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PubMed1997

Bacterial vaginosis and intraamniotic infection.

OBJECTIVE: We sought to determine the predictors of intraamniotic infection with use of the presence or absence of vaginal microbes and clinical variables. STUDY DESIGN: Vaginal fluid was collected and analyzed on 936 of 2711 (35%) consecutive patients who were delivered over a 7-month period. Subjects were followed up prospectively for the development of intraamniotic infection. Intraamniotic infection was defined as an intrapartum fever > 37.8 degrees C plus at least two of the five following variables: maternal or fetal tachycardia, leukocytosis, tender uterus, or foul-smelling amniotic fluid. Bacterial vaginosis score and the presence or absence of aerobic vaginal organisms were independent microbial variables. Demographic, maternal, labor, and delivery characteristics were independent clinical variables. Stepwise logistic regression analysis was used to develop adjusted odds ratios for predicting intraamniotic infection (expressed as odds ratio [95% confidence interval]). Selection bias and microbiologic reliability were measured. RESULTS: A bacterial vaginosis score of 7 to 10 (odds ratio 1.7, [95% confidence interval 1.0 to 3.9]), nulliparity (2.1 [1.3 to 3.4]), each hour of internal fetal electrode (1.2 [1.0-1.3]); and, each vaginal examination (1.7 [1.0-3.9]) were predictors of intraamniotic infection. Selected aerobic vaginal organisms such as group B streptococci or gram-negative rods were not predictive. Reanalysis with a bacterial vaginosis score > or = 4 revealed similar predictors of intraamniotic infection. Bacterial vaginosis had an adjusted odds ratio of 1.85 (1.16 to 2.9). Selected higher risk populations, vaginal examinations > or = 6 (n = 365), or rupture of membranes > or = 7 hours (n = 421) did not change the risk of a bacterial vaginosis score > or = 4 (adjusted odds ratio 1.87 and 1.98, respectively). CONCLUSION: Abnormal vaginal flora combines with clinical variables to increase the risk of intraamniotic infection.

Adult↗
PubMed2003

The effect of neoadjuvant chemotherapy on estrogen and progesterone receptor expression and hormone receptor status in breast cancer.

BACKGROUND: Neoadjuvant chemotherapy may decrease tumor volume to allow breast conservation surgery. Its effect on estrogen and progesterone receptor (ER/PR) expression and hormone receptor (HR) status is controversial. METHODS: From February 2001 to July 2002, 56 breast cancer patients treated with neoadjuvant chemotherapy and 56 non-neoadjuvant therapy (control) patients with adequate tissue samples were identified. Quantitative ER/PR expression was analyzed in preneoadjuvant or preoperative core biopsies and final surgical specimens. Changes between the two groups were compared to determine if alterations were due to neoadjuvant chemotherapy or tissue sampling. RESULTS: The ER/PR expression changed in 34 (61%) neoadjuvant chemotherapy patients and 27 (48%) control patients. These expression changes resulted in HR status (positive/negative) alterations in 3 patients (5%) in both groups. Age, histology, chemotherapy regimen, and neoadjuvant response did not predict change. CONCLUSIONS: Hormone receptor status changed in 5% of neoadjuvant chemotherapy and control groups due to tissue sampling. As these changes may impact treatment, HR expression reanalysis in final surgical specimens is recommended.

Breast Neoplasms↗
PubMed1998

Trapping and wiggling: elastohydrodynamics of driven microfilaments.

We present an analysis of the planar motion of single semiflexible filaments subject to viscous drag or point forcing. These are the relevant forces in dynamic experiments designed to measure biopolymer bending moduli. By analogy with the "Stokes problems" in hydrodynamics (motion of a viscous fluid induced by that of a wall bounding the fluid), we consider the motion of a polymer, one end of which is moved in an impulsive or oscillatory way. Analytical solutions for the time-dependent shapes of such moving polymers are obtained within an analysis applicable to small-amplitude deformations. In the case of oscillatory driving, particular attention is paid to a characteristic length determined by the frequency of oscillation, the polymer persistence length, and the viscous drag coefficient. Experiments on actin filaments manipulated with optical traps confirm the scaling law predicted by the analysis and provide a new technique for measuring the elastic bending modulus. Exploiting this model, we also present a reanalysis of several published experiments on microtubules.

Actin Cytoskeleton↗
PubMed2001

1,3-Butadiene, isoprene and chloroprene: reviews by the IARC monographs programme, outstanding issues, and research priorities in epidemiology.

1,3-Butadiene, isoprene and chloroprene have all been evaluated more than once by the IARC Monographs Programme on the Evaluation of Carcinogenic Risks to Humans, most recently in February 1998 (Volume 71). Summaries are available on-line at http://monographs.iarc.fr. 1,3-Butadiene is currently classified in Group 2A (probably carcinogenic to humans), on the basis of limited evidence for increased occupational cancer risk in humans plus sufficient evidence of carcinogenicity at multiple organ sites in rats and especially in mice exposed by inhalation. Four epidemiologic studies are available on cancer risk among workers exposed to 1,3-butadiene, one large study among styrene-butadiene rubber (SBR) workers, and one large and two small studies among 1,3-butadiene production workers. The results of the study of SBR workers suggest an association between butadiene exposure and leukaemia risk, which is consistent with the results of the large study of production workers. This latter study also suggested an increased risk of lymphoreticulosarcoma (ICD-8, 200). The major factors hampering the assessment of the available results are (i) possible misclassification of lymphoid and haematopoietic neoplasms, (ii) limitations in the assessment of past exposure (with the exception of the study of SBR workers) and (iii) a potential confounding effect of agents other than butadiene. Future research priorities include (i) the incorporation of newly developed biomarkers of exposure, (ii) the possible application of intermediate biomarkers, (iii) the replication of the study among SBR workers, possibly in Europe, and (iv) reanalysis of existing data in light of revisions of the classifications of leukaemias and lymphomas in the International Classification of Diseases for Oncology, Third Edition (2000). Isoprene is classified in Group 2B (possibly carcinogenic to humans), on the basis of sufficient evidence for carcinogenicity at multiple organ sites in both mice and rats, especially male mice, exposed by inhalation. No epidemiologic studies are available on cancer risk from occupational exposure to isoprene. Such studies could be conducted within the framework of existing or future studies of SBR workers, assuming that isoprene exposure can be disentangled from butadiene and styrene exposure. Chloroprene is classified in Group 2B on the basis of sufficient evidence for carcinogenicity at multiple organ sites in both mice and rats exposed by inhalation. Studies of chloroprene exposed workers now include chemical workers from the United States, China and Armenia as well as shoe workers from Russia. The results of the studies from China, Armenia and Russia suggest an excess risk of liver cancer. The risk of other neoplasms was not consistently increased. Limitations of available studies include possible bias from cohort enumeration, follow-up, and choice of reference population. In most studies the exposure assessment was poor, the possible confounding effect of co-exposures was not addressed and the statistical power was low. The pathology of the cases of liver cancer should be reviewed. Future research priorities include a replication of available studies in well-defined populations and the development of biomarkers of exposure.

Animals↗
PubMed1998

Comparison between the CEDIA and EMIT II immunoassays for the determination of benzodiazepines.

We evaluated a new, qualitative immunoassay for benzodiazepines in urine using CEDIA technology on the Hitachi 747 and compared its performance to an immunoassay using EMIT II methodology on the same instrument. A total of 500 urine samples received for routine drug screen analysis were prospectively examined for benzodiazepines by both methods. Samples producing positive results by either immunoassay method were analyzed by gas chromatography-mass spectrometry (GC-MS). Available medical records were reviewed for patients whose samples produced discrepant immunoassay results or that were positive in both immunoassays but negative by GC-MS. Samples that produced negative results in both immunoassays were not subjected to GC-MS analysis. Therefore, identification of an immunoassay result as a false negative only occurred when the sample produced a positive value in only one of the two immunoassays and was confirmed as positive by either GC-MS or medical record review. Following initial immunoassay screening and confirmation by GC-MS, a medical record review and reanalysis of GC-MS data was performed. After this in-depth analysis of the data, the CEDIA method produced 60 true-positives, 7 false positives and no false negatives. The EMIT II method produced 47 true positives, 1 fase positive and 13 false negatives. These differences appear to be due to the CEDIA assay being more sensitive for detection of lorazepam.

Benzodiazepines↗
PubMed2000

Syntactic structure assembly in human parsing: a computational model based on competitive inhibition and a lexicalist grammar.

We present the design, implementation and simulation results of a psycholinguistic model of human syntactic processing that meets major empirical criteria. The parser operates in conjunction with a lexicalist grammar and is driven by syntactic information associated with heads of phrases. The dynamics of the model are based on competition by lateral inhibition ('competitive inhibition'). Input words activate lexical frames (i.e. elementary trees anchored to input words) in the mental lexicon, and a network of candidate 'unification links' is set up between frame nodes. These links represent tentative attachments that are graded rather than all-or-none. Candidate links that, due to grammatical or 'treehood' constraints, are incompatible, compete for inclusion in the final syntactic tree by sending each other inhibitory signals that reduce the competitor's attachment strength. The outcome of these local and simultaneous competitions is controlled by dynamic parameters, in particular by the Entry Activation and the Activation Decay rate of syntactic nodes, and by the Strength and Strength Build-up rate of Unification links. In case of a successful parse, a single syntactic tree is returned that covers the whole input string and consists of lexical frames connected by winning Unification links. Simulations are reported of a significant range of psycholinguistic parsing phenomena in both normal and aphasic speakers of English: (i) various effects of linguistic complexity (single versus double, center versus right-hand self-embeddings of relative clauses; the difference between relative clauses with subject and object extraction; the contrast between a complement clause embedded within a relative clause versus a relative clause embedded within a complement clause); (ii) effects of local and global ambiguity, and of word-class and syntactic ambiguity (including recency and length effects); (iii) certain difficulty-of-reanalysis effects (contrasts between local ambiguities that are easy to resolve versus ones that lead to serious garden-path effects); (iv) effects of agrammatism on parsing performance, in particular the performance of various groups of aphasic patients on several sentence types.

Humans↗
PubMed2002

The P600 as an indicator of syntactic ambiguity.

In a study using event-related brain potentials, we show that the current characterization of the P600 component as an indicator of revision processes (reanalysis and repair) in sentence comprehension must be extended to include the recognition of syntactic ambiguity. By comparing the processing of ambiguous and unambiguous sentence constituents in German, we show that the P600 is elicited when our language processing system has syntactic alternatives at a certain item given in the input string. That the P600 is sensitive to syntactic ambiguity adds crucial evidence to current debates in psycholinguistic modelling, as the results clearly favour parallel models of syntactic processing which assume that ambiguity is recognized and costly.

Adult↗
PubMed1999

Breast cancer risk: perception versus reality.

Evidence that breast cancer is hormonally mediated has fueled women's concern that use of oral contraceptives (OC) will increase their risk of developing the disease. A recent reanalysis of combined worldwide epidemiologic evidence regarding the relationship between breast cancer risk and use of combination OC provides reassurance that there is little or no association between OC use and breast cancer. Ten or more years after discontinuation of OC use, there is no difference in cumulative risk of breast cancer among OC ever-users and never-users. The risk of breast cancer diagnosis is slightly elevated in current OC users and remains slightly elevated until about 10 years after OC discontinuation. Once recency of use is taken into account, other characteristics have little additional effect. There is no increase in breast cancer risk with increasing dose or duration of OC use and no difference in risk related to type of estrogen or progestin used. Moreover, those breast cancers diagnosed in OC ever-users were found to be significantly more likely to be localized than those diagnosed in same-age never-users.

Adult↗
PubMed1999

Lunelle monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension): effects of body weight and injection sites on pharmacokinetics.

A new contraceptive option, medroxyprogesterone acetate (MPA) and estradiol cypionate (E2C) (MPA/E2C, Lunelle Monthly Contraceptive Injection), will soon be available for women in the US. This article reports the results of a US trial that assessed the effects of body weight and injection site on the pharmacokinetics of MPA, the progestin mediating contraceptive efficacy. This assessment was part of a nonrandomized, open-label, multicenter US study in healthy women receiving a monthly injection of MPA/E2C for 60 weeks. A total of 77 women (aged 18-47 years) at four centers participated in the pharmacokinetics assessment during the sixth or the seventh injection. For determination of serum MPA concentration-time profiles, blood samples were collected before the sixth and seventh injections (day 0) and on days 3, 7, 14, 21, and 28 after the sixth and seventh monthly administrations. For effects of injection site, MPA pharmacokinetics were compared at injection sites of the arm, hip, and leg. The pharmacokinetics of MPA, determined at the sixth and seventh injection, were not significantly affected by injection sites. The mean area under the curve (AUC0-28), however, was different between the arm and the leg injection sites; the difference was < 20%. More important, the average MPA trough concentrations (Cmin) at the fifth and sixth monthly injections were similar (range 0.42-0.51 ng/mL) for the three injection sites and well above the threshold levels of 0.10-0.20 ng/mL required to suppress ovulation. For effects of body mass index (BMI) on pharmacokinetics, women were stratified into three groups: thin/normal (BMI 18-28, n = 48), obese (BMI 29-38, n = 23), and highly obese (BMI > 38, n = 6). There were no significant differences in the pharmacokinetics of MPA among the three BMI categories. The only significant difference (p = 0.0387) was the AUC0-28 between BMI 18-28 and BMI 29-38. Because of the small sample size in the highly obese group, a reanalysis was performed by pooling subjects of the obese and highly obese groups. Results of the pooled statistical analysis remained the same. In summary, these results suggest that minor differences observed in the MPA pharmacokinetics--whether due to injection site or body weight or both--have no impact on the contraceptive efficacy of MPA/E2C, as trough concentrations (Cmin) are well above the threshold levels required to suppress ovulation. No dose adjustment is necessary based on body weight or injection site.

Adult↗
PubMed2003

Integrating gender and number information in Spanish word pairs: an ERP study.

The aim of the current study was to explore the integration processes of gender and number morphological features, since it has been proposed that grammatical gender and number features might be associated with different strength with the word stem in lexical representation. Event related potentials (ERPs) were recorded using a 128-channel sensor net while twenty-four volunteers read Spanish word pairs and performed a syntactic judgment task. The word pairs which could agree or disagree in gender or number or in gender and number at the same time, were formed by a noun and an adjective (e.g. faro-alto [lighthouse-high]). A negativity around 400 msec with posterior distribution, which has been related to lexical integration processes, was found in response to both gender and number violations. No differences were found between gender disagreement, number disagreement and the double disagreement. Therefore, ERPs suggest that integration of gender and number features may not be different, and that the detection of disagreement may work under a binary state, since the double disagreement condition did not differ from the others. In addition, a subsequent component (identified as P3) showed delayed latencies in the gender disagreement condition as compared to the number disagreement condition, while the double disagreement conditions showed a shorter peak latency than the other two disagreement conditions and similar to the agreement condition. The variations in the latency of the P3 component, which has been related to categorization processes, suggest that these processes are quickly triggered by the accumulation of two incongruent as compared to one disagreement features, and that reanalysis is costlier in the case of gender disagreement as compared to the number disagreement.

Adult↗
PubMed2000

Improving the clinical diagnosis of personal neglect: a reformulated comb and razor test.

Beschin and Robertson (1997) devised a simple clinical test of left personal neglect, which characterises personal grooming behaviour according to the proportion of the total activity that is directed to the left side of the body. Although this test proved highly reliable, and more sensitive than prior diagnostic techniques, its formulation may yet be improved. The present paper reports a reanalysis of Beschin and Robertson's (1997) data, using additional control subjects, and a formula which characterises personal neglect as a lateral bias of behaviour rather than as a lateralised deficit. It is shown that this formula greatly enhances the test's sensitivity to the behavioural abnormalities of brain damaged patients, and it is recommended that this modification be adopted for the future diagnosis of personal neglect.

Aged↗
PubMed1989

Simultaneous reading of braille with the two hands: reply to Millar (1987).

Millar (1987) argues that when braille readers scan a passage of text with the two hands side by side, the reading fingers actually alternate contacts with the letters. Reanalysis of her data shows that they provide little support for that claim. On the other hand, unlike a majority of the subjects studied by Bertelson et al. (1985), Millar's subjects do apparently not engage in simultaneous exploration of the end of one line and the beginning of the next one by different fingers. The suggestion offered by Millar that our findings result from an inadequate analysis of the data is rejected. The difference between the two sets of data should for the time being be considered as reflecting genuine differences between the populations that were sampled in the two studies.

Blindness↗
PubMed1989

Simultaneous reading with the two hands: reply to Bertelson and Mousty.

Bertelson and Mousty's criticisms of Millar's (1987) analyses rest on a misapprehension of the nature and purpose of the measures that were used. Millar (1987) used two measures to test a prediction from the hypothesis that fast braillists use the two hands to read different portions of text simultaneously. The study was not about scanning. Bertelson and Mousty's criticism and reanalysis of Millar's (1987) data is shown to be based on unsupported assumptions, and a misunderstanding of the first measure. Details about the first measure are given. It is shown that the findings from the two measures agree and are in the opposite direction to that predicted by the hypothesis. There could be a number of reasons for the difference between Bertelson et al. (1985) and Millar's (1987) data. They need further study.

Blindness↗
PubMed2003

Using measurement error models to assess effects of prenatal and postnatal methylmercury exposure in the Seychelles Child Development Study.

Studies of the effects of environmental exposures on human health typically require estimation of both exposure and outcome. Standard methods for the assessment of the association between exposure and outcome include multiple linear regression analysis, which assumes that the outcome variable is observed with error, while the levels of exposure and other explanatory variables are measured with complete accuracy, so that there is no deviation of the measured from the actual value. The term measurement error in this discussion refers to the difference between the actual or true level and the value that is actually observed. In the investigations of the effects of prenatal methylmercury (MeHg) exposure from fish consumption on child development, the only way to obtain a true exposure level (producing the toxic effect) is to ascertain the concentration in fetal brain, which is not possible. As is often the case in studies of environmental exposures, the measured exposure level is a biomarker, such as the average maternal hair level during gestation. Measurement of hair mercury is widely used as a biological indicator for exposure to MeHg and is the only indicator that has been calibrated against the target tissue, the developing brain. Variability between the measured and the true values in explanatory variables in a multiple regression analysis can produce bias, leading to either over or underestimation of regression parameters (slopes). Fortunately, statistical methods known as measurement error models (MEM) are available to account for measurement errors in explanatory variables in multiple regression analysis, and these methods can provide an (either "unbiased" or "bias-corrected") estimate of the unknown outcome/exposure relationship. In this paper, we illustrate MEM analysis by reanalyzing data from the 5.5-year test battery in the Seychelles Child Development Study, a longitudinal study of prenatal exposure to MeHg from maternal consumption of a diet high in fish. The use of the MEM approach was made possible by the existence of independent, calibration data on the magnitude of the variability of the measurement error deviations for the biomarker of prenatal exposure used in this study, the maternal hair level. Our reanalysis indicated that adjustment for measurement errors in explanatory variables had no appreciable effect on the original results.

Adult↗
PubMed2002

Role of spin trapping and P2Y receptor antagonism in the neuroprotective effects of 2,2'-pyridylisatogen tosylate and related compounds.

2,2'-Pyridylisatogen tosylate (PIT) is both an allosteric modulator of P2Y receptors, and an immine oxide, acting as a spin trap for free radicals. PIT (10 mg kg(-1), i.p.) was found to be a powerful neuroprotective agent in protecting against the lesions induced by 15 micro g S-bromo-willardiine injected into the cortex or white matter of 5-day-old mice pups. As the multiple effects of PIT may induce both beneficial and deleterious effects, a reanalysis of the structure-activity relationship was undertaken. PIT (50 micro M) and 2,3'-pyridylisatogen were potent antagonists of responses to ATP in the taenia preparation of the guinea-pig caecum, but 2,3'-nitrophenylisatogen was not. The reactive immine oxide group could be substituted by a keto moiety (N-(2'-pyridyl)phthalide) while maintaining antagonism of responses to ATP, equivalent to PIT. Thus, antagonism of P2Y receptors was not restricted to the isatogen nucleus. Other spin traps did not antagonise P2Y receptors, although dimethyl-pyrroline-N-oxide (DMPO) increased the sensitivity of responses to ATP. Both N-(2'-pyridyl)phthalide and 2,3'-nitrophenylisatogen was less neuroprotective than PIT (10 mg kg(-1), i.p.) in protecting against the S-bromo-willardiine-induced lesions in mice, implying that both antagonism of P2Y receptors and the immine oxide moiety may be important for the neuroprotective effects of PIT. However, the usefulness of the neuroprotection was limited because, in motoneurones obtained from rat embryos, PIT (10-100 micro M) exacerbated cell death.

Animals↗
PubMed1997

The active site region of the vitamin K-dependent carboxylase includes both the amino-terminal hydrophobic and carboxy-terminal hydrophilic domains of the protein.

In order to localize the active site of the vitamin K-dependent carboxylase, we developed an affinity probe containing the propeptide and the first two carboxylatable glutamate residues conserved in many native substrates. This probe crosslinked to both the hydrophobic amino-terminal and hydrophilic carboxy-terminal domains of the carboxylase, in contrast with previous work which localized both the catalytic and the propeptide binding site within the amino-terminal hydrophobic domain. Amino acid analysis revealed that the mass of an amino-terminal fragment is seriously underestimated by SDS-PAGE. Reanalysis of the published data in light of this information suggests that a portion of the propeptide binding site resides within the carboxy-terminal hydrophilic domain.

Amino Acid Sequence↗
PubMed1993

Assessment of human sperm acrosome reaction by flow cytometry: validation and evaluation of the method by fluorescence-activated cell sorting.

OBJECTIVE: To determine the applicability of flow cytometry to assess human sperm acrosome reaction. DESIGN: Prospective evaluation of semen samples incubated overnight for the development of spontaneous acrosome reaction or exposed to the calcium ionophore A23187 (5 microM) for 3 hours for induction of the acrosome reaction. SETTING: University-affiliated tertiary care center. PATIENTS: Normal healthy volunteers. INTERVENTIONS: The spermatozoa were stained with fluorescein isothiocyanate (FITC)-labeled pea agglutinin. The labeled samples were assessed visually and also subjected to analytic flow cytometry and fluorescence-activated cell sorting. MAIN OUTCOME MEASURES: Acrosome reaction assessed visually and by flow cytometry. RESULTS: Flow cytometric analysis showed a single peak of FITC fluorescence in the washed semen samples. A second peak of lower FITC fluorescence intensity was noted after overnight incubation or exposure to A23187, suggesting loss of fluorescence, which indicated the occurrence of the acrosome reaction. There was a statistically significant correlation between the assessment by the two methods (n = 41). However, although the mean difference between the methods was small (2.49%), the difference between the two methods for each individual sample can vary between -24% to +29%. When the sperm cells were subjected to cell sorting based on green fluorescence intensity, reanalysis and visual scoring verified that the low intensity peak contained a majority of acrosome-reacted spermatozoa (77.52% +/- 2.39%). CONCLUSION: These results validated the flow cytometric method for assessment of acrosome-reacted spermatozoa. Although flow cytometry is more objective and less time consuming when many samples are assessed at the same time, the visual method remains a useful and practical procedure in the clinical andrology laboratory.

Acrosome↗
PubMed1999

Utility of isotachophoresis-capillary zone electrophoresis, mass spectrometry and high-performance size-exclusion chromatography for monitoring of interleukin-6 dimer formation.

The utility of isotachophoresis-capillary zone electrophoresis (ITP-CZE) and high-performance size-exclusion chromatography (HPSEC) was investigated for determination of dimeric and monomeric recombinant human interleukin-6 (rhIL-6). Using ITP-CZE heterogeneity of dimeric rhIL-6 could be revealed resolving two peaks in the electropherograms, while with HPSEC dimeric rhIL-6 eluted as one homogeneous fraction. Both protein forms were monitored during incubation of monomeric rhIL-6 at different pH and temperature. The selectivity of counterflow ITP-CZE in conjunction with the low concentration determination limits enabled reanalysis of HPSEC fractions for identification of the dimer in the electropherograms. Both ITP-CZE and HPSEC were shown to be suitable to monitor the dimerization of rhIL-6, similar monomer-to-dimer peak area ratios were obtained throughout the incubation. Dimer formation kinetics increased with decreasing pH and with increasing temperature, it was entirely suppressed at neutral pH and room temperature. In contrast to HPSEC, ITP-CZE enabled separation of further still unidentified artifacts apparently formed during incubation of rhIL-6. CZE analysis in conjunction with electrospray ionization mass spectrometry revealed the non-covalent binding character of the dimeric rhIL-6 complex and facilitated interpretation of the electropherograms.

Chromatography, Gel↗