摘要:

SummaryOBJECTIVESmoking is a risk factor for the development of thyroid‐associated ophthalmopathy, an inflammatory process primarily affecting the fibroblasts in extraocular muscles. We wished to determine whether the extraocular muscle fibroblasts are more sensitive than dermal fibroblasts to T‐cell derived cytokines, as a reason for this anatomical localization, and whether hypoxia alters fibroblast function, as one explanation for the susceptibility conferred by smoking.DESIGNFibroblasts derived from the skin or extraocular muscles of healthy subjects were cultured with cytokines under normal (5% CO2:95% air) and hypoxic (5% C02:95% N2) conditions.MEASUREMENTSGlycosaminoglycan, protein and DNA synthesis were measured by assessing incorporation ofd‐6‐3H‐glucosamine,3H‐amino acids, and3H‐thymidine respectively.RESULTSα‐lnterferon and interleukin‐6 had no effect on fibroblasts,γ‐Interferon, tumour necrosis factor and inter‐leukin‐1 stimulated glycosaminoglycan synthesis; this effect was greater in orbital than in dermal fibroblasts withγ‐interferon and interleukin‐1 (P<0.05). The same cytokines stimulated total protein with a greater response in orbital fibroblasts withγ‐interferon. Interleukin‐1 inhibited DNA synthesis in orbital fibroblasts but stimulated DNA synthesis in dermal fibroblasts (P<0.01); tumour necrosis factor also displayed a differential effect (P<0.01). Hypoxia caused a significant increase in glycosaminoglycan, protein and DNA synthesis in both types of fibroblasts, under both basal and cytokine‐treated conditions (P<0.05).CONCLUSIONSExtraocular muscle fibroblasts respond differently from dermal fibroblasts following cytokine stimulation, which may explain in part the anatomical localization of ophthalmopathy. Hypoxia stimulates fibroblasts and this could contribute, as an enhancing factor, to the adverse effe

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02445.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEIncreasing dietary sodium intake increases blood pressure in some subjects with essential hypertension. Atrial natriuretic factor (ANF) has a potential role in modifying these changes. The purpose of this study was to observe the blood pressure and plasma ANF responses to low and high sodium diets in subjects with essential hypertension to see if the plasma ANF and blood pressure responses were related.DESIGNAn in‐patient study of subjects taking their normal diet (day 1), a 12 mmol sodium diet for 6 days and a 250 mmol diet for 6 days.PATIENTSSeven men with essential hypertension.MEASUREMENTSContinuous 24 hour urine collections were analysed for sodium excretion. Blood pressure was recorded at 0900, 1205 and 1700 h on days 1, 7 and 13. Blood was taken at 0900 h (fasting supine overnight) and at 1200 h (after 2 hours erect posture) on the above days for plasma ANF, plasma renin activity (PRA) and serum aldosterone.RESULTSUrinary sodium excretion was (mean±SEM) 11±1 mmol on day 5 of the low sodium diet, and 294±17 mmol during the fifth day of the high sodium diet. Plasma ANF (supine and erect) was significantly lower (2 8±0 6, 1 6±0 2 pmoi/l) on the low sodium diet when compared to the high sodium diet (8 6±2 4, 5 0±1 6 pmol/l (P<0 05)). Supine and erect PRA and serum aldosterone were significantly higher on the low compared to the high sodium diet. Blood pressure responses were heterogeneous rather than bimodal. Mean arterial blood pressure was 107±3 mmHg on the low sodium diet and 111±4 mmHg on the high sodium diet (P<0 05). Changes of blood pressure did not correlate with the changes of plasma ANF.CONCLUSIONSFailure of plasma atrial natriuretic factor to rise with increasing dietary sodium did not therefore determine the blood pressure reponse to the change in dietary sodium. No link was established between plasma atrial natriuretic factor response and sodium s

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02446.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEInhibitors of cellular T4 transport leading to diminished plasma T3 production have been identified as 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid (CMPF) and indoxyl sulphate in uraemia and bilirubin and non‐esterified fatty acids (NEFA) in critically ill patients with hyperbilirubinaemia. We question whether other factors are responsible for the altered thyroid hormone parameters observed in mild illness and during calorie restriction.PATIENTSWe studied (I) 18 non‐uraemic patients with non‐thyroidal illness (NTI) (T4 5±60, T3 ±1 1 and rT3 ±0 45 nmoI/I) with serum molar ratios of bilirubin:albumin ±0 17 and NEFA:albumin ±2 6. These molar ratios have been shown to be the minimum ratios which inhibited T4 transport into rat hepatocytes; (ii) four obese euthyroid subjects on 600 kcal/day for 10–14 days. This diet is known to inhibit the unidirectional T4 transport into human liverin vivo.MEASUREMENTSWe measured iodide production from125I‐T4 by incubating rat hepatocytes with 10% human serum. The deiodination of T4 was used as an index of cellular transport of T4in vivo.RESULTSThe mean iodide production from125I‐T4 by rat hepatocytes in the presence of 10% serum from NTI patients (98±17%, mean±SD) was not significantly different from the normals (100 ±9%). Calorie restriction in euthyroid obese subjects resulted in a small but significant reduction (‐12%) of iodide production. Calorie restriction increased the total serum NEFA by 91 %.CONCLUSIONSOur study demonstrates that CMPF, indoxyl sulphate, bilirubin and NEFA are not responsible for the inhibition of T4 tissue uptake in patients with mild illness. In addition, studies with calorie restricted obese subjects indicate that high concentration of NEFA during calorie restriction inhibits T4 tissue uptake. This inhibition may partly explain the lower p

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02447.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEWe wished to analyse the relative value and diagnostic accuracy of bilateral simultaneous inferior petrosal sinus blood sampling for plasma ACTH measurements when compared with pituitary magnetic resonance imaging (MRI) for the preoperative localization of microadenoma (tumour diameter3 0 in CRH‐stimulated peak samples in 15 of 17 patients (88%). Anatomical variations of the inferior petrosal sinus, precluding reliable conclusions about lateralization of pituitary venous ACTH drainage, were observed in five of 20 patients (25%). Adding the three patients with technical failure and one patient who presented with a macroadenoma (tumour diameter 11 mm), this left interpretable data with regard to lateralization of the microadenomas in only 11 of 20 patients (55%). In 15 of 20 patients (75%) a pituitary microadenoma was found at MRI. In 14 of these 15 patients (93%) a tumour was indeed found at that position at subsequent transsphenoidal operation. Concordance between the lateralization by the intersinus gradient and microadenoma localization by MRI was observed in six of 11 cases (55%) when using basal samples and in seven of 11 cases (64%) when using peak samples obtained after stimulation with CRH. Concordance between the lateralization by the intersinus gradient and subsequent microadenoma localization at surgery was observed in seven of 11 patients (64%) before and in eight of 11 cases (73%) after CRH stimulation. Reversal of the intersinus gradient after CRH stimulation, suggesting a shift in the lateralization to the contralateral side of the gland, was found in three of 12 cases (25%).CONCLUSIONSBilateral simultaneous inferior petrosal sinus blood sampling for plasma ACTH measurements before and after CRH stimulation successfully confirmed the diagnosis of pituitary dependent Cushing's disease in 15 of 17 patients (88%) in whom this diagnosis was suspected on the basis of conventional biochemical testing. Magnetic resonance imaging, however, is superior to bilateral simultaneous inferior petrosal sinus blood sampling for the localization/lateralization of pituitary microadenomas in patients with Cushing's disease. Therefore, bilateral simultaneous inferior petrosal sinus blood sampling should be reserved for the assessment of those patients with Cushing's syndrome in whom either the results of biochemical tests are equivocal and/or subsequent pituitary magnetic resonance imaging gives unconvincing resu

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02448.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEThe release of growth hormone (GH) from the anterior pituitary is partly under cholinergic control. Pyridostigmine, the acetylcholinesterase inhibitor, releases GH by this mechanism. Pyridostigmine/GH responses have been reported as enhanced in depression. The aim of the current study was to examine such responses during a manic episode.DESIGNA between subjects design was employed.SUBJECTSSeven male manic patients and seven male healthy controls were studied. They were matched in terms of age and body mass index.MEASUREMENTSGH response to pyridostigmine (120 mg) challenge was measured as the net increase above baseline. Cortisol levels were also measured.RESULTSRelease of GH in the manic patients was significantly enhanced and their baseline Cortisol levels were elevated.CONCLUSIONSThese results demonstrate enhanced pyridostigmine/GH responsiveness in mania which may be due to enhanced somatostin tone or increased cholinergic receptor responsivity.

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02449.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVELittle is known about the relative circulating concentrations of growth hormone releasing hormone (GHRH) 1‐44 NH2and 1‐40 OH in response to dynamic GH stimulation. We therefore studied the concentrations of growth hormone‐releasing hormone (GHRH) 1‐44 NH2and 1‐40 OH in the peripheral plasma of normal male subjects during GH stimulation tests.DESIGNTests were performed at 0900 h after an overnight fast. Stimulation tests, commenced at 0 minutes, included α‐adrenergic activation with adrenaline (10μg/min from 0 to 30 minutes) following β‐blockade with propranolol (1.5 mg/min from ‐10 to 0 minutes), α2‐adrenergic activation with clonidine 150μg i.v., insulin hypoglycaemia (0.15 U/kg soluble insulin),l‐arginine infusion (30 g from 0 to 30 minutes),l‐dopa (500 mg orally) and oral glucose (100 g). SUBJECTS Groups of healthy male volunteers aged 20‐42 years, all within 10% of ideal body weight. MEASUREMENTS Serum GH and plasma GHRH 1‐44 NH2 and 1‐40 OH were measured at intervals for between 60 and 390 minutes, depending on the stimulation test. RESULTS There were no significant changes in either GHRH 1‐44 or 1‐40 following a‐adrenergic activation with propranolol/adrenaline infusion, a2‐adrenergic activation with i.v. clonidine, insulin‐induced hypoglycaemia or arginine infusion despite the expected rise in GH levels.After oral glucose, GH was initially suppressed with a late rise. There were no changes in GHRH 1‐44 or 1‐40 levels during either phase of this response. Afterl‐dopa GH levels peaked at 90 minutes, 24.5 ± 11.0 mU/l (mean ± SEM). At 0 minutes GHRH 1‐44 and 1‐40 levels were 3.25 ± 0.89 and 4.93 ± 1.28 pmol/l respectively and rose in both cases, peaking at 60 minutes at 4.23 ± 1.01 and 7.55 ± 1.80 pmol/l (P<0.05). At no time was there any evidence of differential secretion of GHRH 1‐44 or 1‐40.CONCLUSIONSWe have confirmed previous studies demonstrating a small rise in GHRH before the GH response tol‐dopa. However, in all other situations of pharmacological stimulation of GH release we were unable to detect any significant changes in GHRH 1‐44 or 1‐40 levels. It seems most likely that peripheral GHRH does not reflect hypothalamic secretion. As yet

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02450.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVESWe assessed whether the obesity observed in growth hormone deficient adults is maintained by a reduction in energy expenditure. We studied the effects of exogenous growth hormone on energy expenditure and body composition.DESIGNWe performed an open study with growth hormone administered at 0 5 units per kilogram ideal body weight per week for 3 months.PATIENTSSeven growth hormone deficient adults were studied. Thirty‐eight healthy volunteers had their resting metabolic rate measured, with seven of them proceeding to have their total energy expenditure assessed.MEASUREMENTSTotal energy expenditure was measured by the doubly labelled water method (D2018), resting metabolic rate by ventilated hood indirect calorimetry, and fat free mass from the dilution volume of oxygen‐18. Body composition and components of energy expenditure were assessed before, at 2 weeks and at the end of the 3‐month treatment period on exogenous growth hormone.RESULTSGrowth hormone deficient adults did not have a low total energy expenditure compared to healthy controls (13 12vs12 75 MJ/24 h) with only one patient expending less than 10 MJ/24 h. None had a resting metabolic rate lower than the 95% confidence limits of normality. The amount of energy expended on physical activity and thermogenesis was significant (6 54 MJ/24 h) and was similar to healthy controls (6 47 MJ/24 h).Resting metabolic rate increased by 15 9% after 14 days on exogenous growth hormone and was elevated 12‐1% after 3 months treatment but the ratio to fat‐free mass remained unaltered. Total energy expenditure increased by 13 4% after 14 days therapy. Fat‐free mass increased significantly after 3 months treatment by (mean) 4 5 kg with no change in fat mass and no loss in body weight.CONCLUSIONSObesity maintenance in growth hormone deficient adults is not a consequence of reduced total energy expenditure or a reduced exercise energy output. There was also no evidence for an energy sparing mechanism. Energy expenditure was increased by exogenous growth hormone but was not associated with a loss in fat mass or body weight suggesting the need for dietetic advice for those already obese at the outset

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02451.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEBesides effects on body composition, bone mineral content and lipid metabolism, GH seems to influence quality of life, according to previous studies of limited numbers of patients with GH deficiency of childhood and adult origin. In this study psychological well‐being was assessed in a large number of patients with GH deficiency of adult origin.DESIGNA follow‐up study of patients with hypopituitarism on routine replacement therapy withl‐thyroxine, cortisone acetate and sex steroids.PATIENTSEighty‐six patients (51 men, mean age 55.4 years and 35 women, mean age 54.9 years) diagnosed as having growth hormone deficiency on the basis of low IGF‐I concentration or a maximum GH response less than 5 mU/l after an insulin/glucagon tolerance test.MEASUREMENTSQuality of life was measured with a self‐rating questionnaire, the Nottingham Health Profile, and the results were compared with the results from 86 controls matched for age, gender, marital status and socioeconomic class. Furthermore, the observed and expected number of disablement pensions were calculated.RESULTSThe mean total score of the patients was higher, i.e. worse (P<0.05), than that of the matching controls, indicating a higher level of perceived health problems among the patients. There were higher scores (poorer life quality) for energy (P<0.001), social isolation (P<0.01), emotional reaction (P= 0.056) and sex life (P<0.001) among patients compared with controls. Finally, the observed number of disablement pension among the patients tended to be higher than expected (19vs12.4,P= 0.09).CONCLUSIONSAdult patients with GH deficiency have a decreased psychological well‐being in terms of energy, social isolation and emotional reaction and a disturbed sex life compared with normals. Furthermore, there is a tendency to a higher frequency of ear

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02452.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEand DESIGN The immediate early gene locus AP‐1, incorporating the cellular oncogenesc‐fosandc‐jun(and their oncoprotein products Fos and Jun respectively) play a key role in regulating cell growth and differentiation. Themyc‐gene is also known to promote cell growth. In order to investigate the possible role of these oncogenes in human pituitary adenomas, Fos, Jun and Myc oncoprotein immunoreactivities were assessed in surgically resected pituitary adenomas in relation to in‐vivo characteristics (hormone secretion, size and invasiveness) and an in‐vitro index of cell proliferation (Ki‐67 immunoreactivity). Thirty‐three human pituitary adenomas and 16 normal pituitary glands were examined.MEASUREMENTSOncoprotein immunoreactivity was recorded as present (+) or absent (‐), and Ki‐67 labelling indices were scored quantitatively. Tumour size was scored from CT scan appearances and radiographic evidence of bone erosion was noted.RESULTSOncoprotein immunoreactivity was present in a total of 32/33 cases. Myc immunoreactivity was restricted to the only ACTH‐secreting tumour in the series (1/33). Ki‐67 immunoreactivity was present in 24/32 cases and labelling indices varied from 0.1 to 3.2%.CONCLUSIONSOncoprotein immunoreactivity did not correlate with hormonal profile, bone erosion or the size of the proliferating compartment estimated by Ki‐67 labelling indices. Although oncoprotein expression is common in human pituitary adenomas, its significance

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02453.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEIt is not known whether gamma‐aminobutyric acid (GABA) is involved in control of pulsatile LH secretion in human beings. Previous work by our group has shown that manipulation of the GABAergic system with sodium valproate does not affect pulsatile LH secretion in normal women in the late follicular phase. However, it has been suggested that steroid levels are critical for the influence of GABA upon hormone secretion; in particular, progesterone has been said to enhance inhibition by GABA. In this work we studied the effect of sodium valproate on pulsatile LH secretion in medium‐late luteal phase of normal women.DESIGNSix normal young women were studied over an 8‐hour period in two successive menstrual cycles. On each occasion blood samples were taken every 10 minutes between 1000 and 1800 h. We administered 400 mg of sodium valproate every 8 hours on the 7 days preceding their second cycle and additional 400 mg at 0900 and 1400 h on the day of the study. Ovulation day was estimated by means of serial ovarian ultrasound examinations and confirmed by serum progesterone concentrations.MEASUREMENTSIn each cycle, LH, oestradiol and progesterone were determined by radioimmunoassay and sodium valproate by repolarization fluorescence spectrophotometry. The series of LH levels was smoothed for 1‐minute sampling periods by means of a spline function and analysed by means of a program developed in our laboratory and written in Fortran 77. The program deconvolved the signal and calculated the pulse area, pulse duration, interpulse interval and number of pulses. LH pulse identification on the deconvolved signals was performed using our own method based on Friedman's non‐parametric statistic. The statistical significance of differences between parameters was estimated using the Mann‐Whitney test and Wilcoxon signed rank test.RESULTSThere were no significant differences in LH pulse area, pulse duration, interpulse interval or number of pulses with the administration of sodium valproate.CONCLUSIONSActivation of the GABAergic system with sodium valproate had no biologically significant effect on the mid‐late luteal phase pulsatile LH secretion in

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02454.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY