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Biomedical subjects

T Griffiths

Publications and source records attributed to T Griffiths.

15 recordsLinked to original sources
PubMed1988

Randomized trial comparing aminoglutethimide with high-dose medroxyprogesterone acetate in therapy for advanced breast carcinoma.

A total of 218 postmenopausal patients were entered in a prospective randomized trial comparing aminoglutethimide (AG) and high-dose medroxyprogesterone acetate (MPA) as second-line hormonal therapy for advanced breast carcinoma. All responses were assessed by the criteria of the International Union Against Cancer. The response rates were 27% (29 of 106 patients) for AG and 31% (35 of 112) for MPA, but if stabilization of previously progressive disease is included, then the overall response rates were 51% (54 of 106) and 54% (61 of 112) for patients receiving AG or MPA, respectively. There was no difference in response to the two drugs at any site of disease, and the durations of response and survival were identical for the two drugs. The time to response was significantly shorter for patients treated with MPA (median, 8.7 wk) than for those treated with AG (median, 15.3 wk) (chi 2 = 9.96, 1 df, P = .0016). The percentage of patients experiencing toxic effects was equivalent in both arms, although the patterns and time courses of these effects were different.

Aminoglutethimide↗
PubMed1987

Evaluation of psychological treatment in primary care.

As clinical psychology services to primary care have grown considerably in recent years, several papers have examined the impact of such services. Benefits to patients following contact with the psychologist have been described, but the few studies which have used control groups have -not shown long-lasting effects. However, assessing the global effects of psychological treatment creates several methodological problems, and many of the studies have serious shortcomings in their use of sampling procedures and dependent measures. Clear results are unlikely to emerge from such studies because psychological treatment is not a single entity but encompasses a number of interventions for different types of problem. A more differentiated approach to evaluation is needed to assess the effectiveness of psychological treatment services in primary care.

Humans↗
PubMed1984

Blockade of N-methyl-D-aspartate receptors may protect against ischemic damage in the brain.

In rats ischemia of the forebrain induced by a 30-minute occlusion of the carotid artery, followed by 120 minutes of arterial reperfusion, produced ischemic lesions of selectively vulnerable pyramidal cells in both hippocampi. Focal microinfusion into the dorsal hippocampus of 2-amino-7-phosphonoheptanoic acid, an antagonist of excitation at the N-methyl-D-aspartate-preferring receptor, before ischemia was induced protected against the development of ischemic damage. It is proposed that excitatory neurotransmission plays an important role in selective neuronal loss due to cerebral ischemia.

2-Amino-5-phosphonovalerate↗
PubMed1984

Status epilepticus: the reversibility of calcium loading and acute neuronal pathological changes in the rat hippocampus.

Light and electron microscopy (with the combined oxalate-pyroantimonate technique for the electron microscopic visualization of intracellular calcium) were used to compare the hippocampal pathology in rats killed immediately after 1.5-2 h of L-allylglycine-induced seizures with that in rats allowed 15-60 min of a seizure-free "recovery" period before perfusion fixation. Following 1.5 h of seizure activity, cellular pathology included astrocytic swelling and dark cell degeneration of pyramidal and polymorphic neurons. This was accompanied by a marked increase in the amount of calcium pyroantimonate deposits, particularly in swollen and disrupted mitochondria of CA1 and CA3 basal dendrites and in certain neuronal cell bodies in the CA1 and CA3 regions and the hilus. After a seizure-free period of between 30 and 60 min the hippocampi showed almost complete recovery except for a few remaining dark, shrunken cells. The majority of these were presumed to be interneurons. The ultrastructural changes were consistent with the observations by light microscopy. By 60 min, excess calcium deposits had disappeared except in the dark cells in which intracellular vacuoles retained deposits. We conclude that most of the pathological changes observed after 1.5 h of L-allylglycine induced status epilepticus, including the mitochondrial calcium "overload" are reversible. At 1 h after termination of status epilepticus apparently irreversible pathology (dark cell change, "ischaemic cell change") concerns predominantly the polymorphic neurons.

Animals↗
PubMed1984

Calcium overload in selectively vulnerable neurons of the hippocampus during and after ischemia: an electron microscopy study in the rat.

Light and electron microscopy has been used to study the cytopathological changes in the rat hippocampus directly after a 30-min period of forebrain ischemia and after 30 or 120 min of reperfusion. The fine structural localization of calcium has been demonstrated using the oxalate/pyroantimonate procedure. Cellular changes considered typical of ischemia (swelling of astrocytic processes, distention of mitochondria, condensation of cytoplasm, "ischemic cell change") are most prominent after 30 min of reperfusion. At this time, dense calcium pyroantimonate deposits are evident in swollen mitochondria in pyramidal and hilar neurons. After 120 min of reperfusion, substantial restitution has occurred; most mitochondria appear normal and there are few calcium deposits. However, a small number of selectively vulnerable neurons (hilar and pyramidal neurons) show dense condensation (ischemic cell change) with multiple vacuoles containing calcium deposits. The role of excessive calcium entry and mitochondrial calcium overload during the reperfusion period in determining the death of selectively vulnerable neurons is discussed.

Animals↗
PubMed1983

Intracellular calcium accumulation in rat hippocampus during seizures induced by bicuculline or L-allylglycine.

Using electron microscopy and the combined oxalate-pyroantimonate technique, free calcium ions were located in the hippocampus of control rats and of those that had undergone status epilepticus induced by L-allylglycine or bicuculline. The validity of this technique was established by the use of the calcium chelating agent ethylene glycol bis(beta-aminoethyl ether), N,N'-tetra-acetic acid and by an X-ray microanalytical technique. In control material, calcium deposits were visible in synaptic vesicles and multivesicular bodies, in parts of the Golgi apparatus, mitochondria, lysosomes, and in glial and neuronal nuclei. Following 2 h of status epilepticus, cellular pathology included astrocytic swelling, and dark cell degeneration of pyramidal neurons. This was accompanied by a marked increase in the amount of calcium pyroantimonate deposits, particularly in swollen and disrupted mitochondria of CA1 and CA3 basal dendrites, and in selected neuronal cell bodies in the CA1 and CA3-4 regions. We propose that enhanced calcium entry into neurons and consequent overloading of the capacity of mitochondria for calcium sequestration is part of the cytotoxic mechanism leading to selective neuronal loss in the hippocampus in status epilepticus.

Allylglycine↗
PubMed1981

Sub-etioplast localization of the enzyme NADPH: protochlorophyllide oxidoreductase.

The membranes from oat etioplasts have been separated by sucrose density gradient centrifugation into a heavy fraction of density 1.20 mg/ml (prolamellar body fraction) and a light fraction of density 1.12 mg/ml (prothylakoid fraction). The light fraction was shown to be enriched in protein, protochlorophyllide and the chloroplast enzyme CF1-ATPase, but to be deficient in saponins. In the electron microscope this fraction appeared as swollen vesicles. In contrast the heavy fraction appeared considerably enriched in crystalline, tubular material and was on analysis found to contain most of the etioplasts' saponin but with reduced protein and pigment. In the same experiments the enzyme NADPH: protochlorophyllide oxidoreductase showed the same distribution pattern as the CF1-ATPase suggesting its location on the prothylakoids.

Adenosine Triphosphatases↗
PubMed1979

Interstitial cystitis.

Twenty histologically proven cases of interstitial cystitis were investigated in an attempt to find evidence of a possible autoimmune mechanism in its aetiology. HLA tissue typing was performed, autoantibody profiles were obtained, and a questionnaire of the patients' past history completed, especially with respect to other autoimmune conditions. An experiment was designed to test the effect of sodium cromoglycate on rat bladders. The results are discussed in relation to the management of patients with interstitial cystitis.

Aged↗
PubMedDate not supplied

Early changes in the rat hippocampus following seizures induced by bicuculline or L-allylglycine: a light and electron microscope study.

Status epilepticus was induced in thirteen paralysed and ventilated rats by the injection of either bicuculline or L-allylglycine. After 1-2 h of seizure activity the animals were intracardially perfused with a 2% glutaraldehyde/3% paraformaldehyde solution. Hippocampal blocks from each rat were processed for light and electron microscopy. The effects of L-allylglycine were more severe than those of bicuculline. Changes include perivascular and perineuronal swelling of astrocytic processes, and neuronal alterations which were graded as follows: Grade I (least severe), neuronal cytoplasm appears slightly darker than usual; Grade II, condensed or dark neurons, usually with microvacuoles; and Grade III classical 'ischaemic cell change'--the cytoplasm and karyoplasm is dark and shrunken, with or without microvacuoles. Many of the microvacuoles originate from mitochondria. In a few cases swollen and disrupted mitochondria are also seen is distended basal dendrites of the CA3 and CA1 pyramidal neurons. Dentate granule cells appear unaffected. The hippocampal neuronal alterations induced by seizure activity include those of 'ischaemic cell change'. The pathogenetic factors common to hypoxia/ischaemia and status epilepticus remain to be identified.

Allylglycine↗
PubMedDate not supplied

Kainic acid seizures and the reversibility of calcium loading in vulnerable neurons in the hippocampus.

The threshold pathological changes in the rat hippocampus following systemic administration of kainic acid (12-15 mg/kg) have been studied in relation to i the duration of EEG seizure activity and ii calcium accumulation in post-synaptic neurons, using the oxalate-pyroantimonate method. The reversibility of the pathological changes and calcium loading has been studied from 40 min to 48 h after the termination of seizure activity. Little or no changes were visible 2-3 h after 12 mg kainic acid per kg, but changes were obvious in most hippocampi directly after 2-3.5 h of seizure activity induced by 15 mg kainic acid per kg. These consisted of generalized swelling of perineuronal and perivascular astrocytic processes, neuronal hyperchromasia and microvacuolation, and swelling of CA1 basal dendrites. 'Ischaemic cell change' occurred in a small number of pyramidal neurons. Calcium accumulated in mitochondria of basal dendrites and in the soma of pyramidal neurons in CA1 and CA3. Astrocytic and dendritic swelling and mitochondrial calcium accumulation were rapidly reversed during 40 min of seizure suppression with diazepam. Calcium accumulation in astrocytic processes recovered more slowly (greater than or equal to 4 h). After a recovery period of 24-48 h, ischaemic cell changes were seen only in very occasional pyramidal neurons. The pattern of pathological changes is very similar to that seen after L-allylglycine or bicuculline-induced seizures. If the dendritic and other changes are a direct consequence of agonist actions at excitatory amino acid receptors (pre- or post-synaptic) then similar actions must be occurring in seizures induced by agents acting primarily on GABAergic inhibition.

Animals↗