Treatment of childhood Hodgkin's disease with ABVD without radiotherapy

Seventeen previously untreated children with Hodgkin's disease were treated with six courses of the combination adriamycin, bleomycin, vinblastine, and DTIC (ABVD), without radiotherapy, from 1984–1987. In all patients, complete remission was attained. After a median follow-up period of 73.5 months (range 59–98 months), five patients had a relapse after 4, 5, 11, 21, and 34 months, respectively, from attainment of complete remission. In 12 patients with stages I and II, two relapses occurred. Three out of five patients with stage III and stage IV developed a relapse. Based upon these results, we conclude that ABVD might be an appropriate treatment for newly diagnosed children with Hodgkin's disease stages I and II. However, for children with stages III and IV, more intensive treatment is needed. Radio-therapy should be withheld for children with refractory disease, residual disease, or relapse. © 1996 Wiley-Liss, Inc.     

Coronary artery bypass grafts: assessment of graft patency and native coronary artery lesions using 16-slice MDCT

The objective of this study was to evaluate the accuracy of electrocardiography (ECG)-gated 16-slice multidetector-row computed tomography (MDCT) in detection of stenosis of bypass grafts and native coronary arteries in patients who have undergone coronary artery bypass grafting (CABG). ECG-gated contrast-enhanced MDCT using 12×0.75-mm collimation was performed in 20 patients with recurrent angina 4.75 years after undergoing CABG. A total of 50 grafts, 16 arterial and 34 venous, were examined. All graft and coronary segments were evaluated for stenosis in comparison with conventional coronary angiography (CCA). Among the 80 arterial graft segments, 62 could be assessed (77.5%). Sensitivity, specificity, and positive and negative predictive values for stenosis were 96.2%, 97.2%, 96.2%, and 97.2%, respectively. In a total of 180 venous graft segments, 167 could be assessed. Sensitivity, specificity, and positive and negative predictive values for stenosis were 98.5%, 93.9%, 91.8%, and 98.9%, respectively. MDCT could assess 179 of 260 native coronary artery segments (68.8%).Sensitivity, specificity, and positive and negative predictive values for stenosis were 92.1%, 76.9%, 87.5%, and 84.7%, respectively. Sixteen-slice MDCT provides excellent image quality and diagnostic accuracy in detection of graft and coronary artery lesions in patients with suspected graft dysfunction.     

A quantitative and qualitative comparison of fibrin glue, albumin, and blood as agents to pretreat porous vascular grafts

Recent reports suggest that fibrin glue can be used to seal porous vascular grafts prior to insertion, but this ability has not been quantitatively compared to existing methods. We compared blood loss from and handling characteristics of grafts pretreated with either fibrin glue (FG) (Tisseel), albumin autoclaving (AA), or blood preclotting (BP). Five 6-cm segments of 6-mm internal diameter grafts, both knitted and woven double velour Dacron were treated in each group (30 specimens). Human blood was forced through the BP group until clotted; AA segments were soaked in 25% human albumin and autoclaved for 10 min; FG segments were treated with a topical application of Tisseel (0.5 ml/graft) followed by treatment with topical thrombin + CACl (0.5 ml/graft). Graft ends were sealed and attached to a transducer/syringe pump mechanism which pumped heparinized human blood into the graft at 100 mm Hg intraluminal pressure. All blood that leaked through the grafts over 2 min was collected and the amount was averaged for the five grafts in each group. Graft handling was characterized as either pliable or stiff. Blood pretreatment caused 21 +/- 2 and 13 +/- 4 cc/2 min of leak in knitted and woven grafts, respectively. Albumin autoclaving resulted in 9 +/- 2 and 1 +/- 0.5 cc of leak (P less than 0.01 compared to blood), while fibrin glue produced 2 +/- 2 and 0.4 +/- 0.5 cc leaks (P less than 0.01 compared to blood). Both blood and fibrin glue produced soft pliable grafts, while albumin pretreatment resulted in stiff grafts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Split immune response after oral vaccination of mice with recombinant Escherichia coli Nissle 1917 expressing fimbrial adhesin K88

Enterotoxigenic Escherichia coli (ETEC) are a leading cause of diarrhoea in piglets and newborn calves. Massive efforts have therefore been made to develop a vaccine for the induction of protective mucosal immunity against ETEC. Since it has been shown that the probiotic strain E. coli Nissle 1917 (EcN) can serve as a safe carrier for targeted delivery of recombinant molecules to the intestinal mucosa, we constructed the recombinant strain EcN pMut2-kanK88 (EcN-K88) stably expressing the determinant for the K88 fimbrial adhesin of ETEC on the bacterial surface.After oral application of EcN-K88 to mice for one week, EcN-K88 as well as wild-type EcN and EcN mock-transformed with the plasmid vector only could be detected in faecal samples for a minimum of 7 days after the last feeding, indicating that EcN can transiently colonise the murine intestine. Oral application of EcN-K88 resulted in significant IgG serum titres against K88 as early as 7 days after the initial feeding with EcN-K88, but no significant IgA titres. In contrast, we failed to detect any specific T cell responses towards the K88 antigen both in spleen and mesenteric lymph nodes. Although dendritic cells readily upregulated maturation and activation markers in response to K88 stimulation, accompanied by secretion of interleukin (IL)-12, IL-6, IL-10, and tumour necrosis factor, restimulation of T cells from mice having received EcN-K88 with K88-loaded dendritic cells did not result in detectable T cell proliferation and IL-2 secretion, but rather induced an IL-10 bias. While the serum antibody responses clearly demonstrate that K88 is recognized by the humoral immune system, our findings indicate that oral application of probiotic EcN expressing the K88 fimbrial adhesin does not induce a selective T cell response towards the antigen.     

Downregulation of Plk1 Expression By Receptor-Mediated Uptake of Antisense Oligonucleotide-Loaded Nanoparticles

Human serum albumin (HSA) nanoparticles represent a promising tool for targeted drug delivery to tumor cells. The coupling of the antibody trastuzumab to nanoparticles uses the capability of human epidermal growth factor receptor 2 (HER2)-positive cells to incorporate agents linked to HER2. In our present study, we developed targeted nanoparticles loaded with antisense oligonucleotides (ASOs) against polo-like kinase 1 (Plk1). We evaluated the receptor-mediated uptake into HER2-positive and -negative breast cancer and murine cell lines. We performed quantitative real-time PCR and Western blot analyses to monitor the impact on Plk1 expression in HER2-positive breast cancer cells. Antibody-conjugated nanoparticles showed a specific targeting to HER2-overexpressing cells with cellular uptake by receptor-mediated endocytosis and a release into HER2-positive BT-474 cells. We observed a significant reduction of Plk1 mRNA and protein expression and increased activation of Caspase 3/7. Thus, this is the first report about ASO-loaded HSA nanoparticles, where an impact on gene expression could be observed. The data provide the basis for the further development of carrier systems for Plk1-specific ASOs to reduce off-target effects evoked by systemically administered ASOs and to achieve a better penetration into primary and metastatic target cells. Treatment of tumors using trastuzumab-conjugated ASO-loaded HSA nanoparticles could be a promising approach to reach this goal.     

Leukemic iris infiltration as the only site of relapse in a child with acute lymphoblastic leukemia: temporary remission with high-dose chemotherapy

A 12-year-old Caucasian boy developed leukemic hyphema with iris infiltration as the only relapse site during the third complete remission of his acute lymphoblastic leukemia. With high-dose methotrexate, high-dose cytosine-arabinoside plus teniposide, and a 5-week course of vincristine, prednisolone, and L-asparaginase, a complete remission could be achieved. Maintenance treatment was reinstituted for 1 year. However, after stopping the treatment, the iris infiltrate reappeared, and this time the eye was irradiated after chemotherapeutic reinduction. Seven months later, the boy remains in complete remission. The pathogenesis of leukemic iris infiltration is discussed briefly.