Anesthesia and the developing brain: a way forward for clinical research

It is now well established that many general anesthetics have a variety of effects on the developing brain in animal models. In contrast, human cohort studies show mixed evidence for any association between neurobehavioural outcome and anesthesia exposure in early childhood. In spite of large volumes of research, it remains very unclear if the animal studies have any clinical relevance; or indeed how, or if, clinical practice needs to be altered. Answering these questions is of great importance given the huge numbers of young children exposed to general anesthetics. A recent meeting in Genoa brought together researchers and clinicians to map a path forward for future clinical studies. This paper describes these discussions and conclusions. It was agreed that there is a need for large, detailed, prospective, observational studies, and for carefully designed trials. It may be impossible to design or conduct a single study to completely exclude the possibility that anesthetics can, under certain circumstances, produce long‐term neurobehavioural changes in humans; however , observational studies will improve our understanding of which children are at greatest risk, and may also suggest potential underlying etiologies, and clinical trials will provide the strongest evidence to test the effectiveness of different strategies or anesthetic regimens with respect to better neurobehavioral outcome.     

A randomised controlled trial of the effectiveness of soft silicone multi‐layered foam dressings in the prevention of sacral and heel pressure ulcers in trauma and critically ill patients: the border trial

The prevention of hospital acquired pressure ulcers in critically ill patients remains a significant clinical challenge. The aim of this trial was to investigate the effectiveness of multi‐layered soft silicone foam dressings in preventing intensive care unit (ICU) pressure ulcers when applied in the emergency department to 440 trauma and critically ill patients. Intervention group patients (n = 219) had Mepilex^® Border Sacrum and Mepilex^® Heel dressings applied in the emergency department and maintained throughout their ICU stay. Results revealed that there were significantly fewer patients with pressure ulcers in the intervention group compared to the control group (5 versus 20, P = 0·001). This represented a 10% difference in incidence between the groups (3·1% versus 13·1%) and a number needed to treat of ten patients to prevent one pressure ulcer. Overall there were fewer sacral (2 versus 8, P = 0·05) and heel pressure ulcers (5 versus 19, P = 0·002) and pressure injuries overall (7 versus 27, P = 0·002) in interventions than in controls. The time to injury survival analysis indicated that intervention group patients had a hazard ratio of 0·19 (P = 0·002) compared to control group patients. We conclude that multi‐layered soft silicone foam dressings are effective in preventing pressure ulcers in critically ill patients when applied in the emergency department prior to ICU transfer.     

Role of substance P in suppressing growth hormone release in the rat.

To evaluate a possible physiological role of endogenous substance P (SP) in the control of growth hormone (GH; somatotropin) secretion, a specific antiserum against SP (anti-SP) was injected intraventricularly (3 microliters into the third cerebral ventricle) in unanesthetized unrestrained normal male rats. Control rats received an equivalent volume of normal rabbit serum (NRS). Intraventricular injection of the NRS lowered plasma GH concentrations significantly. The lowering was detected on first measurement at 10 min after injection and was maximal at 30 min. This was followed by a return toward the initial levels. Third ventricular injection of antiserum significantly increased plasma GH in comparison with control animals injected with NRS. The effect was observed within 10-20 min, and levels remained elevated for the 120-min duration of the experiment. To confirm the possible inhibitory role of endogenous SP on GH release, 3 microliters of 0.9% NaCl (saline) alone or saline containing a specific antagonist of SP, [D-Pro2,D-Trp7,9]SP, was injected into the third ventricle of normal male rats. The antagonist also increased plasma GH significantly (P less than 0.005) within 5 min compared with values in the saline-injected control group. Levels remained elevated for 30 min but had returned toward control values 60 min after injection. In contrast, synthetic SP significantly decreased plasma GH when injected intravenously or intraventricularly compared with plasma GH in the control saline-injected group. To investigate a possible direct action of SP on GH release from the anterior pituitary gland, we incubated synthetic SP with dispersed anterior pituitary cells for 1 hr. The release of GH from incubated anterior pituitary cells was not affected at any dose of SP (10(-9) to 10(-6) M) tested. These data strongly indicate that endogenous SP has a physiological inhibitory role in the control of GH secretion at the level of the hypothalamus in the male rat.     

Infection of donor lymphocytes with human T lymphotrophic virus type 1 (HTLV-I) following allogeneic bone marrow transplantation for HTLV-I positive adult T-cell leukaemia

Summary. Human T lymphotrophic virus type 1 (HTLV-I) associated leukaemia has a poor prognosis even with chemotherapy. We describe a patient with adult T-cell leukaemia treated with allogeneic bone marrow transplantation from an HTLV-I negative identical sibling donor. During follow-up after bone marrow transplantation, HTLV-I could be repeatedly isolated inspite of anti-viral prophylaxis. The patient died of an acute encephalitis and HTLV-I could be detected in autopsy material from the brain. By a PCR-based technique using short tandem repeats (STRs) it was shown that the patient's haemopoiesis was of donor origin. This shows the infection of donor cells in vivo by an aetiological agent which has been implicated in the leukaemogenic process for adult T-cell leukaemia.     

Deletion of tyrosine hydroxylase gene reveals functional interdependence of adrenocortical and chromaffin cell system in vivo

Catecholamines are produced in the medulla of the adrenal gland and may participate in the intraglandular regulation of its cortex. We analyzed the adrenal structure and function of albino tyrosine hydroxylase-null (TH-null) mice that are deficient in adrenal catecholamine production. Adrenal catecholamines were markedly reduced, and catecholamine histofluorescence was abrogated in 15-day-old TH-null mice. Chromaffin cell structure was strikingly altered at the ultrastructural level with a depletion of chromaffin vesicles and an increase in rough endoplasmic reticulum compared with wild-type mice. Remaining chromaffin vesicles lined up proximally to the cell membrane in preparation for exocytosis providing a "string-of-pearls" appearance. There was a 5-fold increase in the expression of proenkephalin mRNA (502.8 +/- 142% vs. 100 +/- 17.5%, P = 0.016) and a 2-fold increase in the expression of neuropeptide Y (213.4 +/- 41.2% vs. 100 +/- 59.9%, P = 0.014) in the TH-null animals as determined by quantitative TaqMan (Perkin-Elmer) PCR. Accordingly, immunofluorescence for met-enkephalin and neuropeptide tyrosine in these animals was strongly enhanced. The expression of phenylethanolamine N-methyl transferase and chromogranin B mRNA was similar in TH-null and wild-type mice. In TH-null mice, adrenocortical cells were characterized by an increase in liposomes and by tubular mitochondria with reduced internal membranes, suggesting a hypofunctional state of these steroid-producing cells. In accordance with these findings, plasma corticosterone levels were decreased. Plasma ACTH levels were not significantly different in TH-null mice. In conclusion, both the adrenomedullary and adrenocortical systems demonstrate structural and functional changes in catecholamine-deficient TH-null mice, underscoring the great importance of the functional interdependence of these systems in vivo.     

Early arterial stasis during resin-based yttrium-90 radioembolization: incidence and preliminary outcomes

Objectives

This study was conducted to determine the incidence of early stasis in radioembolization using resin yttrium-90 (Y-90) microspheres, to evaluate potential contributing factors, and to review initial imaging outcomes.

Methods

Patients in whom early stasis occurred were compared with those in whom complete delivery was achieved for tumour type and vascularity, tumour : normal liver ratio (T : N ratio) at technetium-99m-macroaggregated albumin (Tc-99m-MAA) angiography, previous intra-arterial therapy, and infusion site (left, right or whole liver). Tumour response was evaluated at 3 months and defined according to whether a partial response and stable disease versus progressive disease were demonstrated.

Results

A total of 71 patients underwent 128 Y-90 infusions in which 26 (20.3%) stasis events occurred. Hypervascular and hypovascular tumours had similar rates of stasis (17.4% versus 27.8%; P = NS). The mean ± standard deviation T : N ratio was 3.03 ± 1.54 and 3.66 ± 2.79 in patients with and without stasis, respectively (P = NS). Stasis occurred in 14 of 81 (17.3%) and 12 of 47 (25.5%) infusions following previous intra-arterial therapy and in therapy-naïve territories, respectively (P = NS). Early stasis occurred in 15 of 41 (36.6%) left, 10 of 65 (15.4%) right and one of 22 (4.5%) whole liver infusions (P < 0.001). Rates of partial response and stable disease were similar in the stasis (88.3%) and non-stasis (76.0%) groups (P = NS).

Conclusions

Early stasis occurred in approximately 20% of infusions with similar incidences in hyper-and hypovascular tumours. Whole-liver therapy reduced the incidence of stasis. Stasis did not appear to affect initial imaging outcomes.