EVIDENCE FOR MEDETOMIDINE AS A SELECTIVE AND POTENT AGONIST α2-ADRENORECEPTORS

• 1 The activity on α-adrenoreceptors of medetomidine (±)-4-(α,2,3-trimethylbenzyl)imidazole), an α-methyl derivative of detomidine, has been characterized in vivo and in vitro using detomidine, MPV 207, MPV 295, azepexole, clonidine and xylazine for reference purposes.
• 2 Medetomidine (1–100 μg/kg i.v.) was a hypotensive and bradycardic compound in anaesthetized rats. Furthermore, it induced vasopressor (PD₅₀ 1.7 μg/kg) and sympatho-inhibitory (ID₅₀ 1.6 μg/kg) actions in pithed rats, the effects being antagonized by idazoxan (0.3 mg/kg i.v.) but not by prazosin (0.1 mg/kg i.v.). Medetomidine (30–300 μg/kg i.m.) had an α₂-adrenoreceptor mediated sedative effect on chicks.
• 3 Medetomidine was, overall, more potent than detomidine, MPV 207, clonidine, xylazine, MPV 295 or azepexole in central (sedation in the chick) and peripheral (cardiac presynaptic in the pithed rat) actions on α₂-adrenoreceptors. Clonidine had, however, about an equal potency to medetomidine in the vascular smooth muscle of the pithed rat.
• 4 Like detomidine and MPV 295, medetomidine had no agonistic activity in the rat aortic ring, but high concentrations antagonized methoxamine-induced contractions, giving a pA₂ value of 5.68 for α₁-adrenoreceptor antagonism.
• 5 The overall lipophilicity (log P') of medetomidine in the octanol/buffer (pH 7.4, 24–26°C, HPLC technique) was 2.80.
• 6 In summary, the experimental data suggest that medetomidine is a lipophilic compound with selective α₂-adrenoreceptor-stimulating properties and high potency. It may, therefore, prove to be a suitable pharmacologic tool for interventions in α₂-adrenoreceptor mediated effects in the autonomic nervous system.

     

Gonial angles and condylar and ramus height of the mandible in complete denture wearers—a panoramic radiograph study

summary It has been accepted that the shape of the mandibular base, and especially the gonial angle of the mandible, correlates with the function of the jaw closing muscles. The gonial angles of the mandible and condylar and ramus heights of 30 complete denture wearers (18 women, 12 men, mean age 61 years, range 42–74 years) coming for renewal of their dentures were measured using panoramic radiographs. The mean period of edentulousness was 26 years (range 10–53 years). No statistically significant difference was observed between the sexes in the the sizes of gonial angles and condylar and ramus heights. The right gonial angle was statistically significantly smaller than the left one and correlated negatively with the ramus height in both sides but positively with the increased EMG activity in the right masseter muscle. The size of the gonial angle and the condylar and ramus heights did not correlate with the age of the patients, edentulous period or alveolar ridge resorption.     

Electrophysiological evidence for cross-modal plasticity in humans with early- and late-onset blindness

It is commonly believed that sensory deprivation can lead to cross-modal reorganization in an immature hut not in a mature brain. The results of the present study suggest, however, that plasticity between sensory modalities is possible even in adults: activity indicating involvement of parietal or occipital brain areas in pitch-change discrimination was found in individuals blinded after childhood. Event-related brain potentials of early blinded (before the age of 2 years). late-blinded (12–28 years of age), and sighted adults were recorded to stimulus sequences consisting of standard tones occasionally replaced by deviant tones. Even when participants were not attending to auditory stimuli, the deviant tones elicited the mismatch negativity (MMN) in each group. There were no significant MMN front-back scalp distribution differences among the groups. However, when participants were detecting deviant stimuli, these stimuli elicited N2 and P3 waves that were posterior in distribution in both groups of blind participants relative to those of the sighted participants. These results suggest that cross-modal reorganization may occur even in the mature human brain.     

THE USE OF IMMUNOHISTOCHEMISTRY TO IMPROVE SENSITIVITY AND SPECIFICITY IN THE DIAGNOSIS OF SYSTEMIC MYCOSES IN PATIENTS WITH HAEMATOLOGICAL MALIGNANCIES

The original histomorphological diagnoses in a series of 34 mycotic lesions from 23 patients with haematological malignancies were re-evaluated by immunohistochemistry. A panel of antibodies was used to identify the agents of aspergillosis, candidosis, fusariosis, scedosporiosis (pseudallescheriosis), and zygomycosis. Apart from improving the diagnosis of aspergillosis, candidosis, and zygomycosis, the application of immunohistochemistry also disclosed three lesions of aspergillosis which had been overlooked during the original screening. It is concluded that the use of immunohistochemistry for the diagnosis of common opportunistic mycoses will not only increase diagnostic specificity, but will also reveal more tissue infections than the conventional histomorphological examination of traditionally stained sections. © 1997 by John Wiley & Sons, Ltd.     

Analgesics and Risk of Coronary and other Death in Middle-aged Men in Eastern Finland

Abstract The association between oral analgesics and the risk of death from ischaemic heart disease (IHD), cardiovascular disease, disease other than IHD, and any disease was studied in a cohort of 3 551 men aged 30–59 years, based on a random sample from the population of eastern Finland. A number of potential coronary risk factors were allowed for in multiple logistic models. On the basis of these data, a regular use of oral analgesics is associated with a decreased risk of death from IHD. The relative risk was 0.6 with 95 % confidence interval (CI) of 0.2–0.9 for IHD death and 0.6 (95 % CI = 0.4–0.9) for cardiovascular death. No significant association was found between oral analgesics and the risk of death from diseases other than IHD.     

Determinants of femoral and carotid artery atherosclerosis

Abstract. Objectives . The aim of the study was to find the most important determinants of early atherosclerosis in the carotid and femoral arteries. Design . Carotid and femoral maximal intima media thickness (IMT) was measured 19 months after the first of 4 risk factor measurements. Setting . Department of Community Health and General Practice, University of Kuopio, and Occupational Health Care in Pyhäsalmi Mine, Finland. Subjects . The subjects comprised 60 male volunteers aged from 32 to 65 years from amongst 277 workers at the Pyhäsalmi Mine, Finland. Subjects were invited for an ultrasound examination, in order of serum total cholesterol content, until the required figure of 60 cases was achieved. Main outcome measures . Carotid and femoral maximal intima media thickness. Results . Systolic blood pressure (P < 0.01), serum total cholesterol (P < 0.01), age (P = 0.01) and pack-years smoked (P = 0.02) were independent determinants of maximal carotid artery IMT, and total cholesterol (P = 0.01), age (P = 0.03) and pack-years smoked (P = 0.01) for maximal femoral artery IMT. For the latter, plasma fibrinogen concentration (P = 0.10) was the next factor to enter the multiple regression model. Body mass index, heart rate, serum HDL cholesterol, triglycerides, urate, apolipoprotein A,*** antithrombin III, lipid peroxides, vitamin E and plasma vitamin C had no significant association with either maximal carotid or femoral IMT or the mean of the carotid and femoral IMT. Conclusions . Systolic blood pressure, serum total cholesterol, age and pack-years smoked are the most important determinants of early atherosclerosis in the carotid artery and total cholesterol, age and pack-years smoked in the femoral artery. Prevention should take into consideration these findings. The role of plasma fibrinogen and oxidized low density lipoprotein would require re-evaluation in larger populations studied longitudinally.     

Factors Associated with Changes in Serum Cholesterol during a Community-based Hypertension Programme

ABSTRACT A cohort of 1 019 male and 1 232 female hypertensives, aged 25–59 years, based on a random population sample, was followed for five years during a community-based cardiovascular prevention programme. A small mean reduction in serum cholesterol level was found. The observed changes in casual serum cholesterol values were partly due to the regression to the mean. The reductions were most marked in elderly people and in those with high baseline serum cholesterol values. The partial regressions of the cholesterol change were computed in subgroups by age, sex and baseline serum cholesterol level. Changes in weight in men and in age in women were the strongest independent predictors of the change in serum cholesterol. Changes in dietary fat intake were also associated with the change in serum cholesterol. Only a small part of the total variation in the change in serum cholesterol was explained by the regression models. The results indicate that reduction of the serum cholesterol level among hypertensive persons, especially men, was caused by changes in their dietary habits.     

Is there an Association between Serum Cholesterol and Blood Pressure Changes?

ABSTRACT. A community-based programme to influence the risk factors of coronary heart disease was carried out in North Karelia, Eastern Finland in 1972-77. The evaluation, based on examination of large cross-sectional random samples at the outset and at the end of the period, showed a greater reduction in both serum cholesterol and blood pressure levels in North Karelia than in a matched reference area. A random cohort of 293 men and 321 women who were studied both in 1972 and in 1977 did not use antihypertensive drugs on either occasion. Among these people the change in blood pressure was positively associated with the change in serum cholesterol even when age, initial blood pressure, changes in body mass and number of blood pressure measurements were allowed for. This finding supports the hypothesis that changes in fat consumption lead to changes in blood pressure, but this hypothesis needs further investigation.     

Effect of elimination of occlusal interferences on signs and symptoms of craniomandibular disorder in young adults

Sixty-two dental students judged not to be in need of treatment for craniomandibular disorder (CMD) were randomly divided into two groups, one receiving occlusal adjustment and the other mock adjustment. A double-blind study design was applied. After 2 years of education in dentistry, including courses in stomatognathic physiology, the increase in the subjective symptoms of CMD was significantly greater in the placebo control group than in the treatment group. The difference between the groups in the increase of sites tender to palpation was less clear, showing only a trend. However, the increase was statistically significant within the placebo group but not within the treatment group. Prophylactic occlusal adjustment thus appears to be effective in reducing the occurrence of symptoms of CMD, and possibly also the occurrence of clinical signs.     

Evaluation of masticatory muscles of edentulous patients by computed tomography and electromyography

summary On account of its tissue resolution capacity, computed tomography (CT) is an excellent method for the examination and quantitative analysis of the masticatory muscles. The aim of the present study was to evaluate the influence of the long edentulous period by CT on the structure of the main masticatory muscles in 10 edentulous patients and to study their functioning by electromyography (EMG) in connection with the renewal of the dentures. CT scanning was performed before prosthodontic treatment and EMG recordings of the masseter and temporal muscles before treatment and 4 weeks and 6 months after insertion of the new dentures. The results suggest, however, that a long edentulous period is visible not only in the functioning of the masticatory muscles, in terms of decreased EMG activity, but also as decreased density of the muscles which implies muscle atrophy, as seen by CT in the masseter and medial pterygoid muscles.