Tag: melamine

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Craig Langman’s Editorial on the Melamine Crisis from The Journal


Craig Langman (who has made a previous appearance on PBFluids) wrote an editorial for the Melamine article and pair of letters to The Journal (one from Wang et al. from Taiwan and the other from Ho et al. from Hong Kong).

He recommends the same advice I have been giving for Americans who have adopted Chinese infants:

How should physicians in other parts of the world care for Chinese infants who may have been exposed to melamine-contaminated powdered infant formula? The American Society of Pediatric Nephrology suggests a conservative approach in asymptomatic infants,PDF since stones presumed to have been induced by melamine ingestion appear to be passed easily after hydration, and there are currently no follow-up reports on the children studied by Guan et al. and Wang et al. Performance of abdominal ultrasonography in all potentially exposed Chinese children living in the United States would be likely to cost many millions of dollars, an expenditure difficult to justify, given that both unaffected and affected children may have no symptoms and that the meaning of a stone in an asymptomatic child is uncertain.

Langman emphasizes that each study is unable to estimate a true incidence because the populations studied were not representative of the population at risk.

He also teases the reader by mentioning that stones, which are increasing in frequency among adults, seem to be increasingly common among children. He states that this may be due to dietary and lifestyle issues but doesn’t even entertain the possibility that melamine exposure here in the U.S. and around the world may be responsible. This possibility was first suggested in an insightful article in Slate. We know that melamine is found in the U.S., we don’t know how long it has been here.

My personal sense is that the Slate article is just scaring people unnecessarily. if the increase in stones was do to melamine we would know it. We would know it because stones that are removed by interventions are always analyzed in a stone lab. The stones in China that were due to melamine were made of uric acid and melamine. If even a single stone in the U.S. was found to be melamine the whole medical world would go ape.

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The Jounal Delivers a Bumper Crop of Melamine Articles.

The primary article is an analysis of 589 children by Na Guan

Methods

All of the children’s parents were given a survey to establish demographic data and judge exposure. The investigators questioned parents on the brand and amount of formula ingested and matched it up to government data on the amount of melamine in each brand. Children were then put through varying degrees of biochemical and ultrasound testing.

All the children were under 36 months of age, the population most at risk of melamine stones.

The primary outcome was the presence of kidney stones.
The General Administration of Quality Supervision and Quarnatine of the PRC analyzed 22 brands of formula and reported the amount of melamine. The researchers then categorized each formula as:
  1. High melamine (over 500 ppm)
  2. Moderate melamine (less than 150 pm)
  3. No-melamine.
Ultrasounds were reported as:
  1. Definite stones
  2. Suspected stones (increased sporadic, punctiform echogenicity in the kidneys or pyelocalyceal system)
  3. No stones
Result
The all important table 1.
In 589 exams they found definite 50 stones, 112 suspected stones and 427 children were stone free.

Most of the children with stones did not oliguria, dysuria or edema. Only two of 34 stone formers (6%) had hematuria and only 1 had leukoturia (3%). None of the children with suspected stones had hematuria and only one had leukocyturia (1.3%).

Microalbuminuria was found in more of the children with stones (10%) or suspected of having stones (13.6%) compared to the stone free children (5.6%). Symptoms were not helpful in distinguishing stone formers from the stone free.

Fifty-six children had serum creatinine checked (22 with stones, 21 with suspected stones and 13 without). All of the creatinines were normal.

Interestingly 62 of 404 children had a calcium to creatinine ratio that exceeded age based targets. The 15% rate of hypercalciuria was not associated with stone risk in this study (p=0.34).

In multivariate analysis exposure to high-melamine milk (7x as likely) and pre-term birth (4.5x as likely) were significantly associated with stone formation.

The primary conclusion is that the physical and biochemical lab add nothiong to the evaluation of melamine stones. The birth history and the melamine exposure assessment are critical but need to be followed up by an ultra-sound.

The authors note that only 23 of 121 children exposed to high-melamine formula developed stones

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Melamine Crisis: The Death Penalty


Just as we saw in the contaminated pharmaceutical disaster the heavy hand of communist China comes down on Zhang Yujun and Geng Jinpin both who were sentenced to capital punishment for their roles in the Melamine Milk Contamination Tragedy. A third man, Gao Junjie, was sentenced to death for his role but received a two year reprieve so he still may escape the firing squad.

Good luck with that.

The chairwoman of Sanlu Group, Tian Wenhua, was sentenced to life in prison for her company’s role in this. Can you imagine a CEO or Chairman of the Board getting that kind of sentence in the US? Of course I was equally shocked when they executed the head of the Chinese FDA for the pharmaceutical scandal.

China is different.

Source: New York Times

My previous posts on Melamine

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Melamine makes the big time: The Journal

The New England Journal of Medicine this week did a Perspective piece on Melamine. Its amazing to me how a health crisis this big has been essentially ignored up to now by the core medical journals.

The article is in depth and insightful. It suggests, as my former fellow did, that the combination of both melamine and cyanuric acid produced the latest epidemic.

The article continues the obscurity and confusion that comes from mixing parts per million and mg per kilogram.

Since there are insufficient data from humans, the WHO meeting recommended a tolerable daily intake (TDI) of 0.2 milligrams per kilogram of body weight for melamine and 1.5 milligrams per kilogram of body weight for cyanuric acid. The executive summary stated that the TDI is “applicable to the whole population, including infants.” However, exposure to both melamine and cyanuric acid may confer a higher risk, and there are unknowns about long-term renal and other risks. The current limit set by the FDA for melamine in food is 2.5 parts per million, calculated on the basis of ingestion by a person weighing 60 kg.

The article links to a report produced by the above mentioned WHO meeting. It provides exposure data from the Chinese Centers for Disease Control and Prevention:

The dietary exposure based on the consumption of melamine-adulterated infant formula in China at the median levels of melamine reported in the most contaminated brand was estimated to range from 8.6 to 23.4 mg/kg body weight per day, based on data provided by the Chinese Center for Disease Control and Prevention.

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Melamine in the eggs, melamine in pesticide

Hong Kong discovers high levels of melamine in chinese eggs:

Hong Kong said last week it would test meat, vegetables and processed food for melamine, a move that underlines concerns about food safety in the former British colony which returned to Chinese rule in 1997.

It imposed a cap on melamine in September, restricting it to no more than 2.5 milligrams per kilogram, while melamine found in food meant for children under three and lactating mothers should be no higher than one mg per kg.
The level of melamine found in the eggs was 4.7 mg per kg, the newspapers said.

The newest revelations on melamine toxicity involves vegetables that are sprayed with the insecticide cyromazine. This derivative of melamine degrades back into melamine resulting in the contamination.

Recently, experts have investigated and confirmed that melamine has also been found in lettuce, water cress, tomatoes, mushrooms, potatoes and other agricultural products. There is 17 milligrams (0.000037 lbs) of melamine per kilogram (2.20 lbs) of mushrooms.

Cyromazine itself apparently has very little toxicity:

Cyromazine is practically nontoxic (acutely) to mammals and birds. Exposure estimates for these organisms are 0.05 ppm. Acute toxicity for birds is 1785 ppm maximum. Safety factor is 105-106 for birds. Acute toxicity for mammals is 1000 ppm maximum. Safety factor is again 105 – 106.

Cyromazine

melamine

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Some details on one of the deaths from the melamine milk contamination

This article talks about the family of the first infant to die from melamine milk contamination. The child, Yi Kaixuan was only 6 months old. He died back in May, months before any information about the contamination came out.

But on April 20, the baby wouldn’t stop crying and had problems urinating. Jiao took him to the village clinic, but they couldn’t pinpoint a problem.

Alarmed, Yi left his construction job and returned home. The family headed for the Gansu provincial capital, Lanzhou. On April 30, they took the baby to two city hospitals. Doctors were stunned, Yi said. They said they’d never seen a child with so many kidney stones, and the situation was critical.

A frenzy of testing followed, and the bills piled up past $145. The parents didn’t sleep all night, waiting.

Around noon the next day, a doctor came to tell them their baby had died.

Tragic.

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Former Felllow makes good


Rakesh Lattupalli just graduated from our fellowship in June. He was an exceptional fellow. He just finished a scientific article on the Melamine outbreak. Rakesh was the person who got me interested in the subject. The article is a nice overview of some of the scientific data on melamine toxicity.

Like me, he feels that melamine is not likely to be the entire story and a second co-factor will be identified that is critical to the development of nephrolithiasis. He suggests cyanuric acid as a possible candidate.

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Melamine milk poisoning continues to make headlines


White Rabbit candies are being pulled from the shelves for failing to have less than 2.5 mg/kg melamine.

The Chinese press reported another 380 sick children in Beijing at the same time as they are declaring the milk safe. Though this seems to be a contradiction, my feeling is that stones in children will be showing up for months after the milk supply is clean as kidney stones can lie asymptomatic for months (years?) in the renal pelvis before spontaneously moving into the ureters where they cause pain, obstruction and hematuria.

The Taiwanese press provides a shockingly sophisticated article on the problems with our current toxicity knowledge of melamine and the associated debate on limits of safety. In addition to discuss limits of tolerability it goes into the differing methods of detection including high performance liquid chromatography (HPLC), liquid chromatography-tandem mass spectrometry (LC-MS/MS), gas chromatography-mass spectrometry (GC-MS). The LC-MS/MS method is apparently the most sensitive assay. One confusing aspect of the article is they swithc freely between mg/kg and ppm. One mg/kg is equal to 1 ppm.

A friend was staying with us over the week-end. She and her husband adopted a little girl from China. She was drinking chinese formula 6 months ago. She is doing well, no symptoms and when she came over she had a “kidney test.” The mother asked me if she should do anything. My answer was that her daughter likely was exposed to melamine as it looks like this practice of spiking milk with melamine has been going on for awhile. I added that since her daughter was doing well and not having colicky pain, a diagnosis of nephrolithiasis would not change what you do. I recommended against doing a renal ultra-sound and wait for any symptoms which would likely never occur.