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Biomedical subjects

M C Evans

Publications and source records attributed to M C Evans.

At least 91 records · Page 5Linked to original sources

Adjuvant radiotherapy for stage I, grade 2 endometrial adenocarcinoma and adenoacanthoma with limited myometrial invasion.

All cases of endometrial adenocarcinoma from January 1970 to December 1980 treated at the Geisinger Medical Center were reviewed retrospectively. One hundred eighty-eight cases of stage I grade 2 adenocarcinoma of favorable histologic subtype (adenocarcinoma, adenoacanthoma) and limited myometrial invasion (less than one-third of the myometrium) were identified. Surgery and adjuvant radiotherapy was used in 136 cases, and 52 cases were treated with surgery alone. There was no statistically significant difference between the two groups in menopausal status, parity, exogenous estrogen, obesity, hypertension, diabetes, or uterine size. Five-year survival for the surgery and radiotherapy group was 94% (128 of 136), and the recurrence rate was 2.2% (three of 136). The five-year survival for the surgery-alone group was 98% (51 of 52), and the recurrence rate was 1.9% (one of 52). There was no statistically significant difference in five-year survival or recurrence between the two groups. This study suggests that surgery alone is adequate treatment for stage I grade 2 adenocarcinoma of favorable histologic subtype and limited myometrial invasion. This study also shows a possible benefit in the combined use of histologic subtype, grade, and myometrial invasion as prognostic indicators and as guides for adjuvant radiotherapy.

Adenocarcinoma↗

Admission thyroid function testing in elderly patients.

The free thyroxine index (FTI) was measured in 307 elderly patients admitted to two geriatric units. The initial FTI was abnormal in 41 (13.3%), being raised in 27 and low in 14 patients. On further testing, these abnormalities were found to be either transient or of no clinical significance in 36 of the 41 patients (88%). Only five of the 307 patients (1.6%) were finally treated for previously undiagnosed thyroid disease and of these three improved (1%). Thyroid disease identified by routine screening, and not suspected from the history and clinical findings, was present in only two patients (0.7%). In view of these findings we suggest that thyroid screening is no more justified in the elderly than in younger hospitalised patients.

Aged↗

Detection of familial dysalbuminaemic hyperthyroxinaemia.

A simple test of in vitro thyroxine binding to serum proteins was used to screen serum samples from euthyroid patients with unexplained increases in the free thyroxine index. A diagnosis of familial dysalbuminaemic hyperthyroxinaemia was presumed in 14 unrelated subjects and six first degree relatives. Increased binding of thyroxine to thyroxine binding prealbumin was diagnosed in one woman with four unaffected relatives. Seven patients with familial dysalbuminaemic hyperthyroxinaemia had been treated for presumed thyrotoxicosis: two had typical Graves' disease and one subacute thyroiditis. Four other patients had been mistakenly treated with radioactive iodine or antithyroid drugs. In previously treated patients familial dysalbuminaemic hyperthyroxinaemia was suspected from the combination of a high serum thyroid stimulating hormone concentration and a normal but invalid free thyroxine index. Physicians should be cautious in accepting a diagnosis of thyrotoxicosis based mainly on a raised serum thyroxine concentration.

Adolescent↗

Role of proton motive force in phototactic and aerotactic responses of Rhodopseudomonas sphaeroides.

Rhodopseudomonas sphaeroides grown under nonrigorous anaerobic conditions in the light developed components of a branched respiratory electron transfer chain, and a photosynthetic electron transfer chain. Both respiratory pathways were sensitive to rotenone and high concentrations of cyanide, but oxygen uptake was only partially inhibited by the addition of low concentrations of cyanide or antimycin A. When incubated anaerobically in the dark, R. sphaeroides responded positively to an oxygen gradient in the absence of rotenone. In the presence of rotenone, aerotaxis only occurred when the antimycin A-sensitive branch of the pathway was functioning, although both branches still reduced oxygen. Although there was electron movement along the respiratory chain, aerotaxis only occurred in response to a change in proton motive force. When incubated anaerobically in the light, the movement of R. sphaeroides up a light gradient depended on photosynthetic electron transport. When incubated aerobically, high-intensity actinic illumination inhibited oxygen uptake and aerotaxis. In a low-intensity light gradient the phototactic response was inhibited by oxygen. These results are discussed in relation to the interaction of the electron transfer chains and their roles in controlling tactic responses in R. sphaeroides.

Chemotaxis↗

Regional brain glucose metabolism in chemically-induced seizures in the rat.

Measurement of regional brain glucose metabolism may give information concerning the mechanism of neuronal cell death developing after prolonged periods of epileptic activity. Regional brain glucose utilization was measured in paralyzed ventilated rats during seizures induced by L-allylglycine, kainic acid and bicuculline using the [14C]deoxyglucose method. Regional brain glucose concentration was measured in another series of rats, after similar periods of seizure activity, to permit a more accurate calculation of the lumped constant. In L-allylglycine-induced seizures regional brain glucose concentration did not vary from control values, so no correction of the lumped constant was necessary. Regional brain glucose utilization increased throughout the brain, the largest increase being in the hippocampus (control 36 +/- 6 mumol 100 g-1 min-1; seizure 120 +/- 12 mumol 100 g-1 min-1). In kainic acid-induced seizures, brain glucose concentration fell in the hippocampus, involving some correction of the lumped constant. Increases in glucose utilization were limited primarily to the hippocampus, with some involvement of the inferior colliculus. The ventral hippocampus showed the largest increase in glucose utilization (control 34 +/- 5 mumol 100 g-1 min-1; seizure 167 +/- 10 mumol 100 g-1 min-1). In bicuculline-induced seizures, in starved rats, brain glucose concentration fell in all regions investigated and no increase in regional glucose utilization was recorded. In L-allylglycine and kainic acid-induced seizures, the hippocampus, a region vulnerable to neuronal damage, shows the largest increase in glucose utilization. Studies involving bicuculline need further investigation, due to severe perturbation of brain and plasma glucose concentration.

Allylglycine↗

Goitre and thyroid dysfunction during chronic amiodarone treatment.

We measured thyroid function in a cross-sectional survey of 37 unselected patients receiving chronic amiodarone treatment. Palpable goitre was presented in 17 patients and was a new finding in ten. Despite frequent elevations of serum free T4 (67%) or free T4 index (43%), all 37 patients were clinically euthyroid with a normal or decreased serum free T3 or free T3 index. Mean urine iodide/creatinine excretion was increased 13-fold. Three patterns of thyroid function were seen; in 21 patients with normal TRH responses, the mean basal serum TSH was significantly elevated. Five patients had biochemical hypothyroidism which did not require treatment. Eleven patients had evidence of thyroid autonomy and the three patients with absent TRH responses each gave a past history of goitre or thyrotoxicosis; a trial of carbimazole treatment in these three was without clinical benefit. The observed spectrum of subclinical goitre and thyroid dysfunction may result from an unpredictable thyroid response to excessive free iodide combined with a weak goitrogenic effect of amiodarone mediated by increased TSH secretion.

Adult↗

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↗

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↗

Clinical and biochemical evaluation of patients with hirsutism.

Patients with moderate to severe hirsutism presenting over an 18-month period to an endocrine clinic were assessed by clinical evaluation and hormone measurements. Hair growth rate was estimated by a photographic technique and the severity of hirsutism graded using an objective scale. Of 43 patients, 9 had polycystic ovaries and the remainder were considered to have idiopathic hirsutism. The most severely affected group had significantly increased hair growth rates compared with less clinically affected subjects, and 47% of this group showed objective features of virilization. However, apart from a significantly higher 24-hr urine 17-ketosteroid excretion all other hormonal patterns were not significantly different between severely and mildly affected patients. Serum levels of testosterone (T), sex hormone-binding globulin (SHBG), free T (calculated from T and SHBG values), and androstenedione (A) were abnormal in 44%, 51%, 60% and 60% of patients respectively, whereas plasma levels of the specific adrenal androgen DHAS were increased in 40% of patients. There was an overlap between patients with elevated hormone levels, although isolated elevation of T, A or DHAS were seen in 9%, 19% and 3% of patients respectively. In 19% of patients all serum androgen measurements were normal. Gonadotrophin levels were significantly lower in the more severely affected group. Thus androgen levels in patients with idiopathic hirsutism or polycystic ovaries, show considerable overlap with measurements in normal subjects, and elevated plasma androgens may be of adrenal (DHAS) or combined adrenal/ovarian (T, A) origin.

17-Ketosteroids↗

Low thyroxine levels in some hyperprolactinemic patients due to dopaminergic suppression of thyrotropin.

The serum free T4 index (FT4I) was at or below the lower limit of normal in 8 of 55 unselected patients with hyperprolactinemia. Serum levels of T3 were normal and none of the patients had clinical evidence of hypothyroidism. In patients with low FT4I the serum TSH was within the normal range and TSH was released normally after administration of TRH, indicating normal pituitary TSH reserve. Serum TSH also increased after administration of the dopamine antagonist domperidone. The TSH response to domperidone was significantly greater in the hyperprolactinemic group with low FT4I compared with either normal subjects or hyperprolactinemic patients with normal FT4I, suggesting that depression of FT4I was due to increased dopaminergic activity. Administration of the dopamine antagonist metoclopramide for 4 days led to a supranormal rise in FT4I in 3 of 5 patients with low FT4I. Thus, a minority of hyperprolactinemic patients have a low FT4I which appears due to excessive hypothalamic production of dopamine.

Adult↗

Anticonvulsant action in the photosensitive baboon, Papio papio, of a novel beta-carboline derivative, ZK 91296.

The anticonvulsant action of ethyl-5-benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylate (ZK 91296) has been studied in Senegalese baboons, Papio papio, with photosensitive epilepsy. Myoclonic and paroxysmal electroencephalographic responses to stroboscopic stimulation are diminished or abolished for 2-4 h after ZK 91296, 0.25-4 mg/kg, i.v. Radioreceptor assay of plasma ZK 91296 indicates rapid clearance (t 1/2 alpha, 5-20 min and beta, 60-90 min). In this model of generalised epilepsy ZK 91296 is similar to diazepam in potency but has a longer duration of action.

Animals↗

The motile and tactic behaviour of Pseudomonas aeruginosa in anaerobic environments.

ATP generated by the anaerobic metabolism of L-arginine in Pseudomonas aeruginosa was used to maintain the membrane potential. Although both the ATP concentration and membrane potential were lower than in aerobically incubated bacteria, motility and chemotaxis were almost normal. Venturicidin stopped anaerobic motility by abolishing the membrane potential. The addition of venturicidin to aerobic bacteria caused an increase in the membrane potential, but a decrease in internal ATP concentration, resulting in bacteria which were motile but non-chemotactic. The membrane potential was the only requirement for continued motility but ATP was required in addition for chemotaxis.

Adenosine Triphosphate↗

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↗

Cortical GABA turnover during bicuculline seizures in rats.

The rate of cortical gamma-aminobutyric acid (GABA) turnover was estimated by determining the rate of GABA accumulation following inhibition of GABA transaminase by gamma-vinyl-GABA (1.5 g/kg, i.v.) in paralysed, ventilated rats. During 1 h of bicuculline-induced seizures (1.2 mg/kg, i.v.) the rate of accumulation of cortical GABA level is approximately threefold greater than in the control group receiving gamma-vinyl-GABA alone, suggesting that the GABA shunt activity increases in parallel with the increase in overall cortical metabolic rate observed during bicuculline seizures. Pretreatment with gamma-vinyl-GABA did not affect the bicuculline-induced changes in other major cortical amino acids.

Aminocaproates↗

Effect of cyproterone acetate on glucocorticoid secretion in patients treated for hirsutism.

The effect of cyproterone acetate (CA) on adrenal glucocorticoid secretion was studied in 35 women with hirsutism. Patients were treated for 9 months with 100 mg CA orally 10 days each month, administered in reverse sequence with 21 days of a combination oral contraceptive containing 50 micrograms ethinyloestradiol and 2 mg CA. During treatment one patient had a mildly impaired plasma cortisol response to insulin-induced hypoglycaemia and 2 patients showed slight reduction of the plasma cortisol response to ACTH. Responses to metyrapone were normal in all patients tested. Overall, the mean response to these tests was significantly greater during CA treatment compared with pre-treatment measurements, probably due to effects of oestrogen on cortisol-binding globulin. In all patients urinary cortisol excretion remained normal and no patient demonstrated any features of steroid insufficiency. Thus it appears that CA has no untoward effect upon glucocorticoid secretion when given in high dosage for prolonged periods to hirsute women.

17-Hydroxycorticosteroids↗