Browsed by
Author: Stephen J. Klemawesch, MD

Bacteriophages

Bacteriophages

When intestinal bacteria that are part of the microbiome were first linked to obesity it seemed to be a scientific curiosity.  That was in 2007.  Now fast forward 14 years and the microbiome has become the subject of hundreds of thousands of research projects around the globe.  This research has led to the understanding of how our gut bacteria can influence the development of many human diseases including asthma and allergy.  Not to over simplify all this research but it comes down to the fact that our gut bacteria effectively give us a second genome (genetic makeup) and an additional endocrine organ. 

Now, the current focus of research is shifting to the viruses that infect bacteria (aka bacteriophages).  Yes Virginia, there is a Santa Claus and believe it or not viruses infect bacteria.  This fact has actually been known for quite some time.  What wasn’t known until just recently is what, if any, impact those bacteriophages might have on human health. 

The National Academy of Science recently published novel research in this area.  The scientists found over 2000 specific bacteriophages that were strongly associated with human diseases.  Two of the diseases most correlated with the viruses were obesity and Parkinson’s disease.  What was especially shocking was the finding that many of the viral genetic sequences were integrated into the human chromosomal DNA.  This viral research is too new to lead to any practical recommendations but hopefully that will be forthcoming. 

Acetaminophen

Acetaminophen

Acute liver injury caused by accidental or intentional acetaminophen overdose is well known.  If ingested all at once, 30 acetaminophens are lethal by causing acute liver failure. 

One of the metabolites of acetaminophen is N-acctyl-p-benzoquinone imine (NAPQI) which is produced by the liver enzyme system P-450.  Glutathione stores in the liver detoxify this otherwise harmful metabolite.  Acute overdose can deplete the glutathione stores in the liver and this will cause the liver cells to die. 

New research published in the journal Hepatology indicates that acute liver injury can occur from “normal” doses of acetaminophen in the right (wrong) setting.  Eighty-nine hospital cases of acute liver injury in an academic medical center were caused by doses of acetaminophen of 3,000 to 4,000 mg a day (4,000 mg is the largest recommended dose) when combined with either fasting for 24 hours or excess alcohol intake or both.  The authors of the article suggested people who fast periodically or who use alcohol liberally be aware of this potential pitfall.  Fasting depletes the liver of resources as the liver is a source for energy supplies when no calories are consumed.  Excess alcohol monopolizes the liver’s metabolism and makes it difficult to handle the breakdown of medicines. 

Covid Q-Tips:

Covid Q-Tips:

-Social isolation is still a good strategy and it works. 

-Early Covid infection can be successfully treated with monoclonal antibodies casirivimab and imdevimab given as a one-time injection or IV infusion.

-Post-exposure prophylaxis can also be given to high-risk individuals who have been exposed to someone with active Covid 19 infection before they develop the infection themselves.  The same monoclonal antibodies are used.

Dear Dr. K; I received BCG treatments for my bladder cancer. Now I hear it is being used for diabetes. Is that true?

Dear Dr. K; I received BCG treatments for my bladder cancer. Now I hear it is being used for diabetes. Is that true?

The one second answer is “yes”, but there is an over 100-year-old story behind that.  BCG, properly called Bacillus Calmette-Guerin is a live attenuated (weakened) form of tuberculosis.  The vaccine has been around for 100 years and is routinely given to children in nearly all non-Western countries to prevent TB.  Not long after the vaccine was developed in the 1920’s scientists noted a significant decrease in childhood death rates not only from TB but from many unrelated infections.  More recent studies in elderly patients showed a marked reduction in all forms of respiratory infections in mature adults receiving BCG as compared to a placebo shot. 

These observations have led to a broader scope of research on BCG around the globe.  Here in the US, Harvard Medical School is a front runner in this research.  As weird as it may seem it turns out that BCG can not only boost good immunity but paradoxically can also calm an overactive immune system that is causing auto-immune disease.  The Harvard team found that BCG triggers the immune system to produce TNF-alpha which does two important jobs.  TNF-alpha fights all types of bacterial and viral infections but it also helps the body make T-regulatory cells (T-regs) which act as

“referees” to prevent collateral damage during immune responses. 

Unlike type II diabetes, which is due to obesity causing insulin resistance with very high insulin levels, Type I diabetes is due to a lack of insulin production by the pancreas because of an auto-immune destruction of the cells that produce insulin.  BCG given as type I diabetes is developing can save some of the pancreas cells that produce insulin before they are all destroyed. 

Alzheimer’s disease is currently viewed as an auto-immune disease in the brain where chronic inflammation leads to the amyloid plaque (scar tissue) that disrupts nerve connections.  A research group in Israel recently reported on a large cohort of people with bladder cancer.  Those who received BCG as a treatment for their bladder cancer had a 2.4 percent occurrence of Alzheimer’s years later versus an 8.9 percent occurrence in a group who did not receive BCG. 

This observation has sparked ongoing trials of using BCG in treating early Alzheimer’s and also in MS (multiple sclerosis) another auto-immune brain disease.  Other ongoing areas of research using BCG include preventing Covid 19 infection, treating eczema and asthma. 

The United States and some other Western nations have never adopted the use of BCG as a prevention for TB, opting instead to treat individual cases as they occur.  Pending the outcome of these recent research trials, that policy might change. 

IgG Food Testing

IgG Food Testing

IgG food testing (also known as food sensitivity testing) was recently discussed in an editorial from Yale in the Annals of Allergy, Asthma and Immunology.   The physicians at Yale sited the American Academy of Allergy and Immunology and the European Academy of Allergy and Clinical Immunology in recommending strongly against the use of IgG food testing. 

IgG (Immunoglobulin G) is one of the main immune proteins in humans.  It serves both “recognition” and “protection” functions.  Homeland Security might serve as a reasonable metaphor.  The latter has an extensive database of all individuals residing within and entering into the United States.  It also can serve to protect from terrorists.  Similarly, our immune system makes IgG antibodies of recognition against all substances that enter our bodies including the foods that we eat.  Hence, we all have a myriad of IgG antibodies directed toward/recognizing these foods. 

When a patient has IgG food testing done there is typically a long list of “positive foods” which are rated from mildly to strongly positive.  Unfortunately, this list is used as a guide for food elimination to try and treat clinical symptoms. 

Since food allergy (10% of the population) and food intolerances (20% of the population) are so common, it is often the luck of the draw with an avoidance of many foods that the patient will actually feel better.

But this clinical improvement comes at the cost of an often nutritionally poor diet and is due to the interdiction of one food (among many) that might actually be an allergen or an intolerance and not because the IgG antibody is causing the allergy or intolerance.

Allergy is caused by a different immune protein (IgE) Immunoglobulin E.  And food intolerance is caused by digestive enzyme deficiencies or other physiologic issues with the gastro-intestinal tract. 

Companies/laboratories that offer IgG food testing make claims that the test can help with a variety of medical problems including IBS (irritable bowel syndrome), joint pain, migraines, fatigue, and skin rash.  IgG food testing and associated elimination diets can lead to an emotional burden and negative health consequences. 

A too strict elimination of foods can cause nutritional deficiencies.  Also, insurance companies usually do not

cover the cost of the tests (which are significant) because medical insurers recognize it as a non-standard process.

In 2004 the Mayo Clinic did a study in people with IBS.  Half of the group had IgG food testing and were told to avoid the positive foods; the other half of the study group were placed on a sham diet not based on any testing.  The clinical outcome was the same in both groups. 

Covid-19 and Immunocompromised Patients

Covid-19 and Immunocompromised Patients

There is still much to learn about Corona virus.  One area that is particularly problematic is how to protect patients that are immunocompromised (roughly 5% of the US population) due to organ transplant, auto-immune/rheumatic diseases, cancer, and dialysis. 

It has been long understood that the efficacy of many vaccines is attenuated in immunocompromised patients and this also seems to be the case for Covid-19 vaccines.  Timing of the vaccine is important and it should be administered between chemotherapy cycles.  For patients with stable rheumatology conditions suspending daily doses of mycophenolate and methotrexate for 1 to 2 weeks is advised. 

A very small study has been done on administering a third dose of the m-RNA vaccine or administering the Johnson & Johnson vaccine to patients who already received two doses of an RNA vaccine.  In the patients who had only very low antibody titers after their first two m-RNA vaccines, 100% developed excellent titers after a 3rd vaccine.  However, in the patients with no detectable antibodies after their first two m-RNA vaccines, only 25% developed high antibody titers.  Much larger study trials are underway to better address this issue.  For the time being as America is unmasking, the previous guidelines for mask wearing and social isolation are still advised for immunocompromised patients. 

Dear Dr. K; Any good news on Covid vaccines?

Dear Dr. K; Any good news on Covid vaccines?

The answer is yes: they are working well and luckily the foibles are generally mild.  Globally there are eleven different vaccines currently in use, but so far only 2% of the world’s population has been vaccinated.  We need to do better, including vaccines that don’t have elaborate requirements for transport or refrigeration.  Another 251 vaccines are at some stage of development including 60 that are entering human trials.  Let me tell you about some of the very promising ones. 

Vaxxinity Pharmaceuticals has created a vaccine using proteins from the Corona Virus spike protein that are the ones that allow the virus to attach to and invade human cells.  Another company, Novavax, has also developed a spike protein vaccine but theirs is directed to the entire protein, not just the “latch-on” portion.  Both vaccines are very promising and early trials indicate they will work against corona variants. 

Vaxart Pharmaceuticals had developed on oral vaccine that uses the common cold virus (adenovirus) to carry pieces of the corona virus through a hybrid technology.  Johnson and Johnson and AstraZeneca use the same technology in their injected vaccines which work very well. 

There are two big advantages for an oral vaccine.  One is that it is easily administered, not requiring refrigeration.  The other is a dual protection mechanism.  Oral vaccines, uniquely, provide both “blood stream” protection (as do all injected vaccines) but also mucus membrane protection.  Oral vaccines lead to antibodies being present on the mucus membranes of the nose,

mouth and lungs as a first line of defense against the virus.  Historically there was a similar segue for polio vaccines from Dr. Salk’s injected vaccine to Dr. Sabin’s oral “sugar cube” vaccine.

Another advantage of Vaxart is that it elicits an immune response to both the spike protein and the N protein on the Corona virus (Johnson and Johnson and AstraZeneca only elicit spike protein antibodies).  This may be important for mutant variants because they alter the spike protein much more rapidly than the N protein. 

Valneva Pharmaceuticals is using a killed whole virus vaccine with two adjuvants (substances that enhance immune response).  Several killed virus vaccines are already in use (made by Sinopharm, Sinovac and Bharat Biotech) but they do not include the immune booster adjuvants. 

Inovio Pharmaceuticals uses a DNA vaccine that is injected just under the skin with multiple tiny needles and then zapped into cells via a handheld wand that releases a split-second pulse of electricity.  From there the cells produce the spike protein which cues an immune response.  No other vaccine uses this delivery system.  So far, patients report much less discomfort from the vaccine and also fewer side effects.  Since the vaccine consists of only DNA and saline it can be stored at room temperature. 

Q-Tips: pollen allergy

Q-Tips: pollen allergy

We are currently in grass pollen season and soon to be added is ragweed pollen.  People with grass pollen allergy may have worse symptoms this time of year if they ingest foods that share allergenic components with the pollen.  These grass related foods are: melons, oranges, kiwi, tomato, and peanut.  Ragweed related foods include: melons, banana, artichoke, cucumber, zucchini, echinacea, chamomile and hibiscus tea.

Fluvoxamine for Covid-19?

Fluvoxamine for Covid-19?

Many drugs have been considered for treatment of Covid-19 and several monoclonal antibodies have been granted emergency use authorization by the FDA.  However, the only FDA approved drug for treating Covid-19 is the IV antiviral Remdesivir that inhibits RNA polymerase. 

Fluvoxamine is one of many SSRI’s (Selective Serotonin Reuptake Inhibitors) that are used to treat anxiety and depression.  However, Fluvoxamine is structurally unrelated to the other SSRI’s.  In addition to its serotonin modulating activity, it is a strong agonist (stimulator) of sigma-1 receptors in the endoplasmic reticulum. 

Sigma-1 receptor stimulation has been shown to limit SARS-COV-2 replication and to modulate the inflammatory response to sepsis in animals.  It is the overwhelming inflammatory response called cytokine storm that causes the life threatening acute respiratory distress syndrome in Covid-19. 

So far, two very small studies in humans have been very promising.  In a double-blind study of 152 people with Covid-19, ½ received fluvoxamine and ½ placebo.  Clinical deterioration occurred in none of the fluvoxamine recipients whereas 6 of the placebo group deteriorated. 

A second non-placebo-controlled study was done in 113 people with Covid-19.  The participants were free to choose taking the medicine or not.  Of the fluvoxamine receivers (65 in number) all were well after two weeks.  In those not accepting the drug (48 in number) six were hospitalized, two were on ventilators and one died. 

Now these are very small trials, so good science requires expanded studies.  Right now, there is a large placebo-controlled trial under way which should be completed by September.

Mother and Fetus Get Well Together

Mother and Fetus Get Well Together

Hereditary Angioedema (HAE) is an inherited deficiency of functional C-1-esterase inhibitor (C-1-INH) and is characterized by unpredictable recurrent episodes of painful often disabling swelling of the abdomen or face or extremities. 

In the recent past several new drugs have become available to treat this condition.  One of the most exciting ones is Ruconest,

which is a C-1-esterase inhibitor made by recombinant technology.  Thus, it works by replacing what the patient fails

to make (or fails to make in a functional protein).  By way of explanation C-1-esterase inhibitor is a “gate-keeper” or “watch-dog” for inappropriate activation of our complement system proteins.  If the complement system is activated when it is not needed, it makes the individual sick by causing the tissue swelling which is the hallmark of HAE.

In women with HAE, variations in hormones such as the menstrual cycle or pregnancy can bring on attacks.  A case in point was recently published in the medical literature of a 23-year-old woman who experienced multiple attacks of angioedema during her pregnancy.  Because Ruconest is technically not a drug but a pure replacement protein it is felt to be safe to use during pregnancy.   At 38 weeks the woman had a severe attack as she was going into labor.  Because of concern for the fetus an ultrasound was done and the baby was also having an attack of facial angioedema.  The woman received Ruconest and as her swelling subsided so too did her infant sons swelling.  By the time he was delivered he was back to normal.  This is the first documented account of fetal angioedema successfully treated while treating the mother.