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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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- Axelson, Olav, 1937-, et al.
(author)
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Regulatory toxicology and pharmacology.
- 2003
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In: International journal of occupational and environmental health. - 1077-3525 .- 2049-3967. ; 9, s. 386-389
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Journal article (peer-reviewed)
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- Fields, Randall R., et al.
(author)
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Usher syndrome type III : revised genomic structure of the USH3 gene and identification of novel mutations
- 2002
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 71:3, s. 607-617
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Journal article (peer-reviewed)abstract
- Usher syndrome type III is an autosomal recessive disorder characterized by progressive sensorineural hearing loss, vestibular dysfunction, and retinitis pigmentosa. The disease gene was localized to 3q25 and recently was identified by positional cloning. In the present study, we have revised the structure of the USH3 gene, including a new translation start site, 5′ untranslated region, and a transcript encoding a 232–amino acid protein. The mature form of the protein is predicted to contain three transmembrane domains and 204 residues. We have found four new disease-causing mutations, including one that appears to be relatively common in the Ashkenazi Jewish population. We have also identified mouse (chromosome 3) and rat (chromosome 2) orthologues, as well as two human paralogues on chromosomes 4 and 10.
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- Danielsson, Erik, et al.
(author)
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Dry etching and metallization schemes in a GaN/SiC heterojunction device process
- 2000
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In: Materials Science Forum. - : Trans Tech Publications Inc.. - 0255-5476 .- 1662-9752. ; 338-342, s. 1049-1052
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Journal article (peer-reviewed)abstract
- Dry etching and metallization schemes are described for a GaN/SiC heterojunction. GaN was reactive ion etched in a chlorine based chemistry (Cl2/Ar), and an ICP etch was used on 4H-SiC using a fluorine based chemistry (SF6/Ar/O2). The etch rates obtained on GaN was above 400 nm/min. High sample temperature from self heating and large dc-bias was the probable cause for the high etch rate. The ICP etch rate on SiC approached 320 nm/min, and the etch selectivity to GaN was >100. The metallization was based on Ti for both n-GaN and p-SiC. TLM and Kelvin structures were used to extract the specific contact resistivity, ÏC. After a 950 °C anneal in N2 ÏC on the GaN samples were below 1·10-6 Ωcm2 for sputtered contacts in room temperature, and an order of magnitude higher with evaporation. On p-SiC no ohmic behavior was found with a doping of 4·1018 cm-3, but the same contact metallization on highly doped areas (>1020 cm-3) showed ohmic behavior with ÏC below 10-4 Ωcm2.
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