Is Gulf War Syndrome actually chronic Lyme disease?

Symptoms of Gulf War Syndrome and chronic Lyme disease are very similar. Lyme disease is a condition which can be difficult to diagnose since one of the main features of the condition, the erythema migrans rash, may be absent or overlooked and serological testing for Lyme disease may be falsely negative. Symptoms of Lyme disease may not became apparent until years after exposure to the causative organism. Military personnel during training in the field are at risk of tick bites and it may be that those who developed Gulf War Syndrome entered the conflict with latent Lyme disease. There has been no systematic examination of Gulf War Syndrome sufferers for chronic Lyme disease and it is hypothesized that chronic Lyme disease has been overlooked as a cause of Gulf War Syndrome. To address this it is suggested that sufferers of Gulf War Syndrome or similar illnesses should be examined by physicians who have experience diagnosing and treating large numbers of patients with Lyme disease.     

Is the pathogen of prion disease a microbial protein?

Though considerable circumstantial evidence suggests that the pathogen of prion disease is proteinaceous, it has not yet been conclusively identified. Epidemiological observations indicate that a microbial vector is responsible for the transmission of natural prion disease in sheep and goats and that the real causative agent may correspond to a structural protein of that microorganism. The microbial protein should resemble prion protein (PrP) and may replicate itself in the host by using mammalian DNA. A similar phenomenon was already described with a protein antigen of the ameba Naegleria gruberi (1–4). The various serotypes of the microbial protein may account for the existence of scrapie strains. It is proposed that many microbial proteins may be capable of replicating themselves in mammalian cells eliciting and sustaining thereby degenerative and/or autoimmune reactions subsequent to infections with microorganisms.     

Is it Fabry disease?

Fabry disease is caused by mutations in the GLA gene that lower α-galactosidase A activity to less than 25–30% of the mean normal level. Several GLA variants have been identified that are associated with relatively elevated residual α-galactosidase A. The challenge is to determine which GLA variants can cause clinical manifestations related to Fabry disease. Here, we review the various types of GLA variants and recommend that pathogenicity be considered only when associated with elevated globotriaosylceramide in disease-relevant organs and tissues as analyzed by mass spectrometry. This criterion is necessary to ensure that very costly and specific therapy is provided only when appropriate.Genet Med 18 12, 1181–1185.     

A role for peripheral blood fibrocytes in Lyme disease?

It is proposed that peripheral blood fibrocytes will be a new and important player in the pathogenesis of Lyme disease. Peripheral blood fibrocytes are a circulating leukocyte subpopulation that: (a) express collagen; (b) are an abundant source of cytokines, chemoattractants and growth factors; and (c) are able to recruit and activate naive T-cells and memory T-cells. We predict that peripheral blood fibrocytes will represent a new and important antigen-presenting cell which will play an important role in directing the immune response from the pathogenic Th1 to the protective Th2 response cell in Borrelia infections.     

The multiple semantics hypothesis: Multiple confusions?

Abstract

In this paper we discuss the issue of multiple versus unitary semantics. We argue that the notion of multiple semantics (as currently articulated) does not, in fact, represent a theory of semantic organisation but is, instead, an arbitrary conjunction of a set of independent assumptions which are either unmotivated or, if motivated, equally compatible with a unitary semantics hypothesis. Furthermore, the empirical evidence that has been cited as support for this hypothesis is equally compatible with variants of the unitary semantics hypothesis. A model of semantic processing—the Organised Unitary Content Hypothesis (O.U.C.H.)—that is able to account for reported patterns of dissociation of performance is discussed briefly.     

Is the sugar always sweet in intestinal inflammation?

Immune responses are mediated mainly by protein/protein interactions. In addition, protein/carbohydrate (sugar) interactions through specific protein families termed lectin and chi-lectin are also involved in several immune and biological responses under not only the state of health but also inflammatory conditions. Interestingly, recent studies have identified unexpected roles of animal lectins (galectin-1 and galectin-4) and chi-lectin (chitinase 3-like-1) in intestinal inflammation. Galectin-1 contributes to the suppression of intestinal inflammation by the induction of effector T cell apoptosis. In contrast, galectin-4 is involved in the exacerbation of this inflammation by specifically stimulating intestinal CD4⁺T cells to produce IL-6. CHI3L1 enhances the host/microbial interaction that leads to the exacerbation of intestinal inflammation. In this review, we discuss a novel aspects of lectin/carbohydrate interactions in intestinal inflammation.     

Is autism an autoimmune disease?

Autism spectrum disorder (ASD) is a spectrum of behavioral anomalies characterized by impaired social interaction and communication, often accompanied by repetitive and stereotyped behavior. The condition manifests within the first 3 years of life and persists into adulthood. There are numerous hypotheses regarding the etiology and pathology of ASD, including a suggested role for immune dysfunction. However, to date, the evidence for involvement of the immune system in autism has been inconclusive. While immune system abnormalities have been reported in children with autistic disorder, there is little consensus regarding the nature of these differences which include both enhanced autoimmunity and reduced immune function. In this review, we discuss current findings with respect to immune function and the spectrum of autoimmune phenomena described in children with ASD.     

Is hypertension an inflammatory disease?

Hypertension has been recognized as a multi-factorial trait resulting from the effect of a combination of environmental and genetic factors, including excess dietary salt or alcohol intake, stress, age, genetics and family history, obesity, physical inactivity, as well as high saturated fat diet. During the past few years, however, a large amount of information has been collected on the vascular inflammation, indicating that inflammation may involve in the initiation as well as development of hypertension and allowing us to reconsidering the pathogenic mechanisms of hypertension. Evidence from animal models as well as patients, have indicated that hypertension, an established major risk factor for coronary artery disease, has been suggested to exert pro-inflammatory actions through the increased expression of several mediators, including leukocyte adhesion molecules, chemokines, specific growth factors, heat shock proteins, endothelin-1, and angiotensin. The association between inflammation and hypertension recalls also a similar association between low-grade inflammation and other components of the metabolic syndrome, and endothelial dysfunction as well as increased serum levels of C-reactive protein in patients with hypertension. Is hypertension an inflammatory disease? This question has stimulated research on the role of vascular inflammation in hypertension. A better understanding of the inflammatory mechanism in hypertension may, therefore, contribute to novel therapeutic strategies to decrease the morbidity as well as mortality of hypertension, and alleviated hypertensive target organ damage.     

Is cancer a transmittable disease?

A direct, horizontal and natural transmission of neoplasic cells has only recently been accepted by the biomedical community. There are three known examples in mammals: the Tasmanian Devil Tumor Disease, the Canine Transmissible Venereal Tumor and a similar disease in Sirian Hamsters. These diseases are not anecdotic cases only, but provide support for the cancer clonal evolution hypothesis.     

The amyloid hypothesis: let sleeping dogmas lie?

The ‘amyloid hypothesis’ has guided research into Alzheimer’s disease (AD) for more than a decade. A detailed review of the relevant data led us to conclude that some data, particularly those from transgenic mice, are inconsistent with the predictions of the amyloid hypothesis. Instead, most data are consistent with the notion that amyloid-β (Aβ) peptide is neuroprotective. The majority of commentators agreed with our analysis but some were unwilling to abandon the amyloid hypothesis until the outcome of anti-Aβ therapeutic trials puts the matter beyond debate. All acknowledged that we had highlighted flaws in the amyloid hypothesis which must be addressed. To stimulate a critical reappraisal of the amyloid hypothesis we have proposed the ‘bioflocculant hypothesis’ which posits that Aβ serves to bind neurotoxic solutes (pathogens, proteins and metal ions) so that they can be phagocytosed and prevented from causing further damage. The hypothesis makes clear predictions that are readily falsifiable, and it has already gained credibility by predicting the recent negative outcome of Aβ vaccination trials in humans.     

The Snodgrass repair: is stenting always necessary?

To evaluate the need for stenting in Snodgrass hypospadias repairs. Sixty-five boys underwent hypospadias repairs between April 1996 and July 2001. A variety of techniques were employed. Snodgrass repair was performed in 39 patients, MAGPI in 18, Glanular approximation procedures in 4, Mathieu procedures in 3 and one Duckett Onlay-flap. Seventeen patients, all Snodgrass repairs, had placement of a urethral stent for one week postoperatively. Follow-up at six weeks and one year or when toilet-trained was carried out on all patients. A Fisher's exact test was performed analysing the difference in outcome of the distal Snodgrass repairs depending on the presence or absence of a urethral stent. The patient age at the time of surgery ranged from 8-115 months, with a median of 21 months. Postoperative complications included 1 stent migration, 1 urethral diverticulum and 4 fistulas. Also in one patient part of the ventral skin flap on one side sloughed away, this was debrided and allowed to close by secondary intention. The fistula rate in the entire group is 6%, with an incidence of 10.5% in patients undergoing Snodgrass repair. In the cases having Snodgrass repair for meatal position other than mid- or proximal shaft there was no statistical difference in the incidence of fistula whether or not a stent was used. The long-term follow-up of the entire group indicates that 5 patients developed meatal narrowing, 3 in stented Snodgrass repairs, one patient who had a MAGPI and one GAP patient. Otherwise the long-term outcome of the surgery has been excellent for the entire group. We believe that stenting can be abandoned in distal repairs without compromising patient outcomes.     

Is sleep-disordered breathing associated with miscarriages? An emerging hypothesis

Sleep-disordered breathing (SDB) is a common disorder that has numerous medical consequences including cardiovascular morbidity. The clinical presentation in women is frequently vague, leading to its under-recognition in this population. Sleep is known to influence several female hormonal cycles including estrogen, progesterone, prolactin, luteinizing hormone (LH), and follicle stimulating hormone (FSH); consequently, sleep disruption may have adverse effects on female health including pregnancy. Miscarriage, defined as the loss of a pregnancy in the first trimester, occurs in one in four pregnancies; in up to half of cases, the cause may be unknown. Risk factors for miscarriage include increased age, increased weight, and a history of polycystic ovarian syndrome, all of which are also risk factors for SDB. Since SDB is frequently accompanied by sleep fragmentation and intermittent hypoxemia, we speculate that these factors may contribute to miscarriage risk. If this is the case, then treatment of SDB may be a possible intervention for subsequent pregnancies.     

The hygiene hypothesis: does it function worldwide?

PURPOSE OF REVIEW: This article intends to be a systematic review of papers published during 2003-2004 quoted in a Medline search for 'hygiene hypothesis'. The worldwide perspective of the article does not refer just to a geographical concept, but tries also to address the question of whether the consensus on the hypothesis is global or whether it applies to all types of allergic or immunologic disease, to any age sample or infectious agent. Furthermore, the article outlines those clinical and experimental studies which, in the authors' opinion, may represent significant contributions to a better understanding of the hygiene hypothesis and may guide further investigations on the subject. RECENT FINDINGS: The association between a reduced exposure to infectious agents (as a part of a changed lifestyle) and a higher prevalence of atopy seems now to be confirmed by consistent evidence. Mechanisms underlying this association, however, are not yet completely clear (immune deviation or immune regulation). SUMMARY: Further experimental and clinical studies are needed, with special reference to the time, duration and intensity of exposure to any specific infectious agent which is related to well-defined allergy outcomes. The background information for using microbial products in allergy prevention and treatment is still limited.     

Is childhood asthma an inflammatory disease?

There is now extensive evidence that asthma results from inflammation in large and small airways, and that the degree of inflammation reflects the clinical severity of the disease. Most of this evidence, however, has come from studies in adult patients. Evidence in children comes largely from indirect studies such as measurements of peripheral blood cells and inflammatory markers, rather than from direct bronchoscopic examination. Studies in adults show that inflammation in asthma is characterized by eosinophilia, epithelial damage, and bronchial hyperresponsiveness, and that activation of allergen-specific T cells plays an important role in orchestrating the inflammatory process. In children, indirect evidence of inflammation comes from the observation that anti-inflammatory agents such as inhaled corticosteroids improve symptoms and bronchial hyperresponsiveness, reduce the number of asthma exacerbations, and limit the progressive decline in lung function. Further evidence comes from measurements of nitric oxide and hydrogen peroxide (potential inflammatory markers) in exhaled air, and of inflammatory mediators in plasma and urine. As in adults, there is evidence that lymphocytes play an important role in orchestrating the inflammatory process. The immunologic profile appears to shift from a Th1-type cytokine profile to an allergenrelated Th2-type profile prior to birth Such a Th2 predominance constitutes a risk factor for the subsequent development of bronchial hyperresponsiveness and asthma in response to allergen.     

Is celiac disease an autoimmune disorder?

Celiac disease, which results from an immune reaction to ingested cereal gluten proteins, has several autoimmune features. In particular, celiac disease patients produce highly disease specific IgA and IgG autoantibodies to tissue transglutaminase when they are on a gluten-containing diet, and they have small intestinal intraepithelial lymphocytes which can mediate direct cytotoxicity of enterocytes expressing MIC molecules in an antigen non-specific manner. Similar to typical autoimmune disorders, celiac disease has a multifactorial aetiology with complex genetics, and several autoimmune diseases are commonly presented by patients with celiac disease. Much has been learned about the immunology of celiac disease in recent years, and there is overwhelming evidence that the immune response to gluten is central to the pathogenesis. In light of this, the many autoimmune phenomena associated with celiac disease are thought-provoking, and they challenge us to rethink the boundaries between autoimmunity and immunopathology.