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At least 1,369 records · Page 76Linked to original sources
PubMed2001

Effect of prenatal treatment on the risk of intracranial and ocular lesions in children with congenital toxoplasmosis.

BACKGROUND: Hydrocephalus, intracranial calcification and retinochoroiditis are the most common manifestations of tissue damage due to congenital toxoplasmosis, but the effect of prenatal treatment on these outcomes is unclear. We aimed to determine the effect of prenatal treatment for toxoplasmosis on the risk of intracranial and ocular lesions in congenitally infected children at 3 years of age. METHODS: A cohort of mothers identified during pregnancy with toxoplasma infection and their 181 liveborn children with confirmed congenital toxoplasmosis was retrospectively analysed to determine the presence of intracranial and ocular lesions. As few women are not treated, we compared the effects of the treatment potency (pyrimethamine-sulfadiazine versus spiramycin or no treatment), and the timing of treatment, on the risks of intracranial lesions, time to detection of ocular lesions, and detection of any lesions (intracranial or ocular) by 3 years of age. Analyses took account of the gestation at maternal seroconversion. RESULTS: There was no evidence for an effect of pyrimethamine-sulfadiazine on intracranial, ocular or any lesions by 3 years: odds ratio (OR) for any lesions 0.89 (95% CI : 0.41, 1.88). There was no evidence of an effect of delayed treatment on ocular lesions (hazard ratio = 0.69, 95% CI : 0.28, 1.68) or any lesions by 3 years of age (OR = 0.44, 95% CI : 0.16, 1.19). CONCLUSIONS: Our study failed to detect a beneficial effect of early or more potent anti toxoplasma treatment on the risks of intracranial or ocular lesions in children with congenital toxoplasmosis. However, larger, prospective studies, which determine the effect of prenatal treatment on long-term developmental outcomes are required to justify changes in clinical practice.

Anti-Bacterial Agents↗
PubMed2003

Comparison of methods for analysing cluster randomized trials: an example involving a factorial design.

BACKGROUND: Studies involving clustering effects are common, but there is little consistency in their analysis. Various analytical methods were compared for a factorial cluster randomized trial (CRT) of two primary care-based interventions designed to increase breast screening attendance. METHODS: Three cluster-level and five individual-level options were compared in respect of log odds ratios of attendance and their standard errors (SE), for the two intervention effects and their interaction. Cluster-level analyses comprised: (C1) unweighted regression of practice log odds; (C2) regression of log odds weighted by their inverse variance; (C3) random-effects meta-regression of log odds with practice as a random effect. Individual-level analyses comprised: (I1) standard logistic regression ignoring clustering; (I2) robust SE; (I3) generalized estimating equations; (I4) random-effects logistic regression; (I5) Bayesian random-effects logistic regression. Adjustments for stratification and baseline variables were investigated. RESULTS: As expected, method I1 was highly anti-conservative. The other, valid, methods exhibited considerable differences in parameter estimates and standard errors, even between the various random-effects methods based on the same statistical model. Method I4 was particularly sensitive to between-cluster variation and was computationally stable only after controlling for baseline uptake. CONCLUSIONS: Commonly used methods for the analysis of CRT can give divergent results. Simulation studies are needed to compare results from different methods in situations typical of cluster trials but when the true model parameters are known.

Breast Neoplasms↗
PubMed2004

Are social comparisons of homes and cars related to psychosocial health?

BACKGROUND: It has been suggested that perceiving oneself to be inferior to those around one is a psychosocial risk factor associated with ill health. The aim of this study was to examine whether negative social comparisons of the worth of two common assets (homes and cars) were related to psychosocial health (i.e. lower self-esteem and mastery, higher anxiety, and depression). METHODS: A postal questionnaire was sent to a random sample of adults in the West of Scotland (sampling from the 1997 electoral roll, response rate was 50%, achieved sample 2838). RESULTS: Having adjusted for socio-demographic variables, rating one's house/flat as worth less than others was associated with lower self-esteem (P < 0.001) and mastery (P < 0.001) and higher depression (P < 0.007) and anxiety (P < 0.012). Rating one's car as worth less than others was not significantly associated with these psychosocial variables. CONCLUSIONS: Our findings lend some support, but only in relation to the home, to the hypothesis that perceiving oneself to be worse off in relation to those around is related to poorer psychosocial health.

Adult↗
PubMed1994

Human microvascular endothelial cell toxicity caused by Brazilian purpuric fever-associated strains of Haemophilus influenzae biogroup aegyptius.

An in vitro cytotoxicity model that uses an immortalized human microvascular endothelial cell line (HMEC-1) differentiates Brazilian purpuric fever (BPF)-associated Haemophilus influenzae biogroup aegyptius (HAE) strains from non-BPF-associated HAE strains. Toxic strains produced a characteristic HMEC-1 phenotype at an MOI of < 1 bacterium/1000 tissue culture cells (TCC). Nontoxic strains required MOIs of > 1000 bacteria/TCC to produce an observable effect. The cytotoxic phenotype was characterized by the presence of large clumps of HMEC-1 cells, which detached from the monolayer within 48 h of inoculation by HAE cells. The cytotoxic phenotype was observed with 100% of BPF-associated HAE (40/40) and 14% of non-BPF-associated HAE (8/57; P < .001). The ability to study a BPF-associated phenotype in vitro using human microvascular cells should enhance our knowledge of BPF pathogenesis.

Cell Line↗
PubMed2004

The chalcone xanthohumol inhibits triglyceride and apolipoprotein B secretion in HepG2 cells.

The present study examined the role of xanthohumol (XN), a plant chalcone, on apolipoprotein B (apoB) and triglyceride (TG) synthesis and secretion, using HepG2 cells as the model system. The data indicated that XN decreased apoB secretion in a dose-dependent manner under both basal and lipid-rich conditions (as much as 43% at 15 micromol/L). This decrease was associated with increased cellular apoB degradation. To determine the mechanism underlying this effect, we examined triglyceride availability, a major factor in the regulation of apoB secretion. XN inhibited the synthesis of TG in the microsomal membrane and the transfer of this newly synthesized TG to the microsomal lumen (decreases of 26 and 64%, respectively, under lipid-rich conditions), indicating that TG availability is a determining factor in the regulation of apoB secretion under the experimental conditions. The inhibition of TG synthesis was caused by a reduction in diacylglycerol acyltransferase (DGAT) activity, which corresponded to a decrease in DGAT-1 mRNA expression, but not DGAT-2 expression. Microsomal triglyceride transfer protein (MTP) may also control the rate of TG transfer from the microsomal membrane to the active lumenal pool. XN decreased MTP activity in a dose-dependent manner (as much as 30%). Whether the reduction in TG accumulation in the microsomal lumen is predominantly due to DGAT and/or MTP activity remains unknown. In summary, the data suggest that xanthohumol is a potent inhibitor of apoB secretion.

Acyltransferases↗
PubMed2005

Microsomal triglyceride transfer protein gene expression and ApoB secretion are inhibited by bitter melon in HepG2 cells.

Momordica charantia or bitter melon is traditionally used as an antidiabetic agent in Asia, Africa, and South America. Recent studies indicate that bitter melon can also lower plasma lipids and VLDL in diabetic animal models as well as animals fed a high-fat diet, suggesting an effect on lipoprotein metabolism. The aim of this study was to delineate the cellular and molecular mechanisms involved in the lipid-lowering properties of bitter melon and regulation of apolipoprotein B (apoB). Human hepatoma cells, HepG2, treated with bitter melon juice (BMJ) for 24 h reduced apoB secretion with and without the addition of lipids (P < 0.05). However, BMJ did not increase apoB secretion in cells treated with N-acetyl-leucyl-leucyl-norleucinal, indicating a lack of effect on the proteasomal degradation pathway. BMJ reduced the secretion of new triglycerides (P < 0.05) and decreased microsomal triglyceride transfer protein (MTP) mRNA expression, suggesting that lipid bioavailability and lipidation of lipoprotein assembly are likely involved in decreased apoB secretion. Interestingly, BMJ increased the nuclear translocation of the mature form of sterol regulatory element-binding protein-1c (SREBP-1c, P < 0.05), involved in MTP secretion. Our data suggest that BMJ is a potent inhibitor of apoB secretion and TG synthesis and secretion that may be involved in the plasma lipid- and VLDL-lowering effects observed in animal studies.

Apolipoproteins B↗
PubMed1998

Marfan Database (third edition): new mutations and new routines for the software.

The Marfan database is a software that contains routines for the analysis of mutations identified in the FBN1 gene that encodes fibrillin-1. Mutations in this gene are associated not only with Marfan syndrome but also with a spectrum of overlapping disorders. The third version of the Marfan database contains 137 entries. The software has been modified to accommodate four new routines and is now accessible on the World Wide Web at http://www.umd.necker.fr

Computer Communication Networks↗
PubMed1993

Modeling age- and time-specific incidence from seroprevalence:toxoplasmosis.

New forms of catalytic epidemic models were developed to estimate the incidence of primary toxoplasmosis infection from age- and time-specific seroprevalence data collected from persons aged 0-100 years in South Yorkshire, England, 1969-1990. Piecewise constant and exponential polynomial functions were used to assess the way in which incidence depended on age and time, and to guide the choice of parametric models suitable for prediction. Incidence estimates were biased unless both age- and time-dependence were allowed for. New findings on the epidemiology of this infection emerged. Incidence appears to have fallen sixfold between 1915 and 1970, but has remained stable for the last 20 years. There is a marked peak in incidence in childhood. The incidence throughout the childbearing period is currently estimated to be 0.07 or less per 100 susceptible persons per year. However, these predictions were highly sensitive to assumptions about incidence in childhood, and the 95% confidence limits for a range of models were between 0.003 and 0.32% per year. Age- and time-specific seroprevalence data can be collected inexpensively on a mass population basis, and, with appropriate incidence modeling, may prove to be a powerful method for the study of infectious disease and for incidence prediction.

Adolescent↗
PubMed2000

The effects of neonatal screening for sickle cell disorders on lifetime treatment costs and early deaths avoided: a modelling approach.

BACKGROUND: The aim of the study was to calculate the cost to the UK National Health Service of providing treatment services for patients with sickle cell disorders. The rates of differential morbidity and mortality, in the first 10 years of life, between screen-detected early diagnosed and clinically presenting late diagnosed cohorts of sickle cell disorder patients are also estimated. METHOD: A cost model was developed, based on predictions of survival and the incidence of sickle cell disorder-related events. Direct data from the NHS are lacking, so data were incorporated from disparate sources. Patients with sickle cell disorders were divided into two categories: those with sickle cell anaemia and those with sickle HbC disease. RESULTS: Differentiating between sickle cell anaemia and sickle HbC disorder patients, the results show that the undiscounted (discounted at 6 per cent) lifetime treatment costs range from pound sterling 92323 (pound sterling 24917) to pound sterling 185614 (pound sterling 53861). The number of early deaths avoided per 100 births, as a result of early diagnosis through screening, ranges from 0.57 to 1.25. CONCLUSIONS: The resulting estimates may act as a guide to those involved in the planning of health care provision with regard to the resources required to treat sickle cell disorder patients. Such information may also be incorporated into the evaluation of both antenatal and neonatal screening programmes for sickle cell disorders.

Adolescent↗
PubMed2004

Cyanogenesis in Eucalyptus polyanthemos seedlings: heritability, ontogeny and effect of soil nitrogen.

Cyanogenic plants release cyanide from endogenous cyanide-containing compounds (generally cyanogenic glycosides) and thus have an effective means of chemical defense. The capacity for cyanogenesis can be highly variable, even among individuals within a population. The genetic, environmental and developmental factors determining this variability are poorly understood, particularly in tree species. We used Eucalyptus polyanthemos Schauer subsp. vestita L. Johnson & K. Hill to quantify aspects of the regulation of cyanogenic capacity, which in this species is determined by foliar cyanogenic glycoside concentration. A half-sibling progeny trial, based on seed collected from open-pollinated trees covering a range of cyanogenic capacities, was used to assess the heritability of cyanogenesis in E. polyanthemos. Narrow sense heritability (h(2) +/- 1 SE) was estimated to be 0.82 +/- 0.20 from an intra-class correlation and 0.78 +/- 0.11 from a standardized progeny-parent regression. Foliar cyanogenic glycoside concentrations were on average about 70% lower in seedlings than in maternal trees, suggesting that there is a developmental delay in the accumulation of cyanogenic capacity in this species. The high h(2) values indicate that cyanogenic capacity is largely genetically determined and that environmental factors have little effect. To test this supposition, we grew seedlings at two soil nitrogen (N) concentrations (N influences cyanogenic capacity in some species) and found no appreciable effect on cyanogenic glycoside concentration, biomass partitioning or relative growth rate. Highly cyanogenic seedlings grew more slowly than seedlings with lower cyanogenic capacities, and relative growth rate was positively associated with net assimilation rate in seedlings in both N treatments.

Cyanides↗
PubMed1995

Necrosis of malignant gliomas after intratumoral injection of 201Tl in vivo in the rat.

Fourteen adult Fischer 344 rats were inoculated in vivo unilaterally in the caudate nucleus in the brain with malignant RG 2 glioma cells. By 3 weeks a tumor with a diameter of 3-6 mm normally develops. Ten animals which survived the repeated periods of anesthesia and thallium (Tl) injections (intratumorally three times of 201Tl, 15-23 days after inoculation) showed a prolonged retention of radioactivity at the site of injection with no uptake in other organs except for the kidneys. Singular circumscribed necroses were found post-mortem at the site of injection, comprising malignant glioma tumor tissue, which in six animals was absent, in three animals was markedly reduced in size compared with controls and in one animal had the expected size. In four animals metastases were found in distant locations in the brain; in three of these cases there was a retention of radioactivity in the tumor. The selective necrotizing effect on the tumor cells is interpreted as mainly due to emission of Auger electrons from intracellularly accumulated 201Tl, giving rise to very high energy deposition in the vicinity of the cell nucleus. The results should also have implications for the treatment of human malignant gliomas.

Animals↗
PubMed1991

Antigen detection, virus culture, polymerase chain reaction, and in vitro antibody production in the diagnosis of vertically transmitted HIV-1 infection.

Polymerase chain reaction (PCR), virus culture (V), antigen detection (Ag), and in vitro antibody production (IVAP) assays may be useful for the early detection of vertically transmitted HIV-1 infection in infants under 18 months of age, when a diagnosis cannot be based on seropositivity because of maternal antibody persistence. To assess the reliability of these procedures and to correlate diagnostic results with infection status, 101 children born to HIV-1-seropositive mothers were evaluated by all these techniques within the first 6 months of life. The children were then followed up to the age of at least 18 months, when diagnosis was made on the basis of AIDS or AIDS-related complex (ARC) onset or persistence of HIV-1 seropositivity. Out of 27 children classified as infected according to the above criteria, 25 (92.5%) were repeatedly positive in IVAP test, 22 (81.5%) in the first PCR analysis, and only 19 (70.3%) in the initial V assay. On further testing, a total of 24 children (88.9%) were found positive in PCR assay, and 23 (85.2%) in V test. All these assays were found to be more sensitive than antigen detection for HIV-1 infection diagnosis, but the antigenaemia was shown to be a useful prognostic marker of disease onset. We also found that both Ag and IVAP assays could give false-positive results in the first 2 months of life, which severely limits their diagnostic value during this period of time. False-positive results in PCR assay could occur at any time of the tested period and were unrelated to the child's age.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗
PubMed1992

Two methods for assessing the risk-factor composition of the HIV-1 epidemic in heterosexual women: southeast England, 1988-1991.

OBJECTIVE: The prevalence of HIV-1 in the heterosexual population in southeast England between 1988 and 1991 was examined using two methods. DESIGN AND METHODS: First, district neonatal seroprevalence was compared on a geographical basis to social and demographic variables reflecting risk-factor prevalence. Second, over the same period eight children who developed AIDS within the first 12 months of life were born. RESULTS: The differences in seroprevalence between districts could be explained by the proportion of livebirths to women born in parts of Africa. An estimated 92% of neonatal seropositives could be associated with this demographic variable. The proportions of livebirths to women born in other countries, the prevalence of notified injecting drug use, and area measures of social deprivation, were only poorly related to HIV seroprevalence, and had no additional explanatory value. Seven of the eight (87.5%) children who developed AIDS in the first year were born to black women from Africa. CONCLUSIONS: Both methods suggest that a high proportion of heterosexually transmitted HIV in southeast England has been imported.

Adult↗
PubMed1997

Uptake of interventions to reduce mother-to-child transmission of HIV in the United Kingdom and Ireland.

OBJECTIVES: To describe the uptake of interventions to reduce mother-to-child transmission of HIV infection. DESIGN: Voluntary confidential reporting of HIV infection in pregnancy and childhood; telephone interview with key professionals in all London maternity units. SUBJECTS AND SETTING: HIV-infected pregnant women and children in the United Kingdom and Ireland. MAIN OUTCOME MEASURES: Trends in breastfeeding, use of zidovudine, mode of delivery and terminations of pregnancy. RESULTS: Between 1990 and 1995, 14 (4%) out of 314 women diagnosed with HIV infection before delivery breastfed compared with 109 (77%) out of 142 diagnosed after delivery. Since 1994, zidovudine use has increased in each 6-month period (14, 39, 67, and 75%; chi 2 = 17.5, P < 0.001), although in 1995 it was the policy of only 48% of London maternity units to offer zidovudine to HIV-infected women. During 1995, 44% of HIV-infected women were delivered by elective Cesarean section. Since 1990, 20% of women first diagnosed in pregnancy were reported to have their pregnancy terminated. CONCLUSIONS: Although detection of previously undiagnosed HIV infection in pregnancy remains low in the United Kingdom, and particularly in London, HIV-infected pregnant women who are aware of their status are increasingly active in taking up interventions to reduce transmission to their infants. If all HIV-infected women attending for antenatal care in London consented to testing and took up interventions and termination of pregnancy at the rates observed in this study, the number of vertically infected babies born in London each year could be reduced from an estimated 41 to 13.

Abortion, Induced↗