Effects of mTOR inhibitor–related proteinuria on progression of cardiac allograft vasculopathy and outcomes among heart transplant recipients

We have previously described the use of sirolimus (SRL) as primary immunosuppression following heart transplantation (HT). The advantages of this approach include attenuation of cardiac allograft vasculopathy (CAV), improvement in glomerular filtration rate (GFR), and reduced malignancy. However, in some patients SRL may cause significant proteinuria. We sought to investigate the prognostic value of proteinuria after conversion to SRL. CAV progression and adverse clinical events were studied. CAV progression was assessed by measuring the Δ change in plaque volume (PV) and plaque index (PI) per year using coronary intravascular ultrasound. Proteinuria was defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL. Overall, 137 patients were analyzed (26% with proteinuria). Patients with proteinuria had significantly lower GFR (P = .005) but similar GFR during follow-up. Delta PV (P < .001) and Δ PI (P = .001) were significantly higher among patients with proteinuria after adjustment for baseline characteristics. Multivariate Cox regression analysis showed higher all-cause mortality (hazard ratio 3.8; P = .01) with proteinuria but similar risk of CAV-related events (P = .61). Our results indicate that proteinuria is a marker of baseline renal dysfunction, and that HT recipients who develop proteinuria after conversion to SRL have less attenuation of CAV progression and higher mortality risk.     

Minimum alveolar concentration of desflurane and hemodynamic responses in neonates, infants, and children.

We sought to determine the minimum alveolar concentration (MAC) and hemodynamic responses to desflurane in 72 fasting and unpremedicated full-term neonates, infants, and children up to 12 yr of age. The patients were divided into six groups (n = 12) according to age. After awake tracheal intubation, neonates were anesthetized with desflurane in oxygen and air. Infants greater than 1 month of age and all older children were anesthetized with desflurane in 100% oxygen, and their tracheas were intubated without muscle relaxation. MAC was determined using the "up-and-down technique" and logistic regression. Heart rate and systolic arterial pressure were recorded awake, at approximately 1 MAC desflurane before skin incision and at approximately 1 MAC during the peak hemodynamic responses to skin incision. We found that the relationship between MAC (mean +/- standard deviation) as determined by the up-and-down technique and age was quadratic, reaching a maximum value in infants 6-12 months of age: in neonates 0-1 month MAC was 9.16 +/- 0.02%, in infants 1-6 months 9.42 +/- 0.06%, in infants 6-12 months 9.92 +/- 0.44%, in children 1-3 yr 8.72 +/- 0.59%, in children 3-5 yr 8.62 +/- 0.45%, and in children 5-12 yr 7.98 +/- 0.43%. MAC values obtained using logistic regression were similar. Heart rate decreased an average of 16% before skin incision in infants 6-12 months of age and children 1-3 and 3-5 yr of age when compared to awake values (P less than 0.025) but did not change significantly in the remaining three groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Novel noninvasive techniques for studying renal function in man

Renal artery stenosis is a major cause of renovascular hypertension in humans, and may lead to ischemic nephropathy and end-stage renal disease. The mechanisms responsible for the progressive renal functional and structural alterations have not been fully elucidated, partly because of the lack of reliable, noninvasive techniques capable of quantifying renal regional hemodynamics and function distal to a stenosis in the renal artery. Novel imaging tools now enable quantification of concurrent intrarenal (cortical and medullary) hemodynamics, segmental nephron dynamics (intratubular transit times and fluid concentrations), and renal function in the intact kidney. Fast computed tomography (CT) scanners, such as electron beam CT, allow discrimination of subtle alterations in renal perfusion and segmental nephron function consequent to changes in renal perfusion pressure, both within and below the range of renal blood flow autoregulation. This technique provides an opportunity to define intrarenal perfusion patterns and function in animals and patients with renal artery stenosis, and may provide insight into the effects of chronic unilateral or bilateral renovascular disease on both the hypoperfused and contralateral kidneys. This methodology may thereby prove to be very useful in the evaluation of renal disease in general, and the renovascular hypertensive patient in particular.     

Comparison of remifentanil versus regional anaesthesia in children anaesthetised with isoflurane/nitrous oxide. International Remifentanil Paediatric Anaesthesia Study group

We compared the efficacy and safety of a remifentanil (0.25 microg x kg(-1) x min(-1)-based balanced anaesthetic technique with a bupivacaine-based regional anaesthetic technique in an open label, multicentre study in 271 ASA physical status 1 or 2 children aged 1-12 years. Subjects requiring major intra-abdominal, urological or orthopaedic surgery were randomly allocated to receive either intravenous remifentanil (group R; n = 185) or epidural bupivacaine (group B; n = 86) with isoflurane/nitrous oxide for their anaesthesia. The majority of children in both groups (85% in group R, 78% in group B) showed no defined response to skin incision, and although the mean increase in systolic blood pressure (+11 mm Hg) was significantly greater in group R than in group B, this change did not represent a serious haemodynamic disturbance. More children in group R (31%) required interventions to treat hypotension and/or bradycardia than those in group B (12%), but these were easily managed by administration of fluids or anticholinergic drugs. Adverse events, mainly nausea and/or vomiting, occurred in 45% of group R and 42% of group B (NS). The adverse event profile of remifentanil in this study was typical of a potent mu-opioid receptor agonist. Remifentanil was as effective as epidural or caudal block in providing analgesia and suppressing physiological responses to surgical stimuli in children aged between 1 and 12 years undergoing major abdominal, urological, or orthopaedic surgery under isoflurane/nitrous oxide anaesthesia.     

Target RNA capture and cleavage by the Cmr type III-B CRISPR–Cas effector complex

The effector complex of the Cmr/type III-B CRISPR (clustered regularly interspaced short palindromic repeat)–Cas (CRISPR-associated) system cleaves RNAs recognized by the CRISPR RNA (crRNA) of the complex and includes six protein subunits of unknown functions. Using reconstituted Pyrococcus furiosus Cmr complexes, we found that each of the six Cmr proteins plays a critical role in either crRNA interaction or target RNA capture. Cmr2, Cmr3, Cmr4, and Cmr5 are all required for formation of a crRNA-containing complex detected by native gel electrophoresis, and the conserved 5′ repeat sequence tag and 5′-OH group of the crRNA are essential for the interaction. Interestingly, capture of the complementary target RNA additionally requires both Cmr1 and Cmr6. In detailed functional studies, we determined that P. furiosus Cmr complexes cleave target RNAs at 6-nucleotide (nt) intervals in the region of complementarity, beginning 5 nt downstream from the crRNA tag and continuing to within ∼14 nt of the 3′ end of the crRNA. Our findings indicate that Cmr3 recognizes the signature crRNA tag sequence (and depends on protein–protein interactions with Cmr2, Cmr4, and Cmr5), each Cmr4 subunit mediates a target RNA cleavage, and Cmr1 and Cmr6 mediate an essential interaction between the 3′ region of the crRNA and the target RNA.     

Resilience in families with a member with chronic pain: a mixed methods study

Aims and objective. To measure and explore between 2007–2010 measure and explore the nature of family resilience in the context of families with a member with chronic pain. Background. Chronic pain impacts on the entire family. The literature suggests that it is possible to strengthen resilience in individuals with chronic conditions, but little is known about the impact of chronic pain on family resilience. Design. A explanatory sequential mixed method study was undertaken. Methods. In the initial quantitative phase, assessment measures were administered using the Connor‐Davidson Resilience Scale, Family Impact of Pain Scale, Medical Outcomes Study Short Form 36 and Medical Outcomes Study Social Support Survey. Data were collected and analysed from 31 family cases (n = 67 participants). In the second, qualitative phase, follow‐up semi‐structured interviews were undertaken with 10 families to help explain the quantitative results. Results. The impact of pain on the family was high overall, but the perceived impact was greater for the person with pain. Resilience scores were above average for both the person with pain and other family members. However, the person with pain scored lower on the resilience scale than other members of the family. The families scored high for social support overall, while the person with pain perceived they had greater support than their family members. Conclusions. Identifying the strengths or resilient properties inherent in families and using those strengths in the planning and implementation of care, especially of chronic conditions such as chronic pain, is pivotal to quality health outcomes. Relevance to clinical practice.  It is important that nurses and healthcare professionals include family members when planning and delivering care for persons with chronic pain. Identification of strengths within families can help tailor nursing interventions to meet family needs.