Reduced-intensity hematopoietic cell transplantation in older patients with AML/MDS: umbilical cord blood is a feasible option for patients without HLA-matched sibling donors

Umbilical cord blood (UCB) has increased access to hematopoietic cell transplantation (HCT) for patients without HLA-matched sibling donors (MSD). We compared outcomes of HCT using MSD (N=38) or UCB (N=60) among older patients (age ≥ 55 years) with AML or myelodysplastic syndromes (MDS). All patients received a reduced intensity regimen consisting of CY, fludarabine and 200 cGy TBI. Median age at HCT was 63 years for MSD and 61 years for UCB recipients. Among UCB recipients, 95% received two UCB units and 88% received 1-2 locus HLA-mismatched units to optimize cell dose. OS at 3-years was 37% for MSD and 31% for UCB recipients (P=0.21). On multivariate analysis, donor source (MSD vs UCB) did not impact risks of OS, leukemia-free survival and relapse or treatment-related mortality. UCB is feasible as an alternative donor source for reduced-intensity conditioning HCT among older patients with AML and MDS who do not have a suitable MSD.     

A Survey of Parent Satisfaction with Pediatric Neuropsychological Evaluations

Satisfaction with pediatric neuropsychological evaluations was surveyed by asking parents or guardians of children who completed pediatric neuropsychological evaluations at a large children's hospital over a 2-year period to complete a 30-item rating scale. The scale included items drawn from published measures of consumer satisfaction, and incorporated a well-validated measure of general satisfaction. A total of 338 surveys were distributed, with 117 completed, for a return rate of 35%. Respondents were generally similar to non-respondents, except that respondents had a higher average level of maternal education and were more likely to have been referred for neuropsychological evaluations by sources outside the hospital. Parents were generally satisfied with pediatric neuropsychological evaluations, although some parents indicated that the evaluations did not provide as much help as expected. A factor analysis of the survey instrument revealed four dimensions of satisfaction: General Satisfaction, Clinician Acceptance/Empathy, Provision of Help, and Facilities/Administrative Assistance. Maternal education was negatively correlated with all four factors, but no other demographic, patient, or clinician variables were significantly related to satisfaction. Future studies could survey physicians and educators to provide a more complete understanding of satisfaction with pediatric neuropsychological evaluations.     

Segmental and metrical complexity during non-word repetition in adults who stutter

Non-word repetition is weaker for adults who stutter (AWS) compared to adults who do not stutter (AWNS) as phonological demands increase. However, non-word stimuli used in previous studies varied by length, but did not vary with regard to segmental or metrical complexity. The purpose of the present study was to examine the unique influence of these two distinct types of complexity on non-word repetition in AWS and AWNS via administration of the Test of Phonological Structure (TOPhS). Twenty-four adults (12 AWNS, 12 AWS) repeated 96 non-words within a soundproof booth immediately after auditory presentation. All 96 non-word targets included on the TOPhS were one to four syllables in length and ranked based on segmental complexity (simple, moderate and complex) and metrical complexity (simple, moderate and complex). No main effect of metrical complexity was detected between groups, and no differences in accuracy were observed for non-words with simple or moderate segmental complexity. However, AWS were significantly more likely to produce a phonemic error when repeating words with complex segmental structure than AWNS, irrespective of metrical complexity. Segmental complexity may contribute to the differences in phonological working memory in AWS when controlling for metrical complexity and length.     

Electrical and optical study of nerve impulse-evoked ATP-induced, P2X-receptor-mediated sympathetic neurotransmission at single smooth muscle cells in mouse isolated VAS deferens

Simultaneous electrophysiology and confocal microscopy were used to investigate purinergic neurotransmission at single smooth muscle cells (SMCs) in mouse isolated vas deferens, and to explore the relationship between two high-resolution P2X-receptor-mediated measures of per pulse ATP release: transient peaks in the first time derivative of the rising phase of excitatory junction potentials (EJPs) recorded in single SMCs ('discrete events'; DEs) and neuroeffector Ca(2+) transients (NCTs) in the impaled SMCs. This study shows that discrete events represent neurotransmitter release onto the impaled cell. First, the median amplitude of the first derivative of the EJP was larger when there was a coincident NCT in the impaled cell, compared with instances when no coincident NCT occurred. Second, the time-to-peak amplitude of the first derivative was shorter if there was a coincident NCT in the impaled cell, compared with when no coincident NCT was observed within the field. Surprisingly, first derivative amplitude increased with the distance (of the corresponding NCT) from the microelectrode. The microelectrode did not locally inhibit the functional quantal size as there was no effect of distance on the normalized NCT amplitude. When the significant effect of distance (between the microelectrode and NCTs) on the first derivative amplitude was removed, there was no correlation between the unstandardized residual (of distance vs. first derivative amplitude) and NCT amplitude. The absence of a correlation between DE and NCT amplitudes suggests that the NCT amplitude is a poor measure of quantal size. The usefulness of NCTs hence lies primarily in locating neurotransmitter release and measuring changes in local release probability.     

Development and psychometric evaluation of the patient knowledge of,and attitudes and behaviours towards pressure ulcer prevention instrument (KPUP)

The Patient Knowledge of, and Attitude and Behaviour towards Pressure Ulcer Prevention Instrument (KPUP) was developed and validated using a two‐stage prospective psychometric instrument validation study design. In Stage 1, the instrument was designed, and it is psychometrically evaluated in Stage 2. To establish content validity, two expert panels independently reviewed each item for appropriateness and relevance. Psychometric evaluation included construct validity and stability testing of the instrument. The questionnaire was administered to a convenience sample of 200 people aged more than 65 years, living independently in the community; reliability and stability were assessed by test/retest procedures, with a 1‐week interval. Mean knowledge scores at ‘test’ were 11.54/20 (95% CI = 11.10‐11.99, SD: 3.07), and ‘retest’ was 12.24 (95% CI = 11.81‐12.66, SD: 2.93). For knowledge, correlation between the test/retest score was positive (r=. 60), attitude section‐inter‐item correlations ranged from r = −.31 to r = .57 (mean intraclass correlation coefficient of r = .42), and internal consistency for the retest was the same as the test (α = .41 for the eight items). For health behaviours, individual inter‐item correlations for test items ranged from r = −.21 to r = .41 for the 13 standardised items. Psychometric testing of the KPUP in a sample of older persons in the community provided moderate internal consistency and general high test‐retest stability.     

Stress-induced suppression of the gonadotropin-releasing hormone pulse generator in the female rat: a novel neural action for calcitonin gene-related peptide

In addition to its role as a potent vasodilator, calcitonin gene-related peptide (CGRP) is centrally involved in a variety of stress responses, including activation of the hypothalamo-pituitary-adrenocortical axis. It is well known that stress suppresses the activity of the hypothalamic GnRH pulse generator, the central regulator of LH and FSH pulses, resulting in reproductive dysfunction. The aim of this study was to test the hypothesis that CGRP has a critical role in mediating stress-induced suppression of pulsatile LH secretion in the rat. Ovariectomized rats were implanted with intracerebroventricular and iv cannulae. Central administration of CGRP (75 pmol-1.2 nmol) into the lateral cerebral ventricle resulted in a profound, dose-dependent suppression of LH pulses, which was reversed by a CGRP receptor antagonist (CGRP(8-37),1 nmol). Although the site of action of CGRP remains to be established, the induction of c-Fos expression in the preoptic area and hypothalamic paraventricular nucleus might suggest an involvement of these brain regions. Intravenous administration of CGRP did not affect LH pulses. Coadministration (intracerebroventricular) of CGRP (400 pmol) with a CRH antagonist (alpha-helical CRF(9-41), 26 nmol) partly blocked the CGRP-induced suppression of LH pulses. Furthermore, CGRP(8-37) (1 nmol) completely blocked hypoglycemic stress-induced suppression of LH pulses. These results suggest that the suppression of pulsatile LH secretion by central administration of CGRP may be mediated in part by CRH, and that CGRP may play a pivotal role in the normal physiological response of stress-induced suppression of the hypothalamic GnRH pulse generator, and hence the reproductive system.     

Effect of alcohol administration on plasma growth hormone response to insulin-induced hypoglycemia.

Plasma growth hormone (HGH) response to insulin-induced hypoglycemia was assessed in a group of normal adult volunteers, with and without prior consumption of ethanol. A significant difference was found in peak HGH concentrations on the two occasions, indicating that prior consumption of ethanol attenuates the normal HGH response to insulin-induced hypoglycemia. It is suggested that ethanol may deplete catecholamine stores in the neurons of the ventromedial nucleus of the hypothalamus and may thereby impair secretion of growth hormone releasing factor. Under certain circumstances this could be of importance in the pathogenesis of alcohol-induced hypoglycemia.     

Biology of sepsis: Its relevance to pediatric nephrology

Because of its multi-organ involvement, the syndrome of sepsis provides clinical challenges to a wide variety of health care providers. While multi-organ dysfunction triggered by sepsis requires general supportive critical care provided by intensivists, the impact of sepsis on renal function and the ability of renal replacement therapies to modulate its biologic consequences provide a significant opportunity for pediatric nephrologists and related care providers to impact outcomes. In this review, we aim to highlight newer areas of understanding of the pathobiology of sepsis with special emphasis on those aspects of particular interest to pediatric nephrology. As such, we aim to: (1) review the definition of sepsis and discuss advances in our mechanistic understanding of sepsis; (2) review current hypotheses regarding sepsis-induced acute kidney injury (AKI) and describe its epidemiology based on evolving definitions of AKI; (3) review the impact of renal failure on the immune system, highlighting the sepsis risk in this cohort and strategies that might minimize this risk; (4) review how renal replacement therapeutic strategies may impact sepsis-induced AKI outcomes. By focusing the review on these specific areas, we have omitted other important areas of the biology of sepsis and additional interactions with renal function from this discussion; however, we have aimed to provide a comprehensive list of references that provide contemporary reviews of these additional areas.