Rheumination

Six Pack a Day Abs

It is well known that COPD patients have weak muscles which contributes to their respiratory problems. It has been thought that the weakness was likely secondary to the chronic lung disease and it's resulting sedentary lifestyle. In a recent article in Chest Montes de Oca et al. show that the effect of cigarettes may,in fact, be direct. They biopsied the vastus lateralis muscle of 14 long time smokers that did not have COPD by pulmonary function testing and were able to demonstrate differences in comparison with a control group of non-smokers with similar sedentary lifestyles. The muscles of the smokers had atrophy of the type1 fibres and a shift to glycolytic rather than oxidative metabolism. There was no sign of inflammation,however.
I guess it's no big surprise that cigarettes are toxic to muscle, as they are to a myriad of other tissues, but it does raise the question as to whether cigarettes may have a greater impact on musculo-skeletal physiology than was suspected to date.

My Valentine Every Day

Occasionally, while preparing to inject a knee or shoulder, my proviodine splatter will form the shape of a heart. A pleasant midday happenstance, reminding me of how lucky I am to be with the woman I married.

Etanercept On My Mind

We've all seen minor miracles with the use of biologics,but I must admit this odd sounding story matches most of them. Tobinick and Gross had performed a small study using etanercept in the treatment of Alzheimer patients. The drug was administered via a perispinal extrathecal injection, used to increase delivery to the CNS. The initial study was based on the idea that Alzheimer's may have an inflammatory element, mediated by TNF. Patients were assessed monthly after the drug was administered but the authors noted that they were seeing nearly immediate results, immediate meaning within minutes. In an article published in the open access Journal of Neuroinflammation, the authors present a single case study of the immediate results of etanercept use. After the drug was given, the authors noted a change in the patient within ten minutes, although actual testing occurred about two hours later. At that time they noticed fairly dramatic improvement in several cognitive tests. As an example, the patient could only remember one object in the Boston Naming Test pre-treatment and nine post-treatment. The Montreal Cognitive Assessment score rose from 7 of a possible 30, to 15 of 30. While the study was single case, unblinded and so far not replicated, it is still rather impressive. (Not replicated,but the authors note that this kind of result is not exceptional)
The explanation could not be an anti-inflammatory one, of course, and it appears that the effect may be related to another use of the TNF molecule that is coming to light . Glial cells in the brain secrete TNF (and other gliotransmitters) which act on neural tissue as a synaptic modulator. Excess TNF inhibits synaptic transmission and this could be partly responsible for the cognitive deficit noted in Alzheimer's disease. This inhibitory effect might then be altered by the administration of anti-TNF agents like etanercept.
This leads to the question as to whether ant-TNF agents, given peripherally can have a CNS effect. TNF does cross the blood- brain barrier, not by diffusion but by a saturable transport mechanism. It would be interesting to know if the high levels in the chronically inflamed rheumatoid or SLE populations have a TNF mediated CNS effect. As well, I'd like to know if decreasing it to normal explains the often rapid increase in patient's energy and well-being seen after the use of biologics. Then again, if there is a transport mechanism for TNF across the blood-brain barrier, I would think this means that TNF serves some important role in the brain and I wonder if chronically suppressing it might have some long term neurological sequelae in our patients. I haven't heard a peep about this possibility, but is anybody looking?

Crystal Clear, But Clearly Not Crystal

After more than fifteen years of clinical rheumatology, I'm not easily surprised. I don't mean the " gee that is unusual for a vasculitis" kind of surprise; we get that every second or third day. I mean the stand back with a "what the ..." kind of surprise. The kind I mean is like the time during residency when I drained a pleural effusion from one of my cancer patients to find that I was draining pure adriamycin,the result of a central line that was placed right in his pleural space. But today was the day. I was called to see a patient with known gout, treated with prednisone, who developed a painful elbow during tapering. The exam was somewhat difficult because of generalized edema of the extremities,but there appeared to be both a joint effusion and a bursal swelling, although the bursa did not appear to be very inflamed. Because the patient developed the synovitis while on prednisone, was a cancer patient, and had a recent pulmonary infection, I decided to tap the joint to rule out infection. I tried the joint first since the bursa didn't look all that inflammatory and easily got fluid,but as I aspirated, the fluid looked strikingly transparent. It looked like tap water, or perhaps IV fluid. (The color of the fluid on the left is what you would normally expect, on the right is the fluid I got)

I was so startled that I stopped with needle in place and looked the scene over to be sure that I hadn't somehow needled some sort of catheter and was aspirating normal saline. Nothing. I pulled out five ml and then tried the bursa as I hadn't found anything inflammatory in the joint. Same result.
Although the fluid was obviously non-inflammatory I checked it out under the microscope just out of curiousity. Nothing much. In fact, all I saw was about one single rbc per high power field. ( It is strangely relaxing to watch a single rbc tumble across your visual field; highly recommended)
I never actually diagnosed the painful condition. I doubt the effusions aspirated had anything to do with it. I suspect there was a goutty peri-arthritis with a coincidental effusion from the anasarca, or perhaps a sympathetic effusion which was particularly clear because of the anasarca. It resolved with an increase in prednisone dose. In any case, my first anasarca joint effusion.