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PubMed1996

Coronary artery spasm in patients with normal or near normal coronary arteries. Long-term follow-up of 277 patients.

Most studies on the natural course of coronary artery spasm in patients with normal or nearly normal coronary arteries are based on medium-term follow-up in small populations. The present series includes 277 successive patients with a median follow-up of 89 months (range: 1 to 198 months). There were 206 men and 71 women whose mean age was 53.6 +/- 9.3 years. They were all assessed with coronary arteriography which revealed no stenoses greater than 50%. Spasm was confirmed during the coronary arteriography in 157 patients (56.7%), by a positive provocation test following the arteriography in 113 patients (40.8%), and by an electrocardiogram which showed Prinzmetal's variant angina in seven patients (2.5%). The majority of patients, 264 (95.3%) were treated with calcium channel blockers. At the end of this study: 35 patients (12.6%) were lost to follow-up; 20 patients (7.2% died) including 10 (3.6%) from cardiac causes; 18 patients (6.5%) experienced myocardial infarction in 11 of whom repeat coronary arteriography consistently demonstrated one or more significant stenoses (greater than 70%); 109 patients (39%) had persistent angina, in 52 of whom the severity (more than one episode per month) warranted repeat coronary arteriography which detected significant stenosis in 19 cases; 95 patients (34.3%) were asymptomatic. Multivariate statistical analyses showed that only predictors of major coronary events (death, myocardial infarction or angina requiring repeat coronary arteriography) were systemic hypertension or the finding of minor parietal irregularities on the initial coronary arteriogram. Conclusion. Despite treatment with calcium channel blockers, persistent or recurrent episodes of angina are frequently observed whereas complications such as myocardial infarction or death are rare.

Adult↗
PubMed1999

Quantitative characterization and study of the relationship between constitutive-facultative skin color and phototype in Caucasians.

In this study constitutive and facultative colorimetric values were quantified to determine the physiologic changes in Caucasian skin color and to define the correlation between skin color and phototype assessed according to the Fitzpatrick method. Our population consisted of 401 subjects ranging in age from 24 to 28 years with similar life styles. Skin color was measured with a Minolta CR-200 colorimeter on the upper medial quarter of the buttock (constitutive color) and on the cheek (facultative color). Advanced multivariate statistical analysis allowed differentiation between constitutive and facultative skin color in relation to the phototype to be quantified. Moreover, Kullback divergence showed that the probability of correctly determining a subject's phototype is high when the variables of constitutive and facultative skin color are considered together. This interesting result makes it possible, in the future, to use colorimetric values of exposed and nonexposed skin, together with determination of Fitzpatrick phototype and of other phenotypic characters, to better predict cutaneous sun reactivity.

Adult↗
PubMedDate not supplied

The nonsurgical treatment of patients with periodontal disease: results after 6.4 years.

In a previous study involving patients at the dental clinic of the Detroit Receiving Hospital, 87% of teeth that initially had been recommended for surgery or extraction were spared either treatment through a combination of debridement and short-term usage of antimicrobial agents. The object of the present study was to determine what changes occurred to these teeth after 6.4 years in the maintenance phase of treatment. Patients were scheduled for maintenance therapy at three-month intervals over a period of 6.4 years. They were evaluated "annually" (that is, the patients were scheduled for annual visits) for surgical needs by a clinician who was not aware of the treatment received by the patients. Multivariate statistical models were used to determine which variables predicted subsequent surgical needs. The initial treatment benefits were sustained, as the majority of patients showed no increase in surgical needs after 6.4 years. When relapse occurred, those who were smoking when the study began and an increased number of sessions of debridement were predictors. Surgical needs were reduced when metronidazole was dispensed after the first and second annual examinations.

Age Factors↗
PubMed1997

Identification of protein coding regions in the human genome by quadratic discriminant analysis.

A new method for predicting internal coding exons in genomic DNA sequences has been developed. This method is based on a prediction algorithm that uses the quadratic discriminant function for multivariate statistical pattern recognition. Substantial improvements have been made (with only 9 discriminant variables) when compared with existing methods: HEXON [Solovyev, V. V., Salamov, A. A. & Lawrence, C. B. (1994) Nucleic Acids Res. 22, 5156-5163] (based on linear discriminant analysis) and GRAIL2 [Uberbacher, E. C. & Mural, R. J. (1991) Proc. Natl. Acad. Sci. USA 88, 11261-11265] (based on neural networks). A computer program called MZEF is freely available to the genome community and allows users to adjust prior probability and to output alternative overlapping exons.

Base Sequence↗
PubMed1998

Morphometric multivariate analysis of field samples of adult Anopheles arabiensis and An. gambiae s.s. (Diptera: Culicidae).

The Afrotropical complex of sibling species Anopheles gambiae Giles includes the most efficient vectors of human malaria south of the Sahara. Anopheles arabiensis Patton and An. gambiae s.s. Giles are the members of the complex more adapted to the human environment. They are sympatric and synchronic over most of their distribution range; however, they show a different involvement in malaria transmission, with An. gambiae being more anthropophilic and endophilic than An. arabiensis. Discriminating between them is essential for a correct assessment of epidemiological parameters. The identification is currently achieved through recognition of species-specific chromosomal inversions or by molecular biology techniques. Both methods require considerable technical resources, not always available in the field. We carried out a morphometric analysis of field and laboratory samples of An. arabiensis and An. gambiae s.s. from sites in Madagascar, Burkina Faso, Mali, and Liberia to evaluate the degree of morphological differentiation. We examined 17 morphometric characters in samples representing each of the geographic sites. All of the measures were significantly larger for An. arabiensis (regardless of the collection site), demonstrating an intrinsic greater body size of this species. To assess the reliability associated with the multivariate statistic, we applied the discriminant function analysis, which provided a method for predicting to which group a new case will most likely be assigned. In a blind experiment, the morphometric method correctly identified approximately 85% of field-collected An. arabiensis and An. gambiae s.s., which provided a relatively simple method to approximate the relative frequencies of the 2 species in areas in which their concurrent presence was already known. The influence of laboratory conditions on the morphometrics of the 2 species was also analyzed.

Animals↗
PubMedDate not supplied

[Disordered higher mental functions in lesions of different parts of the caudate nucleus].

The relation between deterioration in higher mental functions and localization of the brain pathological process was studied in 22 patients with arteriovenous malformation in the head or/and the body of the caudate nucleus using the methods of multivariate statistics and structurally organized neuropsychological information. It was shown that the lesions in the caudate nucleus body resulted in disturbances of the spatial functions. Pathological foci in the head of the caudate nucleus were associated with memory disorders (the right-side foci were accompanied by deterioration in the visual memory and the left-side ones by that in the audio-verbal memory) and modification of programming and control of voluntary activity.

Adolescent↗
PubMed2000

Nonhistological diagnosis of human cerebral tumors by 1H magnetic resonance spectroscopy and amino acid analysis.

We describe a multivariate analysis procedure to classify human cerebral tumors nonhistologically in vitro, combining the use of 1H magnetic resonance spectroscopy (MRS) with automatic amino acid analysis of biopsy extracts. Eighty-one biopsies were obtained surgically and classified histologically in eight classes: high-grade astrocytomas (class 1, n = 19), low-grade astrocytomas (class 2, n = 10), normal brain (class 3, n = 9), medulloblastomas (class 4, n = 4), meningiomas (class 5, n = 18), metastases (class 6, n = 8), neurinomas (class 7, n = 9), and oligodendrogliomas (class 8, n = 4). Perchloric acid extracts were prepared from every biopsy and analyzed by high resolution 1H MRS and automatic amino acid analysis by ionic exchange chromatography. Intensities of 27 resonances and ratios of resonances were measured in the 1H MRS spectra, and 17 amino acid concentrations were determined in the chromatograms. Linear discriminant analysis provided the most adequate combination of these variables for binary classifications of a biopsy between any two possible classes and in multiple choice comparisons, involving the eight possible classes considered. Correct diagnosis was obtained when the class selected by the computer matched the histological diagnosis. In binary comparisons, consideration of the amino acid profile increased the percentage of correct classifications, being always higher than 75% and reaching 100% in many cases. In multilateral comparisons, scores were: high-grade astrocytomas, 80%; low-grade astrocytomas, 74%; normal brain, 100%; medulloblastomas, 100%; meningiomas, 94.5%; metastases, 86%; neurinomas, 100%; and oligodendrogliomas, 75%. These results indicate that statistical multivariate procedures, combining 1H MRS and amino acid analysis of tissue extracts, provide a valuable classifier for the nonhistological diagnosis of biopsies from brain tumors in vitro.

Algorithms↗
PubMed2006

The assessment of plant metabolite profiles by NMR-based methodologies.

NMR-based metabolic profiling techniques can simultaneously track changes in many plant metabolites and have found a number of applications in both systems biology and biosafety. Together with multivariate statistical analyses, NMR spectroscopy has been successfully applied to the characterisation of various herbs and plant products for quality control, authentication, determining geographical origin and for detecting adulteration of products. Additionally, the metabolic consequences of plant extracts have been demonstrated in experimental animals and in man using NMR-based metabonomics approaches to characterise the response. Here the application of NMR spectroscopy and chemometric tools for analysing plant-based products and their metabolic consequences are considered with particular emphasis on deconvolving biological complexity and minimising confounding biological variability with analytical 'noise'.

Animals↗
PubMed2000

Hypothyroidism after iodine-131 or surgical therapy for Graves' disease hyperthyroidism.

BACKGROUND: The aim of this work was to describe late permanent hypothyroidism after iodine-131 or surgery, and to seek predictive factors of hypothyroidism for the two treatments. MATERIAL: From 1979 to 1994, 462 patients with Graves' disease hyperthyroidism underwent definitive treatment. Three hundred and fifty-five patients were treated with low calculated doses of iodine-131, and 107 patients with subtotal thyroidectomy. Life-table analysis was performed and the cumulative incidence of hypothyroidism was calculated by Kaplan-Meier's method, and survival (euthyroidism) within the groups was compared by the Mantel-Cox method. RESULTS: Of the 355 patients treated with one dose of 6.6 1.9 mCi of iodine-131, 246 became euthyroid after one dose, and 109 needed 2 or more doses. Twenty-two patients received one or more doses higher than 10 mCi. The probability of euthyroidism at 145 months after low-dose was 10. 19% and age, sex, pretreatment with antithyroid drugs, previous subtotal surgery did not influence the final outcome. Of the 107 surgically treated patients the probability of euthyroidism at 144 months was 56.1%. Age, sex, duration of hyperthyroidism, duration of antithyroid treatment, weight of thyroid resected, did not influence the final outcome. The weight of the thyroid remnant was 5.4 1.5 g and the multivariate statistical model by conditional logistic regression showed that the weight of thyroid remnant was the only variable that influenced long-term thyroid function. CONCLUSIONS: There is no ideal dose of iodine-131 that would correct hyperthyroidism in Graveś disease without risk of hypothyroidism. Surgery is an alternative definitive treatment with a risk of hypothyroidism within the 2 first years, and a cumulative risk of hypothyroidism lower than with iodine-131.

Adult↗
PubMed1995

Combination of computerized morphonuclear and multivariate analyses to characterize in vitro the antineoplastic effect of alkylating agents.

The influence of 13 anticancer alkylating agents on cell proliferation, cell cycle parameters, and morphonuclear characteristics was monitored in vitro on three neoplastic cell lines. This monitoring was carried out by means of the digital cell image analysis of Feulgen-stained nuclei. This computer-assisted microscope analysis of chromatin texture made it possible to assess 15 morphonuclear parameters. These 15 parameters were submitted to multivariate analyses, that is, principal-components analyses followed by the canonical transformation of the data. The 13 alkylating agents included four nitrogen mustards (chlormethine, chlorambucil, melphalan, and cyclophosphamide), two nitrosoureas (carmustine and lomustine), two platinum analogues (cisplatine and carboplatine), two ethyleneimine derivatives (thiotepa and investigational PE1001), one antibiotic (mitomycin C), one alkylsulfonate (busulfan), and one triazene (dacarbazine). The mouse MXT mammary and the human J82 and T24 bladder tumor cell lines were used in this study. The results show that these alkylating agents induced specific modifications to the chromatin pattern according to the subclass to which they belong. In other words, the multivariate statistical analyses of the 15 parameters made it possible to identify, at least partly, distinct subclasses of alkylating agents according to their mechanisms of action. As a validation of the methodology, the results also show that most of the alkylating agents induced an increase in the percentage of cells in the G2 phase, while some sometimes induced an increase in the percentage of cells in the S phase of the cell cycle.

Adenocarcinoma↗
PubMed1998

Optimization of phosphorus localization by EFTEM of nucleic acid containing structures.

Energy Filtered Transmission Electron Microscopy (EFTEM) has been used to study nucleic acids localization in unstained thin sections of virus-infected cells. For this purpose, phosphorus maps (P-maps) have been obtained by applying the N-windows Egerton model for background subtraction from data acquired by a non-dedicated TEM Jeol 1200EXII equipped with a post-column PEELS Gatan 666-9000 and a Gatan Image Filter (GIF-100). To prevent possible errors in the evaluation of elemental maps and thus incorrect nucleic acid localization, we have studied different regions of swine testis (ST) cells with similar local density containing either high concentration of nucleic acids (condensed chromatin and ribosomes) or a very low concentration (mitochondria). Special care was taken to optimize the sample preparation conditions to avoid as much as possible the traditional artifacts derived from this source. Selection of the best set of pre-edge images for background fitting was also considered in order to produce "true P-maps". A new software for interactive processing of images series has been applied to estimate this set. Multivariate Statistical Analysis was used as a filtering tool to separate the "useful information" present in the inelastic image series (characteristic signal) from the "non-useful information" (noise and acquisition artifacts). The reconstitution of the original image series preserving mainly the useful information allowed the computation of P-maps with improved signal-to-noise ratio (SNR). This methodology has been applied to study the RNA content of maturation intermediate coronavirus particles found inside infected cells.

Animals↗
PubMed1999

Costs of Mini Mental State Examination-related cognitive impairment.

OBJECTIVE: To investigate the relationship between cognitive impairment, measured with the Mini Mental State Examination (MMSE), and the cost of care. DESIGN: The study uses data from the Kungsholmen project, a population-based study in Sweden in which people 75 years and older were observed over time. The initial study population (n = 1810) was divided into 4 health states based on the MMSE. A Markov model was constructed from the transition probabilities between different states between the first and second phases of the study. The expected cost of cognitive impairment for a period of 10 years was estimated for the cohort of patients studied. MAIN OUTCOME MEASURES AND RESULTS: There was a strong correlation between cognitive impairment in terms of the MMSE and the annual cost of care. A multivariate statistical analysis showed that a decrease in the MMSE by 1 point was associated with an increase in the cost of care of 15,000 Swedish kronor (SEK) [$US2000; 1995 values]. CONCLUSIONS: The results show that large savings are possible if the decline in cognitive functioning can be prevented. The model developed can be used to estimate the impact on cost of care of treatments which reduce the cognitive decline in patients with Alzheimer's disease.

Aged↗
PubMedDate not supplied

[Pregnancies complicated by hemorrhage and birth of low birth weight infants in Cotonou (Benin)].

The effect of bleeding during pregnancy on the outcome remains unclear. Nevertheless, some of these pregnancies go to term, raising the question of the effects on the new-born infant. The data concerning a possible correlation with low birth weight are ambiguous. Furthermore, there are few studies of this issue in developing countries. We studied 2168 women giving birth to single children chosen at random in two maternity services in Cotonou (Benin) in 1990. Data was collected by two trained midwives interviewing the women and from the medical files 24 hours after delivery. One hundred and thirty seven mothers (6.2%) reported bleeding during pregnancy. Multivariate statistical analysis indicated that this was associated with preterm birth of low birth weight infants: OR = 4.09 (2.2-7.6) for bleeding during the first trimester, OR = 2.29 (1.1-6.9) during the second and OR = 4.79 (2.1-11.9) during the third. Only bleeding during the third trimester correlated with a significant retardation of intrauterine growth [OR = 2.33 (1.4-7.3)] according to model fitting. Thus, despite possible bias in this retrospective study, bleeding during pregnancy appears to be a predictor of low birth weight in Cotonou (West Africa).

Adult↗
PubMed1996

Intrinsic versus imposed curvature in cyclical oligomers: the portal protein of bacteriophage SPP1.

Large cyclical oligomers may be formed by (curvi-) linear polymerization of monomers until the n(th) monomer locks in with the first member of the chain. The subunits in incomplete structures exhibit a natural curvature with respect to each other which can be perturbed when the oligomer closes cyclically. Using cryo-electron microscopy and multivariate statistical image processing we report herein a direct structural observation of this effect. A sub-population (approximately 15%) of incomplete oligomers was found within a sample of SPP1 bacteriophage portal proteins embedded in vitreous ice. Whereas the curvature between adjacent subunits of the closed circular 13-fold symmetric oligomer is 27.7 degrees, in these incomplete oligomers the angle is only 25.8 degrees, a value which almost allows for a 14-subunit cyclical arrangement. A simple model for the association of large cyclical oligomers is suggested by our data.

Microscopy, Electron↗
PubMed2000

Allelic loss of chromosome 1p and radiotherapy plus chemotherapy in patients with oligodendrogliomas.

INTRODUCTION: Allelic loss of the short arm of chromosome 1 predicts radiographic response to chemotherapy and long overall survival times in patients with anaplastic oligodendrogliomas. Using a database of patients with oligodendrogliomas in whom chromosome 1p status was known, we explored whether allelic loss of 1p also predicted longer duration of tumor control when radiotherapy was part of the initial treatment of these patients. MATERIALS AND METHODS: We measured progression-free survival following radiotherapy in a cohort of patients with World Health Organization (WHO) Grade II and WHO Grade III oligodendrogliomas. The effects on progression-free survival of patient age, Karnofsky performance score (KPS), tumor grade when irradiated and chromosome 1p status were examined by univariate and multivariate statistical analyses. For the subset of patients with newly diagnosed anaplastic oligodendrogliomas, relationships between use of chemotherapy, chromosome 1p status and progression-free survival were also examined. RESULTS: Fifty-five patients (29 male, 26 female; ages 18-75 years; median, 44 years; KPS 50-90, median 80) were irradiated for either a WHO Grade II (n = 19) or Grade III (n = 36) oligodendroglioma. Twenty-eight patients had chemotherapy immediately prior to radiotherapy, and 27 had chemotherapy at progression following radiotherapy. The median radiation dose was 54 Gy in 30 fractions. Loss of heterozygosity (LOH) at chromosome 1p was evident in 36 tumors and absent in 19. Overall median progression-free survival after radiotherapy was 40.4 months. Median progression-free survival was 55.0 months for patients whose tumors harbored 1p loss vs. 6.2 months for those patients whose tumors retained both copies of chromosome 1p (p < 0.001). On both univariate and multivariate analyses, chromosome lp loss was the principal independent predictor of longer progression-free survival for patients with Grade II and III oligodendrogliomas. For Grade III oligodendrogliomas, chemotherapy as an adjunct to radiotherapy prolonged tumor control for those patients whose tumors harbored allelic loss of chromosome 1p (p = 0.004). CONCLUSION: These data suggest allelic loss of chromosome 1p in patients with oligodendroglial neoplasms predicts longer progression-free survival among patients receiving radiotherapy +/- chemotherapy as part of their initial treatment. Chromosome 1p loss may be an important stratification variable in future therapeutic trials of oligodendroglioma.

Adolescent↗
PubMed2003

New methods and software tools for high throughput CDR3 spectratyping. Application to T lymphocyte repertoire modifications during experimental malaria.

Immune repertoires of T or B cells are very often studied by Complementary Determining Region 3 (CDR3) spectratyping. However, data obtained with this method is usually subject to a biased eye analysis. We developed recently the ISEApeaks software package to retrieve and handle peak data from automated sequencers, from which CDR3 spectratype data is obtained. We describe a general strategy for CDR3 spectratype analysis based on two new specific modules and multivariate statistics. The first module addresses the crucial problem of peak smoothing. The second is a toolbox for the analysis of CDR3 spectratypes, which includes perturbation computation, recurrent peak finding, expansion assessment and datamining. To illustrate our approach, we assessed the complex TCRB repertoire modifications induced by Plasmodium berghei ANKA (PbA) infection. This global and exhaustive repertoire analysis approach is of general interest for T- and B-lymphocyte repertoire studies and is currently used in human cohorts in various pathologies and during clinical trials.

Algorithms↗
PubMed2004

Synonymous codon usage analysis of the mycobacteriophage Bxz1 and its plating bacteria M. smegmatis: identification of highly and lowly expressed genes of Bxz1 and the possible function of its tRNA species.

The extent of codon usage in the protein coding genes of the mycobacteriophage, Bxz1, and its plating bacteria, M. smegmatis, were determined, and it was observed that the codons ending with either G and / or C were predominant in both the organisms. Multivariate statistical analysis showed that in both organisms, the genes were separated along the first major explanatory axis according to their expression levels and their genomic GC content at the synonymous third positions of the codons. The second major explanatory axis differentiates the genes according to their genome type. A comparison of the relative synonymous codon usage between 20 highly- and 20 lowly expressed genes from Bxz1 identified 21 codons, which are statistically over represented in the former group of genes. Further analysis found that the Bxz1- specific tRNA species could recognize 13 out of the 21 over represented synonymous codons, which incorporated 13 amino acid residues preferentially into the highly expressed proteins of Bxz1. In contrast, seven amino acid residues were preferentially incorporated into the lowly expressed proteins by 10 other tRNA species of Bxz1. This analysis predicts for the first time that the Bxz1-specific tRNA species modulates the optimal expression of its proteins during development.

Codon↗
PubMed1995

[Multivariate analysis of graft survival prognostic factors in renal transplantation].

OBJECTIVE: The aim of this paper is to identify the variables that could be of interest in the outcome of a series of cadaveric kidney transplantation performed at the University Hospital, Navarra School of Medicine, by means of multifactorial and multivariate statistical analyses. METHOD: We analyzed 307 cadaveric kidney transplantation performed since 1976 at the University Hospital, School of Medicine, University of Navarra. Two series are included: the historical and the actual. The former did not include cyclosporine A in the immunosuppressor protocol. RESULTS: The first step was to compare survival in both series. The cyclosporine A series had a better survival, which was statistically significant (p < 0.0001). The prognostic factors in both series were also analyzed. The influence of the different variables were studied in the survival distribution. The worse prognostic variables of the historical group on allograft survival were donor's age (particularly between 20 and 50 years old), delayed graft function, serum creatinine level greater than 2.5 mg/dl at the first month following transplantation, general surgical complications, and vascular and other complications. In the actual group, the allografts with the worst survival were in those that received 4-10 pre-transplant blood transfusions, those with more that 2 HLA-DR mismatches, the hyperimmunized receptors with a level of pre-formed cytotoxic antibodies greater than 50%, those who rejected the allograft in the initial post-transplant period, those with a serum creatinine level greater than 2.5 mg/dl and those who presented surgical complications in general and urinary and vascular complications in particular. CONCLUSIONS: The multivariate analysis reveals that the prognostic factors of the historical group were delayed graft function, surgical complications, HLA A+B mismatches and the donor's age. In the actual group, the factors were receptor's age, surgical complications, large ischemia time, peak reactive antibody and number of rejections.

Actuarial Analysis↗