Iron metabolism was studied in 10 patients with malignant histiocytosis (MH), in 16 patients with histiocytosis-X (Langerhans cell histiocytosis) and in 34 patients with reactive proliferation of the mononuclear phagocytes (MPS). Eight MH patients had a considerably increased level of serum ferritin (SF). The average level of SF was 6070 +/- 957 mg/l for MH patients, which is significantly greater than the SF level for HX and RH patients. The study of the serum ferritin profiles suggests that the main pathogenetic mechanism of hyperferritinaemia in MH is the synthesis and secretion of ferritin by neoplastic mononuclear phagocytes. From this, hyperferritinaemia in MH may be considered as pathognomic of this disease and used as an additional diagnostic criterion. In addition, SF is the most informative parameter for the clinical practice among the indices of the functional state of MPS.
In Chuvash polycythemia, homozygous von Hippel-Lindau (VHL) 598C>T leads to increased hypoxia inducible factor-1α and 2α, thromboses and lower systemic blood pressures. Circulating homocysteine, glutathione, γ-glutamyltransferase and cysteinylglycine concentrations were higher in 34 VHL598C>T homozygotes than in 37 normal controls and cysteine was lower. Multivariate analysis showed elevated homocysteine independently associated with higher mean systemic blood pressures and elevated glutathione was associated with lower pressures to a similar degree. Among VHL598C>T homozygotes, homocysteine was elevated with low and normal folate concentrations, consistent with a possible defect in the remethylation pathway. The elevated glutathione and γ-glutamyltranserase levels correlated positively with cysteinylglycine, consistent with possible upregulation of a glutathione synthetic enzyme and γ-glutamyltransferase. Cysteinylglycine correlated inversely with cysteine, consistent with possible reduced cysteinyldipeptidase activity. We conclude that upregulated hypoxia-sensing may influence multiple steps in thiol metabolism. The effects of the resultant elevated levels of homocysteine and glutathione on systemic blood pressure may largely balance each other out.
Increased PRV-1 mRNA expression and the presence of Jak2(V617F) mutation in peripheral blood granulocytes are specific markers for chronic myeloproliferative disorders (MPD), which facilitate the differential diagnosis between polycythemia vera (PV) and secondary erythrocytosis (SE) and may be helpful for monitoring treatment efficacy in MPD patients. We evaluated the presence of the Jak2V617F mutation and increased PRV-1 mRNA expression along with previously established markers - erythropoietin (EPO) independent colony formation (EEC) and erythropoietin level for diagnosis of PV and assessment of treatment efficiency. Increased PRV-1 expression was found in 37 out of 46 patients diagnosed with PV (80%), in 4 out of 15 patients diagnosed with essential thrombocythemia (ET) (27%) and in 4 out of 8 patients with chronic idiopathic myelofibrosis (CIMF) (50%), and increased PRV-1 expression plus EEC formation was observed in 19 of 36 examined MPD patients indicating the superiority of PVSG and WHO bone marrow criteria for the diagnosis of ET, PV and CIMF. We could confirm a very high sensitivity, specificity and utility of the Jak2(V617F) mutation for differential diagnosis between PV and SE. Spontaneous EEC, serum EPO levels, PRV-1 expression was evaluated in 22 PV patients who carried the Jak2(V617F) mutation. A concordance of increased PRV-1 expression and presence of Jak2(V617F) mutation in 19/22 (85%); of increased PRV-1/Jak2/EEC in 14/22 (63%); and of Jak2/PRV-1/EEC/low Epo level in 10/22 (45%) patients was found indicating the superiority of the presence of Jak2(V617F) mutation for the diagnosis of PV. IFN-alpha therapy in patients with PV was more effective then hydroxyurea treatment and significantly reduced increased PRV-1 expression together with higher levels of Jak2(V617F) mutation (50-100%) in PV patients treated with hydroxy urea (HU) and lower levels of Jak2(V617F) mutation (35-90%) in PV patients treated with IFN-alpha. Normal PRV-1 expression level was observed in 44% of PV patients who achieved clinical remission and only in 3% of patient who did not. These preliminary observations indicate that the Jak2(V617F) mutation in particular and PRV-1 overexpression appear to be suitable markers for monitoring treatment efficiency in prospective randomised clinical studies comparing pegylated interferon and hydroxyurea in well defined PV patients with a clear indication for cytoreductive therapy.
Цель исследования. Оценка динамики уровня цитокинов, ферритина и эндотелина в периферической крови и фильт рате у пациентов с полиорганной дисфункцией на фоне проведения ПВГДФ. Материал и методы. Обследовано 28 больных в возрасте от 32 до 69 лет с тяжестью состояния по шкале APACHЕ II от 31 до 36 баллов. Результаты. Выявлено, что до проведения ПВГДФ у больных отмечался повышенный уровень провоспалительных цитокинов в плазме крови. Во время ПВГДФ элиминировалось значительное количество цитокинов, причем уровень некоторых цитокинов в фильтрате был выше, чем в плазме крови, вероятно, в результате диссоциации медиаторов воспалитель ной реакции при прохождении через экстракорпоральный контур. Заключение. Отмечено, что уровни TNF α α, IL 2, IL 6 и IL 10 у выживших больных были значительно выше, а IL 1β β и ферритина ниже, чем у умерших. К концу лече ния отмечена тенденция к нормализации цитокинов у выживших больных. После проведения дальнейших исследова ний будут определены возможности использования уровня некоторых цитокинов в качестве прогностических факто ров оценки тяжести состояния больного. Ключевые слова: цитокины, ПВГДФ, полиорганная дисфункция. Objective: to evaluate changes in the levels of cytokines, ferritin, and endothelin in the peripheral blood and filtrates of patients with multiple organ dysfunctions during continuous high volume hemodiafiltration (CHVHDF). Subjects and methods:Twenty eight patients aged 32 to 69 years with the severity of disease of 31 to 36 APACHE II scores were exam ined. Results. Prior to CHVHDF, the patients were found to have elevated plasma proinflammatory cytokines. During CHVHDF, the bulk of cytokines were eliminated, the levels of some cytokines were higher in the filtrate than in the plas ma, presumably, due to the dissociation of inflammatory mediators passing through the extracorporeal circuit. Conclusion. In survivors, the levels of TNF α α, IL 2, IL 6, and IL 10 were much higher, but those of IL 1β β and ferritin were lower than those in deceased patients. By the end of treatment, there was a trend for cytokines to become normal in the survivors. The possibilities of using the level of some cytokines as predictors for the evaluation of patients' condition will be determined after further studies.
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