Sequential comparison of low dose rate and hyperfractionated high dose rate endobronchial radiation for malignant airway occlusion.

A pilot trial (S2) was conducted at the University of Wisconsin to determine the feasibility, efficacy, and toxicity of hyperfractionated high dose rate endobronchial radiation. To avoid multiple bronchoscopies, an optimized hyperfractionated schema was derived from the linear-quadratic model. Utilizing a single bronchoscopy, 31 patients with malignant airway occlusion received 4 Gy x 4 fractions over 2 days at 2 cm from source center using a high dose rate remote afterloader. Response and morbidity were compared to a previous trial (S1) in which 66 patients were treated with conventional low dose rate endobronchial radiation. Response was assessed by change in performance status, symptom resolution, percent of lifetime rendered symptom-free or improved, and radiographic reaeration. These parameters were highly comparable between the two groups. The mean ECOG performance status improved from 2.2 to 1.8 for S1 and 2.1 to 1.6 for S2; symptom improvement or resolution was noted in 78% for S1 and 79% for S2; lifetime rendered symptom-free or improved was 54% for S1 and 57% for S2; and the overall radiographic response rate was 78% for S1 and 85% for S2. The overall incidence of fistulae was 7/101. We conclude that endobronchial radiation is an effective and safe modality for palliation, and hyperfractionated high dose rate endobronchial radiation achieves responses similar to low dose rate endobronchial radiation with a similar complication rate.     

American Society of Nuclear Cardiology review of the ACCF/ASNC appropriateness criteria for single-photon emission computed tomograph myocardial perfusion imaging (SPECT MPI)

Conclusion  The ACCF/ASNC AC for SPECT MPI provides recommendations for the appropriate use of SPECT MPI. After the publication of the AC document in 2005, the AC has been used by nuclear cardiology practices with many clinical studies evaluating the list of indications in routine clinical practice. From these data. ASNC recommends minor but important changes to the indication list, suggesting the addition of 6 new indications and the modification of the definitions for “chest pain syndrome” and “CHD high risk.”. An objective review of existing indications focused on only those indications that had significant variability among the reviewers (n=20). These indications were reviewed in the presence of existing and new evidence-based data, and ASNC recommends that the grades for 6 indications be re-evaluated. The AC for SPECT MPI will require periodic review as new evidence becomes available or as clinical practice evolves. ASNC recognizes the importance of these criteria to improve the quality of patient care, and it will continue to play a key role in assembling the information for this ongoing review. From the current summary of evidence, ASNC consensus opinions, and ASNC recommendations in this document, ASNC strongly recommends that the AC guidelines be reviewed Prepared by the American Society of Nuclear Cardiology Quality Assurance Subcommittee for Quality in Imaging Standards. Reviewed by members of the American Society of Nuclear Cardiology Quality Assurance Committee. Approved by the American Society of Nuclear Cardiology Board of Directors, September 6, 20.     

Thalidomide protects endothelial cells from doxorubicin-induced apoptosis but alters cell morphology

Summary.  Antiangiogenesis agents are now being used in clinical trials to reduce the risk of recurrence of cancer. Several of these agents, however, are associated with thrombosis, especially when used in combination with chemotherapy. Antiangiogenesis and thrombosis are both endothelial-related activities, and we therefore evaluated one presumed antiangiogenesis agent (thalidomide) on intact cultured endothelial cells, and on cultured endothelial cells injured by preincubation with doxorubicin. We evaluated cell viability, caspase-3 activation, morphology of cells using light microscopy, and protease activated receptor-1 (PAR-l) expression. In our experiments, doxorubicin induced a dose- and incubation time-dependent and caspase-3-mediated apoptosis of endothelial cells. Thalidomide alone caused no changes in intact endothelial cells in terms of morphology, cell viability or activation of caspase-3. In contrast, when thalidomide was added to doxorubicin-injured endothelial cells, there was protection from cell death, increase in viability of endothelial cells, induction of differentiation and formation of neotubules. Doxorubicin reduced the expression of thrombin receptor, PAR-1, as evaluated by immunostaining and flow cytometry. Thalidomide did not alter PAR-1 expression in untreated cells but restored its expression reduced by doxorubicin. These findings suggest that thalidomide may be procoagulant, not by enhancing doxorubicin-mediated endothelial cell injury, but by altering the expression of PAR-1 on injured endothelium and resulting in endothelial dysfunction, which may explain hypercoagulability in patients treated with chemotherapy followed by thalidomide.     

Resolution of peripheral artery catheter-induced ischemic injury following prolonged treatment with topical nitroglycerin ointment in a newborn: a case report.

Tissue ischemia, necrosis, and gangrene are uncommon but well-described complications of arterial catheterization in the neonate. Treatment options for progressive tissue necrosis following arterial embolization and/or vasospasm are limited in these patients secondary to unpredictable pharmacokinetics and risks associated with systemic anticoagulation or vasodilatation in newborns. We report a case of a multidose regimen of topical 2% nitroglycerin ointment for reversing severe tissue ischemia following peripheral arterial line placement. The favorable response in this infant suggests that topical nitroglycerin therapy should be considered as potential therapy to ameliorate the effects of vascular compromise following arterial line placement in neonates.     

A new regimen of amsacrine with high-dose cytarabine is safe and effective therapy for acute leukemia

Amsacrine and high-dose cytarabine (HiDAc), when administered as single agents, are effective treatment of acute leukemia. When used in combination, a high remission rate is also possible. We treated 47 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and blastic phase of chronic myelogenous leukemia (CML) with a combination of amsacrine and HiDAc. The patients received amsacrine 200 mg/m2 daily for three days and, concurrently, HiDAc 3 g/m2 over three hours once daily for five days. Of 20 evaluable patients with AML in relapse, there were 12 remissions; of seven additional patients with primary refractory AML, there were two remissions, and of 12 patients with ALL in relapse, there were eight remissions. The three patients with blastic phase CML and the three patients with biphenotypic leukemia did not respond. Nausea, vomiting, stomatitis, hepatic dysfunction, and diarrhea were common, but cutaneous, conjunctival, and significant cerebellar and cerebral side effects were absent. We conclude that this regimen is highly effective therapy for AML and ALL and is also safe, eliminating the major toxicities encountered with HiDAc.     

Injection drug use and patterns of highly active antiretroviral therapy use: an analysis of ALIVE, WIHS, and MACS cohorts

Background  

Sustained use of antiretroviral therapy has been consistently shown to be one of the primary predictors of long-term effectiveness. Switching and discontinuation reflect patient and provider decisions that may limit future treatment options. In this study, we utilize data reported at semi-annual study visits from three prospective cohort studies, the AIDS Link to IntraVenous Exposure (ALIVE), the Women's Interagency HIV Study (WIHS), and the Multicenter AIDS Cohort Study (MACS), to investigate determinants of HAART modification with a particular focus on reported injection drug use (IDU).     

The human hematopoietic progenitor cell antigen (CD34) in vascular neoplasia.

The human hematopoietic progenitor cell antigen CD34 is synthesized and expressed by early normal hematopoietic progenitor cells and by many acute leukemias. Anti-CD34 antibodies also have been reported to stain blood vessels in tissue sections, and, more recently, CD34 mRNA has been detected in vascular endothelial cells. Therefore, the authors studied the diagnostic utility of immunohistochemical CD34 antigen detection in tumors of endothelial cell derivation and compared the results with stains for von Willebrand (vW) factor. A wide variety of epithelial and mesenchymal neoplasms also were examined to assess the specificity of CD34 for vascular neoplasia. Seven cases of angiosarcoma (seven of seven), five cases of Kaposi's sarcoma (five of five), and eight cases of epithelioid hemangioendothelioma (eight of eight) were moderately to strongly positive for CD34. This reactivity was equally intense in frozen sections, alcohol-fixed tissue, and formalin-fixed specimens. In many cases, the malignant endothelial cells stained more strongly than adjacent benign endothelium. Moreover, in most cases CD34 positivity was quantitatively and qualitatively stronger than staining for vW factor. Two cases of hemangiopericytoma (two of two) were CD34 positive but stained less intensely than the angiosarcomas, Kaposi's sarcomas, or hemangioendotheliomas. Five of six cases of hemangioma also stained positively for CD34; the nonreactive tumor in this group was the only one among 28 vascular neoplasms studied that was not reactive for CD34. In comparison, 9 of the 28 vascular tumors did not stain for vW factor. Three hundred fifty-seven tumors of nonvascular derivation also were examined for CD34 antigen expression. Focal light staining was seen in one pulmonary squamous cell carcinoma; moderate to intense staining was observed in half of the epithelioid sarcomas studied (8 of 16) and in a minority of leiomyosarcomas (3 of 22). These findings indicate that CD34 is a sensitive and relatively specific marker for neoplasms of vascular origin.     

Defining the role of radiosurgery in the management of brain metastases.

The role of stereotactic radiosurgery in the management of recurrent and newly diagnosed brain metastases was evaluated prospectively. From December 1988 to March 1991, 58 lesions in 40 patients were treated with accelerator-based stereotactic radiosurgery. All patients were followed for a minimum of 6 months or to death. The primary purpose was to determine the impact of radiosurgery on local control and its subsequent effects on quality of life. An overall tumor control rate of 82% with a complete response rate of 43% were achieved. As anticipated, the response rate for smaller tumors was substantially better than that for larger tumors (78% for lesions < 2 cm3; 50% for lesions > or = 10 cm3). Although the overall in-field progression rate was 18.5%, only 1/23 (4%) complete responders subsequently recurred. The in-field failure rate is highly comparable with recently published surgical data. Progression outside the brain was noted in two-thirds of patients. One quarter of the deaths were neurologic. The median survival for this minimally selected patient population was 6.5 months. Stereotactic radiosurgery was also associated with improved quality of life as measured by Karnofsky score, neurologic function, and steroid dependence. Long-term steroid dependence was encountered in only four patients. We conclude that stereotactic radiosurgery can be used effectively in patients with brain metastases. In this series, a high tumor response rate was achieved which was associated with improved quality of life.