Treatment options in acromegaly. Benefits and costs.
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Acromegaly↗
Biomedical subjects
K K Ho
Publications and source records attributed to K K Ho.
Growth hormone-induced insulin resistance and its relationship to lipid availability in the rat.
The role of increased lipid availability in the generation of insulin resistance by growth hormone has not been established. We investigated this in rats infused with saline (controls) or human growth hormone (hGH) (500 micrograms x kg-1 x 24 h-1) for 5 h or 3 days. hGH infusion increased basal plasma insulin at 5 h (335 +/- 33 vs. 197 +/- 15 [controls]; P < 0.005) and at 3 days (396 +/- 34 vs. 218 +/- 14 pmol/l; P < 0.0001). Plasma nonesterified fatty acid (0.26 +/- 0.01 vs. 0.21 +/- 0.01 [controls] g/l) and liver long-chain acyl-CoA (21.2 +/- 1.9 vs. 14.1 +/- 1.1 [controls] nmol/g wet wt) were elevated at 5 h (P < 0.01 for both) but were below control levels after 3 days of hGH infusion (P < 0.01 for both); indirect calorimetry after 3 days demonstrated decreased lipid oxidation. Clamp studies showed similar degrees of peripheral insulin resistance at 5-h and 3-day hGH infusion (glucose disposal reduced by 25% versus controls). Insulin-stimulated glucose metabolic index (Rg') in red gastrocnemius muscle (red muscle) was reduced (P < 0.05 and P < 0.01) at 5 h and 3 days of hGH infusion, respectively (e.g., 5 h, 10.0 +/- 1.8 vs. 24.1 +/- 4.4 [controls] micromol x 100 g-1 x min-1), whereas insulin-mediated muscle glycogen synthesis was reduced (P < 0.03) only in rats infused with hGH for 3 days. We conclude that in the rat, hGH rapidly induces persistent peripheral insulin resistance and basal hyperinsulinemia. However, the transient nature of increased lipid mobilization suggests that it is not an important factor in the manifestation of muscle insulin resistance during prolonged hGH elevation. The persistent insulin resistance is not associated with increased lipid oxidation but is associated with hyperinsulinemia and reduced insulin-mediated muscle glycogen synthesis.
Adipose Tissue↗
Congenitally absent third molars in 12 to 16 year old Singaporean Chinese patients: a retrospective radiographic study.
Third molars have been associated with a host of pathologies and there are risks involved with their surgical removal. They also have the highest incidence of congenital absence of all the permanent teeth. The aim of this study was to determine the prevalence and distribution of congenitally missing third molars in local Chinese patients. The orthopantomographic radiographs of 786 Singaporean Chinese patients aged 12 to 16 years were examined. It was found that 562 (71.5%) of the children had all 4 third molars. Varying degrees of third molar agenesis were noted in the other 224 (28.5%) children. Of these, 43 (5.5%) showed total absence of third molars. There was no significant difference in agenesis between the right and left sides and no sexual predilection was noted. However, more third molars were missing from the maxilla compared to the mandible, the ratio being 3:2.
Adolescent↗
In-hospital and one-year economic outcomes after coronary stenting or balloon angioplasty. Results from a randomized clinical trial. Stent Restenosis Study Investigators.
BACKGROUND: Coronary stenting has been shown to improve initial success, reduce angiographic restenosis, and reduce the need for repeat revascularization compared with conventional balloon angioplasty (PTCA). Although previous studies have demonstrated that initial hospital costs for stenting are considerably higher than those for conventional PTCA, the impact of coronary stenting on long-term medical care costs remains unknown. METHODS AND RESULTS: Between January 1991 and June 1993, 207 consecutive patients with symptomatic coronary disease requiring revascularization of a single coronary lesion were randomized to receive initial treatment by either PTCA (n = 105) or Palmaz-Schatz coronary stent implantation (n = 102) in the multicenter STRESS trial. Detailed resource utilization and cost data were collected for each patient's initial hospitalization and for any subsequent hospital visits for 1 year after randomization. Compared with conventional angioplasty, coronary stenting resulted in additional catheterization laboratory costs, increased vascular complications, and longer length of stay. Initial hospital costs were thus approximately $2200 higher for stenting than for PTCA ($9738 +/- 3248 versus $7505 +/- 5015; P < .001). Over the first year of follow-up, however, patients assigned to initial stenting were less likely to require rehospitalization for a cardiac condition and underwent fewer subsequent revascularization procedures. Follow-up medical care costs thus tended to be lower for stenting than for conventional angioplasty ($1918 +/- 4841 versus $3359 +/- 7100, P = .21). Nonetheless, cumulative 1-year medical care costs remained higher for patients undergoing initial stenting ($11,656 +/- 5674 versus $10,865 +/- 9073, P < .001). Even after adjustment for the higher incidence of vascular complications in the stent group, total 1-year costs were $300 higher for stenting than for balloon angioplasty. CONCLUSIONS: Elective coronary stenting, as performed in the randomized STRESS trial, increased total 1-year medical care costs by approximately $800 per patient compared with conventional angioplasty. Future studies will be necessary to determine whether ongoing refinements in stent design, implantation techniques, and anticoagulation regimens can narrow this cost difference further by reducing stent-related vascular complications or length of stay.
Aged↗
Estrogen, lipid oxidation, and body fat.
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Adipose Tissue↗
Defining growth hormone deficiency in adults.
The absence of a distinct clinical syndrome calls for a strategy to reliably identify patients with hyposomatotropism. However, there is no consensus as to the most appropriate method of defining growth hormone (GH) deficiency in adults. Since GH secretion falls with senescence and is also reduced by obesity, both of these factors must be controlled for in such an evaluation. We have investigated the relative diagnostic merits of measuring (1) peak GH response to insulin-induced hypoglycemia (ITT), (2) mean 24-hour GH concentration derived from 20-minute sampling (IGHC), (3) serum IGF-I levels, and (4) serum insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) levels. These tests were undertaken in 23 patients considered GH-deficient from extensive organic pituitary disease and in 35-sex-matched normal subjects of similar age and body mass index. The ITT was the only test capable of distinguishing patients with organic GH deficiency from matched normal subjects. The sensitivity of the GH radioimmunoassay (0.2 ng/mL) limited the utility of IGHC measurements, since many subjects from both groups had undetectable values. Using a GH assay with a 100-fold greater sensitivity, we found a better but still incomplete separation of values between the two groups. There was a significant overlap of IGF-I and IGFBP-3 values, with only a third of GH-deficient subjects having low IGF-I values. The limitation of IGF-I has been confirmed by others, although its sensitivity as a diagnostic test is greater in young adults. We conclude that organic GH deficiency in adults can be reliably diagnosed by the ITT.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Subcutaneous injection of an analog of neuropeptide FF prevents naloxone-precipitated morphine abstinence syndrome.
There is evidence that neuropeptide FF (NPFF) has antiopiate activity and may play a role in opiate dependence and subsequent abstinence syndrome. A fragment of NPFF was modified at the C-terminal in an effort to convert it to an NPFF antagonist. It was also dansylated at the N-terminal in an effort to render it more lipophilic and increase its penetration of the blood-brain barrier. Third ventricle administration of the resulting compound, dansyl-PQRamide (0.75 microgram and 1 microgram), dose-dependently antagonized the quasi-morphine abstinence activity of NPFF (10 micrograms) in opiate-naive rats. Subcutaneous injection of dansyl-PQRamide (13 mg/kg) in chronically morphine-infused rats attenuated opiate dependence as indicated by prevention of naloxone-precipitated abstinence syndrome. Dansyl-PQRamide displaced radiolabelled ligand from NPFF receptors in a concentration-dependent manner with a Ki of 13 microM, and had a half-life over 300 times longer than NPFF under aminopeptidase digestion.
Animals↗
Oestrogen effects on calcitriol levels in post-menopausal women: a comparison of oral versus transdermal administration.
BACKGROUND AND OBJECTIVES: In some studies oral oestrogen therapy in post-menopausal women has been shown to increase both total and free 1,25-dihydroxyvitamin D (calcitriol) levels, suggesting that oestrogen therapy may prevent post-menopausal bone loss, in part, by increasing calcium absorption as a result of raised calcitriol levels. Transdermal oestrogen, however, has not been shown to increase calcitriol levels although it prevents bone loss. These two routes of administration have not previously been directly compared in the same subjects at bioequivalent doses as assessed by FSH and LH suppression. DESIGN AND PATIENTS: In a randomized cross-over study, 15 women at least 12 months post-menopausal (mean age 56 years (range 50-66)) were randomized to either oral conjugated equine oestrogen (1.25 mg daily) or transdermal 17 beta-oestradiol (100 micrograms daily) for 12 weeks after which each subject changed over to the alternative medication. For the last 12 days of each medication, 10 mg medroxyprogesterone acetate (MPA) was added to the treatment protocol. A fasting blood sample was taken at baseline and at the end of each treatment period prior to administration of the MPA. MEASUREMENTS: Serum calcium, phosphorus, albumin, bicarbonate, intact parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (calcitriol), 25-hydroxyvitamin D (25OHD), vitamin D-binding protein (DBP) were measured. The free calcitriol index was calculated as the molar ratio of calcitriol to DBP. Free calcitriol was measured by centrifugal ultrafiltration. RESULTS: The degree of suppression of FSH and LH was similar with the two routes of oestrogen administration. Total calcitriol was significantly higher with oral oestrogen treatment compared to transdermal oestrogen and compared to baseline (mean +/- SEM, baseline 80 +/- 5; oral oestrogen 102 +/- 8; transdermal oestrogen 82 +/- 4) as was DBP (mean +/- SEM, baseline 5.2 +/- 0.2; oral oestrogen 6.9 +/- 0.4; transdermal oestrogen 5.8 +/- 0.2) which accounted for the rise in calcitriol. Free calcitriol measured by equilibrium dialysis showed no rise with either oestrogen preparation. Phosphorus was not different between treatment groups and fell with both oestrogen treatments (baseline 1.32 +/- 0.15, oral oestrogen 1.23 +/- 0.10, transdermal oestrogen 1.17 +/- 0.16) and PTH rose with both treatments (baseline 1.33 +/- 0.21, oral oestrogen 1.52 +/- 0.27, transdermal oestrogen, 1.99 +/- 0.32). Calcium was not different between treatment groups and was not different from baseline. CONCLUSIONS: These results show that in this study the total calcitriol rose after oral but not transdermal oestrogen due to a rise in vitamin D-binding protein. Free calcitriol was not affected by oral or transdermal oestrogen treatment despite a fall in plasma phosphorus and a rise in PTH, both of which are considered agonists for calcitriol production. We may therefore conclude that neither oral nor transdermal oestrogen replacement routinely stimulates free calcitriol levels. In the studies where a rise in free calcitriol was noted, the degree of suppression of bone resorption by oestrogen may have been greater, thus producing a larger demand for calcium due to filling of a larger bone remodelling space with consequent stimulation of calcitriol levels.
Administration, Cutaneous↗
Paraneoplastic pemphigus triggered by radiotherapy.
Paraneoplastic pemphigus is a recently described autoimmune disease characterized by painful mucosal ulceration and polymorphous skin lesions in association with an underlying neoplasm. Distinct autoantibodies bind desmoplakin I, desmoplakin II, bullous pemphigoid antigen and an uncharacterized 190 kDa antigen. A case is presented of paraneoplastic pemphigus that developed after radiotherapy for non-Hodgkin's lymphoma in a 53 year old man. Multiple skin biopsies showed a lichenoid reaction without acantholysis. Immunofluorescence and mucosal biopsies were required to establish the correct diagnosis. Corneal opacities resembling lichenoid graft-versus-host disease and retinal haemorrhages, which developed in the patient, have not been previously documented. Despite high doses of immunosuppressive agents and plasmaphoresis, the patient eventually died from respiratory failure.
Acantholysis↗
Sodium-lithium countertransport kinetics in IgA nephropathy: relation to plasma lipids and renal impairment.
We have investigated the activity and kinetics of sodium-lithium countertransport (SLC) in patients with IgA nephropathy and their relationship to plasma lipids. Standard SLC activity, the Michaelis constant (Km) and maximum velocity (Vmax) were measured in patients who had IgA nephropathy with either normal serum creatinine (IgA-NRF), or raised serum creatinine (IgA-IRF), and normal subjects (NC). The standard SLC activity was raised in hypertensive patients with IgA-NRF due to a raised Vmax in association with hyperlipidaemia. The Km was significantly lower and Vmax also tended to be lower in IgA-IRF. Km and Vmax were not different in IgA-NRF compared with the NC. There was no difference in the mean standard SLC activity between all three groups. The low Km and low Vmax resulted in a normal standard SLC activity being observed in IgA-IRF which is similar to the situation we have observed in a proportion of diabetic patients with nephropathy. The low Km in patients with IgA nephropathy may be due to inheritance associated with familial essential hypertension or to an acquired change of the kinetics related to a change in the environment of the plasma membrane during the development of renal impairment.
Adult↗
Measurement of growth hormone-binding protein in the rat by a ligand immunofunctional assay.
We have developed a ligand immunofunctional assay (LIFA) for quantifying the circulating functional GH-binding protein (GHBP) in the rat. This two-site solid-phase assay uses a capture monoclonal antibody (4.3) specific to the hydrophilic C-terminal segment of rat GHBP (rGHBP), saturation of binding with human GH, and a detection system of rabbit antihuman GH polyclonal antibody and peroxidase-conjugated antirabbit immunoglobulin G antibody. Results were compared with Scatchard estimates derived by immuno-precipitation with monoclonal antibody 4.3. This assay was used to determine the GHBP levels in male and female rats and to investigate the diurnal properties and dynamics of GH and GHBP interaction in 15-min blood sampling over a 6-h period. The dynamic range of the rLIFA was 0.15-20.0 nM recombinant rGHBP, with intraassay and interassay coefficients of variation of 10.5% (n = 20) and 12.9% (n = 12), respectively. Serum GHBP levels determined by the rLIFA and those derived from Scatchard estimates were strongly correlated (n = 8; beta = 0.55; r2 = 0.89; P = 0.0005). Male rats had lower GHBP levels (6.5 +/- 0.7 nM; mean +/- SE; n = 14) than female rats (35.4 +/- 2.7 nM; n = 15; P = 0.0001). In the diurnal study, male rats had higher GH peaks (312.5 +/- 121.6 ng/ml; n = 7) than female rats (96.5 +/- 15.4 ng/ml; n = 9; P < 0.0001). In contrast to the pulsatile secretion of GH, GHBP levels in both sexes remained stable and showed no relationship to secretory pulses of GH. However, the GH bursts significantly altered the distribution of the GH-GHBP complex in male rats. By saturation and mass analysis, the greater GH pulsatile secretion in male rats resulted in occupancy of GHBP from less than 5% at nadir to about 80% at secretory peaks, in contrast to the less than 5-15% range of GHBP occupancy in female rats. In male rats, greater than 80% of GH at secretory peaks existed in the free form, whereas in female rats, 16-23% of GH existed in the free form during pulsatile secretion. In summary, the rLIFA shows good correlation to Scatchard analysis using an identical antibody. We conclude that this assay provides a rapid, sensitive, and accurate measurement of the circulating functional GHBP in the rat, and that it facilitates the study of GH and GHBP dynamics under a range of physiological conditions.
Animals↗
Adults with growth hormone deficiency have abnormal body composition but normal energy metabolism.
We compared body composition and energy metabolism in a cross-sectional study involving 21 GH-deficient (GHD) and 29 normal adults. Fifteen subjects from each group were pair-matched for age, sex, height, and weight. Comparison of body composition by dual energy x-ray absorptiometry in the 15 pairs showed that GHD subjects had a significantly greater fat mass (23.9 +/- 1.8 vs. 19.8 +/- 2.6 kg; P = 0.02), lower bone mineral content (2.6 +/- 0.1 vs. 2.9 +/- 0.1 kg; P = 0.06), and lower fat-free soft tissue mass (FFSTM; 45.8 +/- 2.5 vs. 48.9 +/- 2.6 kg; P = 0.02). To determine which subcompartment changes were responsible for the reduced FFSTM in GH deficiency, extracellular water (ECW) was measured by 24Na dilution in 11 of the subject pairs, and body cell mass (BCM) was derived by subtracting ECW from FFSTM. The GHD subjects had lower ECW (19.4 +/- 1.0 vs. 21.0 +/- 1.0 kg; P = 0.05) and BCM (26.6 +/- 1.9 vs. 28.6 +/- 2.1 kg; P = 0.08) than their normal counterparts, with the difference approaching statistical significance. When the relationship between ECW and FFSTM was compared in the larger group of 18 GHD and 27 normal subjects, no statistically significant difference was found between the 2 regression lines, indicating that ECW and BCM were proportionately reduced in GH deficiency. Energy expenditure and fuel utilization before and after a standardized mixed meal were measured by indirect calorimetry in 12 matched pairs of GHD and normal subjects. Comparison of energy expenditure and fuel utilization showed no significant difference in fasting or postprandial energy expenditure, or carbohydrate or fat oxidation rates between the two groups. We conclude that GHD adults have an increased FM, a reduced FFSTM due to a proportionate reduction in ECW and BCM, and no detectable disturbance in energy metabolism.
Adult↗
Evaluation and application of a highly sensitive assay for serum growth hormone (GH) in the study of adult GH deficiency.
Previous work from our laboratory addressing the diagnosis of GH deficiency in adults showed that RIA measurement of the 24-h integrated GH concentration (IGHC) was unable to discriminate between hypopituitary and age-, sex-, and body mass index-matched normal subjects because of the occurrence of undetectable levels (< 200 ng/L) within both groups. In contrast, full separation was achieved using stimulation by the insulin tolerance test (ITT). The data showed no significant relationship between IGHC and insulin-like growth factor-I (IGF-I) within either group. To determine whether limited sensitivity obscured diagnostic and physiological information, we assessed and modified a commercially available enzyme-linked immunosorbent assay (Elegance GH ELISA, Bioclone Australia) to achieve a high sensitivity (1 ng/L) and applied it to the study of IGHC and the relationship to IGF-I in a study group of 30 normal and 19 subjects with severe organic hypopituitarism. Using this assay, the IGHCs from all subjects were detectable and correlated significantly with detectable values obtained by RIA (n = 24; r = 0.80; P = 0.0001). Mean IGHC in normal subjects was significantly higher than that in hypopituitary subjects (852 +/- 131 vs. 97 +/- 28 ng/L), but the IGHCs from the two groups were not completely separate. Twenty-six percent of hypopituitary subjects had IGHC values within the normal range (111-3454 ng/L). IGHC decreased with age in normal subjects. Age stratification improved the separation, but an overlap remained in the young (< 50 yr old) and old (> 50 yr old) groups. Measurement of 12-h nocturnal IGHC levels improved the separation between hypopituitary and normal subjects in the young subjects only. IGHC was significantly related to IGF-I in hypopituitary (r = 0.59; P = 0.0084) and normal subjects (r = 0.55; P = 0.0017) and in the combined groups (r = 0.64; P = 0.0001). The data show that a sensitive ELISA reliably quantifies IGHC in normal and hypopituitary subjects. IGHCs in hypopituitary patients are lower, but not clearly separated from values in normal counterparts despite their having unequivocally impaired GH responses to ITT. We conclude that 1) IGHC in normal subjects can be reliably defined by sensitive ELISAs; 2) the diagnostic utility of the IGHC does not match the reliability or simplicity of an ITT, and 3) GH is a significant regulator of IGF-I in both normal and reduced states of GH secretion.
Adolescent↗
Energy metabolism and substrate oxidation in acromegaly.
Short term GH administration increases lipid breakdown and oxidation (lipidox) and reduces glucose uptake and carbohydrate oxidation (CHOox). It is not clear whether similar shifts in substrate oxidation occur in acromegaly, and our aim was to investigate this. Using indirect calorimetry, we compared energy expenditure, CHOox, and lipidox in 20 acromegalic patients and 20 normal subjects pair-matched for sex, age, height, and weight. Investigations were performed in the basal state (12-h fast) and during a 75-g oral glucose tolerance test (OGTT). Acromegalic patients had significantly higher fasting glucose levels and greater glucose and insulin responses during an OGTT than normal subjects. Fasting nonesterified free fatty acid and insulin-like growth factor (IGF)-binding protein-1 levels were similar in the two groups, and both were acutely suppressed by oral glucose to the same degree. Basal energy expenditure was significantly greater in the acromegalic patients (1682 +/- 49 vs. 1540 +/- 45 Cal/24 h; P < 0.05), who showed a trend toward higher basal CHOox. Oral glucose resulted in a significantly higher rise in energy expenditure in the normal compared to the acromegalic subjects. During the OGTT, CHOox significantly increased in both groups, but rose to a higher level in the acromegalic patients (177 +/- 10 vs. 138 +/- 9 mg/min; P = 0.004). Oral glucose significantly reduced lipidox in both groups, but lipidox was reduced to a significantly lower level in the acromegalic patients (32 +/- 4 vs. 46 +/- 3 mg/min; P = 0.004). In acromegaly, basal CHOox (r = 0.56; P = 0.01) and postglucose CHOox (r = 0.79; P = 0.0001) were both positively correlated to IGF-I, but not to insulin and/or glucose. In normal subjects, postglucose CHOox was positively correlated to IGF-I. In summary, hyperinsulinemia in acromegaly was associated with higher glucose levels and a blunted thermogenic response to glucose, and displayed no relationship to the pattern of substrate oxidation. CHOox was increased, and lipidox was reduced in acromegaly, and the extent of IGF-I elevation was related to CHOox in the basal and postglucose states. We conclude that 1) the chronic effects of GH excess on substrate oxidation differ from the short term effects of GH administration; 2) impaired insulin action in acromegaly extends to effects on energy expenditure; and 3) IGF-I may be an important regulator of substrate oxidation in acromegaly.
Acromegaly↗
Do androgens regulate growth hormone-binding protein in adult man?
To determine whether adult serum GH-binding protein (GHBP) is regulated by androgen, serum GHBP concentrations were compared between 20 normal and 18 hypogonadal men matched for age and body mass index, and the effect of im testosterone treatment (250 mg testosterone enanthate) on GHBP levels in the 18 hypogonadal men was studied. Nine of the hypogonadal subjects had coexistent GH deficiency. Serum GHBP concentration was measured by a ligand immunofunctional assay. The mean serum GHBP level in untreated hypogonadal men was not significantly different from that of normal men (0.98 +/- 0.15 vs. 1.17 +/- 0.16 nmol/L). The mean serum insulin-like growth factor I (IGF-I) level was significantly lower in the hypogonadal men (132 +/- 22 vs. 206 +/- 17 ng/mL; P < 0.01). Basal testosterone (3.7 +/- 0.7 nmol/L) in hypogonadal men increased during treatment to a mean level of 29.1 +/- 2.8 nmol/L, which was not significantly higher than that in normal men (22.6 +/- 1.9 nmol/L). The mean serum GHBP level in hypogonadal men fell significantly during treatment to 0.60 +/- 0.11 nmol/L (P = 0.0003), whereas the serum IGF-I level rose significantly to 151 +/- 26 ng/mL (P < 0.04). The decrease in GHBP level was significant in both the GH-sufficient and GH-deficient subjects (P < 0.02 in both instances), whereas the increase in IGF-I level was significant in the GH-sufficient group (199 +/- 22 to 235 +/- 29 ng/mL; P < 0.04) but not in the GH-deficient group (53 +/- 7 to 55 +/- 5 ng/mL; P > 0.8). Thus, serum GHBP is normal in hypogonadal men but is reduced by testosterone treatment irrespective of endogenous GH-secretory status. It was concluded that the effect of testosterone on GHBP is pharmacological and occurs independent of GH mediation.
Adolescent↗
A comparison of the effects of oral and transdermal estrogen replacement on insulin sensitivity in postmenopausal women.
Previous studies have shown that oral, but not transdermal, administration of estrogen stimulates GH secretion in postmenopausal women. Because GH impairs insulin action, the impact of estrogen replacement therapy on carbohydrate metabolism may be influenced by the route of administration. The aim of this study was to prospectively compare the effects of oral and transdermal estrogen replacement on glucose tolerance and insulin sensitivity in postmenopausal women. In an open label, randomized, cross-over study, nine postmenopausal women were randomized to transdermal estrogen patches (Estraderm-TTS 100) or oral conjugated estrogen (Premarin, 1.25 mg) daily for 12 weeks and then crossed over to receive the alternative treatment for a further 12 weeks. An oral glucose tolerance test and hyperinsulinemic euglycemic clamp (HEC) were performed before treatment and at the end of 10 weeks of treatment. Oral and transdermal estrogen both significantly reduced LH to the same degree. Mean GH did not significantly change with transdermal estrogen, but rose significantly during oral estrogen therapy. Peak and mean glucose and insulin levels during the oral glucose tolerance test were not altered by estrogen therapy and were not significantly different between treatments. Mean glucose and insulin levels were maintained at an identical level during the HEC performed at pretreatment and during estrogen therapy. The mean glucose infusion rate required to maintain euglycemia during the HEC (mean +/- SEM, pretreatment, 40.4 +/- 4.8 mumol/kg.min) was unaltered by oral (39.8 +/- 4.6 mumol/kg.min) or transdermal estrogen treatment (42.1 +/- 4.2 mumol/kg.min). However, during the transdermal estrogen phase (60 +/- 10 mumol/L), the mean nonesterified free fatty acid concentration was suppressed to a significantly lower level during the HEC than during the oral estrogen phase (120 +/- 20 mumol/L; P < 0.05). We conclude that compared to the oral route, transdermal estrogen therapy is associated with a slight, but significant, improvement of insulin action on lipid metabolism. However, in the short term, the route of estrogen replacement therapy does not have a major impact on glucose metabolism in postmenopausal women.
Administration, Cutaneous↗
Serum concentrations of insulin-like growth factors (IGFs), IGF binding proteins 1 and 3 and growth hormone binding protein in obese women and the effects of growth hormone administration: a double-blind, placebo-controlled study.
Obesity is associated with suppressed growth hormone (GH) concentrations but relatively little is known about insulin-like growth factors(IGFs) and binding proteins for GH and IGFs (GHBP and IGFBPs) and the modulatory effect of GH administration. In a double-blind, crossover design we studied the impact of 5 weeks of placebo or GH administration (0.03 mg.kg-1 body wt.day-1) in nine obese women (mean +/- SEM: age 30.4 +/- 2.4 years; body mass index 37.0 +/- 2.8 kg/m2) on IGF-I, IGF-II, IGFBP-1 and -3 and GHBP. Serum IGF-I (microgram/l) levels were subnormal and increased significantly following GH (117 +/- 16 (placebo) vs 434 +/- 33 (GH) vs 198 +/- 15 (control (p < 0.01)). By contrast, serum IGF-II (microgram/l) levels were in the normal range and remained unchanged (608 +/- 20 (placebo) vs 647 +/- 40 (GH) (NS)). Serum IGFBP-3 was in the normal range and increased significantly during GH treatment, although relatively less than IGF-I, such that the molar ratio between IGF-I and IGFBP-3 increased with GH treatment, whereas the ratio between IGF-I + IGF-II and IGFBP-3 remained unchanged. Serum IGFBP-1 was low in the placebo situation but became further and almost completely suppressed during GH treatment. During a 2-h hyperinsulinemic, euglycemic glucose clamp, IGFBP-1 decreased in the placebo study and remained suppressed during GH. Serum GHBP (nmol/l) levels were elevated substantially compared to non-obese controls (p < 0.001) and did not change during GH treatment (2.37 +/- 0.36 (placebo) vs 2.21 +/- 0.25 (GH) vs 0.80 +/- 0.19 (control)).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Sequence of cassava ribulose-1,5-bisphosphate carboxylase small subunit precursor cDNA.
The cDNA sequence of cassava ribulose-1,5-bisphosphate carboxylase small subunit rbcS precursor has been determined. The cassava rbcS precursor cDNA contains 266 nucleotides (nts) of 5' untranslated region, 546 nts of coding region, 280 nts of 3' untranslated region and a poly (A) tail of 70 nts. The 5' untranslated region is characterized by some unusual features which include two plausible open reading frames, several repeated sequences and a putative Shine-Dalgarno sequence. The predicted amino acid sequence shows that the precursor consists of a 59 amino acid transit peptide followed by the 123 amino acid rbcS sequence. Cassava rbcS shares 82% amino acid sequence identity with a rubber rbcS sequence.
Amino Acid Sequence↗