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Biomedical subjects

T Schettler

Publications and source records attributed to T Schettler.

17 recordsLinked to original sources
PubMed2001

Health risks posed by use of Di-2-ethylhexyl phthalate (DEHP) in PVC medical devices: a critical review.

BACKGROUND: Polyvinyl chloride plastics (PVC), made flexible through the addition of di-2-ethylhexyl phthalate (DEHP), are used in the production of a wide array of medical devices. From the late 1960s, leaching of DEHP from PVC medical devices and ultimate tissue deposition have been documented. METHODS: A critical review of DEHP exposure, metabolism, and toxicity data from human and animals studies was undertaken. A brief analysis of alternatives to DEHP-plasticized PVC for use in medical device manufacture was completed. RESULTS: DEHP leaches in varying concentrations into solutions stored in PVC medical devices. Certain populations, including dialysis patients and hemophiliacs may have long-term exposures to clinically important doses of DEHP, while others, such as neonates and the developing fetus, may have exposures at critical points in development. In vivo and in vitro research links DEHP or its metabolites to a range of adverse effects in the liver, reproductive tract, kidneys, lungs, and heart. Developing animals are particularly susceptible to effects on the reproductive system. Some adverse effects in animal studies occur at levels of exposure experienced by patients in certain clinical settings. DEHP appears to pose a relatively low risk of hepatic cancer in humans. However, given lingering uncertainties about the relevance of the mechanism of action of carcinogenic effects in rodents for humans and interindividual variability, the possibility of DEHP-related carcinogenic responses in humans cannot be ruled out. CONCLUSIONS: The observed toxicity of DEHP and availability of alternatives to many DEHP-containing PVC medical devices presents a compelling argument for moving assertively, but carefully, to the substitution of other materials for PVC in medical devices. The substitution of other materials for PVC would have an added worker and community health benefit of reducing population exposures to DEHP, reducing the creation of dioxin from PVC production and disposal, and reducing risks from vinyl chloride monomer exposure.

Animals↗
PubMed2001

The precautionary principle in environmental science.

Environmental scientists play a key role in society's responses to environmental problems, and many of the studies they perform are intended ultimately to affect policy. The precautionary principle, proposed as a new guideline in environmental decision making, has four central components: taking preventive action in the face of uncertainty; shifting the burden of proof to the proponents of an activity; exploring a wide range of alternatives to possibly harmful actions; and increasing public participation in decision making. In this paper we examine the implications of the precautionary principle for environmental scientists, whose work often involves studying highly complex, poorly understood systems, while at the same time facing conflicting pressures from those who seek to balance economic growth and environmental protection. In this complicated and contested terrain, it is useful to examine the methodologies of science and to consider ways that, without compromising integrity and objectivity, research can be more or less helpful to those who would act with precaution. We argue that a shift to more precautionary policies creates opportunities and challenges for scientists to think differently about the ways they conduct studies and communicate results. There is a complicated feedback relation between the discoveries of science and the setting of policy. While maintaining their objectivity and focus on understanding the world, environmental scientists should be aware of the policy uses of their work and of their social responsibility to do science that protects human health and the environment. The precautionary principle highlights this tight, challenging linkage between science and policy.

Decision Making↗
PubMed2001

Toxic threats to neurologic development of children.

Learning disabilities, attention deficit hyperactivity disorder, developmental delays, and emotional and behavioral problems are among childhood disabilities of increasing concern. Interacting genetic, environmental, and social factors are important determinants of childhood brain development and function. For many reasons, however, studying neurodevelopmental vulnerabilities in children is challenging. Moreover, inadequate incidence and trend data interfere with full understanding of the magnitude of the problem. Despite these difficulties, extensive laboratory and clinical studies of several neurodevelopmental toxicants, including lead, mercury, polychlorinated biphenyls, alcohol, and nicotine, demonstrate the unique vulnerability of the developing brain to environmental agents at exposure levels that have no lasting effect in adults. Historically, understanding the effects of these toxicants on the developing brain has emerged slowly while generations of children are exposed to unsafe levels. Unfortunately, with few exceptions, neurodevelopmental toxicity data are missing for most industrial chemicals in widespread use, even when populationwide exposures are documented. The personal, family, and communitywide costs of developmental disabilities are profound. In addition to the need for more research, a preventive public health response requires mitigation of exposures to potential neurodevelopmental toxicants when available evidence establishes the plausibility of harm, despite residual toxicologic uncertainties.

Affective Symptoms↗
PubMed1993

Influence of acetylsalicylic acid on a Listeria monocytogenes infection.

The influence of acetylsalicylic acid (ASA, CAS 50-78-2) on the Listeria monocytogenes infection in balb/c mice was investigated. One day prior to lethal or sublethal infection, balb/c mice were treated intravenously with therapeutic concentrations of ASA alone or ASA in combination with murine recombinant interferon gamma, a lymphokine produced by T-helper cells. Three days post-infection, parasite burdens of spleen and liver were determined by the colony-forming unit assay. It was shown that the prophylactic application of ASA in a concentration of 5 mg/kg body weight resulted in a more than 10-fold reduction of viable Listeria monocytogenes in spleen and liver of balb/c mice. In addition, the combination of a suboptimal dosage of interferon gamma with ASA resulted in a significantly higher survival rate compared to the untreated controls.

Animals↗
PubMed1992

Pharmacokinetics and relative bioavailability of a new chewable, buffered acetylsalicylic acid tablet formulation in comparison to a conventional plain tablet.

The pharmacokinetics of acetylsalicylic acid (ASA) and its main metabolite salicylic acid (SA) following single dose administration of a new chewable, buffered ASA tablet formulation and a conventional plain ASA tablet formulation were investigated in 12 healthy male subjects. The volunteers received in a randomized, crossover design two pharmaceutical units of both formulations containing 500 mg ASA each after an overnight fast on an empty stomach. ASA and SA in the collected plasma and urine samples were determined using an internally standardized validated HPLC method. Regarding the normalized extent parameters for ASA, an increase of about 114% for the maximum concentration (Cmax,norm) and about 16% for the area under the curve (AUC0----infinity,norm) was found for the new chewable, buffered tablet formulation as compared to the plain tablet. Comparing the corresponding parameters for the main metabolite, both formulations were statistically equivalent. The quotient of normalized areas (QAUC0-20min, norm/AUC0----infinity,norm) for ASA was higher by about 124% for the new formulation, indicating an increased and faster absorption during the first 20 min after administration. The time of the concentration maximum did not differ statistically. These data indicate that the new chewable, buffered ASA tablet formulation shows a significant benefit as compared to the plain ASA tablet. The new tablet produced higher plasma ASA concentrations in a shorter time, which is clinically important since higher ASA concentrations are assumed to be related to an improved analgesic efficacy.

Adolescent↗
PubMed1992

Effect of acetylsalicylic acid, ascorbate and ibuprofen on the macrophage system.

The influence of ascorbic acid (CAS 50-81-7), acetylsalicylic acid (CAS 50-78-2) and ibuprofen (CAS 15687-27-1) on macrophages of C57BL/6 mice was investigated in vitro. It has been shown that ascorbic acid or acetylsalicylic acid alone did not stimulate or inhibit the production of interleukin-6, whereas a combination of both substances caused a significant stimulation. The viral replication in L929 fibroblasts was not affected by ascorbate and/or acetylsalicylic acid. In addition, the tumor-necrosis factor (TNF) synthesis of peritoneal macrophages was neither stimulated nor inhibited by both substances, alone or in combination. The oxygen radical production, however, was definitely inhibited by ascorbic acid, the effect of acetylsalicylic acid was far less marked, but at the high concentrations the inhibition was clearly discernible. Ibuprofen, a propionic acid derivate, was able to reduce the replication of vesicular stomatitis virus in L929 fibroblast cells. At the highest concentration of ibuprofen, 100 micrograms/ml, 34% of the fibroblast were able to survive. This protective effect declined as the ibuprofen concentration decreased. Ibuprofen could not stimulate peritoneal macrophages to secrete TNF, whereas the oxygen radical production was significantly reduced. In addition, ibuprofen activated mouse macrophages to produce interleukin-6 in a dose dependent way. The results of the in vitro experiments presented clearly show that ascorbic acid, acetylsalicylic acid in ibuprofen influenced the unspecific immune system.

Animals↗
PubMed1986

Radioimmunoassay for human osteocalcin using an antibody raised against the synthetic human (h37-49) sequence.

Radioiodination of synthetic human 37-49 osteocalcin requires optimal labeling conditions in order to obtain a maximum of mono- and di-iodinated tracer with little contamination by tri- and tetra-iodinated products or "radio-damage." The antibody raised against osteocalcin(h37-49) had the highest affinity for the C-terminal peptide used for iodination and the larger peptide (h30-49). The intact bovine osteocalcin (b1-49) revealed less immunoreactivity. This C-terminal specific radioimmunoassay detected the intact human osteocalcin in HPLC purified plasma and peritoneal dialysate from patients with terminal renal insufficiency and in extracted human bone. Some quantities of osteocalcin peptides with a higher hydrophobicity were predominantly detected in uremic plasma. These peptides that had a higher molecular weight than the intact human molecule might represent aggregated forms of the intact bone-derived osteocalcin. Immunoreactivity in plasma samples from healthy individuals revealed a remarkable difference as to which substance was employed for anticoagulation. Compared to heparin, the addition of EDTA largely reduced the osteocalcin immunoreactivity, implying that conformational changes within the N-terminal portion (containing the Gla- and Cys-residues) are extended to the C-terminal portion.

Antibodies↗
PubMed1984

Osteoporosis: a bone turnover defect resulting from an elevated parathyroid hormone concentration within the bone-marrow cavity?

Recently the bone-marrow cavity blood concentration of parathyroid hormone (PTH) has been shown to exceed that of the peripheral blood. As PTH is a primary modulator of bone cell activity, altered levels of the hormone in the bone-marrow blood may play a significant role in the aetiology of bone disease. We therefore measured PTH concentrations in marrow cavity and venous blood of 9 osteoporotic and 14 control subjects using sequence specific radioimmunoassays for intact and mid-carboxyl (Mid-C) regional human PTH (hPTH). Intact and Mid-C PTH levels were identical in the peripheral blood of control and osteoporotic subjects. Furthermore, bone-marrow cavity blood concentrations of Mid-C PTH, whilst universally higher than those found in peripheral blood, were also comparable in the osteoporotic and control subjects. The sole difference in the PTH composition of bone-marrow cavity blood from osteoporotic subjects was an increased concentration of intact PTH. The origins and consequences of elevated levels of intact PTH within the marrow cavity blood of osteoporotic subjects are discussed.

Bone Marrow↗
PubMed1984

Analysis of immunoreactive and biologically active human parathyroid hormone-peptides by high-performance-liquid-chromatography.

A combination of high-performance-liquid-chromatography (HPLC), sensitive radioimmunoassays and a homologous in vitro bioassay was used to characterise human parathyroid hormone (hPTH)-peptides in human parathyroid adenoma and plasma. Chromatography of several synthetic hPTH-peptides allows the calibration of the HPLC column. On the basis of sequence hydrophobicity the elution position of peptides can be predicted. A model for the determination of the minimal peptide sequence of each peptide has been developed which based on immunological and physico-chemical properties allows the characterisation of unknown hPTH-peptides. Using this technique the heterogeneity of circulating hPTH-peptides in human plasma has been examined. Plasma extracts from healthy individuals, osteoporotic, hyperparathyroid and pseudo-hyperparathyroid patients were investigated. A uniform pattern in the heterogeneity of hPTH-peptides was detected. Using parathyroid adenoma as reference disease specific changes were characterised.

Adenoma↗
PubMedDate not supplied

Precaution: belief, regulatory system, and overarching principle.

The precautionary principle has been incorporated as a belief statement in international agreements for more than a decade. The 1998 Wingspread definition of the principle was the first to bring together four components that, in the past two years, have formed the elements of a broader, overarching approach to precaution that is a robust basis for its specific implementation: prompt action even in the face of scientific uncertainty, burden of proof and persuasion on proponents of potentially hazardous technologies, assessment of alternatives, and transparency. This broad approach to precaution is in direct conflict with the simplistic, easily manipulated principles and methods of risk-assessment-based risk management being exported by U.S. officialdom. In contrast to risk assessment, precaution, broadly defined, incorporates the full range of human intelligence in the task of protecting human health and the environment: flexibility, foresight, fairness, thoughtful consideration, and honesty.

Decision Making, Organizational↗