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- Trainer, P J, et al.
(författare)
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Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.
- 2000
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Ingår i: The New England journal of medicine. - 0028-4793. ; 342:16, s. 1171-7
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist.
- 2001
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Ingår i: Lancet (London, England). - 0140-6736. ; 358:9295, s. 1754-9
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Tidskriftsartikel (refereegranskat)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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- DaSilva, Luiz A., et al.
(författare)
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Network mobility and protocol interoperability in ad hoc networks
- 2004
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Ingår i: IEEE Communications Magazine. - 0163-6804 .- 1558-1896. ; 42:11, s. 88-96
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Tidskriftsartikel (refereegranskat)abstract
- The integration of various network-level functions, including routing, management, and security, is critical to the efficient operation of a mobile ad hoc network. In this article we focus on network mobility (rather than node mobility), implying the movement of entire subnetworks with respect to one another, while individual users initially associated with one such subnetwork may also move to other domains. One example is a battlefield network that includes ships, aircraft, and ground troops. In this "network of networks", subnets (e.g. shipboard networks) may be interconnected via a terrestrial mobile wireless network (e.g., between moving ships). We discuss the design and implementation of a new ad hoc routing protocol, a suite of solutions for policy-based network management, and approaches for key management and deployment of IPsec in a MANET. These solutions, in turn, are integrated with real-time middleware, a secure radio link, and a topology monitoring tool. We briefly describe each component of the solution, and focus on the challenges and approaches to integrating these components into a cohesive system to support network mobility. We evaluate the effectiveness of the system through experiments conducted in a wireless ad hoc testbed.
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- Gachet, S, et al.
(författare)
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A probabilistic approach to the use of pollen indicators for plant attributes and biomes: an application to European vegetation at 0 and 6 ka
- 2003
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Ingår i: Global Ecology and Biogeography Letters. - 0960-7447. ; 12:2, s. 103-118
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Tidskriftsartikel (refereegranskat)abstract
- Aim This paper presents a probabilistic method for the characterization of pollen taxa using attributes, and for the reconstitution of past biomes. The probabilities are calculated on the basis of European floristic and pollen databases sufficiently large and exhaustive to provide robust estimates. Location The analysis is based on data from approximately 1000 sites throughout Europe. Method We use all the pollen data from the European Pollen Database (EPD), which contains about 50 000 pollen assemblages distributed across Europe and covering the period from the Last Glacial Maximum to the present. Using existing floras, each pollen taxon has been characterized by allocating one or more modes of several attributes, chosen according to the biogeography and phenology of the taxon. With this information, conditional probabilities are defined, representing the chance of a given attribute mode occurring in a given pollen spectrum, when the taxa assemblage is known. The concept of co-occurrence is used to provide a greater amount of information to compensate for difficulties in the identification of pollen grains, allowing a better interpretation when there is little diversity in the pollen assemblage. Results The method has been validated using a dataset of modern samples against existing methods of biome classification and remote sensing data. An application is proposed in which the new method is used to produce biomes for pollen data 6000 years ago. This confirms previous results showing an extension of the deciduous forest to the north, east and south, explained by milder winters in western and northern Europe, and cooler and wetter climate in the Mediterranean region. Conclusion The results show the new method to be efficient, reliable and flexible and to be an improvement over the previous method of biomization. They will be used to test simulations of earth system models running on periods with climate significantly different from the present day, enabling a robust test of the validity of applying these models to the future.
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- Aguilar, A., et al.
(författare)
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Double photodetachment from the Cl[-]ion
- 2004
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Ingår i: Physical Review A - Atomic, Molecular, and Optical Physics. - 2469-9926 .- 2469-9934. ; 69:2
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Tidskriftsartikel (refereegranskat)abstract
- The correlated process involving the photodetachment of two electrons from the [Formula Presented] ion has been investigated over the photon energy range 20–45 eV. In the experiment, a beam of photons from the Advanced Light Source (ALS) was collinearly merged with a counterpropagating beam of [Formula Presented] ions from a sputter ion source. The [Formula Presented] ions produced in the interaction region were detected, and the normalized signal was used to monitor the relative cross section for the reaction. An absolute scale for the cross section was established by measuring the spatial overlap of the two beams and by determining the efficiency for collection and detection of the [Formula Presented] ions. The overall magnitude and shape of the measured cross section for this process agrees well with an R-matrix calculation. The calculation identifies the dominant mechanism leading to the production of the [Formula Presented] ion as being a direct nonresonant process involving the ejection of a pair of electrons from the valence shell. Less important is the indirect nonresonant process that involves the production and decay of core-excited and doubly excited states of the Cl atom in an intermediate step. Direct and indirect resonant mechanisms involving the excitation of a single [Formula Presented] core electron or more than one valence electron of the [Formula Presented] ion were found to be insignificant in the energy range studied.
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