Long-term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: a report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

The purpose of this study was to determine the long-term results of allogeneic bone marrow transplantation for chronic myeloid leukemia. A retrospective analysis was carried out of the outcome of 373 consecutive transplants performed at 38 European institutions between 1980 and 1988 and reported to the registry of the European Group for Blood and Marrow Transplantation. All transplants were carried out for first chronic phase of chronic myelogenous leukemia using unmanipulated marow cells from HLA-identical sibling donors. The probability of survival and leukemia-free survival at 8 years were 54% (95% CI: 49-59) and 47% (95% CI: 41-52) respectively. The probabilities of developing acute GVHD (II-IV) at 100 days and chronic GVHD at 4 years after transplant were 47% (95% CI: 41-53) and 52% (95% CI: 46-58) respectively. The probabilities of transplant-related mortality and leukemic relapse 8 years after BMT were 41% (95% CI: 36-48) and 19% (95% CI: 14-25), respectively. Transplant within 12 months of diagnosis was associated with reduced transplant-related mortality (34 vs 45%, P = 0.013) and resulted in improved leukemia-free survival (52 vs 44%, P = 0.03). The probability of relapse was significantly reduced in patients who developed chronic GVHD (RR = 0.33, P = 0.004). The probability of relapse occurring more than 2 years after transplant was increased more than five-fold in patients transplanted from a male donor (RR = 5.5, P = 0.006). Sixty-seven patients in hematologic remission were studied for residual disease by two-step RT/PCR for BCR-ABL mRNA and 61 (91%) tested negative. We conclude that bone marrow transplantation can induce long-term survival in approximately one-half of CML patients; the majority of survivors have no evidence of residual leukemia cells when studied by molecular techniques. The probability of late relapse is increased with use of a male donor.     

Transfer of lymphocytic choriomeningitis disease in beta 2-microglobulin-deficient mice by CD4+ T cells

In this study we have investigated the role of CD4+, MHC class II-restricted cytotoxic T lymphocytes (CTLs) in the disease caused by lymphocytic choriomeningitis virus (LCMV) in beta 2-microglobulin deficient (beta 2m-) mice. Intracranial (i.c.) infection with LCMV resulted in death of six out of 11 beta 2m- mice. Mice that survived showed a marked loss in body weight. Death and loss of body weight could be prevented by immunosuppressing the mice with irradiation or cyclosporine prior to i.c. injection of LCMV. This treatment also prevented induction of virus-specific, MHC class II-restricted CTL following peripheral inoculation with LCMV. In vivo depletion of CD4+ cells with antibody also prevented death following i.c. injection whereas in vivo depletion of CD8+ cells had no effect. Disease could be transferred to recipient beta 2m- mice by adoptive transfer of beta 2m- derived immune spleen cells. Transfer of non-immune spleen cells did not result in illness. In vitro treatment of immune spleen cells with anti-CD4 antibody and complement eliminated class II-restricted CTL activity and also prevented mortality of recipients after adoptive transfer. Treatment with anti-CD8 antibody had no effect. We were unable to transfer LCM disease to beta 2m- recipients by adoptive transfer of immune spleen cells from C57BL/6 mice. These results suggest that, unlike normal mice, the pathology of LCM disease in beta 2m- mice is dependent upon virus-specific, CD4+CD8-, MHC class II-restricted T cells.     

Heterogeneity in susceptibility to metronidazole among Helicobacter pylori isolates from patients with gastritis or peptic ulcer disease

Combination therapies that include metronidazole (MTZ) are the most successful therapies used in eradicating Helicobacter pylori. In this study, the prevalence and the relevance of heterogeneity in susceptibility to MTZ among H. pylori populations of 156 patients were evaluated. The results of this study show that 37 patients (24%) were infected with MTZ-resistant H. pylori (MIC > or = 8 micrograms/ml). Furthermore, 33% (52 of 156) of the patients were found to be infected with H. pylori populations heterogeneous for their susceptibility to MTZ. The reassessment of the MICs of MTZ for these 52 H. pylori populations revealed MTZ resistance in 28 of them, increasing the number of MTZ-resistant H. pylori populations among the 156 patients to 65 (42%). Out of 20 isolates, 2 (10%) heterogeneous in their susceptibility to MTZ also appeared to be heterogeneous at the genome level as determined by randomly amplified polymorphic DNA fingerprinting. In conclusion, the results show the limitations and risk of possible misinterpretations when only a single colony, picked from the primary H. pylori populations isolated from patients, is analyzed for its susceptibility to MTZ.     

The role of urodynamics in the evaluation of voiding dysfunction in men after cerebrovascular accident

PURPOSE: The etiology of voiding dysfunction was determined in men after a cerebrovascular accident who were at risk for obstructive uropathy to evaluate whether the cause of voiding dysfunction could be predicted by the type (obstructive or irritative) or onset of symptoms. MATERIALS AND METHODS: We evaluated 38 men with complaints of voiding dysfunction following a cerebrovascular accident. All patients were of the age when bladder outlet obstruction secondary to benign prostatic hyperplasia would otherwise be prevalent. After a comprehensive history and physical examination, all patients underwent multichannel urodynamic studies at a medium fill rate (20 to 50 ml. per minute). Findings were classified by the Abrams-Griffiths nomogram as obstruction, no obstruction or equivocal. RESULTS: Mean patient age was 70 years (range 54 to 87). Patients were grouped according to the presenting voiding complaints (purely irritative in 42%, purely obstructive in 34% or mixed in 24%). In 34 patients (89%) the onset of symptoms paralleled the occurrence of the cerebrovascular accident. Detrusor hyperreflexia was noted in 82% of the patients. There was no statistically significant difference in the occurrence of detrusor hyperreflexia among the 3 symptom groups (Fisher's exact test). Pressure-flow analysis clearly showed obstruction in 24 patients (63%), no obstruction in 9 (24%) and equivocal results in 5 (13%) according to the nomogram. There was no statistically significant difference in the incidence of obstruction among the 3 symptom groups (Fisher's exact test). CONCLUSIONS: Presenting symptoms did not predict the urodynamic findings of bladder outlet obstruction or detrusor hyperreflexia. The significant incidence of onset of symptoms after stroke suggests that the cerebrovascular accident induced voiding dysfunction in the face of preexisting bladder outlet obstruction may exacerbate the symptoms of the latter condition or vice versa.     

Chest pain centers

Conceptually, the Chest Pain Center model is nothing more than a system of delivering health care. It is a model that all hospitals can embrace as a framework for organizational decision making in meeting the heart-care needs of their communities. It also provides a framework for clinical decision making. By adopting some or all of the common features of the model, hospitals develop a common language, similar to what took place when CCUs first opened in the 1960s. Application of evidence-based clinical practice is promoted. Approaches that account for both clinical outcomes and financial outcomes will be further refined. One result will be simultaneous improvement in clinical outcomes and a decrease in costs, but the most important aspect of the Chest Pain Center model is that it puts the patient first.     

T cell responsiveness correlates differentially with antibody isotype levels in clinical and asymptomatic filariasis

To establish the relationships among T and B cell responses, active infection, and clinical manifestations in lymphatic filariasis, filarial-specific lymphocyte proliferation, IgG antibody isotypes, and IgE levels were determined in an exposed population: 31 asymptomatic amicrofilaremics, 43 microfilaremics, 12 symptomatic amicrofilaremics, and 52 elephantiasis patients. Lymphocyte proliferation was higher in elephantiasis patients and asymptomatic amicrofilaremics than in microfilaremics (P < .004). A proportion of asymptomatic amicrofilaremics (32%), elephantiasis patients (37%), and symptomatic amicrofilaremics (58%) showed antigen-specific lymphocyte unresponsiveness, and lymphocyte proliferation to filarial antigens correlated negatively with specific IgG4 levels (rho = -0.315, P < .001). As elevated specific IgG4 is an indicator of active infection, it is argued that active infection may result in lymphocyte hyporesponsiveness irrespective of clinical category. Of those with elevated specific IgE levels and high T cell proliferative responses, 70% had elephantiasis, suggesting these factors have a role in pathology. However, the existence of a proportion of elephantiasis patients with low anti-filarial IgE and T cell unresponsiveness to filarial antigens suggests that elephantiasis can be caused by distinct processes.     

A numerical model for the dissolution of spherical particles in binary alloys under mixed mode control

A general numerical model is described for the dissolution kinetics of spherical particles in binary systems for any combination of first order reactions at the particle-matrix interface and long distance diffusion within the matrix. The model is applicable to both finite and infinite media and handles both complete and partial particle dissolution. It is shown that interfacial reactions can have a strong effect on the dissolution kinetics, the solute concentration at the particle-matrix interface and the solute concentration profile in the matrix.     

A role for B cells in the development of T cell helper function in a malaria infection in mice

B cell knockout mice are unable to clear a primary erythrocytic infection of Plasmodium chabaudi chabaudi. However, the early acute infection is controlled to some extent, giving rise to a chronic relapsing parasitemia that can be reduced either by drug treatment or by adoptive transfer of B cells. Similar to mice rendered B-cell deficient by lifelong treatment with anti-mu antibodies, B cell knockout mice (muMT) retain a predominant CD4+ Th1-like response to malarial antigens throughout a primary infection. This contrasts with the response seen in control C57BL/6 mice in which the CD4+ T-cell response has switched to that characteristic of Th2 cells at the later stages of infection, manifesting efficient help for specific antibodies in vitro and interleukin 4 production. Both chloroquine and adoptive transfer of immune B cells reduced parasite load. However, the adoptive transfer of B cells resulted in a Th2 response in recipient muMT mice, as indicated by a relative increase in the precursor frequency of helper cells for antibody production. These data support the idea that B cells play a role in the regulation of CD4+ T subset responses.