Salivary clearance of caffeine in children.

Background: Measurement of salivary caffeine (1,3,7-trimethylpurine-2,6-dione or 1,3,7-trimethylxanthine) clearance can, in principle, be used to assess hepatic function, diagnose chronic hepatic disease and conduct investigations of substrates of hepatic cytochrome P450 (CYP) isozymes in children, without recourse to venepuncture. However, little is known about childhood sexual dimorphism of hepatic CYP isoforms. Furthermore, the association, if any, between salivary caffeine clearance and age in children has not hitherto been established. The aims of this study were to assess whether salivary caffeine clearance differs between boys and girls and whether it varies with age during childhood. Methods: Following at least 24 h' abstinence from dietary caffeine, nine boys (mean (standard error) age 9.6 (1.1) y) and eight girls (mean age 11.0 (1.2) y), none of whom was a smoker or suffered from chronic hepatic disease, ingested an oral caffeine dose titrated by body mass, namely 3 mg kg-1. Salivary samples collected two and 14 h later underwent spectrophotometric caffeine analysis. Results: The boys and the girls were age matched. The mean caffeine clearance in the boys was 2.47 (0.33) mL min-1 kg-1, while that in the girls was 2.20 (0.31) mL min-1 kg-1 (p = 0.56). The salivary caffeine clearance was negatively correlated with age (r = -0.59, p = 0.01). Conclusion: Stratification by sex appears to be unnecessary when considering childhood salivary caffeine clearance or when conducting investigations in children of CYP1A2 and xanthine oxidase substrates. Furthermore, childhood salivary caffeine clearance is negatively correlated with age.

Detection of 41-kDa bacterial flagellin protein by the lymphocyte transformation test-memory lymphocyte immunostimulation assay.

BACKGROUND/OBJECTIVES: Diagnosis of human infection by various species of the bacterial genus Borrelia is mainly reliant on serological testing, polymerase chain reaction (PCR) or culture but such serological tests have been reported to have heterogeneous sensitivities, while Borrelia PCR and culture have been reported as being of modest diagnostic value. It has been suggested that the adjunctive use of the lymphocyte transformation test-memory lymphocyte immunostimulation assay (LTT-MELISA) may be helpful in this regard; however, the clinical usefulness of this assay has been questioned. The Borrelia immunodominant 41-kDa flagellin protein almost always gives rise to a marked human antibody response following infection. It was therefore decided to determine whether the LTT-MELISA detects the human antibody response to this antigen. METHODS: Blood samples from consecutive patients with possible borreliosis attending a clinic were independently tested by both Western blots and LTT-MELISA. RESULTS: After omitting cases with indeterminate Western blot results and equivocal LTT-MELISA results, multiple linear regression modelling demonstrated that the 41-kDa flagellin immunoglobulin (Ig) M level was predictable from two LTT-MELISA variables (F 2,51 = 5.981, P = 0.005). Similarly, the corresponding 41-kDa IgG model also contained two LTT-MELISA variables (F 2,57 = 3.700, P = 0.031). CONCLUSION: It is concluded that the LTT-MELISA appears to be able to detect the response to this antigen.

Is there a sex difference in adult salivary clearance of caffeine (1,3,7-trimethylpurine-2,6-dione)?

BACKGROUND: The salivary caffeine clearance is a non-invasive, safe, saliva-based method for assessing hepatic function and diagnosing chronic liver disease. The elimination of caffeine from the body follows first-order kinetics and principally involves catabolism by hepatic CYP1A2, with a half-life usually between three and 7 h. It is known that this process is affected by age and smoking tobacco. It has been suggested that sex might also be important, but there is scant evidence for this. The aim of this study was to assess whether there is a sex difference in salivary caffeine clearance in adults. METHODS: A cohort of 213 adults was studied. They were all non-smokers and none suffered from chronic liver disease. They consisted of 67 men (mean age 40.0 years) and 146 women (mean age 44.7 years). Following a period of dietary caffeine abstinence lasting at least 24 h, each subject ingested a single oral dose in the morning of caffeine, at a dose of 3 mg per kg body mass. Salivary samples were collected at 2 h and 14 h post-caffeine ingestion and were spectrophotometrically assayed for their caffeine concentrations. RESULTS: The two groups were matched for age. The mean (standard error) salivary caffeine clearance in the male subjects was 1.51 (0.10) mL min-1 kg-1, while that in the female subjects was 1.60 (0.07) mL min-1 kg-1 (p = 0.495). CONCLUSION: This relatively large study provides no evidence of a sex difference in salivary caffeine clearance.

The effect of supplementation with Scutellaria baicalensis on hepatic function.

The dried root of the angiosperm Scutellaria baicalensis, also known as Chinese skullcap or Baikal skullcap, is widely used in traditional Chinese medicine, Korean traditional medicine and as a nutritional supplement; several studies have indicated that both the supplement and some of its ingredients may have clinically beneficial actions. However, the National Institutes of Health official guidance states that the use of Scutellaria "has been implicated in rare instances of clinically apparent liver injury" and that "the onset of symptoms and jaundice occurred within 6-24 weeks of starting skullcap, and the serum enzyme pattern was typically hepatocellular", with marked increases in serum alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin levels. Careful perusal of all such published case reports showed that in each case the patient was concurrently taking at least one other supplement which had an established association with hepatic dysfunction. The authors hypothesised that long-term supplementation with Scutellaria baicalensis does not lead to hepatic dysfunction. The aim of this study was to test this hypothesis by assessing liver function before and after starting supplementation with Scutellaria baicalensis. Pre- and post-supplementation serum assays of alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin were carried out in 17 patients (16 female) of average age 38.6 (standard error 4.4) years who had each taken 1335 mg dried root daily for an average of 444 (71) days. The mean baseline versus follow-up values for each liver function test were: alanine transaminase: 25.7 (2.6) IU/L v. 25.1 (1.7) IU/L; aspartate transaminase: 22.1 (1.1) IU/L v. 23.5 (1.3) IU/L; alkaline phosphatase: 63.7 (4.6) IU/L v. 63.3 (3.9) IU/L; and bilirubin: 6.1 (0.6) µM v. 6.0 (0.7) µM. None of these changes was statistically significant; indeed, three of the four parameters showed a non-significant decrease over time. Furthermore, none manifested clinical symptoms or signs of hepatic dysfunction during Scutellaria supplementation. These results suggest that daily intake of a relatively high level of Scutellaria baicalensis for over a year is not associated with any biochemical or clinical evidence of hepatic dysfunction. Indeed, Scutellaria baicalensis has been shown in murine experiments to have hepatoprotective actions.

The effect of successful low-dose immunotherapy ascertained by provocation neutralization on lymphocytic calcium ion influx following electric field exposure.

Background Low-dose immunotherapy affects baseline levels of intracellular calcium. However, the effect of background electric fields is yet to be ascertained. The aim of this study was to test the following hypotheses: desensitization by low-dose immunotherapy is associated with reduced calcium ion influx during electric field exposure; the effect of low-dose immunotherapy on intracellular calcium ion concentration does not depend on electric field exposure; and the intracellular calcium ion concentration is amplified by electric field exposure. Methods The experimental design was balanced and orthogonal. Intracellular lymphocytic calcium ion concentrations were assayed in 47 patients, following incubation with picogram amounts of 12 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. Duplicates were also exposed to an electric field which replicated the frequency spectrum measured in a non-Faraday shielded room. Results A significant or trend-level main effect was found for low-dose immunotherapy for: benzoate; formaldehyde; metabisulfite; natural gas; nitrosamines; organophosphates; salicylate; azo-dyes and precursors; nickel; and petrol (gasoline) exhaust. Significant or trend-level main effects for electric field exposure were observed for: formaldehyde; mercury (inorganic); natural gas; nickel; nitrosamines; petrol exhaust; salicylate; benzoate; and metabisulfite. There was no evidence of a statistical interaction between these two factors. Electric field exposure was associated with a higher intracellular calcium ion concentration. Conclusion There was support for all three hypotheses. The results suggest that patients may experience increased sensitivity to allergens as a result of exposure to everyday electric fields.

Prevention of Infection in Adults Receiving Intravenous Antibiotic Treatment via Indwelling Central Venous Access Devices.

BACKGROUND: The use of indwelling Central Venous Access Devices (CVADs) is associated with the development of bloodstream infections. When CVADs are used to administer systemic antibiotics, particularly second- or higher-generation cephalosporins, there is a particular risk of developing Clostridium difficile infection. The overall bloodstream infection rate is estimated to be around 1.74 per 1000 Central Venous Catheter (CVC)-days. OBJECTIVE: We hypothesised that daily oral administration of the anion-binding resin colestyramine (cholestyramine) would help prevent infections in those receiving intravenous antibiotic treatment via CVADs. METHOD: A small case series is described of adult patients who received regular intravenous antibiotic treatment (ceftriaxone, daptomycin or vancomycin) for up to 40 weeks via indwelling CVADs; this represented a total of 357 CVC-days. In addition to following well-established strategies to prevent C. difficile infection, during the course of the intravenous antibiotic treatment the patients also received daily oral supplementation with 4 g colestyramine. RESULTS: There were no untoward infectious events. In particular, none of the patients developed any symptoms or signs of C. difficile infection, whereas approximately one case of a bloodstream infection would have been expected. CONCLUSION: It is suggested that oral colestyramine supplementation may help prevent such infection through its ability to bind C. difficile toxin A (TcdA) and C. difficile toxin B (TcdB); these toxins are able to gain entry into host cells through receptor-mediated endocytosis, while anti-toxin antibody responses to TcdA and TcdB have been shown to induce protection against C. difficile infection sequelae.

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 treatment 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 patients (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 neutrophil 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 predicted by routine baseline blood indices.

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.

Recovery from Cogwheel Rigidity and Akinesia and Improvement in Vibration Sense and Olfactory Perception following Removal of an Epoxy-Oleic Acid DNA Adduct.

The epoxy fatty acid cis-12,13-epoxy-oleic acid, which acts as a DNA adduct, may be generated during long-term storage of many seed oils, including those used in cooking, with frying oils and fried foods being a major source in the modern human diet. Removal of this epoxy fatty acid from the locus of the N-formyl peptide receptors was associated with recovery from cogwheel rigidity and akinesia as well as with improvement in vibration sense and olfactory perception.

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

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.

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.

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.

The potential use of cholestyramine to reduce the risk of developing Clostridium difficile-associated diarrhoea in patients receiving long-term intravenous ceftriaxone.

Intravenous pharmacotherapy with the third-generation cephalosporin ceftriaxone is unfortunately associated with a relatively high incidence of Clostridium difficile-associated diarrhoea. Cholestyramine (colestyramine) is an anion-binding resin which can bind luminal C.difficile toxin A (TcdA) and toxin B (TcdB) and which may be beneficial in the treatment of recurrent antibiotic-associated pseudomembranous colitis. We therefore hypothesised that concomitant oral cholestyramine might reduce the risk of C.difficile-associated diarrhoea in patients receiving long-term intravenous ceftriaxone. A pilot study was carried out in which it was found that only three out of 46 (6.5%) such patients being treated with 2 g ceftriaxone daily for Lyme borreliosis, who also received 4 g cholestyramine daily, developed C.difficile-associated diarrhoea. This is smaller than a published report of the incidence of this complication in six out of 26 (23.1%) patients following 1-3 days' treatment with 1 g intravenous ceftriaxone, but without oral cholestyramine (p=0.06). We therefore recommend that a larger, double-blind placebo-controlled trial be carried out to test this hypothesis.

Hyperosmia in Lyme disease.

Neurological involvement in Lyme disease has been reported to include meningitis, cranial neuropathy and radiculoneuritis. While it is known that in some cases of asceptic meningitis patients may develop hyperosmia, the association between hyperosmia and Lyme disease has not previously been studied. Objective To carry out the first systematic study to ascertain whether hyperosmia is also a feature of Lyme disease. Method A questionnaire regarding abnormal sensory sensitivity in respect of the sense of smell was administered to 16 serologically positive Lyme disease patients and to 18 control subjects. Results The two groups were matched in respect of age, sex and body mass. None of the 34 subjects was suffering from migraine. Eight (50%) of the Lyme patients and none (0%) of the controls suffered from hyperosmia (p=0.0007). Conclusion This first systematic controlled study showed that Lyme disease is associated with hyperosmia.

Hyperosmia in Lyme disease / Hyperosmia na doença de Lyme

Neurological involvement in Lyme disease has been reported to include meningitis, cranial neuropathy and radiculoneuritis. While it is known that in some cases of asceptic meningitis patients may develop hyperosmia, the association between hyperosmia and Lyme disease has not previously been studied. Objective To carry out the first systematic study to ascertain whether hyperosmia is also a feature of Lyme disease. Method A questionnaire regarding abnormal sensory sensitivity in respect of the sense of smell was administered to 16 serologically positive Lyme disease patients and to 18 control subjects. Results The two groups were matched in respect of age, sex and body mass. None of the 34 subjects was suffering from migraine. Eight (50%) of the Lyme patients and none (0%) of the controls suffered from hyperosmia (p=0.0007). Conclusion This first systematic controlled study showed that Lyme disease is associated with hyperosmia. .

Tem sido descrito acometimento neurológico na doença de Lyme: meningite, neuropatia de nervos cranianos, e radiculoneurite. É bem conhecida a ocorrência de hiperosmia em alguns casos de meningites assépticas, mas a associação de hiperosmia com doença de Lyme ainda não foi relatada. Objetivo Conduzir um estudo sistemático para investigar se a hiperosmia é característica também da doença de Lyme. Método Foi aplicado um questionário pesquisando a ocorrência de sensibilidade anormal em relação ao sentido da olfação a 16 pacientes com sorologia positiva para doença de Lyme e a 18 controles normais. Os dois grupos foram pareados em relação a idade, sexo e massa corporal. Nenhum dos 34 sujeitos sofria de enxaqueca. Resultados Foi detectada hiperosmia em 8 sujeitos com doença de Lyme (50%) enquanto que a hiperosmia não apareceu em nenhum sujeito do grupo controle (p=0,0007). Conclusão Doença de Lyme está associada à hiperosmia. .

The association of lyme disease with loss of sexual libido and the role of urinary bladder detrusor dysfunction.

PURPOSE: The primary aim was to carry out a pilot study to compare the loss of sexual libido between a group of Lyme disease patients and a group of matched controls. The secondary aim was to evaluate whether loss of libido in Lyme disease patients is associated with urinary bladder detrusor dysfunction. METHODS: A group of 16 serologically positive Lyme disease patients and 18 controls were queried directly about loss of libido. RESULTS: The 2 groups were matched with respect to age, sex, body mass index, and mean arterial blood pressure. None of the 34 subjects was taking medication that might affect sexual libido or had undergone a previous operative procedure involving the genitourinary tract. Of the 16 Lyme disease patients, 8 (50%) had no loss of libido, and of the 18 controls, none had loss of libido (P<0.001). In the Lyme disease patient group, there was no statistically significant relationship between loss of libido and urinary bladder detrusor dysfunction (P=0.61). CONCLUSIONS: This pilot study suggested an association between Lyme disease and loss of libido. Moreover, this loss of libido did not seem to be associated with urinary bladder detrusor dysfunction. Given these results, we recommend further studies to confirm the association.

Respiratory modulation of cardiac vagal tone in Lyme disease.

AIM: To conduct the first systematic test of the hypothesis that modulation of cardiac vagal tone is impaired in Lyme disease. METHODS: The response of cardiac vagal tone to respiratory modulation was measured in 18 serologically positive Lyme disease patients and in 18 controls. RESULTS: The two groups were matched in respect of age, sex, body mass, mean arterial blood pressure, mean resting heart rate and mean resting cardiac vagal tone. The mean maximum cardiac vagal tone during deep breathing in the Lyme disease patients [11.2 (standard error 1.3)] was lower than in the matched controls [16.5 (standard error 1.7); P = 0.02]. CONCLUSION: Respiratory modulation of cardiac vagal tone is impaired in Lyme disease, which suggests that Lyme disease may directly affect the vagus nerve or the brainstem.

Diagnostic use of the lymphocyte transformation test-memory lymphocyte immunostimulation assay in confirming active Lyme borreliosis in clinically and serologically ambiguous cases.

The aim of this study was to carry out an independent evaluation of the proposition that the lymphocyte transformation test-memory lymphocyte immunostimulation assay (LTT-MELISA) may be diagnostically useful in the confirmation of active Lyme borreliosis in clinically and serologically ambiguous cases. Blood samples from 54 patients consecutively presenting to a British center with clinical suspicion of Lyme borreliosis were tested for this disease by immunoglobulin M (IgM) and immunoglobulin G (IgG) Western blots and by LTT-MELISA. Forty-five of these patients had Western blot results which were negative for both IgM and IgG by the criteria of the Centers for Disease Control and Prevention (CDC); of these patients, 19 (42%) were LTT-MELISA-positive. Two of the patients who had IgM positive results by the CDC criteria were LTT-MELISA-negative. It is concluded that, for putative European-acquired Lyme borreliosis infections, it would be sensible to carry out both the LTT-MELISA and Western blot assay.

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.

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 pilot's 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.