Intrinsic spinal cord lesions complicating epidural anaesthesia and analgesia: report of three cases.

Serious neurological complications related to epidural anaesthesia and analgesia are only rarely reported. We describe the clinical and radiological features of three patients who sustained intrinsic spinal cord lesions after attempted epidural catheterisation. In each case there was an early onset of motor and sensory impairment after the procedure and MRI demonstrated similar, extensive, paracentral, high signal intensity lesions within the cord on T2 weighted images. Possible mechanisms to explain these MRI appearances are discussed. It is proposed that the most likely cause of these lesions was direct trauma to the spinal cord during the procedure and subsequent injection of fluid into the spinal cord producing localised hydromyelia. The prognosis in each case was for a gradual recovery of motor function but spinothalamic sensory impairment and severe spontaneous pain over the affected area persisted.

Effects of restricted knee flexion and walking speed on the vertical ground reaction force during gait.

Although lower extremity immobilization, including restricted knee flexion, is commonly used in rehabilitation, the effect of angle of knee restriction and walking speed on the vertical ground reaction forces during gait is unclear. Force plate measurements were made on 36 healthy males walking at three different speeds when knee flexion was unrestricted and restricted to both 10 and 25 degrees. Analysis of variance and post hoc analyses showed significant increases in four characteristics of the vertical ground reaction force in the restricted leg and in two characteristics in the unrestricted leg during walking with restricted knee flexion. Loading rate and unloading rate for the restricted leg and peak force for both legs showed significant speed-knee flexion restriction interactions. At the fast walking speed, two significant differences were found between knee flexion restrictions of 10 and 25 degrees. The clinical implications of these findings are that restricted knee flexion during gait may significantly alter the forces applied to both lower limbs.

Expression of the FOX1 gene of Saccharomyces cerevisiae is regulated by carbon source, but not by the known glucose repression genes.

We have investigated the regulation of expression of the FOX1 gene of Saccharomyces cerevisiae which encodes acyl-CoA oxidase, the first enzyme in the peroxisomal beta oxidation of fatty acids. We have found that the FOX1 steady state mRNA level is repressed by glucose, partially induced by ethanol (but not by raffinose) and fully induced by oleic acid as a carbon source. Glucose repression was observed even if cultures were grown to stationary phase; however, if the glucose supply was limited initially then partial induction of FOX1 mRNA occurred upon growth to high cell density. A variety of mutants are known to affect the glucose repression of many genes, including the FOX3 gene which encodes the thiolase activity in peroxisomal beta oxidation. However, upon examination none of these mutants showed de-repression of FOX1 expression. Similarly we investigated the role of two inducers of genes encoding peroxisomal enzymes (namely SNF1 and ADR1). No evidence was found to suggest that either of these plays a significant role in the induction of FOX1 mRNA levels. These observations indicate that the regulation of FOX1 is under the control of as yet unidentified genes involved in catabolite repression and suggest that the regulatory circuit influencing acyl CoA oxidase activity, and hence beta oxidation and peroxisome function, is significantly different than that which might have been assumed from other studies.

The yeast protein Gcr1p binds to the PGK UAS and contributes to the activation of transcription of the PGK gene.

Analysis of the upstream activation sequence (UAS) of the yeast phosphoglycerate kinase gene (PGK) has demonstrated that a number of sequence elements are involved in its activity and two of these sequences are bound by the multifunctional factors Rap1p and Abf1p. In this report we show by in vivo footprinting that the regulatory factor encoded by GCR1 binds to two elements in the 3' half of the PGK UAS. These elements contain the sequence CTTCC, which was previously suggested to be important for the activity of the PGK UAS and has been shown to be able to bind Gcr1p in vitro. Furthermore, we find that Gcr1p positively influences PGK transcription, although it is not responsible for the carbon source dependent regulation of PGK mRNA synthesis. In order to mediate its transcriptional influence we find that Gcr1p requires the Rap1p binding site, in addition to its own, but not the Abf1p site. As neither a Rap1p nor a Gcr1p binding site alone is able to activate transcription, we propose that Gcr1p and Rap1p interact in an interdependent fashion to activate PGK transcription.

The yeast co-activator GAL11 positively influences transcription of the phosphoglycerate kinase gene, but only when RAP1 is bound to its upstream activation sequence.

Transcription of the yeast phosphoglycerate kinase gene (PGK) is activated by an array of nuclear factors including the multifunctional protein RAP1. We have demonstrated that the transcriptional co-activator GAL11, which was identified as an auxiliary factor to GAL4 and which is believed to interact with the zinc finger of the trans-activator, positively influences the level of PGK transcription on both fermentable and non-fermentable carbon sources. This positive effect is only observed when the RAP1 site in the upstream activation sequence (UAS) is present, implying that GAL11 acts through RAP1. Expression of the RAP1 gene is not reduced in the gal11 background, and in vivo footprinting shows that GAL11 does not influence RAP1 DNA-binding activity. Therefore the effect of GAL11 on PGK transcription must be mediated at the PGK UAS, presumably as part of the activation complex. It has been proposed that RAP1 may act as a facilitator of GCR1 binding at the PGK UAS and therefore it is conceivable that the target for GAL11 may in fact be GCR1. A further implication of this study is that GAL11 can interact with proteins such as RAP1 or GCR1 that are apparently structurally dissimilar from GAL4 and other zinc finger DNA-binding proteins.

Neonatal intracranial lesions following placental abruption.

A case-controlled study of the cerebral ultrasound appearances of neonates following placental abruption was undertaken. Twenty-nine index subjects (median gestation 29 weeks) were identified over a 2-year period with gestation- and sex-matched controls. Placental abruption was associated with a four-fold increased incidence of periventricular leukomalacia and extensive periventricular haemorrhage, without increased mortality. Ten infants (34%) developed cystic periventricular leukomalacia following placental abruption, compared with three (10%) in the control group. Intraventricular haemorrhage (excluding subependymal haemorrhage) and haemorrhage into the brain parenchyma occurred in 21 (72%) infants in the abruption group, compared with 14 (48%) in the control group (P < 0.05).

Vigabatrin in intractable childhood epilepsy: a retrospective study.

The effects of vigabatrin were studied over a 6-month period in 43 patients with intractable epilepsy. Children with complex partial seizures, with or without secondary generalization, responded best with more than one-half achieving a greater than 50% reduction; generalized tonic-clonic seizures also improved but there was no significant change in absence or myoclonic seizures. Four patients are seizure-free on monotherapy with vigabatrin. The drug was well tolerated with few side effects.

Cerebral neoplastic angioendotheleosis complicated by hypercalcaemia.

This is a case report of a 67 year old man who presented with a fluctuating level of consciousness and myoclonic jerks caused in part by hypercalcaemia. The diagnosis of cerebral neoplastic angioendotheleosis was only made later on brain biopsy and is the first report of the occurrence of hypercalcaemia in neoplastic angioendotheleosis.

Cerebral blood flow, blood volume and oxygen utilization. Normal values and effect of age.

Regional cerebral blood flow (CBF), oxygen extraction ratio (OER), oxygen utilization (CMRO2) and blood volume (CBV) were measured in a group of 34 healthy volunteers (age range 22-82 yrs) using the 15O steady-state inhalation method and positron emission tomography. Between subjects CBF correlated positively with CMRO2, although the interindividual variability of the measured values was large. OER was not dependent on CMRO2, but highly negatively correlated with CBF. CBV correlated positively with CBF. When considering the values of all the regions of interest within a single subject, a strict coupling between CMRO2 and CBF, and between CBF and CBV was found, while OER was constant and independent of CBF and CMRO2. In 'pure' grey and white matter regions CMRO2, CBF and CBV decreased with age approximately 0.50% per year. In other regions the decline was less evident, most likely due to partial volume effects. OER did not change or showed a slight increase with age (maximum in the grey matter region 0.35%/yr). The results suggest diminished neuronal firing or decreased dendritic synaptic density with age.

A clinical comparison of atracurium and vecuronium in women undergoing laparoscopy.

In a double-blind, prospective, randomised trial in 30 women undergoing laparoscopy, atracurium and vecuronium were compared in equipotent (2 X ED95) doses. In the atracurium group, first twitch depression was significantly greater at one minute, and degree of fade significantly greater at one and two minutes, but thereafter neuromuscular monitoring showed no significant difference between the groups. Clinically there was no significant difference between the drugs. Mild intraoperative hypotension was equally common in both groups as was sinus bradycardia. Reversal and recovery were comparable in the two groups. Neostigmine was required in all patients and in three (one atracurium, two vecuronium) a second dose was required in all patients and in three (one atracurium, two vecuronium) a second dose was administered on clinical grounds. Antagonism of the neuromuscular block is required with surgery of this duration despite the intermediate duration of action of the relaxant drugs.

No fault compensation for personal injury in New Zealand: some implications for anaesthetists.

In recent years, there has been an increase in medico-legal and disciplinary actions against doctors, some involving anaesthetists. While this has occurred at a time of increasing questioning of doctors' decisions, in New Zealand there has been the added dimension of a major change in the law related to personal injury. Under the provisions of the Accident Compensation Act there are no grounds for a civil action against a doctor in respect of a medical misadventure. The only provision for recompense is through the Accident Compensation Corporation. With the removal of the punitive aspect of civil actions against doctors, there has been an increase in complaints through other channels. The anaesthetist is particularly vulnerable because of the immediacy with which an adverse event is likely to cause obvious harm to a patient. This can only be countered by high standards of practice, together with careful record keeping.

Cerebral haemodynamic changes after extracranial-intracranial bypass surgery.

Regional cerebral blood flow, oxygen utilisation, fractional oxygen extraction, and cerebral blood volume were measured by positron emission tomography in twelve patients with carotid artery occlusion. Follow-up studies were carried out at a mean interval of eleven weeks after extracranial-intracranial bypass surgery. Clinical improvement was observed in three patients who had presented with frequent transient ischaemic attacks. One patient with multiple vascular occlusions suffered a stroke at the time of surgery. Follow-up studies showed an increase of regional cerebral blood flow in only two of the twelve patients. In the group as a whole, there was no significant change of cerebral blood flow, oxygen consumption or fractional oxygen extraction after bypass surgery. The most consistent post-operative change, observed in eleven of the twelve patients, was a fall of cerebral blood volume in the cortical territory of the bypassed carotid artery (p less than 0.01). This effect was most marked in patients with bilateral carotid occlusion, in whom there was often an accompanying fall of blood volume in the contralateral hemisphere. The post-operative findings were consistent with an increase of regional cerebral perfusion pressure as a result of the bypass procedure. Although this effect is potentially of value, those patients with most to gain from bypass surgery may also run the highest risk of peri-operative cerebral ischaemia.

The Anaesthetic Mortality Assessment Committee 1979-1984.

A review of 324 cases reported to the Anaesthetic Mortality Assessment Committee over a five year period confirms a low incidence of cases associated primarily with anaesthesia. The committee has identified potential problem areas affecting anaesthesia which require continued vigilance on the part of the anaesthetist. These include the fluid balance of patients, the potential for hypothermia, altered patterns of drug action in the elderly and critically ill and the influence of other disease processes-notably those affecting the heart. As well there are the rare problems more directly associated with anaesthesia such as hypersensitivity reactions and malignant hyperpyrexia. Technical problems during anaesthesia such as misplacement of the endotracheal tube are not commonly associated with death, but because they are preventable, are of particular importance.

Regional cerebral blood flow and oxygen metabolism in dementia due to vascular disease.

Regional cerebral blood flow (CBF), oxygen utilisation (CMRO2) and fractional oxygen extraction (OER) were measured by positron emission tomography in patients with multi-infarct dementia. A matched reduction of both CBF and CMRO2 in the majority of patients indicated that in general, reduced cerebral perfusion in this condition is appropriate for the reduced metabolic demands of a damaged brain. Only in a very small minority of patients with dementia associated with bilateral carotid artery occlusion was CBF inappropriately low and OER raised. In these exceptional cases with critical cerebral perfusion, surgical measures to increase CBF could theoretically arrest or slow down the progress of dementia.