A phase II study of continuous infusion recombinant human granulocyte- macrophage colony-stimulating factor as an adjunct to autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma in first remission

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) clearly hastens myeloid recovery in patients with relapsed hematologic malignancies undergoing autologous bone marrow transplantation (ABMT). In efforts to further improve neutrophil engraftment and shorten hospital stay in ABMT patients, rhGM-CSF was administered by a potentially more potent route (continuous infusion) to non-Hodgkin's lymphoma (NHL) patients with better BM reserve (first remission). Time to myeloid engraftment was compared with that of NHL patients treated in first remission at our institution on a similar ABMT protocol but without growth factor support (controls). Median neutrophil engraftment (absolute neutrophil count, 500 cells/microL) in first remission patients treated with rhGM-CSF was 14 days, compared with 22 days in controls (P = .0001). Hospital stays were also significantly reduced for rhGM-CSF patients (P = .0003). Platelet engraftment did not differ between the two groups. Persistent fever and generalized serositis were the primary toxicities. rhGM-CSF, delivered by this route, was efficacious but more toxic than 2-hour rhGM-CSF infusions previously reported by other investigators. Future alterations in both dose and schedule may retain comparable efficacy yet diminish toxicity.     

A Randomized Trial to Compare Alternative Educational Interventions to Increase Colorectal Cancer Screening in a Hard-to-Reach Urban Minority Population with Health Insurance

This randomized controlled trial assessed different educational approaches for increasing colorectal cancer screening uptake in a sample of primarily non-US born urban minority individuals, over aged 50, with health insurance, and out of compliance with screening guidelines. In one group, participants were mailed printed educational material (n = 180); in a second, participants’ primary care physicians received academic detailing to improve screening referral and follow-up practices (n = 185); in a third, physicians received academic detailing and participants received tailored telephone education (n = 199). Overall, 21.5 % of participants (n = 121) received appropriate screening within one year of randomization. There were no statistically significant pairwise differences between groups in screening rate. Among those 60 years of age or older, however, the detailing plus telephone education group had a higher screening rate than the print group (27.3 vs. 7.7 %, p = .02). Different kinds of interventions will be required to increase colorectal cancer screening among the increasingly small population segment that remains unscreened. ClinicalTrials.gov Identifier: NCT02392143.     

T cell subsets and cellular immunity in end-stage renal disease

The T lymphocyte population was studied by immunofluorescent staining with monoclonal antibodies and laser flow cytometry in the blood of 50 patients with end-stage renal disease undergoing long-term maintenance intermittent hemodialysis. The absolute number of T cells was lower in patients receiving dialysis for more than one year (p less than 0.001), as was the absolute count of helper T cells (p less than 0.005). In patients under 30 years of age, the absolute number of helper T cells was markedly reduced, whereas the number of suppressor/cytotoxic T lymphocytes was not changed. In patients between the ages of 30 and 60 years, both helper and suppressor cells were significantly reduced. In patients over 60 years of age, only the number of helper T cells was reduced. The in vitro response of patients' lymphocytes was reduced both in the mixed lymphocyte reaction (p less than 0.01) and after phytohemagglutinin stimulation (p less than 0.001). Natural killer cytotoxicity of patients' peripheral blood mononuclear cells, however, was unaffected.     

Provoked and spontaneous high-frequency, low-amplitude, respirophasic noise transients in patients with implantable cardioverter defibrillators

INTRODUCTION: Ventricular oversensing (OS) of respirophasic noise transients may cause spurious detections and therapies and pacing inhibition among patients with implantable cardioverter defibrillators (ICDs). The incidence of OS and its relationship to clinical variables and ICD system design are unknown. METHODS AND RESULTS: Three hundred twenty-nine patients performed provocative respiratory maneuvers at rest during intrinsic rhythm and continuous ventricular pacing. OS resulting in spurious ventricular detections was provoked in 3 (0.9%) of 329 patients during intrinsic rhythm and 34 (10.3%) of 329 during pacing. Noise transients not recognized and marked as sensed events, but visually evident on the local endocardial ventricular electrogram, were provoked in an additional 23 (7.0%) of 329 patients. Multivariate logistic regression identified history of spontaneous OS (P < 0.0005, odds ratio 9.7, 95% confidence interval [CI] 1.9 to 50.0), automatic gain control device (P < 0.0005, odds ratio 5.3, 95% CI 2.6 to 10.8) or integrated bipolar lead (P = 0.05, odds ratio 2.6, 95% CI 1.0 to 7.25), and male gender (P = 0.008, odds ratio 3.7, 95% CI 1.2 to 11.1) as predictive of provocable OS. Spontaneous OS resulting in spurious ventricular detections and therapies occurred in 12 (3.6%) patients during follow-up. Eleven of 12 spontaneous episodes occurred in male patients during ventricular pacing; 11 of 12 patients had automatic gain control devices and integrated bipolar leads. CONCLUSION: OS is commonly provoked in ICD patients during ventricular pacing and may occur spontaneously, causing spurious tachyarrhythmia therapies and pacing inhibition. Differences in the incidence of spontaneous and provoked OS between ICD systems can be explained on the basis of unique features of automatic sensing systems and sensing lead design.     

The role of auditory and visual models in the production of bimanual tapping patterns

An experiment was designed to determine the effectiveness of auditory and visual models in the learning of a 2:3 bimanual tapping pattern. Participants were randomly assigned to an auditory model, visual model, auditory + visual model, or a control (visual metronome) group. The task for all groups was to tap a left side force transducer with the left hand and a right side force transducer with the right hand in attempt to produce the desired 2:3 bimanual coordination pattern. The auditory model consisted of a series of tones representing the goal pattern played prior to each practice trial. The visual model consisted of a visual display representing the goal tapping pattern. Visual pacing metronomes were provided to the control group. The right and left side metronomes flashed during the trial in a pattern representing the goal tapping pattern. Subjects in all groups performed 14 practice trials consisting of 15 s each devoted to tapping the goal pattern (total practice time = 3.5 min). A retention test without the aid of the models or metronomes was administered following the practice trials. The results for the model groups indicated extremely effective performance of the bimanual coordination patterns for the auditory, visual, and auditory + visual model conditions with not only the relative, but also the absolute characteristics of the models exhibited during retention testing. Retention performance for the visual metronome condition was less accurate and more variable than the three model conditions. In addition, the auditory + visual model condition resulted in retention performance that was more stable than the auditory model condition.     

A guide to performing difficult bimanual coordination tasks: just follow the yellow brick road

Both discrete and continuous bimanual coordination patterns are difficult to effectively perform when the two limbs are required to perform different movements patterns, move at different velocities and/or move different amplitudes unless some form of integrated feedback is provided. The purpose of the present experiment was to determine the degree to which a complex bimanual coordination pattern could be performed when integrated feedback and movement template are provided. The complex bimanual coordination pattern involved reciprocal movements of the two limbs under different difficulty requirements. As defined by Fitts’ index of difficulty (ID), the left arm (ID = 3, A = 16°, W = 4°) task was of lower difficulty than the right arm task (ID = 5, A = 32°, W = 2°). Note that the left and right limb movements are also different in terms of movement time, movement velocity, accuracy requirements and amplitude as well as one movement was continuous and the other intermittent. Participants were provided 2 blocks of 9 trials in the bimanual condition (30 s/trial). Following the bimanual phase, participants performed two unimanual test trials—one with each limb. The results demonstrated that the performance for each limb in the bimanual condition was similar to the performance for the same limb and conditions in the unimanual control conditions. The similarity was indicated by the same movement speed, movement structure, endpoint variability and hit rates for the bimanual and unimanual conditions. The results support our hypothesis that people can overcome the intrinsic difficulties associated with performing complex bimanual coordination patterns when provided appropriate perceptual information feedback that allows them to detect and correct coordination errors.     

Fragile X‐associated tremor/ataxia syndrome (FXTAS) in grey zone carriers

The grey zone (GZ; 45–54 CGG repeats in the FMR1 gene) is considered a normal allele; however, several studies have found a high frequency of GZ in movement disordered populations. Here, we describe neurological features of fragile X‐associated tremor/ataxia syndrome (FXTAS) in two carriers of GZ alleles, although FXTAS has been defined as occurring only in premutation carriers (55–200 CGG repeats). Both patients had family members who had premutation and were diagnosed with FXTAS. The presence of relatively high GZ alleles with elevated fragile X mental retardation 1 mRNA (FMR1‐mRNA) combined with a family history of FXTAS that may represent a facilitating genetic background for FXTAS are the factors that led to the presence of FXTAS in these individuals with a GZ allele. Further research into clinical involvement of GZ alleles is recommended and the definition of FXTAS may require revision.