摘要:

SUMMARYFusaric acid, an inhibitor of dopamine β‐hydroxylase, which converts dopamine to noradrenaline, lowered the blood pressure and induced a subjective improvement in patients with phaeochromocytoma. These effects may be due either to an impairment of catecholamine biosynthesis or to a direct action on the blood vessels. The use of this drug in the treatment of patients with inoperable malignant phaeochromocytoma or neuroblastoma may improve symptoms and prolong surviv

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1985.tb00142.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARYA radioimmunoassay was optimized to measure serum TSH with maximum sensitivity (sTSH). With this assay sTSH was$5 mIU/l in 52% of patients thus avoiding the need for further testin

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1985.tb00143.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARYA radioimmunoassay is described for D‐Ser (tBu)6AZA Gly10GnRH (ICI 118630) in serum of prostate cancer patients treated chronically with this peptide to produce a medical castration. With125I‐118630 as the label, and an anti‐GnRH serum, the specificity of the assay is directed to the N‐terminal end of the peptide, and putative degradation products have<6% cross‐reactivity. The assay appears specific for intact 118630 which, after subcutaneous administration of 250 μg, has a half‐time of disappearance from the serum of 4·9 ± 0·4 h and a volume of distribution of 13·7 ± 0·8 litres. Continuous subcutaneous infusion of 120 μg 118630/d gave stable serum concentrations of between 2–3 ng/ml for up to 63 d which were very similar to values predicted from pharmacokinetic analysis of the analogue clearance rate. This contrasts with the ‘peak and trough’ pattern of serum 118630 levels measured in two subjects after 118630 administration from a subcutaneous implant containing 3·6 mg of peptide in a biodegradable formulation. Serum 118630 levels peaked at between 6–8 ng/ml 15 d after the implant and fell to<1 ng/ml at 29 d, immediately before the next implant. Serum 118630 levels following a second 3·6 mg implant were almost identical with respect to absolute concentration and time to peak value as after the first implant. This assay will be of value not only for evaluation of the pharmacokinetics of GnRH analogue release from new long‐acting formulations, but also for correlation of serum peptide concentrations with pituit

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1985.tb00144.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARYStudies on intact animals and isolated rat hepatocytes have shown that arginine vasopression (AVP) stimulates glycogen phosphorylase to break down gly‐cogen and raise plasma glucose concentrations. Since no similar work has been performed on healthy human adults, the effect of moderate (25 pmol/min) and high (75 pmol/min) dose AVP infusion on plasma glucose, intermediary metabolites, glucose kinetics, and circulating glucagon and insulin concentrations was investigated. After AVP infusion, plasma glucose rose from 4±9 ± 0±1 to a peak of 5±70±2 mmol/1 (P<0<001), but no changes in blood lactate, pyruvate, alanine, glycerol or 3‐hydroxybutyrate concentrations were observed. The glucose rise was accounted for entirely by an increase in the rate of appearance of glucose from 11±9 ± 0±43 to 13±38 · 0±63 μmol/kg/min (P<0·001). Infusion of AVP also increased plasma glucagon concentrations from 38 ± 8 to 79 ± 20 pg/1 (P<0·01). The hyperglycaemic effect of AVP may be mediated solely by stimulation of glucagon release, but we cannot exclude direct stimulation of glycogen pho

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1985.tb00145.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARYTwo unrelated boys (C.C. 13 years; J. W. 18 years) presenting with early puberty and episodes of aggressive behaviour were found to have hypernatraemia and hypodipsia. Plasma vasopressin (AVP) levels were inappropriately low in relation to plasma osmolality, but the patients did not have diabetes insipidus since 24 h urinary volumes were2000 mg AI/1/h) although aldosterone concentrations were normal. Excretion of a water load (20 ml/kg) was delayed, but plasma renin and aldosterone fell with increased naturesis. An infusion of 0±85 mol/l saline produced a rise in AVP in C.C. but not in J.W. Insulin and hypotension resulted in the release of AVP in both boys suggesting a selective defect of osmoreceptor function. Hyperprolactinaemia and an exaggerated PRL response to TRH were also noted but no intracranial lesion was demonstrable on CT scan. These boys appear to have a hypothalamic syndrome with early puberty, hyperprolactinaemia, hypodipsia and osmoreceptor dysfunction which may be associated with aggressive behaviour

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1985.tb00146.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARYA case of atypical pituitary dependent Cushing's disease is reported. The patient presented with clinical symptoms similar to those of the ectopic ACTH syndrome; notably a marked hypokalaemic alkalosis, widely fluctuating plasma cortisol levels, greatly elevated plasma ACTH levels, and failure to suppress both plasma cortisol and ACTH levels following high dose oral dexamethasone. However, a large aggressive pituitary tumour was detected by skull X‐ray and computed tomography. Removal of the pituitary tumour led to full remission of the patient's Cushing's syndrome. Pro‐opiomelanocortin (POMC) related peptides in the plasma and tumour tissue extract of this patient have been characterized by gel‐filtration and Concanavalin‐A Sepharose affinity chromatography, indicating processing of POMC in a manner more usually associated with ectopic

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1985.tb00147.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARYPatients with thyrotoxic Graves' disease were treated daily for 10 d with 1 g sodium ipodate, an iodine rich X‐ray contrast agent which impairs outer ring (5′‐) deiodination of T4 to T3, or with 12 drops of a saturated solution of potassium iodide (SSKI). T4, T3 and reverse T3 (rT3) concentrations were measured before, during, and 5 and 10 d after the administration of each drug. SSKI therapy induced a decrease in the serum T4 concentration from 14·7 ± 1·3 μg/dl (mean ± SE) to a nadir of 7±9 ± 0·9 on days 9 and 10 of therapy, all values reaching the normal range by day 9; a decrease in the serum T3 concentration from 402 ± 43 ng/dl to a nadir of 143 ±20 on day 10, remaining elevated in all patients until day 5 and decreasing into the normal range in all except one patient on days 9 and 10; and no change in the serum rT3 concentration. Serum T4 and T3 concentrations returned to baseline values 10 d after withdrawal of SSKI. In contrast sodium ipodate therapy induced only a modest decrease in the serum T4 concentration from 15±± 0·7 μg/dl to a nadir on day 9 of 11·3 ± 1·0 and serum T4 remained above the normal range in most patients until day 8; a striking and rapid decrease (within 12 h) in the serum T3 concentration from 340 ± 36 ng/dl to mean values ranging from 79 to 85 during the last 5 d of therapy, with most values below the normal range during the last 3 d; and a marked increase in the serum rT3 concentration from 111 ±15 ng/dl to a peak value of 376 ± 59 on day 5. A significant rebound increase in serum T4 (18·7± 1·7 μg/dl;P<0·01) and serum T3 (512 ± 72;P<0·01) concentrations as compared to pretreatment values occurred 10 days after sodium ipodate was discontinued. We conclude that although

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1985.tb00148.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARYWe have investigated the effects of atropine (specific muscarinic cholinergic inhibition) on the nocturnal secretion of GH during the first cycle of stage IV sleep in six normal volunteers and three tall adolescents. Atropine was administered orally in a dose of 0·6 mg (n= 8) or 1·8 mg (n= 4) 30 min before expected sleep and the sampling repeated. Peak GH level without atropine was 45·3 mU/l (range 5·7 to 92·0): both doses of atropine abolished sleep associated GH secretion. Spontaneous daytime GH secretion was demonstrated during five 6 h sampling periods in three normal adults. There was a significant decrease in spontaneous daytime GH secretion when the sampling was repeated after atropine 0·6 mg or 1·8 mg. We conclude that inhibition of GH secretion using anticholinergic drugs should be further investigated in the management of excessive growth hormone sec

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1985.tb00149.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARYIopanoic acid (1 g/d) was used together with propylthiouracil (1200 mg/d) in the treatment of a patient with very severe hyperthyroidism and associated cardiac failure. Although serum total T3 decreased by 75% within 48 h and reached normal after 72 h, free T3 levels did not fall to normal. Total and free T4 remained markedly elevated and features of hyperthyroidism persisted. Estimations of theoreticalin vivooccupancy of nuclear thyroid hormone receptors, based on serum free T4 and free T3, suggest that the marked decrease in total T3 would not result in a corresponding decrease in thyroid hormone action. Hence, estimates of potential benefit from oral cholecystographic contrast agents, based only on measurements of total T3, may be unduly optimistic. When temporary agranulocytosis developed in this patient, the prior use of iopanoic acid, by markedly reducing thyroidal iodine uptake, restricted the therapeutic options. Caution should, therefore, be exercised in the use of iodine‐containing contrast media as adjunctive antithyroid agent

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1985.tb00150.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

SUMMARYThe ability of Graves' sera to interact with the TSH receptor crosslinked to a125I‐labelled photoactive derivative of TSH has been investigated. Crosslinked complexes were prepared using non‐purified detergent solubilized human thyroid and guinea pig fat TSH receptors. Affinity purified porcine TSH receptor preparations were also used. After crosslinking, the crosslinked TSH‐TSH receptor complexes were separated from aggregates and free TSH on Sephacryl S‐300, incubated with test sera followed by immunoprecipitation using anti‐IgG or Protein A. Using non‐purified human TSH receptors crosslinked to TSH, a mean ± SD of 12±· 4·9% of the crosslinked complex was immunoprecipitated with Graves' sera (n= 7) compared with 10·3 · 2·6% with Hashimoto sera (n= 6;P>0±4) and 3·8 · 1·0% with normal sera (n= 6;P<0·004). These values were markedly reduced when TSH receptor preparations free of other thyroid autoantigens (guinea pig fat TSH receptors) were used. Under these conditions immunoprecipitation with Graves' sera (n= 24) was 1·6 · 1·3% compared with 0·8 · 0·6% for Hashimoto sera (n= 13) and 0·8 · 0·4% for normal sera (n= 2;P= 0·003). In addition complexes formed between TSH and affinity purified porcine TSH receptors gave low immunoprecipitation values for Graves' (1·44 · 0·73%;n= 20) and Hashimoto sera (1·7 · 0·94;n= 11) which were not significantly different (P= 0·4). Overall, therefore, the effects of Graves' and Hashimoto sera were similar and the amounts of material immunoprecipitated were markedly reduced when TSH receptor preparations containing reduced amounts of other autoantigens were used. Consequently the Graves' sera did not appear to interact specifically with crosslinked TSH‐TSH receptor complexes. However the Graves' sera studied did contain TSH receptor antibodies which could inhibit the binding of labelled TSH to TSH receptors in the preparations used and our results suggest that the binding of TSH and these antibo

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1985.tb00151.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY