Clinical Studies
In 1970, investigators at Boston University conducted a small, randomized placebo-controlled trial to determine if tetracycline would treat rheumatoid arthritis. They used 250 mg of tetracycline a day.
Their study showed no improvement after one year of tetracycline treatment. Several factors could explain their inability to demonstrate any benefits.
Their study used only 27 patients for a one-year trial, and only 12 received tetracycline, so noncompliance may have been a factor. Additionally, none of the patients had severe arthritis. Patients were excluded from the trial if they were on any anti-remittive therapy.
Finnish investigators used lymecycline to treat the reactive arthritis in Chlamydia trachomatous infections. Their study compared the effect of the medication in patients with two other reactive arthritis infections: Yersinia and Campylobacter.
Lymecyline produced a shorter course of illness in the Chlamydia induced arthritis patients, but did not affect the other enteric infections-associated reactive arthritis. The investigators later published findings that suggested lymecycline achieved its effect through non-antimicrobial actions. They speculated it worked by preventing the oxidative activation of collagenase.
The first trial of minocycline for the treatment of animal and human rheumatoid arthritis was published by Breedveld. In the first published human trial, Breedveld treated ten patients in an open study for 16 weeks. He used a very high dose of 400 mg per day. Most patients had vestibular side effects resulting from this dose.
However, all patients showed benefit from the treatment, and all variables of efficacy were significantly improved at the end of the trial.
Breedveld expanded on his initial study and later observed similar impressive results. This was a 26-week double-blind placebo-controlled randomized trial with minocycline for 80 patients. They were given 200 mg twice a day.
The Ritchie articular index and the number of swollen joints significantly improved (p < 0.05) more in the minocyline group than in the placebo group. Investigators in Israel studied 18 patients with severe rheumatoid arthritis for 48 weeks. These patients had failed two other DMARD. They were taken off all DMARD agents and given minocycline 100 mg twice a day. Six patients did not complete the study -- three withdrew because of lack of improvement, and three had side effects of vertigo or leukopenia. All patients completing the study improved. Three had complete remission, three had substantial improvement of greater than 50 percent, and six had moderate improvement of 25 percent in the number of active joints and morning stiffness. APPENDIX TWO: Make Certain You are Assessed for Fibromyalgia You need to be very sensitive to this condition when you have rheumatoid arthritis as it is frequently a complicating condition. Many times, the pain will be confused with a flare-up of the RA. You need to aggressively treat this problem. If it is ignored, the likelihood of successfully treating the arthritis is significantly diminished. Fibromyalgia is a very common problem. Some experts believe that 5 percent of people are affected with it. Over 12 percent of the patients at the Mayo Clinic's Department of Physical Medicine and Rehabilitation have this problem, and it is the third most common diagnosis by rheumatologists in the outpatient setting. Fibromyalgia affects women five times as frequently as men. Signs and Symptoms of Fibromyalgia One of the main features of fibromyalgia is morning stiffness, fatigue, and multiple areas of tenderness in typical locations. Most people with fibromyalgia complain of pain over many areas of their body, with an average of six to nine locations. Although the pain is frequently described as being "all over," it is most prominent in the neck, shoulders, elbows, hips, knees, and back. Tender points are generally symmetrical and on both sides of the body. The areas of tenderness are usually small (less than an inch in diameter) and deep within the muscle. They are often located in sites that are slightly tender in normal people. People with fibromyalgia, however, differ in having increased tenderness at these sites than the average person. Firm palpation with the thumb (just past the point where the nail turns white) over the outside elbow will typically cause a vague sensation of discomfort. Patients with fibromyalgia will experience much more pain and will often withdraw the arm involuntarily. More than 70 percent of patients describe their pain as profound aching and stiffness of muscles. Often it is relatively constant from moment to moment, but certain positions or movements may momentarily worsen the pain. Other terms used to describe the pain are "dull" and "numb." Sharp or intermittent pain is relatively uncommon. Patients with fibromyalgia also often complain that sudden loud noises worsen their pain. The generalized stiffness of fibromyalgia does not diminish with activity, unlike the stiffness of rheumatoid arthritis, which lessens as the day progresses. Despite the lack of abnormal lab tests, patients can suffer considerable discomfort. The fatigue is often severe enough to impair activities of work and recreation. Patients commonly experience fatigue on arising and complain of being more fatigued when they wake up than when they went to bed. Over 90 percent of patients believe the pain, stiffness, and fatigue are made worse by cold, damp weather. Overexertion, anxiety and stress are also factors. Many find that localized heat, such as hot baths, showers, or heating pads, give them some relief. There is also a tendency for pain to improve in the summer with mild activity, or with rest. Some patients will date the onset of their symptoms to some initiating event. This is often an injury, such as a fall, a motor vehicle accident, or a vocational or sports injury. Others find that their symptoms began with a stressful or emotional event, such as a death in the family, a divorce, a job loss, or similar occurrence. Pain Location Patients with fibromyalgia have pain in at least 11 of the following 18 tender point sites (one on each side of the body): 1.Base of the skull where the suboccipital muscle inserts. 2.Back of the low neck (anterior intertransverse spaces of C5-C7). 3.Midpoint of the upper shoulders (trapezius). 4.On the back in the middle of the scapula. 5.On the chest where the second rib attaches to the breastbone (sternum). 6.One inch below the outside of each elbow (lateral epicondyle). 7.Upper outer quadrant of buttocks. 8.Just behind the swelling on the upper leg bone below the hip (trochanteric prominence). 9.The inside of both knees (medial fat pads proximal to the joint line). Treatment of Fibromyalgia There is a persuasive body of emerging evidence that indicates that patients with fibromyalgia are physically unfit in terms of sustained endurance. Some studies show that exercise can decrease fibromyalgia pain by 75 percent. Sleep is also critical to improvement, and many times, improved fitness will also correct the sleep disturbance. Normalizing vitamin D levels has also been shown to be helpful to decrease pain as has topical magnesium oil supplementation. Allergies, especially to mold, seem to be another common cause of fibromyalgia. There are some simple interventions using techniques called Total Body Modification (TBM) 800-243-4826. APPENDIX THREE: Antibiotic Therapy with Minocin There are three different tetracyclines available: simple tetracycline, doxycycline, or Minocin (minocycline). Minocin has a distinct and clear advantage over tetracycline and doxycycline in three important areas: 1.Extended spectrum of activity 2.Greater tissue penetrability 3.Higher and more sustained serum levels Bacterial cell membranes contain a lipid layer. One mechanism of building up a resistance to an antibiotic is to produce a thicker lipid layer. This layer makes it difficult for an antibiotic to penetrate. Minocin's chemical structure makes it the most lipid soluble of all the tetracyclines. This difference can clearly be demonstrated when you compare the drugs in the treatment of two common clinical conditions. Minocin gives consistently superior clinical results in the treatment of chronic prostatitis. In other studies, Minocin was used to improve between 75-85 percent of patients whose acne had become resistant to tetracycline. Strep is also believed to be a contributing cause to many patients with rheumatoid arthritis. Minocin has shown significant activity against treatment of this organism. Important Factors to Consider When Using Minocin Unlike the other tetracyclines, Minocin tends not to cause yeast infections. Some infectious disease experts even believe that it has a mild anti-yeast activity. Women can be on this medication for several years and not have any vaginal yeast infections. Nevertheless, it would be prudent to take prophylactic oral lactobacillus acidophilus and bifidus preparations. This will help to replace the normal intestinal flora that is killed with the Minocin. Another advantage of Minocin is that it tends not to sensitize you to the sun. This minimizes your risk of sunburn and increased risk of skin cancer. However, you must incorporate several precautions with the use of Minocin. Like other tetracyclines, food impairs its absorption. However, the absorption is much less impaired than with other tetracyclines. This is fortunate because some people cannot tolerate Minocin on an empty stomach and have to take it with a meal to avoid GI side effects. If you need to take it with a meal, you will still absorb 85 percent of the medication, whereas tetracycline is only 50 percent absorbed. In June of 1990, a pelletized version of Minocin also became available, which improved absorption when taken with meals. This form is only available in the non-generic Lederle brand, and is a more than reasonable justification to not substitute for the generic version. Clinical experience has shown that many patients will relapse when they switch from the brand name to the generic. In February, 2006 Wyeth sold manufacturing rights of Minocin to Triax Pharmaceuticals (866-488-7429). Clinically, it has been documented that it is important to take Lederle brand Minocin as most all generic minocycline are clearly less effective. A large percentage of patients will not respond at all, or not do as well with generic non-Lederle minocycline. Traditionally it was recommended to only receive the brand name Lederle Minocin. However, there is one generic brand that is acceptable, and that is the brand made by Lederle. The only difference between Lederle generic Minocin and brand name Minocin is the label and the price. The problem is finding the Lederle brand generic. Some of my patients have been able to find it at Wal Mart. Since Wal Mart is one of the largest drug chains in the US, this should make the treatment more widely available for a reduced charge. Many patients are on NSAID's that contribute to microulcerations of the stomach, which cause chronic blood loss. It is certainly possible to develop a peptic ulcer contributing to this blood loss. In either event, patients are frequently receiving iron supplements to correct their blood counts. IT IS IMPERATIVE THAT MINOCIN NOT BE GIVEN WITH IRON! Over 85 percent of the dose will bind to the iron and pass through your colon unabsorbed. If iron is taken, it should be at least one hour before Minocin, or two hours after. A recent, uncommon, complication of Minocin is a cell-mediated hypersensitivity pneumonitis. Most patients can start on 100 mg of Minocin every Monday, Wednesday, and Friday evening. Doxycycline can be substituted for patients who cannot afford the more expensive Minocin. It is important to not give either medication daily, as this does not seem to provide as great a clinical benefit. WARNING: Tetracycline type drugs can cause a permanent yellow- grayish brown discoloration of your teeth. This can occur in the last half of pregnancy, and in children up to eight years old. You should not routinely use tetracycline in children. If you have severe disease, you can consider increasing the dose to as high as 200 mg three times a week. Aside from the cost of this approach, several problems may result from the higher doses. Minocin can cause quite severe nausea and vertigo, but taking the dose at night tends to decrease this problem considerably. However, if you take the dose at bedtime, you must swallow the medication with TWO glasses of water. This is to insure that the capsule doesn't get stuck in your throat. If that occurs, a severe chemical esophagitis can result, which can send you to the emergency room. For those physicians who elect to use tetracycline or doxycycline for cost or sensitivity reasons, several methods may help lessen the inevitable secondary yeast overgrowth. Lactobacillus acidophilus will help maintain normal bowel flora and decrease the risk of fungal overgrowth. Aggressive avoidance of all sugars, especially those found in non-diet sodas will also decrease the substrate for the yeast's growth. Macrolide antibiotics like Biaxin or Zithromax may be used if tetracyclines are contraindicated. They would also be used in the three pills a week regimen. Clindamycin The other drug used to treat rheumatoid arthritis is clindamycin. Dr. Brown's book discusses the uses of intravenous clindamycin, and it is important to use the IV form of treatment if the disease is severe. In my experience nearly all scleroderma patients require a more aggressive stance and use IV treatment. Scleroderma is a particularly dangerous form of rheumatic illness that should receive aggressive intervention. A major problem with the IV form is the cost. The price ranges from $100 to $300 per dose if administered by a home health care agency. However, if purchased directly from Upjohn, significant savings can be had. If you have a milder illness, the oral form of clindamycin is preferable. With a mild rheumatic illness (the minority of cases), it is even possible to exclude this from your regimen. Initial starting doses for an adult would be a 1200 mg dose once a week. Please note that many people do not seem to tolerate this medication as well as Minocin. The major complaint seems to be a bitter metallic type taste, which lasts about 24 hours after the dose. Taking the dose after dinner does seem to help modify this complaint somewhat. If this is a problem, you can lower the dose and gradually increase the dose over a few weeks. Concern about the development of C. difficile pseudomembranous enterocolitis as a result of the clindamycin is appropriate. This complication is quite rare at this dosage regimen, but it certainly can occur. It is also important to be aware of the possibility of developing a severe and uncontrollable bout of diarrhea. Administration of acidophilus seems to limit this complication by promoting the growth of the healthy gut flora. If you have a resistant form of rheumatic illness, intravenous administration should be considered. Generally, weekly doses of 900 mg are administered until clinical improvement is observed. This generally occurs within the first 10 doses. At that time, the regimen can be decreased to every two weeks with the oral form substituted on the weeks where the IV is not taken. What to Do if You Fail to Respond The most frequent reason for failure to respond to the protocol is lack of adherence to the dietary guidelines. Most people eat too many grains and sugars, which disturbs insulin physiology. It is important that you adhere as strictly as possible to the guidelines. A small minority, generally under 15 percent of patients will fail to respond to the protocol described above, despite rigid adherence to the diet. These individuals should already be on the IV clindamycin. It appears that hyaluronic acid, which is a potentiating agent commonly used in the treatment of cancer, may be quite useful in these cases. It seems that hyaluronic acid has very little to no direct toxicity but works in a highly synergistic fashion when administered directly in the IV bag with the clindamycin. Hyaluronic acid is also used in orthopedic procedures. The dose is generally from 2 to 10 cc into the IV bag. Hyaluronic acid is not inexpensive, however, as the cost may range up to $10 per cc. You also need to use some caution, as it may precipitate a significant Herxheimer flare reaction. Bibliography 1.Pincus T, Wolfe F: Treatment of Rheumatoid Arthritis: Challenges to Traditional Paradigms. AnnInternMed 115:825-6, Nov 15 1991. 2.Pincus T: Rheumatoid arthritis: disappointing long-term outcomes despite successful short-term clinical trials. J Clin Epidemiol 41:1037-41, 1988. 3.Brooks PM: Clinical management of rheumatoid arthritis. Lancet 341 :286-90, 1993. 4.Pincus T, Callahan LF: Remodeling the pyramid or remodeling the paradigms concerning rheumatoid arthritis - lessons learned from Hodgkin's Disease and coronary artery disease. JRheumatol 17:1582-5, 1990. 5.Reah TG: The prognosis of rheumatoid arthritis. Proc R Soc Med 56:813-17, 1963. 6.Wolfe F, Hawley DJ: Remission in rheumatoid arthritis. J Rheumatol 12:245-9, 1985. 7.Kushner I, Dawson NV: Changing perspectives in the treatment of rheumatoid arthritis. JRheumatol 19:1831-34, 1992. 8.Pinals RS: Drug therapy in rheumatoid arthritis a perspective. Br J Rheumatol 28:93-5, 1989. 9.Klippel JH: Winning the battle, losing the war? Another editorial about rheumatoid arthritis. JRheumatol 17:1118-22. 1990. 10.Healey LA, Wilske KR: Evaluating combination drug therapy in rheumatoid arthritis. J Rheumatol 18:641-2, 1991. 11.Wolfe F: 50 Years of antirheumatic therapy: the prognosis of rheumatoid arthritis. J Rheumatol 17:24-32, 1990. 12.Gabriel SE, Luthra HS: Rheumatoid arthritis: Can the long term be altered? Mayo Clin Proc 63:58-68, 1988. 13.Harris ED: Rheumatoid arthritis: Pathophysiology and implications for therapy. NEngl JMed 322:1277-1289, May 3, 1990. 14.Schwartz BD: Infectious agents, immunity and rheumatic diseases. Arthr Rheum 33 :457-465, April 1990. 15.Tan PLJ, Skinner MA: The microbial cause of rheumatoid arthritis: time to dump Koch's postulates. J Rheumatol 19:1170-71. 1992. 16.Ford DK: The microbiological causes of rheumatoid arthritis. JRheumatol 18:1441-2, 1991. 17.Burmester GR: Hit and run or permanent hit? Is there evidence for a microbiological cause of rheumatoid arthritis? J Rheumatol 18:1443-7, 1991. 18.Phillips PE: Evidence implications infectious agents in rheumatoid arthritis and juvenile rheumatoid arthritis. Clin EXD Rheumatol 1988 6:87-94. 19.Sabin AB: Experimental proliferative arthritis in mice produced by filtrable pleuropneumonia-like microorganisms. Science 89:228-29, 1939. 20.Swift HF, Brown TMcP: Pathogenic pleuropneumonia-like organisms from acute rheumatic exudates and tissues. Science 89:271-272. 1939. 21.Clark HW, Bailey JS, Brown TMcP: Determination of mycoplasma antibodies in humans. Bacteriol Proc 64:59, 1964. 22.Brown Tmcp, Wichelausen RH, Robinson LB, et al: The in vivo action of aureomycin on pleuropneumonia-like organisms associated with various rheumatic diseases. J Lab Clin Med 34: 1404-1410. 1949. 23.Brown TMcP, Wichelhausen RH: A study of the antigen-antibody mechanism in rheumatic diseases. Amer JMed Sci 221:618, 1951. 24.Brown TMcP: The rheumatic crossroads. Postgrad Med 19:399-402, 1956. 25.Brown TMcP, Clark HW, Bailey JS, et al: Relationship between mycoplasma antibodies and rheumatoid factors. ArthrRheum 13:309-310, 1970. 26.Clark HW, Brown TMcP: Another look at mycoplasma. Arthr Rheum 19:649-50, 1976. 27.Hakkarainen K, et al: Mycoplasmas and arthritis. Ann Rheumat Dis 51: S70-72; l992. 28.Rook, GAW, et al: A reppraisal of the evidence that rheumatoid arthritis and several other idiopathic diseases are slow bacterial infections. Ann Rheum Dis 52:S30-S38; 1993. 29.Clark HW, Coker-Vann MR, Bailey JS, et al: Detection of mycoplasma antigens in immune complexes from rheumatoid arthritis synovial fluids. Ann Allergy 60:394-98, May 1988. 30.Wilder RL: Etiologic considerations in rheumatoid arthritis. Ann Intern Med 101 :820-21, 1984. 31.Bartholomew LE: Isolations and characterization of mycoplasmas (PPLO) from patients with rheumatoid arthritis, systemic lupus erythematosus and Reiter's syndrome. Arthr Rheum 8:376-388. 1965. 32.Brown TMcP, et al: Mycoplasma antibodies in synovia. Arthritis Rheum 9:495, 1966. 33.Hernandez LA, Urquhart GED, *** WC: Mycoplasma pneumonia infection and arthritis in man. Br Med J 2: 14- 16. 1977. 34.McDonald MI, Moore JO, Harrelson JM, et al: Septic arthritis due to Mycoplasma hominis. Arth Rheum 26: 1044-47, 1983. 35.Williams MH, Brostoff J, Roitt IM: Possible role of Mycoplasma fermenters in pathogenesis of rheumatoid arthritis. Lancet 2:277-280 1970 36.Jansson E, Makisara P, Vainio K, et al: An 8-year study on mycoplasma in rheumatoid arthritis. Ann Rheum Dis 30:506-508, 1971. 37.Jansson E, Makisara P, Tuuri S: Mycoplasma antibodies in rheumatoid arthritis. Scan J Rheumatol 4: 165-68, 1975. 38.Markham JG, Myers DB: Preliminary observations on an isolate from synovial fluid of patients with rheumatoid arthritis. Ann Rheum Dis, S 1-7 1976. 39.Tully JG, et al: Pathogenic mycoplasmas: cultivation and vertebrate pathogenicity of a new spiroplasma. Science 195:892-4, 1977. 40.Fahlberg WJ, et al: Isolation of mycoplasma from human synovial fluids and tissues. Bacteria Proceedings 66:48-9, 1966. 41.Ponka A: The occurrence and clinical picture of serologically verified Mycoplasma pneumonia infections with emphasis on central nervous system, cardiac and joint manifestations. Ann Clin Res II (suppl) 24, 1979. 42.Hernandez LA, Urquhart GED, *** WC: Mycoplasma pneumonia infections and arthritis in man. Br Med J2:14-16, 1977. 43.Ponka A: Arthritis associated with Mycoplasma pneumonia infection. Scand J Rheumatol 8:27-32, 1979. 44.Stuckey M, Quinn PA, Gelfand EW: Identification of T-Strain mycoplasma in a patient with polyarthritis. Lancet 2:917-920. 1978. 45.Webster ADB, Taylor-Robinson D, Furr PM, et al: Mycoplasmal septic arthritis in hypogammaglobuinemia. Br Med J 1 :478-79, 1978. 46.Ginsburg KS, Kundsin RB, Walter CW, et al: Ureaplasma urealyticum and Mycoplasma hominis in women with systemic lupus erythematosus. Arthritis Rheumatism 35 429-33, 1992. 47.Cole BC, Cassel GH: Mycoplasma infections as models of chronic joint inflammation. Arthr Rheum 22:1375-1381, Dec 1979. 48.Cassell GH, Cole BC: Mycoplasmas as agents of human disease. N Engl J Med 304: 80-89, Jan 8, 1981. 49.Jansson E, et al: Mycoplasmas and arthritis. Rheumatol 42:315-9, 1983. 50.Camon GW, Cole BCC, Ward JR, et al: Arthritogenic effects of Mycoplasma arthritides T cell mitogen in rats. JRheumatol 15:735-41, 1988. 51.Cedillo L, Gil C, Mayagoita G, et al: Experimental arthritis induced by Mycoplasma pneumonia in rabbits. JRheumatol 19:344-7, 1992. 52.Baccala R, Smith LR, Vestberg M, et al: Mycoplasma arthritidis mitogen. Arthritis Rheumatism 35:43442, 1992. 53.Brown McP, Clark HW, Bailey JS: Rheumatoid arthritis in the gorilla: a study of mycoplasma-host interaction in pathogenesis and treatment. In Comparative Pathology of Zoo Animals, RJ Montali, Gigaki (ed), Smithsonian Institution Press. 1980. 259-266. 54.Clark HW: The potential role of mycoplasmas as autoantigens and immune complexes in chronic vascular pathogenesis. Am J Primatol 24:235-243, 1991. 55.Greenwald, rheumatoid arthritis, Goulb LM, Lavietes B, et al: Tetracyclines imibit human synovial collagenase in vivo and in vitro. RhPn fol 14:28-32. 1987. 56.Goulb LM, Lee HM, Lehrer G, et al: Minocycline reduces gingival collagenolytic activity during diabetes. JPeridontRes 18:516-26, 1983. 57.Goulb LM, et al: Tetracyclines imibit comective tissue breakdown: new therapeutic implications for an old family of drugs. Crit Rev Oral Med Pathol 2:297-322, 1991. 58.Ingman T, Sorsa T, Suomalainen K, et al: Tetracycline inhibition and the cellular source of collagenase in gingival revicular fluid in different periodontal diseases. A review article. J Periodontol 64(2):82-8, 1993. 59.Greenwald rheumatoid arthritis, Moak SA, et al: Tetracyclines suppress metalloproteinase activity in adjuvant arthritis and, in combination with flurbiprofen, ameliorate bone damage. J Rheumatol 19:927-38, 1992. 60.Gomes BC, Golub LM, Ramammurthy NS: Tetracyclines inhibit parathyroid hormone induced bone resorption in organ culture. Experientia 40:1273-5, 1985. 61.Yu LP Jr, SMith GN, Hasty KA, et al: Doxycycline inhibits Type XI collagenolytic activity of extracts from human osteoarthritic cartilage and of gelantinase. JRheumatol 18:1450-2, 1991. 62.Thong YH, Ferrante A: Effect of tetracycline treatment of immunological responses in mice. Clin Exp Immunol 39:728-32, 1980. 63.Pruzanski W, Vadas P: Should tetracyclines be used in arthritis? J Rheumatol 19: 1495-6, 1992. 64.Editorial: Antibiotics as biological response modifiers. Lancet 337:400-1, 1991. 65.Van Barr HMJ, et al: Tetracyclines are potent scavengers of the superoxide radical. Br J Dermatol 117:131-4, 1987. 66.Wasil M, Halliwell B, Moorhouse CP: Scavenging of hypochlorous acid by tetracycline, rifampicin and some other antibiotics: a possible antioxidant action of rifampicin and tetracycline? Biochem Pharmacol 37:775-8, 1988. 67.Breedveld FC, Trentham DE: Suppression of collagen and adjuvant arthritis by a tetracycline. Arthritis Rheum 31(1 Supplement)R3, 1988. 68.Trentham, DE; Dynesium-Trentham rheumatoid arthritis: Antibiotic Therapy for Rheumatoid Arthritis: Scientific and Anecdotal Appraisals. Rheum Clin NA 21: 817-834, 1995. 69.Panayi GS, et al: The importance of the T cell in initiating and maintaining the chronic synovitis of rheumatoid arthritis. Arthritis Rheum 35:729-35, 1992. 70.Sewell KL, Trentham DE: Pathogenesis of rheumatoid arthritis. Lancet 341 :283-86, 1993. 71.Sewell KE, Furrie E, Trentham DE: The therapeutic effect of minocycline in experimental arthritis. Mechanism of action. JRheumatol 33(suppl):S106, 1991. 72.Panayi GS, Clark B: Minocycline in the treatment of patients with Reiter's syndrome. Clin Erp Immunol 7: 100-1, 1989. 73.Pott H-G, Wittenborg A, Junge-Hulsing G: Long-term antibiotic treatment in reactive arthritis. Lancet i:245-6, Jan 30, 1988. 74.Skinner M, Cathcart ES, Mills JA, et al: Tetracycline in the Treatment of Rheumatoid Arthritis. Arthritis and Rheumatism 14:727-732, 1971. 75.Lauhio A, Leirisalo-Repo M, Lahdevirta J, et al: Double-blind placebo-controlled study of three-month treatment with Iymecycline in reactive arthritis, with special reference to Chlamydia arthritis. Arthritis Rheumatism 34:6-14, 1991. 76.Lauhio A, Sorsa T, Lindy O, et al: The anticollagenolytic potential of Iymecycline in the long-term treatment of reactive arthritis. Arthritis Rheumatism 35: 195-198, 1992. 77.Breedveld FC, Dijkmans BCA, Mattie H: Minocycline treatment for rheumatoid arthritis: an open dose finding study. JRheumatol 17:43-46, 1990. 78.Kloppenburg M, Breedveld FC, Miltenburg AMM, et al: Antibiotics as disease modifiers in arthritis. Clin Exper Rheumatol l l(suppl 8):S113-S115, 1993. 79.Langevitz P, et al: Treatment of resistant rheumatoid arthritis with minocycline: An open study. J Rheumatol 19: 1502-04, 1992. 80.Tilley, B, et al: Minocycline in Rheumatoid Arthritis: A 48 week double-blind placebo controlled trial. Ann Intern Med 122:81, 1995. 81.Mills, JA: Do Bacteria Cause Chronic Polyarthritis? N Enel J Med 320:245-246. January 26, 1989. 82.Rothschild BM, et al: Symmetrical Erosive Peripheral Polyarthritis in the Late Archaic Period of Alabama. Science 241:1498-1502, Sept 16, 1988. 83.Clark, HW, et al: Detection of Mycoplasma Antigens in Immune Complexes From Rheumatoid Arthritis Synovial Fluids. Ann Allergy 60:394-398, May 1988. 84.Res PCM, et al: Synovial Fluid T Cell Reactivity Against 65kD Heat Shock Protein of Mycobacteria in Early Chronic Arthritis. Lancet ii:478-480, Aug 27, 1988. 85.Cassell GH, et al: Mycoplasmas as Agents of Human Disease. N Engl J Med 304:80-89, Jan 8, 1981. 86.Breedveld FC, et al: Minocycline Treatment for Rheumatoid Arthritis: An Open Dose Finding Study. J Rheumatol 17:43-46, January 1990. 87.Phillips PE: Evidence implicating infectious agents in rheumatoid arthritis and juvenile rheumatoid arthritis. Clin Exp Rheumatol 6:87-94. 1988. 88.Harris ED: Rheumatoid Arthritis, Pathophysiology and Implications for Therapy. N Engl J Med 322:1277-1289, May 3, 1990. 89.Clark HW: The Potential Role of Mycoplasmas as Autoantigens and Immune Complexes in Chronic Vascular Pathogenesis. Am Jof Primatology 24:235-243. 1991. 90.Silman AJ: Is Rheumatoid Arthritis an Infectious Disease? Br Med J 303:200 July 27, 1991. 91.Clark HW: The Potential Role of Mycoplasmas as Autoantigens and Immune Complexes in Chronic Vascular Pathogenesis. Am J Primatol 24:235-243, 1991. 92.Wheeler HB: Shattuck Lecture Healing and Heroism. NEngl JMed 322:1540-1548, May 24, 1990. 93.Arnett FC: Revised Criteria for the Classification of Rheumatoid Arthritis. Bun Rheum Dis 38:1-6, 1989. 94.Braanan W: Treatment of Chronic Prostatitis. Comparison of Minocycline and Doxycycline. Urology 5:631-636, 1975. 95.Becker FT: Treatment of Tetracycline-Resistant Acne Vulgaris. Cutis 14:610-613. 1974. 96.Cullen, SI: Low-Dose Minocycline Therapy in Tetracycline-Recalcitrant Acne Vulgaris. Cutis 21:101-105, 1978. 97.Mattuccik, et al: Acute Bacterial Sinusitis. Minocycline vs.Amoxicillin. Arch Otolaryngol Head Neck Surgery 112:73-76, 1986. 98.Guillon JM, et al: Minocylcine-induced Cell-mediated Hypersensitivity Pneumonitis. Ann Intern Med 117:476-481, 1992. 99.Gabriel SE, et al: Rifampin therapy in rheumatoid arthritis. J Rheumatol 17: 163-6, 1990. 100.Caperton EM, et al: Cefiriaxone therapy of chronic inflammatory arthritis. Arch Intern Med 150:1677-1682, 1990. 101.Ann Intern Med 117:273-280, 1992. 102.Clive DM, et al: Renal Syndromes Associated with Nonsteroidal Antiinflammatory drugs. NEngl JMed 310:563-572. March 1 l994. 103.Piper, et al: Corticosteroid Use and Peptic Ulcer Disease: Role of Non-Steroidal Anti-inflammatory Drugs. Ann Intern Med 114:735-740, May 1, 1991. 104.Allison MC, et al: Gastrointestinal Damage Associated with the Use of Nonsteroidal Antiinflammatory Drugs. N Engl J Med 327:749-54, 1992. 105.Fries JF:Postmarketing Drug Surveillance: Are Our Priorities Right? JRheumatol 15:389-390, 1988. 106.Brooks PM, et al: Nonsteroidal Antiinflammatory Drugs Differences and Similarities. NEngl JMed 324:1716-1724, June 13, 1991. 107.Agrawal N: Risk Factors for Gastrointestinal Ulcers Caused by Nonsteroidal Anti-inflammatory Drugs (NSAIDs). J Fam Prac 32:619-624, June 1991. 108.Silverstein, F: Nonsteroidal Anti-Inflammatory Drugs and Peptic Ulcer Disease. Postgrad Med 89:33-30, May 15, 1991. 109.Gabriel SE, et al: Risk for Serious Gastrointestinal Complications Related to Use of NSAIDs. Ann Intern Med 115:787-796 1991. 110.Fries JF, et al: Toward an Epidemiology of Gastropathy Associated With NSAID Use. Gastroent 96:647-55, 1989. 111.Armstrong CP, et al: NSAIDs and Life Threatening Complications of Peptic Ulceration. Gut 28:527-32, 1987. 112.Murray MD, et al: Adverse Effects of Nonsteroidal Anti-Inflammatory Drugs on Renal Function. AnnInternMed 112:559, April 15, 1990. 113.Cook DM: Safe Use of Glucocorticoids: How to Monitor Patients Taking These Potent Agents. Postgrad Med 91:145-154, Feb. 1992. 114.Piper JM, et al: Corticosteroid Use and Peptic Ulcer Disease: Role of Nonsteroidal Anti-inflammatory Drugs. Ann Intern Med 114:735-740, May 1, 1991. 115.Thompson JM: Tension Myalgia as a Diagnosis at the Mayo Clinic and Its Relationship to Fibrositis, Fibromyalgia, and Myofascial Pain Syndrome. Mayo Clin Proc 65:1237-1248, September 1990. 116.Semble EL, et al: Therapeutic Exercise for Rheumatoid Arthritis and Osteoarthritis. Seminars in Arthritis and Rheumatism 20:32-40, August 1990. 117.O'Dell, J, Haire, C, Palmer, W, Drymalski, W, Wees, S, Blakely, K, Churchill, M, Eckhoff, J, Weaver, A, Doud, D, Erickson, N, Dietz, F, Olson, R, Maloney, P, Klassen, L, Moore, G, Treatment of Early Rheumatoid Arthritis with Minocycline or Placebo: Results of a Randomized, Double-Blind, Placebo-Controlled Trial, Arthritis & Rheumatism, 1997, 40:5, 842-848. 118.Tilley, BC, Alarcón, GS, Heyse, SP, Trentham, DE, Neuner, R, Kaplan, DA, Clegg, DO, Leisen, JCC, Buckley, L, Cooper, SM, Duncan, H, Pillemer, SR, Tuttleman, M, Fowler, SE, Minocycline in Rheumatoid Arthritis: A 48-Week, Double-Blind, Placebo-Controlled Trial, Annals of Internal Medicine, 1995, 122:2, 81-89. 119.Bluhm, GB, Sharp, JT, Tilley, BC, Alarcon, GS, Cooper, SM, Pillemer, SR, Clegg, DO, Heyse, SP, Trentham, DE, Neuner, R, Kaplan, DA, Leisen, JC, Buckley, L, Duncan, H, Tuttleman, M, Shuhui, L, Fowler, SE, Radiographic Results from the Minocycline in Rheumatoid Arthritis (MIRA) Trial, Journal of Rheumatology, 1997, 24:7, 1295-1302. 120.Breedveld, FC, Editorial: Minocycline in Rheumatoid Arthritis, Arthritis & Rheumatism, 1997, 40:5, 794-796. 121.Breedveld, FC, Letters: Reply to Minocycline-Induced Autoimmune Disease, Arthritis & Rheumatism, 1998, 41:3, 563-564. 122.Fox, R, Sharp, D, Editorial: Antibiotics as Biological Response Modifiers, The Lancet, 1991, 337:8738, 400-401. 123.Greenwald, rheumatoid arthritis, Golub, LM, Lavietes, B, Ramamurthy, NS, Gruber, B, Laskin, RS, McNamara, TF, Tetracyclines Inhibit Human Synovial Collagenase In Vivo and In Vitro, Journal of Rheumatology, 1987, 14:1, 28-32. 124.Griffiths, B, Gough, A, Emery, P, Letters: Minocycline-Induced Autoimmune Disease: Comment on the Editorial by Breedveld, Arthritis & Rheumatism, 1998, 41:3, 563. 125.Kloppenburg, M, Breedveld, FC, Miltenburg, AMM, Dijkmans, BAC, Antibiotics as Disease Modifiers in Arthritis, Clinical and Experimental Rheumatology, 1993, 11: Suppl. 8, S113-S115. 126.Kloppenburg, M, Breedveld, FC, Terwiel, JPh, Mallee, C, Dijkmans, BAC, Minocycline in Active Rheumatoid Arthritis: A Double-Blind, Placebo-Controlled Trial, Arthritis & Rheumatism, 1994, 37:5, 629-636. 127.Kloppenburg, M, Mattie, H, Douwes, N, Dijkmans, BAC, Breedveld, FC, Minocycline in the Treatment of Rheumatoid Arthritis: Relationship of Serum Concentrations to Efficacy, Journal of Rheumatology, 1995, 22:4, 611-616. 128.Lauhio, A, Leirisalo-Repo, M, Lähdevirta, J, Saikku, P, Repo, H, Double-Blind, Placebo-Controlled Study of Three-Month Treatment with Lymecycline in Reactive Arthritis, with Special Reference to Chlamydia Arthritis, Arthritis & Rheumatism, 1991, 34:1, 6-14. 129.Lauhio, A, Sorsa, T, Lindy, O, Suomalainen, K, Saari, H, Golub, LM, Konttinen, YT, The Anticollagenolytic Potential of Lymecycline in the Long-Term Treatment of Reactive Arthritis, Arthritis & Rheumatism, 1992, 35:2, 195-198. 130.Paulus, HE, Editorial: Minocycline Treatment of Rheumatoid Arthritis, Annals of Internal Medicine, 1995, 122:2, 147-148. 131.Pruzanski, W, Vadas, P, Editorial: Should Tetracyclines be Used in Arthritis?, Journal of Rheumatology, 1992, 19:10, 1495-1497. 132.Sieper, J, Braun, J, Editorial: Treatment of Reactive Arthritis with Antibiotics, British Journal of Rheumatology, July 1998. 133.Baseman, JB, Tully, JG, Mycoplasmas: Sophisticated, Reemerging, and Burdened by Their Notoriety, CDC's Emerging Infectious Diseases, 1997, 3:1, 21-32. 134.Franz, A, Webster, ADB, Furr, PM, Taylor-Robinson, D, Mycoplasmal Arthritis in Patients with Primary Immunoglobulin Deficiency: Clinical Features and Outcome in 18 Patients, British Journal of Rheumatology, 1997, 36:6, 661-668. 135.Hakkarainen K, Turunen, H, Miettinen, A, Karppelin, M, Kaitila, K, Jansson, E, Mycoplasmas and Arthritis, Annals of Rheumatic Diseases, 1992, 51, 1170-1172. 136.Hoffman, RH, Wise, KS, Letters: Reply to Mycoplasmas in the Joints of Patients with Rheumatoid Arthritis and Other Inflammatory Rheumatic Disorders, Arthritis & Rheumatism, 1998, 41:4, 756-757. 137.Schaeverbeke, T, Bébéar, C, Lequen, L, Dehais, J, Bébéar, C, Letters: Mycoplasmas in the Joints of Patients with Rheumatoid Arthritis and Other Inflammatory Rheumatic Disorders: Comment on the Article by Hoffman et al., Arthritis & Rheumatism, 1998, 41:4, 754-756. 138.Schaeverbeke, T, Gilroy, CB, Bébéar, C, Dehais, J, Taylor-Robinson, D, Mycoplasma fermentans, But Not M penetrans, Detected by PCR Assays in Synovium from Patients with Rheumatoid Arthritis and Other Rheumatic Disorders, Journal of Clinical Pathology, 1996, 49, 824-828. 139.Aoki, S, Yoshikawa, K, Yokoyama, T, Nonogaki, T, Iwasaki, S, Mitsui, T, Niwa, S, Role of Enteric Bacteria in the Pathogenesis of Rheumatoid Arthritis: Evidence for Antibodies to Enterobacterial Common Antigens in Rheumatoid Sera and Synovial Fluids, Annals of Rheumatic Diseases, 1996, 55:6, 363-369. 140.Blankenberg-Sprenkels, SHD, Fielder, M, Feltkamp, TEW, Tiwana, H, Wilson, C, Ebringer, A, Antibodies to Klebsiella pneumoniae in Dutch Patients with Ankylosing Spondylitis and Acute Anterior Uveitis and to Proteus mirabilis in Rheumatoid Arthritis, Journal of Rheumatology, 1998, 25:4, 743-747. 141.Ebringer, A, Ankylosing Spondylitis is Caused by Klebsiella: Evidence from Immunogenetic, Microbiologic, and Serologic Studies, Rheumatic Disease Clinics of North America, 1992, 18:1, 105-121. 142.Erlacher, L, Wintersberger, W, Menschik, M, Benke-Studnicka, A, Machold, K, Stanek, G, Söltz-Szöts, J, Smolen, J, Graninger, W, Reactive Arthritis: Urogenital Swab Culture is the Only Useful Diagnostic Method for the Detection of the Arthritogenic Infection in Extra-Articularly Asymptomatic Patients with Undifferentiated Oligoarthritis, British Journal of Rheumatology, 1995, 34:9, 838-842. 143.Gaston, JSH, Deane, KHO, Jecock, RM, Pearce, JH, Identification of 2 Chlamydia trachomatis Antigens Recognized by Synovial Fluid T Cells from Patients with Chlamydia Induced Reactive Arthritis, Journal of Rheumatology, 1996, 23:1, 130-136. 144.Gerard, HC, Branigan, PJ, Schumacher Jr, HR, Hudson, AP, Synovial Chlamydia trachomatis in Patients with Reactive Arthritis/ Reiter's Syndrome Are Viable But Show Aberrant Gene Expression, Journal of Rheumatology, 1998, 25:4, 734-742. 145.Granfors, K, Do Bacterial Antigens Cause Reactive Arthritis?, Rheumatic Disease Clinics of North America, 1992, 18:1, 37-48. 146.Granfors, K, Merilahti-Palo, R, Luukkainen, R, Möttönen, T, Lahesmaa, R, Probst, P, Märker-Hermann, E, Toivanen, P, Persistence of Yersinia Antigens in Peripheral Blood Cells from Patients with Yersinia Enterocolitica 0:3 Infection with or without Reactive Arthritis, Arthritis & Rheumatism, 1998, 41:5, 855-862. 147.Inman, RD, The Role of Infection in Chronic Arthritis, Journal of Rheumatology, 1992, 19, Supplement 33, 98-104. 148.Layton, MA, Dziedzic, K, Dawes, PT, Letters to the Editor: Sacroiliitis in an HLA B27-negative Patient Following Giardiasis, British Journal of Rheumatology, 1998, 37:5, 581-583. 149.Mäki-Ikola, O, Lehtinen, K, Granfors, K, Similarly Increased Serum IgA1 and IgA2 Subclass Antibody Levels against Klebsiella pneumoniæ Bacteria in Ankylosing Spondylitis Patients With/Without Extra-Articular Features, British Journal of Rheumatology, 1996, 35:2, 125-128. 150.Morrison, RP, Editorial: Persistent Chlamydia trachomatis Infection: In Vitro Phenomenon or in Vivo Trigger of Reactive Arthritis?, Journal of Rheumatology, 1998, 25:4, 610-612. 151.Mousavi-Jazi, M, Boström, L, Lövmark, C, Linde, A, Brytting, M, Sundqvist, V-A, Infrequent Detection of Cytomegalovirus and Epstein-Barr Virus DNA in Synovial Membrane of Patients with Rheumatoid Arthritis, Journal of Rheumatology, 1998, 25:4, 623-628. 152.Nissilä, M, Lahesmaa, R, Leirisalo-Repo, M, Lehtinen, K, Toivanen, P, Granfors, K, Antibodies to Klebsiella pneumoniæ, Escherichia coli, and Proteus mirabilis in Ankylosing Spondylitis: Effect of Sulfasalazine Treatment, Journal of Rheumatology, 1994, 21:11, 2082-2087. 153.Svenungsson, B, Editorial Review: Reactive Arthritis, International Journal of STD & AIDS, 1995, 6:3, 156-160. 154.Tani, Y, Tiwana, H, Hukuda, S, Nishioka, J, Fielder, M, Wilson, C, Bansal, S, Ebringer, A, Antibodies to Klebsiella, Proteus, and HLA-B27 Peptides in Japanese Patients with Ankylosing Spondylitis and Rheumatoid Arthritis, Journal of Rheumatology, 1997, 24:1, 109-114. 155.Tiwana, H, Walmsley, RS, Wilson, C, Yiannakou, JY, Ciclitira, PJ, Wakefield, AJ, Ebringer, A, Characterization of the Humoral Immune Response to Klebsiella Species in Inflammatory Bowel Disease and Ankylosing Spondylitis, British Journal of Rheumatology, 1998, 37:5, 525-531. 156.Wilkinson, NZ, Kingsley, GH, Sieper, J, Braun, J, Ward, ME, Lack of Correlation Between the Detection of Chlamydia trachomatis DNA in Synovial Fluid from Patients with a Range of Rheumatic Diseases and the Presence of an Antichlamydial Immune Response, Arthritis & Rheumatism, 1998, 41:5, 845-854. 157.Wollenhaupt, J, Kolbus, F, Weißbrodt, H, Schneider, C, Krech, T, Zeidler, H, Manifestations of Chlamydia Induced Arthritis in Patients with Silent Versus Symptomatic Urogenital Chlamydial Infection, Clinical and Experimental Rheumatology, 1995, 13:4, 453-458. 158.Alarcon, GS, Tilley, B, Cooper, S, Clegg, DO, Trentham, DE, Pillemer, SR, Neuner, R, Fowler, S, Letter: Another look at minocycline, Bulletin on the Rheumatic Diseases, 1996, 45(8), 6-7. 159.Amin, AR, Attur, MG, Thakker, GD, Patel, PD, Vyas, PR, Patel, RN, Patel, IR, Abramson, SB, A novel mechanism of action of tetracyclines: effects on nitric oxide synthases, Proceedings of the National Academy of Sciences of the United States of America, 1996, 93(24), 14014-14019. 160.Ayuzawa, S, Yano, H, Enomoto, T, Kobayashi, H, Nose, T, The Bi-Digital O-Ring Test used in the successful diagnosis & treatment (with antibiotic, anti-viral agents & oriental herbal medicine) of a patient suffering from pain & weakness of an upper extremity & Barre-Lieou syndrome appearing after whiplash injury: A case report, Acupuncture & Electro-Therapeutics Research, 1997, 22(3-4), 167-174. 161.Bitar, CN, Steele, RW, Use of prophylactic antibiotics in children, Advances in Pediatric Infectious Diseases, 1995, 10, 227-262. 162.Bluhm, GB, Sharp, JT, Tilley, BC, Alarcon, GS, Cooper, SM, Pillemer, SR, Clegg, DO, Heyse, SP, Trentham, DE, Neuner, R, Kaplan, DA, Leisen, JC, Buckley, L, Duncan, H, Tuttleman, M, Li, S, Fowler, SE, Radiographic Results from the Minocycline in Rheumatoid Arthritis (MIRA) Trial, Journal of Rheumatology, 1997, 24(7), 1295-1302. 163.Brandt, KD, Modification by oral doxycycline administration of articular cartilage breakdown in osteoarthritis, Journal of Rheumatology, 1995, Supplement 43, 149-151. 164.Breedveld, FC, Editorial: Minocycline in Rheumatoid Arthritis, Arthritis & Rheumatism, 1997, 40(5), 794-796. 165.Breedveld, FC, Letters: Reply to Minocycline- Induced Autoimmune Disease, Arthritis & Rheumatism, 1998, 41(3), 563-564. 166.Bullingham, R, Shah, J, Goldblum, R, Schiff, M, Effects of food and antacid on the pharmacokinetics of single doses of mycophenolate mofetil in rheumatoid arthritis patients, British Journal of Clinical Pharmacology, 1996, 41(6), 513-516. 167.Burton, IE, Moussa, KM, Sanders, PA, Agranulocytosis in rheumatoid arthritis associated with long-term flucloxacillin for staphylococcal osteomyelitis, Acta Haematologica, 1995, 94(4), 196-198. 168.Canvin, JM, Madhok, R, Letter: Minocycline in rheumatoid arthritis, Annals of Internal Medicine, 1995, 123(5), 392. 169.Caruso, I, Twenty years of experience with intra-articular rifamycin for chronic arthritides, Journal of International Medical Research, 1997, 25(6), 307-317. 170.Currie, BJ, Are the currently recommended doses of benzathine penicillin G adequate for secondary prophylaxis of rheumatic fever?, Pediatrics, 1996, 97(6, Page 2), 989-991. 171.Ebell, MH, Minocycline for rheumatoid arthritis, Journal of Family Practice, 1995, 40(5), 497-498. 172.Elkayam, O, Yaron, M, Zhukovsky, G, Segal, R, Caspi, D, Toxicity profile of dual methotrexate combinations with gold, hydroxychloroquine, sulphasalazine and minocycline in rheumatoid arthritis patients, Rheumatology International, 1997, 17(2), 49-53. 173.Evdoridou, J, Roilides, E, Bibashi, E, Kremenopoulos, G, Multifocal osteoarthritis due to Candida albicans in a neonate: serum level monitoring of liposomal amphotericin B and literature review, Infection, 1997, 25(2), 112-116. 174.Galland, L, Letter: Minocycline and rheumatoid arthritis revisited, Annals of Internal Medicine, 1995, 123(5), 392-393. 175.Griffiths, B, Gough, A, Emery, P, Letters: Minocycline- Induced Autoimmune Disease: Comment on the Editorial by Breedveld, Arthritis & Rheumatism, 1998, 41(3), 563. 176.Hanemaaijer, R, Sorsa, T, Konttinen, YT, Ding, Y, Sutinen, M, Visser, H, van Hinsbergh, VW, Helaakoski, T, Kainulainen, T, Ronka, H, Tschesche, H, Salo, T, Matrix metalloproteinase-8 is expressed in rheumatoid synovial fibroblasts and endothelial cells: Regulation by tumor necrosis factor-alpha and doxycycline, Journal of Biological Chemistry, 1997, 272(50), 31504-31509. 177.Herdy, GV, Editorial: The challenge of secondary prophylaxis in rheumatic fever [Portuguese, Original Title: Desafio da profilaxia secundaria na febre reumatica, Arquivos Brasileiros de Cardiologia, 1996, 67(5), 317. 178.Herdy, GV, Souza, DC, Barros, PB, Pinto, CA, Secondary prophylaxis in rheumatic fever: Oral antibiotic therapy versus benzathine penicillin [Portuguese, Original Title: Profilaxia secundaria na febre reumatica: Antibioticoterapia oral versus penicilina benzatina], Arquivos Brasileiros de Cardiologia, 1996, 67(5), 331-333. 179.Herrick, AL, Grennan, DM, Griffen, K, Aarons, L, Gifford, LA, Lack of interaction between flucloxacillin and methotrexate in patients with rheumatoid arthritis, British Journal of Clinical Pharmacology, 1996, 41(3), 223-227. 180.Houck, HE, Kauffman, CL, Casey, DL, Minocycline treatment for leukocytoclastic vasculitis associated with rheumatoid arthritis, Archives of Dermatology, 1997, 133(1), 15-16. 181.Iwata, M, Ida, M, Oda, S, Takeuchi, E, Nakamura, Y, Horiguchi, T, Sato, A, Bronchiolitis obliterans preceding rheumatoid arthritis: effect of clarithromycin [Japanese], Nippon Kyobu Shikkan Gakkai Zasshi ^Ö Japanese Journal of Thoracic Diseases, 1996, 34(11), 1271-1276. 182.Kassem, AS, Zaher, SR, Abou Shleib, H, el-Kholy, AG, Madkour, AA, Kaplan, EL, Rheumatic fever prophylaxis using benzathine penicillin G (BPG): two- week versus four-week regimens: comparison of two brands of BPG, Pediatrics, 1996, 97(6, Page 2), 992-995. 183.Kim, NM, Freeman, CD, Minocycline for rheumatoid arthritis, Annals of Pharmacotherapy, 1995, 29(2), 186-187. 184.Kloppenburg, M, Dijkmans, BA, Breedveld, FC, Antimicrobial therapy for rheumatoid arthritis, Baillieres Clinical Rheumatology, 1995, 9(4), 759-769. 185.Kloppenburg, M, Dijkmans, BA, Verweij, CL, Breedveld, FC, Inflammatory and immunological parameters of disease activity in rheumatoid arthritis patients treated with minocycline, Immunopharmacology, 1996, 31(2-3), 163-169. 186.Kloppenburg, M, Mattie, H, Douwes, N, Dijkmans, BA, Breedveld, FC, Minocycline in the treatment of rheumatoid arthritis: relationship of serum concentrations to efficacy, Journal of Rheumatology, 1995, 22(4), 611-616. 187.Kuznetsova, SM, Petrova, NK, Lecture: Antibiotics in the prevention of rheumatic fever [Russian, Original Title: Antibiotiki v profilaktike revmatizma (lektsiia)], Antibiotiki i Khimioterapiia, 1996, 41(2), 43-51. 188.Lai, NS, Lan, JL, Treatment of DMARDs-resistant rheumatoid arthritis with minocycline: a local experience among the Chinese, Rheumatology International, 1998, 17(6), 245-247. 189.Langevitz, P, Livneh, A, Bank, I, Pras, M, Minocycline in rheumatoid arthritis, Israel Journal of Medical Sciences, 1996, 32(5), 327-330. 190.Lauhio, A, Salo, T, Tjaderhane, L, Lahdevirta, J, Golub, LM, Sorsa, T, Letter: Tetracyclines in treatment of rheumatoid arthritis, The Lancet, 1995, 346(8975), 645-646. 191.McKendry, RJ, Is rheumatoid arthritis caused by an infection?, The Lancet, 1995, 345(8961), 1319-1320. 192.Meehan, R, Letter: Minocycline in rheumatoid arthritis, Annals of Internal Medicine, 1995, 123(5), 391-392. 193.Nordstrom, D, Lindy, O, Lauhio, A, Sorsa, T, Santavirta, S, Konttinen, YT, Anti-collagenolytic mechanism of action of doxycycline treatment in rheumatoid arthritis, Rheumatology International, 1998, 17(5), 175-180. 194.O'Dell, JR, Haire, CE, Palmer, W, Drymalski, W, Wees, S, Blakely, K, Churchill, M, Eckhoff, PJ, Weaver, A, Doud, D, Erikson, N, Dietz, F, Olson, R, Maloley, P, Klassen, LW, Moore, GF, Treatment of Early Rheumatoid Arthritis with Minocycline or Placebo: Results of a Randomized, Double- Blind, Placebo- Controlled Trial, Arthritis & Rheumatism, 1997, 40(5), 842-848. 195.Panush, RS, Thoburn, R, Should minocycline be used to treat rheumatoid arthritis?, Bulletin on the Rheumatic Diseases, 1996, 45(2), 2-5. 196.Patmas, MA, Letter: Minocycline in rheumatoid arthritis, Annals of Internal Medicine, 1995, 123(5), 391-392. 197.Paulus, HE, Editorial: Minocycline treatment of rheumatoid arthritis, Annals of Internal Medicine, 1995, 122(2), 147-148. 198.Pillemer, SR, Fowler, SE, Tilley, BC, Alarcon, GS, Heyse, SP, Trentham, DE, Neuner, R, Clegg, DO, Leisen, JC, Cooper, SM, Duncan, H, Tuttleman, M, Meaningful improvement criteria sets in a rheumatoid arthritis clinical trial: MIRA Trial Group, Minocycline in Rheumatoid Arthritis, Arthritis & Rheumatism, 1997, 40(3), 419-425. 199.Ryan, ME, Greenwald, rheumatoid arthritis, Golub, LM, Potential of tetracyclines to modify cartilage breakdown in osteoarthritis, Current Opinion in Rheumatology, 1996, 8(3), 238-247. 200.Sieper, J, Braun, J, Editorial: Treatment of Reactive Arthritis with Antibiotics, British Journal of Rheumatology, 1998, 37(7), 717-720. 201.Smith, GN Jr, Yu, LP Jr, Brandt, KD, Capello, WN, Oral administration of doxycycline reduces collagenase and gelatinase activities in extracts of human osteoarthritic cartilage, Journal of Rheumatology, 1998, 25(3), 532-535. 202.Tilley, BC, Alarcon, GS, Heyse, SP, Trentham, DE, Neuner, R, Kaplan, DA, Clegg, DO, Leisen, JC, Buckley, L, Cooper, SM, Duncan, H, Pillemer, SR, Tuttleman, M, Fowler, SE, Minocycline in rheumatoid arthritis: A 48-week, double-blind, placebo-controlled trial, MIRA Trial Group, Annals of Internal Medicine, 1995, 122(2), 81-89. 203.Trentham, DE, Dynesius-Trentham, rheumatoid arthritis, Antibiotic therapy for rheumatoid arthritis: Scientific and anecdotal appraisals, Rheumatic Diseases Clinics of North America, 1995, 21(3), 817-834. 204.Wilson, C, Senior, BW, Tiwana, H, Caparros-Wanderley, W, Ebringer, A, Antibiotic sensitivity and proticine typing of Proteus mirabilis strains associated with rheumatoid arthritis, Rheumatology International, 1998, 17(5), 203-205. 205.Yu, LP Jr, Burr, DB, Brandt, KD, O'Connor, BL, Rubinow, A, Albrecht, M, Effects of oral doxycycline administration on histomorphometry and dynamics of subchondral bone in a canine model of osteoarthritis, Journal of Rheumatology, 1996, 23(1), 137-142. 206.Ted R. Mikuls, Rheumatoid arthritis incidence: What goes down must go up? Arthritis and Rheumatism, 2010, 62(6), 1565 – 1567, If you like what you read, please consider donating to help support my blog, even as little as $5 will help.