Granulocyte antibodies in leukaemic chronic lymphoproliferative disorders

The anti-granulocyte activity of serum from patients with B-cell chronic lymphocytic leukaemia (CLL) and other lymphoproliferative disorders was investigated. Granulocyte-binding IgG was measured in 34 patients with CLL, 13 patients with hairy cell leukaemia, one patient with prolymphocytic leukaemia, two patients with Sézary cell leukaemia, and seven patients with chronic T-cell lymphocytosis who had a predominance of circulating large granular lymphocytes. Anti-granulocyte activity was absent in CLL and its variants, but present in the majority of granulocytopenic patients with chronic T-cell lymphocytosis. In one of these patients, granulocytopenia was associated with complement-activating IgG granulocyte antibody. Thus, antibody-mediated granulocyte injury appears to be an unusual occurrence in chronic lymphocytic leukaemia, but is a frequent complication of chronic T-cell lymphocytosis.     

Neuropsychological assessment, neuroimaging, and neuropsychiatric evaluation in pediatric and adult patients with sickle cell disease (SCD)

Traditionally, neuropsychological deficits due to Sickle Cell Disease (SCD) have been understudied in adults. We have begun to suspect, however, that symptomatic and asymptomatic Cerebrovascular Events (CVE) may account for an alarming number of deficits in this population. In the current brief review, we critically evaluated the pediatric and adult literatures on the neurocognitive effects of SCD. We highlighted the studies that have been published on this topic and posit that early detection of CVE via neurocognitive testing, neuropsychiatric evaluations, and neuroimaging may significantly reduce adult cognitive and functional morbidities.     

Cocaine decreases self-control in rats: a preliminary report

Cocaine abuse is often associated with behavior that takes into account short-term, but not long-term consequences. However, there has been no empirical research concerning the effects of cocaine on self-control (choice of a larger, more delayed reinforcer over a smaller, less delayed reinforcer). In the present research, when food-deprived rats repeatedly chose between a larger, more delayed food reinforcer and a smaller, less delayed food reinforcer, chronic intraperitoneal injections of 15 mg/kg cocaine (but not 10 mg/kg fluoxetine) decreased the rats' choices of the larger, more delayed reinforcer. Cocaine can decrease rats' self-control.     

Rabbit classically conditioned eyelid responses do not reappear after interpositus nucleus lesion and extensive post-lesion training.

The left eyelid responses of four rabbits were classical conditioned by pairing a tone conditioned stimulus and air puff unconditioned stimulus. After conditioned responses were well-established, the left interpositus nucleus was lesioned and 150-200 post-lesion training sessions, distributed over 10 months, were given. In three of the rabbits, no anticipatory conditioned responses were observed on paired trials and responses were at or below spontaneous blinking rates on 2,500 ms CS-alone trials that were also presented. Post-lesion conditioned responses were present when the right side was trained. The fourth rabbit showed few post-lesion conditioned responses on paired trials but eventually showed 80% conditioned responses on tone-alone trials. Histological analysis of the lesion extents indicate that a portion of the anterior interpositus nucleus was spared in this rabbit. These results argue that unlike other cerebellar lesion effects reported in the literature, where some recovery of function is normally noted, the effects of interpositus nucleus lesions are somewhat unique in that conditioned response abolition is seen as long as 10 months after the lesion.     

Trans-perineal implantation of radio-opaque treatment verification markers into the prostate: an assessment of procedure related morbidity, patient acceptability and accuracy.

On-line imaging of prostate markers can be used to compensate for errors in radiation delivery. This study assessed the patient acceptability and morbidity associated with the trans-perineal route of implantation. A minority experienced acute pain or bleeding. Placement was accurate in all but one subject. An operator related learning curve exists. Although this is an invasive procedure most patients found it acceptable. Implementation for routine clinical practice is feasible.     

Development of a PCR-SSOP approach capable of defining the natural killer cell inhibitory receptor (KIR) gene sequence repertoires

A molecular typing method based on polymerase chain reaction (PCR) amplification of three different target domains (immunoglobulin domains 1 and 3, and the transmembrane-cytoplasmic domain), followed by hybridisation with 26 digoxigenin-labelled sequence-specific oligonucleotide probes (SSOP) has been established for the polymorphic killer inhibitory receptor (KIR) genes. In addition to identifying the 12 KIR subfamilies, our PCR-SSOP typing approach could also distinguish the putative alleles, NKB1 and NKAT3, that comprise the KIR3DL1 subfamily. Ninety unrelated blood donors and 13 families (52 individuals), including both parents, were subjected to our KIR PCR-SSOP typing approach. All 12 KIR subfamilies, including a 2DS5 variant sequence, were present in the 90 individuals and displayed varied phenotype frequencies: 2DL1 (0.96), 2DL2 (0.31), 2DL3 (0.95), 2DS1 (0.56) 2DS2 (0.51), 2DS3 (0.27), 2DS4 (0.96), 2DS5v (0.35), 3DS1 (0.47), 3DL1 (0.96), 3DL2 (1.0) and 2DL4 (1.0). A total of 23 different KIR phenotypes were defined in this study, and 10 of these were only found on one occasion in one individual, indicating considerable diversity in the KIR phenotype profiles within the Irish population. Most individuals (93%) possessed the complement of inhibitory KIR specificities for the three well-defined HLA-B and -C ligands. An unusual probe pattern for 3DS1 was observed in 3 individuals indicating a variant 3DS1 gene sequence with changes at nucleotide positions 1185-1186, within the cytoplasmic domain. Sequencing analysis revealed a new single nucleotide polymorphism in exon 3 of 3DL1 NKB1(195, G-A) and a 22-bp deletion polymorphism in exon 5 of 2DS4 (nucleotides 777-798 deleted). A number of strong KIR associations were observed, namely 2DL1 with 2DL3, 2DS4 with 3DL1, 2DL2 with 2DS1/2DS2/2DS3, 2DS1 with 2DS3/2DS5v/3DS1, 2DS2 with 2DS3 and 2DS5v with 3DS1. Analysis of the KIR segregation observed in the 13 families confirmed these strong associations and permitted the definition of a number of partial KIR haplotypes, e.g. 2DL2-2DS1-2DS2-2DS3-3DL1. The segregation analysis concluded that at least 3 distinct gene loci encode 2DL1-4 and at least 4 gene loci encode the non-inhibitory KIR2DS1-2DS5. In the case of 3DL1-2 and 3DS1, our data suggests 3 gene loci, one for each subfamily.     

Athletes’ and Coaches’ Perceptions of Nutritional Advice: Eating More Food for Health and Performance

Background: Low energy availability results in physiological adaptations which contribute to unfavourable health outcomes. Little information exists on perceptions of nutritional advice to eat more food to maintain health and enhance performance. The aim of this study was to explore athletes’ and coaches’ perceptions towards advice to athletes to eat larger than their current quantities of food and to explore how nutritionists could deliver this advice. Methods: Semi-structured interviews (~20 min in length) were conducted using online communication technology, audio-recorded, and transcribed verbatim. The interview explored perceptions of the nutritional advice provided, its role in health and performance, and the challenges to eating larger amounts of food. Data were analysed using NVIVO 1.2 using an inductive thematic approach. Results: Nine elite athletes (female = 6; males = 3) and nine high-performance coaches (female = 3; male = 6) completed the semi-structured interviews. Athletes reported improved training consistency, fewer injuries and illnesses, and improved resilience when consuming adequate energy and nutrients to meet their needs. Lack of time and meal preparation difficulties were the main challenges faced to fuelling. Conclusions: Although education about under-fuelling is important, motivating, enabling, and supporting athletes to change behaviour is pivotal to increasing athlete self-awareness and to make long-term nutritional changes.     

Does epidural analgesia influence the mode of delivery in primiparae managed actively? A preliminary study of 1250 women

We studied 1250 primiparous women with a singleton pregnancy, gestational age at delivery of 37-42 weeks, with a single live fetus, vertex presentation whose first and second stages of labour were managed according to strict criteria for the active management of labour. 568 (45%) received epidural analgesia (bupivacaine 0.25%) during labour, and the other 682 (55%) received either Entonox, pethidine or no analgesia. The spontaneous vaginal delivery rate in the epidural group was 67% (95% confidence interval [CI] 63-71%), lower than that in the non-epidural group (87%, 95% CI 84-90%). All instrumental delivery rates were higher in the epidural group. However, the rotational forceps rate in the epidural group (2.5%, 95% CI 1.4-4.1%) was only marginally higher than in the non-epidural group (0.9%, 95% CI 0.3-1.9%). Women who were induced were more likely to request an epidural (56%: 95% CI 50-61%) than those with spontaneous onset of labour (41%: 95% CI 38-45%). Whether labour was spontaneous or induced, a higher proportion of women who received epidural required oxytocin augmentation. The effects of combinations of epidural analgesia, the need for oxytocin augmentation and induction of labour on mode of delivery were additive. This preliminary study suggests that a high rate of spontaneous vaginal delivery can be achieved with epidural analgesia when labour is actively managed.     

Making sense of the revised CPT codes

This year's CPT code revisions were supposed to eliminate problems resulting from codes not keeping pace with lab technology, but errors in the revisions have provided new thorns equally capable of drawing blood. Here's how not to get stuck.     

Factors predicting the acute effect of pamidronate on serum calcium in hypercalcemia of malignancy

Summary In this study we retrospectively reviewed results of the first 9 days of treatment with pamidronate at doses of 30 mg (n=13), 45 mg (n=9), and 90 mg (n=13) in an attempt to see what factors influenced the response of serum calcium to pamidronate.The nadir of serum calcium obtained post treatment was correlated with pretreatment levels of nephrogenous cyclic adenosine monophosphate (NcAMP), the renal tubular threshold for phosphate reabsorption (TmPO4), and the renal tubular threshold for calcium reabsorption (TmCa). Using the post treatment serum calcium levels, patients were divided into good and poor responders depending on whether a normal serum calcium was obtained.Pretreatment NcAMP was significantly correlated with the magnitude of the response of serum calcium (r=0.45, P=0.0001). Pretreatment NcAMP was significantly higher in the poor responders (mean±SEM): 65.0±9.4 nmol/liter GF (poor responders) versus 29.6±6.3 (good responders), P=0.004. NcAMP as a predictor of the acute response of serum calcium showed a sensitivity of 93% and a specificity of 72%. Pretreatment TmPO4 was negatively correlated with the serum calcium response post treatment (r=-0.41, P=0.003). However, though TmPO4 tended to be lower in the poor responders, this was not statistically significant [0.65 mmol/liter GF±0.09 (poor responders) versus 0.76 mmol/liter GF±0.06 (good responders)]. As a predictor of the acute response of serum calcium, TmPO4 was less good with a sensitivity of 70% and specificity of 58%. No significant correlation was present between TmCa and the serum calcium response. A significant negative correlation was evident between NcAMP and TmPO4 (r=-0.35, P=0.003), however, no significant correlation was evident between NcAMP and TmCa or TmPO4 and TmCa.These results suggest that in a hypercalcemic patient where evidence exists for the presence in circulation of a factor with PTH-like activity (i.e., NcAMP is elevated or TmPO4 is low) the response of serum calcium to pamidronate is less good. NcAMP would appear to be a useful predictor of the response of serum calcium, whereas TmPO4 is less discriminating.