Protein C and soluble thrombomodulin in relation to tumor necrosis factor-alpha in critically ill septic patients and their correlation with sofa score

The objective of this study was to investigate the influence of sepsis on protein C [PC] activity and soluble thrombomodulin [s-TM] in relation to tumor necrosis factor-alpha [TNF-alpha]. Also, to orrelate these parameters with the SOFA score and serum lactate concentration as predictors of morbidity and mortality in septic patients. Thirty two adult patients [17 with sepsis and 15 with severe sepsis] in the intensive care unit [ICU], as well as 10 healthy age- and sex- matched controls were accrued to the study. The results showed that the baseline values of PC activity were significantly lower in both groups of septic patients compared to the controls, whereas, the serum levels of s-TM, TNF-alpha and lactate were significantly higher in the former compared to the latter. Moreover, survivors in both patient groups had higher PC activity and lower serum levels of s-TM, TNF-alpha and lactate compared to non survivors, both on day [1] and day [3] of ICU admission with variable statistical significance reflecting the heterogeneity of sepsis and the well-known individual patient variation. In addition, day [3] samples showed significant increase in PC activity and reduction in serum levels of s-TM, TNF-alpha, lactate and SOFA scores in survivors and the reverse in non survivors compared to baseline levels. Also, baseline PC activity was correlated negatively with SOFA score but not with serum TNF-alpha in both groups of septic patients. It was also negatively correlated with serum TM and lactate in sepsis but not in severe sepsis

Study of P-glycoprotein [multi-drug resistance gene] expression in acute lymphoblastic leukemia in the elderly: correlation with cytogenetics and response to induction chemotherapy

Elderly patients with acute lymphoblastic leukemia [ALL] have only rarely been included in clinical trials. The aim of this work was to investigate some of the biologic characteristics of ALL in the elderly by cytogenetic analysis and by studying of P-glycoprotein [P-gp] or multidrug resistance [MDR-1] protein expression at initial presentation. Twenty patients with newly-diagnosed beta-lineage ALL were accrued to the study. They were divided into two groups; group I: ten patients aged <60 years, and group II: ten patients aged >/= 60 years. They were subjected to history taking, clinical examination, complete blood count [CBC] and bone marrow [BM] aspiration with immunophenotyping to establish the diagnosis. Cytogenetic analysis was done by the G-banding technique and estimation of P-gp in ALL blast cells was performed by flow cytometry. All patients were in a good performance status and induction chemotherapy was instituted according to standard protocol for ALL. Complete remission [CR] was achieved in 50% of patients in group I and 40% in group II. No significant difference was found between the two groups regarding P-gp expression in pretreatment samples. However, a highly significant difference was noted on comparing CR and non-CR patients in both groups as regards P-gp expression [t=20.89, p=0.00]. Cytogenetic analysis revealed that 20% of patients in group I and 60% of cases in group II had cytogenetic abnormalities. No significant difference was found between CR and non-CR patients as regards the cytogenetic status. Also, there was no significant difference between patients with normal and those with abnormal karyotypes as regards P-gp expression. Failure to respond to chemotherapeutic drugs in ALL in the elderly seems to be a multifactorial phenomenon. Further clinical trials evaluating the disease features, outcome, and new therapeutic approaches are warranted

Study of some prognostic factors in patients with aggressive non-hodgkin's lymphoma

The aim of this work was to study the serum level of soluble CD25 [sCD25], CD44 [sCD44] and [sCD95] as prognostic factors in the assessment of response to standard treatment protocols in patients with aggressive non-Hodgkin's lymphoma [NHL]]. Also, to correlate them with the known adverse prognostic markers of the disease. Twenty five patients with newly-diagnosed untreated aggressive NHL [REAL/WHO] and ten healthy age and sex-matched control subjects were enrolled in the study. The age of the patients ranged between 34 and 60 years with a mean of 48.6 +/- 8.1 years and the male to female ratio was 1.3:1. At presentation and just before administration of the fifth cycle of conventional CHOP regimen, all patients were subjected to: full history taking, through clinical examination, complete blood count [CBC], bone marrow aspiration/trephine biopsy, biochemical profile, activity markers assessment [erythrocyte sedimentation rate [ESR], serum lactate dehydrogenase [LDH], and beta-2 microglobulin [beta-2M]], imaging studies and estimation of serum sCD25, sCD44, and sCD95 by ELISA technique. The mean values of the three biological factors were significantly higher in pre-treatment samples as compared to the controls. However, there was a significant reduction in the mean values in the follow-up samples compared to the pre-treatment mean values. Patients who achieved complete response [CR] [48%] showed significantly lower mean values of sCD25, sCD44, and sCD95 than non-CR patients [32% with partial response [PR], and 20% with no response [NR]], both before and after therapy. Also, there were significant positive correlations between each of sCD25, sCD44, and sCD95 and other known adverse prognostic features such as age, advanced Ann Arbor stage, higher risk groups of age-adjusted International Prognostic Index [IPI], ESR, LDH, and beta-2M. Again, sCD25, sCD44, and sCD95 correlated positively with each other, Multivariate regression analysis showed that sCD25 [p<0.001], sCD44 [p<0.001], and sCD95 [p = 0.002] turned out to have independent prognostic value. Moreover, we could demonstrate cut off levels for the three biological markers; all patients presenting with values equal to or below these levels achieved CR [2325 pg/ml for sCD25, 540 ng/ml for sCD44, and 8650 pg/ml for sCD95]. In conclusion, the serum sCD25, sCD44, and sCD95 are independent prognostic factors that could predict disease outcome and response to standard CHOP regimen in patients with aggressive NHL. Measurement of these factors at diagnosis may improve prognostic factors models and serve as targets for therapy leading to better cure rate and reducing unnecessary toxicity

Serum prolactin level in patients with hepatitis C-associated thrombocytopenia

Aim: Hepatitis C virus [HCV] has been recognized as the cause of thrombocytopenia occurring in patients with chronic hepatitis C, possibly through autoimmune mechanisms. Prolactin [PRL] is a potent immunomodulator that may play a role in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus [SLE]. The objective of this study was to estimate serum PRL level in patients with HCV-associated thrombocytopenia and those with chronic idiopathic thrombocytopenic purpura [ITP], in an attempt to find any possible role of this hormone in these autoimmune disorders. Subjects and The study was carried out on 70 patients divided into 3 groups: group I, included 30 patients with chronic HCV infection and thrombocytopenia [mean age: 47.25 +/- 8.6 years]; group II included 20 patients with chronic HCV and normal platelet counts [mean age: 42.2 +/- 8.5 years]; and group III, comprised 20 patients with chronic ITP [off-steroid therapy] who were HCV-negative. Their mean age was 42 +/- 12.5 years. Basal level of PRL was determined by chemiluminescence, and autoantibody profile [antinuclear antibodies [ANA], anti-double stranded DNA [anti-ds DNA], anti-smooth muscle antibodies [ASMA], anti-mitochondrial antibodies [AMA], and cryoglobulins] was performed in all patients. In group I, the mean platelet count was significantly lower compared to group II [P=0.00], but was significantly higher than group III [P=0.0002]. The mean serum PRL was higher in group I compared to group II and group III, however, the difference showed marginal statistical significance [P=0.058, P=0.057, respectively]. The autoantibody profile did not differ significantly between the three studied groups. The mean serum PRL was significantly higher in females than males in all studied groups [P<0.05]. Correlation studies in group I showed that the platelet count correlated negatively with the female sex. However, we found no significant correlation between serum PRL level and platelet count and no association between PRL level and the different autoantibodies studied. Conclusions: Our preliminary results suggest that the role of hyperprolactinemia in the triggering or promoting the autoimmune process responsible for HCV-associated thrombocytopenia is quite questionable. Prolactin seems to be poorly involved in the etiopathogenesis of both HDV-associated thrombocytopenia and chronic ITP. However, additional studies are warranted to elucidate the possible role of bromocriptine in the management of hyperprolactinemic thrombocytopenia in patients with chronic HCV infection

Prognostic value of serum leptin in patients with acute myefogenous leukemia

Aim: Leptin is a hormone secreted by adipocytes that regulates body weight and energy expenditure. Leptin receptors can be expressed by acute myelogenous leukemia [AML] cells and leptin may affect leukemic hematopoiesis. In addition, leptin may function as a stress-related hormone and may contribute to the anorexia and wasting syndrome of cancer and infections. The present work aimed at estimating the serum leptin level in patients with AML at presentation and after induction chemotherapy in order to extrapolate its possible alteration with infection in these patients and its role in influencing hematopoietic recovery following chemotherapy. Subjects and Thirteen newly diagnosed AML patients, 7 males and 6 females [mean age: 40.54 +/- 13.5 years] and ten healthy age- and sex-matched controls were enrolled in the study. Serum leptin was estimated by the ELLSA technique. In AML patients, the pretreatment mean serum leptin [15.8 +/- 19.8 ng/ml] did not differ significantly from the controls [8.25 +/- 7.25 ng/ml]. Post-chemotherapy, the mean serum leptin level [12.1 +/- 14 ng/ml] decreased compared to the pre-therapy level. However, this decrease was not statistically significant. A significant positive correlation was found between serum leptin and body mass index [BMI], both at presentation [r=0.777, P=0.002] and post-chemotherapy [r=0.557: P=0.048], and serum leptin was significantly higher in female as compared to male patients before and after chemotherapy [P=0.001 and P=0.024, respectively]. No significant correlation was found between serum leptin and any of the studied parameters [hemoglobin, total leukocytic count, platelet count, bone marrow blast percent, absolute neutrophilic count and days to hematopoietic recovery]. Also, no significant difference was found between patients who achieved complete remission [n=6] and those who achieved partial remission [n=5] regarding the serum leptin both before and after therapy. Comparing the mean serum leptin levels in patients who developed chemotherapy-induced neutropenic sepsis [n=11] and those who did not develop sepsis [n=2], the level was significantly higher in the former than in the latter, both before [P-0.005] and after [P=0.012] chemotherapy. Conclusions: The findings of the present study support the hypothesis that leptin is a stress-related hormone involved in the host defense of acute inflammation and may be important for survival. However, further studies are warranted to clarify the potential diagnostic, prognostic and therapeutic roles of leptin in patients with AML