Private health care in developing countries.
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Delivery of Health Care↗
Biomedical subjects
E Smith
Publications and source records attributed to E Smith.
Plasminogen activator inhibitor-1 regulates tumor growth and angiogenesis.
Elevated expression of plasminogen activator inhibitor-1 (PAI-1) in tumors is associated with a poor prognosis in many cancers. Reduced tumor growth and angiogenesis have also been reported in mice deficient in PAI-1. These results suggest that PAI-1 may be required for efficient angiogenesis and tumor growth. In the present study, we demonstrate that PAI-1 can both enhance and inhibit the growth of M21 human melanoma tumors in nude mice and that this appears to be due to PAI-1 regulation of angiogenesis. Quantitative analysis of angiogenesis in a Matrigel implant assay indicated that in PAI-1 null mice angiogenesis was reduced approximately 60% compared with wild-type mice, while in mice overexpressing PAI-1, angiogenesis was increased nearly 3-fold. Furthermore, addition of PAI-1 to implants in wild-type mice enhanced angiogenesis up to 3-fold at low concentrations but inhibited angiogenesis nearly completely at high concentrations. Together, these data demonstrate that PAI-1 is a potent regulator of angiogenesis and hence of tumor growth and suggest that understanding the mechanism of this activity may lead to the development of important new therapeutic agents for controlling pathologic angiogenesis.
Animals↗
Aromatic hydrocarbon "humps" in the marine environment: unrecognized toxins?
Gas chromatographic analysis of the hydrocarbons of environmental samples often reveals that unresolved complex mixtures (UCMs) or gas chromatographic "humps" of aliphatic and aromatic hydrocarbons are most abundant--yet little consideration seems to have been given to the possible toxicological impacts of hydrocarbon "humps". Here we show, using a well-accepted bioassay, that monoaromatic components of a UCM of hydrocarbons from a crude oil elicit a sublethal toxic response in a typical marine pollution indicator organism (the mussel, Mytilus edulis). Furthermore, coastal U.K. mussels shown previously to have unexplained impaired health contained high concentrations of UCMs, including monoaromatic UCMs. These findings may have important implications for our understanding of the toxicological sublethal effects of oil residues in the environment. Given the relatively resistant nature of UCM hydrocarbons, the effects of both acute oil spills and more chronic discharges may need further consideration.
Animals↗
[To die alone, a big city problem?].
The question whether being found dead is a problem related to living in a big city was examined by using death certificates from a 3-month period in 1994. The rates of persons found dead were higher for both sexes in the City of Copenhagen than in the rural County of Storstrøm. The age distribution showed that the rate increased with advancing age. The vast majority were found dead in their own home, although the rate was higher in Copenhagen than in Storstrøm. Whereas the manner of death was natural for the majority of cases in both areas, more deaths with an uncertain manner of death were recorded in Copenhagen than in Storstrøm (32% vs 9%). In general, suicide or accident was more often reported in those found dead in the County of Storstrøm than in those in Copenhagen. The cause of death was unknown in 46% of deaths in Copenhagen where 16% had died from external causes, proportions that were 58% and 21%, respectively, in Storstrøm. The rate of legal autopsies was higher in subjects with an uncertain manner of death than in the rest, and was also associated with an age below 40 years. We conclude that being found dead is related to living in a big city, although the reason(s) for this remains unidentified.
Adult↗
[Screening of donor blood for viral markers. Anti-HIV, HBsAg and anti-HTLV-I/II in Denmark 1990-1999].
INTRODUCTION: We describe the results of donor blood screening in Denmark for anti-HIV-1/2 in the period 1990-1999 and for anti-HCV, HBsAg, and anti-HTLV-I/II in the period 1994-1999. METHODS: Danish blood banks report the results of donor blood screening to the State Serum Institute on a monthly basis. This study concerns the data reported in the above two period. Reports from the years given above are worked out in the present study. RESULTS: The frequencies of infection among candidate donors are for HIV: 4.8 per 100,000; hepatitis C: 52.7 per 100,000; and hepatitis B: 60 per 100. The yearly incidences of new infections among the 260,000 regular donors in Denmark are for HIV: 0.42 per 100,000 regular donors; hepatitis C: 0.64 per 100,000 regular donors; and hepatitis B: 0.70 per 100,000 regular donors. All donations in Denmark were tested for anti-HTLV-I/II in the period 1 April 1994 to 1 October 1997, after which only candidate donors were tested. The frequency of HTLV-I infection in previously untested donors was 1 in 60,000 and that of HTLV-II infection 1 in 150,000. The frequency of HTLV-I infection among candidate donors was 1 in 50,000 and that of HTLV-II infection 1 in 100,000. No seroconverters have been found.
Adult↗
[Risk of disease transmission via donor blood in Denmark at the turn of the century].
INTRODUCTION: Published results of donor blood screening in Denmark were used to calculate the risks of window phase donations. METHODS: The main parameter was the frequencies of a confirmed positive donation from regular donors per 100,000 donations are: 0.34, for HIV; 0.47 for hepatitis C virus; 0.53 for hepatitis B virus; and nil for HTLVI/II. The mean interdonation interval between donations from regular donors is six months year. Window phase duration were estimated to be 22 days for anti-HIV; 10 weeks for anti-HCV; and 56 days for HBsAg. Blood from candidate donors is not used in Denmark. Thus, the risk of a window phase donation equals the risk of a window phase donation in donations from regular donors. RESULTS: The risks of window phase donations in Denmark are: 1 in 2,000,000 for HIV; 1 in 500,000 for hepatitis C; 1 in 250,000 for hepatitis B; and immeasurably low for HTLVI/II. DISCUSSION: The measures taken nowadays to prevent infection from allogeneic blood transfusion have resulted in a risk reduction of HIV transmission by a factor 50 and of HCV transmission by a factor 400, compared with the risks prevailing in Denmark in the early 1980s. The present very low risk renders obsolete predeposited autologous blood solely on the indication to prevent infection. Zero risk of transmission of HIV and HCV might be approached by introducing NAT screening for these viruses.
Biomarkers↗
Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice.
The cyclooxygenase (COX)-2 gene encodes an inducible prostaglandin synthase enzyme that is overexpressed in adenocarcinomas and other tumors. Deletion of the murine Cox-2 gene in Min mice reduced the incidence of intestinal tumors, suggesting that it is required for tumorigenesis. However, it is not known if overexpression of Cox-2 is sufficient to induce tumorigenic transformation. We have derived transgenic mice that overexpress the human COX-2 gene in the mammary glands using the murine mammary tumor virus promoter. The human Cox-2 mRNA and protein are expressed in mammary glands of female transgenic mice and were strongly induced during pregnancy and lactation. Female virgin Cox-2 transgenic mice showed precocious lobuloalveolar differentiation and enhanced expression of the beta-casein gene, which was inhibited by the Cox inhibitor indomethacin. Mammary gland involution was delayed in Cox-2 transgenic mice with a decrease in apoptotic index of mammary epithelial cells. Multiparous but not virgin females exhibited a greatly exaggerated incidence of focal mammary gland hyperplasia, dysplasia, and transformation into metastatic tumors. Cox-2-induced tumor tissue expressed reduced levels of the proapoptotic proteins Bax and Bcl-x(L) and an increase in the anti-apoptotic protein Bcl-2, suggesting that decreased apoptosis of mammary epithelial cells contributes to tumorigenesis. These data indicate that enhanced Cox-2 expression is sufficient to induce mammary gland tumorigenesis. Therefore, inhibition of Cox-2 may represent a mechanism-based chemopreventive approach for carcinogenesis.
Animals↗
Prevalence of psychiatric disorders among persons convicted of driving while impaired.
BACKGROUND: Large numbers of convicted drunk drivers are entering alcohol treatment programs, yet little information is available about their need for psychiatric treatment. This study of convicted drunk drivers estimates lifetime and 12-month prevalence of DSM-III-R psychiatric disorders (alcohol and drug abuse and dependence, major depressive disorder, dysthymic disorder, generalized anxiety disorder, posttraumatic stress disorder, and antisocial personality disorder) and compares rates with estimates from a US population-based survey. METHODS: Six hundred twelve women and 493 men, aged 23 to 54 years, convicted of driving while impaired, who had been referred to a screening program in Bernalillo County, New Mexico, were located and interviewed using the Diagnostic Interview Schedule between January 25, 1994, and June 30, 1997. Psychiatric diagnoses were compared with findings from the National Comorbidity Survey for the western region of the United States, conducted between September 14, 1990, and February 6, 1992. RESULTS: Eighty-five percent of female and 91% of male offenders reported a lifetime alcohol-use disorder, compared with 22% and 44%, respectively, in the National Comorbidity Survey sample. Thirty-two percent of female and 38% of male offenders had a drug-use disorder, compared with 16% and 21%, respectively, in the National Comorbidity Survey sample. For offenders with alcohol-use disorders, 50% of women and 33% of men had at least 1 additional psychiatric disorder other than drug abuse or dependence, mainly posttraumatic stress disorder or major depression. CONCLUSION: Drunk-driving offenders need assessment and treatment services not only for alcohol problems but also for drug use and the other psychiatric disorders that commonly accompany alcohol-related problems.
Adult↗
Production of butyrylcholinesterase by Caco-2 cells: lack of relationship with triglyceride production.
Elevated levels of butyrylcholinesterase activity occur under a number of hypertriglyceridemic conditions, including diabetes and obesity. This study examines whether butyrylcholinesterase activity has a direct effect on triglyceride production, using Caco-2 cells, a human intestinal adenocarcinoma cell line. Caco-2 cells were incubated with 500 microM oleate to stimulate triglyceride production, and butyrylcholinesterase activity was measured in the cellular homogenate. Butyrylcholinesterase activity was approximately 3 x 10(-3) micromol/min per milligram protein. Although triglyceride production increased by almost five-fold after 18 h of stimulation with oleate, butyrylcholinesterase activity was not increased. Furthermore, inhibition of butyrylcholinesterase activity using 1 mM tetraisopropylpyrophosphoramide did not significantly affect triglyceride production or secretion. Human insulin (100 microU/ml) increased the production of butyrylcholinesterase without increasing triglyceride production. This demonstrates that stimulation of fatty acid production and butyrylcholinesterase activity occur by independent mechanisms and suggests that their correlation in hyperlipidemic conditions is not due to a direct relationship in production in situ.
Butyrylcholinesterase↗
Awareness of infertility in men with cystic fibrosis.
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Adolescent↗
Evaluation of urinary continence and voiding function: early results in men with neo-urethral modification of the Hautmann orthotopic neobladder.
PURPOSE: At our institution we use the Hautmann orthotopic bladder replacement with a chimney and neo-urethral modification. A neo-urethral tube allows tension-free intestino-urethral anastomosis, thus providing application of this procedure for patients who may otherwise not qualify due to the inability of the small bowel to reach the urethra. However, this neo-urethral tube may also enhance continence by providing significant intra-abdominal urethral length. Conversely, such a modification may be associated with a higher degree of urinary retention. Early evaluation and reporting on the results of this procedure appear warranted. MATERIALS AND METHODS: From April 1996 to March 2000, 14 consecutive male patients underwent cystoprostatectomy and urinary reconstruction with Hautmann repair using chimney and neo-urethral modifications. We performed a retrospective analysis of urinary function and continence with data obtained from patient questionnaires completed preoperatively and at each postoperative office visit. The examining physician chart notes were reviewed for information about urinary retention. The American Urological Association symptom score and voiding bother index were used to assess urinary function and bother, respectively. Urinary continence was defined as the complete absence of any form of urinary leakage protection. RESULTS: Of the 14 patients 12 were completely continent day and night, with a median followup of 17 months. There were 2 patients who wore pads less than 7 months after surgery. Improvement of urinary continence appeared to continue up to 12 months postoperatively. Despite this encouraging effect, when our data were compared to the published literature, we noted a somewhat increased incidence of patients requiring clean intermittent catheterization to manage significant post-void urinary residuals. We had no patients with urethro-intestinal strictures who required clean intermittent catheterization. CONCLUSIONS: The neo-urethral tube modification appears to have a significant and favorable impact on urinary continence while seeming to be associated with a trend towards an increased rate of chronic urinary retention. Longer followup will be required to determine whether this higher rate of chronic urinary retention will remain stable or change with time.
Aged↗
Pollutant concentrations of stormwater and captured sediment in flood control sumps draining an urban watershed.
Levee sump systems are used by many riverine communities for temporary storage of urban wet weather flows. The performance and transport of stormwater pollutants in sump systems, however, have not been systematically studied. Although flow of stormwater through a sump system is regulated solely by flood-control requirements, these sumps may function as sedimentation basins that provide purification of stormwater. The objective of this paper is to present a case study of stormwater and sediment analysis for conventional pollutants in flood control sumps in an urban watershed. Two sumps of highly variable physical and hydraulic characteristics were selected for analysis. The results suggest that: (1) first-flush samples may not give an accurate picture of outfall concentrations of stormwater to the sump; (2) time-variable concentrations of pollutants in a sump are related to the hydraulic characteristics of the basin; and, (3) post-event sediment analysis provides verification of pollutant capture in the sumps. This study is an initial step toward development of a more comprehensive management model for flood control sumps that incorporates their hydraulic performance for quantitative assessment of pollutant loads, pollutant discharges, and pollutant removals with respect to the sumps.
Enterobacteriaceae↗
In utero intervention in a patient with prune-belly syndrome and severe urethral hypoplasia.
Prenatal ultrasound scanning of a 20-year-old woman at 17 weeks of gestation revealed findings suggestive of bladder outlet obstruction, including bladder distension, dilated bilateral ureters, urinary ascites, and oligohydramnios. Vesicoamniotic shunts were placed with decompression of the bladder and correction of the amniotic fluid levels. Labor was induced at 36 weeks' gestation. At birth, the infant was noted to have prune-belly syndrome with severe urethral hypoplasia, a variant usually associated with a poor prognosis, necessitating vesicostomy for bladder drainage. We present a case of a patient with prune-belly syndrome and bladder outlet obstruction in whom early intervention resulted in an excellent outcome with preservation of renal and pulmonary function.
Adult↗
Pseudohypoaldosteronism associated with ureterocele and upper pole moiety obstruction.
A 2-month-old girl was diagnosed with a febrile urinary tract infection. Subsequent studies revealed a right renal duplication anomaly with a poorly functioning upper pole moiety subtended by an intravesical ureterocele. The patient was also found to have hyperkalemia, hyponatremia, and elevated serum aldosterone. After antibiotic therapy, the urinary tract infection resolved, although the electrolyte and hormonal abnormalities persisted. At 4 months of age, a right upper pole heminephrectomy was performed. The patient's electrolyte and hormonal levels normalized. This case represents an unusual case of pseudohypoaldosteronism presenting with urinary tract infection and obstructed upper pole moiety that resolved after surgical intervention.
Anti-Bacterial Agents↗
Prior exposure of mice to Fusobacterium nucleatum modulates host response to Porphyromonas gingivalis.
Multiple periodontal pathogens sequentially colonize the subgingival niche during the conversion from gingivitis to destructive periodontal disease. An animal model of sequential immunization with key periodontal pathogens has been developed to determine whether T- and B-lymphocyte effector functions are skewed and fail to protect the host from pathogenic challenge. The present study was performed to evaluate the immunomodulatory effect of exposure to Fusobacterium nucleatum prior to Porphyromonas gingivalis. Group 1 (control) mice were immunized with phosphate-buffered saline, group 2 were immunized with F. nucleatum prior to P. gingivalis and group 3 were immunized with P. gingivalis alone. All the T-cell clones derived from group 2 demonstrated type 2 helper T-cell clone (Th2 subsets), whereas those from group 3 mice demonstrated Th1 subsets. Exposure of mice to F. nucleatum prior to P. gingivalis interfered with the opsonophagocytosis function of sera against P. gingivalis. In adoptive T-cell transfer experiments, in vivo protective capacity of type 2 helper T-cell clones (Th2) from group 2 was significantly lower than type 1 helper T-cell clones (Th1) from group 3 against the lethal dose infection of P. gingivalis. Western blot analysis indicated a different pattern of recognition of P. gingivalis fimbrial proteins between sera from group 2 and group 3. In conclusion, these studies suggest that exposure of a host to F. nucleatum prior to the periodontal pathogen P. gingivalis modulates the host immune responses to P. gingivalis at the humoral, cellular and molecular levels.
Adjuvants, Immunologic↗
Creation of genome-wide protein expression libraries using random activation of gene expression.
Here we report the use of random activation of gene expression (RAGE) to create genome-wide protein expression libraries. RAGE libraries containing only 5 x 10(6) individual clones were found to express every gene tested, including genes that are normally silent in the parent cell line. Furthermore, endogenous genes were activated at similar frequencies and expressed at similar levels within RAGE libraries created from multiple human cell lines, demonstrating that RAGE libraries are inherently normalized. Pools of RAGE clones were used to isolate 19,547 human gene clusters, approximately 53% of which were novel when tested against public databases of expressed sequence tag (EST) and complementary DNA (cDNA). Isolation of individual clones confirmed that the activated endogenous genes can be expressed at high levels to produce biologically active proteins. The properties of RAGE libraries and RAGE expression clones are well suited for a number of biotechnological applications including gene discovery, protein characterization, drug development, and protein manufacturing.
Cell Line↗
The determination of alkylphenols in aqueous samples from the Forth Estuary by SPE-HPLC-fluorescence.
Nonylphenol and octylphenol have been identified as endocrine disrupters with the ability to cause reproductive deformities in a number of organisms. A normal phase high-performance liquid chromatography (HPLC) method with fluorescence detection was developed with a mobile phase of cyclohexane/methyl-tertiary-butyl ether (MTBE) (70 + 30). The extraction of the alkylphenols from the water samples was evaluated using solid-phase extraction (SPE) with a C2 packing sorbent. The complete method was validated and the limit of detection calculated to be 0.15 ppb (microg l(-1)). The method was novel for the analysis of specific alkylphenols in an aqueous matrix. A survey of the Forth Estuary in May 2000 resulted in no detectable amounts of nonyl- or octylphenol, whilst a survey during August of the same year produced concentrations ranging from 0.17-1.90 ppb for nonylphenol and 0.17-1.28 ppb for octylphenol. These results are compared with other river and estuarine studies with concentrations considered in terms of toxicity to aquatic organisms. The concentrations determined in the Forth Estuary are consistent with a contaminated though not grossly polluted estuarine system.
Chemistry Techniques, Analytical↗
Human papillomavirus testing for triage in a referral population.
OBJECTIVE: This study evaluated the Digene HPV Assay Hybrid Capture System(R) as a triage method. METHODS: Results of an HPV assay were compared with a final tissue diagnosis of cervical intraepithelial neoplasia 2 (CIN2) or greater. These results were stratified based on Pap smear diagnosis and evaluated in 4 triage algorithms. RESULTS: Of the 4 algorithms evaluated, the highest savings came from not performing colposcopy for patients with repeat atypical squamous cells of undetermined significance (ASCUS), but that resulted in missing nine patients with CIN2 and CIN3 histology. HPV testing failed to diagnose 67% (6 out of 9) to 48% (10 out of 21) of patients with underlying CIN2 and CIN3. CONCLUSIONS: Although HPV high-risk positive results correlate with high-grade histology, it is associated with significant false negatives. The HPV low-risk test is not clinically useful. These tests were poor methods to triage patients in our population.
Journal Article↗