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Focal infection theory is the historical concept that many chronic diseases, including systemic and common ones, are caused by focal infections. In present medical consensus, a focal infection is a localized infection, often asymptomatic, that causes disease elsewhere in the host, but focal infections are fairly infrequent and limited to fairly uncommon diseases. (Distant injury is focal infection's key principle, whereas in ordinary infectious disease, the infection itself is systemic, as in measles, or the initially infected site is readily identifiable and invasion progresses contiguously, as in gangrene.) Focal infection theory, rather, so explained virtually all diseases, including arthritis, atherosclerosis, cancer, and mental illnesses.
An ancient concept that took modern form around 1900, focal infection theory was widely accepted in medicine by the 1920s. In the theory, the "focus of infection" might lead to secondary infections at sites particularly susceptible to such microbial species or toxin. Commonly alleged foci were diverse—appendix, urinary bladder, gall bladder, kidney, liver, prostate, and nasal sinuses—but most commonly were oral. Besides dental decay and infected tonsils, both dental restorations and especially endodontically treated teeth were blamed as foci. The putative "oral sepsis" was countered by tonsillectomies and tooth extractions, including of endodontically treated teeth and even of apparently healthy teeth, newly popular approaches—sometimes leaving individuals toothless—to treat or prevent diverse diseases.
Drawing severe criticism in the 1930s, focal infection theory—whose popularity zealously exceeded consensus evidence—was discredited in the 1940s by research attacks that drew overwhelming consensus of this sweeping theory's falsity. Thereupon, dental restorations and endodontic therapy became again favored. Untreated endodontic "disease" retained mainstream recognition as fostering systemic disease. But only alternative medicine and later biological dentistry continued highlighting sites of dental treatment—still endodontic therapy, but, more recently, also dental implant, and even tooth extraction, too—as foci of infection causing chronic and systemic diseases. In mainstream dentistry and medicine, the primary recognition of focal infection is endocarditis, if oral bacteria enter blood and infect the heart, perhaps its valves.
Entering the 21st century, scientific evidence supporting general relevance of focal infections remained slim, yet evolved understandings of disease mechanisms had established a third possible mechanism—altogether, metastasis of infection, metastatic toxic injury, and, as recently revealed, metastatic immunologic injury—that might occur simultaneously and even interact. Meanwhile, focal infection theory has gained renewed attention, as dental infections apparently are widespread and significant contributors to systemic diseases, although mainstream attention is on ordinary periodontal disease, not on hypotheses of stealth infections via dental "treatment". Despite some doubts renewed in the 1990s by conventional dentistry's critics, dentistry scholars maintain that endodontic therapy can be performed without creating focal infections.
With the 1950s introduction of antibiotics, attempts to explain unexplained diseases via bacterial etiology seemed all the more unlikely. By the 1970s, however, it was established that antibiotics could trigger bacteria's switch to their L phase. Eluding detection by traditional methods of medical microbiology, bacterial L forms and the similar mycoplasma—and, later, viruses—became the entities expected in the theory of focal infection. Yet until the 1980s, such researchers were scarce, largely via scarce funding for such investigations.
Despite the limited funding, research established that L forms can adhere to red blood cells and thereby disseminate from foci within internal organs such as the spleen, or from oral tissues and the intestines, especially during dysbiosis. Perhaps some of Weston Price's identified "toxins" in endodontically treated teeth were L forms, thought nonexistent by bacteriologists of his time and widely overlooked into the 21st century. Apparently, dental infections, including by uncultured or cryptic microorganisms, contribute to systemic diseases.
In one case, cloxacillin, ceftriaxone, and amphotericin B were tried.
Two patients survived after being successfully treated with a therapy consisting of flucytosine, pentamidine, fluconazole, sulfadiazine and azithromycin. Thioridazine was also given. Successful treatment in these cases was credited to "awareness of "Balamuthia" as the causative agent of encephalitis and early initiation of antimicrobial therapy."
Even with treatment, the condition is often fatal, and there are very few recorded survivors, almost all of whom suffered permanent neurocognitive deficits. Antifungal drugs including ketoconazole, miconazole, 5-flucytosine and pentamidine have been shown to be effective against GAE-causing organisms in laboratory tests.
The treatment includes lowering the increased intracranial pressure and starting intravenous antibiotics (and meanwhile identifying the causative organism mainly by blood culture studies).
Hyperbaric oxygen therapy (HBO2 or HBOT) is indicated as a primary and adjunct treatment which provides four primary functions.
Firstly, HBOT reduces intracranial pressure. Secondly, high partial pressures of oxygen act as a bactericide and thus inhibits the anaerobic and functionally anaerobic flora common in brain abscess. Third, HBOT optimizes the immune function thus enhancing the host defense mechanisms and fourth, HBOT has been found to be of benefit when brain abscess is concomitant with cranial osteomyleitis.
Secondary functions of HBOT include increased stem cell production and up-regulation of VEGF which aid in the healing and recovery process.
Surgical drainage of the abscess remains part of the standard management of bacterial brain abscesses. The location and treatment of the primary lesion also crucial, as is the removal of any foreign material (bone, dirt, bullets, and so forth).
There are few exceptions to this rule: "Haemophilus influenzae" meningitis is often associated with subdural effusions that are mistaken for subdural empyemas. These effusions resolve with antibiotics and require no surgical treatment. Tuberculosis can produce brain abscesses that look identical to conventional bacterial abscesses on CT imaging. Surgical drainage or aspiration is often necessary to identify "Mycobacterium tuberculosis", but once the diagnosis is made no further surgical intervention is necessary.
CT guided stereotactic aspiration is also indicated in the treatment of brain abscess.
Yersiniosis is usually self-limiting and does not require treatment. For severe infections (sepsis, focal infection) especially if associated with immunosuppression, the recommended regimen includes doxycycline in combination with an aminoglycoside. Other antibiotics active against "Y. enterocolitica" include trimethoprim-sulfamethoxasole, fluoroquinolones, ceftriaxone, and chloramphenicol. "Y. enterocolitica" is usually resistant to penicillin G, ampicillin, and cephalotin due to beta-lactamase production.
Vitamin D/Sunlight
Omega-3 Fatty Acids
Probiotics/Microflora
Antioxidants
Treatments for autoimmune disease have traditionally been immunosuppressive, anti-inflammatory, or palliative. Managing inflammation is critical in autoimmune diseases. Non-immunological therapies, such as hormone replacement in Hashimoto's thyroiditis or Type 1 diabetes mellitus treat outcomes of the autoaggressive response, thus these are palliative treatments. Dietary manipulation limits the severity of celiac disease. Steroidal or NSAID treatment limits inflammatory symptoms of many diseases. IVIG is used for CIDP and GBS. Specific immunomodulatory therapies, such as the TNFα antagonists (e.g. etanercept), the B cell depleting agent rituximab, the anti-IL-6 receptor tocilizumab and the costimulation blocker abatacept have been shown to be useful in treating RA. Some of these immunotherapies may be associated with increased risk of adverse effects, such as susceptibility to infection.
Helminthic therapy is an experimental approach that involves inoculation of the patient with specific parasitic intestinal nematodes (helminths). There are currently two closely related treatments available, inoculation with either Necator americanus, commonly known as hookworms, or Trichuris Suis Ova, commonly known as Pig Whipworm Eggs.
T cell vaccination is also being explored as a possible future therapy for autoimmune disorders.
Healing is prolonged, and usually takes 6–10 weeks. The ulcer heals by secondary intention.
Small extramacular lesions (lesions not threatening vision) may be observed without treatment. Sight-threatening lesions are treated for 4–6 weeks with triple therapy consisting of pyrimethamine, sulfadiazine, and folinic acid. During treatment with pyrimethamine, leukocyte and platelet counts should be monitored weekly. Folinic acid protects against the decrease in platelets and white blood cells induced by pyrimethamine.
Prednisone may be used for 3–6 weeks to reduce macular or optic nerve inflammation and can be started on day 3 of antibiotic therapy. Corticosteroids should not be used without concurrent antibiotic treatment or in immunocompromised patients due to the risk of exacerbation of the disease. Currently, there is no published evidence from randomized controlled trials demonstrating that corticosteroids would be an effective adjunct for treating ocular toxoplasmosis.
Trimethoprim-Sulfamethoxazole has been shown to be equivalent to triple therapy in the treatment of ocular toxoplasmosis and may be better tolerated. Clindamycin and azithromycin can also be considered as alternative therapies. Spiramycin may be used safely without undue risk of teratogenicity and may reduce the rate of transmission to the fetus.
AIDS patients require chronic maintenance treatment.
Massage therapy using trigger-point release techniques may be effective in short-term pain relief. Physical therapy involving gentle stretching and exercise is useful for recovering full range of motion and motor coordination. Once the trigger points are gone, muscle strengthening exercise can begin, supporting long-term health of the local muscle system.
Myofascial release, which involves gentle fascia manipulation and massage, may improve or remediate the condition.
A systematic review concluded that dry needling for the treatment of myofascial pain syndrome in the lower back appeared to be a useful adjunct to standard therapies, but that clear recommendations could not be made because the published studies were small and of low quality.
Posture evaluation and ergonomics may provide significant relief in the early stages of treatment. Movement therapies such as Alexander Technique and Feldenkrais Method may also be helpful.
Gentle, sustained stretching exercises within a comfortable range of motion have been shown to decrease pain thresholds. Regular, non-intense activity is also encouraged.
There is as yet inadeqaute data from randomised controlled trials.
Treatment with HAART and ACE inhibitors/Angiotensin receptor blockers has been shown to be beneficial and should be given to all patients unless otherwise contra-indicated. General renoprotective measures and the treatment of the complications of nephrotic syndrome and kidney failure are adjunctive.
Corticosteroid treatment can be useful in patients who do not respond to the above treatment. There is some evidence that ciclosporin might be helpful in selective cases, however further trials are required on both steroids and ciclosporin before these drugs can become standardised treatment if at all.
Eye and skin infections caused by "Acanthamoeba spp." are generally treatable. Topical use of 0.1% propamidine isethionate (Brolene) plus neomycin-polymyxin B-gramicidin ophthalmic solution has been a successful approach; keratoplasty is often necessary in severe infections. Although most cases of brain (CNS) infection with "Acanthamoeba" have resulted in death, patients have recovered from the infection with proper treatment.
Antiviral therapy: as early as possible
10~15mg/kg every 8 hours for 14~21d
5~10mg/kg every 12hours for 14~21d
immune therapy: interferon
symptomatic therapy
High fever: physical regulation of body temperature
Seizure: antiepileptic drugs
high intracranial pressure-20%mannitol
Infections: antibiotic drugs
There are many treatments and procedures associated with wart removal. A review of clinical trials of various cutaneous wart treatments concluded that topical treatments containing salicylic acid were more effective than placebo. Cryotherapy appears to be as effective as salicylic acid, but there have been fewer trials.
Another product available over-the-counter that can aid in wart removal is silver nitrate in the form of a caustic pencil, which is also available at drug stores. In a placebo-controlled study of 70 patients, silver nitrate given over nine days resulted in clearance of all warts in 43% and improvement in warts in 26% one month after treatment compared to 11% and 14%, respectively, in the placebo group. The instructions must be followed to minimize staining of skin and clothing. Occasionally pigmented scars may develop.
Several randomized, controlled trials have found that zinc sulfate, consumed orally, often reduces or eliminates warts. The zinc sulfate dosage used in medical trials for treatment of warts was between 5 and 10 mg/kg/day. For elemental zinc, a lower dosage of 2.5 mg/kg/day may be appropriate as large amounts of zinc may cause a copper deficiency. Other trials have found that topical zinc sulfate solution or zinc oxide are also effective.
A 2014 study indicates that lopinavir is effective against the human papilloma virus (HPV). The study used the equivalent of one tablet twice a day applied topically to the cervices of women with high-grade and low-grade precancerous conditions. After three months of treatment, 82.6% of the women who had high-grade disease had normal cervical conditions, confirmed by smears and biopsies.
Studies of fat-soluble garlic extracts have shown clearing in greater than 90% of cases. The extract is applied twice daily and covered with an adhesive bandage. Improvements show within 2–4 weeks and total clearing in an average of 6–9 weeks.
The ideal treatment for IgAN would remove IgA from the glomerulus and prevent further IgA deposition. This goal still remains a remote prospect. There are a few additional caveats that have to be considered while treating IgA nephropathy. IgA nephropathy has a very variable course, ranging from a benign recurrent hematuria up to a rapid progression to chronic kidney failure. Hence the decision on which patients to treat should be based on the prognostic factors and the risk of progression. Also, IgA nephropathy recurs in transplants despite the use of ciclosporin, azathioprine or mycophenolate mofetil and steroids in these patients. There are persisting uncertainties, due to the limited number of patients included in the few controlled randomized studies performed to date, which hardly produce statistically significant evidence regarding the heterogeneity of IgA nephropathy patients, the diversity of study treatment protocols, and the length of follow-up.
Patients with isolated hematuria, proteinuria < 1 g/day and normal renal function have a benign course and are generally just followed up annually. In cases where tonsillitis is the precipitating factor for episodic hematuria, tonsillectomy has been claimed to reduce the frequency of those episodes. However, it does not reduce the incidence of progressive kidney failure. Also, the natural history of the disease is such that episodes of frank hematuria reduce over time, independent of any specific treatment. Similarly, prophylactic antibiotics have not been proven to be beneficial. Dietary gluten restriction, used to reduce mucosal antigen challenge, also has not been shown to preserve kidney function. Phenytoin has also been tried without any benefit.
A subset of IgA nephropathy patients, who have minimal change disease on light microscopy and clinically have nephrotic syndrome, show an exquisite response to steroids, behaving more or less like minimal change disease. In other patients, the evidence for steroids is not compelling. Short courses of high dose steroids have been proven to lack benefit. However, in patients with preserved renal function and proteinuria (1-3.5 g/day), a recent prospective study has shown that 6 months regimen of steroids may lessen proteinuria and preserve renal function. However, the risks of long-term steroid use have to be weighed in such cases. It should be noted that the study had 10 years of patient follow-up data, and did show a benefit for steroid therapy; there was a lower chance of reaching end-stage renal disease (renal function so poor that dialysis was required) in the steroid group. Importantly, angiotensin-converting enzyme inhibitors were used in both groups equally.
Cyclophosphamide had been used in combination with anti-platelet/anticoagulants in unselected IgA nephropathy patients with conflicting results. Also, the side effect profile of this drug, including long term risk of malignancy and sterility, made it an unfavorable choice for use in young adults. However, one recent study, in a carefully selected high risk population of patients with declining GFR, showed that a combination of steroids and cyclophosphamide for the initial 3 months followed by azathioprine for a minimum of 2 years resulted in a significant preservation of renal function. Other agents such as mycophenolate mofetil, ciclosporin and mizoribine have also been tried with varying results.
A study from Mayo Clinic did show that long term treatment with omega-3 fatty acids results in reduction of progression to kidney failure, without, however, reducing proteinuria in a subset of patients with high risk of worsening kidney function. However, these results have not been reproduced by other study groups and in two subsequent meta-analyses. However, fish oil therapy does not have the drawbacks of immunosuppressive therapy. Also, apart from its unpleasant taste and abdominal discomfort, it is relatively safe to consume.
The events that tend to progressive kidney failure are not unique to IgA nephropathy and non-specific measures to reduce the same would be equally useful. These include low-protein diet and optimal control of blood pressure. The choice of the antihypertensive agent is open as long as the blood pressure is controlled to desired level. However, Angiotensin converting enzyme inhibitors and Angiotensin II receptor antagonists are favoured due to their anti-proteinuric effect.
Treatment depends on the grade (I-III) but typically consist of cortisone, rituximab and chemotherapy (etoposide, vincristine, cyclophosphamide, doxorubicin). Methotrexate has been seen to induce LYG. Interferon alpha has been used by the US National Cancer Institute with varying results. In recent years hematopoietic stem cell transplantation has been performed on LYG-patients with relative good success; a 2013 study identifying 10 cases found that 8 patients survived the treatment and were disease free several years later. Two of the disease free patients later died, one from suicide and one from graft versus host disease after a second transplantation 4 years later. The remaining two patients died from sepsis after the transplantation.
There is no known cure for FMD. However, treatment focuses on relieving symptoms associated with it. Medical management is the most common form of treatment. The best approach to medically managing these patients is constantly being reevaluated as more information is learned about the disease.
Diet modification is often recommended as a first-line method of self-treatment for interstitial cystitis, though rigorous controlled studies examining the impact diet has on interstitial cystitis signs and symptoms are currently lacking. Individuals with interstitial cystitis often experience an increase in symptoms when they consume certain foods and beverages. Avoidance of these potential trigger foods and beverages such as caffeine-containing beverages including coffee, tea, and soda, alcoholic beverages, chocolate, citrus fruits, hot peppers, and artificial sweeteners may be helpful in alleviating symptoms. Diet triggers vary between individuals with IC; the best way for a person to discover his or her own triggers is to use an elimination diet. Sensitivity to trigger foods may be reduced if calcium glycerophosphate and/or sodium bicarbonate is consumed. The foundation of therapy is a modification of diet to help patients avoid those foods which can further irritate the damaged bladder wall.
The mechanism by which dietary modification benefits people with IC is unclear. Integration of neural signals from pelvic organs may mediate the effects of diet on symptoms of IC.
Pediatric FMD medical and surgical treatments or interventions are available. Treatment is determined by factors such as age and disease location but routinely involve controlling hypertension, re-establishing vascular flow, clot prevention, and improving lifestyle such as diet, exercise and smoking cessation.
Medical therapy for pediatric population may involve the use of angiotensin-converting enzyme inhibitor (ACE inhibitors) and/or angiotensin II receptor blockers, multiple anti-hypertensive medications, diuretics, calcium channel blockers, and beta-blockers. Prevention of thrombosis of affected arteries may be taken through administration of an antiplatelet medication such as aspirin.
Percutaneous transluminal renal angioplasty (PTRA) remains the gold standard for renal-artery FMD. This treatment is useful when hypertension is difficult to control; patient is intolerant to the anti-hypertensive medications, non-complainant to medication regime and patient loss of renal volume due to ischemia. PTRA can also aide in preventing a lifelong dependency on a medication for such a young patient. According to Meyers, “effective PTRAs result in cured or controlled blood pressure, which is often signified by reductions in plasma renin activity and angiotensin II levels, and when compared with surgery, percutaneous balloon angioplasty is less costly, able to be performed on an outpatient basis, results in lower morbidity, and the use of stenting is not primarily necessary.” However, there is a subset of the pediatric population that are resistant to PTRA. Adverse events may include, “recurrent stenosis, arterial occlusion with renal loss, and arterial rupture with extravasations and pseudo aneurysm formation and may require surgical intervention.
Treatment is generally supportive. Rest, hydration, antipyretics, and pain or anti-inflammatory medications may be given as needed.
Herpes simplex virus, varicella zoster virus and cytomegalovirus have a specific antiviral therapy. For herpes the treatment of choice is aciclovir.
Surgical management is indicated where there is extremely increased intracranial pressure, infection of an adjacent bony structure (e.g. mastoiditis), skull fracture, or abscess formation.
The majority of people that have viral meningitis get better within 7-10 days.
"Toxoplasma" infection can be prevented in large part by:
- cooking meat to a safe temperature (i.e., one sufficient to kill "Toxoplasma")
- peeling or thoroughly washing fruits and vegetables before eating
- cleaning cooking surfaces and utensils after they have contacted raw meat, poultry, seafood, or unwashed fruits or vegetables
- pregnant women avoiding changing cat litter or, if no one else is available to change the cat litter, using gloves, then washing hands thoroughly
- not feeding raw or undercooked meat to cats to prevent acquisition of "Toxoplasma"
Prolonged and intense rainfall periods are significantly associated with the reactivation of toxoplasmic retinochoroiditis. Changes promoted by this climatic condition concern both the parasite survival in the soil as well as a putative effect on the host immune response due to other comorbidities.
The antihistamine hydroxyzine failed to demonstrate superiority over placebo in treatment of IC patients in a randomized, controlled, clinical trial.
Amitriptyline has been shown to be effective in reducing symptoms such as chronic pelvic pain and nocturia in many patients with IC/BPS with a median dose of 75 mg daily. In one study, the antidepressant duloxetine was found to be ineffective as a treatment, although a patent exists for use of duloxetine in the context of IC, and is known to relieve neuropathic pain. The calcineurin inhibitor cyclosporine A has been studied as a treatment for interstitial cystitis due to its immunosuppressive properties. A prospective randomized study found cyclosporine A to be more effective at treating IC symptoms than pentosan polysulfate, but also had more adverse effects.
Oral pentosan polysulfate is believed to repair the protective glycosaminoglycan coating of the bladder, but studies have encountered mixed results when attempting to determine if the effect is statistically significant compared to placebo.
Avoidance is the primary treatment. Better alternatives are Nocturnal or Daily Dialysis, which are far more gentle processes for the new dialysis patient. Dialysis disequilibrium syndrome is a reason why hemodialysis initiation should be done gradually, i.e. it is a reason why the first few dialysis sessions are shorter and less aggressive than the typical dialysis treatment for end-stage renal disease patients.