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- Trainer, P J, et al.
(author)
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Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.
- 2000
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In: The New England journal of medicine. - 0028-4793. ; 342:16, s. 1171-7
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Journal article (peer-reviewed)abstract
- 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.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.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.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.
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- van der Lely, A J, et al.
(author)
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Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist.
- 2001
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In: Lancet (London, England). - 0140-6736. ; 358:9295, s. 1754-9
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Journal article (peer-reviewed)abstract
- Pegvisomant is a new growth hormone receptor antagonist that improves symptoms and normalises insulin-like growth factor-1 (IGF-1) in a high proportion of patients with acromegaly treated for up to 12 weeks. We assessed the effects of pegvisomant in 160 patients with acromegaly treated for an average of 425 days.Treatment efficacy was assessed by measuring changes in tumour volume by magnetic resonance imaging, and serum growth hormone and IGF-1 concentrations in 152 patients who received pegvisomant by daily subcutaneous injection for up to 18 months. The safety analysis included 160 patients some of whom received weekly injections and are excluded from the efficacy analysis.Mean serum IGF-1 concentrations fell by at least 50%: 467 mg/L (SE 24), 526 mg/L (29), and 523 mg/L (40) in patients treated for 6, 12 and 18 months, respectively (p<0.001), whereas growth hormone increased by 12.5 mg/L (2.1), 12.5 mg/L (3.0), and 14.2 mg/L (5.7) (p<0.001). Of the patients treated for 12 months or more, 87 of 90 (97%) achieved a normal serum IGF-1 concentration. In patients withdrawn from pegvisomant (n=45), serum growth hormone concentrations were 8.0 mg/L (2.5) at baseline, rose to 15.2 mg/L (2.4) on drug, and fell back within 30 days of withdrawal to 8.3 mg/L (2.7). Antibodies to growth hormone were detected in 27 (16.9%) of patients, but no tachyphylaxis was seen. Serum insulin and glucose concentrations were significantly decreased (p<0.05). Two patients experienced progressive growth of their pituitary tumours, and two other patients had increased alanine and asparate aminotransferase concentrations requiring withdrawal from treatment. Mean pituitary tumour volume in 131 patients followed for a mean of 11.46 months (0.70) decreased by 0.033 cm(3) (0.057; p=0.353).Pegvisomant is an effective medical treatment for acromegaly.
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- Edwards, N.V., et al.
(author)
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Optical characterization of wide bandgap semiconductors
- 2000
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In: Thin Solid Films. - 0040-6090 .- 1879-2731. ; 364:1, s. 98-106
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Journal article (peer-reviewed)abstract
- Our work primarily concerns the characterization of wide-gap III-V nitride semiconductors, nondestructively and at variable temperature, with spectroscopic ellipsometry (SE) and reflectometry in the spectral range from 1.5 to 6 eV. In the case of GaN, there are three main concerns associated with such data: (a) the quantification of the dispersion of the index of refraction with energy, (b) the removal of surface overlayers in real-time, and (c) the determination of the variation of valence bands with biaxial stress and the quantification of residual stress in thin films. The SE and reflectance capabilities provide (1) broadband spectra from 1.5 to 6 eV, which yield information about (a) below the bandgap and (b) above it, and (2) high resolution spectra (less than 1 meV at 3.4 eV) in the vicinity of the gap (3.3-3.6 eV), which enables (c). Here we will discuss issues concerning the relation of (c) to GaN material and growth parameters, though similar data for other wide bandgap materials will be discussed where relevant. Specifically, optimal heterostructure design for potential valence band engineering applications will be discussed in the context of trends in residual stress as a function of film thickness, growth temperature and substrate orientation for GaN/AlN/6H-SiC heterostructures. Standard heterostructures are mostly compressive for samples less than about 0.7 µm thick, are tensile up to about 2 µm and then abruptly become less tensile with stress values near 1 kbar thereafter. Additionally, these trends can be circumvented for moderately thick (approximately 2 µm) GaN layers (normally>2 kbar, tensile) by the introduction of a `buried interface' approach, namely, a strain mediating layer (SML) above the standard high-temperature AlN buffer layer designed to yield a range of compressive stresses from 0 to 2 kbar. The strain characteristics but also the growth rates of subsequently deposited nitride layers can be modulated by changing the growth parameters of the SML. This is achieved by in situ techniques during crystal growth without degrading the optical and structural properties of the deposited layer, as confirmed by XRD, SEM, PL, and AFM data taken on the overlying GaN layers. These results are interpreted in terms of coefficient of thermal expansion data for the layers and data concerning the planarization of GaN layers and growth behavior in non-(0001) directions.
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- Carlsson, Gunnar E, 1930, et al.
(author)
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A survey of the use of mandibular implant overdentures in 10 countries.
- 2004
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In: The International journal of prosthodontics. - 0893-2174. ; 17:2, s. 211-7
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Journal article (peer-reviewed)abstract
- PURPOSE: This preliminary international survey compared provision of implant-retained overdentures to fixed implant-supported prostheses for edentulous mandibles. MATERIALS AND METHODS: Questionnaires based on a 2001 Swedish study were sent to prosthodontists and specialist clinics in nine additional countries. RESULTS: Response rate varied from 53% to 100% in 10 national surveys and should allow careful comparison of results. The relationship between implant overdentures and fixed implant-supported prostheses in treatment of edentulous mandibles varied much; in Sweden, the proportion of overdentures was 12%, whereas it was 93% in The Netherlands. In all countries, the most common reason for choice of the overdenture was reduced cost. In all but two countries, the majority of respondents thought that patients with implant overdentures were equally or more satisfied with overdentures as those with fixed implant-supported prostheses. CONCLUSION: There were great differences among the 10 countries in choice of implant treatment of the edentulous mandible. The relative proportion of mandibular overdentures to fixed prostheses was low in Sweden and Greece and varied from one to two thirds in the other countries, except The Netherlands.
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- Chamberlain, Aaron K, et al.
(author)
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Ultrastructural organization of amyloid fibrils by atomic force microscopy
- 2000
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In: Biophysical Journal. - : Cell Press. - 0006-3495 .- 1542-0086. ; 79:6, s. 3282-3293
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Journal article (peer-reviewed)abstract
- Atomic force microscopy has been employed to investigate the structural organization of amyloid fibrils produced in vitro from three very different polypeptide sequences. The systems investigated are a 10-residue peptide derived from the sequence of transthyretin, the 90-residue SH3 domain of bovine phosphatidylinositol-3'-kinase, and human wild-type lysozyme, a 130-residue protein containing four disulfide bridges. The results demonstrate distinct similarities between the structures formed by the different classes of fibrils despite the contrasting nature of the polypeptide species involved. SH3 and lysozyme fibrils consist typically of four protofilaments, exhibiting a left-handed twist along the fibril axis. The substructure of TTR(10-19) fibrils is not resolved by atomic force microscopy and their uniform appearance is suggestive of a regular self-association of very thin filaments. We propose that the exact number and orientation of protofilaments within amyloid fibrils is dictated by packing of the regions of the polypeptide chains that are not directly involved in formation of the cross-beta core of the fibrils. The results obtained for these proteins, none of which is directly associated with any human disease, are closely similar to those of disease-related amyloid fibrils, supporting the concept that amyloid is a generic structure of polypeptide chains. The detailed architecture of an individual fibril, however, depends on the manner in which the protofilaments assemble into the fibrillar structure, which in turn is dependent on the sequence of the polypeptide and the conditions under which the fibril is formed.
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