Feasibility of monitoring peripheral blood to detect emerging clones in children with acute lymphoblastic leukemia†

Relapse‐enriched somatic variants drive drug resistance in childhood acute lymphoblastic leukemia. We used digital droplet‐based polymerase chain reaction to establish whether relapse‐enriched mutations in emerging subclones could be detected in peripheral blood samples before frank relapse. Although limitations in sensitivity for some probes hindered detection of certain variants, we successfully detected variants in NT5C2 and PRPS1 at a fractional abundance of 0.005% to 0.3%, 41 to 116 days before relapse. As mutations in both these genes confer resistance to thiopurines, early detection protocols using peripheral blood could be implemented to preemptively alter maintenance therapy to extinguish resistant clones before overt relapse.     

Missed opportunities for participation in prevention of mother to child transmission programmes: Simplicity of nevirapine does not necessarily lead to optimal uptake, a qualitative study

Background  

The objective of this study was to examine missed opportunities for participation in a prevention of mother-to-child transmission (PMTCT) programme in three sites in South Africa. A rapid anthropological assessment was used to collect in-depth data from 58 HIV-positive women who were enrolled in a larger cohort study to assess mother-to-child HIV transmission. Semi-structured interviews were conducted with the women in order to gain an understanding of their experiences of antenatal care and to identify missed opportunities for participation in PMTCT.     

Periocular anaesthesia: technique, effectiveness and complications with special reference to postoperative ptosis

The effectiveness of periocular anaesthesia and its complications were examined in 100 successive cataract operations. The patients were divided into 3 groups according to the duration of ocular compression with an Autopressor device after administration of periocular anaesthesia. In the control group, no compression was used (C-O, n = 36 patients). In the other two groups, compression was used for 10 (C-10, n = 32) and for 20 (C-20, n = 32) min. No differences in globe or orbicular akinesia were found between the groups. At 10 min, immobilisation of the globe in different directions was attained in 60.1-84.5% of the patients. Compression for an additional 10 min did not significantly improve the akinesia. In contrast, the hitherto undescribed loss of light perception increased with time: 15 patients at 10 min and 22 at 20 min were unable to see light. Chemosis and haematomas in the upper eyelid occurred more often in C-0 than in the other 2 groups. One day postoperatively the average palpebral aperture was smaller in C-0 than in the other two groups. The frequent postoperative ptosis (74.3% on the 1st day) decreased rapidly, but on postoperative day 7, 9 patients still had ptosis. In only one patient was ptosis still recognizable at 6 weeks postoperatively. No serious complications occurred. This study demonstrates that periocular anaesthesia with ocular compression is a suitable method for cataract surgery.     

Absence of beta-adrenergic receptor involvement in cerebrovascular dilation by halothane in monkeys

We determined, in monkeys, whether halothane-induced cerebrovascular dilation is mediated by beta-adrenergic receptors and whether cerebrovascular tone progressively returns to baseline values during prolonged halothane anesthesia. Total cerebral blood flow (CBF), cerebral perfusion pressure, plasma halothane concentration, and arterial blood gas tensions and pH were measured in 14 rhesus monkeys mechanically ventilated with 0.5% (inspired) halothane, 33% O2 and balance N2O. Halothane was increased to 2.0% and the measurements repeated 30 and 60 min later. Then either 0.9% NaCl (controls n = 6) or propranolol (n = 8), 1.0 mg/kg was infused intravenously over 10 min, and the measurements repeated at 70, 90, 120, and 150 min. After 30 min at 2.0% halothane, CBF increased in the controls by 50% (P less than 0.05) from 92 +/- 8 (mean +/- SD) to 137 +/- 39 ml X 100 g-1 X min-1 and in the propranolol group by 30% (P less than 0.05) from 106 +/- 33 to 137 +/- 28 ml X 100 g-1 X min-1. After 2.5 hr of 2.0% halothane anesthesia, CBF remained elevated above baseline levels, but by only 28 and 23% in the control and propranolol groups, respectively. Cerebrovascular resistance was identical in both groups (0.55 +/- 0.33 vs 0.53 +/- 0.13 mm Hg X ml-1 X 100 g 1 X min 1). The results show that there is only a 10-20% return of CBF toward baseline levels after up to 2.5 hr of 2% halothane anesthesia. The results also indicate that halothane-induced cerebrovascular dilation is not mediated by beta-adrenergic receptors.     

Redirecting the humoral immune response against Streptococcus mutans antigen P1 with monoclonal antibodies

The adhesin P1 of Streptococcus mutans has been studied as an anticaries vaccine antigen. An anti-P1 monoclonal antibody (MAb) bound to S. mutans prior to mucosal immunization of mice was shown previously to alter the amount, specificity, isotype, and biological activity of anti-P1 antibodies. The present study was undertaken to screen this and four additional anti-P1 MAbs for immunomodulatory activity when complexed with S. mutans and administered by a systemic route and to evaluate sera from immunized mice for the ability to inhibit adherence of S. mutans to immobilized human salivary agglutinin. All five MAbs tested influenced murine anti-P1 serum antibody responses in terms of subclass distribution and/or specificity. The effects varied depending on which MAb was used and its coating concentration. Two MAbs promoted a more effective, and two others a less effective, adherence inhibition response. An inverse relationship was observed between the ability of the MAbs themselves to inhibit adherence and the ability of antibodies elicited following immunization with immune complexes to inhibit adherence. Statistically significant correlations were demonstrated between the levels of anti-P1 serum immunoglobulin G2a (IgG2a) and IgG2b, but not of IgG1 or IgG3, and the ability of sera from immunized animals to inhibit bacterial adherence. These results indicate that multiple anti-P1 MAbs can mediate changes in the immune response and that certain alterations are potentially more biologically relevant than others. Immunomodulation by anti-P1 MAbs represents a useful strategy to improve the beneficial immune response against S. mutans.     

Comparison of the smoking behaviour and attitudes of smokers who attribute respiratory symptoms to smoking with those who do not.

General practitioners' (GPs') advice against smoking helps smokers to stop; unfortunately, GPs cannot predict which patients will quit following advice. This postal questionnaire survey suggests that where smokers attribute their respiratory symptoms to smoking, they are eight times (95% confidence interval [CI] = 3.0-23.3) more likely to believe that their health will improve if they stop smoking and six times (95% CI = 1.4-23.3) more likely to intend to stop smoking.