RESUMO
The effect of high-dose chemotherapy and autografting on bone turnover in myeloma is not known. A study of 32 myeloma patients undergoing blood or marrow transplant (BMT), conditioned with high-dose melphalan, was done. Bone resorption was assessed by urinary free pyridinoline (fPyr) and deoxypyridinoline (fDPyr), expressed as a ratio of the urinary creatinine concentration. Bone formation was assessed by serum concentration of procollagen 1 extension peptide (P1CP) and bone-specific alkaline phosphatase (BSAP). Eighteen cases had normal fPyr and fDPyr at transplant, and in all but one of these cases the level remained normal throughout subsequent follow-up. In contrast, in 14 cases urinary fPyr and fDPyr levels were increased at transplant. In these cases, both fPyr and fDPyr fell to normal levels over the next few months (P = .0009 and.0019, respectively). fPyr and fDPyr levels at transplant and their trends post-BMT were unrelated to the use of pre-BMT or post-BMT bisphosphonate or post-BMT interferon. Nine cases had elevated P1CP or BSAP at transplant, which rapidly normalized. In most patients there was an increase in P1CP and/or BSAP several months post-transplant. In conclusion, increased osteoclast activity may be present even in apparent plateau phase of myeloma. High-dose chemotherapy with autografting may normalize abnormal bone resorption, although the effect may take several weeks to emerge and may be paralleled by increased osteoblast activity. The findings provide biochemical evidence that autografting may help normalize the abnormal bone turnover characteristic of myeloma. (Blood. 2000;96:2697-2702)
Assuntos
Fosfatase Alcalina/sangue , Aminoácidos/urina , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Remodelação Óssea , Reabsorção Óssea/etiologia , Transplante de Células-Tronco Hematopoéticas , Isoenzimas/sangue , Mieloma Múltiplo/complicações , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Reabsorção Óssea/sangue , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/urina , Carmustina/administração & dosagem , Ácido Clodrônico/uso terapêutico , Terapia Combinada , Citarabina/administração & dosagem , Progressão da Doença , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Mieloma Múltiplo/urina , Osteoclastos/metabolismo , Podofilotoxina/administração & dosagem , Condicionamento Pré-Transplante , Transplante Autólogo , Resultado do TratamentoRESUMO
We report the case of a patient who presented with a prodromal illness suggestive of viral infection, subsequently confirmed as parvovirus B19, who had a lupus anticoagulant present. Her IgG anti-cardiolipin antibody was normal (7.0 units/ml) but her IgM anti-cardiolipin was elevated (55 units/ml). These later returned to normal. Parvovirus B19 infection may be associated with the presence of lupus anticoagulant.
Assuntos
Inibidor de Coagulação do Lúpus/sangue , Infecções por Parvoviridae/complicações , Parvovirus B19 Humano , Adulto , Cardiolipinas/imunologia , Feminino , Humanos , Imunoglobulina M/sangue , Infecções por Parvoviridae/sangue , Infecções por Parvoviridae/imunologiaRESUMO
X-linked sideroblastic anemia (XLSA) is caused by mutations of the erythroid-specific delta-aminolevulinate synthase gene (ALAS2) resulting in deficient heme synthesis. The characteristic hypochromic, microcytic anemia typically becomes manifest in the first three decades of life. Hematologic response to pyridoxine is variable and rarely complete. We report two unrelated cases of highly pyridoxine-responsive XLSA in geriatric patients previously diagnosed with refractory anemia and ringed sideroblasts. A previously unaffected 77-yr-old male and an 81-yr-old female were each found to have developed severe hypochromic, microcytic anemia with ringed sideroblasts in the bone marrow, which responded dramatically to pyridoxine with normalization of hemoglobin values. Sequence analysis identified an A to C transversion in exon 7 (K299Q) of the ALAS2 gene in the male proband and his daughter. In the female proband a G to A transition was identified in exon 5 (A172T). This mutation resulted in decreased in vitro stability of bone marrow delta-aminolevulinate synthase activity. Each patient's recombinant mutant ALAS2 enzyme had marked thermolability. Addition of pyridoxal 5'-phosphate in vitro stabilized the mutant enzymes, consistent with the observed dramatic response to pyridoxine in vivo. This late-onset form of XLSA can be distinguished from refractory anemia and ringed sideroblasts by microcytosis, pyridoxine-responsiveness, and ALAS2 mutations. These findings emphasize the need to consider all elderly patients with microcytic sideroblastic anemia as candidates for XLSA, especially if pyridoxine responsiveness is demonstrated.
Assuntos
5-Aminolevulinato Sintetase/genética , Anemia Refratária/genética , Anemia Sideroblástica/genética , Eritrócitos/enzimologia , Ligação Genética , Piridoxina/farmacologia , Cromossomo X , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Medula Óssea/enzimologia , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Mutação , Reação em Cadeia da PolimeraseRESUMO
We report the characterization of three variant antithrombins with reduced heparin binding as the primary abnormality. Two of these variants, antithrombin Southport (Leu 99 to Val, 2759 C to G) and antithrombin Vienna (Gln 118 to Pro, 5349 A to C) were novel, whereas the third, Pro 41 to Leu, has been previously described as antithrombin Basel. All three variants exhibited reduced binding for heparin on crossed immunoelectrophoresis and in a quantitative monoclonal antibody-based assay. The mutations were characterized by direct sequence analysis of enzymatically amplified genomic DNA and all affected individuals were heterozygous for the mutations. These three mutations do not occur at the sites of the basic amino acids directly involved in heparin binding nor do they result in a change in charge of the affected residue. It seems probable that they reduce heparin affinity either by perturbing the initial contact site involved in the heparin-binding domain (Arg 47, Arg 129 and possibly Arg 24), or by preventing the subsequent heparin-induced conformational change.
Assuntos
Antitrombinas/genética , Heparina/metabolismo , Mutação Puntual , Trombose/genética , Adulto , Antitrombinas/metabolismo , Feminino , Humanos , Imunoeletroforese Bidimensional , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Trombose/sangueAssuntos
Anemia Hemolítica/etiologia , Incompatibilidade de Grupos Sanguíneos , Sistema do Grupo Sanguíneo Duffy , Imunoglobulinas Intravenosas/uso terapêutico , Sistema do Grupo Sanguíneo de Kell , Sistema do Grupo Sanguíneo Kidd , Metilprednisolona/uso terapêutico , Reação Transfusional , Anemia Hemolítica/tratamento farmacológico , Anemia Hemolítica/terapia , Incompatibilidade de Grupos Sanguíneos/tratamento farmacológico , Incompatibilidade de Grupos Sanguíneos/terapia , Terapia Combinada , Emergências , Feminino , Hemorragia/terapia , Prótese de Quadril/efeitos adversos , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/terapiaAssuntos
Neoplasias Cerebelares/patologia , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma não Hodgkin/patologia , Neoplasias Primárias Múltiplas/patologia , Idoso , Neoplasias Cerebelares/diagnóstico por imagem , Feminino , Humanos , Linfoma não Hodgkin/diagnóstico por imagem , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Síndrome , Tomografia Computadorizada por Raios XRESUMO
A patient is described who developed a malignant inflammatory fibrous histiocytoma of vertebral bone (MFH) 4 months after the onset of acute lymphoblastic leukaemia. This is the first report of the simultaneous occurrence of these two conditions. Similarities to the more frequent occurrence of another histiocytic malignancy, histiocytic medullary reticulosis, following acute lymphoblastic leukaemia, are noted. The usefulness of gallium scanning to monitor the response of this tumour to treatment is demonstrated.
Assuntos
Histiocitoma Fibroso Benigno/etiologia , Leucemia Linfoide/complicações , Vértebras Lombares , Neoplasias Primárias Múltiplas/etiologia , Neoplasias da Coluna Vertebral/etiologia , Doença Aguda , Adulto , Humanos , MasculinoRESUMO
The fatty acid composition of membrane phospholipids of stimulated and unstimulated platelets was studied in six normal volunteers given a daily dietary supplement of a fish oil rich in eicosapentaenoic acid (EPA) for 4 weeks. The supplement was equivalent to 1.8 g of EPA daily. Thromboxane synthesis and platelet aggregation responses to sodium arachidonate, thrombin and the ionophore A23187 were also investigated. A marked increase in the relative EPA content of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was noted after 2 and 4 weeks fish oil supplementation. However, there was no incorporation into phosphatidylinositol (PI) or phosphatidylserine (PS). The relative arachidonic acid (AA) content of PC and PE was significantly reduced at 2 and 4 weeks but that of PI and PS remained unchanged. Significant reductions in the relative linoleic acid content of total phospholipids, PC and PE were also noted. Stimulation of platelets obtained after 4 weeks fish oil supplementation by thrombin and A23187 was associated with a marked reduction in the AA content of PI and a minor reduction in that of PE. There was no change in the relative proportions of EPA in PI, PS, PC or PE after stimulation. Throughout the study there were no significant changes in platelet aggregation responses or in platelet thromboxane production. Our results indicate that the incorporation of EPA into the platelet membrane phospholipids is selective and that if PI is the major source of AA for platelet prostaglandin biosynthesis then the reported beneficial effects of EPA on haemostasis cannot be explained on the basis of its incorporation into and mobilization from the platelet membrane phospholipid pool.
Assuntos
Plaquetas/metabolismo , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos/metabolismo , Óleos de Peixe/administração & dosagem , Fosfolipídeos/metabolismo , Adulto , Ácido Araquidônico , Ácidos Araquidônicos/metabolismo , Plaquetas/efeitos dos fármacos , Calcimicina/farmacologia , Membrana Celular/metabolismo , Cromatografia , Dieta , Ácido Eicosapentaenoico , Feminino , Humanos , Masculino , Trombina/farmacologiaRESUMO
In a study of platelets from 13 patients with acute myeloid leukaemia abnormal aggregation and release reactions were found. A previously unrecognised quantitative defect of thromboxane B2 production may, at least in part, explain these findings. In contrast to a previous report, we were unable to show a convincing storage pool defect in these platelets. The platelet membrane glycoproteins were largely normal.
Assuntos
Plaquetas/metabolismo , Leucemia Mieloide Aguda/sangue , Agregação Plaquetária , Difosfato de Adenosina/sangue , Trifosfato de Adenosina/sangue , Adolescente , Adulto , Idoso , Feminino , Glicoproteínas/sangue , Humanos , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Contagem de Plaquetas , Serotonina/sangue , Tromboxano B2/sangueRESUMO
Of 53 children with lymphoblastic leukaemia in their first remission who reached the fourth year after stopping treatment, 4 have subsequently relapsed and their cases are described. All are boys and 3 were over 10 at diagnosis despite there being only 6 such patients in the group overall. This suggests that teenage males are at special risk of late relapse and should not be considered cured on criteria applicable to younger females.
Assuntos
Leucemia Linfoide/epidemiologia , Fatores Etários , Criança , Pré-Escolar , Inglaterra , Feminino , Humanos , Masculino , Recidiva , Fatores Sexuais , Fatores de TempoRESUMO
A 37-year-old female developed what appeared to be the typical cutaneous manifestations of urticaria pigmentosa. These preceded the peripheral blood changes of acute null cell lymphoblastic leukaemia and skin biopsy revealed that the cutaneous changes were due to leukaemic infiltration. Chemotherapy resulted in clearance of the rash. The importance of skin biopsy in patients presenting with suspected urticaria pigmentosa is emphasized.
Assuntos
Leucemia Linfoide/diagnóstico , Neoplasias Cutâneas/diagnóstico , Urticaria Pigmentosa/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , HumanosRESUMO
Reports suggest that the low incidence of ischaemic heart disease in Greenlandic Eskimos is related to the effect of a diet rich in eicosapentaenoic acid on platelet reactivity and plasma lipid concentrations. A double blind randomised investigation was therefore conducted of the effects on blood viscosity of dietary supplementation with an oil rich in this fatty acid (1.8 g/day, given as fish oil) and an eicosapentaenoic acid poor oil (as corn/olive oil) in patients with peripheral arterial disease. A statistically significant reduction in whole blood viscosity was observed at seven weeks in those patients receiving the eicosapentaenoic acid rich oil. No changes in plasma viscosity, haemoglobin concentration, packed cell volume, or platelet count were seen. A significant fall in plasma triglyceride concentration was also noted only in the patients receiving oil rich in eicosapentaenoic acid; plasma concentrations of cholesterol and high density lipoprotein cholesterol were unchanged. It is concluded that rheological changes that result from a diet rich in eicosapentaenoic acid may contribute to the suggested protective effects of such a diet against arterial disease and that such changes are of potential therapeutic importance in established arterial disease.