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Author: Stephen J. Klemawesch, MD

Dear Dr. K – 

Dear Dr. K – 

Should I skip exercising on the day I get my allergy shot? Aerobic exercise? Weight/resistance exercise? 

The simple answer is “No”, but you know I love to palaver, so here’s the long answer!  

First off, Americans in general do not get any or adequate exercise so I don’t want to contribute to unhealthy behavior. By the way you posed your question I suspect you might have been a girl scout and learned field expediencies for snake bite. Part of that tutelage is “lie still and especially don’t run”. The reason for that admonition is increased cardio-blood flow would circulate the venom more quickly.  

But that snake wisdom does not pertain to allergy shots. These are administered subcutaneously and not intramuscularly. Thus, using your muscles either aerobically or with weights does not impact the shot. Some people experience mild awareness that they received their shot in terms of some local itching/warmth. The adrenal release of extra cortisol and adrenaline that occurs with exercise can abrogate this.  

With respect to intramuscular shots such as pneumonia, tetanus and flu, it is still ok to exercise the recipient arm but best done in moderation for a day or two. 

CRISPR for HANE (HAE) 

CRISPR for HANE (HAE) 

OK, sorry for the acronyms but I just couldn’t resist. CRISPR stands for clustered regularly interspaces short palindromic repeats, so maybe you’ll forgive me. HANE is hereditary angioneurotic edema (commonly known as Hereditary Angioedema). The New England Journal of Medicine recently published research done at Amsterdam University using the CRISPR gene editing tool to treat/cure hereditary angioedema.  

HAE is a genetic disorder that is autosomal dominant (only requires one defective gene) that affects one in 50,000 people, but it can be a debilitating and sometimes fatal condition that requires lifelong treatment. These treatments are both preventative and crisis management in nature. The work, but they require frequent dosing to achieve control. Because of this the Amsterdam Scientists did a small study (27 patients) to see if gene editing could fix the problem. They used the CRISPR technology to edit the gene which encodes Kallikrein BI (KLKBI) the primary source of PR kallikrein. This editing resulted in a reduction in total plasma kallikrein levels which had been the cause of the angioedema attacks. The levels were reduced by 86% and 73% of the patients ended up attack free. Currently, gene editing therapy costs 3 to 4 million dollars do the cost will need to come down to make it economically viable. 

Broncho-Vaxom  

Broncho-Vaxom  

Broncho-vaxom is an extract of respiratory bacteria that is used outside the United States to treat and prevent bronchitis and sinusitis. It is a mixture of lipopolysaccharides from these bacteria: Hemophilus influenza, Streptococcus pneumoniae, Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus sanguinis and Moraxella catarrhalis.  

It has been evaluated using placebo controlled blinded studies in both children and adults. In adults with COPD, it reduced the frequency of infection by 29% and in smokers/ex-smokers by 40%. In children it reduced sinus/ear/bronchial infections by 52%.  

It is an oral formulation that works via the gut-lung axis. Pathogens are detected by our immune system by pattern recognition receptors found on dendrite cells. Exposing our gut dendrite cells to the broken-down bacteria teaches them better recognition of these bacteria and this new knowledge is transferred to our respiratory membranes. It also leads to specific antibody production of IgA and IgG Directed against these bacteria. Finally, it improves cilial function (the tiny little hairs on our respiratory membranes that sweep out bacteria) and reduces air way inflammation. Another condition helped by Broncho-Vaxom is bronchiectasis, a difficult to treat form of chronic bronchitis. Finally, there is also research ongoing to use it to prevent the development of asthma in small children. Boston Children’s Hospital has a large ongoing study in this regard. 

Stress Sex and Illness 

Stress Sex and Illness 

Despite the headline, this is not an “R Rated” article, but rather a discussion of hormonal molecular physiology. Cortisol and testosterone might seem to be totally different compounds but they are actually very closely related. Cortisol’s formula is C21H30O5 while that of testosterone is C19H28O2, plus they share the identical five hydrocarbon ring structure. Another similarity is that they both can reduce immune function. This is one reason males are more prone to illness than females.  

Our adrenal glands primarily produce aldosterone, cortisol and adrenalin, but also small amounts of the sex hormones estrogen, progesterone and testosterone.  

Our gonads produce estrogen, progesterone and testosterone in different proportions based on our sex. It all comes down to slight modifications of the hydrocarbon ring structure that they all have in common.  

It has been known for quite some time that elevated cortisol, either exogenous (from our adrenal glands) or exogenous (from pharmaceuticals), impairs immune function.  

The higher the elevation the greater the immune suppression. What has more recently been learned is that testosterone has a similar effect even at normal levels but more so at higher levels.  

The main reason for elevation of endogenous cortisol is stress, both acute and chronic. This is one reason people frequently get sick on a trip or a vacation. Our adrenal glands make adaptive changes for even the pleasant disruptions of locale, diet, activity, sleep and wake times associated with travel. The attendant elevation of cortisol makes illness more likely. 

The immune dysregulation from cortisol and testosterone occurs in both the innate and adaptive arms of over immune function. Over innate immune system, which is the more primitive system and shared with less complex organisms, works to a large degree by pattern recognition receptors. These receptors are suppressed by cortisol and testosterone. The adaptive arm of over immune function relies on its ability to proliferate the formation/function of both T-cells and B-cells. This ability is suppressed by cortisol and testosterone. Moreover, they also promote lymphocyte apoptosis (cellular suicide).  

TIL:  Tumor Infiltrating Lymphocyte Therapy 

TIL:  Tumor Infiltrating Lymphocyte Therapy 

TIL is a recently FDA approved therapy for treating certain types of metastatic cancer.  It has been referred to as a “living drug” as it is made up of the individual patients T lymphocytes.  It does so by taking cancer-targeting T cells from the patient’s own tumor and then growing them into billions more of the same cells in the lab and then re-infusing them into the patient.   This massive influx of warrior T cells can destroy the tumor whereas the previous small number of T cells were just holding it at bay.  

The initial FDA approval is for metastatic melanoma, but it’s used for other solid tumors such as breast, pancreas and colon cancers.   

TIL is not the first use of immune cells to fight cancer.  CAR T-Cell therapy is another FDA approved method to fight certain “liquid” cancers, primarily leukemia, lymphoma, and multiple myeloma.  So far it has not proven effective for solid cancers.  CAR T-Cell therapy is so named because it involves making a chimeric antigen receptor (CAR) on T-cells.  It uses genetic engineering to modify the patient’s own T-cells so they can recognize (and then destroy) a specific cancer cell signal (antigen).  CAR-T therapy has helped and cured thousands of patients but one drawback of its use is that it is tricky to find a molecular signal (antigen) that is totally unique to the cancer.  Since healthy cells may also share this molecular signal, they can sometimes be damaged by the chimeric T-cells.  TIL on the other hand doesn’t modify the innate targeting system of the T-cells it simply uses a normal immune cytokine IL-2 (interleukin-2) to boost cell growth.  As it turns out one “target” that the TIL cells seem to pick out is the mutated protein that would otherwise control healthy cell growth.  Once this protein undergoes a Jekyll-Hyde transformation it allows uncontrolled cell growth otherwise known as cancer.   

Leukocyte Activation and COVID-19 Vaccine Reactions 

Leukocyte Activation and COVID-19 Vaccine Reactions 

Luckily severe allergic reactions (anaphylaxis) to COVID-19 vaccines have been rare, averaging about 8 events per million vaccines.  However, since the Corona virus continues to circulate there will be an ongoing need for vaccination.  Based on current research it seems that most of these adverse events are reactions to polyethylene glycol (PEG).  However, attempts using traditional allergy testing techniques which look for IgE mediated sensitivity have led to poor discriminatory value in people who have had allergic reactions and poor predictive value when used to try and prophylactically identify individuals at high risk for allergic reactions.  This frustration has led to research to identify a more reliable test.  Georgetown University has used a research test called leukocyte activation with surprisingly good results.  The test is done by adding PEG to a sample of the patients’ blood and then analyzing it to see if the leukocytes (white blood cells) become activated.   

So far this is just a research tool but it could lead to a readily available testing mechanism, much as the home Covid test swab has become.   

Dear Dr. K – 

Dear Dr. K – 

I read that there might be a new asthma controlling shot that is given just every six months.  Is that true?  

Yes, it is true.  Researchers at Oxford University have just completed two phase 3A randomized placebo control trials that look very promising.  The new drug is depemokimab and it is a monoclonal antibody (note the “mab” at the end of its name) that binds to Interleukin 5.  In fact, it has an incredibly strong binding affinity for Interleukin 5 which allows for just twice a year dosing.  Interleukin 5 is an inflammation causing cytokine that is responsible for the growth, recruitment, activation and survival of eosinophils.  Eosinophils are white blood cells that are the cause of most asthma.  Make the eosinophils go away and you make the asthma go away.    

There are other currently available drugs that are also very effective in controlling asthma that target Interleukin 5.  But they require more frequent dosing.  Also, all of these medications are only indicated in severe asthma that is not adequately controlled with inhaled steroids.   

In the two Oxford trials, depemokimab was very effective in improving asthmatic symptoms and in reducing exacerbations.  The side effect profile was similar to that of the placebo control.  Still, it won’t be available until it meets FDA approval.   

Processed Milk and EOE 

Processed Milk and EOE 

There is mounting evidence that processed milk is the primary cause for the newly developing epidemic of eosinophilic esophagitis (EOE).  The rise of EOE began after the widespread consumption of ultra heat treatment (UHT) pasteurization and micro fluidization homogenization of our milk in the early 1990’s.   

Louis Pasteur recommended heating milk to 72° C for 15 seconds.  UHT heats milk to 140° C.  Homogenization is a process to reduce the fat droplet size so that milk doesn’t separate in the container.  This highly processed milk makes it very pleasing to the eye (uniformly white) and gives it a long shelf life.  In fact, it actually does not require refrigeration.  But in the American market consumers’ unease about drinking non-refrigerated milk has led to most milk being sold cold.  Prior to this ultra processing the cold was necessary to preserve the milk.   

Unfortunately, this ultra-processing (UP) markedly alters both the fat and the protein in milk in a way that creates inflammation in the esophagus.  Also, there are small amounts of detergent residue in milk.  Very strong detergents are used to clean the processing equipment in order to prevent biofilms.  This detergent residue causes a chemical injury that disrupts the normal intact cellular barrier in the esophagus.  These micro-fissures in the esophageal membrane allow the penetration of fat-protein nanoparticles which in turn instigate the incursion of the eosinophils.  Prior to UP there was no detergent residue in milk and the milk proteins/fats were large and did not infiltrate the esophageal lining. 

Finally, there is early evidence that strictly avoiding cow milk and its products (cheese, butter, yoghurt, ice cream) leads to healing of EOE.    

Magical Metal Magnesium 

Magical Metal Magnesium 

Magnesium with its atomic number (AN12) is sandwiched between sodium (AN11) and aluminum (AN13) on the periodic table.  It also sits above calcium (AN20).  All four elements are metals.  Magnesium and calcium have two “available” electrons in their outermost orbital ring, which can help explain some of the medicinal applications of magnesium.   

Magnesium is found in all cells in all organisms both plant and animal.  It is indispensable for health as it is an essential cofactor for ATP (adenosine triphosphate) the battery molecule that powers all of our cells.  It is also a cofactor for hundreds of cellular enzymes.  In addition, it regulates metabolism of sugars, fats and proteins, helps control nerve and muscle function, regulates cardiac rhythm, modulates blood vessel tone and regulates hormone secretion.   

Whew.  With all those important jobs you would think we would hear more about magnesium and that there might be more than three medical conditions where it is the drug of choice.   

There are a number of medical applications where it isn’t the drug of choice.  It has GI benefits as both an antacid and a laxative.  It can increase the seizure threshold for epileptics.  It can lessen the frequency of migraines.  It can help muscle spasms including tetany.  It is integral for good bone matrix formation.  One unwanted side effect of long use protein pump inhibitors is their impact on micronutrient absorption including magnesium and thereby reducing bone density.   

But, the three conditions where it is the treatment of choice are torsade de pointes, acute asthma exacerbation, and preeclampsia/eclampsia.   Torsade de pointe is a life-threatening form of ventricular tachycardia.  It is often resistant to treatment with standard Anti arrhythmias such as beta blockers.   

Eclampsia/preeclampsia is a condition in pregnant women that can threaten the woman’s life and the baby’s.  The mother experiences fluid retention and elevated blood pressure which if severe can cause a seizure or stroke for the women and death for the baby.  Preeclampsia is helped by oral magnesium.  Eclampsia is treated with intravenous magnesium.   

In severe hospitalized asthma, magnesium is used both intravenously and also by adding it to the albuterol used in nebulizer treatments.  

Its mechanism of action has been best understood in asthma but it probably applies to all the conditions just described.  It is a natural calcium channel blocker.  Calcium channels are portals of flow for calcium ions in many tissues.  In bronchial smooth muscle calcium channels can cause the constriction of these muscles which in turn narrows the airways.  Blocking the channel with magnesium allows the muscles to relax and the airways to open.  Remember in the introduction to this article the close proximity of calcium and magnesium and the two available electrons in the outer shell.  This allows magnesium to bump calcium out of the channel, kind of a “preferred passenger status”.   

Dear Dr. K; 

Dear Dr. K; 

I just turned 65 and I want to get a pneumonia vaccine, but quite honestly, I’m confused by the choices.   

The confusion is not unique to you.  There has been a longitudinal/temporal change/improvement in the vaccine.   To cut to the chase the CDC Advisory Committee on Immunization Practices recommends you (as previously unvaccinated) receive PCV21 followed a year later by PPSV23.   

By way of explanation, PPSV stands for pneumococcal polysaccharide vaccine.  It is the original vaccine and is similar in formulation to the tetanus vaccine.  PCV stands for pneumococcal conjugate vaccine.  In this format the polysaccharide antigens are conjugated to a diphtheria protein to elicit a more robust immune response.  With the learning curve of time, scientists have found using both formats leads to the best and most durable immune response.   

The earliest conjugate vaccine was PCV13 (protecting against 13 of the most common pneumonia types).  Over time PCV15, PCV20 and then PCV21 have come along.  PCV21 includes 8 serotypes not included in any of the other vaccines.  Hence, the CDC’s current advice.