Background and Purpose-To evaluate whether cisplatin-induced stroke is mediated by vascular toxicity with release of prothrombotic endothelial and platelet-derived microparticles (MPs).
Methods-Endothelialand prothrombotic (Annexin V ϩ ) circulating MPs were quantified by flow cytometry in 18 patients with cancer, before and 3 days after administration of cisplatin, and compared with 18 healthy controls. Thrombin-antithrombin complex and prothrombin fragments (F 1ϩ2 ) were measured as markers of the activation of the coagulation. Results-In patients with cancer, baseline levels of circulating prothrombotic, endothelial and platelet-derived MPs were similar to healthy controls and decreased significantly after administration of cisplatin. High-baseline MPs levels were observed in 5 patients who received cisplatin for a second or third cycle. A high-baseline activation of the coagulation was observed in all patients without further increase after cisplatin infusion. Conclusion-Cisplatin treatment is immediately followed by a decrease in circulating levels of endothelial and platelet-derived MPs. However, a transient increase in MPs is observed at the second and third infusion, and this may contribute to the cisplatin-induced stroke.
2-CDA had a high activity even in heavily pretreated and refractory patients with low-grade lymphoproliferative disorders. In contrast to previously published studies, infections, mainly opportunistic, were a serious side effect in our study. In patients with severe lymphopenia at therapy initiation, the value of prophylactic anti-infective treatment should be studied.
Summary. Clinical trials with intravenous cladribine infusions in pretreated patients with Waldenström's macroglobulinaemia have shown a response rate of 40%. Our pharmacokinetic studies revealed that the bioavailability of subcutaneous cladribine is complete but that the concentration-time profile is very different from intravenous administration. We designed this phase II multi-institutional trial to study the activity and toxicity of cladribine given as s.c. bolus injections in patients with symptomatic Waldenström's macroglobulinaemia.Between May 1993 and October 1995, 25 patients were accrued: male/female 18/7, median age 65 years (range 44-85). All except one patient had been pretreated with more than one regimen (median 2, range 0-10). 18 patients had progressed under previous therapy and six were in relapse. All patients received cladribine for a total dose of 0 . 5 mg/kg per cycle as s.c. bolus injections divided over 5 d at у 4 week intervals, for a maximum of six cycles.All 25 patients were evaluable for toxicity and response. A total of 67 cycles were administered (median 3 cycles, range 1-6). Overall response rate including disease stabilization which had been progressive under previous therapy was 68%. 10 patients (40%, 95% CI 21-61%) achieved a partial remission. Seven responders had been progressive under previous therapy. Maximum responses were reached no later than the third cycle. Median time to treatment failure and remission duration were 4 . 4 (range 0 . 5-33) and 8 months (5-29), respectively. Four patients (16%) suffered from infections W.H.O. grade у 2 (pneumonia grade 2, Staphylococcus septicaemia grade 3, viral encephalitis and pneumonia, both grade 4 with complete resolution). No other severe adverse events were observed. Cladribine given as s.c. 5 d bolus injections was found to be active in pretreated Waldenström's macroglobulinaemia and resulted in durable remissions.
We report a Swiss-Spanish family three members of which have the clinical picture of thalassemia intermedia. Restriction endonuclease mapping of the alpha-globin cluster and digestion with Mae I of the in vitro amplified 5' segment of the beta-globin gene shows a combination of triplicated alpha globin locus, anti-3.7 kb type, with heterozygous codon 39 C----T beta (0) thalassemic mutation. These, as well as 16 similar cases reported in the literature, permit the following conclusion: a single extra alpha-globin gene gives rise to a clinically significant degree of dyserythropoietic anemia only when it interacts with a severe beta(+) or beta(0) thalassemic mutation.
Iron deficiency anaemia was induced in rabbits by repeated bleeding. The leucocyte alkaline phosphatase (LAP) of 26 +/- 28 units was significantly reduced compared with control values of 233 +/- 35 units (P less than 0.001). Leucocyte NBT reduction was also diminished, both in Hanks solution (P less than 0.01) and in autologous serum (P less than 0.001). After administration of iron, these values returned to normal. The results suggest that reduced LAP may reflect a deficiency of iron dependent constituents which are necessary for the integrity of normal granulocyte metabolism.
Correspondence 157 species (table I)'. Serum (rose bengal-positive, Wright 1:160, immunofluorescence 1:160) and CSF (rose bengal-positive, immunofluorescence 1:64) Brucella serology were positive and the patient was treated with daily rifampin, 900 mg, plus doxycycline, 200 mg, for 8 weeks with complete recovery. Brucellosis and tuberculosis are still endemic in our country. When the central nervous system is involved, the clinical picture and CSF analysis (elevation of protein, decreased glucose, and lymphocytic pleocytosis) may appear similar [6]. Fortunately, CSF and blood serology in neurobrucellosis are rarely negative, especially when a complete battery of tests is available, such as rose bengal and Wright agglutination, Coombs' test, and indirect immunofluorescence (as is the case in our hospital) or ELISA [7]. However, in the absence of these examinations, a correct diagnosis may be difficult [8]. Increased (>9 units/l) ADA in CSF has been reported to have a sensitivity of 1 and specificity of O.99 in the diagnosis of tuberculous meningitis [9]. However, patients with neurobrucellosis were not included in the control groups. False-positive results have been reported in cases of purulent meningitis [9, 10], but that condition could hardly be confused with tuberculous meningitis. However,neurobrucellosis can easily be mistaken for tuberculous meningitis. On the basis of our data, we think that physicians in countries where brucellosis and tuberculosis are endemic should take care when interpreting increased ADA in CSF, at least until neurobrucellosis can be definitively excluded.
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