glycol

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Maurice Glenn Turner, a police officer in
Cobb County, Georgia, went to the
emergency room on March 2, 1995,
complaining of flu-like symptoms.
He was treated there, and when he felt
better, he went home.
The next morning, he was found dead.
Dr. Brian Frist, the local medical examiner,
found nothing abnormal except for left
ventricular hypertrophy. He signed
Glenn’s death out as “some complication
related to an enlarged heart.”
At this point, what is your differential
diagnosis?
Officer Glenn’s widow Lynn, a 911
dispatcher, collected around $153,000
in death benefits.
Within a few days, she leased an
apartment with her boyfriend, Forsyth
county sheriff’s deputy Randy Thompson,
who later also became a fireman.
They did not marry, but they had a son in
1995 and a daughter in 1998. Fireman
Randy insured himself for $200,000.
The relationship ran into problems because
of Lynn’s extravagant spending habits.
Randy moved out and Lynn went into debt.
However, he continued to visit her.
On January 21, 2001, Randy went to the
emergency room for a severe stomachache and vomiting. He was treated and
released.
Lynn made Randy some green Jell-O
to help him settle his stomach.
The next morning, he was found dead.
Dr. Mark Koponen, the local medical
examiner could find nothing wrong except
for some crystals in the kidneys and
some coronary artery atherosclerosis.
He signed it out as sudden coronary death.
At this point, what is your differential
diagnosis?
Fireman Randy’s girlfriend Lynn collected
around $36,000 in death benefits.
Officer Glenn’s mother read about Fireman
Randy’s death in the newspaper. She
contacted Fireman Randy’s mother. Both
families felt that something was not right.
They talked with Dr. Koponen, who sent
blood and urine to forensic toxicologist
Chris Tilson.
Blood samples are routinely tested
by several methods, including
gas chromatography, which picks
up voltaile acids and alcohols.
Dr. Tilson found ethylene glycol, but
not in quantities sufficient to cause death.
He sent more samples to National Medical
Services, a forensic reference lab.
NMS found toxic levels of ethylene glycol.
Dr. Koponen changed the cause of death
to ethylene glycol poisoning.
Dr. Frist exhumed Officer Glenn and found
lethal levels of ethylene glycol as well.
Julia Lynn Turner was indicted for
Officer Glenn’s murder in 2001, and stood
trial in May, 2004.
A veterinary nurse described how Lynn
had asked her in detail about the effects
of antifreeze on cats.
Other witnesses testified that she said she
only cared about the insurance money,
and that Officer Glenn had remarked that
he was afraid she would try to kill him.
The jury also heard about Fireman
Randy’s cause of death.
Toxicologist Chris Tilson explained his own
error – a misplaced decimal point.
Manufacturers testified that their
embalming fluids did not contain
ethylene glycol, thereby refuting the
defense’s only real argument.
Dr. Kris Sperry, the chief medical examiner
for the Georgia Bureau of Investigation,
made the clinical correlations.
Dr. Frist, the original medical examiner,
described some experiments that he had
done. Lime Jell-O and Gator-Ade can be
laced with ethylene glycol without
significantly changing the look or taste.
Lynn was found guilty of murdering
Officer Glenn with malice. She got life
in prison.
Ethylene Glycol
Because of its low molecular weight
and the fact that it will not boil off,
ethylene glycol is a superb antifreeze.
It is odorless, colorless,
and sweet-tasting.
Fluorescein is added to antifreeze in the US,
and it will appear in the urine if ethylene
glycol has been ingested, alerting doctors.
Around 90,000 animals and 4000 humans
ingest ethylene glycol each year in the US.
Here, Mark Trail’s dog Andy is shown
discovering a pool of antifreeze.
The problems develop when the molecule
is metabolized to the three potent acids –
glycolic acid, glyoxylic acid, and oxalic acid.
Calcium oxalate crystals are familiar, and
in ethylene glycol poisoning, they cause
renal damage and appear in the urine.
Here’s a touch prep from the kidney of a
dog that died of ethylene glycol poisoning.
The crystals are birefringent.
It is probably these crystals that do the
mechanical damage to brain and kidney.
Always take a moment to calculate the
anion gap. By custom, Na – Cl – HCO3
Normal range is 8-16 mEq/L
Anion gap above 16 mEq/L?
Remember:
ketoacidosis
lactic acidosis (shock / exertion)
aspirin poisoning
ethylene glycol poisoning
uremia
isopropanol, isoniazid, other Rx’s
certain uncommon metabolic illnesses
Treating ethylene glycol poisoning:
Support
Bicarbonate
Ethanol (slows metabolism)
Dialysis
How do you do it?
There have been other instances of
criminal poisonings.
On July 7, 2004, Maryann Neabor, an
emergency medical technician, fatally
poisoned her former brother-in-law
with ethylene glycol in pineapple juice.
James Keown, a Jefferson City, Missouri,
radio personality, was arrested on the air
in 2005.
He is charged with chronically poisoning
his wife, Julie, for her insurance money.
In 2004, Maureen Plambeck was charged
with poisoning her former sister-in-law
with antifreeze in Margarita mix.
The victim recovered. The defense was
that she was trying to save the life of
another family member.
Scooby was a golden retriever in
Albuquerque who was maliciously
poisoned with ethylene glycol.
Scooby got his due in April 2005, when
New Mexico joined California and
Oregon in mandating that a bitter-tasting
compound be added to antifreeze.
Two ethylene glycol molecules linked
as an ether is diethylene glycol.
This is a sweet, syrupy liquid that is
somewhat less toxic than ethylene glycol,
but still not good to ingest. Exactly
how it does damage remains unknown.
Diethylene glycol is the main ingredient
in “Sterno.”
It was the deadly
ingredient in the
1938 sulfanilamide
disaster in the US…
Raspberry flavor
Unfortunately, delicious
… and the 1995-6 Haitian acetaminophen
catastrophe.
In 1985, some Austrian winemakers
turned “dry” wine to “sweet” wine by
adding diethylene glycol.
One would have had to drink two bottles
daily for a week to get sick, but this was
still bad business. Regulations followed.
This tale gave rise to the urban legend
that the French had put antifreeze in wine.
An 1990 episode of “The Simpsons”
commemorated this.
The Crepes
of Wrath
Bart became a hero for exposing a plot
by French winemakers to add antifreeze
to their wine.
“Sierra” is propylene glycol. Much less
toxic, but more expensive, it appeals to
motorists who are concerned about animals.
It’s also not
quite so good
an antifreeze.
Why not?
Okay.
There’s more.
Ryan Stallings:
Three month old white male brought
to Children’s Hospital, St. Louis,
July 1989
1 day history of feeding intolerance
followed by increased lethargy and
tachypnea
In the Cardinal
Glennon
Children’s
ER, Ryan was
found to have
pH 7.02
Anion gap 26.3
Bicarb 3 mMol/L
Ketonuria
At this point, what is your differential
diagnosis?
On the second hospital day, St. Louis U’s
toxicology lab reported:
Serum Acetone
3700 umol/L
= 215 mg/L
Blood Ethylene
Glycol
180 mg/L
Smith Kline Beecham, an independent
lab, confirmed the presence of deadly
levels of ethylene glycol.
Your lecturer led the College of American
Pathologists’ team that did this lab’s
inspection a few years ago.
Ryan improved, but continued to be
lethargic and to feed poorly.
The physicians believed the child had
been poisoned, and he was placed in
a foster home.
On September 1, Ryan’s mother Patricia
was allowed a supervised visit, and fed
him with a bottle.
On September 4, Ryan was hospitalized
again, with lethargy, muscle spasms, and
hyperventilation. His pH was 6.9.
He was treated with IV ethanol, but died
soon afterwards. St. Louis Hospital’s lab
found 119 mg/L of ethylene glycol in his
blood. Smith-Kline confirmed this by gas
chromatography.
St. Louis also reported that “traces of
ethylene glycol” were found on the bottle.
Patricia Stallings was arrested for murder.
Patricia Stallings spent the next seven
months in jail, and then gave birth to
a second son, David Jr., who was put in
foster care.
Within two weeks, David became acidotic
and unresponsive, and was hospitalized.
He was found almost at once to have
vitamin B12-unresponsive methylmalonic
acidemia.
Methylmalonyl-CoA mutase is required
to transform L-methylmalonyl-CoA into
succinyl-CoA.
If the enzyme
is missing…
Methylmalonic acid is elevated in the
blood…
… as is propionic acid (its decarboxylation
product) and its various secondary
metabolites.
Of course, there was talk about a
lab error and a death from a metabolic
disorder. The state did its homework.
Before the trial, the prosecutor actually
asked Dr. Christopher Long to turn
over a sample of Ryan’s blood to the
local subspecialty lab.
Dr. James Shoemaker, who ran the lab,
found a large amount of methylmalonic
acid, plus traces of ethylene glycol.
Dr. Shoemaker presented this information
at a conference. The team decided that
little Ryan probably did indeed have
methylmalonic acidemia.
But they concluded that it was still
ethylene glycol poisoning, because of the
crystals in the brain and the presence of
ethylene glycol in the bottle. They had the
idea that the ethylene glycol in Ryan’s
blood had “dissipated” in storage.
Patricia Stalling’s lawyer did not attempt to
obtain any expert support for the idea that
Ryan’s death was not due to ethylene
glycol poisoning.
Patricia Stallings was convicted of murder.
“Unsolved Mysteries” got ahold of the
case. Dr. William Sly, chief of Biochemistry
at SLU, watched the show and got
together with Dr. Shoemaker.
They went back to the specimens, and
used a more sophisticated technique…
… coupling a Hewlett-Packard 5890
gas chromatograph …
… to a VG mass spectrometer.
Gas chromatography….
Solid line is Ryan Stallings
Dotted line is normal serum + 900 mg/L ethylene glycol
Gas chromatography….
Solid line is Ryan Stallings spiked with ethylene glycol, no IS
Dotted line is Ryan Stallings with internal standard
Mass spectrum for ethylene glycol
Mass spectrum for propionic acid
The two
fragmentation
patterns are not
at all similar.
There was actually NO ethylene glycol in
the blood. The old gas chromatograph
technique mistook propionic acid
for ethylene glycol.
Huge amounts of propionic acid,
plus methylmalonic, acetic,
b-hydroxybutyric, and
b-hydroxyisovaleric acids proved
the diagnosis of methylmalonic acidemia.
The prosecutor still could not explain
the crystals in the brain. He contacted
Yale’s Piero Rinaldo, who knew the
answer.
Everybody had overlooked the obvious.
Babies metabolize big doses of ethanol
into oxalic acid.
The “ethylene glycol” on the bottle turned
out to be residue from the ethylene
oxide used to sterilize collection equipment.
In an unprecedented move, the prosecutor
asked the judge to declare trial counsel
incompetent, and order a new trial.
The prosecutor then dropped the charges,
and Patricia Stallings was freed.
Okay.
There’s more.
A previously healthy 6 month old girl
was admitted to a community hospital.
Mother had noted decreased activity,
increased irritability, poor feeding, and
decreased urination over 3 days. On the
day of admission, the child had begun
to vomit and become lethargic, pale,
tachypneic, and hypotonic.
Admitting labs:
pH 7.12
pCO2 12 torr
pO2 320 torr
Bicarb 4 mmol/L
Anion gap 24
UA: 100-120 rbc/hpf, 3-8 wbc/hpf
Tox screen did not show ethylene glycol.
At this point, what is your differential
diagnosis?
The community hospital sent the child
to Mass General, where the anion gap
and all the other abnormal labs were
normal by the next day. All cultures were
negative.
The blood showed a very high level of
glycine. Urine contained traces of three
dicarboxylic acids (adipic, suberic,
and octenedioic).
The folks at Mass General were much too
clever to fall into the trap of assuming this
was ethylene glycol poisoning.
They expected that with the Stallings
fiasco, there would be no faulty reporting
about ethylene glycol! They decided
this must be another curious genetic
disorder causing a metabolic acidosis,
perhaps one that had never been reported.
They decided to “wait and see.”
Six days later, the child was back at the
community hospital with the same
symptoms. pH was 7.18, bicarbonate was
7, and anion gap was 28. The child
was given bicarbonate and sent back to
Mass General, where everything rapidly
reverted to normal.
Despite a lot of assays, all turning out
normal, the Mass General team decided
she had some disorder of fatty acid
metabolism, and placed her on a low-fat
diet.
Two months later, she was back at the
community hospital with the same
abrupt onset of the same symptoms and
lab findings.
This time, she was
transferred to
Children’s in Boston.
Children’s checked the urine for organic
acids. It was loaded with glycolic acid
and some unidentified peaks. Blood
glycine was three times normal.
Serum collected on
the day of admission
turned out to contain
high levels of
ethylene glycol.
Really.
It turned out that, unbeknownst to the
community hospital and Mass General,
the toxicology screens did not include
ethylene glycol among the substances
for which they searched.
The district attorney and social services
people investigated. The parents fired
the baby-sitter “whose work schedule
paralleled the onset of illness.”
A bottle of infant formula in the refrigerator
contained 220 mg/dL of ethylene glycol.
There was none in the lot of formula
from which this had been obtained.
The child has had no sequelae.
What did we learn?
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