Monday, October 31, 2005
Knee developments
Today I took a hike through the woods with our dog. The sky was blue with white fluffy clouds that set off the yellows and reds of the remaining leaves. Hopefully this exercise is not too much to soon for my recently operated on knee. So far so good. My injury has severely limited our walks and I am concerned that Gidget is getting little flabby not to mention me.
Saturday, October 29, 2005
Fox hunt in Stow and knee surgery recovery and oxycontin or oxycodone
The Old North Bridge Hounds held a mock fox hunt in Stow MA at the Delaney park. The day was beautiful and the field was impressive with the women in their black coats with the senior men in their red or “pink” coats. An excellent tea was held at a new member’s house across the street from the park. Because of my knee I was not able to help with laying the drag but arrived in time to congratulate the “Foxes” good efforts. While my knee has improved significantly it is not done yet. There is a continual ache that I treat with ibuprofen or Tylenol avoiding the opiates that worked so well. A friend suggested that oxycontin and oxycodone were different drugs. They are really the same thing. As noted below, drug abusers often take the drug by snorting the powder or injecting an extract to expand the effect. In my past life in drug testing it provided difficulties as it is stronger on a weight basis than heroin and therefore less is used to get high. As less is used there is less in the body and detecting it is more difficult. It is addictive and produces tolerance so should be used only for a short time and with care. I moved to other pain relievers as soon as I could to avoid the problems of tolerance and addiction. For me ibuprofen seems to work better than acetaminophen.
From www.streetdrugs.org
Oxycodone (OxyContin, Percocet, Percodan)
Oxycodone is a central nervous system depressant. Oxycodone's action appears to work through stimulating the opioid receptors found in the central nervous system that activate responses ranging from analgesia to respiratory depression to euphoria. People who take the drug repeatedly can develop a tolerance or resistance to the drug's effects. Thus, a cancer patient can take a dose of oxycodone on a regular basis that would be fatal in a person never exposed to oxycodone or another opioid. Most individuals who abuse oxycodone seek to gain the euphoric effects, mitigate pain, and avoid withdrawal symptoms associated with oxycodone or heroin abstinence.Oxycodone has a high abuse potential and is prescribed for moderate to high pain relief associated with injuries, bursitis, dislocation, fractures, neuralgia, arthritis, and lower back and cancer pain. It is also used postoperatively and for pain relief after childbirth. OxyContin, Percocet, Percodan, and Tylox are trade name oxycodone products.OxyContin is designed to be swallowed whole; however, abusers ingest the drug in a variety of ways. OxyContin abusers often chew the tablets or crush the tablets and snort the powder. Because oxycodone is water soluble, crushed tablets can be dissolved in water and the solution injected. The latter two methods lead to the rapid release and absorption of oxycodone.
Friday, October 28, 2005
Less weight more brain
Ciliary neurotrophic growth factor (CNTF), was first identified as a protein that helps neurons survive and specialize. But researchers studying CNTF found an unexpected side effect: Mice and people given the compound lost their appetite and shed dramatic amounts of weight. And unlike most weight loss drugs, those taking CNTF or a related compound called Axokine didn't have the urge to binge as soon as treatment stopped. "Many of us found the effect absolutely stunning," says Jeffrey Flier of Harvard Medical School in Boston, Massachusetts.
A genetically engineered mutein of CNTF being tested under the name Axokine by Regeneron Pharmaceuticals for treatment of human motor neuron diseases.
Unfortunately people taking Axokine developed antibodies against the drug and the effects were short lived. However, Flier’s studies in mice showed that the drug stimulated neuronal growth in the brain’s hypothalamus know as a regulatory center. More neurons were created that responded to the natural appetite suppressor Leptin thus reducing hunger .
This drug is not a small molecule but a genetically engineered protein and therefore more likely to elicit an immune response than a small molecule. It is interesting that Regeneron is working on a PEGilated version of this protein. This process involves attaching molecules of the short polymer polyethylene glycol to the surface of the protein. The idea is that the PEG molecules keep the immune system from recognizing and attacking the protein so protected. Perhaps there is more to come.
A genetically engineered mutein of CNTF being tested under the name Axokine by Regeneron Pharmaceuticals for treatment of human motor neuron diseases.
Unfortunately people taking Axokine developed antibodies against the drug and the effects were short lived. However, Flier’s studies in mice showed that the drug stimulated neuronal growth in the brain’s hypothalamus know as a regulatory center. More neurons were created that responded to the natural appetite suppressor Leptin thus reducing hunger .
This drug is not a small molecule but a genetically engineered protein and therefore more likely to elicit an immune response than a small molecule. It is interesting that Regeneron is working on a PEGilated version of this protein. This process involves attaching molecules of the short polymer polyethylene glycol to the surface of the protein. The idea is that the PEG molecules keep the immune system from recognizing and attacking the protein so protected. Perhaps there is more to come.
Thursday, October 27, 2005
Embryonic stem cells without killing babies
Advanced Cell Technologies of Worcester MA has developed mouse embryonic stem cells from developing embryos without killing the embryos. If applied to humans this would take away the objection to embryonic stem cells based on the death of the embryo that provided them. ACT has been a leader in human stem cell technology for some time. The cells were taken from the “blastomere” stage of embryonic development. At this state the embryo is a big ball of cells. After the stem cells were removed the blastomeres were put back and development allowed to proceed. The stem cells so isolated were able to maintain their “stemcellness” for 50 generations showing that they were stable in that form and would not degenerate into cancer like forms.
Tuesday, October 25, 2005
Recovery from surgery
Today was rainy but because I am home bound it was not a problem. My brother in law was with us overnight and it was enjoyable talking with him about family and business. Things were going very well with my knee until it did my exercises. The pain increased significantly so I guess that I sort of over did it. I started taking the meds and hope that I can get back to where I was in short order. The Rotary meeting is tomorrow but I don’t think I will be able to make it if things don’t improve.
Monday, October 24, 2005
Arthroscopic surgery complete at Nashoba Valley Hospital
Today the broken cartilage was removed from my injured knee. I was impressed by the friendliness and professionalism of the staff and surgeon. My wife gave great support. I have kept the medications as low as possible and was not in extreme pain. When I was in high school many years ago I broke the meniscus in my left leg. This was before arthroscopic surgery and was more involved as I was in the hospital a couple of days. They did a spinal that gave me severe headaches. This time there were no problems and I was out of the hospital by late afternoon. Medicine advances.
Saturday, October 22, 2005
Fox Hunt with a Wedding
Today was the blessing of the hounds for the Old North Bridge Fox Hunt. This solemn event was combined with the marriage of a hunt member to another hunter from Tennessee. Everything went off beautifully with the marriage ceremony in a green pasture under an arch of flowers. The hunt members attended the wedding on their horses in full dress with “pink” coats and green collars giving three cheers after the bride was kissed. The minister then moved to the waiting hounds and with the newly married couple blessed the hounds. With the festivities completed the riders took off after the hounds through the trails of Concord. I wasn’t able to help lay the drag because of a knee problem but watched with the chief fox who laid the drag as the hounds followed the scent through a field. They did a rather good job of following the scent through the grass. An excellent tea took place after the hunt with abundant champagne. Near the end of the tea my wife called me over to meet someone. It turned out to be the daughter of the master of her first hunt which she joined when we lived in New Jersey. We hadn’t seen Meg in years. It was a real treat.
Friday, October 21, 2005
Macular Degeneration and siRNA
Macular degeneration is the leading cause of severe vision loss in people 60 years of age or older in the United States and throughout many parts of the world.
The treatment for macular degeneration listed below is a major accomplishment for two reasons. First, it is a treatment for a disease that is becoming more prevalent as the population ages. Second, the therapy uses the new siRNA technology. This treatment uses a short strand of RNA in a special configuration that turns off a vascularization gene by binding with its RNA. It is the sequence of the siRNA that makes it specific for the endothelial growth factor (VEGF) gene and causes the proteins manufacture to be turned off. The technique is very general so can be applied to almost any gene. I believe that siRNA will bring about a revolution in medicine.
Phase II Trial Starts for siRNA Therapy for Wet AMD
10/19/2005
Acuity Pharmaceuticals initiated a Phase II trial for Cand5, its lead product candidate for the treatment of wet age-related macular degeneration (wet AMD), following successful completion of Phase I trial.
According to the company, this is the first-ever Phase II program for a small interfering RNA (siRNA) therapy, based on the gene silencing technology of RNA interference (RNAi).
Acuity, founded in 2002, has an exclusive license to several types of RNAi intellectual property from the University of Pennsylvania, including both broad-based and target-focused applications.
“Cand5 is safe and well-tolerated in patients with wet AMD,” said Jonathan L. Prenner M.D., of UMDNJ—Robert Wood Johnson Medical School and an investigator for Acuity’s Phase I study.
Cand5’s RNAi mechanism silences the genes that promote the overgrowth of blood vessels that lead to vision loss in wet AMD by shutting down the production of vascular endothelial growth factor (VEGF), which has been shown to be the central stimulus in the development of wet AMD.
By stopping production of VEGF at the source, Cand5 is expected to have efficacy advantages over other types of therapies for wet AMD, which work by inhibiting VEGF only after it has already been produced in the the eye, explained Dale Pfost, Ph.D., president and CEO of Acuity.
“A single molecule of Cand5 repeatedly stops hundreds of VEGF molecules. This sustained duration of action could result in less frequent delivery, perhaps only four to five times per year,” asserted Dr. Pfost.
Acuity’s Phase I trial, an open label, dose-escalation study that included 15 patients, tested five dose levels administered by intravitreal injection at six-week intervals. Cand5 was shown to be safe and well tolerated following repeat administration of the escalating dose levels, up to 3.0 mg per eye.
This study also included a pharmacokinetic analysis indicating that the study drug was not present in the plasma of any of the patients at any of the doses tested. This absence of systemic exposure to Cand5 is signficant since powerful VEGF inhibitors have the potential to cause serious adverse effects if present systemically, notes Dr. Pfost.
Wet Age-Related Macular Degeneration
Wet Macular Degeneration occurs when abnormal blood vessels start to grow on the center of your retina. These new blood vessels may be very fragile and often leak blood and fluid. The blood and fluid can damage your macula or create a scar on your retina, causing vision problems. Damage to the macula can occur rapidly, causing a noticeable loss of central vision. The vision loss from wet macular degeneration may be permanent, because abnormal blood vessels and scar tissue are actually replacing normal retina tissue. Once lost, these light-sensitive cells in your retina cannot be replaced.
An early symptom of wet macular degeneration is vision change, when straight lines appear wavy. For example, you may notice that your door frames appear wavy instead of straight. If you notice this condition or other changes in your vision, contact your eye care professional immediately for a comprehensive dilated eye exam. Treatments are available that may slow and reduce vision loss associated with wet macular degeneration. You should report any changes in vision to an eye care professional as soon as you notice them.
It is estimated that more than 2 million people in the United States currently have wet macular degeneration, with an increase of 200,000 new cases
Thursday, October 20, 2005
Putting the boat to bed
Today Tiny and I drove up to South Freeport to get the dingy ready for the winter and take anything that would freeze off the Windchaser. I removed the motor from the dingy and took it into the marina for winterizing. The Dingy was full of water but we managed to pull it up on the dock and in the process remove most of the water. The bottom was a real mess with marine growth. I was considering taking it home in the truck but because of all the growth we just turned it over and put it in the dingy rack on the dock. I will go up in a few weeks to retrieve it and the winterized motor. Tiny and I took four garbage bags of stuff off the boat and carted it home. A lot of it was left over soda and water. It is amazing how much stuff one can store on a boat. Some of it we will use over the winter and some I will probably cart back up next Spring. It was rather windy so I didn’t remove the sails and will leave that for the dock crew.
Tiny and I had a nice lunch of lobster stew at the Muddy Rudder and headed west past lake Sebago, through Conway NH, over the Kancamagus trail and home on the NH pike. It was a beautiful ride although it was past foliage peak in the mountains.
Tiny and I had a nice lunch of lobster stew at the Muddy Rudder and headed west past lake Sebago, through Conway NH, over the Kancamagus trail and home on the NH pike. It was a beautiful ride although it was past foliage peak in the mountains.
Wednesday, October 19, 2005
getting ready for the freeze
The hurricane is coming for us. Tomorrow I go to South Freeport with a friend to take things off the boat before they pull it. Once it is on stanchions up in the air if there is any thing on board that can freeze it will. I even had a bottle of Joy detergent freeze one year. In the spring the detergent that had oozed out of the bottle created quite a mess. My knee is painful but tolerable and hopefully the arthroscopy will work and the pain will stop.
Tuesday, October 18, 2005
MRI and knee surgery
Yesterday I met with my orthopedist to review MIR images of my right knee prior to surgery next Monday to remove those pieces of the meniscus cartilage that were broken loose. It was amazing how clear the MIR images were of the knee structure and how obvious it was that something was missing. The outside of the knee had a distinct layer of cartilage and the inside had none. The cartilage showed up as a dark area next to the bone. In the space between the bones there was some dark material which may be the cartilage which was broken from the inner circumference of the meniscus. They gave me all sorts of exercises to do to strengthen the muscles around the knee prior to surgery. I assume that I will also have to do them after the slicing and dicing.
MRI is a magical technique which uses a very strong magnetic field coupled with radio waves to create pictures of soft tissue. It is better with soft tissues than cat scans which use X-rays. The link given with this post provides a background on MRI for those with a technical bent. The technique used to be called NMR or nuclear magnetic resonance and was used extensively in chemistry to define how different atoms were connected to other atoms in complex molecules. Basically, in a strong magnetic field certain atomic nuclei with act like little radio transmitters when stimulated by a radio frequency pulse. The chemical environment of the nuclei determines the wavelength of the weak radio frequency response. Thus, by looking at the frequency of the response one can tell something about the chemical bonding in the vicinity of the molecule that is responding.
The early techniques did not produce images but numbers. With advances in computers and imaging techniques it was possible to configure NMR to produce images. However, the N or Nuclear in NMR caused people to believe that radioactive materials were used in the technique. The N only means that the technique looks at the magnetic properties of atomic nuclei and there is nothing radioactive about it. Therefore the name was changed from NMR to MRI or magnetic resonance imaging. Such instruments are difficult to construct (typically 2 million $ per device). It is even more of a problem to define how they work but the URL provided makes a good stab at an explanation.
Sunday, October 16, 2005
House warming
Today we went to a house warming in Newton. They had done a nice job redoing a home that still had plaster and lath in the walls when they started the remodeling. The location is very good being close to the “T”, Newton Center and Boston. We knew few people at the house warming but met one fellow who was acquainted with an old hunt member and had been to a few teas. This “old hunt member” had been a diplomat and retired to a castle in Ireland. He also became a Master of the Galway Blazers fox hunt.
My knee is still painful. Today at Wal-Mart I purchased an adjustable cane. It doesn’t really support one like crutches but is a lot easer to use. Tomorrow I visit the orthopedist and if the MRI confirms the diagnosis get the knee fixed. If they can’t see the broken piece of cartilage then I may just have to live with the problem.
My knee is still painful. Today at Wal-Mart I purchased an adjustable cane. It doesn’t really support one like crutches but is a lot easer to use. Tomorrow I visit the orthopedist and if the MRI confirms the diagnosis get the knee fixed. If they can’t see the broken piece of cartilage then I may just have to live with the problem.
Thursday, October 13, 2005
There really were amazons. A recent PBS Nova program described archeology and DNA analysis that concluded that the warrior women from Homer’s Iliad and Greek history really did exist. Female burials in warrior garb similar to that on ancient Greek art were excavated in Southern Russia. Mitochondrial DNA analysis was conduced on a number of samples from the graves. These were compared to a rare blond girl from a nomadic tribe close to the Chinese border. A least one sample was identical to the mitochondrial DNA of the young girl. One gets one’s mitochondrial DNA only from one’s mother. So the maternal line has continued for 2,500 years. This is amazing as there are so few blond Mongolians. One might have expected this female line to have become extinct as every time a women has no children or only boys her mitochondrial DNA becomes extinct. Because of infant mortality even one daughter may not be enough to continue the line as that daughter may die before having children. Perhaps the nomadic Mongolians have large families increasing the probability of at least one female living to child bearing age. It is interesting that the amazons existed but amazing that such a close relative is alive today.
Wednesday, October 12, 2005
Medical Data Availability
Health Care Data
During my the workup of my knee problems a blood workup was done. The data from which I have entered into a spreadsheet that I keep containing results of previous tests. This allows me to evaluate my status over time. I highly recommend it. When in the emergency room I had to give my medical history three times. Each recitation was probably somewhat different with the last being most complete as past problems kept creeping into my mind as the day progressed. But I am sure that even the last attempt at full disclosure was incomplete. Such data should all be in a database that is instantly available to the physician of the moment. However, all the new privacy laws are making this more difficult even as technology makes it more doable. Hence I keep my own database. The tactic is good for the occasional review of the pace of my degeneration but not of much use if you don’t have your laptop in the emergency room. Perhaps I should put the file on my solid state “flash” drive so that the pertinent data could be entered into any local computer with a USB port.
During my latest clinical experience a CAT Scan was preformed. A picture of one scan in provided to prove to the doubters that I actually do have a brain
Sunday, October 09, 2005
The Singularity and evolution
Will the advance in computing power create a mind greater than ours in the next 20 years. Will it serve us or us it? This is the topic of Ray Kurweil's new book "The Singularity is Near:a When Humans Transcend Biology". Again the anthropic principal raises its head. Isn’t it amazing that we are here at this point in time in the history of the universe?
Today was a rainy day so I worked out at Holiday Health. It seems that I need exercise to feel well. My knee with the broken cartilage provides a continual dull throbbing pain but one gets use to it. The stationary bicycle provided some exercise with an increase in heart rate without an increase in pain. My mood is improved. We will see how I feel tomorrow.
Today was a rainy day so I worked out at Holiday Health. It seems that I need exercise to feel well. My knee with the broken cartilage provides a continual dull throbbing pain but one gets use to it. The stationary bicycle provided some exercise with an increase in heart rate without an increase in pain. My mood is improved. We will see how I feel tomorrow.
Saturday, October 08, 2005
The cost of fuel has really hit
We just booked some flights over the internet. The prices looked good and we happily proceeded to checkout. After entering too much information an error came back to say that prices had changed. They had doubled, a fact that was not mentioned until the end of the booking process. This was a travel site and not an airline site. Their information was bad either through poor software design or a hope that if they gave you an old price you would still book the flight even though the price had gone up. We left that site and went to Orbitz with gave us the correct prices which were bad but real. We were able to book flights that were less than those from the site we tried first but certainly far above the cost of this same trip last year. I guess that the fuel prices have really hit the industry.
Friday, October 07, 2005
Bad knees are no fun
Today I am to visit the orthopedist to see what can be done with my knee. The crutches help but are a pain to use so often during the day I just hobble around without them. Yesterday during the yearly visit my dermatologist he advised me to get an MRI as soon as possible. He was told to wait to see how things went with his injured knee. They did not go well. Eventually he was operated on but the damage was done and now he has arthritis in that knee. Considering how fragile we are it is amazing that we make it as long as we do. What is needed is a regeneration procedure to re-set the clock.
Wednesday, October 05, 2005
Intelligent design vs evolution
Austrian Cardinal Christoph Schoenborn, shown here during a Mass in St. Peter's Basilica in April, says he sees "no problem combining belief in the Creator with the theory of evolution, under one condition — that the limits of a scientific theory are respected." Per MSNBC
I personally don’t see the problem. The scientific method doesn’t allow miracles and intelligent design requires them. By definition intelligent design does not belong in a science course as it doesn’t belong in a math classroom. It is by definition a different animal. This doesn’t mean that intelligent design doesn’t belong in school. It is appropriate to be discussed in history, government and sociology classes as it is a major factor in human history and sociology. I believe that it should be taught in school along with the other world views such as those of the Maya, Chinese and other civilizations.
Even our most advanced cosmological theories have a problem with how things got started. They just keep pushing the problem back to an earlier time. Initially it was the big bang. Now it is 11 dimensional banes or membranes that bang into one another to create universes of which ours is just one example. Another major theory has the continual creation of new universes so that everything that can happen does happen in some universe. Whenever there is a choice all possibilities happen but in different universes. We die many times during our life but each time in a different universe.
There are many strange things in the bible such as Jonah living in the whale. However, modern cosmology derived by the scientific method and appropriate to be taught in school is much stranger. Modern scientific thought presents a world view as do most religions. Perhaps the only consistent solution to what should be taught in school is to eliminate all world views, those derived by the scientific method and those derived but other means.
No, I don’t really mean this. It would be most appropriate to provide students with an overview of all world views.
I personally don’t see the problem. The scientific method doesn’t allow miracles and intelligent design requires them. By definition intelligent design does not belong in a science course as it doesn’t belong in a math classroom. It is by definition a different animal. This doesn’t mean that intelligent design doesn’t belong in school. It is appropriate to be discussed in history, government and sociology classes as it is a major factor in human history and sociology. I believe that it should be taught in school along with the other world views such as those of the Maya, Chinese and other civilizations.
Even our most advanced cosmological theories have a problem with how things got started. They just keep pushing the problem back to an earlier time. Initially it was the big bang. Now it is 11 dimensional banes or membranes that bang into one another to create universes of which ours is just one example. Another major theory has the continual creation of new universes so that everything that can happen does happen in some universe. Whenever there is a choice all possibilities happen but in different universes. We die many times during our life but each time in a different universe.
There are many strange things in the bible such as Jonah living in the whale. However, modern cosmology derived by the scientific method and appropriate to be taught in school is much stranger. Modern scientific thought presents a world view as do most religions. Perhaps the only consistent solution to what should be taught in school is to eliminate all world views, those derived by the scientific method and those derived but other means.
No, I don’t really mean this. It would be most appropriate to provide students with an overview of all world views.
Monday, October 03, 2005
Testing
The emergency room at the local hospital gave the diagnosis for the knee but also proceeded with a workup for a heart problem because I was dizzy after the event. Blood tests, EKG, Cat Scan, Heart monitoring all came back negative. I am now moping around home on crutches trying to get an appointment for repair of the damaged knee. Unfortunately I am no longer foxing or sailing. I left the cardiologist wearing a heart monitor. In the evening we had a great dinner of rack of lamb with friends. Thanks Pam. I hope the wine didn’t affect the heart monitor.
Sunday, October 02, 2005
Installing a garbage disposal can be painful.
I was sitting cross legged on the floor in front of the sink installing a new garbage disposal. In getting up I torqued my right leg and broke the cartilage in my right knee. The job wasn’t done so I hobbled around down into the basement to turn on the circuit breaker and back and forth to the sink. I got the job done.
Saturday, October 01, 2005
Fox Hunt in Concord
For readers of this blog, a picture of the dragon found in the Delaney woods is now available on my September 27th post.
Steve, Pam, Kathy and I met on Estabrook road in Concord to lay the drag for today’s hunt. We have cut back on the amount of drag used and the hounds seem to be able to follow this level without problem. If too much drag is laid it may diffuse over a wide area making the actual line of the drag more difficult for the hounds to follow. It was a chilly morning but before long we were shedding layers and the day ended clear and warm. It was a great day for foxing and riding. The hunt went well with no broken bones and no hounds lost.
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