Dr Graham Exelby

As I head into 50 years in medicine (45 years in general practice), experience has taught me that we never stop learning. The need to keep asking “why” and not just accepting “what is the accepted” has taken me in a direction where I see health as a combination of what we inherit (our genes), what we do with our lifestyles, and what life’s circumstances inflict on us.

 

I graduated from University of Queensland in 1973, working in Southport then Charters Towers, Mt Isa then Texas (Qld) before returning to the Gold Coast in 1978 at Mermaid Beach.  Those country years were a valuable period of learning self-sufficiency and how to work out problems.

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I was joined by Jack Ashwin in 1985, and we built the Mermaid Central Medical Clinic which opened in January 1991.   The Clinic now proudly welcomes my daughter Leigh as a GP.

Learning to treat problems like atopic eczema and irritable bowel syndrome (IBS) with diet was a significant factor in a direction change that challenged a lot of traditional thought, courtesy of Dr Merv Garrett, an allergist and pioneer in food intolerance Australia.

 

15 years ago my life in medicine changed forever, having to confront Postural Orthostatic Tachycardia Syndrome or POTS in my family following a fairly minor operation.  Firstly acting as in a support role, then as my colleagues simply had no explanation for it, or how to treat it, my second role as researcher was launched.   And the patient became my teacher.

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Then as I journeyed down the rabbithole that is POTS and Fibromyalgia things started to come together.  COVID-19 then answered many of the questions that kept popping up- how a virus (and here add trauma, mould, parasites, sustained stress) can activate threat receptors (Toll-like receptors, or TLRs) which then activate Mast Cells that are responsible for the cytokine storm that is what happens in COVID.

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Simplified, Covid activates the TLRs which then activate mast cells which produce inflammatory cytokines, especially Interleukins 6 (IL-6) and 8 (IL-8) and Tissue Necrosis Factor alpha (TNFa) which cause damage in tissues including microglial cells, and this process is responsible for the characteristic Small Fibre Neuropathy (SFN) and from this the autonomic instability of dysautonomia, POTS and Long-COVID.

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The level of inflammation is so severe in COVID that microemboli are often formed and from this we get inflammatory and microembolic damage. Sometimes amyloid is also found in the fibrin clots, which leads in the future to the same linking into Alzheimers and Parkinson’s Diseases.    Using DNA again, looking at problems such as the common APO E4 and LPa mutations, generally ignored in medicine, we have looked at ways to manage the vascular, liver and dementia risks they provide.

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The addition of DNA assessments from Dr Valerio Vittone revealed common threads of DNA mutations in these syndromes, and a way to tackle these disabling conditions. DNA mutations in mast cells, the COMT, methylation, oxidative stress and other mutations have opened the door to successful treatments, ignoring the normal advice given in Long Covid to “accept your lot.”

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I have combining research from many areas over the years, and this is continuing as I continue to pursue the craniovascular and glymphatic changes in the brain, as well as tackling areas where genetic factors are critical such as:

• Homocysteine and APO E4 (the importance of these forgotten measures have been highlighted in Covid management)

• Aortic root and arch dilatation

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Major influences on my work:

• Firstly the need to learn from family, to ignore ineffective management and seek solutions

• The pioneering work of Merv Garrett in diet,

• Lawrence Afrin and his cohorts in the USA on mast cell activation syndrome

• Griffith University work on brainstem connectivity, glymphatic function and TRP mutations that affect natural killer cell function and glymphatic function itself

• Kjetil Larsen and others in Thoracic Outlet, Jugular Outlet Syndrome and the impact of neck pathology and posture on craniovascular perfusion

• The regular assistance from Dr Valerio Vittone, Profs Pete Smith and Jon Jenkins when the "going gets tough" and I cannot see a clear direction, and more recently from Drs Kevin Lee (endocrinology and nuclear medicine) and Rebecca Ryan (gastroenterologist with special interest in mast cells).

• Most importantly with help from Dr Valerio Vittone, the underlying DNA mutations that lie behind both POTS and Long Covid and most diseases.

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Techniques being employed include:

• Dynamic ultrasounds to assess major areas such as the Thoracic Outlet, Median Arcuate Ligament Syndrome, Nutcracker and May-Thurner Syndromes and relevance in particular in POTS (and resistant Long Covid). Standard angiography in a lying position does not see the changes seen in dynamic scanning

• Retinal photography and Carotid Intimal Thickness Scanning, started in 2008 as tools to assess small and medium vessel disease, now expanded to assess vertebral artery flow.   The cardiovascular damage from Covid cannot be measured by cholesterol, and needs a finite assay which these provide

• Heart rate variability studies in postural assessments of POTS, fibromyalgia as similar diseases

• Holter monitoring calibrated for heart rate variability to assess patterns of autonomic instability

• SPECT and other scanning to assess cerebral perfusion. Planned is the introduction of a Transcranial Doppler to assess vascular flow to complete the unlocking of the difficult craniovascular perfusion abnormality in POTS and POTS-like Long Covid.

• Continuing detailed history and alignment with DNA

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Research from Griffith University is unlocking the chronic fatigue syndrome, and this this the knowledge of how sleep disorder and new medications such as Low Dose Naltrexone can impact on the function of the newly discovered “Glymphatic System” which drains toxins from the brain.

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Research from Kjetil Larsen and others in Thoracic Outlet Syndrome (TOS) and Jugular Outlet Syndrome have been invaluable in controlling POTS and Fibromyalgia syndromes. Others have been looking at the cervical spine and how damage there can cause migraine and dysfunction craniovascular perfusion. Here once again, the glymphatics figure highly. The complex mechanical dysfunction from the neck and thoracic outlet affecting both craniovascular perfusion as well as glymphatic function is explored in the website in both POTS and Long Covid documents.

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By taking a thorough history in all facets of a person’s life, with a family history, and using appropriate investigations, early identification means that potential problems can be halted and may be reversed. The addition of DNA testing is a very valuable tool in many of the complex problems that we deal with.

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The DNA and epigenetic work with Dr Valerio Vittone is showing where future should be in medicine, when combined with sound clinical assessment, backed by appropriate use of the tools available to clinicians.

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As the current research progresses in Covid, there is glimpse into the near-future with better management of many diseases, including Alzheimers, Parkinson's, Multiple Sclerosis, cancer, auto-immune diseases, and even arthritis as the pathways are being unlocked. On a personal note, the use of H2 blocker famotidine has produced a major improvement in arthritis pain- and research does show the importance of TLR3 in this condition. Even in cancers, old medication such as Zolendromic acid has a place in breast and prostate cancer, the benefits most likely through it's effect on mast cells. New products are being developed in cancers targetting TLR3, and this begs the question whether famotidine and nizatidine will also work in this area. Time will tell as medicine moves into very exciting new areas.

 

My primary areas of interest are Long Covid, POTS and their co-morbidities, especially migraine, IBS and fibromyalgia.   I have been researching POTS and Fibromyalgia for over 10 years, and now work with Dr Valerio Vittone (Ph.D) in DNA and disease association, Mr David Haynes in Kiiko Matsumoto acupuncture in management of autonomic instability and Ms Holly Charlton in dietary management. 

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As mentioned above, there is also 12 years of cardiovascular research with emphasis on retinal photography and carotid intimal thickness as tools to improve risk assessment, now with Mr Alan Ming, optometrist using superior retinal photography.  These has been now shown to be applicable to monitoring cardiovascular risk in Long Covid, in particular with the risks associated with APO E4 and Lipoprotein A.

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My particular speciality is linking the various DNA mutations, in particular mast cell mutations, with dietary, mechanical and other factors that affect the autonomic system (dysautonomia), craniovascular dysfunction and glymphatic dysfunction.   This complex system has particular relevance in the research that is commencing around the world into glymphatic dysfunction in Alzheimers and Parkinson’s Diseases.

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-Graham Carl Exelby