Radiotherapy in the treatment of low-grade astrocytomas

Between 1954 and 1986 inclusive, 160 children in the North West Region of England were registered with histologically proven lowgrade astrocytomas (grade 1 or 2). Ten died before receiving any treatment, and a further seven died within 28 days of surgery, leaving 143 children whose survival in relation to treatment modality is the subject of this paper. Low-grade astrocytomas are responsive to radiation therapy. This treatment has no clear benefit to offer children with superficial tumours that can be resected completely or nearly so, but significantly improves survival rates when tumours are deep-seated and not amenable to excision.     

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.     

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.     

Disposition of Tablet and Capsule Formulations of Digoxin in the Elderly

Study Objective . To compare digoxin tablets and liquid-filled capsules with respect to excretion of the drug and its metabolites in urine and feces at steady state. Design . A randomized, crossover trial, each period lasting 3 weeks, with no washout period. Setting . A university hospital. Patients . Six patients, five of whom were elderly, with histories of gastrointestinal disorders, such as hypochlorhydria, intestinal bacterial overgrowth, and inflammatory bowel disease. Interventions . The patients received digoxin once/day in either tablet or capsule form for 3 weeks, and then were switched to the other formulation. Total urinary and fecal excretion from the last 3 days of each regimen were analyzed for the drug and metabolites. Measurements and Main Results . No statistically significant differences were found between tablets and capsules in recovery of digoxin or its metabolites in urine or feces (p=0.05). One subject had a 4-fold increase in urinary drug excretion and 50% decrease in fecal excretion after taking the capsules compared with tablets. Intersubject variability in extent and type of metabolite excretion was greater than intrasubject variability. Conclusions . Fecal analyses may be an accurate way to classify patients as formers of digoxin reduction products.     

RENIN GENE POLYMORPHISM ASSOCIATED WITH ALDOSTERONE RESPONSIVENESS TO THE RENINANGIOTENSIN SYSTEM IN PATIENTS WITH ALDOSTERONE-PRODUCING ADENOMAS

1. Aldosterone levels in patients with unilateral aldosterone-producing adenomas may be responsive or unresponsive to the renin-angiotensin system, with the former often previously misdiagnosed as bilateral adrenal hyperplasia. 2. In tumours from patients in the responsive subgroup, renin mRNA is expressed in greater amounts than in tumours from patients in the unresponsive subgroup, or in normal adrenals. 3. We compared the frequency of four renin gene polymorphisms in peripheral blood DNA from the two subgroups and found significant associations between BglI, TaqI and HinfI restriction fragment length polymorphisms (RFLP) and aldosterone responsiveness. 4. Allelic variation in the constitutive renin gene was associated with a specific cause of hypertension.