89 research outputs found
A single-dose comparison of the acute effects between the new somatostatin analog SOM230 and octreotide in acromegalic patients
Treatment with the somatostatin receptor (sst) subtype 2 predominant
analogs octreotide and lanreotide induces clinical and biochemical cure in
approximately 65% of acromegalic patients. GH-secreting pituitary
adenomas, which are not controlled, also express sst(5). We compared the
acute effects of octreotide and SOM230, a new somatostatin analog with
high affinity for sst(1,2,3,5) on hormone release in acromegalic patients.
In a single-dose, proof-of-concept study, 100 microg octreotide and 100
and 250 microg SOM230 were given s.c. to 12 patients with active
acromegaly. Doses of 100 and 250 microg SOM230 dose-dependently suppressed
GH levels from 2-8 h after administration (-38 +/- 7.7 vs. -61 +/- 6.7%,
respectively; P < 0.01). A comparable suppression of GH levels by
octreotide and 250 microg SOM230 was observed in eight patients (-65 +/- 7
vs. -72 +/- 7%, respectively). In three patients, the acute GH-lowering
effect of 250 microg SOM230 was significantly superior to that of
octreotide (-70 +/- 2 vs. -17 +/- 15%, respectively; P < 0.01). In one
patient, the GH-lowering effect of octreotide was better than that of
SOM230. Tolerability for SOM230 was good. Glucose levels were initially
slightly elevated after octreotide and SOM230, compared with control day,
whereas insulin levels were only significantly suppressed by octreotide.
We conclude that SOM230 is an effective GH-lowering drug in acromegalic
patients with the potential to increase the number of patients controlled
during long-term medical treatment
The current status of species recognition and identification in Aspergillus
The species recognition and identification of aspergilli and their
teleomorphs is discussed. A historical overview of the taxonomic concepts
starting with the monograph of Raper & Fennell
(1965) is given. A list of
taxa described since 2000 is provided. Physiological characters, particularly
growth rates and the production of extrolites, often show differences that
reflect phylogenetic species boundaries and greater emphasis should be placed
on extrolite profiles and growth characteristics in species descriptions.
Multilocus sequence-based phylogenetic analyses have emerged as the primary
tool for inferring phylogenetic species boundaries and relationships within
subgenera and sections. A four locus DNA sequence study covering all major
lineages in Aspergillus using genealogical concordance theory
resulted in a species recognition system that agrees in part with phenotypic
studies and reveals the presence of many undescribed species not resolved by
phenotype. The use of as much data from as many sources as possible in making
taxonomic decisions is advocated. For species identification, DNA barcoding
uses a short genetic marker in an organism”s DNA to quickly and easily
identify it to a particular species. Partial cytochrome oxidase subunit 1
sequences, which are used for barcoding animal species, were found to have
limited value for species identification among black aspergilli. The various
possibilities are discussed and at present partial β-tubulin or
calmodulin are the most promising loci for Aspergillus
identification. For characterising Aspergillus species one
application would be to produce a multilocus phylogeny, with the goal of
having a firm understanding of the evolutionary relationships among species
across the entire genus. DNA chip technologies are discussed as possibilities
for an accurate multilocus barcoding tool for the genus
Aspergillus
Human inhibitor of the first component of complement, C1 : characterization of cDNA clones and localization of the gene to chromosome 11
C1 inhibitor is a heavily glycosylated plasma protein that regulates the activity of the first component of complement (C1) by inactivation of the serine protease subcomponents, C1r and C1s. C1 inhibitor cDNA clones have been isolated, and one of these (pC1INH1, 950 base pairs) has been partially sequenced. Sequence analysis demonstrates that the C1 inhibitor is a member of the serpin "superfamily" of protease inhibitors. In the region sequenced, C1 inhibitor has 22% identity with antithrombin III, 26% with alpha 1-antitrypsin and alpha 1-antichymotrypsin, and 18% with human angiotensinogen. C1 inhibitor has a larger amino-terminal extension than do the other plasma protease inhibitors. In addition, inspection of residues that are invariant among the other protease inhibitors shows that C1 inhibitor differs at 14 of 41 of these positions. Thus, it appears that C1 inhibitor diverged from the group relatively early in evolution, although probably after the divergence of angiotensinogen. Southern blot analysis of BamHI-digested DNA from normal individuals and from rodent-human somatic cell hybrid cell lines (that contain a limited but varied human chromosome complement) was used to localize the human C1 inhibitor gene to chromosome 11
Outcomes-Adjusted Reimbursement in a Health-Care Delivery System
This paper considers a health-care delivery system with two noncooperative parties: a purchaser of medical services and a specialized provider. A dynamic principal-agent model that captures the interaction between the two parties is developed. In this model, patients arrive exogenously, receive periodic treatment from the provider, suffer costly complications that require hospital care, and eventually exit the system in death. The provider chooses the intensity of treatment in each period, incurs an associated cost, and is reimbursed by the purchaser according to observed patient outcomes. The purchaser's problem is to determine a payment system that will induce treatment choices maximizing total social welfare. The optimal payment system, referred to as the outcomes-adjusted payment system, is identified. It consists of a prospective payment per patient and a retrospective payment adjustment based on adverse short-term patient outcomes. This system induces the most efficient delivery of medical services by combining the immediate "threat" of a retrospective payment adjustment with the future reward of prospective payments generated by surviving patients. A numerical example is provided in the context of Medicare's End-Stage Renal Disease program. The example compares the optimal system to systems that are currently in place. The results suggest that the purchaser can achieve significant gains in patient life expectancy by switching to the outcomes-adjusted payment system, but this requires accurate information about treatment technology, patient characteristics, and provider preferences. The life-expectancy gains do not involve increased medical expenditures.Health-Care Financing, Fee for Service, Capitation, Principal-Agent Models, Dynamic Incentives, End-Stage Renal Disease
Quantification of Allosteric Interactions at G Protein–Coupled Receptors Using Radioligand Binding Assays
Quantification of Allosteric Interactions at G Protein Coupled Receptors Using Radioligand Binding Assays
The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5
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