Parkinson's disease (PD) is characterized by movement disorders, including bradykinesia. Analysis of inherited, juvenile PD, identified several genes linked via a common pathway to mitochondrial dysfunction. In this study, we demonstrate that the larva of the Drosophila parkin mutant faithfully models the locomotory and metabolic defects of PD and is an excellent system for investigating their inter-relationship. parkin larvae displayed a marked bradykinesia that was caused by a reduction in both the frequency of peristalsis and speed of muscle contractions. Rescue experiments confirmed that this phenotype was due to a defect in the nervous system and not in the muscle. Furthermore, recordings of motoneuron activity in parkin larvae revealed reduced bursting and a striking reduction in evoked and miniature excitatory junction potentials, suggesting a neuronal deficit. This was supported by our observations in parkin larvae that the resting potential was depolarized, oxygen consumption and ATP concentration were drastically reduced while lactate was increased. These findings suggest that neuronal mitochondrial respiration is severely compromised and there is a compensatory switch to glycolysis for energy production.parkin mutants also possessed overgrown neuromuscular synapses, indicative of oxidative stress, which could be rescued by overexpression of parkin or scavengers of reactive oxygen species (ROS). Surprisingly, scavengers of ROS did not rescue the resting membrane potential and locomotory phenotypes. We therefore propose that mitochondrial dysfunction in parkin mutants induces Parkinsonian bradykinesia via a neuronal energy deficit and resulting synaptic failure, rather than as a consequence of downstream oxidative stress.

The aim of this study was to compare the efficacy of two inotropic infusions in treating low BP in preterm neonates. Forty infants with median gestational age 27 weeks (range 23-33) were studied. At trial entry the infants, who all had a systolic BP < 40 mmHg despite receiving a colloid infusion, were randomized to receive either a dopamine or dobutamine infusion. The infusions were commenced at a rate of 5 micrograms/kg per min and, if necessary, this was increased over the 3 h study period to 15 micrograms/kg per min. There was no significant difference in the gestational or postnatal age or baseline BP of the 20 infants who received dopamine and those 20 who received dobutamine. Three hours after commencing the infusions, although there was no difference in the rate of inotrope infusion between the two groups, the infants who received dopamine had a significantly higher systolic BP, a median of 39 mmHg (range 30-58) compared to a median of 34 mmHg (range 21-46) in the dobutamine group, P < 0.05. In addition, 10 infants who received dopamine, but only 3 who received dobutamine, had a systolic BP > 40 mmHg (P < 0.05). We conclude that dopamine rather than dobutamine infusion is more efficacious in improving the BP of preterm neonates.

Colloid infusions are often given to treat hypotension in preterm infants. The aim of this work was to assess whether it was the amount of protein or the volume of the colloid infused which accounted for the observed increase in blood pressure. Sixty preterm infants were randomised (20 in each group) to receive 5 ml/kg 20% albumin, 15 ml/kg fresh frozen plasma, or 15 mI/kg 4 5% albumin. All infusions were given at a rate of 5 ml/kg/hour in addition to maintenance fluids. The infants were randomised when hypotensive (systolic blood pressure less than 40 mm Hg for two hours). There was no significant difference in the blood pressure of the three groups before or one hour after beginning the infusion. The mean increase in blood pressure one hour after completing the infusion, however, was significantly lower in infants receiving 20% albumin: 9% compared with 17% in the group receiving 4-5% albumin, and 19% in the group receiving fresh frozen plasma. It is concluded that the volume infused rather than albumin load is important in producing a sustained increase in blood pressure. (Arch Dis Child 1992,67:1185 Colloid infusions are often used to treat hypotension in sick preterm infants. This hypotension may result from hypovolaemia due to fluid losses via the kidney and skin and increased leakage from capillaries in the lungs, or from myocardial depression due to asphyxia or hypoxia and resulting poor cardiac output. In the latter instance it seems preferable to avoid a large fluid load, but there are no data available to assess whether the improvement in blood pressure is the result of the protein or of the volume load infused. The aim of this study, therefore, was to compare the effects of colloid infusions of different volumes and protein content on blood pressure levels in hypotensive preterm infants and thus to determine the most efficacious type of colloid infusion. load. They were randomised by drawing a sealed envelope which instructed that they should receive one of three treatments: 5 ml/kg 20% albumin (200 g/l albumin-that is, 1 g/kg of albumin), or 15 ml/kg fresh frozen plasma (total protein 80 g/l, albumin 50 g/lthat is, 2 g/kg of protein or 0 75 g/kg of albumin), or 15 ml/kg 4 5% albumin (45 g/l albumin-that is, 0-675 g/kg of albumin). All infusions were given at a rate of 5 ml/kg/hour in addition to maintenance fluids. Thus the 20% albumin infusion was completed in one hour, but the other two infusions only after three hours. Systolic blood pressure was measured one hour after beginning the infusion and one hour after completing the infusion, and also four hours after beginning the infusions (that is, one hour after completing fresh frozen plasma and 4 5% albumin infusion, but three hours after completing the 20% albumin infusion).Systolic blood pressure was measured either from an indwelling arterial catheter sited for clinical purposes or using a non-invasive Doppler method. All blood pressure measurements were made with the infant in the supine position. Measurements were not made if the infa...

We assessed the effect of albumin infusion on weight loss and ventilation requirement in sick premature infants. Thirty infants, median gestational age 29 weeks, were entered into a randomised controlled trial, at a median of 2 days of age. The infants, all with an albumin level < or = 30 g/l, received either 5 ml/kg of 20% albumin or 5 ml/kg of their maintenance fluids (placebo), both given as part of the total daily fluid requirement. The response to the infusion was assessed by comparing two periods; 12 h immediately prior to the infusion and 12-24 h after the infusion. Albumin infusion was associated with a significant increase in albumin level and a significant reduction in weight, but in the placebo group there was a significant increase in weight. There were, however, no significant changes in the peak inspiratory pressure in response to either infusion. There was only a modest reduction (< 15%) in the inspired oxygen concentration, which occurred in both groups, but reached statistical significance only following the albumin infusion. We conclude that our results suggest that albumin infusion in "hypoalbuminaemic" sick preterm infants is unlikely to alter their respiratory status.

It is essential to have regular, accurate blood pressure (BP) monitoring of sick preterm infants. Invasive direct arterial BP measurements are often recommended, but it was our clinical experience that such measurements may not be possible in all infants. We therefore assessed the proportion of infants receiving neonatal intensive care in whom reliable arterial BP measurements could be made, the accuracy of a non-invasive method (Doppler technique) and established a reference range of BP results related to postnatal age using this non-invasive technique. Arterial catheters were established in 44 infants (study population) of the 45 in whom access was attempted. Median gestational age was 27 weeks and birth weight 949 g. Over the 1st week, however, arterial catheters had to be removed because of complications or improving respiratory status. From those catheters that remained in situ, accurate measurements were not always possible because of damping; by day 7 only 22 catheters remained in situ and 14% of the arterial waveforms were damped. Doppler systolic BP measurements correlated well with the accurate (non-damped) arterial results (r = 0.96, P less than 0.01). Systolic blood pressure was measured on all 44 infants daily for the 1st week using the Doppler technique and increased linearly with increasing postnatal age (r = 0.92, P less than 0.01) from a mean of 41.7 mmHg on day 1 to 49.3 on day 7. We conclude that Doppler non-invasive BP monitoring is a useful method for regular monitoring of sick preterm neonates as it can be applied accurately, unlike direct arterial monitoring, to all patients.