Inhibited apoptosis and drug resistance in acute myeloid leukaemia

Despite extensive investigation into mechanisms of drug resistance in acute myeloid leukaemia (AML), the aetiology of therapeutic resistance is unclear. We found that five leukaemia cell lines (K562, HL-60, CEM, CEM induced to overexpress bcl-2, and REH) displayed parallel sensitivity to four antileukaemia drugs with different mechanisms of action, with K562 generally being the least sensitive and REH being the most sensitive. The amount of spontaneous apoptosis in the cell lines after serum-free culture paralleled their drug sensitivity: K562 cells displayed the least apoptosis at 24 h (2.50 ± 0.24%) and REH the most (24.47 ± 8.22%). The extent of spontaneous apoptosis of leukaemic blasts from 39 patients with newly diagnosed de novo AML also correlated with the success of the intensive, infusional cytarabine-based induction therapy. There was a median of 19.5% (range 3.6–64%) apoptotic AML cells after 24 h of serum-free culture in patients who entered a complete remission compared with 4.2% (1.8–7.0%) apoptotic AML cells in patients who did not achieve a complete remission ( P  = 0.0007). Thus, inhibited apoptosis was associated with both in vitro and in vivo pan-resistance to antileukaemic chemotherapy. The cause of inhibited apoptosis in AML is probably a function of interactions among multiple signals that influence apoptosis. Assessment of spontaneous apoptosis may serve as an important prognostic factor for AML.     

Androgen receptor gene and sex-specific Alzheimer's disease

Women are at a 2-fold risk of developing late-onset Alzheimer's disease (AD) (onset at 65 years of age or older) compared with men. During perimenopausal years, women undergo hormonal changes that are accompanied by metabolic, cardiovascular, and inflammatory changes. These all together have been suggested as risk factors for late-onset AD. However, not all perimenopausal women develop AD; we hypothesize that certain genetic factors might underlie the increased susceptibility for developing AD in postmenopausal women. We investigated the Androgen Receptor gene (AR) in a clinical cohort of male and female AD patients and normal control subjects by sequencing all coding exons and evaluating the length and distribution of the CAG repeat in exon 1. We could not establish a correlation between the repeat length, sex, and the disease status, nor did we identify possible pathogenic variants. AR is located on the X chromosome; to assess its role in AD, X-inactivation patterns will need to be studied to directly correlate the actual expressed repeat length to a possible sex-specific phenotypic effect.     

The diagnosis and management of allergic reactions in patients sensitized to non-specific lipid transfer proteins

Sensitization to one or more non-specific lipid transfer proteins (nsLTPs), initially thought to exist mainly in southern Europe, is becoming accepted as a cause of allergic reactions to plant foods across Europe and beyond. The peach nsLTP allergen Pru p 3 is a dominant sensitizing allergen and peaches a common food trigger, although multiple foods can be involved. A frequent feature of reactions is the requirement for a cofactor (exercise, alcohol, non-steroidal anti-inflammatory drugs, Cannabis sativa) to be present for a food to elicit a reaction. The variability in the food and cofactor triggers makes it essential to include an allergy-focused diet and clinical history in the diagnostic workup. Testing on suspected food triggers should also establish whether sensitization to nsLTP is present, using purified or recombinant nsLTP allergens such as Pru p 3. The avoidance of known trigger foods and advice on cofactors is currently the main management for this condition. Studies on immunotherapy are promising, but it is unknown whether such treatments will be useful in populations where Pru p 3 is not the primary sensitizing allergen. Future research should focus on the mechanisms of cofactors, improving diagnostic accuracy and establishing the efficacy of immunotherapy.     

Value of Extended Warming in Patients Undergoing Elective Surgery

Perioperative temperature management is imperative for positive surgical outcomes. This study assessed the clinical and wellbeing benefits of extending normothermia by using a portable warming gown. A total of 94 patients undergoing elective surgery were enrolled. They were randomized pre-operatively to either a portable warming gown or the standard warming procedure. The warming gown stayed with patients from pre-op to operating room to postrecovery room discharge. Core temperature was tracked throughout the study. Patients also provided responses to a satisfaction and comfort status survey. The change in average core temperature did not differ significantly between groups (P = 0.23). A nonsignificant 48% relative decrease in hypothermic events was observed for the extended warming group (P = 0.12). Patients receiving the warming gown were more likely to report always having their temperature controlled (P = 0.04) and significantly less likely to request additional blankets for comfort (P = 0.006). Clinical outcomes and satisfaction were improved for patients with extended warming.Key words: Perioperative warming, Hypothermia, Warming gown, Patient warming unitIntra-operative management of core temperature has been shown to reduce postoperative complications including infections, risk of blood transfusions, and length of hospital stay.¹ Core temperature at induction has been demonstrated to be a significant risk for development of perioperative hypothermia.² Research findings in support of avoiding hypothermia (core temperature <36°) during surgery and the impact of lower temperature on patient recovery is well documented.^3,4 These include increased bleeding during surgery, increased infection rates, increased length of stay, as well as, ultimately, a higher mortality rate.^1,5,6Perioperative normothermia has also been shown to reduce postoperative complications.³ Most recently it has been suggested that active warming commencing preoperatively is more effective in achieving normothermic admission temperatures to postanesthesia recovery than warming commenced intra-operatively.⁴ That complications are reduced with preoperative warming is well established. These findings further suggest that extended warming significantly reduces rates of hypothermia over the standard warming just during surgery and at this time, no study has been performed.This study was conducted with three objectives in mind. The first objective was to compare rates of hypothermia (core temp < 36°) recorded intra-operatively in both a standard warming procedure group and an extended perioperative warming group. The second objective was to examine the association between normothermia extension and well-being. The third objective was to describe the costs of extended warming (peri-operative warming gown) and compare it to the standard warming procedure.