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Biomedical subjects

A G Brown

Publications and source records attributed to A G Brown.

At least 19 recordsLinked to original sources

The use of forensic botany and geology in war crimes investigations in NE Bosnia.

From 1997 to 2002 the United Nations International Criminal Tribune for the former Yugoslavia (ICTY) undertook the exhumation of mass graves in NE Bosnia as part of the war crimes investigations aimed at providing evidence for the prosecution of war criminals in The Hague. This involved the location and exhumation of seven former mass graves (primary sites) dug following the fall of Srebrenica in July 1995. These primary mass graves were secretly and hurriedly exhumed three months later and most of the bodies or body parts transported and reburied in a large number of secondary sites many of which were subsequently exhumed by ICTY. The aim of the pollen and soil/sediment studies was to provide an 'environmental profile' of the original site of the samples and use this to match the relocated bodies to the original mass graves. This was part of completing the chain of evidence, providing evidence of the scale and organization of the original atrocities and the subsequent attempts to conceal the evidence related to them. All the primary sites were located in areas of contrasting geology, soils and vegetation, and this allowed matching of the sediment transported in intimate contact with the bodies to the original burial sites, which in some cases were also the execution sites. In all, over 24 sites were investigated, over 240 samples collected and analyzed under low power microscopy and 65 pollen sub-samples fully analyzed. The pollen and sediment descriptions were used in conjunction with the mineralogy (using XRD) of primary and secondary sites in order to provide matches. These matches were then compared with matching evidence from ballistic studies and clothing. The evidence has been used in court and is now in the public domain. It is believed this is the first time 'environmental profiling' techniques have been used in a systematic manner in a war crimes investigation.

Bosnia and Herzegovina↗

Anaesthetic implications of uterine artery embolisation in management of massive obstetric haemorrhage.

The latest triennial report on maternal deaths has recommended the consideration of uterine artery embolisation in management of cases of massive obstetric haemorrhage. We have been using interventional radiology to manage both expected and unanticipated postpartum bleeding in our centre. Three case reports are presented to highlight the value of this technique and issues relating to the anaesthetic and postoperative management of these patients are discussed.

Adult↗

Post partum pneumothorax: two case reports and discussion.

Pneumothorax is a rare event during pregnancy. We present two cases of pneumothorax occurring after caesarean section under general anaesthesia, including one tension pneumothorax. We summarise risk factors for developing a pneumothorax during pregnancy and discuss differential diagnosis and the anaesthetic management in the labour ward.

Journal Article↗

Mammalian and Drosophila dachshund genes are related to the Ski proto-oncogene and are expressed in eye and limb.

We have isolated mammalian homologues of the Drosophila dachshund gene. Two domains of high conservation, one of which contains an alpha-helical, coiled-coil motif, show similarity to the Ski family of genes. We therefore propose that Dachshund belongs to a superfamily including these genes. Mouse Dachshund (Dach) is expressed in the eye and limb, structures affected by the Drosophila loss-of-function mutant, and rib primordia, CNS and genital eminence. Pax6 and Dach show overlapping but non-identical expression patterns. Dach expression is unaffected in smalleye mouse brain, indicating that Pax6 is not directly activating Dach. In Drosophila eye development dachshund is a component of an interacting network of proteins. Genes homologous to many of these exist in mammals; Dach joins this expanding group.

Amino Acid Sequence↗

Electrophysiological evidence that spinomesencephalic neurons in the cat may be excited via spinocervical tract collaterals.

Extracellular microelectrode recordings were made from spinomesencephalic tract (SMT) neurons in the lumbosacral spinal cord of cats anaesthetized with chloralose and paralysed with gallamine triethiodide. The SMT cells were antidromically fired from the posterolateral parts of the superior colliculus and the intercollicular region, were located in laminae IV to VIII, and had response properties and axonal conduction velocities similar to those described previously. The effects of stimulating the dorsolateral funiculus of the cervical cord at C3 and rostral C1, below and above the termination of spinocervical tract (SCT) axons in the lateral cervical nucleus, were examined on 33 SMT cells. The strength of stimulation was adjusted so that at C3 it was above threshold for antidromic activation of SCT cells and at C1 was below threshold for activation of the same cells. Seven (21%) SMT neurons were excited from C3 but not from C1. The remaining 26 (79%) were excited from both C3 and rostral C1 and 23 (70% of these) were excited significantly more from C3. That is, 91% of the total sample were either excited only from C3 or more strongly from C3 than from rostral C1. We discuss the possible neuronal systems involved and conclude that the greater excitatory effects from C3 are most likely due to antidromic activation of the SCT. The shortest latency effects from C3 indicate a monosynaptic linkage between SCT cells with the fastest axons and the SMT. The longer latency actions may be due to monosynaptic connexions from SCT cells with slower conducting axons, to di- or polysynaptic actions from SCT cells with fast axons, or a combination of both. SMT cells are another population of spinal neurons, in addition to postsynaptic dorsal column, spinothalamic and dorsal horn spinocerebellar neurons, which receive excitation via SCT collaterals.

Animals↗

Prolapsed intervertebral disc after epidural analgesia in labour.

Back pain and minor neurological symptoms are commonly experienced postpartum, often being attributed to non-specific causes such as maternal obstetric factors, or the use of epidural analgesia. We report a case in which neurological problems associated with a prolapsed intervertebral disc occurred after epidural analgesia in labour and a normal vaginal delivery.

Adult↗

Recent examples of novel secondary metabolites.

Modern trends in the detection, isolation and characterization of leads for novel therapeutic compounds are reviewed. Some current biological test systems (immunological, chemical, enzymic, receptor, etc.) and examples of their successful application are highlighted including the structures of selected novel and prospective metabolites.

Anti-Infective Agents↗

Effects of upper cervical spinal cord stimulation on neurons in the lumbosacral enlargement of the cat: spinothalamic tract neurons.

Extracellular microelectrode recordings were made from deep spinothalamic tract neurons in the lumbosacral spinal cord of cats anaesthetized with chloralose and paralyzed with gallamine triethiodide. The effects of upper cervical spinal cord stimulation were tested on 43 spinothalamic tract neurons, by stimulation of the ipsilateral dorsolateral funiculus at C3 and rostral C1 using five or six shocks at 333 Hz. The strength of cervical stimulation was adjusted so that the C3 shock was above threshold for antidromic activation of spinocervical tract neurons but the same strength of shock applied at C1 was below threshold for the same neurons. Four of the 43 spinothalamic cells (9%) were not influenced by upper cervical stimulation. The remaining 39 spinothalamic tract cells (91%) were all excited from the upper cervical cord. Twenty-seven of these (63%) were excited more strongly from C3 than from C1, 4 (9%) were excited more strongly from C1 than from C3, and the remaining eight cells (19%) showed no significant differences between their responses to stimulation at C1 and C3. There were no obvious differences between those spinothalamic tract neurons showing differential effects from C1 and C3 and those showing no such effects. The neuronal systems possibly responsible for the differential effects from C3 and C1 on spinothalamic tract neurons are discussed. We conclude that the most likely candidate system for the greater excitation from C3 compared with C1 is the subset of spinocervical tract neurons with axon collaterals in the lumbosacral enlargement and that the spinothalamic tract is a further ascending path, in addition to the postsynaptic dorsal column path, that receives excitatory input from spinocervical axon collaterals. The greater excitation from C1 compared with C3 is interpreted as due to excitation from C1 and a mixture of excitation and inhibition from C3. The responsible neuronal systems seem likely to be either the spinocervical neurons with axon collaterals operating on the spinothalamic tract via inhibitory interneurons, or cells in the lateral cervical nucleus with axons descending to the lumbosacral cord.

Animals↗

Plasma lipase concentration as an aid to the early detection of pancreas disease in farmed Atlantic salmon (Salmo salar).

Plasma lipase concentrations were determined in Atlantic salmon post smolts at weekly intervals on two farms from late June. On one farm there was a significant increase (P < 0.001) in lipase concentration which coincided with a suspicion of pancreas disease on clinical grounds. A definitive diagnosis was subsequently confirmed by histopathology. The exercise was repeated on 10 farms in the following year and the results provided additional evidence of the value of monitoring lipase concentration as an indication of pacreas disease at an earlier stage than it can be detected by clinical signs and histopathology alone.

Animals↗

Gender differences in the phenotypic expression of Alzheimer's disease in Down's syndrome (trisomy 21).

Twenty-eight individuals with typical Down's syndrome (DS) phenotype (17 males and 11 females; age range: 10-74 years) were investigated for gender differences in the phenotypic expression of Alzheimer-type pathology (ATP). Quantitative neuropathology was performed in the 4 neocortical lobes of the right hemisphere, by counting senile plaques (SP), and neurofibrillary tangles (NFT). ATP was present in 25 middle-aged (> 40 years) individuals (16 males and 9 females). Females had significantly higher (p = 0.03) mean neocortical NFT densities (36.6 per mm2; s.e.m. +/- 6.6) than males (17.9 per mm2; s.e.m. +/- 4.7). None of the females had NFT densities below 10 per mm2, compared with 6 males in whom NFT were either absent or seen in very low densities (< 4 per mm2). Assessment of SP densities in the same cortical regions showed non-significant differences in females (42.4 per mm2; s.e.m. +/- 5.1) compared with males (33.6 per mm2; s.e.m. +/- 2.1). There was clinical evidence of dementia in all the female (8/8) individuals who were prospectively assessed, compared with only 54% (7/13) of males. The male individuals without clinical dementia had absent or low neocortical NFT densities regardless of high SP densities. Female DS cases (mean age: 48.8 years; s.e.m. +/- 1.9) had an earlier onset of dementia than males (mean age: 53.6 years; s.e.m. +/- 1.3; p = 0.05). Female middle-aged DS individuals have an earlier onset, and a more severe form of AD which correlates with higher neocortical NFT rather than SP density.

Adenosine Triphosphate↗

Differential ascending projections from neurons in the cat's lateral cervical nucleus.

Extracellular microelectrode recordings were made from single cells of the lateral cervical nucleus (LCN) in cats anaesthetized with chloralose and paralysed with gallamine triethiodide. The cells were tested for antidromic activation from the contralateral medial lemniscus and the contralateral tectum. Seventy-two LCN units were recorded which projected to one or both targets. Sixty (83%) projected through the medial lemniscus, and of these 36 (50% of the total) also projected to the tectum, whereas 24 (33%) projected through the medial lemniscus only; 12 (17%) projected only to the tectum. Twenty-nine units (40%) were excited by moving hairs of the coat but not by pinch of the skin, and 9 (31%) of these projected to the tectum, 11 (38%) through the medial lemniscus and 9 (31%) to both targets. Forty units (56%) were excited by hair movement and noxious pinch, and 3 (7%) of these projected to the tectum, 10 (25%) through the medial lemniscus and 27 (68%) to both targets. Three units (4%) had no discernible receptive fields and they all projected through the medial lemniscus, but not to the tectum. Of the 12 units projecting only to the tectum, 11 had receptive fields completely or partially on the trunk. Units projecting either through the medial lemniscus only, or through the medial lemniscus and also into the tectum, had receptive fields more widely distributed: these included small fields on the fore- and hind feet, on the limbs and also, a minority, on the trunk. Units with glove- or stocking-like receptive fields projected through the medial lemniscus. The results show that while most LCN cells project through the medial lemniscus, those excited by hair movement alone preferentially project either to the tectum or through the medial lemniscus, but not by both routes. The differences in receptive field properties of the differently projecting units are discussed in terms of the possible functions of the spinocervical system.

Afferent Pathways↗

Preoperative and postoperative oxygen saturation in the elderly following spinal or general anaesthesia--an audit of current practice.

We have compared the incidence of preoperative and postoperative oxygen desaturation in 20 elderly patients undergoing dynamic hip screw insertion for fractured neck of femur, allocated randomly to two groups to receive subarachnoid anaesthesia (SA, n = 10) or a general anaesthetic (GA, n = 10). Oximetry data were recorded during the preoperative night and the first 48 hours after surgery using Satmaster. Data associated with zero amplitude signal were automatically invalidated by the software and decreases in SpO2 which were preceded by contemporaneous changes in signal amplitude which conformed to a previously described template were assumed to be artefactual and were discarded from final data analysis. Data demonstrated a wide interpatient variability. However, those patients who desaturated preoperatively continued to do so in the postoperative period. The differences between the preoperative and postoperative oximetry profiles were examined for each patient and demonstrated a significantly longer time spent with SpO2 < 90% in the GA group compared with the SA group, in all the recorded time periods, except on the day of surgery. The SA group showed an improvement in oxygen saturation postoperatively when compared to the preoperative night, spending less time with an SpO2 < 85%. We conclude that the subarachnoid anaesthetic technique was associated with a lower incidence of postoperative oximetry desaturation when compared with general anaesthetic for these elderly patients undergoing repair of fractured neck of femur.

Aged↗

Identified hair follicle afferent boutons in the spinal cord of the cat are enriched with L-glutamate-like immunoreactivity.

Hair follicle afferent boutons in the spinal dorsal horn of the cat were examined for L-glutamate enrichment. Two hair follicle afferent axons were labelled intra-axonally with horseradish peroxidase, and post-embedding immunogold reactions of L-glutamate were performed on thin sections containing horseradish peroxidase-labelled boutons. Quantitative analysis showed that hair follicle boutons were associated with immunogold reactions for L-glutamate which were almost twice as dense as average values for dorsal horn tissue. Further analysis revealed that hair afferent boutons displayed 2.3-times the average gold particle density associated with post-synaptic dendrites and 3-times the average immunogold density for L-glutamate of structures which were known to be immunoreactive for GABA. This enrichment of L-glutamate in identified hair afferent terminals supports the idea that the amino acid is a neurotransmitter of hair follicle primary afferent axons.

Afferent Pathways↗

Lumbosacral spinal neurons in the cat that are candidates for being activated by collaterals from the spinocervical tract.

Lumbosacral spinal neurons activated via the spinocervical tract were stained by intracellular injection of horseradish peroxidase in cats anaesthetized with chloralose and paralysed with gallamine triethiodide. The neurons were activated orthodromically by single shock stimulation of the ipsilateral dorsolateral funiculus at the second to third cervical segment, but not from the rostral part of the first cervical segment. Twenty nine cells were recovered from the histological material and subsequently reconstructed from transverse sections. Sixteen cells (55%) had axons that projected ipsilaterally to the lateral funiculus and their somata were located in two regions of the spinal cord, one group in the dorsal horn (laminae IV-V) and the other in the intermediate gray matter (laminae VI-VII). The axons of 10 of these cells gave off collaterals, and in seven of them the collaterals ramified in the grey matter deep to the cell body. The axons of five cells (17%) projected medially towards the central canal, four crossing the mid line in the ventral white commissure and ascending in the contralateral ventral funiculus. Only one of these cells had an axon collateral that crossed into the contralateral dorsal horn. Of the remaining eight cells, three had no obvious long axons but had many local axon collaterals, the axons of three cells were not stained, one had an axon projecting towards the ipsilateral ventral funiculus and one was a motoneuron and its axon projected into a ventral root. A feature of the dendritic trees of many cells was their wide spread in the mediolateral and/or the dorsoventral directions, although no dendrites reached dorsally into lamina II. Twenty-two cells (76%) were excited by moving hairs and by noxious pinch, three (10%) by hair movement alone, two (7%) by noxious pinch and pressure, and for two cells (7%) no receptive field could be found. It is concluded that not only postsynaptic dorsal column neurons receive input from the spinocervical tract but also other cells in the dorsal and ventral horns and the intermediate gray matter. Possible identities for these cells are discussed.

Animals↗

Evidence for a new tumour suppressor locus (DBM) in human B-cell neoplasia telomeric to the retinoblastoma gene.

Roughly 25% of human B-cell chronic lymphocytic leukaemias (CLL) are characterized by a chromosomal lesion involving 13q14. This region contains the retinoblastoma gene (RB1). We have used a variety of techniques to determine whether RB1 or some other locus is the critical region in 11 cases of low grade B-cell malignancy (mainly CLL), all with deletions or translocations involving 13q14. In all cases, except the one with minimal disease, there was deletion or a structural lesion in the region of D13S25, with at least 4 cases showing homozygous disruption. We conclude that D13S25 lies close to a tumour suppressor locus whose inactivation contributes to the initiation or progression of low grade B-cell malignancy. This locus is located at least 530 kilobases telomeric to RB1.

Alleles↗