Primary therapy and survival among patients with nodular lymphocyte-predominant Hodgkin lymphoma: a population-based analysis in the Netherlands, 1993–2016

In this nationwide, population-based study, we assessed trends in primary treatment and survival among 687 patients with nodular lymphocyte-predominant Hodgkin lymphoma (75% males; median age, 40 years; and 74% stage-I/II disease) diagnosed in the Netherlands between 1993–2016. There were no noteworthy changes in the application of primary therapy over time among adult patients across the different disease stages and age groups. Survival among various subgroups of adult patients was largely comparable to the expected survival of the general population. A particularly encouraging finding was that young adult patients experienced virtually no excess mortality, as compared to the general population.     

A randomized clinical trial and subgroup analysis to compare flexion–distraction with active exercise for chronic low back pain

Many clinical trials on chiropractic management of low back pain have neglected to include specific forms of care. This study compared two well-defined treatment protocols. The objective was to compare the outcome of flexion–distraction (FD) procedures performed by chiropractors with an active trunk exercise protocol (ATEP) performed by physical therapists. A randomized clinical trial study design was used. Subjects, 18 years of age and older, with a primary complaint of low back pain (>3 months) were recruited. A 100 mm visual analogue scale (VAS) for perceived pain, the Roland Morris (RM) Questionnaire for low back function, and the SF-36 for overall health status served as primary outcome measures. Subjects were randomly allocated to receive either FD or ATEP. The FD intervention consisted of the application of flexion and traction applied to specific regions in the low back, with the aid of a specially designed manipulation table. The ATEP intervention included stabilizing and flexibility exercises, the use of modalities, and cardiovascular training. A total of 235 subjects met the inclusion/exclusion criteria and signed the informed consent. Of these, 123 were randomly allocated to FD and 112 to the ATEP. Study patients perceived significantly less pain and better function after intervention, regardless of which group they were allocated to (P<0.01). Subjects randomly allocated to the flexion–distraction group had significantly greater relief from pain than those allocated to the exercise program (P=0.01). Subgroup analysis indicated that subjects categorized as chronic, with moderate to severe symptoms, improved most with the flexion–distraction protocol. Subjects categorized with recurrent pain and moderate to severe symptoms improved most with the exercise program. Patients with radiculopathy did significantly better with FD. There were no significant differences between groups on the Roland Morris and SF-36 outcome measures. Overall, flexion–distraction provided more pain relief than active exercise; however, these results varied based on stratification of patients with and without radiculopathy and with and without recurrent symptoms. The subgroup analysis provides a possible explanation for contrasting results among randomized clinical trials of chronic low back pain treatments and these results also provide guidance for future work in the treatment of chronic low back pain.     

Dorsal cortical regions subserving visually guided saccades in humans: an fMRI study

Neurophysiological studies in non-human primates have identified saccade-related neuronal activity in cortical regions including frontal (FEF), supplementary (SEF) and parietal eye fields. Lesion and neuroimaging studies suggest a generally homologous mapping of the oculomotor system in humans; however, a detailed mapping of the precise anatomical location of these functional regions has not yet been achieved. We investigated dorsal frontal and parietal cortex during a saccade task vs. central fixation in 10 adult subjects using functional magnetic resonance imaging (fMRI). The FEF were restricted to the precentral sulcus, and did not extend anteriorly into Brodmann area 8, which has traditionally been viewed as their location in humans. The SEF were located in cortex along the interhemispheric fissure and extended minimally onto the dorsal cortical surface. Parietal activation was seen in precuneus and along the intraparietal sulcus, extending into both superior and inferior parietal lobules. These findings localize areas in frontal and parietal cortex involved in saccade generation in humans, and indicate significant differences from the macaque monkey in both frontal and parietal cortex. These differences may have functional implications for the roles these areas play in visuomotor processes.      

Cytogenetic studies on a patient with prepubertal breast cancer: A case report

Summary Cytogenetic studies were carried in a 10 year old girl with prepubertal breast cancer for assessing inherited genetic susceptibility to chromosome breakage. The girl presented with a tumour in the left breast. Histologically it was diagnosed as secretory carcinoma (SC). Chromosome anomalies observed in phytohemagglutinin (PHA-P) stimulated lymphocytes were del(2)(q33), del(3)(p24), del(7)(q22) and dup(12)(p11p12). The regions involved have been reported in breast tumors. These loci, detected in peripheral blood lymphocytes (PBL), could be the sites susceptible to breakage, its subsequent effect being manifested in the target (breast) tissue.     

Rituximab, Anti-CD20, Induces In Vivo Cytokine Release But Does Not Impair Ex Vivo T-Cell Responses

Pre-formed HLA antibodies (Ab), reported as panel-reactive antibody (PRA), prolong transplant waiting time. We hypothesized that rituximab (RIT) could reduce PRA via B-cell depletion. As part of a Phase I study of single RIT dose, we studied in vivo and ex vivo effects on T-cell immune responses. Nine subjects (n = 3) were treated at 50, 150, and 375 mg/m(2). Serum interleukin-1alpha (IL-1alpha), IL-6, IL-12, tumor necrosis factor beta (TNF-beta), and interferon-gamma (IFN-gamma) were measured by enzyme-linked immunosorbent assay (ELISA). T-cell function was monitored with T-cell proliferation assays. IL-6 levels rose in eight patients (7.15 +/- 4.38 pg/mL to 86.22 +/- 77.08, p = 0.021). The high-dose group had detectable TNF-betapost rituximab infusion (874.7 +/- 1466.5 pg/mL). There was no decline in T-cell proliferation in response to phytohemagglutinin or allogeneic lymphocyte stimuli. Stimulation indices in the presence of both concentrations of tetanus toxoid rose significantly at 4 weeks.     

Hepatitis C virus (HCV) NS5B nonnucleoside inhibitors specifically block single-stranded viral RNA synthesis catalyzed by HCV replication complexes in vitro

Replication complexes of hepatitis C virus synthesized two major species of viral RNA in vitro, double stranded and single stranded. NS5B nonnucleoside inhibitors inhibited dose dependently the synthesis of single-stranded RNA but not double-stranded RNA. Moreover, replication complexes carrying a mutation resistant to a nonnucleoside inhibitor lost their susceptibilities to the inhibitor.