26 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
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
Analysis of shared heritability in common disorders of the brain
Paroxysmal Cerebral Disorder