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At least 613 records · Page 34Linked to original sources
PubMed2005

Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials.

OBJECTIVES: Pharmacological treatment of Alzheimer's disease focuses on correcting the cholinergic deficiency in the central nervous system with cholinesterase inhibitors. Three cholinesterase inhibitors are currently recommended: donepezil, rivastigmine, and galantamine. This review assessed the scientific evidence for the recommendation of these agents. DATA SOURCES: The terms "donepezil", "rivastigmine", and "galantamine", limited by "randomized-controlled-trials" were searched in Medline (1989-November 2004), Embase (1989-November 2004), and the Cochrane Database of Systematic Reviews without restriction for language. STUDY SELECTION: All published, double blind, randomised controlled trials examining efficacy on the basis of clinical outcomes, in which treatment with donepezil, rivastigmine, or galantamine was compared with placebo in patients with Alzheimer's disease, were included. Each study was assessed independently, following a predefined checklist of criteria of methodological quality. RESULTS: 22 trials met the inclusion criteria. Follow-up ranged from six weeks to three years. 12 of 14 studies measuring the cognitive outcome by means of the 70 point Alzheimer's disease assessment scale--cognitive subscale showed differences ranging from 1.5 points to 3.9 points in favour of the respective cholinesterase inhibitors. Benefits were also reported from all 12 trials that used the clinician's interview based impression of change scale with input from caregivers. Methodological assessment of all studies found considerable flaws--for example, multiple testing without correction for multiplicity or exclusion of patients after randomisation. CONCLUSION: Because of flawed methods and small clinical benefits, the scientific basis for recommendations of cholinesterase inhibitors for the treatment of Alzheimer's disease is questionable.

Alzheimer Disease↗
PubMed1985

Failure to respond to growth hormone releasing hormone (GHRH) in acromegaly due to a GHRH secreting pancreatic tumor: dynamics of multiple endocrine testing.

Growth hormone releasing hormone (GHRH) has recently been isolated and sequenced from pancreatic tumors secreting GHRH. Patients with untreated acromegaly due to a pituitary tumor respond to exogenous administration of GHRH with a further rise of their elevated basal growth hormone (GH) levels. For the first time, we report the effects of exogenously administered synthetic GHRH in a patient with acromegaly due to a GHRH secreting pancreatic tumor. The diagnosis was established by high peripheral IR-GHRH levels (1100 pg/ml) and an arterio- venous tumor gradient of IR-GHRH. In this patient GH failed to respond to 1 microgram/kg of exogenous GHRH with the pancreatic tumor in situ; however, further increase of serum GH levels occurred after TRH administration, hypoglycemia and oral glucose administration. After removal of the tumor, serum GH levels decreased and a normal response to GHRH and TRH were demonstrated. The extract of the tumor contained 1.7 micrograms IR-GHRH per g wet tissue. Thus, lack of response to exogenous GHRH in untreated acromegaly may indicate the presence of an ectopic GHRH producing tumor.

Acromegaly↗
PubMed1991

[A simple multiple maze test to estimate learning and memory in mice: application to the effect of scopolamine on learning and memory].

The apparatus consists of a home cage, a maze cage and a starting box. A maze with four right-middle-left decisions was placed in the maze cage. The starting box was attached and a water tap was placed at an area corresponding to the entrance of the maze. The exit of the maze and the home cage are connected with a tunnel. Food was placed in the home cage. 1) Mice were housed for 10 hr a day in the apparatus and then removed to another cage for fasting. One trial a day was carried out after fasting for more than 12 hr. In each trial, a mouse was put at the starting box, and then the number of errors (entering a blind alley) and the time until the mouse reached the home cage were counted. The mouse passed through the maze with a small number of errors and time. 2) Administration of scopolamine (0.125-0.5 mg/kg, i.p.) to a mouse that had mastered the maze transiently disturbed the maze performance dose-dependently. 3) Mice were housed for 4 hr a day. Scopolamine (0.25 mg/kg, i.p.) was administered either before or after the housing. Scopolamine disturbed the maze performance in the case of both procedures. These results suggest that the method is useful for estimating the memory in mice.

Animals↗
PubMed2005

Advances in myeloma genetics and prospects for pharmacogenomic testing in multiple myeloma.

Pharmacogenomic studies in multiple myeloma, a neoplasia of clonally expanded malignant bone marrow plasma cells, are helping to set the stage for individualized therapy. Although relatively few in numbers, these studies are already providing new therapeutic targets and avenues for drug discoveries as well as contributing to novel prognostic markers in multiple myeloma. High-throughput mutation screening of the kinome promises to identify further novel targets for therapy. Genetics and gene expression profiling technology have improved molecular-based patient stratification and prognostic staging, expanded knowledge of the molecular mechanism of chemotherapeutic agents, and provided a better understanding of myeloma bone disease. The use of pharmacogenomic strategies in myeloma is thus already changing medical practice.

Humans↗