Disease refractory

Radiation is an important modality in the treatment of symptomatic metastatic disease. The most common indication for treatment with radiation therapy is painful bone metastases or other localized sites of disease refractory to systemic therapy. Radiation therapy gives significant pain relief to approximately 90% of patients who are treated for painful bone metastases. Radiation is also an important modality in the palliative treatment of metastatic brain lesions and spinal cord lesions, which respond poorly to systemic therapy, as well as eye or orbit lesions and other sites where significant accumulation of tumor cells occurs. Skin and/or lymph node metastases confined to the chest wall area also may be treated with radiation therapy for palliation (e.g., open wounds or painful lesions). 

Pinto A, Borrutto G, Deall Anna A, Turco L, Ferried A An open, uncontrolled trial of oral rifaximin, a non-absorbable antibiotic, in inflammatory bowel disease refractory to conventional therapy. Eur J Clin Res 1997,9 217-224. 

At high risk for HF Structural heart Structural heart disease Refractory HF... 

Unlabeled Uses Cardiopulmonary bypass surgery hemodialysis pulmonary hypertension associated with acute respiratory distress syndrome, systemic lupus erythematosus, or congenital heart disease refractory CHF severe community-acquired pneumonia... 

Unlabeled Uses Treatment of Paget s disease refractory to other therapy... 

A 54-year-old woman with an 8-year history of pemphigus vulgaris had a flare-up of her disease, refractory to oral glucocorticoids, after taking nifedipine for 2 years for hypertension. The nifedipine was withdrawn and she was given high-dose immunosuppressant treatment with prednisone and azathioprine. The lesions subsided promptly and cleared totally within several weeks. 

Tepler I, Schwartz G, Parker K, et al. Phase I trial of an in-terleukin-2 fusion toxin (DAB486IL-2) in hematologic malignancies Complete response in a patient with Hodgkin s disease refractory to chemotherapy. Cancer. 1994 73 1276-1285. 

PATIENTS WITH DYSIMMUNE NEUROLOGICAL DISEASES REFRACTORY TO HIGH PROLONGED DOSES OF PREDNISONE PLUS AZATHIOPRENE OR CYCLOPHOSPHAMIDE HAVE SHOWN MODERATE TO DRAMATIC IMPROVEMENT. THESE INCLUDE CHRONIC DYSCHWANNIAN NEUROPATHY DYSNEURONAL ... 

Localized disease refractory to medical therapy or associated with compromise of organ function [e.g., tracheal or bronchostenosis (50-52), mass lesions encroaching the orbit or optic chiasm (44)] may require percutaneous or surgical management or intralesional CS therapy (3,50,52). For tracheobronchial WG, treatment modalities include CO2 or Nd YAG laser, dilatation, intratracheal CS injections, placement of Silastic airway stents, tracheostomy, laryngeal-tracheal reconstmction, and partial tracheal resection (3,50,51,53,215-218). Silastic stents may provide sustained relief of symptoms in some patients, but are associated with... 

Transfusion-induced autoimmune disease has been a significant complication in the treatment of patients who require multiple platelet transfusions. Platelets and lymphocytes carry their own blood group system, ie, the human leukocyte antigen (HLA) system, and it can be difficult to find an HLA matched donor. A mismatched platelet transfusion does not induce immediate adverse reactions, but may cause the patient to become refractory to the HLA type of the transfused platelets. The next time platelets with an HLA type similar to that of the transfused platelets are transfused, they are rejected by the patient and thus have no clinical efficacy. Exposure to platelets originating from different donors is minimized by the use of apheresis platelets. One transfusable dose (unit) of apheresis platelets contains 3-5 x 10 platelets. An equal dose of platelets from whole blood donation requires platelets from six to eight units of whole blood. Furthermore, platelets can be donated every 10 days, versus 10 weeks for whole blood donations. 

In passive immunotherapy immune globulin (Ig) is an effective replacement in most forms of antibody deficiency (14). In the past, plasma was used instead of immune globulin, but plasma is rarely indicated in the 1990s because of the risk of disease, particularly AIDS, transmission. Because plasma contains many factors in addition to immunoglobulins (Igs), plasma is, however, of particular value in patients with protein-losing enteropathy, complement deficiencies, and refractory diarrhea. 

Inhalation of certain fine dusts may constitute a health hazard. Eor example, exposure to siUca, asbestos, and beryllium oxide dusts over a period of time results ki the potential risk of lung disease. OSHA regulations specify the allowable levels of exposure to kigestible and respkable materials. Material Safety Data Sheets, OSHA form 20, available from manufacturers, provide information about hazards, precautions, and storage pertinent to specific refractory products. 

The glucan synthase inhibitor caspofungin (intravenous formulation) is new on the market for the treatment of invasive aspergillosis in patients whose disease is refractory to, or who are intolerant of, other therapies. During the clinical trials fever, infused vein complications, nausea, vomiting and in combination with cyclosporin mild transient hepatic side effects were observed. Interaction with tacrolismius and with potential inducer or mixed inducer/inhibitors of drug clearance was also seen. 

Proteasomal inhibition represents a novel strategy in cancer treatment and the small molecule Bortezomid (PS-341, Velcade ) has been approved for the treatment of refractory and relapsed multiple myeloma, a proliferative disease of plasma cells. Bortezomid inhibits an active site in a proteasome subunit and remarkably shows selective cytotoxicity to cancer cells. Although the underlying mechanisms are not completely understood bortezomid apparently induces a cell stress response in these tumor cells followed by caspase-dependent apoptosis. Whether bortezomid is beneficial for the treatment of other proliferative disease is currently being tested in clinical trials. 

Dantrolene is the mainstay of MH treatment. It has long been available for the treatment of muscle spasm in cerebral palsy and similar diseases. It is a hydantoin derivative that was first synthesized in 1967, and reported to be effective in the treatment of porcine MH in 1975. Also in 1975, dantrolene was shown to be more effective than procainamide in the treatment of human MH, which until that time was the drug of choice. However, the intravenous preparation was not made available until November 1979. It significantly lowered mortality. The half-life of dantrolene is estimated to be 6-8 hr. Dantrolene s primary mode of action is the reduction in calcium release by the sarcoplasmic reticulum. Dantrolene also exerts a primary antiarrhythmic effect by increasing atrial and ventricular refractory periods. Side effects of dentrolene include hepatotoxicity, muscle weakness, ataxia, blurred vision, slurred speech, nausea, and vomiting. Dantrolene is not contraindicated in pregnancy, but it does cross into breast milk and its effect on the neonate is unknown. 

The Vaughan-Williams classification of antiarrhythmic drugs has been criticized for a number of reasons. The classification is based on the effects of drugs on normal, rather than diseased, myocardium. In addition, many of the drugs may be placed into more than one class. For example, the class IA drugs prolong repolarization/refractoriness, either via the parent drug8,9 or an active metabolite,10 and therefore also maybe placed in class III. Sotalol is also a 3-blocker, and therefore fits into class II. Amiodarone inhibits sodium and potassium channels, is a non-competitive inhibitor of 3-receptors, and inhibits calcium... 

Surgical intervention is a potential treatment option in patients with complications such as fistulae or abscesses, or in patients with medically refractory disease. Ulcerative colitis is curable with performance of a total colectomy. Patients with UC may opt to have a colectomy to reduce the chance of developing colorectal cancer. Patients with CD may have affected areas of intestine resected. Unfortunately, CD may recur following surgical resection. Repeated surgeries may lead to significant malabsorption of nutrients and drugs consistent with development of short-bowel syndrome. 

Limited evidence indicates that cyclosporine, or possibly tacrolimus, may be effective as salvage therapy for patients who fail intravenous corticosteroid therapy.2 Surgical intervention may ultimately be necessary for medically refractory disease. 

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