Macular Degeneration and Diabetic Retinopathy Can be Reversed
Two major eye diseases and leading causes of blindness — age-related macular degeneration and diabetic retinopathy — can be reversed or even prevented by drugs that activate a protein found in blood vessel cells, researchers at the University of Utah School of Medicine and several other institutions have announced in a new study.
Damage from both diseases was prevented and even reversed when the protein, Robo4, was activated in mice models that simulate age-related macular degeneration (AMD) and diabetic retinopathy, according to Dean Y. Li, M.D., Ph.D., senior author of the study published March 16 in Nature Medicine online.
Robo4 treated and prevented the diseases by inhibiting abnormal blood vessel growth and by stabilizing blood vessels to prevent leakage. Abnormal blood vessel growth and leakage are two primary factors in both age-related macular degeneration (AMD) and diabetic retinopathy. But the study’s ramifications go beyond eye diseases.
Serious infections such as SARS (Severe Acute Respiratory Syndrome), for example, kill people when an infection destabilizes blood vessels, allowing fluids to leak into the lungs. Tumors hijack blood vessel growth to feed on nutrients and grow. Although this study did not prove Robo4 would treat those diseases, Li believes it merits investigation.
“Many diseases are caused by injury or inflammation destabilizing blood vessels and causing them to leak fluid into adjacent tissues as well,” said Li, professor of internal medicine and an investigator with the University’s Program in Human Molecular Biology and Genetics. “We found a natural pathway – the Robo4 pathway – that counterattacks this by stabilizing blood vessels.”
“This discovery has significant implications for developing drugs that activate Robo4 to treat AMD and diabetic retinopathy,” said Kang Zhang, M.D., Ph.D., associate professor of ophthalmology and visual sciences at the University of Utah’s John A. Moran Eye Center and an investigator with the University’s Program in Human Molecular Biology and Genetics. Li and Zhang’s laboratories closely collaborated on the research, using the same animal models of AMD and diabetic retinopathy that are required for drug development. The collaboration means the time required to test the approach in people could be shortened, perhaps by years. Nonetheless, both Zhang and Li caution that getting new drugs to market still would take a number of years.
Randall J. Olson, M.D., director of the University’s John A. Moran Eye Center and professor and chair of ophthalmology and visual sciences, called Li’s finding historic.
“This is a major breakthrough in an area where the advances have been minimal,” Olson said. “We are excited about taking this opening and moving the frontier forward with real hope for patients who have but few, often disappointing, options.”
Age-related macular degeneration is the most common cause of legal blindness in people age 65 or older and is expected to become an increasingly common and costly health issue as the number of older people in United States increases. Diabetic retinopathy is the most common cause of legal blindness in working-age Americans. Currently, there are an estimated 21 million people with diabetes.
Cryoablation Cures Early Kidney Cancer
Two papers presented today at the Society of Interventional Radiology’s 33rd Annual Scientific Meeting show that cryoablation — the minimally invasive interventional radiology treatment to freeze primary kidney tumors without surgery — is 95 percent effective when the tumors are four centimeters or smaller and nearly 90 percent effective for tumors up to seven centimeters, when the disease is confined to the kidney at one-year follow-up. The one-year benchmark is established and well-accepted within the medical community to gauge the success rate of a treatment option because most kidney tumors would be visible at one year with a CAT scan or MRI. “This interventional radiology treatment can effectively kill localized kidney tumors on an outpatient basis for most patients while offering a fast recovery time and an excellent safety profile,” said Christos Georgiades, M.D., Ph.D., interventional radiologist at Johns Hopkins Hospital in Baltimore, Md. When the disease is confined to the kidney, the intent of treatment is curative. Using imaging to pinpoint the tumor, the interventional radiologist inserts a thin probe through the skin and guides it into the tumor below. The probe freezes and kills the tumor during the procedure.
The study at Johns Hopkins Hospital showed nearly 95 percent efficacy for localized tumors up to four centimeters and nearly 90 percent efficacy for tumors up to seven centimeters, with the lesions showing as dead tissue (scar) with no recurrences at one-year follow-up imaging. The ongoing study currently includes approximately 70 lesions in 60 patients with primary renal cell carcinoma. Of the three patients who failed treatment (5 percent), one had a 10-centimeter tumor that physicians did not expect to cure, but there is only one centimeter of residual tumor that they plan to re-treat when the patient returns. The other two failures were in patients with larger tumors (7–10 centimeters), and physicians plan to treat those two patients again. One has only a half-centimeter residual tumor 18 months later. Thus, the secondary efficacy (after re-treatment) is expected to be close to 100 percent.
“The current gold standard treatment is laparoscopic partial nephrectomy surgery, but—given the high success of interventional cryoablation — that may change. We expect that the two treatments will be shown to be equivalent in a comparative study that is ongoing now at Johns Hopkins. The interventional radiology treatment is less invasive and easier on the patient,” noted Georgiades.
In addition to the patients who have the smaller tumors of four centimeters or less, this treatment offers a potentially curative option for patients with localized tumors who are not eligible for surgery. Many patients have other diseases that make surgery very high risk, cannot undergo the anesthesia and do not have any other option. Also, people with borderline kidney function, only one kidney or multiple recurring tumors had no options until now, he explained. “I want to get a message out, mostly to my colleagues, because they will encounter many patients who have these treatable cancers but they cannot have treatment or surgery because of other diseases. Until a few years ago, we in the medical community simply followed these patients; we didn’t treat the cancer for fear we may make things worse if we try to treat risky patients. But for many patients that’s no longer the case,” said Georgiades.
This interventional radiology treatment spares the majority of the healthy kidney tissue and can be repeated if needed. The treatment is very safe, and most patients are sent home the same day as the procedure. The rest go home the next day. The most common complication is a bruise (hematoma) around the kidney that goes away by itself.
The study from Barbara Ann Karmanos Cancer Institute in Detroit, Mich., involved 65 people and 81 masses, of which 61 were primary renal cell carcinoma (RCC), 6 oncocytoma, 1 angiomyolipoma, 8 renal benign or inflammatory lesions and 1 metastatic lesion. The average tumor size in this study was 2.8 centimeters. At 1.3 years average follow-up time (0.2–5 years), the majority of tumors continue to image as dead tissue. In contrast to heat, the cryoablation zone continues to shrink after cryotherapy, reducing up to 90 percent in volume by 12 months without scarring or strictures. Only 6 percent (5 of 81 tumors) had a local tumor recurrence, and these were limited to patients with multiple tumors in the kidney or an early probe failure. It is crucial to use enough cryoprobes to get sufficiently cold temperatures to kill all tumors and extend the visible ice approximately one centimeter beyond all tumor margins, similar to a surgical margin. Complications are avoided by liberal use of saline to push away the adjacent bowel, allowing tumors in nearly any location of the kidney to be treated.
“This interventional treatment is not a widely known procedure yet, even to other physicians, and patients are going to have to pursue it on their own,” added Georgiades. The treatment is widely available in the United States at all major institutions and some smaller institutions as well; it is usually covered by health insurance. The Food and Drug Administration (FDA) has approved cryoablation for use in soft tissue tumors, of which renal cell carcinoma is one. More information can be found at http://www.SIRweb.org.
Medical Myths Debunked
Is your doctor telling you old wives’ tales?
The British Medical Journal recently reported that many people, including physicians, often believe common health myths.
Dr. Aaron Carroll, co-author of the study said “We got fired up about this because we knew that physicians accepted these beliefs and were passing this information along to their patients.” The professor of pediatrics at the Indiana University School of Medicine is concerned that these ‘rumors have become facts’ in mainstream culture.
The misconceptions in question?
1. Eight glasses of water a day
According to the American Nutrition Council, their 1945 recommendation was that people need to ingest eight glasses of fluid for a total of 64 ounces each day. Ignored in the statement was that much of that necessary fluid is found in food, especially fruits and vegetables.
Freeman Stare, founder of the Harvard’s School of Public Health, added that other liquids (including so-called diuretics) also count, such as coffee and beer.
2. Turkey induces drowsiness
Yes, the chemical in turkey called tryptophan can cause drowsiness. However, turkey contains no more tryptophan than chicken or beef or pork.
The truth is that most people only eat turkey during a ‘feast’ which usually also features wine and overindulgence.
3. Humans use 10% of their brain power
This “goes against everything that you learn in medical school,” said Dr. Rachel Vreeman, a pediatrics research fellow at Indiana University and co-author of the report.
MRI and Pet scans show no dormant areas of the brain. Metabolic studies of how brain cells process chemicals reveal no non-functioning sections. Vreeman and Carroll believe that the myth was propagated by early motivational speakers in the 1900's to convince people that they had not reached their full potential.
4. Shaved hair grows back bigger The hair grows back with a blunt edge which seems thicker initially. However, it gets worn over time and reverses back to its natural thickness and texture.
5. Dark light ruins eye sight
Reading in the dark may cause eyestrain. It will subside with rest. But there is no evidence of permanent problems said Vreeman.
6. Hair and fingernails grow after death
No. “As the body’s skin is drying out, soft tissue, especially skin, is retracting. The nails appear much more prominent as the skin dries out. The same is true, but less obvious, with hair. As the skin is shrinking back, the hair looks more prominent or sticks up a bit,” Vreeman said.
She added “Whenever we talk about this work, (many doctors) express disbelief. But after we carefully lay out medical evidence, they are willing to accept that these beliefs are actually false.”
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