Re: adult mito/meta doctors/Laurie

April 13, 2005

-Thanks Laurie,

I have a sad face at present as the neuro who ordered the biopsy

asked in 1996 what meds I was on but never again after that on my

yerly 5 minute check-up..They did the biopsy in 2003 and in the

hospital I was just marked as self-medicating on my chart by the

nurse who asked what I took,Thyroxin and simvastatin only,I know

they were concerned about my hypertension/taccychardia not being

treated tthough..the nurses not the neuro that is..

When I saw a different neuro in the hospital he seemed shocked by my

meds and results and told me to increase the thyroxin and stop the

statin..that was when after 3/4 weeks I felt less floppy/wobbly..no

explanations were given though..I can only assume from this that the

lab and original neuro may *POSSIBLY* have not allowed for this fact

either when reading results..

I think that I will have to sit down and think very carefully and

prepare some questions for my mito doc about this point..especially

as after being off statins for 18 months he has now put me on

Lipitor I believe is the US word for our Avorstatin and i have been

feeling sort of floppy since about 6 weeks after starting the meds..

I did see an article recently to say that they are now thinking off

doing a combi. drug here comprising off Simvastatin/Q10 which really

does make me wonder about stains for anyone at all..

Gillian

-- In , Laurie Fitzgerald

wrote:

> Gillian

>

> Some people can be diagnosed with frozen muscle tissue, but others,

> like me, require the fresh.

>

> As far as I know labs are not told of the drugs being taken. It is

up

> to the doctor to interpret what the lab has found in light of the

> meds. This is why many doctors want you all but critical meds for

> several weeks before the biopsy.

>

> laurie

>

> On Tue, 12 Apr 2005 11:57:30 -0500, Barbara Seaman

> wrote:

> >

> > Gillian,

> >

> > Reposting what I posted Dec 29, 2004 on fresh vs. frozen. I'm

not an

> > expert,

> > so I can only quote experts. According to these experts, one can

measure

> > the

> > activity of individual respiratory chain enzymes in frozen

tissue. What

> > cannot be done in frozen tissue is look at overall OXPHOS

capacity. This

> > latter testing requires live cells. According to the Ann Clin

Biochem

> > abstract, approx 25% cases of mito manifest only as reduced

overall OXPHOS

> > capacity. In these cases, the enzyme activity in individual

complexes is

> > normal, even though there is reduced overall OXPHOS capacity.

Therefore,

> > the

> > Ann Clin Biochem paper suggests that using frozen tissue for

diagnosis

> > would

> > yield a diagnosis for approx 75% of mito cases, but miss 25% of

> > cases---those in which complex activity is normal but overall

OXPHOS

> > capacity is reduced. These numbers presuppose viable tissue and

valid lab

> > protocols. Note my original comments and disclaimers below.

> >

> > Gillian, re your question on drugs: Unfortunately, not all labs

require

> > that

> > a history accompany specimens. A good lab will require detailed

history and

> > design testing accordingly.

> >

> > B

> >

> > Some of you might be interested in this info from DiMauro on the

MDA site:

> >

> > QUESTION: Can you tell if a mitochondrial myopathy is or is not

maternally

> > inherited by a frozen muscle biopsy alone? What information does

a fresh

> > biopsy give as opposed to a frozen biopsy?

> >

> > REPLY from MDA: Salvatore DiMauro, M.D., Prof. of Neurology, New

York

> >

> > A frozen muscle biopsy can provide clues suggesting a

mitochondrial DNA

> > (mtDNA) mutation and, therefore, maternal inheritance of the

adequate for

> > histochemistry, evidence of scattered cytochrome c oxidase-

deficient

> > (COX-negative) fibers, having a " mosaic " distribution among COX-

positive

> > (normal) fibers, is a good indication of a mtDNA mutation,

probably

> > affecting mtDNA genes involved in protein synthesis (such as

tRNA genes);

> > (ii) biochemical analysis of respiratory chain enzymes may

reveal decreased

> > activities of those complexes that contain mtDNA-encoded

subunits, i.e.

> > complexes I, III, and IV (complex V is not assayed routinely in

frozen

> > tissue). This is additional circumstantial evidence of a mtDNA

mutation

> > affecting mitochondrial protein synthesis.

> >

> > A fresh muscle biopsy allows careful isolation of a

mitochondrial fraction;

> > the isolated mitochondria can be used to assess respiration and

> > phosphorylation using different substrates and an oxygen

electrode

> > ( " polarographic analyses " ), or to study ATP synthesis from ADP

and

> > radio-labeled inorganic phosphate (Pi). These studies can provide

> > information on the site of a metabolic block in the electron

transport

> > chain

> > (complexes I to IV) and on the function of ATP synthetase

(complex V).

> >

> > ------------

> > There is also an interesting 2003 abstract on the subject:

> >

> > Ann Clin Biochem. 2003 Jan;40(Pt 1):3-8.

> >

> > http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?

PrId=3152&uid=12542905

> > &db=PubMed&url=http://www.ingentaselect.com/rpsv/cgi-bin/cgi?

body=linker&ini

> > =nlm&reqidx=issn=0004-5632vl=40is=Pt%201yr=2003mn=Janpg=3> Click

here to

> > read

> > Some practical aspects of providing a diagnostic service for

respiratory

> > chain defects.

> >

> > Janssen AJ, Smeitink JA, van den Heuvel LP.

> >

> > Nijmegen Centre for Mitochondrial Disorders, Department of

Pediatrics,

> > University Medical Centre Nijmegen, Geert Grooteplein 10, PO Box

9101, 6500

> > HB Nijmegen, The Netherlands.

> >

> > The oxidative phosphorylation system (OXPHOS) is organized into

five

> > multi-protein complexes, comprising four complexes (I-IV) of the

> > respiratory

> > chain and ATP synthase (complex V). OXPHOS has a vital role in

cellular

> > energy metabolism and ATP production. Enzyme analysis of

individual OXPHOS

> > complexes in a skeletal muscle biopsy remains the mainstay of the

> > diagnostic

> > process for patients suspected of mitochondrial cytopathy.

Practical

> > guidelines are presented to provide optimal conditions for

performance of

> > laboratory investigations and a reliable diagnosis. A fresh

muscle biopsy

> > is

> > preferable to a frozen muscle sample because the ****overall

capacity of

> > the

> > OXPHOS system**** can be measured in a fresh biopsy. In about

25% of

> > patients referred for muscle biopsy to our centre, reduced

substrate

> > oxidation rates and ATP+creatine phosphate production rates were

found

> > ****without any defect in complexes I-V**** and the pyruvate

dehydrogenase

> > complex. Investigation of frozen muscle biopsy alone may lead to

> > false-negative diagnoses in many patients. In some patients, it

is

> > necessary

> > to investigate fibroblasts for prospective diagnostic purposes.

An exact

> > diagnosis of respiratory chain defects is a prerequisite for

rational

> > therapy and genetic counselling. Provided guidelines for specimen

> > collection

> > are followed, there are now reliable methods for identifying

respiratory

> > chain defects.

> >

> > As I understand it, this says something similar to DiMauro but

may be a

> > little easier to understand. They both say that complexes I-IV

can be

> > assayed in frozen tissue, but to look at ****overall OXPHOS

capacity*** one

> > needs

> > fresh tissue. According to this abstract of a study in the

Netherlands,

> > about 25% of their mito cases do not manifest as specific

deficiencies in

> > one of the complexes, but only show up as reduced overall OXPHOS

> > capacity--which can only be measured in fresh tissue. If

correct, this

> > would

> > mean that 25% of mito patients could only get a diagnosis from

fresh muscle

> > tissue. I don't know if all experts agree with these authors (or

their

> > percentages) that a person can have normal activity in complexes

I-V and

> > still have reduced overall OXPHOS capacity that causes disease.

But this

> > distinction may explain why Dr. Korson and others feel some of

their

> > patients with typical mito symptoms do have mito in spite of

normal complex

> > I-V activity in muscle.

> >

> > B

> >

> > _____

> >

> > From: gillianstumps [mailto:gill@s...]

> > Sent: Tuesday, April 12, 2005 11:08 AM

> > To:

> > Subject: Re: adult mito/meta doctors/RH

> >

> > Okay, now I really am muddled up, yes I know that is easy with

me

> > but have just got my report out...and I quote..

> > The conclusion of the muscle biopsy which was taken from the

left

> > quadriceps shows an excess of cytochrome oxidase negative

fibres. It

> > was felt that these were relatively mild abnormalities but did

raise

> > the possibility of a mitochondrial cytopathy. A piece of FROZEN

> > muscle was then analysed for enzyme activity and the data was

> > consistent with deficiencies in Complex 1 and 1V...

> >

> > So would the enzyme reading be moderately right on frozen muscle

and

> > as a general query to the group does anyone know if the labs are

> > told of any prescription meds you have been taking which could

> > affect the readings..I am thinking here of statins and other

basic

> > drugs...just me thinking...

> >

> > Gillian

> >

> > > > > > >

> > > > > > > Kim,

> > > > > > > Hi! Where about are you in Illinois? I am in

> > Cedar

> > > > > Rapids,

> > > > > > > Iowa, but have family spread throughout Iowa and

Illinois,

> > > > plus

> > > > > a few

> > > > > > > other states. Dr. Peltier up in Milwaukee, does work

with

> > > > adult

> > > > > mito

> > > > > > > patients. There are a few on this list that have seen

> > her,

> > > but

> > > > > > > experiences have been different for each one. You can

e-

> > mail

> > > > me

> > > > > off list

> > > > > > > if you have any questions about her.

> > > > > > >

> > > > > > > Smiles,

> > > > > > > a

> > > > > > >

> > > > > > > On Mon, 11 Apr 2005 21:40:45 -0000 " klaga5 "

> > > > writes:

> > > > > > >

> > > > > > > I'm in Illinois.

> > > > > > > Kim

> > > > > > > --- In , Laurie Fitzgerald

> > > > > > >

April 13, 2005

> I did see an article recently to say that they are now thinking off

> doing a combi. drug here comprising off Simvastatin/Q10 which

> really

> does make me wonder about stains for anyone at all..

When Merck did their initial research on statins, they patented both

the statin drug and adding CoQ10 to the formulation. Their research

showed that adding the CoQ10 was necessary to minimize side effects,

but too expensive for general marketing.

I've meant to look up the JAMA report on this, but haven't gotten a

chance to.

I wonder, have others had success with Omega-3 capsules or flax

seed / flax seed oil to lower their cholesterol?

Take care,

RH

> -- In , Laurie Fitzgerald

> wrote:

> > Gillian

> >

> > Some people can be diagnosed with frozen muscle tissue, but

others,

> > like me, require the fresh.

> >

> > As far as I know labs are not told of the drugs being taken. It

is

> up

> > to the doctor to interpret what the lab has found in light of the

> > meds. This is why many doctors want you all but critical meds for

> > several weeks before the biopsy.

> >

> > laurie

> >

> > On Tue, 12 Apr 2005 11:57:30 -0500, Barbara Seaman

> > wrote:

> > >

> > > Gillian,

> > >

> > > Reposting what I posted Dec 29, 2004 on fresh vs. frozen. I'm

> not an

> > > expert,

> > > so I can only quote experts. According to these experts, one

can

> measure

> > > the

> > > activity of individual respiratory chain enzymes in frozen

> tissue. What

> > > cannot be done in frozen tissue is look at overall OXPHOS

> capacity. This

> > > latter testing requires live cells. According to the Ann Clin

> Biochem

> > > abstract, approx 25% cases of mito manifest only as reduced

> overall OXPHOS

> > > capacity. In these cases, the enzyme activity in individual

> complexes is

> > > normal, even though there is reduced overall OXPHOS capacity.

> Therefore,

> > > the

> > > Ann Clin Biochem paper suggests that using frozen tissue for

> diagnosis

> > > would

> > > yield a diagnosis for approx 75% of mito cases, but miss 25% of

> > > cases---those in which complex activity is normal but overall

> OXPHOS

> > > capacity is reduced. These numbers presuppose viable tissue and

> valid lab

> > > protocols. Note my original comments and disclaimers below.

> > >

> > > Gillian, re your question on drugs: Unfortunately, not all labs

> require

> > > that

> > > a history accompany specimens. A good lab will require detailed

> history and

> > > design testing accordingly.

> > >

> > > B

> > >

> > > Some of you might be interested in this info from DiMauro on

the

> MDA site:

> > >

> > > QUESTION: Can you tell if a mitochondrial myopathy is or is not

> maternally

> > > inherited by a frozen muscle biopsy alone? What information

does

> a fresh

> > > biopsy give as opposed to a frozen biopsy?

> > >

> > > REPLY from MDA: Salvatore DiMauro, M.D., Prof. of Neurology,

New

> York

> > >

> > > A frozen muscle biopsy can provide clues suggesting a

> mitochondrial DNA

> > > (mtDNA) mutation and, therefore, maternal inheritance of the

> related

> > > disorder. The clues are of two types: (i) if the biopsy is

> adequate for

> > > histochemistry, evidence of scattered cytochrome c oxidase-

> deficient

> > > (COX-negative) fibers, having a " mosaic " distribution among COX-

> positive

> > > (normal) fibers, is a good indication of a mtDNA mutation,

> probably

> > > affecting mtDNA genes involved in protein synthesis (such as

> tRNA genes);

> > > (ii) biochemical analysis of respiratory chain enzymes may

> reveal decreased

> > > activities of those complexes that contain mtDNA-encoded

> subunits, i.e.

> > > complexes I, III, and IV (complex V is not assayed routinely in

> frozen

> > > tissue). This is additional circumstantial evidence of a mtDNA

> mutation

> > > affecting mitochondrial protein synthesis.

> > >

> > > A fresh muscle biopsy allows careful isolation of a

> mitochondrial fraction;

> > > the isolated mitochondria can be used to assess respiration and

> > > phosphorylation using different substrates and an oxygen

> electrode

> > > ( " polarographic analyses " ), or to study ATP synthesis from ADP

> and

> > > radio-labeled inorganic phosphate (Pi). These studies can

provide

> > > information on the site of a metabolic block in the electron

> transport

> > > chain

> > > (complexes I to IV) and on the function of ATP synthetase

> (complex V).

> > >

> > > ------------

> > > There is also an interesting 2003 abstract on the subject:

> > >

> > > Ann Clin Biochem. 2003 Jan;40(Pt 1):3-8.

> > >

> > > http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?

> PrId=3152&uid=12542905

> > > &db=PubMed&url=http://www.ingentaselect.com/rpsv/cgi-bin/cgi?

> body=linker&ini

> > > =nlm&reqidx=issn=0004-5632vl=40is=Pt%201yr=2003mn=Janpg=3>

Click

> here to

> > > read

> > > Some practical aspects of providing a diagnostic service for

> respiratory

> > > chain defects.

> > >

> > > Janssen AJ, Smeitink JA, van den Heuvel LP.

> > >

> > > Nijmegen Centre for Mitochondrial Disorders, Department of

> Pediatrics,

> > > University Medical Centre Nijmegen, Geert Grooteplein 10, PO

Box

> 9101, 6500

> > > HB Nijmegen, The Netherlands.

> > >

> > > The oxidative phosphorylation system (OXPHOS) is organized into

> five

> > > multi-protein complexes, comprising four complexes (I-IV) of the

> > > respiratory

> > > chain and ATP synthase (complex V). OXPHOS has a vital role in

> cellular

> > > energy metabolism and ATP production. Enzyme analysis of

> individual OXPHOS

> > > complexes in a skeletal muscle biopsy remains the mainstay of

the

> > > diagnostic

> > > process for patients suspected of mitochondrial cytopathy.

> Practical

> > > guidelines are presented to provide optimal conditions for

> performance of

> > > laboratory investigations and a reliable diagnosis. A fresh

> muscle biopsy

> > > is

> > > preferable to a frozen muscle sample because the ****overall

> capacity of

> > > the

> > > OXPHOS system**** can be measured in a fresh biopsy. In about

> 25% of

> > > patients referred for muscle biopsy to our centre, reduced

> substrate

> > > oxidation rates and ATP+creatine phosphate production rates

were

> found

> > > ****without any defect in complexes I-V**** and the pyruvate

> dehydrogenase

> > > complex. Investigation of frozen muscle biopsy alone may lead to

> > > false-negative diagnoses in many patients. In some patients, it

> is

> > > necessary

> > > to investigate fibroblasts for prospective diagnostic purposes.

> An exact

> > > diagnosis of respiratory chain defects is a prerequisite for

> rational

> > > therapy and genetic counselling. Provided guidelines for

specimen

> > > collection

> > > are followed, there are now reliable methods for identifying

> respiratory

> > > chain defects.

> > >

> > > As I understand it, this says something similar to DiMauro but

> may be a

> > > little easier to understand. They both say that complexes I-IV

> can be

> > > assayed in frozen tissue, but to look at ****overall OXPHOS

> capacity*** one

> > > needs

> > > fresh tissue. According to this abstract of a study in the

> Netherlands,

> > > about 25% of their mito cases do not manifest as specific

> deficiencies in

> > > one of the complexes, but only show up as reduced overall OXPHOS

> > > capacity--which can only be measured in fresh tissue. If

> correct, this

> > > would

> > > mean that 25% of mito patients could only get a diagnosis from

> fresh muscle

> > > tissue. I don't know if all experts agree with these authors

(or

> their

> > > percentages) that a person can have normal activity in

complexes

> I-V and

> > > still have reduced overall OXPHOS capacity that causes disease.

> But this

> > > distinction may explain why Dr. Korson and others feel some of

> their

> > > patients with typical mito symptoms do have mito in spite of

> normal complex

> > > I-V activity in muscle.

> > >

> > > B

> > >

> > > _____

> > >

> > > From: gillianstumps [mailto:gill@s...]

> > > Sent: Tuesday, April 12, 2005 11:08 AM

> > > To:

> > > Subject: Re: adult mito/meta doctors/RH

> > >

> > > Okay, now I really am muddled up, yes I know that is easy with

> me

> > > but have just got my report out...and I quote..

> > > The conclusion of the muscle biopsy which was taken from the

> left

> > > quadriceps shows an excess of cytochrome oxidase negative

> fibres. It

> > > was felt that these were relatively mild abnormalities but did

> raise

> > > the possibility of a mitochondrial cytopathy. A piece of FROZEN

> > > muscle was then analysed for enzyme activity and the data was

> > > consistent with deficiencies in Complex 1 and 1V...

> > >

> > > So would the enzyme reading be moderately right on frozen

muscle

> and

> > > as a general query to the group does anyone know if the labs

are

> > > told of any prescription meds you have been taking which could

> > > affect the readings..I am thinking here of statins and other

> basic

> > > drugs...just me thinking...

> > >

> > > Gillian

> > >

> > > > > > > >

> > > > > > > > Kim,

> > > > > > > > Hi! Where about are you in Illinois? I am

in

> > > Cedar

> > > > > > Rapids,

> > > > > > > > Iowa, but have family spread throughout Iowa and

> Illinois,

> > > > > plus

> > > > > > a few

> > > > > > > > other states. Dr. Peltier up in Milwaukee, does work

> with

> > > > > adult

> > > > > > mito

> > > > > > > > patients. There are a few on this list that have

seen

> > > her,

> > > > but

> > > > > > > > experiences have been different for each one. You

can

> e-

> > > mail

> > > > > me

> > > > > > off list

> > > > > > > > if you have any questions about her.

> > > > > > > >

> > > > > > > > Smiles,

> > > > > > > > a

> > > > > > > >

> > > > > > > > On Mon, 11 Apr 2005 21:40:45 -0000 " klaga5 "

>

> > > > > writes:

> > > > > > > >

> > > > > > > > I'm in Illinois.

> > > > > > > > Kim

> > > > > > > > --- In , Laurie Fitzgerald

> > > > > > > >

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