Hello, those of you who are still with me,

As I indicated yesterday, I found it necessary to support my written words
with a diagram. Rather than clog up the system, both Bill Levinson and Simon
Coles have undertaken to make the charts plus the descriptive texts which=20
go with them available on their Web Sites. On this occasion I will also append the Ch=
artC words to this email.  I expect Simon and Bill will post the URLs when they are a=
vailable.

=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=20
=20
         CHART C - SHOWING PRIMARY AND OVERDRIVE AREAS OF OPERATION
         ----------------------------------------------------------
        =20
1) This chart is an 'idealised' version of the chart which is prepared by the
   the subject, when preparing data for my Analysis program. The right hand
   vertical axis is the condition scale, which each person must calibrate by=20
   assigning particular aches,degree of tremo, localised pains, etc to certain s
   values on the scale.  the idea is that if you were to start in the Off=20
   condition, having taken a tablet, the physical changes, feelings, etc.
   which when expressed in the _2 to +2 units, would produce a reasonably
   consistant plot. It takes a bit of practice, but after a bit of practice
   it becomes almost automatic.
  =20
2) The three bell-shaped lines in black represent three tablets, taken at the
   optimum time so that the combined effect is linear, and produces stable=20
   operation in the yellow 'Primary target area. When I first ran the program
   to see if my predictions were correct, the result was almost as good as that,
   apart from the local effect of meals.
  =20
3) Although it was not necessary to pursue the effects beyond the +1 levwl, I
   inevitably at times strayed into the +2 area (by accidentally taking too

much Sinemet), and back in 1994 I wrote:" The computer model appears to=20
   simulate my subjective reaction to levodopa over the mid to low dose range
   (+1=A0to -2, but not over the high dose +1 to +2 ramge. The time duration
   of an overdose condition seems to be out of all proportion to the levodopa=20
   quantity."  At that time, I simply marked it down as oneof life's little
   mysteries and carried on.
  =20
4) When I joined the Parkinsn list, I was amazed to see that several people
   were deliberately driving themselves into the yellow blob which I have=A0
   called the overdrive region, by taking large doses of Sinemet in the early=20
   morning, and then coasting along with a few boosters during the day. (See=20
   the red line.)The strange thing about operating in the overdrive zone is=20
   that it takes less sinemet to get into, and stay in the overdrive region=20
   than it takes to operate in the Primary target.
  =20
5) The people operating in this area seem to agree that although many PD=20
   symotoms remain, they are milder and can be tolerated. In the interests of
   furthering the cause of science, I tried driving myself up the red line,
   by taking an extra Sinemet 100/25 when I got up in the morning. I had no
   trouble getting into the overdrive region, and found that for me, the=20
   level of dyskinesia was totally unacceptable, and did terrible things to=20
   my collapsed vertebrae. Maybe it varies for different people, or maybe
   they just grit their teeth and carry on, but I couldn't live like that.
  =20
6) The people who use this method of operation agree on one key fact: At the
   end of the day, these high-flyers have got to come down to the ground.=20
   As the subjects descend through the no-mans zone around condition =3D1 ,=20
   they have to run the gauntlet of really strong dykinesias - there is=20
   apparently no escaping it.=20
  =20
   I wonder if this is your diphasic dyskinesia, David ?
  =20
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D

Another entirely unrelated possibility occurs to me, concerning the=20
protective  properties of Carbidopa, whose job is to protect the levodopa
as it travels from the small intestine to the brain. We know that only a=20
fraction of the original intake survives the trip, but it appears to me that=20
during the cycle of a single tablet, the Carbidopa could go through phases
in which it was more or less successful at its job. Thus we could find that
as the end of the cycle for that tablet, the Carbidopa finally bludgeons
the opposition into submission, thus allowing a strong dose of Sinemet=20
through at the end.
Regards,
--=20
Brian Collins  <[log in to unmask]>