The post-anaesthetic recovery unit at the Royal Hallamshire Hospital, Sheffield.
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Anesthesia, General↗
Biomedical subjects
J Hardy
Publications and source records attributed to J Hardy.
Intra- and extra-dopamine-synaptosomal localization of monoamine oxidase in striatal homogenates from four species.
MAO-A and MAO-B activities within and outside dopaminergic synaptosomes in homogenates of striatal tissue from pig, cat, rat and human brains have been studied by using a specific "low substrate concentration technique" with dopamine. It was found that within the synaptosomes, MAO-A activity predominated in all species. Outside the synaptosomes there were more pronounced differences and only in the rat did MAO-A predominate, while in the other species MAO-B predominated. When estimating MAO-A and -B activities with a conventional method the activity of MAO-B predominated in man, cat and pig. Thus, also in species where the MAO-B activity (as estimated in a conventional way) was dominating, the intrasynaptosomal deamination of dopamine was brought about mainly by MAO-A. The "low substrate concentration technique", more adequately reflects physiological conditions by taking into account the higher concentration of monoamine transmitter substrates within the monoamine neurons. With this technique it was found that in all species (with the possible exception of man) the oxidation rate was higher within than that outside the DA-synaptosomes. In man the unavoidable longer time between death and estimation of the enzyme activity may be the cause of the deviating result.
Animals↗
A disorder of cortical GABAergic innervation in Alzheimer's disease.
Synaptosomal gamma-aminobutyric acid (GABA) uptake has been used as a biochemical marker for GABAergic terminals in controls and Alzheimer disease brains. Use of this marker suggests a large (ca. 70%) loss of cortical and hippocampal GABA terminals in Alzheimer brain. To explain this observation we suggest that neuron loss in this disorder occurs via a process of cortical retrograde degeneration. This scheme reconciles our findings with previous neurochemical measurements on Alzheimer disease brains and also better reconciles the biochemistry with the histology of the disorder.
Aged↗
Region-specific loss of glutamate innervation in Alzheimer's disease.
Synaptosomal D-aspartate has been used as a marker for glutamate neurons in control and in postmortem Alzheimer's disease brains. This technique shows a marked (60%) decrease of the glutamate uptake site in cortical and hippocampal regions. There were no significant changes in subcortical regions. We interpret these results as indicating loss of, or damage to, cortical glutamatergic innervation. These losses probably represent the biochemical correlate of pyramidal neuron damage in Alzheimer's disease.
Alzheimer Disease↗
Do tetrahydroaminoacridine (THA) and physostigmine restore acetylcholine release in Alzheimer brains via nicotinic receptors?
In the presence of 9-amino-1,2,3,4-tetrahydroacridine (THA) 10(-4) M or physostigmine 10(-4) M, the in vitro 3H-Acetylcholine (3H-ACh) release from control cortical slices was significantly reduced. In contrast, THA 10(-4) M and physostigmine 10(-4) M significantly increased the release of 3H-ACh in AD/SDAT brain tissue. This facilitating effect on 3H-ACh release was partially blocked (50%) in the presence of the nicotinic antagonist d-tubocurarine 10(-6) M indicating a possible interaction via nicotinic receptors. The muscarinic antagonist atropine 10(-5) M significantly increased the 3H-ACh release both in control and AD/SDAT brains, thus indicating preservation of muscarinic autoreceptors in the AD/SDAT cortical tissue. In receptor competition studies with 3H-nicotine, 3H-ACh and 3H-quinuclidinyl benzilate (3H-QNB) as receptor ligands, THA interfered with both nicotinic and muscarinic receptor ligand binding, while physostigmine had much less effect.
Acetylcholine↗
Hyperprolactinemia associated with clinically silent adenomas: endocrinologic and pathologic studies; a report of two cases.
Pituitary adenomas containing adrenocorticotropic hormone (ACTH) in one case, and ACTH, beta-lipotropin, and beta-endorphin in the other, were demonstrated in two patients who had amenorrhea-galactorrhea and hyperprolactinemia with no manifestation of Cushing's disease. Neither adenoma contained prolactin (PRL). Initial bromocriptine therapy resulted in cessation of amenorrhea-galactorrhea and normalization of PRL levels. However, there was radiologic evidence of tumor enlargement in both patients. After pituitary adenomectomy, the two patients resumed regular menses and normal PRL dynamics. These patients illustrate the need for bromocriptine therapy for possible enlargement of their pituitary adenomas. The diagnosis of silent corticotroph adenoma should be kept in mind.
Adenoma↗
Distinctive features of prolactin secretion in acromegalic patients with hyperprolactinaemia.
We have investigated the relationship between the plasma PRL concentrations of 98 untreated acromegalic patients and the GH levels during basal and dynamic conditions. Hyperprolactinaemia was present in 27 patients. In patients with marked hyperprolactinaemia (PRL greater than 80 ng/ml or greater than 1600 mU/l), basal plasma PRL and the TRH-induced response correlated with basal plasma GH (correlation coefficients of 0.9, P less than 0.001 and 0.74, P less than 0.02, respectively). The PRL response to TRH also correlated with GH response to TRH (r = 0.38, P less than 0.01). In contrast, in patients with moderately elevated PRL (20 to 80 ng/ml), and in those with normal plasma PRL (less than 20 ng/ml or less than 400 mU/l), no such correlations were found. Immunostaining for PRL was positive in 24 out of 25 adenomas of patients with hyperprolactinaemia, while no PRL was found in the tumour tissue of 10 normoprolactinaemic patients. In conclusion, our data suggest the existence of two populations of acromegalic patients with hyperprolactinaemia, one group with correlations between GH and PRL secretion, and the other without.
Acromegaly↗
Cyclical edema and hypokalemia due to occult episodic hypercorticism.
Yearly episodes of edema, hypokalemia, anxiety, and depression were found to be due to cortisol and deoxycorticosterone surges secondary to a pituitary adenoma in a woman without any of the usual clinical features of Cushing's syndrome. During the long clinical remissions, she had no recognizable laboratory abnormality. She had two episodes in the year following incomplete transphenoidal pituitary tumor resection, but has had none in 2 yr since receiving radiotherapy. The episodes were caused by mineralocorticoid actions of large ACTH-induced increases in cortisol and deoxycorticosterone secretion. A history of episodic edema and hypokalemia, often attributed in women to surreptitious diuretic abuse, requires a careful search for hypercorticism even in the absence of clinical Cushing's syndrome.
Adenoma↗
Arterial supply of the human anterior pituitary gland.
The vascular anatomy of the anterior lobe (AL) of 182 previously injected human pituitary glands was examined. Three different techniques of injection using India ink and acrylic paints were performed to establish a direct arterial supply to the AL. In 81% of the cases, end-arteries were found in the AL. Their participation in the vascularization of the adenohypophysis is variable from a small subcapsular area to almost the entire lateral parts of the AL. Arteries playing some role in the perfusion of the AL are subdivided into infra- and supradiaphragmatic, according to their topography in relation to the diaphragma sellae. Evidence of the presence of end-arteries in the AL is in disagreement with the generally accepted concept of a purely portal supply to this part of the pituitary gland.
Adolescent↗
The diagnostic accuracy of preoperative CT scanning in the evaluation of pituitary ACTH-secreting adenomas.
Between 1980 and 1985, 35 patients (26 women and nine men) who had coronal CT scans of the sella turcica for suspected ACTH-secreting pituitary adenoma underwent transsphenoidal exploration. The CT examinations were performed with a fourth-generation EMI scanner (CT 7070). The reports of the preoperative CT examinations were compared with the findings at transsphenoidal exploration; in cases with negative CT scans, the decision to operate was based on biochemical evidence of Cushing's disease. In 27 patients, distinct adenomas were found at surgery; in the eight others, total hypophysectomy (four cases) or resection of the central core of the pituitary gland (four cases) was performed. Three patients had macroadenomas, all of which had been identified correctly on preoperative CT scan. Among the 24 microadenomas (less than 10 mm diameter), 14 had been correctly identified on preoperative CT scan while 10 were found in patients with negative scans. The CT examinations in these 35 patients showed probable adenomas in 20 cases, of which 17 (85%) were confirmed at surgery. In the other three cases (15%), adenomas were not found. Among the 15 patients with negative CT scans, 10 (66.6%) had distinct adenomas found at surgery. Coronal CT scans for ACTH-secreting adenomas had a sensitivity of 63%, a specificity of 62.5%, and an overall accuracy rate of 62.8%. Thus, in our experience, CT scanning with current state-of-the-art equipment has poor diagnostic accuracy in Cushing's disease. The possible reasons for this are that most of the adenomas in this series were microadenomas less than 6 mm in diameter, and that ACTH microadenomas probably show almost the same degree of enhancement with contrast medium as the surrounding normal pituitary tissue.
Adenoma↗
Oral administration of erythrocyte membrane antigen does not suppress anti-Rh(D) antibody responses in humans.
The effects of prior oral administration of erythrocyte membrane preparations (Oral Rh antigen) on the serum anti-Rh(D) antibody response has been evaluated in non-sensitized Rh(D)-negative male volunteers, and in female volunteers sensitized previously by Rh(D)-positive fetal blood during pregnancy. Sixty-one percent (11/18) of males who received oral Rh antigen (either D-positive or D-negative) before intravenous challenge with Rh(D)-positive cells produced detectable antibodies; of these 11, six received oral Rh(D)-negative antigen and five received oral Rh(D)-positive antigen. Seventy-two percent (13/18) of control males, who had received no prior oral Rh antigen, produced antibodies following challenge with Rh(D)-positive cells. Three out of six pre-sensitized females who received oral D-positive or D-negative Rh antigen for 4 weeks, but without intravenous challenge, increased their anti-Rh(D) antibody levels which peaked after 11-18 weeks: two had received Rh(D)-positive antigen, and one Rh(D)-negative antigen. These data indicate that administration of oral Rh antigen before parenteral immunization does not significantly suppress the anti-Rh(D) antibody response. Indeed, oral administration of either Rh(D)-positive or Rh(D)-negative antigen can boost systemic antibody in pre-sensitized females. These results do not support the rationale of treating Rh-sensitized pregnant women with oral Rh antigen.
Administration, Oral↗
Microsurgical anatomy of the pituitary gland and the sellar region. 1. The pituitary gland.
The microsurgical anatomy of the pituitary gland was studied on dissections of 250 cadaver sphenoidal blocks and on detailed operative reports of 266 patients who underwent transsphenoidal hypophysectomy (185 breast cancer patients and 81 patients with diabetic retinopathy). Whereas the various measurements (width, length, height, weight) and the structures of the two lobes of the pituitary gland were studied in cadavers, texture, consistency, color, and attachment to surrounding structures were best observed during surgical procedures. These latter aspects of the pituitary gland were correlated with the age, sex, and hormonal status of the patients. Variations in the shape, size, and appearance of the pituitary gland are frequent. Knowledge of such variations is important for a precise microsurgical approach to the sellar region.
Adult↗
Microsurgical anatomy of the pituitary gland and the sellar region. 2. The bony structures.
Measurements of the sella turcica (depth, length, width, volume, thickness of the floor, intraclinoid distance, length of tuberculum sellae) were made in cadaver sphenoid blocks, skulls, and in patients undergoing transsphenoidal surgery. Variations in the sphenoidal septae, sinuses and bulging of surrounding structures (carotid arteries and optic nerves) were studied. Results were compared with observations made during surgery and with data reported in the literature. Anatomic variations of the sella turcica and sphenoid sinus may complicate surgical intervention in the region of the sella turcica. However, these variations were never, in our experience, the cause for interruption of transsphenoidal surgery.
Cadaver↗
An in-service training programme for recovery room nurses.
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Humans↗
Osteochondrosis-like lesion of the anconeal process in two horses.
A suspected lesion of osteochondrosis dissecans involving the anconeal process of the humeroradial joint (elbow) was found in 2 horses. In horse 1, the lesion was found during routine lameness examination, during which alleviation of the lameness was achieved after intra-articular anesthesia of the elbow. In horse 2, the lesion was found at necropsy. Horse 1 responded satisfactorily to intra-articular treatment with hyaluronic acid. Both horses also had other joints affected with osteochondrosis dissecans.
Animals↗
Physostigmine restores 3H-acetylcholine efflux from Alzheimer brain slices to normal level.
A technique was developed, which made it possible to study the in vitro release of 3H-acetylcholine (3H-ACh) from human post mortem brain tissue, collected with short post-mortem delay (2,5-22 hours), both from controls and patients with Alzheimer's disease (AD/SDAT). The tritium (3H) release was investigated during potassium stimulation, and AD/SDAT cortical slices were found to release a decreased amount of 3H compared to control brain slices. Physostigmine, 10(-5) and 10(-4) M, has no significant effect on the release of 3H from control slices, while physostigmine 10(-4) M increased the evoked release from AD/SDAT brain slices over threefold, nearly to the control level.
Acetylcholine↗
Effect of insulin-like growth factors on human foetal, adult normal and tumour pituitary function in tissue culture.
To determine the direct effects of insulin-like growth factors (IGFs) on hormone release by the human pituitary gland, human foetal, adult normal and tumour pituitary tissues were maintained in culture for 2 to 4 weeks and tested with acute (3 h) exposures to different preparations of IGF peptides. Adult normal pituitaries and adenomas were tested with a semipurified preparation of IGFs, free of immunoreactive insulin, containing IGF-I and IGF-II in a ratio of approximately 1:4. Human foetal pituitaries were tested with the semipurified IGFs as well as more purified preparations of IGF-I and IGF-II. Culture media were assayed for hGH, hPrl, hACTH and hLH using specific radioimmunoassays. Both foetal (n = 16 (No. of pituitaries), 33 (No. of observations] and normal adult (n = 3, 16) human pituitaries cultures responded to the semipurified IGFs (2-25 ngEq/ml for foetal and 2-4 ngEq/ml for adult pituitaries) with a significant decrease in hGH release compared to basal (P less than 0.01) whereas the GH-secreting pituitary tumours showed no effect when tested with from 2 to 25 ngEq/ml (n = 8, 129, NS). The effect of IGFs on human foetal somatotrope activity was dose-related for both the semipurified IGFs (2-25 ngEq/ml, n = 16, 33) and IGF-I or IGF-II (10-100 ng/ml; n = 3, 18).(ABSTRACT TRUNCATED AT 250 WORDS)
Adenoma↗
Human corticotroph cell adenomas.
Sixty-one pituitary corticotroph adenomas from 47 patients with Cushing's disease, 10 with Nelson's syndrome, and four eucorticoid patients were studied by light microscopy, immunoperoxidase, and electron microscopy. Seventy nine percent of all tumors and 70% of Nelson's cases were microadenomas, sometimes minute. A contiguity between the posterior lobe and the adenoma was seen in ten cases. Spontaneous infarction of the tumor with remission of Cushing's syndrome occurred in one case. Light microscopy revealed that the adenoma cells were basophilic and contained PAS-positive granules also staining with Herlant tetrachrome and lead-hematoxylin. The granules stained positively with antiserum to adrenocorticotrophic hormone (ACTH), beta-lipotropic hormones (beta-LPH) and beta-endorphin. The most characteristic ultrastructural finding was the presence of perinuclear bundles of microfilaments found in all our cases. Oncocytic changes were seen in three tumors. Four silent corticotroph adenomas, two of them originally microadenomas that had enlarged to enclosed adenomas while being treated with bromocriptine for hyperprolactinemia and one a large diffuse invasive tumor, did not differ in their microscopic, immunocytological, or ultrastructural features.
Adenoma, Basophil↗