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.     

Increased membraneous calcium concentrations in primary hypertension: a causal link to pathogenesis?

BACKGROUND: Disturbance in calcium metabolism has been suggested in the pathogenesis of hypertension, however, membrane calcium content in humans has not been studied in detail yet in primary hypertension. We compared plasma, intracellular and membrane calcium concentrations in erythrocytes of patients with essential hypertension and in healthy, normotensive control subjects to determine a possible alteration of membrane calcium in primary hypertension. SUBJECTS AND METHODS: Thirty-four never treated patients with essential hypertension were included and 34 healthy, age- and sex-matched volunteers served as controls. Atomic absorption spectroscopy was used for measurement of intracellular and membrane calcium content in erythrocytes and plasmalemmal preparations. RESULTS: Plasma and intracellular Ca(++) concentrations were not significantly different between hypertensives and controls (plasma: 2.59 +/- 0.18 vs2.50 +/- 0.16 mmol/l, intracellular: 1.89 +/- 0.20 mmol/l vs 1.97 +/- 0.24 mmol/l, NS resp., mean +/- s.e.m.). However, membrane calcium content was significantly higher in hypertensive patients compared to control subjects (2.38 +/- 0.28 micromol/g membraneous protein vs0.86 +/- 0.32 micromol/g membrane protein, P < 0.01). Membrane calcium content was correlated to mean arterial blood pressure (r = 0.59, P < 0.01). CONCLUSION: Membrane calcium content is significantly increased in patients with untreated primary hypertension and correlates to blood pressure levels. This data suggest, that an membrane mechanism may contribute to alterations in calcium metabolism and to the pathogenesis of primary hypertension.     

Helicobacter pylori and colorectal neoplasia: Is there a causal link?

Ever since Helicobacter pylori(H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from casecontrol and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori /H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation.     

Subclinical cardiovascular disease in plaque psoriasis: Association or causal link?

Background

Psoriasis patients have a high prevalence of cardiovascular events and are thought to have a relative risk increase of 25% as compared to the general population. However, a causal relationship between psoriasis and cardiovascular disease has not been established. We sought to perform a systematic review of existing data regarding the presence of endothelial dysfunction and subclinical atherosclerosis in patients with plaque psoriasis.

Methods

A systematic literature search was performed, using Medline database and Ovid SP for relevant literature up to November 2012. Twelve studies met inclusion criteria from an initial search result of 529 articles.

Results

Among the twelve studies meeting inclusion criteria, two (17%) reported increased mean coronary artery calcification (CAC) in psoriatic patients. Six studies (50%) showed carotid intima–media thickness [CIMT] increase in psoriasis. Five studies (42%) examined flow mediated dilation [FMD], of which three showed decreased FMD in psoriasis patients. One study (8%) each demonstrated a decreased coronary flow reserve and increased arterial stiffness as assessed by pulse wave velocity.

Conclusions

Patients with psoriasis have an increased burden of subclinical atherosclerosis and endothelial dysfunction. Patients with greater severity and/or disease duration should be targeted for primary screening for cardiovascular disease risk reduction     

Is there a causal link between psychological disorders and functional gastrointestinal disorders?

Psychological disorders, most notably anxiety and depressive disorders, somatization and catastrophizing, often precede or exacerbate functional gastrointestinal disorder (FGID) symptoms and correlate with symptom severity and health outcomes. Mounting evidence shows that psychological distress alters gut immunity, in particular mast cell activation, leading to a potentiation of sensory nerves and aberrant visceral pain perception. On the other hand, psychological stressors modulate the processing of incoming sensory signals by the brain, thereby contributing to FGID symptom development. A better understanding of the molecular mechanisms underlying stress-induced changes in the immune system or brain processing is crucial for the development of novel beneficial therapeutic strategies.     

Increased thrombin activity after allergen challenge: a potential link to airway remodeling?

In addition to its central role in hemostasis, thrombin may play a role in inflammation and remodeling. To investigate the contribution of thrombin to allergic airway inflammation in asthma, we used an enzymatic assay to determine thrombin activity in bronchoalveolar lavage fluid obtained from 19 subjects with atopic asthma before (Day 0) and 48 hours after (Day 2) segmental bronchoprovocation with antigen. Thrombin activity increased from 0 (0, 2.9) on Day 1 to 41.1 (0.3, 75.6) U x 10(-3)/ml on Day 2 (p = 0.002) and correlated with total protein levels in lavage fluid on Day 2 (r = 0.885, p < 0.001). After antigen challenge, thrombin activity also showed significant correlations with interleukin-5 (r = 0.66, p = 0.002), transforming growth factor beta1 (r = 0.70, p < 0.001), fibronectin (r = 0.85, p < 0.001) and tissue factor (r = 0.55, p = 0.03) levels in lavage fluid. Furthermore, Day 2, but not Day 0 lavage fluid, induced proliferation of human airway fibroblasts. This mitogenic effect was significantly reduced with hirudin, a specific thrombin inhibitor. Taken together, our findings suggest that allergen-driven airway inflammation in asthma is associated with enhanced potential for fibroblast proliferation that is related, at least in part, to increased thrombin activity. We propose that enhanced thrombin activity provides a potential link between allergic inflammation and initiation of airway remodeling.     

Does the microbiome play a causal role in spondyloarthritis?

The purpose of this study is to review the potential causal role of the microbiome in the pathogenesis of spondyloarthritis. The method used for the study is literature review. The microbiome plays a major role in educating the immune response. The microbiome is strongly implicated in inflammatory bowel disease which has clinical and genetic overlap with spondyloarthritis. The microbiome also plays a causal role in bowel and joint disease in HLA B27/human beta 2 microglobulin transgenic rats. The mechanism(s) by which HLA B27 could influence the microbiome is unknown but theories include an immune response gene selectivity, an effect on dendritic cell function, or a mucosal immunodeficiency. Bacteria are strongly implicated in the pathogenesis of spondyloarthritis. Studies to understand how HLA B27 affects bacterial ecosystems should be encouraged.     

Attention Deficit Hyperactivity Disorder and substance use disorders: is there a causal link?

Attention-deficit hyperactivity disorder (ADHD), characterized by restless, inattentive and hyperactive behaviours, is a relatively common childhood disorder that affects approximately 5% of the general population. There has been controversy about whether ADHD increases risks of developing substance use disorders. The available evidence suggests that, in the absence of conduct disorder , ADHD is not associated with an increased risk of substance use problems in males. There is only limited evidence on the role of ADHD in the aetiology of substance use disorders among females. While ADHD has traditionally been considered as a childhood disorder, it may also occur in adults; research needs to examine the extent to which ADHD in adulthood increases the risk of substance use disorders.     

Viruses and inflammatory bowel disease: is there evidence for a causal association?

There has been a resurgent interest in potential microbial etiologies of inflammatory bowel disease (IBD). Over the past decade there have been both epidemiological and tissue studies exploring the potential role of paramyxoviruses in IBD, particularly Crohn's disease. This article will review the evidence and hence plausibility of a causal association between these viruses and IBD.     

Development of a meningioma in a patient with acromegaly during octreotide treatment: are there any causal relationships?

Somatostatin receptors are highly expressed in almost all meningiomas but in this setting their functional role is not clear. A 59-yr-old woman had been treated with octreotide after an unsuccessful operation for a GH-secreting pituitary adenoma. After 8 yr of treatment, a nuclear magnetic resonance (NMR) scan disclosed a 3 cm meningioma of the tentorium. Mean GH was 2.2 ng/ml and IGF-I 325 ng/ml. Meningioma was resected and tissue was digested to obtain tumor cell suspension. Aim of the study was to measure epidermal growth factor (EGF)-induced proliferation of cultured meningioma cells in the presence of either somatostatin or octreotide. Cells were grown to semiconfluency in Dolbecco's modified eagle medium (D-MEM) supplemented with 10% fetal calf serum (FCS). After 48 h in D-MEM without serum, the medium was replaced by fresh medium plus recombinant EGF (10 ng/ml) and somatostatin or octreotide were added in the final concentrations of 1, 10 and 100 nM. 20 h later 1 microcgCi of 3H-thymidine was added to each well. After 4 h, incorporated radioactivity was measured. While octreotide did not influence significantly cell growth at the three dose tested, somatostatin increased thymidine incorporation dose-dependently (peak 100 nM: 150% +/- 27% vs medium plus EGF, p<0.05). Octreotide effectively suppressed GH secretion in our acromegalic patient but is unlikely that its long-term use could have stimulated the growth of meningioma since it did not significantly influence the in vitro proliferation of the meningioma cells. These results suggest that somatostatin-mediated proliferative effect on meningioma cells is not mediated by the subtype 2 of the somatostatin receptor.     

Driving with cardiac devices in Australia. Does a review of recent evidence prompt a change in guidelines?

Australian Driving Guidelines for patients with pacemakers and implanted cardioverter defibrillators are in line with many around the world, with some minor differences. Some aspects of these guidelines lack contemporary evidence in key decision‐making areas and make broad recommendations regarding groups with heterogeneous populations. In addition, more recent studies suggest lower rates of adverse events in some patients with these devices than previously thought. Through a systematic literature review, along with discussion of current guidelines, we combine new evidence with well established risk assessment tools to ask the following questions: (i) Given the heterogeneity of patient risk within the defibrillator population, should guidelines allow for further individualisation of risk and subsequent licensing restrictions?; and (ii) Could some patients with primary prevention automated cardioverter defibrillators be able to hold a commercial driving licence?