Autologous Bone Marrow Repopulation following High Dose Cyclophosphamide and Allogeneic Marrow Transplantation in Aplastic Anaemia

Two patients are described who received allogeneic bone marrow transplantation for aplastic anaemia. Both patients rejected their grafts but subsequently repopulated their marrow with autologous haematopoietic cells. The significance of this phenomenon and its relationship to the possible pathogenesis and therapy of aplastic anaemia and discussed.     

Safety and efficacy of exisulind for treatment of recurrent prostate cancer after radical prostatectomy

PURPOSE: We evaluated the safety and efficacy of exisulind for delaying disease progression in men with increasing prostate specific antigen (PSA) after radical prostatectomy. MATERIALS AND METHODS: A total of 96 men with increasing PSA after radical prostatectomy were randomized to receive placebo (49) or 250 mg. exisulind twice daily (47) for 12 months. The primary efficacy parameter was the difference in change from baseline PSA between the placebo and exisulind groups. The PSA doubling time was also evaluated before and during study. A subgroup analysis classified patients based on the risk of developing metastatic disease. RESULTS: Compared with placebo, exisulind significantly suppressed the increase in PSA in all patients (p = 0.017). The results were also statistically significant in men at high risk for metastasis (p = 0.0003) and those who could not be classified according to risk (p = 0.0009). In addition, median PSA doubling time was lengthened in high risk patients on exisulind (2.12 month increase) compared with those on placebo (3.37 month decrease, p = 0.048). Exisulind was well tolerated. CONCLUSIONS: Exisulind inhibited the increase in PSA overall and prolonged PSA doubling time in high risk patients compared with placebo. These results suggest that Exisulind has the potential to extend the time from biochemical recurrence to the need for androgen deprivation therapy. Exisulind was well tolerated in this patient population. Our results support further study of Exisulind in the treatment of patients with prostate cancer.     

The HLA Dictionary 2004: a summary of HLA-A, -B, -C, -DRB1/3/4/5 and -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens

This report presents serologic equivalents of human leucocyte antigen (HLA)-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5 and -DQB1 alleles. The dictionary is an update of the one published in 2001. The data summarize equivalents obtained by the World Health Organization Nomenclature Committee for factors of the HLA System, the International Cell Exchange, the National Marrow Donor Program, recent publications and individual laboratories. This latest update of the dictionary is enhanced by the inclusion of results from studies performed during the 13th International Histocompatibility Workshop and from neural network analyses. A summary of the data as recommended serologic equivalents is presented as expert assigned types. The tables include remarks for alleles, which are or may be expressed as antigens with serologic reaction patterns that differ from the well-established HLA specificities. The equivalents provided will be useful in guiding searches for unrelated hematopoietic stem cell donors in which patients and/or potential donors are typed by either serology or DNA-based methods. The serological DNA equivalent dictionary will also aid in typing and matching procedures for organ transplant programs whose waiting lists of potential donors and recipients comprise of mixtures of serologic and DNA-based typings. The tables with HLA equivalents and a questionnaire for submission of serologic reaction patterns for poorly identified allelic products will be made available through the WMDA web page: www.worldmarrow.org. and in the near future also in a searchable form on the IMGT/HLA database.     

Characteristics of untreated AIDS-related cytomegalovirus retinitis. I. Findings before the era of highly active antiretroviral therapy (1988 to 1994)

PURPOSE: To identify factors related to variations in the appearance of untreated AIDS-related cytomegalovirus (CMV) retinitis in severely immunodeficient individuals before the availability of highly active antiretroviral therapy (HAART) and to draw inferences regarding early events in the natural history of CMV retinitis based on clinical findings. DESIGN: Retrospective, observational case series. METHODS: We evaluated a series of 100 adult patients with AIDS and newly diagnosed CMV retinitis before the HAART era who were not being treated with specific anti-CMV therapy. Demographic factors, ophthalmic findings, and the influence of drug therapy (zidovudine, acyclovir) on lesion characteristics were evaluated. Lesion border opacity was scored using a four-point scale of severity. RESULTS: Lesions could be categorized by type (fulminant/edematous or indolent/granular) in only 66% of eyes. Severe lesion border opacity (4+) was related to presence of zone 1 lesions (P = .032) and greater extent of disease (P = .004). Acyclovir use was associated with less severe opacity (P = .029) and less zone 1 involvement (P = .016). Early lesions were adjacent to vessels in 73% of eyes; the fovea was involved in 13% of eyes. CONCLUSIONS: Lesion location and drug use that affects virus activity may influence the severity of lesion border opacity, a measure that may be more useful than lesion type in future clinical studies of CMV retinitis. In contrast to earlier concepts, CMV retinitis does not seem to be a fovea-sparing disease. Findings in this study can serve as a reference for investigations into possible changes in CMV retinitis since the introduction of HAART.     

Granulocyte Colony Stimulating Factor and MT1-MMP Involved in Development of Atherosclerosis in Apolipoprotein E-Deficient Mice

Objectives Genetic deficiency of macrophage colony stimulating factor （M-CSF） in atherosclerosis-prone （apoE-/-） mice markedly reduces formation of atheroma. But Little is known about the potential effects of other colony stimulating factors（ CSF）, such as granulocyte CSF（ G-CSF）, on atherosclerosis. This study tested the hypothesis that G-CSF would be involved in development of atherosclerotic plaque. Methods apoE-/- mice fed with a Western-style diet （0. 15% cholesterol） were injected subcutaneously with recombinant human G-CSF（ 10 rag/day） dally for 9 weeks then sacrificed. The matrix metalloproteinase （MMP） 2 and MMP9 in serum of mice were measured by Gelatin Zymography analysis and c-kit and membrane typel-MMP （MT1-MMP） antigens were detected using fluorescence activated cell sorting （FACS）. Meanwhile, complete blood counts （CBC） and serum cholesterol, relative fractions of VLDL, LDL, and HDL were evaluated by spectrophotometric techniques and high performance liquid chromatography （HPLC） respectively. Atherosclerotic Lesions of the aorta were also analyzed by histological methods. Results G-CSF treatment resulted in increased proportions of circulating monocytes （ 6.9 ± 2. 2 % vs. 3.8 ± 0. 3 % ; P 〈 0. 05 ）, and decreased serum levels of total cholesterol（ 1225 ± 594 vs. 1991 ± 1009; P 〈 0. 005 ） compared to control mice. A greater proportion of bone marrow cells from G-CSF treated mice expressed MT1-MMP （ 14. 5 ± 5.5% vs. 6. 2 ± 5.0%, P 〈 0. 05 ） compared to bone marrow cells from vehicle treated mice. G-CSF treatment was also associated with smaller atheromatous plaque, and decreased oil red O staining. Conclusions G-CSF lowers serum cholesterol, increases circulating monocytes, increases bone marrow cell expression of MT1-MMP, inhibits plaque development, and decreases lipid and macrophage infiltration into developing plaque.     

Neutrophil Function in Bone Marrow Transplant Recipients

The neutrophil function of seven patients receiving allogeneic bone marrow transplantion was studied. Five of the patients had been transplanted for aplastic anaemia and two for acute leukaemia. Determinations were made of neutrophil phagocytosis, chemotaxis, random migration, and microbicidal activity for Candida albicans and Staphylococcus aureus. One patient showed a decreased ability to kill C. albicans at a time when she had active pneumonia due to Pneumocystis carinii. The remainder of the studies showed normal neutrophil functions. No differences were observed in the patients who had graft versus host disease [GvH] from those without GvH. These studies suggest that defects in phagocytic neutrophil function do not contribute significantly to the impaired host defenses in recipients of bone marrow transplantation.     

Advanced MR imaging of acute stroke: the University of California at Los Angeles endovascular therapy experience

Rapid implementation of multimodal MR imaging, including diffusion-perfusion imaging before and following endovascular therapies for treatment of acute ischemic stroke, has yielded novel observations and expanded contemporary knowledge of acute stroke pathophysiology. For more than a decade at the University of California at Los Angeles, an intensive imaging strategy has been used to establish stroke diagnosis, delineate early patterns of cerebral ischemia, and monitor response to various reperfusion techniques. Angiographic findings before thrombolysis have substantiated stroke subtype, and documentation of concomitant recanalization has provided considerable insight regarding the vascular and imaging correlates of intra-arterial therapies. MR imaging studies have progressively characterized the complex pathophysiology of acute ischemic stroke, providing imaging strategies and models that may be used to optimize acute stroke care. The ensuing review emphasizes salient aspects of these neuroimaging studies, addressing numerous facets of acute stroke pathophysiology.