The pharmacology and pharmacokinetics of high-dose methocarbamol in horses

The haemodynamic, respiratory and behavioural effects and pharmacokinetics of methocarbamol were studied in eight healthy, adult horses after intravenous (i.v.) and oral administration of large dosages. Heart rate, cardiac output, mean pulmonary arterial blood pressure, systolic, diastolic and mean aortic blood pressure, respiratory rate and arterial blood gases did not change after either i.v. (30 mg/kg bodyweight [bwt]) or oral (50 and 100 mg/kg bwt) dosages of methocarbamol. Mild to moderate depression was observed in five of eight horses administered i.v. methocarbamol, and in all horses administered oral methocarbamol. Plasma methocarbamol concentration declined very rapidly during the initial or rapid disposition phase after i.v. administration; the terminal elimination half-life ranged from 59 to 90 mins. Peak plasma methocarbamol concentrations following oral administration occurred within 15 to 45 mins and oral bioavailability ranged from 50.7 to 124 percent.     

Investigation and significance of short saphenous vein incompetence

In this study, 186 limbs with varicose veins or venous skin changes were examined using duplex ultrasonography. Limbs were classified on the basis of short saphenous or popliteal venous incompetence and the number of limbs with venous ulceration (active or healed) recorded. Short saphenous incompetence did not produce a significant increase in the incidence of ulceration, whereas popliteal reflux produced an increase in the risk of ulceration which was statistically significant when compared with limbs without reflux in these two veins (chi 2 = 4.55, P = 0.003). There was no significant difference in the proportion of limbs with concomitant long saphenous reflux between these two groups. Short saphenous reflux is not important in the pathogenesis of venous ulceration. Popliteal reflux is an important factor in the pathogenesis of venous ulceration. More attention should be paid to the surgical correction of popliteal reflux when present in limbs with venous ulceration that fail to heal by conservative measures.     

An experimental technique for estimating regional myocardial segment work in vivo

We determined the capabilities and limitations of an experimental approach to measure segment work (force x distance) of myocardial regions in the in vivo beating heart. In 18 open-chest anesthetized dogs, segment length was measured using ultrasonic dimension transducers, and developed force was measured with miniature force transducers. Work was defined as the integrated multiples of instantaneous force and shortening during a single (averaged) beat, corresponding to the area under the length-force loop. Changes in work over a range of 9.78 x 10(-4) to 2.93 x 10(-2) J/g/min were produced by vena caval constriction, aortic constriction, atrial pacing, and isoproterenol (0.5 and 1.0 micrograms/kg/min). Work was measured in both major and minor axes. In 60% of the animals, work in the minor axis was 9.2-fold greater than in the major axis. In the others, all interventions changed regional work to the same extent in both axes (r = 0.802; p < 0.05). Work changes were also compared between the base, anterior, and posterior walls. The response was directionally similar in all regions, ranging from -79 +/- 1% during caval occlusion to 278 +/- 98% during isoproterenol. The effective size of the measured muscle mass was limited to the transducer area because the amplitude and pattern of both force development and segment shortening were not changed until deep myocardial cuts were as close as 2 mm from the measuring area. We conclude that work measurement in the minor axis is quantitatively representative of fiber work in that region.     

Thinness at birth in a northern industrial town

OBJECTIVE: To determine whether babies in an area of Britain with unusually high perinatal mortality have different patterns of fetal growth to those born elsewhere in the country. DESIGN: Measurement of body size in newborn babies. SETTING: Burnley (perinatal mortality in 1988 15.9/1000 total births) and Salisbury (perinatal mortality 10.8/1000 total births), England. SUBJECTS: Subjects comprised 1544 babies born in Burnley, Pendle, and Rossendale Health District, and 1025 babies born in Salisbury Health District. MAIN OUTCOME MEASURES: Birthweight, length, head, arm and abdominal circumferences, and placental weight were determined. RESULTS: Compared with babies born in Salisbury, Burnley babies had lower mean birthweight (difference 116 g, 95% confidence interval (CI) 77,154), smaller head circumferences (difference 0.3 cm, 95% CI 0.2, 0.4), and were thinner as measured by arm circumference (difference 0.3 cm, 95% CI 0.3, 0.4), abdominal circumference (difference 0.5 cm, 95% CI 0.4, 0.6) and ponderal index (difference 0.8 kg/m3, 95% CI 0.6, 1.0). The ratio of placental weight to birthweight was higher in Burnley (difference 0.6%, 95% CI 0.4, 0.9). These differences were found in boys and girls and did not depend on differences in duration of gestation or on the different ethnic mix of the two districts. Mothers in Burnley were younger, shorter in stature, had had more children, were of lower social class, and more of them smoked during pregnancy than mothers in Salisbury. These differences did not explain the greater thinness of their babies. CONCLUSIONS: Babies born in Burnley, an area with high perinatal mortality, are thin. The reason is unknown. Poor maternal nutrition is suspected because Burnley babies have a higher ratio of placental weight to birthweight. The greater thinness at birth of Burnley babies could have long term consequences, including higher rates of cardiovascular disease.