Biomedical subjects

C Parkinson

Publications and source records attributed to C Parkinson.

At least 19 recordsLinked to original sources

PubMed2006

Reductions of circulating matrix metalloproteinase 2 and vascular endothelial growth factor levels after treatment with pegvisomant in subjects with acromegaly.

BACKGROUND: Vascular endothelial growth factor (VEGF) is involved in activation of the matrix metalloproteinase (MMP) system; the latter is implicated in atherosclerosis and cardiovascular disease. Patients with acromegaly have reduced life expectancy primarily due to cardiac disease. AIM: This study assessed plasma MMPs and VEGF levels in patients with active acromegaly (IGF-I > 130% upper limit of normal), and on treatment with pegvisomant. SUBJECTS AND METHODS: Twenty patients [nine female, mean age 56.1 +/- 13.8 yr (mean +/- sd)] were studied at baseline and on pegvisomant therapy and compared with data from 25 healthy volunteers (12 female; 56.6 +/- 14.2 yr). Plasma MMP-2, MMP-9, and VEGF levels were measured. RESULTS: Serum IGF-I fell from a baseline (mean +/- sd) level of 620.1 +/- 209.3 ng/ml to 237.5 +/- 118.5 ng/ml on pegvisomant (doses 10-60 mg; P < 0.001). MMP-2 levels at baseline were significantly higher in patients compared with healthy controls (380.7 +/- 204.8 vs. 207.4 +/- 62.6 ng/ml; P < 0.001), but with treatment a significant reduction in MMP-2 [380.7 +/- 204.8 vs. 203.0 +/- 77.4 ng/ml; P < 0.001] and VEGF (283.4 +/- 233.6 vs. 229.1 +/- 157.4 pg/ml; P = 0.008) was noted. There was no significant difference in MMP-9 levels between patients and controls at baseline (797.5 +/- 142.1 vs. 788.3 +/- 218.0 ng/ml; P = 0.87) or between baseline and posttreatment levels (797.5 +/- 142.1 vs. 780.0 +/- 214 ng/ml; P = 0.76). CONCLUSIONS: Our novel data demonstrate that treatment of acromegaly with pegvisomant leads to reductions in MMP-2 and VEGF concentrations. Further studies are required to determine the significance of these findings with relation to cardiac disease.

Acromegaly↗

PubMed2005

Disease activity in acromegaly may be assessed 6 weeks after discontinuation of pegvisomant.

OBJECTIVE: Pegvisomant, a modified growth hormone (GH) molecule, is a novel medical therapy for acromegaly that functions as a GH receptor antagonist. Serum GH cannot be used as a marker of disease activity in patients taking this form of therapy, partly because GH levels rise on pegvisomant and partly because the drug cross-reacts with many routine GH assays. The purpose of this study was to assess the time for which it is necessary to discontinue pegvisomant prior to biochemical reassessment of acromegaly. DESIGN AND METHODS: This was a retrospective study of 13 patients (seven male, median age 61 years, range 43-77) enrolled in two separate, open-label studies of the efficacy and tolerability of pegvisomant in the treatment of acromegaly. All had been taking a stable dose of pegvisomant (median dose 15 mg daily, range 10-30) as monotherapy for at least 3 months before discontinuing the drug. After discontinuation of pegvisomant, serum IGF-I was measured at 0, 2, 4, 6 and 8 weeks in all patients. Serum GH (single sample) was measured in nine patients at 2, 4, 6 and 8 weeks, but not at baseline on account of the cross-reactivity of pegvisomant with the GH assay. RESULTS: Mean serum IGF-I rose from 210+/-105 ng/ml (S.D.) at baseline to 392+/-175 ng/ml at 2 weeks after discontinuation of pegvisomant (P < 0.0001). Although there was no statistically significant change in mean serum IGF-I beyond 2 weeks (412+/-181, 392+/-152 and 399+/-150ng/ml at 4, 6 and 8 weeks respectively; P = 0.13 (2 vs 4 weeks), 0.31 (4 vs 6 weeks) and 0.46 (6 vs 8 weeks), serum IGF-I rose by more than twice the interassay coefficient of variation (CV) in two of the 13 patients between weeks 2 and 4. The standard deviation of the difference in serum IGF-I between time points was calculated. The values declined from 118% (weeks 0-2) 17%, 19.7% and 10% (weeks 2-4, 4-6 and 6-8 respectively). The expected measure if there was no systematic change in base would be 15% (1.4 x interassay CV). Mean serum GH was virtually unchanged at 2-8 weeks after cessation of pegvisomant therapy. CONCLUSIONS: These results suggest that the activity of acromegaly may be assessed by serum IGF-I levels 6 weeks after the discontinuation of pegvisomant.

Acromegaly↗

PubMed2003

Pegvisomant in the treatment of acromegaly.

Epidemiological studies have highlighted the need for tight control of growth hormone (GH) and insulin-like growth factor I (IGF-I) in patients with acromegaly. Studies highlighting the events involved in GH receptor signaling have allowed the development of a pegylated GH receptor antagonist (pegvisomant) for use in humans, which has been designed to outcompete GH for the GH receptor, but which contains a position 120 amino acid substitution that prevents recruitment of a second GH receptor. This process of receptor dimerisation is crucial for signal transduction and IGF-I generation. Clinical trials of pegvisomant suggest it is the most effective treatment for acromegaly to date, as this therapy is capable of normalising serum IGF-I in up to 97% of patients when doses of 40 mg per day are used. This paper reviews the development of pegvisomant and the clinical experience in patients with acromegaly to date.

Acromegaly↗

PubMed2003

The effect of pegvisomant-induced serum IGF-I normalization on serum leptin levels in patients with acromegaly.

BACKGROUND: In humans, serum leptin correlates positively with fat mass. GH is lipolytic and patients with active acromegaly have lowered serum leptin compared to age, sex and body mass index (BMI)-matched controls, but a direct influence of GH on serum leptin remains unclear. In patients with acromegaly, total leptin increases following successful pituitary surgery and during somatostatin (SMS) analogue therapy (despite no change in BMI) but whether this represents changes in soluble leptin receptor, bound or free leptin is unclear. Pegvisomant, a GH receptor antagonist capable of normalizing serum IGF-I in over 97% of patients, represents a novel treatment strategy in acromegaly and its effect on leptin has not previously been reported. PATIENTS: Sixteen patients (nine male (M), seven female (F), median age 52 years, range 27-78 years) with active acromegaly (serum IGF-I at least 30% above the upper limit of an age-related reference range) were studied. Serum IGF-I was normalized in all subjects with pegvisomant [mean duration 7 months (range 3-11 months), median dose 20 mg/day (range 10-40 mg/day)]. A single batch measurement of leptin, bound leptin (BL), soluble leptin receptor (SLR), insulin and glucose were performed on samples from baseline and first occurrence of serum IGF-I normalization. RESULTS: As in normal subjects, females with acromegaly had higher baseline serum leptin [median M = 6.1 (range 1.6-58.7), F = 25.9 (range 3.19-54.1) ng/ml; P = 0.04], which correlated positively with BMI (R = 0.78, P = 0.0004). Forward step-wise regression analysis demonstrated that BMI and gender accounted for 90% of the variance in mean serum log10 leptin. Pegvisomant-induced serum IGF-I normalization was associated with a rise in serum leptin [8.9 (range 1.6-58.3) to 12.7 (range 2.3-90.8) ng/ml, P < 0.0001]. Although the absolute increase was not significantly different, mean percentage increase was greater in men (M = 66.6 +/- 51%, F = 11.8 +/- 16%, P = 0.017) despite similar serum IGF-I and BMI in male and female subjects at baseline. No change in BL or SLR accompanied serum IGF-I normalization [0.27 (range 0.15-1.26) to 0.27 (range 0.14-1.2) nmol/l, P = 0.27 and 3.2 (range 1.2-6.8) to 2.7 (range 1-7.4) nmol/l, P = 0.5, respectively]. After normalization of serum IGF-I, a correlation between BMI and leptin remained (R = 0.86, P < 0.0001) and together BMI and gender accounted for 87% of the variance in mean log10 serum leptin (P = 0.0002). CONCLUSION: Pegvisomant-induced serum IGF-I normalization in patients with active acromegaly is associated with a significant increase in total, and by implication, free leptin.

Acromegaly↗

PubMed2003

Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal.

Active acromegaly is associated with increased biochemical markers of bone turnover. Pegvisomant is a GH receptor antagonist that normalizes serum IGF-I in 97% of patients with active acromegaly. We evaluated the effects of pegvisomant-induced serum IGF-I normalization on biochemical markers of bone and soft tissue turnover, as well as levels of PTH and vitamin D metabolites, in 16 patients (nine males; median age, 52 yr; range, 28-78 yr) with active acromegaly (serum IGF-I at least 30% above upper limit of an age-related reference range). Serum procollagen III amino-terminal propeptide (PIIINP) and type I procollagen amino-terminal propeptide, osteocalcin (OC), bone-related alkaline phosphatase, C-terminal cross-linked telopeptide of type I collagen (CTx), albumin-corrected calcium, intact PTH, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D [1,25-(OH)(2) vit D], urinary type 1 collagen cross-linked N-telopeptide/creatinine ratio, and urinary calcium (24 h collection) were measured (single-batch analysis) at study entry and after IGF-I normalization, along with sera from 32 age- and sex-matched controls. Compared with controls, PIIINP, OC, and CTx were significantly elevated in patients at baseline. Pegvisomant-induced serum IGF-I normalization (699 +/- 76 to 242 +/- 28 micro g/liter, P < 0.001) was associated with a significant decrease in PIIINP, markers of bone formation (type I procollagen amino-terminal propeptide, OC, and bone-related alkaline phosphatase), and resorption (CTx and urinary type 1 collagen cross-linked N-telopeptide/creatinine ratio). 1,25-(OH)(2) vit D decreased and intact PTH increased significantly, but 25-hydroxy vitamin D was unaffected. A significant decline in calculated calcium clearance was observed. The decrease in serum IGF-I correlated positively with the decrease of serum PIIINP (r = 0.7, P < 0.01). After normalization of serum IGF-I, there was no statistical difference between patients and controls for any parameters for which control data were available. In conclusion, GH excess is associated with increased bone and soft tissue turnover. Pegvisomant-induced normalization of serum IGF-I results in a decrease in markers of bone and soft tissue turnover to levels observed in age-matched controls, and these changes are accompanied by an increase in PTH and a decrease in 1,25-(OH)(2) vit D. These data provide further evidence of the effectiveness of pegvisomant in normalizing the altered biological effects of GH hypersecretion.

Acromegaly↗

PubMed2002

Serum lipoprotein changes following IGF-I normalization using a growth hormone receptor antagonist in acromegaly.

OBJECTIVE: Active acromegaly is associated with altered lipid metabolism. The purpose of this study was to investigate the effect of serum IGF-I normalization on serum lipoproteins and insulin, in patients with acromegaly receiving the GH receptor antagonist pegvisomant. PATIENTS: Twenty patients (9 male, mean age 58.7 years, range 28-79) with active acromegaly (baseline serum IGF-I > 130% the age-related upper limit of normal) received pegvisomant and achieved a normal serum IGF-I [585.2 +/- 54.3 (mean +/- SEM) to 169.2 +/- 13.9 ng/ml, P < 0.0001]. MEASUREMENTS: Total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein B (apo B), apolipoprotein A1 (apo A1), lipoprotein a [Lp(a)] and insulin were measured in a single batch analysis on samples obtained at baseline and the first occasion of serum IGF-I normalization. Low-density lipoprotein (LDL) was calculated using the Friedewald formula. Paired analysis was performed using Student's paired t-test and the Wilcoxon signed rank test. RESULTS: Normalization of serum IGF-I resulted in an increase in TC (5.0 +/- 0.3 to 5.7 +/- 0.4 mmol/l, P = 0.0068), an increase in LDL (3.0 +/- 0.25 to 3.7 +/- 0.31 mmol/l, P = 0.0093) and an increase in apo B (110.6 +/- 7.76 to 127.1 +/- 8.86 mg/l, P = 0.014). TC and LDL increased in all but four patients. Despite a significant fall in fasting insulin levels (9.9 to 8.3 mU/l, range 8.85-19.8 to 6.33-11.6, P < 0.001) and insulin resistance (2.7 to 1.9, range 1.2-10.4 to 1-6.2, P < 0.001), mean serum TG and HDL levels were unaffected by IGF-I normalization. The protein component of HDL, apo A1, increased (153 +/- 4 to 166.4 +/- 5.43 mg/l, P = 0.026) and Lp(a) declined (median 342 to 235 mg/l, range 60-1013 to 74-671), P = 0.0035). Baseline serum TC and LDL were below the age- and sex-matched mean population value but after normalization of serum IGF-I the distribution of serum TC and LDL values was similar to that of the general population. CONCLUSIONS: Active acromegaly is associated with lowered mean serum TC and LDL. Successful management using pegvisomant increases lowered baseline serum TC and LDL levels, restoring the distribution of values to that of the general population, and improves insulin resistance. These findings are consistent with the reported lipoprotein changes following GH administration to normal and GH-deficient individuals.

Acromegaly↗

PubMed2002

Gender and age influence the relationship between serum GH and IGF-I in patients with acromegaly.

BACKGROUND: In patients with acromegaly serum IGF-I is increasingly used as a marker of disease activity. As a result, the relationship between serum GH and IGF-I is of profound interest. Healthy females secrete three times more GH than males but have broadly similar serum IGF-I levels, and women with GH deficiency require 30-50% more exogenous GH to maintain the same serum IGF-I as GH-deficient men. In a selected cohort of patients with active acromegaly, studied off medical therapy using a single fasting serum GH and IGF-I measurement, we have reported previously that, for a given GH level, women have significantly lower circulating IGF-I. OBJECTIVE: To evaluate the influence of age and gender on the relationship between serum GH and IGF-I in an unselected cohort of patients with acromegaly independent of disease control and medical therapy. METHODS: Sixty (34 male) unselected patients with acromegaly (median age 51 years (range 24-81 years) attending a colonoscopy screening programme were studied. Forty-five had previously received pituitary radiotherapy. Patients had varying degrees of disease control and received medical therapy where appropriate. Mean serum GH was calculated from an eight-point day profile (n = 45) and values obtained during a 75-g oral glucose tolerance test (n = 15). Serum IGF-I, IGFBP-3 and acid-labile subunit were measured and the dependency of these factors on covariates such as log10 mean serum GH, sex, age and prior radiotherapy was assessed using regression techniques. RESULTS: The median calculated GH value was 4.7 mU/l (range 1-104). A significant linear association was observed between serum IGF-I and log10 mean serum GH for the cohort (R = 0.5, P < 0.0001). After simultaneous adjustment of the above covariates a significant difference in the relationship between mean serum GH and IGF-I was observed for males and females. On average, women had serum IGF-I levels 11.44 nmol/l lower than men with the same mean serum GH (P = 0.03, 95% CI 1.33-21.4 nmol/l). Age significantly influenced the relationship and for a given serum GH, IGF-I was estimated to fall by 0.37 nmol/l per year (P = 0.04, 95% CI 0.015-0.72). CONCLUSIONS: In keeping with previous observations of relative GH resistance in normal and GH-deficient females we have observed lower serum IGF-I levels for equivalent mean serum GH levels in females patients with acromegaly. This gender-dependent difference is independent of disease activity and the use of concomitant medical therapy. Additionally, we have demonstrated that for a given serum GH level, age significantly influences IGF-I concentrations in patients with acromegaly. These data have important implications for the use of serum IGF-I and GH as markers of disease activity in acromegaly.

Acromegaly↗

PubMed2002

Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly.

An understanding of the events that occur during GH receptor (GHR) signaling has facilitated the development of a GHR antagonist (pegvisomant) for use in humans. This molecule has been designed to compete with native GH for the GHR and to prevent its proper or functional dimerization-a process that is critical for GH signal transduction and IGF-I synthesis and secretion. Clinical trials in patients with acromegaly show GHR blockade to be an exciting new mode of therapy for this condition, and pegvisomant may have a therapeutic role in diseases, such as diabetes and malignancy, in which abnormalities of the GH/IGF-I axis have been observed. This review charts the discovery and development of GHR antagonists and details the experience gained in patients with acromegaly.

Acromegaly↗

PubMed2002

A comparison of the effects of pegvisomant and octreotide on glucose, insulin, gastrin, cholecystokinin, and pancreatic polypeptide responses to oral glucose and a standard mixed meal.

Standard medical therapy for patients with acromegaly includes somatostatin analogs. Owing to the widespread expression of somatostatin receptors, these may be associated with unwanted effects, such as altered glucose tolerance and impaired gut hormone release. Pegvisomant is a novel pegylated GH analog that competes with wild-type GH for GH-receptor binding sites but contains a position 120, amino acid substitution that prevents functional GH receptor dimerization, a known prerequisite for GH signal transduction and generation of IGF-I. We have studied the short-term effects of these two therapies (pegvisomant 20 mg/d for 7 d and octreotide 50 microg thrice daily for 7 d) on glucose tolerance and stimulated gut hormone release in six healthy male volunteers in an open-label, random-order, cross-over study. Subjects were assessed at baseline (oral glucose tolerance test and standard mixed meal) and on d 6 and 7 of each therapy with a minimum washout of 2 wk between treatments. Area under the curve and peak responses were analyzed using one-way repeated-measures ANOVA (on ranks where appropriate). Pegvisomant had no effect on glucose tolerance or stimulated gut hormone response during an oral glucose tolerance test and a standard meal. In contrast, octreotide significantly increased fasting plasma glucose, lowered fasting plasma insulin, and led to deterioration in glucose tolerance; three subjects developed impaired glucose tolerance and one diabetes mellitus by World Health Organization criteria. Octreotide significantly impaired stimulated release of cholecystokinin, gastrin, insulin, and pancreatic polypeptide. In conclusion, pegvisomant, unlike octreotide, is not associated with deterioration in glucose tolerance and impairment of stimulated gut hormone release in normal males.

Administration, Oral↗

PubMed2001

Clinical use of a growth hormone receptor antagonist in the treatment of acromegaly.

The elucidation of the mechanisms by which growth hormone (GH) interacts with its receptor has facilitated the design of compounds that function as GH-receptor antagonists. One such compound, B2036, has been conjugated to polyethylene glycol to produce a drug, pegvisomant, that has a powerful ability to lower circulating concentrations of insulin-like growth factor I (IGF-I), the principal mediator of GH action, in patients with acromegaly and to improve the symptoms and signs associated with GH excess. This article describes the mechanism of action of GH-receptor antagonists, reviews the preclinical and clinical data on the use of pegvisomant and discusses some of the challenges that lie ahead in judging the efficacy of a treatment that, unlike established therapies for acromegaly, does not aim to modify the underlying cause of acromegaly, namely excess GH secretion, but aims to lower serum IGF-I levels to normal.

Acromegaly↗

PubMed2001

The relationship between serum GH and serum IGF-I in acromegaly is gender-specific.

In patients with acromegaly, there is a linear association between log10 serum GH and IGF-I. Healthy females secrete three times more GH than males but have broadly similar serum IGF-I levels, and in adult GH deficiency, the dose of exogenous GH required to achieve a given serum IGF-I is significantly greater in females than males. We report the influence of gender on the relationship between serum GH and IGF-I in subjects with active acromegaly. A single, fasted, serum sample was obtained from 153 subjects with active disease (87 males; median age, 47.8 yr; range, 20-82 yr) in whom serum IGF-I was at least 30% above the upper limit of an age-related reference range after washout from medical therapy. A linear correlation between serum IGF-I and log10 serum GH was observed (r = 0.53; P < 0.0001), but this relationship was significantly influenced by gender. For a given serum GH value, females were estimated to have serum IGF-I values 82 ng/ml less than males [P < 0.02; 95% confidence interval (CI), 15.2-149]. In females receiving oral E, mean serum IGF-I for a given GH value was 130 ng/ml lower than in males (P = 0.01; 95% CI, 29.8-230.2) but only 60 ng/ml less than the remaining 45 females (NS; P = 0.2). This study demonstrates a gender difference in the relationship between serum GH and IGF-I in patients with active acromegaly consistent with relative GH resistance observed in normal and GHD females, which may, in part, be mediated by E. This observation has important implications for the use of IGF-I as a measure of disease activity.

Acromegaly↗

PubMed2001

The place of pegvisomant in the management of acromegaly.

Conventional treatments for acromegaly include surgery, radiotherapy, dopamine agonists and somatostatin (SMS) analogues, which effect disease control by lowering circulating growth hormone (GH). Due to variability in tumour characteristics, combinations of these treatment modalities leave a significant number of patients with sub-optimal serum GH and insulin-like growth factor-I (IGF-I) levels, which have been linked to increased morbidity and mortality. The GH receptor antagonist pegvisomant is a genetically engineered analogue of GH that prevents functional dimerisation of the growth hormone receptor (GHR); a process that is critical to GH action at the cellular level. A crucial amino acid substitution at Gly(120) to Arg(120) within the third alpha helix of the antagonist prevents functional GHR dimerisation. Pegvisomant represents a novel treatment for acromegaly as, unlike existing treatment modalities, the effectiveness of pegvisomant is independent of pituitary tumour characteristics. Initial clinical studies in patients with active acromegaly have demonstrated serum IGF-I normalisation in over 90% of patients receiving 20 mg per day, such that, in terms of serum IGF-I normalisation, pegvisomant now represents the most effective medical treatment for acromegaly. Although there are limited long-term data on the use of pegvisomant and questions regarding pituitary tumour growth and altered liver function remain, this therapy offers the prospect of serum IGF-I normalisation in the vast majority of patients with active acromegaly.

Acromegaly↗

PubMed2001

Successful treatment of resistant acromegaly with a growth hormone receptor antagonist.

BACKGROUND/OBJECTIVE: Pegvisomant is a pegylated analogue of human GH and functions as a potent GH receptor antagonist. This novel mode of action gives it the potential to achieve biochemical control in patients with acromegaly whose disease activity cannot be satisfactorily controlled by conventional therapy. We have documented the clinical details of seven patients with residual active acromegaly after surgery and/or radiation therapy successfully treated with pegvisomant. PATIENTS/METHODS: Seven patients (four male, mean age 47 years, range 34-67 years) who participated in two separate clinical trials of pegvisomant have completed 2 years (four patients) or 1 year (three patients) of treatment. All had active acromegaly (mean serum GH level >5 mU/l; serum IGF-I elevated for age) that could not be controlled with standard medical therapy (dopamine agonist and/or a somatostatin analogue) following appropriate primary treatment with surgery and/or radiotherapy. RESULTS: On a median dose of 20 mg/day (range 15-40) pegvisomant, serum IGF-I fell from a mean of 920+/-351 ng/ml (s.d.) to 258+/-91 ng/ml and was normalised in all seven patients. These changes were associated with improvements in soft tissue enlargement and general well being. Treatment was well tolerated and no change in pituitary tumour size was evident on MRI scans performed every 6 months. CONCLUSIONS: Treatment with pegvisomant is safe and efficacy is maintained after 2 years. Serum IGF-I may be normalised in patients who are refractory to conventional therapy.

Acromegaly↗

PubMed2000

Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.

BACKGROUND: Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone. METHODS: We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly. RESULTS: The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups. CONCLUSIONS: On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.

Acromegaly↗

PubMed2000

Pegvisomant: a growth hormone receptor antagonist for the treatment of acromegaly.

Growth hormone receptor (GHR) dimerization is a prerequisite to the generation of growth hormone (GH) action. Pegvisomant is a GHR antagonist that has been designed to bind to the GHR at the cell surface and hence block this process. Initial studies suggest that pegvisomant is a highly effective antagonist of GH action in patients with acromegaly. The blockade of GH action, rather than the inhibition of pituitary GH secretion, represents a novel concept in the medical management of acromegaly. In this review, the design, efficacy, challenges and future role of pegvisomant are discussed.

Acromegaly↗

PubMed1999

Epithelial tumours of the adult kidney.

The epithelial tumours of the adult kidney, in particular renal cell carcinoma (RCC), are a variety of neoplasms that can be classified by morphology and genotype. Although most are well characterised, typical and less typical tumour variants are recognised. There is evidence to indicate that stage is one of the most important prognostic factors, irrespective of tumour subtype. However, the appropriate handling of nephrectomy specimens is essential for accurate evaluation of diagnostic and prognostic factors in RCC. The problem of how to achieve more objective nuclear grading is still unresolved. The use of diagnostic decision support systems offers the possibility of a flexible approach to this problem, while still utilising morphological criteria. The histopathological analysis remains important, but new techniques of molecular and cell biology will be providing new tools of extraordinary power to sharpen the diagnosis and give it a biological interpretation.

Adult↗

PubMed1999

Relatives' lived experiences of complementary therapies in a critical care department--a phenomenological study.

This phenomenological study examined relatives' lived experiences of complementary therapies in the Department of Critical Care Medicine at Royal Hobart Hospital. Participants in the study, 20 relatives of critically ill patients, were involved in a non-structured, audiotaped interview. Subsequently, transcripts were analysed using a phenomenological transformative process to identify common themes in the text. Study findings suggested four emerging conceptual categories, which with further analysis uncovered the essence of the phenomenon as extending and enriching a caring atmosphere.

Adolescent↗

PubMed1999

Growth hormone receptor antagonists therapy for acromegaly.

Knowledge of the interaction between growth hormone (GH) and the growth hormone receptor (GHR) has led to the rational design of a GHR antagonist. An analogue of GH able to block the action of GH at the cellular level offers greater specificity of effect compared with current medical therapies and is not dependent on tumour characteristics. This chapter reviews the interaction between GH and the GHR, and discusses the outstanding issues regarding GHR antagonist therapy in acromegaly.

Acromegaly↗