An essential part of toxicologic research involves assessing the risk from exposure to chemicals, drugs, or other potentially harmful substances. Epidemiologic information establishes an association but not a causal relationship between risk factors and adverse health outcomes. Controlled experiments in laboratory animals, however, provide insight into the agent-outcome relationship and aid in establishing low-risk exposure levels for humans. This is especially true in studies of reproduction and development since epidemiologic data are often limited. While controlled experiments reduce certain difficulties inherent in interpreting epidemiologic data, there still remains the problem of careful evaluation of statistical information. This note addresses issues in the interpretation of statistical variability in fitting dose-response models and estimating exposures associated with a low (or at least specified) level of risk.

2,4,5-Trichlorophenoxyacetic Acid↗

PubMedDate not supplied

Protein content and biophysical properties of tracheal aspirates form neonates with respiratory failure.

BACKGROUND: We aimed at assessing the quality and quantity of protein-leakage across the alveolar-capillary membrane and its influence on surfactant function during the early neonatal period in preterm infants compared to newborns both with respiratory failure. PATIENTS AND METHODS: We therefore prospectively analyzed total protein, elastase-alpha1-proteinase inhibitor complex (E-alpha1-PI) and alpha2-macroglobulin concentrations in tracheal aspirates from 31 infants < or = 32 weeks gestational age (group 1 : 29.3 +/- 2 weeks, 1214 +/- 410 g [means +/- SEM]) and from 21 neonates > 32 weeks (group 2 : 37.5 +/- 3 weeks, 2890 +/- 600 g [means +/- SEM]) and measured their surface activity in the pulsating bubble surfactometer. RESULTS: Day 1 total protein and alpha2-macroglobulin levels indicated an initial high leakage that declined to day 3 in both groups (from 1652 +/- 241 to 708 +/- 227 mg/l; p < 0.05; resp. from 28 +/- 6 to 12 +/- 4 mg/l [means +/- SEM]). In group 2 E-alpha1-PI concentrations were significantly elevated at day 1 compared to group 1 (15 754 +/- 5766 versus 3320 +/- 1056 microg/l [means +/- SEM]). In both groups a high minimum surface tension (15 - 30 mN/m) was recorded from day 1 - 4. CONCLUSIONS: These results suggest in larger newborns a secondary surfactant deficiency due to protein-leakage to play an important role in the pathogenesis of respiratory failure. The increased alveolar-capillary membrane permeability might be caused by inflammatory ARDS-like mechanisms.

Birth Weight↗

PubMedDate not supplied

The effect of endotoxin on in vivo rat alveolar macrophage phagocytosis.

This study was performed to explore whether alveolar macrophage (AM) phagocytosis would be impaired during endotoxemia. Therefore, we characterized in vivo AM phagocytic function in rats following either intravenous (i.v.) or intratracheal (i.t.) administration of lipopolysaccharide (LPS). The i.v. administration of LPS to rats at dosages of 0, 1, 2, and 5 mg/kg showed that increasing LPS doses were significantly associated with increased AM phagocytosis of 198Au colloid (P < .01), decreased recovery of AMs in bronchoalveolar lavage (BAL) (P = .017), no significant differences in neutrophil recovery by lavage (P = .15), or in the concentration of albumin in BAL (P = .14). Across the dosages of LPS administered i.t. (i.e., 0, 1, 5, and 10 mg/kg), there was no difference in AM phagocytosis (P = .29), a significant decrease in AM recovery (P = .002), a significant increase in neutrophil number (P = .01), and little effect on the concentration of albumin (P = .06). Thus, we found that the administration of endotoxin to rats did not impair in vivo AM phagocytic function. In fact, our findings suggest that the i.v. administration of LPS may increase AM phagocytosis of 198Au.

Albumins↗

PubMedDate not supplied

Outpatient taxol and carboplatin chemotherapy for suboptimally debulked epithelial carcinoma of the ovary results in improved quality of life: an Eastern Cooperative Oncology Group Phase II Study (E2E93).

PURPOSE: The combination of a platinum compound and paclitaxel is a standard treatment for ovarian cancer. In this cooperative group trial, paclitaxel and carboplatin were combined in an outpatient schedule to determine the clinical benefit, toxicities, and effect on quality of life. PATIENTS AND METHODS: Women with International Federation of Gynecology and Obstetrics stage II to IV epithelial ovarian cancer with suboptimal residual disease (> 1 cm) were eligible. Paclitaxel, 150 mg/m2, was given over 3 hours, followed by carboplatin (area under the curve, 5). This was repeated every 4 weeks for six cycles. Quality of life was assessed using the Functional Assessment of Cancer Therapy-Ovarian Cancer scale. Fifty-nine patients were enrolled, 38 with measurable disease and 21 with evaluable disease. RESULTS: The response rate (complete response + partial response) was 72%. The progression-free interval for patients with measurable disease was 17.5 months and for patients with evaluable disease was 11.1 months. Median survivals were 30.1 months (measurable) and 25.7 months (evaluable). Toxicities were modest. Quality-of-life scores improved significantly during therapy. DISCUSSION: This regimen is ideal for most women with advanced ovarian cancer because it is convenient and well tolerated, with response and survival comparable to those of more aggressive regimens. Overall quality-of-life scores and physical well-being scores improved throughout this outpatient treatment regimen for most patients.

Adult↗

PubMedDate not supplied

[Assessment of the risk of occipitocervical dislocation in inflammatory rheumatic diseases].

In this mainly retrospective study we examined by means of tomographic and computer tomographic findings various manifestations and courses of cranio-cervical subluxations in chronic inflammatory rheumatic diseases and the resulting neurological complications. Even in marked cranio-cervical subluxations neurological complications are rarely observed. More serious anterior atlanto-axial subluxation represents the highest risk for spinal cord injury as a result of the mobility of the atlas. A subsequent vertical (upward) atlanto-axial subluxation occurring particularly in serious courses of illness reduces this risk since it is generally to be found together with a fixation of the atlas. This also applies to a possible pseudobasilar invagination. As a result of our studies we found ways of using CT to achieve further information. We could also derive guidelines for the indication of operative treatment. In view of the further development of surgical methods and variations in operative risk dependent on the preoperative situation, these recommendations can only be provisional.

Adolescent↗