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Biomedical subjects

A Chott

Publications and source records attributed to A Chott.

At least 127 records · Page 7Linked to original sources

Interferon-alpha-induced morphological changes of megakaryocytes: a histomorphometrical study on bone marrow biopsies in chronic myeloproliferative disorders with excessive thrombocytosis.

Interferon(rIFN)-alpha, a successful therapeutic agent in the control of thrombocytosis, has been shown to suppress human megakaryopoiesis. We investigated bone marrow biopsies from 12 patients with thrombocytosis due to chronic myeloproliferative disorders. Prior to treatment as well as during rIFN-alpha-2c therapy, several morphometric parameters of megakaryopoiesis were evaluated. Megakaryocyte density decreased significantly in all patients, megakaryocyte size decreased in polycythaemia vera, agnogenic myeloid metaplasia, and essential thrombocythaemia, but increased in chronic myeloid leukaemia. The various changes observed during therapy indicate an inhibitory effect of rIFN-alpha-2c on megakaryopoiesis and suggest a selective influence on megakaryocytes at various stages of maturation. Increased numbers of pyknotic (bare) nuclei may reflect a shortening of megakaryocyte life-span. No remarkable changes were found in the fibre content of the bone marrow.

Aged↗

Long-term alpha-interferon therapy in myelodysplastic syndromes.

The myelodysplastic syndrome (MDS) is characterized by a high probability of leukemic transformation and frequently lethal infections or bleeding episodes. Up to now, no generally accepted form of therapy has been established for MDS. Previous trials with alpha-interferon (IFN-alpha) have shown some beneficial effects. We studied the effects of long-term application of IFN-alpha at higher dosages in patients with "low-risk" MDS. Ten patients were included in the study; eight were treated for a period of 6-36 months. IFN-alpha was administered at a median dosage of 9, 6, 4 mU/week during the first, second, and third year, respectively. Response was determined by the status of peripheral blood and bone marrow. Prolonged exposure to IFN resulted in a response rate of 3/10 (30%). In an additional case, disease progression was retarded during the third year of therapy. The incidences of infections and bleeding events subsided notably. After the withdrawal of IFN, hematological and clinical parameters rapidly deteriorated in some patients. The observed improvement of the patients' susceptibility to infections possibly prolongs their survival and seems to justify further trials on IFN treatment in patients with MDS.

Aged↗

Long-term interferon therapy for thrombocytosis in myeloproliferative diseases.

31 patients with thrombocytosis associated with myeloproliferative disorders were included in a prospective trial of long-term interferon therapy. 6 patients (19%) had side-effects which required withdrawal of interferon within one year. 22 patients (71%) achieved and maintained a complete response (platelet count less than 440 x 10(9)/l) for at least twelve months, with reduction or abolition of symptoms associated with thrombocytosis and a significant fall in bone-marrow megakaryocytes. At twelve months, 25 patients were randomly allocated to maintenance or withdrawal of interferon. Thrombocytosis recurred rapidly when treatment was stopped, but a second remission could be achieved by resumption of interferon therapy.

Aged↗

Alpha-fetoprotein-positive adenocarcinoma of the pancreas.

A case of a poorly differentiated ductal adenocarcinoma arising in the body and tail of the pancreas with diffuse intraabdominal metastases in an adult is reported. Serum alpha-fetoprotein (AFP) level was markedly elevated in this patient, but fell transiently when a partial tumor response to combination chemotherapy was achieved. Both the occurrence of biochemical and anatomical responses, and the immunohistochemical finding of AFP in the tumor tissue clearly indicate that oncofetal protein is produced by the tumor cells. The patient survived 10.5 mo after the onset of symptoms.

Antineoplastic Combined Chemotherapy Protocols↗

Primary peripheral T cell lymphoma in a kidney transplant under immunosuppression with cyclosporine A.

A 56-year-old patient received a cadaveric renal allograft because of primary cystic kidney disease. The donor was a 28-year-old man who died from head trauma. No other major illnesses were present at the time of transplantation. Immunosuppression was performed with cyclosporine A and steroids. After 3 months, the patient presented with fever and abdominal pain which was located in the region of the allograft. Ultrasonography demonstrated a tumor mass at the renal transplant hilus that was suspected to be an infected hematoma. Kidney biopsy from the cortex revealed only severe morphologic signs of cyclosporine A toxicity which was due to high cyclosporine A levels during the first 2 months after transplantation. The patient died from pulmonary embolism 6 months posttransplant. Histologic evaluation of the tumor specimens obtained at autopsy showed an extensive infiltration of the renal hilus and the medulla by a peripheral T cell lymphoma of the large-cell type. The T cell origin was confirmed by immunohistochemistry using the T cell-associated monoclonal antibodies UCHL-1 and MT1.

Adult↗

Ki-67 immunoreactivity in breast carcinomas in relation to transferrin receptor expression, estrogen receptor status and morphological criteria. An immunohistochemical study.

The number of proliferating cells was determined by Ki-67 antibody in 107 primary breast carcinomas. These results were compared with transferrin receptor (TrfR) expression, estrogen receptor (ER) status, histologic type, tumor grade, size and axillary lymph node status. The percentage of Ki-67-positive cells ranged from 0.9 to 26.4%. The proportion of Ki-67-positive cells was highest in medullary carcinomas. Immunoreactivity of Ki-67 in relation to TrfR expression showed significant correlation (p = 0.0001). An inverse relationship between ER status and Ki-67 positivity existed (p = 0.0001). 88 cases were subjected to histologic grading. There was a significant relationship showing an increase of Ki-67 immunoreactivity with decrease of tumor differentiation (p = 0.0001). The distribution of Ki-67 reactivity in relation to tumor size and nodal status of the axilla revealed positive correlations (p = 0.02; p less than 0.05). In conclusion, the use of Ki-67 monoclonal antibody as a marker for cell proliferation represents a method to get kinetic data inhering prognostic value.

Antibodies, Monoclonal↗

Long-term remission in a patient with erythroleukemia following interferon-alpha treatment.

A patient in second relapse of acute erythroleukemia (AEL) was treated with 10 MU of recombinant interferon (IFN)-alpha subcutaneously for 24 days after he had failed standard chemotherapy. Besides fever up to 38.9 degrees C and a transient raise in liver function parameters, treatment was well tolerated but had to be discontinued because of a severe decrease in white blood cell and platelet count. After termination of IFN treatment, both cell populations showed a continuous rise during the following weeks and hemoglobin increased concomitantly. Partial remission could be reached as was demonstrated by a decrease in PAS-positive erythroblasts in bone marrow biopsy. Further studies with IFN in patients with AEL refractory to cytostatic chemotherapy are recommended.

Adult↗

Recombinant alpha-interferon (alpha-IFN) for progressive hairy-cell leukemia (HCL): a study in previously untreated nonsplenectomized patients.

Ten nonsplenectomized patients (5 males, 5 females) with hairy-cell leukemia were treated with recombinant alpha-IFN. The median age of patients was 54 years (32-76 years). The time between diagnosis and onset of treatment ranged from 1-120 months. Initially the patients received 5 x 10(6) I.U. daily by intramuscular or subcutaneous injections for 10 weeks. Thereafter the dose of IFN was reduced to 5 x 10(6) I.U. 3 x weekly and after 6 months to 5 x 10(6) I.U. 2 x weekly for at least 6 months. The median time of patient follow-up is 23 months (4-28 months). Three complete remissions were achieved after 3-24 months and five partial remissions after 4-18 months. One patient showed improvement after 3 months, and one patient died from cerebral hemorrhage after 5 weeks. In eight of ten patients peripheral blood cell counts normalized after a median of 7 months (1.5-11 months). A marked reduction in spleen size was observed in all seven patients who had splenomegaly at study entry. Two of three patients who interrupted therapy have relapsed after 2 and 6 months. We conclude that alpha-interferon is an effective method of first-line treatment in patients with HCL.

Adult↗

Deficiency of pluripotent hemopoietic progenitor cells in myelodysplastic syndromes.

Pluripotent (CFU-MIX), erythroid (BFU-E) and granulocyte/macrophage (CFU-GM) progenitor cells were examined in bone marrow (BM) from 23 patients with myelodysplastic syndromes (MDS). Patients were grouped according to the FAB classification: Refractory anemia (RA), n = 3; RA with ring sideroblasts (RARS), n = 3; RA with excess of blasts (RAEB), n = 8; RA with excess of blasts in transformation (RAEBt), n = 7; chronic myelomonocytic leukemia (CMML), n = 2. In FAB groups RA, RARS, RAEB and RAEBt CFU-GM concentrations were normal or decreased but both CMML-patients had increased CFU-GM values. Abnormal cluster growth was observed in 9 of 23 MDS-patients. BFU-E colony formation was subnormal in all cases. Mixed-colony assay values were at the lower limit of controls in one patient and decreased in the remaining 22 MDS-patients. A similar growth pattern of hemopoietic progenitor cells was observed in 19 patients with acute nonlymphocytic leukemia (ANLL), who were studied for comparison. These data suggest a quantitative or qualitative/functional defect of the pluripotent progenitor cell compartment as the major cause for the cytopenia in MDS-patients.

Aged↗

Skeletal involvement in hairy cell leukemia.

The clinical and radiographic aspects of two patients with destructive bone lesions, complicating the course of hairy cell leukemia are presented. The findings are compared with those of 27 previously published cases. The most prominent features of this rare skeletal disorder are osteolysis and widespread or localized demineralisation with predilection for the femoral head and neck. Localized persisting pain is the leading clinical symptom in all cases. Magnetic resonance imaging is helpful in evaluating the extent of bone marrow infiltration and demonstrates focal areas of decreased signal intensity in sites of radiographically detectable bone destruction as well as in bones that appear normal on plain films.

Bone Neoplasms↗

Peripheral T cell lymphoma presenting primarily as lethal midline granuloma.

This clinicopathologic study reports seven patients who primarily presented with ulcerative and destructive lesions of the upper aerodigestive tract and face, clinically consistent with so-called lethal midline granuloma (LMG). Histologically, the infiltrates were composed of atypical lymphoid cells that displayed angiocentricity and angiodestruction. In five patients, involvement of distant sites such as skin, lungs, lymph nodes, and bone marrow occurred, and in two cases, the disease remained localized. Immunomorphologic analysis, using monoclonal antibodies to frozen and paraffin sections, provided evidence for the diagnosis of peripheral T cell lymphoma (PTL) in all cases. The midline tumors were classified as diffuse mixed or diffuse large cell lymphoma occurred at distant sites. According to modern PTL classification systems, the lesions could be classified as pleomorphic T cell lymphomas. Those five patients who presented with or progressed to large cell lymphoma died within 18 months (mean, 7 months), whereas the two patients with localized disease are alive after 10 and 36 months, respectively. The size of the atypical lymphoid cells may be of prognostic significance since the large cell compartment seems to represent the major growth fraction in these PTLs.

Adult↗

Poorly differentiated, neuron-specific enolase positive round cell tumor with two translocations t(11;22) and t(21;22).

The authors describe a highly malignant, disseminated round cell tumor originating in the ninth rib of a 14-year-old boy. Extensive studies by means of light and electron microscopic examination, histocytochemistry and immunocytochemistry and cytogenetic analysis revealed an undifferentiated, neuron-specific enolase positive round cell tumor with a unique karyotype: 45,XY,-21,t(11;22)(q23;q11), der(22)t(21;22)(q11.2;p11). Thus, despite the absence of definite morphologic features, such as Homer-Wright rosettes, neurosecretory granules and cytoplasmatic processes, these findings suggest a neuroectodermal origin of this bone tumor.

Adolescent↗

Immunocytochemical markers of uncommon pancreatic tumors. Acinar cell carcinoma, pancreatoblastoma, and solid cystic (papillary-cystic) tumor.

Nine acinar cell carcinomas of the pancreas, 2 pancreatoblastomas, 16 solid-cystic (papillary-cystic) tumors, and 20 ductal adenocarcinomas were immunocytochemically investigated using antisera against four pancreatic enzymes (alpha-amylase, lipase, trypsinogen, chymotrypsinogen), four pancreatic hormones, neuron specific enolase (NSE), alpha-1-antitrypsin (AAT), carcinoembryonic antigen (CEA), and CA 19-9. Lipase, trypsinogen, and chymotrypsinogen, but no alpha-amylase were detected in all acinar cell carcinomas and pancreatoblastomas. In contrast, solid-cystic tumors (SCT) were negative for pancreatic enzymes but 2 of 16 stained with NSE. No neuroendocrine granules or pancreatic hormones could be demonstrated. AAT was found in all tumors except ductal adenocarcinomas, which stained with CEA and CA 19-9. The study established pancreatic enzymes (except alpha-amylase) as immunocytochemical markers for acinar cell carcinomas and pancreatoblastomas. There is as yet no marker specific for SCT, which would elucidate the obscure histogenetic origin and phenotypic differentiation of these tumors.

Adolescent↗

Interferon-alfa corrects thrombocytosis in patients with myeloproliferative disorders.

During previous therapeutic trials with interferon, decreased levels of peripheral platelet counts have been observed. Taking advantage of this effect, we investigated the efficacy of recombinant interferon (rec-IFN) in the treatment of thrombocytosis in myeloproliferative diseases. A total of 15 patients with polycythemia vera, essential thrombocytosis, or chronic myeloid leukemia received rec-IFN-alfa at initial doses of 25-70 x 10(6) units/week; maintenance therapy following week 8 of treatment consisted of 20-35 x 10(6) units/week rec-IFN. Observation periods ranged from 24 to 48 weeks. Significant reductions in the number of platelets were noted in all cases; 12/15 patients achieved platelet counts below 440 x 10(9)/l and maintained those normal values for at least 4 weeks. The number of bone marrow megakaryocytes, which had been increased prior to treatment, diminished during rec-IFN therapy, while the previously shortened platelet half-life further decreased with rec-IFN treatment. During rec-IFN-induced remission, the plasma levels of platelet factors, the activity of natural killer cells, and platelet aggregation showed changes between slight improvement and normal values. Severe side effects were only observed with the highest rec-IFN doses; dosage adjustments were effective in improving or eliminating all treatment-related symptoms. Rec-IFN may prove to be a valuable therapeutic alternative to cytostatic treatment of thrombocytosis in myeloproliferative disorders.

Aged↗

Neuron specific enolase demonstration in the diagnosis of a solid-cystic (papillary cystic) tumour of the pancreas.

Immunoreactivity to neuron specific enolase (NSE) was demonstrated in a solid-cystic (papillary cystic) tumour of the human pancreas, employing immunohistochemical methods. Positive staining for NSE was found with two different antisera. In addition, sodium-dodecyl-sulphate-polyacrylamide-gel-electro-phoresis (SDS-PAGE) of tumour homogenate revealed a distinct band reacting with a NSE antiserum. However, we failed to detect any hormonal products or neuroendocrine granules in the tumour. Therefore the authors advise caution in using the enzyme as a differential diagnostic tool, especially in surgical pathology of epithelial pancreatic neoplasms occurring in young females. In individual cases electron microscopy will be necessary since solid-cystic tumours of the pancreas consistently show large intracytoplasmic zymogen-like granules.

Electrophoresis, Polyacrylamide Gel↗