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Biomedical subjects

M G Hadfield

Publications and source records attributed to M G Hadfield.

At least 37 records · Page 2Linked to original sources

Regional brain monoamine levels and utilization in middle-aged rats.

Significant changes in monoamine levels and utilization were noted in certain brain regions of middle-aged Fisher 344 rats when compared with young adult controls. In the prefrontal cortex and septum, 3,4 dihydroxyphenylglycol (MHPG) and the MHPG/norepinephrine (NE) ratio were decreased. The septum also showed increases in dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) but there was a decrease in the DOPAC/DA ratio. The striatum showed an increase in the MPHG/NE ratio and an increase in DOPAC. The hippocampus and thalamus showed an increase in 5-hydroxyindoleacetic acid (5HIAA). This demonstrates that selected neurotransmitter systems in the brain are altered at an early stage of senescence. This could lead to ensuing neurological deficits.

3,4-Dihydroxyphenylacetic Acid↗

Granulomatous angiitis of the nervous system: a case report of long-term survival.

In 1977, a 61-year-old man developed an occipital hemorrhage, and a biopsy specimen revealed granulomatous angiitis of the nervous system. No concurrent infection or systemic vasculitis was present. After initial treatment with steroids and cyclophosphamide, the patient did well on chronic steroids alone for 4 years. He then independently stopped taking the steroids and suffered a second hemorrhage. Steroids were reinstated, and he did well for 3 more years before he experienced a third hemorrhage. Intravenous steroids were given acutely and tapered to a chronic maintenance dose. Although granulomatous angiitis of the nervous system usually causes death within weeks to months of the appearance of symptoms, the patient is still alive more than 12 years since the tissue-proven diagnosis. This unusually long survival is attributed to the continued use of steroids, even when the patient is asymptomatic.

Central Nervous System Diseases↗

Caffeine and regional brain monoamine utilization in mice.

Caffeine (100 and 200 mg/kg, 30 min., i.p.) selectively altered the regional utilization of monoamines in the brains of mice. This depended upon the specific neurotransmitter and metabolite studied. Caffeine increased serotonin (5HT) utilization a dramatic ten-fold in the OB but decreased 5HT utilization in the HT. No 5HT changes were seen in other brain regions. Caffeine markedly increased norepinephrine (NE) utilization in the olfactory bulbs (OB), olfactory tubercles (OT), prefrontal cortex (PC), amygdala (AMY), hypothalamus (HT) and hippocampus (HC). Caffeine increased dopamine (DA) utilization in the OB, OT, PC, septum (SP), HT and thalamus (TH) but by various metabolic routes. The selective regional alterations in monoamine utilization produced by caffeine may be relevant to caffeine's central stimulatory effects. Limbic structures are predominantly involved. These changes may have important clinical and research implications. For example, the profound effect of caffeine on OB monoamines indicates that it may serve as a meaningful tool in olfactory research, including the bulbectomy model. Caffeine may also be useful in other limbic system behavioral models.

3,4-Dihydroxyphenylacetic Acid↗

Isolation-induced fighting in mice and regional brain monoamine utilization.

The utilization of norepinephrine, dopamine and serotonin was measured in ten brain regions of isolated fighting mice and resting control animals. Fighting produced a markedly significant change in the utilization of dopamine (P greater than 0.006), but not in norepinephrine or serotonin. However, important trends were identified in the latter systems which warrant further testing. This study highlights the importance of dopaminergic participation in fighting behavior.

Aggression↗

Rimcazole (BW 234 U) and regional monoamine concentrations in mouse brain.

Rimcazole (BW 234 U), a novel agent with antipsychotic potential, was administered i.p. (50 mg/kg) to adult male ICR mice 30 minutes before brain removal. Regional HPLC analysis of central monoamine levels showed no change in the DOPAC/DA ratio for any tissue as compared with values obtained from control saline treated animals. However, the MHPG/NE ratio was increased in the septum, striatum, hypothalamus and thalamus and there was a reciprocal decrease in the 5HIAA/5HT ratio in the septum. The data are consistent with a known lack of rimcazole affinity for dopamine receptors and indicate the involvement of alternate neurotransmitter systems in the actions of this drug.

3,4-Dihydroxyphenylacetic Acid↗

Anterior horn changes of motor neuron disease associated with demyelinating radiculopathy.

Morphologic study of the spinal cord of a patient with generalized motor deficits revealed changes in the anterior horns characterized by the selective loss of large motor neurons, gliosis and the abnormal accumulation of 10 nm filaments which appeared as argyrophilic spheroids in the perikarya and axons of motor neurons. The ventral roots were predominantly affected and showed a variable loss of axons. The remaining axons displayed prominent onion-bulb formations, frequent axonal sprouting and occasionally evidence of active demyelination. The coexistence of a demyelinating motor radiculopathy and anterior horn changes simulating those of amyotrophic lateral sclerosis (ALS) may contribute to our understanding of the unresolved question of whether the neuronal perikaryon or its axon is the primary target in the pathogenesis of ALS. These observations also indicate that a rigid separation of pathogenetic mechanisms into neuronopathy, axonopathy and myelinopathy may not be always possible.

Axons↗

Large brain metastasis not shown by computerized tomography.

We have described a patient with metastatic small cell carcinoma of the lung in whom cranial CT and contrast-enhanced CT failed to show metastases. When the patient died four days later, two sizable intracerebral metastatic foci were found at autopsy. Reviewing previously reported causes of nonvisualization of lesions, we have speculated on reasons for the lack of CT findings in this case.

Aged↗

Xanthogranulomatous colloid cyst of the third ventricle.

This is a case report of a xanthogranulomatous colloid cyst of the 3rd ventricle. Possible etiologies for this rare entity, along with the clinical problems that may be associated with it, and the differential diagnosis are discussed.

Adult↗

Echovirus meningomyeloencephalitis with administration of intrathecal immunoglobulin.

Echovirus meningomyeloencephalitis was treated with cerebral intraventricular immunoglobulin. This case includes a complete examination of the central nervous system (CNS) supported by viral culture studies, immunoperoxidase staining and electron microscopy. Neuronal loss was most severe in the cerebellum and spinal cord. This may lead to the ataxia and a poliomyelitis-like syndrome often seen in cases of echovirus meningomyeloencephalitis. Focal encephalitic lesions, antigen-antibody reactions and live virus were found at numerous levels of the CNS in spite of intrathecal and intravenous immunoglobulin therapy. This mode of therapy and the electron microscopic features noted in echovirus infections are discussed.

Adult↗

A comparison of in vivo and in vitro amphetamine on the synaptosomal uptake of dopamine in mouse striatum.

Amphetamine (AMPH) produced competitive uptake inhibition of 3H-dopamine (DA) in synaptosomes obtained from mouse striatum--whether it was injected beforehand into living animals or simply added to the incubation medium. However, the in vivo drug doses required to produce this effect were high (ED50 = 65 mg/kg.) as compared with the in vitro doses (ED50 = 2.5 X 10(-6) M).

Amphetamine↗

Dopamine: mesocortical vs nigrostriatal uptake in isolated fighting mice and controls.

Acute isolation-induced fighting in mice produced a striking 'dose-dependent' increase in Km and Vmax for DA uptake in mesocortical nerve endings (synaptosomes) but no significant changes for these uptake constants in nigrostriatal terminals. The selective response of the mesocortical system to fighting is similar to that reported for other affective paradigms and stress. Several controls were carried out simultaneously to sort out neurotransmitter responses due to aggressive behavior from those due to secondary behaviors which accompany fighting. Non-significant or borderline increases in Km and Vmax for mesocortical DA uptake were noted in (i) animals permitted to witness fighting but prevented from participating, (ii) those subjected to the stress of a mock-fighting situation and (iii) animals simply handled by the investigator, but in no case were the control values increased to the magnitude produced by fighting. (iv) Group-housed animals showed no mesocortical response when placed in the arena with isolated mice. They retired to the corners and would not fight. These mild to negative control findings indicate that the marked cortical responses seen in the fighting animals are not due to (i) anticipation of the fight, (ii) physical stress and motor activity, (iii) placing the animals in the combat arena, or (iv) isolation. Significant changes in nigrostriatal DA reactivity were noted only in the isolated animals prevented from fighting where there was a decrease in Km and Vmax for DA uptake.

Aggression↗

Cocaine: peak time of action on isolation-induced fighting.

Cocaine (35 mg/kg i.p.) produced a peak increase in fighting duration in isolated male ICR mice at 30 minutes. However, the crest of this peak ranged from 15--45 minutes. During the offset period (45--120 min.), fight duration remained elevated, but at a lower level. At 240 and 360 minutes, fighting had essentially returned to control levels. The results coincide with peak effects reported by others for locomotor activity, stereotypy, and other cocaine-induced behaviors in animals but later than physiological and subjective parameters measured in human volunteers (cocaine addicts) after intravenous and intranasal administration of the drug.

Administration, Intranasal↗

Mesocortical vs nigrostriatal dopamine uptake in isolated fighting mice.

Preferential uptake of dopamine occurred in mesocortical vs striatal synaptosomes obtained from acutely fighting isolated male ICR mice. Specifically, both Km and Vmax were significantly increased in the prefrontal cortex but not the caudate-putamen. The findings are similar to selective changes in mesocortical activity produced by various 'affective' stimuli as reported by others and they signal that higher DA emotive centers are importantly involved in agonistic behavior.

Aggression↗

Pathologic findings in mucopolysaccharidosis type IIIB (Sanfilippo's sydnrome B).

The pathologic changes in a rare case of mucopolysaccharidosis (MPS) type IIIB or Sanfilippo's syndrome B (absence of alpha-N-acetylglucosaminidase) are presented, along with the biochemical findings. Comparisons were made with other reported cases of MPS III subtypes and related storage disorders in terms of clinical, light microscopic, electron microscopic, and chemical findings, and a correlation of the ultrastructural changes made with the severe neurological dysfunction noted in this disorder. At present, MPS III subtypes cannot be separated from one another by morphological means because the same expression and distribution of lesions may be encountered among differing subtypes.

Adolescent↗