Unusual absence of endothelium-dependent or -independent vasodilatation to purines or pyrimidines in the rat renal artery

BACKGROUND: Adenosine triphosphate (ATP) is a cotransmitter with noradrenaline (NA) in sympathetic perivascular nerves. It has a dual role in the maintenance of vascular tone as ATP, released from endothelial cells during shear stress or hypoxia, induces vasodilatation via endothelial P2Y receptors or by direct action on smooth muscle. The role and distribution of P2 receptors is well characterized for many blood vessels but not for the rat renal artery. This study aims to determine whether ATP is a vasoconstrictor cotransmitter with NA and whether ATP induces vasodilatation via the endothelium or smooth muscle. METHODS: On isolated rat renal arteries, electrical field stimulation (EFS) in the absence and presence of antagonists to P2X receptors and alpha1-adrenoceptors was examined. Concentration-response curves were constructed to NA, ATP, alpha,beta-methylene ATP (alpha,beta-meATP), uridine triphosphate (UTP), and 2-methylthio ADP (2-MeSADP) on low tone. Curves to acetylcholine (ACh), 2-MeSADP, and UTP were constructed on raised tone. Immunofluorescent localization of P2X and P2Y receptor subtypes was performed. RESULTS: Electrical field stimulation induced vasoconstriction, partially inhibited by the P2X receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, and predominantly by prazosin. Exogenous NA and ATP mimicked EFS; immunostaining for P2X1 and P2X2 receptors was expressed on vascular smooth muscle. Unusually, ATP, 2-MeSADP, and UTP failed to induce vasodilatation. Acetylcholine induced vasodilatation. alpha,beta-meATP, 2-MeSADP, and UTP induced vasoconstriction via P2X1, P2Y1, and P2Y2 receptors, respectively. Immunostaining for P2X1, P2Y1, and P2Y2 receptors was expressed on the vascular smooth muscle. CONCLUSION: Adenosine triphosphate and NA are cotransmitters in sympathetic nerves supplying the rat renal artery, NA being the dominant partner. The novel feature of this vessel is that purines and pyrimidines do not produce either endothelium-dependent or -independent vasodilatation; P2X1, P2Y1, and P2Y2 receptors on the smooth muscle all mediate vasoconstriction.     

Laparoscopically supervised PEG at time of Nissen fundoplication: a safe option

BACKGROUND/PURPOSE: Children with gastroesophageal reflux disease (GERD) often have associated feeding difficulties that warrant the insertion of a feeding gastrostomy at the time of the antireflux procedure. Options for gastrostomy tube insertion at the time of laparoscopic Nissen fundoplication (LNF) include laparoscopic gastrostomy, percutaneous endoscopic gastrostomy (PEG), and classic open gastrostomy. The complication rate of PEG may be decreased if it is placed under laparoscopic supervision. The purpose of this paper is to describe our experience with laparoscopically supervised PEG tube placement at the time of antireflux procedure. METHODS: A retrospective chart review was conducted on all children undergoing a PEG tube placement at the time of the LNF. Perioperative complications were recorded. RESULTS: Forty-four patients had attempted PEG tube placement at the time of the LNF. In 3 (7%) cases, laparoscopic supervision was crucial in the prevention of a complication. No major PEG-related complications were recorded. In 43% of patients, minor PEG tube problems arose in the postoperative period: all were transient and/or easily correctable. Management of all these problems was in an outpatient setting. Follow-up ranged from 11 to 41 months. CONCLUSIONS: PEG tube placement at the time of a LNF is safe and effective. A combined laparoscopic and endoscopic approach minimizes complications. This method also allows for an intra- and extraluminal evaluation of the fundoplication at its completion.     

Consensus guidelines for sustained neuromuscular blockade in critically ill children

BACKGROUND: The United Kingdom Paediatric Intensive Care Society Sedation, Analgesia and Neuromuscular Blockade Working Group is a multidisciplinary expert panel created to produce consensus guidelines on sedation, analgesia and neuromuscular blockade in critically ill children and forward knowledge in these areas. Neuromuscular blockade is recognized as an important element in the care of the critically ill and adult clinical practice guidelines in this area have been available for several years. However, similar clinical practice guidelines have not previously been produced for the critically ill pediatric patient. METHODS: A modified Delphi technique was employed to allow the Working Group to anonymously consider draft recommendations in up to three Delphi rounds with predetermined levels of agreement. This process was supported by a total of four consensus conferences and once consensus had been achieved, a systematic review of the available literature was carried out. RESULTS: A set of consensus guidelines was produced including six key recommendations. An evaluation of the existing literature supporting these recommendations is provided. CONCLUSIONS: Multidisciplinary consensus guidelines for maintenance neuromuscular blockade in critically ill children (excluding neonates) have been successfully produced and are supported by levels of evidence. The Working Group has highlighted the paucity of high quality evidence in these important clinical areas and this emphasizes the need for further randomized clinical trials in this area.     

Kinematic and temporal interactions of the lumbar spine and hip during trunk extension in healthy male subjects

Kinematic properties of trunk extension are considered sensitive differentiators of movement between asymptomatic and low back pain subjects. The aim of this study was to quantify the continuous interaction of the hip and lumbar spine kinematics and temporal characteristics as a function of direction during the task of trunk bending backwards and returning to the upright position in healthy young subjects. The sagittal hip and lumbar spine kinematics during the extension task were examined in 18 healthy male subjects. Five trials of trunk extension were recorded for each subject and paired t-tests were then used to determine significant differences (P < 0.05) between the mean lumbar and the hip time-normalized kinematic and temporal variables. The data from the full cycle of trunk extension was analyzed with respect to movement initiation, time to reach peak velocity and peak angular displacement during the full cycle of trunk extension. Three distinct phases of movements were identified based on the continuous movement trajectories of velocity and angular displacement in the lumbar spine and hip; that of extension, return and, a terminal overcorrection phase. There were significant differences identified in the respective mean peak angular velocities of the lumbar spine (21.7 +/- 8.6, 37.0 +/- 14.7, 8.3 +/- 5.0 deg/s) when compared with those of hip (14.6 +/- 6.1, 21.7 +/- 8.5, 5.4 +/- 3.5 deg/s) in each of these three phases. The lumbar spine initiated the movement of trunk extension when bending backwards and returning to the upright position significantly early than that of the hip. These results highlight that in normal healthy adults there is the tendency for the lumbar spine to dominate over the hip during the task of backward trunk bending in terms of the amount and velocity of movement. At the end of extension the kinematics of the lumbar spine and hip kinematic are characterized by a terminal overcorrection phase marking the completion of the movement.     

Human myoblast engraftment is improved in laminin-enriched microenvironment

BACKGROUND: One major challenge in developing cell therapy for muscle diseases is to define the best condition for the recipient's muscle to niche donor cells. We have examined the efficiency of human myoblast transplantation in an immunodeficient animal model, after local irradiation, as well as the potential impact of laminin on myoblast behavior. METHODS: Human myoblasts were injected into preirradiated tibialis anterior muscles from immunodeficient mice. The donor cell engraftment, proliferation, and laminin content within the transplanted muscles were evaluated by immunocytochemistry. Additionally, the effect of laminin upon myoblast proliferation, migration, and survival was ascertained in vitro. RESULTS: Engraftment of human myoblasts into the skeletal muscle of immunodeficient Rag2-/gammac-/C5- mice presubjected to local irradiation provided the best niche for myoblast engraftment, as demonstrated by the number of viable and proliferating donor cells found in the host muscle. Local irradiation significantly enhanced laminin deposition within the recipient's muscle and donor cells were preferentially located in laminin-enriched areas. The same batch of myoblasts used for in vivo injections also responded to laminin in vitro with increased proliferation and cell survival, as well as an improved migratory response. CONCLUSIONS: We show that local irradiation enhances the laminin content in the host muscle microenvironment and provides a better engraftment of human myoblasts. In addition, laminin increases myoblast proliferation, survival, and migration in vitro. These data provide combined in vivo and in vitro evidence that laminin status should be taken into account when designing experimental and clinical cell therapy strategies for muscle disease.     

Late diagnosis of ectodermal dysplasia syndrome

This case study reports the clinical, skin biopsy and molecular findings in a 56‐year‐old Filipino man with the autosomal recessive ectodermal dysplasia disorder, Schöpf‐Schulz‐Passarge syndrome, the precise nature of which was established only after reading of a similar case in this journal. In addition to the late diagnosis, successful clinical management of his acral hyperkeratosis and ulceration has been difficult, with oral retinoids exacerbating the skin fragility.     

Red-cell GSH regeneration and glutathione reductase activity in G6PD variants in the Ferrara area

Summary. Red-cell studies were carried out on three groups of G6PD-deficient subjects with different G6PD variants from the Ferrara area of Northern Italy. Red-cell GSH and activities of G6PD, glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were measured. A method was developed to measure red-cell GSH regeneration after oxidation of endogenous GSH in whole blood by diamide and only this clearly distinguished the variants from each other and from normal. Regeneration by 1 h was lowest in the Mediterranean variant, 0–10.2% in contrast to 93–98% in normal. A predisposition to a haemolytic crisis after ingestion of fava beans was not clearcut, but subjects appeared to be at risk if GSH regeneration at 1 h was less than 30% of the endogenous level, and red-cell FAD⁺ was very high indicated by high in vitro GR activity and inhibition by added FAD⁺.
It is suggested that the most informative tests in G6PD deficiency are measurements of GSH regeneration in intact red cells plus GR activity and/or red-cell flavin compounds.