Higher Plasma Lactate Dehydrogenase Research Articles

Hematological and biochemical profiles of canine CD45- T lymphomas are different from other immunophenotypes.

Background:Canine multicentric lymphomas are lymphoproliferative malignancies that have increased in recent decades. The patient’s treatment and prognosis are determined by the grade, histological type, and lymphoma immunophenotyping. Aim:To investigate the paraclinical signs and survival time in canines with different lymphoma immunophenotypes.Methods:Over 2 and a half years, 47 untreated dogs were diagnosed with multicentric lymphoma at the Veterinary School Hospital of Uruguay. The disease was clinically and cytologically diagnosed, and immunophenotyping was determined by flow cytometry. After the immunophenotyping, most of the patients were grouped into the following: B (LB), T aggressive (LTCD45+), or T-zone lymphoma (LTCD45−). The patients’ haematological values, calcemia, lactate dehydrogenase (LDH) levels, and plasmatic electrophoretic profiles were all determined immediately after that. Results:Of all canine lymphomas, 55.3% were B, 31.9% were LTCD45+, and 10.6% were TCD45−. Only 2.2% were classified as nonB/nonT, and survival time differed between groups. Patients with LTCD45− lymphomas had a mean life span of 641 days after diagnosis, followed by LB (166 days) and LTCD45+ (62 days). Red blood cell count, hematocrit, and hemoglobin levels did not differ between groups. However, the LTCD45− group had significantly higher lymphocyte levels than the LTCD45+ and LB groups (p = 0.01 and 0.006, respectively). Levels of albumin, alpha-1, and alpha-2 globulins did not differ between groups. On the other hand, gamma globulins levels in the LTCD45− were higher than in the other lymphoma groups. The presence of hypercalcemia and high plasma LDH levels were associated with patient severity. Only the TCD45+ group had hypercalcemia although both the LB and TCD45+ groups had elevations in LDH activity. Interestingly, there was a direct relationship between high LDH values (greater than 500 IU/l) and lower survival in TCD45+ lymphomas. Conclusion:Survival time and hematological and biochemical patterns differed among canine lymphomas immunophenotypes. Patients of LTCD45− phenotype showed higher lymphocyte counts and gamma globulin levels and more prolonged survival. Serum LDH activity may provide additional prognostic information in high-grade T-cell lymphoma.

Modulation of Hemolytic and Hemoglobin/Heme Scavenging Profiles in Sickle Cell Anemia, Hereditary Spherocytosis and Paroxysmal Nocturnal Hemoglobinuria

Sickle Cell Anemia (SCA), Hereditary Spherocytosis (HS) and Paroxysmal Nocturnal Hemoglobinuria (PNH) can share some clinical complications, such as leg ulcers and priapism, due to hemolytic processes. Intravascular hemolysis (IVH) results in the release of cell-free hemoglobin (Hb) and heme into the circulation, potentially causing depletion of nitric oxide, oxidative stress and inflammation. We compared the hemolytic profile and heme/Hb scavenging profiles of patients with SCA on hydroxyurea therapy (SCAHU; 15-30 mg/kg/day for ≥ 2 months) or not (SCA), hereditary spherocytosis (HS), splenectomized HS (SHS) and paroxysmal nocturnal hemoglobinuria not on eculizumab therapy (PNH). Blood samples were collected from patients and from healthy volunteers (CON). Plasma levels of heme, haptoglobin (Hp) and hemopexin (Hpx) were quantified by colorimetric assay or ELISA. Fetal hemoglobin (HbF) was determined in the SCA groups by HPLC. Reticulocytes (RET) and cell counts were determined using an automated flow cytometry hematology system and serum levels of lactate dehydrogenase (LDH) and unconjugated bilirubin (UCB) were quantified by a modular colorimetric automation system. As expected, plasma heme was significantly elevated in the SCA group, compared to the CON group and with intermediate values in the SCAHU group (57.4±9.3, 24.5±2.9, 43.2±4.5µM, respectively, p<0.05, N≥10), correlating significantly and negatively with HbF levels in the SCA patients (r=-0.94, p<0.01). Accordingly, RET and UCB were significantly increased in SCA, compared to CON, with SCAHU presenting intermediate values (RET: 16.2±1.4; 1.9±0.1; 11.5±1.2%; UCB: 2.1±0.7; 0.2±0.0; 1.44±0.2 mg/dL; respectively, p<0.01, N≥10), indicating increased red cell turnover and heme catabolism in SCA. No significant elevations in plasma heme were observed in the HS and SHS groups, compared to CON (35.3±3.8 and 34.5±10.0µM; P>0.05, N≥10), although RET and UCB levels were significantly elevated in HS (8.27±1.07 % and 1.72±0.57 mg/dL, P<0.01, N≥13), but not SHS (2.80±0.17 % and 0.99±0.66 mg/dL, N≥11), perhaps indicating a redistribution of extravascular hemolysis (EHV) to low-level IVH in SHS. Surprisingly, plasma heme was not significantly elevated in PNH individuals studied (36.5±4.0 µM, N≥10), even though concentrations of plasma LDH were the highest in this patient group (1196±305 U/L; compared to 182±8, 352±73, 407±38. 211±19 and 182±28 U/L for CON, SCA, SCAHU, HS, SHS, respectively, P<0.01; N≥10) and LDH correlated significantly with plasma heme in this group (r=0.905, P<0.01 for PNH). RET and UCB presented and intermediate values in PNH (5.35±1.21% and 0.84±0.18 mg/dL, P<0.05, N≥10, compared to CON). To investigate whether hemolytic profiles may be modulated by the Hb and heme scavengers, Hp and Hpx, we measured these proteins in the circulations of patients. Hp was significantly depleted in SCA, SCAHU, HS and PNH (1.0±0.4, 1.0±0.6, 37.8±0.16, 12.3±10.2, respectively, compared to 142.9±20.6 mg/dL in CON, p<0.05; N≥10), while SHS presented similar levels to those of CON (189.9±38.8 mg/dL, N=5). In contrast, somewhat surprisingly, Hpx levels varied considerably in each patient group, with a significant depletion only observed in the SHS group (12.2±0.3, 15.9±5.4, 15.0±3.8, 6.0±1.5, 1.5±0.4, 17.8±5.0mg/dL for CON, SCA, SCAHU, HS, SHS, PNH, respectively; P<0.05, SHS compared to CON, N≥10). As such, plasma heme was slightly lower in PNH than in SCA, in association with very high plasma LDH, suggesting that either IVH is slightly less severe or that Hb/heme scavenging is more efficient in the PNH population studied than in SCA. While EHV may be abolished by splenectomy in HS, intermediate heme levels may suggest that some IVH, or reduced heme catabolism, may still occur in some of these patients. Interestingly, depleted Hp stores were coupled with maintained (or even elevated) Hpx levels in SCA and PNH, indicating that hemolytic processes may stimulate Hpx production, potentially via a heme-oxygenase-1 (HO-1)-dependent pathway. Furthermore, significantly diminished levels of Hpx in SHS suggest a role for the spleen in Hpx maintenance, possibly due to the importance of this organ for HO-1 activity. In conclusion, while parameters suggestive of hemolysis can be observed in SCA, HS and PNH, specific profiles of hemolytic markers and heme catabolism indicate that hemolytic events may be modulated differently in these diseases. DisclosuresConran:Bayer AG: Research Funding. Almeida:Jassen & Cilag: Other: Currently employed with.

Elevated levels of plasma lactate dehydrogenase is an unfavorable prognostic factor in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer, receiving treatment with gefitinib or erlotinib.

Treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been shown to prolong survival in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). The present study performed a retrospective analysis to investigate the association between the plasma lactate dehydrogenase (LDH) levels and survival in patients with EGFR mutation-positive NSCLC receiving treatment with EGFR-TKIs. The medical charts of patients with EGFR mutation-positive NSCLC who were receiving treatment with EGFR-TKIs at Toyama University Hospital between 2007 and 2014 were assessed. The data from 65 patients were included in the analysis. Patients with higher plasma LDH levels exhibited shorter progression-free survival (6.2 vs. 13.2 months; P<0.01) and overall survival (10.5 vs. 36.1 months; P<0.01) periods compared with patients with lower plasma LDH levels. A Cox proportional hazards model identified that the plasma LDH level was associated with the progression-free survival (P=0.05) and overall survival (P<0.01). An association was demonstrated between the pretreatment plasma LDH level and the survival in patients with EGFR mutation-positive NSCLC receiving treatment with EGFR-TKIs. Close observation is required in EGFR mutation-positive NSCLC patients exhibiting high plasma LDH levels following the initiation of treatment with EGFR-TKIs.

Very high levels of lactate dehydrogenase at diagnosis predict central nervous system relapse in acute promyelocytic leukaemia

Very high levels of lactate dehydrogenase at diagnosis predict central nervous system relapse in acute promyelocytic leukaemia

Spontaneous Intracerebral Hemorrhage in Northeast Malaysian Patients: A Four-Year Study

The aim of this study was to compare nonsurgical versus stereotactic aspiration of intracerebral hematomas in relation to clinical aspects, computed tomographic imaging features of the brain, laboratory parameters and specific risk factors that may influence the outcome in southeast Asian Malay patients. Fifty-five of the patients with intracerebral hemorrhage (ICH) underwent stereotactic aspiration and 57 did not. Analysis was done on risk factors, locations and treatments of ICH, and the final outcomes measured by the Glasgow Outcome Scale. A total of 112 patients were evaluated. Mean age was 52 years with ages ranging from 12 to 80 years. Hypertension was seen in 60.7% of patients with ICH. The mortality rate was 25% by 3 months. 58.9% had a poor final outcome, while 41.1% had a good outcome. The selected variables were incorporated into models generated by multiple logistic regression method analysis to define the significant predictors of outcome. Significant predictors of outcome were the Glasgow Coma Scale score on admission, the duration of surgery and the total volume of the hematoma. Significant predictors of mortality were high total white blood cell differential count, low plasma protein, and high plasma lactate dehydrogenase and brain edema. The study suggests that stereotactic aspiration of patients with ICH does not offer any definite advantage over conservative treatment.

Prevention of catecholamine-induced cardiac damage and death with a nucleoside transport inhibitor.

The effect of a potent and specific nucleoside transport inhibitor, R 75,231, on catecholamine-induced cardiac toxicity has been studied in rabbits. Epinephrine (1 mg/kg) or norepinephrine (2.5 mg/kg) subcutaneously were lethal in 25 (42%) of 60 control animals, while survivors showed major myocardial damage, as judged from high plasma lactate dehydrogenase (LDH) and its myocardial isoenzyme (LDH1) after 24 h. When a low dose of R 75,231 (0.1 mg/kg) was given intravenously either 1 h before or 1 h after the catecholamine insult, only 1 of 60 animals died. The plasma total LDH and the LDH1 myocardial isoenzyme were low in these animals compared with untreated survivors. Studies ex vivo on isolated perfused hearts confirmed that with treatment using R 75,231, there was both left ventricular nucleoside retention and functional preservation after in vivo exposure of the animals to epinephrine. R 75,231 did not affect the peripheral venous hyperglycemic response to epinephrine. Nucleoside transport inhibition offers a new approach to the prevention and treatment of several cardiac disorders characterized by a pathogenic effect of catecholamines.