Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred seventy-six canine lymphomas were classified morphologically using four of the major human lymphoma classification schemes (Rappaport, Lukes-Collins, Kiel, and the Working Formulation). All 176 dogs received the same chemotherapeutic protocol. Sixty-two of these lymphomas had their immunophenotypes established by examination of cell surface markers by automated cytofluorography. Several different morphologic types of canine lymphoma were identified and these were comparable to morphologic categories in human classification schemes. Follicular and low grade lymphomas were rare. The two most common morphologic types were diffuse large cell (centroblastic) and immunoblastic. The Kiel classification appeared to be the most useful human scheme for classifying the canine lymphomas. Cytofluorographic analysis was generally straightforward, and 60 of the 62 lymphomas were placed into one of three immunophenotypic categories: 27 pan-T(LQ1)+SIg+, 21 pan-T(LQ1)-SIg+, and 12 pan-T(LQ1)+SIg-. Two of the lymphomas could not be characterized immunologically because a pre-existing or reactive non-neoplastic population of lymphocytes made interpretation of single cell suspension analysis difficult. The authors identified correlations between morphology and survival and disease-free remission; dogs with high-grade tumors generally survived the longest and had the longest remissions. No correlations were identified between high concentrations of serum lactate dehydrogenase, age, sex, or stage of disease, and morphology, immunophenotype, remission, or survival times. A significant correlation between clinical illness and survival time was documented. The median age of the dogs was nine years, no significant effect of sex on prevalence was observed, and some breeds were significantly overrepresented. Significant morphologic-immunophenotypic correlations included shorter remission and survival times for T-cell tumors than B-cell tumors, and a highly significant correlation between the pan-T(LQ1)+SIg-"T cell" phenotype and hypercalcemia.
 ...
PMID:Lymphomas in dogs. A morphologic, immunologic, and clinical study. 236 61

Carbetimer (carboxyimamidate) is a low molecular weight derivative of ethylene/maleic anhydride polymer. This compound has demonstrated antitumor activity against several animal models with a daily x 5 schedule appearing most effective. A phase I clinical study of the daily x 5 schedule repeated every 28 days was therefore performed. Forty-one evaluable patients received 66 evaluable cycles of Carbetimer at daily doses ranging from 100-11,000 mg/m2. Hypercalcemia was the dose limiting toxicity with both patients at the 11,000 mg/m2 daily dose level and one patient who received 6 cycles of drug at the 4200 mg/m2 dose level developing severe hypercalcemia not explained by the underlying malignancy. Mild nausea, concentration and rate dependent arm pain at the site of infusion, proteinuria, and coagulopathy were also seen. Calcium balance studies revealed hypercalciuria, suggesting increased mobilization of calcium rather than renal retention. In vitro coagulation studies revealed concentration dependent prolongation of the partial thromboplastin time and thrombin time. No complete or partial responses were seen. However mixed response or biochemical response (reduction in serum lactic dehydrogenase) were seen in 5 patients with melanoma or renal cancer. Due to unacceptable toxicity at the 11,000 mg/m2 daily dose level, Carbetimer 8500 mg/m2 is the recommended dose for a 5-day treatment schedule every 28 days. Special attention should be directed toward possible activity against melanoma and renal cancer.
 ...
PMID:Phase I trial of a 5-day course of carbetimer. 238 16

Experiments were performed to investigate the effects of polychlorinated biphenyl (PCB) on calcium metabolism, femur morphometry, and nephrotoxicity. Male Fischer 344 rats were dosed daily intragastrically (ig) for 5, 10 or 15 weeks with 0, 0.1, 1, 10 or 25 mg PCB/kg body weight. After 5, 10 and 15 weeks, liver weight and liver-to-body weight ratio were increased at the 2 higher dose levels. Overt toxicity was observed at the highest dose level after 10 and 15 weeks as evidenced by significantly smaller body weight. Urinary alkaline phosphatase and lactate dehydrogenase activities were elevated at 5, 10 and 15 weeks of PCB exposure and the kidney-to-body weight ratios were elevated at the 10 and 25 mg/kg dose levels after 10 and 15 weeks of exposure indicating nephrotoxicity. Hypercalcemia was present at the highest dose level after 5 and 10 weeks of exposure but serum calcium concentration was normal at 15 weeks. Serum triglycerides were significantly elevated after 5 weeks of exposure but were significantly decreased after 10 and 15 weeks of PCB exposure. Serum cholesterol was significantly elevated at the 2 higher dose levels at all 3 periods. Femur density was increased at the 10 mg/kg dose level after 5 weeks, at all dose levels after 10 weeks and at all dose levels which did not demonstrate overt toxicity after 15 weeks of PCB exposure. Cross-sectional, medullary and cortical areas of the midpoint of the femur were significantly decreased at the higher dose levels after 10 and 15 weeks of exposure. The percent medullary area though was significantly decreased after 10 and 15 weeks of PCB exposure indicating that not only was there a decrease in medullary size but a decrease relative to the cortical bone area. These changes in bone morphometry resulted in a significantly weaker bone after 15 weeks of exposure at the highest dose level. These results demonstrate that PCB exposure effects calcium metabolism and bone morphometry and is nephrotoxic.
 ...
PMID:Polychlorinated biphenyl (Aroclor 1254) induced changes in femur morphometry calcium metabolism and nephrotoxicity. 250 9

Although conferring a grave prognosis in patients with malignant lymphoma, high levels of serum lactic dehydrogenase (LDH) are usually not seen in patients with multiple myeloma, a more indolent tumor composed mainly of B cells in their terminal stage of differentiation. Thus, only 2 of 118 patients in earlier phases of myeloma showed marked LDH elevations to more than 500 U/L, whereas such abnormalities were present in 12 of 64 patients with advanced disease progressing despite treatment with vincristine, doxorubicin (Adriamycin), dexamethasone (VAD) (median LDH level, 700 U/L). High LDH levels were associated with high serum levels of beta-2-microglobulin, hypercalcemia, extraosseous disease features, a short preceding clinical course as well as a short subsequent survival time. A poor prognosis was also noted in patients with lower LDH in whom marked increments were induced by high-dose chemotherapy; thus, LDH elevations to greater than 300 U/L present before or found after high-dose cytotoxic therapy were observed in about 50% of patients with VAD-resistant myeloma and define a new clinical entity with features of extraosseous disease and an unusually aggressive course ("high-grade myeloma"). The shorter survival of newly diagnosed patients with high-normal compared with those with low-normal LDH levels (less than 200 U/L), regardless of tumor mass, suggests the presence in some patients of a tumor subpopulation with high LDH production that escapes growth control with standard treatment. Staging of multiple myeloma should therefore include measurements of serum LDH levels in addition to beta-2-microglobulin analysis and tumor mass estimation.
 ...
PMID:High serum levels of lactic dehydrogenase identify a high-grade lymphoma-like myeloma. 264 15

To elucidate the clinicopathologic features of non-Hodgkin's lymphoma (NHL) in Taiwan, 123 adult patients with proven NHL were studied. They were classified according to the international working formulation as: low grade (LG), 12.2%; intermediate grade (IG), 42.3%; and high grade (HG) lymphoma, 45.5%. The most common subtypes were diffuse large cell (26.8%) and large cell immunoblastic (26.8%) lymphomas. Follicular lymphoma accounted for only 8.9% (11 cases). Complete remission rates for LG, IG and HG lymphomas were 53%, 35% and 34%, respectively. LG lymphoma had a significantly better survival than that of IG and HG lymphomas. The IG lymphoma encompassed a heterogeneous group of patients with varying prognoses but the overall survival curve was indistinguishable from that of HG lymphoma. Clinically, 66% of HG, 77% of IG and 86% of LG lymphoma presented with advanced disease. LG lymphoma had high frequencies of hepatosplenomegaly (30-50%) and bone marrow involvement (53%), whereas skin, bone and central nervous system involvement occurred exclusively in IG and HG lymphomas. Mild anemia was common and occurred in 40-50% of the patients. Hyperimmunoglobulinemia was found in 50-60% of all 3 grades of lymphoma, monoclonal gammopathy in 3 cases of IG lymphoma, and hypercalcemia in 4 cases of IG and HG lymphomas. Elevated serum lactate dehydrogenase occurred mainly in IG and HG lymphomas and was an important prognostic factor. In conclusion, the characteristic features of NHL in Taiwan include: (1) a high proportion of HG lymphoma and low proportions of LG and follicular lymphomas; (2) a heterogeneous patient composition of IG lymphoma with an unfavorable overall prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Adult non-Hodgkin's lymphoma in Taiwan area: a clinicopathologic study of 123 cases based on working formulation classification. 276 10

The clinical and pathological features of T-cell type malignant lymphoma related to human T-cell leukemia virus (HTLV) were investigated in eight patients presenting lymphadenopathy. Biopsy of lymph nodes showed an histology of diffuse non-Hodgkin's lymphoma. All patients were positive for anti-ATLA antibody and HTLV proviral DNA in the lymph node cells. Most patients showed pronounced hypercalcemia and high serum levels of lactic dehydrogenase. All patients died between 3 and 17 months (mean 8 months) after the onset of disease. HTLV-related malignant lymphoma should be added to the spectrum of ATL, being classified as a lymphoma type ATL.
 ...
PMID:Lymphoma type adult T-cell leukemia--a clinicopathologic study of HTLV related T-cell type malignant lymphoma. 300 98

We describe five patients with adult T-cell leukemia/lymphoma (ATL) with neither integration of human T-cell leukemia virus type I (HTLV-I) into their leukemia cells nor anti-HTLV-I antibody in their sera. These findings indicate that HTLV-I may not have been involved in leukemogenesis in these patients. The clinicohematological, cytopathological, and immunological features of HTLV-I-negative ATL were exactly the same as those of HTLV-I-associated ATL. Leukemia cells with pleomorphic nuclei, generalized lymphadenopathy, hepatosplenomegaly, skin lesions, hypercalcemia, and elevated lactate dehydrogenase levels, all of which are characteristic features of typical ATL, were also seen in these patients with HTLV-I-negative ATL. Leukemia cells expressed T3, T4, and pan-T-cell antigens in three cases, and T3 and pan-T-cell antigens in two. All five patients had lived in ATL-nonendemic areas. The finding of HTLV-I-negative ATL suggests that factor(s) other than HTLV-I infection may be involved in ATL leukemogenesis.
 ...
PMID:Adult T-cell leukemia/lymphoma not associated with human T-cell leukemia virus type I. 301 71

We have observed five patients with smoldering adult T-cell leukemia (ATL) who had skin lesions as premonitory symptoms. The illness developed slowly, but flared up after several years. Skin lesions appeared in the form of erythema, papules, or nodules. Infiltration of the skin by ATL cells was slight, and the proportion of ATL cells in the peripheral blood was 0%-2%. The serum lactate dehydrogenase (LDH) value was within normal range and was not associated with hypercalcemia; lymphadenopathy, hepatosplenomegaly, and bone marrow infiltration were very slight. In most cases, hypergammaglobulinemia was seen, and in one case, monoclonal hypergammaglobulinemia was observed. All five patients had lived in an area in which ATL was endemic, and their anti-ATLA antibodies were positive; none had ever received a blood transfusion. One patient developed typical ATL after more than 13 yr of illness and died of renal insufficiency. Another patient developed typical ATL after 5 yr of illness and died of cryptococcus meningitis. Based on clinical and pathologic differences, we believe that these cases should be distinguished from typical ATL cases for the purposes of prognosis and treatment.
 ...
PMID:A proposal for smoldering adult T-cell leukemia: a clinicopathologic study of five cases. 622 22

A possible involvement of cyclic nucleotides (cAMP and cGMP) in the regulation of cardiac contractility and glycolysis during hypoxia was examined in spontaneously beating rat atria. A reduction of the high oxygen saturation (HiOxSa) of the incubation medium from 95-100% to half produced a rapid decline of the amplitude. The deterioration of 50% was seen after 30 sec. of hypoxia. The decline was partly antagonized by noradrenaline (NA, 1 X 10(-6) M) or hypercalcaemia (5.7 X 10(-3) M instead of 1.9 X 10(-3) M). The cAMP level remained unchanged during the first 12 min. of hypoxia, but the cGMP content increased gradually and reached a significantly increased level in 4-8 min. Paradoxically, the production of lactate decreased, after 30 sec. of hypoxia, but accelerated then 2-4 min. after the onset of hypoxia. The depletion of creatine phosphate and ATP stores was initiated after 2 min. of hypoxia. The arterial content of the active forms of phosphofructokinase and lactate dehydrogenase gradually rose during hypoxia. Sodium nitroprusside (SNP, 1 X 10(-4) M) and NA produced increases in cGMP and cAMP levels, respectively, both in HiOxSa and hypoxia. SNP induced a slight and NA a marked increase in the amplitude in HiOxSa. Verapamil (1 X 10(-6) M) decreased the contractility, but did not affect the levels of cAMP and cGMP. Both SNP and verapamil decreased the lactate production, but they could not resist the NA-induced increase in the atrial lactate level. Hypercalcaemia increased the amplitude but slightly reduced the lactate production in HiOxSa. 45Ca-uptake was reduced to about 35 per cent of control as measured between 5 and 10 min. of hypoxia. It is concluded that the lack of oxygen could have direct and parallel effects on the sarcolemma and on the mitochondria. The former could result in the deterioration of contractility and the latter in the termination of aerobic energy production. Cyclic nucleotides are not involved in either of these phenomena. However, at the low rate of anaerobic glycolysis, e.g. in HiOxSa or at the very early stage of hypoxia, cGMP could inhibit and cAMP accelerate the lactate production.
 ...
PMID:On the role of cyclic nucleotides in the regulation of cardiac contractility and glycolysis during hypoxia. 627 32

Two 8-yr-old children, a boy and girl, are described with Cushing's syndrome secondary to ectopic ACTH-secreting pancreatic islet cell carcinomas. The girl, seen 28 yr ago, had strong presumptive evidence of ectopic ACTH production and hypercalcemia. The boy, studied recently, had strikingly elevated concentrations of plasma ACTH (1,500 pg/ml) and beta-lipotropin (beta LPH; 2,500 pg/ml) and showed no suppression of urinary 17-hydroxycorticoids or cortisol with low and high dose dexamethasone. He had increased plasma calcitonin (257 pg/ml), glucagon (442 pg/ml), lactate dehydrogenase (497 IU/liter), and alpha-fetoprotein (5,144 pg/ml). He also had hypokalemic alkalosis with elevated plasma deoxycorticosterone (70 ng/ml) and PRA (6.9 ng/ml.h) but normal plasma aldosterone (8.2 ng/dl) and 18-hydroxycorticosterone (7.6 ng/dl). Preoperative localization of the tumor was accomplished by computed tomographic scan of the abdomen with concurrent barium enema. Cell-free translation of the tumor mRNA produced authentic proopiomelanocortin of 35,000 mol wt, indicating that the ACTH and beta LPH were produced by the tumor from a common precursor. After removal of a large amount of metastatic tissue from the boy, clinical progression of the remaining tumor was monitored by measuring plasma ACTH and beta LPH. Episodic secretion of ACTH and beta LPH was demonstrated by taking frequent plasma samples while suppressing pituitary ACTH with oral dexamethasone. Chemotherapy and radiation proved ineffective in controlling the growth of his tumor.
 ...
PMID:Endocrine, histological, and biochemical studies of adrenocorticotropin-producing islet cell carcinoma of the pancreas in childhood with characterization of proopiomelanocortin. 630 81


<< Previous 1 2 3 4 5 6 Next >>