Risk factors for carotid atherosclerosis: the Kuopio Ischaemic Heart Disease Risk Factor Study

We assessed the severity of carotid atherosclerosis in 412 men from eastern Finland aged 42, 48, 54 or 60 years at examination with B-mode ultrasonography in 1987 in the Kuopi ischaemic Heart Disease Risk Factor Study (KIHD). Thirty-seven per cent of participants had intimal-medial thickening, 10% had plaques and 2% had stenosis. Age (P less than 0.001), cigarette-years (P less than 0.001), serum LDL cholesterol (P = 0.005), low income (P = 0.020) and low alcohol consumption (P = 0.048) had significant partial associations with the severity of carotid atherosclerosis. A linear regression model including these variables and plasma fibrinogen (NS) and serum HDL-cholesterol (NS) accounted for 33% of the variation in atherosclerosis severity. Our data provide further evidence on the role of smoking and LDL-cholesterol in atherosclerosis.     

Reversible endoneurial changes after nerve injury

Summary Endoneurial changes in the rat sciatic nerve were studied during Wallerian degeneration and subsequent regeneration. After total axotomy two different experimental models were used. In the first the cut ends of the sciatic nerves were left free to allow reinnervation. In the second model the distal end of the transected nerve was sutured to the adjoining muscle to prevent regeneration. Within 2 weeks after the axomoty, a Wallerian type of degeneration was seen with axonal destruction and phagocytosis of myelin sheaths. After 4 weeks endoneurial fibroblastic cells formed circular structures around the Schwann cell columns, i.e., the bands of Buengner in both groups. These fascicle-like structures became more pronounced in the non-regenerating nerves up to 8 weeks, while during reinnervation the cellular reaction in the endoneurium nearly disappeared within this time. Ultrastructurally, the endoneurial fibroblast-like cells showed marked phagocytotic activity and also fragments of basement membrane on their surface. The appearance of thin (25–30 nm in diameter) collagen fibrils closely related to the basement membrane was noted around the bands of Buengner, as well as the appearance of an amorphous extracellular gap between the newly synthetized thin collagen fibrils and normal endoneurial collagen (50–60 nm). The reversible endoneurial compartmentation seems to be important for maintaining the nerve structure, serving as a support for axonal regeneration in addition to the bands of Buengner.Supported in part by grants from the Emil Aaltonen Foundation and from the Research and Science Foundation of Farmos (to V. S.) and institutional grants (to Dept. Med. Chem.) from the Sigrid Jusélius Foundation and the Turku University Foundation     

Serum copper and the risk of acute myocardial infarction: a prospective population study in men in eastern Finland

The authors investigated the association of serum copper concentration with the risk of acute myocardial infarction in 1,666 randomly selected men aged 42, 48, 54, or 60 years who had no symptomatic ischemic heart disease at entry. Baseline examinations in the Kuopio Ischaemic Heart Disease Risk Factor Study in Eastern Finland were done during 1984 to 1988. In Cox multivariate survival models adjusting for age, examination year, ischemic electrocardiogram in exercise, maximal oxygen uptake, diabetes, family history of ischemic heart disease, cigarette-years, mean systolic blood pressure, serum high density lipoprotein (HDL) cholesterol subfraction HDL2 and low density lipoprotein (LDL) cholesterol concentrations and blood leukocyte count, serum copper concentration in the two highest tertiles (1.02-1.16 mg/liter and 1.17 mg/liter or more) associated with 3.5-fold (95% confidence interval (Cl) 1.3-9.4, p less than 0.05) and 4.0-fold (95 percent Cl 1.5-10.8, p less than 0.01) risk of acute myocardial infarction. These data indicate that high copper status, reflected by elevated serum copper concentration, is an independent risk factor for ischemic heart disease.     

Importance of the interaction of midazolam and cimetidine

Six healthy volunteers were given in an open study 15 mg of midazolam orally, and a couple of weeks later the same treatment preceded by 400 mg of cimetidine orally. We followed midazolam serum concentrations and the following pharmacodynamic parameters for five hours: subjective sedation, Maddox wing readings, critical flicker fusion frequency and peak velocity of saccadic eye movements. A statistically significant change was found in Cmax and total AUC between the two sessions. The pharmacodynamic responses differed also clearly from each other suggesting a significant change in midazolam effect even after a single oral dose of cimetidine.     

Cerebrospinal fluid rhinorrhea: depiction with MR cisternography in dogs

Canine cerebrospinal fluid rhinorrhea, which occurs frequently in purebred beagles, was demonstrated in two dogs on magnetic resonance images after cisternal introduction of gadolinium-DTPA dimeglumine.     

The analgesic action of dexmedetomidine--a novel alpha 2-adrenoceptor agonist--in healthy volunteers.

The analgesic efficacy of dexmedetomidine (DEX)--a novel alpha 2-adrenoceptor agonist--was studied in man. Single intravenous doses of fentanyl (FEN; 2 micrograms/kg), DEX (0.25, 0.50 and 1.0 micrograms/kg) and placebo were administered to 5 healthy male volunteers in a double-blind, crossover study in randomized order. The analgesic effect of the different treatments was measured by determining the time course of pain threshold with dental dolorimetry and by quantitating subjective pain induced by a standard ischemic pain stimulus on the upper arm using a visual analogue scale (VAS). The drugs were generally well tolerated. FEN and DEX both had analgesic effects on ischemic pain, which was seen as a statistically significant decrease in subjective VAS ratings. FEN appeared to be more effective than DEX; the difference was not, however, statistically significant. Neither of the drugs affected the pain threshold measurements.     

Antioxidants and platelets

It is postulated that antioxidants reduce platelet activity by the stimulation of prostacyclin synthetase by scavenging synthesis-inhibiting peroxides. The experimental and clinical evidence supporting this theory is inconclusive. Clinical trials suggest that vitamin E reduced platelet aggregability. Nonexperimentally, a strong association has been observed between low serum selenium concentration and increased platelet aggregability. These findings suggest that antioxidants have an important role in the regulation of platelet function.     

Plasmin and plasminogen activator activities in tear fluid during corneal wound healing after anterior keratectomy

Plasmin can degrade fibronectin and laminin, two important components of the extracellular matrix facilitating cell sliding and healing following a wound. In this study we investigated the relationship between the tear fluid level of plasmin and plasminogen activator and the healing of a corneal wound. Anterior keratectomy (AKE) was performed for seven rabbits (11 eyes). Eight eyes were rewounded after re-epithelialization. Tear fluid samples were collected with capillaries before wounding and during wound healing. Plasmin and plasminogen activator (PA) activities were determined using radial caseinolysis procedures. After AKE the plasmin concentrations increased rapidly, from a mean (+/- SEM) of 3.9 +/- 0.9 micrograms/ml to a mean of 37.9 +/- 7.8 micrograms/ml (p less than 0.01), and decreased during wound healing. Rewounding also resulted in an increase in plasmin concentration in the tear fluid (from a mean of 2.9 +/- 0.6 micrograms/ml to a mean of 5.0 +/- 1.1 micrograms/ml; p greater than 0.05). The PA activity showed an inverse trend as it decreased after AKE from a mean of 2.0 +/- 0.6 IU/ml to a mean of 0.3 +/- 0.1 IU/ml (p less than 0.001). During wound healing and re-epithelialization, the PA activity increased again, to 2.1 +/- 0.3 IU/ml (p less than 0.001). Abrasion of the newly grown epithelium in eight eyes caused a second elevation of PA activity which was not significant. This study demonstrates a close association between the healing of corneal wounds and changes in the plasmin and PA activities in tear fluid. Determination of the activity of these enzymes may therefore be useful for monitoring corneal wound healing.