Prognostic value of geriatric and cardiac parameters for one-year mortality in older heart failure patients. A multicentre, observational, prospective study.

PURPOSE: Heart failure is prevalent among older people and has a poor prognosis. The aim of this study is to identify potential prognostic, geriatric, and cardiac parameters which could help clinicians identify older heart failure patients at high risk for one-year mortality. METHODS: The multicentre, observational cohort study which included 147 heart failure patients aged ≥75 years, hospitalized in the cardiac or geriatric department in two hospitals. One-year survival was the outcome measure. For univariate analysis Chi-square test and independent sample T-test were used; for multivariate analysis Logistic regression and Cox regression for time-dependent analysis. RESULTS: One-year mortality was 28% (41/147). One-year survivors and non-survivors did not differ in the following characteristics: age, gender, sodium level at hospital discharge, ejection fraction, NYHA Class, basic and instrumental activities of daily living, and the presence of a geriatric risk profile. There was a significant lower systolic blood pressure at discharge in non-survivors compared to one-year-survivors (mean 125.26 mmHg vs. 137.59 mmHg). Non-survivors had more severe underlying comorbidities according to the age adjusted Charlson Comorbidity index (CCI) (mean 8.80 vs. 7.40).Both logistic and Cox regression showed a higher risk and rate of mortality with decreasing systolic blood pressure at discharge (OR 0.963, p=0.001 and HR 0.970, p<0.001) and with increasing CCI (OR 1.344, p=0.002 and HR 1.269, p=0.001); the other variables were not significantly related. CONCLUSION: Lower blood pressure and more severe comorbidities, but not functionality nor the presence of a geriatric risk profile, are related to one-year mortality in older, in-hospital heart failure patients.

Food contamination with polychlorinated biphenyls and dioxins in Belgium. Effects on the body burden.

The core paper of this debate shows that persistent organic pollutant residues of the 12 chemicals targeted for a phase out under the Stockholm Convention are present in almost all categories of food in the US food supply. For dioxins, the study does not use measured data, but is based upon potential dioxin residues in selected food items. Polychlorinated biphenyls are not included in the study. In this paper we discuss selected data of polychlorinated biphenyl and dioxin concentrations in Belgian food. Some of these exposures are chronic, others are attributable to incidents. Both result in high body burdens in Belgium. The paper also compares the current concentrations in food with the recent standards launched by the EU for dioxins in food, and discusses whether these values adequately protect European citizens.

The Belgian PCB and dioxin incident of January-June 1999: exposure data and potential impact on health.

In January 1999, 500 tons of feed contaminated with approximately 50 kg of polychlorinated biphenyls (PCBs) and 1 g of dioxins were distributed to animal farms in Belgium, and to a lesser extent in the Netherlands, France, and Germany. This study was based on 20,491 samples collected in the database of the Belgian federal ministries from animal feed, cattle, pork, poultry, eggs, milk, and various fat-containing food items analyzed for their PCB and/or dioxin content. Dioxin measurements showed a clear predominance of polychlorinated dibenzofuran over polychlorinated dibenzodioxin congeners, a dioxin/PCB ratio of approximately 1:50,000 and a PCB fingerprint resembling that of an Aroclor mixture, thus confirming contamination by transformer oil rather than by other environmental sources. In this case the PCBs contribute significantly more to toxic equivalents (TEQ) than dioxins. The respective means +/- SDs and the maximum concentrations of dioxin (expressed in TEQ) and PCB observed per gram of fat in contaminated food were 170.3 +/- 487.7 pg, 2613.4 pg, 240.7 +/- 2036.9 ng, and 51059.0 ng in chicken; 1.9 +/- 0.8 pg, 4.3 pg, 34.2 +/- 30.5 ng, and 314.0 ng in milk; and 32.0 +/- 104.4 pg, 713.3 pg, 392.7 +/- 2883.5 ng, and 46000.0 ng in eggs. Assuming that as a consequence of this incident between 10 and 15 kg PCBs and from 200 to 300 mg dioxins were ingested by 10 million Belgians, the mean intake per kilogram of body weight is calculated to maximally 25,000 ng PCBs and 500 pg international TEQ dioxins. Estimates of the total number of cancers resulting from this incident range between 40 and 8,000. Neurotoxic and behavioral effects in neonates are also to be expected but cannot be quantified. Because food items differed widely (more than 50-fold) in the ratio of PCBs to dioxins, other significant sources of contamination and a high background contamination are likely to contribute substantially to the exposure of the Belgian population.

Surprising findings following a Belgian food contamination with polychlorobiphenyls and dioxins.

We found that 12.1% of Belgian export meat samples from chicken or pork, unrelated to the PCB/dioxin crisis from 1999, contained more than 50 ng polychlorinated biphenyls (PCBs)/g fat and that 6.5% of samples contain more than 20 ng/g fat for the sum of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and its metabolites. Part of this background contamination stems from imported animal feed ingredients (fish flour and grains), sometimes contaminated by recent use of DDT, as can be deduced from the ratio between DDT and its main metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE). However, after comparing PCB concentrations in fish flour and grains with those found in meat, we suggest that the high concentrations stem from recycled fat. This is the first paper describing background concentrations of PCBs in animal meat from Belgium.

Institutional, Legal, and Economic Instruments in Ghana's Environmental Policy.

/ This paper reviews the state of the environment in Ghana and explores the potential for the use of institutional, legal, and economic instruments in environmental management in the specific context of this developing country.The environmental situation in Ghana is characterized by desertification, land degradation, deforestation, soil erosion, and inadequate water supply in the northern regions of the country. The population as a whole is growing at a rate of 3% per annum, with even greater urban growth rates, due to rural out-migration. Large parts of the coastal zone in the south are rapidly developing to become one large suburbanized area. Water quality is particularly threatened in the urban and industrialized areas, which are mainly located in the southern part of the country. The coastal lagoons and coastal waters are moderately to heavily polluted. Erosion extends along the whole Ghanaian coast with excesses, for example, in the Keta area, where during the last century over 90% of the original buildings have been washed awayby the sea. The obvious environmental consequences of the mining sector are illustrative of the environmental threats caused by a fast growing industry and industrializing agriculture, in a country where environmental policy is only in its formative years. Desertification, food insecurity and coastal erosion all contribute to an increasing number of environmental refugees.Environmental policy in Ghana is a post-Rio phenomenon. Environmental laws, a Ministry of Environment, Science and Technology, an advisory National Committee for the Implementation of Agenda 21, and a fully mandated environmental administration have been established. This administration advocates a progressive attitude towards environmental legislation and points out the specific utility of economic and legal instruments in environmental management in this relatively fast developing country.The choice of instruments for environmental management is increasingly influenced by the specific state of African environmental and technological capacity and by a call for the recognition of the role of traditional customs in nature conservation. This African perspective on environmental management is further intensified by an unmet need for regional, transboundary cooperation in the West African subcontinent. This specific West African context calls for an elaboration of an effective capacity-building program for environmental management in the area.KEY WORDS: Environmental profile; Environmental policy; Legal instruments; Economic instruments; African perspective; State of the environmenthttp://link.springer-ny.com/link/service/journals/00267/bibs/24n3p337.html

Chromosome studies and fertility treatment in women with ovarian failure.

In vitro fertilization and embryo transfer or gamete (or zygote) intra-Fallopian transfer after ovum donation were performed in 16 patients with primary or secondary amenorrhea, associated with chromosome abnormalities. The patients showed the wide range of (mostly X) chromosome abnormalities characteristic for women with primary or premature ovarian failure. Four of these patients became pregnant and three of them have delivered healthy infants with a normal karyotype. This pregnancy rate is far superior to the accepted fertility figure in these patients. When these results were compared with the fertility treatment results of three other groups of women with absent ovarian function (1. ovarian dysgenesis; 2. surgical castration; 3. premature menopause) but with a normal 46,XX karyotype, no difference in treatment efficiency could be detected. These results offer a promising approach for the treatment of infertility in agonadal patients with chromosome aberrations.

The role of fluorinated pyrimidine analogues in the induction of the in vitro expression of the fragile X chromosome.

The modes of action of 5-fluoro-2'-deoxyuridine (FdUrd) and 5-fluoro-2'-deoxycytidine (FdCyd) were studied in PHA-stimulated lymphocytes from normal volunteer donors and a fragile X patient. In both cell types, FdUrd and FdCyd inhibited cell proliferation at concentrations of 3 x 10(-8) M. Thymidylate synthetase was identified as the decisive target for the action of both FdUrd and FdCyd, as judged from the following observations: First, addition of thymidine to the culture medium was able to counteract both FdUrd and FdCyd toxicities, whereas addition of dCyd had no observable effect. Second, inhibition of the in situ thymidylate synthetase activity measured as an increase in the level of [3H]-dThd incorporation coincided with the inhibition of cell proliferation. Third, the inhibition of the thymidylate synthetase-dependent incorporation of [3H]-dUrd into newly synthesized DNA coincided with the inhibition of cell proliferation. The effects of FdUrd and FdCyd on the in vitro expression of fragile site Xq27 of fragile X chromosomes was shown to be based on the depletion of the intracellular pool of thymidine-5'-monophosphate (dTMP), as judged from the following observations: First, both the FdUrd- and FdCyd-dependent induction of site Xq27 coincided with the antiproliferative effects of the respective fluoropyrimidines. Second, addition of thymidine (dThd) to the culture medium both prevented the expression of site Xq27 and neutralized the cytotoxicity of FdUrd and of FdCyd. On the basis of these findings, we provide further evidence for the concept that the fragile X site is located in an AT-rich region.

Chromosome aberrations in 500 couples referred for in-vitro fertilization or related fertility treatment.

Cytogenetic studies were performed in 500 couples referred for in-vitro fertilization or gamete (zygote) intra-Fallopian transfer. Thirteen individuals (1.3%) with chromosomal abnormalities were found. Four major types of anomalies were observed: reciprocal translocations (n = 3), inversions (n = 2), iso-Xq chromosomes (n = 2) and sex chromosome number mosaics (n = 4). Moreover two males with respectively a 47,XYY and a 47,XY,mar+ karyotype were identified. These data pointed to a higher incidence of chromosomal aberrations in this infertile population as compared to a neonatal population without obvious chromosomal pathology. Analysis of the chromosomes which were involved in hyperdiploidy and hypodiploidy in the 30,000 metaphases evaluated, showed a high proportion of cells that had lost or gained an X-chromosome. A puzzling finding was the statistically significant low incidence of 45,X metaphases (0.9%) in women of couples treated on andrological indication as compared to the frequency of 45,X chromosome complements in women with tubal disease (4.0%) or of couples with an idiopathic (4.3%) or mixed female and male (6.7%) indication.

Comparative in vitro cytogenetic studies in mercury-exposed human lymphocytes.

As part of a long-term cytogenetic research project on mercury, we studied the in vitro clastogenic capacity of HgCl2 and CH3HgCl as well as their influence on chromosome segregation by means of a computer-aided chromosome distribution study in metaphase plates. As in other in vitro studies published elsewhere, we exposed human peripheral blood lymphocytes to different concentrations of the mercury compound during a limited period of the pre-DNA synthetic stage (G1-S) or from that stage up to mitosis (G1-M). For both exposure periods and both mercury compounds we observed a rather important clastogenic effect as well as a dissociation of the (normally highly associated) acrocentrics. The results do indicate, in conjunction with previously published data, that mercury compounds alter the chromosome segregation at lower concentrations than those observed for clastogenicity. Moreover, the effects on chromosome segregation are not necessarily due to binding to spindle proteins. Binding to--and inactivation of RNA polymerase I may for example be another mechanism of action which is more important for the inorganic form of mercury than for the organic form.

NOR variability in twins.

The number of AgNOR (NOR+) and the amount of AgNOR (NORM+) were analysed by means of two multilevel analyses of variance in a total of 12 twin pairs: 3 female and 4 male MZ and 5 male DZ pairs. In the first analysis, only zygosity was controlled; in the second, chromosome types D and G were controlled as well as the interaction between chromosome type and zygosity. For NOR+ and NORM+, when chromosome types D and G are not distinguished, the within-pair variance is greater, though not significantly, in DZ than in MZ pairs; but it is highly significantly greater when chromosome type (D or G type) is under control. This confirms an important genetic determination of NOR+ and NORM+ when in the ANOVA model the D and G types are controlled. However, nongenetic factors also influence the Ag-NOR patterns, but not enough to conceal the genetically defined rDNA pattern. Indeed, about 50% of the cells transcribe their rDNA in a way not closely dependent on the rDNA background and significant intrapair differences of NOR+ pattern exist in MZ twins.

Failure of a peripheral dopaminergic marker in Parkinson's disease.

[3H]-spiperone binding on human lymphocytes did not reveal the occurrence of dopamine receptors. However, lower values were observed in Parkinsonism and the displaceable binding was increased after levodopa treatment although this was not specific only for levodopa and, furthermore, was not correlated with the clinical symptomatology. This non-specific binding in lymphocytes corresponds to trapping, presumably in lysosomes and thus does not reflect the dopaminergic receptors state in Parkinson's disease.

Immunocytochemical localization of chromatin regions UV-microirradiated in S phase or anaphase. Evidence for a territorial organization of chromosomes during cell cycle of cultured Chinese hamster cells.

Chinese hamster cells (M3-1 line) in S phase were laser-UV-microirradiated (lambda, 257 nm) at a small site of the nucleus. Cells were fixed either immediately thereafter or in subsequent stages of the cell cycle, including prophase and metaphase. The microirradiated chromatin was visualized by indirect immunofluorescence microscopy using antibodies specific for UV-irradiated DNA. During the whole post-incubation period (4-15 h) immunofluorescent labelling was restricted to a small part of the nucleus (means, 4.5% of the total nuclear area). In mitotic cells segments of a few chromosomes only were labelled. Following microirradiation of chromosome segments in anaphase, immunofluorescent labelling was observed over a small part of the resulting interphase nucleus. A territorial organization of interphase chromosomes, i.e. interphase chromosomes occupying distinct domains, has previously been demonstrated by our group for the nucleus of Chinese hamster cells in G1. Our present findings provide evidence that this organization pattern is maintained during the entire cell cycle.

C heterochromatin variation in couples with recurrent early abortions.

The possible influence of the high polymorphic C heterochromatic regions of human chromosomes 1, 9, 16, and Y on meiotic chromosome segregation was investigated. Faulty chromosome segregation may be the result of either an abnormal quantity of C heterochromatin on the homologues, or disequilibrium between the homologues. The aim of our study was to determine whether either a variation in the amounts of total C heterochromatin or differences in the amounts of C heterochromatin between homologues could lead to faulty chromosome segregation. The study was performed on C banded metaphases obtained from peripheral lymphocyte cultures of 15 couples with recurrent early abortions and 15 control couples, all Caucasians. Analysis of variance was first performed on separate metaphases to measure intra-individual, inter-individual, and between population variation in a hierarchical model. Since the significant intra-individual differences covered the other parameters we performed, secondly, a one way analysis of variance on the mean values of metaphases per person in order to measure the inter-individual and between population variation. The results did not show a relationship between C heterochromatin lengths and occurrence of recurrent abortions.

Comparison of chromosome associations in human lymphocytes arrested by colcemid, nocodazole, or cycloheximide.

The method of "generalized distances" was applied to compare the effects on homologous interchromosomal distances of colcemid, the routinely used tubulin inhibitor with the effects of two other metaphase arrestants: nocodazole, also a tubulin inhibitor and cycloheximide, an inhibitor of protein synthesis which preserves somatic association. More homologous pairs were associated in the cycloheximide treatment than in the other two procedures; however, while several chromosomes which tend to lie toward the center of the metaphase plate showed somatic association in the various treatments, we found no evidence for somatic association of the larger, more peripherally located chromosomes in human cells in any of our treatments (chromosome pair 7 excepted in the colcemid sample).

UV micro-irradiation of the Chinese hamster cell nucleus and caffeine post-treatment. Immunocytochemical localization of DNA photolesions in cells with partial and generalized chromosome shattering.

UV micro-irradiation of a small part of the Chinese hamster nucleus and caffeine post-incubation often results in shattered chromosomes at the first post-irradiation mitosis. In some of these mitotic cells, chromosome shattering is restricted to a few chromosomes spatially related in a small area of the metaphase spread; in others, shattering includes the whole chromosome complement. These 2 types of damage have been called partial and generalized chromosome shattering (PCS and GCS). Using antisera that specifically react with UV-irradiated DNA, we identified micro-irradiated chromatin in interphase nuclei and in mitotic cells with PCS or GCS by indirect immunofluorescence microscopy. In PCS, immunofluorescence staining was found in the damaged area, while the surrounding intact chromosomes were not stained. In GCS, staining was also restricted to a small region of the shattered chromosome complement. In other experiments, cells synchronized in G1 were micro-irradiated in the nucleus, pulse-labelled with [3H]thymidine and post-incubated with caffeine. Autoradiographs of cells with GCS showed unscheduled DNA synthesis restricted to a small chromatin region. Our data present direct evidence that the distribution of DNA photolesions does not coincide with the sites of chromosomal damage in GCS. As a working, hypothesis, we propose that an indirect mechanism is involved in the induction of GCS by which DNA photolesions in a small nuclear segment induce shattering of both micro-irradiated and non-irradiated chromosomes.

[Problems and future perspectives in the treatment of Parkinson's disease]. / Problemen en toekomstperspectieven bij de behandeling van de ziekte van Parkinson.

The most prominent neuropathological lesions in Parkinson's disease have been found in the substantia nigra. The neurochemical alterations are numerous; the most prominent one is the imbalance between acetylcholine and dopamine, the latter transmitter being deficient. Up to now the striato-nigral dopaminergic receptor is the best investigated and the most useful target for an effective therapy. However, a more specific modulation, stimulation or blockade of these receptors, could strongly reduce the occurrence of the side-effects and the drug resistance that are to be seen after a dopamine substitution started too early or too vigorously.

Chromosome distribution studies in XXY karyotypes.

The method of 'generalised distances' was applied to characterise the relative position of the metaphase chromosomes in a population of XXY subjects (180 metaphases from 28 subjects). The most striking observation was that the presence of an extra gonosome coincided with a disturbance of the normally stable centromere-centre distribution pattern. The distribution analysis gave no clear cut evidence for the induction of gonosomal trisomy XXY by chromosome association. No significant association was observed between X and X or X and Y but there was a smaller distance between X and Y in XXY karyotypes than in XY karyotypes. As far as autosomes are concerned, the XXY karyotypes were characterised by a less central location of the acrocentrics without a clear decrease of association frequencies of these acrocentrics, and the C heterochromatin rich chromosomes were more often associated than in the XX and XY control populations. These data do not support the idea that gonosomal trisomies result from chromosome associations, but favour the hypothesis that spindle degeneration as a result of intrafollicular ageing of C heterochromatin polymorphism may be responsible for non-disjunctions.