Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten consecutive patients with metastatic gastrinoma that increased in size over time were studied prospectively during treatment with monthly cycles of streptozotocin (3 g/m2), 5-fluorouracil (1.2 g/m2), and adriamycin (40 mg/m2) to determine the response rate and time-courses of changes during chemotherapy and to assess various methods of evaluating the effect of chemotherapy. Forty percent of patients demonstrated an initial objective response (greater than or equal to 25% decrease in tumor size with no new lesions) and 60% failed chemotherapy (greater than or equal to 25% increase in tumor size or appearance of new lesions). The mean dose of streptozotocin was 27 g/m2 with objective responses occurring at 3.7 +/- 0.7 mo and failures at 4.5 +/- 0.7 mo. Responses lasted 9.7 +/- 2.8 cycles and no complete responses occurred. Survival was not significantly different in responders versus nonresponders (26 +/- 11 vs. 15 +/- 4.8 mo, p greater than 0.1). Changes in serum gastrin concentration, basal acid output, or sensitivity to a given dose of histamine H2-receptor antagonist did not reflect changes in tumor size. Computed tomography and angiography were the best methods to assess changes in tumor size during chemotherapy, whereas liver-spleen scan and ultrasound were relatively insensitive. All patients developed side effects with chemotherapy: 100% had vomiting, 80% alopecia, 40% transient proteinuria, and 20% leukopenia. The present results indicate that chemotherapy with streptozotocin, 5-fluorouracil, and adriamycin is much less effective in patients with extensive metastatic gastrinoma than previously reported. Computed tomography scanning is the method of choice to assess changes in tumor size. Changes in serum gastrin concentration, acid secretion, or tumor size assessed by liver-spleen scan or ultrasound are not sensitive indicators of the tumor response during chemotherapy.
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PMID:Prospective study of chemotherapy in patients with metastatic gastrinoma. 296 88

Renal disease with distinctive pathologic features developed in two young women who had placental site trophoblastic tumors. The renal abnormalities were manifested by proteinuria in both cases and by hematuria in one case; blood pressure was elevated in one of the patients. Pathologic examination of the kidneys showed distinctive glomerular abnormalities, characterized mainly by the presence of occlusive eosinophilic deposits in many of the glomerular capillary lumina, most of which stained for fibrinogen-related antigens and IgM by immunohistochemical techniques. Ultrastructural examination showed the deposits to consist mainly of granular material that contained packets of fibrillar material with the appearance of fibrin. The uterine tumors were composed of mononucleated and multinucleated cells with abundant cytoplasm that infiltrated between the muscle bundles of the myometrium; in both tumors there was prominent deposition of eosinophilic material that had the tinctorial properties of fibrin and that stained for fibrinogen and IgM in immunoperoxidase studies. The renal abnormalities disappeared after hysterectomy in one case; the other patient, who was receiving chemotherapy and had disseminated intravascular coagulation, died with leukopenia and sepsis. The clinical and pathologic features in these cases suggest that the renal abnormalities were related to the uterine tumors and that the production of immune complexes and/or the activation of intravascular coagulation by the tumors were pathogenetic mechanisms.
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PMID:A distinctive glomerular lesion complicating placental site trophoblastic tumor: report of two cases. 298 14

The antihypertensive effect of enalapril maleate, a new converting enzyme inhibitor, was evaluated in a multiclinic, double-blind, randomized study in patients with mild to moderate essential hypertension. The analyses were done in two ways, with patients who violated the entry criteria of the protocol excluded, and according to the intention to treat principle. Enalapril in dosages of 10 to 40 mg daily administered alone or concomitantly with hydrochlorothiazide was compared to propranolol (80 to 240 mg daily) alone or concomitantly with the diuretic. The study showed that enalapril significantly lowered both systolic and diastolic blood pressure. At each timepoint measured in the course of 26 weeks of therapy, the patients in the enalapril group consistently had greater decreases in blood pressure than patients in the propranolol group although not always significantly. The enalapril treatment group had a decrease in the mean arterial blood pressure of 22.2 mmHg compared to the propranolol group of 17.9 mmHg at the end of the study. These results were similarly independent of the way the data were analyzed. Fewer patients in the enalapril group required the addition of hydrochlorothiazide to maintain optimal control of blood pressure. Enalapril was found to be safe and well tolerated over the long-term of 48 weeks. Side effects such as leukopenia and taste perversions believed to be sulfhydryl-related were not encountered. The occurrence of rash and proteinuria was rare. Thiazide-induced hypokalemia, hyperuricemia and hyperglycemia appeared to be attenuated by enalapril. The favorable efficacy and side-effect profile provide the basis for enalapril to be a drug of choice when initiating antihypertensive therapy.
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PMID:Long-term enalapril--a new converting enzyme inhibitor--in the treatment of mild to moderate essential hypertension, results of a worldwide multiclinic study. Comparing two ways of analyzing data. 300 72

Twenty-five patients with gastrointestinal tumors (stomach 13, colon 8, pancreas 2, liver 2) were treated with a combination chemotherapy regimen consisting of CDDP (30 mg/m2/day d 1, 2) and 5-FU (500 mg/m2/day d 1-3), repeated every 3 or 4 weeks. The patients comprised 14 males and 11 females with a median age of 50 years (range 24-69), and a median performance status of 80% (range 40-100%). Thirteen patients had had prior chemotherapy. Partial response was observed in 2 patients (colon and liver), which lasted for 2 months each, respectively. No objective response was observed in 11 patients evaluable for gastric cancer. Non-hematological toxicities were nausea (92%), vomiting (56%), proteinuria (17%), transient elevation of BUN (8%), and hepatotoxicity (11%). Leukopenia and thrombocytopenia were observed in 71% and 25%, respectively. However, these toxicities were mild to moderate, and generally well tolerated.
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PMID:[Combination chemotherapy of cis-diamminedichloroplatinum (CDDP) and 5-fluorouracil (5-FU) in gastrointestinal tumors]. 301 30

A 9-year-old dog with a 2-month history of weight loss and a 1-week history of blindness had an IgA-forming myeloma. Seemingly, the blindness was a result of bilaterally detached retinas. The dog also had leukopenia, anemia, hypoalbuminemia, hyperglobulinemia, and proteinuria as well as lytic lesions in the cervical portion of the spine and high IgA concentrations in serum and urine. Evaluation of aspirates from the subretinal spaces revealed lymphocytes in a proteinaceous fluid. Histologically, retinal lesions consisted of vascular endothelial cell damage and intraretinal cysts and hemorrhages.
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PMID:Blindness in a dog with IgA-forming myeloma. 318 88

Systemic lupus erythematosus (SLE) is considered to be the quintessential autoimmune disease. It has not been possible to induce SLE in animal models by DNA immunization or by challenge with anti-DNA antibodies. We herewith report a murine model of SLE-like disease induced by immunization of C3H.SW female mice with a common human monoclonal anti-DNA idiotype (16/6 idiotype). Following a booster injection with the 16/6 idiotype, high levels of murine anti-16/6 and anti-anti-16/6 antibodies (associated with anti-DNA activity) were detected in the sera of the immunized mice. Elevated titers of autoantibodies reacting with DNA, poly(I), poly(dT), ribonucleoprotein, autoantigens [Sm, SS-A (Ro), and SS-B (La)], and cardiolipin were noted. The serological findings were associated with increased erythrocyte sedimentation rate, leukopenia, proteinuria, immune complex deposition in the glomerular mesangium, and sclerosis of the glomeruli. The immune complexes in the kidneys were shown to contain the 16/6 idiotype. This experimental SLE-like model may be used to elucidate the mechanisms underlying SLE.
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PMID:Induction of a systemic lupus erythematosus-like disease in mice by a common human anti-DNA idiotype. 325 23

Data about adverse events can be particularly useful when assessing newly marketed drugs. However, spontaneous reporting of adverse events does not generally provide sufficient or highly accurate data on incidence and prevalence. In order to provide the most complete and accurate data, a postmarketing surveillance program (PMSP) for auranofin (AF) oral gold therapy for rheumatoid arthritis (RA) was conducted in the Federal Republic of Germany (FRG) from December 1982 through December 1985. The objectives of the program were to observe a large population treated with AF for more than a year; to compare the safety profile of AF with experience from clinical trials; and to register rare or previously unknown adverse events. The program included 2,777 patients with RA from 928 test centers. Disease duration was less than 2 years in 29%. 2-5 in 23.2%, 5-10 in 32.5%, and more than 10 in 13.3% (no data for 2%); disease was mild or moderate in 67.4% and severe in 29.9% (no data for 2.7%). Auranofin was given 6 mg/day as either two 3-mg tablets at breakfast or 1 tablet at breakfast and 1 at the evening meal. Laboratory studies and efficacy, as indicated by increase in grip strength and decrease in number of tender and swollen joints, were monitored regularly. A total of 1,595 patients completed 1 year of treatment with AF. Withdrawals included 12.9% for adverse events, 4.2% for insufficient therapeutic effect, and 33.1% for a variety of administrative or technical reasons. The most common adverse event was alteration in stool pattern, which occurred in 22.5% of patients, compared with 46.6% in worldwide AF clinical trials. Other gastrointestinal symptoms occurred in 17.4%, compared with 22.4% worldwide. The occurrence of most adverse events in the PMSP was much less than in worldwide studies, for example: skin rash 7.3% vs. 24.2% worldwide, pruritus 4.2% vs. 16.6%, proteinuria 1.0% vs. 5.0%, and leukopenia 0.7% vs. 1.9%. These discrepancies may be explained by the method of monitoring employed in the postmarketing study, which favored the reporting of only clinically relevant adverse events. The pattern of occurrence of adverse events was similar to that seen during other AF trials, indicating that any intolerance to AF occurs primarily within the first 6 months of treatment. However, hematologic or nephrologic adverse events appear to be independent of time on therapy, with a constant monthly prevalence of about 0.1-0.2%.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Postmarketing experience with auranofin in the Federal Republic of Germany. 329 83

An examination of the principal physiological actions of angiotensin II should make it clear why in vivo attempts to inhibit the rate of angiotensin II generation have been an attractive avenue in pursuing control of high blood pressure. The major physiological effect of angiotensin II relates to its direct pressor effect, but there are supplementary blood pressure regulating actions. Therefore, if we limit the rate of angiotensin II generation by inhibiting the angiotensin converting enzyme (ACE) we should expect to control high blood pressure in a number of clinical syndromes. This paper reviews the future of ACE inhibitors in the treatment of conditions such as hypertension associated with unilateral renal artery stenosis, essential hypertension and severe and previously unresponsive hypertension, with respect not only to efficacy but also to the side-effect profile and ancillary properties. Side effects seen with this class of drug are cough, rashes (both morbilliform and urticarial) and, rarely, angio-oedema. Proteinuria, nephrotic syndrome, leukopenia and taste disturbance were previously reported with captopril but only taste disturbance, and that less frequently, is apparent at the lower doses now employed. Several studies have examined the 'quality-of-life' aspects of ACE therapy and have usually but not always reported favourably. There are features of the ACE inhibitors which make them attractive drugs, and while we should be cautious because of limited experience, we should critically and creatively examine their properties over the next years.
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PMID:Angiotensin converting enzyme inhibition in hypertension. 331 25

Diagnosis of multiple myeloma is based on the triad paraproteinemia, osteolytic bone lesions and bone marrow plasma cell infiltration. Clinically, rheumatoid-like pain induced by osteolytic skeletal lesions often prevails. Occasionally, foudroyant bacterial infections - the most frequent cause of death in myelomatosis - or acute/subacute renal failure or rarely, acute hemi- or paraparesis precede diagnosis. Establishment of diagnosis early in the course of the disease and improved cytostatic and symptomatic treatment has led to a decrease in episodes of hyperviscosity-syndromes. Severe renal insufficiency due to Bence-Jones proteinuria prevails in 20% of patients already at time of diagnosis. With increasing duration of the disease, frequency of renal insufficiency further increases. Hypercalcemia with consecutive dehydration and renal insufficiency usually is a complication of long-standing disease. Anemia, leukopenia and thrombo-cytopenia are not only side effects of cytostatic treatment, but also consequences of tumor-induced suppression of hematopoiesis. Polyneuropathies are common in myelomatosis. They probably are the result of specific and/or unspecific binding of paraproteins to myelin sheaths. Effective treatment for this complication is not available at present. Thrombohemorrhagic complications are more frequent in patients with myeloma than in the control group of other hospitalized patients. Non-secretory myeloma, osteoblastic myeloma and Takatsuki syndrome are variants of myelomatosis. Solitary and extramedullary plasmocytoma are different, potentially curable entities. Prognosis is especially poor in patients with plasma cell leukemia and poor in primary amyloidosis.
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PMID:[The clinical picture of multiple myeloma]. 353 47

To understand the role of neutrophil leukocytosis in hemolytic uremic syndrome, we studied the changes in neutrophil function in the modified generalized Shwartzman reaction in rabbits. This model resembles hemolytic uremic syndrome associated with endotoxemia. At the end of an endotoxin infusion, we observed leukopenia, thrombocytopenia, and a decrease in hematocrit associated with schistocytosis. Plasma B-glucuronidase levels increased and this was associated with a decrease in neutrophil content of the enzyme. The chemotactic index and neutrophil aggregation to zymosan-activated serum were impaired compared to controls. The neutrophil procoagulant content increased after endotoxin infusion. The serum creatinine concentration and proteinuria increased in the endotoxin-treated animals. The changes returned to normal by 48 h. Renal cortical malondialdehyde, a reflection of lipid peroxidation, was higher in the endotoxin-treated animals than in the controls. We have shown enzyme release by neutrophils, impairment of chemotaxis and aggregation, increased procoagulant content in neutrophils, and evidence of lipid peroxidation in renal cortical tissue in this model. These observations raise the possibility that leukocytes may have a role in the pathogenesis of the hemolytic uremic syndrome.
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PMID:Neutrophil function in an experimental model of hemolytic uremic syndrome. 355 Jun 73


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