Diagnosis and treatment of human dormancy-related sequellae

• US 20060052278A1
• Filed: 08/18/2005
• Published: 03/09/2006
• Est. Priority Date: 05/23/2002
• Status: Active Grant

• Current Assignee: Michael Powell
• Original Assignee: Michael Powell
• Inventors: Powell, Michael
• Granted Patent: US 7,485,298 B2
• Time in Patent Office: Days
• US Class Current: 514/1
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease
• CPC Class Codes: G01N 33/78 Thyroid gland hormones , e.g. T3, T4, TBH, TBG or their receptors
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

New methods for diagnosis and treatment of human dormancy syndrome-related sequellae are provided. Human dormancy syndrome (HDS) is characterized by elevated serum ratio of rT3/fT3 compared to a population of normal subjects. HDS includes fibromyalgia, chronic fatigue, cancer, autoimmune disease, obesity and related dormancy conditions. Dormancy and HDS-related sequellae are imposed on humans by infection with lipopolysaccharide (LPS; or endotoxin)-producing organisms, especially those that are intracellular and those that create antigens that stimulate the TLR pathways. In such instances, the elimination or neutralization of the LPS signal along with the infectious source is required to impact the sequellae of HDS. Treatment includes use of novel and non-obvious doses of antibiotics, optionally including agents that decrease the adverse effects of endotoxin.

Claims

1. A method for treating cancer and/or autoimmune disorder in a patient, comprising the steps of:

(a) identifying a patient susceptible to therapy, said patient having;

(i) a diagnosed cancer or autoimmune disorder;

(ii) a rT3/fT3 ratio of greater than about 4; and

(iii) at least one other finding selected from the group consisting of

elevated levels of;

fungal or bacterial DNA, Chlamydia, Mycoplasma, alpha 2-macroglobulin, alpha-fetoprotein, angiotensin II, Bcl-2, Bcl-XL c-fos, c-jun, ACE activity, CGRP, calsequestrin, CEA, catalase cathespin B, cIAP-2, connexin 43, CRF, COX-2 activity, d-dimer, endothelin-1, endotoxin, enkephalin, epithelial growth factor, FADD, fas ligand and/or fas/APO 1 ratio, FLIP, gastrin, ghrelin, glutathione peroxidase, FABP, heme oxygenase-1, hormone-sensitive lipase, HSP70, HIF-1, ICAM-1, IGF-1, IL-6, JNK, kallikrein, kinin, lipoxygenase, MAPK, Mcl-1, activation of the moesin-ezrin system, neuropeptide Y, neurotensin, NF kappa B, pancreatic triglyceride lipase, PDK, peptide YY, prolactin, prostcyclin, PGE2, protein kinase C, resistin, rT3, serine protease, substance P, superoxide dismutatse, survivin, TNF alpha, tyrosine hydroxylase, UCP2 &

3 activity, VIP, vasopressin or VEGF;

decreased levels of alpha-1 antitrypsin, antithrombin III, apolipoprotein, ascorbic acid, Bax, Bid, Bad, C1-esterase inhibitor, caspase, caveolin-1, cystatin, cytochrome-c oxidase, dopamine, Factor V, fT3, glyceraldehyde-3-phosphate dehydrogenase activity, GSH/GSSG ratio, IGFBP, junB, melatonin, Na/K ATPase activity, nitric oxide, orexin-A, hypocretin-1, altered oxytocin levels, decreased p53, PARP, PPAR gamma, ROCK-2, secretin, serotonin or TRAIL activity;

(b) initiating therapy with at least one antibiotic until at least one sign of endotoxemia is observed;

(c) continuing step (b) until at least one sign of endotoxemia decreases; and

(d) adding at least one additional antibiotic to the regimen of step (b).

2. The method of claim 1, further comprising inhibiting the enzyme 5-D1 to elevate serum fT3 levels, so that the ratio of serum rT3/fT3 decreases to below about 4.

3. The method of claim 1, further comprising stimulating the enzyme 5′

-D1 to increase fT3 production so that the ratio of serum rT3/fT3 decreases to below about 4.

4. The method of claim 1, further comprising inhibiting the enzyme 5-D1 and stimulating at least one of the enzymes 5′

-D2 and 5′

-D1 so that the ratio of serum rT3/fT3 is below about 4.

5. The method of claim 1, further comprising administering T3 to decrease the ratio of serum rT3/fT3 to below about 4.

6. The method of claim 1, wherein said patient has elevated levels of fungus or Chlamydia pneumoniae, fungus or Chlamydia pneumoniae DNA or immunofluorescent stains for fungus or Chlamydia pneumoniae in the thyroid gland.

12. The method of claim 1, wherein said first antibiotic is amoxicillin, zithromax, rifampin, doxycycline and metronidazole.

13. The method of claim 1, wherein said additional antibiotic is flagyl.

15. The method of claim 1, further comprising administering one or more agents to reduce adverse effects of endotoxin selected from the group consisting of an endotoxin binding or endotoxin neutralizing agent, an agent to inhibit NF kappa B activity, an agent to inhibit ACE, Vitamin C, Vitamin B12, an agent to inhibit cyclooxygenase-2 (COX-2), an omega-3 oil, an agent to inhibit interleukin-6 (IL-6), an agent to inhibit metalloproteinase activity or an agent to protect the liver from endotoxin damage.

16. The method of claim 15, wherein said agent to inhibit metalloproteinase activity is doxycycline or minocycline.

17. The method of claim 15, wherein said endotoxin neutralizing agent is selected from the group consisting of charcoal;

cholestyramine, Lipram™ and

Pangestyme™

.

18. The method of claim 15, wherein said agent to inhibit NF kappa B is selected from the group consisting of Zestril™

(lisinopril), an angiotensin converting enzyme (ACE) inhibitor, Quercetin™

, Vitamin D, magnesium, zinc, and selenium.

19. The method of claim 15, wherein said agent to reduce prostaglandin E2 is omega 3 oil, Vitamin C or a non-steriodal antiinflammatory (NSAID).

20. The method of claim 19, wherein said NSAID is Celebrex™

or aspirin.

21. The method of claim 15, wherein said agent to inhibit interleukin-6 (IL-6) is hydroxychloroquine (Plaquenil™

).

22. The method of claim 15, wherein said agent to protect the liver is Thistilyn™

.

7. A method for diagnosing a human dormancy syndrome-related sequel in a human, comprising the steps of:

(a) determining the presence of a finding selected from the group consisting of;

an elevated level of;

fungal or bacterial DNA, Chlamydia, Mycoplasma, alpha 2-macroglobulin, alpha-fetoprotein, angiotensin II, Bcl-2, Bcl-XL c-fos, c-jun levels and/or ACE activity, CGRP, calsequestrin, CEA, catalase cathespin B, cIAP-2, connexin 43, CRF, COX-2 activity, d-dimer, endothelin-1, endotoxin, enkephalin, epithelial growth factor, FADD, fas ligand and/or the fas/APO 1 ratio, FLIP, gap junction activity, gastrin, ghrelin, glutathione peroxidase, FABP, heme oxygenase-1, hormone-sensitive lipase, HSP70, HIF-1, ICAM-1, IGF-1, IL-6, JNK, kallikrein, kinin, lipoxygenase, MAPK, Mcl-1, activation of the moesin-ezrin system, neuropeptide Y, neurotensin, NF kappa B, pancreatic triglyceride lipase, PDK, peptide YY, prolactin, prostcyclin, PGE2, protein kinase C, resistin, rT3, serine protease, substance P, superoxide dismutatse, survivin, TNF alpha, tyrosine hydroxylase, UCP2 &

3 activity, VIP, vasopressin or VEGF or a decreased level of alpha-1 antitrypsin, antithrombin III, apolipoprotein, ascorbic acid, Bax, Bid and/or Bad, C1-esterase inhibitor, caspase, caveolin-1, cystatin, cytochrome-c oxidase, dopamine, Factor V, fT3, glyceraldehyde-3-phosphate dehydrogenase activity, GSH/GSSG ratio, IGFBP, junB, melatonin levels, Na/K ATPase activity, nitric oxide, orexin-A, hypocretin-1, altered oxytocin levels, decreased p53, PARP, PPAR gamma, ROCK-2, secretin, serotonin or TRAIL activity;

(b) calculating the ratio of rT3/fT3, wherein said ratio is above about 4; and

(c) determining the presence of one or more findings selected from the group consisting of persistent fatigue, cognitive impairment, weight gain, depression, alopecia, constipation, insomnia, sleep apnea, loss of libido, cold intolerance, exercise intolerance, addiction to stimulants, history of Raynaud'"'"'s Syndrome, dislipidemia, atherosclerosis, syndrome X, peripheral vascular disease, type II diabetes, dementia, demyelinating disease, muscle tension headache, migraine, fibrocystic breast disease, cancer, breast cancer, prostate cancer, ovarian cancer, cholelithiasis, pulmonary artery hypertension, pulmonary fibrosis, COPD, asthma, systemic hypertension, infertility, fibromyalgia, chronic fatigue syndrome, chronic pain, obesity, lupus, scleroderma, rheumatoid arthritis, sarcoidosis, vasculitis, myositis, ankylosising spondylitis, psoriatic arthritis, reactive arthritis, Reiter'"'"'s syndrome, Becet'"'"'s, polymyalgia rheumatica, viral, bacterial and/or fungal infection, septic shock, osteopenia, osteoporosis, pneumonia, narcolepsy, hypertension, liver disease, esophageal dysmotility, inflammatory bowel disease, renal disease, Parkinson'"'"'s disease, coma, impaired stage 4 sleep, irritable bowel syndrome, elevated sympathetic nervous system activity, dysregulated HPA, mitochondrial impairment, compulsivity, hypervigilance, dissociation, impaired natural killer cell activity, elevated CSF substance P levels, blunted growth hormone response during provocation testing, orthostatic hypotension and altered cerebral blood flow.

8. A method for treating a human dormancy syndrome-related sequel in a patient, comprising inhibiting the enzyme 5-D1 to elevate serum fT3 levels, so that the ratio of serum rT3/fT3 decreases to below about 4.

9. A method for treating a human dormancy syndrome-related sequel in a patient, comprising stimulating the enzyme 5′

-D1 to increase T3 production so that the ratio of serum rT3/fT3 decreases to below about 4.

10. A method for treating human dormancy syndrome-related sequel in a patient, comprising inhibiting the enzyme 5-D1 and stimulating at least one of the enzymes 5′

-D2 and 5′

-D1 so that the ratio of serum rT3/fT3 is below about 6.

11. A method for treating human dormancy syndrome-related sequel in a patient, comprising administering T3 to decrease the ratio of serum rT3/fT3 to below about 4.

14. A method for treating cancer in a patient, comprising:

(a) administering amoxicillin or doxycycline (100 mg/2×

/day) or minocyn (100 mg 2×

/day) for 2 weeks;

then

(b) along with the antibiotic of step (a), administering zithromax (250-500 mg 3×

/week) or ketek (100 mg 2×

/day) for 2 weeks;

then

(c). administering metronidazole (500 mg 2×

/day) for 5 days;

then

(d) ceasing treatment with metronidazole for two weeks while maintaining steps (a) &

(b) above);

then

(e) administering metronidazole (500 mg 2×

/day) for 5 days on, 2 weeks off until symptoms of endotoxemia decrease;

then

(f) administering metronidazole at a dose of 1000 mg 2×

/day or 2000 mg 2×

/day untiltumor cell death occurs.