Francesco Pietrogrande

Bisphosphonate-associated jawbone osteonecrosis: a correlation between imaging techniques and histopathology

OBJECTIVES Recently, jawbone osteonecrosis has been reported as a potential adverse effect of bisphosphonates administration. This paper considers and highlights histopathologic and radiologic features of this condition. STUDY DESIGN Eleven patients, owing to unresponsiveness to conservative treatment and uncontrollable pain, underwent surgical resection of diseased jawbone after extensive hyperbaric oxygen therapy. A thorough clinical, laboratory, and imaging study was performed. Surgical specimens underwent histopathologic and immunohistochemical evaluation. RESULTS Computerized tomography (CT) scans showed increased bone density, periosteal reaction, and bone sequestration in advanced stages. With magnetic resonance imaging (MRI), exposed areas showed a low signal in T1- and T2-weighted and inversion recovery images, which suggests low water content and is histopathologically correlated with paucity in cells and vessels (osteonecrotic pattern). Unexposed diseased bone was characterized by T1 hypointensity and T2 and IR hyperintensity, which suggests high water content and inflammation, associated with hypercellularity, osteogenesis, and hypervascularity (osteomyelitic pattern). CONCLUSIONS Diseased bone extends beyond the limits of the bone exposed in the oral cavity. Histopathologic examination correlated well with CT and MRI, which are the choice for the evaluation of bisphosphonate-associated jawbone osteonecrosis.

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 Sjögrens 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.

Is radiation a risk factor for atherosclerosis? An echo-color doppler study on hodgkin and non-hodgkin patients

Aims and background The aim of the present paper was to study the role of irradiation in the atherosclerotic process in patients affected by Hodgkin and non-Hodgkin lymphoma. Methods We studied 84 subjects, 42 with Hodgkin or non-Hodgkin disease and 42 controls. All 42 cases had been irradiated and were comparable in terms of risk factors for atherosclerosis. All 84 subjects underwent echo-color Doppler of the arterial axis (carotids, abdominal aorta, and femoral arteries), and the intima-media thickness was measured. Results The irradiated cases had a greater intima-media thickness in the carotid district, even after dividing them according to age and sex; males were affected more than females. The irradiated patients were at greater risk of developing cardiovascular events than the controls. Conclusions An echo-color Doppler of the carotid district is advisable in all patients who have been submitted to radiotherapy, and the patients with a significantly greater than normal intima-media thickness need a strict follow-up, and antioxidant or antiaggregant therapy should be considered.

Measurement of serum monoclonal components: comparison between densitometry and capillary zone electrophoresis.

Abstract Quantitative measurement of serum monoclonal protein (M-protein) is one of the most important tools for monitoring disease activity in monoclonal gammopathies. The aims of this study were to evaluate serum M-protein quantification by capillary zone electrophoresis (CZE) and to compare results with those obtained by densitometric scanning of high-resolution agarose gel electrophoresis (HRE-AGE). The evaluation was carried out on 82 samples from patients with various monoclonal gammopathies. All the suspected M-proteins were confirmed and characterised by immunofixation on agarose gel (IFE). CZE was performed on a Paragon CZE™ 2000 system (Beckman Coulter). Passing-Bablok regression was: y (CZE)=1.27×(HRE-AGE)–5.21g/L. The correlation coefficient was 0.92. Bland-Altman analysis demonstrated a mean difference of −1.83g/L (95% CI −0.76 to −2.90) with clear evidence of a concentration-related bias. Densitometry gave higher values at low M-spikes (<20g/L), whereas CZE gave higher values at large M-spikes (>20g/L). The concentration-related bias was found to be independent of the immunoglobulin isotype. In conclusion, to compare previous results obtained by M-protein densitometric scanning with those obtained by direct measurement of CZE peaks, the calculation of a univocal transforming factor appears to be unreliable.

Low-dose fludarabine increases rituximab cytotoxicity in B-CLL cells by triggering caspases activation in vitro

Rituximab maintenance therapy provides a significant benefit in patients with indolent B-cell non-Hodgkin lymphoma (NHL). Based on its efficacy in improving response to chemotherapy, the anti-CD20 antibody is currently under evaluation as maintenance therapy also in patients with B-CLL. We evaluated rituximab-mediated cytotoxicity in 10 B-CLL cases pretreated in vitro with non-cytotoxic concentrations of fludarabine. This combination induced a synergic cytotoxic effect in 8 out of 10 patients at a mean level of 26.15 ± 13.9%, compared to 8.05 ± 5.3% cytotoxicity observed with rituximab alone. Consistent with the viability assay, we found an increased caspase-3 activity together with activation of caspase-9 in B-CLL cells sensitive to sequential non-cytotoxic fludarabine and rituximab exposure. Non-cytotoxic fludarabine concentrations may sensitize B-CLL cells to rituximab-mediated cytotoxicity via caspase-3 activation.

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.

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.

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 ergota mine activity on α-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.

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.

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.