Synergistic effect of low dose Cyclosporine A and human interleukin 10 overexpression on acute rejection in rat lung allotransplantation

Objective: Electroporation mediated transfer of plasmid DNA into peripheral muscle results in high transfection efficiency. The aim of this study was to investigate the effect of gene transfer of human IL-10 (hIL-10) into the tibialis anterior muscle (MTA) in combination with low dose Cyclosporine A (CsA) on acute rejection of lung allografts in the rat. Methods: Lung allotransplantation was performed from male BN donor to male Fisher F344 rats. Gene transfer was achieved by intramuscular injection into the MTA of the recipient followed by electroporation (4×20 ms impulses at 200 V/cm) 24 h prior to the transplantation. Group A (n=5) received CsA (2.5 mg/kg bw ip) for 5 days post-transplant and group B (n=5) 2.5 μg of PCIK hIL-10 (plasmid expression vector containing human CMV immediate early gene promoter and enhancer) and a low dose CsA (2.5 mg/kg bw i.p.). Graft function was assessed by blood gas at day 5 after exclusion of the native lung. Animals were sacrificed and blood was drawn to measure serum hIL-10 levels (ELISA) and tissue was sampled for histological grading of rejection. Results: Local expression of hIL-10 was confirmed at the mRNA level by in situ hybridization. All group A control animals showed severe signs of rejection. At day 5 all grafts in group B showed good gas exchange mean PaO2 233±123 mmHg, vs 44±8 mmHg in group A. Histological examination revealed moderate to severe rejection in all animals in group A (IIIB, ISHLT) in contrast to low moderate rejection in group B (II–IIIA). hIL-10 serum levels on day 5 were 14±7 pg/ml in group B vs. 0 in group A. Conclusions: Electroporation mediated hIL-10 overexpression in a peripheral muscle of the recipient in combination with low dose CsA reduces acute rejection in this model of rat lung allotransplantation.     

Spinal manipulation in a case of sacral fracture: presentation in a chiropractic office

A case is presented involving the successful management of symptoms following a sacral fracture. Treatment was primarily comprised of sacroiliac joint manipulation. The importance of accurate diagnosis, realistic risk/benefit assessment, and appropriate treatment is emphasized in considering contraindications of spinal manipulative therapy.     

Health-related quality of life parameters as prognostic factors in a nonmetastatic breast cancer population: an international multicenter study.

PURPOSE: The purpose of this research was to evaluate whether baseline health-related quality of life (HRQOL) parameters are prognostic factors for survival in locally advanced breast cancer patients. Although the literature highlights the important role of HRQOL parameters in predicting survival in advanced metastatic disease, little evidence exists for earlier stages. PATIENTS AND METHODS: The overall sample consisted of 448 patients randomly assigned to receive cyclophosphamide, epirubicin, and fluorouracil versus epirubicin, cyclophosphamide, and granulocyte colony-stimulating factor. Patients were enrolled in 12 countries. HRQOL baseline scores were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap resampling technique was used to assess the stability of the outcomes. Bootstrap results were then applied for model averaging purposes as a means to account for the observed model selection uncertainty. RESULTS: The final multivariate model retained inflammatory breast cancer (T4d) as the only factor predicting overall survival (OS) with a hazard ratio of 1.375 (95% CI, 1.027 to 1.840; P =.03). The presence of inflammatory breast cancer lowers the median survival time from 6.6 to 4.2 years (36% reduction). None of the preselected HRQOL variables were prognostic for OS or disease-free survival, in either the univariate or multivariate analysis. CONCLUSION: Our findings suggest that baseline HRQOL parameters have no prognostic value in a nonmetastatic breast cancer population.     

Thoracoscopic splanchnicectomy for pain relief in unresectable pancreatic cancer

HYPOTHESIS: Unilateral truncal thoracoscopic splanchnicectomy (TS) provides safe and effective treatment for pain relief in patients with unresectable pancreatic cancer. DESIGN: Before-and-after trial of 24 patients undergoing 25 TS procedures. SETTING: Surgical unit at a university teaching hospital. PATIENTS: A consecutive sample of 24 patients with severe pain due to unresectable (primary or recurrent) pancreatic cancer refractory to drug therapy and with a life expectancy of less than 6 months. INTERVENTION: The key point of the reported operation is intrathoracic carbon dioxide insufflation, which allows a more distal division of the greater splanchnic nerve and a 2-port technique. MAIN OUTCOME MEASURES: Pain and the effect of this symptom on quality of life were assessed before and after TS using a 10-point visual analog pain scale (VAS) and the Nottingham Health Profile questionnaire, respectively. RESULTS: Four TS procedures were technical failures because of pleural adhesions. One patient required a contralateral procedure 12 weeks after TS. Mean (+/- SD) preoperative VAS basal score was 7.4 +/- 1.7. Twenty-four hours after TS, it was reduced to 0.6 +/- 1.0. Significant reduction of VAS scores persisted over the first 3 months after TS (P<.001). Recurrence of pain of low intensity (mean VAS basal score, 4.2) was observed in 8 patients. Significant improvement (P<.001) in each area covered by the Nottingham Health Profile questionnaire was reported at 1 month after TS. CONCLUSION: Thoracoscopic splanchnicectomy offered substantial short-term relief of pain in patients with unresectable pancreatic cancer, and significantly ameliorated the quality of their residual life.     

RBE of 20 kV and 70 kV X-rays determined for survival of V 79 cells

The survival curves of V 79 cells were compared for various types of sparsely ionizing radiation: 20 kV, 70 kV and 42 MV X-rays, 60Co gamma-rays and 40 MeV electrons. A carefully calibrated thin window chamber was used for accurate dosimetry. The survival curves for cells exposed to 20 kV X-rays and 70 kV X-rays differed from that for 60Co gamma-rays only by a dose-scaling factor t(RBE). RBE with respect to 60Co gamma-rays could then be considered as dose-independent: 1.19 +/- 0.06 for 70 kV X-rays and 1.40 +/- 0.07 for 20 kV X-rays. RBE of 42 MV X-rays and 40 MeV electrons was not significantly different from 1.     

Long-term follow-up of patients with moderate aplastic anemia and pure red cell aplasia treated with daclizumab

Background

Pure red cell aplasia and moderate aplastic anemia are marrow failure states with an immune pathogenesis. Previously, we described short-term improvements in blood counts in two pilot studies treating moderate aplastic anemia (mAA) and pure red cell aplasia (PRCA) patients with daclizumab, a humanized monoclonal antibody to the interleukin-2 receptor; we now report our long-term experience with a larger cohort of patients.

Design and Methods

After a median follow-up period of 4.8 years, 19 of 45 (42%) evaluable mAA patients and 10 of 26 (38%) patients with PRCA responded by three months and 2 additional mAA patients responded by six months following administration of the drug.

Results

Seven of 28 (25%) mAA patients achieved long-term packed red blood cell PRBC transfusion independence, and all PRCA responders achieved long-term transfusion PRBC transfusion independence.

Conclusions

Red cell transfusion-independence prior to treatment in mAA patients predicted response. The only significant adverse treatment-related events were transient rashes and arthralgias. Daclizumab is safe and effective, and produces lengthy remissions in patients with PRCA and mAA.     

Impact of early abciximab administration on myocardial reperfusion in patients with ST-segment elevation myocardial infarction pretreated with 600 mg of clopidogrel before percutaneous coronary intervention

Early rapid platelet inhibition with abciximab before primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) is suggested as beneficial. In previous studies on early abciximab administration clopidogrel was administered in cathlab in low loading dose. We investigated the role of early abciximab administration on top of early clopidogrel 600 mg loading dose in patients with STEMI treated with PPCI. A total of 73 non-shock STEMI < 6 h patients admitted to remote hospitals with anticipated delay to PPCI < 90 min were randomly assigned to three study groups—24 pts received abciximab before transfer to cathlab (early = group EA), 27 in cathlab during PPCI (late = group LA) and in 22 abciximab administration was left to operator’s discretion during PPCI (selective = SA; given in 22.7% of patients). All patients received clopidogrel (600 mg), aspirin and heparin (70 U/kg) before transfer to cathlab. Angiography revealed more frequent infarct-related artery patency (TIMI 2 + 3: EA vs LA vs SA: 45.8 vs 18.5 vs 13.6%, P = 0.024), better myocardial tissue perfusion (MBG 2 + 3: EA vs LA vs SA: 45.8 vs 14.8 vs 13.6%, P = 0.02) in EA group in baseline angiography. There was no difference in these angiographic parameters and ECG ST-segment resolution after PPCI. In multivariate analysis early abciximab administration was an independent predictor of infarct-related artery patency in baseline angiography (OR 6.5; 95% CI 1.83–23.1; P = 0.004). Early abciximab administration before transfer for PPCI in patients with STEMI pretreated with 600 mg of clopidogrel results in more frequent infarct-related artery patency and better myocardial tissue perfusion before PPCI.