the ulnar nerve was unidentifiable. The palmar cutaneous branch of the ulnar nerve separated from the ulnar nerve 5 to 11 cm distal to the medial epicondyle of the humerus to divide into its terminal branches in the distal forearm. Four patterns were detected: ulnar, radioulnar, vessel-related, and radial. These shared a consistent vascular branch, which sent 2 branches to the ulnar artery just proximal to the distal ulnar tunnel. Using a tyrosine hydroxylase antibody-based immunohistochemistry technique the nerve was shown to carry sympathetic fibers. Motor fibers were ruled out with Karnovsky's stain, which was used in combination with the tyrosine hydroxylase method in 10 specimens.
OBJECTIVE: To investigate the production of cytokines by T cells in patients with rheumatoid arthritis (RA), reactive arthritis (REA) and osteoarthritis (OA). METHODS: The lymphokines interleukin (IL)-2, IL-4, interferon gamma (IFN-gamma) and tumour necrosis factor beta (TNF-beta), as well as the monokines IL-1, IL-6 and TNF-alpha, were measured by immunoassays in sera and synovial fluid (SF) from patients with RA, REA and OA. In addition, cytokine expression was studied by immunohistochemistry in synovial membrane tissue sections from patients with RA and OA. RESULTS: Almost 60% of RA sera contained at least one of the cytokines investigated, though in low concentrations, whereas cytokines were generally not detectable in sera from REA and OA patients. In contrast, cytokines were found in virtually all SF; thus, the majority of SF from RA patients contained IFN-gamma (median level 17 pg/ml) in addition to the monokines IL-6 (4700 pg/ml) and TNF-alpha (157 pg/ml). IFN-gamma and IL-6 (but not TNF-alpha) were also frequently measured in SF from REA patients, whereas OA samples typically contained only IL-6. Immunohistochemical analysis of tissue sections from RA patients revealed lymphokine expression in 0.1-0.3% of T cells, particularly IL-2 and IFN-gamma, and to a lesser extent also IL-4. Interestingly, the expression of TNF-alpha and IL-6 by synovial T cells was also observed. The majority of cytokine-expressing T cells were CD4-positive T-helper cells typically found in perivascular areas, whereas cytokine-producing CD8-positive T cells were found distributed throughout the synovium. As expected, in specimens from OA patients, T cells were much less abundant and expression of cytokines could not be detected. CONCLUSION: These data clearly demonstrate production of cytokines by T cells in RA synovial tissue, indicating that activated T cells play a role in the pathophysiological events of RA.
We report a case of idiopathic myelofibrosis with trisomy 13 as the sole clonal aberration, as demonstrated by metaphase cytogenetics. The clinical course was especially poor in this case, with death in blast crisis occurring within two weeks from diagnosis. The dismal outcome bears striking similarity to two previous cases of idiopathic myelofibrosis and trisomy 13 reported in the literature. Therefore trisomy 13 may be a predictor of a rapidly fatal outcome in this otherwise indolent disease. Fluorescence in situ hybridisation (FISH) with a chromosome 13 specific probe may enhance the detection of this aberration, since only 50% of cases of idiopathic myelofibrosis are karyotyped successfully using conventional techniques.
We studied 42 intestinal T-cell lymphomas (ITLs) to establish a simple and reproducible classification. The ITLs were classified into pleomorphic small cell (n = 3), monomorphic medium-sized cell (n = 10), pleomorphic medium and large cell (n = 17), immunoblastic (n = 1), and anaplastic large cell (n = 9) lymphomas. Two cases were unclassifiable. Overlapping histologic features were noted between some cases and also within the same tumor and between multiple lesions of the same patient. Histologic evidence of enteropathy was present in most cases. The ITLs expressed cytoplasmic CD3 and antigens associated with cytolytic function (TIA-1, granzyme B), but not CD4 and CD5. Six of the 10 monomorphic medium-sized cell lymphomas were CD56+ T-cell lymphomas. Because of the histologic heterogeneity in some ITLs, we suggest a classification system with 2 main categories: (1) small to medium-sized cell, comprising pleomorphic small and monomorphic medium-sized cell lymphomas; and (2) large cell, comprising the remaining subtypes. The differential diagnosis includes B-cell lymphomas, tumors of histiocytic origin, anaplastic carcinoma, and malignant melanoma.
The tissue concentrations of urokinase-type plasminogen activator (u-PA), urokinase-type plasminogen activator receptor (u-PAR), plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were investigated by an ELISA technique in normal and malignant samples of the prostate from 24 patients undergoing radical prostatectomy for organ-confined prostate cancer. The median concentration of u-PA was significantly higher in cancerous than in normal prostate tissue (p = 0.006). No significant increase of u-PAR, PAI-1 and t-PA was found in cancer tissue in comparison with the benign samples (p > 0.05). Assessment of the relationship between fibrinolytic proteins and DNA ploidy revealed an increased u-PA, u-PAR and PAI-1 in diploid prostate cancer as compared with the normal controls. However, in aneuploid cancer u-PA remained high but u-PAR and PAI-1 were decreased. This led to a higher local concentration of u-PA in aneuploid samples than in normal prostate and in diploid prostate cancer. No alteration of median t-PA was found in benign prostate or in diploid or aneuploid prostate cancer. The altered expression of u-PA, u-PAR and PAI-1 in diploid and aneuploid prostate cancer suggests a possible role of fibrinolytic proteins in the different biologic behavior of tumors, and may be one explanation for the higher metastatic potential of aneuploid tumors.
A 53-year old woman developed slowly progressive dysarthria, mild enlargement of the tongue and dysphagia since 1 year ago. All neurological differential diagnoses that could have explained the bulbar symptoms were excluded. The swallowing sequence was pathologic and immunoglobulins were markedly reduced. A bone marrow biopsy revealed light chain myeloma grade III. Amyloid deposits were found in the tongue but not in the kidneys. Oro-pharyngeal amyloidosis was held responsible for the described complaints. It is concluded that multiple myeloma must be considered in the differential diagnosis of bulbar paralysis and that biopsy of specific lesions is necessary to confirm local amyloidosis.