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Biomedical subjects

M Cassin

Publications and source records attributed to M Cassin.

14 recordsLinked to original sources

Extracorporeal photochemotherapy induces the production of tumor necrosis factor-alpha by monocytes: implications for the treatment of cutaneous T-cell lymphoma and systemic sclerosis.

Extracorporeal photopheresis (ExP) has been shown to be an efficacious and well-tolerated therapy in the treatment of cutaneous T-cell lymphoma (CTCL) and systemic sclerosis. However, the precise mechanisms of its action have not been defined. Because of a correlation between the development of fever in the early phase of treatment of CTCL and subsequent anti-tumor responses, we examined the production of the proinflammatory, pyrogenic cytokines tumor necrosis factor-alpha (TNF), IL-6, IL-1 alpha, and IL-1 beta before and after ExP. Monocytes were purified from peripheral blood specimens of normal volunteers (n = 4) or from peripheral blood specimens of CTCL (n = 6) or systemic sclerosis (n = 3) patients that were obtained immediately prior to ExP and also directly from the photopheresis unit after ExP, just prior to reinfusion into the patient. Monocytes were then cultured under various conditions for 16 h, after which the culture supernatants were collected and assayed for specific cytokine production. ExP induced a significant increase in the production of TNF (p less than 0.008) and IL-6 (p less than 0.05) as compared to non-ExP-treated cells, whereas no significant differences were observed in IL-1 alpha (p less than 0.5) and IL-1 beta (p less than 0.2) production following ExP. Exposure of monocyte cultures to IFN-gamma (100 U/mL) either before or after ExP further enhanced TNF production by 4 to 28 times. In contrast, incubation with IFN-alpha (100 U/mL) had no significant effect on TNF production. Addition of TNF (500 U/ml) to monocyte cultures obtained prior to ExP resulted in a slight but insignificant increase in TNF production in 2 of 10 cases. However, when monocytes obtained prior to ExP were incubated with 8-methoxypsoralen (8-MOP, 100 ng/ml), exposed to ultraviolet light A (UVA, 2J/cm2), washed, and then incubated with TNF, a significant increase (p less than 0.01) in TNF production was observed in 8 of 10 cases, suggesting that the combination of 8-MOP and UVA may sensitize cells to TNF. Based on studies of endotoxin (LPS)-stimulated production of TNF by monocytes, levels of endotoxin in culture reagents or photopheresis equipment could not account for the increased production of TNF following treatment by ExP. Increased TNF production as a result of ExP may have important implications for treating both CTCL and systemic sclerosis because, in the case of CTCL, it could mediate numerous anti-tumor effects, whereas, in the case of systemic sclerosis, it could suppress collagen synthesis and induce collagenase production.

Endotoxins

Aberrant cytokine production by Sezary syndrome patients: cytokine secretion pattern resembles murine Th2 cells.

Sezary syndrome (SzS), the leukemic stage of cutaneous T-cell lymphoma (CTCL), is typically a CD4+ T-cell lympho-proliferative disease characterized by numerous immunologic abnormalities, including decreased T-cell responses to antigens and mitogens, decreased natural killer and lymphocyte-activated killer cell activities, eosinophilia, and increased levels of immunoglobulins, particularly IgE and IgA. Because this constellation of abnormalities is reminiscent of the pleiotropic in vitro activities of IL-4 and IL-5, we examined the possibility that malignant T cells in SzS may be producing increased amounts of IL-4 with a concomitant decrease in IL-2 and IFN-gamma production. Such a cytokine secretion pattern would be similar to that produced by murine Th2 cells. Serum IL-4 enzyme-linked immunosorbent assay measurements revealed that 33% of SzS patients (n = 21) had levels of IL-4 significantly higher (mean, 7.2 pg/ml; range, 0-48, p less than 0.05) than normal controls (mean, 1.59; range, 0-3.1). Although the majority of tested patients had elevated serum IgE, no direct correlation between serum IL-4 levels and serum IgE levels was observed. Peripheral blood mononuclear cells (PBMC) isolated from SzS patients and stimulated with phytohemagglutinin (PHA) produced significantly higher levels of interleukin (IL)-4 and significantly lower levels of IL-2 and interferon (IFN)-gamma than did PBMC from normal controls (p less than 0.02, p less than 0.05, and p less than 0.02, respectively). PBMC from SzS patients in remission produced IL-4 and IL-2 levels similar to that of the normal controls. To determine if IFN-gamma could inhibit the increased IL-4 production by PHA-stimulated PBMC from SzS patients, IFN-gamma was added to culture at 0, 24, or 48 h prior to the addition of PHA. Significant decreases in IL-4 production were seen only in cultures incubated with IFN-gamma for 24 and 48 h prior to the addition of PHA. IL-2 levels were not affected by IFN-gamma incubation. The increased IL-4 and decreased IL-2 and IFN-gamma production by PBMC from SzS patients suggests that Sezary cells have a cytokine profile similar to murine Th2 cells. Moreover, this cytokine secretion pattern may play an integral role in the immunopathogenesis of advanced CTCL. The results also suggest that IFN-gamma be a useful component in the spectrum of therapeutic approaches to SzS.

Animals

[The multiple coronary spasm as the cause of acute ischemic events. A case report of a simultaneous spasm of the anterior descending and the circumflex during coronary angiography].

A case of simultaneous coronary artery spasm during coronary arteriography is reported. The patient, a 48-year-old male smoker, with an important family history of sudden death, underwent coronary angiography 5 months after anterior myocardial infarction. There were no lesions in the coronary arteries at the angiographic study. At the end of the procedure there was a sudden contemporary spasm of the anterior descending and circumflex coronary arteries. This severe condition was resolved with intra-arterial nitroglycerin. The relevance of multicoronary spasm as a cause of acute ischemic events and the possible influence of family history are discussed.

Acute Disease

Combined therapy for Sézary syndrome with extracorporeal photochemotherapy and low-dose interferon alfa therapy. Clinical, molecular, and immunologic observations.

Extracorporeal photochemotherapy is a well-tolerated treatment of palliative benefit for patients with the Sézary syndrome, but up to 25% of patients do not respond to this form of therapy. Interferon alfa is a glycoprotein with immunomodulatory properties that is also an active agent in the treatment of Sézary syndrome; however, dose-related toxic effects often limit its long-term use. A patient with rapidly advancing Sézary syndrome was treated with a combination of extracorporeal photochemotherapy and low doses of subcutaneous interferon alfa-2b. In addition to the almost complete clearing of his skin lesions and the marked diminution of his extensive lymphadenopathy after 16 weeks of combined therapy, disappearance of the malignant T-cell clone from the peripheral blood was documented by Southern blot analysis. Normalization of the peripheral blood lymphocyte phenotypic profile and an increase in natural killer cell activity were also observed. The excellent clinical response to combined therapy has been sustained, without adverse effects, during 18 months of treatment and 22 months of continued follow-up. The long-term disappearance of the malignant clone from the blood of a patient with Sézary syndrome in response to therapy has not been previously described and thus represents a novel observation. Extracorporeal photochemotherapy and low-dose interferon alfa are well-tolerated therapies that, when combined, may have additive efficacy in the treatment of Sézary syndrome. These results suggest that further exploration of this therapeutic combination is warranted.

Combined Modality Therapy

[ST segment elevation after elective electric cardioversion].

From a group of 142 patient with atrial fibrillation or atrial flutter treated with DC shock, we selected 5 cases who showed a marked ST segment elevation immediately after electrical cardioversion. Only two patients, who received high voltage DC shock (950 and 1220 Joules) revealed prolonged and significant increase of CPK values. Our data suggest that ST segment transitory elevation after DC shock should probably not be considered a sign of myocardial injury even though this could be the case when high voltage DC shocks are used.

Adult

[Postoperative pseudoaneurysm of the ascending aorta. Report of a case].

Pseudoaneurysm of the ascending aorta is a rare complication after cardiac surgical procedures. This report illustrates a case of postsurgical pseudoaneurysm of the ascending aorta with ischemic clinical episodes due to compression of the right coronary artery. The patient underwent aortic and mitral valve replacement 6 years previously. The usefulness of echocardiography, computerized axial tomography and angiography is emphasized.

Aortic Diseases

[Equilibrium angioscintigraphic evaluation of sequential changes in right ventricle function in patients with lower myocardial infarct and ischemic co-involvement of the right ventricle: long-term study].

The purpose of this study was to define the sequential changes in global and regional right ventricular function, using equilibrium gated radionuclide angiography, following transmural inferior myocardial infarction (IMI) and associated ischemic right ventricular involvement. 24 patients with IMI underwent radionuclide angiography within 72 hours of onset of chest pain; subsequent studies were done at 13 +/- 5 days and at 6 +/- 2 months. Scintigraphic evidence of ischemic right ventricular involvement was defined by depression of right ventricular ejection fraction (less than 40%) and regional wall motion abnormalities (hypo-a-dyskinesia of right ventricular free wall). Significant improvement of global right ventricular ejection fraction was observed in 15 patients at the second study, and in 21 patients at the third study. Right ventricular regional wall motion showed similar improvement from the initial to the final studies. Significant changes in right ventricular function occurred without concurrent changes in global and regional left ventricular ejection fraction. We concluded that patients with IMI and ischemic right ventricular involvement show frequently improvement of global and regional right ventricular function over time. This changes tend to occur early and without significant modifications in left ventricular function. The good prognosis observed in our patients, despite the high incidence of in hospital complications, might be related to the improvement of right ventricular function.

Adult

[Fibrinolysis and hemorrhage after streptokinase in acute myocardial infarct].

The purpose of this study is to analyze the relationship between occurrence of hemorrhagic complications, kinetic of fibrinogen degradation-regeneration and the changes of prothrombin time (PT), partial thromboplastin time (PTT), after intravenous administration of Streptokinase (SK), 1.500.000 U., in acute myocardial infarction. 45 selected patients with acute myocardial infarction had pretreatment analysis and serial post-SK measurement of fibrinogen levels, PT, PTT (for 48 hours). Basal fibrinogen levels were 3.2 g/l and displayed significant depression for 18 hours (0.30-0.46 g/l) and normalization after 30 hours from SK infusion. Similar behaviour showed PT and PTT. Minor bleeding was identified in 25 patients. In bleeders mean fibrinogen levels, PT, PTT before and maximum changes after SK were not significantly different compared with non bleeders. We conclude that SK infusion produces important and prolonged changes of fibrinogen levels, PT, PTT; hemorrhagic risk is not related, however, to the extent of lytic state, but probably to pre-existent vascular derangement, predisposing to bleeding complications during fibrinolytic therapy. Therefore we believe to be prudent to delay the infusion of heparin for 12-18 hours after SK administration, when fibrinogen levels are beginning to increase.

Female

[High prevalence of 2d and 3d grade atrioventricular block in patients with acute myocardial infarct and right ventricular ischemic involvement].

43 consecutive patients with acute inferior myocardial infarction (IMI) were evaluated with 12-lead electrocardiogram plus four additional right precordial lead V3R, V4R, V5R, V6R and equilibrium gated radionuclide angiography (EGRA) to detect ischemic right ventricular involvement. All patients were continuously monitored on the average 6 days; 11 of 43 patients had an episode of second or third degree atrioventricular block. Ischemic right ventricular involvement was diagnosed by electrocardiographic criteria in 60%, and by scintigraphic criteria in 70% of 43 patients with IMI. Utilization of electrocardiogram and EGRA for diagnosis of right ventricular involvement permit us to identify a subgroup of patients with IMI at high risk of developing second or third atrioventricular block (38% with ecg criteria and 33% with radionuclide criteria respectively) as regards those without right ventricular involvement (6% and 8%).

Adult

[Isolated right ventricular infarct. Description of a case].

We report a case of extensive isolated right ventricular infarction, which was the result of proximal occlusion of a small right coronary artery in a dominant left coronary arterial system. The diagnosis and treatment of right ventricular infarction are discussed and the literature is reviewed.

Echocardiography