Analysis of heat-shock protein expression in myeloid leukaemia cells by flow cytometry

Expression of heat-shock proteins (hsp) was analysed in the leukaemic cells of 12 patients with acute myeloid leukaemia (AML) and nine patients with chronic myeloid leukaemia (CML). Using monoclonal antibodies to hsp70, hsp90 and hsp60 (ML30, a mycobacterial antigen with homology to human hsp60), we measured hsp levels by flow cytometry of permeabilized cells. Mononuclear cells from 10 healthy volunteers were also examined. The results demonstrate that hsp expression is significantly increased (P<0'01) in the circulating cells of patients with AML compared with cells from CML patients, and compared with normal peripheral blood mononuclear cells. This increased pattern of expression was found for all three heat-shock protein families included in this study. Mononuclear cells from leukaemic patients showed a heterogenous pattern of hsp expression, between different patients, between cells from individual patients, and between the different hsp proteins examined. It is possible that hsp expression relates to the differentiation state or proliferative potential of these leukaemic cells.     

Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial

Laboratory trials have demonstrated the efficacy of nicotine replacement in smoking cessation bur absolute success races are low. For many, nicotine gum is hard to use and transdermal nicotine is slow-acting and passive. A new, faster-acting nicotine nasal spray (NNS) can provide easily self-administered relief from cigarette withdrawal. The NNS was tested for safely and efficacy in smoking cessation. Two hundred and fifty-five smokers were randomized to NNS or a piperine placebo. Drug use was limited to 8–32 doses/day for 6 months. Subjects were tested while smoking and at post-cessation daily (week 1) with follow-up at weeks 2, 3, 6 and at 3 months, 6 months and 1 year. Continuous abstinence analyses (CO ≤8 ppm.; no slips) showed that NNS significantly enhanced success rates over placebo overall (p < 0.001) and at all test intervals. Differences at key intervals between active and placebo were: 63% vs. 40% (day 5), 51% vs. 30% (week 3), 43% vs. 20% (6 weeks), 34% vs. 13% (3 months), 25% vs. 10% (6 months) and 18% vs. 8% (1 year). Side effects were common but tolerable. Cotinine measures showed that replacement of nicotine approximated 30% of smoking levels. Hazard functions revealed relapse risks peaked at day 1, day 5 and 3 weeks for strict abstinence. It is concluded NNS is safe, efficacious and a viable alternative treatment for smoking cessation.     

Interleukin-12 suppresses filaria-induced pulmonary eosinophilia, deposition of major basic protein and airway hyperresponsiveness

Tropical Pulmonary Eosinophilia (TPE) is a severe form of allergic asthma caused by the host inflammatory response to filarial helminths in the lung microvasculature, and is characterized by pulmonary eosinophilia, increased filarial-specific IgG and IgE antibodies, and airway hyperresponsiveness. The current study examined the effect of IL-12 on pulmonary eosinophilia, deposition of eosinophil major basic protein and airway hyperresponsiveness in mice inoculated i.v. with Brugia malayi microfilariae. Injection of recombinant murine IL-12 modulated the T helper (Th) response in the lungs from Th2- to Th1-like, with elevated IFN-γ, and decreased IL-4 and IL-5 production. Consistent with this shift in cytokine response, antigen-specific IgG2a was elevated, and IgG1 and total serum IgE were decreased. In addition, eosinophils in BAL fluid from IL-12 treated mice were reduced from 56% to 11%, and there was no detectable MBP on respiratory epithelial cells. Importantly, IL-12 suppressed airway hyperresponsiveness compared with saline-injected control animals. Taken together, these data clearly demonstrate that by modulating Th associated cytokine production, IL-12 down-regulates filaria-induced lung immunopathology .     

Differential item functioning related to ethnicity in an oral health‐related quality of life measure

International Journal of Paediatric Dentistry 2010; 20: 435–441 Objective. To assess whether an oral health‐related quality of life (OHRQoL)measure showed differential item functioning (DIF) by ethnicity. Methods. A simple random sample of 12‐ and 13‐year‐old schoolchildren enrolled in the Taranaki District Health Board’s school dental service, New Zealand. Each child (n = 430) completed the Child Perception Questionnaire (CPQ_11‐14) in the dental clinic waiting room, prior to a dental examination. The dataset included age, gender, ethnicity, and deprivation status. The general principle of the analytic plan was that equal scores from each CPQ_11‐14 item were expected from both non‐Mäori and Mäori groups regardless of their ethnic group. Ordinal logistic regression was performed. The dependent variables were the CPQ_11‐14 items. The ethnicity group and each CPQ_11‐14 domain score were the independent variables. Non‐uniform DIF was assessed through adding an interaction term for each CPQ_11‐14 sub‐scale. Results. Non‐uniform DIF was found in two items, one in the Functional Limitations sub‐scale and another in the Social Well‐being sub‐scale. Uniform DIF was found in one item of the Emotional Well‐being sub‐scale. Conclusion. Both non‐uniform and uniform DIF by ethnicity was found in three of 37 items of the CPQ_11‐14 questionnaire, showing it is important to perform DIF analysis when applying OHRQoL measures.     

British Society for Haematology,slide session,annual scientific meeting,Glasgow, 2008

A morphology session is held each year at the Annual Scientific Meeting of the British Society of Haematology. Prior to the meeting this year, eight morphology cases were made available to BSH members as glass slides and also digitally as ‘virtual slides’. A panel of invited commentators who had no prior knowledge of the diagnosis discussed the eight cases. An initial limited history and blood count are given with representative images from the case material; this is followed by the discussants’ comments and suggested diagnosis. The actual clinical diagnosis is then given with other relevant information.     

Free testosterone levels in umbilical‐cord blood predict infant head circumference in females

Aim Fetal androgens influence fetal growth as well as postnatal neurocognitive ability. However, to our knowledge, no published study has prospectively examined the impact of early‐life androgens on infant brain growth. We report the association between circulating fetal androgen levels, measured from umbilical‐cord blood at birth, and a proxy measure of brain growth: head circumference. Method Participants were 82 unselected female infants from a large representative birth cohort (mean gestational age 39.4wks, SD 1.7). Umbilical‐cord blood was obtained at birth and analysed for androgen concentrations (total testosterone, androstenedione, dehyrdroepiandrosterone, and its sulphated metabolite). Head circumference and two other measures of growth – weight (mean 3311.4g, SD 461.3) and length – were measured within 3 days of birth and again at approximately 1 year of age (mean age 13.1mo, SD 1.1). Results Multivariate linear regressions found an inverse association between levels of free testosterone and growth in head circumference (correlation=?.24), even when adjusting for sociodemographic/obstetric covariates and head size at birth. Growth in weight and length could not be predicted by free testosterone concentration. Interpretation This is the first report of an association between prenatal androgen levels and postnatal growth in head circumference. These findings suggest that early‐life androgens may impact brain development during infancy.     

Interpretation of in-vitro thyroid function tests during pregnancy

Summary. In-vitro thyroid function tests are difficult to interpret in pregnancy because of, among other things, the effect of oestrogens on thyroid binding globulin (TBG) concentrations. In an attempt to clarify the position, serum concentrations of total thyroxine (T₄), free T₄, TBG, T₄/TBG ratio, tri-iodothyronine (T₃) and thyroid stimulating hormone (TSH) were measured. Total T₄ and TBG concentrations rose to above the non-pregnant reference range by 20 weeks. The T₄/TBG ratio fell to hypo-thyroid values by 20 weeks but although the free T₄ level was lower in the third trimester compared with values in the first and second trimesters, only a few subjects had hypothyroid values. The TSH values remained unchanged throughout pregnancy. The significance of these changes is discussed and reference ranges for these hormones at each trimester are provided.     

Recognition by medical and nursing professionals of malnutrition and risk of malnutrition in elderly hospitalised patients

Objective:  To determine the prevalence of malnutrition in a population of elderly hospitalised patients and to explore health professionals' perceptions and awareness of signs and risks of malnutrition and treatment options available.
Subjects and design:  One hundred elderly patients and 57 health professionals from medical wards of a tertiary teaching hospital. Quantitative and qualitative study design using a validated malnutrition assessment tool (Mini Nutritional Assessment) and researcher-designed questionnaire to assess health professionals' knowledge of nutrition risk factors.
Main outcome measures:  Mini Nutritional Assessment score, nutrition risk category and themes in health professionals' knowledge and awareness of malnutrition and its risk factors.
Results:  Thirty per cent of patients were identified as malnourished while 61% were at risk of malnutrition. Documentation by health professionals of two major risk factors for malnutrition—recent loss of weight and appetite—were poor with only 19% and 53% of patients with actual loss of weight or appetite, respectively, identified by staff and only 7% and 9% of these patients, respectively, referred for dietetic assessment. While health professionals' knowledge of important medical risk factors for malnutrition was good, their knowledge of malnutrition risk factors such as recent loss of weight and loss of appetite was poor. Medical staff focused on biochemical factors when assessing nutrition status, while nursing staff focused on skin integrity and turgor.
Conclusion:  Malnutrition in elderly hospitalised patients remains a significant problem with low rates of recognition and referral by medical and nursing staff. Considerable scope exists to develop training and education tools and to implement an appropriate nutrition screening policy to improve referral rates to dietitians.