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PubMed2004

Mode of delivery and development of atopic disease during the first 2 years of life.

It has been hypothesized that cesarean delivery might have an impact on the development of atopic diseases because of its gut flora modulating properties. In the present study, we analysed the association between cesarean delivery and atopic diseases using data of 2500 infants enrolled in the LISA-Study, a German prospective multicenter birth cohort study. Data on symptoms and physician-diagnosed atopic diseases were gathered by questionnaires shortly after birth and at infant's age 6, 12, 18, and 24 months. In addition, sensitization to common food and inhalant allergens was assessed by measuring specific immunoglobulin E (IgE) using the CAP-RAST FEIA method at the age of 2 yr. Confounder-adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated by multiple logistic regression. We found a positive association between cesarean delivery and occurrence of at least one episode of wheezing [aOR 1.31 (95% CI 1.02-1.68)] and of recurrent wheezing [1.41 (1.02-1.96)] during the first 2 yr of life. Furthermore, effect estimates for allergic sensitization defined as at least one specific IgE >/=0.70 kU/l against any allergen [1.48 (0.98-2.24)], against food allergens [1.64 (1.03-2.63)], and against inhalant allergens [1.75 (0.98-3.12)] were increased. Symptoms of atopic dermatitis [1.21 (0.92-1.59)], physician-diagnosed atopic dermatitis [1.04 (0.79-1.39)], and symptoms of allergic rhinoconjunctivitis [1.40 (0.80-2.44)] were only marginally increased in children delivered by cesarean section. In conclusion, our results suggest that cesarean delivery may be an additional risk factor for wheezing and allergic sensitization at least to food allergens up to the age of 2 yr. This should be considered when cesarean section is done for other than medical reasons.

Cesarean Section↗

PubMed2001

Exposure to endotoxin decreases the risk of atopic eczema in infancy: a cohort study.

BACKGROUND: Previous studies have shown a protective effect of early exposure to cats and dogs on the development of atopic eczema, asthma, allergic rhinitis, and atopic sensitization in later life. In particular, a higher microbial exposure to endotoxin in early childhood might contribute to this effect. OBJECTIVE: We examined the associations between bacterial endotoxin in house dust and atopic eczema, infections, and wheezing during the first year of life in an ongoing birth cohort study (LISA). METHODS: Data of 1884 term and normal-weight neonates with complete information on exposure to biocontaminants and confounding variables were analyzed. House dust from the mothers' and the children's mattresses was sampled 3 months after birth. Endotoxin content was quantified by using a chromogenic kinetic limulus amoebocyte lysate test. RESULTS: During the first 6 months of life, the risk of atopic eczema was significantly decreased by endotoxin exposure in dust from mothers' mattresses in the fifth quintile (odds ratio [OR], 0.50; 95% CI, 0.28-0.88), whereas the risk was increased for respiratory infections (OR, 1.69; 95% CI, 1.25-2.28) and cough with respiratory infection, bronchitis, or both (OR, 1.73; 95% CI, 1.28-2.33). The risk of wheezing was also significantly increased during the first 6 months of life (OR, 2.37; 95% CI, 1.40-4.03). For the entire first year of life, these associations attenuated, except for the risk of wheezing, which remained significant (OR, 1.60; 95% CI, 1.10-2.30). CONCLUSION: Our findings support the hygiene hypothesis that exposure to high concentrations of endotoxin very early in life might protect against the development of atopic eczema within the first 6 months of life, along with an increased prevalence of nonspecific respiratory diseases.

Air Pollution, Indoor↗

PubMed1999

Commitment to apoptosis by GD3 ganglioside depends on opening of the mitochondrial permeability transition pore.

We have studied the effects of GD3 ganglioside on mitochondrial function in isolated mitochondria and intact cells. In isolated mitochondria, GD3 ganglioside induces complex changes of respiration that depend on the substrate being oxidized. However, these effects are secondary to opening of the cyclosporin A-sensitive permeability transition pore and to the ensuing swelling and cytochrome c depletion rather than to an interaction with the respiratory chain complexes. By using a novel in situ assay based on the fluorescence changes of mitochondrially entrapped calcein (Petronilli, V., Miotto, G., Canton, M., Colonna, R., Bernardi, P., and Di Lisa, F. (1999) Biophys. J. 76, 725-734), we unequivocally show that GD3 ganglioside also induces the mitochondrial permeability transition in intact cells and that this event precedes apoptosis. The mitochondrial effects of GD3 ganglioside are selective, in that they cannot be mimicked by either GD1a or GM3 gangliosides, and they are fully sensitive to cyclosporin A, which inhibits both the mitochondrial permeability transition in situ and the onset of apoptosis induced by GD3 ganglioside. These results provide compelling evidence that opening of the permeability transition pore is causally related to apoptosis.

Animals↗

PubMed2000

The mitochondrial permeability transition, release of cytochrome c and cell death. Correlation with the duration of pore openings in situ.

We investigated the relationship between opening of the permeability transition pore (PTP), mitochondrial depolarization, cytochrome c release, and occurrence of cell death in rat hepatoma MH1C1 cells. Treatment with arachidonic acid or induces PTP opening in situ with similar kinetics, as assessed by the calcein loading-Co(2+) quenching technique (Petronilli, V., Miotto, G., Canton, M., Colonna, R., Bernardi, P., and Di Lisa, F. (1999) Biophys. J. 76, 725-734). Yet depolarization, as assessed from the changes of mitochondrial tetramethylrhodamine methyl ester (TMRM) fluorescence, is rapid and extensive with arachidonic acid and slow and partial with. Cyclosporin A-inhibitable release of cytochrome c and cell death correlate with the changes of TMRM fluorescence but not with those of calcein fluorescence. Since pore opening must be accompanied by depolarization, we conclude that short PTP openings are detected only by trapped calcein and may have little impact on cell viability, while changes of TMRM distribution require longer PTP openings, which cause release of cytochrome c and may result in cell death. Modulation of the open time appears to be the key element in determining the outcome of stimuli that converge on the PTP.

Animals↗

PubMed2006

Atopic eczema in children: another harmful sequel of divorce.

BACKGROUND: Different lifestyle factors seem to be associated with the risk for atopic diseases and some studies suggest that stress increases the risk of allergic sensitization, asthma and atopic eczema. Only few studies have investigated the association of early stressful life events and atopic eczema (AE) in children. SUBJECTS AND METHODS: Parents of participants of the ongoing LISA birth cohort study were asked to give information on life events, such as severe disease or death of a family member, unemployment, or divorce of the parents. Lifetime prevalence of AE and incidence after the assessment period for life events were compared. RESULTS: Prevalence of AE until the age of 4 years was 21.4%. Reported life events within the first 2 years were: severe disease (17.5%) or death (8.4%) of a family member, divorce/separation (3.4%), and unemployment (2.7%). Divorce/separation was associated with a significantly [odds ratio (OR) 3.59, 95% confidence interval (CI) 1.69-7.66] increased and disease with a significantly (OR 0.29, 95% CI 0.13-0.68) decreased incidence of AE for the subsequent 2 years of life. No effect was seen for unemployment. CONCLUSIONS: Divorce/separation of the parents and severe disease of a family member influence the risk of developing AE.

Child↗

PubMed2002

Allergens and endotoxin on mothers' mattresses and total immunoglobulin E in cord blood of neonates.

The current authors examined whether mite and cat allergen and bacterial endotoxin levels in dust of the mothers' mattresses were associated with cord blood immunoglobulin (Ig)E (CB-IgE) levels in newborns. Data from 1,332 term and normal weight neonates, from an ongoing birth cohort study, influences of life-style related factors on the immune system and the development of allergies in childhood (LISA), with complete information on exposure to biocontaminants in mattress dust and CB-IgE were analysed. Two thirds of CB-IgE were undetectable (<0.35 kU x L(-1)). Thus, 0.35 and 0.45 kU x L(-1) (4th quartile) were chosen as cut-offs. Nonparametric smoothing (generalised additive models) showed statistically significant confounder-adjusted associations between elevated CB-IgE levels (> or = 0.45 kU x L(-1)) and log-transformed exposures to cat (linear), mite (inverse u-shaped), and endotoxin (u-shaped). After adjustment for covariables, elevated CB-IgE levels (logistic regression using the 1st-4th quartiles of exposure) were positively associated with high cat-allergen exposure and medium exposure to mite allergen, but were inversely associated with exposure to endotoxin. The associations were similar, but somewhat weaker, when 0.35 kU x L(-1) was used as cut-off. These results, showing an association between prenatal allergen and endotoxin exposures and immunoglobulin E production, suggest that the development of foetal immune responses may be affected.

Allergens↗

PubMed2006

U.S. elementary and secondary schools: equalizing opportunity or replicating the status quo?

Although education pays off handsomely in the United States, children from low-income families attain less education than children from more advantaged families. In this article, Cecilia Elena Rouse and Lisa Barrow investigate why family background is so strongly linked to education. The authors show that family socioeconomic status affects such educational outcomes as test scores, grade retention, and high school graduation, and that educational attainment strongly affects adult earnings. They then go on to ask why children from more advantaged families get more or better schooling than those from less advantaged families. For low-income students, greater psychological costs, the cost of forgone income (continuing in school instead of getting a job), and borrowing costs all help to explain why these students attain less education than more privileged children. And these income-related differences in costs may themselves be driven by differences in access to quality schools. As a result, U.S. public schools tend to reinforce the transmission of low socioeconomic status from parents to children. Policy interventions aimed at improving school quality for children from disadvantaged families thus have the potential to increase social mobility. Despite the considerable political attention paid to increasing school accountability, as in the No Child Left Behind Act, along with charter schools and vouchers to help the children of poor families attend private school, to date the best evidence suggests that such programs will improve student achievement only modestly. Based on the best research evidence, smaller class sizes seem to be one promising avenue for improving school quality for disadvantaged students. High teacher quality is also likely to be important. However, advantaged families, by spending more money on education outside school, can and will partly undo policy attempts to equalize school quality for poor and nonpoor children.

Achievement↗

PubMedDate not supplied

Can theology have a role in "public" bioethical discourse?

Lisa Sowle Cahill takes up the methodological issue of how substantive religious perspectives can be communicated in a pluralistic society. Cahill sees public discourse about bioethics as embodying a commitment to dialogue among traditions, religious and nonreligious, that have common concerns.

Abortion, Induced↗

PubMedDate not supplied

Using negative pressure therapy for healing of a sternal wound.

Lisa Clubley and Lorraine Harper examine the treatment provided to a patient who had cardiac surgery and developed complications that resulted in the development of an extensive open sternal wound. The consultant surgeon responsible for the care made a decision to use negative pressure therapy (vacuum-assisted closure) despite such therapy for a wound of this nature being contraindicated in the manufacturer's clinical guidelines

Adult↗

PubMedDate not supplied

Empirical studies assessing the quality of health information for consumers on the world wide web: a systematic review.

CONTEXT: The quality of consumer health information on the World Wide Web is an important issue for medicine, but to date no systematic and comprehensive synthesis of the methods and evidence has been performed. OBJECTIVES: To establish a methodological framework on how quality on the Web is evaluated in practice, to determine the heterogeneity of the results and conclusions, and to compare the methodological rigor of these studies, to determine to what extent the conclusions depend on the methodology used, and to suggest future directions for research. DATA SOURCES: We searched MEDLINE and PREMEDLINE (1966 through September 2001), Science Citation Index (1997 through September 2001), Social Sciences Citation Index (1997 through September 2001), Arts and Humanities Citation Index (1997 through September 2001), LISA (1969 through July 2001), CINAHL (1982 through July 2001), PsychINFO (1988 through September 2001), EMBASE (1988 through June 2001), and SIGLE (1980 through June 2001). We also conducted hand searches, general Internet searches, and a personal bibliographic database search. STUDY SELECTION: We included published and unpublished empirical studies in any language in which investigators searched the Web systematically for specific health information, evaluated the quality of Web sites or pages, and reported quantitative results. We screened 7830 citations and retrieved 170 potentially eligible full articles. A total of 79 distinct studies met the inclusion criteria, evaluating 5941 health Web sites and 1329 Web pages, and reporting 408 evaluation results for 86 different quality criteria. DATA EXTRACTION: Two reviewers independently extracted study characteristics, medical domains, search strategies used, methods and criteria of quality assessment, results (percentage of sites or pages rated as inadequate pertaining to a quality criterion), and quality and rigor of study methods and reporting. DATA SYNTHESIS: Most frequently used quality criteria used include accuracy, completeness, readability, design, disclosures, and references provided. Fifty-five studies (70%) concluded that quality is a problem on the Web, 17 (22%) remained neutral, and 7 studies (9%) came to a positive conclusion. Positive studies scored significantly lower in search (P =.02) and evaluation (P =.04) methods. CONCLUSIONS: Due to differences in study methods and rigor, quality criteria, study population, and topic chosen, study results and conclusions on health-related Web sites vary widely. Operational definitions of quality criteria are needed.

Evaluation Studies as Topic↗

PubMed2000

Evaluation of somatic and reproductive immunotoxic effects of the porcine zona pellucida vaccination.

Immunological, immunocytochemical and fertility analyses were performed to determine the potential toxic side effects of porcine zona pellucida (pZP) vaccinations on target animals, including horses and dogs. The study was designed to determine the effect of antibodies, raised against highly purified pZP, on somatic tissues. Immunocytochemical studies performed with fixed tissues showed that rabbit anti-pZP antiserum did not crossreact with brain, heart, lung, kidney, liver, bladder, stomach, small intestine, large intestine, muscle, skin, spleen, pancreas, or lymph node of either the dog or horse. To determine the effect or oral intake on nontarget animals, female rabbits were fed a contraceptive vaccine containing pZP glycoproteins and the synthetic trehalose dicorynomycolate in drakeol (S-TDCM) adjuvant. Enzyme-linked immunoadsorbent assay (LISA) analyses showed that rabbits fed with the adjuvanted pZP proteins did not develop circulating anti-pZP IgG antibodies that crossreacted with pZP. Furthermore, fertility studies performed on rabbits fed with adjuvanted pZP revealed no significant differences in the number of embryos or stage of the embryos produced between the treated and control animals. Results of these studies suggest that the pZP vaccine delivered to dogs or horses in field studies have no recognizable somatic tissue effects. Moreover, there were no side effects on nontarget animals should they eat the vaccine. This substantiates field trials results about the safety of the pZP immunocontraceptive vaccine.

Adjuvants, Immunologic↗

PubMed2000

A physical-based model for the simulation of neoplastic growth and metastasis.

BACKGROUND AND OBJECTIVES: It is possible to formulate models capable of reproducing the main details of the physical processes involved in the evolution of biological systems. The complexity of the problem requires to begin with a simple and universal model for the description of the cellular growth, to be adapted successively to the local conditions found in clinically observed neoplastic growths. METHODS: A model based on the Local Interaction Simulation Approach (LISA) has been formulated for the simulation of growth, diffusion, and metastasis of neoplasms. The vascularization is described by a blood vessel located on one edge of the specimen in which a constant and homogeneous flow is assumed. A nutrient density is defined to mimic the blood flow within the tissue. RESULTS: Photograms taken at proper times may identify the main characteristics of the tumor evolution and describe its volume variations in a transversal section. Furthermore, it is possible to monitor constantly the volume of the neoplasm and of the necrotic tissue as a function of time, as well as the portion of cells that have migrated in the blood vessel. CONCLUSIONS: In spite of strong simplifying assumptions, the model presents good qualitative agreement with clinical data, which may be further improved by more detailed information about cancer cells properties or local vascular system patterns.

Animals↗

PubMed2001

Teaching critical appraisal skills in health care settings.

BACKGROUND: Critical appraisal is the process of assessing and interpreting evidence by systematically considering its validity, results and relevance to an individual's work. Within the last decade critical appraisal has been added as a topic to many medical school and UK Royal College curricula, and several continuing professional development ventures have been funded to provide further training. OBJECTIVES: To assess the effects of teaching critical appraisal skills to health professionals, on the process of care, patient outcomes and knowledge of health professionals. SEARCH STRATEGY: We searched The Cochrane Library (to Issue 2 2000), MEDLINE (1966 to 1997), EMBASE (1980 to 1997), Eric (1966 to 1997), Cinahl (1982 to 1997), Lisa (1976 to 1997), Sigle (1980 to 1997), Science Citation Index (1981 to 1997), PsycLit (1974 to 1997), the world-wide-web, and reference lists of articles. We also contacted major medical education centres. SELECTION CRITERIA: Randomised trials, controlled clinical trials, controlled before and after studies and interrupted time series analyses of educational interventions teaching critical appraisal to health professionals. The outcomes were: process of care; patient mortality, quality of life, and satisfaction; and health professional knowledge/awareness based upon objective, standardised, validated instruments. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and three reviewers independently assessed study quality. MAIN RESULTS: One USA hospital-based randomised trial was included involving 44 doctors. The outcome assessed was critical appraisal knowledge. Process of care, patient health or attitude/awareness outcomes were not assessed. Critical appraisal teaching was reported to have resulted in a 25% improvement (adjusted figure) in critical appraisal knowledge in the intervention group compared to a 6% improvement in the control group, which was statistically significant (p=0.02). REVIEWER'S CONCLUSIONS: There is evidence that critical appraisal teaching has positive effects on participants' knowledge, but as only one study met the inclusion criteria the validity of drawing general conclusions about the effects of teaching critical appraisal is debatable. There are large gaps in the evidence as to whether teaching critical appraisal impacts on decision-making or patient outcomes. It is also unclear whether the size of benefit seen is large enough to be of practical significance, or whether this varies according to participant background or teaching method. The evidence supporting all outcomes is weakened by the generally poorly designed, executed and reported studies that we found.

Decision Making↗

PubMed2001

Evaluation of hepatitis C antibody testing in saliva specimens collected by two different systems in comparison with HCV antibody and HCV RNA in serum.

Two different ELISA assays, the Ortho HCV 3.0 ELISA (Ortho Diagnostics Systems) and the Mono-Lisa anti-HCV Plus (Sanofi Diagnostics Pasteur) were evaluated for the detection of hepatitis C virus (HCV) antibody in saliva samples. Specimens were collected from 152 individuals who participated in a longitudinal cohort study on HIV infection, and who used illicit drugs. Saliva specimens were collected using two different systems: Salivette (Sarstedt) and Omni-Sal (Saliva Diagnostic Systems). Saliva specimens were tested following modified protocols by both ELISAs, and the results were compared with serum specimens that were tested according to the instructions of the manufacturer. Serum samples of 102 (67%) participants were positive by both assays, and 50 persons were negative for HCV antibody. A total of 99 of the 102 serum specimens were confirmed as positive using Ortho Riba HCV 3.0 (Ortho Diagnostics System) and Deciscan HCV (Sanofi Diagnostics Pasteur), and 3 yielded discrepant results. As no cut-off level is known for testing saliva samples by ELISA, 3 different levels were chosen: mean (M) + 1 standard deviation (SD), M + 2 SD, and M + 3 SD of the optical densities of saliva tests of the 50 HCV serum antibody negative persons. At a level of M + 1 SD and M + 2 SD the Salivette/Mono-Lisa combination gave the greatest proportion of HCV antibody positive saliva specimens obtained from the 102 HCV serum antibody positive participants, 88% and 79%, respectively. Differences between the various collection systems and assay combinations were not significant statistically. In 76 of the 102 persons with HCV antibodies in serum, HCV RNA was detected in serum. Salivary presence of HCV RNA, however, could not be demonstrated. The results show that the assays compared are unsuitable for diagnostic use, but the sensitivities of the assays are acceptable for use in epidemiological studies.

Adult↗

PubMed2002

The influence of maternal exposure to volatile organic compounds on the cytokine secretion profile of neonatal T cells.

Indoor VOC (volatile organic compound) exposure has been shown to be correlated with airway symptoms and allergic manifestations in children. An investigation was conducted within an ongoing birth cohort study (LISA: Lifestyle-Immune System-Allergy) of the association between maternal exposure to VOCs and immune status at birth, in particular the cytokine secretion profile of cord-blood T cells. In a randomly selected group of 85 neonates, cytokine-producing cord-blood T cells were analyzed using intracellular cytokine detection. VOC exposure was measured in children's dwellings by passive sampling, while parents were asked to complete questionnaires about possible sources of VOC exposure. Adjusted odds ratios (ORs) were calculated by logistic regression based on categorized quartiles. A positive association was found between elevated percentages of interleukin-4-producing (IL-4) type 2 T cells and exposure to naphthalene (OR = 2.9) and methylcyclopentane (OR = 3.3). Exposure to tetrachloroethylene was associated with reduced percentages of interferon-gamma-producing (IFN-gamma) type 1 T cells (OR = 2.9). In addition, smoking during pregnancy was correlated with a higher indoor air concentration of naphthalene (OR = 3.8), new carpets in infants' bedrooms with elevated methylcyclopentane concentrations (OR = 4.1), and home renovation with a higher trichloroethylene burden (OR = 4.9). Our data suggest that maternal exposure to VOC may have an influence on the immune status of the newborn child.

Adult↗

PubMed1991

Studies on the pathogenicity of Listeria monocytogenes.

The characterization of mutants of Listeria monocytogenes with reduced virulence properties is described. Reduction in the amount of the extracellular protein p60 (encoded by the ipa gene) leads to cell filaments with impaired invasiveness. Mutants which cannot synthesize listeriolysin are still invasive but unable to survive within phagocytic cells. One type of listeriolysin-negative mutants is defective in the synthesis of a positive regulatory element PrfA which coordinately regulates the listeriolysin gene (lisA) together with several other genes, including those for a phosphatidylinositol-specific phospholipase and a metalloprotease.

Antigens, Bacterial↗

PubMed1991

Identification of two calpastatin forms in rat skeletal muscle and their susceptibility to digestion by homologous calpains.

Two forms of calpastatin, differing in their specificity for the homologous calpain isozymes I and II, have been separated from rat skeletal muscle extracts and purified to homogeneity. Calpastatin I, the first form to elute in chromatography on DE32, is more effective against calpain I, while calpastatin II is more effective as an inhibitor of calpain II. Based on their molecular mass (approximately 105 kDa) both calpastatin forms belong to the high molecular mass class found in muscles of other animal species (Murachi, T., 1989, Biochem. Int. 18, 263-294). For calpain I, which is active with low (mu-M) concentrations of Ca2+, maximum inhibition with either calpastatin form was observed over a wide range of Ca2+ concentrations. With calpain II, which requires high (mM) concentrations of Ca2+ for activity, maximum inhibition required Ca2+ concentrations above 1 mM. Both calpastatin forms were found to be highly sensitive to degradation by calpain II, but almost completely resistant to degradation by calpain I. Degradation of calpastatin by calpain II is competitively inhibited by the addition of a calpain substrate. Isovaleryl carnitine (IVC), an intermediate product of L-leucine catabolism, previously demonstrated to be a potent and specific activator of rat skeletal muscle calpain II (Pontremoli, S., Melloni, E., Viotti, P. L., Michetti, M., Di Lisa, F., and Siliprandi, N., 1990. Biochem. Biophys. Res. Commun. 167, 373-380) greatly enhances the rate of degradation of calpastatins by calpain II. IVC, which decreases the Ca2+ requirement for maximal calpain II activity, also decreases the concentration of Ca2+ required for digestion of the inhibitor. For calpain II, regulation by either calpastatins may occur only in the presence of high [Ca2+].

Animals↗

PubMed1988

Mercury content of some marine fish from the southern Caribbean Sea.

The mercury concentration in muscle and liver of 63 specimens, comprising 17 species of edible fish from coastal waters of the Caribbean Sea near Cumaná, was determined by cold vapour atomic absorption spectrophotometry. The Hg content of edible muscle tissue, expressed on a fresh weight basis, varied from 0.048 microgram g-1 in lisa (Mugil curema) to 0.190 microgram g-1 in tajali (Trichiurus lepturus), with an average value of 0.096 +/- 0.042 microgram g-1. The corresponding values for liver varied from 0.135 microgram g-1 in lebranche (Mugil brasiliensis) to 0.361 micrograms g-1 in tajali (Trichiurus lepturus), with an average value of 0.269 +/- 0.059 microgram g-1. Of the 17 species analysed, seven had a mercury concentration greater than 0.10 microgram g-1 and the remainder contained less than 0.08 microgram g-1 in edible muscle tissue.

Animals↗