Beta carotene uptake into atherosclerotic plaque: Enhanced staining and preferential ablation with the pulsed dye laser

The yellow color of atherosclerotic plaque is due to the presence of carotenoids, which absorb light between 430–530 nm and account for the preferential ablation of plaque by the pulsed dye laser operating at 480 nm. This study was designed to examine tissue uptake of β-carotene and the effect of uptake on arterial plaque ablation. Forty-two atherosclerotic NZW rabbits were given intravenous β-carotene at a dose of 40 mg/kg, twice weekly and killed between 1 hour and 28 days after the initial injection. β-carotene was not detected in control specimens but was significantly greater in plaque than in normal wall at all time points following β-carotene injection (P < 0.04 Mann Whitney U test). The ablation threshold was significantly lower in β-carotene treated plaque than in untreated plaque or normal arterial wall (P < 0.01, Fisher's exact test). In this model β-carotene is preferentially taken up into arterial plaque, resulting in increased absorption of laser radiation at 480 nm and enhanced tissue ablation. © 1993 Wiley-Liss, Inc.     

A pharmacokinetic comparison of cyclosporin oral solution and cyclosporin capsules in heart and lung transplant recipients

Pharmacokinetic profiles were obtained for 16 heart or lung recipients following the administration of identical doses of cyclosporin as oral solution and capsules on consecutive days. A comparison of pharmacokinetic parameters (AUC, C_max, C_min and t_max) showed that there were no significant differences between the two formulations except for the t_max, which was significantly longer for the capsules. The mean variation in day-to-day trough levels produced by the two different forms was 25.6%. A retrospective study was carried out of consecutive cyclosporin levels in patients at steady state on oral solution. The mean variation in day-to-day trough levels was 32.3%. This was not significantly different from the variation in consecutive trough levels seen in the oral solution/capsule comparison. This study shows that cyclosporin capsules can be substituted for oral solution without causing acute changes in cyclosporin blood levels, and that the pharmacokinetics of the two formulations are similar.This work was carried out in partial fulfillment of the requirements for the Master of Science Degree in Clinical Pharmacy, University of London     

The palmar radiocarpal ligaments: A study of adult and fetal human wrist joints

The palmar radiocarpal ligaments were studied with use of fifty-four dissected adult cadaver wrists and serial sections on twenty-three wrists from fetuses ranging in size from 23 to 230 millimeters crown-rump length. Three palmar radiocarpal ligaments were clearly identified: the radioscaphocapitate, long radiolunate, and short radiolunate ligaments. The radioscaphocapitate ligament originates from the radial styloid process and inserts into the radial aspect of the waist of the scaphoid, hemicircumferentially around the distal pole of the scaphoid and interdigitates with fibers from the palmar aspect of the triangular fibrocartilage complex just palmar to the head of the capitate, with only a minor insertion distally into the body of the capitate. The long radiolunate ligament originates just ulnar to the radioscaphocapitate ligament, being separated from it throughout its course by the interligamentous sulcus. The long radiolunate supports, but is separate from, the palmar aspect of the scapholunate interosseous ligament, and inserts into the radial half of the palmar surface of the lunate. The short radiolunate ligament, previously not described, originates just palmar to the lunate facet of the distal radius articular surface and inserts as a flat sheet of fibers into the proximal margin of the palmar surface of the lunate. Each ligament is intracapsular, enveloped within a continuous superficial fibrous stratum and deep synovial stratum.     

Complement Activation and Cytokine Generation After Modified Fontan Procedure

Background. The modified Fontan procedure separates the systemic and pulmonary circulations in patients born with a functional single ventricle. Delayed recovery is frequently observed after this procedure. It was our hypothesis that complement activation or cytokine generation may contribute to the pathophysiology of this problem.

Methods. We measured activated complement C3, thromboxane B₂, interleukin-6, and tumor necrosis factor- levels by immunoassay in 16 patients undergoing Fontan procedure. Patient plasma samples were obtained preoperatively, on initiation of cardiopulmonary bypass, after administration of protamine, and 1, 4, 8, and 24 hours postoperatively.

Results. There was no early or late mortality in this cohort of patients. Low cardiac output developed in 3 of 16 patients, and pleural effusions developed in 5. The median length of hospital stay was 9 days. Activated complement C3 levels increased from a baseline of 1,486 ± 564 to 4,600 ± 454 ng/mL after cardiopulmonary bypass and administration of protamine, and returned to baseline by 24 hours. The level of interleukin-6 increased from 42 ± 32 to 176 ± 22 pg/mL and at 24 hours remained elevated at 71 ± 15 pg/mL. Neither thromboxane B₂ nor tumor necrosis factor- levels increased significantly.

Conclusions. The data demonstrate threefold to fourfold increases in activated complement C3 and interleukin-6, indicating that both humoral and cellular systems are affected. It is our conclusion that complement and cytokine activation may contribute to the delayed recovery observed after Fontan procedure.     

Cardiovascular risk factors in the population of 2 regions covered by the MONICA-France regions: Strasbourg and Toulouse

Cardiovascular risk factors were studied from 1985 to 1987 in two population samples from the French regions of the Bas-Rhin (BR) (Strasbourg) and the Haute-Garonne (HG) (Toulouse). 1,257 men and women in the BR and 1,323 in the HG, aged 35-64, participated in the survey. A common investigation methodology in harmony with the MONICA protocol, was used. The mean weight was higher among the male (5 kg) and female (6 kg) populations living in the BR than in the HG. Even after age, body mass index and tobacco consumption adjustments, arterial systolic blood pressure was higher in the male population of the BR (145 mm Hg) than in the HG (133 mm Hg). Similar differences were observed among the female population. A higher proportion of hypertensive subjects whatever the sex and the age group was noted in the BR. The proportion of smokers, and the quantity of tobacco they smoked, did not differ between the two centers. Adjusted total cholesterolemia was higher in the HG, with mean differences of 0.32 mmol/l among the men and 0.35 mmol/l among the women. In the case of HDL cholesterol, the differences were 0.23 mmol/l among the men and 0.34 mmol/l among the women, explaining in large part the differences of the mean levels of total cholesterol.     

Effect of Simultaneous Didanosine Administration on Itraconazole Absorption in Healthy Volunteers

Study Objective . To investigate the effect of simultaneously administered didanosine (ddI) on the absorption of a single dose of itraconazole. Design . Randomized, crossover, unblinded single-dose pharmacokinetic study in healthy volunteers. Comparisons of itraconazole alone and itraconazole with simultaneous ddI were performed on days 1 and 15. Setting . A university medical center. Patients . Seven healthy men and women. Six subjects (86%) completed the study; one was removed due to the development of a rash. Interventions . Volunteers received a single 200-mg oral dose of itraconazole or itraconazole with concomitant oral ddI 300 mg (two 150-mg tablets) dispersed in 240 ml water. Each regimen was separated by a 2-week washout period. Serum samples were obtained frequently for 12 hours after the dose. Measurements and Main Results . Concentrations of itraconazole were determined using a microbiologic assay. Individual concentrations in serum versus time data were evaluated by linear regression analysis. Peak serum concentration and time to peak were determined by visual inspection of each individual's serum concentration-time curve. A mean ± SD peak serum itraconazole concentration of 0.90 ± 0.30 μg/ml was observed at 3.0 ± 0.7 hours when itraconazole was administered alone, compared with undetectable levels in all patients during therapy with ddI. Conclusions . Simultaneous oral administration of ddI significantly decreases absorption of itraconazole. These drugs should not be administered concurrently.