I. Kelman Cohen

Cooling the foot to prevent diabetic foot wounds: A proof-of-concept trial

The etiology of neuropathic diabetic foot wounds can be summarized by the following formula: pressure x cycles of repetitive stress = ulceration. The final pathway to ulceration consists of an inflammatory response, leading to tissue breakdown. Mitigation of this response might reduce the risk of ulceration. This proof-of-concept trial evaluates whether simple cooling of the foot can safely reduce the time to thermal equilibrium after activity. After a 15-min brisk walk, the six nondiabetic volunteers enrolled were randomly assigned to receive either air cooling or a 10-min 55 degrees F cool water bath followed by air cooling. The process was then repeated with the intervention reversed, allowing subjects to serve as their own controls. There was a rise in mean +/- SD skin temperature after 15 min of activity versus preactivity levels (87.8 degrees +/- 3.9 degrees versus 79 degrees +/- 2.2 degrees F; P = .0001). Water cooling immediately brought the foot to a point cooler than preactivity levels for all subjects, whereas air cooling required an average of nearly 17 min to do so. Ten minutes of cooling required a mean +/- SD of 26.2 +/- 5.9 min to warm to preactivity levels. No adverse effects resulted from the intervention. We conclude that cooling the foot may be a safe and effective method of reducing inflammation and may serve as a prophylactic or interventional tool to reduce skin breakdown risk.

Analysis of fibrogenic processes in denervated tissues of spinal cord injury patients.

To test the hypothesis that altered collagen metabolism is a contributing factor in the apparent delayed wound healing in denervated regions of spinal cord injury (SCI) patients, a tissue implant (PVA) was used to directly measure collagen deposition. Sterile PVA implants were placed subcutaneously in the inner aspect of the upper arm above the cord injury (innervated) and in the inner aspect of the upper leg below the cord injury (denervated) of 20 spinal cord injury patients and compared to eight healthy volunteers. On day 14, the implants were removed and analyzed histologically by tri-chrome stain and biochemically for hydroxyproline as a measure of collagen deposition. No remarkable histologic differences were observed in the sponge material removed from the upper regions compared to the lower denervated regions of the spinal cord injury patients. Sponges from both areas were infiltrated with fibroblasts containing well-developed rough endoplasmic reticulum and large quantities of trichrome-positive collagen. Likewise, upper and lower histology of controls was identical and nondistinguishable from the corresponding sections obtained from the spinal cord injury patients. Quantitation of the hydroxyproline in the arms of the spinal cord injury patients (n = 20) showed 4.3 ± 0.7 nmol hydroxyproline per milligram of sponge compared to 4.1 ± 0.4 nmol/mg in the denervated regions of the lower limb. The hydroxyproline content in the arms of control volunteers was 5.2 ± 0.7 nmol/mg compared to 3.9 ± 0.8 nmol/mg in the leg (n = 8). These observations suggest that fibrogenic processes in denervated regions are not reduced significantly compared to innervated regions.

The Evolution of Wound Healing

Man’s struggle to heal wounds is as old as history itself. As life forms evolved from single cell life to amphibian and finally mammal, the pristine ability to heal by regeneration was lost and thus repairs by inflammation and subsequent deposition of matrix protein (scar) evolved as the method of mammalian healing. This evolutionary change leading to scar (the deposition of collagen) seems to be the key to preventing regeneration. It is well known that when the point is reached on the ladder where regeneration on longer occurs, inflammation and collagen deposition are the difference. In fact, if one takes a form of life, which seems the first link between regeneration and scar formation and a collagen cross-linking inhibitor is fed to the animal, then regeneration will once again occur! If we could only bridge this gap, imagine how successful we could become in the management of diabetic wounds. Although uncertain regarding why this occurred in the evolutionary process, it is hypothesized that as mammals became sophisticated, they needed rapid healing to protect themselves from other predators and to eke out a physical survival in a very hostile environment. In early-recorded history, the Egyptians repaired wounds with primitive suture materials (such as insect claws) and used clean sheets on surgical fields to prevent “suppuration.”; The Greeks, led by Hippocrates, devised methods of treatment for primary wounds and chronic wounds. They used various gauze materials empirically which included wine, milk, honey, and other substances in open wounds similar to our treatment today. Today, one can assign scientific rationale to some of these ancient empirical choices. For example, the complex sugars of honey are known to suppress the growth of Gram-positive bacteria. Wine will suppress pseudomonas proliferation. Milk products may contain cytokines or serve as buffers to control wound pH. Although the ancients had no idea that pus was actually is made up of proteins and dead leukocytes, they understood that drainage of localized products of infection was a good sign (laudable pus). They understood that when signs opf inflammation could not be localized that death would inevitably follow. During the early Roman era, Celsius, unaware of the existence of bacteria, did recognize and describe the cardinal signs of clinical infection being (1) rubor—erythema, (2) tumor—swelling, (3) dolor—pain, and (4) calor—heat.