Identification of risk groups for development of central nervous system leukemia in adults with acute lymphocytic leukemia

The risk of development of CNS leukemia was investigated in 153 adults with acute lymphocytic leukemia (ALL) who received systemic combination chemotherapy without CNS prophylaxis. Overall, 31 patients (20%) developed CNS leukemia after a median of 6 months of therapy; the estimated 1-year incidence of CNS leukemia was 21% (SE, 3.9%). Characteristics significantly associated with CNS involvement included the presence of elevated hemoglobin creatinine, alkaline phosphatase, fibrinogen, and lactic dehydrogenase levels; B-cell leukemia; and high leukemic cell proliferative activity. Multivariate analysis identified lactic dehydrogenase levels of greater than or equal to 600 U/L and greater than or equal to 14% of cells in the S + G2M compartment to have independent additive poor prognostic significance. Patients were categorized into different risk groups for CNS leukemia with 1-year incidences ranging from 4% to 55%. While related to a high occurrence of CNS leukemia at diagnosis (33%) and subsequently (100%), the low incidence of B-cell disease excluded it from the multivariate analysis. The use of systemic chemotherapy containing multiple agents with good CNS penetration and in high doses (VAD regimen) in 90 patients was associated with a trend for lower CNS leukemia at 1 year (15% v 31%), especially in the low-risk category. We propose to develop future therapies for adults with ALL that include risk-oriented CNS prophylactic approaches.     

Bulk cryopreservation of lymphocytes in glycerol

The authors describe a method for freezing large amounts of peripheral blood lymphocytes (PBL) in a 20 percent glycerol solution. Between 0.6 and 4.3 X 10(9) cells in autologous plasma were frozen in polyethylene freezing bags in a final volume of 50 ml. The recovery after thawing averaged 89 +/- 14 percent with a mean viability by trypan blue dye exclusion of 80 +/- 7 percent (n = 11). In aliquots of fresh and frozen-thawed PBL from the same subjects radiolabeled with 111In, the radiolabeling efficiency for both fresh and thawed cells was 49 +/- 15 percent (p = 0.98, n = 5). The mitogen mean stimulation indices for glycerol-frozen cells (471 with phytohemagglutinin-M, 176 with pokeweed mitogen, and 380 with concanavalin A) were superior to those of cells frozen by a standard technique with dimethylsulfoxide (DMSO) (141, 47, and 123; p less than 0.05) and comparable to those of fresh PBL (403, 75, and 147). In a mixed lymphocyte culture, glycerol-frozen PBL showed significantly greater responsiveness to a pool of stimulator cells than did PBL frozen in DMSO (p = 0.03). Thawed cells are viable and functional as demonstrated by their response to mitogens and their ability to stimulate and respond in mixed lymphocyte culture.     

IgM-Associated Primary Diffuse Mesangial Proliferative Glomerulonephritis: Natural History and Prognostic Indicators

Fifty-four adults with primary mesangial proliferative glomerulonephritisand IgM deposition were observed for a minimum of three yearsor until end-stage renal failure. The actuarial renal survivalwas 80 per cent at 5 years and 64 per cent at 10 years; multivariateanalysis identified microscopic haematuria, extent of mesangialproliferation and global glomerular sclerosis as independentprognostic indicators.     

Characteristics of white cell-reduced red cells stored in tri-(2- ethylhexyl)trimellitate plastic

BACKGROUND: Standard blood storage containers contain extractable plasticizers that accumulate in blood during storage and are an unintended transfusion product. However, extractable plasticizers have a protective effect on the red cell membrane and improve red cell storage variables. Prestorage white cell reduction also improves selected red cell storage variables. STUDY DESIGN AND METHODS: The study evaluated whether the beneficial effect of prestorage white cell reduction would offset the negative effect of the absence of extractable plasticizer in red cells stored in AS-3 for 42 days at 4 degrees C. Filtered red cells stored in polyvinylchloride containers with the nonextracting plasticizer, tri-(2-ethylhexyl)trimellitate (TEHTM), were compared to unfiltered red cells stored in polyvinylchloride containers with the extractable plasticizer di-(2- ethylhexyl)phthalate (DEHP). RESULTS: Poststorage supernatant potassium and red cell osmotic fragility were significantly higher in white cell- reduced TEHTM units than in unfiltered DEHP units. The mean 24-hour recovery of the filtered TEHTM red cells was significantly lower than that of the unfiltered DEHP red cells (69.1 +/− 7.4% vs. 77.1 +/− 5.1%, p < 0.05, n = 8). CONCLUSION: These data demonstrate that white cell reduction before 42-day storage in TEHTM containers with currently approved preservatives does not yield an acceptable red cell component.     

Major histocompatibility complex markers and red cell antibodies to the Rh (D) antigen. Absence of association

Between 20 and 35 percent of Rh(D) antigen-negative individuals do not develop antibodies to D even after multiple transfusions of Rh-positive red cells. To evaluate the possibility that antibody production after exposure to the D antigen was related to a major histocompatibility complex immune response gene, analysis of the HLA genotypes of 38 Rh-sensitized women and their families was performed. No significant deviations were found in the frequency of any individual HLA class I, II, or III allele or of any extended haplotype (fixed allelic combinations of HLA-B, HLA-DR, and the complement components BF, C2, C4A, and C4B). Type 1 errors due to the extreme allelic polymorphism of the HLA system, as well as the ethnic variation in patient groups, may have contributed to HLA allele-antibody responder relationships reported in earlier studies.     

Training of 'first-aid' trainers: a medical school example in Turkey.

OBJECTIVE: A student-oriented basic life support and first-aid training is practical to enlarge the number of qualified people in the field. In this study, we aimed to describe and discuss the training process of a group of medical students at Hacettepe University, School of Medicine and their assessment as basic life support and first-aid trainers. METHODS: A '6-hour' 'Training the Trainers' course was conducted and participants' demonstration and coaching skills were evaluated by using a 3-point scale (1 - needs improvement; 2 - competently performed; 3 - proficiently performed). In total, 31 students out of 45 volunteers were certified as trainers. RESULTS: All of the students proficiently performed 'explain the aim of the demonstration', 'motivate participants to use checklists', and 'motivate the participants to ask questions' for demonstraton skills. Similarly, they all got the maximum grade for 'answer the questions of the participant', 'discuss the coach role of the participant', 'apply the skills', and 'follow up with the participant by using the checklist' as steps of coaching skills. None of the skills within the checklists needed improvement for any of the candidates. CONCLUSION: Although there are limitations, we hope that our experience of the Training the Trainers course will be useful for readers to highlight the importance of skill-based peer education on a very important public health concern, especially for the developing countries.     

Ultrastructural, lectin histochemical and immunohistological observations on Merkel cell tumors

The clinicopathological and ultrastructural findings of 10 cases of Merkel cell tumor (MCT) are presented. Three patients died rapidly due to tumor dissemination. The tumor cells in eight out of the 10 cases were positive for neuron-specific enolase, however, all were negative for the ten polypeptide hormones examined, as well as for the argentaffin and argyrophil reactions. One of the patients had suffered from chronic lymphocytic leukaemia. Particularly in this case, but also in the others, the differentiation of MCT from a malignant lymphoma necessitated immuno-histological, lectin histochemical and ultrastructural studies. The focal peanut agglutinin positivity of the tumor cells in 6 out of the 10 MCTs seems to be a characteristic feature of these cells.     

RENAL DISEASE ASSOCIATED WITH ANTINEUTROPHIL CYTOPLASMIC ANTIBODY: 39 PATIENTS OVER A 5-YEAR PERIOD

SUMMARY We have reviewed 39 adult patients who presented over a 5-year period with biopsy confirmed renal disease in association with positive antineutrophil cytoplasmic antibody (18 with C-ANCA, 21 with P-ANCA). Twenty-three (59%) had primary systemic vasculitis, typically with aggressive renal histology including focal necrotising and crescentic glomerulonephritis. In the remaining patients a wide range of clinical syndromes and renal histological appearances were apparent: 30 had abnormal renal function (serum creatinine >140 μmol/l), including 17 who were initially dialysis-dependent. Intensive immunosuppression was administered in 33 cases. When response was assessed at 3 months, renal function was stable or improved in 17 (52%), 5 of whom were able to discontinue dialysis. There was, however, an appreciable early mortality and, at latest follow-up (1–57 months), 12 patients had died and 8 were on the dialysis programme. On immunosuppression, ANCA became negative in the majority (median time 1.5 months) but recurred during clinical relapse in 11 cases. In asymptomatic patients (12 cases), the reappearance of ANCA positivity did not herald clinical relapse. The ANCA assay has increased awareness of systemic vasculitis but not removed the need for histological confirmation before instituting immunosuppression.     

Comparative evidence for a link between Peyer's patch development and susceptibility to transmissible spongiform encephalopathies

Background  

Epidemiological analyses indicate that the age distribution of natural cases of transmissible spongiform encephalopathies (TSEs) reflect age-related risk of infection, however, the underlying mechanisms remain poorly understood. Using a comparative approach, we tested the hypothesis that, there is a significant correlation between risk of infection for scrapie, bovine spongiform encephalopathy (BSE) and variant CJD (vCJD), and the development of lymphoid tissue in the gut.