English lab confirms that mad cow disease in PR Brazil was atypical 4 years ago
English lab confirms
that mad cow disease in PR was atypical
13/12/16 às 13:43 AEN
12.13.16 at 13:43 AEN
Inácio Kroetz, diretor
presidente da Adapar (foto: AEN) Inacio Kroetz, CEO of Adapar (photo: AEN)
Quatro anos após a
suspeita de ocorrência da “doença da vaca louca” em um bovino no município de
Sertanópolis, no Norte do Paraná, o laboratório de referência da Organização
Mundial da Saúde Animal (OIE), em Weybridge, no Reino Unido, emitiu laudo
confirmando, mais uma vez, que houve uma manifestação atípica da doença. Four
years after the suspected occurrence of "mad cow disease" in a cattle
in the municipality of Sertanópolis, in the north of Paraná, the reference
laboratory of the World Organization of Animal Health (OIE) in Weybridge, UK,
issued a report Confirming, once again, that there was an atypical
manifestation of the disease.
A emissão do laudo
ocorreu em 21 de novembro passado, após realização de ensaios “in vivo” com
camundongos e testes moleculares complementares. The report was issued on
November 21, after performing in vivo tests with mice and complementary
molecular tests. O laudo mantém o Brasil com status de “risco insignificante”
para a doença junto ao órgão internacional, que é o status de maior segurança.
The report maintains Brazil with status of "insignificant risk" for
the disease with the international body, which is the status of greater
security.
CREDIBILIDADE - De
acordo com o laudo, o serviço veterinário oficial do Paraná, representado pela
Agência de Defesa Agropecuária do Paraná (Adapar), autarquia vinculada à
Secretaria da Agricultura e Abastecimento, “cumpriu rigorosamente o que é
preconizado no Código Sanitário para Animais Terrestres da OIE, quanto às ações
de vigilância para a “doença da vaca louca” - encefalopatia espongiforme
bovina. CREDIBILITY - According to the report, the official veterinary service
of Paraná, represented by the Agrarian Defense Agency of Paraná (Adapar), an
agency linked to the Secretariat of Agriculture and Supply, "strictly
complied with the provisions of the Terrestrial Animal Health Code of OIE, on
surveillance actions for "mad cow disease" - bovine spongiform
encephalopathy.
“Foi seguido todo o
protocolo para doenças com síndrome nervosa e conseguimos chegar nesse
diagnóstico, comprovado pelo laboratório inglês”, afirma o diretor -presidente
da Adapar, médico veterinário Inácio Kroetz. "The entire protocol for
diseases with nerve syndrome has been followed and we have been able to arrive
at this diagnosis, as proven by the English laboratory," says the
director-president of Adapar, veterinary doctor Inácio Kroetz. “Com isso, a
Adapar saiu fortalecida e com credibilidade perante a OIE”, acrescentou Kroetz.
"With that, Adapar was strengthened and credible before the OIE,"
added Kroetz.
Os estudos realizados na
Inglaterra mostram que a chance de ocorrência da doença na forma atípica, como
foi verificada no Paraná, é de 0,35 casos por um milhão de bovinos testados.
Studies conducted in England show that the chance of occurrence of the disease
in the atypical form, as verified in Paraná, is 0.35 cases per one million
cattle tested.
Portanto, o fato de o
Paraná ter sido capaz de detectar a ocorrência da doença nesta forma, comprova
a lisura e a sensibilidade da vigilância sanitária para a doença. Therefore,
the fact that Paraná was able to detect the occurrence of the disease in this
way, proves the smoothness and sensitivity of sanitary surveillance for the
disease.
CASO - Em dezembro de
2010, foi atendido um caso de morte de um bovino no município de Sertanópolis e
o protocolo de investigação para síndrome nervosa foi aplicado para descartar
ocorrência de raiva bovina, pois havia sido registrado caso anterior dessa
doença, nessa propriedade. CASE - In December 2010, a case of death of a bovine
animal in the municipality of Sertanópolis was attended and the protocol of
investigation for nervous syndrome was applied to rule out the occurrence of
bovine rabies, since it had been registered previous case of this disease, in
this property.
Tratava-se de uma vaca,
com 13 anos de idade, sem apresentar sinais neurológicos, que veio a morrer na
propriedade, de causa natural ou indefinida. It was a cow, 13 years old,
without presenting neurological signs, that died in the property, of natural or
indefinite cause.
Foram coletadas partes
específicas do sistema nervoso central do animal para análise nos laboratórios
do Serviço Veterinário Oficial que, após vários estudos, detectou a presença do
príon, inicialmente sem especificar se na forma clássica, ou atípica. Specific
parts of the central nervous system of the animal were collected for analysis
in the laboratories of the Official Veterinary Service which, after several
studies, detected the presence of the prion, initially without specifying
whether in the classical or atypical form.
Estudos complementares,
à época, diagnosticaram a forma atípica da doença, portanto, de menor
gravidade. Complementary studies, at the time, diagnosed the atypical form of
the disease, therefore, of lesser severity. A amostra continuou sendo avaliada
para diagnóstico confirmatório no laboratório do Reino Unido, que fez testes
biológicos durante quatro anos, o que permitiu concluir que se tratava
indiscutivelmente de um príon da forma atípica. The sample continued to be
evaluated for confirmatory diagnosis in the UK laboratory, which did biological
tests for four years, which allowed to conclude that it was indisputably a
prion of the atypical form.
A simples detecção do
príon em bovinos de idade avançada não permite afirmar que se trata de
encefalopatia espongiforme bovina na sua forma clássica e, devido a isto,
vários estudos complementares foram levados a efeito. The simple detection of
the prion in older bovine animals does not allow the assertion that it is
bovine spongiform encephalopathy in its classical form and because of this a
number of complementary studies have been carried out. O primeiro diagnóstico
seguro que detectou o príon neste caso, e no Brasil, ainda assim na sua forma
atípica, foi registrado em 2012. The first reliable diagnosis that detected the
prion in this case, and in Brazil, even in its atypical form, was registered in
2012.
FORMAS DA DOENÇA -
Segundo o diretor presidente da Adapar, atualmente são conhecidas duas formas
de encefalopatia espongiforme bovina, a clássica e a atípica, que são
diferentes quanto à epidemiologia. FORMS OF DISEASE - According to Adapar's
CEO, two forms of bovine spongiform encephalopathy, classical and atypical, are
now known, which are different in epidemiology.
A forma clássica é
transmitida por rações contaminadas com o príon e pode ocorrer quando bovinos
jovens ingerem rações que contenham proteína de origem animal, de bovinos
principalmente – no caso farinhas de carne – quando os animais que deram origem
a estas farinhas tenham sido portadores do príon. The classical form is
transmitted by feeds contaminated with the prion and may occur when young
bovines ingest feeds containing animal protein, mainly bovine - in the case of
meat meal - when the animals that gave rise to these flours have been carriers
of the prion .
E a forma atípica da
doença, como a verificada no Paraná, é causada por príons cuja diferença pode
ser diagnosticada por terem peso molecular maior ou menor do encontrado na
forma clássica. And the atypical form of the disease, such as that found in
Paraná, is caused by prions whose difference can be diagnosed by having a
molecular weight greater or less than that found in the classical form. Esta
forma, até onde se sabe, é de aparecimento espontâneo, não sendo relacionada à ingestão
de alimento contaminado, portanto pode ocorrer em qualquer lugar do mundo,
especialmente em bovinos com idade avançada, acima de nove anos. This form, so
far as it is known, is spontaneous in appearance and is not related to the
ingestion of contaminated food, so it can occur anywhere in the world,
especially in cattle aged up to nine years.
A “doença da vaca
louca”, com nome científico de encefalopatia espongiforme bovina, é causada por
uma partícula de proteína patogênica denominada príon, que degenera o sistema
nervoso central de bovinos. The "mad cow disease", scientifically
named bovine spongiform encephalopathy, is caused by a pathogenic protein
particle called the prion, which degenerates the central nervous system of
cattle.
Como consequência o
animal acometido apresenta sinais nervosos como excitação à luz e a ruídos,
cegueira, falta de coordenação motora, tremores, entre outros. As a
consequence, the affected animal shows nervous signs such as excitation to
light and noise, blindness, lack of motor coordination, tremors, among others.
Porém esses sinais não
são suficientes para o diagnóstico da doença, pois são comuns a outras doenças
do sistema nervoso de bovinos. However, these signs are not enough to diagnose
the disease, as they are common to other diseases of the nervous system of
cattle.
O período de incubação é
longo, em torno de cinco anos até o aparecimento dos primeiros sinais, portanto
pode ser considerada uma doença de animais adultos. The incubation period is long,
around five years until the first signs appear, so it can be considered a
disease of adult animals.
A forma clássica da
doença tem grande impacto socioeconômico, por motivos sanitários,
principalmente porque afeta o comércio internacional de material genético e
carne bovina. The classical form of the disease has a great socioeconomic
impact, due to health reasons, mainly because it affects the international
trade of genetic material and beef.
É fundamental e
obrigatória a comunicação imediata, pelos produtores rurais, às autoridades de
defesa sanitária animal, diante de manifestação clínica de sinais nervosos em
bovinos, principalmente quando manifestados de forma crônica e progressiva,
esclarece o médico veterinário. It is fundamental and obligatory the immediate
communication by the rural producers to the authorities of animal health
protection, in view of the clinical manifestation of nervous signs in cattle,
especially when manifested in a chronic and progressive way, clarifies the
veterinarian.
Também deve ser
denunciado o fornecimento de cama de frango ou outros alimentos que possam
conter proteínas e gorduras de origem animal na alimentação de bovinos. The
supply of poultry litter or other foodstuffs which may contain animal proteins
and fats in the feeding of bovine animals should also be reported.
see also ;
Bovine spongiform
encephalopathy, Brazil
Information received on
02/05/2014 from Dr Figueiredo Marques Guilherme Henrique , Director,
Departamento de Saúde Animal , Ministério da Agricultura, Pecuaria e
Abastecimento , Brasilia, Brazil
>>>Atypical
BSE, or “mad cow” disease, is a form of the prion disease not associated with
the animal’s consumption of feed.<<<
don't you just love it
when the officials just make stuff up $$$
*** What irks many
scientists is the USDA’s April 25 statement that the rare disease is “not
generally associated with an animal consuming infected feed.”
The USDA’s conclusion is
a “gross oversimplification,” said Dr. Paul Brown, one of the world’s experts
on this type of disease who retired recently from the National Institutes of
Health. "(The agency) has no foundation on which to base that statement.”
The present study
demonstrated successful intraspecies transmission of H-type BSE to cattle and
the distribution and immunolabeling patterns of PrPSc in the brain of the
H-type BSE-challenged cattle. TSE agent virulence can be minimally defined by
oral transmission of different TSE agents (C-type, L-type, and H-type BSE
agents) [59]. Oral transmission studies with H-type BSE infected cattle have
been initiated and are underway to provide information regarding the extent of similarity
in the immunohistochemical and molecular features before and after
transmission.
In addition, the present
data will support risk assessments in some peripheral tissues derived from
cattle affected with H-type BSE.
*** This supports the
theory that the importation of BSE contaminated feedstuff is the source of
C-type BSE in Canada.
*** It also suggests a
similar cause or source for atypical BSE in these countries. ***
P.9.21
Molecular
characterization of BSE in Canada
Jianmin Yang1, Sandor
Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1
1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE
BSE Reference Laboratory, Canada; 3University of Calgary, Canada
Background: Three BSE
types (classical and two atypical) have been identified on the basis of
molecular characteristics of the misfolded protein associated with the disease.
To date, each of these three types have been detected in Canadian cattle.
Objectives: This study was conducted to further characterize the 16 Canadian
BSE cases based on the biochemical properties of there associated PrPres.
Methods:
Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase
K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases
was determined using modified Western blot analysis.
Results: Fourteen of the
16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian
H and L-type BSE cases exhibited size shifts and changes in glycosylation
similar to other atypical BSE cases. PK digestion under mild and stringent
conditions revealed a reduced protease resistance of the atypical cases
compared to the C-type cases. N terminal- specific antibodies bound to PrPres
from H type but not from C or L type. The C-terminal-specific antibodies
resulted in a shift in the glycoform profile and detected a fourth band in the
Canadian H-type BSE.
Discussion: The C, L and
H type BSE cases in Canada exhibit molecular characteristics similar to those
described for classical and atypical BSE cases from Europe and Japan. *** This
supports the theory that the importation of BSE contaminated feedstuff is the
source of C-type BSE in Canada. *** It also suggests a similar cause or source for
atypical BSE in these countries. ***
see page 176 of 201
pages...tss
Singeltary reply ;
Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary
reply ;
P.4.23
Transmission of atypical
BSE in humanized mouse models
snip...see full text
report here ;
Monday, May 5, 2014
Brazil BSE Mad Cow
disease confirmed OIE 02/05/2014
Thursday, September 26,
2013
Brazil evaluate the
implementation of health rules on animal by-products and derived products SRM
BST TSE PRION aka MAD COW DISEASE
Friday, December 07,
2012
ATYPICAL BSE BRAZIL 2010
FINALLY CONFIRMED OIE 2012
Wednesday, December 19,
2012
Scientific Report of the
European Food Safety Authority on the Assessment of the Geographical BSE Risk
(GBR) of Brazil
Wednesday, January 29,
2014
Another Suspect case of
Creutzfeldt-Jakob disease investigated in Brazil
Monday, August 1, 2016
USDA Announces Reopening
of Brazilian Market to U.S. Beef Exports and the Potential for Transmissible
Spongiform Encephalopathy TSE prion disease
Release No. 0175.16
Tuesday, September 27,
2016
Classical Scrapie
Diagnosis in ARR/ARR Sheep in Brazil
Acta Scientiae
Veterinariae, 2015. 43(Suppl 1): 69.
Saturday, April 23, 2016
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.
Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with ef?ciency comparable to that of cattle BSE. While the ef?ciency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.
snip...
R. BRADLEY
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
SCRAPIE WS-01: Prion
diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
P.86: Estimating the
risk of transmission of BSE and scrapie to ruminants and humans by protein
misfolding cyclic amplification
Morikazu Imamura, Naoko
Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama National Institute of Animal
Health; Tsukuba, Japan
To assess the risk of
the transmission of ruminant prions to ruminants and humans at the molecular
level, we investigated the ability of abnormal prion protein (PrPSc) of typical
and atypical BSEs (L-type and H-type) and typical scrapie to convert normal
prion protein (PrPC) from bovine, ovine, and human to proteinase K-resistant
PrPSc-like form (PrPres) using serial protein misfolding cyclic amplification
(PMCA).
Six rounds of serial
PMCA was performed using 10% brain homogenates from transgenic mice expressing
bovine, ovine or human PrPC in combination with PrPSc seed from typical and
atypical BSE- or typical scrapie-infected brain homogenates from native host
species. In the conventional PMCA, the conversion of PrPC to PrPres was
observed only when the species of PrPC source and PrPSc seed matched.
However, in the PMCA
with supplements (digitonin, synthetic polyA and heparin), both bovine and
ovine PrPC were converted by PrPSc from all tested prion strains. On the other
hand, human PrPC was converted by PrPSc from typical and H-type BSE in this
PMCA condition.
Although these results
were not compatible with the previous reports describing the lack of
transmissibility of H-type BSE to ovine and human transgenic mice, our findings
suggest that possible transmission risk of H-type BSE to sheep and human.
Bioassay will be required to determine whether the PMCA products are infectious
to these animals.
>>>Although
these results were not compatible with the previous reports describing the lack
of transmissibility of H-type BSE to ovine and human transgenic mice, our
findings suggest that possible transmission risk of H-type BSE to sheep and
human.<<<
Sunday, August 28,
2016
CONFIDENTIAL
Transmissible Spongiform
Encephalopathy TSE Prion and how Politics and Greed by the Industry spread
madcow type diseases from species to species and around the globe
TSE PRIONS AKA MAD COW
TYPE DISEASE, LIONS AND TIGERS AND BEARS, OH MY!
see more here ;
Tuesday, September 06, 2016
A comparison of classical and H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism in wild type and EK211 cattle following intracranial inoculation
Tuesday, August 9, 2016
Concurrence with OIE Risk Designations for Bovine Spongiform Encephalopathy [Docket No. APHIS-2015-0055]
BILLING CODE: 3410-34-P
DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service
Saturday, July 23, 2016
BOVINE SPONGIFORM
ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND SRM REMOVAL UNITED
STATE OF AMERICA UPDATE JULY 2016
Tuesday, July 26, 2016
*** Atypical Bovine
Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016
Saturday, July 16, 2016
Importation of Sheep,
Goats, and Certain Other Ruminants [Docket No. APHIS-2009-0095]RIN 0579-AD10
WITH great disgust and
concern, I report to you that the OIE, USDA, APHIS, are working to further
legalize the trading of Transmissible Spongiform Encephalopathy TSE Pion
disease around the globe.
THIS is absolutely
insane. it’s USDA INC.
Thursday, August 4, 2016
Secretary's Advisory
Committee on Animal Health [Docket No. APHIS-2016-0046] TSE PRION DISEASE
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
http://jama.jamanetwork.com/article.aspx?articleid=1031186
Terry S. Singeltary Sr.
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