ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00982.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00983.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00984.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE The aim was to investigate the long‐term evolution of circulating growth hormone antibodies (GH‐AB) during and after treatment with methionyl‐recombinant human growth hormone (met‐rhGH).DESIGN AND PATIENTS The investigation was performed on serum samples of 46 growth hormone deficient children, treated for at least 12 months with met‐rhGH. Twenty patients had never been treated with hGH (previously untreated patients, Group I). Twenty‐six subjects were previously treated with pituitary extracted hGH (treated patients, Group II).MEASUREMENTS Serum levels of GH‐AB were measured by radioimmunoassay using charcoal precipitation of free ligand.RESULTS Fifteen patients (75%) of Group I and three patients (12%) of Group II developed GH‐AB. In 15 GH‐AB positive patients the antibodies became detectable during the first year of treatment with met‐rhGH. In three patients, however, the GH‐AB appeared during the second year. Once present, the GH‐AB remained detectable throughout the period of treatment with met‐rhGH. In six patients in whom treatment with met‐rhGH was stopped, GH‐AB levels decreased rapidly. In nine patients in whom treatment with met‐rhGH was changed to rhGH, the levels of GH‐AB decreased and ultimately became undetectable. In two patients GH‐AB remained present during administration of rhGH. No effect of GH‐AB on the growth‐promoting effect of met‐rhGH could be documented, either during the first or during the second year of treatment.CONCLUSIONS This study confirms the high immunogenicity of met‐rhGH, especially in patients not treated earlier with hGH. Once present, the GH‐AB remain detectable throughout the period of treatment with met‐rhGH. After stopping met‐rhGH treatment or changing to rhGH the GH‐AB disappear rapidly in most patients. No effect of GH‐AB on th

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00985.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE Studies in rodents have shown GH binding protein (GHBP) levels to be dependent on the mode of GH administration. The aim is to determine whether GHBP levels in man are also modulated by the pattern of GH administration.PATIENTS Six GH deficient subjects participated in a randomized study in which 2 IU GH were administered either as (i) a continuous 24‐hour infusion, (ii) two intravenous boluses or (iii) eight intravenous boluses every 3 hours. In a second study, six normal men received a single subcutaneous injection of 0 2 U/kg GH and GHBP activity was measured over 24 hours. Control data were obtained from an untreated group of six age‐matched normal men.MEASUREMENTS GHBP activity was measured by immunoprecipitation using a monoclonal antibody that recognizes the human GHBP, and expressed as percentage specific binding of125I‐GH in 50 μl of serum.RESULTS GHBP activity was not significantly different between the GH deficient and normal subjects. GHBP activity did not rise significantly during GH administration with each of the three intravenous patterns of delivery nor were there any significant differences between treatments. in the second study, GHBP activity did not change significantly following subcutaneous GH injection nor did results differ from untreated normal controls.CONCLUSIONS The level of GHBP in man is not dependent on GH secretory status or altered by short‐term GH treatment or the mode of administration. These findings stand in contrast to GH treatment effects in rodents and suggest that GH regulation of GHBP may be different between

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00986.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We have investigated the effects of cholinergic modulation with pirenzepine and pyridostigmine and of GH pretreatment on the subsequent GH response to a maximal stimulatory dose of GH‐releasing hormone (GHRH) in patients with insulin dependent diabetes mellitus (IDDM). We have also investigated the relationship between the differences in metabolic control and other parameters of disease state with the differences in GH responses in IDDM.PATIENTS Thirteen male subjects with IDDM and no clinical evidence of complications were selected based on HbA, levels to provide a wide range of metabolic control. Seven normal subjects were also studied.DESIGN Twelve of the subjects with IDDM and six normal subjects received pirenzepine 200 mg and pyriostigmine 120 mg pretreatment 60 minutes and GH pretreatment 3 hours before an i.v. injection of GHRH (1–44) (80 μg) in random order. All subjects underwent a control study with GHRH alone.MEASUREMENTS Serum GH and plasma glucose were measured at regular intervals throughout the study. Fasting plasma glucose and HbA, were measured before each study to provide measures of metabolic control.RESULTS Subjects with IDDM demonstrated exaggerated GH responses to GHRH compared to normals. Pirenzepine significantly reduced GH responses in both normal and diabetic subjects. However, the GH response to GHRH after pirenzepine was higher in subjects with IDDM (mean GH: IDDMvsnormals; 8.1 ± 1.3vs2.9 ± 0.7 mU/l,P<0.05). Pyridostigmine 120 mg significantly augmented the GH response to GHRH in normal subjects. In diabetic subjects, pyridostigmine failed to increase GH response to GHRH compared to GHRH alone (mean GH: pyridostigminevscontrol: 75.7 ± 12.6vs38.9 ± 5.4 mU/l,P= NS). GH responses to GHRH after pyridostigmine pretreatment in both normal and diabetic subjects did not differ and the GH response to GHRH after pyridostigmine in normal subjects did not differ from the GH response to GHRH alone in diabetic subjects. In normal subjects, GH pretreatment significantly reduced subsequent GH responsiveness to GHRH (Δpeak GH 26.4 ± 5.2vs7.7 ± 5.4 mU/I,P<0.04). In contrast, GH pretreatment did not cause any significant reduction in GH responsiveness to GHRH In diabetics (Δpeak GH 53.6 ± 9.7vs33.4 ± 11 mU/I,P= NS). No significant correlation was demonstrated between measures of diabetic control and the responses to GHRH alone or after cholinergic modulation and GH pretreatment.CONCLUSION These data suggest that ambient hypothalamic cholinergic tone in diabetes is high, and of similar degree to the enhanced cholinergic tone in normal subjects pretreated with pyridostigmine. We suggest that in diabetic subjects, the reduced responsiveness to autofeedback may be secondary to the enhanced cholinergic tone demonstrated in these patients. The mechanisms linking the uncontrolled diabetic state to this abnormal neuroregulation of GH remains unkn

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00987.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We studied changes in pituitary response to GnRH during the luteal‐follicular transition of the human menstrual cycle.DESIGN Normally cycling women were investigated during two consecutive menstrual cycles. In each woman, GnRH tests were performed during the two LH surges and several times during the luteal‐follicular transition. Data for analysis were available in all women on days −8, −6, −4, −2, −1,1, 2, 3, 4, 5 and 7 in relation to the onset of second menstruation (day 1).PATIENTS Five normally ovulating parous women were studied.MEASUREMENTS Pituitary response to GnRH was calculated as the net increase in LH and FSH at 30 minutes (ΔLH and ΔFSH) above the basal value.RESULTS ΔLH and ΔFSH showed a similar pattern of significant changes during the luteal‐follicular transition. They decreased progressively from days −8 to 1 and increased on day 2. ΔLH and ΔFSH then decreased on days 3 and 4 and showed a further increase on days 5 and 7. In contrast to these changes, basal FSH levels increased from days −2 to 1 and remained high up to day 5, while basal LH levels showed a trend to increase only after the onset of menses.CONCLUSIONS These results demonstrate that the increase In basal FSH secretion during the luteal‐follicular transition is GnRH independent. It is suggested that LH and FSH release under the stimulation by GnRH is regu

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00988.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We investigated the effect of intramuscular injections of long‐acting bromocriptine in patients with macroadenomas.STUDY DESIGN AND PATIENTS Thirty patients with PRL‐secreting pituitary macroadenomas were treated with repeated 4‐weekly intramuscular injections of 50 or 100 mg of a long‐acting, repeatable bromocriptine formulation for six to 37 injections, amounting to a total of 473 injections. Twenty patients received parenteral bromocriptine as primary therapy, ten had persisting hyperprolactinemia after previous therapies including pituitary surgery (n= 7), oral bromocriptine (7), and pituitary Irradiation (2).MEASUREMENTS A PRL day profile was obtained and the patients' clinical status and historyweredocumented, at intervals. Detailed clinical, laboratory, and radiological (pituitary nuclear magnetic resonance or computed tomography scan) evaluations were performed at baseline, after 1 injection and every 6th injection therafter.RESULTS In all patients PRL was suppressed from a mean ± SEM pretreatment level of 32 620 ± 8680 to 4480 ± 1140 mU/l on the third day after the first injection. In 12 patients PRL levels normalized (<400 mU/l) with the first to fourth injection, in three additional patients PRL levels normalized after 8–15 months. In 19 patients PRL was suppressed to less than 1000 mU/l. In three patients PRL did not decrease to less than 50% of pretreatment; in two of them on oral bromocriptine prior to this study there had been a comparable low efficacy. Of 28 patients with macroadenomas (median height 22 mm) tumour shrinkage was evident in 15 by nuclear magnetic resonance or computed tomography scan 28 days after the first injection, and in three additional patients after 6 months. There was further regression in seven cases after 12, 18 or 24 injections. Adenoma size (mean SEM) decreased to 66 ± 7% of the pretreatment value. The 40 adverse events noted in 20 of 30 patients during 24 hours after the first injection were similar to known side‐effects of oral bromocriptine, nausea and postural hypotension being the most frequent. With repeated injections, on average 0 6 adverse events were noted per injection (mostly mild asthenia). There were no local adverse reactions at the injection site.CONCLUSION We conclude that long‐acting repeatable bromocriptine in patients with macroprolactinomas offers a safe and efficacious primary treatment that ensures compliance and gives long‐term control. Adverse reactions are comparable to oral bromocriptine but subside with

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00989.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We investigated the pharmacokinetics and biological effects of 1‐deamino‐8‐d‐arginine vasopressin (dDAVP) in healthy adults after intravenous, subcutaneous, intranasal, peroral, sublingual and intrarectal administration.DESIGN Eight normal volunteers were studied over an 8‐hour period after each drug administration, separated by at least one week. For intravenous and subcutaneous administration, the subjects received 2 μg of dDAVP. The intranasal and sublingual doses were 20 μg and the rectal dose was 50 μ. Oral administration of dDAVP was effected with a 200‐μg tablet.MEASUREMENTS Plasma and urinary levels of dDAVP were measured using a specific and sensitive radioimmunoassay.RESULTS A significant increase of urine osmolality was observed after all routes of administration, except the sublingual and intrarectal for up to 8 hours after administration. After intravenous administration, the half‐life of elimination (t) of dDVAP was 78 ± 10 minutes. An extensive adsorption of dDAVP to the plastic syringe was found with intravenous but not with subcutaneous administration. Using the area under the curve of dDAVP from the subcutaneous administration as a reference, bioavailability was found to be 3.4% after intranasal administration and 0.1% after oral administration. After sublingual and intrarectal routes of administration no detectable dDAVP was found in the blood; however, low amounts were found in the total 24‐hour urine.CONCLUSION The bioavailability of dDAVP seems lower than previously reported after intranasal and

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00990.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We determined the effects of physiological (non‐hypotensive) increments of plasma atrial natriuretic factor (ANF) on the vasopressin and hypothalamic‐pituitary‐adrenal response to insulin induced hypoglycaemia. DESIGN Single blind, placebo controlled, randomized study of the effect of vehicle alone or ANF (2.5 pmol/kg/min for 120 minutes) commencing 30 minutes before bolus administration of insulin (0 15 U/kg body weight).RESULTS ANF infusion raised venous plasma ANF levels four to five‐fold (mean level 32 ± 0.3 pmol/l at time of insulin injection) without affecting resting blood pressure or heart rate. After insulin, the fall in plasma glucose and rise in plasma adrenaline and noradrenaline were similar in both studies. In contrast, the responses in plasma arginine vasopressin (P<0.02) and in plasma angiotensin II (P<0.05) were inhibited by ANF. Plasma corticotrophin releasing factor, ACTH and Cortisol responses to hypoglycaemic stress did not differ significantly in the presence and absence of ANF.CONCLUSION We conclude that four to five‐fold acute increase in plasma ANF, while attenuating vasopressin and angiotensin II responses to hypoglycaemia, does not inhibit the hypothalamic, pituitary and adrenal responses or inhibit sympathetic nervous activation in

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00991.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY