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Biomedical subjects

R Hall

Publications and source records attributed to R Hall.

At least 307 records · Page 17Linked to original sources
PubMed1985

Differential effects of acute DA receptor blockade with domperidone on LH and TSH release in patients with hyperprolactinemia.

Since dopamine (DA) has been implicated in the inhibitory control of both TSH and LH, we have compared TSH and LH levels following dopamine (DA) receptor blockade with domperidone in patients with hyperprolactinemia due to presumed prolactinomas. Eight euthyroid patients (aged 19-37 yr) with presumed prolactinomas each received domperidone (10 mg iv) at 11:00 and 23:00 h and tests were separated by at least one week. Basal TSH levels were significantly greater at 23:00 than at 11:00 h (2.7 +/- 0.5 vs 1.7 +/- 0.4 mU/l, mean +/- SE, p less than 0.01) whereas basal LH levels did not differ. All subjects showed clear rises in basal TSH levels following drug administration and these were significantly greater at 23:00 than at 11:00 h (p less than 0.02 at each time point). In contrast there was no alteration in LH levels following drug administration at either time of day. These data suggest that the mechanisms underlying the dopaminergic control of TSH and LH are different in these patients. Furthermore the data argue against an anterior pituitary or median eminence site of action of DA in the inhibition of LH release in hyperprolactinemia since domperidone does not penetrate the blood brain barrier to any appreciable extent.

Adult↗
PubMed1985

An in vivo steady-state method for the determination of catecholamine biosynthesis in the rat brain using high-performance liquid chromatography with electrochemical detection.

A technique is described for the measurement of steady-state catecholamine (CA) synthesis in the rat brain in vivo, using [3H]tyrosine incorporation with high-performance liquid chromatography (HPLC) and electrochemical detection. Adult male rats chronically implanted with lateral intracerebroventricular (i.c.v.) cannulas, were injected i.c.v. with [3H]tyrosine. CA and tyrosine content and specific activity were measured in mediobasal hypothalamus, anterior hypothalamus and striatum. A time-dependent increase in CA synthesis occurred in all tissues over 20 min post-i.c.v. injection. The technique described may prove to be useful in the assessment of central neurotransmitter turnover in various physiological and pharmacological settings.

Animals↗
PubMed1985

Site-specific whole glove chemical permeation.

This study explored chemical permeation of latex neoprene gloves by acetone. Twenty-three specific glove sites were monitored to determine the breakthrough time and the challenge liquid concentration at steady-state. In summation, the thinnest parts of the gloves, which are the backs, the palms, and the interstices between the fingers, exhibited the shortest breakthrough times and largest steady-state concentrations. The thickest parts of the gloves, the fingertips, exhibited the longest breakthrough times and least steady-state concentrations. The backs or palms are appropriate specimens to use for chemical permeation testing.

Acetone↗
PubMed1985

The effects of cholinergic blockade on the growth hormone and prolactin response to insulin hypoglycaemia.

The effect of cholinergic blockade on growth hormone (GH) and prolactin (PRL) secretion during insulin-induced hypoglycaemia was assessed in six normal male volunteers (mean age 23, age range 21-25). Each subject underwent two insulin tolerance tests with and without atropine. GH responses were significantly lower 45 min after insulin administration with atropine (17.5 +/- 2.5 mU/l (mean +/- SEM) than with placebo (37.6 +/- 3.6 mU/l, P less than 0.0006). In contrast PRL responses were higher (P less than 0.01) at 45 and 90 min after insulin during treatment with atropine. These data demonstrate that cholinergic mechanisms are involved in stimulatory and inhibitory pathways in the medication of the respective GH and PRL responses to insulin induced hypoglycaemia in man.

Adult↗
PubMed1985

The influence of oestrogens on the sensitivity of PRL, TSH and LH to the inhibitory actions of dopamine in hyperprolactinaemic patients.

The effects of oestrogen priming on the response of serum PRL, LH and TSH to dopamine (DA) infusion have been studied in hyperprolactinaemia. Seven hyperprolactinaemic females (aged 22-57 years; basal PRL 911-5130 mU/l, normal less than 420 mU/l), had submaximal DA infusions (0.06 micrograms/kg/min) over 3 h. The DA was repeated at the same dose after pretreatment with ethinyl oestradiol (E2) 100 micrograms daily by mouth for 3 d, and after a further 2 week interval, following pretreatment with tamoxifen (TAM) 20 mg twice a day by mouth for 3 d. Ethinyl oestradiol pretreatment stimulated a rise in basal PRL levels in all subjects (mean +/- SE, mU/l; 2903 +/- 761 vs 2293 +/- 684, P less than 0.05) while TAM produced a higher but more variable increase in basal PRL levels (mean +/- SE, mU/l; 3402 +/- 757, P = n.s.). The individual increments in basal PRL levels after both E2 and TAM pretreatment showed a significant positive correlation with the greater decrement in PRL levels during E2 and TAM primed DA infusions (E2, r = 0.93, P less than 0.01, TAM, r = 0.83, P less than 0.05). E2 pretreatment produced a rise in basal LH levels in 5/7 patients, and there was a significant positive correlation between the rise in basal LH levels after E2 and the decremental change in LH levels in E2 primed DA infusions (r = 0.94, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Lack of effect of the TRH related dipeptide histidyl-proline diketopiperazine on TSH and PRL secretion in normal subjects, in patients with microprolactinomas and in primary hypothyroidism.

We have studied the effects of the TRH related dipeptide histidyl-proline diketopiperazine [cyclo (His-Pro)] on basal and stimulated TSH and PRL secretion in normal volunteers, in patients with microprolactinomas and in patients with primary hypothyroidism. Cyclo (His-Pro), 400 micrograms intravenously did not alter basal TSH or PRL levels in normal males and females and was also without effect upon the elevated basal TSH and PRL levels in patients with primary hypothyroidism and microprolactinomas respectively. The same dose of cyclo (His-Pro) did not affect the TSH or PRL response to TRH (100 micrograms i.v.) in normal male volunteers. These data indicate that cyclo (His-Pro) does not affect TSH and PRL secretion in man at this dosage. It is also unlikely that this molecule will be of any therapeutic benefit in states of hyperprolactinaemia.

Adult↗
PubMed1985

The absence of any effect of methimazole on in vitro cell-mediated cytotoxicity.

Two recent studies have reported that antithyroid drugs inhibit killer (K) and natural killer (NK) cell function in vitro, which could be relevant to the changes in these cell populations during treatment of Graves' disease. In contrast to these reports we have found no in vitro effect of pharmacologically relevant concentrations of methimazole (MMI) (100 mumol/l) on (i) NK cell function using K562 cells or MOLT-4 cells as targets, (ii) K cell function using antibody-dependent cytotoxicity assays with L929 cells or thyroid-antigen-coated chick red cells, or (iii) monocyte-dependent cytotoxin-mediated killing of L929 cells. Enhanced cytotoxicity was found with 1 mmol/l MMI in some of these assays but this was not consistent since it occurred only in certain individual cultures. Since we have shown previously that 100 mumol/l MMI inhibits oxygen radical generation, the present results add to the evidence that these radicals are not directly involved in cell-mediated cytotoxicity and do not support the concept that antithyroid drugs have a significant effect on antibody-dependent cell-mediated cytotoxicity in Graves' disease.

Adult↗
PubMed1985

Relationships between the circadian rhythms of TSH, prolactin and cortisol in surgically treated microprolactinoma patients.

Pharmacological doses of glucocorticoids inhibit TSH release both in vivo and in vitro and since the circadian rhythms of TSH and cortisol show a reciprocal relationship, the hypothesis has been advanced that changes in cortisol levels may be a primary determinant of circadian TSH changes. We have tested this hypothesis by studying the relationship between circadian cortisol and TSH rhythms in subjects before and during blockade with metyrapone. Seven patients were studied during their routine post-operative assessment following selective transethmoidal adenomectomy for microprolactinomas. PRL levels were restored to normal (less than 420 mU/l) in all patients by surgery (pre-op: 930-2752 mU/l, post-op: 33-376 mU/l) and the patients also had normal pituitary function in other respects. Blood was sampled hourly for 24 h before and on the third day of treatment with metyrapone (250 mg, 2 hourly). In order to compare circadian rhythms, hormonal data were subjected to cosinor analysis which involved fitting of the data with a cosine function using the method of least squares. The 6% cross reactivity of the cortisol antibody with 11-deoxycortisol was taken into account during the calculation of results. All subjects showed a normal cortisol rhythm which was strikingly blunted during metyrapone treatment. Group mean (+/- SD) TSH mesors, amplitudes and acrophases for control and metyrapone treated subjects were 1.5 +/- 0.26, 1.29 +/- 0.48; 0.46 +/- 0.26, 0.23 +/- 0.13 and -49 degrees +/- 9.8 degrees; -62 degrees +/- 2.7 degrees respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Reciprocal ST depression in acute myocardial infarction.

ST segment depression in leads remote from those showing ST elevation during acute myocardial infarction has been attributed to benign electrical phenomena, distant myocardial ischaemia, or extensive myocardial damage. Eighty four consecutive survivors under 55 years of age with a first transmural myocardial infarction were studied. All patients had exercise tests six weeks after infarction and coronary angiography a mean of three months after infarction. Thirty eight (75%) of the 51 inferior and 19 (58%) of the 33 anterior infarcts showed reciprocal ST depression of greater than or equal to 1 mm during the acute phase. Ten (26%) of the 38 patients with inferior infarcts and reciprocal depression had ST depression in the same leads on exercise. There was concomitant disease of the left anterior descending artery in four (40%) of these 10 patients and in five (18%) of the 28 with inferior infarcts with reciprocal depression but without ST depression in the same leads on exercise. Five (26%) of the 19 patients with anterior infarcts with associated reciprocal depression and four of the 14 without reciprocal depression had important right coronary artery disease. In patients with inferior infarction important disease of the left anterior descending artery could not be predicted by ST depression in particular lead groups. Therefore reciprocal ST depression during acute myocardial infarction does not predict concomitant disease in the coronary artery supplying the reciprocal territory.

Arrhythmias, Cardiac↗
PubMed1985

Pituitary function with a solitary intrasellar plasmacytoma.

A solitary intrasellar plasmacytoma with marked pituitary fossa destruction and yet near normal pituitary gland function is described. We suggest that a minimal disturbance of endocrine function together with a radiologically abnormal pituitary fossa indicates that the primary lesion may lie outside the pituitary fossa.

Aged↗
PubMed1985

Morbidity of simple cholecystectomy and cholecystectomy with transduodenal sphincteroplasty.

Exploration of the common bile duct via transduodenal sphincteroplasty is thorough and provides an opportunity for the natural passage of retained calculi. However, this procedure destroys both the sphincter ampulla and sphincter choledochus, the sequelae of which are unknown. Fifty patients who had a transduodenal sphincteroplasty performed between 1970 and 1980 were randomly selected and compared with 50 patients who only had cholecystectomy. They were all seen in the outpatient department, assessed on a modified Visick scale and had liver function tests performed. There was no statistical difference in the subjective quality of result or in the liver function of the sphincteroplasty group when compared with the cholecystectomy patients, which suggests that destruction of the sphincters does not appear to be harmful to the patient.

Cholecystectomy↗
PubMed1985

The effects of thyroid hormone deprivation in vivo and in vitro on growth hormone (GH) responses to human pancreatic (tumor) GH-releasing factor (1-40) by dispersed rat anterior pituitary cells.

Anterior pituitary cells from euthyroid and hypothyroid male rats have been cultured as monolayers for 3 days with or without 5 nM T3 and stimulated with either human pancreatic GH-releasing factor 1-40 (hpGRF), TRH, or the Ca2+ channel ionophore A23187. Basal GH secretion was reduced in the hypothyroid cultures (P less than 0.001) and basal TSH secretion increased (P less than 0.001). Culture with T3 increased GH secretion and intracellular GH content in euthyroid and hypothyroid cultures but suppressed TSH secretion with no effect on intracellular TSH content in either euthyroid or hypothyroid cultures. hpGRF released more GH from euthyroid [3.52 +/- 0.2 (SE) micrograms/6 h X 10(5) cells] than hypothyroid cultures of (0.17 +/- 0.01 micrograms/6 h X 10(5) cells, P less than 0.001) without a change in ED50 (approximately 0.02 nM). The reduction in hpGRF-induced GH release remained significant when corrected for the reduced intracellular GH content in the hypothyroid cultures. hpGRF-induced GH release also declined relative to A23187-induced GH release in hypothyroid cultures. Culture with 5 nM T3 doubled maximum hpGRF-induced GH release in euthyroid cultures and increased maximum release 10-fold in hypothyroid cultures without altering the ED50 of hpGRF action. In contrast, T3 suppressed TRH-induced TSH release in euthyroid cultures but was without effect on TRH-induced TSH release in the hypothyroid cultures. T3 did not effect the ED50 of TRH action (2-5 nM). In summary, hypothyroid rat anterior pituitary cells in culture have a reduced maximal GH response to hpGRF, but the same ED50. hpGRF activity can be partially restored by physiological concentrations of T3 in vitro.

Animals↗
PubMed1985

The effects of hyperthyroidism on experimental autoimmune thyroiditis in the rat.

The effects of hyperthyroidism on experimental autoimmune thyroiditis were investigated in the rat. Rats were given T4 twice daily by sc injection in amounts sufficient to raise circulating hormone levels 10-fold 4 h after administration. Thyroiditis was induced by immunization with rat thyroglobulin (Tg) in complete Freund's adjuvant, and the severity of the disease was assessed by comparison with saline-treated controls. Thymic and splenic hypertrophy were found in T4-treated animals, whereas lymph node wt decreased. The levels of Tg antibodies did not differ between animals given saline and those given T4, but the expected sustained rise in control animals was not seen in those treated with T4; in addition, there was a significant decrease in the amount of Tg antibody produced by in vitro culture of lymph node lymphocytes from T4-treated rats. Continuous T4 administration lowered the number of T cells in the circulation, but the number of phenotypically identified helper cells remained the same. The most striking effects of T4 were to ameliorate the intensity of histologically defined thyroiditis and lower the response of lymph node T cells to the nonspecific mitogen, phytohemagglutinin. These results show that excessive T4 does not, as previously suggested, enhance the immune response in autoimmune thyroid disease: on the contrary, suppression is found with the dose and model we have used. In view of the magnitude of this effect, it is now important to identify the site of T4 action and investigate how this effect contributes to the autoimmune response in Graves' disease.

Animals↗
PubMed1985

Alpha 1-adrenoreceptors and alpha 1-adrenoreceptor-mediated thyrotropin release in cultures of euthyroid and hypothyroid rat anterior pituitary cells.

TSH responses to adrenergic agonists have been measured in 3-day monolayer cultures of euthyroid and hypothyroid male rat anterior pituitary (AP) cells. Responses were qualitatively similar in that (-)epinephrine and (-)norepinephrine had the same ED50 in each culture (ED50 = approximately 6 and 16 nM, respectively) and demonstrated the same alpha 1-adrenergic specificity. Hypothyroid cultures secreted approximately twice as much TSH per cell as euthyroid cultures over the 2-h experimental period. (-)Epinephrine produced a 95 +/- 8% (mean +/- SE) release of TSH relative to basal secretion in euthyroid cultures and only 62 +/- 7% release in the hypothyroid cultures (P less than 0.01). The comparable figures for (-)norepinephrine were 62 +/- 7% and 38 +/- 5%, respectively (P less than 0.05). In absolute terms, adrenergic agonists released the same amount of TSH from euthyroid and hypothyroid cultures. In contrast, TRH (and the Ca+2 channel ionophore A23187) released twice as much TSH from the hypothyroid cells as in the euthyroid cultures. Epinephrine-induced TSH release was significantly impaired (P less than 0.001) when either euthyroid or hypothyroid cells were cultured without thyroid hormones. In contrast, TRH-induced TSH release was enhanced (P less than 0.001) in the euthyroid cultures. [3H]Dihydroergocryptine [( 3H]DHE) was used to quantify alpha 1-adrenoreceptors on the same cell preparations as those used to derive the functional data (see above). Prazosin (1 microM) was used to define nonspecific binding of [3H]DHE. Specific binding to euthyroid cells had a Kd of 5.8 +/- 4 nM and a maximum binding capacity of 2.2 +/- 0.4 fmol/10(5) cells (n = 5). In parallel cultures of hypothyroid cells, the Kd (6.2 +/- 5 nM) was not significantly different, whereas the maximum binding capacity (1.4 +/- 0.3 fmol/10(5) cells) was significantly reduced (P less than 0.05). Adrenergic compounds showed a rank order of potency of prazosin greater than (-)epinephrine greater than or equal to (-)norepinephrine greater than or equal to yohimbine greater than clonidine against the binding of 5 nM [3H]DHE to euthyroid and hypothyroid cells. The amount of [3H]DHE binding per cell that each adrenergic compound was able to displace at saturating concentrations was less in hypothyroid cells than in euthyroid cells. There was no change in the ED50 values of these compounds in the same experiments.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Failure to demonstrate cell-mediated immune responses to thyroid antigens in Graves' disease using in vitro assays of lymphokine-mediated migration inhibition.

The use of in vitro assays of cell-mediated immunity has provided evidence of a defect in thyroid antigen-specific T suppressor cells in the peripheral blood of patients with autoimmune diseases. We employed a direct assay of T lymphocyte migration inhibition in an attempt to demonstrate cell-mediated immune responses to thyroid antigens in untreated patients with hyperthyroid Graves' disease and examined the influence of (1) a variety of antigen preparations, (2) different assay conditions, and (3) the HLA-DR3 status of normal subjects on this system. There was no significant difference in the migration of lymphocytes from 13 untreated patients with hyperthyroid Graves' disease to a crude 800 X g supernatant antigen preparation of normal human thyroid when incubated at either 20 or 37 C compared with the response of 13 normal subjects. The mean migration index was 57 +/- 22 (+/- SD) in the Graves' patients compared with 65.2 +/- 19.9 in the normal subjects at 20 C and 83 +/- 16.9 in the Graves' patients compared with 86.6 +/- 15.1 in the normal subjects at 37 C. Similarly, there was no significant difference in the migration indices obtained with T cells from Graves' patients and normal subjects using an 800 X g supernatant prepared from the thyroid glands of 2 patients with Graves' disease, incubated at 20 or 37 C (44.0 +/- 22.5 in the Graves' patients compared with 45.7 +/- 12.8 in the normal subjects at 20 C and 67.9 +/- 20.8 in the patients compared with 72 +/- 12.6 in the controls at 37 C). In contrast, the migration indices calculated for 20 C incubation were significantly lower than the corresponding value at 37 C using 800 X g normal thyroid antigen (P less than 0.05) and 800 X g Graves' thyroid antigen (P less than 0.01) in both patient and control groups. An identically prepared uterine antigen produced a similar reduction in the migration indices at 20 C compared with those at 37 C in 6 normal donors (P less than 0.05), but no temperature effect was found when 8 normal subjects were tested with purified protein derivative of tuberculin. The responses of 12 normal individuals to 800 X g supernatants of the normal and Graves' thyroid antigens were not influenced by the HLA-DR3 antigen.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens↗