Jean A. Monro

Autoantibodies to Nervous System-Specific Proteins Are Elevated in Sera of Flight Crew Members: Biomarkers for Nervous System Injury

This descriptive study reports the results of assays performed to detect circulating autoantibodies in a panel of 7 proteins associated with the nervous system (NS) in sera of 12 healthy controls and a group of 34 flight crew members including both pilots and attendants who experienced adverse effects after exposure to air emissions sourced to the ventilation system in their aircrafts and subsequently sought medical attention. The proteins selected represent various types of proteins present in nerve cells that are affected by neuronal degeneration. In the sera samples from flight crew members and healthy controls, immunoglobin (IgG) was measured using Western blotting against neurofilament triplet proteins (NFP), tubulin, microtubule-associated tau proteins (tau), microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and glial S100B protein. Significant elevation in levels of circulating IgG-class autoantibodies in flight crew members was found. A symptom-free pilot was sampled before symptoms and then again afterward. This pilot developed clinical problems after flying for 45 h in 10 d. Significant increases in autoantibodies were noted to most of the tested proteins in the serum of this pilot after exposure to air emissions. The levels of autoantibodies rose with worsening of his condition compared to the serum sample collected prior to exposure. After cessation of flying for a year, this pilots clinical condition improved, and eventually he recovered and his serum autoantibodies against nervous system proteins decreased. The case study with this pilot demonstrates a temporal relationship between exposure to air emissions, clinical condition, and level of serum autoantibodies to nervous system-specific proteins. Overall, these results suggest the possible development of neuronal injury and gliosis in flight crew members anecdotally exposed to cabin air emissions containing organophosphates. Thus, increased circulating serum autoantibodies resulting from neuronal damage may be used as biomarkers for chemical-induced CNS injury. The authors thank all of the participants who volunteered to take part in this case study. The technical work of Dr. Hagir B. Suliman and the art work of Sheref M. Abou-Donia are appreciated. This study was supported in part by the Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.

Urinary Bladder Detrusor Dysfunction Symptoms in Lyme Disease

Purpose Symptoms of urinary bladder detrusor dysfunction have been rarely reported in Lyme disease. The aim was to carry out the first systematic study to compare the prevalence of such symptoms in a group of Lyme disease patients and a group of matched controls. Methods A questionnaire relating to detrusor function was administered to 17 serologically positive Lyme disease patients and to 18 control subjects. Results The two groups were matched in respect of age, sex, body mass, and mean arterial blood pressure. None of the 35 subjects was taking medication which might affect urinary function and none had undergone a previous operative procedure on the lower urinary tract. Six of the Lyme patients (35%) and none of the controls (0%) had symptoms of detrusor dysfunction (P<0.01). Conclusions This first systematic controlled study confirms that Lyme disease is associated with urinary bladder detrusor dysfunction. Further evaluation of detrusor function is warranted in this disease.

A Molecular Neurobiological Approach to Understanding the Aetiology of Chronic Fatigue Syndrome (Myalgic Encephalomyelitis or Systemic Exertion Intolerance Disease) with Treatment Implications

Currently, a psychologically based model is widely held to be the basis for the aetiology and treatment of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME)/systemic exertion intolerance disease (SEID). However, an alternative, molecular neurobiological approach is possible and in this paper evidence demonstrating a biological aetiology for CFS/ME/SEID is adduced from a study of the history of the disease and a consideration of the role of the following in this disease: nitric oxide and peroxynitrite, oxidative and nitrosative stress, the blood–brain barrier and intestinal permeability, cytokines and infections, metabolism, structural and chemical brain changes, neurophysiological changes and calcium ion mobilisation. Evidence is also detailed for biologically based potential therapeutic options, including: nutritional supplementation, for example in order to downregulate the nitric oxide-peroxynitrite cycle to prevent its perpetuation; antiviral therapy; and monoclonal antibody treatment. It is concluded that there is strong evidence of a molecular neurobiological aetiology, and so it is suggested that biologically based therapeutic interventions should constitute a focus for future research into CFS/ME/SEID.

The effect of artesunate on short-term memory in Lyme borreliosis

Lyme borreliosis is associated with memory deficits. While this may be related to cerebral infection by Borrelia bacteria, it may also be caused by concomitant co-infection by Babesia protozoa. The anti-malarial artemisinin-derivative artesunate has been shown to be effective against a number of Babesia species and to have efficacy against human cerebral malaria. We hypothesised that concomitant administration of artesunate in Lyme borreliosis patients would help alleviate the severity of self-reported short-term memory impairment. This hypothesis was tested in a small pilot study in which patients were treated with both an intravenous antibiotic and oral artesunate (20mg four times per day); treatment was associated with a reduction in the severity of short-term memory difficulties (P≃0.08). In light of these findings, we recommend that a formal randomised, placebo-controlled study be carried out.

Desensitization to chemical and food sensitivities by low-dose immunotherapy ascertained by provocation neutralization is associated with reduced influx of calcium ions into lymphocytes

Abstract Background Food and chemical sensitivities have detrimental effects on health and the quality of life. The natural course of such sensitivities can potentially be altered through various types of allergen-specific immunotherapy, including low-dose immunotherapy. The molecular mechanism by which low-dose immunotherapy causes desensitization has not thus far been elucidated. While resting lymphocytes maintain a low cytosolic calcium ion concentration, antigen receptor signaling results in calcium ion influx, predominantly via store-operated calcium channels. We therefore hypothesized that desensitization by low-dose immunotherapy is associated with reduced influx of calcium ions into lymphocytes. The aim of this study was to test this hypothesis. Methods Intracellular lymphocytic calcium ion concentrations were assayed in a total of 47 patients, following incubation with picogram amounts of the test allergens, using a cell-permeable calcium-sensing ratiometric fluorescent dye and fluorescence spectroscopy, both at baseline and following successful provocation neutralization treatment with low-dose immunotherapy. Results Low-dose immunotherapy was associated with a reduction in lymphocytic intracellular calcium ion concentration following treatment of: 23 % for metabisulfite sensitivity (p<0.0004); 12 % for salicylate sensitivity (p<0.01); 23 % for benzoate sensitivity (p<0.01); 30 % for formaldehyde sensitivity (p<0.0001); 16 % for sensitivity to petrol exhaust (p<0.003); 16 % for natural gas sensitivity (p<0.001); 13 % for nickel sensitivity (p<0.05); 30 % for sensitivity to organophosphates (p<0.01); and 24 % for sensitivity to nitrosamines (p<0.05). Conclusions Low-dose immunotherapy may affect baseline levels of intracellular calcium in lymphocytes, supporting the premise that allergens affect cell signaling in immune cells and provocation neutralization immunotherapy helps to promote more normal immune cell signaling.

Co-administration of α-lipoic acid and glutathione is associated with no significant changes in serum bilirubin, alkaline phosphatase or γ-glutamyltranspeptidase levels during the treatment of neuroborreliosis with intravenous ceftriaxone.

Abstract Background: While pharmacotherapy with intravenous ceftriaxone, a third-generation cephalosporin, is a potential treatment of Lyme neuroborreliosis, there is concern that it can cause the formation of biliary sludge, leading to hepatobiliary complications such as biliary colic, jaundice and cholelithiasis, which are reflected in changes in serum levels of bilirubin and markers of cholestatic liver injury (alkaline phosphatase and γ-glutamyltranspeptidase). It has been suggested that the naturally occurring substances α-lipoic acid and glutathione may be helpful in preventing hepatic disease. α-Lipoic acid exhibits antioxidant, anti-inflammatory and anti-apoptotic activities in the liver, while glutathione serves as a sulfhydryl buffer. The aim of this study was to determine whether co-administration of α-lipoic acid and glutathione is associated with significant changes in serum levels of bilirubin, alkaline phosphatase and γ-glutamyltranspeptidase during the treatment of Lyme neuroborreliosis with long-term intravenous ceftriaxone. Methods: Serum levels of bilirubin, alkaline phosphatase and γ-glutamyltranspeptidase were measured in 42 serologically positive Lyme neuroborreliosis patients before and after long-term treatment with intravenous ceftriaxone (2–4 g daily) with co-administration of oral/intravenous α-lipoic acid (600 mg daily) and glutathione (100 mg orally or 0.6–2.4 g intravenously daily). Results: None of the patients developed biliary colic and there were no significant changes in serum bilirubin, alkaline phosphatase or γ-glutamyltranspeptidase levels over the course of the intravenous ceftriaxone treatment (mean length 75.0 days). Conclusions: Co-administration of α-lipoic acid and glutathione is associated with no significant changes in serum bilirubin, alkaline phosphatase or γ-glutamyltranspeptidase levels during the treatment of neuroborreliosis with intravenous ceftriaxone.

The effect of pulsed electromagnetic field therapy on food sensitivity.

Abstract Owing to the involvement of the immune system in the etiology of food sensitivity, and because pulsed electromagnetic field therapy is associated with beneficial immunologic changes, it was hypothesized that pulsed electromagnetic fields may have a beneficial effect on food sensitivity. A small pilot study was carried out in patients suffering from food sensitivity, with the antigen leukocyte antibody test being employed to index the degree of food sensitivity in terms of the number of foods to which each patient reacted. It was found that a 1-week course of pulsed electromagnetic field therapy, consisting of one hour’s treatment per day, resulted in a reduction in the mean number of reactive foods of 10.75 (p < 0.05). On the basis of these results, a larger study is warranted.

Pattern Of Dysautonomia In Patients With Functional Gastrointestinal Disorders

desaturations (p = 0.001) and 1 arousal (p N 0.05). No apneas were followed by desaturation and arousal. Hypopneas were the most frequent respiratory event and occurred primarily during sleep stage 1 and 2. In all FD-patients, we recorded 362 hypopneas with subsequent oxygen-desaturation that were followed by only 51 arousals. 12 hypopneas (p b 0.001) occurred in 3 controls (p= 0.085) and were followed by 3 arousals (p= 0.002).

The risk of lead contamination in bone broth diets.

The preparation and consumption of bone broth is being increasingly recommended to patients, for example as part of the gut and psychology syndrome (GAPS) diet for autism, attention-deficit hyperactivity disorder, dyslexia, dyspraxia, depression and schizophrenia, and as part of the paleolithic diet. However, bones are known to sequester the heavy metal lead, contamination with which is widespread throughout the modern environment. Such sequestered lead can then be mobilised from the bones. We therefore hypothesised that bone broth might carry a risk of being contaminated with lead. A small, blinded, controlled study of lead concentrations in three different types of organic chicken broth showed that such broths do indeed contain several times the lead concentration of the water with which the broth is made. In particular, broth made from skin and cartilage taken off the bone once the chicken had been cooked with the bones in situ, and chicken-bone broth, were both found to have markedly high lead concentrations, of 9.5 and 7.01 μg L(-1), respectively (compared with a control value for tap water treated in the same way of 0.89 μg L(-1)). In view of the dangers of lead consumption to the human body, we recommend that doctors and nutritionists take the risk of lead contamination into consideration when advising patients about bone broth diets.

Biochemical and Haematological Predictors of Reduced Neutrophil Granulocyte Count associated with Intravenous Ceftriaxone Treatment

Background: Intravenous treatment with ceftriaxone, a commonly used third-generation cephalosporin, is associated with a risk of the potentially fatal side-effect of neutropenia. Objective: The first systematic study to determine whether six to 12 days’ intravenous ceftriaxone treat-ment is associated with a reduction in the neutrophil count and the extent to which biochemical and/or haematological parameters routinely measured at baseline predict such a fall. Method: Baseline and follow-up haematological and biochemical blood indices were measured in 86 pa-tients (mean age 39.4 years; 55 female) receiving 2 g intravenous ceftriaxone daily. Results: At follow-up, the mean (standard error) neutrophil count had fallen from 3.93 × 109 (0.16 × 109) L-1 to 3.15 × 109 (0.15 × 109) L-1 (p < 0.000001). This reduction was predictable according to the following multifactor linear regression model: (baseline neutrophil count (× 109 L-1)) – (follow-up neu-trophil count (× 109 L-1)) = 76 + 159.2(baseline haematocrit) – 14.5(baseline red blood cell count (× 1012 L-1)) – 0.724(baseline mean corpuscular volume (fL)) + 0.474(baseline neutrophil count (× 109 L-1)) + 0.0448(baseline total iron binding capacity (μM)) + 7.15(baseline calcium ion concentration (mM)) – 13.2(baseline corrected calcium ion concentration (mM)) + 0.0166(baseline alkaline phosphatase (IU L-1)). The residuals were normally distributed and model testing by random partition of the original data into two parts, with training of the model using the first part and model testing with the second part, gave highly satisfactory results. Conclusion: Intravenous ceftriaxone treatment is associated with a fall in neutrophils, which can be pre-dicted by routine baseline blood indices