Re: Brain MRI scan under general anaesthetic - tomorrow

[Guest guest]

Please no propophol....let me get home to send u some info on the no nos doe ASD

kids

Isa

Enviado desde mi oficina móvil BlackBerry® de Telcel

[ ] Brain MRI scan under general anaesthetic - tomorrow

We have this tomorrow (our daughter cannot speak more than a few syllables and

has very serious problem here):

General Anaesthetic choice between:

Gas: nitrous oxide + sebofluoride (organic flouride)

IV: propofol

Dye: unlikely to use, but could use organic cyclic gadallium

Agenda: No food or drink most of night. Go to hospital ward bed

8.30 am. Questions. Anaesthetic where Sophie will sleep completely. 30-60

minute scan. Wake up. Go home

Comments please regarding safety.

(NB: we are looking to measure: brain inflammation levels, any tumour, any

lesions, de-myelination of nerves, possibly toxic metals)

[Guest guest]

Please can ou send it to me asap as we are having scan tomorrow and my little 5

year old girl needs me to make the right decision on this

>

> From: isaguzmandiaz2@...

> Date: Tue, 7 Sep 2010 06:04:26 +0000

> Subject: Re: [ ] Brain MRI scan under general anaesthetic -

tomorrow

>

> Please no propophol....let me get home to send u some info on the no nos doe

ASD kids

>

> Isa

>

>

>

> Enviado desde mi oficina móvil BlackBerry® de Telcel

>

>

>

> [ ] Brain MRI scan under general anaesthetic - tomorrow

>

>

>

> We have this tomorrow (our daughter cannot speak more than a few syllables and

has very serious problem here):

>

>

>

> General Anaesthetic choice between:

>

>

>

> Gas: nitrous oxide + sebofluoride (organic flouride)

>

> IV: propofol

>

>

>

> Dye: unlikely to use, but could use organic cyclic gadallium

>

>

>

> Agenda: No food or drink most of night. Go to hospital ward bed

>

> 8.30 am. Questions. Anaesthetic where Sophie will sleep completely. 30-60

minute scan. Wake up. Go home

>

>

>

> Comments please regarding safety.

>

>

>

> (NB: we are looking to measure: brain inflammation levels, any tumour, any

lesions, de-myelination of nerves, possibly toxic metals)

>

>

>

>

>

>

>

>

>

>

[Guest guest]

hi peter we had an mri scan it did not help us much 3 years ago, except to say

all his brain was functioning properly but no follow on what to do next ! That

's the NDS service for you!!! Isobel

>

> We have this tomorrow (our daughter cannot speak more than a few syllables and

has very serious problem here):

>

> General Anaesthetic choice between:

>

> Gas: nitrous oxide + sebofluoride (organic flouride)

> IV: propofol

>

> Dye: unlikely to use, but could use organic cyclic gadallium

>

> Agenda: No food or drink most of night. Go to hospital ward bed

> 8.30 am. Questions. Anaesthetic where Sophie will sleep completely. 30-60

minute scan. Wake up. Go home

>

> Comments please regarding safety.

>

> (NB: we are looking to measure: brain inflammation levels, any tumour, any

lesions, de-myelination of nerves, possibly toxic metals)

>

[Guest guest]

Hi Isobel

If the MRI scan shows nothing, then you dont have to worry about things like

inflammation, de-myelination, lesions which would be picked up

So thats a great result in my opinion

Thanks

From: isobelwiza@...

Date: Tue, 7 Sep 2010 13:37:19 +0000

Subject: [ ] Re: Brain MRI scan under general anaesthetic -

tomorrow

hi peter we had an mri scan it did not help us much 3 years ago, except to say

all his brain was functioning properly but no follow on what to do next ! That

's the NDS service for you!!! Isobel

>

> We have this tomorrow (our daughter cannot speak more than a few syllables and

has very serious problem here):

>

> General Anaesthetic choice between:

>

> Gas: nitrous oxide + sebofluoride (organic flouride)

> IV: propofol

>

> Dye: unlikely to use, but could use organic cyclic gadallium

>

> Agenda: No food or drink most of night. Go to hospital ward bed

> 8.30 am. Questions. Anaesthetic where Sophie will sleep completely. 30-60

minute scan. Wake up. Go home

>

> Comments please regarding safety.

>

> (NB: we are looking to measure: brain inflammation levels, any tumour, any

lesions, de-myelination of nerves, possibly toxic metals)

>

[Guest guest]

Nitrous oxide is a big no no with our asd kids.  Can you ask for an

alternative?  NO will increase oxidative stress and do damage.  They must have

an alternative that they can offer to families with kids on the spectrum.

nancy j

a child is diagnosed with

asd every 20 seconds

From: peter <peter_2_@...>

Subject: [ ] Brain MRI scan under general anaesthetic - tomorrow

Date: Tuesday, September 7, 2010, 3:50 AM

 

We have this tomorrow (our daughter cannot speak more than a few syllables

and has very serious problem here):

General Anaesthetic choice between:

Gas: nitrous oxide + sebofluoride (organic flouride)

IV: propofol

Dye: unlikely to use, but could use organic cyclic gadallium

Agenda: No food or drink most of night. Go to hospital ward bed

8.30 am. Questions. Anaesthetic where Sophie will sleep completely. 30-60

minute scan. Wake up. Go home

Comments please regarding safety.

(NB: we are looking to measure: brain inflammation levels, any tumour, any

lesions, de-myelination of nerves, possibly toxic metals)

[Guest guest]

sorry , l wasn`t  right, it is Nitrous Oxide which causes irreversible

oxidation damage in the brains of ASD kids.  here is the info:

lsa

Re: regression after nitrous oxide

The next PDF came from www.nomercury.org

IMMEDIATE COMMUNICATION

Activation of methionine synthase by insulin-like growth

factor-1 and dopamine: a target for neurodevelopmental

toxins and thimerosal

M Waly1, H Olteanu2, R Banerjee2, S-W Choi3, JB Mason3, BS 4, S

Sukumar4, S Shim1,

A Sharma1, JM Benzecry1, V-A Power-Charnitsky1 and RC Deth1

1Department of Pharmaceutical Sciences, Northeastern University,

Boston, MA 02115, USA;2Biochemistry Department,

University of Nebraska, Lincoln, NE 68588, USA; 3Vitamin Metabolism

Laboratory, USDA Human Nutrition Research Center

on Aging at Tufts University, Boston, MA 02111, USA; 4Sidney Kimmel

Comprehensive Cancer Center at s Hopkins,

Baltimore, MD 21231, USA

the following PDF came from

http://content.nejm.org/

Volume 349:45-50 July 3, 2003 Number 1Next

Adverse Effect of Nitrous Oxide in a Child with

5,10-Methylenetetrahydrofolate Reductase Deficiency

R. Selzer, Ph.D., S. Rosenblatt, M.D., Renata Laxova,

M.D., and Kirk Hogan, M.D., J.D.

Find Similar Articles

PubMed CitationNitrous oxide irreversibly oxidizes the cobalt atom of

vitamin B12, thereby inhibiting the activity of the

cobalamin-dependent enzyme methionine synthase (or

5-methyltetrahydrofolate–homocysteine S-methyltransferase; Enzyme

Commission code EC 2.1.1.13). Methionine synthase catalyzes the

remethylation of 5-methyltetrahydrofolate and homocysteine to

tetrahydrofolate and methionine (Figure 1). Methionine, by way of its

activated form, S-adenosylmethionine, is the principal substrate for

methylation in many biochemical reactions, including assembly of the

myelin sheath, methyl substitutions in neurotransmitters, and DNA

synthesis in rapidly proliferating tissues.1

View larger version (13K):

[in this window]

[in a new window]

Figure 1. The Folate and Homocysteine Metabolic Cycles and the

Enzymatic Site of Nitrous Oxide Toxicity.

Co denotes cobalt.

We report the neurologic deterioration and death of a child

anesthetized twice with nitrous oxide before the diagnosis of

5,10-methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20)

deficiency (Online Mendelian Inheritance in Man number 236250) was

established.2 MTHFR catalyzes the synthesis of

5-methyltetrahydrofolate. Sequence analysis of RNA transcripts and

genomic DNA from the patient and his family members, together with

direct assays of MTHFR activity in fibroblasts, revealed that the

enzyme deficiency was caused by a novel MTHFR mutation (1755GA), which

changes the conserved methionine at position 581 of the enzyme to

isoleucine; this mutation is coinherited with two other, common MTHFR

polymorphisms (677CT and 1298AC), each of which is associated with

depressed enzyme function.3,4 We propose that a nitrous oxide–induced

defect of methionine synthase superimposed on an inherited defect of

MTHFR caused the patient's death.

Case Report

Details of the patient's clinical course and biochemical and

pathological findings were reported by Beckman et al. in 1987.2 In

brief, the child appeared normal until three months of age, when a

mass in the left leg was noted. It was not known before the patient's

surgery that his father and one of his uncles had serum levels of

total homocysteine above 20.0 µmol per liter and above 30.0 µmol per

liter, respectively (normal range, 5.4 to 13.9). The proband's

sibling, who was receiving lifelong therapy with high-dose vitamin B

supplements, had a homocysteine level of 4.3 µmol per liter. Neither

the father nor the sibling had received nitrous oxide. On preoperative

assessment for excisional biopsy of the mass, the patient's physical

status was deemed class I according to the American Society of

Anesthesiologists criteria (class I denotes good health and class V

critical illness). After premedication with atropine and induction of

anesthesia with sodium thiopental and succinylcholine, the child's

trachea was intubated; anesthesia was maintained with 0.75 percent

halothane and 60 percent nitrous oxide in oxygen for 45 minutes.

The surgical biopsy revealed an infantile fibrosarcoma, and resection

of the mass was performed on the fourth day after the biopsy. After

induction of anesthesia with halothane, the child was anesthetized for

270 minutes with 0.75 percent halothane and 60 percent nitrous oxide.

At the conclusion of the operation, his trachea was extubated, and he

was transferred while awake to the intensive care unit. He was

discharged on the seventh postoperative day in apparently good health.

Seventeen days later (25 days after the resection), the patient was

admitted because of seizures and episodes of apnea. On examination,

the infant was severely hypotonic, without reflexes and with ataxic

ventilation. Cranial computed tomography showed generalized atrophy of

the brain, with enlarged prepontine and medullary cisterns. The urine

was positive for homocystine (1.30 µmol per milligram of creatinine

[normal value, 0]) but negative for organic acids and methylmalonic

acid. The plasma homocystine level was elevated, at 0.6 mg per

deciliter (normal value, <0.01), and the methionine level was low, at

0.06 mg per deciliter (normal mean [±SD] value, 0.48±0.18); the

vitamin B12 level was normal, at 403 pg per milliliter (297 pmol per

liter) (normal range, 150 to 800 pg per milliliter [111 to 590 pmol

per liter]). The serum folate level, measured by radioimmunoassay, was

3.8 ng per milliliter (8.5 nmol per liter) (normal range, 2.5 to 15.0

ng per milliliter [5.6 to 33.4 nmol per liter]), and the level of

folate in the cerebrospinal fluid was 26.0 ng per milliliter (57.9

nmol per liter) (normal range, 10.6 to 85.0 ng per milliliter [23.6 to

189.2 nmol per liter]).

The patient died at 130 days of age (46 days after the resection)

after a respiratory arrest. An autopsy showed asymmetric cerebral

atrophy and severe demyelination, with astrogliosis and

oligodendroglial-c ell depletion in the midbrain, medulla, and

cerebellum. The values for MTHFR activity in cultured fibroblasts

reported post mortem were 1.22 and 0.8 nmol of formaldehyde produced

per milligram of protein per hour (normal mean value, 5.04±1.36) with

and without flavinadenine dinucleotide, respectively. The simultaneous

control values were 6.4 and 5.4 nmol of formaldehyde produced per hour

per milligram of protein with and without flavinadenine dinucleotide,

respectively.5

Methods

The investigations were carried out with approval of the University of

Wisconsin's institutional review board. Written informed consent was

obtained from all the participants.

Fibroblast Culture and MTHFR Activity

Fibroblasts were cultured from skin-punch biopsy specimens obtained

from both parents and from the patient's stored samples. MTHFR

activity was measured at confluence, as previously described.6 All the

assays were performed in duplicate, with simultaneous assay of a

normal control.

Preparation and Sequence Analysis of Genomic DNA

Genomic DNA was isolated from the cultured fibroblasts from the

patient and both parents and from either blood or buccal cells from

other relatives. Each of the 11 MTHFR exons was amplified from genomic

DNA by the polymerase chain reaction (PCR) with the use of newly

designed intronic primers.7,8 (The sequences of the primers are listed

in Supplementary Appendix 1 with the full text of this article at

http://www.nejm.org.) The patient's and both parents' PCR products

were bidirectionally sequenced. A novel mutation in the patient's DNA

at nucleotide 1755 (exon 10) and two previously described frequent

polymorphisms at positions 677 (exon 4) and 1298 (exon 7) in the MTHFR

gene were analyzed in the genomic DNA from the parents and other

relatives with the use of the restriction enzymes NlaIII, HinfI, and

MboII, as previously described.3,4 Family members were also screened

as previously described for common polymorphisms in the genes encoding

enzymes that regulate folate and homocysteine metabolism; these

polymorphisms have been implicated in the pathogenesis of neural-tube

defects, other congenital anomalies, and cardiovascular and neoplastic

disease.9 The polymorphisms include those that encode methionine

synthase (MTR; the polymorphism results in the substitution of glycine

for aspartic acid at residue 919),10 methionine synthase reductase

(MTRR; the polymorphism results in the substitution of methionine for

isoleucine at residue 22),11 and cystathionine -synthase (CBS; the

polymorphism is a 68-bp duplication).12

RNA Analysis

To evaluate the expression of an intact copy of the predominant 7.2-kb

MTHFR isoform,13 RNA was isolated from the patient's cultured

fibroblasts. A 2206-bp product containing the entire coding region was

amplified by PCR from the complementary DNA (cDNA) transcript and

sequenced in full. The 7.2-kb cDNA product was amplified as seven

overlapping fragments ranging from 1.0 to 2.2 kb in size, as verified

by gel electrophoresis. (The primers used to sequence the cDNA

transcript and to amplify the cDNA as overlapping fragments are listed

in Supplementary Appendixes 2 and 3, respectively, with the full text

of this article at http://www.nejm.org.) Bands corresponding to the

expected fragment sizes were excised, and the first 300 bases of the

5' and 3' ends were sequenced to allow positive identification of each

fragment. Fragments from the patient and an unrelated control were

then compared.

Results

Enzyme Activity in Fibroblasts

The patient's MTHFR activity in two replicates was 0.76 and 0.03 nmol

of formaldehyde per milligram of protein per hour (normal mean value,

13.3±4.6 with the use of the current method of measurement6), with a

simultaneous normal control of 11.52 nmol of formaldehyde per

milligram of protein per hour. MTHFR activity in the father and mother

(1.8 and 6.1 nmol of formaldehyde per milligram of protein per hour,

respectively) was reduced, with a control level of 9.5 nmol of

formaldehyde per milligram of protein per hour.

Genomic DNA-Sequence Analysis

The patient was found to be heterozygous for a novel mutation, 1755GA

in exon 10, which causes a substitution of isoleucine for methionine

at residue 581 (M581I)14 (GenBank accession number, NM_005957).

Restriction-enzyme analysis confirmed the presence of the 1755GA

mutation in the heterozygous patient, his father, his brother, one

uncle, and one aunt, but not in 100 control chromosomes. The patient

was also heterozygous for a 677CT mutation in exon 4 (resulting in a

substitution of valine for alanine at residue 222) and a 1298AC

mutation in exon 7 (resulting in a substitution of alanine for

glutamic acid at residue 429). In addition to being heterozygous for

1755GA, the father was homozygous (TT) for the 677CT mutation and

homozygous (AA) at 1298A (Figure 2). The mother was heterozygous for

both common polymorphisms and homozygous (wild type) at 1755G. The

sibling's haplotype was identical to that of the patient in all coding

regions. The novel mutation at 1755GA was therefore transmitted to the

patient from a paternal chromosome, in cis configuration with the

677CT mutation. Two of the father's four siblings had haplotypes

identical to the father's haplotype and were heterozygous for the

1755GA mutation and homozygous for the 677CT mutation (Table 1).

View larger version (6K):

[in this window]

[in a new window]

Figure 2. Nucleotide Changes in the MTHFR Gene in the Patient and

His Parents.

In addition to the coding changes, the patient (the proband) and his

mother were heterozygous for a substitution of adenine for cysteine at

position 2355, which is 375 bases (in the 3' direction) from the stop

codon, on the same chromosome as the 1298C polymorphism. This

substitution is in a region of unknown importance. Asterisks denote

DNA-sequence variants. The open bars represent the MTHFR gene, and the

black bars the remainder of each chromosome in the pair.

View this table:

[in this window]

[in a new window]

Table 1. Polymorphisms in the Patient and Members of His Family.

We sequenced 25 to 40 bases beyond all intronic boundaries to look for

altered splice junctions. There were no substitutions in the 5' and 3'

untranslated regions flanking the MTHFR gene, within or proximate to a

putative binding site for a transcription factor or an actual start

site mapped by Gaughan et al.13 and Homberger et al.15 The DNA

sequence approximately 550 bp in the 3' direction from the MTHFR stop

codon and a 400-bp segment encompassing the distal 3'-polyadenylation

site contained several polymorphisms, but none at sites with

recognized functional significance.

We also performed genomic analysis of the genes encoding methionine

synthase, methionine synthase reductase, and cystathionine -synthase.

Genotypes at these loci for all members of the pedigree are provided

in Table 1.

RNA Analysis

No size differences were observed among the seven MTHFR cDNA

fragments, indicating that the patient's fibroblasts expressed an

intact MTHFR transcript. The 2.2-kb product contained the entire

coding region of the transcript and was used to sequence a region

beginning 50 bp in the 5' direction from the translational start site

and ending 150 bp downstream of the stop codon. This product was of

the expected length, and no alternate splicing variants were detected.

The entire product was sequenced and compared with the published

sequence14 (GenBank accession number, NM_005957). The presence of the

heterozygous common polymorphisms 677CT and 1298AC, as well as the

heterozygote substitution 1775GA, was confirmed.

Discussion

The inactivation of methionine synthase by nitrous oxide has been

demonstrated with purified enzyme,16 in cultured cells,17,18 in animal

models,19 and in humans.20,21,22 The mean half-time of inactivation is

46 minutes. Residual methionine synthase activity more than 200

minutes after the start of nitrous oxide administration approaches

zero.21 Mice, pigs, and rats exposed to nitrous oxide have delayed

recovery of enzyme activity for periods of four days or

more.19,23,24,25 Recovery in cultured cells indicates that nitrous

oxide–mediated inhibition is irreversible, with de novo synthesis of

the enzyme required to restore activity.26

The untoward consequences of nitrous oxide anesthesia in our patient

are reminiscent of two recent case reports. In the first, an

eight-month-old child had acute neurologic deterioration six days

after an 80-minute period of anesthesia with nitrous oxide.27 In the

second, a four-month-old child was admitted because of hypotonia,

dehydration, and acidosis three weeks after surgery that had involved

a 180-minute period of anesthesia with nitrous oxide.28 Both children

were found to have severe dietary cobalamin deficiency. These

instances of methionine synthase inhibition have a time course and

clinical features similar to those observed in our patient but were

nonlethal, perhaps because they were elicited after only a single

exposure to nitrous oxide. Moreover, our patient had an inborn error

of metabolism in an essential precursor in a metabolic pathway, rather

than an acquired deficiency, and nitrous oxide was delivered on two

occasions only a few days apart.

Severe MTHFR deficiency is an autosomal recessive disorder

characterized by progressive hypotonia, convulsions, and psychomotor

retardation. The clinical presentation may be subtle, with the

disorder manifested as developmental disability in the setting of

moderate homocystinuria and hyperhomocysteinemia and low-to-normal

levels of plasma methionine.29 Twenty-nine mutations in MTHFR are

associated with severe deficiency, with a resulting activity level

that is usually 0 to 30 percent of control activity.7,8,14,30,31,32,33

Most patients are heterozygous for multiple MTHFR substitutions; a

small minority are homozygous for mutations at this locus. The 1755GA

substitution identified in our patient occurs in a phylogenetically

conserved region of the MTHFR protein (as assessed with BLASTP

software, version 2.2.1). This region, which is thought to be

essential for functional protein folding,34 is a " hot spot " for

mutations leading to MTHFR deficiency (1711CT, 1727CT, 1762AT, and

1768GA).7,8 The heterozygous presence of the 1755GA substitution in

the patient's father, brother, one uncle, and one aunt and its absence

in 100 independent control chromosomes suggest that it is not a benign

variant.

Compound heterozygosity for the common MTHFR alleles 677CT and 1298AC,

as seen in the patient, his mother, and his brother, causes elevations

in the plasma homocysteine level4 that are associated with a 50 to 60

percent decrement in enzyme activity.35 In the absence of coding

mutations elsewhere in the MTHFR gene or evidence of a mutant splice

variant, our patient's deficient enzyme activity may be attributable

to compound heterozygosity for the novel 1755GA mutation, with the

prevalent 677CT polymorphism on the same (paternal) chromosome and the

1298AC mutation on the maternal chromosome. It has recently been shown

that when mutations causing severe MTHFR deficiency are expressed in

cis configuration with the common 677CT variant, the resultant

phenotype is markedly aggravated.34

Every year, approximately 45 million persons in North America undergo

anesthesia, and nitrous oxide constitutes a major component in about

half these procedures.36 Because of the growing use of nitrous

oxide,37,38,39,40,41 patients with known mutations associated with

mild or severe abnormalities in folate-cycle enzymes are increasingly

likely to receive nitrous oxide. On the strength of the current

findings, we believe that patients with a diagnosis of severe MTHFR

deficiency should not receive nitrous oxide as anesthesia. In the case

of emergency procedures, patients whose clinical presentation fits

that of severe MTHFR deficiency, even if the disorder has not been

diagnosed, should also not receive nitrous oxide. In the case of

elective procedures, patients whose clinical presentation fits that of

severe MTHFR deficiency should be evaluated, and the diagnosis should

be ruled out before anesthesia with nitrous oxide is contemplated.

Supported by grants from the Doris Duke Foundation and the University

of Wisconsin Department of Anesthesiology Research and Development

Fund (to Dr. Hogan) and the Canadian Institutes of Health Research (to

Dr. Rosenblatt).

We are indebted to Singh Sekhon, Ph.D. (University of Wisconsin,

Madison), for the fibroblast cultures and to H. , M.D.

(Metabolite Laboratories, Denver), for the assays of total homocysteine.

Source Information

From the Departments of Anesthesiology (R.R.S., K.H.) and Medical

Genetics (R.L.), University of Wisconsin Medical School, Madison; and

the Departments of Human Genetics, Medicine, Pediatrics, and Biology,

McGill University, Montreal (D.S.R.).

Address reprint requests to Dr. Hogan at the Department of

Anesthesiology, B6/319 Clinical Sciences Center, 600 Highland Ave.,

Madison, WI 53792, or at khogan@....

References

1. Chiang PK, Gordon RK, Tal J, et al. S-adenosylmethionine and

methylation. FASEB J 1996;10:471-480.[Abstract/Full Text]

2. Beckman DR, Hoganson G, Berlow S, Gilbert EF. Pathological findings

in 5,10-methylene tetrahydrofolate reductase deficiency. Birth Defects

Orig Artic Ser 1987;23:47-64.[Medline]

3. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor

for vascular disease: a common mutation in methylenetetrahydrofolate

reductase. Nat Genet 1995;10:111-113.[iSI][Medline]

4. van der Put NM, Gabreels F, s EM, et al. A second common

mutation in the methylenetetrahydrofolate reductase gene: an

additional risk factor for neural-tube defects? Am J Hum Genet

1998;62:1044-1051.[CrossRef][iSI][Medline]

5. Kanwar YS, Manaligod JR, Wong PW. Morphologic studies in a patient

with homocystinuria due to 5,10-methylenetetrahydrofolate reductase

deficiency. Pediatr Res 1976;10:598-609.[Abstract]

6. Rosenblatt DS, Erbe RW. Methylenetetrahydrofolate reductase in

cultured human cells. I. Growth and metabolic studies. Pediatr Res

1977;11:1137-1141.[iSI][Medline]

7. Sibani S, Christensen B, O'Ferrall E, et al. Characterization of

six novel mutations in the methylenetetrahydrofolate reductase (MTHFR)

gene in patients with homocystinuria. Hum Mutat

2000;15:280-287.[CrossRef][iSI][Medline]

8. Kluijtmans LA, Wendel U, s EM, van den Heuvel LP, Trijbels

FJ, Blom HJ. Identification of four novel mutations in severe

methylenetetrahydrofolate reductase deficiency. Eur J Hum Genet

1998;6:257-265.[CrossRef][iSI][Medline]

9. Schwahn B, Rozen R. Polymorphisms in the methylenetetrahydrofolate

reductase gene: clinical consequences. Am J Pharmacogenomics

2001;1:189-201.

10. Harmon DL, Shields DC, Woodside JV, et al. Methionine synthase

D919G polymorphism is a significant but modest determinant of

circulating homocysteine concentrations. Genet Epidemiol

1999;17:298-309.[CrossRef][iSI][Medline]

11. A, Platt R, Wu Q, et al. A common variant in methionine

synthase reductase combined with low cobalamin (vitamin B12) increases

risk for spina bifida. Mol Genet Metab

1999;67:317-323.[CrossRef][iSI][Medline]

12. Tsai MY, Bignell M, Schwichtenberg K, Hanson NQ. High prevalence

of a mutation in the cystathionine beta-synthase gene. Am J Hum Genet

1996;59:1262-1267.[iSI][Medline]

13. Gaughan DJ, Barbaux S, Kluijtmans LA, Whitehead AS. The human and

mouse methylenetetrahydrofolate reductase (MTHFR) genes: genomic

organization, mRNA structure and linkage to the CLCN6 gene. Gene

2000;257:279-289.[CrossRef][iSI][Medline]

14. Goyette P, Sumner JS, Milos R, et al. Human

methylenetetrahydrofolate reductase: isolation of cDNA mapping and

mutation identification. Nat Genet 1994;7:551-551.

15. Homberger A, Linnebank M, Winter C, et al. Genomic structure and

transcript variants of the human methylenetetrahydrofolate reductase

gene. Eur J Hum Genet 2000;8:725-729.[CrossRef][iSI][Medline]

16. Frasca V, Riazzi BS, s RG. In vitro inactivation of

methionine synthase by nitrous oxide. J Biol Chem

1986;261:15823-15826.[Abstract/Full Text]

17. Christensen B, Rosenblatt DS, Chu RC, Ueland PM. Effect of

methionine and nitrous oxide on homocysteine export and remethylation

in fibroblasts from cystathionine synthase-deficient, cblG, and cblE

patients. Pediatr Res 1994;35:3-9.[Abstract]

18. Fiskerstrand T, Ueland PM, Refsum H. Folate depletion induced by

methotrexate affects methionine synthase activity and its

susceptibility to inactivation by nitrous oxide. J Pharmacol Exp Ther

1997;282:1305-1311.[Abstract/Full Text]

19. Kondo H, Osborne ML, Kolhouse JF, et al. Nitrous oxide has

multiple deleterious effects on cobalamin metabolism and causes

decreases in activities of both mammalian cobalamin-dependent enzymes

in rats. J Clin Invest 1981;67:1270-1283.[iSI][Medline]

20. Koblin DD, Waskell L, JE, Stokstad EL, Eger EI II. Nitrous

oxide inactivates methionine synthetase in human liver. Anesth Analg

1982;61:75-78.[Abstract]

21. Royston BD, Nunn JF, Weinbren HK, Royston D, Cormack RS. Rate of

inactivation of human and rodent hepatic methionine synthase by

nitrous oxide. Anesthesiology 1988;68:213-216.[iSI][Medline]

22. Christensen B, Guttormsen AB, Schneede J, et al. Preoperative

methionine loading enhances restoration of the cobalamin-dependent

enzyme methionine synthase after nitrous oxide anesthesia.

Anesthesiology 1994;80:1046-1056.[iSI][Medline]

23. Deacon R, Lumb M, J, et al. Inactivation of methionine

synthase by nitrous oxide. Eur J Biochem 1980;104:419-423.[Abstract]

24. Molloy AM, Orsi B, Kennedy DG, Kennedy S, Weir DG, JM. The

relationship between the activity of methionine synthase and the ratio

of S-adenosylmethionine to S-adenosylhomocysteine in the brain and

other tissues of the pig. Biochem Pharmacol

1992;44:1349-1355.[CrossRef][iSI][Medline]

25. Koblin DD, JE, Deady JE, Stokstad EL, Eger EI II.

Inactivation of methionine synthetase by nitrous oxide in mice.

Anesthesiology 1981;54:318-324.[iSI][Medline]

26. Riedel B, Fiskerstrand T, Refsum H, Ueland PM. Co-ordinate

variations in methylmalonyl-CoA mutase and methionine synthase, and

the cobalamin cofactors in human glioma cells during nitrous oxide

exposure and the subsequent recovery phase. Biochem J

1999;341:133-138.[CrossRef][iSI][Medline]

27. Felmet K, Robins B, Tilford D, Hayflick SJ. Acute neurologic

decompensation in an infant with cobalamin deficiency exposed to

nitrous oxide. J Pediatr 2000;137:427-428.[CrossRef][iSI][Medline]

28. McNeely JK, Buczulinski B, Rosner DR. Severe neurological

impairment in an infant after nitrous oxide anesthesia. Anesthesiology

2000;93:1549-1550.[iSI][Medline]

29. Rosenblatt DS, Fenton WA. Inherited disorders of folate and

cobalamin transport and metabolism. In: Scriber CR, Beaudet AL, Sly

WS, Valle D, eds. The metabolic & molecular bases of inherited

disease. 8th ed. Vol. 3. New York: McGraw-Hill, 2001:3897-933.

30. Goyette P, Christensen B, Rosenblatt DS, Rozen R. Severe and mild

mutations in cis for the methyelentetrahydrofolate reductase (MTHFR)

gene, and description of five novel mutations in MTHFR. Am J Hum Genet

1996;59:1268-1275.[iSI][Medline]

31. Goyette P, Frosst P, Rosenblatt DS, Rozen R. Seven novel mutations

in the methylenetetrahydrofolate reductase gene and genotype/phenotype

correlations in severe methylenetetrahydrofolate reductase deficiency.

Am J Hum Genet 1995;56:1052-1059.[iSI][Medline]

32. Tonetti C, Amiel J, Munnich A, Zittoun J. Impact of new mutations

in the methylenetetrahydrofolate reductase gene assessed on

biochemical phenotypes: a familial study. J Inherit Metab Dis

2001;24:833-842.[CrossRef][iSI][Medline]

33. Homberger A, Linnebank M, Sewell A, Suormala T, Fowler B, Koch HG.

Severe methylenetetrahydrofolate reductase deficiency: two novel

genotypes with different clinical course. J Inherit Metab Dis

2001;24:Suppl 1:50-50. abstract.

34. Goyette P, Rozen R. The thermolabile variant 677CT can further

reduce activity when expressed in cis with severe mutations for human

methylenetetrahydrofolate reductase. Hum Mutat

2000;16:132-138.[iSI][Medline]

35. Weisberg I, Tran P, Christensen B, Sibani S, Rozen R. A second

genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR)

associated with decreased enzyme activity. Mol Genet Metab

1998;64:169-172.[CrossRef][iSI][Medline]

36. Orkin FK, SJ. Scope of modern anesthetic practice. In:

RD, ed. Anesthesia. 5th ed. Vol. 2. Philadelphia: Churchill

Livingstone, 2000:2577-85.

37. Peretz B, Katz J, Zilburg I, Shemer J. Response to nitrous-oxide

and oxygen among dental phobic patients. Int Dent J

1998;48:17-23.[iSI][Medline]

38. Keating HJ III, Kundrat M. Patient-controlled analgesia with

nitrous oxide in cancer pain. J Pain Symptom Manage

1996;11:126-130.[CrossRef][iSI][Medline]

39. Luhmann JD, Kennedy RM, Porter FL, JP, Jaffe DM. A

randomized clinical trial of continuous-flow nitrous oxide and

midazolam for sedation of young children during laceration repair. Ann

Emerg Med 2001;37:20-27.[CrossRef][iSI][Medline]

40. Castera L, Negre I, Samii K, Buffet C. Patient-administered

nitrous oxide/oxygen inhalation provides safe and effective analgesia

for percutaneous liver biopsy: a randomized placebo-controlled trial.

Am J Gastroenterol 2001;96:1553-1557.[CrossRef][iSI][Medline]

41. Krauss B. Continuous-flow nitrous oxide: searching for the ideal

procedural anxiolytic for toddlers. Ann Emerg Med

2001;37:61-62.[CrossRef][iSI][Medline]

>

> May I also get the article, my NT son who is 2 years younger than our

> autistic son will be having a hernia operation, and I am very concerned

> about anesthesia.

>

> S.Park

>

>

>

>

>

>

________________________________

De: B <peter_2_@...>

Para: autism mercury <autism treatment >

Enviado: martes, 7 de septiembre, 2010 6:06:11

Asunto: RE: [ ] Brain MRI scan under general anaesthetic - tomorrow

 

Please can ou send it to me asap as we are having scan tomorrow and my little 5

year old girl needs me to make the right decision on this

>

> From: isaguzmandiaz2@...

> Date: Tue, 7 Sep 2010 06:04:26 +0000

> Subject: Re: [ ] Brain MRI scan under general anaesthetic -

>tomorrow

>

> Please no propophol....let me get home to send u some info on the no nos doe

>ASD kids

>

> Isa

>

>

>

> Enviado desde mi oficina móvil BlackBerry® de Telcel

>

>

>

> [ ] Brain MRI scan under general anaesthetic - tomorrow

>

>

>

> We have this tomorrow (our daughter cannot speak more than a few syllables and

>has very serious problem here):

>

>

>

> General Anaesthetic choice between:

>

>

>

> Gas: nitrous oxide + sebofluoride (organic flouride)

>

> IV: propofol

>

>

>

> Dye: unlikely to use, but could use organic cyclic gadallium

>

>

>

> Agenda: No food or drink most of night. Go to hospital ward bed

>

> 8.30 am. Questions. Anaesthetic where Sophie will sleep completely. 30-60

>minute scan. Wake up. Go home

>

>

>

> Comments please regarding safety.

>

>

>

> (NB: we are looking to measure: brain inflammation levels, any tumour, any

>lesions, de-myelination of nerves, possibly toxic metals)

>

>

>

>

>

>

>

>

>

>

[Guest guest]

,

What you can do, to limit any effects of nitrous oxide, is to load your daughter

up with mB12, B6 and folate today and for the next 2 weeks.

The issue with nitrous oxide is that it depletes B12 (irreversible oxidation of

cobalt atom). IF you are already B12 deficient with elevated homocysteine,

nitrous oxide can cause a build up of Methylmalonic acid (MMA) in the blood

which can cause some neurological decline. I'm missing some steps here.

This does not happen to all ASD kids. Although it is a risk, it is not a given

that your daughter will regress from the use of nitrous oxide.

If you are now totally freaked out, you can have your child's blood level of

homocysteine measured (if they will do that for you). The people that died had

severe MTHFr deficiencies... and that might not even be an issue for your child.

One child had 2 back to back surgeries. I do not know what tests you have

completed in the past (MTHFR is a genetic test) or what supplements you

currently use.

Good luck to you. I hope you find some answers.

Pam

> >

> > May I also get the article, my NT son who is 2 years younger than our

> > autistic son will be having a hernia operation, and I am very concerned

> > about anesthesia.

> >

> > S.Park

> >

> >

> >

> >

> >

> >

>

>

>

> ________________________________

> De: B <peter_2_@...>

> Para: autism mercury <autism treatment >

> Enviado: martes, 7 de septiembre, 2010 6:06:11

> Asunto: RE: [ ] Brain MRI scan under general anaesthetic -

tomorrow

>

>  

>

> Please can ou send it to me asap as we are having scan tomorrow and my little

5

> year old girl needs me to make the right decision on this

>

> >

> > From: isaguzmandiaz2@...

> > Date: Tue, 7 Sep 2010 06:04:26 +0000

> > Subject: Re: [ ] Brain MRI scan under general anaesthetic -

> >tomorrow

> >

> > Please no propophol....let me get home to send u some info on the no nos doe

> >ASD kids

> >

> > Isa

> >

> >

> >

> > Enviado desde mi oficina móvil BlackBerry® de Telcel

> >

> >

> >

> > [ ] Brain MRI scan under general anaesthetic -

tomorrow

> >

> >

> >

> > We have this tomorrow (our daughter cannot speak more than a few syllables

and

> >has very serious problem here):

> >

> >

> >

> > General Anaesthetic choice between:

> >

> >

> >

> > Gas: nitrous oxide + sebofluoride (organic flouride)

> >

> > IV: propofol

> >

> >

> >

> > Dye: unlikely to use, but could use organic cyclic gadallium

> >

> >

> >

> > Agenda: No food or drink most of night. Go to hospital ward bed

> >

> > 8.30 am. Questions. Anaesthetic where Sophie will sleep completely. 30-60

> >minute scan. Wake up. Go home

> >

> >

> >

> > Comments please regarding safety.

> >

> >

> >

> > (NB: we are looking to measure: brain inflammation levels, any tumour, any

> >lesions, de-myelination of nerves, possibly toxic metals)

> >

> >

> >

> >

> >

> >

> >

> >

> >

> >

[Guest guest]

I have never- not once seen any child that benefited from the MRI. Every MRI I

have seen is normal and it only put the child at greater risk.

Remember she probably has a vaccine injury or environmental exposures due

primarily because of metals and toxins. If I had to do it all over again. I

would skip the MRI allllll together. There is no need at this time unless there

are extenuating circumstances.

For her safety, don't do it.

It is diagnostic and adds no value. More harm!

Get a genetics blood test and remove metals. Then, re-evaluate your position.

Ask around, has any child with the issues like our kids had positive findings?

Probably not or very rare. All they are left with is the damage the MRI caused

in the first place.

On Sep 7, 2010, at 5:50 AM, " peter " <peter_2_@...> wrote:

> We have this tomorrow (our daughter cannot speak more than a few syllables and

has very serious problem here):

>

> General Anaesthetic choice between:

>

> Gas: nitrous oxide + sebofluoride (organic flouride)

> IV: propofol

>

> Dye: unlikely to use, but could use organic cyclic gadallium

>

> Agenda: No food or drink most of night. Go to hospital ward bed

> 8.30 am. Questions. Anaesthetic where Sophie will sleep completely. 30-60

minute scan. Wake up. Go home

>

> Comments please regarding safety.

>

> (NB: we are looking to measure: brain inflammation levels, any tumour, any

lesions, de-myelination of nerves, possibly toxic metals)

>

>

[Guest guest]

My child's MRI revealed Chari I Malformation that was corrected surgically with

some improvement. I would do another MRI if I could afford it to see what's

going on now.

________________________________

From: " countmybaby@... " <countmybaby@...>

" " < >

Cc: " " < >

Sent: Tue, September 7, 2010 2:02:37 PM

Subject: Re: [ ] Brain MRI scan under general anaesthetic -

tomorrow

I have never- not once seen any child that benefited from the MRI. Every MRI I

have seen is normal and it only put the child at greater risk.

Remember she probably has a vaccine injury or environmental exposures due

primarily because of metals and toxins. If I had to do it all over again. I

would skip the MRI allllll together. There is no need at this time unless there

are extenuating circumstances.

For her safety, don't do it.

It is diagnostic and adds no value. More harm!

Get a genetics blood test and remove metals. Then, re-evaluate your position.

Ask around, has any child with the issues like our kids had positive findings?

Probably not or very rare. All they are left with is the damage the MRI caused

in the first place.

On Sep 7, 2010, at 5:50 AM, " peter " <peter_2_@...> wrote:

> We have this tomorrow (our daughter cannot speak more than a few syllables and

>has very serious problem here):

>

> General Anaesthetic choice between:

>

> Gas: nitrous oxide + sebofluoride (organic flouride)

> IV: propofol

>

> Dye: unlikely to use, but could use organic cyclic gadallium

>

> Agenda: No food or drink most of night. Go to hospital ward bed

> 8.30 am. Questions. Anaesthetic where Sophie will sleep completely. 30-60

>minute scan. Wake up. Go home

>

> Comments please regarding safety.

>

> (NB: we are looking to measure: brain inflammation levels, any tumour, any

>lesions, de-myelination of nerves, possibly toxic metals)

>

>

[Guest guest]

Isa, I am trying to reach about something very urgent offline.

Is your this email at dot com?

I had sent you a message and it returned undelivered.

If you have time you can write to me offline sasmitamishra at hotmail dot com.

sasmita

>

> Please no propophol....let me get home to send u some info on the no nos doe

ASD kids

> Isa

>

> Enviado desde mi oficina móvil BlackBerry® de Telcel

>

> [ ] Brain MRI scan under general anaesthetic - tomorrow

>

> We have this tomorrow (our daughter cannot speak more than a few syllables and

has very serious problem here):

>

> General Anaesthetic choice between:

>

> Gas: nitrous oxide + sebofluoride (organic flouride)

> IV: propofol

>

> Dye: unlikely to use, but could use organic cyclic gadallium

>

> Agenda: No food or drink most of night. Go to hospital ward bed

> 8.30 am. Questions. Anaesthetic where Sophie will sleep completely. 30-60

minute scan. Wake up. Go home

>

> Comments please regarding safety.

>

> (NB: we are looking to measure: brain inflammation levels, any tumour, any

lesions, de-myelination of nerves, possibly toxic metals)

>

>

>

>

>

>

[Guest guest]

Here's your first then. My son's showed several areas of inflammation and

punctuate focii. Our DAN said we all know ASD kids have it but he's never seen

it show up on an MRI before. That's my son though....never has results like most

kids and doesn't respond to supps or meds like most either

Kerrie

Sent from my iPhone

On Sep 7, 2010, at 2:02 PM, countmybaby@... wrote:

> I have never- not once seen any child that benefited from the MRI. Every MRI

I have seen is normal and it only put the child at greater risk.

> Remember she probably has a vaccine injury or environmental exposures due

primarily because of metals and toxins. If I had to do it all over again. I

would skip the MRI allllll together. There is no need at this time unless there

are extenuating circumstances.

> For her safety, don't do it.

> It is diagnostic and adds no value. More harm!

> Get a genetics blood test and remove metals. Then, re-evaluate your position.

>

> Ask around, has any child with the issues like our kids had positive findings?

Probably not or very rare. All they are left with is the damage the MRI caused

in the first place.

>

>

>

>

> On Sep 7, 2010, at 5:50 AM, " peter " <peter_2_@...> wrote:

>

>> We have this tomorrow (our daughter cannot speak more than a few syllables

and has very serious problem here):

>>

>> General Anaesthetic choice between:

>>

>> Gas: nitrous oxide + sebofluoride (organic flouride)

>> IV: propofol

>>

>> Dye: unlikely to use, but could use organic cyclic gadallium

>>

>> Agenda: No food or drink most of night. Go to hospital ward bed

>> 8.30 am. Questions. Anaesthetic where Sophie will sleep completely. 30-60

minute scan. Wake up. Go home

>>

>> Comments please regarding safety.

>>

>> (NB: we are looking to measure: brain inflammation levels, any tumour, any

lesions, de-myelination of nerves, possibly toxic metals)

>>

>>

>

>

>

[Guest guest]

Isa, Can you please share this with the rest of us as well?

Thanks, a H>

>

> Please no propophol....let me get home to send u some info on the no nos doe

ASD kids

> Isa

>

> Enviado desde mi oficina móvil BlackBerry® de Telcel

>

> [ ] Brain MRI scan under general anaesthetic - tomorrow

>

> We have this tomorrow (our daughter cannot speak more than a few syllables and

has very serious problem here):

>

> General Anaesthetic choice between:

>

> Gas: nitrous oxide + sebofluoride (organic flouride)

> IV: propofol

>

> Dye: unlikely to use, but could use organic cyclic gadallium

>

> Agenda: No food or drink most of night. Go to hospital ward bed

> 8.30 am. Questions. Anaesthetic where Sophie will sleep completely. 30-60

minute scan. Wake up. Go home

>

> Comments please regarding safety.

>

> (NB: we are looking to measure: brain inflammation levels, any tumour, any

lesions, de-myelination of nerves, possibly toxic metals)

>

>

>

>

>

>