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Excess mortality among 5,064 victims of arsenic poisoning from
ingestion of arsenic-contaminated "Morinaga dry-milk" in 1955: a
prospective study from 1982 to 2004.Nippon
Koshu Eisei Zasshi. 2007 Apr;54(4):236-45.
OBJECTIVES: A
prospective cohort study was conducted to assess the excess
mortality among victims of arsenic poisoning who had ingested
"Morinaga dry-milk" that was contaminated with arsenic compounds in
1955. METHODS: We identified and enrolled 5,064 individuals who had
ingested contaminated Morinaga dry-milk when they were aged two
years or younger, in 1982 (mean age: 27.4 years) and they were
followed until 2004 (mean length of follow-up: 22.3 years). The
death certificates of subjects who died between 1982 and 2004 were
examined. The risk of death was assessed by the ratio of the
observed number (O) to the expected number of deaths (E), calculated
from the mortality rate among Osaka residents. RESULTS: The O/E
ratio for all causes of death was 1.3 (O = 211, P < 0.01).
Significant excess mortality was observed for diseases of the
central nervous system (O/E = 5.4) or circulatory system (O/E =
1.4), external causes (O/E = 1.4) and traffic accidents (O/E = 2.0).
Excess mortality from all causes appeared 0 to 4 years after study
enrollment (O/E = 2.1, P < 0.01), and then the O/E ratio decreased
to unity (O/E = 1.2) beyond 10 years after study enrollment. The 352
males who were unemployed at the time of enrollment in the study
showed significantly elevated risk of death from all causes (O/E =
3.3), death from disease of the central nervous system (O/E = 36.7),
circulatory system (O/E = 3.7) or respiratory system (O/E = 5.7),
and death from external causes (O/E = 3.4). CONCLUSION: This
prospective cohort study showed that excess mortality from all
causes among the victims of arsenic poisoning from ingestion of
arsenic-contaminated "Morinaga dry-milk" in 1955 decreased to unity
when they reached middle age.
Defective
adrenergic responses in patients with arsenic-induced peripheral
vascular disease.
Angiology. 2007 Apr-May;58(2):161-8.
Blackfoot
disease is an endemic arsenic-induced peripheral vascular disease in
southern Taiwan. The main pathologic feature is atherosclerosis,
which may relate to imbalances of the adrenergic system. The purpose
of this study is to investigate the peripheral adrenergic responses
of patients with blackfoot disease. Eight patients with blackfoot
disease and four age-matched healthy controls were enrolled in this
study. Baseline cutaneous perfusion was measured with a laser
Doppler flowmeter. The response of alpha-adrenoceptors in the
cutaneous microcirculation was assessed with laser Doppler flowmetry
with iontophoresis of phenylephrine into the nailfold. In vitro
binding with (125)I-cyanopindolol determined beta-adrenoceptor
density in lymphocytes. The cyclic adenosine monophosphate (cAMP)
level at baseline and after isoproterenol stimulation reflects
lymphocyte beta-adrenergic responsiveness. Results revealed
persistently decreased skin perfusion in patients with blackfoot
disease. In contrast, there was a transient decrease in skin
perfusion in healthy controls after iontophoresis of phenylephrine.
Both beta-2 receptor density and isoproterenol-stimulated cAMP
levels in lymphocytes decreased. Increased peripheral
alpha-adrenergic response and decreased beta-2-adrenergic response
are related to increased vascular tone and result in
atherosclerosis. Our findings of accentuated alpha-adrenergic
response in microcirculation and decreased lymphocyte
beta-2-adrenoceptor response play an important role in the
pathogenesis of atherosclerosis in blackfoot disease.
Bronchiectasis in persons with skin lesions resulting from arsenic
in drinking water.
Epidemiology. 2005 Nov;16(6):760-5.
BACKGROUND: Arsenic is a unique human carcinogen in that it causes
lung cancer by exposure through ingestion (in drinking water) as
well as through inhalation. Less is known about nonmalignant
pulmonary disease after exposure to arsenic in drinking water.
METHODS: We recruited 108 subjects with arsenic-caused skin lesions
and 150 subjects without lesions from a population survey of over
7000 people in an arsenic-exposed region in West Bengal, India.
Thirty-eight study participants who reported at least 2 years of
chronic cough underwent high-resolution computed tomography (CT);
these scans were read by investigators in India and the United
States without knowledge of the presence or absence of skin lesions.
RESULTS: The mean (+/-standard deviation) bronchiectasis severity
score was 3.4 (+/-3.6) in the 27 participants with skin lesions and
0.9 (+/-1.6) in the 11 participants without these lesions. In
subjects who reported chronic cough, CT evidence of bronchiectasis
was found in 18 (67%) participants with skin lesions and 3 (27%)
subjects without skin lesions. Overall, subjects with arsenic-caused
skin lesions had a 10-fold increased prevalence of bronchiectasis
compared with subjects who did not have skin lesions (adjusted odds
ratio=10; 95% confidence interval=2.7-37). CONCLUSIONS: These
results suggest that, in addition to being a cause of lung cancer,
ingestion of high concentrations of arsenic in drinking water may be
a cause of bronchiectasis.
Arsenic
contamination in water, soil, sediment and rice of central India.Environ
Geochem Health. 2005 Apr;27(2):131-45.
Arsenic
contamination in the environment (i.e. surface, well and tube-well
water, soil, sediment and rice samples) of central India (i.e.
Ambagarh Chauki, Chhattisgarh) is reported. The concentration of the
total arsenic in the samples i.e. water (n = 64), soil (n = 30),
sediment (n = 27) and rice grain (n = 10) were ranged from 15 to 825
microg L(-1), 9 to 390 mg kg(-1), 19 to 489 mg kg(-1) and 0.018 to
0.446 mg kg(-1), respectively. In all type of waters, the arsenic
levels exceeded the permissible limit, 10 microg L(-1). The most
toxic and mobile inorganic species i.e. As(III) and As(V) are
predominantly present in water of this region. The soils have
relatively higher contents of arsenic and other elements i.e. Mg,
Al, Si, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Ga, Zr, Sn, Sb,
Pb and U. The mean arsenic contents in soil of this region are much
higher than in arsenic soil of West Bengal and Bangladesh. The
lowest level of arsenic in the soil of this region is 3.7 mg kg(-1)
with median value of 9.5 mg kg(-1). The arsenic contents in the
sediments are at least 2-folds higher than in the soil. The sources
of arsenic contamination in the soil of this region are expected
from the rock weathering as well as the atmospheric deposition. The
environmental samples i.e. water, soil dust, food, etc. are expected
the major exposure for the arsenic contamination. The most of people
living in this region are suffering with arsenic borne diseases
(i.e. melanosis, keratosis, skin cancer, etc.).
Blackfoot
disease and arsenic: a never-ending story.J
Environ Sci Health C Environ Carcinog Ecotoxicol Rev.
2005;23(1):55-74.
Blackfoot
disease (BFD) is an endemic peripheral vascular disease confined to
the southwestern coast of Taiwan. This article reviews the
epidemiology, clinical manifestations and diagnosis, pathology,
etiology and pathogenesis of this disease. Sporadic cases of BFD
occurred as early as in the early 20th century, and peak incidence
was noted between 1956 and 1960, with prevalence rates ranging from
6.51 to 18.85 per 1,000 population in different villages. Typical
clinical symptoms and signs of progressive arterial occlusion mainly
found in the lower extremities, but in rare cases, the upper
extremities might also be involved. Ulceration, gangrene and
spontaneous or surgical amputation were typical fate. An extensive
pathological study concluded that 30% of the BFD patients had
histologic lesions compatible with thromboangiitis obliterans and
70% showed changes of arteriosclerosis obliterans. Epidemiologic
studies carried out since mid-20th century revealed that BFD was
associated with the consumption of inorganic arsenic from the
artesian wells. Recent studies confirmed the existence of
preclinical peripheral vascular disease, subclinical arterial
insufficiency and defects in cutaneous microcirculation in the
residents of the endemic villages. A more recent study suggested
that the methylation capacity of arsenic can interact with arsenic
exposure in the development of peripheral vascular disease among
residents of BFD-endemic areas. The incidence of BFD decreased
dramatically after the implementation of tap water in these villages
over the past 2-3 decades. The atherogenicity of arsenic could be
associated with its effects of hypercoagulability, endothelial
injury, smooth muscle cell proliferation, somatic mutation,
oxidative stress, and apoptosis. However, its interaction with some
trace elements and its association with hypertension and diabetes
mellitus could also explain part of its higher risk of developing
atherosclerosis. Although humic substances have also been suggested
as a possible cause of BFD, epidemiologic studies are required to
confirm its etiologic role.
Arsenic
exposure and cardiovascular disease: a systematic review of the
epidemiologic evidence.
Am J Epidemiol. 2005 Dec
1;162(11):1037-49.
Arsenic exposure is a likely cause of blackfoot disease and a
potential risk factor for atherosclerosis. The authors performed a
systematic review of the epidemiologic evidence on the association
between arsenic and cardiovascular outcomes. The search period was
January 1966 through April 2005. Thirteen studies conducted in
general populations (eight in high-arsenic areas in Taiwan, five in
other countries) and 16 studies conducted in occupational
populations were identified. Exposure was assessed ecologically in
most studies. In Taiwan, relative risks comparing the highest
arsenic exposure category with the lowest ranged from 1.59 to 4.90
for coronary disease, from 1.19 to 2.69 for stroke, and from 1.66 to
4.28 for peripheral arterial disease. In other general populations,
relative risks ranged from 0.84 to 1.54 for coronary disease, from
0.69 to 1.53 for stroke, and from 0.61 to 1.58 for peripheral
arterial disease. In occupational populations, relative risks ranged
from 0.40 to 2.14 for coronary disease mortality and from 0.30 to
1.33 for stroke mortality. Methodologic limitations, however,
limited interpretation of the moderate-to-strong associations
between high arsenic exposure and cardiovascular outcomes in Taiwan.
In other populations or in occupational settings, the evidence was
inconclusive. Because of the high prevalence of arsenic exposure,
carefully performed studies of arsenic and cardiovascular outcomes
should be a research priority.
Arsenic
intoxication: information and case report.Rev
Med Inst Mex Seguro Soc. 2005
Jan-Feb;43(1):57-60.
Arsenic
intoxication is a true medical emergency with a high fatality rate,
characteristic of acute and massive hemolysis. Inhalation of 250 ppm
of arsine gas is instantly lethal. Exposure to 25 to 50 ppm for 30
minutes is lethal. Arsine is a colorless gas with a garlic scent,
entering the organism by breathing and passing directly into the
circulation. Its hemolytic activity is due to its ability to cause a
fall in erythrocyte-reduced glutathione content. Manifestations are
suggestive of a general toxic state with alterations of
consciousness, from confusion until delirium, crash, hematuria,
jaundice and renal insufficiency. This can generate confusion and
difficulty in the diagnosis and in the opportune treatment to avoid
death or sequelae. This type of intoxication must be suspected in
electrolysis process workers or those working with lead, copper,
zinc, iron, gold, silver and tin. In the present case, sources for
arsenic ingestion in the organism were discarded and the presence of
arsine in the workplace was confirmed. In spite of the administered
treatment, the patient experienced renal insufficiency.
Manifestation of arsenicosis patients and factors determining the
duration of arsenic symptoms in Bangladesh.Toxicol
Appl Pharmacol. 2005 Oct
1;208(1):78-86.
This study
analyzed a total of 1482 arsenicosis patients living in 6 of 496
upzilas (sub-districts) of Bangladesh, who were identified through
household screening and then confirmed by a trained medical team
headed by medical officer. Melanosis was common (97%) among them but
about two-thirds (68.7%) of the patients were suffering from
keratosis. Average age was 36 years and average duration of arsenic
symptoms was 3 (median) years. About 50% of the patients had been
drinking tubewell water more than 24 years. Melanosis was
significantly associated with younger patients (P=0.031), shallower
tubewell (P=0.005), and complication of conjunctivitis (P<0.001).
Keratosis was also significantly associated with older age
(P=0.022), shallower tubewell (P<0.001), complication of
conjunctivitis (P<0.001), bronchitis (P<0.001), loss of appetite
(P<0.001), and wasting (P<0.001). Duration of arsenic symptoms was
significantly associated with older age (P<0.001), male (P=0.002),
married (P<0.001), smoking (P=0.002), longer duration of consuming
tubewell water (P<0.001), complication of conjunctivitis (P=0.002),
loss of appetite (P<0.001), wasting (P=0.006), and social problem
faced having arsenicosis (P=0.040). Multivariate odds ratio (OR) and
95% confidence interval (CI) indicated that keratosis (OR=2.00; 95%
CI: 1.56-2.56) was significantly associated with longer duration of
arsenic symptoms; loss of appetite (OR=1.40; 95% CI: 1.12-1.74) was
a significant complication for longer duration. Similarly smoking
(OR=1.33; 95% CI: 1.06-1.68) was positively associated with longer
duration of arsenic symptom. These findings will help the policy
makers of Bangladesh to understand about the factors that may affect
the severity condition of the patients through prolongation of
arsenic symptoms.
Assessment
of DNA damage in peripheral blood lymphocytes of individuals
susceptible to arsenic induced toxicity in West Bengal, India.Toxicol
Lett. 2005;159(1):100-12.
Assessment
of DNA damage was carried out using alkaline comet assay in
lymphocytes of 30 individuals exposed to high levels of arsenic
(247.12+/-18.93 microg/l) through contaminated groundwater in North
24 Parganas district, West Bengal, India. All of them exhibited high
arsenic contents in nail (4.20+/-0.67 microg/g), hair (2.06+/-0.20
microg/g) and urine (259.75+/-33.89 microg/l) samples and manifested
various arsenical skin lesions. Unexposed samples were collected
from 30 residents of the unaffected East Midnapur district with very
little or no exposure to arsenic (7.69+/-0.49 microg/l) in drinking
water. The results were evaluated principally by manual analysis of
comets and partly by computerized image analysis. Both the
analytical methods exhibited a high degree of agreement in results.
The exposed participants expressed significantly higher DNA damage
(p < 0.01) in their lymphocytes than the unexposed participants.
Alkaline comet assay was also combined with formamidopyrimidine-DNA
glycosylase enzyme digestion to confirm that arsenic induced
oxidative base damage in the lymphocytes. Significant positive trend
effects of comet lengths in relation to arsenic levels in water
prove that DNA damage can be used as a sensitive biomarker of
arsenic exposure. This study demonstrates that arsenic induced
significant DNA damage in the exposed participants, which could
correspond to a higher susceptibility to arsenic induced toxicity
and carcinogenicity.
Social
implications of arsenic poisoning in Bangladesh.Soc
Sci Med. 2005 Nov;61(10): 2201-11.
Besides its toxicity, groundwater arsenic contamination creates
widespread social problems for its victims and their families in
Bangladesh. There is, for instance, a tendency to ostracise
arsenic-affected people, arsenicosis being thought of as a
contagious disease. Within the community, arsenic-affected people
are barred from social activities and often face rejection, even by
their immediate family members. Women with visible arsenicosis
symptoms are unable to get married and some affected housewives are
divorced by their husbands. Children with symptoms are not sent to
school in an effort to hide the problem. This paper employs mainly
qualitative methods to interpret people's understandings about the
toxic impact of groundwater arsenic poisoning on their social lives.
Arsenic-affected patients in southwest Bangladesh were asked to
determine their 'own priorities' in measuring arsenic toxicity on
their social activities and to explore their perceptions about their
own survival strategies. We found that patients' experiences reveal
severe negative social impacts, and a sharp difference of
perceptions about arsenic and social issues between arsenicosis
patients and unaffected people.
Massive
acute arsenic poisonings.Forensic
Sci Int. 2005 Jul 16;151(2-3):273-7.
Arsenic
poisonings are still important in the field of toxicology, though
they are not as frequent as about 20-30 years ago. In this paper,
the arsenic concentrations in ante- and post-mortem materials, and
also forensic and anatomo-pathological aspects in three cases of
massive acute poisoning with arsenic(III) oxide (two of them with
unexplained criminalistic background, in which arsenic was taken for
amphetamine and one suicide), are presented. Ante-mortem blood and
urine arsenic concentrations ranged from 2.3 to 6.7 microg/ml,
respectively. Post-mortem tissue total arsenic concentrations were
also detected in large concentrations. In case 3, the contents of
the duodenum contained as much as 30.1% arsenic(III) oxide. The high
concentrations of arsenic detected in blood and tissues in all
presented cases are particularly noteworthy in that they are very
rarely detected at these concentrations in fatal arsenic poisonings.
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