Biomedical subjects

H M Kvasnicka

Publications and source records attributed to H M Kvasnicka.

At least 91 records · Page 5Linked to original sources

PubMed1999

Bone marrow histopathology in chronic myelogenous leukemia (CML)--evaluation of distinctive features with clinical impact.

Bone marrow features in stable-phase chronic myelogenous leukemia (CML) are characterized by a striking heterogeneity which is determinable by appropriate means including representative pre-treatment trephine biopsies, immunohistochemistry and morphometry. Cell lineages involved to a variable extent consist not only of neutrophil granulopoiesis, but include also megakaryocytes, erythroid precursors, resident macrophages and lymphocytes. Moreover, the stromal compartment, in particular reticulin and collagen fibers, plays a pivotal role in the disease process. Following morphometric analysis significant correlations may be calculated between histological parameters and clinical-laboratory findings. Relevant interactions are detectable between number of megakaryocytes and their precursors with fiber density. This findings is in line with the close functional relationships between megakaryopoiesis and fibroblasts regarding the complex pathomechanisms of myelofibrosis. Moreover, other correlations are observable between reduction of erythropoiesis or increase in fibers with clinical features like anemia, percentages of myelo- and erythroblasts in the peripheral blood, spleen size or LDH level. These variables are in keeping with more advanced stages of CML which indicate a transition to myeloid metaplasia and thus exert a significant impact on survival. Consequently, the different risk profiles of patients are determined by both clinical and morphological parameters of predictive value. Regarding the latter, extent of myelofibrosis, amount of erythroid precursors and numbers of myeloerythroblasts in the peripheral blood are significantly associated with prognosis. For this reason, it should be mandatory to enter morphological criteria into prospective clinical trials on CML, not only for diagnostic purpose, but also for a proper evaluation of different survival patterns.

Animals↗

PubMed1999

Clinicopathological diagnosis and differential criteria of thrombocythemias in various myeloproliferative disorders by histopathology, histochemistry and immunostaining from bone marrow biopsies.

Differentiation of essential thrombocythemia (ET) from thrombocythemias occurring in various subtypes of chronic myeloproliferative disorders (MPDs) is controversial, because of the lack of uniform clinical and morphological criteria. A retrospective clinicopathologic study was performed on 375 patients presenting with a MPD and a platelet count exceeding 500 x 10(9/)l. For comparison 35 patients with reactive thrombocytosis (RT) and five patients with a myelodysplastic syndrome (MDS-5q(-) syndrome) were enrolled into this study. In addition to a complete clinicopathological work-up, procedures included histochemical and immunological staining techniques and morphometry of bone marrow biopsies for proper evaluation of megakaryocytes (CD61) and erythroid precursors (Ret40f). Because of the high patient's age on admission, relative survival rates with corresponding disease-specific loss of life expectancy were calculated. Analysis of clinical and morphological characteristics, in particular megakaryopoiesis revealed features which enabled a clear-cut distinction between thrombocythemias in MPDs and thrombocythemic states in MDS. This rationale proved to be most important for the diagnostic discrimination of the 33 patients with initial (prefibrotic) stages of idiopathic myelofibrosis (IMF) from ET (40 patients). A new set of relevant criteria for the diagnosis of IMF with special regard to early stages and its distinction from ET has been proposed. Hemorrhagic episodes were more frequently observed in ET than in thrombocythemias associated with polycythemia vera (PV). Computation of specific loss of life expectancy revealed two extremes: thrombocythemia in CML (81%) and ET (3%), whereas thrombocythemias in PV and IMF did not show a significantly different life loss (19-22%). The revised criteria for ET, PV and IMF are reliable by taking histopathological features from bone marrow biopsies into consideration, particularly for the diagnosis of ET and its differentiation from thrombocythemias as a presenting symptom accompanying the various subtypes of MPDs.

Aged↗

PubMed1998

Detection of the bcr/abl gene in bone marrow macrophages in CML and alterations during interferon therapy--a fluorescence in situ hybridization study on trephine biopsies.

A fluorescence in situ hybridization (FISH) study was performed on trephine biopsies of the bone marrow in chronic myelogenous leukaemia (CML) to evaluate the bcr/abl translocation in macrophages before and during interferon (IFN) therapy. Mature macrophages and osteoclasts were identified by the monoclonal antibody PG-M1, which recognizes a fixative-resistant epitope of the CD68 molecule. In contrast to a control group, in 145 of 479 (30 per cent) macrophages of the CML bone marrow, a positive fusion signal was found, together with corresponding translocation sites in the surrounding myeloid cells. In patients following IFN treatment for approximately 12 months and with haematological/cytogenetic remission by clinical standards, this number was reduced to 10 of 136 (9 per cent) macrophages. In addition, the few multinucleated osteoclasts of the untreated CML bone marrow displayed positive translocation spots. This finding supports the hypothesis that stromal macrophages and osteoclasts are of haematogenic stem cell origin. Moreover, clinical remission and reduction of bcr/abl-positive macrophages under IFN therapy lend support to the hypothesis that the presence of malignant stromal macrophages may contribute to the selective expansion of leukaemic precursors and the suppression of normal haematopoiesis in CML.

Antigens, CD↗

PubMed1998

Effect of IFN-alpha on normal human hematopoiesis: an immunohistochemical and morphometric study on trephine biopsy specimens.

To elucidate the effects of interferon-alpha (IFN-alpha) on normal human bone marrow in vivo, an immunomorphometric study was performed using trephine biopsy specimens without hematopoietic pathology. Samples were derived from patients with mycosis fungoides but no marrow involvement, who were undergoing low-dose IFN-alpha treatment. Parameters included density of reticulin (argyrophilic) fibers, CD61+ megakaryocytes, PGM1+ macrophages, the GSA-I lectin-expressing (activated) macrophage subpopulation, proliferative activity (PCNA staining), and apoptosis. Following IFN-alpha therapy (3 x 3 x 10(6) U/week between 6 and 21 months), morphometric evaluation of sequential bone marrow examinations revealed a significant increase in the number of megakaryocytes and the amount of reticulin fibers. Additionally, there was an overall decrease in PCNA+ cells, accompanied by a reduction in the incidence of apoptotic bodies. On the other hand, total number of macrophages and their activated subfraction remained unchanged. Opposed to in vitro findings, a fibrogenetic capacity of IFN-alpha associated with megakaryocyte growth was detectable. Moreover, contrasting with effects of IFN-alpha treatment in chronic myelogenous leukemia, the incidence of apoptosis was significantly reduced. This feature was assumed to contribute to a maintenance of steady-state hematopoiesis expressed by a nonaltered bone marrow cellularity in our specimens.

Biopsy↗

PubMed1998

Impact of clinical and morphological variables in classification and regression tree-based survival (CART) analysis of CML with special emphasis on dynamic features.

To determine parameters of predictive value in CML, a retrospective clinico-pathological study was performed. This included laboratory data and (pretreatment) bone marrow biopsies of 120 patients with a monotherapy by busulfan (BU) and 50 patients with interferon-alpha 2b (IFN) treatment. Median survival in the BU group was 39 months and in the IFN-treated patients 65 months. Morphological features (CD61-positive megakaryocytes, argyrophilic fibres, pseudo-Gaucher cells) were evaluated by morphometry. Additionally, we measured the incidence of apoptosis (in situ end-labelling technique) and the expression of the proliferating cell nuclear antigen (PCNA). The ratio between the proliferative and apoptotic cell fraction was coined leukaemia turnover index (LTI). In order to estimate the impact of clinical and various morphological as well as dynamic features of prognostic significance, a multivariate analysis was carried out using the classification and regression tree approach (CART). Discrimination of single disease parameters revealed that fibrosis remained the most significant variable for survival in both therapeutic groups. Indicators of myeloid metaplasia such as occurrence of erythro-normoblasts and/or splenomegaly were important clinical parameters for prognosis. Inclusion of morphological as well as dynamic disease features in risk classification resulted in a substantial improvement of prognostic efficiency compared to other predictive scores which could be demonstrated by means of ROC-analysis.

Adult↗

PubMed1997

Prognostic factors in idiopathic (primary) osteomyelofibrosis.

BACKGROUND: Prognostic variables for idiopathic (primary) osteomyelofibrosis (IMF) are ill-defined because of the lack of large control studies based on uniform diagnostic criteria. METHODS: A retrospective clinicopathologic study was performed on 250 consecutively recruited patients (115 males and 135 females) with an established diagnosis of IMF. In contrast to previous studies, the current study cohort encompassed the full spectrum of initial to advanced stages of the disease process according to laboratory data and particularly histology. Because of the relatively high patient age on admission (median, 66.5 years), relative survival rates with corresponding life expectancies and disease specific life loss were calculated. Moreover, a classification and regression tree (CART) analysis was performed to segregate the study patients into subgroups with significantly different prognosis. RESULTS: Analysis of the life expectancy and the proportion of deaths attributable to IMF showed a global reduction in life expectancy of 31%. Further calculation disclosed a consistently greater impact of disease in older patients. Age, hemoglobin level on admission, and leukocyte and thrombocyte counts remained as the most relevant parameters for prognosis in multivariate consideration (CART analysis) and facilitated a clear-cut separation into three risk groups. The life expectancy of low risk patients was approximately 10 times higher than that of high risk patients (22.07 years vs. 2.25 years). CONCLUSIONS: These results are in keeping with the assumption that features signaling bone marrow insufficiency are associated with a worsening of survival. Generalization, indicated by myeloid metaplasia, can occur at every stage, even in so-called hypercellular phases of IMF. Conversely, myelofibrosis alone is not necessarily predictive of poor survival.

Analysis of Variance↗

PubMed1997

Apoptosis and proliferation (PCNA labelling) in CML--a comparative immunohistological study on bone marrow biopsies following interferon and busulfan therapy.

A comparative morphometric analysis was performed on smears and trephine biopsies of normal bone marrow and in chronic myelogenous leukaemia (CML) to assess the effects of therapy on apoptosis and cell proliferation. The in situ end-labelling (ISEL) technique was used for the demonstration of programmed cell death, in combination with the monoclonal antibody PG-M1 to identify macrophages. Cell proliferation was evaluated by employing the monoclonal antibody PC10 directed against proliferating cell nuclear antigen (PCNA). In CML (48 patients), significantly higher rates of apoptosis were observed than in normal bone marrow (smears, frozen sections, and paraffin-embedded samples) of 15 patients. In contrast, the PCNA labelling index of CML was not different from controls. In bone marrow tissue derived from CML patients, about 36 per cent of apoptotic bodies were ingested with CD68-positive macrophages. Study of the histotopographical distribution of labelled cells revealed that in CML, in contrast to the normal bone marrow, programmed cell death and PCNA activity were concentrated along the paratrabecular generation zone. In 28 patients with CML treated with interferon (IFN), sequential trephine biopsies displayed a significant enhancement of apoptosis which was associated with a decrease in PCNA reactivity. In contrast to this finding, no such alterations could be observed in 24 patients who received busulfan (BU) monotherapy. This study furthers the understanding of cell kinetics in CML. IFN therapy induces apoptosis and suppresses cell proliferation. The rate of programmed cell death prior to therapy and the extent of IFN-triggered apoptosis exert a significant predictive impact on survival. In this study, ISEL-positive (apoptotic) cells and bodies do not correspond to unscheduled cell repair as detected by PCNA immunoreactivity.

Adult↗

PubMed1997

Fluorescence in-situ hybridization (FISH) reveals that in chronic myelogenous leukaemia (CML) following interferon-alpha therapy, normalization of megakaryocyte size is associated with the loss of bcr/abl translocation.

AIMS: In addition to predominant granulocytic proliferation, bone marrow morphology in Philadelphia chromosome positive (Ph1+) CML is characterized by atypical dwarf or microforms of megakaryocytes. However, following therapy with interferon-alpha 2b (IFN), these micromegakaryocytes occur less frequently. The purpose of this study was to elucidate whether the reappearance of normal megakaryocytes may be associated also with a reduction of the bcr/abl-positive cell clone. METHODS AND RESULTS: Fluorescence in-situ hybridization (FISH) technique in combination with immunomorphometry (CD61) was performed on trephine biopsies. A total of 311 CD61-positive megakaryocytes, including precursors and atypical microforms, were evaluated in pre-treatment specimens derived from 11 patients with Ph1+ CML. A specific fusion site marking the bcr/abl translocation was found in 87% of megakaryocytes which showed a size of 169 +/- 35 microns2. In untreated patients, atypical microforms (size 200 microns2) were observed in 66% of the total megakaryocytic population. Following IFN therapy 369 megakaryocytes could be analysed in sequential examinations and were found to display a significant decrease (63%) in positive fusion signals. In addition there was also a significant enhancement in average size (252 +/- 66 microns2) reflecting a reduction in the number of micromegakaryocytes (43%). These findings were particularly conspicuous in three patients with a major to complete cytogenetic remission. CONCLUSIONS: A normalization of megakaryocyte size following IFN therapy in CML is significantly associated with a loss of the bcr/abl translocation site and therefore indicates a (partial) recovery of normal haematopoiesis.

Fusion Proteins, bcr-abl↗

PubMed1997

Incidence of apoptosis in HIV-myelopathy, myelodysplastic syndromes and non-specific inflammatory lesions of the bone marrow.

Myelodysplastic syndromes, AIDS-related myelopathy and non-specific inflammatory reactions (mostly rheumatoid myelitis) are characterized by normo- to hypercellular bone marrow, but frequently display cytopenias in the peripheral blood. In the current study we have addressed the question whether this situation reflects an increased programmed cell death in haemopoiesis. For this purpose, the in situ end-labelling technique was applied to formalin-fixed and paraffin-embedded trephine biopsies derived from patients and a control group without any haematological disorder. Results were evaluated by morphometry. Significantly more apoptotic cell death was observed in the haemopoietic marrow of patients with either disease. Using double-immunohistochemistry with the monoclonal antibody PG-MI (CD68), we were able to demonstrate that approximately one third of the apoptotic cells were ingested by macrophages. Our findings are in keeping with previously published data that postulated increased frequencies of macrophages in these disorders as well as raised serum levels of TNF-alpha.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Apoptosis (programmed cell death) in idiopathic (primary) osteo-/myelofibrosis: naked nuclei in megakaryopoiesis reveal features of para-apoptosis.

There is general agreement that apoptosis (programmed/physiological cell death) plays an important role in regulating normal hematopoiesis and that so-called naked nuclei (NN) present end stages of megakaryopoiesis. Using in situ end-labeling techniques (ISEL), a morphometric analysis was performed on bone marrow trephine biopsies repeatedly derived from patients with idiopathic (primary) osteo-/myelofibrosis (IMF). The purpose of this study was to quantify apoptosis and to elucidate its relationship with NN of megakaryopoiesis. Moreover, evolution of this phenomenon during progression of myelofibrosis (assessed by morphometry of silver-stained sequential biopsies) and its predictive value were investigated. In IMF, morphometric measurements revealed a rate of ISEL-positive cells that was significantly higher than previously published data on the normal bone marrow and in patients with acute myeloblastic leukemia, but lower than in the myelodysplastic syndromes. However, NN with their tightly packed (nuclear) lobules and condensed chromatin were not reactive. Statistical evaluation failed to show a significant correlation between incidence of apoptotic cells and fiber density or an increase in this feature associated with progression of fibro-osteosclerotic marrow changes and prognosis. The failure of NN to react in ISEL implicates an absence of DNA fragmentation characteristic of apoptosis. For this reason our findings are in keeping with the assumption that NN are compatible with para-apoptosis.

Apoptosis↗

PubMed1997

Clinicopathological impact of the interaction between megakaryocytes and myeloid stroma in chronic myeloproliferative disorders: a concise update.

In this report an attempt has been made to discuss some of the issues pertinent to myelofibrosis complicating chronic myeloproliferative disorders (CMPDs) that are significantly associated with megakaryocyte function. In this context, biochemical, clinical and particularly morphological features were reviewed. Morphological findings based on elaborate techniques were in keeping with the assumption that in chronic myeloid leukemia (1) the number of CD61-positive megakaryocytes, and in particular their precursors were the parameters most closely associated with myelofibrosis (2) an increased content of reticulin fibers in follow-up biopsies significantly correlated with laboratory data indicative of a high tumor burden (anemia, peripheral blasts, hepatosplenomegaly) and thus a more advanced stage of the disease process (3) even a slight increase in reticulin, i.e. doubling of the normal fiber density was associated with a worse prognosis independent of therapeutic regimens given (4) Dynamics of myelofibrosis was significantly influenced by treatment. In this context, calculation of the myelofibrosis progression index (MPI) revealed a higher score following interferon therapy compared with busulfan. In addition, in idiopathic myelofibrosis (5) the evolution of myelofibrosis was unpredictable and according to the MPI, progression occurred at a relatively low rate (6) proliferation and dilatation of sinusoids accompanying intravascular hematopoiesis and collagen type IV deposits were predominant features in later (fibro-osteosclerotic) stages in the course of disease (7) transmural migration of megakaryocytes demonstrated by three dimensional reconstruction revealed a mole-like tunneling through the thickened sinusoidal wall. A very careful assessment of the numerous correlations between bone marrow features and laboratory data will allow clinicians and pathologists to gain a better insight into the mutual relationships between hematological and morphological findings in CMPDs.

Cell Communication↗

PubMed1996

Effect of interferon therapy on bone marrow morphology in chronic myeloid leukemia: a cytochemical and immunohistochemical study of trephine biopsies.

The effect of interferon (IFN) therapy on bone marrow features in chronic myeloid leukemia (CML) has been studied on successive trephine biopsies (mean interval 13 +/- 8 months) by cytochemical and immunohistochemical methods in combination with morphometry and in comparison with a control group of patients who received monotherapy by busulfan (BU). Following IFN administration (IFN-alpha frequently in combination with IFN-gamma), there was a decrease in neutrophil granulopoiesis accompanied by a significant expansion of erythroid precursors and increased numbers of hemosiderin-laden macrophages. These changes corresponded with the hematologic response in 21 of the 25 patients investigated. Numbers of megakaryocytes and reticulin/collagen fiber density increased during treatment. Most conspicuously, in responding patients atypical micromegakaryocytes, usually characterizing CML, were partially replaced by normal-sized cells of this lineage. These features are in keeping with the assumption of a reappearance of the normal hematopoietic cell clone as the result of IFN therapy, which was not found in the BU-treated control group. On the other hand, a relevant subpopulation of micromegakaryocytes (about 30%) was still maintained. This result probably relates to the failure to improve myelofibrosis more effectively. Analysis of cell proliferation (proliferating cell nuclear antigen-PCNA) and apoptosis (in situ end labeling) revealed a reduction in PCNA labeling and increased numbers of cells undergoing programmed death. Identification of the activated subset of macrophages (alpha-D-galactosyl residues expression) by appropriate lectin histochemistry disclosed an increase in the number of GSA-I binding cells. These findings were exclusively limited to IFN administration and reflect an inhibitory effect of IFN on cell proliferation and stimulation of programmed cell death. The latter phenomenon probably results in increased phagocytosis of clonally transformed myeloid cells by GSA-I-positive (activated) macrophages.

Adult↗

PubMed1996

Apoptosis in acute myeloblastic leukemia: follow-up study on trephine biopsies of the bone marrow.

A clinicopathological study on 87 adult patients presenting with "de novo" acute myeloblastic leukemia (AML) was performed to assess the rate of apoptosis before and during chemotherapy and its predictive impact on clinical course. Evaluation included trephine biopsies of the bone marrow and the situ end-labeling technic (ISEL) for the identification of programmed cell death in large and intact hemopoietic tissue areas. In comparison with a control group of 21 patients without any hematological disorder, morphometric analysis revealed no significantly different numbers of apoptotic cells in AML at the onset of disease and following sequential examinations at intervals ranging between 10 to 19 months. Moreover, the incidence of programmed cell death was not associated with the subgroups of the FAB classification and statistics failed to show a relationship with survival or remission status. In conclusion, these findings are in keeping with the assumption that apoptosis occurs with the same frequency in recovering normal hemopoiesis in complete or partial remission, in manifest AML and relapse. In the latter conditions, enhancement of proliferation is not associated with an increase in the apoptotic index.

Acute Disease↗

PubMed1996

Idiopathic primary osteo-myelofibrosis: a clinico-pathological study on 208 patients with special emphasis on evolution of disease features, differentiation from essential thrombocythemia and variables of prognostic impact.

A retrospective clinico-pathological study was performed on 208 consecutively recruited patients (94 males, 114 females, median age 67 years) with idiopathic (primary) osteo-/ myelofibrosis (IMF). According to bone marrow histology (cellularity) as well as extent (semiquantitative grading) and quality (reticulin/collagen) of myelofibrosis, stages of the disease process were determined. At closure of this study (observation time 65 months) 133 patients were dead and 75 alive and median survival was 56 months. The wide spectrum of clinical signs and symptoms and laboratory data on admission was reflected by a corresponding variety of histological features. Significant differences of hematological values could be calculated between patients with or without early reticulin fibrosis (fiber scores 0 and 1) and advanced fibro-osteosclerotic stages (fiber scores 2 and 3). Evolution of disease features was elicited by longitudinal follow-up studies and sequential bone marrow biopsies. Morphometric assessment of fiber density in patients without preceding chemotherapy revealed an unpredictable and varying progression of myelofibrosis associated with alterations of certain laboratory parameters (hemoglobin level, spleensize, thrombocytosis). Differentiation from essential (primary) thrombocythemia (ET) was required in 25 patients who fulfilled the postulated diagnostic criteria. In fact, this group was consistent with hypercellular, early stages of IMF without relevant reticulin fibrosis and an excessively raised platelet count (> or = 1000 x 10(9)/1). Discrimination was only feasible by regarding histology carefully, particularly abnormalities of megakaryopoiesis and follow-up data. Parameters of predictive value indicating a significant loss in life expectancy in comparison with a sex- and age-adjusted normal population included: age (> or = 60 years), hemoglobin levels (< or = 10 g/dl), thrombocyte count (< or = 600 x 10(9)/1) and the presence of myeloblasts and promyelocytes. Statistical analysis disclosed that in the so-called early stages of IMF without relevant myelofibrosis, findings indicative for extramedullary hemopoiesis or generalization of the disease process exerted an unfavourable influence on survival.

Aged↗

PubMed1996

Interferon therapy, but not busulfan restores normal-sized megakaryopoiesis in CML--a comparative histo- and immunomorphometric study.

To assess possible alterations of megakaryocytes associated with interferon (IFN) and busulfan (BU) therapy of Ph(1+)-CML, an immunohistochemical and morphometric study was performed on trephine biopsies of the bone marrow taken before and at varying intervals during treatment. For the identification of megakaryopoiesis and its endoreduplicative activity the monoclonal antibodies CD61 (anti-platelet glycoprotein IIIa) and PC10 raised against proliferating cell nuclear antigen (PCNA) were used. We compared 60 specimens from 20 patients following IFN alpha-2b administration (in combination with IFN gamma in seven patients) with 57 specimens from 22 patients after monotherapy with BU. A close correlation with clinical follow-up studies revealed that in the IFN-treated group the prevalence of atypical micro-megakaryocytes, usually characterizing CML, was conspicuously reduced in repeatedly taken bone marrow samples. Initially, even an increase in size which was levelled to normal values during maintenance therapy was observed. These features were most prominently expressed in the 13 patients with a complete hematologic and/or partial cytogenetic response. Associated with this phenomenon was a significant enhancement of the PCNA-labelling index which indicated a stimulation of endoreduplicative (endomitotic) activity necessary for achieving normal size and ploidy. In the second group of patients treated by BU these changes were absent. For this reason, our findings are in keeping with the assumption that during IFN treatment, there is at least partial recovery and expansion of a putative normal (Ph1-) megakaryopoiesis. In conclusion, megakaryocyte morphology, i.e. normalization in size, is thought to be a useful indicator to evaluate the response to IFN in CML patients.

Adult↗

PubMed1996

Effects of interferon treatment on the macrophage population in the bone marrow of patients with Ph1+-CML.

In Ph1+-CML the abnormal function of bone marrow stroma was related to the presence of clonally transformed macrophages (MAs). Moreover, previous in vitro studies revealed that activation (phagocytosis, cytotoxicity) of MAs was associated with a pronounced increase in alpha-D-galactosyl residues on their membranes. Stimulation of this cell population has been shown to be easily accomplished by interferon (IFN) treatment. The latter caused an enhanced expression of binding sites for the lectin Griffonia simplicifolia isotype I-B4 (GSA-I), specific for this carbohydrate moiety. The present immuno- and lectinhistochemical study was designed to quantify MA subsets of the bone marrow in patients with Ph1+-CML under IFN therapy. For comparison a control group with monotherapy by busulfan (BU) was included. Identification of the total MA population was carried out by a monoclonal antibody against CD68 (PG-M1) and for the characterization of its activated fraction, the lectin GSA-I was employed. In both therapeutic groups morphometric analysis revealed a conspicuous increase in PG-M1-positive MAs in sequential trephine biopsies. However, following IFN therapy the relative amount of the GSA-I fraction was maintained or even increased and accompanied by enhanced apoptosis. On the other hand, BU generated a significant reduction of this subpopulation and the number of apoptotic cells as well. This finding is probably related to the immunomodulatory activity of IFN associated with MA activation and secretion of biogenic mediators. These are thought to belong partly to the so-called tumor necrosis factor superfamily, which is known to stimulate programmed cell death (apoptosis).

Adolescent↗

PubMed1995

Clinical and histological features retain their prognostic impact under interferon therapy of CML: a pilot study.

In 55 patients with Ph1+ CML under interferon (IFN) monotherapy, an immunohistochemical and morphometric study on pretreatment bone marrow biopsies was performed to evaluate the prognostic impact of clinical as well as histological disease features. For identification of megakaryocytes we used the PAS stain and CD61 to calculate the subfraction of precursors (pro- and megakaryoblasts). Demonstration of macrophages and their different subsets was carried out by PG-M1 (CD68) and the GSA-1 lectin. The erythroid precursors were stained by Ret40f (anti-glycophorin C). Density of argyrophilic (reticulin plus collagen) fibers was determined by applying Gomori's silver impregnation method. Clinical variables like state of hematological response to IFN administration, age, spleen and liver size, myeloblasts plus promyelocytes, basophils as well as basophils and eosinophils exerted a predictive capacity by univariate statistical analysis. However, when entering these factors into previously published risk models, i.e., the so-called Sokal score and its modifications, to assess subgroups with different survival patterns or relative risk groups, a clear-cut discrimination was not feasible. Bone marrow features of prognostic value consisted of megakaryocytes and their precursors, fibers, and pro- and erythroblasts. Only when including histological variables into a formerly reported Cox model, could a significant separation of patients into the different categories or relative risk groups be computated. In conclusion, the present data emphasize the prognostic impact of histological parameters to be considered in all clinical trials on CML.

Adult↗

PubMed1995

Dual-energy X-ray absorptiometry at the lumbar spine in German men and women: a cross-sectional study.

A cross-sectional, population-based study of 238 randomly selected females and 224 males with German ethnic background (aged 20-80 years) was carried out to establish lumbar spine bone mineral density (BMD) values, using dual X-ray absorptiometry (DXA), for a German population. Comparison was made to the reference range provided by the manufacturer of the DXA equipment. No sex difference in peak spine BMD was found in our study (1.091 +/- 0.114 g/cm2 for males versus 1.070 +/- 0.113 g/cm2 for females, n.s.). Different patterns of bone loss could be detected in both sexes. In premenopausal women there was no significant correlation between age and BMD (y = 1.044 + 0.00047x, r = 0.03, P = 0.73) whereas reduction of female BMD at the spine was demonstrated in postmenopausal women (y = 1.189-0.0041x, r = -0.28, P = 0.01), underscoring the important role of the menopause for later manifestation of spinal osteoporosis in women. In contrast, in males we found no significant change of BMD with aging (y = 1.071-0.0007x, r = -0.08, P = 0.25). Employing commonly used exclusion criteria, BMD values of the study subjects were found mostly within the normal range of BMD. The major finding of our study was good concordance between female data of our study population and the reference data provided by the manufacturer. Clinically significant discrepancies between our data and the Hologic reference range for males could be detected. Our data on males (30-39 years of age) were up to 7% lower than those provided by the manufacturer, probably due to differences in sampling procedures.

Absorptiometry, Photon↗