Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 68 year old man with prostatic carcinoma and extensive painful osteoblastic metastases was discovered to have hypocalcemia (serum calcium 7.1 mg/dl) without evidence of hypoalbuminemia, renal failure or malabsorption. Baseline studies revealed hypocalciuria (24 hour urine calcium less than 5 mg/day), normal serum phosphate (3.4 mg/dl), low tubular reabsorption of phosphate (68 percent), undetectable serum calcitonin, normal serum 25-hydroxyvitamin D, slightly elevated serum parathyroid hormone level and increased urinary cyclic AMP (8.87 mumol/g creatinine). These studies were compatible with secondary hyperparathyroidism. The intravenous administration of parathyroid extract produced no further change in urinary phosphate but a 25-fold increase in nephrogenous cyclic AMP. Three days administration of intramuscular parathyroid extract slowly and temporarily restored serum calcium to normal levels while increasing urinary cyclic AMP and phosphate. Chemotherapy with cyclophosphamide and 5-fluorouracil rendered the patient free of pain while reducing serum acid and alkaline phosphatase levels and restoring serum total and ionized calcium and urinary cyclic AMP excretion to normal.
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PMID:Hypocalcemia with osteoblastic metastases in patient with prostate carcinoma. A cause of secondary hyperparathyroidism. 724 80

Hypercalcemia of malignancy is most commonly due to the effects of parathyroid hormone-related peptide, which acts as a humoral factor to cause generalized osteoclast-mediated bone resorption and reabsorption of calcium by the kidney tubule, and may also act as a local resorptive factor adjacent to bone metastases. Local resorptive mechanisms are less common causes of malignant hypercalcemia than previously believed. Treatment begins with intravenous fluid rehydration, followed by a furosemide diuresis and the bisphosphonate pamidronate, 60-90 mg, intravenously. Gallium nitrate is an efficacious but inconvenient alternative to pamidronate. Calcitonin combined with pamidronate is a reasonable initial therapy for severe hypercalcemia to hasten normalization of the serum calcium. Steroids should be reserved for hypercalcemia due to tumor production of 1,25 dihydroxyvitamin D, or for steroid-responsive malignancies. Oral or parenteral bisphosphonates can be used to maintain normocalcemia. In addition to improving the morbidity of acute hypercalcemia, bisphosphonate therapy has been shown to reduce bone pain and pathological fractures in patients with bone metastases, and calcitonin also has a potent analgesic effect in these patients. Treatment for hypercalcemia should therefore be considered in the majority of patients in the palliative care setting.
J Pain Symptom Manage 1995 Apr
PMID:Hypercalcemia of malignancy in the palliative care patient: a treatment strategy. 754 27

Osteoporosis is a major public health problem occurring primarily among the postmenopausal population. Osteoporosis is a preventable disease, but despite several advances in its prevention, treatment of the established disease to date remains a major challenge to be managed by primary care physicians. Stabilisation of bone mass and prevention of falls are of paramount importance in any therapeutic programme for osteoporotic patients with established vertebral fractures. Drug therapy for osteoporosis can be divided operationally into 2 main categories: those that inhibit bone resorption, and thus reduce bone turnover, and those that stimulate bone formation, exerting an anabolic effect. Therapeutic agents that inhibit bone remodeling would appear to be best suited to those patients with high turnover osteoporosis (about 30%). Included in this category are calcium, vitamin D and its metabolites, gonadal steroids, calcitonin, ipriflavone and bisphosphonates. Although estrogen replacement therapy has been proven to be effective in older females, calcitonin appears to be the treatment of choice for this population since it stabilises or increases bone mass and also has reported analgesic properties. Drugs that stimulate bone remodeling or bone formation would be best suited to patients with low turnover osteoporosis (about 70%). The agent in this class that is widely used is sodium fluoride. New therapies include intermittent injections of synthetic parathyroid hormone, and cyclic bisphosphonates to activate then depress resorption and formation. Any attempts to stabilise the skeleton with any drug regimen must be accompanied by an adequate calcium supply, i.e. 1200 to 1500 mg/day). The theoretical basis of tailoring treatment for osteoporosis to the underlying histology has not yet been fully proven, but there is increasing experimental support to this approach. Drugs that inhibit bone turnover, such as calcitonin, appear to be effective in increasing bone mass for 1.5 to 2 years, about the time it would take to replenish the remodeling space in a patient with high turnover osteoporosis. In contrast, although bone mass appears to increase for as long as 5 years in patients treated with sodium fluoride, there has been no consistent reduction in occurrence of vertebral or hip fractures. Paget' disease of bone is a focal disorder of the skeleton characterised by excessive resorption and subsequently disorganised formation of bone. The aetiology of the disease is unknown. Paget's disease may be mono-ostotic or polyostotic; pain and bone deformities due to enlargement of skeletal segments represent the main clinical aspects. However, in many patients the disease may be asymptomatic.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Management of osteoporosis and Paget's disease. An appraisal of the risks and benefits of drug treatment. 781

Forty-three patients with secondary or autonomous hyperparathyroidism complicating chronic renal failure (CRF) underwent total parathyroidectomy (PTX) (follow-up 2-18 years, mean 8.7 years). Five were on conservative treatment for CRF, 35 on regular dialysis, and only three had a functioning allograft. At PTX, the most frequent findings were uncontrollable hypercalcaemia, musculo-skeletal pain, radiographic changes in the phalanges, and raised plasma parathyroid hormone (PTH) concentration. Pre-operatively, all patients were loaded with dihydrotachysterol or 1-alpha-OH cholecalciferol. Postoperatively, they were maintained on tapering doses of the same drugs and, briefly, oral calcium supplements. Five glands were identified and removed in two patients, four in 35 patients, three in three patients and only two in one patient. All had changes of hyperplasia and adenoma formation, except for one with a parathyroid carcinoma. Prompt symptomatic and radiographic improvement occurred, with normalization of plasma calcium and alkaline phosphatase. Postoperative PTH levels were available in 33 patients (23 by intact PTH assay): they were persistently high in 10/33 (2/23 intact); normal in seven (6 intact); low in 11 (3 intact), and undetectable in four (3 intact). Thus, PTX was incomplete in the majority of patients. Following transplantation, 3/20 (3/18 intact) patients still had detectable PTH. Only one patient developed symptomatic recurrent parathyroid disease requiring re-operation, and complications were few. Small dosages of vitamin D continue to be required, but not calcium supplementation, and no clinical effects of possible adynamic bone have been noted. At later renal transplantation in 27 patients, an easily treatable, uncomplicated hypocalcaemia was noted in 33%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term follow-up after total parathyroidectomy without parathyroid reimplantation in chronic renal failure. 782 May 43

Calciphylaxis is a rare disease associated with hemodialysis or transplantation, high parathyroid hormone values, and increased serum calcium x phosphate (Ca x P) product. Only four patients on continuous ambulatory peritoneal dialysis have been reported with this condition. We report five cases presenting within a 2-year period with severe calf pain and tenderness with extensive nonulcerating large, hard, and tender subcutaneous plaques in the calves. Calcium deposition was confirmed radiologically and by bone scanning. Four patients were on continuous ambulatory peritoneal dialysis, and the other was not yet on dialysis. High serum Ca x P product was found in three of these patients at onset of the condition. Two patients had normal parathyroid hormone levels at onset. Calcium salts and/or calcitriol had been taken prior to onset in three patients. When presenting in this fashion, the diagnosis can be easily made by the uniqueness of the physical findings in the legs. Our observation suggests that the condition should no longer be considered rare and is not confined to hemodialysis patients. Furthermore, it can occur in predialysis patients.
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PMID:Calciphylaxis presenting with calf pain and plaques in four continuous ambulatory peritoneal dialysis patients and in one predialysis patient. 787 32

57 patients with advanced prostate cancer and a failure of prior hormonal treatment were selected for a double-blind placebo-controlled trial, in which they were randomly allocated to receive either clodronate (C) or placebo concomitantly with the basic cancer treatment, estramustine phosphate (E) (560 mg daily). The treatment was started intravenously with 300 mg of C or placebo in 5 consecutive days, and thereafter maintained orally with 1600 mg of C or identical placebo daily for 3 months. Bone biopsies were taken at admission and at 3 months. Measurements of serum calcium, phosphate, alkaline phosphatase, prostate-specific antigen and creatinine were made at the time of both bone biopsies and at 1 month. Serum intact parathyroid hormone and vitamin D metabolites were measured at admission and at 3 months. Because of several discontinuations, the study groups at final analysis comprised 20 patients taking E + C and 19 patients taking E and placebo. Bone resorption, as judged by eroded surface and osteoclast number, was markedly increased especially in biopsies taken from tumour-involved bone. Treatments with E + C or E both induced a significant decrease in bone resorption, but were associated with the development of hypocalcaemia, secondary hypoparathyroidism, hypophosphataemia and severe impairment of mineralisation of newly formed bone, i.e. osteomalacia. Since the patients were not vitamin D deficient, we conclude that osteomalacia resulted from a relative deficiency of calcium and phosphate. The transiency of pain relief achieved with anti-resorptive agents in the treatment of bone metastases from prostate cancer may be due to the development of osteomalacia.
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PMID:The effect of clodronate on bone in metastatic prostate cancer. Histomorphometric report of a double-blind randomised placebo-controlled study. 791 32

This 20 year old man suffered increasingly from multifocal bone- and back pain over the last 6 months. Painful weakness of the left leg with dysesthesia of the 4th and 5th toe, a weight loss of 15 kg and polydipsia and pollakiuria had developed. The clinical workup disclosed hard tumors in the right mandible and tibia, a waddling gait with bilateral sign of Trendelenburg, reduced muscular force in the left leg with missing achilles tendon reflex and a loss of sensibility in the distal S1 segment, epigastric tenderness on pressure and hypertension with a value of 160/100 mmHg. X-rays revealed multiple cystic bone lesions at all sites. Hypercalcemia and massively elevated parathyroid hormone were measured. Since the parathyroids were enlarged on sonography, primary hyperthyroidism with fibrosing osteitis v. Recklinghausen was diagnosed.
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PMID:[Bone pain, polydipsia, polyuria]. 818 45

We have evaluated the value of specific bone resorption markers in monitoring metastatic bone disease to define the duration of action of a single high-dose pamidronate infusion. Twenty patients received a single infusion of pamidronate 120 mg for painful bone metastases. Ten out of these 20 patients also received a second infusion. They were evaluated at baseline, 2, 4 and 8 weeks after each infusion. A composite pain questionnaire, serum and urine tests were carried out at these time points. Bone resorption markers measured included urinary calcium, hydroxyproline and two new markers: pyridinoline and deoxypyridinoline. Reference values were defined by 20 healthy controls matched by age and sex. Pamidronate induced a profound fall in bone resorption with a maximal effect within the first month after therapy. Changes in urinary calcium levels were confounded by a rise of 100% in the parathyroid hormone levels. Before treatment, pyridinoline and deoxypyridinoline were increased in 70% of patients, while urinary calcium was increased in only 40% of them. Thirteen patients had a > or = 50% fall in deoxypyridinoline levels and were considered as biochemical responders. These patients had a mean reduction in pain score of about 30% of baseline levels, which was significantly higher than the seven non-biochemical responders. In conclusion, urinary calcium is not a precise marker of bone resorption. Deoxypyridinoline seems to be the most specific bone resorption marker in cancer patients. Biochemical responders have the most benefit from pamidronate in terms of pain relief. This suggests that patients may benefit from more potent or repeated infusions of bisphosphonates.
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PMID:Metabolic effects of pamidronate in patients with metastatic bone disease. 862 69

Although the short-term outcome of total parathyroidectomy combined with autotransplantation in cases of renal osteodystrophy has been reported by many investigators, few studies have been made on the long-term outcome of this surgical technique. We recently examined the long-term outcome of this surgery by following 19 cases for more than one year (range: 12-70 months, mean: 31.7 months). During the follow-up period, changes in subjective symptoms, biochemical parameters and bone mineral density (BMD) were monitored. At the end of the follow-up period, C-parathyroid hormone (C-PTH) and alkaliphosphatase (ALP) were significantly lower than their preoperative levels. Ca, P and %BMD showed no significant change from their preoperative levels, although %BMD tended to be higher than its preoperative level. Depending on the presence or absence of osteoarticular pain at the end of the follow-up period, the patients were divided into the improved group and the non-improved group. Of the 5 patients allocated to the non-improved group, 4 were female and only 1 was male. C-PTH and ALP were significantly higher in the non-improved group. %BMD was higher in the improved group than in the non-improved group, although this difference was not significant. In the non-improved group, 2 patients were suspected of having extra parathyroids, 1 was suspected of having recurrence, and 2 were suspected of having postoperative osteomalacia. Postoperative reduction in BMD was only seen in females, suggesting its relationship to postmenopausal osteoporosis.
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PMID:[Long-term effect after total parathyroidectomy with autotransplantation for secondary hyperparathyroidism]. 871 83

Pruritus is a significant symptom among patients receiving hemodialysis. However, its underlying mechanisms remain obscure. Substance P, a neuropeptide, has been implicated in the mediation of pain and some itch sensations. Local application of capsaicin depletes the peripheral neurons of substance P and may block the conduction of pain or pruritus. This study aims to assess the efficacy and safety of capsaicin 0.025% cream in the treatment of hemodialysis-related pruritus and to further explore the underlying pathomechanism. Nineteen hemodialysis patients with idiopathic, moderate (n = 5) to severe (n = 14) pruritus were examined in a double-blind, placebo-controlled, crossover study and 17 of them completed the study. Topical agent of capsaicin or placebo base cream was applied to localized areas of pruritus 4 times a day. The severity of pruritus and treatment-related side effects (cutaneous burning/stinging sensations, dryness, or erythema) were evaluated weekly. The results showed (1) that 14 of 17 patients reported marked relief and 5 of these 14 patients had complete remission of pruritus during capsaicin treatment (Wilcoxon signed-ranks test, 2p < 0.001); (2) capsaicin was significantly more effective than placebo (Mann-Whitney rank sum test, 2p < 0.001) and a prolonged antipruritic effect was observed 8 weeks posttreatment; (3) no serious side effects were noted during the study and (4) there were no significant changes in serum concentrations of albumin, calcium, phosphorus, alkaline phosphatase, or intact parathyroid hormone during the treatment with either capsaicin or placebo. In summary, the present study indicates indirectly that idiopathic pruritus in some patients on maintenance hemodialysis may be transmitted by substance P from the peripheral sensory neurons to the central nervous system. Topical capsaicin with the unique pharmacological effect is demonstrated to markedly improve the pruritus of these patients.
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PMID:Hemodialysis-related pruritus: a double-blind, placebo-controlled, crossover study of capsaicin 0.025% cream. 873 Apr 31


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