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ANTI-AGING
BIOMEDICINE.
HIGH TECH BIO-MEDICAL TECHNOLOGIES FOR DISEASE TREATMENT
AND LIFE EXTENSION.
EXPERIMENTAL AND CLINICAL DATA.
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Klinika Neurologii Instytutu Neurologii
Collegium Medicum Uniwersytetu Jagiellonskiego ul. Botaniczna
3, 31-503 Krakow.
Autonomic dysfunction in idiopathic
Parkinson's disease (IPD) is common and occurs in
70% of patients. The aim of the study was to evaluate
autonomic mechanisms regulating cardiovascular system
during tilt up test in IPD patients. The examination
was performed in 35 patients with IPD (26 male and
9 female, mean age 60 +/- 9) and matched with gender
and age 35 controls subjects (healthy volunteers,
mean age 59 +/- 9). Patients were divided into two
groups: group I--early stage of disease (n = 20) and
group II--advanced stage of the disease (n = 15).
The tilt test in IPD patients and in the control group
lasted 3 minutes. In both groups tilt test was performed
with a head-up tilt position of 60 degrees (tilt table
Manumed, Netherlands). In both groups 30:15 ratio
were lower than in the control group 1.03 +/- 0.08,
0.97 +/- 0.09 v 1.23 +/- 0.1 respectively (p = 0.001).
In the second group the heart-rate variability after
the tilt test was lower 6.2 +/- 4/min than in the
control group 10.2 +/- +/- 1.9/min and group I 8.8
+/- 4/min (p = 0.01). The decrease of the systolic
pressure in response to the tilt test was the highest
in group II (16 +/- 14 mmHg), in the control group
4 +/- 7 mmHg, in group I 13 +/- 11 mmHg (p = 0.001).
Ortostatic hypotension in IPD occurs in 36% of patients
in an early stage and in 47% of patients in an advanced
stage of the disease. The use of the tilt test enables
the early diagnosis of cardiovascular disturbances
in IPD.
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Nervenklinik und Poliklinik,Neurologie,
Universitatskliniken des Saarlandes,Homburg/Saar.
Patients with idiopathic Parkinson's
disease display a 60% degeneration of the nigrostriatal
neurons before motor symptoms have progressed enough
to allow clinical diagnosis. It is clear that any
neuroprotective therapy starting at such a late stage
can have no substantial effect on the disease progression.
Therefore, earlier diagnosis must be the goal of future
research,when at most mild motor or non-motor symptoms
are present or when only risk factors can be identified.
Evidence of various gene mutations associated with
idiopathic Parkinsonism raise the hope that these
or other biological markers will allow earlier identification
of patients at risk. A possibly significant vulnerability
factor for developing Parkinson's disease can also
be demonstrated by means of transcranial sonography.
Since the individual tests are not sufficiently specific
or sensitive, a gradual, precise, and inexpensive
battery of tests needs to be developed for the successful
identification of a risk group for this disease. The
extent of damage to the dopaminergic system in these
patients can be quantified using nuclear techniques.
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Divisione di Medicina Interna,
Ospedale di Circolo, Universita dell'Insubria, Viale
Borri 57, 21100 Varese, Italy.
BACKGROUND: Different coagulation
abnormalities according to stroke subtypes have been
reported. We have assessed the clinical utility of
D-dimer, a product of fibrin degradation, in the early
diagnosis of stroke subtypes. METHODS: Patients hospitalized
after an acute ischemic cerebrovascular event underwent
D-dimer assay (STA Liatest D-Dimer) (reference level,
<0.50 micro g/mL) on days 1, 6 +/- 1, and 12 +/-
1 and were studied to identify stroke subtypes. RESULTS:
We included 126 patients (mean age, 75.5 years) and
63 age-matched control subjects. Stroke subtypes were
cardioembolic in 34 patients (27%), atherothrombotic
in 34 (27%), lacunar in 31 (25%), and unknown in 27
(21%). At all 3 measurements, D-dimer levels were
significantly higher in the cardioembolic group (mean
+/- SEM, 2.96 +/- 0.51, 2.58 +/- 0.40, and 3.79 +/-
0.30 micro g/mL, respectively) than in the atherothrombotic
(1.34 +/- 0.21, 1.53 +/- 0.26, and 2.91 +/- 0.23 micro
g/mL, respectively) (P<.05) and lacunar (0.67 +/-
0.08, 0.72 +/- 0.15, and 0.64 +/- 0.06 micro g/mL,
respectively) groups (P<.01). The difference was
also significant between the latter 2 groups (P<.01).
We found no difference between the lacunar group and
controls (0.53 +/- 0.14 micro g/mL). According to
day 1 measurements, the optimal cutoff point for predicting
cardioembolic stroke was 2.00 micro g/mL, resulting
in a specificity of 93.2% and in a sensitivity of
59.3%. For predicting lacunar stroke, the cutoff point
was 0.54 micro g/mL, with a specificity of 96.2% and
a sensitivity of 61.3%. CONCLUSION: The increasing
use of the D-dimer assay in clinical practice could
be extended to patients presenting with acute cerebrovascular
ischemic events to help predict stroke subtype.
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Research Institute Neurosciences
Vrije Universiteit, Department of Neurology, Vrije
Universiteit Medical Center, Amsterdam, The Netherlands.
Olfactory dysfunction is a
common finding in patients with Parkinson's disease
(PD). As most studies reported on odor identification
in more advanced and treated PD, we administered an
odor detection, discrimination, and identification
test to a heterogeneous, partly de novo, group of
patients. Forty-one non-demented PD patients, 24 of
whom had untreated early PD, and 18 healthy controls,
were examined. Odor identification and discrimination
data were corrected for odor detection scores. PD
patients scored significantly lower on all olfactory
tests. Interestingly, the subgroup of de novo patients
with early PD also showed significant olfactory disturbances
compared with healthy subjects. Within the PD group,
using multiple regression analysis, we found a significant,
negative correlation between odor discrimination measures
and disease The present study is the first to describe
decreased performance of PD patients on odor discrimination,
in addition to the already well-established deficits
in odor detection and identification. Furthermore,
odor discrimination measures were related to disease
severity, possibly indicating that at least some aspects
of olfactory dysfunction in PD may be secondary to
ongoing degenerative processes in PD. As significant
olfactory impairments were found in early, de novo
PD, olfactory tests may be useful in the early diagnosis
of PD.
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Department of Neurology, University
of Saarland, Gebaude 90, 66421 Homburg/Saar, Germany.
In idiopathic Parkinson's disease
(IPD) approximately 60 % of the nigrostriatal neurons
of the substantia nigra (SN) are degenerated before
neurologists can establish the diagnosis according
to the widely accepted clinical diagnostic criteria.
It is conceivable that neuroprotective therapy starting
at such an 'advanced stage' of the disease will fail
to stop the degenerative process. Therefore, the identification
of patients at risk and at earlier stages of the disease
appears to be essential for any successful neuroprotection.
The discovery of several genetic mutations associated
with IPD raises the possibility that these, or other
biomarkers, of the disease may help to identify persons
at risk of IPD. Transcranial ultrasound have shown
susceptibility factors for IPD related to an increased
iron load of the substantia nigra. In the early clinical
phase, a number of motor and particularly non-motor
signs emerge, which can be identified by the patients
and physicians years before the diagnosis is made,
notably olfactory dysfunction, depression, or 'soft'
motor signs such as changes in handwriting, speech
or reduced ambulatory arm motion. These signs of the
early, prediagnostic phase of IPD can be detected
by inexpensive and easy-to-administer tests. As one
single instrument will not be sensitive enough, a
battery of tests has to be composed measuring independent
parameters of the incipient disease. Subjects with
abnormal findings in this test battery should than
be submitted to nuclear medicine examinations to quantify
the extent of dopaminergic injury and to reach the
goal of a reliable, early diagnosis.
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MRC Cyclotron Unit, Hammersmith
Hospitals, London, United Kingdom.
Current accepted clinical criteria
for the diagnosis of Parkinson's disease (PD) provide
high sensitivity for detecting parkinsonism but generally
show poor specificity for identifying brainstem Lewy
body disease. Biochemical markers that can be used
to reliably diagnose clinical and preclinical PD have
thus far been sought unsuccessfully. It is now known
that some PD kindreds have a mutation of the alpha-synuclein
gene, but this cannot be used as a genetic marker
for most familial and sporadic cases. Functional imaging
provides a means of discriminating typical from atypical
PD, revealing characteristic patterns of loss of dopaminergic
function. In addition, PET and SPECT show preserved
levels of striatal metabolism and dopamine receptor
binding in PD, whereas levels are reduced in the atypical
variants. [18F]Dopa PET can also detect preclinical
PD. In one series there was a reported 40% prevalence
of preclinical dopaminergic dysfunction in asymptomatic
adult relatives of familial PD patients. Finally,
PET and SPECT can both be used to follow PD progression
objectively. Such studies suggest an annual 4 to 12%
loss of dopamine terminal function in early PD and
a preclinical disease window of only a few years.
In the future, functional imaging is likely to play
an increasingly important role in assessing the efficacy
of putative neuroprotective agents.
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Department of Neurology, North
Shore University Hospital/Cornell University Medical
College, Manhasset, NY 11030, USA.
Early-stage Parkinson's disease
(EPD) is often clinically asymmetric. We used 18F-fluorodeoxyglucose
(FDG) and PET to assess whether EPD can be detected
by a characteristic pattern of regional metabolic
asymmetry. To identify this pattern, we studied 10
EPD (Hoehn and Yahr stage I) patients (mean age 61.1
+/- 11.1 years) using 18F-FDG and PET to calculate
regional metabolic rates for glucose. The scaled subprofile
model (SSM) was applied to metabolic asymmetry measurements
for the combined group of EPD patients and normal
subjects to identify a specific covariation pattern
that discriminated EPD patients from normal subjects.
To determine whether this pattern could be used diagnostically,
we studied a subsequent group of five presumptive
EPD patients (mean age 50.9 +/- 18.3), five normal
subjects (mean age 44.6 +/- 15.3), and nine patients
with atypical drug-resistant early-stage parkinsonism
(APD) (mean age 44.6 +/- 14.0). In each member of
this prospective cohort, we calculated the expression
of the EPD-related covariation pattern (subject scores)
on a case-by-case basis. We also studied 11 of the
EPD patients, five patients with APD, and 10 normal
subjects with 18F-fluorodopa (FDOPA) and PET to measure
presynaptic nigrostriatal dopaminergic function, and
we assessed the accuracy of differential diagnosis
with both PET methods using discrimination analysis.
SSM analysis disclosed a significant topographic contrast
profile characterized by covariate basal ganglia and
thalamic asymmetries. Subject scores for this profile
accurately discriminated EPD patients from normal
subjects and APD patients (p < 0.0001). Group assignments
into the normal or parkinsonian categories with FDG/PET
were comparable to those achieved with FDOPA/PET,
although APD and EPD patients were not differentiable
by the latter method. Metabolic brain imaging with
FDG/PET may be useful in the differential diagnosis
of EPD.
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MRC Cyclotron Unit, Hammersmith
Hospital, London, U.K.
A number of neurodegenerative
diseases can manifest as parkinsonian disorders. Structural
imaging, such as CT and MRI, is of limited value for
differentiating these diseases. PET can demonstrate
the selective patterns of disruption of regional cerebral
metabolism and neurotransmitter systems associated
with subcortical degenerations, such as Parkinson's
disease, striatonigral degeneration, progressive supranuclear
palsy, and corticobasal degeneration. It can also
determine, where underlying Parkinson's disease may
be suspected, whether nigral dysfunction is present
in patients with isolated tremor or drug-associated
rigidity. Finally, PET can detect the presence of
subclinical disruption of the dopaminergic system
in at-risk subjects, such as relatives of patients
with Parkinson's disease, or subjects exposed to nigral
toxins, such as MPTP. With the advent of putative
neuroprotective agents for Parkinson's disease, PET
can help identify patients with early disease who
might benefit from therapy with these agents and monitor
their disease progression.
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Department of Pharmacology, University
of Gothenburg, Sweden.
This paper is a preliminary
report of work aiming to elucidate the possible use
of 5-S-cysteinyl metabolites of catechols in the cerebrospinal
fluid as markers in the early diagnosis of Parkinson's
disease (PD). The rationale for this approach is the
hypothesis that this disorder is caused by a failure
of antioxidative mechanisms to prevent the excessive
autoxidation of dopamine and other catechols that
yields highly reactive and cytotoxic semiquinones
and quinones. 5-S-cysteinyl adducts of these quinones
have been detected in human brains, analyzed postmortem,
and appear to be formed at an increased rate in elderly
individuals, who show an increased loss of dopaminergic
neurons.
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Gertrudis-Klinik Biskirchen,
Parkinson-Zentrum.
Parkinson's disease is a chronic-progressive
neuro-degenerative syndrome, which should be diagnosed
as early as possible because of the therapeutic success
in the beginning. Knowing the initial symptoms and
using modern technical devices like SPECT and PET
we shall be able to influence the course and the prognosis
of the disease positively. The application of a current
combined drug-therapy and in addition physiotherapy,
speech-therapy and psychotherapy enable us to provide
quality of life or to restore it. Repeated treatments
in Parkinson medical centers intensify the efficacy
of therapeutic efforts. Nevertheless even in early
stages patients and physicians can be confronted with
social medical problems like defining the degree of
disability or the time for receiving a pension. The
knowledge of specific disease-related findings will
help to judge all these problems in accordance with
the needs of the patients.
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