Use of the haematopoietic progenitor cell parameter in optimizing timing of peripheral blood stem cell harvest.

BACKGROUND AND OBJECTIVES: Timing of peripheral blood stem cell (PBSC) harvest is typically based on quantification of peripheral blood (PB) CD34+ cells. CD34 enumeration is expensive, requires expertise and takes a minimum of 1-2 h to perform. The Sysmex XE2100 is an automated haematology analyser that can rapidly and inexpensively identify haematopoietic progenitor cell (HPC) populations in PB. The aim of this study was to examine if HPC can be used to optimize timing of PBSC harvest. MATERIALS AND METHODS: White blood cell (WBC), HPC and CD34 counts were determined in a total of 60 mobilized donors. Data were analysed to examine the utility of WBC and HPC counts in predicting preharvest CD34+ counts. RESULTS: In adults presenting for autologous collection, a PB HPC threshold of > 30/microl predicts a preharvest CD34+ count of > 20/microl with sensitivity of 86% and positive predictive value (PPV) of 100%. Among paediatric patients with a diagnosis of neuroblastoma, an HPC threshold of > 16/microl yielded sensitivity and PPV of 100%, while in children with other diagnoses, an HPC cut-off of > 44/microl yielded sensitivity and PPV of 67% and 100%, respectively. Eighty per cent of adequately mobilized allogeneic donors were identified using an HPC threshold > 15/microl, with a PPV of 100%. PB WBC can also aid in predicting CD34 counts in most patient groups, albeit with lower sensitivity than HPC. CONCLUSION: By virtue of being a sensitive and accurate predictor of preharvest CD34+ counts, our data support the use of the HPC parameter in optimizing the timing of PBSC harvest.

Medium-term results of the Bernese periacetabular osteotomy in the treatment of symptomatic developmental dysplasia of the hip.

We studied the medium-term outcome of the Bernese periacetabular osteotomy in 52 patients (58 hips) with symptomatic developmental dysplasia of the hip and a mean age of 37.6 years (13 to 48). The operations were performed between 1993 and 2005 by the senior author with a mean follow-up of 66.7 months (13 to 153). There were 42 women (47 hips) and ten men (11 hips). Of these patients, 24 (30 hips) had an osteotomy on the right side and 22 (28 hips) on the left. Six patients had bilateral operations. The clinical outcome was assessed using the modified Merle d'Aubigne scale, and pre- and post-operative radiological evaluation using the modified Tonnis osteoarthritis score, the centre-edge angle, the acetabular index, the status of Shenton's line, and the cross-over sign. The mean centre-edge angle and the acetabular index were 14 degrees (2 degrees to 34 degrees ) and 23.6 degrees (0 degrees to 40 degrees ) before operation, and 36.6 degrees (16 degrees to 72 degrees ) and 7.9 degrees (0 degrees to 28 degrees ) after, respectively (p < 0.001, analysis of variance (ANOVA)). Shenton's line was intact in 23 hips (39.6%) before operation and in 48 hips (82.8%) after. The cross-over sign was present in 31 hips (53.4%) before and in three hips (5.2%) after operation (p < 0.001, ANOVA). The total Merle d'Aubigne clinical score improved from a mean of 12.6 (9 to 15) to 16.0 (12 to 18) points (p < 0.001, ANOVA). Only four hips required subsequent total hip replacement. Our results indicate that the Bernese periacetabular osteotomy provides good symptomatic relief for patients with little to no arthritis (Tonnis type 0 or 1) with an underlying deformity that can be corrected to a position of a stable, congruent hip joint.

Powder specific active dispersion for generation of pharmaceutical aerosols.

Dry powder inhalers are increasingly employed to deliver pharmaceutical aerosols. Efficient mechanisms of particle dispersion are central to their success in disease therapy. Creation of a powder aerosol requires the input of energy to transition the static powder bed into an entrained aerosol. The purpose of this study was to investigate the effects of input of vibrational energy into a powder on aerosol entrainment. Rotating drum characterization of powder flow was performed on lactose and maltodextrin excipients blended with albuterol sulfate. Dispersion experiments were conducted using an entrainment tube and a vibration actuator, vibrational energy input being derived from analysis of powder flow data from rotating drum analysis. Results of analysis of the rotating drum data showed that with increasing rotational speed powders reached a constant state of fluidization with a mean avalanche time dependent on the powder. Dispersion experiments demonstrated that the input of vibrational energy increased the dose emission while the input of frequencies specific to the powders improved the reproducibility. Frequency analysis of the vibration signals indicated that the reproducibility was determined by the bandwidth of the signal. This work suggests that an ability to tailor energy input to match the flow properties of a given powder formulation may significantly improve reproducibility of dose delivery from active dry powder inhalers.

Ethanol modulation of excitatory and inhibitory synaptic transmission in rat and monkey dentate granule neurons.

BACKGROUND: The physiological mechanisms underlying the behavioral and cognitive effects of ethanol are not fully understood. However, there is now compelling evidence that ethanol acts, at least in part, by modulating the function of a small group of proteins that mediate excitatory and inhibitory synaptic transmission. For example, intoxicating concentrations of ethanol have been shown to enhance GABAergic synaptic inhibition and depress glutamatergic excitatory neurotransmission in a number of brain regions. Because all of these electrophysiological studies have been performed in rodent brain slice or neuronal culture preparations, direct evidence that ethanol exerts similar effects on synaptic transmission in the primate central nervous system is lacking. METHODS: We have therefore developed methods to perform patch-clamp electrophysiological recordings from neurons in acutely prepared monkey (Macaca fascicularis) hippocampal slices. We have used these methods to compare the acute effects of ethanol on excitatory and inhibitory synaptic transmission in rat and monkey dentate granule neurons. RESULTS: Under our recording conditions, ethanol significantly potentiated gamma-aminobutyric acid type A inhibitory postsynaptic currents in both rat and monkey neurons. In addition, ethanol significantly inhibited NMDA, but not AMPA, excitatory postsynaptic currents in dentate granule neurons from both species. Notably, no significant differences were observed in any of the pharmacological properties of inhibitory or excitatory synaptic responses recorded from rat and monkey neurons. CONCLUSIONS: These data suggest that the differences in the behavioral effects of ethanol that have been observed between rats and higher-order mammals, such as monkeys and humans, may not reflect differences in the sensitivity of some of the major synaptic sites of ethanol action. Moreover, our results provide empirical evidence for the use of rodent brain slice preparations in elucidating synaptic mechanisms of ethanol action in the primate central nervous system.

Ethanol antagonizes kainate receptor-mediated inhibition of evoked GABA(A) inhibitory postsynaptic currents in the rat hippocampal CA1 region.

Many studies have demonstrated that ethanol reduces glutamatergic synaptic transmission primarily by inhibiting the N-methyl-D-aspartate subtype of glutamate receptor. In contrast, the other two subtypes of ionotropic glutamate receptor (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and kainate) have generally been shown to be insensitive to intoxicating concentrations of ethanol. However, we have previously identified a population of kainate receptors that mediate slow excitatory postsynaptic currents in the rat hippocampal CA3 pyramidal cell region that is potently inhibited by low concentrations of ethanol. In this study, we examined the effect of ethanol on kainate receptor-mediated inhibition of evoked GABA(A) inhibitory postsynaptic currents (IPSCs) in the rat hippocampal CA1 pyramidal cell region. Under our recording conditions, bath application of 1 microM kainate significantly inhibited GABA(A) IPSCs. This inhibition seemed to be mediated by the activation of somatodendritic kainate receptors on GABAergic interneurons and the subsequent activation of metabotropic GABA(B) receptors, because the kainate inhibition was largely blocked by pretreating slices with a GABA(B) receptor antagonist. Ethanol pretreatment significantly antagonized the inhibitory effect of kainate on GABA(A) IPSCs, at concentrations as low as 20 mM. In contrast, ethanol did not block the direct inhibitory effect of a GABA(B) receptor agonist on GABA(A) IPSCs. The results of this study suggest that modest concentrations of ethanol may antagonize presynaptic, as well as postsynaptic, kainate receptor function in the rat hippocampus.

Physiological determinants of performance on an indoor military obstacle course test.

Obstacle courses (OCs), physical challenge courses, and confidence courses are valuable in training and assessing military troops. However, OCs are not well characterized with regard to physical demands and requisite abilities. The purpose of this study was to evaluate the physical capabilities associated with success on an OC. Male subjects (N = 47) were assessed on an OC, skinfolds, upper and lower body aerobic and anaerobic power, muscular strength, and endurance. Faster performers were lighter (p < 0.003), leaner, and, relative to body weight, averaged greater arm anaerobic peak and mean power, leg aerobic power, one-repetition maximum leg press, and one-repetition maximum latissimus dorsi pull-down, than slower performers. There were significant correlations between OC time and weight (0.59), percent fat (0.54), anaerobic leg mean power (-0.43), arm anaerobic peak (-0.48) and mean power (-0.48), and arm (-0.51) and leg aerobic power (-0.53), all expressed relative to body weight. A three-variable regression model accounted for 35% of the variation in OC time. Good performers on this OC displayed many diverse physical capabilities.

Perinatal manganese exposure: behavioral, neurochemical, and histopathological effects in the rat.

Manganese chloride (Mn) was dissolved in the drinking water (0, 2, or 10 mg/ml) of dams and their litters from conception until postnatal day (PND) 30. Parturition was uneventful in the Mn-exposed rats and no physical abnormalities were observed. The rats exposed to 10 mg/ml Mn showed a 2.5-fold increase in cortical Mn levels. Their weight gain was attenuated from PND 9-24 and they were hyperactive at PND 17. Neither the 2 nor the 10 mg/ml Mn-exposed groups differed from the controls on the elevated plus apparatus or on the Morris water maze and the radial arm maze. Brain monoamine levels and choline acetyltransferase activity were affected. Tyrosine hydroxylase immunohistochemistry showed that dopamine cells of the substantia nigra were intact. Glial fibrillary acidic protein immunoreactivity was not increased in cortex, caudate, and hippocampus. However, both the low- and high-dose Mn-exposed groups showing thinning of the cerebral cortex. This could have resulted from perinatal malnutrition or from a direct effect of Mn on cortical development.