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Post by Lisa Petrison on Dec 17, 2011 14:58:35 GMT -5
Neurotoxicol Teratol. 2005 Jan-Feb;27(1):29-46. A time-series study of sick building syndrome: chronic, biotoxin-associated illness from exposure to water-damaged buildings. Shoemaker RC, House DE. Chronic Fatigue Center, 500 Market Street, Suite 103, Pocomoke City, MD 21851, United States. The human health risk for chronic illnesses involving multiple body systems following inhalation exposure to the indoor environments of water-damaged buildings (WDBs) has remained poorly characterized and the subject of intense controversy. The current study assessed the hypothesis that exposure to the indoor environments of WDBs with visible microbial colonization was associated with illness. The study used a cross-sectional design with assessments at five time points, and the interventions of cholestyramine (CSM) therapy, exposure avoidance following therapy, and reexposure to the buildings after illness resolution. The methodological approach included oral administration of questionnaires, medical examinations, laboratory analyses, pulmonary function testing, and measurements of visual function. Of the 21 study volunteers, 19 completed assessment at each of the five time points. Data at Time Point 1 indicated multiple symptoms involving at least four organ systems in all study participants, a restrictive respiratory condition in four participants, and abnormally low visual contrast sensitivity (VCS) in 18 participants. Serum leptin levels were abnormally high and alpha melanocyte stimulating hormone (MSH) levels were abnormally low. Assessments at Time Point 2, following 2 weeks of CSM therapy, indicated a highly significant improvement in health status. Improvement was maintained at Time Point 3, which followed exposure avoidance without therapy. Reexposure to the WDBs resulted in illness reacquisition in all participants within 1 to 7 days. Following another round of CSM therapy, assessments at Time Point 5 indicated a highly significant improvement in health status. The group-mean number of symptoms decreased from 14.9+/-0.8 S.E.M. at Time Point 1 to 1.2+/-0.3 S.E.M., and the VCS deficit of approximately 50% at Time Point 1 was fully resolved. Leptin and MSH levels showed statistically significant improvement. The results indicated that CSM was an effective therapeutic agent, that VCS was a sensitive and specific indicator of neurologic function, and that illness involved systemic and hypothalamic processes. Although the results supported the general hypothesis that illness was associated with exposure to the WDBs, this conclusion was tempered by several study limitations. Exposure to specific agents was not demonstrated, study participants were not randomly selected, and double-blinding procedures were not used. Additional human and animal studies are needed to confirm this conclusion, investigate the role of complex mixtures of bacteria, fungi, mycotoxins, endotoxins, and antigens in illness causation, and characterize modes of action. Such data will improve the assessment of human health risk from chronic exposure to WDBs. PMID: 15681119 [PubMed - indexed for MEDLINE] Attachments:
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Post by Lisa Petrison on Dec 17, 2011 15:00:01 GMT -5
Neurotoxicol Teratol. 2006 Sep-Oct;28(5):573-88. Epub 2006 Aug 7. Sick building syndrome (SBS) and exposure to water-damaged buildings: time series study, clinical trial and mechanisms. Shoemaker RC, House DE. Chronic Fatigue Center, 500 Market Street, Suite 103, Pocomoke City, MD 21851, USA. ritchieshoemaker@msn.com <ritchieshoemaker@msn.com> Occupants of water-damaged buildings (WDBs) with evidence of microbial amplification often describe a syndrome involving multiple organ systems, commonly referred to as "sick building syndrome" (SBS), following chronic exposure to the indoor air. Studies have demonstrated that the indoor air of WDBs often contains a complex mixture of fungi, mycotoxins, bacteria, endotoxins, antigens, lipopolysaccharides, and biologically produced volatile compounds. A case-series study with medical assessments at five time points was conducted to characterize the syndrome after a double-blinded, placebo-controlled clinical trial conducted among a group of study participants investigated the efficacy of cholestyramine (CSM) therapy. The general hypothesis of the time series study was that chronic exposure to the indoor air of WDBs is associated with SBS. Consecutive clinical patients were screened for diagnosis of SBS using criteria of exposure potential, symptoms involving at least five organ systems, and the absence of confounding factors. Twenty-eight cases signed voluntary consent forms for participation in the time-series study and provided samples of microbial contaminants from water-damaged areas in the buildings they occupied. Twenty-six participants with a group-mean duration of illness of 11 months completed examinations at all five study time points. Thirteen of those participants also agreed to complete a double-blinded, placebo-controlled clinical trial. Data from Time Point 1 indicated a group-mean of 23 out of 37 symptoms evaluated; and visual contrast sensitivity (VCS), an indicator of neurological function, was abnormally low in all participants. Measurements of matrix metalloproteinase 9 (MMP9), leptin, alpha melanocyte stimulating hormone (MSH), vascular endothelial growth factor (VEGF), immunoglobulin E (IgE), and pulmonary function were abnormal in 22, 13, 25, 14, 1, and 7 participants, respectively. Following 2 weeks of CSM therapy to enhance toxin elimination rates, measurements at Time Point 2 indicated group-means of 4 symptoms with 65% improvement in VCS at mid-spatial frequency-both statistically significant improvements relative to Time Point 1. Moderate improvements were seen in MMP9, leptin, and VEGF serum levels. The improvements in health status were maintained at Time Point 3 following a 2-week period during which CSM therapy was suspended and the participants avoid re-exposure to the WDBs. Participants reoccupied the respective WDBs for 3 days without CSM therapy, and all participants reported relapse at Time Point 4. The group-mean number of symptoms increased from 4 at Time Point 2 to 15 and VCS at mid-spatial frequency declined by 42%, both statistically significant differences relative to Time Point 2. Statistically significant differences in the group-mean levels of MMP9 and leptin relative to Time Point 2 were also observed. CSM therapy was reinstated for 2 weeks prior to assessments at Time Point 5. Measurements at Time Point 5 indicated group-means of 3 symptoms and a 69% increase in VCS, both results statistically different from those at Time Points 1 and 4. Optically corrected Snellen Distance Equivalent visual acuity scores did not vary significantly over the course of the study. Group-mean levels of MMP9 and leptin showed statistically significant improvement at Time Point 5 relative to Time Points 1 and 4, and the proportion of participants with abnormal VEGF levels was significantly lower at Time Point 5 than at Time Point 1. The number of participants at Time Point 5 with abnormal levels of MMP9, leptin, VEGF, and pulmonary function were 10, 10, 9, and 7, respectively. The level of IgE was not re-measured because of the low incidence of abnormality at Time Point 1, and MSH was not re-measured because previously published data indicated a long time course for MSH improvement. The results from the time series study supported the general study hypothesis that exposure to the indoor air of WDBs is associated with SBS. High levels of MMP9 indicated that exposure to the complex mixture of substances in the indoor air of the WDBs triggered a pro-inflammatory cytokine response. A model describing modes of action along a pathway leading to biotoxin-associated illness is presented to organize current knowledge into testable hypotheses. The model links an inflammatory response with tissue hypoxia, as indicated by abnormal levels of VEGF, and disruption of the proopiomelanocortin pathway in the hypothalamus, as evidenced by abnormalities in leptin and MSH levels. Results from the clinical trial on CSM efficacy indicated highly significant improvement in group-mean number of symptoms and VCS scores relative to baseline in the 7 participants randomly assigned to receive 2 weeks of CSM therapy, but no improvement in the 6 participants assigned placebo therapy during that time interval. However, those 6 participants also showed a highly significant improvement in group-mean number of symptoms and VCS scores relative to baseline following a subsequent 2-week period of CSM therapy. Because the only known benefit of CSM therapy is to enhance the elimination rates of substances that accumulate in bile by preventing re-absorption during enterohepatic re-circulation, results from the clinical trial also supported the general study hypothesis that SBS is associated with exposure to WDBs because the only relevant function of CSM is to bind and remove toxigenic compounds. Only research that focuses on the signs, symptoms, and biochemical markers of patients with persistent illness following acute and/or chronic exposure to WDBs can further the development of the model describing modes of action in the biotoxin-associated pathway and guide the development of innovative and efficacious therapeutic interventions. PMID: 17010568 [PubMed - indexed for MEDLINE] Attachments:
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Post by Lisa Petrison on Dec 17, 2011 16:24:56 GMT -5
Ritchie Shoemaker “Defects in Cognitive Functioning/C4a” 15 April 2009 IACFS/ME Conference, Reno, NV Attachments:
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Post by Lisa Petrison on Dec 17, 2011 16:34:45 GMT -5
Environ Health Perspect. 2001 May;109(5):539-45. Possible estuary-associated syndrome: symptoms, vision, and treatment. Shoemaker RC, Hudnell HK. Source McCready Outpatient Services Center, Pocomoke City, Maryland, USA. The human illness designated as possible estuarine-associated syndrome (PEAS) by the Centers for Disease Control and Prevention (CDC) has been associated with exposure to estuaries inhabited by toxin-forming dinoflagellates, including members of the fish-killing toxic Pfiesteria complex (TPC), Pfiesteria piscicida and Pfiesteria shumwayae. Humans may be exposed through direct contact with estuarine water or by inhalation of aerosolized or volatilized toxin(s). The five cases reported here demonstrate the full spectrum of symptoms experienced during acute and chronic stages of this suspected neurotoxin-mediated illness. The nonspecific symptoms most commonly reported are cough, secretory diarrhea, headache, fatigue, memory impairment, rash, difficulty in concentrating, light sensitivity, burning skin upon water contact, muscle ache, and abdominal pain. Less frequently encountered symptoms are upper airway obstruction, shortness of breath, confusion, red or tearing eyes, weakness, and vertigo. Some patients experience as few as four of these symptoms. The discovery that an indicator of visual pattern-detection ability, visual contrast sensitivity (VCS), is sharply reduced in affected individuals has provided an objective indicator that is useful in diagnosing and monitoring PEAS. VCS deficits are present in both acute and chronic PEAS, and VCS recovers during cholestyramine treatment coincident with symptom abatement. Although PEAS cannot yet be definitively associated with TPC exposure, resolution with cholestyramine treatment suggests a neurotoxin-mediated illness. Comment in Environ Health Perspect. 2002 Mar;110(3):A120-3. PMID: 11401768 [PubMed - indexed for MEDLINE] PMCID: PMC1240316 Free PMC Article Attachments:
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Post by Lisa Petrison on Dec 17, 2011 16:37:01 GMT -5
Environ Health Perspect. 2001 Oct;109 Suppl 5:791-6. Residential and recreational acquisition of possible estuary-associated syndrome: a new approach to successful diagnosis and treatment. Shoemaker RC. McCready Outpatient Services Center, Pocomoke City, Maryland 21851, USA. ritchieshoemaker@msn.com Evidence suggests that the estuarine dinoflagellates, Pfiesteria piscicida Steidinger & Burkholder and P. shumwayae Glasgow & Burkholder, members of the toxic Pfiesteria complex (TPC), may release one or more toxins that kill fish and adversely affect human health. In the current study we investigated the potential for undiagnosed cases of possible estuary-associated syndrome (PEAS), as termed by the Centers for Disease Control and Prevention (CDC), in a population that had residential and/or recreational exposure to TPC-affected estuaries, but that did not have direct contact with fish kills or lesioned fish. Age-adjusted visual contrast sensitivity (VCS) was significantly lower and the presence of PEAS-associated symptoms was much higher in the estuary cohort (n = 77) than in combined-control cohorts (n = 87), one without exposure to bodies of water (n = 53) and one with exposure to marine waters (n = 34). In the estuary cohort, 37 individuals met the CDC case definition for PEAS and had significantly lower VCS than non-PEAS cases. The VCS improved and symptoms abated after 2 weeks of treatment with cholestyramine. Cholestyramine, the original drug approved for treatment of hypercholesterolemia, has previously been reported to enhance the elimination rates of a variety of toxins, presumably by interruption of enterohepatic recirculation through toxin entrapment in its polymeric structure and/or anion-exchange process. Control studies showed that repeated VCS testing alone did not improve VCS scores and that cholestyramine treatment did not affect VCS in patients with elevated cholesterol levels. These results suggested that a) susceptible individuals may acquire PEAS through residential and/or recreational contact with TPC-affected estuaries in the absence of an active fish kill; b) VCS is a useful indicator in PEAS diagnosis and treatment monitoring; and c) PEAS can be effectively treated with cholestyramine. Because the study did not use population sampling techniques, the results do not indicate PEAS prevalence. Furthermore, definitive diagnosis of PEAS and association with TPC toxin(s) must await identification of, and a serologic test for, the putative TPC toxin(s). PMID: 11677191 [PubMed - indexed for MEDLINE] PMCID: PMC1240613 Free PMC Article Attachments:
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Post by Lisa Petrison on Dec 17, 2011 16:49:02 GMT -5
Int Arch Allergy Immunol. 2008;146(3):255-61. Epub 2008 Feb 13.
Complement split products C3a and C4a are early markers of acute lyme disease in tick bite patients in the United States.
Shoemaker RC, Giclas PC, Crowder C, House D, Glovsky MM.
Source
Center for Research on Biotoxin Associated Illnesses, Pocomoke, Md., USA.
Abstract
BACKGROUND:
Current laboratory markers do not readily detect acute Lyme disease. We assessed the utility of complement and its split products as markers of Lyme disease in patients shortly after a tick bite.
METHODS:
Thirty-one consecutive acute Lyme disease patients, 14 with and 17 without erythema migrans (EM) skin rash, seen by a physician within 96 h of a tick bite were matched with 24 consecutive tick bite patients without Lyme disease symptoms and 46 healthy control subjects. Complement and split products measured included factor B, Bb, C4, C3c, C3a(des Arg), C4a(des Arg), C1q- and C3d-containing immune complexes, and C2.
RESULTS:
C2, C4, C3 and factor B levels were within normal ranges in all groups. C3a and C4a levels were significantly higher in acute Lyme disease patients than in tick bite and healthy control groups (both p < 0.001). All acute Lyme disease patients, regardless of EM, had elevated levels of C3a or C4a. Few tick bite controls had elevated levels of C3a (2/20) or C4a (5/24) and only 1 of the healthy control subjects had elevated C3a (0/46) or C4a (1/32).
CONCLUSIONS:
These findings suggest that C3a and C4a may be useful markers of Lyme disease in patients seen shortly after tick bite, even in those without EM.
(c) 2008 S. Karger AG, Basel
PMID: 18270493 [PubMed - indexed for MEDLINE]
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Post by Lisa Petrison on Dec 17, 2011 16:49:54 GMT -5
Adv Ther. 2006 Jan-Feb;23(1):1-11.
Atovaquone plus cholestyramine in patients coinfected with Babesia microti and Borrelia burgdorferi refractory to other treatment.
Shoemaker RC, Hudnell HK, House DE, Van Kempen A, Pakes GE; COL40155 Study Team.
Source
Center for Research on Biotoxin-Associated Illnesses Pocomoke City, Maryland 21851, USA.
Abstract
Ten percent of US patients with Lyme disease are coinfected with Babesia microti. A double-blind, placebo-controlled, crossover trial enrolled 25 patients with confirmed Borrelia burgdorferi/B microti coinfection, abnormal visual contrast sensitivity (VCS), and persistent symptoms despite prior treatment with atovaquone and azithromycin. Patients were randomly assigned to atovaquone suspension or placebo plus cholestyramine for 3 weeks, were crossed over for 3 weeks, and then received open-label atovaquone and cholestyramine for 6 weeks. Symptoms and VCS scores were recorded at baseline and after weeks 3, 6, 9, and 12. Improvements in symptoms and VCS deficits were observed only after at least 9 weeks of treatment. At week 12, 5 patients were asymptomatic, and 16 had a notable reduction in the number of symptoms. The entire cohort demonstrated significant increases in VCS scores. Adverse effects were rare. Patients coinfected with B burgdorferi and B microti derive measurable clinical benefit from prolonged treatment with atovaquone and cholestyramine. Longer-term combination therapy may be indicated.
PMID: 16644602 [PubMed - indexed for MEDLINE]
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Post by Lisa Petrison on Dec 17, 2011 16:50:30 GMT -5
Md Med J. 1997 Nov-Dec;46(10):521-3.
Diagnosis of Pfiesteria-human illness syndrome.
Shoemaker RC.
Abstract
The first case reports of human illness caused by exposure to Pfiesteria piscicida toxin(s) acquired outside of a laboratory are reported. Though Pfiesteria, a toxin-forming dinoflagellate, is responsible for killing billions of fish in estuaries in North Carolina, its role in human illness has remained controversial, in part due to lack of identification of the toxin. A recent fish kill in the rivers of the lower Eastern Shore has permitted careful investigation and identification of a distinct clinical syndrome resulting from exposure to the Pfiesteria toxin--Pfiesteria human illness syndrome (PHIS). Patients have memory losses, cognitive impairments, headaches, skin rashes, abdominal pain, secretory diarrhea, conjunctival irritation, and bronchospasm. Not all patients have all elements of the syndrome.
PMID: 9392940 [PubMed - indexed for MEDLINE]
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Post by Lisa Petrison on Dec 17, 2011 17:44:58 GMT -5
Neurotoxicol Teratol. 2010 Nov-Dec;32(6):633-9. Epub 2010 Jun 4. Defining the neurotoxin derived illness chronic ciguatera using markers of chronic systemic inflammatory disturbances: a case/control study. Shoemaker RC, House D, Ryan JC. Center for Research on Biotoxin Associated Illnesses, Pocomoke, MD, USA. ritchieshoemaker@msn.com BACKGROUND: Ciguatoxins are extremely potent neurotoxins, produced by tropical marine dinoflagellates, that persistently enter into our food web. Over 100,000 people annually experience acute ciguatera poisoning from consuming toxic fish. Roughly 5% of these victims will develop chronic ciguatera (CC), a widespread, multisymptom, multisystem, chronic illness that can last tens of years. CC is marked by disproportionate disability and non-specific refractory symptoms such as fatigue, cognitive deficits and pain, and is suggestive of other illnesses. Its unknown pathophysiology makes both diagnosis and treatment difficult. OBJECTIVES: We wanted to compare objective parameters of visual contrast sensitivity testing, measures of innate immune response and genetic markers in cases to controls to assess the potential for the presence of persistent inflammatory parameters that are demonstrated in other biotoxin associated illnesses at a single specialty clinic. METHODS: Using 59 CC cases and 59 controls we present in retrospective review, in all cases, abnormalities in immune responses paralleling the chronic systemic inflammatory response syndrome seen in several other chronic diseases. RESULTS: This study defines a preliminary case definition using medical history, total symptoms, visual contrast sensitivity, HLA DR genotype analysis, reduction of regulatory neuropeptides VIP and MSH, and multiple measures of inflammatory immune response, especially C4a and TGFβ1, thereby providing a basis for identification and targeted therapy. CONCLUSIONS: CC provides a model for chronic human illness associated with initiation of inflammatory responses by biologically produced neurotoxins. Copyright © 2010 Elsevier Inc. All rights reserved. PMID: 20685390 [PubMed - indexed for MEDLINE] www.survivingmold.com/docs/Resources/Shoemaker%20Papers/NTT6154_ciguatera_11_10.pdfAttachments:
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