[Forced delivery instead of postmortem cesarean section]. / Accouchement forcé en lieu et place de l'opération césarienne post mortem.

The Lex Regia stipulated that no pregnant women shall be buried unless the child has been removed from her womb. The post mortem caesarean delivery was upheld till 1861 by the majority of obstetricians but nevertheless, anterior to the XIXth century, in 1729, Delamotte practiced delivery in the agonising patient in the absence of labour in view to bypass the cesarean section in hope of better child survival. This article describes the beginning of forced ante mortem delivery upon post mortem cesarean section, which contributed to a decrease in child mortality.

[Cadavers and mummies as therapeutic means]. / Le cadavre et la momie utilisés à des fins thérapeutiques.

Sickness befallen onto him, man found that plant and animal derivatives invigorated him. Thereafter, he found a therapeutic benefit in using man as a means of self cure and especially, dead man from violent death. The foam of the skull of cadaver was an excellent antiepileptic as well as blood coming out from a freshly decapitated man. By applying on diseased parts of his body, so as to get rid of inflammation or infection, cadaver's hands were used against tumors of all kinds. Dead human skin were processed into belts and used therein for helping delivery of parturition women. The mummy must be blackish, foul smelling and hard. Those who were whitish, odorless and powder-like, were unfit for use. Mummy powder applied to the nose would stop nose bleeding. Ambroise Paré (1510-1590) was an adversary of those practices.

[Medicinal leeches]. / Les sangsues.

Leeches are hermaphroditic and hematophagous annelids. One important medical species, Hirudo medicinalis, comes from hirudiniculture of fresh water pools. Thanks to their three mandibles with some 300 teeth on their anterior muscular sucker, they easily grab to tissues and by secreting their saliva containing numerous powerful enzymes, such as hyaluronidase, collagenase and inhibitors of platelet aggregation and coagulation, like hirudin, allow blood sucking. Once they are full of blood (up to 15 g of blood), they detach themselves from their prey. Used ever since the 18th Egyptian Dynasty, leeches became famous during the first part of the XIXth century, thanks to a French physician, François Joseph Victor Broussais, known to his adversaries as the "vampire of medicine" for treating various conditions such as phlebotomy, laryngitis, ocular problems, obesity, mental disorders, etc. Overfishing, therapeutic failures and most particularly, the emergence of hygiene, brought the decline of living leeches. In 1884, an extract of leeches was obtained--hirudin and henceforth used. Nowadays, leeches are still used in microsurgery to enhance the venous circulation in finger reimplantation or skin flap transposition. Hirudin is synthesized through recombinant DNA technology and molecules such as lepirudin and desirudin are available on the market as anticoagulant.

Chemometric treatment of vanillin fingerprint chromatograms. Effect of different signal alignments on principal component analysis plots.

This study describes the chemometric treatment of vanillin fingerprint chromatograms to distinguish vanillin from different sources. Prior to principal component analysis, which is used to discriminate vanillin from different origins, the fingerprints are aligned. Three alignment algorithms are tested, correlation optimized warping (COW), target peak alignment (TPA) and semi-parametric time warping (STW). The performance of the three algorithms is evaluated and the effect of the different alignments on the PCA score plots is investigated. The alignment obtained with STW differs somewhat from that with COW and TPA. However, equivalent score plots were obtained regarding the different vanillin groups.

Evaluation of chemometric techniques to select orthogonal chromatographic systems.

Several chemometric techniques were compared for their performance to determine the orthogonality and similarity between chromatographic systems. Pearson's correlation coefficient (r) based color maps earlier were used to indicate selectivity differences between systems. These maps, in which the systems were ranked according to decreasing or increasing dissimilarities observed in the weighted-average-linkage dendrogram, were now applied as reference method. A number of chemometric techniques were evaluated as potential alternative (visualization) methods for the same purpose. They include hierarchical clustering techniques (single, complete, unweighted-average-linkage, centroid and Ward's method), the Kennard and Stone algorithm, auto-associative multivariate regression trees (AAMRT), and the generalized pairwise correlation method (GPCM) with McNemar's statistical test. After all, the reference method remained our preferred technique to select orthogonal and identify similar systems.

Class identity assignment for amphetamines using neural networks and GC-FTIR data.

An exploratory analysis was performed in order to evaluate the feasibility of building of neural network (NN) systems automating the identification of amphetamines necessary in the investigation of drugs of abuse for epidemiological, clinical and forensic purposes. A first neural network system was built to distinguish between amphetamines and nonamphetamines. A second, more refined system, aimed to the recognition of amphetamines according to their toxicological activity (stimulant amphetamines, hallucinogenic amphetamines, nonamphetamines). Both systems proved that discrimination between amphetamines and nonamphetamines, as well as between stimulants, hallucinogens and nonamphetamines is possible (83.44% and 85.71% correct classification rate, respectively). The spectroscopic interpretation of the 40 most important input variables (GC-FTIR absorption intensities) shows that the modeling power of an input variable seems to be correlated with the stability and not with the intensity of the spectral interaction. Thus, discarding variables only because they correspond to spectral windows with weak absorptions does not seem be not advisable.

Development of a ginkgo biloba fingerprint chromatogram with UV and evaporative light scattering detection and optimization of the evaporative light scattering detector operating conditions.

A fingerprint chromatogram of a standardized Ginkgo biloba extract is developed on a monolithic silica column using a ternary gradient containing water, iso-propanol and tetrahydrofuran. For the detection, UV and evaporative light scattering (ELS) detectors are used, the latter allowing detection of the poor UV absorbing compounds as ginkgolides (A-C and J) and bilobalide in the extract. The complementary information between the UV and ELS fingerprint is evaluated. The ELS detector used in this study can operate in an impactor 'on' or 'off' mode. For each mode, the operating conditions such as the nebulizing gas flow rate, the drift tube temperature and the gain are optimized by use of three-level screening designs to obtain the best signal-to-noise (S/N) ratio in the final ELS fingerprint chromatogram. In both impactor modes, very similar S/N ratios are obtained for the nominal levels of the design. However, optimization of the operating conditions resulted, for both impactor modes, in a significant increase in S/N ratios compared to the initial evaluated conditions, obtained from the detector software.

Orthogonality and similarity within silica-based reversed-phased chromatographic systems.

The starting point of this study was a current set of 32 chromatographic systems used to select initial conditions for method development to determine the impurity profile of a drug. The system exhibiting the best selectivity is then selected for further method development. In this current set eight silica-based phases are applied in conjunction with four mobile phases at different pH. In order to save time and resources, the possibilities for a meaningful subset selection were investigated. The most differing systems in terms of selectivity, in other words only the most orthogonal systems, need to be selected. Since the stationary phases are all silica-based, the selectivity differences are examined within a more homogeneous group than if, for instance, also zirconia- or polymer-based columns would be involved. To select the subset of systems also the best overall separation performances are taken into account. The selection is based both on the HPLC-DAD data of a generic set of 68 drugs, and on the LC-MS-DAD results for a mixture of 15 drugs, less different in structure. The orthogonality is evaluated using weighted-average-linkage dendrograms and color maps, both created from the Pearson-correlation coefficients r between normalized retention times r. The Derringer's desirability functions are applied to define the systems with the best overall separation performances. Proposals for different representative subsets of the initial 32 systems are made.

Automatic program for peak detection and deconvolution of multi-overlapped chromatographic signals part I: peak detection.

A series of two papers describing a procedure for automated peak deconvolution is presented. The goal is to develop a package of routines that can be used by non-experienced users. Part I (this paper) concerns peak detection, whereas Part II is dedicated to the deconvolution itself. In this first part, the most interesting features of the peak detection algorithms, which precede the deconvolution step, are outlined. High-order derivatives provide valuable information to assess the number of underlying compounds under a given peak cluster. A smoothing technique was found essential to compute properly the derivatives, since the noise is amplified when differences are calculated. The Savitsky-Golay smoother was applied in combination with the Durbin-Watson criterion to automate the window size selection. This strategy removed the noise without loosing valuable information. In some cases, it was found preferable to split the chromatogram in different elution regions, and apply the Durbin-Watson test and the Savitsky-Golay smoother to each region, separately. The derivatives allowed obtaining estimates of both peak parameters and the corresponding ranges for each eluting compound to be used in the deconvolution. An algorithm oriented to compare peaks from different chromatograms is also presented to perform deconvolution, using information from several related chromatograms.

Automatic program for peak detection and deconvolution of multi-overlapped chromatographic signals part II: peak model and deconvolution algorithms.

Several interlinked algorithms for peak deconvolution by non-linear regression are presented. These procedures, together with the peak detection methods outlined in Part I, have allowed the implementation of an automatic method able to process multi-overlapped signals, requiring little user interaction. A criterion based on the evaluation of the multivariate selectivity of the chromatographic signal is used to auto-select the most efficient deconvolution procedure for each chromatographic situation. In this way, non-optimal local solutions are avoided in cases of high overlap, and short computation times are obtained in situations of high resolution. A new algorithm, fitting both the original signal and the second derivatives is proved to avoid local optima in intermediate coelution situations. This allows achieving the global optimum without the need of background knowledge by the user. A previously reported peak model, a Gaussian with a polynomial standard deviation whose complexity can be modulated to enhance the fitting quality, was applied. However, the original formulation was modified to account baseline outside the peak region. Also, the optimal model complexity was auto-selected via error propagation theory. The method is able to process simultaneously several related chromatograms. The software was tested with both simulated and experimental chromatograms obtained with monolithic silica columns.

Prediction of total green tea antioxidant capacity from chromatograms by multivariate modeling.

In this paper, a fast strategy for determining the total antioxidant capacity of Chinese green tea extracts is developed. This strategy includes the use of experimental techniques, such as fast high-performance liquid chromatography (HPLC) on monolithic columns and a spectrophotometric approach to determine the total antioxidant capacity of the extracts. To extract the chemically relevant information from the obtained data, chemometrical approaches are used. Among them there are correlation optimized warping (COW) to align the chromatograms, robust principal component analysis (robust PCA) to detect outliers, and partial least squares (PLS) and uninformative variable elimination partial least squares (UVE-PLS) to construct a reliable multivariate regression model to predict the total antioxidant capacity from the fast chromatograms.

Updating multivariate calibrations with the delaunay triangulation method.

Multivariate calibrations must be updated when new samples show different spectral characteristics. In this paper, we discuss how to do this when the calibration is performed with a topological multivariate calibration method based on Delaunay triangulation (DT). The updating leads either to the expansion of the original calibration set or to the creation of a new local model. Outliers in the new samples with respect to the original calibration set are first detected and divided in two groups, namely, marginal outliers, which are considered to be extensions of the calibration set and are used for updating the calibration set, and true outliers. If a sufficient number of true outliers are found to be situated close enough to each other, they can form the basis for a new local model. Several updating simulations performed on a real data set show that the updating procedure performs well. The results for prediction with the DT method after updating are comparable to or better than those after updating with partial least squares (PLS) and it is concluded that, in many cases, the DT method is a valuable alternative for multivariate calibration.

Classification of drugs in absorption classes using the classification and regression trees (CART) methodology.

Classification and regression trees (CART) were evaluated for their potential use in a quantitative structure-activity relationship (QSAR) context. Models were build using the published absorption values for 141 drug-like molecules as response variable and over 1400 molecular descriptors as potential explanatory variables. Both the role of two- and three-dimensional descriptors and their relative importance were evaluated. For the used dataset, CART models showed high descriptive and predictive abilities. The predictive abilities were evaluated based on both cross-validation and an external test set. Application of the variable ranking method to the models showed high importances for the n-octanol/water partition coefficient (logP) and polar surface area (PSA). This shows that CART is capable of selecting the most important descriptors, as known from the literature, for the absorption process in the intestinal tract.

Prediction of gastro-intestinal absorption using multivariate adaptive regression splines.

Multivariate adaptive regression splines (MARS) and a derived method two-step MARS (TMARS) were used for modelling the gastro-intestinal absorption of 140 drug-like molecules. The published absorption values for these molecules were used as response variable and calculated molecular descriptors as potential explanatory variables. Both methods were compared and their potential use in quantitative structure-activity relationship (QSAR) context evaluated. The predictive abilities of the models were studied using different sequences of Monte Carlo cross validation (MCCV). It was shown that both types of models had good predictive abilities and that for the data used, MARS gave better results than TMARS. It could be concluded that both methods could be valuable for QSAR modelling.

The chemical composition of idiopathic nonarteriosclerotic cerebral calcifications.

Calculi from a case of cerebral idiopathic nonarteriosclerotic calcification (Fahr's disease) were examined. The stone consists of hydroxyapatite and possesses a typical structure: the calcification process seems to be initiated by the formation of small round bodies that are cemented to each other to form the final stone. Calcified vessels are also present, but seem to be a secondary effect. From a comparison with other calcifications, it is concluded that no pathologic significance should be attached to the relatively high levels of trace metals such as zinc, iron, copper, magnesium, lead, and others, with the possible exception of manganese. The organic matrix of the stone contains large quantities of protein. On hydrolysis of this fraction, an important unidentified ninhydrin-positive peak was found. No mucopolysaccharides were found.

Investigation of the geographical distribution of female cancer patterns in Belgium using pattern recognition techniques.

Different multivariate methods have been applied to obtain an overview of the Belgian female cancer mortality distribution. The resulting maps and figures show the patterns of female cancer mortality to be strongly geographically determined. Two major trends can be derived namely along the north-south axis and along the east-west axis of the country. The cancer sites responsible for these patterns are identified.

Risk of malnutrition in retirement homes elderly persons measured by the "mini-nutritional assessment".

BACKGROUND: The combined influence of age-associated factors such as general health, degree of dependency, diminished odor perception, and poor oral health on the risk for malnutrition was explored. METHODS: A total of 81 persons living in retirement homes took part in the study (mean age 83.4 years, SD = 6.6, range 61-98). The Mini-Nutritional Assessment (MNA) was used to evaluate the risk of malnutrition. Odor perception was measured by the detection threshold for isoamylacetate. The number of drugs taken by each person was counted. General health status was determined by the Medical Outcome Study (MOS) scores. Oral examinations were carried out to count the number of natural teeth and type of dentures. RESULTS: On average, women had slightly, but significantly, lower MNA scores than men (respectively, 23.4, SD = 2.8; and 24.6, SD = 2.6; p = .048). The correlations between age and MNA score and between odor perception and MNA score were not significant. Significant correlations were found between age and number of natural teeth (r = -.26, p = .001) and between MNA score and number of natural teeth (r = .27, p = .001). The mean MNA score of complete denture wearers (22.8, SD = 2.9) was significantly lower than that of partial denture wearers (25.8, SD = 2.9; p = .0005). The total MOS and MNA scores were not correlated, but a significant correlation was found with the subscales mental functioning (r = .29, p = .003), social functioning (r = . 19, p = .045), and perceived health (r = .19, p = .047). No relation was found between the activities of daily living (ADL) and MNA scores. A significant negative correlation was observed between number of drugs taken and the MNA score (r = -.34, p = .001). When participants without risk of malnutrition (MNA > or = 24) were compared with those at risk (MNA = 17-23.5), again, the number of drugs taken was significantly different (on average, respectively, 4.5, SD = 2.9; and 7.0, SD = 2.6; p < .0005). Using multiple regression to test the separate effects of the different independent variables, the number of drugs taken showed a significant negative regression coefficient (beta = -.31, p = .008), as did the mental health score (beta = .27, p =.02), giving a total R2 = .32. The other parameters did not contribute significantly. CONCLUSION: Among the elderly in retirement homes, the health state (as measured by the MOS subscale mental health and by the medication use) appears to be the most clinically relevant parameter to explain the risk for malnutrition. Loss of natural teeth and perceived health are less independently contributing, whereas no contribution derives from decline of odor perception, degree of dependency, and age itself.

Food odor thresholds in relation to age, nutritional, and health status.

Odor perception plays an important role in nutrition. In the present study, the effect of aging and health status on detection of food odors is shown and interrelations with nutritional status are explored. We have tested 26 healthy young (20-25 yrs) and 23 elderly (61-74 yrs) subjects who were screened according to the SENIEUR protocol. Anthropometric measures and blood samples provided 20 parameters of nutritional status. A validated measurement procedure under forced choice conditions was used to quantify the detection thresholds of two food odors of which one had a trigeminal effect and the other mainly had an olfactory effect. There is a significant declining sensitivity for both odors. Our observations indicate that a relation between nutrition and odor perception in the elderly population exists. Whether olfactory deficits cause or are caused by increased nutritional risk deserves further study.

A morphological and chemical study of calcification of the pineal gland.

A general scheme of analysis for the investigation of minute calcification is presented. After low temperature ashing, the samples are subjected to chemical, structural and morphological study, using atomic absorption spectrometry, infrared spectrometry, X-ray diffraction and scanning electron microscopy. Details about the calcification of the human pineal gland are given. The content of trace elements is very high, but within the limits found in other biological apatites. It is concluded that calcification of the pineal is a more general occurence than has been realized.

A morphological and chemical study of calcification of the choroid plexus.

Human choroid plexus was submitted to low temperature ashing (LTA) in order to isolate the calcification. The ashing residue was then subjected to morphological, chemical and structural studies using technics such as scanning electron microscopy, flame and flameless atomic absorption spectrometry, infrared spectrometry and X-ray diffraction. Morphologically, the calcification consisted of wound-up fibers forming granules with a diameter of 0.05 to 0.15 mm. The concretions were identified as cristalline Ca3(PO4)2 and hydroxylapatite. The content of trace elements was high, but within the limits found in other biological apatites. In some cases, however, the Fe content exceeded these limit values.