Epstein-Barr virus lymphoproliferation after bone marrow transplantation

We review 15 cases of secondary B-cell lymphoproliferative disorders that occurred among 2,475 patients who received allogeneic bone marrow transplants (BMTs) at the Fred Hutchinson Cancer Research Center (Seattle) between 1969 and 1987. The histopathologic findings in 14 of the 15 patients spanned a wide spectrum of lymphoproliferative lesions. One patient had features characteristic of angioimmunoblastic lymphadenopathy. Epstein-Barr virus (EBV) genomic sequences were identified by Southern blot analysis in each of the 13 patients evaluated. Ten of the 12 lesions evaluated originated in donor cells. In two patients, who had mixed chimerism after transplantation, the lesions originated in host cells. The combined evidence from immunoglobulin light chain staining and the analysis of immunoglobulin heavy chain gene rearrangement indicated that the lesions in most patients represented polyclonal proliferations that gave rise to clonal subpopulations. The results indicate an overall actuarial incidence of 0.6% for this complication in BMT recipients. Anti-CD3 monoclonal antibody (MoAb) treatment of acute graft-v-host disease (GVHD) and T cell depletion of the donor marrow were statistically significant risk factors, and GVHD appeared to play a contributing role, particularly in the setting of human leukocyte antigen (HLA) disparity. Two patients had no identifiable risk factors. Prophylaxis or treatment with acyclovir had no detectable effect in the patients; all but two died with uncontrolled lymphoproliferation.     

Changes in cognitive functioning following treatment of late-life depression

OBJECTIVE: Knowledge of the relationship between various clinical characteristics and cognitive functioning is advancing, but little is known about the cognitive response to treatment for geriatric depression. The purpose of this study was to examine the cognitive response to treatment for patients with late-life depression. METHOD: Subjects included 45 nondemented, elderly depressed patients who achieved remission after 12 weeks of antidepressant treatment and 20 elderly comparison subjects. All subjects were administered a battery of clinical measures, including cognitive screening instruments, before and after treatment. RESULTS: As a group, the elderly depressed patients showed a small improvement in overall cognitive functioning after treatment. Among depressed patients with concomitant cognitive impairment at baseline, performance on the Mattis Dementia Rating Scale domains of conceptualization and initiation/perseveration improved significantly relative to those of depressed patients with normal cognition. Despite the improvement following treatment, the overall level of cognitive functioning in the elderly depressed patients with cognitive impairment at baseline remained mildly impaired, especially in the memory and initiation/perseveration domains. CONCLUSIONS: Elderly depressed patients with cognitive impairment may experience improvement in specific domains following antidepressant treatment but may not necessarily reach normal levels of performance, particularly in memory and executive functions. This subgroup of late-life depression patients is likely at high risk of developing progressive dementia.     

Trajectories of impairment in amyotrophic lateral sclerosis: Insights from the Pooled Resource Open‐Access ALS Clinical Trials cohort

Introduction: Rate of decline of the Amyotrophic Lateral Sclerosis Functional Rating Scale‐Revised (ALSFRS‐R) score is a common outcome measure and a powerful predictor of mortality in ALS. Methods: Observed rate of decline (postslope) of ALSFRS‐R, its linearity, and its relationship to decline at first visit (preslope) were examined in the Pooled Resource Open‐Access ALS Clinical Trials cohort by using longitudinal mixed effects models. Results: Mean ALSFRS‐R postslope in 3,367 patients was ?0.99 points/month. Preslope and postslope were correlated and had powerful effects on survival. ALSFRS‐R trajectories were slightly accelerated overall, but slope and direction/degree of curvature varied. Subscore decline was sequential by site of onset. Respiratory subscore decline was the least steep. Discussion: Variable curvilinearity of ALSFRS‐R trajectories confounds interpretation in clinical studies that assume linear decline. Subscore trajectories recapitulate phenotypic diversity and topographical progression of ALS. ALSFRS‐R is better used as a multidimensional measure. Muscle Nerve 57 : 937–945, 2018     

Plasma endothelin-1 release during acute stress: role of ethnicity and sex

OBJECTIVES: The purposes of this study were to examine possible ethnic and sex differences in plasma ET-1 levels at rest and in response to acute stress and to examine relationships between ET-1 and vasoconstrictive-mediated BP reactivity to stress. METHODS: Two hundred twenty-two adolescents (mean age = 18.5 +/- 2.8 years; 130 [70 males] EAs and 92 [48 males] AAs) completed two stressors (video game, forehead cold). Hemodynamic measures and blood samples were collected at catheter insertion and before and immediately after the two stressors, separated by 20-minute rest periods. RESULTS: AAs and males exhibited higher levels of SBP and DBP and of TPRI and ET-1 at each sampling point compared with EAs and females, respectively (p values <.001). AAs and males exhibited greater increases in SBP, TPRI, and ET-1 in response to each stressor (p values <.05). Intraindividual correlations between ET-1 and hemodynamic parameters revealed that most individuals exhibited a positive association between ET-1, BP, and TPRI. However, some individuals exhibited a negative association between ET-1 and the above-mentioned hemodynamics, suggesting a compensatory vasodilation mechanism. CONCLUSION: The findings demonstrate significant sex and ethnicity differences in stress-induced vasoconstrictive peptide release and support the hypothesis that these differences may be important in explaining the ethnicity and sex differences in the prevalence of cardiovascular disease.