Dependence of blood clot lysis on the mode of transport of urokinase into the clot--a magnetic resonance imaging study in vitro

Magnetic resonance imaging was employed to study the dependence of clot lysing patterns on two different modes of transport of urokinase into whole blood clots. In one group of clots (nonperfused clots, n1 = 10), access of urokinase to the fibrin network was possible by diffusion only, whereas in the other group (perfused clots, n2 = 10) bulk flow of plasma containing urokinase was instituted through occlusive clots by a pressure difference of 3.7 kPa (37 cm H2O) across 3 cm long clots with a diameter of 4 mm. It was determined separately that this pressure difference resulted in a volume flow rate of 5.05 +/- 2.4 x 10(-2) ml/min through occlusive clots. Perfused clots diminished in size significantly in comparison to nonperfused ones already after 20 min (p less than 0.005). Linear regression analysis of two-dimensional clot sizes measured by MRI showed that the rate of lysis was more than 50-times faster in the perfused group in comparison to the nonperfused group. It was concluded that penetration of the thrombolytic agent into clots by perfusion is much more effective than by diffusion. Our results might have some implications for understanding the differences in lysis of arterial and venous thrombi.     

Cerebral hemorrhagic risk of aspirin or heparin therapy with thrombolytic treatment in rabbits

We studied the incidence of cerebral hemorrhage in an animal model of embolic stroke to determine the safety of aspirin, heparin, and tissue plasminogen activator therapies. We occluded the middle cerebral arteries of rabbits with labeled blood clots and administered either tissue plasminogen activator, heparin, aspirin, tissue plasminogen activator plus aspirin, tissue plasminogen activator plus heparin, or saline at various times after stroke. Compared to saline controls, both the aspirin-only and the tissue plasminogen activator-plus-aspirin groups had a significantly higher incidence of cerebral hemorrhage, whereas the heparin and tissue plasminogen activator combination groups did not. We conclude that aspirin antiplatelet therapy alone may increase the risk of hemorrhagic infarction, whereas heparin or tissue plasminogen activator therapy appears to be relatively safe.     

Lasers in pediatric otolaryngology

Extensive clinical experience and anecdotal evidence indicate that application of laser technology has improved the management of many congenital and acquired diseases of the head and neck in pediatric patients. The general principles of laser surgery, with respect to laser-tissue interaction, must be adhered to at all times to achieve the best surgical effect. Improperly used, the laser can damage normal tissue in the infant's or child's larynx, with devastating consequences.     

Adult body height, self perceived health and mortality in the Swedish population.

STUDY OBJECTIVE: The purpose of the study was to examine adult body height as an indicator of general health. DESIGN: The study was a survey of a randomly selected sample of the adult Swedish population obtained by the Swedish National Central Bureau of Statistics. PARTICIPANTS: The sample studied was identified in 1980-81 and comprised 14,757 persons aged 16-74. Of these, 12,695 (86%) consented to interview. MEASUREMENTS AND MAIN RESULTS: Information was obtained on adult height, socioeconomic status in childhood and adult life, self perceived health, self reported longstanding illness, and mortality during a six year follow up. The numbers of people in three height groups who considered their general health as bad, who reported any longstanding illness or who died during the follow up were compared with the expected numbers in the same groups. The number of persons with reduced health and the number of deaths was larger than expected in the shortest height group. The excess risk of dying in the shortest group (about 20% higher compared to the tallest group) was reduced but not eliminated when present and childhood socioeconomic group was taken into account. Coronary heart disease mortality in particular was linked to height. The shortest group of men and women reported the largest proportion with bad general health and longstanding illness. For the latter the differences between height groups disappeared after controlling for present socioeconomic status. CONCLUSIONS: There is a detectable excess risk of morbidity and mortality from being short. Assuming that the childhood environment is an important determinant of adult stature it is also important for adult health.     

Disposition of a new tetrahydrocarbazole analgesic drug in laboratory animals and man

1. The disposition of AY-30,068 (I), a new tetrahydrocarbazole analgesic drug, was studied in mice, rats, dogs, rhesus monkeys, and man. 2. Oral doses of the 14C-labelled drug in aqueous solution were well absorbed in rodents, but absorption of oral doses of the crystalline drug in dogs was poor. Due to the virtual absence of serum metabolites in rats and dogs, the bioavailability of I was nearly identical to the extent of absorption. Although a small first-pass effect was observed in mice, unchanged I represented a major portion of serum radioactivity. 3. A linear increase in the serum concentrations of I occurred at doses between 0.05 and 25 mg/kg in rats, 0.1 and 50 mg/kg in dogs, and 1-160 mg in man. In rhesus monkeys given a 0.5 mg/kg oral dose, the Cmax and AUC of I were similar to values obtained following a corresponding dose in dogs. 4. After i.v. administration of a 1.0 mg/kg dose the terminal elimination half-life (t1/2 beta) of I was 4 h in mice and 9-10 h in rats and dogs. In rodents, dogs, and several human subjects, the elimination of I was interrupted by secondary peaks. Enterohepatic circulation was confirmed in bile duct cannulated rats, where the t1/2 beta of I was decreased to 2.4 h. In rodents the serum clearance and apparent volume of distribution of I were 0.04-0.2 l/kg.h and 0.5-0.8 l/kg, respectively, and 0.6 l/kg.h and 9.8 l/kg in dogs. 5. In rodents and dogs dosed with 14C-labelled I, radioactivity was excreted almost entirely in the faeces. No unchanged I was detected in rat bile, while about 70% of the radioactivity corresponded to conjugates of parent drug.     

In vitro/in vivo functionality of Catapres-TTS

The in vitro and in vivo functionality of Catapres-TTS, a transdermal therapeutic system that delivers the alpha adrenergic receptor agonist clonidine, is discussed in terms of the drug transport kinetics and resultant plasma drug concentration profiles. The design of Catapres-TTS is presented as an optimization by which the best combination of system performance characteristics is obtained within the inherent limitations of the transdermal drug transport properties and the known pharmacokinetic and pharmacodynamic properties of the drug. Clonidine is a potent antihypertensive agent with a relatively low therapeutic index. For Catapres-TTS, the majority of control over the drug input rate resides within the system, rather than within the skin, which significantly reduces the variability in drug input rate and resulting plasma drug concentration both within and between patients. Moreover, the presence of a rate-control element in the system allows for patterning of the drug release rate. An initial bolus of drug is placed in the contact adhesive layer, where its transport into the skin is not inhibited by the rate control element in the system, for reduction in the time needed to achieve steady state drug input. The selection of the loading dose of drug is described as an optimization between the minimization of the lag time and the maintenance of constant plasma drug concentrations during the crossover period between system applications in chronic therapy.     

Tower Hamlets Health Authority Measles Immunisation Initiative 1987-88

Measles as a cause of childhood death and disability can be prevented by vaccination of 95% of the pre-school population, as in the United States, where proof of measles immunisation is required for school entry. An inner-city London Health Authority used the 1987 World Immunisation Day as the occasion to invite heads of nursery and infant schools to join in a pilot scheme to increase the number of new pupils who were protected. A small but growing number of the schools now include a question about immunisation in their admission routine. The computerised appointment system for child health clinic vaccinations was shown to be unable to give sufficient appointments for older children. School nurses and health visitors organised extra immunisation sessions during the 1988 epidemic.