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Author: Stephen J. Klemawesch, MD

Our intestinal microbiodome — so crowded; so constantly busy

Our intestinal microbiodome — so crowded; so constantly busy

A recent article in The New England Journal of Medicine points out that the human GI tract contains up to 10-million different microbial species. This review of the human intestinal microbiome found bacteria, fungi (yeast), viruses, archaea (specialized bacteria with a resistant cell wall) and algae. More than a billion years of co-evolution of mammals and their gut flora has led to a complex interdependency of the mammal and the microbes, and the microbes with one another.  Humans today are dependent on their gut flora for  important biologic functions including: development of normal immunity, protection against pathogens, elimination of various toxins, regulation of intestinal function, neurologic signaling, bone-density maintenance, synthesis of essential vitamins and neurotransmitters, plus providing 10% of our daily energy requirements. Studies of abnormal gut flora in humans and mouse models have shown a correlation with a variety of Alist serious health issues: cancer, diabetes, asthma, atherosclerosis and autism. The studies also cited improvement through use of specific probiotics. Two bacteria with long names (Christensenellaceae and methanogenic orchaea) are found in lean people with healthy metabolism, but are absent in obese persons with Type II diabetes and insulin resistance. In a study of genetically predisposed infants for Type I diabetes, the introduction of probiotics in their first month of life reduced their risk of developing diabetes by 60%. In studies of people with atherosclerosis, they were found to have a gut flora that broke down the protein in their diet to a chemical that speeds up plaque deposits in arteries.  Research in children of asthmatic parents found that early introduction of probiotics in infancy reduced the risk for developing childhood asthma by 30%. In a mouse model of autism it was found that abnormal gut flora led to an increased production of 4ethylphenylsulfate (4EPS). Improving gut flora with a countering bacteria reduced the 4EPS by 50% and led to a marked improvement in the mouse behavior. Finally, in human cancer studies it was found that taking a probiotic with bifidobacterium improved the response to chemotherapy for melanoma. Also, the probiotic Lactobacillus casei was shown to inhibit progression of colon cancer.

Heavy metals in blood increase asthma

Heavy metals in blood increase asthma

Having elevated levels of the heavy metals lead and cadmium does result in an increased incidence of asthma, as demonstrated in recently published research from Brown University.

Elevated lead levels can be seen in children living in homes with old-fashioned lead paint, and in adults with workplace-exposure to lead fumes.

Elevated cadmium levels are typically only seen due to industrial workplace exposure.

The heavy metals cause a shift in TH1/TH1 response, thus leading to much greater production of IgE, the allergic antibody that causes asthma.

The next phase of the research at Brown University if to see if reduction in the heave metals in the blood stream leads to amelioration of the asthma.

Eczema

Eczema

Dermatology researchers at the University of Oregon recently published two Phase 3 trials of Dupilumab in eczema. Phase 3 trials are the ones that can lead to FDA approval of a new drug. These trials were very successful.

Dupilumab is a human monoclonal antibody against interleukin-4 receptor alpha. Interleukin-4 is a cytokine (inflammatory molecule) that is an important cause of allergic eczema. The studies were done on 1,500 patients with moderate-to-severe eczema that was not responding to topical medications. In one of the trials, patients received injections of Dupilumab weekly, and in the other trial the injections were every two weeks. Both groups showed more than a 75% improvement in their rash compared to placebo. Not only did the rash improve, but there also was great reduction in itching and anxiety/ depression. Finally, quality of life assessments showed marked improvement.  In people with moderate-to severe eczema skin rash can cover large parts of the body’s surface. This rash is accompanied by intense, persistent itching which leads to sleep deprivation and symptoms of anxiety and depression. For many people with this measure of eczema, topical therapies just don’t work. The available systemic treatments are often associated with significant toxicity or side effects. Hence, there is a great need for a safe and effective long-term therapy. Dupilumab seems to fit this need. The two main side effects were injection site swelling (8 to 19%) and conjunctivitis (2 to 5%).

Dear Doc: Why long-term allergy shots for some?

Dear Doc: Why long-term allergy shots for some?

Dear Dr. K: My friend and I, who have both been on allergy shots for four years, went off them. My friend remains allergy-free, but my allergies are coming back again. What gives? That is a simple question to ask, but a more difficult one to answer. Let’s start with how allergy shots work. Actually, we should call them allergy vaccines because all vaccines lead to the production of protective antibodies (called IgG). For example: in the case of tetanus vaccine, it leads to antitetanus antibodies. Similarly, an allergy vaccine against ragweed leads to protective IgG antibodies against ragweed. These IgG antibodies interfere with the allergic antibody (IgE) from interacting with ragweed and hence, prevent the allergy symptoms. The longer a person receives an allergy vaccine, the greater the level of protective antibodies. Everyone who receives allergy shots experiences this response. A second benefit of allergy shots is to gradually turn off IgE production. Unfortunately, this doesn’t happen in everyone. It’s the diminution of IgE that leads to long-term remission from the allergies. Your friend undoubtedly has had this benefit.  A few other issues are worth mentioning. People living in southern climes tend to need allergy shots longer than their northern neighbors. The absence of winter freezes leads to higher levels of both indoor and outdoor allergens year-round. Outdoors is obviously more challenging as there is a year-round growing season. Indoors, both mold and dust mites persist through the winter. This is because of persistent indoor humidity. Up north, the months of dry heating kills indoor mold and dust mites. Finally, there is the issue of animal allergy. People with dog and cat allergy tend to need these allergy shots for a longer period — especially for cat allergy.

which leads to sleep deprivation and symptoms of anxiety and depression. For many people with this measure of eczema, topical therapies just don’t work. The available systemic treatments are often associated with significant toxicity or side effects. Hence, there is a great need for a safe and effective long-term therapy. Dupilumab seems to fit this need. The two main side effects were injection site swelling (8 to 19%) and conjunctivitis (2 to 5%).

Q – Tips: Eustachian Tube dilation

Q – Tips: Eustachian Tube dilation

  • A new technique to dilate the eustachian tube, pioneered at Stanford University, might bring relief to some families of young children with frequent ear infections. Among the sufferers are some with anatomically small or scarred eustachian tubes who experience repeating ear blocking and ear fluid. Until now the only help was putting tubes through the ear drum
Alas, what we have wrought

Alas, what we have wrought

Allergic diseases arise in response to normally innocuous environmental agents, including airborne allergens and the foods we eat.

Why does the immune system cause this mischief and why is it becoming so prevalent?

The answer to both these questions is T-regs.

T-regs, better known as T-regulatory lymphocytes, were first discovered about 20 years ago. However, over the past 10 years scientists have learned the vital role they play in causing allergy. As their name implies, these cells regulate the immune system. When they function normally they regulate the immune system to be tolerant to airborne allergens and foods (that is, to be non-allergic).

As it turns out, it seems to be the proinflammatory environment created since the industrial revolution that has caused the T-regs to go awry. The main environmental factors are modern chemicals, petroleum exhausts, plus our water and food supply that contains chemicals and antibiotics.

One of the biggest arenas in immunologic research is to find a way to get the T-regs back into a friendly mode, despite the pro-inflammatory environment we have created for ourselves.

 

Dear Doc: So carbon monoxide not always harmful?

Dear Doc: So carbon monoxide not always harmful?

Dear Dr. K: I’ve always heard that carbon monoxide is deadly, but then I read it’s being researched as a transplant medicine. What gives?

What gives is the dynamic of toxic levels versus helpful levels. There are many examples of this in the history of medicine. For example, in the pre-antibiotic era, heavy metals such as gold, silver and arsenic were used to treat infections, in very controlled doses.

Even oxygen, which we breathe every day, and can be supplemented for hospitalized patients can be toxic if given at too high a dose.

The same turns out to be true with carbon monoxide (CO). It wasn’t until fairly recently that scientists discovered humans actually produce CO, and that it plays a vital role in many bodily processes.

In the brain, it is a neuro-transmitter, important in learning and memory. In the heart, it keeps blood vessels wide open. In the liver, intestines, kidneys, lungs and reproductive organs it improves natural functions. And in the immune system it improves host resistance and lessens undesirable inflammation.

It is this last property that has led to the research you are alluding to in organ transplant rejection. Carbon monoxide has been shown to prevent transplant rejection in several animal models; it hasn’t been studied yet in humans.

Because CO reduces inflammation it also is being studied in traumatic brain injuries, multiple sclerosis, pulmonary fibrosis and atherosclerosis – all of which have unwanted inflammation as a common denominator.

Three methods of delivering CO as a treatment are being studied: breathing in small amounts, using CO-releasing compounds and using pro drugs to generate extra CO.

Perhaps being stuck in traffic has an upside.

DRESS: Short name for scary new allergic reaction

DRESS: Short name for scary new allergic reaction

DRESS, a helpful acronym for Drug Reaction with Eosinophilia and Systemic Symptoms, is a newly recognized form of allergic reaction. Potentially quite severe, it is important to recognize and stop the offending medication and start proper treatment. The exact pathogenesis is still not fully understood, but it seems to occur because of immune response and reactivation of a latent herpes virus.

A form of rash with facial redness and swelling is common, but a measles-type rash also can occur. Other common symptoms include fever, achiness and lymph node swelling. The most frequently affected internal organs are the liver and kidneys. Blood work can show elevated liver enzymes and kidney factors, and reveal an elevation in a specific white blood cell called the eosinophil.

The drugs most often found to cause DRESS are anticonvulsants and sulfur drugs. Others that have been implicated are Gleevec (an anti-cancer drug), various antibiotics, Amlodipine (a blood pressure medicine), and NSAIDS (non-steroidal anti-inflammatories).

As mentioned above, recognizing DRESS as soon as possible is important so the offending drug can be discontinued. The most effective therapy is the use of steroids. In life-threatening cases, intravenous immunoglobulin has been used.

So far, despite the interplay of viral interaction in causing the condition, no studies have been done on the use of antiviral therapy.

One less parental worry

One less parental worry

Harvard researchers at Boston Children’s Hospital recently finished a detailed study of the use of acetaminophen in asthmatic children. The outcome allows for a sigh of relief.

In 2000 British researchers questioned whether acetaminophen use led to exacerbation of wheezing in children. The concern arose because when children are sick with respiratory infections, this common, over -the-counter drug is frequently used to treat fever. So, the question arose: was it the illness itself or, perhaps, the acetaminophen that caused worsening of asthma?

One reason acetaminophen was a suspect is because it is known to temporarily reduce glutathione in the lungs – a natural compound that has anti-oxidant properties. Because of these concerns, many pediatricians in the U.S. and the U.K. were shying away from the use of acetaminophen in asthmatics. It was for this reason that Harvard undertook a randomized prospective study.

Their results were very reassuring. They found no increased risk of worsening asthma in the acetaminophen group versus the “control group.” Thus, they concluded it is safe to use, and that it’s the infection that worsens the asthma, not the popular drug.