Ah--I don't buy your interpretation in the slightest. What it suggests
is that the sensitivity and specificity of currently available blood
tests may be inadequate, although they do note that "Therefore, though
highly correlated with stored body iron, a measure of bound iron will
fail to identify any harmful effect, unless it is also a marker of
free iron." Thus, at least in the abstract, this does not utterly
invalidate the use of markers like ferritin.

Indeed, one may identify other factors such as weakness, sexual
dysfunction, arthralgia, cardiac symptoms, difficulty breathing to
evaluate the relevance of these tests (see abstract below).

Indeed, there are a variety of methods that can be used. A study of
iron overload in African Americans further suggests a potentially
heritable trade of iron retention that may result in overload.

Ah--in general, yes. But I think the point is that it occurs in some
chronic ailments. I do disagree with Tom's focus on iron in HCV
disease--I think it is a problem that is significant for a subset of
this population but not necessarily central to disease pathogenesis
overall. By contrast, oxidative stress generally and glutathione
depletion specifically may be more critical.

Excessive consumption of red meat is probably contraindicated for a
significant proportion of the population. Another dimension to that
debate, of course, is the environmental one. Consumption of meat
requires a great deal of arable land and water to feed cattle that is
in excess of the energy produced. Aside from the ethical consideration
of the way animals are raised and slaughtered, the risk of diseases
such as BSE and the increased risk of coronary and vascular diseases,
we must recognize that the overpopulated planet on which we reside
cannot sustain the type of consumption Americans typically engage in.
An interesting table in the recent National Geographic underscores the
differences between US consumption and that in China. Given the clear
cutting of jungles and forests to raise these animals for a few
seasons at most before the land reverts to desert, we are doing our
species and life on the planet a bit of a disservice by indulging
excessively or at all in the consumption of red meat.

        George M. Carter

***
Presse Med. 2003 Nov 8;32(36):1716-23.  Related Articles, Links  

 
[Hereditary haemochromatosis]

[Article in French]

Bismuth M, Aguilar-Martinez P, Michel H.

Service d'hepato-gastro-enterologie, Hopital Saint Eloi, Montpellier.
bismuthmichael@hotmail.com

EPIDEMIOLOGY ADN PHYSIOPATHOLOGY: Hereditary haemochromatosis is the
most common genetic disease in France. Its frequency is on average 1
out of 300 French individuals. It is due to excessive dietary iron
absorption, leading to accumulation of iron in the body. Mutations of
the HFE1 gene are responsible for the majority of the case of
haemochromatosis. FROM A CLINICAL POINT OF VIEW: The first clinical
manifestations (weakness, sexual dysfunction, arthralgia, cardiac
symptoms, dyspnoea on effort) can occur after the age of 30 years in
men and 35 years in women (protected for longer by menstruation,
pregnancy and delivery). In the absence of diagnosis, severe
complications can develop during the 5th decade: nervous breakdown,
arthropathy, heart failure, diabetes mellitus, cirrhosis with risk of
progression towards carcinoma, responsible for handicaps and premature
death. DIAGNOSTIC ELEMENTS: The diagnosis is evoked in the case of an
increase in transferrine saturation (>45%), associated or not with
excessive ferritin plasma levels. It is confirmed by the genetic test,
showing homozygotes for the C282Y mutation or compound heterozygotes
for the C282Y and H63D mutations on the HFE1 gene. RMI quantifies
hepatic iron loading and generally avoids the need for a liver biopsy.
The differential diagnosis must exclude secondary iron overload due to
chronic transfusions in congenital or acquired blood diseases, a
polymetabolic syndrome, chronic viral or alcoholic hepatic diseases
and porphyria cutanea tarda. EFFICIENT TREATMENT: Today,
haemochromatosis is still treated by phlebotomy. This consists in
withdrawing 400 to 500ml of blood every week at the initial depletion
stage and subsequently a maintenance therapy in order to maintain
ferritin levels below 50 ng/ml. Paradoxically and through ignorance,
hereditary haemochromatosis remains a serious disease, although its
diagnosis is easy and the treatment simple and effective.

***
Blood Cells Mol Dis. 2003 Nov-Dec;31(3):310-9.  Related Articles,
Links  

 
Genotypic and phenotypic heterogeneity of African Americans with
primary iron overload.

Barton JC, Acton RT, Rivers CA, Bertoli LF, Gelbart T, West C, Beutler
E.

Southern Iron Disorders Center, G-105, 20220 Brookwood Medical Center
Drive, Birmingham, AL 35209, USA. ironmd@dnamail.com

Primary iron overload may be relatively common in African Americans,
but its cause is incompletely understood. Thus, we evaluated genotype
and phenotype characteristics of unselected African American index
patients with primary iron overload who reside in central Alabama. All
had hepatic iron concentration > or =30 micromol/g dry wt or > or =2.0
g of iron mobilized by phlebotomy to achieve iron depletion. Genotype
analyses were performed in African American control subjects from the
same region. There were 23 patients (19 men, 4 women); mean age at
diagnosis was 52 +/- 12 years (1 SD) (range 32-69 years). Nine (39.1%)
reported that they consumed > or =45 g of ethanol daily; five had
chronic hepatitis C. Eight had some form of hemoglobinopathy or
thalassemia. Mean serum transferrin saturation was 56 +/- 28% (range
15-100%). The geometric mean serum ferritin at diagnosis was 1076
ng/mL [95% confidence interval 297-3473 ng/mL]. Increased stainable
liver iron was observed in hepatocytes only in 4 patients, in
macrophages only in 8 patients, and in hepatocytes and macrophages in
8 patients. The mean quantity of iron mobilized by phlebotomy
(corrected for iron absorbed during treatment) was 5.3 +/- 2.0 g
(range 4.0-8.4 g). Iron removed by phlebotomy was greater in patients
with hemoglobinopathy or thalassemia than in those without these forms
of anemia (6.6 +/- 1.3 g vs 3.9 +/- 1.6 g, respectively; P = 0.0144).
Daily consumption of > or =45 g of ethanol or chronic hepatitis C was
not associated with an increased or decreased amount of
phlebotomy-mobilized iron, on the average. The percentage of index
patients positive for HFE C282Y was greater than that of controls (P =
0.0058). The respective percentages of phenotype positivity for HFE
H63D, D6S105(8), and HLA-A*03 were similar in patients and controls.
HFE S65C, I105T, and G93R were not detected in index or control
subjects. Two of 13 patients were heterozygous for the ferroportin
allele nt 744 G-->T (Q248H), although the phenotype frequency of this
allele was similar in patients and 39 controls. Synonymous ferroportin
alleles were also detected in some patients. The ceruloplasmin
mutation nt 1099C-->T (exon 6; Arg367Cys) was detected in 1 of 2
patients tested. Abnormal alleles of beta-2 microglobulin, Nramp2,
TFR2, hepcidin, or IRP2 alleles were not detected in either of the 2
patients so tested. We conclude that primary iron overload in African
Americans is not the result of the mutation of a single gene. HFE
C282Y, ferroportin 744 G-->T, and common forms of heritable anemia
appear to account for increased iron absorption or retention in some
patients.