Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty six patients suffering from Paget's disease in acute exacerbation were treated for three months with 80 u/day of synthetic salmon thyrocalcitonin. A control group of 36 patients received a placebo. A marked improvement in pain was seen in 60% of the treated patients and 15% of the placebo group (p less than 0.001). Functional impairment, when present, was also far more markedly decreased in the treated group (p less than 0.01). In comparison with the control group, the fall in hydroxyprolinuria and alkaline phosphatase levels was highly significant (p less than 0.001). This treatment is active against not only symptoms and signs, but also the biological criteria of activity of the disease. The side-effects of treatment consist above all of hot flashes (35% of cases) and nausea (24%). In only one case was it necessary to stop treatment because of intractable diarrhoea.
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PMID:[Treatment of Paget's disease with salmon thyrocalcitonin. Cooperative double-blind study]. 6 92

Fifteen patients with widespread painful osseous metastases from breast cancer unresponsive to other systemic therapy were treated with mithramycin at dose levels usually used for treating Paget's disease. Ten patients had relief of pain, which was marked and rapid in onset in seven. Mobility was greatly improved in four patients. Healing of bone lesions did not occur and new lesions developed while treatment was being given. Clinical response was associated with a decrease in plasma alkaline phosphatase. Toxicity was mild and consisted of nausea in most patients and a slight decrease in platelet count in one patient. Mithramycin is a useful agent for palliation of painful bone metastases and should be considered for further trials of combination chemotherapy for advanced breast cancer with bone metastases.
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PMID:Effect of mithramycin on widespread painful bone metastases in cancer of the breast. 9 11

Human calcitonin has proven to be an effective drug in the management of Paget's disease. Bone pain decreased in a high percentage of cases and biochemical indices improved in all but a few instances. Radiologic regression of the disease often was seen after several years of treatment. The drug has been uniformly effective when administered to patients who have develped resistance to porcine or salmon calcitonin due to circulating antibodies. The incidence of side effects, mainly facial flushing and nausea, was variable and uncommonly resulted in discontinuation of treatment. Further studies are required to establish the minimum effective dose.
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PMID:Human calcitonin treatment of Paget's disease of bone. 91 95

Clinical interest in salmon calcitonin began in 1972 when this peptide was shown to be effective in the treatment of Paget's disease. Salmon calcitonin is more potent than porcine calcitonin, with human calcitonin intermediate in potency. Salmon calcitonin is a highly effective therapeutic agent in the treatment of Paget's disease. During chronic treatment with salmon calcitonin, alkaline phosphatase activity and urinary hydroxyproline excretion decrease on an average of 50% in patients with Paget's disease. Patients may experience a variety of clinical benefits during chronic treatment, including relief of bone pain, a reversal of neurological deficits, stabilization or improvement of hearing loss, and improvement of vascularity of bone. Radiologic healing of osteolytic lesions in particularly striking with calcitonin treatment. Paget's disease patients prefer treatment with salmon calcitonin administered by means of a nasal spray. Salmon calcitonin has an excellent safety profile and produces mild side effects in a small percentage of patients. The most common side effects associated with salmon calcitonin administration are nausea and facial flushing. It is unusual to observe severe side effects. In about 20% of patients, production of antibodies may neutralize the effects of the exogenously administered calcitonin; these patients respond to human calcitonin. At this time salmon calcitonin should still be considered a valuable therapeutic agent in the treatment of Paget's disease, particularly in patients with osteolytic lesions.
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PMID:Clinical efficacy of salmon calcitonin in Paget's disease of bone. 193 17

Amino-hydroxy-propylidene bisphosphonic acid (APD) is a potent inhibitor of bone resorption. Its oral use in Paget's disease of bone has proved effective and safe when the drug is administered on a long-term basis. Since APD was found not to impair bone mineralization, it was assumed that a long remission would be obtained by administering a high dose of the compound over a very short period of time. Therefore, 12 patients with symptomatic Paget's disease received 1200 mg/d APD orally over 5 consecutive days. Follow-up is 2 months for all patients, 6 months for 6 patients and one year for one patient. Clinical improvement and biochemical remission were observed in all patients. Side effects were negligible (transient nausea in 2 patients and +1 degree C temperature increment noted for 2 days in 3 patients). Urinary hydroxyproline started decreasing within 2 days and became normal as a mean (+/- SEM) after 5 days (1.9 +/- 0.3 mumol/lGF, nl less than 2.3) and in all cases after 15 days. Thereafter it remained within the normal range (1.9 +/- 0.2 mumol/lGF) for 6 months. Plasma alkaline phosphatase activity fell progressively and significantly, and became normal after 1-3 months in all patients but one, a man with very active disease in whom the parameter remained slightly above normal and stable. At the end of the sixth month, mean plasma alkaline phosphatase activity was 100 +/- 13 U/l (nl less than 120 U/l). Plasma calcium and phosphate fell transiently between days 4 and 15.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Paget's disease of bone treated per os with APD in 5 days]. 379 71

Thirteen patients with painful Paget's disease of bone were treated as outpatients with low doses of synthetic salmon calcitonin 22.5-50 mug three times weekly. Treatment produced full remission of pain in a mean time of 5.5 weeks and a mean depression of serum alkaline phosphatase activity of 33%.The interval before symptomatic relief could not be predicted from the variables studied. The ultimate fall in serum alkaline phosphatase activity, however, could be predicted from the initial levels and from the early rate of decrease (P < 0.001). Biochemical resistance to treatment, which occurred in three cases, could be related to the dose and duration of treatment.Prolonged remissions of pain may occur which are not related to biochemical remission, to the dose of calcitonin, or to the duration of treatment. The side effects attributable to salmon calcitonin were transient nausea (in nine patients), transient flushing (in four), diarrhoea (in two), and rash (in one) though in only one patient did treatment have to be withdrawn prematurely because of these effects.
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PMID:Treatment of Paget's disease of bone with synthetic salmon calcitonin. 447 16

Synthetic human calcitonin was used in the treatment of 26 patients over a period of 1-14 months. 17 patients had Paget's disease of the bone, 6 postmenopausal osteoporosis and 3 Sudeck's syndrome. Subjective improvement (reduction of pain, improvement of mobility) was found in 15 patients with Paget's disease, in 4 females with postmenopausal osteoporosis and in all 3 patients with Sudeck's syndrome. Radiographic improvement of bone changes developed only very slowly. These results were confirmed by diminution of the exchangeable calcium pool indicating reduction of rates of osseous degradation. Calcitonin tolerance was acceptable. Transitory nausea and occasional vomiting occurred in 3 patients.
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PMID:[Synthetic human calcitonin in Paget's disease of bone and osteoporosis (author's transl)]. 616 31

One hundred and four patients with Paget's disease of bone received treatment with a calcium/thiazide regimen, salmon calcitonin, or ethane-1-hydroxy-1, 1-diphosphonate (EHDP). Most patients commenced therapy with the calcium/thiazide regimen; in 67% of these, the disease was satisfactorily controlled for some years. When the response was unsatisfactory, calcitonin was given. This was frequently effective, but produced troublesome nausea in 28% of patients. When these side effects were unacceptable, or the response was not adequate, EHDP was given, unless the patient appeared to be at risk of fracture. It is suggested that the calcium/thiazide regimen has a place in the management of Paget's disease; that calcitonin is more frequently effective, but has a high incidence of unpleasant, though not serious, side effects; and that EHDP is a useful agent in the treatment of Paget's disease, but must be administered with care, and does carry a small risk of pathological fracture.
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PMID:Treatment of Paget's disease of bone. 640 39

Ten patients with severe Paget's disease of bone and serum alkaline phosphatase (sAP) greater than 900 IU/l were treated for six months with the oral diphosphonate APD, (3-amino-1-hydroxypropylidene-1, 1-bisphosphonate). By the end of the treatment period there was a reduction in the log mean urine hydroxyproline (uHP) and the log mean sAP of 92% and 87% respectively. In four patients both sAP and uHP fell to within the normal range and remained normal for at least six months after therapy was stopped. Bone scintigraphy showed a fall in 99mTc-MDP uptake in sites of active Paget's disease in all patients and histomorphometry showed no increase in osteoid. Repair of radiological osteolytic lesions was observed in 6/6 patients and progression of tibial osteolytic wedges was arrested in 5/5 patients and reversed in four. This improvement persisted six months after completion of therapy but further wedge progression occurred in one patient whose urine HP remained elevated. There were no serious effects though five patients complained of nausea. The clinical and biochemical responses to APD were equivalent to those observed in the same patients during a previous six month course of combined therapy with human calcitonin (CT) + EHDP except that there was additional biochemical and radiological evidence of bone healing. This study confirms PAD as an effective treatment of severe Paget's disease of bone.
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PMID:Effective oral treatment of severe Paget's disease of bone with APD (3-amino-1-hydroxypropylidene-1,1-bisphosphonate); a comparison with combined calcitonin + EHDP (1-hydroxyethylidene-1,1-bisphosphonate). 644 63

Bisphosphonates are analogues of inorganic pyrophosphate, a naturally occurring chemical in bone. In vitro and animal experiments demonstrated that these agents were effective inhibitors of bone resorption. Subsequently they were applied to a variety of clinical problems in which increased bone resorption was an underlying feature of the pathology. In 1971 etidronate became the first bisphosphonate shown to inhibit bone resorption in humans when it was given to patients with Paget's disease. Subsequently this agent was also found to be useful in treating the hypercalcemia of malignancy. At the present time cyclic etidronate therapy is also used for the prevention of bone loss in patients with osteoporosis and for the prevention of heterotopic ossification in spinal cord-injured patients and in patients after hip replacement. Newer bisphosphonates are generally more potent than etidronate and do not produce a severe mineralization defect as do higher doses of etidronate. Pamidronate and clodronate are highly effective in the management of Paget's disease, hypercalcemia due to malignancy and immobilization, metastatic bone disease, and hematologic malignancies affecting bone. They are also promising agents for the prevention of osteoporosis. Alendronate, risedronate, and CGP 42446 are highly potent bisphosphonates that look very promising for the treatment of all disorders of bone resorption. It is fortunate that adverse reactions are not a prominent feature of bisphosphonate use. The main side effects are nausea and abdominal discomfort, mainly with oral use, a transient increase in bone pain in patients with Paget's disease, and an acute-phase reaction (fever, myalgia, mild leukopenia) in patients receiving aminobisphosphonates. The evolution of bisphosphonate therapy should be considered one of the major therapeutic events of the past 25 years. Future research should define the optimum use of these agents.
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PMID:Bisphosphonates in the treatment of disorders of mineral metabolism. 767 Oct 99


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