Mayo Clin Proc, June 2004, Vol 79
832
Arthur Purdy Stout, the doyen of American soft tissue pa-
thologists, expressed the opinion that the lesions were simply
benign, if exuberant, fibroblastic proliferations.
I was, at that time, assigned to the US Army 406th Medical
Laboratory in Japan. It occurred to me that intravenous iron
dextran might be toxic to the liver, inducing fibrosis similar to
that seen in hemochromatosis and cirrhosis and at injection
sites. My commanding officer provided helpful support and
supervision. I injected a series of rabbits intravenously with
very large amounts of iron dextran (up to 500,000 µg/kg).
Initially, the blood iron levels were extremely high, up to
250,000 µg/dL, and even 6 months later, they were in the
2000- to 3000-µg/dL range. After 6 months, I detected no
fibrosis in the rabbits’ livers. Therefore, I attempted the same
study with mice, made alcoholic by adding 5% ethanol to their
drinking water. The mice lost weight and their hair fell out, but
no fibrosis was induced. I had failed to find an animal model
for the well-known fibroblastic effect of iron on the liver. It
didn’t occur to me that there wasn’t much fibroblastic effect.
Claude O. Burdick, MD
Medical Director
Spectra Laboratories
Fremont, Calif
1. Beutler E. Natural history of hemochromatosis [editorial]. Mayo Clin
Proc. 2004;79:305-306.
2. Chandra RK. The risk of sarcomatous change after iron-dextran
therapy. Indian J Pediatr. 1965;32:75-77.
3. Grasso P. Sarcoma after intramuscular iron injection. BMJ. 1973;2:
667.
In reply: Almost universally, experience has shown that “load-
ing” normal animals with iron does not result in hepatic fibro-
sis. In experimental animals, fibrosis generally has been pro-
duced by iron overload only when some other toxic variable,
such as a choline-deficient high-fat diet,1 is superimposed,
although rare successes in producing liver damage by iron
overloading in rats2 and gerbils3 have been reported.
At one time it was generally believed that the apparent
resistance of experimental animals to the hepatotoxic effect of
iron overload was due entirely to species differences. How-
ever, as Dr Burdick suggests, the same seems to be true in
humans. Saven and I4 reported the case of a 63-year-old pa-
tient who, according to our calculations, had received a total of
52 g of iron in the form of iron dextran over a period of 20
years but had no cirrhosis evident on liver biopsy. It may well
be that most humans tolerate massive iron overload well and
that additional genetic factors or hepatotoxic environmental
factors are needed to produce the severe cirrhosis that occurs
in only a small proportion of patients homozygous for the
C282Y mutation.
Ernest Beutler, MD
The Scripps Research Institute
La Jolla, Calif
1. MacDonald RA, Pechet GS. Experimental hemochromatosis in rats.
Am J Pathol. 1965;46:85-109.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
Letters to the Editor 831
2. Park CH, Bacon BR, Brittenham GM, Tavill AS. Pathology of di-
etary carbonyl iron overload in rats. Lab Invest. 1987;57:555-563.
3. Pietrangelo A, Gualdi R, Casalgrandi G, Montosi G, Ventura E.
Molecular and cellular aspects of iron-induced hepatic cirrhosis in
rodents. J Clin Invest. 1995;95:1824-1831.
4. Saven A, Beutler E. Iron overload after prolonged intramuscular iron
therapy [letter]. N Engl J Med. 1989;321:331-332.
Incidence of Bronchiolitis-Associated Hospitalization
Among Children in Olmsted County, Minnesota
To the Editor: Respiratory syncytial virus (RSV) is the most
frequent cause of severe respiratory infections in young chil-
dren. It is responsible for 80% of cases of bronchiolitis, par-
ticularly during the winter months.1 The incidence of RSV
hospitalization varies among different population groups.2-4
Targeting the use of currently available prophylactic agents5
will require knowledge of local hospitalization rates. We de-
scribe a study of bronchiolitis-associated hospitalization
among children in Olmsted County, Minnesota.
Patients and Methods.—We performed a retrospective
cohort study of all children younger than 24 months old resid-
ing in Olmsted County, Minnesota, from January 1990 to
December 1999. The medical records of all children hospital-
ized during RSV season (defined as November to April each
year) with a diagnosis of RSV infection or bronchiolitis were
reviewed. Birth hospitalizations and nosocomial infections
were excluded. Age- and sex-specific incidence rates were
calculated for the entire study period. The change in bronchi-
olitis incidence over the time period of the study was assessed
by fitting a generalized linear model assuming a Poisson error
distribution with use of the SAS GENMOD procedure (SAS
Institute Inc, Cary, NC).
Results.—From 1990 to 1999, 280 children younger than 2
years old were hospitalized for bronchiolitis or RSV-related
infection in Olmsted County. Of these, 252 (90%) were
younger than 12 months old, and 28 (10%) were between 12
and 23 months old. The median age at diagnosis was 4 months.
Nearly two thirds (63%) of the patients were male. During the
first year of life, the incidence of bronchiolitis hospitalization
was significantly higher among male infants, who had a rate of
17.8 per 1000 (95% confidence interval [CI], 15.0-20.6), com-
pared with the rate in female infants of 11.8 per 1000 (95% CI,
9.4-14.2). The sex-adjusted incidence among children
younger than 12 months old was 14.9 per 1000 (95% CI, 13.0-
16.7). Among children 12 to 23 months old, the sex-adjusted
incidence was 1.5 per 1000 (95% CI, 0.9-2.0).
Among our cases, 40 children (14%) had a history of prema-
ture birth (<36 weeks of gestation), and 47 (17%) had a birth
weight of less than 2500 g. Fifteen children (5%) had congenital
heart disease, and 5 (2%) had bronchopulmonary dysplasia.
Thirty-five children (12%) were diagnosed as having asthma or
reactive airways disease before their hospitalization.
Oxygen therapy was administered to 185 children (66%),
76 (27%) were admitted to the intensive care unit, and 17 (6%)
required mechanical ventilation. The mean hospital stay was
2.7 days (range, 1-15 days). The peak of bronchiolitis hospi-