Gene/Protein Disease Symptom Drug Enzyme Compound
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 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anaplastic large cell Ki-1 lymphoma is an uncommon type of non-Hodgkin's lymphoma that rarely presents primarily in the bone. Three such cases are reported. All patients were young and had bone pain; one had paraparesis as a complication of collapse of the thoracic vertebral body. The involvement was either monostotic or polyostotic. Radiologically, the lesions were lytic and had ill-defined borders. Histologically, the large neoplastic cells had pleomorphic bizarre nuclei, prominent nucleoli, abundant deeply amphophilic cytoplasm, and paranuclear pale hof. They were admixed with variable numbers of inflammatory cells. One case each was of T-cell, B-cell, and non-T non-B lineage. All three cases showed excellent responses to chemotherapy with or without radiation therapy. Recognizing the lymphomatous nature of this highly pleomorphic tumor is important because of its potential curability with appropriate chemotherapy.
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PMID:Anaplastic large cell Ki-1 lymphoma of bone. 165 5

The patient presenting with severe bone pain after primary hormonal therapy, with vertebral collapse, or with uremia resulting from ureteric obstruction should be considered for intravenous stilbestrol diphosphate therapy. The urologist can expect early marked improvement in the patients' mobility and pain, with a reduction in analgesic requirements, from a single 7-day course of treatment. In addition, the drug is inexpensive and free of the side effects commonly associated with cytotoxic therapy. Accurate monitoring of the response is possible with serum prostate-specific antigen measurements, which also enable further therapy to be planned efficiently.
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PMID:Use of intravenous stilbestrol diphosphate in patients with prostatic carcinoma refractory to conventional hormonal manipulation. 199 67

Of 297 patients with metastatic testicular and extragonadal germ cell tumours (GCT), bone involvement was detected clinically in 3% (7/251) of those at first presentation and in 9% (4/46) of relapsed cases. This difference was not statistically significant (95% confidence limits -2%; +14%). Concurrent systemic metastases, commonly involving lung (7/11 cases) and para-aortic lymph nodes (6/11), were present in all patients with bone disease. All affected patients had localized bone pain and lumbar spine was the most frequent site involved (9/11). Spinal cord compression occurred in two patients while a third developed progressive vertebral collapse after chemotherapy and required extensive surgical reconstruction. At median follow-up of 4 years, survival among patients presenting with bone disease (6/7) was similar to overall survival in the whole group (84%) and appeared better than in those with liver (18/26, 69%) or central nervous system (6/9) metastases at presentation. Back pain in metastatic germ cell tumours is often due to retroperitoneal lymphadenopathy but lumbar spine osseus metastases must be recognized early if severe potential complications, such as spinal cord compression, are to be avoided. In this series, bone metastases were not seen in the absence of widespread systemic disease suggesting all solitary bony lesions in GCT patients should be biopsied.
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PMID:Bone disease in testicular and extragonadal germ cell tumours. 322 81

Acid phosphatase activity was determined in serum, cultured fibroblasts, and peripheral blood lymphocytes of six splenectomized adult patients with non-neuropathic Gaucher disease in two Canadian families. Elevated levels of serum acid phosphatase activity (520-711% of normal) were found in four patients who also developed orthopedic complications associated with Gaucher disease, including intermittent bone pain, arthritis, collapse of femoral head, and pathological fractures. Serum acid phosphatase activity in two patients who do not have bone involvement were found to be within the normal range. Contrary to the serum enzyme, acid phosphatase activity in lymphocytes and cultured fibroblasts of all of the patients was within the normal range. Deficient glucocerebrosidase (7.5-15.5% of normal) and acid beta-glucosidase (13.8-27.8% of normal) activities were noted in all probands. Similarly, normal levels of fibroblast and lymphocyte acid phosphatase activity were found in Gaucher heterozygotes whose glucocerebrosidase activity was about 50% of normal. Acid polyacrylamide gel electrophoresis and acid phosphatase activity staining of the patients' sera showed that the elevated acid phosphatase is isozyme type 5 osteoclastic origin. The apparent Michaelis constant, Km, of fibroblast glucocerebrosidase for the natural substrate was 0.6 +/- 0.1 mM for controls and 0.6 +/- 0.2 mM for the patients. These data suggest that the assay of serum acid phosphatase activity for the presumptive diagnosis of Gaucher disease is not completely reliable and that the elevated level of serum acid phosphatase in Gaucher disease is most likely a secondary phenomenon which may be indicative of bone involvement in some patients with this disorder. It also demonstrates the clinical heterogeneity of type 1 Gaucher disease, even among full sibs of the same heterozygous parents.
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PMID:Gaucher disease: comparative study of acid phosphatase and glucocerebrosidase in normal and type-1 Gaucher tissues. 402 86

The presence of bone metastases predicts the presence of pain and is the most common cause of cancer-related pain. Although bone metastases do not involve vital organs, they may determine deleterious effects in patients with prolonged survival. Bone fractures, hypercalcaemia, neurologic deficits and reduced activity associated with bone metastases result in an overall compromise in the patient's quality of life. A metastasis is a consequence of a cascade of events including a progressive growth at the primary site, vascularization phase, invasion, detachment, embolization, survival in the circulation, arrest at the site of a metastasis, extravasion, evasion of host defense and progressive growth. Once cancer cells establish in the bone, the normal process of bone turnover is disturbed. The different mechanisms responsible for osteoclast activation correspond to typical radiologic features showing lytic, sclerotic or mixed metastases, according to the primary tumor. The release of chemical mediators, the increased pressure within the bone, microfractures, the stretching of periosteum, reactive muscle spasm, nerve root infiltration and compression of nerves by the collapse of vertebrae are the possible mechanisms of malignant bone pain. Pain is often disproportionate to the size or degree of bone involvement. A comprehensive assessment including a trusting relationship with the patient, taking a careful history of the pain complaint, the characteristics of the pain, the evaluation of the psychological status of the patient, neurological examination, the reviewing of diagnostic studies and laboratory findings, and individualization of the therapeutic approach, should precede any treatment. Radiotherapy is the cornerstone of the treatment. Low doses given in a single session are safe and effective, and reduce distress and inconvenience associated with repeated session. Radioisotopes are more imprecise in delivering specific doses of radiation, but have less toxicity and easy administration as well as effectiveness in subclinical sites of metastases, although storage, dispensing and administration should be under strict control. Chemotherapy and endocrine therapy are difficult to measure in terms of pain relief. Prophylactic fixation surgery can lead to improved survival and quality of life of patients with bone metastases. Surgical treatment should be undertaken when fracture occurs. Careful selection of patients for surgical spinal decompression is required. The potential benefits of surgical interventions have to be tempered with patient survival. The use of analgesics according to the WHO ladder is recommended. There is no clear evidence that non-steroidal anti-inflammatory drugs (NSAIDs) have a specific efficacy in malignant bone pain. The difficulty with incident pain is not a lack of response to systemic opioids, but rather that the doses required to control the incidental pain produce unacceptable side-effects at rest. Alternative measures are often required. The inhibition of bone resorption and hypercalcaemia can be reduced by the use of bisphosphonates. This class of drugs potentiate the effects of analgesics in improving metastatic bone pain. Invasive techniques are rarely indicated, but may provide analgesia in the treatment of pain resistant to the other modalities. Neural blockade should never be used as the sole modality for malignant bone pain, but should be considered as a helpful in specific pain situations. Careful appraisal and the application of a correct approach should enable the patient with bone metastases to obtain an acceptable pain relief despite the advanced nature of their malignant disease.
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PMID:Malignant bone pain: pathophysiology and treatment. 906 7

The skeleton is a common site of breast carcinoma metastasis; 75% of patients with breast carcinoma demonstrate bone metastases at autopsy. The lytic destruction of bone in these patients is due to excessive osteoclastic activity. By reducing osteoclastic activity, bisphosphonates inhibit bone resorption. Initial studies of breast carcinoma patients were performed with clodronate, a first-generation bisphosphonate. Studies with small cohorts suggested reduction of pain, analgesic requirement, and development of hypercalcemia. A larger randomized, double-blind, placebo-controlled trial of oral clodronate 1600 mg/day demonstrated a significant reduction of the combined rate of all morbid skeletal events (significant reduction of the incidence of vertebral fractures, rate of vertebral deformity, and hypercalcemic episodes). Trends were observed that favored clodronate for the treatment of nonvertebral fractures and radiotherapy for relief of bone pain. There was no survival difference between the clodronate and placebo groups (Paterson et al., J Clin Oncol 1993;11:59-65). Pamidronate is a second-generation aminobisphosphonate that is a much more potent inhibitor of osteoclastic activity. Phase II studies again suggested an improvement in many of the skeletal complications of breast carcinoma. Two large Phase III studies have recently been completed. Women with Stage IV breast carcinoma who were receiving cytotoxic chemotherapy (380 patients) or endocrine therapy (371 patients) and had at least 1 lytic bone lesion were given either pamidronate 90 mg as a 2-hour infusion monthly for 2 years or a placebo infusion. After the two studies were pooled, 367 patients treated with pamidronate and 384 patients given placebo were available for analysis. The median time to first complication (pathologic fracture, vertebral collapse, spinal cord compression, or treatment of bone with radiation or surgery) was 12.7 months for the pamidronate patients and 7.0 months for placebo patients (P = 0.001). The time to first fracture was 25.2 months for pamidronate patients and 12.8 months for placebo patients (P = 0.003). The proportion of patients with fracture was 40% for pamidronate vs. 52% for placebo (P = 0.002); the proportion with radiation administered to bone was 29% for pamidronate vs. 43% for placebo (P = 0.001); and the proportion with any skeletal event was 51% for pamidronate vs. 64% for placebo (P = 0.001). The skeletal morbidity rate (the number of complications per year) at 24 months was 2.4 for the pamidronate group and 3.7 for placebo (P = 0.001). Pain and analgesic use was decreased among the pamidronate patients. There was no difference in survival between the groups. Not all patients responded to the same dose of bisphosphonate. Recent data suggests that patients who have a normalization of their urinary excretion of N-telopeptide have a reduced risk of progression of disease in bone and fracture. In summary, the addition of pamidronate to standard chemotherapy or endocrine therapy produces a sustained reduction in skeletal complications in breast carcinoma patients with osteolytic bone metastases.
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PMID:Bisphosphonates and breast carcinoma. 936 34

Acute lymphatic leukemia presenting with bone pain and spine involvement is a recognized clinicopathologic complex that can mimic a wide range of orthopaedic conditions. Bone pain as the presenting complaint is common, with a reported incidence of 27% to 50%. Radiologic abnormalities associated with leukemia in children has been described previously. In the literature, the incidence of spinal involvement is controversial, but there is agreement that the spine is less commonly involved than are the long bones. At the onset of the disease, only 10% of children have normal peripheral blood counts. If the patient has spinal involvement and a normal leukocyte count, the diagnosis is often unclear. Only three of these patients have been described in the literature; this article adds one more patient with acute lymphatic leukemia with back pain as the main symptom, vertebral collapse, and a normal peripheral blood cell count at the time of initial presentation. It illustrates that delay in diagnosis frequently occurs, with the classic features of the disease being uniformly absent.
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PMID:Vertebral collapse and normal peripheral blood cell count at the onset of acute lymphatic leukemia in childhood. 1064 13

One hundred forty-four patients with breast cancer and osteolytic bone metastases were randomized to receive either oral clodronate 1,600 mg/d (73 patients) or placebo (71 patients), in addition to either chemotherapy or hormonal therapy, for up to 12 months. Patients were withdrawn from the study when the 12 months of treatment had been achieve or a new bone event occurred, which was defined as: hypercalcemia (> 3 mmol/l), increase in, or onset of new bone pain due to metastases, requirement of radiotherapy for bone pain relief, pathological fractures (including vertebral collapse, spinal cord compression) or death due to bone metastases. Patients are well balanced according to age, performance status, bone condition, except for fractures, more frequent in the clodronate group (25% vs 12%). Of the 137 evaluable patients, 69 received oral clodronate and 68 placebo. Clodronate significantly delayed the median time to onset of new bone events compared to placebo, respectively 244 days and 180 days (p = 0.05). Hypercalcemia did not occur in the clodronate group but was observed in four placebo-treated patients. Clodronate-treated patients had a significant reduction in pain intensity compared to placebo (p = 0.01; measured using a visual pain scale) and significantly fewer patients receiving clodronate required analgesics (p = 0.02). The evaluation of global efficacy by physicians and patients indicated that clodronate was more efficacious than placebo (respectively p = 0.02 and p = 0.01). No significant difference in incidence of adverse effects was observed between the two groups. Clodronate therapy significantly delayed the occurrence of new bone events in these patients with bone metastases from breast cancer and adds to treatment of malignant osteolysis.
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PMID:[Double-blinded controlled study comparing clodronate versus placebo in patients with breast cancer bone metastases]. 1149 24

Multiple myeloma (MM) is a plasma cell malignancy characterized by infiltration of bone marrow, bone destruction, infiltration of soft tissues with plasma cells, and suppression of normal hematopoiesis. The production of monoclonal immunoglobulins with or without light chains is a major feature of the disease. Full spectrum of plasma cell dyscrasias include monoclonal gammapathy of undetermined significance, smouldering myeloma, indolent multiple myeloma, and fully developed, symptomatic multiple myeloma. The usual presenting features of MM include bone pain, weakness, fatigue, fever and infection. Neurologic symptoms are less common but one must not forget that MM may present with a neurologic disease. Careful neurologic history and examination are mandatory in patients with MM. Neurologic symptoms may be a direct manifestation of MM or may be due to the immune effect of monoclonal proteins directed against different neural structures. Finally, metabolic consequences (uremia, hypercalcemia, hyperviscosity) of MM may produce a broad spectrum of different neurologic symptoms including headache, blurring of vision, drowsiness, precoma, coma, vertigo, ataxia, hemiparesis and epileptiform seizures. The most common location of bone changes in MM is the thoracic spine, where it causes osteolytic changes with consequent compressive fractures. The most disastrous sequel is paraplegia. Multiple vertebral involvement with the evidence of osteolytic changes in other bones is usual, but solitary vertebral myeloma may occur. Myeloma usually involves the bone of the vertebral body and then spreads into the extradural space. However, patients with solitary extradural myeloma have been reported. Skull myeloma is frequently asymptomatic. It may grow externally or, rarely, there is intracranial expansion. Involvement of the cranial nerves is not rare, with II, V, VI, VII and VIII cranial nerves being most often affected. Isolated intracerebral plasmacytomas are extremely rare. Diagnostic approach includes plain X-rays of the skeleton, which was found to be the method of choice for demonstration of osteolytic changes, whereas magnetic resonance with gadolinium enhancement most reliably displays the degree of vertebral involvement and demonstrates any associated soft tissue mass. Current treatment of osteolytic changes in multiple myeloma include chemotherapy, radiotherapy in combination with dexamethasone, monthly infusions of bisphosphonates, surgical decompression, and kyphoplasty. Therapeutic approach is dictated by the presenting symptoms. In case of pain as the predominant symptom, treatment with chemotherapy and radiotherapy may be appropriate. Compressive symptoms are relieved with dexamethasone followed by radiotherapy and chemotherapy. Surgical decompression is used in patients with vertebral collapse and vertebral instability. Kyphoplasty is a new method used in the treatment of osteolytic changes of vertebral bodies. A viscous cement is injected into the cavity by a balloon-like inflatable bone tampon. It has been successfully employed to improve the quality of life, to reduce pain, and to increase overall functioning in patients with vertebral compression fractures by restoring most of the original height of the vertebral body. Bisphosphonates reduce pain associated with osteolytic changes in multiple myeloma, but also significantly reduce skeletal events (pathologic fracture, spinal cord compression, surgery or irradiation of bone) via unknown mechanism. It seems that bisphosphonates, by inhibiting bone resorption, alter the microenvironment in which the MM cells grow.
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PMID:[Neurologic sequelae of bone changes in multiple myeloma and its therapy]. 1263 Mar 41

Despite highly successful treatments for localized prostate cancer, approximately 35% to 40% of men will eventually experience a detectable rise in serum prostate specific antigen. A portion of these men will go on to experience clinically expressed extracapsular disease, with as many as two-thirds having evidence of bone involvement. Diagnosis of skeletal involvement involves serum markers of disease progression and radiological evaluation. Skeletal-related events are numerous and include bone pain, spinal cord compression, vertebral collapse, and pathological fractures. Current treatments for advanced prostate cancer include individual or combined hormonal therapies, chemotherapy, radiotherapy, surgical treatments, and most recently, antiresorptive medications.
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PMID:Metastatic prostate cancer: complications and treatment. 1289 79


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