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Biomedical subjects

A Whitelaw

Publications and source records attributed to A Whitelaw.

At least 55 records · Page 3Linked to original sources
PubMed1996

Endogenous tissue plasminogen activator in neonatal cerebrospinal fluid.

Tissue type plasminogen activator (tPA) plays a role in differentiation of neurones and activity-dependent structural changes in neurones. We hypothesised that tPA would also be present in CSF during fibrinolysis after intraventricular haemorrhage. We measured tPA antigen in CSF from 13 normal newborn infants and 14 infants with post-haemorrhagic ventricular dilatation (PHVD). tPA was undetectable or at the limit of detection (1 microgram/l) in normal CSF. The CSF tPA concentration ranged from 1.3 to 3.5 micrograms/l in the infants with PHVD. Serial tapping in one infant showed persistence of tPA in the CSF from 3 to 8 weeks of age. We conclude that endogenous tPA may be part of the physiological response to intraventricular haemorrhage or may be present as a result of passive diffusion into the CSF.

Cerebral Hemorrhage↗
PubMed1996

Phase I study of intraventricular recombinant tissue plasminogen activator for treatment of posthaemorrhagic hydrocephalus.

AIM: Phase I study to evaluate intraventricular fibrinolytic treatment with recombinant tissue plasminogen activator (tPA) as a method of clearing blood from the cerebrospinal fluid, and thus preventing permanent hydrocephalus. METHODS: Twenty two preterm infants, aged 7 to 26 days, with progressive posthaemorrhagic ventricular dilatation (ventricular width > 4 mm over 97th centile) received one to five intraventricular bolus injections of 1.0 mg or 0.5 mg tPA at intervals of one to seven days. RESULTS: The mean cerebrospinal fluid concentration of tPA 24 hours after 1 mg was 1860 micrograms/ml. The half life of tPA in cerebrospinal fluid was about 24 hours. Twenty one (95%) infants survived, 12 (55%) without shunt surgery. One infant had secondary intraventricular haemorrhage. CONCLUSION: Intraventricular tPA resulted in survival without a shunt for most of the infants, but with some risk. Failure may have been due to plasminogen deficiency, an inhibitor, or late intervention.

Cerebral Hemorrhage↗
PubMed1996

A piglet survival model of posthypoxic encephalopathy.

The aim of this study was to produce a neonatal piglet model which, avoiding vessel ligation, exposed the whole animal to hypoxia and produced dose-dependent clinical encephalopathy and neuropathologic damage similar to that seen after birth asphyxia. Twenty-three piglets were halothane-anesthetized. Hypoxia was induced in 19 piglets by reducing the fractional concentration of inspired oxygen (FiO2) to the maximum concentration at which the EEG amplitude was below 7 microV (low amplitude) for 17-55 min. There were transient increases in Fio2 to correct bradycardia and hypotension. Posthypoxia, the piglets were extubated when breathing was stable. Four were sham-treated controls. We aimed at 72-h survival; seven died prematurely due to posthypoxic complications. EEG and a videotaped itemized neurologic assessment were recorded regularly. We found that 95% of the animals showed neuropathologic damage. The duration of low amplitude EEG during the insult and the arterial pH at the end of the insult correlated with cortical/white matter damage; r = 0.75 and 0.81, respectively. Early postinsult EEG background amplitude (r = 0.86 at 3 h) and neurologic score (r = 0.79 at 8 h) correlated with neuropathology. Epileptic seizures in seven animals were always associated with severe neuropathologic damage. We conclude that EEG-controlled hypoxia and subsequent intensive care enabled the animals to survive with an encephalopathy which correlated with the cerebral hypoxic insult. The encephalopathy was clinically, electrophysiologically, and neuropathologically similar to that in the asphyxiated term infant. This model is suitable for examining mechanisms of damage and evaluation of potential protective therapies after birth asphyxia.

Animals↗
PubMed1996

Controversies: synthetic or natural surfactant treatment for respiratory distress syndrome? The case for synthetic surfactant.

The choice of surfactant for prophylactic or "rescue" treatment of RDS is dependent on a number of different considerations: a) Randomised controlled trials have shown that natural and synthetic surfactants increase survival whether used prophylactically or as rescue. No statistically significant difference in mortality has been shown when the two types of surfactant have been compared in randomised trials. b) Possible adverse effects of surfactant treatment include: (i) Intraventricular haemorrhage (IVH). Two randomised trials of natural surfactant have shown a significant increase in IVH with natural surfactant treatment. In meta-analyses, IVH has not been significantly reduced despite decreased mortality. Acute changes in cerebral haemodynamics and EEG have been demonstrated following natural surfactant administration. These changes are less marked or absent with synthetic surfactant. (ii) The antigenicity of animal surfactant has not been shown to have clinical consequences. (iii) Prions are infectious particle (resistant to some sterilising techniques) which are responsible for slow encephalopathies, some of which have crossed species barriers. Contamination of bovine surfactant with prion particles from nervous tissue has been a theoretical concern. Synthetic surfactant has no risk of prion contamination. (iv) One natural surfactant has been shown to contain platelet activating factor (PAF). Synthetic surfactants can be made with greater chemical purity. c) Natural surfactants improve oxygenation faster than do synthetic surfactants. A rapid effect is not necessarily better with respect to later outcomes. d) Synthetic surfactant preparations are generally cheaper per dose than natural surfactant preparations. Synthetic surfactant treatment increases survival with less concern about adverse effects and generally lower cost per dose than natural surfactant.

Cerebrovascular Circulation↗
PubMed1995

Low levels of plasminogen in cerebrospinal fluid after intraventricular haemorrhage: a limiting factor for clot lysis?

The aim of this study was to measure plasminogen in the cerebrospinal fluid (CSF) of control neonates with no infection or haemorrhage and in infants who had suffered intraventricular haemorrhage (IVH). A chromogenic substrate method was used. The 16 reference infants had a median CSF plasminogen level of 0.74% of that of normal adult plasma (range 0.17-1.1%). The 11 infants with IVH had a median CSF plasminogen level of 0.55% of normal adult plasma (range 0-4.4%). Six of the IVH infants went on to develop permanent hydrocephalus despite the use of intraventricular plasminogen activators. Endogenous fibrinolysis and the potential for fibrinolytic treatment in the CSF may be limited by low concentrations of plasminogen, and administration of recombinant plasminogen may assist attempts to clear intraventricular blood clots.

Adult↗
PubMed1995

Acute effects of two different doses of magnesium sulphate in infants with birth asphyxia.

The effects of two different doses of magnesium sulphate (MgSO4) were evaluated in a group of 15 full term infants with Apgar scores of < 6 at 10 minutes, studied within 12 hours of delivery. Seven infants received 400 mg/kg MgSO4 and eight received 250 mg/kg. After the larger dose, mean arterial pressure (MAP) fell by a mean of 6 mm Hg (13%) at one hour but was not significantly reduced thereafter. Respiratory depression lasted three to six hours. EEG readings and heart rate were not significantly different. Mean serum Mg2+ increased from 0.79 to 3.6 mmol/l at one hour. After 250 mg/kg MgSO4, MAP, EEG, tone and heart rate were unchanged. One infant developed transient respiratory depression. Mean serum Mg2+ rose from 0.71 to 2.42 mmol/l at one hour. MgSO4 (400 mg/kg) has an unacceptable risk of hypotension; 250 mg/kg MgSO4 was not associated with hypotension although respiratory depression can occur.

Asphyxia Neonatorum↗
PubMed1994

[Retinopathy of prematurity. Cryotherapy can reduce the risk of severe visual impairment].

Retinopathy of prematurity is a main cause of severe visual impairment and blindness in infancy. It is reported that the incidence is increasing along with the growing survival of infants with an extremely short gestation period. Transscleral cryotherapy has been shown to be effective in arresting the progression of the disease into the sight-threatening fibrovascular stages. A structured screening programme starting four to six weeks after birth for infants with less than 31 weeks of gestation is needed to identify the relatively few prematurely born infants for whom this treatment is indicated.

Cryotherapy↗
PubMed1994

Relating health education research to health policy.

This paper argues that research in health education is being driven by a set of implicit values that emphasize formality, rigor and objectivity, and that relatively little attention is being paid to the ways in which research findings are subsequently used. A critique of a detached and formal research perspective is developed around the problems of 'pure' knowledge and the potential incompatibility between this and policy-making processes. In this light, it is suggested that the pursuit of academic research rigor at the expense of practical utility is hindering the development of a stronger research-policy link. The paper then goes on to suggest that in adopting a sharper political orientation, health education research could legitimately become less concerned with the restrictive nature of academic formalism with research. The nature of this type of research, the potential it has as well as its limitations are subsequently explored.

Health Education↗
PubMed1994

Intraventricular streptokinase increases cerebrospinal fluid D dimer in preterm infants with posthaemorrhagic ventricular dilatation.

Failure to lyse multiple small blood clots in the cerebrospinal fluid (CSF) reabsorption pathways may be one of the mechanisms leading to posthaemorrhagic ventricular dilatation (PHVD). It has been suggested that intraventricular administration of streptokinase may resolve PHVD but it is not known whether such treatment produces an increase in fibrin degradation products in the CSF. Ventricular CSF was collected from six infants with PHVD before and during intraventricular treatment with streptokinase 1000 units/h. In all six infants, CSF D dimer increased during streptokinase treatment. Median D dimer before treatment was 1642 micrograms/l and during treatment 5440 micrograms/l (p < 0.05). Undetectable D dimer levels in plasma during streptokinase treatment ruled out the possibility that D dimer had merely diffused into the CSF. This augmentation of local fibrinolysis may have therapeutic potential. There was no evidence of systemic fibrinolysis.

Cerebral Hemorrhage↗
PubMed1993

Endogenous fibrinolysis in neonatal cerebrospinal fluid.

Although many infants with intraventricular haemorrhage (IVH) recover without hydrocephalus, little is known about how blood is cleared from the CSF pathways. Fibrinolytic activity was measured by the fibrin plate method in CSF from 11 normal infants and 17 infants with IVH. Normal CSF showed no fibrinolytic activity. All the samples taken less than 17 days from diagnosis of IVH failed to show fibrinolytic activity. All but 1 of the CSF samples taken between 17 and 60 days of IVH showed fibrinolytic activity. In 1 infant where 14 serial samples were taken, there was no detectable fibrinolysis up to 16 days after IVH but from 19 to 52 days there was definite fibrinolytic activity. Delayed endogenous fibrinolysis in the CSF is common after IVH but may, in some cases, be insufficient to prevent hydrocephalus.

Cerebral Hemorrhage↗
PubMed1993

Erythropoietin, protein, and iron supplementation and the prevention of anaemia of prematurity.

The effectiveness of recombinant human erythropoietin (r-HuEpo) in raising haemoglobin concentrations in very low birthweight infants was examined in a randomised multicentre study. Twenty nine 'healthy' appropriate for gestational age infants with birth weights 900-1400 g entered the study at 3 weeks of age. All infants received breast milk supplemented with 9 g/l human breast milk protein from 3 to 8 weeks of age. Eighteen mg iron was given daily from week 3 and was doubled if serum iron concentration fell below 16.0 mumol/l. Fourteen infants were randomised to receive 100 U/kg r-HuEpo subcutaneously three times a week from week 3 to week 7; 15 infants served as controls. After one week reticulocyte and haemoglobin concentrations were significantly higher in the r-HuEpo treated group and the haemoglobin values remained significantly higher throughout r-HuEpo treatment and at the concentrations observed in full term infants. No adverse effects were associated with the treatment. In stable very low birthweight infants with optimal iron and protein intakes, moderate dose r-HuEpo can produce significant gains in red cell production that may be clinically useful.

Anemia, Neonatal↗
PubMed1992

Low dose intraventricular fibrinolytic treatment to prevent posthaemorrhagic hydrocephalus.

Posthaemorrhagic ventricular dilatation (PHVD) is thought to be due to clots from intraventricular haemorrhage obstructing cerebrospinal fluid pathways involved in reabsorption. Over 60% of infants with progressive PHVD have gone on to require surgical shunt placement. Previous treatments all have major problems. The object of this pilot study was to achieve enough fibrinolysis to restore pathways of cerebrospinal fluid reabsorption and so avoid shunt surgery. Nine preterm infants with progressive PHVD were treated with intraventricular infusion of streptokinase for 12-72 hours. All the infants survived and surgical shunting was required in only one case. A 200% increase in fibrinolytic activity was demonstrated in both ventricular and spinal fluid during streptokinase treatment. There were no cases of infection. Minor rebleeding occurred in one case and was not a serious problem. This represents the first direct therapeutic approach to the pathology of PHVD.

Cerebral Hemorrhage↗
PubMed1991

Acute effects of acetazolamide on cerebral blood flow velocity and pCO2 in the newborn infant.

Twelve infants with hydrocephalus were treated with acetazolamide. In those treated intravenously middle cerebral artery blood flow velocity increased by a median of 86% (range 54-150%). Maximum increase was reached within 2-20 min. The effect lasted as long as 3.5 hours. Intracranial pressure rose by a median of 4 mmHg (range 0-10 mmHg). There was no significant alteration in blood pressure or heart rate. Respiratory rate increased by approximately 10 breaths/min and the tcpCO2 rose by a median 0.2 kPa in infants with normal lungs. In infants treated orally, blood velocity rose by 35-40% at 60-80 min with no increase in intracranial pressure. In four infants with lung disease pCO2 rose by a median of 2.0 kPa (range 0.6 to 3.4 kPa). Acetazolamide was well tolerated in infants with normal lungs but should be used with caution in the presence of lung disease.

Acetazolamide↗
PubMed1991

Cerebral blood flow velocity changes after rapid administration of surfactant.

A computer linked Doppler system was used to make continuous measurements of cerebral blood flow velocity (CBFV) from the middle cerebral artery, mean arterial blood pressure (MAP) from the umbilical artery, and heart rate before, during, and for 20 minutes after the endotracheal administration of 200 mg/kg of porcine surfactant in 10 preterm infants with respiratory distress syndrome. Within two minutes of surfactant administration, there was a median fall of 6 mm Hg (15%) fall in MAP and 36% in CBFV. There was a change in the Doppler spectra with almost complete loss of diastolic velocities. A rapid reduction in pulmonary vascular resistance with consequent left to right ductal shunting is one possible cause. These acute changes in MAP and CBFV after bolus surfactant administration may increase the risk of intraventricular haemorrhage.

Blood Flow Velocity↗
PubMed1991

Hypocapnia and cerebral ischaemia in hypotensive newborn piglets.

This study tested the hypothesis that hypocapnia superimposed upon hypotension produces a further reduction in cerebral blood flow velocity (CBFV). In 12 newborn piglets, CBFV was measured continuously by Doppler ultrasound through an artificial fontanelle. Hypotension was induced by removing 30 ml/kg of blood. Increasing the ventilator rate reduced the average arterial carbon dioxide tension from 5.5 to 2.0 kPa. When mean arterial pressure (MAP) was held steady at 45 mm Hg or above, hypocapnia produced a substantial drop in CBFV but, in all the piglets with MAP below 38 mm Hg, hypocapnia failed to change CBFV by 10%. Hypocapnia produced an increase in lactate in sagittal sinus blood but cerebral venous hypoxanthine concentrations were not affected by hypocapnia. Hyperventilation (without haemorrhage) produced a significant drop in MAP, preventable by infusing colloid. Hypocapnia itself does not further reduce CBFV in the hypotensive piglet. However, the pressure effect of hyperventilation may significantly impair the cerebral circulation.

Animals↗