Cerebrovascular effects of the TRH analogues pGlu-3-methyl-His-Pro amide and pGlu-Glu-Pro amide: a comparison with TRH.

The goal of the study was to assess whether TRH analogues possess cerebrovascular effects similar to the native peptide. The neuropeptide thyrotropin releasing hormone (TRH) elicits cerebrovasodilation in several species under various conditions. The laser-Doppler method was employed to study the effects of TRH and the analogues pGlu-3-methyl-His-Pro amid (M-TRH) and pGlu-Glu-Pro amide. Intravenous (i.v.) injection of 300 microg kg(-1) of TRH elicited cerebrovasodilation and a 62% increase in blood flow within 1 minute. M-TRH, in a dose of 300 microg kg(-1) i.v., elicited a 80% increase in cerebral blood flow. Even a minute dose of M-TRH (625 ng kg(-1)) caused an increase in cerebral blood flow. No clear difference in effects on the cerebral blood flow was observed between spontaneously and mechanically ventilated animals, pGlu-Glu-Pro amide had no cerebrovascular effect.

The neuropeptide TRH has a minor effect on the enzymatic activity of acetylcholinesterase in vitro.

The neuropeptide thyrotropin-releasing hormone (TRH) elicits a variety of physiological effects of which some are due to cholinergic mechanisms. TRH modulates in vivo the effects of compounds affecting acetylcholinesterase (AChE). In the present study the in vitro effects of TRH on the activity of AChE were explored. TRH has no effect at physiologically relevant concentrations. At unphysiologically high concentrations (>5 mM) a slight inhibition was found. This was noticed also when the enzyme was exposed to the amide-free tripeptide analog p-Glu-His-Pro. We conclude that any cholinergic effect of TRH observed in vivo is unlikely to be due to a direct interaction of the peptide with AChE.

A multifactorial intervention to reduce the risk of falling among elderly people living in the community.

BACKGROUND: Since falling is associated with serious morbidity among elderly people, we investigated whether the risk of falling could be reduced by modifying known risk factors. METHODS: We studied 301 men and women living in the community who were at least 70 years of age and who had at least one of the following risk factors for falling: postural hypotension; use of sedatives; use of at least four prescription medications; and impairment in arm or leg strength or range of motion, balance, ability to move safely from bed to chair or to the bathtub or toilet (transfer skills), or gait. These subjects were given either a combination of adjustment in their medications, behavioral instructions, and exercise programs aimed at modifying their risk factors (intervention group, 153 subjects) or usual health care plus social visits (control group, 148 subjects). RESULTS: During one year of follow-up, 35 percent of the intervention group fell, as compared with 47 percent of the control group (P = 0.04). The adjusted incidence-rate ratio for falling in the intervention group as compared with the control group was 0.69 (95 percent confidence interval, 0.52 to 0.90). Among the subjects who had a particular risk factor at base line, a smaller percentage of those in the intervention group than of those in the control group still had the risk factor at the time of reassessment, as follows: at least four prescription medications, 63 percent versus 86 percent, P = 0.009; balance impairment, 21 percent versus 46 percent, P = 0.001; impairment in toilet-transfer skills, 49 percent versus 65 percent, P = 0.05; and gait impairment, 45 percent versus 62 percent, P = 0.07. CONCLUSIONS: The multiple-risk-factor intervention strategy resulted in a significant reduction in the risk of falling among elderly persons in the community. In addition, the proportion of persons who had the targeted risk factors for falling was reduced in the intervention group, as compared with the control group. Thus, risk-factor modification may partially explain the reduction in the risk of falling.

Yale FICSIT: risk factor abatement strategy for fall prevention.

Based on finding a strong association between number of impairments and risk of falling in earlier studies, Yale FICSIT investigators are conducting an intervention trial comparing the effectiveness of usual care plus social visits (SV) and a targeted risk abatement intervention (TI) strategy in reducing falls among at risk community elderly persons. Subjects include members of a participating HMO who are > or = 70 years of age, cognitively intact, not terminally ill, not too physically active, and possess at least one fall risk factor. The targeted risk factors include postural hypotension; sedative use; at least four targeted medications; upper and lower extremity strength and range of motion impairments; foot problems; and balance, gait, and transfer dysfunctions. The interventions include medication adjustments, behavioral change recommendations, education and training, and home-based exercise regimens targeting the identified risk factors. The interventions are carried out by the study nurse practitioner and physical therapist in TI subjects' homes. The SV subjects receive a comparable number of home visits as the TI subjects during which a structured life review is performed by social work students. The primary outcome is occurrence of falls during the 12-month followup. Secondary outcomes include change in mobility performance and fall-related efficacy.

Levodopa in Parkinson disease: a long-term appraisal of mortality.

Mortality rates for a group of patients in a collaborative multicenter study of levodopa (Larodopa) in the treatment of parkinsonism were compared with corresponding mortality rates in the general population adjusted for age and sex distribution in accordance with that of the parkinsonian patients under study. The death rate, conservatively adjusted for dropouts among parkinsonian patients, is estimated to be approximately 33% greater than that for the general population. This is in contrast to an earlier study of Hoehn and Yahr, prior to the advent of levodopa treatment, wherein the mortality rate for parkinsonian patients was shown to be in excess of that in the general population by a factor of 2.9, or nearly 200%.