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Mother-to-child transmission of HIV-1 in Congo, central Africa. Congolese Research Group on Mother-to-Child Transmission of HIV.

OBJECTIVE: To assess the risk of mother-to-child transmission of HIV-1 in a central African population and to study maternal factors associated with perinatal transmission. DESIGN: Prospective cohort study of infants born to HIV-1-positive women and controls born to HIV-1-negative women enrolled sequentially in two prenatal clinics and one maternity hospital in Brazzaville, Congo. SUBJECTS AND METHODS: A total of 118 exposed and 208 control infants were followed from birth for at least 2 years. Assessment of infection in children and computation of transmission rate were made according to the European Economic Community/World Health Organization Ghent guidelines (1992). RESULTS: The transmission rate was 40.4% [95% confidence interval (CI), 30.7-50.1]. Maternal age, parity, history of adverse pregnancy outcome or history of decreased children were not associated with transmission. However, independently, women whose relationship with their infant's father was less than 1 year, or women who had symptoms of HIV-1 during pregnancy had an increased risk of transmission [adjusted odds ratios, 11.1 (95% CI, 2.4-50.2) and 10.3 (95% CI, 2.9-37.1), respectively]. CONCLUSION: The transmission rate observed in Congo is in the upper range of the rates reported in Africa. The uneven distribution of cofactors for perinatal transmission, such as the presence of symptoms of HIV disease during pregnancy, may explain some of the variation observed across studies.

Acquired Immunodeficiency Syndrome↗

Evidence for Serpulina hyodysenteriae being recombinant, with an epidemic population structure.

The population structure of Serpulina hyodysenteriae was investigated using multilocus enzyme electrophoresis. A total of 231 isolates were divided into 50 electrophoretic types (ETs), with a mean genetic diversity of 0.29 for the number of ETs and 0.23 for the number of isolates. Subsets of isolates from two Australian states (71 isolates from Victoria and 68 isolates from Queensland) exhibited as much genetic variation as the entire collection. The calculated index of association (IA) for the number of ETs (0.29 +/- 0.17) was not significantly different from zero, and hence provided evidence for the occurrence of significant genetic recombination accounting for the observed variation between strains. In contrast, the IA for the number of isolates (3.93 +/- 0.03) was significantly different from zero, with seven of the 50 ETs (ETs 4, 6, 13, 14, 20, 33 and 35) containing 51% of all the isolates. Even when multiple isolates from the same farm were removed from the analysis, the IA value for the number of isolates remained significantly greater than zero (IA 9.87 +/- 0.04), indicating that it was not biased by their inclusion. The results suggest that S. hyodysenteriae has an epidemic population structure.

Animals↗

Estimation of soil sorption coefficients of veterinary pharmaceuticals from soil properties.

Environmental exposure assessment of veterinary pharmaceuticals requires estimating the sorption to soil. Soil sorption coefficients of three common, ionizable, antimicrobial agents (oxytetracycline [OTC], tylosin [TYL], and sulfachloropyridazine [SCP]) were studied in relation to the soil properties of 11 different soils. The soil sorption coefficient at natural pH varied from 950 to 7,200, 10 to 370, and 0.4 to 35 L/kg for OTC, TYL, and SCP, respectively. The variation increased by almost two orders of magnitude for OTC and TYL when pH was artificially adjusted. Separate soil properties (pH, organic carbon content, clay content, cation-exchange capacity, aluminum oxyhydroxide content, and iron oxyhydroxide content) were not able to explain more than half the variation observed in soil sorption coefficients. This reflects the complexity of the sorbent-sorbate interactions. Partial-least-squares (PLS) models, integrating all the soil properties listed above, were able to explain as much as 78% of the variation in sorption coefficients. The PLS model was able to predict the sorption coefficient with an accuracy of a factor of six. Considering the pH-dependent speciation, species-specific PLS models were developed. These models were able to predict species-specific sorption coefficients with an accuracy of a factor of three to four. However, the species-specific sorption models did not improve the estimation of sorption coefficients of species mixtures, because these models were developed with a reduced data set at standardized aqueous concentrations. In conclusion, pragmatic approaches like PLS modeling might be suitable to estimate soil sorption for risk assessment purposes.

Adsorption↗

[Comparative study of normal and psoriatic skin using a micromethod for detection of enzymatic activity].

We used a semiquantitative micromethod for detection of enzymatic activity (APIZYM) which allows a fast and simultaneous study of 67 hydrolase and dehydrogenase activities on dermo-epidermic skin samples. This wide investigated field led to the determination of the enzymatic profile (called zymogram) of the samples under study. This method was applied to normal skin and to psoriatic and uninvolved psoriatic skin; our results exhibited the good reproductibility of the method and the homogeneity of the studied samples. The enzymatic activities of the psoriatic skin are, in mean, twice those of normal skin. The uninvolved psoriatic skin showed reactions close to those of the normal skin. These observed variations of those different activities are perfectly similar to literature datas. The APIZYM method, thanks to its easy utilization and its fiability seems extremely interesting in the study of zymogram of cutaneous samples. The use of APIZYM in observations on naevus and malignant melanoma is to be exposed in a following publication.

Adult↗

Epidemiology of human leukemia.

The leukemias show clear geographic, racial, ethnic, age, and gender variation in both incidence and mortality, and the patterns of occurrence differ among subtypes. Despite decades of epidemiologic study, the known and suspected risk factors for leukemia are insufficient to explain more than a small fraction of the observed variation in the occurrence of the leukemias. Important contributions to the literature in 1993 included studies further clarifying the role of known risk factors (ionizing radiation, certain chemotherapeutic agents, and specific occupational chemical exposures) and suspected risk factors (infectious agents, electromagnetic fields, cigarette smoking, other chemotherapeutic agents, and additional occupational chemical exposures) in leukemogenesis.

Female↗

Study on thioridazine 5-sulfoxide epimerization and degradation by capillary electrophoresis.

We present a method for the stereoselective analysis of thioridazine 5-sulfoxide (THD 5-SO) in human plasma based on liquid-liquid extraction with diethyl ether and chiral resolution of the stereoisomers by capillary electrophoresis using hydroxypropyl-beta-cyclodextrin and sulfated beta-cyclodextrin as chiral selectors. The method showed recovery rates of 85.5% for both THD 5-SO (slow-eluting, SE) enantiomers. The coefficients of variation observed in the precision studies, as well as the accuracy values, were below 10%. After validation, the method was used to study the stability and configurational changes of this THD metabolite. Our results showed that both enantiomers of THD 5-SO (SE) were stable under conditions of variation of temperatures (38 degrees C, 4 degrees C and -20 degrees C), pH (5.0, 7.0 and 8.5) and ionic strengths (0.2, 0.5 and 1.0 mol/L). The influence of light on the stability of the THD 5-SO (SE) stereoisomers was also studied using standard solutions prepared in methanol and an inversion in configuration was observed under UV light (254 and 366 nm).

Cyclodextrins↗

Individual differences in the macronutrient preference profile of outbred rats: implications for nutritional, metabolic, and pharmacologic studies.

While screening outbred male Holtzman Sprague-Dawley rats for their macronutrient (protein, carbohydrate, and fat) preferences, we noticed substantial group-to-group variation in the preference profile. This led us to analyze preference data on two hundred and seventy rats collected over a three-year period to determine whether preferences could be predicted. The results led us to conclude that observed variations in macronutrient preference profiles may be secondary to genetic heterogeneity in the outbred population. We have also shown that the outcome of the pharmacologic effects of two agents (insulin and enterostatin) on appetitive behavior will vary from animal to animal within a single group. Accordingly, researchers must be aware that the breeding history of the laboratory animal is a major factor in the outcome of the experiment and interpretation of the findings.

Animal Nutritional Physiological Phenomena↗

An explanation for the variation of the sonophoretic transdermal transport enhancement from drug to drug.

Over the last few decades, application of therapeutic ultrasound (frequency between 1 and 3 MHz and intensity between 1 and 2 W/cm2) has been attempted to enhance transdermal transport of several drugs, a method referred to as sonophoresis. The sonophoretic enhancement of transdermal drug transport was found to vary significantly from drug to drug. In certain cases, ultrasound did not induce any enhancement of transdermal drug transport. This variation in the efficacy of sonophoresis has raised a controversy regarding its applicability as a transdermal delivery enhancer. The objective of this paper is to provide a summary of the literature data on sonophoresis and an explanation for the observed variation of the sonophoretic enhancement from drug to drug. This paper also presents an equation to qualitatively predict whether therapeutic ultrasound may enhance transdermal transport of a given drug based on knowledge of the drug passive skin permeability and octanol-water partition coefficient.

Administration, Cutaneous↗

Monitoring transfusion practices at two university hospitals.

BACKGROUND AND OBJECTIVES: Considering the clinical importance of blood transfusions, the limited knowledge of transfusion practices is remarkable. New methods are needed to elucidate the observed variation of transfusion practices. MATERIALS AND METHODS: All patients transfused or pretransfusion tested (i.e. at risk for blood transfusion) at two tertiary teaching hospitals during the full years of 1997 and 1998 were included in the study. RESULTS: The observed practices contained substantial variance at the level of hospitals. The contributions to the total variance of the different specialities were highly significant, as was the contribution of hospitals to the variance in plasma and platelet transfusions. Significant interactions between hospitals and specialities were observed in transfusion of red cells, plasma and platelets. CONCLUSION: To our knowledge this is the first survey of this size to combine transfusions, diagnoses and biochemical tests, exclusively based on an existing computerized register. The aim is to establish a basis for comparison of local transfusion practices with other commensurate hospitals and regions at a national (and international) level.

Adolescent↗

Reduced spectral density mapping of a partially folded fragment of E. coli thioredoxin.

The backbone dynamics of a partially folded, N-terminal fragment of E. coli thioredoxin were investigated using nuclear magnetic resonance spectroscopy (NMR). Relaxation data were collected at three temperatures and analyzed using reduced spectral density mapping. As temperature was increased, the values for the viscosity normalized J(0) and for J(omegaH) increased, while J(omegaN) decreased. The global trend observed for the viscosity normalized J(0) was consistent with an increase in the hydrodynamic volume of the fragment and suggested the presence of correlated rotational motion in the absence of long range interactions. In addition, the residue specific variation observed for the viscosity normalized J(0) suggested contributions to J(omega) from a range of correlation times that are close to the global correlation time.

Data Interpretation, Statistical↗

Variation in the electrophoretic karyotype analysed by the assignment of DNA probes in Candida albicans.

By using pulsed-field gel electrophoresis, we have separated the entire chromosome bands and examined the electrophoretic karyotypes of 27 strains of Candida albicans. The electrophoretic karyotype varied widely among these strains. Their chromosomal DNAs were resolved into 7-12 bands ranging in size from 0.42 to 3.0 Mb. Most of the separated chromosomal bands were assigned by eight cloned C. albicans DNA probes. These results suggest that the haploid number of C. albicans chromosomes is eight. Each of the probes hybridized specifically to one or two bands of similar size in most strains. With the exception of the MGL1 probe, when two bands were detected by one probe, the size of one of them was very conserved whilst the other was of fairly variable size. The sizes of the chromosome bands assigned by the MGL1 probe were much more variable. As C. albicans is considered to be a diploid organism, it is inferred that the karyotype polymorphism between strains is mainly derived from wide size heterogeneity in one of the homologous chromosomes. Furthermore, we have confirmed species-specific and strain-specific variation in medically important Candida species (C. stellatoidea, C. tropicalis, C. parapsilosis, C. krusei, C. guilliermondii, C. kefyr and C. glabrata). Electrophoretic karyotype analysis is thus useful for species assignation. The TUB2 probe, encoding C. albicans beta-tubulin, hybridized to the chromosomal DNA of all the Candida species examined, but four C. albicans probes exhibited cross-species hybridization with C. stellatoidea only. The karyotype of C. stellatoidea seems to be within the range of the intraspecies variation observed in C. albicans.

Candida albicans↗

Radiation dose at small intestinal biopsies in children: results of a national study.

The radiation dose delivered at small intestinal biopsies in children was investigated in a national study engaging 42 of 43 paediatric departments performing small intestinal biopsies. Measurements were performed with a thermoluminescence system at 257 biopsies. The results show a considerable variation of both duration of fluoroscopy (range 2-660 s; department medians) and radiation dose (range 0.1-14 mSv; department medians). The median of all absorbed doses was 0.69 mSv and the median duration of fluoroscopy 30 s. The observed variation cannot be explained by differences in X-ray equipment only. By optimization of all the technical conditions, such as X-ray equipment, biopsy device and method of sedation, at least a 6-fold reduction of radiation dose was obtained in one department. Especially if the operator is less experienced, it is worthwhile to optimize other factors to achieve the lowest possible radiation dose to the child. Children, coeliac disease, fluoroscopy, radiation dose, radiation risk, small intestinal biopsy.

Adolescent↗

Taxonomic status of Ixodes didelphidis (Acari: Ixodidae).

Ixodes didelphilis Fonseca & Aragão was described in Brazil in 1952 as a new tick species that differed from Ixodes loricatus Neumann by the spiracular plate pattern. We have reared four tick colonies from different geographic areas in the laboratory that were started from single engorged females originally identified as I. didelphidis (BMG, colony ) and I. Iocicatus (CSP, PSP, and TRJ colonies). We analyzed the spiracular plate morphology of F1 adult ticks from each tick colony, compared their biological 11th, and performed a molecular analysis of the second internal transcribed rDNA spacer (ITS2) to test the validity of the species I. didelphidis. The spiracular plate analysis of laboratory F1 adult ticks yielded single females from the four colonies showed variations that invalidate morphological parameters for differentiation of loricatus and I. didelphidis. Biological data of the BMC, CSP, and TRJ colonies were similar. The biology ofthe PSP colony was not evaluated. The ITS2 sequence variations observed between the tick colonies ranged from 1.3 to 4.9%, and the similarity tree constructed by the neighbor-joining method with nucleotide distances showerl that the distances between the samples were similar to what is expected for intraspecific variations found in other ticks species. The morphological and biological results, in conjunction with the ITS2 analysis, supported the conspecificity I. loricatus and I. didelphidis.

Animals↗

Population genetic characteristics of the D1S80 locus in seven human populations.

We have analyzed the allele frequency distribution at the highly polymorphic variable number of tandem repeat (VNTR) locus D1S80 (pMCT118) in seven ethnic populations (namely, New Guinea Highlanders of Papua New Guinea, Dogrib Indians of Canada, Pehuenche Indians of Chile, American and Western Samoans, Kacharis of Northeast India, and German Caucasians) using the polymerase chain reaction (PCR) technique. In the pooled sample of 443 unrelated individuals 20 segregating alleles were detected. A trimodal pattern of allelic distribution is present in the majority of populations and is indicative of the evolutionary antiquity of the polymorphism at this locus. In spite of the observed high degree of polymorphism (expected heterozygosity 56%-86%), with a single exception--the marginally significant P value (0.04) of the exact test in American Samoans--the genotype distributions in all populations conform to their respective Hardy-Weinberg expectations. Summary statistics indicate that, in general, the allele frequency distribution at this locus may be approximated by the infinite allele model. The data also demonstrate that alleles that are shared by all populations have the highest average frequency within populations. Furthermore, the kinship bioassay analysis demonstrates that the extensive variation observed at the D1S80 locus is at the interindividual within population level, which dwarfs any interpopulation allele frequency variation, consistent with the population dynamics of hypervariable polymorphisms. These characteristics of the D1S80 locus make it a very useful marker for population genetic research, genetic linkage studies, forensic identification of individuals, and for determination of biological relatedness of individuals.

Alleles↗

Reproductive cycle, thyroxine and corticosterone in females of the giant swamp frog Dicroglossus occipitalis at the equator.

Females of the giant swamp frog Dicroglossus occipitalis were captured in the tributaries of the Zaïre River near Kisangani, a town situated close to the equator (00 degree 31' N) with virtually constant conditions as to photoperiod, temperature, precipitation, and relative humidity. An annual variation in the reproductive capacity of this species could be demonstrated. A reproductive quiescence with a low gonadal somatic index (GSI), undeveloped eggs, and minimal plasma concentrations of estradiol-17 beta (E2) and progesterone (P4) was found from October to January. E2 and P4 and thyroxine (T4) contents of the thyroids were positively correlated with GSI and egg size. Plasma T4 concentrations, however, were negatively correlated with GSI, whereas variations in corticosterone correlated only with E2. No correlation between plasma concentrations of glucose and GSI or all other hormonal parameters could be found. It is concluded that during egg maturation, increased amounts of E2 and P4 are produced. The observed variations in thyroidal and plasma T4 may be the result of an activation of thyroid function by the peripheral conversion of T4 into triiodothyronine.

Animals↗

UDP-glucuronosyltransferase activity, expression and cellular localization in human placenta at term.

The activity, expression and localization of the UDP-glucuronosyltransferases (UGTs) were investigated in human placenta at term. UGT activity (measured with the substrate 4-methylumbelliferone (4-MU)) was observed in all 25 placentas sampled and maximum velocity (V(max)) ranged 13-fold from 5.1+/-0.9 to 66.9+/-17.5 nmol/min/mg protein (mean+/-SD). Substrate affinity (K(m)) ranged 5-fold from 246+/-24 to 1124+/-422 microM. Using reverse transcriptase-polymerase chain reaction (RT-PCR), expression of the isoforms UGT2B4, 2B7, 2B10, 2B11 and 2B15 was observed in all (12/12) placentas sampled and expression of UGT2B17 was noted in 8/12 placentas. Northern analysis of the UGT2B7 isoform in 12 placentas revealed a 10-fold difference in expression with RT-PCR variability and the 13-fold variation observed in UGT activity. The presence of UGT2B4 and 2B7 proteins (52 and 56kDa, respectively) was demonstrated by Western blotting. The sites of placental UGT2B transcription (in situ hybridization) and protein expression (immunohistochemistry) were located in the syncytium of the placental trophoblasts bordering the placental villi. UGT1A proteins could not be observed with immunohistochemistry or Western blotting and expression could not be observed with RT-PCR. Our discovery of UGT expression and activity at the site of maternal-fetal exchange is consistent with a role for UGTs in detoxification of exogenous and endogenous ligands and the maintenance of placental function through clearance and regulation of steroid hormones.

Female↗

Determinants of waiting time for heart transplants in the United States.

BACKGROUND: Reports have been published on factors affecting the variations in waiting times for kidney and liver transplant candidates who have been registered on the United Network for Organ Sharing's waiting list. This study reports on determinants of waiting time differences that occur in the eleven UNOS regions for heart transplant candidates. METHODS: Retrospective analysis of 11,345 primary heart waiting-list registrations and 15,868 cadaveric donors, from whom 7,043 hearts were recovered and transplanted for the years 1994-96. Because estimated populations in the eleven UNOS regions vary from 10.8 to 43.2 million, analyses utilized Registrations/million population and Transplants/million population to obtain an R/T ratio. The relationship of the R/T ratio to the median waiting time was then examined for different demographic variables. RESULTS: The numbers of new heart candidate registrations, heart transplants performed, and waiting list deaths have undergone little change from 1991 through 1996. National median waiting times varied by basic demographic variables such as ABO blood type, race, age group, and UNOS medical urgency status. In the eleven UNOS regions, registrations per million ranged from 11.5 to 33.0 and transplants per million from 5.3 to 10.7. Registration/Transplant ratios correlated with median waiting times for urgency Status 1 and 2 as well as for blood group O recipients. Correlation with blood type AB recipients was less consistent, in part, due to the small number of AB recipients. CONCLUSIONS: There are wide variations in the number of heart transplant candidate registrations and in the number of heart transplants performed in the eleven UNOS regions. The registration to transplantation ratio correlated with median waiting times in these regions. Factors possibly contributing to the observed variations were examined.

Adolescent↗

Dynamics of ribonuclease H: temperature dependence of motions on multiple time scales.

The temperature dependence of the backbone motions in Escherichia coli ribonuclease HI was studied on multiple time scales by 15N nuclear magnetic spin relaxation. Laboratory frame relaxation data at 285, 300, and 310 K were analyzed using the model-free and reduced spectral density approaches. The temperature dependence of the order parameters was used to define a characteristic temperature for the motions of the backbone N-H bond vectors on picosecond to nanosecond time scales. The characteristic temperatures for secondary structure elements, loops, and the C-terminus are approximately 1000, approximately 300, and approximately 170 K, respectively. The observed variation in the characteristic temperature indicates that the energy landscape, and thus the configurational heat capacity, is markedly structure dependent in the folded protein. The effective correlation times for internal motions do not show significant temperature dependence. Conformational exchange was observed for a large number of residues forming a contiguous region of the protein that includes the coiled coil formed by helices alpha A and alpha D. Exchange broadening in the CPMG experiments decreased with increased temperature, directly demonstrating that the microscopic exchange rate is faster than the pulse repetition rate of 1.2 ms. The temperature dependence of the exchange contributions to the transverse relaxation rate constant shows approximately Arrhenius behavior over the studied temperature range with apparent activation enthalpies of approximately 20-50 kJ/mol. Numerical calculations suggest that these values underestimate the activation barriers by at most a factor of 2. The present results obtained at 300 K are compared to those reported previously [Mandel, A. M., Akke, M., & Palmer, A. G., III (1995) J. Mol. Biol. 246, 144-163] to establish the reproducibility of the experimental techniques.

Amino Acid Sequence↗