Impact of adverse pancreatic injury at surgical procurement upon islet isolation outcome

The consequence of a pancreas injury during the procurement for islet isolation purpose is unknown. The goal of this work was to assess the injuries of the pancreata procured for islet isolation, and to determine their effect on the islet yield. Between January 2007 and October 2013, we prospectively documented every injury of the pancreata processed in our centre for islet isolation. Injuries involving the main duct were classified as major, the others as minor. Donors’ characteristics and islet yields were compared between the groups of injuries. A pancreas injury was identified in 42 of 452 pancreata received for islet isolation (9.3%). In 15 cases, the injury was major (3.3% of all pancreata). Although a minor injury did not affect the islet yield, a major injury was significantly associated with unfavourable outcomes (postpurification mean islet equivalent of 364 ± 181, 405 ± 190 and 230 ± 115 × 10³ for absence of injury, minor injury and major injury, respectively). A major injury was significantly more prevalent in lean and short donors. We recommend assessing the quality of the pancreas in the islet isolation centre before starting the isolation procedure. Each centre should determine its own policy based on its financial resources and on the wait list.     

Respiratory chain deficiency in aged spinal motor neurons

Sarcopenia, muscle wasting, and strength decline with age, is an important cause of loss of mobility in the elderly individuals. The underlying mechanisms are uncertain but likely to involve defects of motor nerve, neuromuscular junction, and muscle. Loss of motor neurons with age and subsequent denervation of skeletal muscle has been recognized as one of the contributing factors. This study investigated aspects of mitochondrial biology in spinal motor neurons from elderly subjects. We found that protein components of complex I of mitochondrial respiratory chain were reduced or absent in a proportion of aged motor neurons–a phenomenon not observed in fetal tissue. Further investigation showed that complex I-deficient cells had reduced mitochondrial DNA content and smaller soma size. We propose that mitochondrial dysfunction in these motor neurons could lead to the cell loss and ultimately denervation of muscle fibers.     

Assessing physical function and activity for survivors of a critical illness: A review of instruments

Background

Functional outcomes and health-related quality of life are important measures for survivors of a critical illness. Studies have demonstrated debilitating physical effects for a significant proportion of surviving patients, particularly those with intensive care unit-acquired weakness. Contemporary practice changes include a focus on the continuum of critical illness, with less sedation and more physical activity including mobility while in ICU, and post-ICU and post-hospitalisation activities to support optimal recovery. How to best assess the physical function of patients at different phases of their recovery and rehabilitation is therefore important.

Purpose

This narrative review paper examined observational and functional assessment instruments used for assessing patients across the in-ICU, post-ICU and post-hospital continuum of critical illness.

Methods

Relevant papers were identified from a search of bibliographic databases and a review of the reference list of selected articles. The clinimetric properties of physical function and HRQOL measures and their relevance and utility in ICU were reported in narrative format.

Findings

The review highlighted many different instruments used to measure function in survivors of ICU including muscle strength testing, functional tests and walk tests, and patient centred outcomes such as health related quality of life. In general, the sensitivity and validity of these instruments for use with survivors of a critical illness has not yet been established.

Conclusion

Based on findings from the review, screening of patients using reliable and valid instruments for ICU patients is recommended to inform both practice and future studies of interventions aimed at improving recovery and rehabilitation.     

Hydrodynamic delivery of human IL-15 cDNA increases murine natural killer cell recovery after syngeneic bone marrow transplantation

Immune deficiency immediately following bone marrow transplantation (BMT) increases susceptibility to opportunistic infections as well as tumor relapse. Natural Killer (NK) cells play important roles in the resistance to virally infected and transformed cells. Interleukin (IL)-15 has been shown to be essential for NK cell development and survival. We administered human (h) IL-15 cDNA (pIL-15) via hydrodynamic delivery to murine recipients undergoing congenic BMT to determine its effects on NK cell reconstitution. Hydrodynamic pIL-15 delivery resulted in high levels of hIL-15 protein in the serum that lasted for several days and then quickly declined. The appearance of hIL-15 was followed by a significant increase of mature donor-derived NK cells within the bone marrow, spleens, and livers of the treated recipients. No accumulation of immature NK cell progenitors was observed. The NK cells from IL-15-treated recipients displayed an activated phenotype and were lytically active toward tumor targets in?vitro to a similar degree as did those cells from recipients treated with control plasmid. This suggests that the predominant effect of IL-15 was a quantitative increase in total NK cell numbers and not qualitative changes in NK cell functions. No toxicities or adverse effects were observed. Studies performed in transplanted mice bearing renal carcinoma tumors demonstrated that this mode of hIL-15 gene delivery resulted in increased antitumor responses. These results support the use of cytokine gene transfer-based regimens as a platform to augment NK cell recovery after BMT.     

Differential perinatal risk factors in children with attention-deficit/hyperactivity disorder by subtype

We compared the attention-deficit/hyperactivity disorder(ADHD) combined subtype (ADHD-C) to the ADHD inattentive subtype (ADHD-I) in terms of genetic, perinatal, and developmental risk factors as well as clinical and neuropsychological characteristics. A total of 147 children diagnosed with ADHD between the ages of 6 and 15 years participated in this study. The parents of the children completed the structured diagnostic interview, the ADHD Rating Scale-IV, the Children’s Behavior Checklist, and structured questionnaires on perinatal risk factors, and the children underwent a neuropsychological test and were genotyped. A total of 502 children without ADHD were recruited from the community as a healthy control group. The ADHD-C children showed more severe externalizing symptoms, showed more deficits in a continuous performance test, and were more likely to have comorbid disorders. Maternal stress during pregnancy, postpartum depression, and changes in the primary caretaker during first 3 years were significantly associated with both ADHD-I and ADHD-C. The ADHD-I group was less likely to have received regular prenatal check-ups and more likely to have had postnatal medical illness than the ADHD-C group. There were no significant differences in the genotype frequencies of the dopamine transporter (DAT1) and the serotonin transporter –linked polymorphic region (5-HTTLPR) polymorphisms between ADHD-I and ADHD-C groups. This study shows that the inattentive subtype of ADHD is different from the combined subtype in many parameters including severity of symptoms, comorbidity, neuropsychological characteristics, and environmental risk factors.     

The effect of diet on intermediary metabolite concentrations in type 2 (non-insulin-dependent) diabetes mellitus

Summary The metabolic response to a standard meal was studied in six Type 2 (non-insulin-dependent) diabetic patients at diagnosis and following 4–6 weeks of dietary treatment. The fall in blood glucose concentration following treatment was accompanied by significant reductions in circulaitng concentrations of lactate, pyruvate, alanine and glycerol. Blood 3-hydroxybutyrate concentrations also fell with treatment.     

Alcohol alters sensory processing to respiratory stimuli in healthy men and women during wakefulness

Study Objectives:

Alcohol can cause sleep-disordered breathing in healthy men, increase O₂ desaturation in men who snore, and worsen obstructive sleep apnea (OSA) severity in men with OSA. These findings are less consistent among women, and the underlying mechanisms are incompletely understood. Respiratory-load sensory processing, which underpins upper-airway and respiratory responses to increased breathing load, is potentially impaired by alcohol. Using respiratory-related evoked potentials (RREPs) during wakefulness, this study aimed to test the hypothesis that alcohol impairs respiratory-load sensory processing and to explore potential sex differences.

Design:

Within-subjects cross-over design in men versus women.

Setting:

Sleep physiology laboratory.

Participants:

Twenty healthy individuals (9 women) aged 18 to 38 years.

Interventions:

Within each subject, RREP waveform components were generated by ∼60 brief early-inspiratory negative-pressure pulses (−13 cm H₂O mask pressure, 200 ms) before and after acute alcohol administration (1.5 mL/kg body weight). Choanal and epiglottic pressures were recorded to monitor stimulus magnitude and upper-airway resistance.

Measurements and Results:

The latency of several RREP waveform components increased after the administration of alcohol (ΔN1 = 11 ± 5 ms, ΔN2 = 6 ± 3 ms, ΔP3 = 26 ± 10 ms), and P2 amplitude decreased (3.4 ± 1.5 μV vs 1.2 ± 0.8 μV). There were no changes in P1 latency or amplitude. During relaxed breathing, nasal resistance increased after alcohol ingestion (1.38 ± 0.16 vs 1.86 ± 0.18 cm H₂O·l^-1·s^-1), but pharyngeal and supraglottic resistances remained unchanged. RREP waveform components and upper-airway resistance measures were not different in men versus women before or after alcohol ingestion.

Conclusions:

These data demonstrate that alcohol alters sensory processing of respiratory neural information, but not early neural transmission (P1), to a similar extent in healthy men and women. Altered sensory processing to respiratory stimuli, as well as nasal congestion, may be important mechanisms contributing to alcohol-related sleep disordered breathing.

Citation:

Eckert DJ; Elgar NJ; McEvoy RD; Catcheside PG. Alcohol alters sensory processing to respiratory stimuli in healthy men and women during wakefulness. SLEEP 2010;33(10):1389-1395.