Case Report #2 - M.W.
This patient is a 48 year old female who presented complaining of pain in both knees due to arthritic changes. An orthopedic surgeon had suggested to her that she would need bilateral total knee replacement surgery. She did not want to undergo such drastic surgeries at this stage in her life and was eager to avoid it by trying an alternate therapy.
She had been active and athletic for most of her life, until a few years ago when her knees started giving her pain. As the pain worsened, she gradually had to give up her normal exercise routine and over the past couple of years had gained weight as well. She is otherwise in good health with no other medical issues. Unfortunately, she had been rather dependent upon non-steroidal anti-inflammatory drugs (NSAID's) to control her pain, typically taking ibuprofen daily.
Her radiology studies showed bilateral medial compartment osteoarthritis, or degenerative changes in both knee joints, especially the inner portion on each leg. This is also consistent with where she experienced her pain. She actually had good range of motion when I saw her, and her pain was only evident when walking up or down steps. She had no evidence of ligament or tendon involvement.
I have all patients fill out a comprehensive pain questionnaire that involves three different types of assessments for pain. These include the Short Form McGill Pain Questionnaire(SF-MPQ), the Visual Analog Scale (VAS), and the Present Pain Inventory Score (PPI). Her answers to these questions on the day of surgery were scored as 20, 67, and 3.5 respectively (for a total score of 91).
We developed a personalized pre-op plan involving supplements that appear to help viability of stem cells, along with her ceasing to take pain medications for the week prior to surgery.
She underwent manual liposuction and stem cell harvesting/isolation. We also drew blood and obtained platelet-rich plasma (PRP). I injected both knees with a mixture of stem cells and PRP, and she left our office with a plan to start physical therapy and also seek metabolic nutrition counseling through her medical plan. She went to the physical therapist 2 days after the procedure.
I saw her back in the office on post-op day #8. She stated that she felt less pain and that the exercises from the therapist seem to be helping strengthen her legs as well. Her pain scores were as follows: SF-MPQ = 14, VAS = 28, and PPI = 1.5, for a total of 44. This is roughly a 50% drop in her pain over one week. She had also avoided using NSAID's since the procedure. More impressive was the fact that in the past she had to help pull herself up her stairs at home by using the hand rail, due to knee pain. Over the past 3 days, she had been walking up the stairs without requiring assistance.
She will continue with physical therapy and her selected supplements, and is awaiting the nutritional service consult as well. This case just serves to illuminate the multiple factors that are involved in successful stem cell therapy. First and foremost, it takes a motivated patient who is willing to actually put in the time and effort necessary to make success happen. And it takes adjustments in diet and exercise to help augment the results.
Monday, January 19, 2015
Tuesday, January 13, 2015
Stem Cells to Improve Failing Vision
In yet another amazing story in regenerative medicine, a woman in Japan received a retinal stem cell graft as therapy for age-related macular degeneration (AMD), as first reported in September, 2014. She is the first of six patients who are to have this treatment, being performed at the RIKEN Center for Developmental Biology in Kobe, Japan.
AMD is a major cause of visual loss and blindness in adults over the age of 50. The most common type is known as "dry" AMD (or central geographic atrophy), wherein vision loss occurs due to the loss of the photoreceptors known as rods and cones. There is no recognized medical or surgical treatment for this condition, although certain vitamin and supplement regimens may help. About 90% of cases are "dry" AMD. (The other type is known as "wet" AMD where vision loss occurs due to the abnormal growth of blood vessels. There are multiple medications that can help with this condition, although some require direct injections into the eye on a routine basis. The goal is to reduce the growth of these blood vessels and eliminate them.)
The woman mentioned earlier had skin cells harvested and then reprogrammed into specialized retinal pigment epithelial cells. This is a type of induced pluipotent stem cell (iPS), wherein a patient's own cells are induced into a stem cell line that is wanted for a particular type of tissue therapy. These cells were then grafted into her eye as a patch with the hope of allowing these cells to maintain her own rods and cones.
Shinya Yamanaka and colleagues at Kyoto University first discovered iPS cells in 2006; Yamanaka was awarded the Nobel Prize for this work in 2012.
Mike Cheetham of the Institute of Ophthalmology at University College London (another site researching human embryonic stem cells and AMD) had this to say in regards to the Japanese trial - "If it goes well, it could be the start of a new era in personalized medicine."
AMD is a major cause of visual loss and blindness in adults over the age of 50. The most common type is known as "dry" AMD (or central geographic atrophy), wherein vision loss occurs due to the loss of the photoreceptors known as rods and cones. There is no recognized medical or surgical treatment for this condition, although certain vitamin and supplement regimens may help. About 90% of cases are "dry" AMD. (The other type is known as "wet" AMD where vision loss occurs due to the abnormal growth of blood vessels. There are multiple medications that can help with this condition, although some require direct injections into the eye on a routine basis. The goal is to reduce the growth of these blood vessels and eliminate them.)
The woman mentioned earlier had skin cells harvested and then reprogrammed into specialized retinal pigment epithelial cells. This is a type of induced pluipotent stem cell (iPS), wherein a patient's own cells are induced into a stem cell line that is wanted for a particular type of tissue therapy. These cells were then grafted into her eye as a patch with the hope of allowing these cells to maintain her own rods and cones.
Shinya Yamanaka and colleagues at Kyoto University first discovered iPS cells in 2006; Yamanaka was awarded the Nobel Prize for this work in 2012.
Mike Cheetham of the Institute of Ophthalmology at University College London (another site researching human embryonic stem cells and AMD) had this to say in regards to the Japanese trial - "If it goes well, it could be the start of a new era in personalized medicine."
Tuesday, October 21, 2014
PRP, Microneedling, and Acne Treatment
Today I want to discuss a patient who came to see me for help in treating her acne scarring. She is a beautiful young woman who has been very self-conscious due to acne scars on her cheeks. The treatment that we chose was microneedling with a Dermapen, combined with platelet-rich plasma (PRP). This is essentially a variation of what is known as a "vampire" treatment, as we take a patient's own blood to isolate the PRP and then use it to treat the damaged skin.
This therapy can be used for a so-called "facelift", or as a tool for rejuvenating the skin.
The Dermapen uses multiple ultra-thin surgical needles that rapidly and repeatedly puncture the skin to make thousands of tiny wounds as the device passes over the treated area. There is no long-term damage, and relatively minimal discomfort. This device alone provokes the body's natural healing response, in effect leading to the production of collagen and elastin. There is also stimulation of new capillary growth. Healthy new skin is produced during this healing response. In the specific case of acne scarring, these tiny needles also help to break up the fibrous and uneven scar tissue, again providing a healthy foundation for new cells.
The addition of PRP is designed to even further enhance cellular growth. I use a combination technique, injecting some of the PRP under the skin while also applying a PRP gel topically to the affected areas. I will not go into detail regarding how PRP works - please see some of my earlier blog entries for more information [PRP (Plasma Therapy) @ http://coloradostemcelltherapy.blogspot.com/2012/05/prp-plasma-therapy.html, and Skin Rejuvenation @ http://coloradostemcelltherapy.blogspot.com/2014/04/skin-rejuvenation_6980.html].
I truly believe that there are improved results by using the combination of the Dermapen with PRP. This mode of therapy can also with other types of scarring, again by breaking up the fibrous scar tissue; it is also useful for reducing fine lines of the face, helping eliminate stretch marks, and in treating sun damage.
This patient has granted permission for me to show her before and after pictures. She originally saw another doctor for 2 microneedling treatments, although these were not very aggressive. She then had a total of 4 procedures with me - 2 microneedling alone, and 2 with PRP. She is still continuing to receive treatments, as she has been very happy so far but wants even more improvement. She is actually seeing me again today for another treatment with PRP.
This therapy can be used for a so-called "facelift", or as a tool for rejuvenating the skin.
The Dermapen uses multiple ultra-thin surgical needles that rapidly and repeatedly puncture the skin to make thousands of tiny wounds as the device passes over the treated area. There is no long-term damage, and relatively minimal discomfort. This device alone provokes the body's natural healing response, in effect leading to the production of collagen and elastin. There is also stimulation of new capillary growth. Healthy new skin is produced during this healing response. In the specific case of acne scarring, these tiny needles also help to break up the fibrous and uneven scar tissue, again providing a healthy foundation for new cells.
The addition of PRP is designed to even further enhance cellular growth. I use a combination technique, injecting some of the PRP under the skin while also applying a PRP gel topically to the affected areas. I will not go into detail regarding how PRP works - please see some of my earlier blog entries for more information [PRP (Plasma Therapy) @ http://coloradostemcelltherapy.blogspot.com/2012/05/prp-plasma-therapy.html, and Skin Rejuvenation @ http://coloradostemcelltherapy.blogspot.com/2014/04/skin-rejuvenation_6980.html].
I truly believe that there are improved results by using the combination of the Dermapen with PRP. This mode of therapy can also with other types of scarring, again by breaking up the fibrous scar tissue; it is also useful for reducing fine lines of the face, helping eliminate stretch marks, and in treating sun damage.
This patient has granted permission for me to show her before and after pictures. She originally saw another doctor for 2 microneedling treatments, although these were not very aggressive. She then had a total of 4 procedures with me - 2 microneedling alone, and 2 with PRP. She is still continuing to receive treatments, as she has been very happy so far but wants even more improvement. She is actually seeing me again today for another treatment with PRP.
 |
| Before |
 |
| After 6 treatments, 4 @ MEND |
Wednesday, September 24, 2014
Stem Cells and Multiple Sclerosis
A new Phase I trial involving the use of stem cells in Multiple Sclerosis (MS) patients is underway in a study by the Cleveland Clinic, Case Western Reserve University, and University Hospitals Seidman Cancer Center. Multiple Sclerosis is an autoimmune disease, wherein the immune system attacks the central nervous system (CNS), both the brain and spinal cord.
So far, 2 patients have undergone the complete process, with another patient expecting to start the process soon. In all, 24 patients with relapsing or progressively worsening MS will be in the trial over the next 2 to 3 years. The protocol calls for harvesting of their own stem cells from bone marrow at the University Hospital, cultivating those cells at a Case Western laboratory, and then returning the stem cells to the patient intravenously at the Cleveland Clinic.
The primary focus of this study is to determine both the feasibility and the safety of such a treatment process. In the process, the researchers will also be looking for any evidence of improvement in the patients, although the trial is not set up to actually gauge either subjective or objective endpoints. This is a conservative study that will only look at safety parameters. If the trial goes well, further Phase II trials would likely follow, with actual treatment endpoints as the focus.
The first patient treated in the trial, Bill White, was first diagnosed with MS about 6 years ago. His first symptoms were fatigue and balance problems. After a while, exercise and even walking became problematic for him, and he eventually had to stop working. The reason for these issues is that in MS, the immune system abnormally attacks the CNS, leading to damage in the protective myelin sheaths, followed by irreversible damage to the axons and even neuronal death. The damage builds up and can progressively worsen over time, or can occur in a relapse and remission format. The process leads to noticeable changes on MRI and the diagnosis can be confirmed by looking at the spinal fluid. Mr. White had the characteristic changes on a scan of his brain in 2007. He has also since undergone treatment with 2 different drugs without seeing much benefit, if any, while subjecting him to a variety of side-effects.
After enrolling in this trial, his stem cells were harvested in March. The stem cells were cultured in the lab for months, and they were eventually injected into his bloodstream in June. Mr. White saw changes very quickly. He stated that "I used to have to use my left arm to lift my left leg up. Now I can lift it up on my own", meaning without the assistance of his arm. And although he still tires when walking, he does so less quickly now. In addition, his vision has improved from 20/50 to 20/20. Objectively, a recent MRI showed no new lesions in his brain. The proposed mechanism of action for the stem cells is in modulating the immune system, causing a decrease in the immune attack on the CNS. Also, the stem cells may be promoting the healing and regrowth of damaged tissues.
Other Phase I trials looking at stem cells and MS will soon be underway in Spain, China, and Iran. These are exciting times for sure, and the idea that a patient's own stem cells could help with the treatment of MS is truly amazing!
So far, 2 patients have undergone the complete process, with another patient expecting to start the process soon. In all, 24 patients with relapsing or progressively worsening MS will be in the trial over the next 2 to 3 years. The protocol calls for harvesting of their own stem cells from bone marrow at the University Hospital, cultivating those cells at a Case Western laboratory, and then returning the stem cells to the patient intravenously at the Cleveland Clinic.
The primary focus of this study is to determine both the feasibility and the safety of such a treatment process. In the process, the researchers will also be looking for any evidence of improvement in the patients, although the trial is not set up to actually gauge either subjective or objective endpoints. This is a conservative study that will only look at safety parameters. If the trial goes well, further Phase II trials would likely follow, with actual treatment endpoints as the focus.
The first patient treated in the trial, Bill White, was first diagnosed with MS about 6 years ago. His first symptoms were fatigue and balance problems. After a while, exercise and even walking became problematic for him, and he eventually had to stop working. The reason for these issues is that in MS, the immune system abnormally attacks the CNS, leading to damage in the protective myelin sheaths, followed by irreversible damage to the axons and even neuronal death. The damage builds up and can progressively worsen over time, or can occur in a relapse and remission format. The process leads to noticeable changes on MRI and the diagnosis can be confirmed by looking at the spinal fluid. Mr. White had the characteristic changes on a scan of his brain in 2007. He has also since undergone treatment with 2 different drugs without seeing much benefit, if any, while subjecting him to a variety of side-effects.
After enrolling in this trial, his stem cells were harvested in March. The stem cells were cultured in the lab for months, and they were eventually injected into his bloodstream in June. Mr. White saw changes very quickly. He stated that "I used to have to use my left arm to lift my left leg up. Now I can lift it up on my own", meaning without the assistance of his arm. And although he still tires when walking, he does so less quickly now. In addition, his vision has improved from 20/50 to 20/20. Objectively, a recent MRI showed no new lesions in his brain. The proposed mechanism of action for the stem cells is in modulating the immune system, causing a decrease in the immune attack on the CNS. Also, the stem cells may be promoting the healing and regrowth of damaged tissues.
Other Phase I trials looking at stem cells and MS will soon be underway in Spain, China, and Iran. These are exciting times for sure, and the idea that a patient's own stem cells could help with the treatment of MS is truly amazing!
Wednesday, September 17, 2014
Stem Cells and PRP Go Mainstream
I was glad to see stem cell therapy and PRP injections getting some love from the mainstream media recently - courtesy of AARP, There was an article in AARP The Magazine from May, 2014, titled "Arthritis:4 Treatments to Try Now", in which the author recommends injections to help with symptoms of osteoarthritis.
Osteoarthritis is the most common form of arthritis, essentially wear and tear on the joints. Over time, the protective cartilage wears down, eventually leading to pain as the bones rub against each other. There are few treatment choices, most of which can have detrimental side effects. Anti-inflammatory medications, or NSAID's (such as ibuprofen and naproxen), can be used to help with the pain, but their use for extended periods can be dangerous for multiple reasons. [I plan to devote an entry on this exact topic at www.ColoradoOnTheMend.blogspot.com soon.] Exercise and physical therapy can also help, but their effectiveness may be diminished due to pain interfering with a patient's ability to proceed long-term. And finally, there is the prospect of surgery - either in an attempt to repair damaged cartilage or with joint replacement. Again, there are serious side effects and potential life-threatening complications with surgery, and there is no guarantee it will work.
That is why PRP and stem cells show such promise - few side effects and a great potential upside. The author mentions a great article from January, 2014, in the Journal of Bone and Joint Surgery titled "Adult Human Mesenchymal Stem Cells Delivered via Intra-Articular Injection to the Knee Following Partial Medial Meniscectomy", wherein patients who received stem cells had increased meniscus volume and a significant reduction in pain compared to the control group. Here is the direct link to that study - http://jbjs.org/content/96/2/90 . Again, we have seen these results with our own patients, and continue to find ways to improve outcomes even more.
The AARP article also mentions newer medications, knee distraction (a procedure involving an external metal frame applied around the joint; the frame must be in place for months, with extensive rehab involved), and cartilage replacement as other therapies to try.
Here is the link to the article - http://www.aarp.org/health/conditions-treatments/info-2014/arthritis-treatments-to-try-now.html
Osteoarthritis is the most common form of arthritis, essentially wear and tear on the joints. Over time, the protective cartilage wears down, eventually leading to pain as the bones rub against each other. There are few treatment choices, most of which can have detrimental side effects. Anti-inflammatory medications, or NSAID's (such as ibuprofen and naproxen), can be used to help with the pain, but their use for extended periods can be dangerous for multiple reasons. [I plan to devote an entry on this exact topic at www.ColoradoOnTheMend.blogspot.com soon.] Exercise and physical therapy can also help, but their effectiveness may be diminished due to pain interfering with a patient's ability to proceed long-term. And finally, there is the prospect of surgery - either in an attempt to repair damaged cartilage or with joint replacement. Again, there are serious side effects and potential life-threatening complications with surgery, and there is no guarantee it will work.
That is why PRP and stem cells show such promise - few side effects and a great potential upside. The author mentions a great article from January, 2014, in the Journal of Bone and Joint Surgery titled "Adult Human Mesenchymal Stem Cells Delivered via Intra-Articular Injection to the Knee Following Partial Medial Meniscectomy", wherein patients who received stem cells had increased meniscus volume and a significant reduction in pain compared to the control group. Here is the direct link to that study - http://jbjs.org/content/96/2/90 . Again, we have seen these results with our own patients, and continue to find ways to improve outcomes even more.
The AARP article also mentions newer medications, knee distraction (a procedure involving an external metal frame applied around the joint; the frame must be in place for months, with extensive rehab involved), and cartilage replacement as other therapies to try.
Here is the link to the article - http://www.aarp.org/health/conditions-treatments/info-2014/arthritis-treatments-to-try-now.html
Tuesday, August 19, 2014
Stem Cells in Stroke Recovery
In the April 8, 2014 edition of the journal Neurology, neurologist Steven Cramer, M.D. and a team from the University of California - Irvine published a meta-analysis reviewing 46 preclinical studies looking at the efficacy of stem cells in treatment of ischemic strokes. The researchers found that 44 of these studies showed significantly improved outcomes over control therapies.
Of particular interest is the fact that the effects of the stem cells on functional recovery were quite beneficial regardless of how they were delivered to the patients, the overall dosage/amount of cells given, and even the timing of treatment in relation to the stroke event. As examples, there were improved outcomes when stem cells were given a month after the stroke, and whether given via a blood vessel or injected directly into the brain. These studies were based mainly on stem cells derived from bone marrow, but adipose (fat) derived stem cells should at least show similar promise, if not more.
Of note, the stem cells that are administered do not appear to actually develop, or differentiate, into neural cells. Thus, the stem cells are not actually replacing the damaged cells by turning into new neural cells. Instead, the stem cells modulate the immune system and help the overall healing process. Stem cells release a wide array of growth factors and chemicals that help to stop damage already occurring in cells, increase the growth of new cells, stimulate growth of a new vascular supply, protect cells at risk, and improve the connective tissue that supports the neural tissue. It is in these ways that the outcomes are greatly improved.
Although all of the studies looked at were preclinical, meaning not actual treatment or trials on humans, the overall results are quite compelling. The next step will be clinical trials on human patients that will then start to define the best practices for the use of stem cells, including ideal timing and dosage.
Of particular interest is the fact that the effects of the stem cells on functional recovery were quite beneficial regardless of how they were delivered to the patients, the overall dosage/amount of cells given, and even the timing of treatment in relation to the stroke event. As examples, there were improved outcomes when stem cells were given a month after the stroke, and whether given via a blood vessel or injected directly into the brain. These studies were based mainly on stem cells derived from bone marrow, but adipose (fat) derived stem cells should at least show similar promise, if not more.
Of note, the stem cells that are administered do not appear to actually develop, or differentiate, into neural cells. Thus, the stem cells are not actually replacing the damaged cells by turning into new neural cells. Instead, the stem cells modulate the immune system and help the overall healing process. Stem cells release a wide array of growth factors and chemicals that help to stop damage already occurring in cells, increase the growth of new cells, stimulate growth of a new vascular supply, protect cells at risk, and improve the connective tissue that supports the neural tissue. It is in these ways that the outcomes are greatly improved.
Although all of the studies looked at were preclinical, meaning not actual treatment or trials on humans, the overall results are quite compelling. The next step will be clinical trials on human patients that will then start to define the best practices for the use of stem cells, including ideal timing and dosage.
Wednesday, August 6, 2014
The Biology of Wound Healing
I have received questions in regards to the mechanism of wound healing, and how stem cells play a part. This entry is (hopefully) an easy-to-understand lesson in the biology behind the process. Please feel free to pose any other questions to me and I will do my best to answer!
I will focus on the healing process of the skin, or the dermis. In general, there are four overlapping phases to dermal wound healing: 1. coagulation/hemostasis 2. inflammatory response 3. cell proliferation 4. remodeling.
Hemostasis starts once the initial injury occurs, compromising the integrity of the underlying blood vessels. As blood escapes from these vessels, platelets interact with collagen and other extracellular matrix substances. It is these stimulated platelets that begin the clotting cascade and release clotting factors and inflammatory cytokines.
The inflammatory phase starts within hours of the initial insult, mainly as neutrophils enter the fibrin clot in response to the cytokines. They are followed by leukocytes and macrophages which work together to neutralize foreign substances and help to sterilize the wounded tissue. It is also during this phase that stem cells are activated by pro-inflammatory mediators. Stem cells modulate the immune response and can help inhibit the activity of mast cells and natural killer cells. In this way, stem cells can attenuate the acute immune response. The inflammatory environment also stimulates stem cells to upregulate prostaglandin E2, favoring dermal tissue regeneration. In summary, stem cells favor wound healing over inflammation, while helping to promote functional regeneration during the next phase.
The proliferation phase begins as these immune cells recruit local reparative cells (including more stem cells) from the surrounding area to form what is called granulation tissue. This granulation tissue is well-vascularized, meaning it has a substantial blood supply, and acts as a scaffold for tissue regeneration. Eventually this is what allows for the wound bed to heal and close off. Stem cells help encourage the construction of a viable vascular supply, through the release of many growth factors.
The process concludes with the remodeling phase, wherein cells called fibroblasts help reorganize the extracellular matrix to reinforce the early granulation tissue and also to produce proteins that help regenerate the skin tissue. Stem cells express certain factors that help in this phase to promote growth of healthy and functioning dermal tissue, tissue that resembles uninjured tissue as opposed to scar tissue.
By understanding this entire process and the role stem cells play in it, we can then use a patient's own stem cells to help in the acute healing process. Stem cells directly applied to or injected into a wound can help with healing through multiple mechanisms, adding to their own injury response. There is also accumulating evidence that stem cells given systemically through an IV will find the injured area through complex signaling and still impart a regenerative effect.
I hope this explanation is not too scientific and not overly filled with "medicalese". If so, please let me know....
I will focus on the healing process of the skin, or the dermis. In general, there are four overlapping phases to dermal wound healing: 1. coagulation/hemostasis 2. inflammatory response 3. cell proliferation 4. remodeling.
Hemostasis starts once the initial injury occurs, compromising the integrity of the underlying blood vessels. As blood escapes from these vessels, platelets interact with collagen and other extracellular matrix substances. It is these stimulated platelets that begin the clotting cascade and release clotting factors and inflammatory cytokines.
The inflammatory phase starts within hours of the initial insult, mainly as neutrophils enter the fibrin clot in response to the cytokines. They are followed by leukocytes and macrophages which work together to neutralize foreign substances and help to sterilize the wounded tissue. It is also during this phase that stem cells are activated by pro-inflammatory mediators. Stem cells modulate the immune response and can help inhibit the activity of mast cells and natural killer cells. In this way, stem cells can attenuate the acute immune response. The inflammatory environment also stimulates stem cells to upregulate prostaglandin E2, favoring dermal tissue regeneration. In summary, stem cells favor wound healing over inflammation, while helping to promote functional regeneration during the next phase.
The proliferation phase begins as these immune cells recruit local reparative cells (including more stem cells) from the surrounding area to form what is called granulation tissue. This granulation tissue is well-vascularized, meaning it has a substantial blood supply, and acts as a scaffold for tissue regeneration. Eventually this is what allows for the wound bed to heal and close off. Stem cells help encourage the construction of a viable vascular supply, through the release of many growth factors.
The process concludes with the remodeling phase, wherein cells called fibroblasts help reorganize the extracellular matrix to reinforce the early granulation tissue and also to produce proteins that help regenerate the skin tissue. Stem cells express certain factors that help in this phase to promote growth of healthy and functioning dermal tissue, tissue that resembles uninjured tissue as opposed to scar tissue.
By understanding this entire process and the role stem cells play in it, we can then use a patient's own stem cells to help in the acute healing process. Stem cells directly applied to or injected into a wound can help with healing through multiple mechanisms, adding to their own injury response. There is also accumulating evidence that stem cells given systemically through an IV will find the injured area through complex signaling and still impart a regenerative effect.
I hope this explanation is not too scientific and not overly filled with "medicalese". If so, please let me know....
Subscribe to:
Posts (Atom)