Medical Articles by Dr. Ray

Dec

2003

Fat Cells Secrete Hormones That Raise Blood Pressure

By Ray Schilling | Diabetes, High Blood Pressure, Hormones, Obesity, Prevention

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 aldosterone 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 testing system.

Fat Cells Secrete Hormones That Raise Blood Pressure

Adipose cells secreting aldosterone releasing factor

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.

Nov. 12, 2003 paper on which this write-up is based: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC283571/

Last edited October 26, 2014

Dec

2003

New Cholesterol-Lowering Drug Reduces Inflammatory Marker

By Ray Schilling | Heart Disease, Prevention, Stroke

With newer knowledge about the process of hardening of the arteries from the ongoing Framingham study it is not surprising 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.

New Cholesterol-Lowering Drug Reduces Inflammatory Marker

Merck and Schering-Plough are now developing a new formulation containing both of these medications as one pill (Vytorin). 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 clinical 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.

P.S. on Oct. 31, 2012: Read the following article about Zetia and Vytorin (the combination pill): http://www.nytimes.com/2008/01/14/business/14cnd-drug.html?_r=0

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

Last edited December 9, 2012

Dec

2003

Help For Patients With Iron Overload

By Ray Schilling | Abdominal Pain, Gastrointestinal Disease, Heart Disease, Hormones, Prevention

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.

Last edited December 9, 2012

Dec

2003

New Tumor Marker For Prostate Cancer Detected

By Ray Schilling | Cancer, Prevention

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 micro-dissection 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 micro-dissection 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 screening 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.

New Tumor Marker For Prostate Cancer Detected

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.

Last edited December 9, 2012

Nov

2003

Growth Factor In Breast Milk A Key In Protecting Infants From Asthma

By Ray Schilling | Lung Disease, Prevention

It has been known for some time that breast milk plays a preventative role in infants. It transmits antibodies and protects from viral illnesses, but it also prevents the infant from developing asthma. Dr. Anne L. Wright, from the University of Arizona in Tucson, and colleagues published a study of 243 infants/mothers in the October issue of the Journal of Allergy and Clinical Immunology (J Allergy Clin Immunol 2003;112:723-728).

They measured cytokines and growth factors in breast milk and examined the infants paying particular attention to wheezing as a symptom of asthma. One of the cytokines, called transforming growth factor (TGF)-beta1, was inversely related to the amount of wheezing in the infants. In other words, the higher the level of this growth factor was in breast milk, the more protected from asthma the infant was. This was a highly significant correlation. After 3 months of being fed with breast milk with the highest level of TGF-beta1 the infants’ asthma rate was reduced by 78% compared to the rate of asthma found in infants fed only short-term with low level TGF-beta1 breast milk.

In their future research the investigators intend to investigate the effects of these breast milk cytokines on the cells, which form the lining of the airways, the immune system and the cells lining the gut in infants. There is already preliminary data to suggest cytokines play an important role in stabilizing these cells.

Growth Factor In Breast Milk A Key In Protecting Infants From Asthma

Breastfeeding prevents asthma

Here is a link to a chapter on asthma from the Net Health Book.

Last edited October 26, 2014

Nov

2003

Stroke Risk Increases With Carotid Artery Disease

By Ray Schilling | Heart Disease, Prevention, Stroke

An important study about the risk of strokes and mini-strokes (called”transient ischemic attacks”) was published in the Oct. 27 edition of the Archives of Internal Medicine. Dr. Daniel J. Bertges and his group followed 1,004 patients between 1988 and 1997 with ultrasound studies of the carotid arteries (carotid artery duplex ultrasound scans). The studies took place at the Pittsburgh Veterans Affairs Medical Center/University of Pittsburgh School of Medicine. Patients were followed with regard to events such as strokes on the side of where the narrowed carotid artery was.

Reversible mini-strokes (medically correct term:”transient ischemic attack” or TIA) were also registered. A total of 1,701 narrowed arteries (called “stenotic arteries”) were found with this ultrasound method. All of the patients initially had no symptoms of the carotid artery stenosis (no dizziness, no fainting, no absence spells or symptoms of TIA or stroke). In 75% of the patients the carotid stenotic lesions were less than 50% meaning that the carotid artery blood flow was acceptable.

Here are some of the risks as the study went on over the years: both TIA and CVA risk in a given patient occurred at a rate of 3.3% per year. Regarding a specific involved artery the risk of developing a TIA as a result of this was 2% per year and the risk to develop a stroke was 2.1% per year. The investigators found that two main factors determined the ultimate progression into a TIA or a stroke and they were as follows. First, if the artery was severely stenosed at the outset, the probability was high that this would progress and be the cause of a stroke. Secondly, the degree of progression when checked with a follow-up duplex ultrasound was another important factor in terms of leading to a subsequent TIA or stroke.

Stroke Risk Increases With Carotid Artery Disease

Carotid artery clot can cause stroke

The composite risk of developing either a TIA or a stroke with a worsening stenotic carotid artery lesion was 1.68-fold. To develop a stroke alone in this scenario the risk was 1.78-fold. Clinical risk factors were of no help in predicting which cases would go on to develop TIA’s or strokes. However, the finding of further progression of a stenotic carotid artery lesion documented on serial duplex ultrasound studies was highly significant.

The authors concluded that there is value in doing serial carotid artery duplex scan studies in the same patient to screen for progressing stenotic lesions in the carotid arteries. When a stenotic lesion is significant enough or progressing fast, intervention by a cardiovascular surgeon with carotid endarterectomy can be done to prevent a stroke or TIA.

Here is a link to a chapter on strokes from the Net Health Book.

Last edited October 26, 2014

Nov

2003

Leeches And Arthritis Pain; Old Facts And New Insights

By Ray Schilling | Arthritis

Leeches have been used for centuries, particularly in Europe, for the treatment of chronic conditions and for arthritis pain. A group of researchers under Dr. Gustav J. Dobos from the University of Essen (Kliniken Essen-Mitte) in Germany published a paper in the Nov. 4, 2003 edition of the Annals of Internal Medicine (Ann Intern Med 2003;139:724-730,781-783) about the use of leeches in osteoarthritis, and particularly with knee arthritis.

In a randomized trial that lasted 91 days the researchers applied 4 to 6 leeches once to the knees of one group of 24 patients and used conventional diclofenac gel topical applications twice daily in a matched control group. On average the leeches fell off after 70 minutes. A simple pain score (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) visual analog scale pain scores) was used to quantitate the pain that the patients experienced in both groups. I have tabulated the results after 7 days of therapy and included the relative improvement in the pain score here, based on their data.

Leeches And Arthritis Pain; Old Facts And New Insights

According to Dr. Dobos there are powerful anti-inflammatories and hyaluronidase in the saliva of the leeches that have not been defined further. Now that these initial investigations have shown a more than 3-fold beneficial effect of the leeches versus conventional anti-inflammatory therapy for osteoarthritis, it is the intention of the group to define the active pharmaceutical ingredient from the leeches further.

Relief from osteoarthritis knee pain using leeches or diclofenac
Arthritis therapy:	WOMAC pain scores improved…	Relative improvement of pain score:
leeches (applied once)	from 19 to 52	64%
diclofenac gel (twice per day for 28 days)	from 42 to 52	19%

Apart from pain control other beneficial effects such as improvements in ranges of motion, swelling and inflammation were also noted, again more so in the group treated with leeches. However, leeches have the disadvantage that they puncture the skin and that they can transmit infections (from Aeromonas hydrophila). It is hoped that in future medication can be developed from this line of work that can be taken in pill form without the dangers of applying leeches.

Here is a link to a review of osteoarthritis from the Net Health Book.

Last edited October 26, 2014

Nov

2003

Blood Clots In Legs Can Be Caused From Long Flights

By Ray Schilling | Health, Lung Disease, Prevention, Uncategorized

A new study from Australia has shown that the risk for developing blood clots in the legs (deep vein thrombosis) is increased 4-fold in the first two weeks after a long-haul airplane flight. This was published on Nov. 8, 2003 in the British Medical Journal (BMJ. 2003;327:1072) with the lead author being Dr. C.W. Kelman of the Commonwealth Department of Health and Ageing, Canberra.

Data was collected of 5,408 patients who had been hospitalized to Western Australian hospitals for deep vein thrombosis between 1981 and 1999. A total of 153 Australians were admitted with blood clots in the leg veins within 100 days of international flights. 46 of these patients developed their blood clots within 14 days of arrival, which was much more than would have been expected in the general population. The researchers found that between 15 days and 100 days following a long-haul flight the risk of developing clots in the deep veins of the legs was not increased from the background rate of the general population. The patients who had developed their blood clots within 14 days of a long flight had a risk that was 4.17-fold higher than the average population’s risk. Of these patients 76% were thought to have developed the clots as a result of a flight. In terms of a yearly risk, if a person does one long-haul flight per year, the probability of developing a clot in the leg veins would be about 12% higher than in a non-traveling comparison group. As this condition is treated effectively with blood thinners, the death rate is quite low, approximately 1 per 2 million long-haul flights.

Blood Clots In Legs Can Be Caused From Long Flights

This would be much lower than the risk of death from car accidents. The authors suggested that more study is needed to determine the risk factors for developing flight induced deep vein thrombosis. When this is known, investigations will be able to concentrate on blood clot prevention from air travel.

Link to a chapter on pulmonary emboli, which can develop from a deep vein thrombus that breaks loose.

Last edited December 9, 2012

Nov

2003

Osteoporosis In Males Is Common

By Ray Schilling | Fitness, Health, Hormones, Prevention, Vitamins and supplements

A new study from the University of Toronto/Ontario has shown that contrary to the conventional teaching ostoporosis is not only a problem in females, but also a problem in males. The Canadian Multicentre Osteoporosis Study (CaMos) showed according to the epidemiologist Natalia Diaz-Granados that in Canada 16% of all women above the age of 50 and 5% of men above the age of 50 developed osteoporosis.

In the past men were thought to be more or less immune to osteoporosis, but this is not so. The results of this study were presented recently at the annual meeting of the American Society for Bone and Mineral Research in Minneapolis. 1,768 of the 2,884 men who were recruited into CaMos were eligible for the study, because they had not taken oral corticosteroids for three months, and bone scans were taken to measure bone density of their upper femurs (upper thigh bones). 89 men (or 5% of the group of 1768) showed osteoporosis. The mean age of this group was 65 years ranging from 50 to 96.

The researchers studied the high risk factors in men with osteoporosis and found that they were remarkably similar to the risk factors in women with osteoporosis. I have summarized the findings here in tabular form.
The study also showed that for men hip fractures seem to be more lethal than for women as within a year after a hip fracture from osteoporosis more men die. If a physician sees a patient and notices 2 or more of the risk factors identified in the table above, a bone scan to screen for osteoporosis should be done.

Osteoporosis In Males Is Common

There are many more unanswered questions with regard to life styles and nutritional information. It is not known from this study whether the men were physically less active and whether there was a higher alcohol abuse and /or nutritional dysbalance with associated vitamin deficiencies. The authors stated that future research will focus on these factors and on whether biphosphonates (alendronate or Fosamax) are as useful in men with osteoporosis as they are in women.

Risk factors for osteoporosis in men
Risk factor:	Explanation:
weight less than normal	this may point to poor nutrition, lack of calcium, vit. D etc.
older men	bone loss occurs slowly with age, both in men and women
history of smoking	smoking reduces blood supply to the nutritional vessels in the bone. This leads to less bone forming cells (osteoblasts)
family history of osteoporosis	one or more genes code for osteoporosis. More research needed in this field to develop new medications
history of fracture beyond the age of 50	osteoporosis leads to brittle bones with more fractures. A fracture in this age group should make the physician suspicious of osteoporosis or a metabolic bone problem

Based on an article in The Medical Post, page 78, Oct. 14, 2003.

Link to a chapter of osteoporosis in my Net Health Book.

Last edited December 9, 2012

Oct

2003

Flu Shot Cuts Death Rate Into Half

By Ray Schilling | Infectious Disease, Lung Disease, Prevention

An earlier publication in the New England Journal of Medicine in March 2003 has shown that the death rate of people 65 years or older who were vaccinated against the flu, dropped into half when they were exposed to the flu and were compared to non-vaccinated controls. On Oct. 9, 2003 Dr. Megan Wren, associate director of the internal medicine residency at Barnes-Jewish Hospital and Washington University School of Medicine, reminded physicians that with the upcoming flu season it is important to include everybody who is healthy at age 50 or older (as the CDC has suggested now for 3 years) with influenza vaccination . Many physicians are still not aware that the rules have been changed to incude younger persons.

Below are recommendations of who should get a vaccination (in table form).

Dr. Wren pointed out that the risk from a flu vaccination is minimal. Contrary to public belief the flu vaccine does not cause fever, unwellness or muscle aches. The only effect is a mildly sore arm at the site of injection.

Flu Shot Cuts Death Rate Into Half

This year the FDA has approved a live flu vaccine that is administered as a nasal spray. This is a live modified flu virus that has been “trained” to only multiply in the colder nasal cavity, but not in the warmer airways. Like with all live viral vaccines pregnant women are not allowed to take this.

Who should get the flu vaccine ?
Group of people:	Comments:
all people age 50 or over	the immune system weakens with age, that’s why complications of the flu are more common in this age group
women who will be in the 2nd or 3rd trimester of a pregnancy during November through to March	protects the fetus from the flu virus in the most vulnerable period of the development of the fetus
chronic heart disease or lung disease (including asthma)	the flu affects the lungs and the heart most readily
chronic kidney or liver disease	these chronic diseases weaken the immune system
people without a spleen and cancer patients	the immune system is weak in these patients
children and adults with any chronic disease including diabetes	chronic illnesses weaken the immune system in young and old
people on imunosuppressive medications	the immune system is weak in these patients
all close family members of any of the above people	the CDC hopes that this stops the spread of the flu into this vulnerable group of patients

Dr. Wren also mentioned that people with chronic illnesses, with immune deficiencies (e.g. AIDS and cancer patients) and healthy patients over the age of 50 cannot take this live vaccine. All others from age 5 to 49 can take it, but presently this is still very costly (one nasal mist application in 2003 is about 50.00$ US).

Last edited December 9, 2012

Who should get the flu vaccine ?

Group of people:

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