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Biomedical subjects

R Pamphlett

Publications and source records attributed to R Pamphlett.

At least 37 records · Page 2Linked to original sources
PubMed1996

Uptake of inorganic mercury by the human brain.

A 24-year-old man injected himself intravenously with metallic mercury in a suicide attempt, and died 5 months later after cutting his wrists. The brain was removed at postmortem and 7-micron paraffin sections were cut from representative blocks. Dense deposits of mercury were found on autometallography in large cortical motor neurons, but in no other cerebral neurons. Smaller mercury deposits were found in the brain stem (in the mesencephalic trigeminal nucleus, noradrenergic neurons, and in neurons for extraocular muscles), the cerebellum (in the dentate nucleus) and in lateral motor neurons in the C2/3 spinal cord. Mercury deposits were found in glial cells in all regions. The finding that elemental mercury enters human cortical motor neurons in preference to other cerebral neurons raises the possibility that this neurotoxin may play a part in the pathogenesis of some human motor neuron diseases.

Adult↗
PubMed1996

Motor neuron uptake of low dose inorganic mercury.

In animals, inorganic mercury can bypass the blood brain barrier and enter motor neurons. We sought to determine the lowest injected dose of mercury that could be detected in mouse motor neurons. Mice were injected intraperitoneally with mercuric chloride in doses from 0.05 to 2 micrograms/g body weight and studied between 5 days and 18 months after injection. After formalin fixation, 7 microns sections of cerebrum, cerebellum, brain stem, spinal cord and kidney were stained with silver nitrate autometallography. Five days after injection, mercury granules were detected at doses from 0.2 microgram/g upwards in the cell bodies of spinal and brain stem motor neurons, more granules being seen at the higher doses. Mercury granules were also seen in 5% of posterior root ganglion neurons. At doses from 0.05 microgram/g upwards mercury was detected 5 days later in renal tubule cells. Mercury was still present in motor neurons 6-11 months after injection, but by this time mercury had been cleared from the kidneys. Low doses of inorganic mercury are therefore selectively taken up and retained by motor neurons, making this neurotoxin a good candidate for a cause of sporadic motor neuron disease.

Animals↗
PubMed1996

Vulnerability of the infant brain stem to ischemia: a possible cause of sudden infant death syndrome.

In infants, extreme extension or rotation of the head can occlude one or both vertebral arteries. We sought to determine whether small communicating arteries or asymmetric vertebral arteries could predispose the brain stem to ischemia should such head movements occur. In 68 infants, the carotid, posterior communicating, precommunicator posterior cerebral, basilar and vertebral arteries were fixed in formalin, embedded in resin, the circumferences measured by image analysis, and the relative conductance of blood in each artery per gram of brain calculated. Conductance in the vertebrobasilar and carotid systems lagged behind increases in brain weight during the postnatal growth spurt. In 81% of infants, conductance through the communicating arteries was less than 25% of basilar artery conductance. Conductance in one vertebral artery was less than half that of the contralateral artery in 41% of infants. In conclusion, the lag in available blood flow and small communicating and asymmetric vertebral arteries may predispose the infant brain stem to ischemia if one or both vertebral arteries are occluded by head rotation or extension. Because these head movements are likely to be accentuated in the prone sleeping position (a risk factor for sudden infant death syndrome), we suggest that vertebral artery occlusion may underlie some cases of sudden unexpected infant death.

Age Factors↗
PubMed1996

Astrocytes in the hypoglossal nuclei of sudden infant death syndrome (SIDS) infants: a quantitative study.

It has been suggested that brain stem hypoxia or ischaemia underlies the sudden infant death syndrome (SIDS), but previous reports of astrocytosis in the brain stems of SIDS infants have been contradictory. A volumetric quantitative technique was, therefore, developed to compare astrocyte numbers and sizes in the hypoglossal nuclei of SIDS and control infants. In 12 SIDS and eight control infants, serial sagittal sections were taken through the hypoglossal nucleus and every tenth section was stained for glial fibrillary acidic protein. Astrocytes were counted in the central 4% of a grid stepped throughout the hypoglossal nucleus, and the heights of 100 astrocyte nuclei were measured with a microcator. Astrocyte number, corrected for section thickness and nuclear height, was divided by the volume of the hypoglossal nucleus to calculate astrocyte density. Numbers of astrocytes did not differ significantly between SIDS (mean number 44729, SD 12096) and control (mean number 46562, SD 11060) infants. Astrocyte nuclear height did not differ significantly between groups (SIDS: mean height 3.98 microns, SD 0.22; control: mean height 3.84 microns, SD 0.31). Astrocyte density was similar in SIDS (mean density 24378 astrocytes/mm3, SD 6155) and control (mean density 23978 astrocytes/mm3, SD 4031) infants. No quantitative evidence of astrocytosis was found in the hypoglossal nuclei of SIDS infants. This implies that SIDS infants die without previous episodes of hypoxia/ischaemia severe enough to damage the brain stem.

Astrocytes↗
PubMed1996

Diagnostic evaluation of the substantia nigra.

An improved method for the histopathological evaluation of the substantia nigra for diagnostic purposes is proposed. This method takes advantage of the natural architecture of the constituent cell clusters of the substantia nigra by combining standardized sections in the horizontal plane and simple quantification. The use of this standardized technique should increase the diagnostic reliability and sensitivity of patterns of cell loss within the substantia nigra.

Brain Stem↗
PubMed1996

Increased inorganic mercury in spinal motor neurons following chelating agents.

Heavy metal toxicity has been implicated in the pathogenesis of motor neuron diseases. In an attempt to assess the efficacy of chelating agents to remove mercury from motor neurons, we quantitated the effect of the chelating agents meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3- dimercaptopropane -1-sulphonate (DMPS) on the burden of inorganic mercury in mouse spinal motor neurons. Mice were injected intraperitoneally with 1.0 mg HgCl2/kg body weight and one week later with either 4,400 mg/kg DMPS, 3,600 mg/kg DMSA or 5% NaHCO3 (control) over 4 weeks. Mercury deposits in motor neurons of 50 micron frozen sections of lumbar spinal cord were visualised with an autometallographic technique. Optical sections of silver-enhanced deposits were acquired using a confocal microscope in reflective mode and the volume of the deposits within the perikaryon was estimated. Mercury deposits occupied significantly more volume in motor neurons after both DMPS (7.4%, SD +/- 0.7%) and DMSA (8.0% +/- SD 0.7%) treatment than in controls (4.3%, SD +/- 1.7%). The higher levels of neuronal inorganic mercury may be due to increased entry of mercury into motor axons across the neuromuscular junction as a result of chelator-induced elevated circulating mercury.

Animals↗
PubMed1995

Motor neuron disease: a primary disorder of corticomotoneurons?

It has been suggested that the primary site of damage in motor neuron disease (MND) is the cortical motor neuron, with secondary degeneration of spinal motor neurons. To test this hypothesis, we sought to determine if loss of corticomotoneurons in MND precedes spinal motor neuron loss. The density of corticomotoneurons was measured in 18 MND and 9 control cases using 10-microns horizontal sections of motor cortex in the hand/arm region. The density of spinal motor neurons was measured in 10-microns transverse sections of the lower cervical spinal cord. Corticomotoneuron and spinal motor neuron densities were decreased in MND cases compared to controls, but in MND cases there was poor correlation (r2 = 0.06) between corticomotoneuron and spinal motor neuron densities. The results indicate that corticomotoneuron and spinal motor neurons are lost at different rates in different MND patients, and that corticomoteneuron loss is unlikely to be a primary event in MND.

Adult↗
PubMed1995

Ubiquitin-positive achromatic neurons in corticobasal degeneration.

A 66-year-old woman presented with an alien limb syndrome without dementia. The course of her illness was unremitting and at autopsy 6 years later her diagnosis was confirmed as corticobasal degeneration without Alzheimer-type pathology. Although the presence of ballooned achromatic cortical neurons and cell loss from the substantia nigra distinguishes such patients, the site and density of achromatic neurons has not previously been quantified. We show that immunohistochemistry for the cell stress protein ubiquitin selectively stains these achromatic neurons, whereas they do not stain for abnormally phosphorylated tau protein. Phosphorylated neurofilament antibodies recognise both ballooned and non-ballooned neurons. In this case, high densities of ubiquitin-positive ballooned neurons were found in frontal cortical regions with the highest densities in layers V and VI of the anterior cingulate cortex. In addition, high densities of ubiquitin-positive ballooned neurons were found in the insular cortex, claustrum and amygdala. These results confirm past reports of frontal pathology, but show that there is also considerable pathology in insular and parahippocampal cortical regions and some subcortical regions. Our findings suggest that the distribution and staining characteristics of ballooned neurons in corticobasal degeneration may help to differentiate these cases pathologically, while the absence of dementia appears to be an important clinical criterion.

Aged↗
PubMed1995

Differences in diaphragm fiber types in SIDS infants.

The diaphragm is a vital respiratory muscle in the sleeping infant. Any changes in diaphragm fiber type number or size could represent either a primary developmental delay or a secondary reaction to increased workload, and could give a clue as to the pathogenesis of sudden infant death syndrome (SIDS). We therefore quantitated by point counting on ATPase histochemistry the numbers and areas of type 1 and 2 fibers in the diaphragm, external intercostal and psoas muscles of 37 SIDS and 20 control infants. The amount of slow, fast and fetal myosin in the diaphragm and psoas muscles was measured by electrophoresis to check the ATPase quantitation. There were fewer type 1 fibers in SIDS (median 30.0%) compared with control (median 40.0%) infants (p < 0.02), whereas the diameter of type 1 fibers in SIDS (median 33.9 microns) was larger than in control (median 30.3 microns) infants (p < 0.007). The total cross-sectional area occupied by type 1 and 2 fibers was similar in both groups. No changes were found in the external intercostal or psoas. The amount of slow and fast myosins correlated well with type 1 and type 2 fibers, respectively. The finding of fewer type 1 (fatigue-resistant) fibers of large diameter in SIDS diaphragms suggests that differences in muscle fiber types may predispose these infants to diaphragm fatigue and respiratory failure.

Diaphragm↗
PubMed1995

Effect of anxiety on performance in multiple choice examination.

Negative scoring of incorrectly answered multiple choice questions has logistic advantages, but may disadvantage anxious students. We therefore attempted to observe the effects of positive and negative marking of true/false questions on the examination performance of medical students with different levels of anxiety. Third-year medical students (141 men, 71 women) completed a Spielberger State-Trait Anxiety Inventory before an examination in pathology in 1994. Students knew there would be penalties for wrong answers in the first half of the examination and no penalties in the second half. Performance on the two halves was compared and effects of levels of anxiety assessed. Students reported slightly higher trait anxiety than American norms. Women students reported higher levels of anxiety than men, and levels for both genders were indicative of a moderately stressful situation. Trait anxiety was not associated with performance in either the negatively or positively marked halves of the examination. For women students, but not men, lower state anxiety was positively associated with higher performance on the negatively marked half of the examination (r = 0.29), but accounted for only 8% of the variance in scores. In our study, anxiety was correlated only slightly with results of a negatively marked examination. We conclude that anxious medical students are not unduly disadvantaged by this method of marking.

Anxiety↗
PubMed1995

Brain stem nuclei in sudden infant death syndrome (SIDS): volumes, neuronal numbers and positions.

It has been suggested that the defect underlying the sudden infant death syndrome (SIDS) lies in brain stem nuclei involved in cardiac and respiratory function. However, most studies have not used rigorous quantitative techniques to assess brain stem nuclear volumes and neuronal numbers. We have measured the volume, neuronal numbers and position of brain stem nuclei in 11 SIDS and 11 aged-matched control infants. Using serial sagittal sections, nuclei involved in maintaining airway patency (hypoglossal, ambiguus and retroambiguus), heart rate (dorsal vagal) and generation of respiratory rhythm (ambiguus and dorsal vagal) were studied. No significant differences were found in nuclear volume increase with age, total neuronal number or nuclear position between SIDS and control cases. These findings support the hypothesis that the nervous system in SIDS may be normal until the final event that kills these infants.

Age Factors↗
PubMed1995

Myelin in SIDS: assessment of development and damage using MRI.

OBJECTIVE: Abnormalities of myelin that have been reported in Sudden Infant Death Syndrome (SIDS) include a delay in development and focal lesions presumed to be secondary to hypoxia. Magnetic resonance imaging (MRI) gives excellent images of white matter and can be used to map the progress of myelination and to demonstrate focal lesions. It was the aim of this study to determine whether any MRI abnormality of myelin could be detected in the brains of SIDS compared to control infants. METHODS: The brains of 28 SIDS and 14 control infants were fixed in formalin and scanned with MRI. The proton density, T2-weighted, and inversion recovery scans were assessed for the presence of focal white matter lesions. The amount of myelin in 26 sites was measured in the proton density scans, using a densitometer. The amount of myelin present could be assessed in 21 of 26 sites. RESULTS: In 15 of 21 sites the amount of myelin for age was the same in SIDS and controls. In three sites the rate of myelination was greater in SIDS than control and in another three sites the amount of myelin for age was greater in SIDS than control infants, but these differences were not seen in infants aged less than 8 months. No focal abnormalities of white matter were seen in either SIDS or control infants. CONCLUSIONS: The development of white matter in brains of SIDS infants less than 8 months old is the same as in controls, and in older SIDS infants white matter development may be slightly advanced compared to controls. No hypoxic changes can be seen in SIDS white matter on MRI.

Brain↗
PubMed1994

Magnetic resonance imaging of postmortem infant brains.

In order to obtain postmortem magnetic resonance images of infant brains, the formalin-fixed brains of 37 infants, ranging in age from 17 days to 17 months, were studied. Factors that improved scan resolution included formalin fixation, not washing the formalin from the brain, imaging the brain with a thin film of water over it, and the use of an extremity coil. The scan resolution was of sufficient quality to direct the histopathologist to regions requiring microscopic examination and to map the progress of myelination.

Autopsy↗
PubMed1994

Spinal cord uptake of lead injected into muscle.

It has been hypothesised that some motor neuron diseases may result from lead (Pb) being retrogradely transported in axons from muscle to spinal cord. To test this hypothesis, we injected mice in the right hindlimb with 0.1 ml of 0.25% or 2.5% Pb. In some animals the sciatic nerve was cut before injection. Pb levels were measured in the lumbar and thoracic spinal cord and the kidney with atomic absorption spectrophotometry (AAS). Four weeks after injection, Pb was found in the spinal cord on AAS, with higher levels in the lumbar than the thoracic cord only in the high-Pb group. Sciatic nerve cut did not inhibit the passage of Pb to the cord. The results suggest that most Pb injected into muscle reaches the spinal cord via the blood or damaged axons, rather than via intact axons. These data do not support the hypothesis of Pb-induced motor neuron disease via retrograde axonal transport from muscle.

Animals↗
PubMed1993

Mitochondrial encephalomyopathy: variable clinical expression within a single kindred.

The clinical manifestations of mitochondrial encephalomyopathy are described in four generations of a single kindred. The age of onset of major neurological disturbance varied from 3-70 years. In some patients, deafness was the only manifestation; in others, recurrent bouts of status epilepticus associated with focal neurological deficits and headache, caused severe disability or death. Examples of all three adult forms of mitochondrial encephalomyopathy: MELAS, MERFF and Kearns Sayre syndrome, were represented within the kindred. Associated features included deafness, short stature, non-insulin-dependent diabetes mellitus, migraine, peptic ulceration and severe constipation. The nt 3243 A-G MELAS mutation was detected in two members of the kindred. This study highlights the diversity of clinical expression of a mitochondrial mutation within a single kindred.

Adolescent↗
PubMed1993

Present and future pathology teaching at the University of Sydney.

Major changes are planned for medical undergraduate teaching at the University of Sydney with the possible introduction of a four-year graduate degree. The reasons for teaching pathology to medical students and how it is now done are outlined. Planned changes in the course are presented to ensure that pathology maintains its pivotal position in marrying the basic and clinical sciences in undergraduate medical education.

Australia↗