Separation of diploid from aneuploid cells in acute lymphoblastic leukaemia

A new method for the separation of diploid and aneuploid cells from blood of patients with leukaemia is described. Density gradient separation using a modified silica particle gradient was combined with analysis of cellular DNA content by flow cytometry. Submicroscopic levels of diploid or aneuploid cells were enriched up to 90% purity. Three patients with acute lymphoblastic leukaemia and no evidence of aneuploid cells after separation are in continuing complete remission after 24.5-47 months. Two patients with aneuploid cells detected after separation expired in relapse 0.5 and 3 months later. Cell separation prior to flow cytometric analysis might be a useful tool to detect submicroscopic levels of aneuploid leukaemic cells in blood and bone marrow, and to predict impending relapse.     

Ketamine’s Antidepressant Efficacy is Extended for at Least Four Weeks in Subjects with a Family History of an Alcohol Use Disorder

Background:

A single subanesthetic infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid and potent antidepressant properties in treatment-resistant major depressive disorder (TRD). As a family history of an alcohol use disorder is a positive predictor of ketamine’s antidepressant response and the strength of the association increases over time, we hypothesized that depressed subjects with a family history of an alcohol use disorder would have greater antidepressant durability and that riluzole would augment and/or extend ketamine’s antidepressant efficacy.

Methods:

Fifty-two TRD subjects received an open-label infusion of ketamine (0.5mg/kg over 40 minutes), and, four to six hours post-infusion, were randomized to either flexible-dose (100–200mg/day) riluzole or placebo in the following proportions: Family History Positive (FHP) riluzole (n = 10), FHP placebo (n = 9), Family History Negative (FHN) riluzole (n = 16), and FHN placebo (n = 17).

Results:

FHP subjects randomized to placebo had a greater antidepressant response than FHN subjects; however, contrary to our initial hypothesis, there was no significant difference in antidepressant efficacy with riluzole. Although potentially underpowered, there was no difference in overall time-to-relapse based on randomization status (riluzole responders: n = 15, placebo responders: n = 17). Yet, time-to-relapse was longer in FHP placebo responders (n = 8) compared to FHN placebo responders (n = 9) with, again, no significant difference in time-to-relapse in FHP riluzole responders (n = 6) compared to FHN riluzole responders (n = 9).

Conclusions:

Ketamine’s extended antidepressant durability in FHP TRD should be considered in the design and analysis of ketamine depression trials.     

Assisted autogenic drainage in infants and young children hospitalized with uncomplicated pneumonia,a pilot study

Background and purpose

Pneumonia is the most important respiratory problem in low‐to‐middle income countries. Airway clearance therapy continues to be used in children with pneumonia and secretion retention; however, there is lack of evidence to support or reject this treatment. This study aimed to investigate the feasibility of a randomized controlled trial (RCT) on the efficacy and safety of assisted autogenic drainage (AAD) compared to standard nursing care in children hospitalized with uncomplicated pneumonia.

Methods

A single‐blinded pilot RCT was conducted on 29 children (median age 3.5 months, IQR 1.5–9.4) hospitalized with uncomplicated pneumonia. The intervention group received standard nursing care with additional bi‐daily AAD, for 10 to 30 min. The control group only received standard nursing care, unless otherwise deemed necessary by the physician or physiotherapist. The primary outcome measure was duration of hospitalization. The secondary outcome measures included days of fever and supplemental oxygen support; respiratory rate (RR) and heart rate adjusted for age; RR and oxygen saturation pre‐, post‐, and 1‐hr post‐treatment; oxygen saturation; adverse events; and mortality.

Results

No difference was found for duration of hospitalization (median 7.5 and 7.0 days for the control and intervention groups, respectively); however, Kaplan–Meier analysis revealed a strong tendency towards a shorter time to discharge in the intervention group (p = .06). No significant differences were found for the other outcome measures at time of discharge. No adverse events were reported. Within the intervention group, a significant reduction in RR adjusted for age was found.

Discussion

As no adverse events were reported, and AAD did not prolong hospitalization; AAD might be considered as safe and effective in young children with uncomplicated pneumonia. However, a larger multicentred RCT is warranted to determine the efficacy of AAD compared to standard nursing care.     

Autoimmune response in mothers of children with congenital and postnatally diagnosed isolated heart block: a population based study

OBJECTIVE: To study the autoimmune response in mothers of children with isolated congenital heart block (CHB) and heart block (HB) diagnosed postnatally. METHODS: We reviewed the Finnish hospital registries for patients born between 1950 and 2000 and diagnosed with isolated HB before the age of 16 years. Clinical data and sera for the determination of autoantibodies were available from 67 mothers of children with CHB and from 37 mothers of children with postnatally diagnosed HB 9.9 years and 22.6 years (mean) after the index delivery, respectively. Maternal antibodies to 52 kDa and 60 kDa SSA and 48 kDa SSB were determined by time-resolved fluoroimmunoassay (TR-FIA) and by immunoblotting. Other marker antibodies for connective tissue diseases (CTD) were determined by immunoblot and/or by immunofluorescence. The control group comprised 136 mothers with primary Sj?gren's syndrome (SS), systemic lupus erythematosus (SLE), or other CTD with healthy children. RESULTS: Sixty of our 67 mothers (90%) of children with CHB had antibodies to SSA or SSB by the methods initially used in this study. When retests and tests performed previously were taken into account, only 3 (4%) of the 67 mothers did not have any autoantibodies. Two (3%) of the 67 mothers had antibodies to dsDNA and one (1%) each to Jo-1/HRS, RNP-70 kDa, and histone proteins. Of 37 mothers of children with postnatally diagnosed HB, only 3 (8%) had any autoantibodies. Increased risk of having a child with CHB was indicated by maternal primary SS and high levels of anti-SSA and anti-SSB by all assays, whereas low risk was indicated by maternal SLE or other CTD and undetectable or low levels of the antibodies. No single anti-SSA or anti-SSB test was clearly superior to others, but in general, immunoblots were more specific than TR-FIA. CONCLUSION: Maternal autoimmune disorder is almost always associated with CHB but only rarely with postnatally diagnosed HB. Anti-SSA and anti-SSB are marker antibodies for mothers of children with CHB, and an increased risk of having an affected child is indicated by maternal primary SS and high titer antibodies to SSA and SSB.     

A team fares well with a fair coach: Predictors of social loafing in interactive female sport teams

The present research aimed to develop and test a theoretical model that links players' perceived justice of the coach to a more optimal motivational climate, which in turn increases players' team identification and cohesion, and results in lower levels of social loafing in female sport teams. Belgian elite female basketball, volleyball, and football players (study 1; N = 259; M_age = 22.6) and Norwegian world‐class female handball players (study 2; N = 110; M_age = 22.8) completed questionnaires assessing players' perceived justice (distributive and procedural), motivational climate, team identification, team cohesion (task and social), and social loafing (perceived and self‐reported). In both studies, confirmatory and exploratory path analyses indicated that perceived justice was positively related to a mastery climate (P < 0.05) and negatively to a performance climate (P < 0.05). In turn, a mastery climate was linked to increased levels of team identification (P < 0.05) and task cohesion (P < 0.05). Consequently, players' perceived and self‐reported social loafing decreased (P < 0.05). The findings of both independent studies demonstrated the impact of coaches' fairness, and consequently, the motivational climate created by the coach on the optimal functioning of female sport teams.