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Laboratory tests

Laboratory tests can compliment symptom reports to provide a more complete clinical picture of patients' progress on the Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis. (MP).

Patients who progress on the MP typically experience immunopathologyA temporary increase in disease symptoms experienced by Marshall Protocol patients that results from the release of cytokines and endotoxins as disease-causing bacteria are killed.. Immunopathology is caused largely by cytokinesAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. generated by the immune response and endotoxins released from dying bacteria. Occasionally, immunopathology will consist of an abnormal lab value such as elevated creatinine, elevated liver enzymes, or low white blood count. This is due to the occurrence of subclinical bacterial inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. that has been revealed by olmesartanMedication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. Also known by the trade name Benicar. 's (Benicar) activation of the immune system.

The levels of the two most important vitamin D metabolites, 25-DThe vitamin D metabolite widely (and erroneously) considered best indicator of vitamin D "deficiency." Inactivates the Vitamin D Nuclear Receptor. Produced by hydroxylation of vitamin D3 in the liver. and 1,25-DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol., can be interpreted using the Vitamin D Metabolite Calculator. A periodic assessment of a patient's serum 25-D level, which is inversely correlated with immune function, is strongly recommended – especially as it declines below 20 ng/ml. Testing 1,25-D as a measure of inflammation is only useful before taking olmesartan.

Baseline inflammatory marker tests such as a complete blood count (CBC) along with a comprehensive metabolic panel (CMP) should also be ordered prior to introducing olmesartan to provide the best possible measure of chronic inflammation in the patient prior to treatment.

Under many circumstances, some laboratory tests can be considered non-essential. Patient and doctor should discuss the decision to perform these tests based on the individual patient's clinical picture and any economic concerns. Every test should be interpreted by the physician in the relevant clinical context.

Vitamin D metabolism

Short of trying the Marshall Protocol itself (i.e. a therapeutic probeA brief trial of the Marshall Protocol to see if it will generate an immunopathological response. The "gold standard" for testing whether a patient is a good candidate for the MP.), the most valid way to determine if the MP is applicable to a patient is by measuring serum levels of two key vitamin D metabolites: 25-D and 1,25-D. 25-D is a measure of innate immune function with higher levels suggesting active immunosuppression. 1,25-D is a measure of inflammation.

Contextual interpretation of a patient's 25-D and 1,25-D results are available using the vitamin D metabolite calculator. When testing the vitamin D metabolites, all relevant instructions, including the freezing of samples, should be closely followed.

It is also possible to test 25-D at home with a home test kit.

Kidney (renal) function

Main article: Kidney (renal) function

Most patients on the MP experience temporary but well-defined increases in various markers of disease state and inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue., consistent with an immunopathological response. Results of blood tests for kidney function can generate considerable angst for Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis. patients and their medical providers. Out of genuine concern for their patients, some physicians consider withholding prescription of olmesartanMedication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. Also known by the trade name Benicar. . Experiences on the MP show that this concern may be mostly unfounded. And that the aberrant test values are to be expected from the nature of the MP treatment.

Doctors may want to assess kidney function by testing creatinine clearance test or BUN and measure other indicators specific to each patient for a baseline and retest as appropriate. Due to immunopathologyA temporary increase in disease symptoms experienced by Marshall Protocol patients that results from the release of cytokines and endotoxins as disease-causing bacteria are killed., lab these values may become temporarily abnormal until the inflammation resolves.

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Example of immunopathology – Patients on the Marshall Protocol tend to experience temporary increase in several antibody titers, and a decline in latter stages of treatment.1)

Other tests

  • complete blood count (CBC) – A test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood. Widely used for regular checkups.
  • antibodies – Expected to increase with immunopathology. (See right.)
  • blood pressurehypotension and dizziness can be exacerbated during recovery on the MP
  • bone density – The primary tool for measuring bone density is a DEXA (also known as DXA) scan. DEXA may provide evidence that treatment is reversing Th1 diseaseAny of the chronic inflammatory diseases caused by bacterial pathogens. related bone loss such as the kind observed in osteoporosis and osteopenia. Results usually do not change course of treatment.
  • colonoscopy – Endoscopic examination of the colon and the distal part of the small bowel with a small camera on a flexible tube. May provide reassurance when fearful of malignancy, but can expose patient to greater infection due to difficulties in sterilizing equipment. Results usually do not change course of treatment.
  • imaging tests – Includes x-ray, magnetic resonance imaging (MRI), and computed tomography (CT Scan). Significant level of interpretation required to determine meaning of resulting image. Exposes patient with chronic inflammation to additional radiation, possibly increasing the risk of cancer. Results tend not to change course of treatment.
  • lung function – For patients with lung involvement, tests of pulmonary function may temporarily decline on the MP, but are expected to improve over time.
  • thyroid function – It is common for patients suffering from chronic diseases to have low levels of thyroid hormones.

How to obtain lab results

Patients should remember they are the most important member of their health care team. Making sure you know what is in your medical records means that they are able to follow-up on questions and in some cases, verify accuracy. A doctor's office personnel can read you the exact numbers with measurements over the phone but patients should get a printed copy of all lab results.

Patients may need to sign a release of information form. Call the clinic's “Release of Information Office” or Medical Records to find out what their procedure is to obtain medical records. A patient should be able to do this all via the phone and mail. Once a signed release form is on file, patients can often just call them and have them mail you copies of the doctor's clinic note and test results after each visit.

It is best to always ask for copies of your lab reports, x-rays reports, clinic notes, etc. A proactive patient knows exactly what is in his/her medical record.

Excessive testing

Patients should be wary of excessive testing and procedures.

In the face of uncertainty and ambiguity, a clinician's natural response might be to order a battery of tests. After all, the more information clinicians obtain, the more confidence they have in the validity of their diagnoses, even when such confidence may not be justified on the basis of the information obtained.

In his paper, “Our stubborn quest for diagnostic certainty: a cause of excessive testing,” JP Kassirer writes:

Absolute certainty in diagnosis is unattainable, no matter how much information we gather, how many observations we make, or how many tests we perform. Our task is not to attain certainty, but rather to reduce the level of diagnostic uncertainty enough to make optimal therapeutic decisions…. We continue to test excessively, partly because of our discomfort with uncertainty.

Jerome Kassirer, MD 3)

In practice, as one approaches diagnostic certainty the useful information returned by diagnostic tests and observations approaches zero.4)

A 2011 article in the Daily Beast showed how some common tests and procedures may do more harm than good.

===== Notes and comments =====

In fact, when presented with the laboratory results of a patient whose markers are increasingly going out of range, most would conclude the patient was undoubtedly becoming sicker. As a consequence, a researcher conducting a study of immunopathology-stimulating therapy couldn’t simply invoke the elevation in cholesterol or decline in white blood cells as indications that microbes were being eradicated.

White blood cells (leukopenia)

find papers showing a decline in WBCs in infectionInstead of thinking that a patient is getting sicker because of lower wbcs you have to consider that wbcs are a sign patients are getting better.Doctors might be encouraged as long as it's not crazy. Even if low WBC is something you would expect tosee - if a low WBC is nothing that's not ideal. These situations require a little more interpretation. You need markers associated with recovery - not just health. What would you expect tosee under the circumstances of immune stimulation?

Other causes of low white blood cell count include: Influenza, systemic lupus erythematosus, Hodgkin's lymphoma, some types of cancer, typhoid, malaria, tuberculosis, dengue, Rickettsial infections, enlargement of the spleen, folate deficiencies, psittacosis and sepsis.

To the treating physician: interpreting laboratory tests Chronic disease is caused by an accumulating intracellular metagenomic microbiotaThe community of bacterial pathogens including those in an intracellular and biofilm state which cause chronic disease.. Because the microbes live inside cells, as the pathogens are killed then the cells which house them will often undergo apoptosis or phagocytosis, and disappear. The relative cell counts can therefore be expected to vary widely during recovery, and different cell types will be out of balance at different times during the recovery process (which takes 2-8 years). It is common for recovering patients to exhibit bloodwork which would normally be assessed as severe lymphopenia or severe anemia, however, these conditions resolve without intervention over the course of several months.

Ferritin is accreted by many of the microbial species. Sometimes the plasma ferritin goes high during recovery, sometimes low. In neither case can the patient be helped by intervention. The fatigue associated with these disease is not caused by the perceived 'anemia' .

During later stages of recovery, the kidney metabolites frequently go out of range, as the kidney heals. Plasma Creatinine can soar to two or three times normal values, although a 24hr Creatinine test will usually give results closer to what a physician expects. None of the more than 1000 seriously ill subjects we have been monitoring (for 2-8 years) have needed dialysis, even though their eGFR frequently measures in the 20s and 30s for months at a time. This results from a deficit in the way Medicine understands and monitors Kidney metabolites, and I discussed these issues in more detail on page 6 of my presentation at West China Hospital during 2009 (attached).

BUN can be expected to soar as the pathogens are killed, and CRP (which is an endogenous antimicrobial) will also temporarily soar, especially in later stages of recovery, after the body's own immune system has been fully restored

I hope this helps, please do not hesitate to contact me at any time. FYI, I have listed below some recent peer-reviewed journal and conference publications from myself and my colleagues.

Sincerely

Trevor

Each of the many individual metabolic changes that occur during the course of an infection must be interpreted in a manner that reflects its longitudinal development and progression over time and its relationship to the evolving phases of the infectious process.(Olteanu, see EndNote)

The total number of discrete metabolic response known to occur during acute and chronic infectious illnesses continues to expand.(Olteanu, see EndNote)

Total Protein test is described here.

Albumin test is describedhere.

Calcium test is describedhere.

Alkaline Phosphatase test is describedhere.

Aspartate Aminotransferase test is describedhere.

Serum glutamic-oxaloacetic transaminase, SGOT

Bilirubin test is describedhere.

CBC (complete blood count) with differential test is described here.

  • basophils
  • eosinophils
  • ferritin

f253:

When serum ferritin is high

Serum ferritin may be high in chronic inflammation, especially if the liver is involved. Treating that inflammation with the MP, is the answer. Periodic increases in ferritin suggest a good Herx response. This article lists the other tests done when a differential diagnosis is needed.

  • hematocrit
  • hemoglobin
  • lymphocytes
  • MCV (mean corpuscular volume)
  • MCHC (mean corpuscular hemoglobin concentration)
  • mean platelet volume
  • natural killer cells
  • neutrophils
  • platelet count
  • RDW (red cell distribution width)
  • WBC (white blood cells)

f317:

The cortisol test is described here.

C-peptide test is described here.

Gamma-Glutamyl Transferase (GGT) test is described here.

Lipase test is described here.

Insulin test is described here.

Phosphorous test is described here.

Chronic disease is caused by an accumulating intracellular metagenomic microbiota. Because the microbes live inside cells, as the pathogens are killed then the cells which house them will often undergo apoptosis or phagocytosis, and disappear. The relative cell counts can therefore be expected to vary widely during recovery, and different cell types will be out of balance at different times during the recovery process (which takes 2-8 years). It is common for recovering patients to exhibit bloodwork which would normally be assessed as severe lymphopenia or severe anemia, however, these conditions resolve without intervention over the course of several months.

Ferritin is accreted by many of the microbial species. Sometimes the plasma ferritin goes high during recovery, sometimes low. In neither case can the patient be helped by intervention. The fatigue associated with these disease is not caused by the perceived 'anemia' .

During later stages of recovery, the kidney metabolites frequently go out of range, as the kidney heals. Plasma Creatinine can soar to two or three times normal values, although a 24hr Creatinine test will usually give results closer to what a physician expects. None of the more than 1000 seriously ill subjects we have been monitoring (for 2-8 years) have needed dialysis, even though their eGFR frequently measures in the 20s and 30s for months at a time. This results from a deficit in the way we understand and monitor Kidney metabolites, and I discussed these issues in more detail on page 6 of my presentation at West China Hospital during 2009 (attached).

BUN can be expected to soar as the pathogens are killed, and CRP (which is an endogenous antimicrobial) will also temporarily soar, especially in later stages of recovery, after the body's own immune system has been fully restored

I hope this helps, please do not hesitate to contact me at any time. FYI, I have listed below some recent peer-reviewed journal and conference publications from myself and my colleagues.

Wikipedia's reference range for blood tests

The total number of discrete metabolic response known to occur during acute and chronic infectious illnesses continues to expand. The most widely recognized of these multiple responses are grouped for discussion into major categories, including changes in nitrogen, amino acid, carbohydrate, lipid, electrolyte, vitamin, and trace element metabolism. Another important mechanism involved in the host response to infection is oxidative stress, which plays a major role in the systemic inflammatory response in bacterial(16178750) and viral infections.(15944946)

I had previously noted on a different thread that my doc tests for some pretty exotic stuff. After starting the MP, my eosiniphilic cationic protein increased dramatically. ECP is an antimicrobial peptide produced by eosinophils. While this type of cell was formerly associated with asthma, the newer research indicates that it attacks mycobacteria.

Phillyguy

https://dspace.creighton.edu/xmlui/handle/10504/7063

Vitamin D and Chemotaxis of Human blood Eosinophils

Asthma is one of the most chronic medical conditions characterized by inflammation of the airways, mucous production, and airway hyperresponsiveness. A hallmark of asthma is the presence and activation of inflammatory cells in the airways, notably eosinophils, mast cells and T lymphocytes. Eosinophils function is related to destructive activity mediated by the toxic effects of the granule proteins and soluble mediators derived by the cells. Vitamin D, as a potent immunomodulator, has an unknown role in the eosinophil-induced asthmatic response. It was previously reported that in vivoA type of scientific study that analyzes an organism in its natural living environment. administration of vitamin D in humans increases the expression of CC chemokine receptor 3 (CCR3) in eosinophils. However, whether or not the effect of vitamin D on eosinophils is direct or indirect is unclear. Calcitriol, the active form of vitamin D, can induce synthesis of Transforming Growth Factor (TGF-β), which is involved in airway remodeling. Eosinophils, which are recruited to the lungs by eotaxin and interleukin 5 (IL-5), are a major source of TGF-β. Therefore, the effect of calcitriol was examined on vitamin D receptorA nuclear receptor located throughout the body that plays a key role in the innate immune response. (VDRThe Vitamin D Receptor. A nuclear receptor located throughout the body that plays a key role in the innate immune response.), CCR3, TGF-β1, and IL-5 receptor (IL-5R), expression in human blood eosinophils. Peripheral blood was drawn from healthy volunteers, and eosinophils, neutrophils, monocytes and lymphocytes were isolated. The purified eosinophils cells (purity >99%; viability >97%) were stimulated with calcitriol (100-300 pM and 100 nM) for 24 hours. The mRNA expression and protein expression of CCR3, VDR, TGF-β1, and IL-5R was examined by real-time PCR and Western blotting. Eosinophil chemotaxis was also assessed using Transwell migration assay and using eotaxin and IL-5 as chemokines. Also, the role of GATA-1which is a member of GATA transcription factor family involved in eosinophil development was examined using siRNA. After calcitriol stimulation of eosinophils, VDR mRNA and protein expression were increased significantly. Eosinophils also had a significant increase in CCR3 mRNA and protein expression of eosinophils as well as a significant increase in mRNA and protein expression of TGF-β1. However, Calcitriol had no effect on IL-5R mRNA transcripts in eosinophils. Calcitriol was found to significantly enhance the migration of eosinophils in response to eotaxin, but it had no effect on the migration of eosinophils in response to IL-5. Calcitriol induced phosphorylation and increase protein expression of GATA-1. siRNA specific for GATA -1 reduced calcitriol-induced phosphorylation and increased GATA-1 protein expression, in addition, calcitriol increased protein levels of CCR3. These results demonstrate that vitamin D can directly act on human blood eosinophils to increase mRNA transcripts of CCR3, TGF-β1 and enhancing migration of eosinophils in response to eotaxin. This suggests a potential role of vitamin D in eosinophil recruitment and migration in inflammatory airways.

My own Doc wanted me to have a biopsy after my PSA doubled in 12 months at an early point in MP recovery… I dissuaded him by citing the European guidelines, which are much more conservative. Anyway, here is something we might want to help Paul put in the MPKB :) Maybe we also want the European guidelines in there too :) https://www.businessweek.com/lifestyle/content/healthday/650257.html..trevor..

Is triglycerides any good indicator of immmuopathology? I suggest this is removed. Inge Lindseth

===== References =====

1)
Proal, A.D. (2009). “Antibodies and infection in the era of metagenome” at 1st International Congress of Antibodies (Beijing).
2)
Ravnskov U. High cholesterol may protect against infections and atherosclerosis. QJM. 2003 Dec;96(12):927-34. doi: 10.1093/qjmed/hcg150.
[PMID: 14631060] [DOI: 10.1093/qjmed/hcg150]
3)
Kassirer JP. Our stubborn quest for diagnostic certainty. A cause of excessive testing. N Engl J Med. 1989 Jun 1;320(22):1489-91. doi: 10.1056/NEJM198906013202211.
[PMID: 2497349] [DOI: 10.1056/NEJM198906013202211]
4)
Johnson HA. Diminishing returns on the road to diagnostic certainty. JAMA. 1991 May 1;265(17):2229-31.
[PMID: 1901611]
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