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PubMed1999

[Megaloblastic anemia in a psychogenic eating disorder].

HISTORY AND ADMISSION FINDINGS: A 68-year-old woman had progressively lost strength over the past 5 years and become bed-ridden. She reported gradually reducing her diet during the last few years, for the last two years restricting herself to oatmeal, biscuits and water. Acute exacerbation of dyspnoea, dizziness, tachycardia and cardiac arrhythmias for the last 3 month necessitated her emergency admission when she was found to have oedema of the limbs and definite jaundice, as well as predominantly distal sensory deficits in the legs, a slightly ataxic gait and poor reflexes in the limbs. INVESTIGATIONS: She was found to have pancytopenia with marked megaloblastic anaemia (haemoglobin 4.8 mg/dl, mean red cell volume 141.8 fl, leukocytopenia 41/nl), marked haemolysis (lactate dehydrogenase 1629 U/l, haptohaemoglobin < 0.1 g/l, total bilirubin concentration 4.5 mg/dl). Pernicious anaemia was excluded: no antibodies against parietal cells and intrinsic factor, and no atrophic gastritis in a gastric biopsy. DIAGNOSIS, TREATMENT AND COURSE: Megaloblastic anaemia due to dietary deficiencies with early funicular myelosis was suspected. After infusion of four erythrocyte concentrates and vitamin B12 administration the symptoms and blood picture improved within days. CONCLUSION: Although dietary causes of megaloblastic anaemia are rare in Central Europe, they must be considered in the differential diagnosis, especially in the elderly and those with psychogenic disorders.

Aged↗
PubMed1988

[Myeloreticulosis of the uterus following acute myeloid leukemia].

Tumorous manifestations of myelosis with or without leukemia are rarely seen today as they appear at a very late stage of the disease. They are of importance to the gynecologist in the differential diagnoses concerning the breast, the endometrium and uterus, the placenta and the fetus. The case report of a myeloreticulosis of the uterus, three years after an acute myeloid leukemia was treated, is described.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

[Allogeneic bone marrow transplantation after fractionated whole body irradiation. Results at the Kiel transplantation center].

Allogeneic bone marrow transplantations were carried out between March 1983 and July 1985 in 31 patients aged 7 to 45 years (median 18 years). Acute lymphoblastic leukaemia in 1st to 5th remission was present in 8 patients, acute myeloblastic leukaemia in 1st and 2nd remission in 4 patients, chronic myeloid leukaemia, with various remission status, in 6 patients, 3 patients had severe aplastic anaemia and there were single cases of myelodysplasia and immature cell megakaryocytic myelosis. Transplantation was carried out during relapse in 8 patients with either acute myeloid or lymphoblastic leukaemia. Phenotypic HLA-identical mothers (n = 2) as well as genotypic HLA-identical siblings (n = 27), and in two cases HLA-non-identical mothers, served as bone marrow donors. In leukaemia patients the conditioning treatment consisted of fractionated total body irradiation and high dose cyclophosphamide or etoposide. Patients with severe aplastic anaemia received cyclophosphamide (4 X 50 mg/kg) and fractionated total nodal irradiation (total dose 8 Gy). 19 patients (61%) survived 14 to 605 days after bone marrow transplantation. 15 patients (48%) continue to remain in complete remission with Karnofsky indices of greater than or equal to 90%. Causes for death were infection (n = 3), interstitial pneumonia (n = 3), relapse (n = 3) as well as single cases involving acute graft-versus-host-disease, non-engraftment of donor marrow and veno-occlusive disease of the liver.

Acyclovir↗
PubMed2003

Metabolic evaluation of 94 patients 5 to 16 years after ileocecal pouch (Mainz pouch 1) continent urinary diversion.

UNLABELLED: PURPOSE In continent urinary diversion metabolic disturbances may be encountered in long-term followup. We evaluated metabolic consequences in patients with a minimum followup of 5 years after Mainz pouch 1 urinary diversion. MATERIALS AND METHODS: At our institution continent urinary diversion using the ileocecal segment was performed between 1983 and 1995 in 458 patients. A total of 94 patients with an ileocecal pouch for a minimum of 5 years were reevaluated for metabolic changes. Median followup was 9.0 years. Routine laboratory parameters, blood gas analysis, vitamin B12, vitamin D25, cross-laps, bone specific alkaline phosphatase, osteocalcin and propeptide of type I collagen were obtained. Bone density was measured in 18 patients. Vitamin B12 changes could be followed longitudinally in 24 patients. RESULTS: Medians of all parameters were in normal ranges. Clinical examinations revealed no signs of megaloblastic anemia, funicular myelosis or osteoporosis. There was no significant decrease of vitamin B12 in the long run. After followup examination we recommended vitamin B12 supplementation in 32% of patients because levels were in the lower normal range or below. A total of 37% of patients continue to take Na+/K+-citrate for prevention of metabolic acidosis. CONCLUSIONS: Patients with an ileocecal pouch and a followup of more than 5 years did not present with clinical symptoms caused by metabolic disturbances. Nevertheless, systematic followup of blood gases in particular and alkali supplementation may have prevented bone demineralization. Followup of vitamin B12 is of concern because about a third of these patients need supplementation.

Acidosis↗
PubMed1975

The Di Guglielmo syndrome: a study of 17 cases. I. Clinical and haematological manifestations.

Based on a series of 17 patients with Di Guglielmo's syndrome, i.e., erythraemic myelosis and erythroleukaemia, a description is given of the clinical and haematological manifestations of this disease. Three cases were anerythraemic, i.e. no erythroblasts were seen in the blood smears, and three were aleukaemic, i.e. no myeloblasts and/or promyelocytes were found in the blood. The percentage of erythroblasts in the bone marrow smears varied from 34 to 96. In all cases, abnormalities (often megaloblastoid changes) of varying severity were observed in the erythroblasts. Proerythroblasts showing erythrophagocytosis, multinuclearity and vacuolation of the cytoplasm are features of great diagnostic importance. Five patients had myeloblasts or promyelocytes containing Auer rods, six had neutrophilic granulocytes showing pseudo-Pelger-Hüet anomaly, and in most cases agranular polymorphonuclears were present. Brief comments are given on the PAS, nuclear arylsulphatase and naphtol-AS-D-chloroacetate-esterase staining methods. Four of five patients studied cytogenetically revealed abnormal stem lines. The survival times after the onset of the disease ranged from 17 days to 20 months. The disease is closely related to myeloblastic leukaemia. In the course of Di Guglielmo's syndrome, the leukaemic component often becomes more conspicuous, so that, in the terminal phase, the disease cannot be distinguished from typical myeloblastic leukaemia. As, in Di Guglielmo's "leukaemia", the diagnostic problems are greater than and different from those in typical myeloblastic leukaemia, it is still reasonable to place this disease in a separate group under acute granulocytic leukaemia.

Adolescent↗
PubMed1984

Histological classification of chronic granulocytic leukaemia.

On the basis of the trephine marrow histology at presentation, 52 Ph1 positive cases of chronic myeloid leukaemia were divided into two subgroups, classical chronic granulocytic leukaemia (CGL) and chronic megakaryocytic granulocytic myelosis (CMGM). In 24 cases in which conventional therapy had preceded trephine biopsy, the distribution of cases between the two groups was found to have been significantly altered. Subsequent analysis was therefore confined to the remaining 28 untreated cases; of these 15 were classified as CGL and 13 as CMGM; no statistically significant difference was found between the two groups in respect of patient's age, leucocyte counts, platelet counts, NAP scores or of occurrence of 'blast' crisis. The differential diagnosis between idiopathic myelofibrosis (IMF) and CMGM subgroup is discussed. It was concluded that classification of chronic myeloid leukaemia on the basis of marrow histology should be restricted to Ph1 positive cases in order to obviate the possible inclusion of cases of IMF within the CMGM subgroup.

Chromosomes, Human, 21-22 and Y↗
PubMed1975

Myeloproliferative disorders with selective differentiation toward megakaryocytic cells. A clinicopathological study of three autopsy cases.

Three autopsy cases of myeloproliferative disorders with selective differentiation toward megakaryocytic cells were reported with a clinicopathological analysis. All of these cases had some common distinctive features; (1) patients, adult of more than 40 years of age, (2) relatively acute fatal course (about 20 to 100 days), (3) continued pancytopenia in the peripheral blood, (4) so-called blast cells, occasionally showing accumulation, according to the length of total duration, in addition to overwhelming predominance of atypical megakaryocytic cells in the bone marrow, and (5) an increased tendency of fibrillosis in the interstitium of the bone marrow corresponding to the more or less prolonged duration of the course. From these facts, they should be compatible with so-called megakaryocytic myelosis. Some relationship between this disorder and myelogenous leukemia, and infiltrative tendency of megakaryocytic cells in the extramedullary organs had also been discussed shortly.

Adult↗
PubMed1978

Some uses of the continuous flow blood separator in the myeloproliferative syndrome.

A continuous flow blood separator was used for leucapheresis in two patients with chronic myeloid leukaemia, complicated by pregnancy and leukastasis respectively, and for thrombocytopheresis in a patient with megakaryocytic myelosis. The cases described, outline some of the clinical uses of this machine in the myeloproliferative syndrome.

Adult↗
PubMed1983

Density distribution and size of megakaryocytes in inflammatory reactions of the bone marrow (myelitis) and chronic myeloproliferative diseases.

Morphometric evaluation was performed on semi-thin sections of core biopsies of the bone marrow and included 20 cases of each group of diseases besides control specimens. (i) Hyperergic myelitis of rheumatic origin. (ii) Chronic granulocytic leukaemia (CGL). (iii) Polycythaemia vera (P. vera). (iv) Chronic megakaryocytic-granulocytic myelosis (CMGM). (v) Myelofibrosis or osteomyelosclerosis (MF/OMS). The following classification of megakaryopoiesis was applied: normal megakaryocytes; giant forms; microforms; intussusceptions; cytoplasmic fragments; naked nuclei. The density distribution shows an increase of megakaryocyte number in those 5 different marrow disorders, ranging from about 13/mm2 in the normal sample up to 65 cells/mm2 in MF/OMS. Microforms are most frequently encountered in CGL, whereas giant megakaryocytes, intussusceptions and many cytoplasmic fragments characterize P. vera, CMGM and MF/OMS. Our measurements suggests 3 distinct categories of bone marrow lesions with corresponding alterations of the megakaryopoiesis: (i) myelitis and CGL; (ii) P. vera; (iii) CMGM and MF/OMS.

Bone Marrow↗
PubMed1989

Is the histological classification of chronic granulocytic leukaemia justified from the clinical point of view?

By means of morphometric techniques, in 100 untreated Ph'-positive chronic granulocytic leukaemia (CGL) patients the main features from the initial bone marrow biopsy were analyzed, with particular attention being paid to morphological and quantitative study of megakaryocytes. The number of megakaryocytes per mm2 of marrow tissue showed a mean value of 25.3 (SD +/- 18.8), and was positively correlated with either platelet counts, blood percentage of basophils and blast cells, or spleen and liver size. Based on the number and morphological characteristics of megakaryocytes, patients were classified as having granulocytic CGL (67 cases) or the so-called chronic megakaryocytic-granulocytic myelosis (33 cases), but except for higher platelet counts and blood percentages of basophils and blast cells in the latter, no relevant clinical, evolutionary or prognostic differences were observed between the groups. Such results cast doubt on the validity of histological classification of CGL from the clinical point of view.

Bone Marrow↗
PubMed1976

Chemotherapy--one of the causes of transient loss of HLA antigens and lymphocyte polyreactivity in patients with blood diseases and malignancies.

Modifications of HLA antigens (transient loss or polyreactivity) were found in thirty-two of fifty-five examined patients with blood diseases (leukaemia, reticulosis, reticulo- and lymphosarcoma, lymphogranuloma, erythroblastoma) and malignant tumours. In two cases of acute myelosis transient alteration of HLA-A 2 antigen in HLA-A 28 was demonstrated. The relationship of HLA antigenic modification to chemotherapy was established, both by analysis of individual cases and by statistical evaluation of serological results in patients with or without chemotherapy (0-01 greater than P greater than 0-001). Chemotherapy is thus one of the causes for the development of HLA antigen modifications in blood diseases and malignant tumours.

Cytotoxicity Tests, Immunologic↗
PubMed1991

Proposed criteria for classification of acute myeloid leukemia in dogs and cats.

Blood and bone marrow smears from 49 dogs and cats, believed to have myeloproliferative disorders (MPD), were examined by a panel of 10 clinical pathologists to develop proposals for classification of acute myeloid leukemia (AML) in these species. French-American-British (FAB) group and National Cancer Institute (NCI) workshop definitions and criteria developed for classification of AML in humans were adapted. Major modifications entailed revision of definitions of blast cells as applied to the dog and cat, broadening the scope of leukemia classification, and making provisions for differentiating erythremic myelosis and undifferentiated MPD. A consensus cytomorphologic diagnosis was reached in 39 (79.6%) cases comprising 26 of AML, 10 of myelodysplastic syndrome (MDS), and 3 of acute lymphoblastic leukemia (ALL). Diagnostic concordance for these diseases varied from 60 to 81% (mean 73.3 +/- 7.1%) and interobserver agreement ranged from 51.3 to 84.6% (mean 73.1 +/- 9.3%). Various subtypes of AML identified included Ml, M2, M4, M5a, M5b, and M6. Acute undifferentiated leukemia (AUL) was recognized as a specific entity. M3 was not encountered, but this subclass was retained as a diagnostic possibility. The designations M6Er and MDS-Er were introduced where the suffix "Er" indicated preponderance of erythroid component. Chief hematologic abnormalities included circulating blast cells in 98% of the cases, with 36.7% cases having >30% blast cells, and thrombocytopenia and anemia in approximately 86 to 88% of the cases. Bone marrow examination revealed panmyeloid dysplastic changes, particularly variable numbers of megaloblastoid rubriblasts and rubricytes in all AML subtypes and increased numbers of eosinophils in MDS. Cytochemical patterns of neutrophilic markers were evident in most cases of Ml and M2, while monocytic markers were primarily seen in M5a and M5b cases. It is proposed that well-prepared, Romanowsky-stained blood and bone marrow smears should be examined to determine blast cell types and percentages for cytomorphologic diagnosis of AML. Carefully selected areas of stained films presenting adequate cellular details should be used to count a minimum of 200 cells. In cases with borderline diagnosis, at least 500 cells should be counted. The identity of blast cells should be ascertained using appropriate cytochemical markers of neutrophilic, monocytic, and megakaryocytic differentiation. A blast cell count of > 30% in blood and/or bone marrow indicates AML or AUL, while a count of < 30% blasts in bone marrow suggests MDS, chronic myeloid leukemias, or even a leukemoid reaction. Myeloblasts, monoblasts, and megakaryoblasts comprise the blast cell count. The FAB approach with additional criteria should be used to distinguish AUL and various subtypes of AML (Ml to M7 and M6Er) and to differentiate MDS, MDS-ER, chronic myeloid leukemias, and leukemoid reaction. Bone marrow core biopsy and electron microscopy may be required to confirm the specific diagnosis. Immunophenotyping with lineage specific antibodies is in its infancy in veterinary medicine. Development of this technique is encouraged to establish an undisputed identity of blast cells. Validity of the proposed criteria needs to be substantiated in large prospective and retrospective studies. Similarly, clinical relevance of cytomorphologic, cytochemical, and immunophenotypic characterizations of AML in dogs and cats remains to be determined.

Journal Article↗
PubMed1999

Molecular detection of c-mpl thrombopoietin receptor gene expression in chronic myeloproliferative disorders.

BACKGROUND: Chronic myeloproliferative disorders (CMPD) originate from a pluripotent haematopoietic progenitor cell but show a marked degree of heterogeneity, especially between Philadelphia chromosome positive and negative disease entities. Abnormal megakaryopoiesis is a frequent finding in CMPD, often associated with thrombocythaemic cell counts. Recent experimental data have suggested that the c-Mpl thrombopoietin receptor, together with its ligand thrombopoietin, are not only the major physiological regulators of megakaryopoiesis and platelet production, but also play a crucial role in chronic myeloproliferation. METHODS: A total of 18 peripheral blood mononuclear cell samples obtained from patients with CMPD (chronic myelocytic leukaemia (CML), n = 10; polycythaemia vera (PV), n = 6; and primary thrombocythaemia (PTH), n = 2) were analysed for c-mpl mRNA using the reverse transcriptase polymerase chain reaction (RTPCR). In another 20 patients (CML, n = 10; chronic megakaryocytic granulocytic myelosis (CMGM), n = 3; PV, n = 3; PTH, n = 4), we compared the number of haematopoietic progenitors expressing c-Mpl, as characterised by coexpression with the CD34 antigen, in the bone marrow using double immunofluorescence staining. RESULTS: c-mpl mRNA was detected in all samples from patients with CML analysed, whereas only two of six PV and one of two PTH samples were positive (p < or = 0.008; chi 2 test). Expression of the c-mpl receptor gene was absent in healthy subjects used as controls. Similarly, an increase of c-Mpl expressing CD34 positive haematopoietic cells was detected in seven of 10 bone marrow aspirates obtained from patients with CML. Increased numbers of c-Mpl positive CD34 positive cells were found in only one of four patients with PTH, whereas in PV and CMGM the numbers of c-Mpl positive CD34 positive cells did not exceed normal values, despite thrombocythaemic cell counts. CONCLUSIONS: These data confirm recent findings showing an impaired expression of the c-mpl thrombopoietin receptor gene in Philadelphia chromosome negative CMPD when compared with patients with Philadelphia chromosome positive CML. The relevance of this observation to the functional and morphological characteristics of abnormal megakaryopoiesis remains unclear. Thrombocythaemic cell counts and a mature phenotype in megakaryocytes occur frequently in Philadelphia chromosome negative CMPD but require an intact c-Mpl receptor under physiological conditions. Therefore, further studies are warranted to elucidate the mechanisms contributing to megakaryopoiesis in CMPD disease entities with decreased c-mpl gene expression.

Adult↗
PubMed1987

Myeloproliferative disease in the dog and cat: definition, aetiology and classification.

The term myeloproliferative disease may be applied to all the non-lymphoid dysplastic and neoplastic conditions arising from the haematopoietic stem cell or its progeny. Thus the chronic and acute myeloid leukaemias, thrombocythaemia, megakaryocytic myelosis, myelofibrosis, the myelodysplastic syndromes and some cases of aplastic anaemia may be viewed as variants of a single disease process. This view is useful in explaining the common occurrence of mixed forms of disease or interconversions between the myeloproliferative diseases. This variability is a consequence of the development of all the haematopoietic lineages from a single class of haematopoietic stem cell by progressive differentiation. The aetiology of the myeloproliferative diseases in the domestic animals is uncertain but feline leukaemia virus infection has been implicated in the cat. These conditions may be classified as aplastic anaemia, as preleukaemic dysplastic conditions with variable cytopenias and morphological abnormalities of blood cells, as smouldering leukaemias, or as leukaemias with a frankly leukaemic blood or bone marrow.

Animals↗
PubMed1978

Feline myeloproliferative disease. Changing manifestations in the peripheral blood.

A 4 1/2-year-old cat had myeloproliferative disease characterized by severe anemia. Peripheral blood had a profusion of relatively normal-appearing nucleated erythroid cells in all stages of development and a few primitive cells with nucleoli. The term "erythremic myelosis" best described the appearance of the peripheral blood. Two weeks later, the peripheral blood picture was that of regenerative anemia. During the next 2 months the cat made an apparent clinical recovery without treatment, but relapsed 3 months after the initial examination. One-fourth of the cells in circulation at the time of relapse contained nucleoli and appeared identical to those described in reticuloendotheliosis in cats. This transition suggested the progressive development of a greater degree of immaturity of erythroid precusors with time. The use of the term "reticuloendotheliosis" in conjunction with feline myeloproliferative disease was considered and determined inappropriate.

Animals↗
PubMed1981

Cerebral venous thrombosis in the rhesus monkey.

Cerebral venous thrombosis was identified in four rhesus monkeys. Two initially showed neurologic signs and three had diarrhea or dysentery. All four had severe intestinal disease, including three cases of ulcerative colitis complicated by extracerebral thromboembolic disease. Central nervous system lesions, confined to the centrum semiovale, were multiple thrombi of internal cerebral veins, perivenular demyelination, and gemistocytic astrocytosis. The lesions resembled those found in people with cerebral venous thrombosis, and support the hypothesis that perivenular demyelination may occur as a sequela to venous occlusion. The lesions were identical to those found in "leukoencephalosis and perivascular myelosis," an entity of unknown cause previously described in monkeys.

Animals↗
PubMed1996

Classification and staging of Ph-negative myeloproliferative disorders by histopathology from bone marrow biopsies.

The present study illustrates characteristic features of histopathology in the 3 non-leukemic, Ph-negative groups of chronic myeloproliferative diseases (CMPD). Attention is paid to the final outcome of CMPD, especially its transformation into acute leukemias and the occurrence of myelofibrosis from bone marrow biopsies (BMB) in a total of 1,716 CMPD patients. Essential thrombocythemia (ET), polycythemia vera (P. vera), and chronic megakaryocytic granulocytic myelosis (CMGM) can readily be distinguished by histopathology from BMB in the great majority of patients without regarding laboratory data, leaving a compartment of about 12% unclassifiable cases. Histologic patterns of staging are the increase in number and pleomorphism of megakaryocytes (MK), increase in number and density of reticulin fibers and collagen fibrosis, and excess of blasts. These 3 criteria are each graded from 0 to 3 in every biopsy. From these, a staging results by means of the histology of BMB in each of the Ph-negative CMPD. This staging provides a classification by defined criteria which permits comparative studies, the possibility of monitoring the individual patients by follow-up histology, and offers a baseline for reliable evaluation of results from therapy protocols.

Acute Disease↗
PubMed1976

Spleno-hepatic tuberculosis due to Mycobacterium kansasii.

A case of tuberculosis of the spleen and liver is described. The organism involved was Mycobacterium kansasii, one of the atypical mycobacteria. The lack of evidence in the literature of primary splenic or hepatic involvement by this organism suggests that it is rare. In this instance it complicated a case of myeloproliferative disease, megakaryocytic myelosis with extra-medullary haemopoiesis, and was not diagnosed until autopsy.

Autopsy↗