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Biomedical subjects

J Miell

Publications and source records attributed to J Miell.

At least 19 recordsLinked to original sources
PubMed2003

Serum sialic acid, a reputed cardiovascular risk factor, is related to serum leptin concentrations in Fijians.

BACKGROUND: Serum sialic acid (TSA) has been shown to be a cardiovascular risk factor and an acute phase reactant, with elevated concentrations associated with increased cardiovascular mortality and to precede the onset of type 2 diabetes. AIM: The purpose of this present study was to test the hypothesis that serum TSA may be related to serum leptin concentrations in healthy individuals. METHODS: Thirty Fijian individuals were studied (8 males and 22 females). They were urban Melanesians living in Raiwaga, a suburb of Suva in Fiji. RESULTS: Serum TSA significantly correlated with subject body mass index (BMI, rho 0.39, P<0.05) and serum leptin concentration (rho 0.44, P<0.05). In stepwise multiple regression analysis serum TSA independently correlated with subject waist/hip ratio (r(2)=0.167, P<0.02) and diastolic blood pressure (r(2)=0.300, P<0.01) but not with age, BMI, serum insulin-like growth factor binding protein (IGFBP-1), fasting plasma glucose or systolic or diastolic blood pressure. CONCLUSIONS: Serum TSA is related to markers of obesity and adipose tissue metabolism which may help to explain why it is a reputed cardiovascular risk factor and why elevated serum TSA concentrations precede the development of type 2 diabetes mellitus.

Adult↗
PubMed2003

Neisseria elongata endocarditis: case report and literature review.

We describe a case of infective endocarditis due to Neisseria elongata, and review the literature. N. elongata is a constituent of the normal oral flora and a rare cause of infective endocarditis. Unfamiliarity with the organism and its rod-shaped morphology may lead to a delay in microbiological diagnosis. Although the organism is relatively sensitive to antibiotics, our experience in the management of the described case and a review of previous reports suggest that antibiotic therapy alone may not be sufficient. It is likely that patients with N. elongata endocarditis will require surgery.

Anti-Bacterial Agents↗
PubMed2002

Serum sialic acid, a possible cardiovascular risk factor is not increased in Fijian Melanesians with impaired glucose tolerance or impaired fasting glucose.

BACKGROUND: Serum total sialic acid (TSA) has been shown to be a strong cardiovascular risk factor with increased concentrations being associated with increased mortality. Serum TSA is also elevated in patients with type 2 diabetes including those with micro- and macrovascular complications. We wished, therefore, to test the hypothesis that serum TSA may be abnormal in individuals with impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), in Fijian Melanesians. METHOD: Twenty-one subjects with IGT (17 women and four men) were recruited along with 20 subjects with IFG (14 women and six men) and 22 normal subjects (12 women and 10 men). Serum TSA was 2.18 +/- 0.027 mmol//L, 2.19 +/- 0.033 mmol/L and 2.24 +/- 0-042 mmol/L in the three groups, respectively, which was not statistically different. Both systolic and diastolic blood pressure were, however, higher in the IGT group compared with the IFG and normal groups (P<0.04). CONCLUSION: Serum TSA is not elevated in Fijian Melanesians with IGT and IFG although it is reported to be elevated in type 2 diabetes mellitus in other populations. Further research is needed to establish why serum TSA is a potent independent cardiovascular risk factor and is elevated in type 2 diabetes mellitus in some populations.

Adult↗
PubMed2001

Plasma leptin in chronic fatigue syndrome and a placebo-controlled study of the effects of low-dose hydrocortisone on leptin secretion.

OBJECTIVE: Previous studies have suggested that chronic fatigue syndrome (CFS) is associated with changes in appetite and weight, and also with mild hypocortisolism. Because both of these features may be related to leptin metabolism, we undertook a study of leptin in CFS. DESIGN: (i) A comparison of morning leptin concentration in patients with CFS and controls and (ii) a randomized, placebo-controlled crossover study of the effects of hydrocortisone on leptin levels in CFS. PATIENTS: Thirty-two medication free patients with CFS but not comorbid depression or anxiety. Thirty-two age, gender, weight, body mass index and menstrual cycle matched volunteer subjects acted as controls. MEASUREMENTS: We measured basal 0900 h plasma leptin levels in patients and controls. All 32 patients were taking part in a randomized, placebo-controlled crossover trial of low dose (5 or 10 mg) hydrocortisone as a potential therapy for CFS. We measured plasma leptin after 28 days treatment with hydrocortisone and after 28 days treatment with placebo. RESULTS: At baseline, there was no significant difference in plasma leptin between patients [mean 13.8, median 7.4, interquartile range (IQR) 18.0 ng/ml] and controls (mean 10.2, median 5.5, IQR 11.3 ng/ml). Hydrocortisone treatment, for both doses combined, caused a significant increase in leptin levels compared to placebo. When the two doses were analysed separately, only 10 mg was associated with a significant effect on leptin levels. We also compared the hydrocortisone induced increase in leptin between those who were deemed treatment-responders and those deemed nonresponders. Responders showed a significantly greater hydrocortisone-induced rise in leptin than nonresponders. This association between a clinical response to hydrocortisone and a greater rise in leptin levels may indicate a greater biological effect of hydrocortisone in these subjects, perhaps due to increased glucocorticoid receptor sensitivity, which may be present in some patients with CFS. CONCLUSIONS: We conclude that, while we found no evidence of alterations in leptin levels in CFS, low dose hydrocortisone therapy caused increases in plasma leptin levels, with this biological response being more marked in those CFS subjects who showed a positive therapeutic response to hydrocortisone therapy. Increases in plasma leptin levels following low dose hydrocortisone therapy may be a marker of pretreatment physiological hypocortisolism and of response to therapy.

Adult↗
PubMed2001

Temporal changes in insulin sensitivity following the development of acute liver failure secondary to acetaminophen.

Insulin resistance in chronic liver disease (CLD) is well documented. This study investigated whether similar changes occur in acute liver failure (ALF). Patients with ALF (n = 10) were recruited within 72 hours of their peak prothrombin time (range 42-120 seconds). All patients were ventilated for encephalopathy (grade III-IV). Peripheral and endogenous insulin sensitivity were assessed by a hyperinsulinemic euglycemic clamp (Human Actrapid 1.5 mU/min/kg) with an infusion of D-[6,6-(2)H(2)] glucose. The clamp was performed on day 0 and then on day 7 and day 14. During the insulin infusion, the mean total peripheral glucose uptake (area under the curve [AUC]) was 1,422 (SD, 1,253), 2,244 (SD, 1,392), and 4,500 (SD, 1,120) micromol/kg on days 0, 7, and 14, respectively. Significant changes occurred from day 0 to 14 (day 14-day 0: 3,078 [95% CI, 1,798 to 4,359]; P =.001) and day 7 to 14 (day 14-day 7: 2,256 [95% CI, 923 to 3,589]; P =.001). No significant difference in endogenous glucose production was demonstrated over time. Mean peripheral insulin sensitivity altered over time, increasing from 0.09 (SD, 0.09) micromol/kg/min/mU/L on day 0 to 0.24 (SD, 0.16) on day 7 and 0.5 (SD, 0.1) on day 14. Significant changes occurred between days 0, 7, and 14 (day 7-day 0: 0.15 [95% CI, 0.04 to 0.26], P =.006; day 14-day 0: 0.4 [95% CI, 0.28 to 0.5], P =.001; day 14-day 7: 0.2 [95% CI, 0.12 to 0.38], P =.001). This study demonstrates that in ALF, impaired peripheral uptake of glucose occurs, peripheral insulin sensitivity being restored at 2 weeks in subjects who survived.

Acetaminophen↗
PubMed2001

Hypothalamo-pituitary-adrenal axis dysfunction in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy.

These neuroendocrine studies were part of a series of studies testing the hypotheses that 1) there may be reduced activity of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome and 2) low-dose augmentation with hydrocortisone therapy would improve the core symptoms. We measured ACTH and cortisol responses to human CRH, the insulin stress test, and D-fenfluramine in 37 medication-free patients with CDC-defined chronic fatigue syndrome but no comorbid psychiatric disorders and 28 healthy controls. We also measured 24-h urinary free cortisol in both groups. All patients (n = 37) had a pituitary challenge test (human CRH) and a hypothalamic challenge test [either the insulin stress test (n = 16) or D-fenfluramine (n = 21)]. Baseline cortisol concentrations were significantly raised in the chronic fatigue syndrome group for the human CRH test only. Baseline ACTH concentrations did not differ between groups for any test. ACTH responses to human CRH, the insulin stress test, and D- fenfluramine were similar for patient and control groups. Cortisol responses to the insulin stress test did not differ between groups, but there was a trend for cortisol responses both to human CRH and D-fenfluramine to be lower in the chronic fatigue syndrome group. These differences were significant when ACTH responses were controlled. Urinary free cortisol levels were lower in the chronic fatigue syndrome group compared with the healthy group. These results indicate that ACTH responses to pituitary and hypothalamic challenges are intact in chronic fatigue syndrome and do not support previous findings of reduced central responses in hypothalamic-pituitary-adrenal axis function or the hypothesis of abnormal CRH secretion in chronic fatigue syndrome. These data further suggest that the hypocortisolism found in chronic fatigue syndrome may be secondary to reduced adrenal gland output. Thirty-two patients were treated with a low-dose hydrocortisone regime in a double-blind, placebo-controlled cross-over design, with 28 days on each treatment. They underwent repeated 24-h urinary free cortisol collections, a human CRH test, and an insulin stress test after both active and placebo arms of treatment. Looking at all subjects, 24-h urinary free cortisol was higher after active compared with placebo treatments, but 0900-h cortisol levels and the ACTH and cortisol responses to human CRH and the insulin stress test did not differ. However, a differential effect was seen in those patients who responded to active treatment (defined as a reduction in fatigue score to the median population level or less). In this group, there was a significant increase in the cortisol response to human CRH, which reversed the previously observed blunted responses seen in these patients. We conclude that the improvement in fatigue seen in some patients with chronic fatigue syndrome during hydrocortisone treatment is accompanied by a reversal of the blunted cortisol responses to human CRH.

Adrenocorticotropic Hormone↗
PubMed1999

Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial.

BACKGROUND: Reports of mild hypocortisolism in chronic fatigue syndrome led us to postulate that low-dose hydrocortisone therapy may be an effective treatment. METHODS: In a randomised crossover trial, we screened 218 patients with chronic fatigue. 32 patients met our strict criteria for chronic fatigue syndrome without co-morbid psychiatric disorder. The eligible patients received consecutive treatment with low-dose hydrocortisone (5 mg or 10 mg daily) for 1 month and placebo for 1 month; the order of treatment was randomly assigned. Analysis was by intention to treat. FINDINGS: None of the patients dropped out. Compared with the baseline self-reported fatigue scores (mean 25.1 points), the score fell by 7.2 points for patients on hydrocortisone and by 3.3 points for those on placebo (paired difference in mean scores 4.5 points [95% CI 1.2-7.7], p=0.009). In nine (28%) of the 32 patients on hydrocortisone, fatigue scores reached a predefined cut-off value similar to the normal population score, compared with three (9%) of the 32 on placebo (Fisher's exact test p=0.05). The degree of disability was reduced with hydrocortisone treatment, but not with placebo. Insulin stress tests showed that endogenous adrenal function was not suppressed by hydrocortisone. Minor side-effects were reported by three patients after hydrocortisone treatment and by one patient after placebo. INTERPRETATION: In some patients with chronic fatigue syndrome, low-dose hydrocortisone reduces fatigue levels in the short term. Treatment for a longer time and follow-up studies are needed to find out whether this effect could be clinically useful.

Adult↗
PubMed1999

The role of insulin-like growth factor binding protein-1 phosphoisoforms in pregnancies with impaired placental function identified by doppler ultrasound.

This study was performed to investigate the hypothesis that insulin-like growth factor binding protein-1 (IGFBP-1) is involved in the pathogenesis of trophoblast invasion and impaired placentation in human pregnancy. The role of total and non-phosphorylated IGFBP-1 in women with fetal growth restriction and in high risk pregnancies identified by uterine artery Doppler ultrasound screening was examined. This was a prospective study of women booked for antenatal care having second trimester anomaly scans and Doppler screening between 22-26 weeks gestation. Women were divided into three groups and compared: normal uterine artery Doppler and normal fetal growth (control group, n = 10); abnormal Doppler and normal fetal growth [bilateral uterine artery notches (BN; n = 16); abnormal Doppler and intrauterine growth restriction (IUGR; n = 8)]. Maternal serum was collected, stored and assayed simultaneously for total and non-phosphorylated IGFBP-1. There was elevated total and non-phosphorylated IGFBP-1 (mean 44.99 +/- 12.19 and 29.61 +/- 10.38 microg/l respectively) in the IUGR group compared with controls (mean 17.96 +/- 3.24 and 12.18 +/- 1.55 microg/l, P < 0.05). This finding suggests that the various IGFBP-1 isoforms, the degree of phosphorylation and the ratios of these different forms locally may be important during trophoblast invasion and may be implicated in clinical manifestations of impaired placentation later in the second trimester.

Female↗
PubMed1996

Reduction in circulating IGF-I and hepatic IGF-I mRNA levels after caecal ligation and puncture are associated with differential regulation of hepatic IGF-binding protein-1, -2 and -3 mRNA levels.

Sepsis is characterized by a severe shift in metabolism, characterized by low IGF-I levels. We have studied the influence of caecal ligation and puncture (CLP) on the levels of circulating IGF-I and hepatic IGF-I and IGF-binding protein (IGFBP)-1, -2 and -3 mRNA in adult male Wistar rats (n = 12) and compared it with sham-operated rats (n = 6). In order to exclude anorexia-induced changes we also studied animals pair-fed to both groups. IGF-I levels were measured by RIA. Steady-state hepatic IGF-I, IGFBP-1, IGFBP-2 and IGFBP-3 mRNA levels were measured by Northern blot analysis using specific rat cDNA probes. Food intake averaged 13.0 +/- 2.0 g/day in the sham-operated rats fed ad libitum during the study period, with a sharp decline in food intake in the CLP animals (2.3 +/- 1.3 g/day). After CLP, there was a significant reduction in circulating IGF-I levels (467.2 +/- 50.9 micrograms/l) compared with sham-operated animals (924.0 +/- 75.3 micrograms/l; P = 0.04) or those pair-fed to the CLP rats (612.5 +/- 52.9 micrograms/l; P = 0.04). Total hepatic IGF-I mRNA levels were significantly reduced (2.57 +/- 0.05 densitometric units (DU) after CLP compared with the sham-operated group (2.71 +/- 0.04); P = 0.04), or their pair-fed controls (2.75 +/- 0.08 DU; P < 0.05). Hepatic IGFBP-3 mRNA levels were lower after CLP (0.37 +/- 0.04 DU) than in the sham-operated animals (0.66 +/- 0.09 DU; P = 0.04) or their pair-fed controls (0.61 +/- 0.05 DU; P = 0.04). On the other hand, hepatic IGFBP-2 mRNA levels were increased after CLP (0.91 +/- 0.11 DU) compared with sham-operated animals (0.28 +/- 0.06 DU; P = 0.01) or with their pair-fed controls (0.22 +/- 0.02; P = 0.01), as were hepatic IGFBP-1 mRNA levels (CLP animals 0.95 +/- 0.11 DU; sham-operated 0.30 +/- 0.04 DU, P = 0.01; pair-fed 0.30 +/- 0.02 DU, P = 0.01). No significant difference between sham-operated animals and their pair-fed controls was observed in circulating IGF-I levels (888.0 +/- 109.3 micrograms/l; P = not significant (N.S.)), hepatic mRNA levels for IGF-I (2.72 +/- 0.06 DU; P = N.S), IGFBP-3 (0.71 +/- 0.07 DU; P = N.S.), IGFBP-2 (0.25 +/- 0.07 DU; P = N.S.) or IGFBP-1 (0.27 +/- 0.06 DU; P = N.S.). In summary, after CLP there was a reduction in both circulating and hepatic IGF-I mRNA levels associated with a specific and differential regulation of hepatic IGFBP-1, -2 and -3 mRNA levels. Although we cannot eliminate a possible effect of surgical stress combined with malnutrition, our results suggest that these changes are a specific effect of sepsis rather than simply a result of surgical stress or poor nutrition alone.

Animals↗
PubMed1995

Fibroblast growth factor-2 (FGF-2) is present in maternal and cord serum, and in the mother is associated with a binding protein immunologically related to the FGF receptor-1.

Fibroblast growth factor-2 (FGF-2) is expressed in human fetal tissues and placenta. We, therefore, determined whether FGF-2 appeared in either fetal or maternal circulations during normal pregnancies [fetuses appropriate for gestational age (AGA)] or those complicated by fetal growth restriction (small for gestational age). Cordocentesis was performed, and matched maternal blood was collected between 19-39 weeks gestation, whereas maternal and cord blood and amniotic fluid (AF) were collected at term. FGF-2 was extracted from maternal serum (MS), cord serum (CS), and AF by heparin-Sepharose affinity chromatography and subjected to Western blot analysis or quantified by specific RIA. Western blot analysis of MS, CS, and AF revealed, in each case, a single immunoreactive FGF-2 species of 18 kilodaltons (kDa), although this was not present in nonpregnant serum. In AGA pregnancies, immunoreactive FGF-2 was present in MS from at least 18 weeks gestation and rose to maximum values at the end of second trimester (weeks 28-31; mean +/- SEM, 342 +/- 62 pmol/L), but by term had declined (weeks 40-42; 104 +/- 24 pmol/L). In CS, FGF-2 immunoreactivity was highest at weeks 18-20 of gestation (662 +/- 144 pmol/L), but thereafter, slowly declined to term (weeks 40-42; 119 +/- 28 pmol/L). Immunoreactive FGF-2 levels in MS and CS of small for gestational age pregnancies in the second trimester tended to be lower than those in AGA pregnancies, but differences were not statistically significant. AF also contained immunoreactive FGF-2 at term (91 +/- 35 pmol/L). Neutral gel chromatography on Sephadex G-200 revealed that FGF-2 immunoreactivity eluted as a broad peak with an apparent molecular size of 55-160 kDa. These same fractions contained peptides of 55-60, 90-95, and 120-130 kDa, which were recognized by antisera against the extracellular domain of the high affinity FGF receptor, FGFR1, after Western blot. Ligand blot analysis of the same nitrocellulose filters using 125I-labeled FGF-2 revealed that the 55- to 60-kDa species specifically bound FGF-2. This binding species was not recognized during Western blot analysis using an antiserum raised against the intracellular tyrosine kinase domain of FGFR1, suggesting that it represents a truncated receptor form. Similar FGFR1 immunoreactive species were present in nonpregnant female and male sera, but were barely detectable in term CS or AF.(ABSTRACT TRUNCATED AT 400 WORDS)

Amniotic Fluid↗
PubMed1994

The pathophysiology of the insulin-like growth factor axis in fetal growth failure: a basis for programming by undernutrition?

Recent evidence suggests that a number of adulthood conditions, including non-insulin dependent diabetes mellitus (NIDDM) and lipid and cardiovascular abnormalities are associated with intra-uterine growth retardation (IUGR). It is possible that this arises from programming of endocrine axes during development as a result of an adverse intra-uterine environment. Insulin-like growth factors (IGFs) are mitogenic polypeptides which stimulate cellular proliferation and differentiation and are important in human fetal development. The functions of IGFs are modulated by specific high affinity binding proteins (IGFBPs). IGFBP-1 is antagonistic to the insulin-like and growth promoting effects of IGF-I, and IGFBP-3 holds IGFs in the circulation by associating with IGFs and an acid labile subunit to form a ternary complex. Using specific radioimmunoassays and fetal serum obtained during diagnostic cordocentesis we have investigated the role of the IGF/IGFBP axis in human fetal development. In a study of 130 singleton pregnancies we have examined levels of immunoreactive IGFs and IGFBPs in normally grown fetuses (AGA), starved small fetuses affected by uteroplacental insufficiency (UPI), and non-starved small fetuses (SGA). IGF-I was significantly lower in the UPI group (n = 14, 7.8 +/- 0.6 micrograms l-1), than in either the SGA group (n = 22, 31.4 +/- 3.5 micrograms l-1, P = 0.0001) or the AGA group (n = 94, 36.3 +/- 1.9 micrograms l-1, P = 0.0001). IGFBP-3 showed similar changes (UPI: 682.6 +/- 50.0 micrograms l-1; SGA: 831.9 +/- 55.5 micrograms l-1; AGA: 847.7 +/- 19.8 micrograms l-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Carrier Proteins↗
PubMed1994

Changes in hepatic insulin-like growth factor-binding proteins -1, -2 and -3 mRNA levels in rats with altered thyroid status.

Changes in thyroid status have a major effect on the GH/insulin-like growth factor (IGF) axis. The majority of IGF in the circulation is bound to specific IGF-binding proteins (IGFBPs) of which six have been cloned and sequenced. We have studied changes in hepatic gene expression of IGFBP-1, -2 and -3, in male Wistar rats rendered hyperthyroid (thyroxine, 200 micrograms/kg per day) or hypothyroid (propylthiouracil, 0.1% daily). Littermates of the same age were used as controls (n = 6 in each group). Thyroxine was measured by radioimmunoassay, and hepatic IGFBP-1, -2 and -3 mRNA levels by Northern blot analysis using specific rat cDNA probes with a 28S ribosomal probe as a loading control. Mean +/- S.E.M. thyroxine levels were 247.0 +/- 44.5 (hyperthyroid group), < 9.0 (hypothyroid group) and 76.0 +/- 4.5 nmol/l (control group). IGFBP-1 and -2 mRNA levels in the hypothyroid animals compared with the controls were significantly increased, but similar levels of expression were found in thyrotoxic and control rats. IGFBP-3 mRNA levels in hypothyroid animals were decreased, and increased in thyrotoxic animals. Thus, in the adult rat, hypothyroidism is associated with increased hepatic IGFBP-1 and -2 gene expression, but decreased IGFBP-3 gene expression, while in thyrotoxicosis there are normal IGFBP-1 and -2 mRNA levels but increased IGFBP-3 gene expression. These results suggest that there is specific and different transcriptional regulation for IGFBP-1, -2 and -3 in hypo- and hyperthyroid rats.

Animals↗
PubMed1992

Assessment of gall bladder dynamics, cholecystokinin release and the development of gallstones during octreotide therapy for acromegaly.

The development of gallstones is a well recognized complication of therapy with the long-acting somatostatin analogue, octreotide in patients with acromegaly. A group of nine acromegalic patients was treated with octreotide at doses of 300-600 micrograms daily for 8 months and the changes in fasting and post-prandial cholecystokinin release, and gall bladder motor function (determined by a radiosotopic technique) were assessed at regular intervals. In addition the development of any gallstones was determined by serial ultrasonography. Fasting cholecystokinin levels showed no significant change over 6 months, whereas the post-prandial levels demonstrated a significant decrease (p less than 0.01) during therapy, yet remained significantly higher than fasting levels. Twenty-four hours after commencing therapy gall bladder ejection fraction was decreased by 57 +/- 23 per cent and gall bladder ejection rate decreased by 63 +/- 19 per cent compared to the pretreatment values, whereas after 6 months' therapy a marked reduction in gall bladder ejection fraction (greater than 35 per cent) and gall bladder ejection rate (greater than 40 per cent) persisted in only four of nine patients. Three of these four patients with persistently impaired gall bladder motor function were subsequently shown to have developed either gallstones or biliary sludge during the course of therapy. We conclude that treatment with octreotide is associated with an impaired post-prandial release of cholecystokinin in all acromegalic patients, but gallstones only develop in those patients who, in addition, have evidence of a persistently impaired gall bladder motor response to cholecystokinin.

Acromegaly↗
PubMed1991

Critically ill patients have high basal growth hormone levels with attenuated oscillatory activity associated with low levels of insulin-like growth factor-I.

OBJECTIVE: The aim was to study the relationship between growth hormone (GH) and insulin-like growth factor-I (IGF-I) in critically ill patients. DESIGN: Case-control study of critically ill patients admitted to the intensive care unit was carried out. PATIENTS: Six critically ill patients (51-78 years) who required ventilation and parenteral nutrition and six age, weight, height, and sex-matched healthy adults were studied. MEASUREMENTS: The patients and controls were studied for two 24-hour periods; the patients before and after starting parenteral feeding, and the controls during a 36-hour fast and when taking meals equivalent in calories and protein to the patients' parenteral feed. Serum GH was measured at 20-minute intervals and analysed by a pulse detection algorithm (Pulsar) and Fourier transformation. IGF-I was measured at 0, 12, and 24 hours. RESULTS: Patients had low serum IGF-I levels compared with controls, whether fasted or fed, despite having mean GH levels similar to fasted controls. For fasted patients vs fasted controls the mean (+/- 1 SD) GH levels were 4.5 +/- 2.0 vs 4.0 +/- 2.4 mU/l respectively, and IGF-I levels at the end of the fast were 0.17 +/- 0.11 vs 0.78 +/- 0.29 U/ml (P = 0.003). Patients showed elevated baseline GH levels compared with controls when fasted and during parenteral feeding (patients vs controls fasted 3.1 +/- 1.9 vs 0.8 +/- 0.5 mU/l, P = 0.01; patients vs controls fed 4.2 +/- 4.5 vs 0.5 +/- 0.04 mU/l, P = 0.028). Fourier transformation confirmed oscillatory GH levels in the controls, fasted or fed, but this activity was attenuated in the patients. Parenteral feeding had no effect on the GH profiles or IGF-I levels of patients, but controls showed greater mean GH levels during their fast than when fed. CONCLUSIONS: We have demonstrated that critically ill patients have low IGF-I levels associated with augmented baseline GH levels which show reduced oscillatory activity. The results would be compatible with the hypothesis that there is an adaptive change in critically ill patients away from the indirect effects of GH (stimulation of IGF-I production and anabolism) and toward the direct effects (lipolysis and insulin antagonism) which increase the availability of energy substrates. The pattern of GH levels seen in our patients may be important in this adaptation.

Abdomen↗
PubMed1991

Life-threatening hypercalcaemia in association with Addisonian crisis.

A 35 year old woman was admitted with acute radial artery occlusion necessitating two operations and thrombolytic therapy. Subsequently a diagnosis of primary hypothyroidism was made and she was commenced on thyroxine replacement therapy. Her condition, however, continued to deteriorate with the development of an Addisonian crisis heralded by, and complicated by, severe, life-threatening hypercalcaemia. This case highlights the importance of considering Addison's disease in any patient whose condition deteriorates after the introduction of thyroxine replacement, and illustrates the often forgotten association of hypercalcaemia and hypoadrenalism.

Addison Disease↗
PubMed1991

Effects of glucocorticoid treatment and acute passive immunization with growth hormone-releasing hormone and somatostatin antibodies on endogenous and stimulated growth hormone secretion in the male rat.

Despite causing marked inhibition of somatic growth, glucocorticoids enhance both the response to GH-releasing hormone (GHRH) and the amplitude of naturally occurring GH secretory pulses in the male rat. The relative contribution of the two major hypothalamic regulatory factors for GH (somatostatin and GHRH) to these observed effects remains speculative. In the present studies, we have investigated endogenous and stimulated GH release in rats pretreated with glucocorticoid or vehicle, and the effects of passive immunoneutralization of somatostatin or GHRH. In an initial study, four groups of eight rats were treated with either saline or various doses of a depot preparation of betamethasone: low dose, 0.85 mg; medium dose, 1.7 mg; high dose, 3.4 mg. All doses significantly suppressed body weight gain, total adrenal weight and concentrations of both plasma corticosterone and pituitary ACTH. Seven days after betamethasone treatment, GH responses to an i.v. injection of 1 microgram human GHRH(1-29) were evaluated during pentobarbitone anaesthesia. Compared with saline-treated controls (peak GH concentration of 506.0 +/- 68.5 micrograms/l), peak GH levels were enhanced by the low dose (704.4 +/- 47.8 micrograms/l, P less than 0.05), unaltered by the medium dose (543 +/- 65.8 micrograms/l) and suppressed by the high dose (312.7 +/- 55.2 micrograms/l, P less than 0.05) of betamethasone. Similarly, the area under the secretory curves was increased by 46% following the low dose (P less than 0.01), unaltered by the medium dose and reduced by 33% after the high dose of betamethasone. In a second study, rats were pretreated for 7 days before blood sampling with either the medium dose of betamethasone or saline. On day 5, 48 h before blood sampling, an indwelling venous catheter was fitted enabling sampling of conscious rats. On the day of study, blood samples were taken at 30-min intervals over an initial 2-h period (10.00-12.00 h). Following the sample at 12.00 h, rats were given the reconstituted and dialysed immunoglobulin fraction from either control sheep serum (NSIgG), sheep anti-rat GHRH serum (GHRHab) or sheep anti-somatostatin serum (SRIHab), and samples were taken for a further 90 min (12.30-14.00 h). Directly after the sample at 14.00 h, GH stimulation was effected in all rats using 1 microgram human GHRH(1-29) with samples taken at 5, 10, 20 and 40 min following stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗