摘要:

SUMMARYThe synthetic substituted corticotrophin analogue,a1–18ACTH, was given intravenously or subcutaneously to thirteen human volunteers in whom endogenous secretion of ACTH had been suppressed with dexamethasone. Plasma levels ofa1–18ACTH over the succeeding 12–24 h were determined by radioimmunoassay and bioassy, together with the fluorometric corticosteroid responses. The plasma disappearance rate ofa1–18ACTH was compared with that of the corticotrophin fragment,a1–24ACTH (tetracosactrin, Synacthen), in both unmodified and depot forms.Plasma levels ofa1–18ACTH were higher and were detectable for longer after intravenous rather than subcutaneous administration. The higher levels were associated with greater and more prologed corticosteroid responses. In addition, the corticosteroid response to the intravenous injection of 1 mg ofa1–18was greater and more prolonged than the response to the intravenous injection of the same dose ofa1–24ACTH. The plasma levels of immunoreactivea1–24ACTH were not detectable for more than 4 h after this dose. After the intramuscular administration of 1 mg of the depot preparation, however, detectable plasma levels persisted for 12 h. It is concluded that the brief corticotrophic activity of unmodifieda1–24ACTH is due mainly to its rapid clearance from the circulation.There was no significant dissociation between the disappearance rates of immuno‐ and bio‐activea1–18ACTH. This contrasted witha1–24ACTH whose bioactivity disappeared from plasma significantly faster than immunoreactivity. This difference probably reflects the greater stability ofa1‐18ACTH In the circulation and this in turn accounts, in part at least, for its prolonged corticotrophic activity.In a separate study the peptides were given intranasally through special applicators to eleven dexamethasone suppressed volunteers. The plasma levels ofa1–18ACTH after a 1 mg dose were lower than when given by other routes but the corteroid response was unaltered. The corticosteroid response to a 1 mg dose of intranasala1–24ACTH was brief and similar to that which followed an intavenous or subcutaneous injection; it was not significantly prolonged if 5 mg was given. It is concluded that intranasala1–24ACTH is unlikely to be of value but itranasala1

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1977.tb02935.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

SUMMARYIn a group of nine perimenopausal women, aged 37–52 years, with dynsfunctional uterine bleeding (DUB), serial measurements were made of urinary total oestrogen and pregnanediol excretion and of plasma gonadotrophin and steroid levels under basal conditions and during dynamic tests (oestrogen provocation and LHRH‐tests). Results were compared to those obtained in a control group of regularly menstruating women, 23–45 years of age. Four different patterns of hypothalamic‐pituitary‐ovarian (H.P.O.) activity were identified in the perimenopausal subjects with DUB. In two patients with a history of persistent anovulation and cystic glandular hyperplasia of the endometrium, basal plasma gonadotrophin levels were normal but there was a failure to release an adequate amount of LH in response to endogenous and exogenous oestrogen stimulation. One subject had regular ovulatory cycles but the follicular phase was shorter and circulating levels of FSH, but not of LH, were higher than in controls. A similar monotropic increase in FSH was also present in a further patient whose cycles were irregular and included an ovulatory cycle with short follicular phase, an ovulatory cycle of normal length and an anovulatory cycle. In the remaining five women follicular development was infrequent and anovulation the rule. FSH and LH levels in these women were elevated despite the presence of circulating 17β‐oestradiol levels in the early‐mid follicular phase range. At the time of menopausal transition in one of these subjects, the decline of plasma 17β‐oestradiol to undetectable levels was associated with a further rise of both gonadotrophins. Conversely, following a prolonged period of follicular development with elevated urinary total oestrogen excretion in another subject, the raised gonadotrophin concentrations were suppressed and the pituitary response to LHRH was within the normal range. LHRH responses in the other four women were augmented. Oestrogen administration failed to induce a normal LH surge in three out of the five subjects. The results indicate that marked changes in the pattern of pituitary gonadotrophin secretion can be found in perimenopausal women with DUB. The observed increase in peripheral levels of FSH (with or without concomitant increase in LH) may be due to a change in hypothalamic‐pituitary sensitivity to the feedback effects of oestrogen. Alternatively, it is possible that these changes result from a decrease in the ovarian secretion of a hypothetical ‘inhibin‐like' substance produced by the growing follicle and for which the name ‘FSH‐release inhibiting subs

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1977.tb02936.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1977.tb03357.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1977.tb03358.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

SUMMARY(1)The bone histology of 233 non‐dialysed and 276 haemodialysed patients with chronic renal failure is reviewed. In non‐dialysed patients osteitis fibrosa occurred in 83.7% and osteomalacia in 23.6% of patients. Osteomalacia was not found in the absence of osteitis fibrosa. In haemodialysed patients there was a more variable bone histology, sometimes resembling non‐dialysed bone disease, but in general with a greater incidence of osteomalacia, especially with increasing time on dialysis. In some patients there was a predominance of osteomalacia accompanied by no or only mild osteitis fibrosa and the serum alkaline phosphatase was normal. (2) The results of treating twenty‐six haemodialysed patients with lα‐hydroxy vitamin D3(lα‐OHD3) are described. Patients with osteomalacia and minimal or no osteitis fibrosa and a normal serum alkaline phosphatase (Group I) in general failed to respond and it is suggested that 1,25‐dihydroxyvitamin D3deficiency is not the sole factor responsible for the osteomalacia in these patients. In contrast, lα‐OHD3therapy was effective in improving osteitis fibrosa and osteomalacia in some patients with moderate to severe degrees of osteitis fibrosa and osteomalacia (Group IIa) and in improving osteitis fibrosa where this occurred

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1977.tb03359.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

SUMMARYPlasma vasopressin concentrations were estimated in twelve patients undergoing cardio‐pulmonary bypass for open heart surgery. In six patients anaesthesia was maintained with 66% nitrous oxide in oxygen, whilst the remaining six additionally received halothane as a vasodilator during the bypass period. Induction of anaesthesia had little effect on plasma vasopressin concentrations, whilst marked increases were seen during surgery and bypass in both groups of patients. However, in those patients receiving halothane, significantly higher concentrations were reached, a maximum 36.1 ± 8.9 (SEM) μu/ml being seen in contrast to 15.4 ± 2.2 μu/ml in the group receiving nitrous oxide in oxygen

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1977.tb02937.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

SUMMARYMorphometric and dynamic studies of iliac crest bone biopsies were carried out in twelve patients with chronic renal failure (six on chronic haemodialysis and six with renal insufficiency) before and after 6 montsh of lα‐hydroxyvitamin D3treatment. Pre‐treatment biopsies showed signs of osteomalacia and hyperparathyroidism. Biopsies taken during treatment showed changes towards normality, indicating a beneficial effect of lα‐hydroxyvit

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1977.tb03360.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

SUMMARYSerum triiodothyronine (T3) and thyroxine (T4) levels were measured in twelve hyperthyroid patients before and after treatment with propranolol, 40 mg four times daily, for 2 weeks. There was a significant fall in serum T3 and a significant rise in serum T4 concentrations in the group as a whole and it was concluded that the clinical effectiveness of propranolol in hyperthyroidism may be mediated in part by its action on the peripheral metabolism of thyroid hormones. Propranolol treatment should be withdrawn gradually as removal of the suppressive action of the drug on thyroid hormone metabolism is potentially hazardous, particularly in patients with ischaemic heart disease.

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1977.tb02938.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

SUMMARYA young man presented with rapidly developing Cushing's syndrome which was due to the ectopic secretion of ACTH and β‐MSH‐like material from hepatic tumour deposits, possibly originating from biliary radicals. This association of the ectopic ACTH syndrome has not previously been described. During the 22 month course of the illness the plasma immunoreactive ACTH and ‘β‐MSH’ concentrations rose by logarithmic progression. The plasma calcitonin concentration was also raised but did not change during the last 12 months. At any stage of the illness the plasma concentration of the ecotopically produced hormones was stable except that after hydrocortisone there were inconstant variations.During the course of the illness the ectopic ACTH became biologically less potent. This ineffectual ACTH was present in the plasma, in the tumour, and in the medium in which the tumour was cultured, in a large molecular weight form. This ‘big ACTH’ differed from the normal ACTH found in the patient's pituitary and from authentic ACTH in its immunochemical character: the C‐terminal antigenic determinant (33–39 region of ACTH) was masked in the large molecular weight form but was uncovered after extraction in neutral buffer and this ‘big ACTH’ was more readily extracted from the tumour at pH 7.0. The tumour tissue also contained immunoreactive β‐MSH‐like material and immunoreactive calcitonin which resembled calc

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1977.tb02939.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

SUMMARYTwenty‐three patients with bone disease and chronic renal failure were treated for periods of 4–28 months with lα‐hydroxyvitamin D3(1α‐OHD3). Improvements in bone histology were consistently seen in patients with features both of osteitis fibrosa and osteomalacia but were not invariably observed in patients with osteitis fibrosa or osteomalacia alone (37 and 50% improved respectively). Several factors influencing the outcome of treatment were assessed on the basis of histological responses in bone. A low level of plasma calcium before treatment, rather than the dose of lα‐OHD3tolerated, was the major detectable factor which favourably affected the histological outcome. Other factors examined, including initial plasma concentrations of phosphate, immunoreactive parathyroid hormone and alkaline phosphatase, and treatment with haemodialysis or dietary supplements of calcium did not apparently influence

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1977.tb03362.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY