Health Newsletter:March 2004
Related Links:| Age-Related Macular Degeneration Blindness Eye Care | Diabetes Diabetes Diet Coffee | Vitamin C Vitamin E Alzheimers Disease | Diabetes Clogged Arteries Heart Attacks | Terminal Cancer Cancer Support Cancer Treatment |
From WebHealth
Contents |
Inflammatory Marker Linked To Blindness
Up to now age-related blindness or "age-related macular degeneration" (AMD) as it is medically called, has been a mystery. The retina is the light-sensitive area of the eye similar to the film in a camera. The "macula" is that part of the retina that has the highest visual acuity. Several studies have been conducted lately regarding age-related blindness that shed more light on this important health hazard of old age, studies that one day might even lead to a cure or powerful preventative measures to avoid it from ever developing.
One such study is the one by Dr. Johanna M. Seddon and co-workers published in the Feb. 11, 2004 issue of the Journal of the American Medical Association. Almost 1000 patients with various degrees of age-related degrees of blindness from the Age-Related Eye Disease Study (AREDS) were classified by the degree of their macular degeneration. I have produced the bar graphs below based on these studies.
Four groups were defined, namely those with no AMD who served as controls, those with mild AMD, those with moderate AMD and those with severe AMD who were legally blind. They suspected that an inflammatory marker in the blood stream of these patients, called C-reactive protein (CRP), might be present in the more severe cases of blindness when compared to the control group who did not have any inflammatory changes in the macula. As can be seen by the bar graph above this is exactly what the test results indicated. They also found that smokers (blue bars) tended to have slightly worse blood tests in terms of CRP (more inflammatory substances circulating in the system) within the same severity category of the age-related eye changes.
When the investigators studied the risk for the highest percentile of the CRP tests within various subgroups to show AMD they found several differences as is shown in the next table. First there was a low probability to develop AMD in a person with a normal looking macula and that risk was set at 1.0 as comparison. In contrast a person with a normal looking macula who smokes has a 1.5-fold risk of developing AMD later. Patients with a moderate degree of AMD have about a 2-fold risk of getting a severe degree of AMD later (smoking or not). It seems that once the inflammatory cycle has started, the process of causing a moderate degree of AMD is so strong that the effect of smoking will not add that much in comparison.
This is the first study of this kind that has established that CRP can be used as a screening for the risk to develop AMD. CRP has already been established as a test for monitoring progress in rheumatoid arthritis or to monitor for the risk of developing a heart attack or stroke.
Another study by Dr. Johanna M. Seddon and co-workers was published recently in the Archives of Ophthalmology. 261 people aged 60 years and older with established AMD were followed for 4.6 years and checked for deterioration. 101 patients had deterioration of their AMD.
The authors analyzed the patients' diet habits and found that increased fat intake was a high risk factor for deteriorating AMD. Both vegetable and animal fat had a 2-to 3-fold increased risk for deterioration of the AMD to a more severe stage (legal blindness). Fish, omega-3 fatty acid and nuts had a protective effect, but only when omega-6 fatty acid (linoleic acid) intake was low in the same group. The studies showed that the risk of age-related blindness was reduced by 40% when patients ate nuts at least once per week. The authors concluded that a "fat conscious diet" would be good for "maintaining good eye health" and at the same time be beneficial for prevention of heart attacks and strokes.
The authors will do further studies to investigate potential ways of helping patients with AMD and to understand the mechanisms of the disease process better.
JAMA 2004;291:704-710
Arch Ophthalmol - 01-DEC-2003; 121(12): 1728-37
Less Diabetes With Coffee
A Dutch Study has shown previously that coffee consumption was reducing the risk for developing diabetes. Now Dr. Salazar-Martinez and co-workers have confirmed this in a study involving even larger numbers of both men and women. This was published in the Annals of Internal Medicine and the research team is from the Harvard School of Public Health, Channing Laboratory, Harvard Medical School, and the Brigham and Women's Hospital, Boston, Massachusetts.
A total of 41,000 men and 84,000 women from the Nurses' Health Study and the Health Professionals' Followup Study were followed between 12 and 18 years. 1,333 men and 4,085 women developed diabetes during the time of observation. All of the data was analyzed carefully by controlling for other factors such as obesity, smoking, high blood pressure etc. to be certain that the only difference in the observed groups was the amount of coffee consumed. According to the authors the gender differences are probably unimportant and may have to do with the different sample sizes. However, as the graph shows clearly, with the consumption of around 4-5 cups of coffee per day there is a significant 30 % drop in risk to develop diabetes.
The Dutch Study showed a 50% drop in risk with 7 cups or more per day and the study here suggests a similar drop with 6 cups or more.
Dr. Frank Hu, associate professor of nutrition and epidemiology at Harvard School of Public Health, who co-authored this study stated that physicians should still recommend to patients first to exercise and to loose weight to control diabetes. It would be premature to recommend heavy coffee consumption to patients for diabetes control.
This beneficial effect was also observed to a lesser extent with decaffeinated coffee, but not with tea. According to Dr. Hu caffeine, chlorogenic acid and magnesium likely play a role in the protective effect with regard to diabetes prevention. Further studies will be done to see whether diabetes patients who drink coffee have a better outcome when they develop a heart attack.
Ann Intern Med - 6-JAN-2004; 140(1): 1-8
Vitamins C And E - A Weapon Against Alzheimers
A study in a recent edition of the Archives of Neurology reports about 4740 patients from Cache County, Utah, who were 65 years or older and were followed over 5 years. At the start it was found that those who had taken vitamin C and E on a regular basis as separate supplements had a 78% lesser risk of developing Alzheimers (correct medical term: "Alzheimer's disease").
5 years later out of 3227 survivors who were at risk 104 more people had developed Alzheimers, but 64% of those who combined vitamin C and E as a supplement did not develop Alzheimers. Dr. Peter Zandi from the Department of Mental Health, Bloomberg School of Public Health, The Johns Hopkins University/ Baltimore, Md was the lead author of this study. He stated that this was only an observational study, but that the data was convincing enough to warrant a full-scale controlled trial to examine the value of anti-oxidant agents (such as vitamin C and E) as a preventative against Alzheimers. There were a number of built-in controls such as vitamin C alone, vitamin E alone and multiple vitamins (including vitamin C and E in smaller dosages) that were all ineffective in preventing Alzheimers. The daily dosages that were necessary for the protective effect were vitamin C 500mg to 1000 mg or more per day as well as 400 IU to 1000 IU of vitamin E per day. The U.S. recommended daily allowance was insufficient for the protective effect. These dosages typically are in the order of 22 IU of vit. E and 75 to 90 mg of vit. C. Vitamin B complex alone was also ineffective in protecting against Alzheimers.
Comments
There are many unanswered questions about Alzheimers, but this paper gives valuable hints in terms of the protective effect of two vitamins (vitamin C and E taken as separate supplements daily). There are other factors such as genetic ones and perhaps a dysregulation of the cholesterol brain metabolism that lead to the production of a glue-like substance, called "beta-amyloid" ,that causes memory loss in Alzheimers patients. Testosterone has recently also been noticed to be important in the prevention of Alzheimers disease. In addition to these vitamin supplements a low glycemic, low fat diet would likely be very beneficial together with a regular exercise program and calorie restriction to prevent Alzheimers disease in many patients (prevention of the metabolic disease).
Arch Neurol - 01-JAN-2004; 61(1): 82-8
Ankle Blood Pressure Reveals Diabetic Problems
One of the complications of diabetes is that ity leads to clogged arteries from peripheral artery disease and this can lead to heart attacks, strokes and circulation problems in the legs.
Recommendations were recently given to physicians in the December edition of the medical journal Diabetes Care that circulation problems in diabetics need to be monitored more stringently to avoid needless amputations.
Medically these circulation problems that affect mainly lower legs and feet are known as "peripheral vascular disease" (or PVD for short). PVD can be detected by the physician checking for ankle pulses. Another valuable and very simple test is to measure the blood pressure in the arm and at each ankle (using the stethoscope just under the inside (medial) ankle bone. If there is a major discrepancy between the arm and ankle blood pressure or if the ankle pulse is missing, this would be a sign of possible PVD. With a diabetic patient it would still be important to get the hemoglobin A1C under control through exercise, a low glycemic diet and possibly anti-diabetic medication. But the patient likely would have to be referred to a cardiovascular surgeon for further testing in order to find out whether there would be hardening of the arteries with circulation problems in the lower leg, the ankle or foot. Dr. Peter Sheehan, the director of the Diabetes Foot & Ankle Center at the New York University school of medicine, stated that many patients and doctors overlook how frequent this condition is. About 33% of diabetic patients who are older than 50 years have PVD, but only a fraction know about it until it is too late. Once a patient has PVD in one of the legs there is a 4-fold risk of getting a heart attack or a stroke, because the hardening of the arteries is happening simultaneously in all of the body's arteries. If the blood pressure is normal at the ankle, Dr. Sheehan recommends to check it again in 5 years.
Who should have the blood pressure check at the ankle? Here is a table that summarizes Dr. Sheehan's recommendations.
*PVD = peripheral vascular disease
Why is it so important to screen for circulation problems in the lower legs? Because this is the area where diabetics tend to get problems that often result in amputations of a foot or lower leg below the knee. With early detection of these problems and intervention by a cardiovascular surgeon often disastrous outcomes can be avoided.
Genetic Manipulation For Terminal Cancer
Two publications recently highlighted the importance of the p53 gene that is located on the human chromosome 17, which has been dubbed the "guardian of the genome".
It appears that its role is to suppress any cell that has damage of the genetic material (of the DNA). If the suppressor gene p53 is not working in a cell, it will continue to divide and become a cancer cell. Only, if the p53 gene is working properly, will the cell go through its normal life cycle, which includes cell birth, a certain period of life and cell death ("apoptosis").
This sounds all very theoretical, but I will demonstrate with two examples from the current medical literature how this knowledge has already been used and will likely be developed further in a practical sense in cancer patients. The first paper has to do with repairing damaged p53 genes directly with genetic modifications. The second paper approaches this problem from a different angle. It deals with the other half of cancers that originate not from genetic defects of the p53 gene, but from an overproduction of inhibitors that are produced in the cell itself, particularly in many cancer cells. A new class of very promising compounds have been developed that can neutralize the action of the inhibitors and normalize p53 function.
1. The cancer treatment specialists at the M.D. Anderson Cancer Center in Houston/Texas have done several clinical trials where they have proven that with the help of gene transfers into tumor cells of lung cancer patients the survival in these previously hopeless cancer patients can be significantly improved. A summary of these studies has been published in the February 2004 edition of the Hematology/Oncology Clinics of North America.
45% to 75% of these types of lung cancers have the p53 gene deficiency and for this reason are particularly difficult to treat as they are not responsive to chemotherapy or radiotherapy. These researchers and many other researchers in this field have shown that the specialist can transfer the missing p53 gene back into the cancer cells in a number of ways and this way change their growth pattern. These modified cancer cells either stop behaving like cancer and the patient is cured (a certain percentage, but not the majority). On the other hand the changed cancer cells can often be rendered more sensitive to chemotherapy and radiotherapy, which happens in about 60 to 70% of the genetically treated cases. Overall it is now possible with a combination of gene therapy and chemotherapy and/or radiotherapy to get about a 50% response rate and about 20% cures on the longterm. In the past all of these patients would have died within a few months from the initial diagnosis. The researchers of that publication stressed that these new treatment approaches are not yet routine in cancer treatment, but that with further refinements there will soon be more hope for these difficult cancer patients. This would be applicable not only for the difficult to treat lung cancer patients, but also for many other types of soft tissue cancers that often have p53 gene deficiencies and that up to now have often been untreateable.
2. The second paper that fits into this topic was published recently in the January 2, 2004 issue of the magazine Science. Researchers from the Hoffmann-La Roche labs in Nutley, New Yersey, have found that a new class of smaller molecules is able to inhibit the main group of oncoproteins known as MDM2 inhibitors that interfere with normal p53 function. The molecular oncologists at Hoffmann-La Roche under chief researcher Lyubomir Vassilev have successfully undertaken research in this complex interaction between the life saving p53 gene action and the undermining effects of various oncogene proteins and in particular the MDM2 inhibitors. There are two such substances of a new class of potential drugs that seem to be particularly promising. The new class of drugs was coined "Nutlins" in honor of the site of where they were discovered. Nutlin-1 has been tested in cultured tumor cells and was able to boost p53 activity resulting in sudden normal function. The cancer cells stopped dividing and disintegrated (due to the normal tumor fighting action of the p53 gene).
Another similar molecule, called Nutlin-3, was fed to nude mice who are deficient in their immune system and that are used by cancer researchers as a model to grow various types of tumors. In this model there was a 90% cure rate, which is unheard of as usually 100% of these nude mice would die from any transplanted tumor. There were no demonstrable side-effects in these mice that survived. Drs. Vassilev and David Heimbrook from the Hoffmann-La Roche cancer drug unit pointed out that this type of effect is much better than any cancer drugs that are presently used, however they added that it will be very difficult to predict how quickly this could be translated into the human situation with clinical trials. There is definitely a niche for treating sarcoma, which is one of the more difficult to treat cancers. Other cancers would be malignant tumors of the connective tissues, of nerves, bones, blood vessels, fat, muscles, deep skin tissues and cartilage. Many of these as well as some lung cancers produce high levels of the MDM2 protein. It is these types of tumors that would be the most likely candidates for early human trials with the Nutlins.
February 2004 edition of the Hematology/Oncology Clinics of North America (Volume 18 • Number 1 • February 2004), published by Saunders, and entitled "Gene replacement therapy for non–small cell lung cancer: a review".
January 2, 2004 issue of the magazine Science.
