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Results for “causality”

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PubMed1999

A clinical analysis of gelatin allergy and determination of its causal relationship to the previous administration of gelatin-containing acellular pertussis vaccine combined with diphtheria and tetanus toxoids.

BACKGROUND: The number of patients with allergic reactions after administration of gelatin-containing live vaccines is increasingly reported in Japan. These allergic reactions appear to be caused by gelatin allergy. It is still unknown how the patients were sensitized to gelatin. OBJECTIVE: To determine the incidence of gelatin allergy and to identify contributing factors to gelatin allergy, we investigated the following clinical aspects: the development of IgE antibodies to gelatin and the relationship of the patients' past history of acellular pertussis vaccine combined with diphtheria and tetanus toxoid (DTaP) to the development of gelatin allergy. METHODS: We evaluated 366 patient reports, submitted from 1994 to 1997, of adverse reactions after immunization with monovalent measles, mumps, and rubella vaccines containing 0.2% gelatin as stabilizer. On the basis of physician reports, the patients were categorized as to the nature of the adverse reaction. We determined the presence of IgE antibodies to gelatin and obtained past immunization history. RESULTS: The 366 reported patients were categorized as follows: 34 with anaphylaxis, 76 with urticaria, 215 with nonurticarial generalized eruption, and 41 with local reactions only. In 206 patients from whom serum was available, IgE antibodies to gelatin were detected in 25 of 27 (93%) with anaphylaxis, 27 of 48 (56%) with urticaria, and 8 of 90 (9%) with a generalized eruption. None of a group of 41 patients with only local reactions at the injected site and none of a control group of 29 subjects with no adverse reaction had such antibodies. Among 202 patients for whom prior vaccine information was available, all had received DTaP vaccines. Among those for whom the prior DTaP vaccine could be determined to contain gelatin or be free of gelatin, 155 of 158 (98%) subjects had received gelatin-containing DTaP vaccines. This rate is higher than would be expected on the basis of the market share of gelatin-containing (vs gelatin-free) DTaP vaccines (75%). Furthermore, before 1993, when a trivalent measles, mumps, and rubella vaccine (with the same 0.2% gelatin content as the monovalent vaccines) was used and administered before DTaP vaccination, no reports of anaphylaxis to the measles, mumps, and rubella vaccine were received. CONCLUSION: Most anaphylactic reactions and some urticarial reactions to gelatin-containing measles, mumps, and rubella monovalent vaccines are associated with IgE-mediated gelatin allergy. DTaP immunization histories suggest that the gelatin-containing DTaP vaccine may have a causal relationship to the development of this gelatin allergy.

Diphtheria-Tetanus-Pertussis Vaccine↗

PubMed2002

Causal relationship between the loss of RUNX3 expression and gastric cancer.

Runx3/Pebp2alphaC null mouse gastric mucosa exhibits hyperplasias due to stimulated proliferation and suppressed apoptosis in epithelial cells, and the cells are resistant to growth-inhibitory and apoptosis-inducing action of TGF-beta, indicating that Runx3 is a major growth regulator of gastric epithelial cells. Between 45% and 60% of human gastric cancer cells do not significantly express RUNX3 due to hemizygous deletion and hypermethylation of the RUNX3 promoter region. Tumorigenicity of human gastric cancer cell lines in nude mice was inversely related to their level of RUNX3 expression, and a mutation (R122C) occurring within the conserved Runt domain abolished the tumor-suppressive effect of RUNX3, suggesting that a lack of RUNX3 function is causally related to the genesis and progression of human gastric cancer.

Animals↗

PubMed2002

The causal links between stress and burnout in a longitudinal study of UK doctors.

Burnout and stress are common, linked problems in health-care workers. We aimed to clarify their causal associations. We assessed stress and the three components of burnout (emotional exhaustion, depersonalisation, and low personal accomplishment) using structural equation modelling in a 3-year longitudinal study of a representative sample of 331 UK doctors. Emotional exhaustion and stress showed reciprocal causation: high levels of emotional exhaustion caused stress (beta=0 189), and high levels of stress caused emotional exhaustion (beta=0 175). High levels of personal accomplishment increased stress levels (beta=0 080), whereas depersonalisation lowered stress levels (beta=-0 105).

Adult↗

PubMed1988

Identification of human herpesvirus-6 as a causal agent for exanthem subitum.

A virus was isolated from the peripheral blood lymphocytes of patients with exanthem subitum, cultured successfully in cord blood lymphocytes, and shown to be antigenically related to human herpesvirus-6 (HHV-6). Morphological features, as studied by thin-section electronmicroscopy, resembled those of herpes group viruses. Convalescent-phase serum samples, tested against the new viral antigen and HHV-6 antigen, showed seroconversion. The results strongly suggest that the newly isolated virus is identical or closely related to HHV-6 and the causal agent for exanthem subitum.

Acute Disease↗

PubMed1999

Sad, glad, or mad hearts? Epidemiological evidence for a causal relationship between mood disorders and coronary artery disease.

OBJECTIVE: To examine the epidemiological evidence to determine if there is sufficient support for the hypothesis that mood disorders convey a risk factor in the pathogenesis of coronary artery disease (CAD). METHOD: Based on a review of the related research on Type A behavioral pattern (TABP) and other variables such as anger and hostility and their relationship to coronary artery disease (CAD), the findings were analyzed to ascertain any clinical patterns or similarities between behaviors of Type A and those in mood disorders. Using the given epidemiological criteria for a causal relationship, the association between the mood and coronary artery disease was explored. RESULTS: There are similar symptoms and behaviors noted among Type A, manic, cyclothymic and hyperthymic individuals. There is sufficient historical and contemporaneous epidemiological evidence to support the notion that mood disorders confer risk for CAD, but it is premature to describe it as a causative factor. Depressive symptoms and general mood disorders emerged as toxic risk factors for CAD. LIMITATION: This article presents only a selective literature review, and it is limited by an epidemiological analyses of secondary sources. The impact of this limitation on the interpretation of the analyses is discussed. CLINICAL RELEVANCE: Patients require scrupulous clinical assessment for the presence of mood disorders including subtype; the stakes are high, since their cardiac health status may depend upon it. Pathophysiological pathways may play a covariate role in both mood and coronary disease, and some tentative hypotheses regarding the role of catchecholamines and cortisol are explored. CONCLUSIONS: There is evidence to justify studying the role of mood as a covariate risk factor in the pathogenesis of CAD. Implications for mental health, public health, primary care practice, and psychometric measurement are discussed. The hypothesis that mood disorders are a cause of CAD requires further research.

Coronary Disease↗

PubMed1999

Causal inference in a clinical trial: a comparative example.

Recently there has been much interest in methods for analyzing clinical trials of treatments that are subject to noncompliance. In this paper I study a small, simple dataset from a clinical trial of immunosuppressive therapy in the treatment of multiple sclerosis. I apply and compare a range of methods: the as-randomized (intention-to-treat) analysis, the as-treated analysis, estimates based on a nonignorable selection model, and Rubin's causal model. The results differ substantially even in this small dataset that exhibits modest noncompliance. For this reason, data analysts should be clear about which parameters are of greatest importance in the analysis of a clinical trial.

Azathioprine↗

PubMed2001

MMR and autism: further evidence against a causal association.

The hypothesis that MMR vaccines cause autism was first raised by reports of cases in which developmental regression occurred soon after MMR vaccination. A previous study found no evidence to support this hypothesis. It has recently been suggested that MMR vaccine might cause autism, but that the induction interval need not be short. The data from the earlier study were reanalysed to test this second hypothesis. Our results do not support this hypothesis, and provide further evidence against a causal association between MMR vaccination and autism.

Adolescent↗

PubMed2000

A causal relationship between unscheduled eicosanoid signaling and tumor development: cancer chemoprevention by inhibitors of arachidonic acid metabolism.

Cancer results from disturbances of cellular signal transduction and data processing at the genetic and epigenetic level. In the early phase of the disease these disturbances are mainly caused by environmental toxic agents, i.e. genotoxic and non-genotoxic carcinogens, whereas endogenous agents derived from dys-regulated metabolic reactions may take over this role at later stages, thereby leading to a state of 'genetic instability' and 'growth autonomy'. Among these metabolic reactions becoming dys-regulated in the course of tumorigenesis, eicosanoid biosynthesis from arachidonic acid seems to play a particular role. A steadily increasing body of evidence indicates a causal relationship between cancer development and an abnormal overexpression of eicosanoid-forming enzymes, i.e. cyclooxygenases and lipoxygenases, in a wide variety of human and animal tumors. This overexpression seems to result from disturbances of cellular signaling cascades such as the Ras-Raf-MAPkinase cascade due to oncogenic gene mutations. Presently, research is focussed on the proinflammatory enzyme cyclooxygenase-2 (COX-2) the pathological overexpression of which has been found to be related to key events of tumor promotion such as cellular hyperproliferation, inhibition of programmed cell death, and tumor angiogenesis. In the mouse skin model of multistage carcinogenesis COX-2-derived prostaglandin F(2alpha) has been indentified as an endogenous tumor promoter. Moreover, genotoxic byproducts of both cylooxygenase and lipoxygenase-catalyzed arachidonic acid metabolism (such as active oxygen species, free radicals etc.) are suspected to contribute to 'genetic instability' and thus to malignant progression of tumor cells. The enzymes of eicosanoid biosynthesis rank therefore among the most attractive targets for cancer chernoprevention. In fact, both nonsteroidal antiinflammatory drugs, i.e. non-specific COX inhibitors, and isozyme-specific COX-2 inhibitors have been shown to inhibit experimental and human cancer development, in the latter case in particular in the large bowel. Beside their role as indicators of neoplastic development eicosanoids may be also used as reporters of skin irritation. Based to this concept an in vitro test system for skin toxicity has been developed in which the release of arachidonic acid and interleukin-1alpha, i.e. two key mediators of acute inflammation, from a human keratinocyte cell line is measured. The excellent correlation found between this mediator release and the effects of various chemical irritants on human skin in vivo indicates that, in the near future, this and related methods may help to do without animal experiments in toxicological testing.

Animals↗

PubMed2003

Graphic modeling of epithelial transport system: causality of dissipation.

The epithelial transport system is a thermodynamic system which is composed of membranes and fluid compartments. The membranes are assumed to be dissipative subsystems in which power dissipates, and fluid compartments are capacitive subsystems in which power is stored. Each subsystem can be subdivided into elementary thermodynamic processes, and can be represented by generalized capacitors, power transducers and resistors in a bond graph. In the modeling of the dissipative subsystem, the causality of the dissipative process was taken into consideration and the representation of power coupling was developed. The dissipative subsystem can be represented by a combination of coupling modules and conductors. Phenomenological equations with parameters from the model were derived. This study shows that the behavior of transport systems can be simulated using these equations.

Biological Transport, Active↗

PubMed1997

Supplementary iron intake and risk of cancer: reversed causality?

Dietary iron intake and body iron stores have been suggested to increase cancer risk, especially colorectal cancer. Within a population-based case-control study in Stockholm county 1993-94, information on dietary and supplementary iron intake were collected through a food frequency questionnaire. An initially noted positive association between intake of supplementary iron and colorectal cancer risk was reversed when intake 5 years prior to cancer diagnosis was subtracted. Reversed causality due to early disease giving symptoms of iron shortage, resulting in iron supplementation, is an issue to consider when a possible association between intake of iron and cancer risk is investigated.

Age Factors↗

PubMed2001

Reinstatement of acquisition performance by the presentation of the outcome after extinction in causality judgments.

Two experiments were conducted with the aim of exploring reinstatement after extinction using a causality judgment task in human beings. In Experiment 1, participants learned first that a fictitious medicine produced a side-effect. The medicine was then presented in extinction. Re-exposure to the side-effect by itself before the test reinstated acquisition performance. Reinstatement was greater when exposure took place in the test context than when it took place in a different context. Experiment 2 replicated reinstatement in a situation that ensured equivalent extinction for the different groups before the test.

Journal Article↗

PubMed2003

Empirical and theoretical implications of additivity between reinstatement and renewal after interference in causal learning.

An experiment explored the effects of context change (renewal) and presentation of the outcome (reinstatement) upon retroactive interference in causal learning. An interference task was used where a sequential relationship between the name of a food and two different outcomes was established (A+|A*). Renewal and reinstatement effects appeared as partial attenuation of retroactive interference. The combination of both treatments produced complete recovery of first-learned information (A+). This complete reversal on the estimations of participants suggests that renewal and reinstatement effects within this paradigm imply partial recovery of the first-learned information, rather than response at a chance level emitted by confused participants. On the other hand, additivity between reinstatement and renewal suggests that reinstatement may be due to the combined effect of different underlying processes.

Journal Article↗

PubMed1998

Development of a PCR test based on a gene region associated with the pathogenicity of Pasteurella multocida serotype B:2, the causal agent of haemorrhagic septicaemia in Asia.

We have developed a PCR assay to detect Pasteurella multocida serotype B:2, the causal agent of Haemorrhagic Septicaemia (HS) in Asia. Nucleotide sequence determination of a 16S rRNA-23S rRNA PCR product unique to B:2 strains was shown to share amino acid sequence homology with a bacteriophage Mu protein. Primers designed from this sequence when tested against a panel of isolates recovered from a wide geographical area and representing a large range of bacterial genera and species, were found to specifically amplify DNA from P. multocida, serotype B:2. Southern hybridisation confirmed the presence of this sequence in only the B:2 serotype of P. multocida, suggesting an association between bacterial virulence and the presence of bacteriophage genes in the bacterial genome. The results of this study demonstrate the potential application of PCR to the diagnosis of HS in cattle and buffalo in Asia. Application of PCR to support diagnosis of HS will greatly improve accuracy, laboratory response time, and will facilitate rational deployment of resources for controlling this disease.

Animals↗

PubMed1993

Is Helicobacter pylori a causal agent in gastric carcinoma?

The aim of this study is to clarify the relationship between Helicobacter pylori (H. pylori) infection and gastric carcinoma. 94 patients with gastric carcinoma and 111 patients with chronic gastritis were involved in this study. They were classified into 3 age groups: Group A (40 years and under), Group B (41-59), Group C (60 years and over). Serum samples were tested for H. pylori IgG antibodies by ELISA and for pepsinogen (PG) by RIA. The ratio of PG I/PG II was used as a marker for atrophic gastritis. Results were as follows. In the incidence of H. pylori antibodies, there was no significant differences between gastric carcinoma and chronic gastritis in any of the groups. In the quantity of H. pylori antibodies, there was no significant difference between gastric carcinoma and chronic gastritis in any of the groups. The ratio of PG I/PG II was significantly decreased in H. pylori positive cases when compared to H. pylori negative cases in each group with chronic gastritis and group A and B with gastric carcinoma. The ratio of PG I/PG II in gastric carcinoma was significantly lower than that of chronic gastritis. As conclusion, from the point of view of the prevalence of H. pylori, it is suggested that H. pylori is not a direct causal agent in the pathogenesis of gastric carcinoma.

Adult↗

PubMed2003

Self-responsibility and the self-serving bias: an fMRI investigation of causal attributions.

We use causal attributions to infer the most likely cause of events in the social world. Internal attributions imply self-responsibility for events. The self-serving bias describes the tendency of normal subjects to attribute the causation of positive events internally ("I am responsible em leader ") and negative events externally ("Other people or situational factors are responsible em leader "). The self-serving bias has been assumed to serve a positive motivational function by enhancing self-esteem. Abnormalities of attributional style have been implicated in both depression and psychosis. We examined the neural basis of both self-responsibility and the self-serving bias using functional magnetic resonance imaging during the performance of attributional decision tasks. We found that the determination of self-responsibility recruits areas previously implicated in action simulation (bilateral premotor cortex and cerebellum), suggesting that such higher order social cognition is related to simpler internal models of goal-directed action. The dorsal striatum, previously implicated in motivated behavior, mediates the self-serving bias.

Adult↗

PubMed1998

Drug trafficking and drug use among urban African-American adolescents: a causal analysis.

OBJECTIVE: To test the hypothesis that involvement in drug trafficking leads to illicit drug use among urban African-American adolescents. METHODS: Self-reports of substance use, illicit drug use, and drug trafficking were obtained at baseline and every 6 months for 24 months from 383 African-American early adolescents. Transitions between involvement in drug trafficking and illicit drug use over time were examined. Path analysis was conducted to examine the causal relation between drug trafficking and drug use. RESULTS: Among the 35 youth who were initially involved only in drug trafficking, 22 (67%) subsequently used illicit drugs. Of the 53 youth who were initially involved only in illicit drug use, only 19 (42%) continued using drugs at later waves (p < 0.05). Path analysis revealed that baseline drug trafficking had a strong effect on subsequent drug trafficking and drug use, whereas baseline drug use did not have an effect on subsequent drug use or drug trafficking. CONCLUSIONS: Initiation of drug trafficking by adolescents appears to lead to sustained involvement in drug-related activities, including continued drug trafficking and drug use. By contrast, initiation of drug use does not necessarily lead to continued involvement in drug-related behaviors.

Adolescent↗

PubMed2002

What is the evidence for a causal link between hygiene and infections?

Even in an era in which access to personal "cleanliness" and a public health infrastructure are readily available in developed countries, illnesses associated with day care centres and homes continue to be a problem. The inhabitants of less developed countries, on the other hand, must contend with an inadequate public health infrastructure, lack of education programmes, and economic limitations in obtaining hygiene products. Therefore, less developed countries carry a greater burden of morbidity and mortality from infectious illnesses. The objective of this review is to examine and assess the epidemiological evidence for a causal relation between hygiene practices and infections. The Medline database was searched from January 1980 to June 2001 and studies were included if the outcome(s) was infection or symptoms of infection, and if the independent variable(s) was one or more hygiene measures. The strength of the association as measured by the relative reduction in risk of illness was appreciable and generally greater than 20%. Despite methodological strengths and limitations of the studies assessed, the weight of evidence collectively suggests that personal and environmental hygiene reduces the spread of infection. The results from this review demonstrate that there is a continued, measurable, positive effect of personal and community hygiene on infections.

Communicable Disease Control↗

PubMed1987

The relationship between pathology and resistance to reinfection with Schistosoma mansoni in mice: a causal mechanism of resistance in chronic infections.

The development of resistance in mice to reinfection with Schistosoma mansoni was recorded during an early chronic infection, and compared with hepatic portal pathological and vascular changes. The latter were assessed using a microsphere injection technique. The degree of acquired resistance was directly dependent on the patent worm burden and the time post-infection. Strong correlations were noted between the development of resistance and the appearance of parasite eggs in the lungs and spleens of infected hosts. Weaker associations were present between resistance and other aspects of the disease pathology, such as portal hypertension and organ weights. The appearance of injected microspheres in the lungs and spleens correlated well with the appearance of eggs in those organs and with the development of resistance. The levels of resistance had risen and microspheres were detected in the lungs, before the development of major extra-hepatic, porta-systemic collateral vessels. It is concluded that intra-hepatic vascular alterations may be a causal factor in the development of resistance, preventing the sequestration of migrating schistosomula in the liver. It is estimated that as much as 70-75% of the recorded resistance can be attributed to this immunologically non-specific mechanism.

Animals↗