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Biomedical subjects

S Becker

Publications and source records attributed to S Becker.

At least 127 records · Page 7Linked to original sources
PubMed1999

Prothrombotic risk factors in childhood stroke and venous thrombosis.

UNLABELLED: Many studies have shown a high percentage of venous thromboses in children to be associated with haematological disorders. However, studies assessing the influence of haemostaseological disorders on paediatric stroke are rare. We compared 26 children with cerebral infarction (median age 2 months, range 0-16.2 years) and 17 with venous thrombosis (median age 4.5 years, range 0-17 years) with regard to prothrombotic risk factors. Prothrombotic disorders were found in 8 out of 26 patients with cerebral infarction (FV Leiden mutation: n = 4; protein C deficiency: n = 1; FV Leiden mutation + protein C deficiency: n = 2; prothrombin mutation G20210A: n = 1) and in 13 out of 17 with venous thrombosis (FV Leiden mutation n = 3; protein C deficiency n = 5; elevated HRGP + PAI: n = 1, combined deficiency of AT, protein C and plasminogen: n = 1; F XII deficiency: n = 1; lupus anticoagulans n = 1; FV Leiden + F XII deficiency + lupus anticoagulans + PAI: n = 1). Comparison of these prevalences with those of 150 healthy paediatric controls showed in children with FV Leiden mutation and/or protein C deficiency an increased risk of cerebral infarction (patients vs. controls: 26.9% vs. 6%; OR 5.77; 95%-CI 1.92-17.3; P = 0.0031) as well as of venous thrombosis (53% vs. 5.3% 19.9; 95%-CI 6-65.6; P < 0.0001). This result is in contrast with reports on thrombophilia in cerebral infarction in adult patients. CONCLUSION: Our results indicate that FV Leiden mutation and protein C deficiency may contribute to the multifactorial aetiology of stroke in early childhood.

Adolescent↗
PubMed1999

Post-trauma coagulation and fibrinolysis in children suffering from severe cerebro-cranial trauma.

UNLABELLED: The present study was designed to evaluate the post-trauma haemostatic changes in 27 children with severe cranio-cerebral trauma defined by a modified Glasgow Coma Score (GCS) < 10. Blood samples for coagulation studies (fibrinogen, von Willebrand factor (vWf), factor VIII:C, antithrombin, protein C, plasminogen, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI), D-dimer) were obtained within two hours of admission, 24 h later, and on days 3-5, 7-9, 21 and 35. Data of this study indicate that alterations of coagulation in paediatric patients are similar to those in adults: On hospitalisation, activated haemostasis was found with decreased fibrinogen, antithrombin and protein C along with enhanced t-PA and PAI. Twenty-four hours later, hypercoagulability with significantly increased vWF and fibrinogen started, with a peak level within the second week. Within 24 h of admission, 17 children developed disseminated intravascular coagulation (DIC) with a clear-cut decrease of antithrombin and fibrinogen together with platelet consumption and enhanced D-dimer. The outcome of children with DIC was significantly poorer than in those without DIC. Complete recovery was seen in five patients; sequelae no handicap and moderate disability were each found in six patients. Severe disability was diagnosed in two children, and fulminant DIC with lethal outcome occurred in eight patients. The GCS (P < 0.01) and the occurrence of DIC (P < 0.005) showed the strongest association with the patients' clinical outcome. CONCLUSION: Our data underline the significance of post-trauma disturbances of the haemostatic system for the clinical course and outcome in children with severe cranio-cerebral injuries.

Adolescent↗
PubMed1999

Occlusion contributes to temporal processing differences between crossed and uncrossed stereopsis in random-dot displays.

Stereoscopic depth discrimination was investigated in crossed and uncrossed directions using stimuli defined by binocular disparity differences embedded in dynamic random-dot stereograms. Across three experiments, fixation was directed to a point on the display screen (which placed crossed stimuli in front of and uncrossed stimuli behind, the background dots of the stereogram), to a point in front of the display screen (which placed both crossed and uncrossed stimuli in front of the background dots), and to a point behind the display screen (which placed both crossed and uncrossed stimuli behind the background dots). Results showed that depth discrimination was always good when the stimuli appeared in front of the background dots of the stereogram, whereas discrimination was always poor when the stimuli appeared behind the background dots. These results suggest that differences between crossed and uncrossed stereopsis as reported in past research arose, in part, from effects related to occlusion.

Depth Perception↗
PubMed1999

Airway epithelial cell-induced activation of monocytes and eosinophils in respiratory syncytial viral infection.

The early inflammatory events in respiratory syncytial viral (RSV) infection are likely to be crucial in the development of clinical disease, which is characterized by bronchiolitis with mononuclear cell inflammation, some eosinophil involvement and airway hyperreactivity. Since RSV replication is restricted to airway epithelial cells, our working hypothesis is that inflammatory cell recruitment by the infected cells will set the stage for late immunopathology. We have identified the selective induction and release of mononuclear cell and eosinophil-attracting beta-chemokines MIP-1alpha and RANTES, but not eotaxin, by RSV-infected airway epithelial cells and herein demonstrated the recruitment of eosinophils and monocytes, but not neutrophils, in response to chemokines produced by infected epithelial cells during viral replication and dissemination. The chemotactic response of both eosinophils and monocytes was inhibited by antibodies to RANTES but not to MIP-1alpha. Interaction of eosinophils or monocytes with RSV-infected epithelial cells resulted in the production of additional beta-chemokines MCP-1 and MIP-1beta, and increased levels of MIP-1alpha. The monocyte containing cultures produced >10 fold the amount of these chemokines compared to eosinophil containing cultures. On the other hand, the levels of RANTES and the lack of eotaxin were not altered in the cocultures, RSV-infected monocytes appeared to be the main source of MIP-1alpha and MIP-1beta, while MCP-1 was derived from monocytes as well as epithelial cells following coculture. These data implicate RANTES as the primary chemokine responsible for selectively recruiting eosinophils and monocytes to the site of RSV infection. This inflammatory response results in the production of high levels of additional chemokines capable of setting up a full-fledged inflammatory response including lymphocytes.

Cell Line↗
PubMed1999

Inflammatory response in humans exposed to 2.0 ppm nitrogen dioxide.

Nitrogen dioxide (NO2) is a common indoor air pollutant, especially in homes with unvented combustion appliances. Epidemiological studies suggest that children living in homes with unvented heating sources are more prone to respiratory infections than children living in homes with lower levels of NO2. However, experimental studies in which human volunteers were exposed acutely to moderate levels of NO2 (0.5-2.0 ppm) have shown little evidence of lung inflammation or decreased host resistance capacity. In the study reported here, 8 healthy volunteers were exposed to 2.0 ppm NO2 and to filtered air for 4 h while undergoing intermittent moderate exercise. Bronchoalveolar lavage was performed the following morning. The lavage was divided into a predominantly bronchial washing (first 20 ml of lavage; BL) and a predominantly alveolar washing (BAL). In the BL, NO2 exposure caused increases in polymorphonuclear neutrophils (PMNs), interleukin 6 (IL-6), IL-8, alpha1-antitrypsin, and tissue plasminogen activator, and decreases in epithelial cells. In the BAL, there were no NO2-induced changes in either cell numbers or soluble mediators. On the other hand, alveolar macrophages from BAL showed a decrease in the ability to phagocytose unopsonized Candida albicans and a decrease in superoxide production. No difference in susceptibility to virus infection was found between the NO2- and air-exposed macrophages. No changes in lung function were observed, but the aerosol bolus recovery technique revealed a statistically significant (p <.05) decrease in the fraction of aerosol recovered following nitrogen dioxide exposure, which is suggestive of small obstructive changes induced by NO2.

Adolescent↗
PubMed1999

Comparison of the transcription and replication strategies of marburg virus and Ebola virus by using artificial replication systems.

The members of the family Filoviridae, Marburg virus (MBGV) and Ebola virus (EBOV), are very similar in terms of morphology, genome organization, and protein composition. To compare the replication and transcription strategies of both viruses, an artificial replication system based on the vaccinia virus T7 expression system was established for EBOV. Specific transcription and replication of an artificial monocistronic minireplicon was demonstrated by reporter gene expression and detection of the transcribed and replicated RNA species. As it was shown previously for MBGV, three of the four EBOV nucleocapsid proteins, NP, VP35, and L, were essential and sufficient for replication. In contrast to MBGV, EBOV-specific transcription was dependent on the presence of the fourth nucleocapsid protein, VP30. When EBOV VP30 was replaced by MBGV VP30, EBOV-specific transcription was observed but with lower efficiency. Exchange of NP, VP35, and L between the two replication systems did not lead to detectable reporter gene expression. It was further observed that neither MBGV nor EBOV were able to replicate the heterologous minigenomes. A chimeric minigenome, however, containing the EBOV leader and the MBGV trailer was encapsidated, replicated, transcribed, and packaged by both viruses.

Ebolavirus↗
PubMed1999

First-cousin matings and congenital heart disease in Saudi Arabia.

BACKGROUND: Consanguinity may be a risk factor that contributes to congenital heart disease in an inbred population, particularly among first cousins; with high rates of intermarriage between relatives, consanguinity is associated with congenital heart disease particularly among first cousins. PATIENTS AND METHODS: This study examines a group of 1,028 consecutive congenital heart disease (CHD) patients identified through the Congenital Heart Disease Registry at King Faisal Specialist Hospital in Riyadh, Saudi Arabia. Families were interviewed by an Arabic-speaking data collector for information on consanguinity and demographic data. After exclusions for nonavailability, data were collected on 949 cases and the proportions of first-cousin consanguinity in the study sample were compared to national population data. A z test of proportions was utilized to test the hypothesis that there are higher proportions of first-cousin consanguinity in the study sample of congenital heart patients than in the general population. FINDINGS: Data indicate that the proportion of first-cousin matings among CHD patients is significantly higher than that of first-cousin intermarriages reported in the general population (p < 0.001). Regional breakdowns of the data substantiate significant differences (p < 0.001) in the proportions of first-cousin consanguinity in the study sample compared to the general population. INTERPRETATION: In a population with a high degree of inbreeding, consanguinity may exacerbate underlying genetic risk factors, particularly for offspring of first-cousin matings. This finding has public health implications for genetic counseling and prevention of some cardiac malformations.

Journal Article↗
PubMed1999

Compartmentalization of the inflammatory response to inhaled grain dust.

Interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and the secreted form of the IL-1 receptor antagonist (sIL-1RA) are involved in the inflammatory response to inhaled grain dust. Previously, we found considerable production of these cytokines in the lower respiratory tract of workers exposed by inhalation to aqueous extracts of corn dust extract. Alveolar macrophages (AM) have long been considered the cell type responsible for producing these cytokines, and only recently has it been realized that airway epithelial cells may also be involved in cytokine production. In order to determine whether airway epithelia are involved in the inflammatory response to inhaled corn dust extract and to compare the magnitude of response of bronchial epithelial cells (BE) and bronchoalveolar lavage (BAL) cells, we used the reverse transcriptase/polymerase chain reaction (RT/PCR) technique in a semiquantitative manner to evaluate the concentration of IL-1beta, IL-6, IL-8, TNF-alpha, and sIL-1RA. Alveolar cells were obtained by BAL, and BE were obtained by endobronchial brush biopsy from 15 grain handlers 6 h after experimental inhalation of saline or an aqueous corn dust extract. After inhalation of saline, BE expressed low but detectable levels of IL-6, IL-8, and IL-1beta (> 1 complementary DNA [cDNA] molecule/cell). After inhalation of corn dust extract, the expression of messenger RNA (mRNA) for IL-1beta and IL-8 in the BE were significantly increased, whereas no change was seen in IL-6, sIL-1RA, and TNF-alpha mRNA expression. Comparing cytokine mRNA levels in BE and BAL cells from the same subjects after inhalation of corn dust extract, BE and BAL cells expressed equivalent amounts of IL-8 mRNA; IL-1beta was 11-fold higher in BAL cells; and TNF-alpha and sIL-1RA were expressed exclusively by BAL cells. Immunostaining for the cytokines in BAL cells showed cytokine protein expression in AMs but not in polymorphonuclear cells (PMNs). On the other hand, sIL-1RA was strongly expressed in both AMs and PMNs. Analysis of cytokine protein levels in endobronchial lavage (EBL) fluid demonstrated that only IL-8 was released in detectable amounts into the airway lumen, whereas all the other cytokines of interest were exclusively found in the BAL fluid. Thus, within 6 h after inhalation exposure to corn dust extract, BE appear to contribute to airway inflammation by producing IL-8. AMs are responsible for most of the IL-1beta and IL-6 production in the alveolar region, whereas AMs and PMNs both produce sIL-1RA. Our findings suggest that the inflammatory response to inhaled grain dust is compartmentalized, involving specific mediators of inflammation released by macrophages, neutrophils, and airway epithelial cells.

Adolescent↗
PubMed1999

Child centered literacy orientation: a form of social capital?

OBJECTIVE: To describe the home literacy environment and to identify financial, human, and social capital variables associated with the presence or lack of Child Centered Literacy Orientation (CCLO) in families with young children who regularly attend pediatric primary care clinics. DESIGN: Cross-sectional case-control analysis of structured parent interviews conducted in two hospital-based and four community-based pediatric clinics in New England. SUBJECTS: Parents of 199 healthy 1- to 5-year-old children whose mean age was 30 +/- 15 (SD) months were interviewed. Parents were primarily mothers (94%) with a mean age of 28 +/- 7 (SD) years 60% of whom were single. Educational levels of study parents varied: 43% had not graduated from high school, 29% had a high school equivalency, and 28% had at least a year of college or vocational training. This was a multiethnic parent group. Sixty-five percent were bilingual or non-English speaking. Fifty-eight percent were born outside of the continental United States. Parents were primarily of low-income status with 85% receiving Women, Infant, and Children (WIC) food supplements, Aid to Families With Dependent Children, and/or Medicaid. RESULTS: Half of the parents interviewed reported that they rarely read books. Sixty percent of children had fewer than 10 books at home and two-thirds of these households contained fewer than 50 books total. When asked open-ended questions, 28% of parents said that sharing books with their child was one of their three favorite activities together, 14% said that looking at books was one of their child's three favorite things to do, and 19% reported sharing books at bedtime at least six times each week. Thirty-nine percent of families had at least one of these three literacy-related responses present and so were said to have a CCLO. A backwards stepwise multiple logistic regression on CCLO was performed with family financial, human, and social capital variables. Parents married or living together (odds ratio [OR] 2.56, 95% confidence interval [CI] = 1.21-5.42), higher adult-to-child ratios in the home (OR 1.92, 95% CI = 1.20-3.05), households speaking only English (OR 2.67, 95% CI = 1.24-5.76), parents reading books themselves at least a few times a week (OR 2.86, 95% CI = 1.38-5.91), and homes with more than 10 children's books (OR 3.3, 95% CI = 1.6-6.83), were all independently and significantly associated with the presence of CCLO. Older child age and higher parent education remain in the model but were not significant at the P <.05 level. Ethnicity and income status were dropped for lack of additional significance from this model, which described 24% of the variance in CCLO. CONCLUSION: Although two-parent families and higher adult-to-child ratios in the home appear to be social capital variables with protective effects, low-income, single-parent, and minority or immigrant families are at significant risk for lacking both children's books and a CCLO. We suggest that CCLO may itself be another form of social capital reflecting parental goals and expectations for their children. We speculate that interventions which provide children's books and information about reading with children to impoverished families with young children may facilitate more parent-child book sharing. Pediatricians and other primary care providers serving underserved populations may have a unique opportunity to encourage activities focusing on young children and promoting literacy.

Analysis of Variance↗
PubMed1999

Concurrent treatment of patients with depression in the community: provider practices, attitudes, and barriers to collaboration.

BACKGROUND: In randomized controlled trials, patients with major depression who receive broad-based collaborative treatment by both primary care physicians (PCPs) and mental health providers (MHPs) have better outcomes than patients who receive usual care. However, little is known about the concurrent treatment of patients with depression in the community. This study describes the perceptions of PCPs of the frequency of concurrent treatment in community settings, the degree of collaboration between co-treating providers, and factors associated with greater interaction and collaboration. METHODS: A survey was distributed to a stratified, random sample of 276 eligible family physicians in Michigan. Primary analyses were descriptive statistics (point estimation) of PCP practice patterns. Secondary analyses explored predictors of collaboration with multivariable regression. RESULTS: A total of 162 eligible PCPs (59%) returned the survey. PCPs reported that they co-treated approximately 30% of their depressed patients with MHPs. They made contact with co-treating MHPs in approximately 50% of shared cases; however, provider contact seldom included joint treatment planning. PCPs perceived collaborative treatments to be more problematic when patients were enrolled in managed care programs. In multivariable regression, co-location of MHP and PCP practices (in the same building) was strongly associated with increased interaction and collaboration (P <.001). CONCLUSIONS: Concurrent treatment of depressed patients is common in the community, but these treatments are less interactive and collaborative than the treatment models proven effective in randomized controlled trails. If concurrent treatments are to become more collaborative-with regular contact and effective communication-co-location of practices appears important.

Community Mental Health Services↗
PubMed1999

Ambulatory surgery center joint ventures involving tax-exempt entities.

This article provides an overview of the tax-exempt related issues for ambulatory surgery center joint ventures involving tax-exempt entities. The article analyzes the key points of analysis of the guidance released by the IRS, in particular General Counsel Memorandum 39862, Revenue Ruling 98-15, and Redlands Surgical Services v. Commissioner of the Internal Revenue Service. These key points include whether the venture results in private inurement to insiders and whether the venture furthers the charitable purposes of the tax-exempt entity. The article also provides practical guidance to analyze the documents and structure of the joint venture to ensure compliance with the IRS guidance. These practical considerations include, among other things, whether the charitable purposes of the tax-exempt entity are clearly expressed in the documents and whether the tax-exempt entity has sufficient control over the joint venture to ensure the charitable purposes are being adhered to.

Charities↗
PubMed1999

Specialty practices consolidate: new litigation emerges. Boman v. Southeast Medical Services Group.

This case is instructive in that it highlights a trend to use the Federal health care statutes in furtherance of a broad array of lawsuits. While the statutes were intended principally to protect the Medicare and Medicaid programs, the statutes are increasingly used to remedy a plethora of conduct. Here, the case is also helpful in that it does not dismiss or downplay the use of the Anti-Kickback Statute for such purpose. Rather, the court simply stated that the practice did not violate the Anti-Kickback Statute.

Fees and Charges↗
PubMed1998

Expression of a tyrosine phosphorylated, DNA binding Stat3beta dimer in bacteria.

The signal transducer and activator of transcription (STAT) proteins deliver signals from the cell membrane to the nucleus. An N-terminally truncated fragment of murine Stat3beta, Stat3betatc (127-722), was produced in bacteria. STAT proteins must be specifically phosphorylated at a single tyrosine residue for dimerization and DNA binding. Therefore, Stat3betatc was coexpressed with the catalytic domain of the Elk receptor tyrosine kinase. Stat3betatc was quantitatively phosphorylated by this kinase domain. Gel filtration chromatography revealed a Stat3betatc dimer. Y705 was identified as the major phosphorylated residue of Stat3betatc. This corresponds to the tyrosine residue which is phosphorylated by the Janus kinase in vivo. The phosphorylated Stat3betatc specifically bound to DNA binding sites. The described protocol allows the production of large amounts of activated protein for biochemical and pharmaceutical studies.

Acute-Phase Proteins↗
PubMed1998

Decreased CD11b expression, phagocytosis, and oxidative burst in urban particulate pollution-exposed human monocytes and alveolar macrophages.

Elevated levels of air pollution particulates < or = 10 microm in diameter (PM10) have been associated with an increase in mortality and morbidity due to pulmonary complications, including pneumonia. Impairment of inflammatory and host defense functions of the alveolar macrophage (AM) may be a precipitating factor. The present study was undertaken to determine whether human AM and blood derived monocytes (MO) modulate the expression of receptors important for phagocytosis of opsonized microbes (CD11b, CD11c), gram-negative bacteria (CD14), extracellular matrix interaction (CD29), and immune responses (CD11a, CD54, HLA-DR) when exposed to particulates obtained from urban air (UAP). Furthermore, phagocytosis of and oxidant generation by opsonized yeast were investigated in particle-exposed cells. AM and MO exposed to UAP for 18 h expressed significantly lower levels of CD11b and CD29. CD14 expression was markedly decreased in MO but not in AM, and CD11c was reduced in AM but not in MO. CD11a, CD54, and HLA-DR were unaltered in both phagocyte populations. Decreased receptor expression was not dependent on particle load in the cells. Phagocytosis of Saccharomyces cerevisiae and the chemiluminescence response were also significantly inhibited by UAP. Time-course studies revealed that decreased oxidant generation was evident already at 3 h postexposure, while significant effects on phagocytosis and CD11b expression were found at 18 h. These data indicate that exposure to particulate pollution is likely to impair host defense functions of AM and MO, which are important in elimination of a variety of pathogens in the lung.

Air Pollution↗