scholarly journals Disease Modifying Treatment of Osteoarthritis with Triple Combination Anti-Microbial Therapy

Author(s):  
Ernest L. Bonner

Background:  The study author, while still a medical student, observed microscopic evidence of chronic inflammation in joint tissue of patients suffering with osteoarthritis and hypothesized that osteoarthritis was caused by an infectious process. After graduating from medical school and entering into private practice, the study author had several patients who informed him that when they were on tetracycline therapy, for reasons other than arthritis, their arthritis symptoms diminished to some extent. After reporting improvement of arthritic symptoms with tetracycline, one of these patients subsequently received metronidazole and while taking both tetracycline and metronidazole reported that his arthritic symptoms improved to an even greater extent, as his joint pain further diminished but did not resolve.  Subsequent treatment of osteoarthritis in other patients included the combination of tetracycline, metronidazole, other antibiotics and some natural products but only when L-lysine was added to the tetracycline and metronidazole combination therapy did the author observe yet further improvement in arthritic pain. Since L-lysine was reported to inhibit the growth of herpes simplex virus, the author and another colleague concluded that acyclovir might be a beneficial addition to the tetracycline, metronidazole, L-lysine combination. This four-component combination treatment resulted in total resolution or a marked diminution of osteoarthritis joint pain, joint tenderness and joint stiffness in most patients treated. It was further determined that L-lysine could be eliminated; that acyclovir could be replaced with valicyclovir; and that tetracycline could be replaced with minocycline or doxycycline. Preliminary studies of patients diagnosed with osteoarthritis and treated with tetracycline alone or the combination of tetracycline and metronidazole demonstrated improvement   in their osteoarthritic symptoms.  However the triple combination of doxycycline (broad spectrum antibiotic), metronidazole (antiprotozoal and antibacterial imidazole) and acyclovir (antiviral purine nucleoside) administered orally twice daily for eight weeks showed marked success in a group of patients suffering with osteoarthritis by substantially eliminating their joint pain, joint tenderness and joint stiffness while overcoming their fatigue and increasing their energy level. The data in this report substantiate that this triple combination is a disease modifying therapy that eliminates or markedly diminishes the symptomatology of osteoarthritis and further supports the hypothesis that osteoarthritis is an infectious disease. Objective:  To evaluate the effect of the triple combination therapy of doxycycline, metronidazole, and acyclovir on the joint pain, joint stiffness and functionality in   patients suffering with osteoarthritis. Design:  Non-blinded study of treatment of patients suffering with osteoarthritis Setting:  Primary care internal medicine practice in Alameda County, California. Sample:  Six adult individuals suffering with osteoarthritis. Patients: Six patients, ages 53 through 82 years.  Patient 1 was treated for 28 days and Patients 2 through 6 were treated for 56 days. Method:  After obtaining informed consent, six patients suffering with osteoarthritis were prescribed a 56 day course of treatment with the triple combination of doxycycline, metronidazole, and acyclovir for treatment of their osteoarthritis. Utilizing the WOMAC index for assessment of the effectiveness of treatment of osteoarthritis, pre-treatment   pain, stiffness and functional limitation, were compared to post-treatment pain, stiffness and functional limitations. Results: Three patients demonstrated total resolution of pain and stiffness and greater than 95% improvement in functional limitations.  One of the remaining three patients demonstrated a 70% improvement in pain, total resolution of stiffness, and an 85% improvement in functional limitations; another one of the three remaining patients demonstrated an 86% improvement in pain, total resolution of stiffness, and a 79% improvement in functional limitations; while the last of the three remaining patients demonstrated at least an 85% improvement in pain, 67% improvement in stiffness, and a 63% improvement in functional limitations. Limitations:  No randomization. No placebo. No control group. Small sample size. Conclusion: The results of treatment of these patients suffering the osteoarthritis support the hypothesis that osteoarthritis is an infectious disease.   These results further suggest that osteoarthritis is, at a minimum, modifiable with the triple combination therapy of doxycycline, metronidazole, and acyclovir and is even curative of with this breakthrough treatment in many cases.   The medical treatment reported in this article represents the first truly Disease Modifying medication therapy developed for osteoarthritis.      Keywords: WOMAC index

Lupus ◽  
1996 ◽  
Vol 5 (1_suppl) ◽  
pp. 45-49 ◽  
Author(s):  
A Kahan ◽  
C-J Menkès

A significant proportion of patients with rheumatoid arthritis have an aggressive, severe disease that may contribute to excess mortality. It has been suggested that early, aggressive therapy might improve the prognosis of these patients with active, severe rheumatoid arthritis. Combinations of disease modifying anti-rheumatic drugs including antimalarials are increasingly used in patients with active disease. While several open trials showed encouraging results, some controlled studies gave less support for the use of combination therapy. Ongoing controlled trials of double or triple combination therapy, such as hydroxychloroquine, methotrexate and sulphasalazine, should help define its place in treating patients with rheumatoid arthritis.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii108-ii108
Author(s):  
Jayeeta Ghose ◽  
Baisakhi Raychaudhuri ◽  
Kevin Liu ◽  
William Jiang ◽  
Pooja Gulati ◽  
...  

Abstract BACKGROUND Glioblastoma (GBM) is associated with systemic and intratumoral immunosuppression. Part of this immunosuppression is mediated by myeloid derived suppressor cells (MDSCs). Preclinical evidence shows that ibrutinib, a tyrosine kinase inhibitor FDA approved for use in chronic lymphocytic leukemia and known to be CNS penetrant, can decrease MDSC generation and function. Also, focal radiation therapy (RT) synergizes with anti-PD-1 therapy in mouse GBM models. Thus, we aimed to test the combination of these approaches on immune activation and survival in a preclinical immune-intact GBM mouse model. METHODS C57BL/6 mice intracranially implanted with the murine glioma cell line GL261-Luc2 were divided into 8 groups consisting of treatments with ibrutinib, RT (10 Gy SRS), or anti-PD-1 individually or in each combination (along with a no treatment control group). Immune cell subset changes (flow-cytometry) and animal survival (Kaplan-Meier) were assessed (n=10 mice per group). RESULTS Median survival of the following groups including control (28 days), ibrutinib (27 days), RT (30 days) or anti-PD-1 (32 days) showed no significant differences. However, a significant improvement in median survival was seen in mice given combinations of ibrutinib+RT (35 days), ibrutinib+anti-PD-1 (38 days), and triple therapy with ibrutinib+RT+anti-PD-1 (48 days, p < 0.05) compared to controls or single treatment groups. The reproducible survival benefit of triple combination therapy was abrogated in the setting of CD4+ and CD8+ T cell depletion. Contralateral intracranial tumor re-challenge in long-term surviving mice suggested generation of tumor-specific immune memory responses. The immune profile of the tumor microenvironment (TME) showed increased cytotoxic CD8+ T cells and decreased MDSCs and regulatory T cells in the triple combination therapy mice compared to controls. CONCLUSION The combination of ibrutinib, focal RT, and anti-PD-1 immune checkpoint blockade led to a significant survival benefit compared to controls in a preclinical model of GBM.


AIDS ◽  
1998 ◽  
Vol 12 (8) ◽  
pp. 879-884 ◽  
Author(s):  
Olivier Tissot ◽  
Jean-Paul Viard ◽  
Cécile Rabian ◽  
Nicole Ngo ◽  
Marianne Burgard ◽  
...  

2017 ◽  
Vol 43 (12) ◽  
pp. 1474-1482 ◽  
Author(s):  
Adile Dikmen ◽  
Kadri Ozer ◽  
Mustafa Gurhan Ulusoy ◽  
Koray Gursoy ◽  
Uğur Koçer

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