Are Hodgkin and non-Hodgkin patients at a greater risk of atherosclerosis? A follow-up of 3 years.

Aims and background are to ascertain whether Hodgkin and non-Hodgkin patients are more affected by atherosclerotic process. We studied 96 patients during a period of 3 years (2003-2007). Patients were assessed in the first year soon after receiving radiotherapy and chemotherapy and then reassessed in the third year. All the cases underwent echo-colour Doppler of the carotid axis, and the intima-media thickness (IMT) was measured. When the two time points were compared, the IMT was greater in the arterial district examined at the first assessment; while at the second there was a reduction in the IMT, so patients seemed to improve with time. Flow-mediated dilatation did not improve. Hodgkin and non-Hodgkin patients experience an increase in IMT during treatment, but afterwards they return in their precedent condition. They seem to have a persistently reduced flow-mediated dilatation. Lymphoma therapy probably predisposes patients to early atherosclerosis, and it would be worth trying to reverse this tendency by administering antioxidant therapy.

Sequential development of large B cell lymphoma in a patient with peripheral T-cell lymphoma.

Lymphomas of different histologic type can occur in the same patient. Two types of lymphomas can be diagnosed in the same lymph node (composite lymphoma) or in different sites. In the latter case, terms as simultaneous and sequential have been proposed to define the detection of two lymphomas at the same time or at different times, respectively.

Hepatosplenic gammadelta T-cell lymphoma presenting with immune-mediated thrombocytopenia and hemolytic anemia (Evans' syndrome).

We describe an unusual case of hepatosplenic T-cell lymphoma in a 61-year-old man who presented with fever, hepatosplenomegaly, anemia, and thrombocytopenia. A spleen biopsy was consistent with T-cell lymphoma. Cytogenetic studies did not reveal chromosome abnormalities. Using the polymerase chain reaction approach, clonality of the T-cell receptor gamma-chain gene rearrangement could be demonstrated, while Southern blot analysis disclosed only a germline configuration of the T-cell receptor beta chain genes. Of interest, an immune-mediated mechanism was demonstrated and was most likely responsible for erythrocyte and platelet destruction; this is, therefore, the first report of gamma T-cell lymphoma in association with Evans' syndrome. Initial steroid treatment was efficacious in limiting autoimmunity but constitutional symptoms did not subside. Chemotherapy (MACOP-B) was successful in obtaining complete clinical remission. Finally, thrombocytopenia in gammadelta T-cell lymphoma patients should be routinely evaluated for platelet autoantibodies.

Prevalence and patterns of symptomatic thromboembolism in oncohematology.

BACKGROUND AND OBJECTIVE: Approximately 15% of patients with cancer will experience a thrombotic episode at some time. Some patients are at particularly high risk depending on the histology of the malignant disease. The aim of the study was to determine the actual prevalence of thrombotic episodes in oncohematologic patients. DESIGN AND METHODS: We conducted a retrospective cohort analysis on a total of 515 patients that were admitted to the out-patients clinic (Institute of Medical Semeiotics) from January 1, 1986 to January 31, 1996. Two main groups were selected for this study: 133 patients suffering from a myeloproliferative disorder and 382 patients affected by a lymphoproliferative disorder. Follow-up lasted a median of 33 months in both groups (range 3-144 months). The difference between the observed events for each group was estimated by the odds ratio and chi square. Age and sex distribution were estimated by the Mann-Whitney test. Distribution of overall survival was estimated by the Kaplan-Meier method and compared between groups (DVT patients and non DVT patients) by the log-rank test. RESULTS: Twenty-three patients experienced a venous thrombotic disorder. The prevalence of deep vein thrombosis (DVT) in myeloproliferative and lymphoproliferative disorders was 8.27% (n = 11) and 3.14% (n = 12) respectively (odds ratio = 0.36; 95% CI = 0.14-0.90; chi-square = 4.94 p = 0.028). DVT was apparently idiopathic in 17 cases. In 4 patients another cancer was present; in the remaining 2 patients the thrombotic episode was associated with other predisposing factors. Although 7 of the 23 patients with DVT died, we cannot find any difference in the overall survival compared to oncohematologic patients who did not experience DVT. INTERPRETATION AND CONCLUSIONS: The prevalence of symptomatic DVT in the oncohematological patients is lower than reported for solid tumor. Patients affected by myeloproliferative disease have a higher risk of developing thrombosis. DVT if well-treated does not influence the survival of oncohematological patients.

A role for platelet-derived growth factor in drug-induced chronic ergotism? A case report.

Generalized vasoconstriction in chronic ergot poisoning is attributed both to the ergotamine activity on alpha-adrenergic receptors and to its direct action on vascular smooth muscle cells. The authors propose that endothelial wall, chronically damaged by ergot alkaloids, releases platelet-derived growth factor (PDGF), which contributes to vasoconstriction and promotes further arterial obstruction. Their hypothesis is supported by the increased PDGF activity found in plasma of a patient suffering from chronic ergotism.

Neutrophil NADPH oxidase activity in chronic myeloproliferative and myelodysplastic diseases by microscopic and photometric assays.

Neutrophil NADPH oxidase is a membrane-bound enzyme complex responsible for the reduction of oxygen to superoxide anion in the respiratory burst. Impaired neutrophil function has often been reported in myeloproliferative diseases and myelodysplastic syndromes (MDSs), but its laboratory features have not been well characterized. Traditionally, NADPH oxidase activity has been evaluated with a microscopic method by nitroblue tetrazolium salt reduction to blue-black insoluble formazan granules identified in positive neutrophils by microscopy. We investigated neutrophil NADPH oxidase in 22 patients with chronic myeloproliferative disorders (cMPDs) and 15 patients with MDSs, using the microscopic method as well as a photometric microplate assay, which monitored the cytochemical reaction for 30 min. The relationship between cMPD and patient susceptibility to infections was also investigated. In the photometric assay, the mean enzyme activity in MDSs and cMPDs was lower than in normal subjects. NADPH oxidase activity was greater in cMPDs (except myelofibrosis) than in MDSs (except chronic myelomonocytic leukemia), and these differences were less evident with microscopy. Moreover, for cMPDs, patients with susceptibility to infections showed a lower NADPH oxidase activity than patients without infections.

Heterozygous type I plasminogen deficiency is associated with an increased risk for thrombosis: a statistical analysis in 20 kindreds.

The prevalence of thrombosis in patients with heterozygous type I plasminogen deficiency was studied. Fifteen kindreds described in the literature and a further five additional kindreds from the authors' Department were gathered. The prevalence of thrombotic events in all the patients with plasminogen deficiency was 23.6% (22 out of 93 patients), which decreased to 9.5% (seven of 74 patients) when the propositi were excluded. The 95 unaffected siblings were asymptomatic. The comparison between the prevalence of thrombosis in patients with plasminogen deficiency, with or without inclusion of the index patients, and in unaffected family members was statistically significant in both instances (P < 0.0001 and P = 0.002, respectively). Analogous results were obtained from construction of thrombosis-free survival curves, which showed that in plasminogen deficient patients, either with or without inclusion of the propositi, the probability of developing thrombotic manifestations is significantly higher than in unaffected siblings (P = 0.002 and P = 0.043, respectively). It is concluded that congenital heterozygous plasminogen deficiency should be considered a risk factor for thrombosis, even though the probability of having a thrombotic event seems to be lower than in other thrombophilic conditions, such as hereditary defects of clotting factor inhibitors.

Superficial hemosiderosis of the central nervous system. A case report.

A case of idiopathic superficial hemosiderosis (SH) of the central nervous system and a review of the literature are presented. The patient suffered from progressive cerebellar ataxia, hearing loss, anosmia, spastic paraparesis, but no mental deterioration. The diagnosis was made with brain and spinal MRI, that showed in T2 weighted images superficial hypointensity of spinal cord, medulla oblungata, pons, mesencephalon, cerebellum and cerebral hemispheres, images that are considered pathognomonic of SH. Repeated spinal fluid examinations were negative, suggesting that evidence of overt subarachnoidal bleeding is not essential in the diagnosis. In patients with SH of unknown etiology no valid therapy is yet available.

Acquired factor VIII:C inhibitor in a patient with Sjögren's syndrome: successful treatment with steroid and immunosuppressive therapy.

A 57-year-old woman affected with Sjögren's syndrome without bleeding history developed spontaneous hematomas at the arms, the left foot and the thigh, cutaneous hemorrhages and hematuria. Routine coagulation tests showed a prolongation of activated partial thromboplastin time associated with a marked reduction of factor VIII activity (VIII: C 5%). Other deficiencies of blood coagulation factors, especially von Willebrand factor, were excluded. Measurement of factor VIII inhibitor revealed an activity of 26.4 Bethesda units/ml. These findings were consistent with the diagnosis of acquired hemophilia A due to the presence of a factor VIII inhibitor. The patient was treated with a combination of prednisone and azathioprine. The therapy led, in a few months, to a significant reduction of factor VIII: C inhibitor and she did not require replacement therapy. Furthermore, there was a complete remission of the bleeding tendency. Long-term therapy for about 3 years induced the complete disappearance of the inhibitor and a full normalization of coagulation tests.

Serum neopterin levels in haematological malignancies.

BACKGROUND: Neopterin is an intermediate in the pathway of pteridines released in vitro from non proliferating activated cells such as macrophages stimulated with interferons. Increased urinary excretion of neopterin has been described in conditions of cell-mediated immune activation and in neoplastic diseases, including haemopoietic tumours. METHODS: We studied by radioimmunoassay serum neopterin levels of 91 patients with haematological malignancies differing in diagnosis, stage, treatment, and disease duration. RESULTS: Mean patient neopterin (13.5 nmol/L) was increased compared to 69 healthy controls (5.4 nmol/L, P < 0.001), and individual levels were related to patient survival (P = 0.006). No relevant differences were found among the various disorders, whilst advanced stages and active diseases had higher levels than initial stages and non-active diseases. Furthermore, off-therapy patients in stable remission did not differ from normals. Among subjects on therapy, patients on alpha-interferon had a higher percentage of (dose-related) neopterin elevation, in spite of a steady disease. CONCLUSIONS: We suggest that serum neopterin dosage has prognostic value in staging and follow-up, and may provide a useful tool for monitoring the therapy (particularly with biological response modifiers) of haematological neoplasias.

Mild haemophilia A fails to protect from coronary artery disease: the report of two cases.

The description of two additional cases of coronary artery disease in haemophiliacs is reported. Both patients are affected by mild haemophilia A. The first one was not aware of his coagulation disorder and therefore he had never been treated with FVIII concentrates, despite the occurrence of severe and recurrent articular and gastric bleeding episodes. He underwent cardiac catheterization that gave evidence of extensive coronary atherosclerosis. Percutaneous transluminal coronary angioplasty (PTCA) was then performed. The second patient had an inferior myocardial infarction. Influence of cardiovascular risk factors in haemophiliacs and the possible role of thrombosis in the pathogenesis of atherosclerosis are discussed.

Pyoderma gangrenosum associated with idiopathic myelofibrosis. Case history.

A case of pyoderma gangrenosum associated with idiopathic myelofibrosis is described. It is important to recognise it, since the treatment with corticosteroids and sulphonamides is frequently effective.

Incidence of thrombocytosis in lymphomas.

Reactive thrombocytosis due to malignancies and in particular those related to lymphomas have not yet been extensively evaluated. We report data on thrombocytosis recognized in 18 out of 101 patients with lymphomas diagnosed in our department over the last 3 years. All showed high platelet counts at the time of diagnosis. The incidence of thrombocytosis seems to be more frequent in males (21.2%) than in females (14.8%) and a slightly higher frequency was found in Hodgkin's disease (21.4%) than in non Hodgkin's lymphomas (16.4%). The incidence of thrombocytosis in lymphomas seems to be similar to that seen in other malignancies and because of this we conclude that a high platelet count cannot be used to distinguish malignancies.

Decreased platelet mitogenic activity in patients with diabetes mellitus.

Platelet-Derived Growth Factor is involved in the atherogenesis and in the genesis of vascular alterations in diabetes mellitus. Its evaluation in platelet extract, by means of the mitogenic stimulation of BALB/c 3T3 fibroblasts, showed significantly reduced values in ten diabetics compared with ten normal controls. Platelet poor plasma mitogenic activity was also evaluated but showed no significant difference. The release of platelet mitogens into the circulation and a resulting acquired platelet defect are suggested. A hypothetical growth inhibitory activity can be surmised, that could both contribute to angiopathy and wound healing defect typical of diabetes mellitus.

Idiopathic myelofibrosis serum induces increased DNA synthesis in BALB/c 3T3 cells.

The effect of heated serum at a concentration of 10% in culture on the in vitro growth of confluent Balb/c 3T3 cells was studied in nine patients with Idiopathic Myelofibrosis and ten normal subjects. Patients showed significant increase in the mitogenic activity in comparison with normals. The growth factors conceivably implied for the observed effect are discussed. Particular attention is paid to Platelet-Derived Growth Factor from which serum mitogenic activity is primarily derived and is thought to take part in the genesis of bone marrow fibrosis.

Changes in the mitogenic activity of platelet-derived growth factor(s) in patients with myeloproliferative disease.

Platelet-derived growth factor (PDGF) is thought to take part in the genesis of bone marrow fibrosis that can be found in patients with myeloproliferative diseases. We evaluated platelet mitogenic activity as the difference between serum and plasma activity in 8 patients with myeloproliferative disease. We observed a trend of lower values in 2 cases of polycythemia vera and 2 cases of essential thrombocythemia, as seen by other authors. Two patients suffering from chronic myeloid leukemia were within the normal range. In contrast, our 2 cases of idiopathic myelofibrosis showed increased levels. If confirmed by further studies, this could suggest a pathogenetic relationship between increased levels of PDGF and bone marrow fibrosis, and give differential diagnostic significance to the PDGF mitogenic assay in myeloproliferative diseases.