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Biomedical subjects

D L Brown

Publications and source records attributed to D L Brown.

At least 163 records · Page 9Linked to original sources

Very echogenic amniotic fluid: ultrasonography-amniocentesis correlation.

Very echogenic amniotic fluid has been variably attributed to meconium, blood, or vernix caseosa. However, most previous reports have been case reports, and most cases have not had proof by amniocentesis. In a larger series of patients with proof by amniocentesis, we sought to determine the relative frequency of these substances as causes of very echogenic amniotic fluid. We retrospectively identified obstetric sonograms in which the amniotic fluid was homogeneously filled with innumerable echogenic particles. The cause of the increased echogenicity was determined by fluid appearance at amniocentesis. Of 86 cases identified, immediate proof by amniocentesis was available in 19 patients for whom the gestational age ranged from 32.8 to 39.4 weeks. Vernix was present in 18 (95%) patients and meconium in one (5%) patient. Very echogenic amniotic fluid in the third trimester is most often due to vernix and infrequently due to meconium. This sonographic finding is not a reliable indicator of meconium or blood in amniotic fluid and should not typically alter antenatal management.

Amniocentesis↗

Transvaginal sonography for diagnosing ectopic pregnancy: positivity criteria and performance characteristics.

Despite the widespread use of TVS for diagnosing EP and extensive literature on the subject, there is no consensus regarding the best positivity criterion for adnexal findings or the performance characteristics of TVS. We conducted a literature search to identify original studies presenting suitable data on the use of TVS for the diagnosis of EP. The data were combined to determine the sensitivity and specificity of four sonographic criteria for EP, listed in order from most to least stringent: Criterion A, living extrauterine pregnancy; criterion B, extrauterine gestational sac containing yolk sac or embryo; criterion C, empty "tubal ring" or extrauterine gestational sac containing yolk sac or embryo; and criterion D, any adnexal mass other than a simple cyst. Positive and negative predictive values were computed using Bayes' theorem. Ten studies involving a total of 2216 patients, 565 with EP and 1651 without EP, were included in our analysis. Based on the combined data from these studies, criteria A, B, and C all have high specificities (99.5-100%) and positive predictive values (97.8-100%) but low sensitivities (20.1-64.6%) and mediocre negative predictive values (78.5-89.1%). Criterion D, the most lax criterion, has the most uniformly excellent characteristics, with only slightly lower specificity (98.9%) and positive predictive value (96.3%) but considerably higher sensitivity (84.4%) and negative predictive value (94.8%). The performance characteristics of TVS criteria for EP, computed by pooling data from published studies, indicate that the appropriate TVS criterion to diagnose EP is any noncystic adnexal mass. These performance characteristics can be used as a basis for comparing TVS with other proposed diagnostic modalities for EP.

Bayes Theorem↗

Clinical significance of isolated fetal pericardial effusion.

Prenatal sonographic identification of a small rim of pericardial fluid, measuring less than 2 mm in thickness, is a normal finding. Pericardial fluid 2 mm or greater in thickness may be associated with structural anomalies or hydrops, but its clinical significance in the absence of these associated findings has not been evaluated. We assessed the outcome in fetuses with isolated pericardial effusions of at least 2 mm thick. Our study population included 52 fetuses with effusions ranging from 2 to 7 mm in thickness. We compared rates of preterm delivery, cesarean section, intrauterine growth retardation, perinatal complications, Apgar scores, and length of neonatal hospital stay in these 52 cases to the overall hospital rates and found no statistically significant difference. We conclude that in the absence of other sonographic abnormalities, the finding of a fetal pericardial fluid collection 2 to 7 mm in thickness is not associated with adverse outcome.

Female↗

Left ventricular echogenic focus in the fetal heart: pathologic correlation.

Echogenic foci within the left ventricle of the heart have been found in a minority of fetuses and generally are believed to be a normal variant. The cause and exact location of these foci have remained speculative, however. We identified three fetuses with this sonographic finding in whom pathologic correlation was available. The only consistent histologic finding present in all three fetuses was mineralization within a papillary muscle; the chordae tendineae were normal. One of the three fetuses had trisomy 21. Echogenic foci within the left ventricle of the fetal heart represent papillary muscle mineralization. Until more data are available to investigate any possible association with aneuploidy, an echogenic focus in the left ventricle should still be considered a normal variant.

Adult↗

Humidity regulation in the management of asthma patients sensitized to house dust mites.

Substances in the faeces of house dust mites are well-recognized as common allergens in the pathogenesis of asthma. There have been many trials of interventions aimed at reducing mite populations in the home, but most have been uncontrolled, too small, or too short to determine with confidence any beneficial effects. Of those which succeeded, very few used methods which reduced mite populations on a permanent basis. House dust mites are sensitive to humidity. Their geographical distribution is closely correlated to the availability of moisture. Very little work has been done on the effects of reducing humidity in the home environment in the long term, with a view to controlling dust mite populations. Two different methods which might reduce humidities to levels which could successfully reduce dust mite numbers are dehumidifiers, and mechanical ventilation with heat recovery (MVHR). To date there has been no work assessing the effectiveness of dehumidifiers and very little (although promising) work on MVHR. We discuss the potential of humidity control as an adjunct to the clinical treatment of asthma.

Animals↗

Automation at the point of care.

Clinical Information Systems (CISs) are systems of microcomputers used at patient bedsides to collect, process, retrieve and display information related to patient care. At our facility, 65 terminals are used in selected units and the CIS has virtually replaced paper charts in daily practice and documentation. Though currently employed in only a small number of hospitals, the use of CISs is expected to grow rapidly during the coming decade.

Computer Systems↗

The incompetent defendant: support systems help avoid future legal problems.

Reducing crime and improving efficiency of our criminal justice system should be facilitated by identifying how to treat and manage mental health patients who are prone to committing criminal acts more effectively. A total of 142 competency evaluations were reviewed from cases evaluated by the Galveston County Forensic Psychiatrist from 1984 to 1990. Examination of data from these defendants allowed us to address the psychiatric needs of these defendants in terms of contact with the mental health system, particularly those who had more than one criminal justice system contact. The latter defendants lacked social support systems and consistent mental health system follow-up to provide stabilization of their condition. It was felt that this was a factor in their more frequent contact with the criminal justice system.

Adolescent↗

The molecular basis of microtubule stability in neurons.

Microtubule (Mt) populations show large differences in dynamic properties (i.e., turnover rates) among cell types, and even within the same cell type at different stages of the cell cycle or stages of differentiation. These differences in dynamic properties are correlated with altered sensitivity to Mt-disassembling drugs (e.g. colchicine) which bind specifically to the Mt protein tubulin and to certain toxic metals which also interact with tubulin (e.g. methylmercury) and result in Mt disassembly. Mts in neurons become progressively more stable and more resistant to such compounds during differentiation. We are using the P19 embryonal carcinoma cell line, which can be induced to differentiate along the neural pathway by retinoic acid, as a model system in which to analyze the development of stable Mts. Our results show that during differentiation there is an evolution in the sorting of tubulin isotypes into the stable Mts. This appears related both to the expression of specific Mt-associated proteins and to concomitant posttranslational modifications of tubulin.

Animals↗

Cytoskeleton and cell adhesion molecules: critical targets of toxic agents.

Normal development of the nervous system depends upon complex physical interactions between cells and their local environment. These interactions are mediated by several families of cell adhesion molecules (CAMs). Differential expression and function of CAMs are operative in neural tube formation, neuron migration, in post-migratory differentiation, and maintenance of mature neural structure. CAMs also facilitate contact-dependent cell processes, such as formation of cell junctions. Temporal regulation of these molecules during development may provide "windows of vulnerability" to toxicants. In addition to their extracellular binding activities, some CAMs have membrane-spanning domains by which they communicate directly with the cytoskeleton, permitting extracellular signals to be rapidly translated into cell responses via modifications in cytoskeletal organization. These cytologic changes are particularly critical during migration, neurite formation and synaptogenesis. Toxic perturbation of adhesion molecules can have catastrophic effects on morphogenetic processes both directly and via events which depend upon cytoskeletal rearrangement. Toxicants can also act directly upon the cytoskeleton, resulting secondarily in changes of the membrane distribution and function of CAMs. Toxicant-induced changes in CAMs and cytoskeleton may occur contemporaneously. Interference of cell adhesion-cytoskeleton interactions may be a pivotal molecular event dictating developmental consequences of neurotoxicant exposure.

Animals↗

Efficient strategies for genomic searching using the affected-pedigree-member method of linkage analysis.

The affected-pedigree-member (APM) method of linkage analysis is a nonparametric statistic that tests for nonrandom cosegregation of a disease and marker loci. The APM statistic is based on the observation that if a marker locus is near a disease-susceptibility locus, then affected individuals within a family should be more similar at the marker locus than is expected by chance. The APM statistic measures marker similarity in terms of identity by state (IBS) of marker alleles; that is, two alleles are IBS if they are the same, regardless of their ancestral origin. Since the APM statistic measures increased marker similarity, it makes no assumptions concerning how the disease is inherited; this can be an advantage when dealing with complex diseases for which the mode of inheritance is difficult to determine. We investigate here the power of the APM statistic to detect linkage in the context of a genomewide search. In such a search, the APM statistic is evaluated at a grid of markers. Then regions with high APM statistics are investigated more thoroughly by typing more markers in the region. Using simulated data, we investigate various search strategies and recommend an optimal search strategy that maximizes the power to detect linkage while minimizing the false-positive rate and number of markers. We determine an optimal series of three increasing cut-points and an independent criterion for significance.

Female↗

Differentiation stages of childhood acute lymphoblastic leukemias with p53 mutations.

Based upon in vitro evidence of p53 involvement in lymphoid differentiation, we assessed immunoglobulin (Ig) and T-cell receptor (TCR) genes in five acute lymphoblastic leukemias (ALLs) with, and 24 ALLs without p53 mutations to compare their genotypic stages. Using Southern blot analysis and complementarity determining region III polymerase chain reaction (CDRIII PCR), 18 cases of B-lineage ALL and 11 cases of T-ALL were studied. Of 20 specimens from 18 B-lineage ALLs, two of four with p53 mutation and two of 16 without mutation had an unrearranged Ig and TCR genotype (p = 0.16; Fisher's exact test). Of 11 cases of T-ALL, the one case with p53 mutation had a rearranged TCR and Ig genotype and a case without mutation was unrearranged. The study indicates that p53 mutation is an infrequent feature of ALL found, nonetheless, in every genotypic subset. The p53 mutations in cases that do not further rearrange may support p53 involvement in lymphoid differentiation, but the heterogeneity in differentiation stages in cases both with and without p53 mutations suggests that regulation of early lymphoid maturation is multifactorial.

Adolescent↗

Polymorphism at codon 36 of the p53 gene.

A polymorphism at codon 36 in exon 4 of the p53 gene was identified by single strand conformation polymorphism (SSCP) analysis and direct sequencing of genomic DNA PCR products. The polymorphic allele, present in the heterozygous state in genomic DNAs of four of 100 individuals (4%), changes the codon 36 CCG to CCA, eliminates a FinI restriction site and creates a BccI site. Including this polymorphism there are four known polymorphisms in the p53 coding sequence.

Base Sequence↗

Effects of taxol and taxol/hyperthermia treatments on the functional polarization of cytotoxic T lymphocytes.

Immunofluorescence staining, electron microscopy, and (51Cr) cytolytic release assays are used to investigate the effects of taxol and taxol/hyperthermia treatments on the microtubule organization and cytolytic activity of cytotoxic T lymphocytes (CTLs). A 4 h treatment of CTLs with 1 microM taxol results in an extensive reorganization of the microtubule system to form one to a few large microtubule bundles that extend from the centrosome. The Golgi apparatus is not disrupted by this treatment and remains associated with the microtubule organizing centre (MTOC). This microtubule reorganization has no effect on the ability of CTLs to orient their MTOC towards a bound target cell, nor on their cytolytic activity. In control CTLs, not treated with taxol, a mild hyperthermia treatment (42 degrees C, 30 min) results in an aggregation of the pericentriolar material, a loss of MTOC orientation, an inhibition of cytolytic activity, and a disorganization of the microtubule system [Knox et al.: Exp. Cell Res. 194:275-283, 1991]. In contrast, in taxol-treated CTLs the stabilized microtubule bundles are unaffected by such hyperthermia treatment; however, the other effects of hyperthermia appear identical in control and taxol-treated CTLs. These results indicate that a dynamic, radially arranged microtubule array is not required for the functional polarization of CTLs and suggest that a component of the pericentriolar material may play a key role in effecting MTOC orientation.

Animals↗

Screening for ovarian cancer: the preliminary experience of a familial ovarian cancer center.

Women with a family history of ovarian cancer represent a high-risk group for the development of epithelial ovarian cancer. From July 1990 through December 1992, 386 women with a first-degree or multiple second-degree relatives with confirmed ovarian cancer were enrolled in a study to assess the utility of screening with transvaginal sonography, color flow doppler, and CA125. The mean age of the group was 41; 85% were premenopausal and 89/384 (23%) had 2 or more relatives with ovarian cancer. An initial ultrasound examination was abnormal in 89/384 (23%), 89% of whom were premenopausal. A persistent ovarian mass was detected in 15 patients and all were surgically proven to be benign. Mean CA125 levels were significantly higher and more variable in pre- vs postmenopausal women. CA125 was > or = 35 U/ml in 42/386 (11%) (36-232 U/ml). All but one of these women were premenopausal and 50% subsequently normalized. Two patients who were surgically explored for a rising CA125 had normal ovaries. An additional 19 patients have undergone prophylactic oophorectomy with no consistent histopathologic abnormality identified. These data demonstrate the difficulty inherent in screening a predominantly premenopausal population and do not clearly establish the efficacy of these modalities in the early detection of ovarian cancer.

Adult↗

Anti-neutrophil cytoplasm antibodies (ANCA) increase neutrophil adhesion to cultured human endothelium.

ANCA have been demonstrated to activate normal neutrophils in vitro. This study demonstrates that ANCA positive IgG and Fab2 fragments increase the adhesion of normal neutrophils to cultured human umbilical vein endothelium (HUVEC), and that preincubation of the endothelial monolayers with tumour necrosis factor (TNF) to activate the endothelium enhances this effect. Preincubation of neutrophils with anti-CD18 monoclonal antibodies inhibited adhesion, suggesting that the observed effect was integrin mediated.

Antibodies, Antineutrophil Cytoplasmic↗