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Biomedical subjects

B Frisch

Publications and source records attributed to B Frisch.

At least 37 records · Page 2Linked to original sources

Histologic, biochemical, and clinical parameters for monitoring multiple myeloma.

In a retrospective and prospective follow-up study from 1968 to 1989, bone marrow biopsy specimens, serum beta-2-microglobulin (SB2M) levels, and the clinical features of 251 patients with multiple myeloma (MM) and 28 patients with monoclonal gammopathy of undetermined significance (MGUS) were investigated. The main histologic variables (tumor cell type, tumor growth, tumor load, and fibrosis), SB2M level, serum thymidine kinase (STK) level, and various clinical parameters were analyzed to determine factors of value in monitoring the clinical phases of activity in MM. Our recently proposed prognostic strategy combining bone marrow histologic type, SB2M level, and signs of organ failure was tested for its ability to (1) diagnose the early and smoldering variants; (2) facilitate decisions on the time of initiation, the type and duration of initial induction therapy in the pretreatment phases (active and rapidly progressive phases); and (3) characterize variations in tumor regression and tumor-host interactions during chemotherapy (early treatment, plateau, relapse, transition, and refractory phases). The results indicate that this clinicopathologic monitoring combines information both on stage and aggressivity of MM and thus facilitates therapeutic decisions in the various clinical phases of MM.

Biomarkers, Tumor↗

Parameters affecting the immunogenicity of a liposome-associated synthetic hexapeptide antigen.

The effect of liposome association on the immunogenicity of the hexapeptide IRGERA was investigated. When administered in the absence of a carrier and adjuvant this peptide, which corresponds to a linear epitope located at the C-terminus of histone H3, was not immunogenic. When mice were immunized with the peptide covalently linked to the surface of small unilamellar vesicles containing monophosphoryl lipid A as adjuvant, a relatively long-lasting response with memory cell induction was observed. The anti-peptide antibodies raised in this way reacted with the cognate sequence in the native histone. In contrast, coupling of the peptide to the surface of large vesicles yielded both an IgM and IgG response of short duration whereas encapsulation of the free peptide in large vesicles was ineffective. These results indicate that with short synthetic peptides, liposomes provide a substitute for a carrier protein. However, an adjuvant has to be incorporated in the vesicles in order to obtain an efficient immune response. Such an approach may be useful for designing synthetic vaccines.

Adjuvants, Immunologic↗

Osteopenia, hematopoiesis, and bone remodelling in iliac crest and femoral biopsies: a prospective study of 102 cases of femoral neck fractures.

Cancellous microanatomy, bone remodelling, and hematopoietic tissue were studied in iliac crest and femoral neck biopsies taken intraoperatively in 102 consecutive patients with displaced intracapsular fractures. About half of the femoral biopsies had osteopenia, and most showed replacement of hematopoietic tissue by fat cells, with absence of osteoblasts and osteoclasts. In contrast, most of the iliac crest biopsies showed relatively less decrease in cancellous bone, while hematopoietic tissue and bone remodelling cells were present in approximately 75%. These results indicate that the iliac crest biopsy does not necessarily reflect cancellous microanatomy, hematopoietic tissue, and bone remodelling at other skeletal sites in any given patient.

Aged↗

Osteoporosis as the sole presentation of bone marrow mastocytosis.

Three (young) adults with severe generalized osteopenia and vertebral compression fractures were studied. Extensive clinical and laboratory investigations were not contributory. Undecalcified bone biopsies demonstrated multiple mast cell granulomas in the marrow in two patients and numerous mast cells diffusely distributed throughout the bone marrow in the third patient. Mast cells may serve as a pathogenic agent in osteoporosis. Therefore, we conclude that isolated skeletal mastocytosis without clinical evidence of mast cell mediator release should be sought in the evaluation of a patient with unexplained severe bone loss.

Adult↗

Comparison of bone marrow histology in early chronic granulocytic leukemia and in leukemoid reaction.

A retrospective study was performed on bone marrow biopsies of 50 untreated patients with leukemoid reactions (LR) and 50 untreated patients with early chronic granulocytic leukemia (CGL). A comparison was made between hematopoietic and adipose tissues, bone and its cells, as well as other stromal components in these two disorders. Histologic and histomorphometric analyses revealed significant differences in trabecular structure, in localization of fat cells, in numbers of sinusoids, capillaries and various stromal elements. No significant differences between LR and CGL were detected in the quantity of erythro- and granulocytopoiesis and of megakaryocytes, but these were smaller in CGL than in LR. This histologic and histomorphometric evaluation demonstrates that certain histologic features may serve as valuable aids in distinguishing LR from CGL.

Adipose Tissue↗

Bone marrow histology and serum beta 2 microglobulin in multiple myeloma--a new prognostic strategy.

Bone marrow biopsies of 720 patients with multiple myeloma (MM) were investigated from 1968-1989. Histologic variables were correlated with clinical parameters and survivals to determine prognostic factors. In 207 of these patients initial levels of serum beta 2 microglobulin (SB2M) were also measured for prognostic evaluation. Four tumour growth patterns were distinguished: interstitial (56%), interstitial/sheets (13%), nodular (15%) and packed marrow (16%) with median survivals of 46, 31, 22 and 16 months. When grouped according to the tumour cell mass in the biopsy, four histologic stages were recognized. Cellular characteristics were used to classify MM into 6 histologic types which were subsequently combined into 3 grades of malignancy: low, intermediate and high, analogous to the malignant lymphomas. With respect to tumour products, only SB2M proved to be a valuable prognostic indicator for staging and follow-up. Complications of MM such as anaemia, azotaemia, osteolytic lesions, hypercalcaemia and hypoalbuminaemia all predicted a poor prognosis, highly significant in the test statistics. We propose a new prognostic approach in MM, comprising 1) parameters defining the tumour itself, 2) the tumour products (SB2M) and 3) the tumour complications. This prognostic strategy combines information both on stage and malignancy of MM and enables definition of smouldering and of aggressive variants of MM at an early stage.

Biomarkers, Tumor↗

Plastic embedded core biopsy: a complementary approach to bone marrow aspiration for diagnosing acute myeloid leukaemia.

Bone marrow aspirates and biopsy specimens were taken at diagnosis from 51 patients with acute myeloid leukaemia (AML). The diagnosis was based on morphological and cytochemical analyses, and the leukaemias were classified by FAB criteria. A considerable difference was observed between the results of bone marrow aspirates and the findings of plastic-embedded bone marrow biopsy specimens, particularly in marrow cellularity, extent of blast cell infiltration, and cell type involved in the leukaemic process. The myelomonocytic cell type seemed to predominate in the sections. In four cases there was considerable marrow infiltration with maturing, but dysplastic, granulocytic cells in the sections, but not in the aspirate smears. Features of potential prognostic importance, such as bone marrow infiltration with inflammatory cells, were easily recognised and quantified in the sections. These results indicate that plastic embedded bone marrow biopsy sections complement the findings of bone marrow aspiration in the diagnosis of AML and may also provide information of independent prognostic importance that cannot be obtained by other means.

Biopsy, Needle↗

Bone biopsies and serum vitamin-D levels in patients with hip fracture.

To assess the correlation between osteoid and vitamin D in patients with a proximal femoral fracture, bone biopsies of the fracture site and the iliac crest were studied; and vitamin-D levels were measured in fasting blood taken on the day of admission. No osteomalacia was found at either site in any of the 95 patients investigated. In 65/95 patients, levels of 25-hydroxy-vitamin D (25-OHD) and 24,25-dihydroxy-vitamin D (24, 25-OH2D) were within the normal range, whereas 30/95 patients were deficient. Because there was no correlation between the amount of osteoid and vitamin-D metabolites in our patients, we concluded that osteomalacia was not a contributory factor in the pathogenesis of the hip fracture.

24,25-Dihydroxyvitamin D 3↗

Visualization of vascular platelet aggregation by plastic embedding and light microscopy.

Previous studies have indicated that platelets play a role in inflammation and microvascular damage but routine histologic preparations do not permit clear visualization of the platelets in tissues. Plastic embedding was used in this study to demonstrate platelet aggregates in the pulmonary vasculature of mice exposed to complement activation. The degree of platelet aggregation in the excised lungs was graded semiquantitatively in a total of 75 mice. Control Balb/c mice had a mean aggregation score of 0.16 while mice which received 0.3 ml zymosan-activated plasma (ZAP) intravenously (iv) had a score of 2.2. Injection of 0.3 or 0.4 ml of ZAP to which epsilon-aminocaproic acid was added prior to incubation with zymosan resulted in a score of 2.6 or 4.7 respectively. Balb/c (C5 sufficient) and AKR/J (C5 deficient) mice injected iv with 1 mg zymosan had scores of 2.9 and 3.2, respectively. Cobra venom factor (CVF) injected iv to Balb/c mice induced a dose-dependent aggregation. Taken together, these results confirm that complement activation products can mediate intrapulmonary platelet aggregation and they also demonstrate the suitability of plastic embedding for visualization of intravascular platelet aggregates under light microscopy.

Animals↗

Interferon-beta induced remission in a hairy cell leukemia patient resistant to interferon-alpha.

Two patients with advanced hairy cell leukemia and pancytopenia responded successfully to intramuscular injections of recombinant interferon-beta, with normalisation of blood counts. One of the patients had developed resistance to interferon-alpha. The in-vivo response was predicted by in-vitro studies showing a beneficial effect of IFN-beta on erythropoiesis in cell cultures derived from these patients.

Bone Marrow↗

Comparative histology of malignant lymphomas in lymph node and bone marrow.

Lymph node and bone marrow biopsies of 226 patients with malignant lymphomas were available for evaluation and comparison. 120 of the 226 lymphoma patients had classifiable infiltration in both lymph node and bone marrow and these were used for comparison. Congruence in the histologic subtypes in lymph node and bone marrow was found in 91 patients (76%). The majority of the 29 cases with divergent histologies showed ML of low grade malignancy in the bone marrow even with long time intervals between the two biopsies. The most notable in this group were seven cases who had ML centroblastic/centrocytic in the lymph node biopsy and ML immunocytic in the bone marrow, although none had a serum M-component. 65 of the 106 patients excluded from comparison had involvement in only one organ, the others had unclassifiable or equivocal histologies in either lymph node or bone marrow or in both. The findings are discussed with respect to the histologic behaviour of the lymphomas. The results show that comparison between lymph node and bone marrow findings in patients with ML is feasible and clinically relevant.

Bone Marrow↗

Histologic classification and staging of chronic lymphocytic leukemia. A retrospective and prospective study of 503 cases.

Bone marrow biopsies of 503 untreated patients with chronic lymphocytic leukemia (CLL) were processed for diagnostic evaluation. Histologic variables were correlated with the initial clinical features registered when the biopsies were taken, to determine factors of value in predicting prognosis. Four cellular characteristics (small round nuclei, notched nuclei, large round nuclei and presence of nucleoli) were used to classify CLL into the following three histologic types: (1) small round, (2) notched and (3) mixed. Patients classified according to these types had significantly different median survival times: 53, 26 and 28 months, respectively. CLL showed three growth patterns in the bone marrow: nodular, interstitial and packed, and these patterns had outstanding prognostic significance at all clinical stages (median survivals of 90, 46 and 28 months, respectively). The results are discussed in relation to the various growth patterns and their significance previously reported in the literature. In addition, the quantity of lymphoid cell burden in the bone marrow served as a useful criterion for histologic staging of CLL, thus supplementing any clinical staging system in use. All three histologic parameters--cell type, growth pattern and tumor cell burden--provide information on prognosis and thus provide a basis for decisions on treatment modalities in CLL.

Adult↗

Changes in trabecular bone, hematopoiesis and bone marrow vessels in aplastic anemia, primary osteoporosis, and old age: a comparative histomorphometric study.

Retrospective histologic analyses of bone biopsies and of post mortem samples from normal persons of different age groups, and of bone biopsies of age- and sex-matched groups of patients with primary osteoporosis and aplastic anemia show characteristic age dependent as well as pathologic changes including atrophy of osseous trabeculae and of hematopoiesis, and changes in the sinusoidal and arterial capillary compartments. These results indicate the possible role of a microvascular defect in the pathogenesis of osteoporosis and aplastic anemia.

Adolescent↗

Histologic classification and staging of multiple myeloma. A retrospective and prospective study of 674 cases.

Bone marrow biopsies of 674 patients with multiple myeloma (MM) were processed for diagnostic evaluation. Histologic variables were correlated with the clinical features to determine factors of value in predicting prognosis. Four of these were used to classify MM into six histologic types: Marschalko type; small cell type; cleaved type; polymorphous type; asynchronous type; and blastic type. These six types were subsequently combined into three prognostic grades: low, intermediate, and high, analogous to the malignant lymphomas. The quantity of plasma cell burden in the biopsy proved to be a useful criterion for histologic staging of MM, supplementing any clinical staging system in use. Both these parameters, grade and stage, provide information required for decisions on treatment modalities, while the effects of therapy can be monitored by sequential biopsies.

Adolescent↗

Antibody-dependent cell-mediated cytotoxicity and phagocytosis of autologous red blood cells in alphamethyldopa-induced haemolysis.

7 alphamethyldopa (AMD)-treated patients with positive direct antiglobulin test (DAT) were investigated. Peripheral blood mononuclear phagocytes of 2 patients suffering from haemolysis caused lysis and phagocytosis of autologous DAT-positive red blood cells (RBC). Eluates from RBC of both patients contained antibodies of IgG1 subclass and supported antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADPh) of the patients' RBC after remission. Both cytotoxic activities were proportional to the serum concentration and to the number of attacking cells. The 5 patients without overt haemolysis did not show in vitro lysis or phagocytosis of autologous RBC. These results suggest that ADCC as well as ADPh participate in the destruction of RBC in AMD-induced haemolysis in vivo.

Aged↗