Review article: Luminex technology for HLA antibody detection in organ transplantation

Since its inception in the early 1960s, the serologically based complement-dependent cytotoxicity (CDC) assay has been the cornerstone technique for the detection of human leucocyte antigen (HLA) antibodies, not only in pre-transplant renal patients, but also in other forms of organ transplantation. Recently, solid phase assays have been developed and introduced for this purpose, and in particular the Flow-based bead assays such as the Luminex system. This latter assay has proved to be far more sensitive than the CDC assay and has revealed pre-sensitization in potential transplant recipients not detected by other methods of HLA antibody detection. However, the clinical implications of this increased sensitivity have not been convincingly demonstrated until recently. This technology for HLA antibody detection permits the evaluation of the clinical importance of antibodies directed at, for example, HLA-DPB1 and HLA-DQA1, which has not been possible to date. There are Luminex issues, however, requiring resolution such as the ability to distinguish between complement fixing and non-complement fixing antibodies and determination of their relative clinical significance. Luminex technology will permit a re-evaluation of the role of HLA antibodies in both early and late antibody-mediated rejection.     

Extraction of Pacing Leads Jailed by a Stent in a Mustard Circulation

A case of successful lead extraction of atrial and ventricular pacing leads “jailed” by a stent in the superior limb of a Mustard baffle in a 40‐year‐old man with surgically corrected transposition of the great arteries and pacemaker pocket infection. Manual traction alone was sufficient to remove the jailed leads with no subsequent complications. (PACE 2010; e65–e67)     

Daytime sleepiness, psychomotor performance, waking EEG spectra and evoked potentials in women with severe premenstrual syndrome

We assessed daytime sleepiness using objective and subjective measures in women with severe premenstrual syndrome (PMS) compared with women without significant premenstrual symptoms. Nine women with severe PMS and eight controls (aged 18−40 years) completed a laboratory-based daytime protocol including the maintenance of wakefulness test (MWT), psychomotor vigilance task (PVT), quantitative waking electroencephalogram (EEG), auditory and visual event-related potentials (ERPs), and sleepiness and mood scales during the mid-follicular and late-luteal (premenstrual) phases of the menstrual cycle. In association with increased perceived sleepiness, fatigue and other premenstrual symptoms in the late-luteal phase, women with PMS performed more poorly on the PVT, with increased lapses and slower reaction times ( P  <   0.05), compared with the follicular phase and controls. However, there were no significant group or menstrual phase differences in latency to sleep on the MWT. Waking spectral EEG power and ERP measures also did not differentiate PMS women when symptomatic. Both groups of women displayed increased spectral power in the delta/theta frequencies (2−6 Hz) and fast alpha frequency (11−12 Hz) in the late-luteal phase relative to the follicular phase. Trait-like differences were apparent in that women with PMS had increased beta1 (12−16 Hz) power and smaller P300 amplitude than controls in both menstrual cycle phases. Our findings indicate that women with severe PMS are subjectively sleepy and fatigued, and show psychomotor slowing when symptomatic compared with when they are symptom-free and compared with controls. However, the ability to maintain wakefulness under soporific conditions, spectral properties of waking EEG and cognitive processing do not vary in synchrony with premenstrual symptoms.     

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.     

Survivorship and the cancer follow-up clinic

In recent years there has been growing interest in the needs of those individuals who have survived cancer. It is now possible to describe the adjustments that these individuals will make, predict when such difficulties will arise, and identify those most vulnerable to adjustment difficulty. The value of the cancer follow-up clinic has also received scrutiny, drawing on work previously undertaken in the cancer screening clinic setting. Issues discussed in the literature include the purpose of follow-up, the most appropriate health care professional to undertake the follow-up clinic, and the financial cost of cancer follow-up. There exists an opportunity for cancer nurses at present to develop roles in the clinic setting, offering patient-centred and cost-effective alternatives to physician-led follow-up.     

The effect of changes in blood gas tension upon the renin-angiotensin system of the newborn infant

Summary. Renin and renin-substrate concentrations were measured in the paired umbilical artery and vein blood of 20 babies born by elective caesarean section, and 36 babies born vaginally. Blood pH, carbon dioxide tension and oxygen tension were measured in all samples. Babies born vaginally were significantly more acidaemic than those delivered by caesarean section. The cord artery blood also had a significantly greater carbon dioxide tension at vaginal delivery. A decrease in pH of either cord artery or vein blood, irrespective of mode of delivery, was associated with an increase in renin concentration. Renin-substrate concentration tended to be lower in the cord vein blood of acidaemic babies born vaginally, such that the ratio renin: renin-substrate concentration was negatively correlated with pH. At caesarean section the renin concentration of cord vein blood was positively correlated with carbon dioxide tension and increased dramatically at oxygen tensions <3kPa. This was not observed in babies born vaginally, but the cord artery substrate concentration in these infants was positively correlated with carbon dioxide tension. Thus changes in the renin-angiotensin system at birth may partly be affected by blood gas tension.     

Gentamicin dosing in neonates: evaluation of a dosing protocol

A study was carried out to examine the dosing of gentamicin and to investigate some of the determinants of serum gentamicin concentrations in neonates at the Royal Hobart hospital, Tasmania, Australia, and to examine the appropriateness of the current dosing protocol (that of the Royal Children's hospital, Melbourne). Clinical and demographic data were retrospectively collected from the records of 39 neonates who had received therapy with gentamicin for suspected or proven septicaemia during the period May to September, 1993. Peak and trough serum concentrations of gentamicin were measured, at least 36 hours after starting therapy. The mean gestational age (± SD) of the sample was 32.3 ± 4.9 weeks, and 30 patients were male. The mean dosage of gentamicin was 4.0 ± 1.3mg/kg/day and the median duration of therapy was 4 days (range 2 to 22 days). Trough serum concentrations of gentamicin ranged from 0.6 to 6.0mg/L (mean 1.9 ± 1.0mg/L), with 35.9 per cent being 2.0mg/L or higher. Peak serum concentrations ranged from 4.3 to 12.9 mg/L (mean 6.1 ± 1.5 mg/L), with 89.7 per cent being between 5.0 and 8.0mg/L. The peak and trough serum concentrations were significantly related, while the total daily dosage of gentamicin and the resulting peak and trough serum concentrations were not significantly related. The trough serum concentration of gentamicin was significantly related to the serum creatinine concentration. Patients who had been dosed correctly according to the protocol were less likely to have a potentially toxic trough serum concentration of gentamicin. Those administered gentamicin every 12 hours tended to have higher serum trough concentrations of the drug than those who received it either 18- or 24-hourly. This study has confirmed that excessive serum concentrations of gentamicin occur frequently in neonates, a situation which may be improved by greater usage of an 18-hourly dosing regimen and prompt adjustment of dosage according to renal function.