The implementation of the 'International Classification of Functioning, Disability and Health' (ICF) in daily practice of neurorehabilitation: an interdisciplinary project at the Kantonsspital of Lucerne, Switzerland.

PURPOSE: The current paper describes the implementation of ICF as a standard language and framework for description of human functioning and disability for common use in every day work by the multiprofessional team. METHOD: An interdisciplinary project team involving all rehabilitation specialities was constituted. The extensive original document of ICF was broken down to a simplified raster for body functions and structures, activities and participation, as well as for contextual factors. These rasters had to cover the most important aspects concerning the patients treated on our unit. Checklists on the basis of these rasters were worked out for use by the different specialized teams. Using these checklists, rehabilitation conferences, form and language of interdisciplinary communication, goal setting and documentation were introduced newly in every day work for the interdisciplinary rehabilitation team, structured strictly based on the ICF-criteria. RESULTS: Since April 2002 the ICF-based processes are implemented in routine work for all members of the rehabilitation staff. First experiences show good acceptance by the team members, improvements in communication and documentation as well as substantial gains in content and handling of rehabilitation conferences. As a result of the implementation we observed, that participation, context and domiciliary interventions gained quite more influence in every day work at the unit. CONCLUSION: Implementation improved considerably the quality of interdisciplinary work processes and contributed to a more systematic approach to rehabilitation tasks by the team members.

Capillary zone electrophoresis for the determination of thiabendazole, prochloraz and procymidone in grapes.

Capillary zone electrophoresis with UV detection was applied to the simultaneous determination of thiabendazole, prochloraz and procymidone in grapes. Electrolyte conditions such as pH, composition and concentration of the buffer, addition of organic solvent and working voltage were checked to obtain a high-performance separation of the three fungicides (by measurement of separation efficiency and resolution). The most critical parameter was the pH of the running buffer. The best separation was achieved in 4 mM phosphate solution at pH 3.5. The repeatability of the migration times, expressed as RSD, was < 0.44%. The three peaks were completely resolved with a separation efficiency up to 100,000 theoretical plates. Solid-phase extraction was used for the isolation and preconcentration of the fungicides, which provided a concentration factor of 10:1 and limits of detection lower than the maximum residue limits. The mean recoveries of the fungicides were 73.75% for thiabendazole, 41.70% for prochloraz and 92.23% for procymidone. This method was used to determine these compounds in 20 real samples taken from a local market.

A second polymorphic form of N,N'-diphenyl-1,4-phenylenediamine.

A new triclinic polymorphic form of N,N'-diphenyl-1,4-phenylenediamine (C(6)H(5)NHC(6)H(4)NHC(6)H(5)) has been obtained through appropriate recrystallization of the orthorhombic form. It crystallized in the centrosymmetric space group P$\overline 1$, with two half molecules as the asymmetric unit.

Phenobarbital selectively promotes initiated cells with reduced TGF beta receptor levels.

Phenobarbital (PB) is a potent tumor promoter in rodent liver. In this study we investigated whether PB selectively promotes a population of initiated cells with reduced levels of transforming growth factor-beta (TGF beta) receptors types I, II and III. Liver tumors were induced in male Fischer F344 rats by diethylnitrosamine (DEN). Following induction the animals were divided into PB-treated (DEN/PB) and untreated groups (DEN). After 3 months of treatment half of the PB-treated rats were removed from PB for the final month (DEN/PB/OFF). At 4 months, the livers from rats in the three treatment groups were removed, tumors excised and frozen with matched surrounding normal liver tissue. The mRNA levels for the TGF beta receptors types I-III were significantly decreased in tumor tissue from DEN/PB rats when compared with surrounding normal liver tissue or tumors from age-matched untreated controls. In tumors from DEN/PB/OFF rats the TGF beta receptor types I-III were also significantly reduced compared with controls and not different to tumors from DEN/PB rats. There was no difference in the mRNA levels for the TGF beta receptors in tumors from rats exposed to DEN alone, when compared with the surrounding normal tissue. These results demonstrate that PB selectively promotes initiated cells with reduced levels of TGF beta types I-III receptors and suggests a mechanistic role for TGF beta in PB-induced liver tumor promotion.

Induction of apoptosis in liver tumors by the monoterpene perillyl alcohol.

The monoterpenes d-limonene and perillyl alcohol (POH) inhibit the growth of mammary tumors. In this investigation we tested whether POH is also effective in reducing liver tumor growth. Diethylnitrosamine was used to induce liver tumors in male Fischer 344 rats. Two weeks after diethylnitrosamine exposure was discontinued, the animals were divided into POH-treated and untreated groups. The mean liver tumor weight for the POH-treated rats after 19 weeks of POH treatment was 10-fold less than that for the untreated animals. POH did not influence tumor cell proliferation but increased the apoptotic index approximately 10-fold. The mRNA levels for the mannose 6-phosphate/insulin-like growth factor II receptor and the transforming growth factor beta type I, II, and III receptors were also significantly increased in the liver tumors from the POH-treated animals when compared to the corresponding receptor mRNA levels in the normal tissue surrounding the tumors and in the tumors of untreated animals. These results demonstrate that POH does not promote the formation of liver tumors, but rather inhibits their growth by enhancing tumor cell loss through apoptosis.

Transforming growth factor-beta receptors type I, II and III in phenobarbital-promoted rat liver tumors.

Rat liver tumors initiated with N-nitrosodiethylamine (DEN) followed by promotion with phenobarbital (PB) were examined for expression of transforming growth factor-beta (TGF beta) type I, II and III receptors. RNase protection and TGF beta 1 affinity labeling assays were used to determine TGF beta receptor steady-state mRNA and protein levels, respectively. We have demonstrated that all three TGF beta receptors are expressed in both normal and malignant hepatic tissues. Long-term PB administration did not alter TGF beta receptor mRNA or protein levels in normal liver. However, type I, II and III TGF beta receptor mRNA and protein levels were decreased by approximately 50% in the DEN-initiated/PB-promoted liver tumors as compared to the receptor levels in normal liver tissue surrounding the tumors. In contrast, TGF beta receptor mRNA and protein levels were unchanged in liver tumors initiated with DEN but not PB-promoted. These data demonstrate that PB promotes the formation of a tumor phenotype that is characterized by a significantly reduced number of TGF beta type I, II and III receptors. This suggests that the down-regulation of TGF beta receptors in PB-promoted hepatic tumors may provide a selective growth advantage to the tumor cells by reducing the ability of TGF beta to inhibit their growth.

Regulation of mannose 6-phosphate/insulin-like growth factor-II receptors and transforming growth factor beta during liver tumor promotion with phenobarbital.

Chronic exposure of rats to the liver tumor promoter phenobarbital (PB) significantly reduces the ability of normal hepatocytes, but not of initiated hepatocytes, to respond to mitogenic stimuli. This reduced proliferative ability of normal hepatocytes was correlated with a marked elevation in hepatic concentration of the potent mito-inhibitory factor, transforming growth factor-beta 1 (TGF-beta 1). PB also increased the mannose 6-phosphate/insulin-like growth factor-II (M6P/IGF-II) receptor concentration in hepatocytes, with a concomitant up-regulation in gene expression. Since the M6P/IGF-II receptor facilitates the proteolytic activation of TGF-beta 1, this suggests that PB increases the capacity of normal hepatocytes to activate TGF-beta 1. In contrast, a subset of preneoplastic lesions induced with N-nitrosodiethylamine did not demonstrate elevated levels of the M6P/IGF-II receptor or TGF-beta 1 in response to PB. These findings emphasize the potential importance of TGF-beta 1 during liver tumor promotion with PB and suggest that reduction of M6P/IGF-II receptor levels in liver tumors may provide the tumor cells with an important selective growth advantage.

Role of FDA in establishing tolerable levels for dioxin and PCBs in aquatic organisms.

When fishery products shipped in interstate commerce contain an environmental contaminant that presents a potential threat to public health, the Food and Drug Administration (FDA) undertakes appropriate regulatory steps to minimize exposure. These efforts range from seizure of the affected product to formal rule-making to establish a limit. The basic provision of the Food, Drug, and Cosmetic (FD&C) Act by which the agency deals with environmental contaminants in the food supply is section 402(a)(1), which deals with poisonous and deleterious substances. Poisonous and deleterious components are deemed to be "added," even if they are natural constituents of food, if any amount is present through the artifice of man. Furthermore, when the level of a naturally occurring toxin is increased in the food through handling and/or processing, the sum of all of the contaminant is deemed to be "added." Unavoidable environmental contaminants may be controlled and/or regulated under this section by the "may render injurious" standard, whereby the agency must demonstrate that there is a significant possibility that exposure to the contaminant could be injurious to human health. "Action levels" are administrative guidelines or instructions to the agency field units that define the extent of contamination at which the agency may regard food as adulterated. Except for polychlorinated biphenyls, for which there is a tolerance established by regulation, FDA has controlled contaminants in aquatic organisms by using action levels. Under section 406 of the FD&C act, the agency can also establish tolerances for unavoidably added poisonous or deleterious substances. This section allows the agency to consider the extent to which a contaminant is unavoidable in food while it limits exposure to the extent necessary to protect the public health. Section 406 requires that the tolerance be established by assessing several factors, including risk. One of these is the capability of processing technology to prevent, reduce, or otherwise control the level of the contaminant. Another factor is the necessity to avoid the needless removal of large amounts of valuable food from the market. Finally, the available analytical and sampling methods must be capable of measuring the contaminant so as to ensure the enforceability of the tolerance. Although the FDA has no statutory authority over intrastate fishing considerations, such as noncommercial fishing, it does provide advice to local or state authorities. It is the best scientific opinion the agency can give, but it is not enforceable per se. Advice is provided when requested by local and state officials where no guideline or tolerance is available, and is meant to deal with local and/or regional public health concerns.(ABSTRACT TRUNCATED AT 400 WORDS)

Toxicity of dibutyltin, tributyltin and other organotin compounds to humans and to experimental animals.

Alkyltin compounds are used as stabilizers and antifouling agents. Food chain accumulation and bioconcentration have been demonstrated in crabs, oysters and salmon exposed to tributyltin oxide. In mammalian species, tributyltin compounds may be metabolized to dibutyltin derivatives and related metabolites. Di- and tributyltins appear to be less potent neurotoxicants than trimethyltins and triethyltins. Dibutyltins and tributyltins produced bile duct damage in rats, mice and hamsters. Tributyltin oxide and dibutyltin and dioctyltin compounds are potent thymolytic and immunotoxic agents in rats. Tributyltin oxide at 5 ppm in the rat diet produced immunotoxicity in a 2-year feeding study, and at 50 ppm increased the incidence of tumors of endocrine origin. In preliminary reports, 5 ppm tributyltin produced no detectable increase in tumor incidence, and 0.5 ppm produced no detectable immunotoxicity in long-term studies. Tributyltin oxide and dibutyltin acetate did not appear to be mutagenic in a large battery of mutagenicity assays but produced base-pair substitutions in one of the bacterial strains tested. Tributyltin oxide produced mutations in Chinese hamster ovary cells, increased the incidence of micronuclei in the erythrocytes of exposed male BALB/c mice, and was highly embryotoxic in vitro. Embryotoxic and teratogenic effects in mice exposed to tributyltin oxide in vivo may have been due either to direct tributyltin oxide action or responses secondary to maternal toxicity. More information is needed to determine the applicability to human risk assessments of the immunotoxicity data derived from rat studies and to establish a definitive tolerable daily intake for tributyltin oxide.

A novel calcium-dependent phosphorylation of a ribosome-associated protein.

The degree of phosphorylation of ribosome-associated proteins of intact GH3 pituitary tumor cells before and after Ca2+ depletion was examined. A 26-kDa ribosome-associated protein was found to dephosphorylate upon Ca2+ depletion of the cells and to re-phosphorylate upon restoration of the cation. This protein was distinct from eukaryotic initiation factor 4E on the basis of subcellular distribution, antigenicity, and susceptibility to dephosphorylation in Ca2+-depleted cells. Temporal correlation was observed between the phosphorylation/dephosphorylation state of the 26-kDa protein, and the stimulation/inhibition of protein synthesis by Ca2+ repletion/depletion. Phosphorylation of the 26-kDa protein was rapidly abolished in Ca2+-repleted cells by the ionophore, A23187, which elevates cytosolic Ca2+ while reducing sequestered cation. Dephosphorylation of the protein and inhibition of protein synthesis occurred at comparable times after addition of ionophore. The novelty of a Ca2+-dependent phosphorylation supported by sequestered rather than cytosolic free Ca2+ is discussed.

Actions of a tumor-promoting phorbol ester in a cloned rat pituitary cell : Potential involvement of changes in Ca(2+) metabolism.

Tumor promoters, such as phorbol myristate acetate (PMA), facilitate carcinogenesis by mechanisms that may involve changes in intracellular Ca(2+) metabolism and distribution of Ca(2+), as well as activation of a Ca(2+)-and phospholipid-dependent protein kinase, referred to as protein kinase C. We compared the actions of PMA on GH3 cloned pituitary cells with those of thyrotropin releasing hormone (TRH), an established Ca(2+)-mobilizing agent. The TRH treatment produced a(45)Ca efflux, inhibited(45)Ca uptake, diminished chlortetracycline fluorescence, and stimulated cAMP accumulation and protein synthesis in a Ca(2+)-dependent manner. Like TRH, PMA produced an efflux of(45)Ca and inhibited(45)Ca uptake; however, the phorbol ester stimulated cAMP accumulation and protein synthesis in the absence of external calcium and failed to alter chlortetracycline fluorescence. The TMB-8, a putative inhibitor of the mobilization of membrane-associated Ca(2+), did not alter PMA-induced stimulation of protein synthesis.The results suggest that PMA-induced changes in Ca(2+) metabolism are not caused by the mobilization of membrane-associated calcium. Alternative proposals are that PMA (1) inhibits Ca(2+) influx and/or (2) mobilizes calcium from nonmembranous storage sites. Further study is needed to characterize the mechanism through which tumor-promoting phorbol esters influence Ca(2+) metabolism and to ascertain the significance of changes in Ca(2+) metabolism to cellular processes affected by these substances.

An investigation of the mechanism of lead-induced relaxation of pigeon crop smooth muscle.

Lead-induced crop dysfunction is probably due to a direct action on the smooth muscle or the neural elements in crop tissue. Strips of crop tissue relax when exposed to lead chloride in vitro. We found that tetrodotoxin and the neurotransmitter antagonists propranolol, sotalol and apamin failed to alter lead-induced relaxation, suggesting that the effect is not neurally mediated. Lead, manganese, cadmium and theophylline inhibited calcium-induced contractions in depolarized crop tissue. However, lead, like the phosphodiesterase inhibitor theophylline and unlike the calcium-influx blocker verapamil, did not inhibit bethanechol- or potassium-stimulated contractions and calcium influx into crop tissue. This suggests that lead does not act by blockade of calcium influx. Lead stimulated cyclic AMP production in cell-free crop membrane preparations. Lead also enhanced manganese stimulation of cyclic AMP production. The results suggest that lead-induced relaxation may be due to stimulation of adenylate cyclase activity resulting in increased intracellular cyclic AMP levels.

Lead induction of crop dysfunction in pigeons through a direct action on neural or smooth muscle components of crop tissue.

Lead acetate solutions administered p.o. to pigeons produce crop stasis. Crop dysfunction may be an indirect effect on crop activity by a direct interaction with the cerebellum or some other site associated with lead-induced ataxia. Alternatively, crop stasis may be due to the direct interaction of lead with sites on the smooth muscle or neural elements in crop tissue. A behavioral test for ataxia was performed on pigeons given lead by crop intubation or i.m. injection. Blood lead concentrations were also monitored. Lead-induced ataxia was separable from lead-induced crop dysfunction depending on the route of lead administration, suggesting that lead-induced crop stasis is not secondary to toxicity at a site associated with ataxia. Intramuscular treatment produced crop stasis more readily than did crop intubation. This probably reflects different mechanisms of absorption and metabolism. A Tris-succinate medium was devised which accommodated the solubility characteristics of lead, permitting studies of crop tissue in vitro. Lead chloride added to crop tissue in tris-succinate medium caused a concentration-related reversible relaxation. Crop circular muscle was more sensitive to Pb++ than was longitudinal muscle, in agreement with the effects of other agonists. The EC30 of crop circular smooth muscle in plasma was 1000 microM PbCl2 compared to 3 microM in Tris-succinate medium. The results suggest that lead induces crop dysfunction by acting either directly on crop smooth muscle or on neural elements in crop tissue.