Jan
23
2021

Review about Human Oncolytic Virus Research in 2020

The British Medical Journal published a review about human oncolytic virus research in 2020. That is to say, the BMJ published this report in July 2020. On the negative side, the report is rather complex with many technical terms. With this in mind, I will keep it as simple as possible for this summary. Notably, oncolytic viruses are a new way of treating cancer. Adenovirus was the most common oncolytic virus in use by cancer research in the past 20 years. It must be remembered, researchers applied this to mainly melanoma and gastrointestinal cancers. In the past I discussed the use of oncolytic viruses in a related post.

History of licencing of oncolytic viruses

  1. The first oncolytic virus was licenced in 2004 in Latvia. This was an RNA virus derived from the native ECHO-7 strain of a picornavirus, called Rigvir. This oncolytic virus was approved for treating melanomas.
  2. Shortly after, in 2005, China approved a genetically modified adenovirus, H101 as an oncolytic virus. The approval was for the treatment of nasopharyngeal carcinoma combined with chemotherapy.
  3. In 2015, the U.S. the FDA approved T-VEC (Talimogene laherparepvec), an attenuated herpes simplex virus, type 1. This new oncovirus encodes granulocyte-macrophage colony-stimulating factor (GM-CSF). This is effective for the local treatment of inoperable, recurrent melanoma. It works for cutaneous, subcutaneous and nodal lesions in patients with recurrent melanoma after initial surgery.

Review of 20 years of human oncolytic virus research

The investigators reported about 97 clinical trials with oncolytic viruses performed between 2000 and 2020. That is to say, this involved 3233 patients with cancer. Most of these trials were phase I (50.5%) trials. There were an additional 6.2% studies, which were phase I/II. 11.3% were phase II clinical trials and only 2.1% were phase III clinical trials. 29.9 % of the literature did not specify what type of trial the investigations were about. However, they likely belonged into the phase I category as they reported on first trials of a therapy on man.

Oncolytic viruses derive from various types of viruses 

The number of studies that used a certain virus-derivative are included in brackets. It must be remembered that most of the studies dealt with six viruses: adenoviruses (30), herpes simplex virus (HSV-1) (23), reovirus (19), poxvirus (12), Newcastle disease virus (NDV) (5) and measles virus (3).

Stimulation of the immune system through GM-CSF

In 24 studies the researchers introduced GM-CSF transgene into an oncolytic virus. GM-CSF is a glycoprotein that is normally produced by granulocytes, a type of white blood cell. In this case, it stimulates dendritic cells, the precursors of T cells to produce killer T cells. Notably, this stimulates the immune system to better fight cancer.

Types of cancer targeted with oncolytic viruses

It is important to realize that the majority of the studies treated melanoma cases and gastrointestinal cancers. Namely, gastrointestinal cancers included esophageal cancer, gastric (stomach) cancer, colorectal cancer and pancreatic cancer. There were 30 studies involving melanomas with 1000 patients. There were 76 clinical trials regarding gastrointestinal cancers with 577 patients.

Moreover, other cancers where oncolytic viruses were studied were head and neck cancer (15 studies) breast and gynecological cancers (31 studies), genitourinary cancers (26 studies), and sarcomas (16 studies).

Other drugs given along with oncolytic viruses

It must be remembered that of the 97 total studies 62.9% were clinical trials where oncolytic viruses were the only therapy. In 37.1% of the studies physicians gave the oncolytic viruses along with cytotoxic chemotherapy, immunotherapy or radiotherapy.

Side effects of treatment with oncolytic viruses

The safety profile for treatment with oncolytic viruses appears to be tolerable. Fever was common, as were chills. Some patients reported nausea and vomiting, flu-like symptoms, fatigue and pain. But these symptoms disappeared within a few days.

Suppression of the bone marrow for a period of time was common, but more so when there was a combination of  oncolytic viruses with chemotherapy. None of the patients transmitted viruses to household contacts or the healthcare team.

Antitumor activity in clinical trials with involvement of oncolytic viruses

An analysis of clinical responses to oncolytic virus therapy showed the following:

  • 1% had disease control, which broke down as follows (items 2,3 and 4)
  • 4% complete control (=cure)
  • 7% partial control
  • 12% stable disease
  • 9% No response to treatment with oncolytic viruses

HSV-1 derived oncolytic viruses had the best response. The responses were not as good with adenovirus, reoviruses and with vaccinia viruses.

Discussion

Researchers of the BMJ publication analysed 97 clinical trials regarding oncolytic viruses over the past 20 years. This showed a number of points worth mentioning.

  1. The goal of oncolytic virus therapy is to induce tumor cell death. Physicians could achieve this indirectly by stimulating the immune system. Oncolytic viruses can stimulate both the innate immune system and the tumor-specific adaptive immune response.
  2. In the earlier years a lot of clinical trials investigated the safety of oncolytic viruses. But it became clear that oncolytic viruses were safe and fairly well tolerated.
  3. Many clinical trials involved oncogenic viruses with GM-CSF recombinant genes. This gene makes the oncolytic virus produce the GM-CSF protein, which stimulates dendritic cells. The end result is that the immune system produces more killer T cells that attack cancer cells, which results in higher cure rates.

More problems with oncolytic viruses

  1. There are still many questions about how oncolytic viruses stimulate the immune system. More basic research is necessary in this field. Despite 20 years of research the cure rate of 3.4% and achieving partial control and stable disease in another 17.7% is not acceptable. Perhaps combinations with other cancer treatment methods may improve the cancer cure rates. The reviewers suggested one such combination, namely immune checkpoint blockade with oncolytic virus therapy.
  2. There is no resolution about which route of administering oncolytic viruses is best. Intratumor application in melanoma cases seems the be optimal. But other solid tumors are difficult to reach. In these cases, intravenous applications were a choice. In this case oncolytic viruses experience dilution in the blood and do not have a high enough concentration when they arrive at the cancer.
Review about Human Oncolytic Virus Research in 2020

Review about Human Oncolytic Virus Research in 2020

Conclusion

In a review researchers discussed the use of oncolytic viruses in cancer therapy over 20 years . Oncolytic viruses are derivatives mostly from adenoviruses, herpes simplex virus (HSV-1), reovirus, poxvirus, Newcastle disease virus (NDV) and the measles virus. In various clinical trials researchers found that disease control was achieve in only 21.1% of treated cases. There was a cure rate of 3.4%, but another 17.7% had partial control of the cancer or stable disease. But 78.9% of treated patients showed no response to treatment with oncolytic viruses. Obviously more research is necessary to improve the cure rates in cancer patients treated with oncolytic viruses. Clinical trials with combinations of immune checkpoint blockade and oncolytic virus therapy would also be helpful. All in all, oncolytic therapy is at this point not yet an effective form of treatment for cancer.

Jul
02
2016

Zika Virus

Recently the question was asked on the news whether it was safe to go to the Olympics in Brazil; so here is some background information about the Zika virus. Zika virus was first isolated from mosquitoes in a forest named Zika forest in Uganda, which was in 1947.

Zika virus belongs into the virus family of Flaviviridae. Other members in that family are dengue fever, West Nile virus, yellow fever and Japanese encephalitis. Since the 1950’s Zika virus has occupied a narrow equatorial belt around the globe (Africa and Asia). But between 2007 and 2016 it spread further to the Americas and to the Pacific. This includes specifically French Polynesia, the Cook Islands, Easter Island and New Caledonia. Since May 2015 Brazil has joined the countries where mosquitoes are infected with Zika virus. This is an important point to know for the coming up Olympics in Rio on August 5 to 21, 2016.

Symptoms of Zika virus

For most people, particularly the young and middle aged ones Zika is  not be that symptomatic. The most common symptoms are a fever, a skin rash, joint aches and red eyes (conjunctivitis). However, when a pregnant woman gets Zika virus, this will likely affect the fetus and will lead to a baby born with a small head (microcephalus), a severe complication from Zika virus. When a woman contracts Zika virus, the virus disappears after about one week. But in men the virus seems to stay longer, particularly in semen. This is why the CDC recommends for men using a condom or refraining from sex when returning from a holiday in a Zika endemic area. It may take up to 8 weeks for the semen to no longer be infective. The CDC recommends that a man who has come down with Zika to use a condom for 6 months.

Treatment of Zika virus

Make sure you get lots of rest. Take acetaminophen for fever or pain. Don’t take aspirin (ASA) or anti-inflammatory medication. Be aware that for between 1 and 3 weeks your blood likely is infectious. You want to avoid a bit from a mosquito and it is sensible to use insect repellants. The same insect could have bitten another person and spread the virus this way. A person who gets the Zika virus depends on the immune system to overcome the infection as there is no cure for this viral infection.

At this point no vaccine against Zika exists. There is research in an attempt to develop a Zika vaccine, which may become available in 2 to 3 years.

Zika virus risk with travel

If you travel to endemic areas, but visit mountainous areas above an elevation of 6,500 feet (2,000 meters) you are safe from Zika transmitting mosquitoes as they do not survive in these heights.

With regard to the Olympic Summer Games in Rio 2016 the CDC recommends to take a few precautions. Use insect repellents. Be aware as a woman that men infected with Zika virus can transmit the virus through sex. If you want to protect yourself from the risk of giving birth to a child with microcephaly, you may decide to use the birth control pill and ask your partner to use a condom. When you return back home, do not plan for a pregnancy for 6 months to avoid the risk.

The only recommendation for the Olympics by the CDC is that pregnant women should categorically not go to the games for fear of getting Zika infection resulting in a bad outcome of the pregnancy with microcephaly.

Microcephaly and other brain abnormalities from Zika virus

The CDC has stated that it is now established that Zika virus can cause microcephaly, but that it likely does not do so in all cases of Zika virus infection.

We know from German measles (rubella) that it can cause serious health risks for the fetus including death.

Zika is similarly neurotropic, meaning that it likes to multiply in nervous tissue including the brain. With rubella there is a vaccine available, which has made it much safer for pregnant women. But with Zika no vaccine is available. The only prevention is to stay away from endemic Zika areas and otherwise use reliable birth control methods.

Zika Virus

Zika Virus

Conclusion

I have briefly reviewed Zika virus in this blog. Unfortunately there are still many gaps in the knowledge of this disease. We need an effective Zika virus vaccine. It would also help to have antiviral antibiotics. Research is necessary to research all of this. For now we need to use prevention and avoid endemic Zika regions by reading updates by the CDC.

Aug
23
2014

Ebola Virus An Emerging Killer Infection

Ebola virus has now infected about 2600 and killed more than 1400 people in its short history. That’s a mortality of about 54% overall.

Two Americans who had been treating patients with Ebola virus disease (formerly called Ebola hemorrhagic fever) in Liberia, West Africa had been treated back in the US at a hospital in Atlanta. They have just been released as cured. They have been treated with an experimental drug called ZMapp. This is a monoclonal antibody from mice against surface components of the Ebola virus.

At this point no safety studies on humans have been performed with ZMapp, but a recent ethics committee meeting of the WHO has determined that the emergency use of ZMapp would be ethically acceptable due to the high death rate of the disease otherwise without treatment.

Other scenarios of killer infections

Several decades back some of the diseases mentioned in this article were basically unknown to the general population, but in the meantime some new infectious diseases have received a lot of media attention.

You will remember that there was an outbreak of anthrax spores by inhalation in 2001 in the US. A recent New England Journal of Medicine report points out that prior to 2001 the death rate of patients who had inhaled anthrax spores was 80% to 90% even with the use of antibiotics. However due to earlier detection and diagnosis, and due to aggressive supportive measures this epidemic of anthrax by inhalation had a mortality of only 45% toward the end or that epidemic. Had there been a new substance used that was ineffective, but harmless otherwise the reduced death rate would have been attributed to the erroneous conclusion that this new drug was effective in reducing mortality rates. This article cautions that rigid safety and effectiveness studies have to be done on ZMapp to ensure that it is a safe and effective drug to treat Ebola virus and that the reduction in death rates is truly from the drug, not just from improved supportive measures.

Other newer infections have been Marburg hemorrhagic fever caused by the Marburg virus. This also belongs to the Filoviridae family of viruses to which Ebola virus belongs as well. Then there is the SARS virus, the cause of severe acute respiratory syndrome. Not too long ago the BSE prion, which is the virus causing bovine spongiform encephalopathy made history.

What do we know about the Ebola virus?

There are 5 strains of the Ebola virus, one of which (the Zaire strain) is responsible for the present outbreak of Ebola virus disease in Africa. Dr. Jon Lai who is associate professor of biochemistry at the Albert Einstein College of Medicine in New York City has developed antibodies in mice that will slow down and attack the aggressive Ebola virus when it enters the human body.

Ebola virus disease occurs in remote villages of the rainforest in Central and West Africa where fruit bats are the natural hosts of Ebola virus. It is transmitted from local fruit bats to animals (monkeys among others), to humans and can then be transmitted to other humans. The virus is not as easily transmitted as colds or the flu. For instance, the Ebola virus does not transmit through the air, food or water. But you can get Ebola virus through skin contact, fluid contact and through needles with blood from an infected person. Also, when surfaces are contaminated with infectious body fluids and you touch this contaminated surface with your skin, the virus will penetrate through the skin and get you infected.

There have been several outbreaks in Africa since 1976 as you can see from this WHO link.

This link also suggests that proper hygiene measure like cleaning of pig and monkey farms with sodium hypochlorite should be effective in inactivating the virus, which makes virus transmission to humans more difficult.

Ebola Virus An Emerging Killer Infection

Ebola Virus An Emerging Killer Infection

Symptoms of Ebola virus disease

Ebola virus disease has an incubation time of 8 to 10 days where the person may complain of some tiredness, but is not sick yet. This is the time when the Ebola virus multiplies. It  paralyzes the immune system and distributes itself through the organ system.

After these initial days of incubation there is a sudden onset of a sore throat, high fever and headaches, lack of appetite, a stomachache and weakness.

Now the Ebola virus disease takes off and becomes life threatening as the major organs are infected with the virus, and as a result, vital organs shut down their functions. As the production of coagulation factors from the liver stops, there is major bleeding from body orifices (nose, ears, eyes, mouth, and bloody diarrhea). A skin rash develops all over the body from bleeding into the skin.

At this point the disease gets out of control as the blood circulation collapses and the affected person dies in shock. Otherwise, if fluid loss can be corrected in time with intravenous fluids, there is the danger to die from multi-organ failure. A few persons manage to survive, if the immune system produces enough antibodies in a timely manner to inactivate the Ebola virus.

Treatment options

At this time there is no effective treatment against the Ebola virus disease. As mentioned earlier, ZMapp is an experimental drug that may have some merit treating Ebola virus disease in the future, but at this point it is considered experimental as human safety studies and effectiveness studies of the drug have not been completed. Any experimental treatment with ZMapp will be part of these studies for the next few years, but production issues will have to be sorted out as well as presently there is not enough ZMapp around to treat all of the Ebola virus infected people in Africa.

This leaves us with the only preventative approach of interrupting the infectious pathway. We do know that there is a geographic zone in Africa where fruit bats, the natural hosts of Ebola virus live. It is in the same geographic zone that all of the known Ebola virus disease cases have originated from. It follows from this that it is safer for humans to live outside that zone. So do not plan sightseeing or other trips into those areas, if you value your life; I should qualify this by saying “until an effective treatment against the Ebola virus has been established”.

Those who bury dead ones who came down with this disease must wear safety suits, which look like space suits. As already indicated, surfaces need to be disinfected with sodium hypochlorite. All of these hygienic measures interrupt the Ebola virus transmission. Quarantine measures need to be strictly enforced for those who are suspected of harboring Ebola virus disease to prevent spreading this disease into the rest of society.

Conclusions

Although the medical puzzle of the Ebola virus disease has not yet been completely solved, there are encouraging facts that have been learnt. The Ebola virus has been around Africa since 1976 and several outbreaks have occurred on this continent since. But spread beyond these borders has been avoided due to strict isolation practices. Even within Africa the worst cases of Ebola outbreaks have occurred mostly in villages where hygienic measures are not adhered to as thoroughly when compared to larger African cities where isolation around Ebola virus disease patients is strictly enforced by the local authorities.

Hopefully with the emergence of an effective treatment this disease will get out of the lime light as did other killer diseases in the recent past.

More information on Ebola virus: http://nethealthbook.com/infectious-disease/infectious-disease-infections/ebola-virus/

Last edited Nov. 8, 2014

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Feb
01
2014

Early Alcohol Use Will Result In Memory Loss Later In Life

Researchers found that heavy alcohol use in males during midlife paves the way to memory loss from dementia later in life.

I thought that this would be a good topic to review the effect of alcohol in general. Alcohol is a known cell poison, yet cardiologists keep on referring to the beneficial effects of that 1 glass of wine per day that will prolong your life. I will attempt to explain these diverse effects, where small amounts are supposed to be good for you while high amounts can be very damaging.

Review of the effects of alcohol

50% of the world population drinks alcohol, 10% to 20% have chronic alcoholism (Ref.1).  Just recently a Guardian news study was released showing that an astounding 25% of Russian men die before reaching the age of 55, compared to only 7% of men in the United kingdom and less than 1% of men in the US. The study looked at the effects of consuming large amounts of vodka.  There are about 10 million chronic alcoholics in the US. Chronic alcohol consumption leads to 100,000 deaths every year in the US. More than 50% of these deaths are from traffic accidents, the rest from medical problems caused by alcohol (Ref.1). Most of the alcohol gets detoxified through the liver cells and is metabolized into acetaldehyde. This involves the cytochrome P-450 system. That means that when a person also takes narcotics, sedatives or psychoactive drugs that are also metabolized through this liver enzyme system drugs and alcohol are taking much longer to be metabolized. This can lead to lethal overdoses that we hear about on TV all the time, hence the warning that you must not mix alcohol with drugs.

Early Alcohol Use Will Result In Memory Loss Later In Life

Early Alcohol Use Will Result In Memory Loss Later In Life

Alcohol is a cell and nerve poison. The most vulnerable organs in the body are the liver, brain, heart, pancreas, bone marrow and stomach. So, here are a number of conditions caused by drinking alcohol:

a)    Anemia: When a person drinks heavily and regularly anemia shows up in a blood test. Alcohol has a toxic effect on the bone marrow, which interferes with the production of red blood cells. But certain vitamins required by the bone marrow to manufacture red blood cells are often also missing in the diet of an alcoholic, which contributes to anemia as well.

b)    Cirrhosis of the liver develops in 10% to 20% of heavy drinkers. With cirrhosis part of the liver cells get replaced by fibrotic tissue and in advanced cases this can lead to a hepatic coma and death. Others are developing alcoholic hepatitis. This is an inflammation of the liver with fever and jaundice where the skin and eyeballs turn yellow. It is associated with severe abdominal pain.

c)    Gastritis: Alcoholic gastritis is common, but often undetected. The affected individual may just have stomach pains for a few days, or vomit food and/or blood in addition. With continued use of alcohol it may turn chronic. Alcoholic gastritis can turn into gastric ulcers with massive bleeding that often lead to death.

d)    Pancreatitis: The pancreas is a particularly vulnerable glandular tissue, which gets damaged by regular alcohol intake and with chronic alcohol intake gets partially replaced by fibrotic tissue causing the feared and painful chronic pancreatitis. This is a condition with vomiting and severe abdominal pains that can be unrelenting.

e)    High blood pressure, seizures, dementia, depression, heart irregularities and nerve damage:

You may ask yourself how all of these conditions would be reasonably under one heading. The heading for this is “nerve damage”. Let me explain: The sympathetic nerve is very sensitive to alcohol toxicity and when the sympathetic nerve fibers are damaged, you will develop high blood pressure. You see your physician, get blood pressure medication, but the pressure is difficult to control, if you continue to drink alcoholic beverages. It does not make sense to just add blood pressure pills and hope that this will cure your problem. Seizures are due to direct nerve damage in the more sensitive parts of the brain, which will cause these areas to produce extra electrical activities, which we call seizures. Again, just treating with anti-seizure medications is not the solution. Avoidance of alcohol is the other part of the treatment schedule. Dementia from heavy alcohol use is due to direct nerve atrophy in the brain. Our brain shrinks normally 1.9% to 2.8% per decade, depending on which research papers you read. But in the presence of heavy drinking the frontal lobe of the brain is particularly vulnerable to brain shrinkage.

As this publication shows, mild and moderate drinkers did not suffer more frontal lobe shrinkage than abstainers, but heavy drinkers had a 1.8-fold higher risk of frontal lobe shrinkage on average when compared to abstainers. It was calculated that alcohol had contributed 11.3% to that frontal lobe shrinkage.

The rest of the toxic effect on the nerve tissue explains why depression would develop. The frontal brain contains most of the serotonin producing nerve cells. When serotonin-producing nerve fibers get damaged, the body does not produce enough serotonin to prevent depression from setting in; GABA producing cells often also get damaged, which causes anxiety. It’s not good enough to just prescribe anxiolytic drugs to which the patient will get addicted. The whole person needs to be treated, and abstinence from alcohol has to be part of the program.

Heart irregularities (atrial fibrillation, ventricular fibrillation) can be life-threatening complications due to the toxic effect of alcohol on the nerve fibers within the heart muscle. Emergency physicians are aware of the connection of these conditions to alcohol consumption. Some people’s hearts are more sensitive to the effects of alcohol than others. The most common cause of temporary atrial fibrillation is excessive alcohol intake (holiday heart) according to Ref. 2.

Finally there is the effect of alcohol on nerves in the body. This explains that heavy alcohol consumers can come down with painful pins-and-needles sensations in their hands and feet or with numbness or loss of muscle strength. When the parasympathetic nervous system is affected embarrassing incontinence or constipation can result. Erectile dysfunction in men is also very common. Viagra and continuing to drink is not the solution.

f)      Gout: This painful formation of uric acid crystals in joints can be precipitated in sensitive individuals by consuming alcohol in combination with eating large helpings of beef. There may be a history of gout in the family. Treatment for this is to refrain from alcohol and avoid foods that are leading to uric acid production when ingested.

g)    Cancer: When the body detoxifies alcohol in the liver, the breakdown product is acetaldehyde, which is a known cancer producing substance. A whole array of cancers are known, which come from heavy, chronic alcohol consumption: cancers in the mouth, larynx, esophagus, stomach, pancreas, liver and colorectal cancer have all been linked to excessive alcohol intake.

h)    Cardiovascular disease: heart attacks and strokes can be caused particularly by binging; it is thought that binging makes platelets from the blood more sticky so they clump together and cause blood clots, which in turn leads to heart attacks and strokes.

i)      Infections: Alcohol weakens the immune system, which is another effect on the bone marrow similar to causing anemia, except that this is the toxic effect on the white blood cells and lymphocytes. Heavy alcohol consumers are more prone to pneumonia, to HIV, sexually transmitted diseases, and tuberculosis.

Cardiology view of preventative alcohol

Despite all of these hair raising toxic effects cardiologists have painted the rosy picture that 1 glass of wine for women and 2 glasses of wine for men per day will prevent heart disease. What is the true story here?

Ref.2 points out that there are about 100 prospective studies that confirm that there is an inverse relationship between mild to moderate alcohol consumption and “heart attack, ischemic stroke, peripheral vascular disease, sudden cardiac death, and death from all cardiovascular causes”. It describes further that the reduction of risk in these various studies was persistent and consisted of a 20% to 45% risk reduction. Using blood tests investigators have found that this is because of an increase of HDL cholesterol, reducing blood clotting, making platelets less sticky and reducing inflammation as evidenced by a reduction of the C-reactive protein. Further research has pinpointed that it is the phenols and resveratrol that are contained in alcoholic beverages that are responsible for the beneficial effects. The bad news is that three glasses of wine or more do the opposite, so does binge drinking. Unless you are extremely disciplined and never increase your allowed limit (1 drink for women, 2 drinks for men) you will CAUSE heart disease rather than PREVENT it (Ref.2). Some people have a family history of breast cancer or colon cancer and they should avoid alcohol altogether; also people coming from alcoholic families should avoid alcohol.

Conclusion

Where does this leave us with regard to prevention of heart attacks, strokes and hardening of the arteries in the legs (peripheral vascular disease)? If you are disciplined and stick to the limits, you could prevent 20% to 45% of cardiovascular risk. The brain study mentioned in the beginning of the blog would also confirm that there was no difference between dementia or brain shrinkage when mild to moderate drinkers were compared to abstainers over 10 years. What is not told by the wine industry is that the same effects that prevent cardiovascular disease in mild to moderate drinkers can also be achieved by natural means: exercising regularly will raise your protective HDL cholesterol; taking ginkgo biloba, flax seed and omega-3 fatty acids thins your blood and the platelets are getting less sticky; omega-3 reduces inflammation and resveratrol elongates telomeres making you live longer. At the A4M conference in Las Vegas in December 2011 there were three speakers who pointed out that even small amounts of alcohol will poison mitochondria of your cells and interfere with normal hormone action. This was enough to make me join those who abstain alcohol completely. One thing has not yet been investigated in long-term studies, namely how small effects of alcohol may affect the body over several decades and over an entire lifetime. Despite all the promises of interest groups that red wine is a trendy drink for those interested in heart health, the fundamental long-term studies are missing. What does a guy do with a healthy heart and a brain that is not functioning too well? I just do not want to be the guinea pig in that worldwide study.

More information on alcoholism: http://nethealthbook.com/drug-addiction/alcoholism/

References:

  1. Kumar: Robbins and Cotran: Pathologic Basis of Disease, Professional Edition, 8th ed. © 2009 Saunders
  2. Bonow: Braunwald’s Heart Disease – A Textbook of Cardiovascular Medicine, 9th ed. © 2011 Saunders

Last edited Nov. 7, 2014