Autonomic denervation & Western Diseases

Erosive lichen planus and reinnervation

2010-11-21T03:45:00.000-08:00

Oral lichen planus is a difficult and distressing condition. It produces painful plaques throughout the oral cavity. No-one knows the cause.

A new paper from Hungary finds abnormal nerves and upregulation of TRPV-1 in biopsied from these plaques. The question arises as to where these nerves come from ? Sources of primary denervation in the oral cavity may be many and varied though the authors did not provide candidates.

Oral lichen planus is a candidate for a Western disease. Does the same apply to vulval lichen planus ?

Aberrant renal artery reinnervation in refractory hypertension

2010-11-18T11:30:00.000-08:00

The Barts group presented their work on line at The Lancet this week. The results are very impressive. The question arises as to what causes abnormal nerves in renal arteries in patients with refractory hypertension ?

We know that abnormal nerves in the female pelvis result from injuries in childbirth and straining during defecation over many years (1). Low birthweight infants (<2500g) have persistent problems with constipation throughout their lives. DP Barker found that many low birthweight babies develop hypertension in later life. Others may develop constipation from high calorie, processed Western diets. DP Burkitt found that Western diets promoted low stool weights and suboptimal bowel habits. Both may be mechanisms for this kind of hypertension - ther emay be others (2).

Autonomic denervation and subsequent reinnervation are found in many Western diseases without apparent understanding. This framework may enable better understanding and better forms of treatment - like this.

(1) www.endometriosisexplained.com
(2) www.western-diseases.com

Autonomic denervation and chronic Western Diseases

2010-10-02T08:53:00.000-07:00

DP Burkitt's classic observations in the 1970's include:
(1) the reduced incidence of chronic diseases in African populations
(2) the differences in diet (low calorie, unrefined, plant-based in Africa),
(3) the differences in intestinal transit time (12 v 40 hrs; Africa v West)
(4) the differences in stool weight (464g in Africa v 110 g in London)

This item suggest that some of the differences in disease incidence arise from differences in physical efforts during defaecation. Physical efforts during defaection complicate 20-30% of Western bowel habits (Heaton, 1992). 1% of adults achieve successful defaecation less than once per week; 0.3% less than once per month (Heaton, 1992). Persistent physical efforts during defaecation cause widespread injuries to midline autonomic nerves resulting in wide-ranging consequences (as set out in previous posts) and different patterns of disease.

The disease is in the "wiring" which has effects in the end organ. At present this view is largely confined to benign disease though it may have effects on many malignant conditions as well. Burkitt identified colorectal cancer as a potential candidate for a "Western cancer" though several others share similar features. More in due course.

Masterclass in neurogastroenterology

2010-06-20T00:31:00.000-07:00

There was a remarkable meeting at the RSM yesterday. A multidisciplinary team led by Professors Qasim Aziz and David Silk described a wholes series of gastrointestinal phenotypes ranging from oesophageal reflux to rectal hypersensitivity in terms of autonomic denervation.

Daniel Sifrin highlighted different patterns of GORD and their response to treatment using novel investigative techniques. David Silk and Gerald Libby gave a remarkable duet on different forms of gastrointestinal neuromuscular diseases and their effects on mood. Chronic idiopathic intestinal pseudo-obstruction or "pain/gas/bloat" syndrome seemed clearly in the specturm of enteric dysmotility particularly with full thickness biopsies demonstrating absence of smooth muscle alpha-actin. Professor Aziz covered the spectrum of disruption of the brain-gut axis discussing upregulation of different neural receptors and their regular association with rare and complex, connective tissue disorders. Mark Scott covered the range of coleorectal dysfunction and Charles Knowles gave a thoughtful surgical overview as a surgical neurogastro-enterologist.

Much new information; much intensive clinical research; clear signs of clinical progress. To my mind it is clear that autonomic dysfunction plays a key role in gastrointestinal disease. What is preventing wider recognition of the progress ? Two key issues spring to mind. Firstly, the lack of widespread morphological awareness of the splanchnic nerves and their pre and postganglionic connections - which have been dissolved in formalin in the post-war years. Secondly, it is the lack of precision in the term "constipation" - it means different things to patients, primary care, researchers, etc - hard, small, infrequent, difficult to pass, physical efforts during defaecation, etc. It is the last that is critical to neural function - nerves do not like stretch. Different shapes and sizes strain in different patterns producing different sites of autonomic injury and ..... Western diseases.

The CEO of the Princess Grace Hospital convened the meeting on behalf of HCA. Given the number and range of questions there was considerable evidence of learning taking place throughout the event. Everything is on www.centraldoctor.co.uk

Michael Pollan's dietary rules and Western diseases

2010-01-05T10:49:00.001-08:00

Michael Pollan sets out some "rules" of diet ini his new book. I have not yet read his book (which I look forward to doing) - only his column. I enjoyed the distinction between "food" and "food products" which may be placed in a more extreme definition: food products have barcodes; food does not ! Try the "no barcodes diet" for a month and you may feel the difference.

The key question is how does a good diet and regular exercise protect you from Western diseases ? A full answer will include both benign and malignant diseases. There is now a developing view that addresses benign diseases. The full argument is set out in the paper on Western dieases on http://www.bristolanatomycourse.co.uk/ and relates to injuries to your autonomic nerves (see Wikipedia for a good description). The full paper is published as "Autonomic denervation and the origins of chronic Western diseases". Prolonged physical efforts during defaecation, prolonged physical efforts during labour, surgery, trauma and other unrecognised injuries to your autonomic nerves result in a wide range of physical consequences that lead to diverse and cumulative mechanisms for Western diseases.

How might your diet and injuries to autonomic nerves result in malignant disease ? Many cancer researchers talk about cancer initiators and promoters. This view is much more speculative though suggests an initiator (injuries to autonomic nerves) acting with a dietary promoter (dairy products in breast and prostate cancer, tobacco in lung cancer). Conventional medicine seems to act in contrary fashion by using serious chemotherapy, radiotherapy and surgery that includes removal of lymph nodes (innervated lymph nodes may assist in controlling local growth)

Much more work to do yet - but, on any base, diet and exercise are keys to "prevention and wellness" as it is difficult to explain the dramatic change in benign and malignant Western disease in the past century; it is too quick to be genetic in origin.

Effects of autonomic denervation

2009-12-04T14:42:00.000-08:00

Walter Cannon set out the first law of autonomic denervation in the 1940's. He found that denervation of a motor unit resulted in supersensitivity in the zone of innervation. The second law of autonomic denervation states that if autonomic nerves are injured then this may have effects on the central nervous system. Formal studies use the term "central sensitisation"..

It is clear that injuries to pelvic autonomic nerves result in:

(1) changes in form - particularly hypoplasia (or hyperplasia in a "generative" organ" e.g. leiomyoma or adenomyosis)
(2) changes in function - including visceral dysmotility as in the uterus and Fallopian tube
(3) susceptibility to infection - denervated epithelia are more susceptible to infection and those infections skew towards opportunistic organisms
(4) susceptibility to toxins - autonomic "irritants" include stress, alcohol, tobacco, drugs, infections, etc (Bannister R, "Autonomic Failure, 2nd Edition)
(5) aberrant reinnervation - which takes several forms and results in hyperalgesiae or allodyniae cf gynaecological symptoms where "light touch causes pain/discomfort"
(6) CNS changes - any changes to peripheral nerves register changes in the central nervous system with varied clinical effects

Developing Dr Cannons' studies there may be as many as six "laws" of autonomic denervation that account for some forms of many chronic diseases through diverse and cumulative mechanisms.

Bohmian dialogue at Mile End

2009-11-26T12:56:00.000-08:00

A meeting to commemorate the life of David Bohm took place on Saturday at The London Hospital, Mile End. Most of the speakers knew Bohm in person and gave precise evidence as to his wide-ranging contributions to C20 physics. His lasting contributions for the rest of us, may be two brief monographs written at the end of his life; "On Creativity" and "On Dialogue". An eclectic 150 attended a very good meeting organised by Claudia from the North London chapter of www.scimednet.org

Basil Hiley set out the physics. Basil is a brilliant mathematician yet seemed slightly dissatisfied with each proof as he presented it; the descriptive words did not seem to match the precise symbols. When asked "What was wrong with C20 physics ?" Basil said "quantum mechanics mucked it up". He suggested that one or two colleagues may have imposed themselves on C20 physics and, upset the flow of thought from Einstein forwards. No names but Pauli and Bohr may be relevant. The imposition of personality on the flow of thought in physics may have been the practical impetus to "dialogue" where Bohm explains the "proprioception" of thought and its unfolding to create the world around us. An implicate order creates an explicate world.

David Peat gave a personal account of his times with "Dave" as the quiet and humble genius who had been "stitched up" by Oppenheimer and put before McCarthy for un-American activities. Expelled from the US and Princeton, Bohm ended up in Birkbeck (via Bristol) where he did further good and great work. Bohm was certainly in the "make me safe" brigade and after his North American nightmare, maintained himself, peacefully, in academic physics in the UK.

Professor Leroy Little Bear, a Blackfoot professor "knew" and "felt" dialague. When asked about the significance of language and time, he said there were 350 ways of conjugating "I am" in Blackfoot, and, time was an elusive concept in that being so much in the moment, it was never clear when they were going to be anywhere - probably not at the meeting at 2 o'clock on Wednesday.

Some good contributions from the floor contribute to a very stimulating day; an appropriate tribute to a remarkable man.

Abstract of "Diabetes, diet and denervation"

2009-11-13T14:46:00.000-08:00

Contemporary theories to explain the autoimmune aetiology of type 1 diabetes mellitus (T1DM) include the "hygiene", "accelerator" and "thrifty phenotype" hypotheses though none accounts for its natural history, or, epidemiology. Early-onset, T1DM is epidemic in Western countries and shares features of its epidemiology with other major childhood diseases.

In the autonomic denervation view, early-onset, T1DM results from injury to autonomic nerves supplying the pancreas through persistent physical efforts during defaecation in infancy. Pancreatic denervation results in loss of islets of Langerhans and reduced insulin production that may present in infancy or later life. Early introduction of cows milk and solids to the infants' diet cause increased rates of bowel problems whereas exclusive breastfeeding in non-Western countries, protects the infant from both constipation and diarrhoea.

What about the extended MHC haplotypes that link to T1DM and other diseases ? Then the question arises as to what is an "autoimmune" disease ? Criteria for an "autoimmune" disease were set out by Witebsky and Rose in 1957. Few, if any, diseases meet those stringent criteria. Over the decades many different conditions have been added to the "autoimmune" dustbin - largely on the basis that their immunohistopathology includes CD4 and CD8 lymphocytes, or, there are MHC associations.

Other important Western diseases may result from the varying effects of injuries to nerves at different sites in the autonomic nervous system.

Diabetes, diet and denervation (ALL and asthma)

2009-11-05T14:22:00.000-08:00

The view that type 1 diabetes results from a neuropathic injury to the islets of Langerhans in infancy as a result of bowel problems secondary to early weaning, has been published this week.

Most of the elements of the hypothesis have evidence to support them including the finding of denervation in human diabetic pancreas (Taborsky, Seattle). Clearly they have not been tested as a whole - is it ethical or reasonable to do so when prevention by six months of exclusive breastfeeding is already established WHO policy ?

Acute lymphoblastic leukaemia and early-onset asthma have high rates in under fives in countries where T1DM is common - Finland is the best example. All three diseases show similar stochastic distributions (age of onset plotted against age of incidence). Splenic and pulmonary denervation may contribute to these two major diseases. There have been extensive studies (80's and 90's) on nerves in asthma though none in ALL.

Leukaemology is mired in the Greaves hypothesis, irradiation and genes whereas diabetologists cannot emerge from the Class 2 linkage studies and autoimmunity. Great for grant-ologists but not so good for understanding causation ?

Endometriosis - a Western disease ?

2009-10-21T14:32:00.000-07:00

Dr John Sampson first proposed that retrograde menstruation gave rise to endometriosis in the 1920's. Contemporary gynaecology does not give a mechanism for this "reverse" flow of menstrual debris from the uterus along the Fallopian tubes. New studies (UK, Australia, Belgium) confirm abnormal nerves in the uterus that may upset the normal pattern of menstruation. Others have shown disordered motility of the Fallopian tubes though without demonstrating abnormal nerves in the Fallopian tubes.

Image provided by Dr Gregory Brodsky.

The image, produced by Dr Gregory Brodsky, shows a cross section of the Fallopian tube as it passes through the uterine muscle (intramural Fallopian tube). Nerve fibres stain brown using an antibody named anti-S100 (standard histological technique). At 2, 6, 8 and 10 o'clock there are collections of abnormal nerves around the Fallopian tube. Nerves are important in propelling material in the correct direction. These abnormal nerves will also promote retrograde menstruation and prevent normal progress of the egg from the ovary to the uterus. Injuries in childbirth and during physical efforts during defecation may contribute to these observations - among other events.

Spalteholz and other matters

2009-09-01T02:40:00.000-07:00

It is an open question at to "what happened to the autonomic plexi in the second half of twentieth century ?" Robert Lee described the precise anatomy of the cardiac and hypogastric plexi though who discovered the coeliac plexus ? In the late nineteenth century many other anatomists confirmed their anatomy including some brilliant German anatomists suchas Spalteholz - who contributed a beautifully illustrated three volume set. Unfortunately the printing plates were lost in WW1. His contribution continues in his earlier editions

Spalteholz' view of the cardiopulmonary plexus in 1896

Angina with normal coronary angiograms

2009-08-29T14:13:00.000-07:00

Cardiologists have struggled for 40 years with patients with angina-like chest pain whose coronary angiograms show no evidence of obstructive coronary artery disease. This is an enigmatic condition that keeps cardiologists awake at night. Patients are usually women, aged 40 to 50 years of age, with typical descriptions of chest pain consistent with angina pectoris. Abnormal non-invasive testing leads to coronary arteriography that shows no signs of coronary artery stenosis - unsettling for both doctor and patient.

Clearly there may be a variety of aetiologies. Persistent and sustained stress may cause such clinical presentations and are benign if the stressors are recognised and removed. A second pattern has resonance in the myometrium. Many women present with premenstrual pain associated with perivascular nerve fibre proliferation. This lesion is caused by injuries during childbirth and, more purely, through persistent physical efforts during defaecation (Fig 1). There are similar lesions in all pelvic organs. Similar patterns have been described in the myocardium by the UCLA group (Chen, et al, many papers). Women have markedly more problems with "constipation" compared to men particularly in their post-reproductive years resulting in a wide range of disorders and diseases, at different ages.

The cardiac plexus sits among the pulmonary veins on the posterior surface of the left atrium. It is rarely seen by cardiologists, the coeliac plexus is rarely seen by diabetologists and the hypogastric plexus almost never seen by gynaecologists. These autonomic plexi may be the source of many Western diseases.

http://www.ncbi.nlm.nih.gov/pubmed/19712795?ordinalpos=4&itool=Email.EmailReport.Pubmed_ReportSelector.Pubmed_RVDocSum

Myocardial reinnervation

2009-08-11T09:30:00.000-07:00

Aberrant myocardial reinnervation with collateral sprouting results from some patterns of myocardial infarction, but there are many arrhythmias that occur without ischaemia or infarction (1). Their cause is unclear.

In the female pelvis, autonomic injury results from childbirth and persistent straining during defecation as well surgical injuries, and, different neural injuries between the CNS and the uterus (2). Traumatic injury to nerve bundles during childbirth results in collateral sprouting and stromal reinnervation in the isthmic myometrium, where uterine nerves enter the organ. One per cent of adults achieve defecation once per week, 0.05% achieve defecation less than once per month (3). Persistent straining causes perivascular nerve fiber proliferation and premenstrual pain (4). Similar patterns occur in myocardium associated with some patterns of angina (1). Do the dermatomes (C2-C5) provide a clinical map to different patterns of myocardial innervation and infarction ?

Few are aware of the precise morphology of autonomic nerves because of their anatomic sites, and, their immersion in formalin destroys fine branches (5). Injuries to branches of cardiac, coeliac and hypogastric plexi underpin many Western diseases. Their causation and prevention are matters of prime concern.

Cow' milk allergy and T1DM

2009-08-09T05:28:00.000-07:00

Cow's milk allergy is a reaction to cows' milk proteins (type I and IV). It affects 2-3% of children though only 0.5% of exclusively breastfed infants. It causes atopic dermatitis, infantile colic, GORD, proctitis, failure to thrive and eosinophilic enteropathy. Lactose intolerance is part of the differential diagnosis.Infant diarrhoea and constipation both cause persistent physical efforts during defaecation with tenesmus. (BMJ 2009;339:b2272, doi 10.1136/bmj.b2275)

The Diabetes in Childhood in Finland cohort showed an increased risk of T1DM with early introduction of cows milk, and, shorter duration of exclusive breastfeeding (Virtanen et al, 1993) Persistent straining in adults injures autonomic nerves in the pelvis creating specific patterns of aberrant reinnervation and pain. Do increased bowel problems in supine infants cause injuries to coeliac nerves with loss of pancreatic nerves and atrophy of iselts of Langerhans ?

Such mechanisms offers a peak for early onset T1DM though also allows for a persistent incidence throughout life through persistent bowel problems that are all too common in Western societies. (Heaton, 1991)

The aetiology of Type 1 diabetes mellitus

2009-08-08T16:41:00.000-07:00

Studies from Seattle confirm denervation of the islets of Langerhans in T1DM. The authors wondered how the "autoimmune " process in T1DM results in loss of islets and their nerves as well ?

Original criteria for autoimmunity included an antigen, autoantibodies and reproduction of the histopathology by injecting the antigen into an animal species (Witebsky's postulates, 1957). In T1DM we have no antigen, some autoantibodies, CD4 and CD8 lymphocytes in the pancreas, and, some HLA associations. Adjacent evidence - but circumstantial. What if primary denervation were the primary source ? (Quinn, Am J Med, 2008)

If autonomic denervation is responsible, then what causes it ? In adult women pelvic denervation arises from childbirth (prolonged second stages) and persistent, physical efforts during defaecation. In supine infants coeliac denervation may result from similar bowel problems associatd with weaning. Finnish mothers have low rates of exclusive breastfeeding, high rates of cows-milk allergy, high rates of infant bowel disorders and the highest rates of T1DM worldwide. A full account follows shortly.

DP Burkitt

2009-08-05T13:20:00.000-07:00

Dennis Burkitt FRS made some important observations in Western diseases in the 1970-80's. He confirmed that many diseases are less common in Africa than Europe including heart disease, bowel disease, vascular disease, diabetes, obesity, autoimmune disease, gynaecology, etc. He noted key differences in diet between an unrefined, plant-based diet and a refined, animal-based diet in Africa and Europe respectively. He also found that daily stool weights in rural Uganda were 464g whereas in Europe they were 110g per day. He attributed the differences in disease epidemiology to the refined Western diet though the precise mechanisms were not clear.

Since Burkitt's observations the incidence of these diseases has increased dramatically. Western diets continue to deteriorate yet we are still short of the mechanisms of disease.

Autonomic denervation and Western Diseases

2009-07-30T14:23:00.000-07:00

"Western Diseases" describes those conditions characteristic of modern affluent Western communities and their lifestyles. The first comprehensive account was that of HC Trowell and DP Burkitt in 1981 in "Western Diseases; their emergence and prevention".

Diet plays a disproprotionate role in their aetiology though bowel habit, childbirth, lack of exercise, posture, gait and many other factors will also contribute. The mechanisms of any particular condition may be multiple, and, have been difficult to determine.

Much evidence has been put together by John Robbins in his series of books http://www.healthyat100.com/ , Professor Jane Plant in her books on the aetiology of breast cancer http://www.janeplant.com/ and many others. One of the key voices in "prevention" and "wellness" is Senator Tom Harkin, US Senator, Iowa. http://harkin.senate.gov/index.cfm

Emerging evidence across many specialties points to common mechanisms including autonomic denervation, and it's later effects.