ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02640.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryBACKGROUND AND OBJECTIVE Recent data Indicate that oral medroxyprogesterone acetate (MPA) has limited unfavourable, neutral or even favourable effects on serum lipid fractions when added to oestrogen replacement therapy. The purpose of this study was to evaluate the serum lipid fractions at the beginning and at the end of each phase of a sequentially combined resplacement cycle comparing the oral and the transdermal routes of oestrogen administration.DESIGN Randomized study with a matched control group. Oral con|ugated oestrogens (OCE, 0‐625 mg) or transdermal oestradiol (TE 50 μg) was taken from day 1 to day 25 and MPA (5mg) added on days 14 to 25. Serum lipids were evaluated on days 1, 14 and 25 of monthly replacement cycles.PATIENTS The early post‐menopausal women In the control group (n = 11) and in the treatment groups (OCE/MPA,n= 15; TE/MPA,n= 17) were evaluated every 3 months for 12 months and every 6 months for another 12 months.MEASUREMENTS Serum levels of triglycerides (TG), cholesterol (C) fractions and apollpoprotelns (Apo) and their respective ratios were measured at months 1,3,6,9, 12,18,24. Menopausal symptoms and uterine bleedings were evaluated in parallel and an endometrial biopsy was performed at the end of the 12th and 24th months of treatment. RESULTS After 14 days of OCE, C, LDL‐C, and Apo B were decreased and TG, HDL‐C and Apo A1 were Increased. The sequential addition of MPA accentuated the reduction of LDL‐C and Apo B but attenuated the elevation of TG, HDL‐C and Apo A1. These changes tended to revert toward baseline during the period free of medication. By contrast, at the end of 14 days of TE there was a non‐significant reduction in TG and LDL components and a limited increase in HDL‐C and Apo A1. During the subsequent addition of MPA there was no significant decrease in TG, LDL‐C or Apo B but an elimination of the increase In HDL components. These combined changes resulted in a significant reduction in the LDL‐C/HDL‐C ratio and a significant elevation in the Apo A1/Apo B ratio only In the OCE/MPA group.CONCLUSION Overall, oral conjugated oestrogens Induced favourable intragroup changes in cholesterol fractions whereas transdermal oestradiol maintained serum lipids at levels not different from baseline. The sequential addition of oral medroxyprogesterone acetate attenuated the beneficial elevation of HDL, did not affect the beneficial effect of oestrogens on ratios of cholesterol fractions and attenuated the unfavourable effect of oral conjugated oestrogens on triglycerides. The partial loss of beneficial effects on lipoproteins during cyclical interruption of hormone therapy would be an argument in favour of the evaluation of continuous regimens of oes‐trogen

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02641.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryMaternal hypothyroidism may be associated with a variety of pregnancy complications.OBJECTIVE We have evaluated the perinatal consequences of maternal hypothyroidism in early and late gestation.DESIGN Retrospective study of pregnant women, with quasi‐experimental design comparing different subjects.SUBJECTS Forty‐three pregnancies In 42 women with hypothyroidism ‐ either biochemically hypothyroid or with a history of hypothyroidism on adequate replacement ‐ and no other preexisting medical conditions.MEASUREMENT Free thyroxine index (FTI), TSH, and haematocrit at Initial antepartum presentation and near term gestation. Pregnancy outcome variables Including: rate of Caesarean section performed for fetal distress in labour, neonatal weight percentile, and gestational age at birth.RESULTS Of 42 hypothyroid pregnancies, six were complicated by fetal distress In labour leading to Caesarean section. Five of these six were severely hypothyroid (defined as FTI ≤ 0.6 (normal range 1.1–4.4)) on initial antepartum presentation. In contrast, of the 36 pregnancies without fetal distress, only four initially presented severely hypothyroid (P<0.001). Conversely, 56% (5/9) of pregnancies which Initially presented severely hypothyroid were subsequently complicated by Caesarean section for fetal distress in labour. This compared to 3% (1/33) among those who presented either mildly hypothyroid or euthyroid on replacement (P<0.0001). Fetal distress correlated with low FTI (P<0.001) and high TSH at Initial presentation. However, It was independent of FTI near term. A relation between fetal distress and TSH near term did not reach statistical significance. Fetal distress also correlated with low maternal haematocrit on admission to labour and delivery (P<0.05), but was Independent of haematocrit and gestational age at Initial presentation, neonatal weight percentile, and gestational age at birth.CONCLUSIONS Severe maternal hypothyroidism early in gestation Is strongly associated with fetal distress in labour. This suggests that (1) Inadequate maternal replacement leads to fetal distress and (2) maternal thyroid status in early gestation may exert Irreversible effects on the fetus, the placenta, and/or on subsequent maternal adaptations to pregnancy. Early adequate replacement therapy Is especially prudent in pregnant women presenting with severe hyp

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02642.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Despite regular transfusion and desferoxamine treatment, growth failure Is commonly seen In adolescent children with β‐thalassaemla major. The growth failure has been thought to be due to GH resistance rather than GH deficiency. We Investigated the effect of GH on short non‐GH deficient children with β‐thalassaemia.DESIGN Recombinant human GH was given In a dose of 0‐14IU/kg/day subcutaneously in an open study.PATIENTS Fifteen prepubertal Chinese children with β‐thalassaemia major (ranging from 7.16 to 14.7 years In age) with height −1.5 SD or more below the population mean for age and a growth velocity of less than 5 cm/year were treated with growth hormone for one year. All children had peak GH response>15mlU/l to insulin Induced hypoglycaemia and normal thyroid function and adrenal reserve.MEASUREMENTS Anthropometric measurements were performed every 3 months. Morning urine was tested twice weekly for glycosuria. Blood count, renal and liver function tests, fasting blood glucose, IGF‐I and fructosa‐mine levels were assessed at entry and every 3 months during treatment. Fasting Insulin was measured before and after 3 and 12 months of GH treatment. Skeletal maturity was assessed before and after one year of treatment.RESULTS Treatment was stopped in two children after 6 months because of poor growth response and noncompliance with treatment and In one child at 9 months because of bone marrow transplantation. In the 13 children, the growth velocity increased from 3.6±0.7 cm/year to 8±1.2 cm/year after one year of GH treatment (P<0.001). IGF‐I was low before treatment (10.1±2.7nmol/l), rising significantly to 15.8±4.8, 18.4±4.6, 19.3±6.4 and 21.9±7.5nmol/l at 3, 6, 9 and 12 months of treatment (P<0.005). The mean pretreatment bone age in the 13 children was 9.58±1.41 years and increased to 10.53±1.43 years after one year of treatment (ΔBA/CA 0.95±0.3 years). None of the patients developed glycosuria or hypertension. There was no significant change in blood count, renal and liver function, thyroid function, fasting blood glucose or insulin concentrations during treatment.CONCLUSION Growth failure In these children with normal GH reserve and low serum IGF‐I concentrations would suggest GH insensltlvity. Supraphyslologlcal doses of exogenous GH can cause a significant increase In serum IGF‐I levels and a significant Improvement in short‐term growth of sho

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02643.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryBACKGROUND AND OBJECTIVE Growth hormone treatment In children with Idiopathic short stature (ISS) leads to growth acceleration in the first years, but the effect on final height is still poorly documented. We therefore studied the long‐term effect of GH therapy in children with Idiopathic short stature.DESIGN We have treated 27 prepubertal children with ISS with recombinant human GH (rhGH) in an initial dosage of 2 IU/m2body surface/day subcutaneously, which was doubled either after the first year if the height velocity increment was less than 2 cm/year, or thereafter if height velocity fell below the P50 for bone age. Growth and bone maturation of the treatment group (ISS group,n= 21) were compared to those of an untreated control group with ISS (ISS controls,n= 27) and of a group of rhGH treated children with isolated GH deficiency (GHD group,n= 7).RESULTS In 9 patients of the ISS group still on treatment, height standard deviation score (HSDS) for chronological age increased from −3.8±0.7 to −2.3±0.9 (mean±standard deviation) over 6 years, while in matched ISS controls HSDS for age did not change. HSDS for age in the GHD group increased from −3.9±0.6 to −1.8±0.7 after 4 years, significantly more than the ISS group. Bone maturation was accelerated In the ISS and GHD groups. HSDS for bone age and predicted adult height did not change in either group. Final height in 12 children of the ISS group was −2.6±1.0 SDS. In the untreated controls final height was similar. A low integrated GH concentration over 24 hours, a low GH peak to provocative stimuli, and minimal initial BA delay predicted a favourable outcome.CONCLUSION rhGH treatment In this group of children with Idiopathic short stature did not increase average final height. Part of the heterogeneity of the response can be attributed to the variation in endogenous GH secretion and initi

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02644.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Hypothyroidism can be complicated by bleeding symptoms such as easy bruising, menorrhagla and sometimes even a severe bleeding tendency with fatal outcome. Usually there is a prolonged bleeding time, or a low plasma concentration of coagulation factor VIII (FVIII) or von Willebrand factor (vWF). The aim of the present study was to investigate the acute haemostatic effect of desmopressin in hypothyroid patients. Another aim was to study the long‐term effect of thyroxine replacement on the plasma concentrations of coagulation factors and to ascertain the duration of thyroxine treatment needed to restore haemostatic function.DESIGN AND PATIENTS The effects of desmopressin, given intravenously over 10 minutes at a dosage of 0.3 μg/kg, and thyroxine treatment on haemostatic function were studied prospectively In 10 patients with hypothyroidism.RESULTS Before treatment only five of the patients manifested bleeding symptoms; one had prolonged bleeding time, and one had low plasma concentrations of vWF: Ag. Desmopressin virtually immediately reduced bleeding time, enhanced platelet adhesiveness, and significantly increased plasma concentrations of FVIII and vWF.The plasma concentrations of FVIII and vWF showed a significant increase after 4 months, whereas 7 months treatment with thyroxine was needed to reduce bleeding time significantly.CONCLUSION Our results suggest that in hypothyroid patients desmopressin may be of value for the acute treatment of bleeding or as cover for surge

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02645.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE We have studied lymphocyte Induced cytotoxicity and the production of interferon gamma (IFN‐α) and tumour necrosis factor alpha (TNF‐α) during coculture of thyrocytes and autologous lymphocytes from patients with Graves' disease and from normal subjects.PATIENTS Thyroid tissues and lymphocytes were obtained from 28 patients with Graves' disease and from 9 control subjects.MEASUREMENTS Lymphocyte induced cytotoxicity was evaluated on autologous thyrocytes using 5 metabolic tests: the MTT assay, the neutral red uptake, lactate dehydrogenase measurement and glutathione assay. IFN‐γ and TNF‐α measurements were performed after 1, 5 or 7 days' coculture.RESULTS The lymphocytes Isolated from peripheral blood (PB lymphocytes) altered the morphology and the metabolism of autologous thyrocytes. The Intrathyroidal lymphocytes Isolated after Dispase digestion were not toxic whereas mechanically Isolated lymphocytes exerted a little toxicity. No difference was seen between Graves' disease and normal cells.The supernatants from cocultures had higher IFN‐γ levels than those from lymphocyte cultures, in coculture, PB lymphocytes secreted more IFN‐γ and TNF‐α than Intrathyroidal lymphocytes. The PB lymphocyte Induced cytotoxicity was not due to IFN‐γ and TNF‐α alone.CONCLUSION Peripheral blood lymphocytes are cytotoxicin vitroto autologous thyrocytes whereas Intrathyroidal lymphocytes exert little or no cytotoxicity according to their isolation method. The mechanisms of lymphocyte Induced toxic

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02646.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02647.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE The alms were to measure concentrations of Inhibin‐A (α‐βAdimer) in peripheral serum during normal human pregnancy, to establish which molecular weight form(s) are present In pregnancy serum and to relate the concentrations of inhlbin‐A to those of oestradlol and progesterone.DESIGN In a retrospective cross‐sectional study 211 serum samples collected at 2‐week Intervals from week 8 to 38 of gestation were analysed for inhlbln‐A by enzyme immunoassay and oestradlol and progesterone by radioimmunoassay. Pooled samples corresponding to first, second and third trimester were subsequently used for fast protein liquid chromatography chromatographic analysis of Inhibln forms present.PATIENTS Blood samples were obtained from normal pregnant women attending the antenatal clinic.RESULTS Concentrations of Inhibin‐A in peripheral serum gradually decreased from 1.76±0.15/μg/l in week 8 of gestation to 0.86±0.12μg/l in week 16 (P<0.01). Concentrations remained low during the second trimester but Increased markedly (P<0.01) during the third trimester reaching a maximal value of 5.68±0.89 μg/l In week 36. Chromatographic analysis of pooled serum samples from the first, second and third trimester showed that the fully processed 31‐kDa molecule is the predominant circulating form of inhlbln‐A throughout human gestation. Likewise, only the 31‐kDa form was Identified in extracts of term placenta which contained ∼20 μg inhibin‐A/kg tissue.CONCLUSION Inhlbin‐A, principally the 31‐kDa form, is present in peripheral blood throughout human gestation at concentrations up to 50 times greater than maximum values found during the spontaneous menstrual cycle (∼100ng/l). The finding of highest serum values during the third trimester and of significant concentrations In term placenta firmly support a placental rathe

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02648.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE The aim of this investigation was to study the effect of relatively high dose IGF‐I therapy given for several months, on serum levels of IGF‐I, IGF‐II and IGFBP‐3, and on IGF‐I pharmacokinetics In patients with growth hormone insensitivity due to GH receptor dysfunction.DESIGN AND PATIENTS Two adolescent subjects from Ecuador were treated with recombinant IGF‐I at a dosage of 120μg/kg s.c. twice dally, in combination with a GnRH analogue for 8 months.MEASUREMENTS Serum was sampled at baseline and at 3–8 months, for determination of IGF‐I, IGF‐II and IGFBP‐3 by radioimmunoassay, and for evaluation of IGFBPs and IGFBP‐3 protease activity by Western ligand blot and protease assay, respectively.RESULTS Peak serum IGF‐I levels ranged from 272 to 492μg/l. Mean serum IGF‐II levels were decreased concurrently with the increase in IGF‐I. Serum IGFBP‐3 levels failed to rise with prolonged IGF‐I treatment. There was no apparent change In the half‐life of IGF‐I during the treatment period.CONCLUSIONS IGF‐I administration does not increase serum levels of IGFBP‐3 or s

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02649.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY