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Biomedical subjects

J D Miller

Publications and source records attributed to J D Miller.

At least 145 records · Page 8Linked to original sources
PubMed1994

Determination of fumonisins in milk.

Fumonisin B1 (FB1) and fumonisin B2 (FB2) were determined in milk by liquid chromatography (LC) following immunoaffinity column cleanup. Recoveries from milk spiked with 5-50 ng each fumonisin/ml averaged 79-109%. The aminopentol hydrolysis product of FB1 (AP1) was determined by LC after cleanup on a C18 solid phase phase extraction column; mean recoveries were 69-83% at spiking levels of 50-100 ng AP1/ml milk. Detection limits were of the order 3-7 ng/ml for FB1 and FB2, and 20-25 ng/ml for AP1. A stability study showed no losses of FB1 and FB2 in milk under conditions of freezing, refrigeration and boiling. A transmission study using four cows dosed with pure FB1 either orally (1.0 and 5.0 mg FB1/kg b.w.) or by i.v. injection (0.05 and 0.20 mg FB1/kg b.w.) showed no detectable residues of FB1 or AP1 in the milk, with or without hydrolytic treatment with beta-glucuronidase/sulfatase to liberate any conjugates.

Administration, Oral↗
PubMed1994

Persistence of circadian rhythmicity in hibernating ground squirrels.

The body temperatures (Tb) of golden-mantled ground squirrels maintained under constant dim light (< 20 1x red light) at an ambient temperature of 10 degrees C were monitored via telemetry throughout the hibernation season. During euthermia, when Tb ranged from 34 to 39 degrees C, these animals exhibited robust circadian Tb rhythms. During bouts of hibernation, when Tb rhythms persisted, although the amplitudes of the rhythms were considerably dampened compared with euthermia. The periods of the intrabout Tb rhythms were within the ranges observed during euthermia and were stable within an individual bout but varied between hibernation bouts. Arousals from hibernation occurred at a fixed phase angle of the Tb cycle. Once the period of an intrabout Tb rhythm was determined, it was possible to predict the timing of arousal from the hibernation bout to within 1 h of any 24-h period. This study confirms previous speculation about the persistence of circadian rhythms in golden-mantled ground squirrels during deep hibernation and demonstrates that the circadian system is involved in the timing of periodic arousals from hibernation.

Animals↗
PubMed1994

Thermal effects on neuronal activity in suprachiasmatic nuclei of hibernators and nonhibernators.

The temperature sensitivity of neuronal firing rates in the suprachiasmatic nuclei (SCN) of the hypothalami of rats and ground squirrels was studied in vitro. SCN from euthermic squirrels were studied during the hibernation season (winter) and during the summer. SCN from hibernating squirrels were also studied. Most properties of SCN cells from hibernators and nonhibernators were similar. Warm- and cold-sensitive neurons were observed in all groups, but cold-sensitive neurons were more common in SCN from hibernating squirrels. No evidence for temperature compensation of firing rate was accumulated; no cell was observed to fire below 16.6 degrees C. If the persistence of circadian rhythmicity is a function of action potential-dependent neurotransmission from the SCN, these results suggest that deep hibernation (5-17 degrees C) should be characterized by an absence of circadian fluctuation in temperature. Two possible adaptations for the shallow torpor seen at somewhat higher temperatures were observed in the SCN: 1) a relatively large population of cold-sensitive neurons and 2) a population of neurons with very high activation energies. Activation energy analysis suggested that most of the temperature-sensitive properties of these cells could be explained in terms of the thermal sensitivity of the sodium channel.

Action Potentials↗
PubMed1994

Analysis of intracerebral hematoma shapes by numerical computer simulation using the finite element method.

The distortion and stress distribution in the brain caused by putaminal hemorrhage were estimated by computer stimulation using the finite element method (FEM). The two-dimensional model of a single cerebral hemisphere contained cortex, white matter, caudate nucleus, lenticular nucleus, thalamus, falx, and lateral ventricle. Five types of intracerebral hemorrhage were modeled at different locations in the lenticular nucleus. The models generated putaminal hematomas of various shapes influenced by the location of the bleeding points. Hematomas caused deformation of the brain, collapse of the lateral ventricle, and destruction of the internal capsule. The stress distribution revealed various patterns influenced by the site of bleeding. The stress in the area of the internal capsule corresponded to the extent of destruction of the internal capsule. This study suggests that FEM modeling of putaminal hemorrhage can provide a useful simulation.

Biomechanical Phenomena↗
PubMed1994

Management and long-term outcome following subarachnoid haemorrhage and intracranial aneurysm surgery in elderly patients: an audit of 199 consecutive cases.

To address the question of managing subarachnoid haemorrhage (SAH) in the older patient, the management and outcome of 199 consecutive patients aged > or = 60 years with a confirmed diagnosis of subarachnoid haemorrhage (n = 186) or an unruptured intracranial aneurysm (n = 13) were reviewed. In seven patients, the cause of the SAH was an arterio-venous malformation and these were excluded from further analysis. Angiography was performed in 141 patients with a complication rate of 2.1%. Angiography was not performed in 51 patients and, in this cohort, the in-patient mortality rate was 68.6% and only 27.5% had a favourable outcome at discharge. Operation was not performed in 21 patients with demonstrated aneurysms for a variety of reasons. In this group, the in-patient mortality rate was 47.6% and 38.1% had a favourable outcome at discharge. Eighty-one patients in good neurological grade underwent surgery for a ruptured aneurysm and six patients underwent surgery for a symptomatic unruptured aneurysm. The surgical mortality was 1.1% and a favourable outcome at discharge was achieved in 83.9% of patients. Thirty-three patients were angiographic negative and there was a favourable outcome in 97% of this group. The management mortality in these selected patients admitted to the Department of Clinical Neurosciences was 24.4% and a favourable outcome was recorded in 66.2% of patients. Long-term follow-up (median 40 months, range 3-120 months) was obtained in 97% of discharged patients. The probability of survival at 60 months for patients in good condition at discharge was 0.826 (95% confidence interval 0.722-0.894).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Role of intracranial pressure monitoring in severely head-injured patients without signs of intracranial hypertension on initial computerized tomography.

Previous studies have suggested that only a small proportion (< 15%) of comatose head-injured patients whose initial computerized tomography (CT) scan was normal or did not show a mass lesion, midline shift, or abnormal basal cisterns develop intracranial hypertension. The aim of the present study was to re-examine this finding against a background of more intensive monitoring and data acquisition. Eight severely head-injured patients with a Glasgow Coma Scale score of 8 or less, whose admission CT scan did not show a mass lesion, midline shift, or effaced basal cisterns, underwent minute-to-minute recordings of arterial blood pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) derived from blood pressure minus ICP. Intracranial hypertension (ICP > or = 20 mm Hg lasting longer than 5 minutes) was recorded in seven of the eight patients; in five cases the rise was pronounced in terms of both magnitude (ICP > or = 30 mm Hg) and duration. Reduced CPP (< or = 60 mm Hg lasting longer than 5 minutes) was recorded in five patients. Severely head-injured (comatose) patients whose initial CT scan is normal or does not show a mass lesion, midline shift, or abnormal cisterns nevertheless remain at substantial risk of developing significant secondary cerebral insults due to elevated ICP and reduced CPP. The authors recommend continuous ICP and blood pressure monitoring with derivation of CPP in all comatose head-injured patients.

Adolescent↗
PubMed1994

Production and purification of fumonisins from a stirred jar fermenter.

The production, isolation and purification of fumonisins from 10 litre liquid cultures are described. Measurements of sucrose, fructose and glucose consumption, oxygen demand, dry weight increase, CO2, and fumonisin production were taken every 48 hours. The specific productivity of fumonisins was found to be similar to that reported for corn cultures but purification was much simpler, yielding an 89% recovery. The method developed for the purification of fumonisins from liquid culture was also applied to a corn culture, resulting in a 70.1% recovery.

Carcinogens, Environmental↗
PubMed1994

Integrated multimodality monitoring in the neurosurgical intensive care unit.

The selection of variables for continuous monitoring in the neurosurgical intensive care unit is based upon the requirement for constant perfusion and oxygenation of the brain and knowledge of the frequency and prognostic significance of abnormal values. Both arterial and intracranial pressure must be considered in the form of cerebral perfusion pressure. Body temperature and arterial oxygen saturation are essential to monitoring. Measurement of jugular venous oxygen saturation and cerebral blood flow velocity provide information of value in determining the source of raised intracranial pressure, the most appropriate means of treating it, and the safety of therapy.

Adult↗
PubMed1994

Transcranial Doppler sonography in aneurysmal subarachnoid hemorrhage.

Following subarachnoid hemorrhage (SAH) from an intracranial aneurysm, ischemic deficits related to cerebral vasospasm still account for significant morbidity and mortality. Operative decisions and timing must be based on the presence of vasospasm and other complications of the hemorrhagic period. Transcranial Doppler sonography provides a noninvasive method for evaluating the status of the intracranial arteries following SAH. The method can, with good reproducibility, identify the patient likely to suffer symptomatic vasospasm, outline the progress of the disease, and serve as a guide to therapy. There are inherent errors produced by the anatomy of the intracranial tree and by peculiarities of the disease. Proximal vasospasm, distal vasospasm, defective autoregulation, and distal infarction with hyperperfusion add confusion to the velocity equation. In experienced hands, however, the method correlates well with the angiographic image of the vessels studied.

Humans↗
PubMed1993

GTP binding and hydrolysis by the signal recognition particle during initiation of protein translocation.

The signal recognition particle (SRP) consists of one RNA and six protein subunits. The N-terminal domain of the 54K subunit contains a putative GTP-binding site, whereas the C-terminal domain binds signal sequences and SRP RNA. Binding of SRP to the signal sequence as it emerges from the ribosome creates a cytosolic targeting complex containing the nascent polypeptide chain, the translating ribosome, and SRP. This complex is directed to the endoplasmic reticulum membrane as a result of its interaction with the SRP receptor, a membrane protein composed of two subunits, SR alpha and SR beta, each of which also contains a GTP-binding domain. In the presence of GTP, SRP receptor binding to SRP causes the latter to dissociate from both the signal sequence and the ribosome. GTP is then hydrolysed so that SRP can be released from the SRP receptor and returned to the cytosol. Here we show that the 54K subunit (M(r) 54,000) of SRP (SRP54) is a GTP-binding protein stabilized in a nucleotide-free state by signal sequences, and that the SRP receptor both increases the affinity of SRP54 for GTP and activates its GTPase. We propose that nucleotide-mediated conformational changes in SRP54 regulate the release of signal sequences and the docking of ribosomes at the endoplasmic reticulum.

Amino Acid Sequence↗
PubMed1993

Does prediction of outcome alter patient management?

A patient's prognosis is a key factor for the clinicians involved in management. We set out to determine if provision of computer-based predictions of outcome after severe head injury resulted in measurable changes in patient management. In particular, we wondered whether introduction of the predictive system would alter the relation between severity of injury and "intensity" of management. 1025 patients admitted to four British neurosurgical units between 1986 and 1989 following a severe head injury, and who were either in coma for 6 h or had an operation for acute intracranial haematoma, were studied. Specified aspects of intensive management were recorded and all patients were followed up after six months. The study had three phases: a baseline period of at least one year before the introduction of computer-based outcome prediction, one year when predictions were provided at specified times, and a final six months when prediction was withdrawn. While predictions were being provided, there was an increase in the use of specified aspects of intensive care in patients predicted to have a good outcome, but a 39% reduction in the use of these same aspects of intensive care in patients predicted to have the worst outcome. There was no evidence that the provision of predictions affected overall outcome, length of stay, or the recording of explicit decisions to limit treatment. We have demonstrated that the introduction of a routine prediction service can alter patient management.

Adult↗
PubMed1993

A GTPase cycle in initiation of protein translocation across the endoplasmic reticulum membrane.

In higher eukaryotes proteins bearing a signal sequence are translocated across the membrane of the endoplasmic reticulum (ER). The initial events of protein translocation are the binding of the signal sequence by the 54 kDa subunit (SRP54) of the signal recognition particle (SRP) and the targeting of the ribosome nascent chain complex to the ER. Targeting is mediated by the binding of SRP to the SRP receptor, a membrane protein comprising two different subunits, SR alpha and SR beta. Interaction of SRP and SR alpha/SR beta causes release of the signal and the engagement of the nascent chain with the membrane-bound translocation apparatus. Both SRP54 and SR alpha contain homologous domains which include a predicted GTPase fold. The transmembrane protein SR beta also contains a GTPase domain, but it is not closely related to those of SRP54 and SR alpha. All three proteins bind GTP specifically, and the SR alpha/SR beta complex stimulates both GTP binding to and GTP hydrolysis by SRP54. We suggest a model for the initiation of protein translocation across the ER in which SR alpha beta catalyses a cycle of GTP binding, hydrolysis and release by SRP54 that regulates its dissociation from the signal sequence.

Animals↗
PubMed1993

Management of intracranial hypertension in head injury: matching treatment with cause.

Raised intracranial pressure (ICP) is common after head injury and strongly associated with mortality and morbidity. Empirical and prophylactic therapy with steroids and barbiturates has proved unsuccessful. Ideally, therapy should be targeted at the predominant cause of the increase in ICP. In head injury these may be (1) an increase in cerebral blood volume best treated by hyperventilation and hypnotic drugs. (2) an increase in brain water content best treated by osmotherapy and (3) increased CSF outflow resistance best treated by CSF drainage. This last cause seldom predominates in head injury. To determine whether it is possible to identify the best therapy in individual head injured patients, we are comparing osmotherapy (mannitol) and hypnotic drugs (thiopentone and gamma-hydroxybutyrate) in selected patients with severe head injury where it is possible to maintain standard conditions of ventilation and stable blood pressure and to measure ICP, CPP, brain electrical activity, PR ratio of the ICP wave form and cerebral AvDO2 before and during each of the two forms of therapy. Effective therapy means that ICP has been reduced to 20 mm Hg with preservation or improvement in CPP. 17 patients have been studied so far and 4 groups identified. Osmotherapy was superior to hypnotic in 5 cases, hypnotic superior to mannitol in 3 cases, both were effective in 5 cases and neither effective in 4 cases. Patients in whom hypnotics were superior tended to be younger, with diffuse rather than focal brain injury, had the highest levels of brain electrical activity prior to treatment and a higher PR ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Damage, Chronic↗
PubMed1993

Transcranial Doppler-sonography in severe head injury.

Ischaemic brain damage is present in over 90% of patients suffering from fatal head injury. Early detection and treatment of ischemia may improve outcome after head trauma. Monitoring of blood flow velocity of the middle cerebral artery by noninvasive transcranial doppler ultrasound provides an alternate means of identifying cerebral ischaemia.

Blood Flow Velocity↗
PubMed1993

Neuropathological and neurophysiological effects of interstitial white matter autologous and non-autologous protein containing solutions: further evidence for a glioma derived permeability factor.

The feline infusion model of brain edema was used to evaluate the pathophysiological effects of 0.6 ml infusions of autologous serum protein (66%), human serum protein (66%), human glioma cyst fluid and a tissue culture medium (TCM) on the structure and function of the forebrain white matter. These infusions increased local white matter water content by between 10.8 and 12.5 ml/100 g brain and were associated with moderate increases in ICP and CSF outflow resistance and a significant decrease in lumped craniospinal compliance. Cortical somatosensory potentials, motor evoked potentials, EEG and local cerebral blood flow (rCBF) at normocapnia were generally unchanged by the various infusions. All infusates except the 66% autologous serum protein infusion impaired rCBF CO2 reactivity. Histologically all infusates caused marked extracellular edema. The autologous serum protein infusion caused no additional histological changes whereas the glioma cyst infusates caused profound endothelial and astrocytic swelling, focal endothelial necrosis, basement membrane disruption, perivascular microglial reaction and pavementation and perivascular migration of polymorphonuclear leukocytes. Similar but less marked changes were seen after infusion of human serum protein whilst the TCM produced only minimal changes. The intensity and extent of Evans Blue extravasation into the forebrain white matter was greatest with glioma cyst infusates and with all infusions reflected the extent to microvascular changes. These studies show that products derived from gliomas cause additional damage to the blood-brain-barrier than that caused by non-autologous serum proteins. These results add further support for the existence of glioma derived permeability factors (GDPF), but suggest neither serum proteins nor glioma derived compounds in the white matter interstitium significantly influence local electrophysiological function. Some limitations of the infusion edema model when using non-autologous infusions and difficulties quantitating brain dysfunction are emphasised.

Animals↗