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The value of screening for Down's syndrome in a
socioeconomically deprived area with a high ethnic
population
Ford C.; Moore A.J.; Jordan P.A.; Bartlett W.A.; Wyldes M.P.;
Jones A.F.; MacKenzie W.E.
Dr. C. Ford, Department Clinical Biochemistry, Birmingham
Heartlands Hospital, Bordesley Green, Birmingham B9 5ST United
Kingdom
British Journal of Obstetrics and Gynaecology (United
Kingdom), 1998, 105/8 (855-859)
Objective: To assess the utility of biochemical antenatal
screening for Down's syndrome in a socioeconomically deprived
area with a high proportion of Asian women from the Indian
Subcontinent.
Design: Audit of Down's syndrome biochemical screening
service over a four-year period.
Setting: Teaching hospital and community antenatal clinic
in inner city Birmingham.
Population: Women booked between October 1992, and December
1996.
Methods: Blood for screening was collected between 14 and
21 weeks gestation, alpha-fetoprotein and intact human
chorionic gonadotrophin were measured in serum and the risk of
Down's syndrome was calculated.
Main outcome measures: Uptakes of screening and
amniocentesis, screen positive rate, odds of being affected
given a positive result, miscarriages associated with
amniocentesis offered following a high risk result, detection
rate, number of Down's cases prevented and a cost analysis.
Outcome measures were compared between Asians and
Caucasians.
Results: Overall 11,974 women (71%) accepted serum
screening. The screen positive rate was 8.3% in Asians and
5.0% in Caucasians. The uptake of amniocentesis in women
following a high risk result was 54% overall (35% Asian, 67%
Caucasian). Nineteen cases of Down's syndrome were identified,
of which 13 occurred in women who opted for biochemical
screening. The detection rate of the biochemical screening
programme was 85% (11/13). Of these 11 cases, six (none of
whom were Asian) elected to have an amniocentesis, of whom
four thereafter had a termination.
Conclusion: In this study the public health benefits of
screening for Down's syndrome in a socioeconomically deprived
area with a high Asian population, were small.
Congenital disorders sharing oxidative stress and
cancer proneness as phenotypic hallmarks: Prospects for joint
research in pharmacology
Pagano G.; Korkina L.G.; Brunk U.T.; Chessa L.; Degan P.; Del
Principe D. ; Kelly F.J.; Malorni W.; Pallardo F.; Pasquier
C.; Scovassi I.; Zatterale A.; Franceschi C.
G. Pagano, Italian National Cancer Institute, Fondazione G,
Pascale, I-80131 Naples Italy
Medical Hypotheses (United Kingdom), 1998, 51/3
(253-266)
In spite of very distinct genotypic assets, a number of
congenital conditions include oxidative stress as a phenotypic
hallmark. These disorders include Fanconi's anaemia, ataxia
telangiectasia, xeroderma pigmentosum and Bloom's syndrome, as
well as two frequent congenital conditions: Down's syndrome
and cystic fibrosis. Cancer proneness is a clinical feature
shared by these disorders, while other manifestations include
early ageing, neurological symptoms or congenital
malformations. The onset of oxidative stress has been related
to excess formation, or defective detoxification, of reactive
oxygen species (ROS). This can arise from either the abnormal
expression or inducibility of ROS-detoxifying enzymes, or by
defective absorption of nutrient antioxidants. Resulting
oxidative injury has been characterized through: (i) DNA,
protein or lipid oxidative damage; (ii) excess ROS formation
(in vitro and ex vivo); (iii) sensitivity to oxygen-related
toxicity; (iv) improvement of cellular defects by either
hypoxia or antioxidants; and (v) circumstantial evidence for
in vivo oxidative stress (as e.g. clastogenic factors).
Investigations conducted so far have been confined to
individual disorders. Comparative studies of selected
indicators for oxidative stress could provide further insights
into the pathogenesis of each individual condition. Such a
unified approach may have wide-ranging consequences for
studies of ageing and cancer.
Glucose effects on cognition in adults with Down's
syndrome
Manning C.A.; Honn V.J.; Stone W.S.; Jane J.S.; Gold
P.E.
C.A. Manning, Department of Neurology, Box 394, Univ. of
Virginia Hlth. Sci. Center, Charlottesville, VA 22908 United
States
Neuropsychology (United States), 1998, 12/3
(479-484)
Glucose enhances memory in a variety of individuals,
including people with Alzheimer's disease. By 35 years of age,
adults with Down's syndrome (DS) develop the characteristic
plaques and tangles found in Alzheimer's disease, despite
findings indicating that not all older DS individuals meet
criteria for dementia. To examine the possibility that glucose
enhances memory in adults with DS (mean age = 35 years, range
= 19-55 years), adults with DS were given a battery of tests
specifically designed for individuals with DS in glucose and
control conditions. No participant met criteria for dementia,
regardless of age. Glucose enhanced performance on tests
requiring both long-term memory and auditory processing. In
addition, increased age was associated with poorer performance
on the majority of tests in the control condition, indicating
that cognitive decline with aging may be more prevalent in DS
than previously believed.
The influence of maternal weight correction
formulas in Asian Down syndrome screening using
alpha-fetoprotein and free beta- human chorionic
gonadotropin
Hsu J.J.; Hsieh T.T.; Soong Y.K.; Kuo B.
Dr. J.J. Hsu, Department Obstetrics and Gynecology, Chang
Gung Memorial Hospital, 199 Tung-Hwa North Road, Taipei
Taiwan
Journal of Maternal-Fetal Investigation (United States),
1998, 8/2 (66-70)
Objective: To investigate the relationship between maternal
weight and serum alpha-fetoprotein (AFP) and free beta-human
chorionic gonadotropin (beta-hCG) levels and to determine the
methodology of correction formulas for influencing the results
of Down syndrome screening in an Asian population.
Methods: 8194 normal singleton pregnancies without any
congenital anomalies were screened using AFP and free beta-hCG
between 14 and 22 weeks of gestation. Down syndrome risk was
calculated by bivariate gaussian algorithm that combined
information from the two biochemical measurements and maternal
age. The all points regression method and median regression
method were used to approach the study cases. Linear and
quadratic regression correction formulas for AFP and free
beta-hCG, either in analyte multiples of the median (MoM) or
log analyte MoM, against maternal weight have been proposed in
this study.
Results: The mean maternal weight is 54.95 plus or minus
7.36 kg in Taiwanese pregnant women during the second
trimester. There is a distinctly inverse relationship between
maternal weight and serum marker levels. The log quadratic
regression correction formula was the most satisfactory
equation fit to the distribution of both AFP and free beta-hCG
levels with a wide weight range. Routine weight correction may
have the small benefit of reducing the screen-positive rate
0.36% at the risk cut-off level of 1:270.
Conclusions: Maternal weight may affect the AFP and free
beta-hCG levels. Although there is no discernible effect in
maternal weight adjustment, it is worth making weight
corrections for serum marker levels in order to reduce
individual variance.
Rapid and simple prenatal DNA diagnosis of Down's
syndrome
Verma L.; Macdonald F.; Leedham P.; McConachie M.; Dhanjal
S.; Hulten M.
Prof. M. Hulten, Molecular Medicine Research Centre,
Department of Biological Sciences, University of Warwick,
Coventry CV4 7AL United Kingdom
Lancet (United Kingdom), 1998, 352/9121 (9-12)
Background. Prenatal diagnosis of chromosomal abnormality
requires cytogenetic analysis of amniotic fetal cells. The
necessary culture time delays diagnosis, is expensive, and
requires substantial scientific expertise. In a masked
prospective study, we investigated the feasibility of PCR
amplification of chromosome 21 markers for the prenatal
diagnosis of Down's syndrome.
Methods. The study population consisted of 2167 pregnant
women, undergoing amniocentesis for prenatal diagnosis. In
this cohort at least 1.5 mL amniotic fluid was available
surplus to the requirements for traditional diagnostic
methods. DNA was extracted from the surplus amniotic fluid and
amplified in fluorescence-based PCR reactions, with three
small-tandem-repeat markers located on chromosome 21. The
products of the reactions were analysed on a DNA sequencer to
identify the presence of two or three copies of chromosome
21.
Findings. In 2083 (97.4%) of 2139 samples of amniotic fluid
that were not macroscopically blood-stained, two DNA markers
gave an informative and correct result, identifying 2053
fetuses as normal and 30 as having trisomy 21 Down's syndrome
(as confirmed by cytogenetic analysis). An extra marker was
informative in 32 of 41 other clear samples. Thus a total of
99.6% informative results was achieved with these three
markers. Macroscopically bloodstained samples (28 [1.3%]) were
unsuitable for DNA testing. They gave a typical but
non-informative result. There were no false-positive or
false-negative results. Interpretation. The PCR-based DNA
diagnostic test has great potential for improved prenatal
diagnosis of Down's syndrome, with the advantage that results
may be available within a day.
Atypical background somatic mutant frequencies at
the HPRT locus in children and adults with Down
syndrome.
Finette BA; Rood B; Poseno T; Vacek P; Pueschel S; Homans
AC
Department of Pediatrics, University of Vermont, Burlington
05401, USA.
Mutat Res (Netherlands) Jul 17 1998, 403 (1-2)
p35-43
People with Down syndrome are 10-30 fold more likely to
develop leukemia than the normal population. To date, little
is known regarding the molecular mechanisms underlying this
phenomenon. We have previously demonstrated that the
spontaneous somatic mutant frequency (Mf) at a reporter gene,
hypoxanthine-guanine phosphoribosyl transferase (HPRT), from a
normal population showed a strict age dependency with an
exponential increase in Mf from birth to late adolescents with
a subsequent linear 2-5% increase per year in adults. In this
study, we compared HPRT Mf in children and adults with Down
syndrome using the HPRT T-cell cloning assay. We determined
the Mf at the HPRT locus in 27 subjects with Down syndrome
from ages 6 months to 53.4 years. Results demonstrated that
background somatic Mf at the HPRT locus in children and adults
with Down syndrome are not dependent on age as seen in a
normal control population. Results also show that adults with
Down syndrome have a significantly lower Mf than normal
adults, and that children with Down syndrome have a
significantly higher Mf than normal children, although the
latter appears to be due to a decreased cloning efficiency
(CE). These observations demonstrate that the frequency of
spontaneous somatic mutations in children and adults with Down
syndrome are atypical compared to normal controls, and suggest
that the genetic mechanisms associated with background somatic
mutational events in children and adults with Down syndrome
may be different.
Centromeric genotyping and direct analysis of
nondisjunction in humans: Down syndrome.
Shen JJ; Sherman SL; Hassold TJ
Department of Genetics and the Center for Human Genetics,
Case Western Reserve University School of Medicine and
University Hospitals of Cleveland, Cleveland, OH 44106,
USA.
Chromosoma (Germany) Jun 1998, 107 (3) p166-72
In species with chiasmate meioses, alterations in genetic
recombination are an important correlate of nondisjunction. In
general, these alterations fall into one of two categories:
either homologous chromosomes fail to pair and/or recombine at
meiosis I, or they are united by chiasmata that are
suboptimally positioned. Recent studies of human
nondisjunction suggest that these relationships apply to our
species as well. However, methodological limitations in human
genetic mapping have made it difficult to determine whether
the important determinant(s) in human nondisjunction is absent
recombination, altered recombination, or both. In the present
report, we describe somatic cell hybrid studies of chromosome
21 nondisjunction aimed at overcoming this limitation. By
using hybrids to "capture" individual chromosomes 21 of the
proband and parent of origin of trisomy, it is possible to
identify complementary recombinant meiotic products, and
thereby to uncover crossovers that cannot be detected by
conventional mapping methods. In the present report, we
summarize studies of 23 cases. Our results indicate that
recombination in proximal 21q is infrequent in
trisomy-generating meioses and that, in a proportion of the
meioses, recombination does not occur anywhere on 21q. Thus,
our observations indicate that failure to recombine is
responsible for a proportion of trisomy 21 cases.
Elucidating the mechanisms of paternal
non-disjunction of chromosome 21 in humans.
Savage AR; Petersen MB; Pettay D; Taft L; Allran K; Freeman
SB; Karadima G; Avramopoulos D; Torfs C; Mikkelsen M; Hassold
TJ; Sherman SL
Department of Genetics, Emory University School of Medicine,
Atlanta, GA 30322, USA.
Hum Mol Genet (England) Aug 1998, 7 (8) p1221-7
Paternal non-disjunction of chromosome 21 accounts for
5-10% of Down syndrome cases, therefore, relative to the
maternally derived cases, little is known about paternally
derived trisomy 21. We present the first analysis of
recombination and non-disjunction for a large paternally
derived population of free trisomy 21 conceptuses ( n = 67).
Unlike maternal cases where the ratio of meiosis I (MI) to
meiosis II (MII) errors is 3:1, a near 1:1 ratio exists among
paternal cases, with a slight excess of MII errors. We found
no paternal age effect for the overall population nor when
classifying cases according to stage of non-disjunction error.
Among 22 MI cases, only five had an observable recombinant
event. This differs significantly from the 11 expected events
( P < 0.02, Fisher's exact), suggesting reduced
recombination along the non-disjoined chromosomes 21 involved
in paternal MI non-disjunction. No difference in recombination
was detected among 27 paternal MII cases as compared with
controls. However, cases exhibited a slight increase in the
frequency of proximal and medial exchange when compared with
controls (0.37 versus 0.28, respectively). Lastly, this study
confirmed previous reports of excess male probands among
paternally derived trisomy 21 cases. However, we report
evidence suggesting an MII stage-specific sex ratio
disturbance where 2.5 male probands were found for each female
proband. Classification of MII cases based on the position of
the exchange event suggested that the proband sex ratio
disturbance was restricted to non-telomeric exchange cases.
Based on these findings, we propose new models to explain the
association between paternally derived trisomy 21 and
excessive male probands.
The 'Severe Impairment Battery': assessing
cognitive ability in adults with Down syndrome.
Witts P; Elders S
S. Tees Community and Mental Health NHS Trust, Normanby,
Middlesbrough, UK.
Br J Clin Psychol (England) May 1998, 37 ( Pt 2)
p213-6
OBJECTIVES: To examine the utility of the 'Severe
Impairment Battery' (SIB--Thames Valley Test Company) in
assessing cognitive ability of adults with Down syndrome .
DESIGN: A within-subject repeated measures design was used
to determine test-retest reliability of the SIB and the
Vineland Adaptive Behaviour Scales (Interview Edition--Survey
Form, 1984) were used to establish SIB criterion validity.
METHODS: Thirty-three adults with Down syndrome (from 152
known to an NHS Trust learning disability service) were
selected on the basis of their or their carers' written
consent. At the first administration of the SIB with the
participant, a staff member completed a Vineland ABS. Thirty
days later, the SIB was readministered to the participant.
RESULTS: Test-retest reliability of the SIB was high as was
criterion validity determined by correlating SIB and Vineland
ABS scores. Floor effects were not encountered.
CONCLUSIONS: The SIB can successfully be used with adults
with Down syndrome to assess cognitive functioning over a wide
range of ability and may be useful, if used longitudinally, in
assessing for deterioration in cognitive functioning
associated with dementia. Methodological limitations are
discussed.
Prenatal diagnosis with use of fetal cells isolated
from maternal blood: five-color fluorescent in situ
hybridization analysis on flow-sorted cells for chromosomes X,
Y, 13, 18, and 21.
Bischoff FZ; Lewis DE; Nguyen DD; Murrell S; Schober W; Scott
J; Simpson JL; Elias S
Department of Obstetrics and Gynecology, Baylor College of
Medicine, Houston, Texas 77030, USA.
Am J Obstet Gynecol (United States) Jul 1998, 179 (1)
p203-9
OBJECTIVE: Currently, prenatal diagnosis of chromosome
abnormalities requires invasive techniques such as
amniocentesis and chorionic villus sampling that carry small
but finite risks of fetal loss. A noninvasive approach is to
isolate fetal cells from maternal blood by flow sorting
followed by genetic interphase analysis with fluorescence in
situ hybridization. Because the ratio of fetal to maternal
cells is relatively low after flow sorting and to detect 90%
to 95% of fetal aneuploidies associated with serious birth
defects, a 5-color fluorescent in situ hybridization strategy
is necessary for simultaneous detection of chromosomes X, Y,
13, 18, and 21 in all flow-sorted nuclei recovered from a
specimen.
STUDY DESIGN: Fetal nucleated red blood cells were isolated
from maternal blood in 40 cases (10.4 to 27.0 weeks'
gestation) by flow cytometry on the basis of positive
selection of CD71+ (transferrin receptor), CD45-, and LDS751
staining. Each case was evaluated for 5-color fluorescent in
situ hybridization efficiency by determining the percentage of
flow-sorted nuclei containing 8 hybridization signals for
chromosomes X, Y, 13, 18, and 21.
RESULTS: A total of 42,312 flow-sorted nuclei from maternal
blood samples were analyzed. In 5 of 16 (31%) cases with a
male fetus, 0.16% of nuclei scored were identified as fetal by
the presence of 1 signal each for chromosomes X and Y. Fetal
trisomy 21 nuclei were accurately detected in 2 cases with a
female fetus, each of which was subsequently confirmed.
CONCLUSIONS: Five-color interphase fluorescent in situ
hybridization analysis can be used to effectively analyze rare
fetal aneuploid nuclei in enriched flow-sorted cells isolated
from maternal blood.
Adoption and fostering of babies with Down
syndrome: a cohort of 593 cases.
Dumaret AC; De Vigan C; Julian-Reynier C; Goujard J; Rosset
D; Ayme S
CERMES-INSERM U.304, Paris, France.
Prenat Diagn (England) May 1998, 18 (5) p437-45
Recently, professionals in France have noticed an increase
in newborns with Down syndrome (DS) being placed for adoption.
The aim of this study was to investigate DS babies given up at
birth for adoption and to consider the possible determinants
of this in order to assess social acceptance of DS. A
retrospective cohort of all living DS babies was collected
from two birth-defect registries (Paris: 1981-1990; Marseilles
area: 1984-1990). Follow-up data were collected:
characteristics of the baby, biological parents and maternity
units, age when given up for adoption, and type of foster
care. The results showed that 19.4 per cent of infants with DS
(115/593) were rejected by their parents. Multiple regression
analysis indicated that foreign origin of the mother, area of
residence, no associated major malformation, maternal age
(15-24 years), and birth rank (> 2) variables were
significantly associated with a lower placement rate. Among
the 115 abandoned infants with DS, 88 came from unknown
parentage (76.5 per cent). For half of them, adoptive
placement (88/115) occurred before the age of 6 months.
Socio-cultural attitudes play a great part in these family
decisions. Equally important is the manner in which
professionals propose adoption as an alternative to these
parents of DS babies. They should be encouraged to consider
all options before making a decision, so that the best
solution can be found for the interest of all.
New triple screen test for Down syndrome: combined
urine analytes and serum AFP.
Bahado-Singh RO; Oz U; Kovanci E; Cermik D; Flores D; Copel
J; Mahoney M; Cole L
Department of Obstetrics and Gynecology, Yale University
School of Medicine, New Haven, CT 06520-8063, USA.
J Matern Fetal Med (United States) May-Jun 1998, 7 (3)
p111-4
In this study we report a new triple test that combines
serum AFP, urine beta-core fragment of hCG, total urine
estriol, and maternal age for calculating individual Down
syndrome odds in the second trimester. The urine beta-core
fragment/estriol ratio was used as a single screening
variable. Analyte levels were measured prospectively in 10
Down syndrome cases and 346 normals. Individual Down syndrome
odds were calculated by multiplying the product of the Down
syndrome likelihood ratios of serum AFP and urine
beta-core/estriol levels by the age-related midtrimester risk.
The screening efficiency of an algorithm that combines urine
beta-core/estriol with maternal age was compared to one that
included serum AFP data. A 90% detection rate for Down
syndrome was obtained at a 4.65% false positive rate. This was
superior to the 75% sensitivity at 5% false positive rate
observed when beta-core/estriol and age alone were used. This
new triple test has a higher screening efficiency than that
generally reported for the traditional serum triple screen and
other urine tests, and it also provides information on the
risk of neural tube defects. If confirmed in larger trials,
the new algorithm could be used as an alternative to the
traditional serum triple screen.
Evidence against the involvement of reactive oxygen
species in the pathogenesis of neuronal death in Down's
syndrome and Alzheimer's disease
Hayn M.; Kremser K.; Singewald N.; Cairns N.; Nemethova M.;
Lubec B.; Lubec G.
Department of Pediatrics, University of Vienna,
Wahringer-Gurtel 18-20, A-1090 Vienna Austria
Life Sciences (USA), 1996, 59/7 (537-544)
It has been proposed that the pathogenesis of Down's
Syndrome (DS) involves reactive oxygen species (ROS) arising
from a gene dosage effect that disproportionately elevates
superoxide dismutase (SOD1) activity. It was also suggested
that generation of ROS might be responsible for neuronal death
in Alzheimer's Disease (AD). Little data on brain ROS in DS
and AD exist; therefore, we determined activities of choline
acetyltransferase (CHAT) and of the oxidative defense enzymes
SOD1 and glutathione peroxidase (GSHPx) in frontal cortex of
aged patients with DS and AD. We also measured levels of
malondialdehyde, which reflects lipid peroxidation, and o-
tyrosine, which represents the hydroxyl radical attack. ChAT
was significantly reduced in cortex of patients with DS (-68%)
and AD (-66%) as compared to controls. There were no
statistically significant differences, however, between
controls and both neurodegenerative disorders for SOD1, GSHPx,
malondialdehyde and o-tyrosine. Our data contradict the only
previous finding on increased SOD1 and ROS in brains of
patients with DS: age as well as methodological differences
might account for the discrepancy. In conclusion, no evidence
for a pathogenetic role of SOD1, GSHPx, lipid peroxidation or
hydroxyl radical attack in aged patients with DS and AD could
be provided.
Sequence of deposition of heterogeneous amyloid
beta-peptides of APO E in Down syndrome: Implications for
initial events in amyloid plaque formation
Lemere CA, Blusztajn JK, Yamaguchi H, Wisniewski T, Saido TC,
Selkoe DJ
Center for Neurologic Diseases, Brigham and Women's Hospital,
Harvard Medical School, Boston, Massachusetts 02115,
USA.
Neurobiol Dis 1996 Feb;3(1):16-32
Patients with trisomy 21 (Down syndrome (DS)) progressively
develop amyloid beta-protein (Abeta) deposits and then other
features of Alzheimer's disease (AD) apparently due to
increased gene dosage and thus expression of the beta-amyloid
precursor protein. Because the neuropathological phenotype in
older DS subjects closely resembles that of AD, the
examination of DS brains of increasing age provides a unique
model of the progression of AD. Here, we characterized the
deposition of several Abeta peptides and apolipoprotein E in
formalin-fixed brain sections from 29 DS subjects between 3
and 73 years old. Amyloid plaque number and the percentage of
cortical area they occupied were quantified by computerized
image analysis. Abeta ending at amino acid 42 (Abeta42) was
the earliest form of Abeta deposited in DS cortex. It was
observed in 7 of 16 young (3-30 years) subjects, with the
earliest deposition occurring at age 12. Abeta ending at
residue 40 (Abeta40) was not detected until similarage 30, a
time when degenerating neurites around Abeta immunoreactive
(IR) plaques were first observed, and the frequency of Abeta40
IR plaques then rose with age. Even in old (51-73 years) DS
subjects, Abeta42 IR plaques were always more abundant than
Abeta40 IR plaques. Abeta peptides starting at aspartate 1 or
pyroglutamate 3 were detected in small subsets of compacted,
neuritic plaques beginning around age 30 and rose with age,
the latter species always exceeding the former. Thus, the
N-termini of the Abeta42 peptides abundantly deposited in very
young DS subjects remain unknown. Apo E was detectable in a
small subset of Abeta42 IR plaques beginning at age 12 and
rose steadily with age; it clearly followed the deposition of
Abeta. Our analysis of very young DS brains suggests that
amyloid plaque formation begins with Abeta42-ending peptides,
and the number and percentage of cortical area of Abeta42
plaques increase very little with advancing age, while other
heterogeneous Abeta species and Apo E progressively accrue
onto plaques containing Abeta42.
Vitamin E and Alzheimer's disease in subjects with
Down's syndrome.
Jackson, C. V.; Holland, A. J.; Williams, C. A.; Dickerson,
J. W.
U Surrey Div of Nutrition & Food Science, Guildford,
England
Journal of Mental Deficiency Research 1988 Dec Vol 32(6)
479-484
Tested the hypothesis that a low level of serum Vitamin E
would be associated with a likelihood of dementia in 24 Ss
(aged 30+ yrs) with Down's syndrome. Blood samples were drawn,
and evidence of deterioration in self-care skills was
assessed. Nine Ss showed evidence of Alzheimer's disease (AD),
and 9 did not. Plasma Vitamin E levels measured in Ss with AD
were lower than in Ss without AD. It is suggested that there
may be an interaction between risk of AD and the protective
action of Vitamin E.
Behavioral disorders, learning disabilities and
megavitamin therapy.
LaPerchia, Phyllis
New York City Board of Education, NY, US
Adolescence 1987 Fal Vol 22(87) 729-738
Reviews research on megavitamin nutritional therapy for
learning disabilities in general, schizophrenia, autism,
mental retardation and Down's syndrome, and hyperkinesis.
Methodological problems in the studies are noted, and a
holistic approach to treating the learning and behaviorally
disabled is advocated.
Macrocytosis and cognitive decline in Down's
syndrome.
Hambidge, D. M.
Princess Alexandra Hosp, Swindon, England
British Journal of Psychiatry 1986 Dec Vol 149
797-798
Questions R. L. Welfare and K. E. Hewitt's (see PA, Vol
74:22330) proposal of a causal relationship between cognitive
decline and macrocytosis in Down's syndrome, suggesting that
both may be related to undetected folate vitamin
deficiency.
Treatment approaches in Down's syndrome: A
review.
Foreman, Philip J.; Ward, James
Newcastle Coll of Advanced Education, Australia
Australia & New Zealand Journal of Developmental
Disabilities
Reviews research into treatment approaches in Down's
syndrome, including pharmacological therapy (e.g., thyroid
treatment, 5-hydroxytryptophan (5-HTP), vitamin and mineral
therapy, cell therapy), the G. Doman (1974) program of
movement patterning, early intervention, and facial plastic
surgery.
A double blind study of vitamin B-sub-6 in Down's
syndrome infants: I. Clinical and biochemical results.
Coleman, Mary et al
Georgetown U School of Medicine
Journal of Mental Deficiency Research 1985 Sep Vol 29(3)
233-240
19 infants with Down's syndrome participated in a
double-blind study of the clinical effects of pharmacological
doses of vitamin B-sub-6 administration, starting under 8 wks
of age and continuing until 3 yrs of age. 10 Ss received the
vitamin and 9 the placebo. No statistically significant
differences were found between the 2 groups in mental age,
height, weight, cranial circumference, or tongue protrusion.
Vitamin B-sub-6 significantly elevated whole blood
5-hydroxytryptamine during the 1st yr. A study of side effects
conducted on a larger open population of 400 Down's syndrome
patients (from infants to aged 12 yrs) found vitamin B-sub-6
to be relatively safe when administered over long periods of
time, with photosensitive blisters as the major
complication.
A double blind study of vitamin B-sub-6 in Down's
syndrome infants: II. Cortical auditory evoked
potentials.
Frager, Joseph; Barnet, Ann; Weiss, Ira; Coleman, Mary
Montefiore Hosp & Medical Ctr, Dept of Medicine, New
York, NY
Journal of Mental Deficiency Research 1985 Sep Vol 29(3)
241-246
Recorded cortical auditory evoked potentials (CAEPs) at 1
and at 3 yrs of age in 19 children with Down's syndrome
participating in a double-blind trial of vitamin B-sub-6 and
placebo that was begun in early infancy and continued for 3
yrs. CAEPs have previously been shown to have abnormally high
amplitude in Down's syndrome patients. The CAEPs of the Ss in
the B-sub-6-treated and placebo groups were compared. Only
minor effects were found in the CAEPs recorded at 1 yr of age.
At 3 yrs of age, however, comparison of the B-sub-6-treated
group and the placebo group revealed significant differences
in both amplitudes and latencies of CAEP components.
Peak-to-peak amplitudes of prominent components were
significantly lower in B-sub-6-treated Ss than in their
placebo controls. Amplitude correlated in some cases with
whole blood serotonin levels. Latencies for several prominent
evoked peaks were significantly longer in B-sub-6-treated Ss.
Findings suggest a difference in neurodevelopmental
trajectories that seems to be a pharmacological effect of
B-sub-6 administration. (17 ref)
Xylose absorption in Down's syndrome.
Williams, Celia A. et al
U Surrey, Div of Nutrition & Food Science, Guildford,
England
Journal of Mental Deficiency Research 1985 Jun Vol 29(2)
173-177
Conducted a standard xylose absorption test in 14 25-61 yr
old Ss with Down's syndrome (DS) and in 14 sex- and
age-matched mentally retarded controls; another 30 14-57 yr
olds with DS were similarly investigated. Mentally retarded Ss
as a group had impaired xylose absorption, and the matched DS
Ss had a significantly reduced xylose absorption when compared
to the mentally retarded controls. It is suggested that the
malabsorption plays a role in a number of the vitamin and
mineral deficiencies found in people with DS.
Nutritional aspects of Down's syndrome with special
reference to the nervous system.
Sylvester, Peter E.
St Lawrence's Hosp, Caterham, England
British Journal of Psychiatry 1984 Aug Vol 145
115-120
Reviews studies that demonstrate that patients with Down's
syndrome (DS) are prone to suffer multiple deficiencies of
vitamins and lifelong shortages of some trace metals. A
significant reason for these deficiencies is malabsorption
from the intestine. Reversal and control by treatment of
vitamin deficiencies have been reported. The brain in DS does
not develop adequately; one area, the hippocampus, which is
concerned with memory, is poorly developed. A major
neuropathological feature of DS is premature aging of the
Alzheimer type. The incidence of aging based on pathological
findings is demonstrated and compared with senile changes in
adults with DS. The role of nutrients is discussed in relation
to damage to the mature brain and to the aging process.
Children's mental retardation study is attacked: A
closer look.
Schauss, Alexander G.; Sommars, Elisabeth
American Inst for Biosocial Research, Tacoma, WA
International Journal of Biosocial Research 1982 Vol 3(2)
75-86
Discusses research done to determine whether nutritional
supplements can help mentally retarded children. The research
has come under the attack from the Committee on Nutrition of
the American Academy of Pediatrics (AAP). R. F. Harrell (1981)
reported that when her team took 22 developmentally disabled
children and placed them on vitamin supplements called the
G-T-C formula in a double-blind, crossover study during an
8-mo period, they were able to consistently cause a
significant increase in all the Ss' IQs. Two ongoing studies
in the area of mental retardation and nutritional supplements
are discussed in an effort to determine attempts to
corroborate Harrell's findings. In the 1st study, 60 Down's
Syndrome schoolchildren (aged 7-14 yrs) are involved in a 6-mo
preexamination stage in which they are undergoing a series of
tests, including tests to detect thyroid problems. These tests
have been chosen to disprove a criticism by the AAP that
suggested improvement in the Harrell children may have been
due to a correction in thyroid problem. In the 2nd study, 40
children with Down's Syndrome are being tested, with half the
Ss receiving the G-T-C formula and the other half receiving
placebos. It is concluded that there is much hope for children
with developmental disabilities in nutritional studies that
examine the possibility of brain regeneration.
Effects of nutritional supplementation on IQ and
certain other variables associated with Down syndrome.
Weathers, Caislin
Georgia Mental Health Inst, Atlanta
American Journal of Mental Deficiency 1983 Sep Vol 88(2)
214-217
In a double-blind study, 24 6-17 yr old Down's syndrome
children (Iqs 30-67 at the start of the study) who were living
at home were given a megadose multivitamin/mineral supplement
for 4 mo. A matched group of 23 children received a placebo in
identical form. Ss' IQ (Stanford-Binet Intelligence Scale),
vision, and visual-motor integration (Beery-Buktenica
Developmental Form Sequence) were tested before and after
supplementation, and weekly checks were made to monitor
behavioral changes. No differences were found on any measures
as a result of supplementation. (10 ref)
Vitamin A and carotene values of institutionalized
mentally retarded subjects with and without Down's
syndrome.
Barden, H. S.
U Illinois
Journal of Mental Deficiency Research 1977 Mar Vol 21(1)
63-74
Assessed vitamin A and carotene values of 44 3-34 yr old
Down's syndrome, 56 3-35 yr old non-Down's syndrome mentally
retarded, and 40 normal 1-25 yr old Ss. Dietary and
environmental uniformity was maintained by utilizing Down's
and non-Down's Ss residing in the same institution. Results
show that Down's Ss showed vitamin A values that were
significantly higher than those of the non-Down's retarded Ss
and similar to those of the normal Ss. Carotene values were
similar in the Down's and non-Down's retarded groups, but were
significantly higher than those of the normal Ss. This
difference in carotene is seen as reflecting in part the high
level of carotenoid products in the institutional diet.
Carotene/vitamin A ratio values are reported, and the
possibility that relatively high ratio values reflected a
decreased efficiency in converting carotene to vitamin A is
discussed. It is suggested that Down's Ss may suffer some
impairment in the utilization of vitamin A at its site of
action.
Sodium-dependent glutamate binding in senile
dementia.
McGeer, Edith G.; Singh, Edith A.; McGeer, Patrick L.
U British Columbia, Kinsmen Lab of Neurological Research,
Vancouver, Canada
Neurobiology of Aging 1987 May-Jun Vol 8(3)
219-223
Investigated sodium-dependent glutamate binding as a
possible index of the integrity of glutamate/aspartate nerve
endings in 7 cortical areas from postmortem brains of 15
persons with senile dementia of the Alzheimer type (SD); 10
controls matched for age, sex, and postmortem delay (PMD); and
single cases of Down's syndrome and Parkinson-dementia.
Results show that binding affinities were variable from brain
to brain. Specific binding site densities showed overall a
significant negative correlation with PMD, a significant
decrease in SD, and a significant correlation in the SD
samples with choline acetyltransferase activities.
Alzheimer-like neurotransmitter deficits in adult
Down's syndrome brain tissue.
Godridge, H.; Reynolds, G. P.; Czudek, C.; Calcutt, N. A. et
al
U Nottingham Medical School, Queen's Medical Ctr,
England
Journal of Neurology, Neurosurgery & Psychiatry 1987 Jun
Vol 50(6) 775-778
Analyzed brain tissue taken at necropsy from 5 cases of
Down syndrome and 6 controls for changes in neurotransmitter
markers. Concentrations of noradrenaline (NA), dopamine and
its major metabolite homovanillic acid, and
5-hydroxytryptamine (5-HT) and its metabolite
5-hydroxyindoleacetic acid were determined by high pressure
liquid chromatography, while choline acetyltransferase (ChAT)
was measured by a radiochemical technique. Significant
reductions in NA, 5-HT and ChAT were found in most cortical
and subcortical regions of the Down syndrome tissue.
Neuropathological lesions were also assessed. Results indicate
profound transmitter deficits and neuropathological
abnormalities in adult patients with Down syndrome that
closely resemble those of Alzheimer's disease.
A report on phosphatidylcholine therapy in a Down
Syndrome child.
Cantor, David S.; Thatcher, Robert W.; Ozand, Pinar; Kumin,
Libby et al
U Maryland School of Medicine, Applied Neuroscience Research
Inst, Baltimore
Psychological Reports 1986 Feb Vol 58(1) 207-217
Presents the case of a 21/2-yr-old Downs syndrome (DS) boy
who was given a phosphatidylcholine supplement (150 mg/kg,
day) over a 7-mo period. Measures of the EEG indicate a
normalization during the treatment period with minor
reoccurrence of abnormalities during a placebo period. S
showed a definitive increase in speech and language skills as
well as general motor skills that exceeded same-aged DS peers
experiencing like training programs. Data suggest that
phosphatidylcholine therapy may be useful for improving
neurophysiological and intellectual functioning of some DS
children.
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