thorough clinical study of sick building syndrome from water damaged buildings,
RC Shoemaker, DE House, Neurotoxicol Terratol, 2005, 2006 -- need for similar
research on chronic methanol (formaldehyde, formic acid) toxicity from liquors
and aspartame: Murray 2007.01.09
http://groups.yahoo.com/group/aspartameNM/message/1397


Subject: [occ-env-med-l] Indoor mold and human illness
Date: 9:59 AM 2007.01.09

Dear Colleagues,

The recent discussions of indoor mold and human illness have lacked
critical and constructive discussion of the recent peer-reviewed
articles on this topic.

Perhaps our forum would benefit from this approach.

Below I offer an abstract from a recent article that describes
a time-series study, a clinical trial, symptoms, an objective indication
of neurologic function, and biochemical parameters and pathways.
Comments on the science (only, please)?

These comments are my own and do not reflect those of the Agency.
I am on the editorial advisory board on the journal, NT&T, and
have previously discussed these data and conclusions with the
authors and others.
---------------------------------------------------

H Kenneth Hudnell, PhD Hudnell.Ken@...
Neurotoxicologist
US Environmental Protection Agency
MD: B105-05
Research Triangle Park, NC 27711
Ph.: 919-541-7866; Fx.: 919-541-3335
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[ abstract from PubMed ]
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, Ritchie C,
House, Dennis E.
Chronic Fatigue Center, 500 Market Street, Suite 103, Pocomoke City, MD 21851,
USA. ritchieshoemaker@...

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
*******************************************************


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
*******************************************************


Neurotoxicol Teratol. 2005 Sep-Oct; 27(5): 733-43. Epub 2005 Aug 15.
Chronic biotoxin-associated illness:
multiple-system symptoms, a vision deficit, and effective treatment.
Hudnell HK.
U.S. Environmental Protection Agency, Office of Research and Development,
National Health and Environmental Effects Research Laboratory,
Neurotoxicology Division, MD:B105-05,
Research Triangle Park, NC 27711, USA. hundell.ken@...

Blooms of toxigenic organisms have increased in spatial and temporal extent due
to human activities and natural forces that alter ecologic habitats and pollute
the environment.

In aquatic environments, harmful algal blooms pose a risk for human health, the
viability of organisms, and the sustainability of ecosystems.

The estuarine dinoflagellate, Pfiesteria piscicida, was discovered in the late
1980s at North Carolina State University as a contaminant in fish cultures.

P. piscicida was associated with fish death in laboratory aquaria, and illness
among laboratory workers who inhaled the mist above aquaria.

Both the fish and humans exhibited signs of toxicity.

During the 1990s, large-scale mortality among fish and other aquatic organisms
was associated with high concentrations of Pfiesteria sp. in estuaries on the
eastern seaboard of North America from New York to Texas.

Illness among humans was associated with direct exposure to estuaries and
exposures to estuarine aerosols around the time of Pfiesteria-related fish
kills.

This review of the scientific literature on associations between Pfiesteria and
human illness identified some of the possible mechanisms of action by which
putative Pfiesteria toxins may have caused morbidity.

Particular attention was given to the Pfiesteria-associated, human-illness
syndrome known as Possible Estuary Associated Syndrome (PEAS).

PEAS was characterized by multiple-system symptoms, deficits in
neuropsychological tests of cognitive function, and rapid and severe decrements
in visual contrast sensitivity (VCS),
an indicator of neurologic function in the visual system.

PEAS was diagnosed in acute and chronic illness cases, and was reacquired during
re-exposure.

Rapid normalization of PEAS signs and symptoms was achieved through the use of
cholestyramine therapy.

Cholestyramine, a non-absorbable polymer, has been used by humans to lower
cholesterol levels since it was approved for that use by the U.S. Food and Drug
Administration in 1958.

When dissolved in water or juice and taken orally, cholestyramine binds with
cholesterol, bile acids, and salts in the intestines,
causing them to be eliminated rather than reabsorbed with bile during
enterohepatic recirculation.

Cholestyramine also has been reported to bind and eliminate a variety of toxic
substances.

The efficacy of cholestyramine therapy in treatment of PEAS supported the
hypothesis that PEAS is a biotoxin-associated illness.
PMID: 16102938


Toxicology. 1996 Aug 16; 112(2): 131-40.
Methanol potentiation of carbon tetrachloride hepatotoxicity: the central role
of cytochrome P450.
Allis JW,
Brown BL,
Simmons JE,
Hatch GE,
McDonald A,
House DE.
National Health and Environmental Effects Research Laboratory, US Environmental
Protection Agency, Research Triangle Park, NC 27711, USA.

Evidence to explain the enhanced hepatotoxicity of carbon tetrachloride (CCl4)
following methanol exposure by inhalation is presented.

Hepatic microsomes prepared from male F344 rats exposed to methanol at
concentrations up to 10,000 ppm showed increased p-nitrophenol hydroxylase
activity but no increase in pentoxyresorufin-O-dealkylase or
ethoxyresorufin-O-deethylase activities.

Hepatic antioxidant levels, glutathione levels and glutathione-S-transferase
activity in methanol-treated animals were not different from controls.

In vitro metabolism of CCl4 was also increased in microsomes from
methanol-treated animals.

Pretreatment with allyl sulfone, a specific chemical inhibitor of cytochrome
P450 2E1,
abolished the difference in microsomal metabolism between exposed and control
animals.

This study shows that methanol exposure induces cytochrome P450 2E1, which
appears to be the principal toxicokinetic mechanism responsible for the
increased metabolism and thus the increased hepatotoxicity of CCl4. PMID:
8814342


http://groups.yahoo.com/group/aspartameNM/message/1366
toxicity in rat brains from aspartame, Vences-Mejia A, Espinosa-Aguirre
JJ et al 2006 Aug: Murray 2006.09.06

http://groups.yahoo.com/group/aspartameNM/message/1373
aspartame rat brain toxicity re cytochrome P450 enzymes, expecially
CYP2E1, Vences-Mejia A, Espinosa-Aguirre JJ et al, 2006 Aug,
Hum Exp Toxicol: relevant abstracts re formaldehyde from methanol
in alcohol drinks: Murray 2006.09.29
*******************************************************


http://groups.yahoo.com/group/aspartameNM/message/1379
short aspartame (methanol, formaldehyde) toxicity research summary:
Murray 2007.01.09

"Of course, everyone chooses, as a natural priority,
to actively find, quickly share, and positively act upon the facts
about healthy and safe food, drink, and environment."

Rich Murray, MA Room For All rmforall@...
505-501-2298 1943 Otowi Road Santa Fe, New Mexico 87505

http://groups.yahoo.com/group/aspartameNM/messages
group with 76 members, 1,397 posts in a public, searchable archive
http://RMForAll.blogspot.com

http://groups.yahoo.com/group/aspartameNM/message/1340
aspartame groups and books: updated research review of 2004.07.16:
Murray 2006.05.11


Aspartame Controversy, in Wikipedia democratic encyclopedia, 72
references (including AspartameNM # 864 and 1173 by Murray), brief
fair summary of much more research: Murray 2007.01.01
http://groups.yahoo.com/group/aspartameNM/message/1395


Coca-Cola carcinogenicity in rats, Ramazzini Foundation, F Belpoggi, M
Soffritti, Annals NY Academy Sciences 2006 Sept, parts of 17 pages:
Murray 2006.12.02
http://groups.yahoo.com/group/aspartameNM/message/1385

Fiorella Belpoggi & Morando Soffritti of Ramazzini Foundation prove
lifetime carcinogenicity of Coca-Cola, aspartame, and arsenic, Annals
of the NY Academy of Sciences: Murray 2006.11.28
http://groups.yahoo.com/group/aspartameNM/message/1382

http://groups.yahoo.com/group/aspartameNM/message/1383 aspartame

http://groups.yahoo.com/group/aspartameNM/message/1384 arsenic


soft drinks and adolescent hyperactivity, mental distress, conduct
problems, Lars Lien, Nanna Lien, Sonja Heyerdahl, Mayne Thoresen, Espen
Bjertness 2006 Oct., A J Pub Health: Murray 2006.10.21
http://groups.yahoo.com/group/aspartameNM/message/1376

http://groups.yahoo.com/group/aspartameNM/message/1375
healthy diet, vitamins, and fish oil help reduce depression and
violence, studies by Joseph Hibbeln, Bernard Gesch, and Stephen
Schoenthaler, articles by Felicity Lawrence in UK Guardian Unlimited
and Pat Thomas in The Ecologist: Murray 2006.10.21


http://groups.yahoo.com/group/aspartameNM/message/1378
11 members of New Mexico legislature sign letter to ban aspartame as a
source of toxic methanol and formaldehyde, Stephen Fox, NM Senator
Gerald Ortiz y Pino: Murray 2006.10.22

http://groups.yahoo.com/group/aspartameNM/message/1374
47 UK Members of Parliament now support aspartame ban initiative of
Roger Williams, MP: Murray 2006.10.16


http://groups.yahoo.com/group/aspartameNM/message/1271
combining aspartame and quinoline yellow, or MSG and brilliant blue,
harms nerve cells, eminent C. Vyvyan Howard et al, 2005
education.guardian.co.uk, Felicity Lawrence: Murray 2005.12.21

http://groups.yahoo.com/group/aspartameNM/message/1277
50% UK baby food is now organic -- aspartame or MSG
with food dyes harm nerve cells, CV Howard 3 year study
funded by Lizzy Vann, CEO, Organix Brands,
Children's Food Advisory Service: Murray 2006.01.13

http://groups.yahoo.com/group/aspartameNM/message/1279
all three aspartame metabolites harm human erythrocyte [red blood cell]
membrane enzyme activity, KH Schulpis et al, two studies in 2005,
Athens, Greece, 2005.12.14: 2004 research review, RL Blaylock:
Murray 2006.01.14

http://groups.yahoo.com/group/aspartameNM/message/1369
Bristol, Connecticut, schools join state program to limit artificial
sweeteners, sugar, fats for 8800 students, Johnny J Burnham, The
Bristol Press: Murray 2006.09.22

http://groups.yahoo.com/group/aspartameNM/message/1341
Connecticut bans artificial sweeteners in schools, Nancy Barnes,
New Milford Times: Murray 2006.05.25

http://groups.yahoo.com/group/aspartameNM/message/1353
carcinogenic effect of inhaled formaldehyde, Federal Institute of Risk
Assessment, Germany -- same safe level as for Canada:
Murray 2006.06.02

http://groups.yahoo.com/group/aspartameNM/message/1352
Home sickness -- indoor air often worse, as our homes seal in
pollutants
[one is formaldehyde, also from the 11% methanol part of aspartame],
Megan Gillis, WinnipegSun.com: Murray 2006.06.01


http://groups.yahoo.com/group/aspartameNM/message/1349
NIH NLM ToxNet HSDB Hazardous Substances Data Bank
inadequate re aspartame (methanol, formaldehyde, formic acid):
Murray 2006.08.19

http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~HwoSfJ:1
HSDB Hazardous Substances Data Bank: Aspartame

ASPARTAME CASRN: 22839-47-0
METHANOL CASRN: 67-56-1
FORMALDEHYDE CASRN: 50-00-0
FORMIC ACID CASRN: 64-18-6


http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L
( becomes formaldehyde in body ): EU Scientific Committee on Foods
2001.07.12: Murray 2004.01.22


http://www.HolisticMed.com/aspartame mgold@...
Aspartame Toxicity Information Center Mark D. Gold
12 East Side Drive #2-18 Concord, NH 03301 603-225-2100

http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 2003.01.12 rmforall EU Scientific Committee on Food,
a whitewash

http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame ( 2002.12.04 ):
59 pages, 230 references

http://groups.yahoo.com/group/aspartameNM/message/1371
Russell L. Blaylock, MD discusses MSG, aspartame, excitotoxins
with Mike Adams: Murray 2006.09.27

http://groups.yahoo.com/group/aspartameNM/message/1372
Mike Adams interviews Randall Fitzgerald on "The Hundred Year Lie:
How Food and Medicine are Destroying Your Health" 2006.06.21:
Murray 2006.09.28
*******************************************************


http://groups.yahoo.com/group/aspartameNM/message/782
RTM: Smith, Terpening, Schmidt, Gums:
full text: aspartame, MSG, fibromyalgia 2002.01.17
Jerry D Smith, Chris M Terpening,
Siegfried OF Schmidt, and John G Gums
Relief of Fibromyalgia Symptoms Following
Discontinuation of Dietary Excitotoxins.
The Annals of Pharmacotherapy 2001; 35(6): 702-706.
Malcolm Randall Veterans Affairs Medical Center,
Gainesville, FL, USA.
BACKGROUND: Fibromyalgia is a common rheumatologic
disorder that is often difficult to treat effectively.
CASE SUMMARY: Four patients diagnosed with fibromyalgia
syndrome for two to 17 years are described.
All had undergone multiple treatment modalities with limited success.
All had complete, or nearly complete,
resolution of their symptoms within months after eliminating
monosodium glutamate (MSG) or MSG plus aspartame from their diet.
All patients were women with multiple comorbidities
prior to elimination of MSG.
All have had recurrence of symptoms whenever MSG is ingested.

Siegfried O. Schmidt, MD Asst. Clinical Prof. siggy@...
Community Health and Family Medicine, U. Florida, Gainesville, FL
Shands Hospital West Oak Clinic Gainesville, FL 32608-3629
352-376-5071
*******************************************************