*** a monthly newsletter ***          

Vol.2, No.12, December 15, 2003

December 2003  HEALTH TOPICS:

New Tumor Marker For Prostate Cancer Detected

According to an upcoming article in the December 15th issue of Cancer (Cancer 2003;98) a research group from the Harvard Medical School,Boston, under Dr. Brian Liu describes a microdissection method where prostatic tissue from 17 suspected cancer patients were examined with a spectroscopic method for a new protein marker, the cellular protein PCa-24). This was found to be positive in 16 of the 17 samples.

In contrast, 12 patients with benign prostatic hyperplasia (also known as BPH or "benign prostatic hypertrophy") showed no trace of this prostate cancer specific protein. As this protein is located inside the prostate cancer cell (it is a cellular protein), one has to obtain a tissue sample through a prostate biopsy. The group under Dr. Liu achieved this through laser capture microdissection, which is described in more detail under this link. Proteomics , which is the method that was used to characterize the prostate cancer specific protein (PCa-24), is briefly discussed under this link, but it is not necessary to understand all of the ramifications of these methods.

What is important regarding the work by the group under Dr. Liu is to note that there is now a very reliable method available to distinguish between the harmless BPH condition and the deadly prostate cancer condition, which requires invasive therapy such as a radical prostatectomy. Both of these conditions can produce high prostate specific antigen (PSA) that can be detected in the blood. Dr. Liu's group plans to develop antibodies to the PCa-24 protein so that eventually there will be a more specific blood test available that could be used in patients with high PSA levels to distinguish between benign and cancerous prostate conditions.

In the future the physician might use the cheaper PSA screeing test to screen for prostate abnormalities and use the more expensive antibody test against the PCa-24 protein that is being developed to determine whether or not prostate cancer might be the underlying cause. Dr. Liu also wants to develop a high resolution body scan where in the case of metastatic prostate cancer the cancer cells would be located exactly where they are with a new imaging technique. These would have a high probability of being specific for prostate cancer, as the antibodies would be highly specific against the prostate cancer protein.

Here is a link to the Net Health Book's chapter on prostate cancer.

Help For Patients With Iron Overload

Patients who are born with an inborn enzyme defect that leads to iron overload (hemochromatosis) and others with secondary hemochromatosis due to sickle cell anemia will benefit from new research by Dr. Gavin Oudit, Dr. Peter Backx, Dr. Peter Liu and others. The researchers at the University of Toronto and Toronto General Hospital have published their findings in the Sept. 15 issue of Nature Medicine.

In animal experiments they found that the same calcium channels that transport calcium to vital organs are also the channels through which poisonous levels of iron are introduced with iron overload disease. In both animal experiments and in the clinical situation, human iron overload affects mainly the pancreas, the heart muscle and the pituitary gland. The authors of this study found that in hemochromatosis patients the calcium channel blockers, such as amlodipine (Norvasc), verapamil or diltiazem will stop the accumulation of toxic levels of iron in these organs.

Dr. Peter Backx, professor of physiology and medicine at U of T in the Heart & Stroke/Richard Lewar Centre of Excellence and senior author of the paper, explained that more detailed research determined that the L-type calcium channels that play a role in the normal calcium transport across the cell membrane are the same channels that allow the iron molecules into the heart muscle cells and into the cells of the other organs that get damaged with hemochromatosis. By using calcium channel blockers, heart drugs that are already on the market, it is possible to prevent accumulation of iron to the point of toxic levels. Up to now the only approach to therapy was to remove excessive iron from the body by expensive iron chelation medication that had to be given intravenously.

Further clinical trials on a larger patient population are necessary to determine who will benefit most from this approach of treating iron overload conditions with calcium channel blockers and what dosage to take. Dr. Peter Liu is another senior author regarding this study and is a cardiologist at the Toronto General Hospital and director of the Heart & Stroke/Richard Lewar Centre of Excellence and professor of medicine and physiology at U of T. He stated that this alternative therapy for heart failure from iron overload cardiomyopathy will likely open the doors for those patients worldwide who could not afford to have expensive chelation done, which is presently the only treatment method to remove the excessive iron. People of North American, European, Mediterranean or Asian descent are more prone to genetic hemochromatosis, thalassemia and sickle cell anemia that can all lead to iron overload requiring this type of therapy.

Here is a link to an article in the University of Toronto News about this research.

New Cholesterol-Lowering Drug Reduces Inflammatory Marker

With newer knowledge about the process of hardening of the arteries from the ongoing Framingham study it is not suprising that the drug companies are shifting the development of cholesterol-lowering drugs to those substances that will reduce inflammation of the arteries as well. In previous issues of the health newsletter I summarized a paper that was published on the importance of the C-reactive protein (also called CRP) in connection with the diagnosis of heart attacks and strokes. I also reviewed an article that pointed out that both CRP and LDL cholesterol are important in determining who is at risk for developing a heart attack or stroke.

In a press release to Reuters on Nov. 13, 2003 Merck & Co. Inc. and Schering-Plough Corp. announced that ezetimib (Zetia), a new cholesterol-lowering drug that is marketed by both companies, was found by their researchers to lower C-reactive protein (CRP) significantly. At the annual meeting of the American Heart Association in Orlando/Fla. these researchers presented a clinical trial showing that ezetimib when used in combination with small amounts of simvastatin (Zocor) lowered CRP by 33%. However, simvastatin alone lowered CRP only by 14.3%. Dr. Christie Ballantyne, a Baylor College cardiologist, pointed out that this new finding was very important. It was important, because it shows that these drugs do not only lower LDL cholesterol, which according to the Framingham study is a known risk factor for heart attacks and strokes. In addition it has now also been proven to lower CRP significantly at the same time, which is another known inflammatory component produced by the blood vessels also associated with heart attacks and strokes.

Merck and Schering-Plough are now developing a new formulation containing both of these medications as one pill. This has the advantage to lower the risk on liver cells of Zocor by being able to lower the dose in the pill. The Zocor component will mainly lower the LDL cholesterol in the blood (and the CRP somewhat as well) and the Zetia component will provide the beneficial effect of the CRP lowering (anti-inflammatory component and LDL lowering). There is another advantage of this combination: Zetia works by inhibiting absorption of cholesterol by the gut, Zocor works by inhibiting cholesterol synthesis in the liver cells. Whenever the mechanism of action is different two drugs in combination are usually better tolerated than if both would work through the same mechanism. However, the companies pointed out that more research and clinicial trials are needed to check out side-effects of Zetia before it would be submitted to the FDA for approval for general prescription by physicians.

Links regarding further information about heart disease (Net Health Book).

Fat Cells Secrete Hormones That Raise Blood Pressure

Fat cells are known to secrete a number of substances that affect the lining of the arteries and that are also known to be associated with the metabolic syndrome. One of the observations that physicians were aware of for some time is that aldosterone, a hormone from the adrenal glands, is often elevated in patients with high blood pressure and obesity or people who are overweight.

Dr. Ehrhart-Bornstein and her group from the University Medical Center, Heinrich Heine University of Düsseldorf in Germany investigated this interaction between fat cell metabolites and the cells of the adrenal cortex in more detail. They used a tissue culture model with human adrenocortical cells (NCI-H295R). To their surprise they found two separate hormone factors that were produced by fat cells and that showed in the tissue culture system a 7-fold increase in aldosterone hormone release. As aldosteron is a mineralocorticoid hormone they called these new releasing hormones mineralocorticoid-releasing factors. Further characterization of these factors demonstrated that one was of a higher molecular structure and was heat-sensitive, the other one was smaller in size and was more heat resistant. Each factor alone lost much of the aldosterone releasing activity, but when recombined they had 93% of the original action. Synthesis of messenger RNA inside the adrenocortical cells was stimulated by a factor of 10-fold from the action of the mineralocorticoid-releasing factors. Other hormones were also somewhat stimulated such as release of cortisol by a 3-fold increase and DHEA by a 1.5-fold increase. Other known substances from fat cells were entirely ineffective in this tesing system.

When asked how this new research might fit in with the observation that loss of fat through calorie restriction has a beneficial effect on high blood pressure, the authors commented that with less fat storage in fat cells during weight loss the production of mineralocorticoid-releasing factors would go down significantly and aldosterone would be released at a much lower rate thus decreasing blood pressure through the aldosterone/angiotensin/renin mechanism.

Here is a link to the original early publication by PNAS online.

Bystanders Become Lifesavers: Immediate CPR Improves Survival

Cardio-pulmonary resuscitation (=CPR) is known to save lives, but it has been known for some time that it has to be applied as early as possible to save lives on the longterm. In a recent study in Ottawa/Ont., which was published recently in the medical journal Circulation, the OPALS study checked out survival data.

OPALS is an acronym for Ontario Prehospital Advanced Life Support Study. One of the lead authors, Dr. Ian Stiell, emphasized that CPR done by bystanders (such as immediate family members) right in the beginning of a cardiac arrest will double the probability of having a survivor with quality of life that is very good.

Here are some detailed figures from that study. Only 14% to 15% of patients who suddenly collapse and are in need of CPR actually receive CPR. There were 8,091 cases of cardiac arrest that occurred between 1995 and 2000 in Ontario. Only 5.2% (418 patients) survived until the time of discharge from the hospital. 4% (324 patients) survived until the timeline of 1 year after the event. Of these the researchers were able to interview 268 survivors.

The following are a few observations from the OPALS study:

1. 85% of cardiac arrests happen at home.

2. 43% of cases are witnessed by bystanders, so if they all would know CPR about 3-times more unconscious patients could receive CPR (14% to 15% times 3 equals about 43%).

3. 65% of cardiac arrests in the OPALS study occurred in men. The authors recommeded that women over 40 should get trained in CPR.

4. Women usually play a more pivotal role in taking care of elderly parents, of their spouse and of children, which puts them more likely into a situation where bystander CPR is required.

5. Family members of heart attack survivors should be encouraged to take a CPR course as the probability of a cardiac arrest is higher in these patients.

6. All 4 links to successful resuscitation are important: CPR by a bystander; defribrillation; rapid access to care; early advanced cardiac life support.

7. Contrary to rumors the longterm outlook of successfully rescuscitated patients is

good and after 1 year the survivors have a quality of life as good as their healthy peers. However, without CPR initially the quality of life is only half as good as those who had someone provide CPR on them. The authors found it difficult to dispel some of the misconception surrounding CPR. Some of the myths are the notions that a person could do some harm by administering CPR or not performing CPR it correctly. They said it is important to be decisive and administer CPR to an unconscious person and call for an ambulance.

Summary: The OPALS study re-emphasized the importance for everybody to learn CPR. You never know when you need this skill. The more people know it, the more lives will be saved.

Here is a link to the University School of Medicine site entitled "Learn CPR - you can do it!"