Biomedical subjects

R Helme

Publications and source records attributed to R Helme.

6 recordsLinked to original sources

PubMed2003

Donepezil in vascular dementia: a randomized, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and tolerability of donepezil in patients with vascular dementia (VaD). METHODS: Patients (n = 616; mean age, 75.0 years) with probable or possible VaD, according to National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche en l'Enseignement en Neurosciences criteria, were randomized to receive donepezil 5 mg/day (n = 208), donepezil 10 mg/day (after 5 mg/day for the first 28 days) (n = 215), or placebo (n = 193) for 24 weeks. RESULTS: Seventy-six percent of the patients enrolled had probable VaD. A total of 75.3% of the 10 mg donepezil group and 80.8% of the 5 mg group completed the study compared with 83.4% of the placebo group. Both donepezil-treated groups showed improvements in cognitive function on the Alzheimer's Disease Assessment Scale-cognitive subscale compared with placebo, with a mean endpoint treatment difference, as measured by the change from baseline score, of approximately 2 points (donepezil 5 mg, -1.65 [p = 0.003]; 10 mg, -2.09 [p = 0.0002]). Greater improvements on the Clinician's Interview-Based Impression of Change-plus version were observed with both donepezil groups than with the placebo group (overall donepezil treatment vs placebo p = 0.008); 25% of the placebo group showed improvement compared with 39% (p = 0.004) of the 5 mg group and 32% (p = 0.047) of the 10 mg group. Withdrawal rates due to adverse events were low (placebo, 8.8%; donepezil 5 mg, 10.1%; 10 mg, 16.3%). CONCLUSIONS: Donepezil-treated patients demonstrated significant improvements in cognition and global function compared with placebo-treated patients, and donepezil was well tolerated.

Adult↗

PubMed2000

Pain and hyperalgesia in osteoarthritis of the hands.

OBJECTIVE: Tissue damage and pain can lead to a change in the stimulus/response characteristics of the nociceptive system. Hyperalgesia has been described in experimental pain states and some clinical conditions, but has not been investigated in osteoarthritis (OA). We sought to establish the presence of hyperalgesia at the thumb in subjects with OA of the hand and to explore any relationship between sensitivity to extrinsic stimuli and the experience of clinical pain. METHODS: Subjects with OA of the hand were divided into groups according to their pain profile. The sample also included pain-free OA cases and pain-free controls. Intensity ratings were obtained for each of 3 types of pain: continuous pain, incident pain, and movement pain. Thermal and mechanical detection and pain thresholds were measured over the forearm and the carpometacarpal joint of the thumb. RESULTS: Lower thermal and mechanical pain thresholds were evident over the thumb relative to forearm in the groups with persistent pain. Subjects complaining only of incident pain, pain-free OA cases, and pain-free controls did not exhibit regional differences in sensitivity to thermal and mechanical stimuli. Increased ratings of continuous pain were associated with lower thermal and mechanical pain thresholds. Variance in movement pain ratings was predicted by mechanical forearm pain thresholds. CONCLUSION: OA in the hands is associated with cutaneous and deep hyperalgesia to thermal and mechanical stimuli. Increased levels of continuous pain are associated with more pronounced hyperalgesia. The associations of movement pain suggest the contribution of central mechanisms in the stimulus/response changes accompanying movement pain.

Aged↗

PubMed1996

Sensory peptides as neuromodulators of wound healing in aged rats.

An intact nociceptor system of primary afferent sensory nerves is important for the initiation of the inflammatory process and successful tissue repair. Dysfunction of this system with age could be a contributing factor for delayed wound healing in the elderly. This study was designed to examine the role of sensory nerves (using capsaicin-pretreated rats) and the effect of aging on the healing of a thermal wound induced on the interscapular region (using a CO2 laser). The healing endpoint was the time when full wound contraction had occurred. The ability of the sensory peptides, substance P (SP) and calcitonin gene-related peptide (CGRP), in modulating wound healing in aged rats was examined by taking into account the modulatory interaction effects between these peptides. A blister model in the rat hind footpad combined with a laser Doppler flowmeter was used initially to establish these vascular interaction effects. The results showed a significant delay in thermal wound healing in both the capsaicin-treated and aged rats. Using the blister model, we demonstrated the ability of SP and CGRP to induce a limited and a prolonged vasodilator response, respectively. When tested together, SP attenuated the vascular effect of CGRP, an effect that was reversed using the tachykinin antagonist spantide II. When injected at the wound site, SP and CGRP were equally potent in promoting wound healing in aged rats. The beneficial effect of taking the interaction effects into account was most evident in a group of rats that received the tachykinin antagonist as part of their initial treatment with CGRP and 6 h later, an injection of SP; the time to complete wound closure was 11.3 +/- 0.6 days compared to 21.0 +/- 0.9 days in aged controls. We contend that would healing in aged rats can be accelerated by exogenous administration of sensory peptides. Furthermore, modulatory interaction effects between sensory peptides should be taken into consideration when designing any treatment protocol that purports to accelerate wound healing.

Aging↗

PubMed1994

Beta A4(25-35) modulates substance P effect on rat skin microvasculature in aged rats: pharmacological manipulation using SEC-receptor ligands.

The primary constituent of the senile plaque core in Alzheimer's disease (AD) is the beta-amyloid protein (beta A4). A discrete 11 amino acid fragment of the beta A4, beta A4(25-35), has been implicated in mediating in vitro neurotoxicity and an inflammatory response surrounding senile plaques in AD via interaction with the Serpin Enzyme Complex (SEC) receptor. Substance P (SP), a neuropeptide of the tachykinin family and a major mediator of neurogenic inflammation, shows sequence homology to beta A4(25-35) and has been shown to protect against the neurotoxicity of beta-amyloid. SP also competes with beta A4(25-35) for binding to the SEC-receptor. SP neurons have also been found to be depleted in AD. Using a blister model of inflammation in the rat hind footpad, we have examined the effect of beta A4(25-35) and its interaction with SP in rat skin microvasculature and determined age-related changes to these phenomena. In addition, pharmacological manipulation of these responses using SEC-receptor ligands (peptide 105Y and 105C) was also undertaken. Because of the evidence for co-existence and co-release of SP and calcitonin gene-related peptide (CGRP) from the peripheral terminals of sensory nerves, it was of interest to examine the interaction of CGRP with beta A4(25-35) on rat skin microvasculature. beta A4(25-35) (10 microM) was perfused over the base of a blister raised on the hind footpad of anaesthetised young and old rats. This was followed by perfusion of SP (1 microM) or CGRP (1 microM) after Ringer's solution. Relative blood flow was monitored using a Laser-Doppler Flowmeter.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid beta-Peptides↗

PubMed1986

Bilateral internuclear ophthalmoplegia in systemic lupus erythematosus.

The case of a 25-year-old female with bilateral internuclear ophthalmoplegia as a presenting feature of systemic lupus erythematosus (SLE) is described. It is important to recognize that bilateral internuclear ophthalmoplegia may be an early manifestation of cerebral involvement in SLE in addition to its occurrence in multiple sclerosis.

Adult↗

PubMedDate not supplied

Angiotensin converting enzyme and substance P changes in blister fluid following afferent nerve stimulation in the rat.

We have examined the effect of electrical nerve stimulation on substance P and angiotensin converting enzyme activity in the interstitial fluid of rat skin using a blister model. Following sciatic nerve stimulation, blister fluid immunoreactive substance P (fmol/ml) was increased from 118 (unstimulated side, s.e.m. = 13, n = 15) to 197 (stimulated side, s.e.m. = 26, n = 15, P less than 0.0125, paired t-test, 14 d.f.). Angiotensin converting enzyme (ACE) activity (nmol HL/ml per h) was reduced in blister fluid from 26.5 (unstimulated side, s.e.m. = 2.4, n = 12) to 22.4 (stimulated side, s.e.m. = 1.4, P less than 0.05, paired t-test, 11 d.f.). Electrical stimulation of afferent nerves inhibits angiotensin converting enzyme activity in vivo. This may contribute to the process of neurogenic inflammation.

Animals↗