From: Rafal Smigrodzki (rms2g@virginia.edu)
Date: Sat Feb 08 2003 - 17:43:40 MST
----- Original Message -----
From: "ct" <tilley314@attbi.com>
To: <extropians@extropy.org>
Sent: Saturday, February 08, 2003 3:51 AM
Subject: RE: Performance enhancement with selegiline
> At 12:56 PM 2/7/2003 -0500, you wrote:
> >gts wrote:
> > > If you were really on top of this subject, Rafal, then I believe you
> > > and I would not be arguing whether selegiline is neuroprotective.
> >
> >### OK, I am just too incompetent to discuss PD with you.
>
> I think it is just a temporary side-effect of off label camaro use!
### Yep, these accelerations can make your eyeballs bounce off the back of
your skull and cause a repetitive concussion injury :-)
Thanks for quoting the American Academy of Neurology practice parameters -
these are the authoritative summaries of available data, and I should have
mentioned them myself - after all, this is what I try to use in my daily
practice whenever possible.
Rafal
-----------------------------
> ====================================================
> PD ~560,000 patients in US
> ~$11billion per annum for PD medication alone
> ====================================================
> Research has shown that levodopa can increase the risk of heart disease in
> Parkinson's patients.
> January 30, 2003 3:58 PM GMT (Datamonitor) - A study published in the
Archives
> of Neurology suggests a link between levodopa and increased homocysteine
> levels. This new evidence of adverse side effects will increase the demand
for
> treatments that can delay the need for levodopa.
> ===========================================================
> http://archneur.ama-assn.org/issues/current/abs/noc20099.html
> ...patients with Parkinson disease (PD) may have elevated homocysteine
> levels resulting from methylation of levodopa and dopamine by catechol
> O-methyltransferase, an enzyme that uses S-adenosylmethionine as a methyl
> donor and yields S-adenosylhomocysteine. Since S-adenosylhomocysteine is
> rapidly converted to homocysteine, levodopa therapy may put patients at
> increased risk for vascular disease by raising homocysteine levels...
> Patients whose homocysteine levels were in the higher quartile had
> increased prevalence of CAD (relative risk, 1.75...
> ===========================================================
> http://www.aan.com/professionals/practice/pdfs/int_par.pdf
> ... Specific questions include:
> 1) does selegiline offer neuroprotection;
> 2) what is the best agent with which to initiate symptomatic treatment in
> de novo PD...
> Using evidence-based principles, a literature review using MEDLINE,
EMBASE,
> and the Cochrane Library was performed to identify all human trials in de
> novo PD between 1966and 1999. Only articles that fulfilled class I or
class
> II evidence were included.
>
> Based on this review, the authors conclude:
> 1) Selegiline has very mild symptomatic benefit (level A, class II
> evidence) with no evidence for neuroprotective benefit(level U, class II
> evidence).
> 2) For PD patients requiring initiation of symptomatic therapy, either
> levodopa or a DA can be used (level A, class I and class II evidence).
> Levodopa provides superior motor benefit but is associated with a higher
> risk of dyskinesia.
>
> Ideally, if a drug were available, initial treatment of PD should slow
> disease progression. Once symptomatic benefit is required, treatment
should
> reduce disability without inducing complications over the long term.
>
> 4. Dopamine agonists are effective for all features of the disease, but
are
> not generally as effective as levodopa and are more expensive than
> levodopa(class I, II).
> 5. Selegiline. Class I evidence suggests a mild therapeutic and partial
> protective effect from selegiline,but confirmation of the neuroprotective
> effect is needed. Selegiline also has antidepressant activity that offers
> modest direct symptomatic benefit for PD
>
> The goal of treatment should be to obtain an optimal reduction of
> parkinsonism with a minimal risk of long-term side effects.
>
> Given the controversy generated by the report of Lees et al. that
mortality
> was increased in patients with PD taking selegiline, studies utilizing
> selegiline in patients already receiving symptomatic therapy were included
> to address the safety of selegiline in this patient population.
>
> Selegiline.What is the role of selegiline in the treatment of early PD?A
> neuroprotective benefit of selegiline through decreased free radical
> production was proposed and resulted in the DATATOP (Deprenyl and
> Tocopherol Antioxidative Therapy of Parkinsonism) clinical trial.
> There is no convincing evidence for increased mortality with selegiline
> whether it is given in combination with levodopa or as monotherapy (class
II).
>
> Recommendations for patients with PD who require symptomatic treatment
> * Initial symptomatic treatment of patients with PD with selegiline in
> order to confer mild,symptomatic benefit prior to the institution of
> dopaminergic therapy may be considered (level A, class II evidence).
> * There is insufficient evidence to recommend the use of selegiline to
> confer neuroprotection in patients with PD (level U).
>
> Conclusions. Cabergoline, ropinirole, and pramipexole treatment of PD
> patients requiring dopaminergic therapy results in fewer motor
> complications(wearing off, dyskinesias, on-off motor fluctuations)than
> levodopa treatment after 2.5 years of follow-up.Cabergoline, ropinirole,
> and pramipexole treatment of PD patients requiring dopaminergic therapy is
> associated with more frequent adverse events including hallucinations,
> somnolence, and edema than levodopa therapy.
> Recommendations. In patients with PD who require the initiation of
> dopaminergic treatment, either levodopa or a dopamine agonist may be used.
> The choice depends on the relative impact of improving motor disability
> (better with levodopa) compared with the lessening of motor complications
> (better with dopamine agonists) for each individual patient with PD (level
> A,class I and class II evidence).
> =============================================================
> Time for one of those Bayesian network thingees.
>
>
>
>
>
> [The Maxwell and Dirac equations, for example, govern most of physics and
> all of chemistry and biology. So, in principle we should be able to
predict
> human behavior, though I can't say I've had much success myself] --Hawking
>
>
>
>
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