A rapid agglutination assay to detect anti-streptokinase antibodies

Background Streptokinase resistance may cause suboptimal thrombolytic therapy. Aim To develop a rapid latex-bead assay to detect streptokinase antibodies. Methods Sera were obtained from 16 patients presenting with acute myocardial infarction (MI) before treatment with streptokinase and 1 and 6 months post treatment, and from 100 controls. Sera were assayed for anti-streptokinase antibodies using a functional streptokinase-neutralising assay. Results Streptokinase-neutralising activity was low in controls (54±5U/ml) and patients prior to treatment (101±18), increasing to 2,110±823 and 1,017±169 at 1 and 6 months (mean±SEM). The latex assay had a sensitivity of 94% and a specificity of 93% for detecting individuals with >350U/ml of streptokinase resistance, which is sufficient to neutralise the drug clinically. Conclusions Estimation of streptokinase resistance using an enzyme immunoassay and a latex bead assay correlated well with serum neutralising activity. This assay can rapidly identify patients who have a high level of streptokinase-neutralising activity.     

Effect of test interruptions on blood lactate during constant workload testing

OBJECTIVE: To determine whether repetitive test interruptions (TI) during constant load testing influence blood lactate concentration (BLC), maximal lactate steady state (MLSS), MLSS workload (P-MLSS), and relative MLSS intensity (Int-MLSS). METHODS: Nineteen males participated in this study. In experiment A, 10 subjects (27.5 +/- 2.9 yr; 183.7 +/- 5.2 cm; 77.4 +/- 3.7 kg) performed 30-min constant load tests: one without TI, one with TI of 30 s, and one with TI of 90 s after every 5 min of cycling at a given workload. In experiment B, nine subjects (28.0 +/- 2.7 yr; 182.9 +/- 6.8 cm; 76.2 +/- 4.5 kg) performed 30-min constant load tests at different workloads until MLSS had been determined for all three TI protocols. RESULTS: In experiment A, the BLC after 30 min net working time (BLC30) was higher (P < 0.001) without TI (6.0 +/- 1.3 mmol.l(-1)) than with TI of 30 s (4.9 +/- 1.4 mmol.l(-1)) or 90 s (4.5 +/- 1.1 mmol.l(-1)). The change in BLC during the final 20 min (DeltaBLC10-30) was greater (P < 0.01) without TI (1.2 +/- 1.0 mmol.l(-1)) than with TI of 30 s (0.2 +/- 0.7 mmol.l(-1)) or 90 s (-0.3 +/- 0.7 mmol.l(-1)). In experiment B, the MLSS was not affected, but P-MLSS and Int-MLSS were lower (P < 0.01) without TI (277.8 +/- 24.4W and 73.7 +/- 7.6%) than with TI of 30 s (300.4 +/- 30.4W and 79.2 +/- 8.0%) or 90 s (310.0 +/- 31.2W and 81.5 +/- 7.1%). Approximately 35% of the variance of BLC30 and DeltaBLC10-30, and 70% of the variance of P-MLSS and Int-MLSS were explained by TI duration (P < 0.001). CONCLUSIONS: TI decreased BLC30 and DeltaBLC10-30 but has no effect on MLSS. Consequently, with TI, the MLSS is achieved at higher P-MLSS and Int-MLSS.     

Coralline hydroxyapatite bone graft substitutes: preliminary report of radiographic evaluation

A new bone graft substitute made by conversion of the calcium carbonate exoskeleton of reef-building sea coral into hydroxyapatite has recently become clinically available. The normal radiographic appearance of two forms of this material is described. In the immediate postoperative period, the exoskeletal architecture of these implants is readily appreciated. With graft incorporation over the ensuing months, their intrinsic structure is gradually lost in association with poor marginal definition. Evolving radiographic findings reflect the biocompatible nature of these implants, which provides the potential for ingrowth of native bone with preservation of the coralline scaffold, resulting in enhanced biomechanical properties.     

Invasive zygomycosis in patients with graft‐versus‐host disease after allogeneic stem cell transplantation

M. Leithauser, C. Kahl, C. Aepinus, F. Prall, M. Maruschke, H. Riemer, D. Wolff, K. Jost, I. Hilgendorf, M. Freund, C. Junghanss. Invasive zygomycosis in patients with graft‐versus‐host disease after allogeneic stem cell transplantation
Transpl Infect Dis 2010: 12: 251–257. All rights reserved Abstract: Invasive mold infections are a threat to immunosuppressed patients such as patients with graft‐versus‐host disease (GVHD) after allogeneic stem cell transplantation (SCT). Up to 10% of SCT recipients develop invasive aspergillosis (IA). Invasive zygomycosis (IZ) may occur during treatment against IA. Here we report 4 SCT patients with GVHD diagnosed with IZ. All patients had received myeloablative hematopoietic SCT and developed chronic GVHD requiring systemic immunosuppression. Underlying diseases were acute lymphocytic leukemia (2), osteomyelofibrosis, and multiple myeloma. All patients had developed pulmonary infiltration that led to initiation of antifungal therapy. Treatment for IA was voriconazole, caspofungin, or itraconazole. Organs involved with zygomycosis were lung, nasal sinus, skin, and kidney. Treatment with liposomal amphotericin and posaconazole was initiated in all patients, and 2 patients also had surgical debridement as well. Despite intensive treatment, no patient survived. IZ is becoming more common in patients with GVHD on successful treatment for IA. Even non‐specific symptoms are suspicious in this group of patients and need to be evaluated by vigorous diagnostics. Despite effective antifungals and surgical intervention, the prognosis is grim in patients with active GVHD, as immunoreconstitution is mandatory for successful management.     

In vivo hematopoietic effects of recombinant interleukin-1 alpha in mice: stimulation of granulocytic, monocytic, megakaryocytic, and early erythroid progenitors, suppression of late-stage erythropoiesis, and reversal of erythroid suppression with erythropoietin

Interleukin-1 alpha (IL-1 alpha) is a macrophage-derived, multifunctional cytokine that broadly potentiates myelopoiesis and induces the synthesis of hematopoietic colony-stimulating factors (CSF) in vitro and in vivo. To evaluate the possibility for use of IL-1 alpha in ameliorating in vivo bone marrow suppression induced by drugs or radiation, we examined the in vivo effects of the cytokine on erythropoietic and other hematopoietic progenitor cells. Normal mice were treated with a single intraperitoneal (IP) injection of recombinant human IL-1 alpha at varying doses and were assayed at various times post-treatment. By six hours postinjection, a significant suppression of mature erythroid progenitors (CFU-E) was observed in animals treated with IL-1 alpha (0.5 micrograms/mouse), with maximum suppression of CFU-E and peripheral blood reticulocyte counts occurring at 24 hours. Decreases in peripheral blood hematocrit did not occur after a single IL-1 alpha injection but were observed after multiple injections of the cytokine. The suppressive effects of IL-1 alpha on late-stage erythropoiesis were abrogated by simultaneous administration of erythropoietin (EPO). At 48 hours post-treatment, a marked stimulation was observed in the numbers of spleen and marrow immature erythroid (BFU-E), macrophage (CFU-M), granulocyte (CFU-G), granulocyte- macrophage (CFU-GM), and megakaryocyte (CFU-meg) progenitor cells. These results demonstrate the potential use of IL-1 alpha as a generalized stimulator of hematopoiesis and show that the cytokine- induced suppression of late-stage erythropoiesis can be prevented by EPO.     

The reciprocal relationship of thrombopoietin (c-Mpl ligand) to changes in the platelet mass during busulfan-induced thrombocytopenia in the rabbit

Thrombopoietin (c-Mpl ligand) has recently been purified and is considered to be the humoral regulator of platelet production. To see whether this molecule possessed the physiologic characteristics necessary to mediate the feed-back loop between blood platelets and the bone marrow megakaryocytes, we determined the relationship between blood levels of thrombopoietin and changes in the circulating platelet mass. We developed a model of nonimmune thrombocytopenia in rabbits by the subcutaneous administration of busulfan. Compared with pretreatment plasma, plasma taken from all thrombocytopenic rabbits at their platelet nadir contained increased amounts of thrombopoietin. All of this activity was neutralized by soluble c-Mpl receptor. We subsequently measured the level of thrombopoietin in the circulation over the entire time course after the administration of busulfan. As the platelet mass declined, levels of thrombopoietin increased inversely and proportionally and peaked during the platelet nadir. With return of the platelet mass toward normal, thrombopoietin levels decreased accordingly. When platelets were transfused into thrombocytopenic rabbits near the time of their platelet count nadir, the elevated levels of thrombopoietin decreased. In addition, platelets were observed to remove thrombopoietin from thrombocytopenic plasma in vitro. These results confirm that thrombopoietin is the humoral mediator of megakaryocytopoiesis and suggest that the platelet mass may directly play a role in regulating the circulating levels of this factor.     

Bile duct obstruction: radiologic evaluation of level, cause, and tumor resectability

In a prospective study of 65 patients with bile duct obstruction, various radiologic modalities were compared for their capability to demonstrate the level and cause of obstruction and to indicate accurately tumor resectability. Ultrasound (US) was performed in 65 patients, computed tomography (CT) in 51, direct cholangiography (DC) in 57, and angiography in 35. The level of obstruction was correctly indicated by US in 95% of patients and by CT in 90%, and the cause was correctly indicated by US in 88%, by CT in 63%, and by DC in 89%. In predicting tumor resectability, US was correct in 71% of patients, compared with 42% for CT, 58% for DC, and 25% for angiography. US therefore appears to be the single most useful modality in the evaluation bile duct obstruction.