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In order to achieve a correct diagnosis of drug anaphylaxis using a radioimmunoassay devoid of interferences, we have studied factors leading to false positive or false negative values of plasma histamine. Different steps in sample collection were studied systematically in 30 normal volunteers. False positive values were found in haemolysed samples, with histamine concentrations being correlated with haemoglobin concentrations, and where plasma was aspirated from the white-cell layer. There was no significant increase when a tourniquet or vacuum tubes were used, or when blood tubes were left at 4 degrees C overnight. In 12 patients who experienced an anaphylactic reaction, histamine disappeared from blood 10 times more slowly than expected. False negative values were found in two pregnant women and one heparinized patient. Histamine was remarkably stable in vitro in blood or plasma samples, whereas it disappeared rapidly when plasma from a pregnant woman or a heparinized patient was added to the sample. We conclude that false positive and false negative values are rare when using this radioimmunoassay.

The modifications of hybridization patterns were studied when Southern blots, carrying stallions DNA samples, were probed with eight synthetic tandem repeats (STRs), related by sequence variations in the basic unit. Because STRs preferentially crosshybridize with genomic VNTRs, they usually give patterns looking more like DNA fingerprints, but we found that even small modifications in the STR monomer could cause major changes in the hybridization profiles and could induce a shift of fingerprint pattern towards the detection of only one or two loci. This enables the use of STRs as direct genetic markers for linkage analysis, without cloning of the corresponding DNA fragment. Moreover, the set of STR variants can suggest consensus sequences allowing some prediction of the banding pattern.

Various chemicals are used for protecting wood samples against fungi, and some of them are released in water, leading to pollution of the water. The kinetics of release of pentachlorophenol in water has here been studied, by considering the diffusion through the wood along the three principal axes of diffusion. The experiments and the modelling of the process is successfully coupled. The numerical model takes the three principal diffusivities, the partition factor, the volumes of wood and water into account. The effect of the length of the wood sample taken along the longitudinal axis of diffusion is especially studied, as the longitudinal diffusivity is much higher than the other two principal diffusivities. The effect of the relative volumes of wood and water is also of considerable interest not only for the concentration of the chemical in water but also for the rate of release.

There is considerable interest in the recycling of food packaging, but also the potential for problems. Any chemical component initially located in the re-used food packaging may be responsible for contamination of the food. The kinetics of this transfer can be established whether the food is liquid or solid. The process is controlled by diffusion in the packaging and by convection in the liquid food or by diffusion in the solid food. A bi-layer package made of a re-used polymer layer and a virgin polymer layer exhibits quite different kinetics for the contamination of the food. The role of the virgin polymer layer or so-called functional barrier can be established either by the kinetics of contaminant transfer or by the profiles of concentration developed through the packaging-food system. Dimensionless numbers are used in order to be of help to anyone in need of precise information on the length of time this functional barrier offers protection of the food.

Prediction of migration from packaging to food is often made using equations which are not always designed specifically for the problem. At least, these equations should overestimate migration, in order to be on the safe side. Integration of Fick's equation under the assumption of 'infinite packaging' provides an equation which is very practical since it requires only a few experimental data. It is shown here that, unfortunately, the use of this equation leads to a systematic underestimation of the diffusivity, by the square of the percentage of migration at steady state. In contrast to widely accepted opinion, this model is not conservative. A conservative approach requires that the diffusivity is determined under finite packaging' assumptions, associated with very large volumes of food and with long term experiments. These equations are applied to the migration of a phenolic antioxidant from polypropylene.

The problem of pollutant transfer in food from a polymer packaging made of a recycled film and a functional barrier is studied from a theoretical point of view. In the present case, the process is controlled by Fickian diffusion through the two films of the polymer packaging in perfect contact and by convection into the food. A numerical model is built, taking all the facts into account: the diffusion of the pollutant through the two polymer films, a convective coefficient of mass transfer on the surface, a partition factor, the volume of the liquid and the thicknesses of the polymer films. The results are expressed by using dimensionless numbers so that they can be used for various cases, viz the kinetics of pollutant transferred into the food and the profiles of concentration of the pollutant through the packaging.

The recent spreading of a subtelomeric region at nine different human chromosome ends was characterized by a combination of segregation analyses, physical mapping, junction cloning, and FISH investigations. The events occurred very recently in human genome evolution as demonstrated by sequence analysis of different alleles and the single location of the ancestral site at chromosome 17qter in chimpanzee and orangutan. The domain successfully colonized most 1p, 5q, and 6q chromosome ends and is also present at a significant frequency of 6p, 7p, 8p, 11p, 15q, and 19p ends. On 6qter, the transposed domain is immediately distal to the highly conserved, single-copy genePDCD2.

The liquid located in a polymer evaporates by following a process controlled by diffusion-evaporation. The general case when the desorption is followed by subsequent shrinkage is studied by considering a spherical polymer with a radial diffusion and a finite rate of evaporation. The volume of the surrounding is so large that it can be considered as infinite. The mathematical treatment is achieved, leading to general equations of radial diffusion and evaporation with a following change in dimension of the polymer. These general equations reduce to the Fick's equation when the amount of substance transferred is small enough. These general equations have no analytical solution, and the problem is resolved by using a numerical method with finite differences. The following parameters are of interest: the diffusivity, the coefficient of mass transfer on the surface, the radius of the empty bead, the relative volume expansion of the polymer due to the presence of the diffusing substance.

The cure of an unsaturated polyester coating was studied by using experiments and a model of the process. Experiments involved spraying the catalyst-resin mixture on a surface and following the hardness of the coating. The numerical model takes into account the heat transferred by convection at the surface of the coating and by conduction through the coating and the surface, as well as the heat generated by the cure reaction. The kinetics of heat evolved from the cure reaction was determined by calorimetry. The effect of various parameters, such as the temperature of the surrounding and the thickness of the coating was studied by considering the state of cure and the hardness.

The correlation between the state of cure of an unsaturated polyester coating and its resistance to ethanol at room temperature is studied. The heat generated by the remainder of the cure reaction at a given time as a fraction of the total heat generated is called the state of cure. Sheets with various states of cure ranging from 75 to 95% were prepared and put in contact with an ethanolic solution at 95% ethanol. The process of ethanol absorption is controlled by transient diffusion with a constant diffusivity. A statement is obtained: the higher the state of cure, the lower the amount of ethanol absorbed and the lower the diffusivity.

Pentachlorophenol is one of the oldest chemicals used for protecting wood against fungi. A drawback for this chemical is its potential release in water when the treated wood is in contact with water. A method of impregnation of wood is described, leading to a low amount of PCP in the wood, and with a non uniform concentration throughout the wood and high concentration on the wood surface. The release of PCP in water from wood samples treated in this new way is studied. When these treated samples are in contact with water, two PCP transports are observed: the one with the usual release in the external water, the other with the diffusion inside the wood from the usual surface. In spite of the low amount of PCP in the wood, protection against fungi may be effective, as the release of PCP is thus low. Modelling and experiments are used for treating the problem.

The release kinetics of a polymeric-controlled release device are determined by its geometry and dimensions. A method to calculate the required size and shape of diffusion-controlled dosage forms to achieve a particular release profile is presented. The diffusion parameters are determined for various drugs (theophylline, diltiazem hydrochloride and caffeine) with thin ethyl cellulose (EC) films, containing different plasticizers [dibutyl sebacate (DBS) and acetyl tributyl citrate (ATBC)]. Computer simulations are then used to predict the drug release kinetics from various dosage forms (e.g. microparticles and cylinders). The practical benefit of these simulations is to optimize the geometry and dimensions of a controlled release device without the need of experimental studies. To verify the theoretical predictions, the release kinetics of theophylline from EC/ATBC microparticles of different size have also been determined experimentally. Good agreement is found between theory and experiment, proving the validity of the presented method.

Abstract: Neuroblastoma is a childhood neural crest tumour, genetically characterized by frequent deletions of the short arm of chromosome 1 and amplification of N-myc. Here we report the first evidence for a neuroblastoma tumour suppressor locus on 4pter. Cytogenetically we demonstrated rearrangements of 4p in 7 out of 26 evaluable tumours (27%). Subsequent analysis of loss of heterozygosity (LOH) by Southern blotting revealed allelic loss of 4p in 16/82 (19.5%) informative neuroblastomas. Taken together cytogenetic and Southern blot analyses showed loss of 4p in 20/86 neuroblastomas analysed (23%). The common deleted region was bordered by the probe D4S123 and encompassed the distal 34 cM of 4p. We found no evidence for genomic imprinting of the 4p locus as the 4p alleles lost in the tumours were of random maternal and paternal origin. LOH4p was found at all disease stages and in every age group. Furthermore LOH4p was present both in cases with and without LOH1p and amplification of N-myc.

An intumescent fire retardant coating can effectively control fire spread and damage. Its dual purpose is to confine the surface spread of flame to the boundaries of an already established fire, and to retard the penetration of heat and flame to and through the coated surface. Our composition expanded and provided an insulation layer between the flame source and the combustion substrate, and liberated a quantity of primarily non-flammable decomposition products which tended to extinguish the flame. The main ingredients of the coating were cellulose acetate butyrate and HMDI (Desmodur N) for Polyurethane, and Chlorowax-70 (chlorinated paraffins) as fire retardant component. This fire retardant coating was applied to wood panels, and tested in a 2-foot tunnel, its flame spread rating being measured. The effects of three parameters of interest were investigated: the type of wood used, the percentage of Chlorowax, and the coating thickness. It was found of interest to study the oxidation of the coating using different techniques, e.g. flash pyrolysis under oxygen and GC/MS for analysis of the decomposed products. Combustion studies of the coating were also conducted using DSC and thermogravimetry, either with the scanning mode or under isothermal conditions. Comparisons were made between the results obtained from pyrolysis and combustion.

This publication surveys the results obtained by means of thermal analysis particularly with DTA and DSC methods in the field of synthetic and natural polymers treated with various flame retardant additives.

Pyrolysis studies of a fire retardant coating were conducted under isothermal conditions by taking into account the kinetic data of the overall reaction and the heat transfer process. The coating was made of Polyurethane and chlorinated paraffin. A 160Μm thick film was heated by free convection from heated air, and conduction through the coating. Profiles of temperature developed through the coating were obtained by calculation, as well as those of loss in weight due to the thermal decomposition. The thermal conduction did not vary because of the formation of a porous char resulting from the coating decomposition.

Polyvinylbezaldehyde reacts with primary amines with an acidic catalyst to give polymeric Schiff bases. The hydrolyses of these imines have been studied in acidic medium at pH=1,2 or in pure water at pH=6.5.

Summary Three polymeric Schiff bases have been synthesized from corresponding monomers and prepared by means of a radical polymerization. These polymers have relatively low molecular masses and their hydrolyses, with release of amines, have been studied in a synthetic gastric liquid of pH=1,2.

Two planktonic foraminiferal oxygen isotope records of ODP Hole 653A (Tyrrhenian Sea) are presented for the time period extending from approximately 0.8 to 3.0 Ma. Six, generally accepted, synchronous bioevents were used to precise the oxygen isotope chronology and to identify the oxygen isotope stages 22 down to 114. Subsequently, this oxygen isotope chronology was used to determine the synchronism or diachronism of various other biostratigraphic events with those recorded in the Singa and Ficarazzi land sections (Italy) and those in other DSDP/ODP sites.

This paper describes the Centre d'Etude du Polymorphisme Humain (CEPH) consortium linkage map of chromosome 9. A total of 124 markers were typed in the CEPH family DNAs by 14 contributing laboratories; of these, 42 loci are ordered on the map with likelihood support of at least 1000:1. The uniquely placed markers include 31 that can be typed by PCR. A further 28 markers that can be typed by PCR are approximately positioned on the map. Multilocus linkage analysis with CR1-MAP has produced male, female, and sex-averaged maps extending for 176, 237, and 209 cM, respectively, while sex-averaged maps produced with MAPMAKER and the multiple two-point program MAP extended for 170 and 129 cM, respectively. The male map contains only two intervals greater than 10 cM, and the mean genetic distance between the 42 uniquely placed loci is 4.3 cM. However, no markers were available to anchor the map at either telomere or the centromere. The results confirm the high level of interference suggested by chiasma maps of chromosome 9. Detailed meiotic breakpoints for three of the families are shown. These can be used to provide rapid placement of any new marker without the need for statistical analysis.

Reusing old plastics as food packaging necessitates the presence of a functional barrier (made of a virgin polymer) between the food and old plastics. The transfer of the potent contaminant through the packaging is controlled by diffusion, leaving aside of the transfer of the food into the packaging. Depending on whether the food is liquid or solid, the process of transfer of the contaminant in the food is controlled either by convection, with a coefficient of convective transfer in the food, or by diffusion. The two processes have been studied in detail and the results are expressed in terms of master curves. Some emphasis is put on the effect of the value of the diffusivity in the food and of the coefficient of mass transfer on the contaminant transfer into the food.

The process of pollutant transfer into food from sandwich packaging of different thicknesses has been studied. The thicknesses of the virgin layers or functional barriers were different, the one in contact with the food being much thicker than the other in contact with the surrounding. A numerical model based on finite differences was built, by considering the following facts: the transient diffusion through the three layers of the packaging with the same and constant diffusivity, the convection at the packaging-food interface with a coefficient of mass transfer, the volumes of food and packaging. Dimensionless numbers were used in order to obtain general results of use in various typical cases. The kinetics of the pollutant transfer into the food, the profiles of concentration of pollutant developed through the packaging, and the concentration-time histories of the pollutant on the surface of the packaging, were calculated for different values of the parameters.

The changes in the effects of oestradiol-17β on body weight, food intake and [1-14C]glucose oxidation in adipocytes were followed in sham-operated, ovariectomized and adrenalectomized–ovariectomized rats to eliminate effects of endogenous progesterone and corticosterone. During the first 5 days oestradiol induced a dramatic fall in food intake and body weight concomitant with a decrease in glucose oxidation by adipocytes, when tested 12 h and 3 days after the beginning of treatment. In-vitro incubations with oestradiol showed that this was a direct effect of this hormone. On the other hand, from days 5 to 14 of treatment, body weight and food intake increased, though they were still lower than in sham-operated controls. On day 14, as values of treated rats tended to reach those of controls, glucose oxidation in adipocytes was stimulated by oestradiol treatment. An insulin effect was still observable and none of these effects was dependent on the adrenal gland.These biphasic changes in the parameters studied could be closely related; moreover, a relationship with other oestradiol actions on metabolism that are known to be corticosterone-dependent could be eliminated.J. Endocr.(1984) 101, 13–19

A DNA probe from a human Y chromosome-derived cosmid detects a single-copy genomic DNA fragment which can appear in different allelic forms shared by both sex chromosomes. Variants at this DNA locus show an autosomal pattern of inheritance, undergo recombination with sexual phenotype and can therefore be described as ‘pseudoautosomal’. Another probe from the same cosmid detects a sequence repeated 15–20 times per haploid genome. These repeats also appear pseudoautosomal and map exclusively to the short-arm terminal region of each sex chromosome.

Oral galenic forms able to control the drug release in stomach are prepared and studied in this paper. A branched polymer is dispersed in a biocompatible polymer as Eudragit. A Polyanhydride is chosen for this branched polymer and it is obtained by reacting the anhydride with the drug and then polymerizing this branched monomer. The process of release of drug is studied by using in vitro tests with synthetic gastric liquid. The process is proved to be controlled by transient diffusion of the liquid into and the drug out of the galenic form, with contant diffusivities . A simple mathematical model is thus able to describe both these matter transfers. Moreover, the branched pulymer itself exhibits a retardancy in the release of drug which is also controlled by diffusion. This retardancy can be of interest, especially in case of accident when the galenic form is broken in the patient's mouth and chewed.

More and more, old food packages should be recycled as new food packages, in spite of the fact that they could be contaminated. In order to protect food from pollution, the new packages consist of bi- or tri-layer polymers, the recycled polymer being surrounded with virgin polymer layers playing the role of functional barriers. As these polymer layers are prepared by co-extrusion at the melting temperature, a diffusion of the contaminant takes place during this short stage. A numerical model with finite differences is built, taking into account the heat transfer by conduction through the polymers and by convection at the external surface, and the diffusion of the contaminant through the polymer layers with a temperature-dependent diffusivity. The results are expressed in terms of profiles of concentration developed through the thickness of the packaging. Dimensionless numbers are used so as to draw master curves of use in various typical cases.

Signs of up to eight stepped Holocene shorelines, which have been reported in a previous study on the east coast of Rhodes Island, have been reinvestigated in detail on the basis of a new geomorphological survey, identification and petrological analysis of many new samples of exposed marine organic crusts and over 30 radiocarbon datings.

A deep-sea core over 16 m long from the crestal area of the Mediterranean Ridge has been investigated with different techniques, including quantitative micropaleontology, stable isotopes (measured on the epipelagic species Globigerinoides ruberand on the mesopelagic species Globorotalia inflata), and clay mineralogy. The resulting record of climatic fluctuations can be cross correlated to other Mediterranean cores by means of isochronous lithologies (tephra layers and sapropels). The climatic record of the Mediterranean is similar in character, phase, and chronology to the records investigated in the equatorial Pacific and in the Caribbean. Isotope stages 1 to 17 have been recognized. Cyclically repeated stagnant cycles resulting in sapropel deposition complicate both the isotopic and the faunal signal. The isotopic investigations reveal that the temperature change in the surface layers of the eastern Mediterranean was no greater than 8°C in the late “glacial” Pleistocene. The chronostratigraphic and biostratigraphic interpretation of Core KS09 indicate that the mean sedimentation rate was 2.4 cm/1000 years, a value very close to the 2.5 cm/1000 years calculated for the entire Quaternary section at DSDP Site 125, also located in the crestal area of the Mediterranean Ridge in the Ionian Basin. The base of KS09 is likely to be very close to the Brunhes/Matuyama boundary dated at 0.7 my.

Summary: Prediction of the drug level in the volume of distribution was made using a numerical model taking into account the following facts: the kinetics of drug release out of the dosage form along the gastrointestinal tract, the kinetics of absorption in the blood compartment and the kinetics of elimination. Various parameters intervene significantly for a given dosage form. Some emphasis was placed upon the rate of elimination of the drug which appears to be the main characteristic for the drug, especially when it is delivered through controlled release dosage forms. The rate of release of the drug out of the dosage form, as well as the dose frequency and the gastrointestinal transit time were also considered. The drug level in the plasma was expressed by the amount of drug as a fraction of the amount of drug initially located in the dosage form.

The concentration-time curve of ciprofloxacin has been assessed in the blood compartment and in the lung tissue following oral administration of the drug. Immediate release and erosion-controlled dosage forms have been examined. A numerical model based on finite differences and taking into account all relevant data has been built: the kinetics of drug release in the gastrointestinal tract, drug absorption in the blood compartment and elimination, and the transient diffusion of the drug through the lung tissue. A partition coefficient for the drug at the tissue-blood interface has been considered to express the drug concentration at the tissue surface. The effect of dose frequency and erosion rate on the antibiotic versus time curves in the plasma and the lung tissue has been studied in detail.

Modeling of the kinetic of moisture adsorption by wood has been studied by using cubic samples. The model is based on an explicit numerical method with finite differences. Experiments have been carried out either for determining the data necessary for calculations (diffusivity, amount adsorbed at equilibrium) and for testing the validity of the model. Two different experiments have been done in case of the longitudinal adsorption: the one by increasing the relative humidity of the atmosphere following a discontinuous step by step process. The other by determining the kinetic adsorption of moisture by samples previously equilibrated under the same conditions when they are contacted with atmosphere at various R. H. Good correlations are obtained between calculated values and experiments in both cases. Although the actual paper is concerned with constant diffusivity, the model is capable to use concentration-dependent diffusivities.

Abstract: The drug level-time history in plasma and lung tissue was calculated with an antibiotic orally delivered in either an immediate-release or a controlled-release dosage form. The drug profiles were compared with experiment results given in the literature. In the same way, the drug level was evaluated in the bronchial secretion in contact with lung tissue. A numerical model, based on finite differences taking all the known facts into account was built and tested with the data found in the literature. Transport of the drug was looked at, including a stage of diffusion through the thickness of the lung tissue and a stage of convection into the bronchial secretion. A few parameters were thus considered, including the thickness of the lung tissue and the diffusivity of the antiobiotic through the tissue, the thickness of the bronchial secretion and the coefficient of convective transport into the sputum which characterizes its viscosity. Two partition factors were also introduced for the drug: between the tissue and the serum and between the lung tissue and the bronchial secretion.

The purpose of this study was to define the bone metabolic properties during the postfracture period in elderly women with hip fracture. Osteocalcin (Oc), a marker of bone formation, was measured in 58 women with hip fracture (77 ± 7 years) admitted to the hospital from their own homes. Serum samples were taken on average 5 h (range 1–21) from fracture and at follow-up, on average 4.6 months later. Comparison was made with 58 age-matched (79 ± 5 years) women. Women with hip fracture had initially 30% lower Oc levels compared to the controls (p = 0.0001). The Oc level was independent of time elapsed from trauma, within 18 h, after which the level further decreased. At follow-up, Oc showed a 44% increase (p = 0.0001) and had reached the level of the controls, but not beyond it. A concomitant, but less marked increase was noted for alkaline phosphatase (ALP) (p = 0.0001). We conclude: that although the bone formation, as assessed by Oc, is apparently lower in elderly women who sustain a hip fracture, the ability to induce a fracture response, with an increased bone turnover during fracture healing is intact. Subsequently, it is essential that a time perspective is applied, as the bone metabolic changes in patients having sustained a fracture are related to the time elapsed from fracture.