Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In untreated patients with inoperable lung cancer, serum levels of alpha1-antitrypsin were found significantly increased in comparison to patients with non malignant diseases of the lung, alpha2-macroglobulin levels were unchanged in both groups of patients. There was also no difference in alpha2-macroglobulins in cancer patients reacting with DNCB and in non-reactors. Thus alpha2-macroglobulin levels do not seem to correlate with the immunestatus of cancer patients. Proteinase inhibitors are involved in a variety of biological processes including blood, clotting, digestion, and sperm capacitation. alpha1-antitrypsin, a alpha-globulin with a molecular weight of about 60,000 has been found to be decreased in patients' serum under several pathological conditions. A clear correlation exists between alpha1-antitrypsin deficiency and hereditary pulmonary emphysema (1, 2), respiratory distress syndrome (3), and juvenile cirrhoses of the liver (4). Elevated serum levels of alpha1-antitrypsin have also been found in some cancer cases. Thirty years ago a cancer test was developed on the basis of differences in the antiproteolytic activity in cancer patients' sera and in patients with other non-neoplastic diseases (5, 6). Several authors have tried to confirm these early data regarding specifity and sensitivity with respect to a screening test for cancer (7, 8). Methods of these authors were based mainly on enzyme substrate inhibition assays by addition of the patients' sera. Recently a commercially available test, based on immune-precipitation according to Mancini (9), has been developed (Behring-Werke, Partigen). By using this standardized method for determinating alpha1-antitrypsin, Harris et al. have recently demonstrated that patients with inoperable lung cancer have significantly elevated levels of this antiprotease in their sera (10), in comparison to patients with non malignant diseases of the lung. alpha2-macroglobulin is a serum protein with a molecular weight of 800,000 and with known antiprotease activity and can therefore bind trypsin, plasmin, elastase, and collagenase and it is known that alpha2-macroglobulin decreases with increasing of age. Changes of alpha-macroglobulin have also been observed in several pathological conditions (11). James et al. 4ave found decreases in serum of myeloma patients (12). An association between the development and function of lymphocytes and alpha2-macroglobulin has been suggested by several authors (13, 14). This alpha2-globulin has also been demonstrated on the surface of peripheral blood lymphocytes (15) and there is evidence that it is synthesized by lymphocytes (16). The purpose of the present study was to determine serum alpha1-antitrypsin levels in patients with inoperable lung cancer and to determine whether there is also an inverse correlation to alpha2-macroglobulin. It was further attempted to correlate alpha2-macroglobulin with general immunological parameters, as it is known that patients with lung cancer show a decreased general immune-reactivity (17).
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PMID:Serum levels of alpha1-antitrypsin and alpha2-macroglobulin in lung cancer. 6 86

A case of multiple nodular pulmonary amyloidosis in a 54-year-old Caucasian man is presented. Discrete symptomless radiodensities had developed in this patient's lungs within a period of three years, leading to a suspicion of a neoplastic process. The amyloid nature of these nodules was demonstrated by biopsy. In this case, as in others previously reported, there was no evidence of systemic disease, and immunoglobulins were normal. Local factors probably play an important part in the pathogenesis of this disease. This entity is to be distinguished from the diffuse type of pulmonary amyloidosis, which has a far graver prognosis. Diffuse alveolar septal amyloidosis is usually associated with primary systemic amyloidosis or multiple myeloma and leads rapidly to respiratory distress.
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PMID:Multiple nodular pulmonary amyloidosis. A case report and comparison with diffuse alveolar-septal pulmonary amyloidosis. 117 15

Several studies have been performed in the last ten-years on the biochemical and physiopathologic properties of angiotensin-converting enzyme (ACE). Human lung and kidney are a rich source of ACE and the enzyme is bound to the plasma-membrane of vascular endothelial cells; however, the small intestine and the choroid plexus are also particularly rich in ACE, where it is concentrated on the surface of cuboidal epithelial cells facing the cerebrospinal fluid. The ACE is a glycoprotein with a molecular weight of 150,000 daltons and it cleaves C-terminal dipeptides of several oligo-peptides, including angiotensin I and bradykinin. It catalyzes conversion of angiotensin I to angiotensin II and induces inactivation of bradykinin. Synthetic acylated tripeptides such as radiolabelled hippuryl-histidyl-leucine and hippuryl-glycyl-glycine have been found to be the most suitable substrates for determining the activity of ACE with radiochemical assays. The mean-normal values for ACE activity is 25 U/ml; there are no significant differences in ACE activity between different sexes and races, but there is significant decrease in adults. The measurement of ACE activity in sarcoidosis suggests the following results: 1) There is a relationship between the increased SACE and LACE activity and active disease and between normal ACE activity and inactive disease. 2) Normal or decreased ACE activity is useful for therapeutic evaluation of sarcoidosis. 3) Increased SACE activity can be a sensitive parameter for predicting clinical relapse of the disease. An increased SACE activity is found in a wide variety of non-sarcoid granulomatous diseases and non-granulomatous systemic diseases. A decreased SACE and LACE activity is found in non-granulomatous pulmonary diseases such as "Adult Respiratory Distress Syndrome", lung cancer and lung toxicity caused by antineoplastic drugs. Moreover, a low preoperative SACE is associated with poor prognosis in lung cancer and its levels may be useful for predicting clinical relapse of this disorder after operation. Finally, a low SACE activity is found in malignant lymphomas, leukemia and multiple myeloma. A relationship is also found between decreased enzyme activity and a poor prognosis and clinical relapse of these diseases.
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PMID:[ACE: physiopathology and role in the diagnosis and prognosis of systemic granulomatosis, neoplasms and lung toxicity caused by antineoplastic agents]. 217 27

A toxic phospholipase A2 (PLA2) was isolated from Taiwan-habu-snake (Trimeresurus mucrosquamatus) venom by sequential chromatographies on CM-52, Sephadex G-75 and S-Sepharose columns. This basic PLA2 has a single polypeptide with an estimated M(r) of 15,000. The PLA2 activity was Ca(2+)-dependent and inactivated by p-bromophenacyl bromide and its specific antibody. The toxic PLA2-induced myotoxic and direct haemolytic effects as well as respiratory distress in mice with an intraperitoneal LD50 of 1.17 micrograms/g body weight. The histological examination showed it caused haemorrhage and congestion in the viscera of mice. It was also cytotoxic to myeloma cells (NS-1), baby-hamster-kidney (BHK) cells and human umbilical endothelial cells. By neutralization experiments with a specific antibody against toxic PLA2, it was found that the enzymic activity of toxic PLA2 is essential for its myotoxicity, but it is not the only factor responsible for the lethal toxicity.
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PMID:Isolation and characterization of a toxic phospholipase A2 from the venom of the Taiwan habu (Trimeresurus mucrosquamatus). 813 82

In this prospective, multicenter, phase 2 study, multiple myeloma (MM) patients with primary resistant disease or recurrent chemosensitive disease, in chemoresistant relapse, or in second or subsequent remission were treated with high-dose chemoradiotherapy followed by autologous peripheral blood stem cell (PBSC) rescue. PBSCs were collected using granulocyte-macrophage colony-stimulating factor (GM-CSF) 5 microg/kg per day subcutaneously for 3 days. Patients underwent high-dose chemoradiotherapy consisting of melphalan (140 mg/m2 x 1 day), cyclophosphamide (60 mg/kg per day x 2 days), methylprednisolone (2 g/d x 7 days), and total body radiation (150 cGy bid x 3 days) followed by peripheral blood stem cell reinfusion (> or = 1.2 x 10(9) mononucleated cells per kg) and GM-CSF support (5 microg/kg per day) and were evaluated for response, survival, and toxicity. Thirty-six patients, median age 53.4 years, completed the study. The mean pretransplantation cumulative melphalan dose was 464 +/- 72 mg. Excluding the 3 patients (8.3%) who failed to engraft, the median times to engraftment and platelet recovery were 10 days (range, 8-39 days) and 17 days (range, 7-67 days), respectively. Four patients (11.1%) died of complications related to the regimen (main causes of death, sepsis and acute respiratory distress syndrome) within the first 100 days. Twenty-two patients (61.1%) achieved complete response (CR), 8 (22.2%) partial response, and 2 (5.5%) no response. Two patients developed myelodysplastic syndrome after achieving CR. For all 36 patients, the probability of overall survival at 5 years was 27.3%. Median survival was 31 months (range, 0.3-81 months) in all patients and 42 months (range, 3.4-81 months) in those with CR. The probabilities of overall and disease-free survival at 5 years for the 22 patients who achieved CR were 43.6% and 15.7%, respectively. This high-dose chemotherapy regimen coupled with PBSC rescue is associated with a high CR rate and is capable of inducing long-term survival in a subset of heavily pretreated patients with primary resistant or recurrent MM.
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PMID:Treatment of primary resistant or relapsed multiple myeloma with high-dose chemoradiotherapy, hematopoietic stem cell rescue, and granulocyte-macrophage colony-stimulating factor. 1097 14

From January 1999 to May 2000 (17 months), 21 strains of streptococci and four strains of enterococci have been isolated from 74 blood cultures in 25 infectious episodes in hematologic patients. They concerned 21 patients, of 21 to 77 years old. These patients suffered from acute leukaemia (14 cases), chronic lymphoid leukaemia (two cases), non-Hodgkin's lymphoma (two cases) or myeloma (three cases). Seventeen patients displayed a single streptococcal or enterococcal episode, two had two episodes in the course of a single stay in the hospital, two others in the course of two different stays. During 16 episodes (64%), the bacteremia occurred within 15 days after the onset of neutropenia consecutive to antimitotic chemotherapy, and in nine episodes (36%) it has occurred after a period exceeding 15 days. In six cases the patients had already received antibiotics with a large antibacterial activity (beta-lactam, fluoroquinolone and/or glycopeptide +/- aminoside) and in four cases a single antibiotic (synergistine or cotrimoxazole). Most streptococci (20/21) were oral streptococci (ten Streptococcus mitis, five S. oralis, two S. sanguis, three S. pneumoniae). A single strain of beta-hemolytic streptococci has been identified as S. dysgalactiae subsp. equisimilis. The enterococci were one strain of Enterococcus faecalis and three E. faecium. Ten streptococci were susceptible to 0.25 mg/L of penicillin G, ten were less susceptible (0.5 < or = MIC < 32 mg/L), and a strain was resistant (MIC = 32 mg/L). Eighteen strains were susceptible to amoxicillin and cefotaxime. For three strains, the MICs of amoxicillin and cefotaxime (8-16 mg/L and 8-32 mg/L, respectively) were higher. Levels of resistance of the enterococci to the beta-lactam (penicillin, amoxicillin, and piperacillin) were variable. All species were susceptible to glycopeptides. Three patients were transferred in intensive care unit for respiratory distress or shock syndrome. Their evolution has remained severe under antibiotherapy comprising beta-lactam or vancomycin associated with an aminoside. This results demonstrate the interest of species identification to adapt the antibiotic treatment and confirms the frequency of oral streptococci in severe bacteremia in neutropenic patients.
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PMID:[Therapeutic impact of streptococcal and enterococcal bacteremia in hematology patients]. 1198 Mar 30

Pulmonary involvement with multiple myeloma occurs infrequently and may be difficult to distinguish from more common primary lung tumours, metastatic disease, or other pleural and parenchymal abnormalities. A patient who developed acute respiratory distress syndrome (ARDS) was subsequently found to have multiple myeloma with involvement of lung parenchyma by neoplastic plasma cells. Only one other report of ARDS in association with multiple myeloma was found, and there are no previous reports where the appearance of ARDS antedated a diagnosis of multiple myeloma. In patients with ARDS, parenchymal involvement from multiple myeloma should be included in the differential diagnosis.
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PMID:Acute respiratory distress syndrome due to pulmonary involvement by neoplastic plasma cells in multiple myeloma. 1664 54

Bortezomib is a proteosome inhibitor with good clinical activity in multiple myeloma. Frequently described side effects are gastrointestinal symptoms, neuropathy, and thrombocytopenia. Even though pneumonia is listed as an infrequent toxicity, severe pneumonitis leading to respiratory distress had not been described until recently. This report was from a single institution in Japan. All these patients had received bone marrow transplant before therapy with bortezomib. To the authors knowledge, this is the first report of life-threatening pulmonary toxicity after bortezomib in a non-Japanese patient and without history of prior autologous peripheral stem cell transplant.
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PMID:Severe pulmonary complications in African-American patient after bortezomib therapy. 1712 39

We report a donor death after right hepatectomy for living donor transplantation due to an undiagnosed myeloma. The 47-year-old donor, who was the 147th case performed in our department, was in excellent health without any abnormalities in the preoperative investigations. Despite an uneventful right hepatectomy without transfusion, the patient developed a partial thrombus of the inferior vena cava with a right proximal pulmonary trunk embolism on postoperative day 6. Subsequently, he developed multiorgan dysfunction leading to a coagulopathy, respiratory distress, and renal failure requiring hemodialysis and mechanical ventilation. This clinical scenario led us to suspect a hematological disorder. Immune electrophoresis showed a monoclonal peak of immunoglobulin G (8.7 g/L), a myelogram revealed an abnormally high level of dystrophic plasmocytes (more than 7%), and biopsies of salivary glands confirmed the diagnosis of immunoglobulin G kappa myeloma. The patient progressively deteriorated because of simultaneous hemorrhagic and infectious pulmonary complications resulting in septic shock. Despite an adequate combination of antimicrobial therapy and pleural drainage, the donor died on postoperative day 57 from multiple organ failure. This unusual cause of donor death after right hepatectomy reinforces the need for an extensive preoperative assessment. We advocate the addition of urinary protein loss and electrophoresis to the standard donor assessment protocol.
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PMID:Living liver donor death related to complications of myeloma. 1924 91

A male, 62-year-old patient presented with chest pain with no apparent cause. Imaging studies revealed solution of continuity of the bone tissue at the level of the sternum, which led to paradoxical respiration. Open reduction and fixation with an LCP plate and screws were performed to address the problem. An important part of the patient's history was lumbar pain treated conservatively with analgesics and muscle relaxants. The pain did not subside and X-rays were done with findings of osteolysis in several parts of the body. The patient had chest pain and respiratory distress and was referred for management. Sternum fractures occur occasionally and are due to high-energy trauma or sports accidents. Treatment is conservative in most cases or may consist of a wire cerclage. Treatment was aimed at fixing the sternum to improve ventilatory mechanics so that the patient could continue with background therapy for multiple myeloma. At 18 weeks the patient is doing fine, X-rays show grade IV healing, and he will go on to the second stage of radiotherapy.
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PMID:[Spontaneous sternum fracture in a pathologic area. Case report and literature review]. 2037 63


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