The behaviour of neurokinin-1-receptor gene knockout (NK1R-/-) mice, which lack functional, substance P-preferring receptors, resembles that of NK1R+/+ mice treated with an antidepressant. Because all antidepressants increase central monoamine transmission, we have investigated whether noradrenergic transmission is increased in NK1R-/- mice and, if so, whether this could influence their behaviour. In anaesthetized subjects, the concentration of extracellular noradrenaline in NK1R-/- mice was two-fourfold greater than in NK1R+/+ mice. Systemic administration of the alpha2-adrenoceptor antagonist, 2-(2,3-dihydro-2-methoxy-1,4-benzodioxan-2-yl)-4,5-dihydro-1H-imidazoline (RX 821002), in anaesthetized or freely moving animals increased extracellular noradrenaline in NK1R+/+ mice only. This suggests that the function of alpha2a-autoreceptors, which modulate noradrenergic transmission, is impaired in NK1R-/- mice. Consistent with this, [35S]GTPgammaS binding to activated alpha2a-adrenoceptors was lower (-70%) in the locus coeruleus, but not the frontal cortex, of NK1R-/- mice compared with their NK1R+/+ counterparts. RX 821002-pretreatment, followed by retrodialysis of the noradrenaline reuptake inhibitor, desipramine, into the frontal cortex of anaesthetized mice increased extracellular noradrenaline to the same extent in the two genotypes. Western blots confirmed that there was no difference in the amount of noradrenaline transporter protein in NK1R-/- and NK1R+/+ mice. Finally, the effects of RX 821002 on certain behaviours in a light/dark exploration box were blunted in NK1R-/- mice, but there was no consistent effect on anxiety-like behaviour in the two genotypes. It is concluded that the greater basal efflux of noradrenaline in NK1R-/- mice is explained by increased transmitter release, coupled with desensitization of somatodendritic alpha2a-adrenoceptors. These changes could contribute to the difference in the behavioural phenotypes.
Research in smoke inhalation has established that free radicals are produced from gases released during combustion and these species impair lung function. Using spin traps and their adducts in an animal model free radicals were measured. Various hyperbaric oxygen regimens were tested in an attempt to attenuate pulmonary damage caused by free radical reactions. Our data demonstrated that persistent oxygen- and carbon-centered free radicals are detectable in intravascular fluids after smoke inhalation. The smoke inhalation model showed however, clearing of spin trap adducts one hour after smoke exposure. Other researchers have found that when 100% oxygen is given at 1 atmosphere absolute (ATA) for 1 h, free radicals were not detectable. However, oxygen given at 2.5 ATA does produce detectable free radicals. With continued exposure at this pressure, the levels of free radicals increase for up to 60 min. This study suggests that the level of free radical induced oxygen toxicity may be a function of oxygen pressure and duration of oxygen exposure.
Amyoplasia is the most common form of arthrogryposis (multiple congenital contractures) and of unknown etiology. It seems to occur in discordant monozygotic twins. The coexistence of other lesions resulting from vascular disruption in fetal life would tend to support a common etiology. Case reportThe patient was the second of twins born at term with a birthweight of 2.05 kg to a 23-year-old primigravida. Antenatal scans at 26 wk showed dilated loops of bowel and also flexion deformities of the lower limbs. Apgar scores were 9 at 1 min and 10 at 5 min. Abnormalities immediately evident were abdominal distension and flexion deformities with contractures of the lower limbs at the hips and knees and characteristic positioning of the upper limbs (Figs 1, 2). Abdominal X-rays showed a picture consistent with intestinal obstruction. At laparotomy, there were seven atresias in the jejunum and ileum (two of these were in continuity with a membrane and one an apple-peel atresia in the terminal ileum) in association with malrotation. Twelve centimetres of dilated jejunum proximal to the first atresia was resected and a total of five anastomoses were performed. A Ladd's procedure was performed for the malrotation with an appendicectomy. The total small bowel length remaining at the end of the operation was 86 cm. She was ventilated for a period of 48 h after birth. Parenteral nutrition was used for 20 d, after which enteral feeds were commenced. She developed conjugated hyperbilirubinaemia in the 2nd week after the operation. Following extensive investigations this appeared to be secondary to TPN cholestasis; bilirubin levels gradually returned to normal.Mobilization of the limbs was started soon after birth, focusing on the flexion deformities of both hips and knees and equinovarus deformities of both feet. There were no fixed deformities in the upper limbs but the left shoulder was held in internal rotation.Magnetic resonance imaging (MRI) of the brain and spinal cord showed signal changes of ischaemia of the brain and atrophy of the upper thoracic cord. MRI of the pelvis and lower limbs showed striking muscle atrophy throughout the pelvis and both lower limbs involving all muscle groups. Erector spinae, psoas and the levators appeared relatively well preserved. Iliacus and obturator internus were grossly atrophic. Both hips were located in the joints. Release of her hip contractures was done at 10 mo of age.Follow-up at 11 mo showed her to be developmentally normal, though her weight and head circumference remain below the 0.4 centile.
Aim Distal radius (DR) fractures are among the commonest fractures seen by orthopaedics. The management of these fractures is dependent on the stability of the fracture, and conservative management is usually favoured for stable fractures. Mobilisation of the wrist following this stable fracture is necessary to avoid the risks of wrist stiffness, complex regional pain syndrome and limitation of function. According to BOAST guidelines for management of DR fractures: patients with a stable fracture should be considered for early mobilisation with a removable support once pain allows. The aim of this study was to determine our unit's adherence to guidelines and review the period of immobilisation of stable DR fractures. Method Retrospective analysis of virtual fracture clinic referrals, ED and clinic notes, imaging and any further correspondence of patients referred to our orthopaedic team between 1/2/20–30/7/20 with isolated DR fracture. Results Of 163 patients referred with DR fracture, 49.7% were deemed to have a stable fracture. Of these patients, only 37% were mobilised early, with the remainder fully immobilised for 6 weeks without active mobilisation protocol. Conclusions A large proportion of patients with stable fractures are not being managed in accordance with BOAST guidelines, therefore a standardised intervention is needed to ensure patients regain maximum possible function. We propose that a new protocol is put in place to screen all DR fractures within our virtual fracture clinic into stable v. unstable pattern and if deemed stable to ensure patient is seen for early physiotherapy face to face or virtually.
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