Evaluation of oral-motor movements and facial mimic in patients with head and neck burns by a public service in Brazil

OBJECTIVES: The purpose of this study was to analyze the characteristics of oral-motor movements and facial mimic in patients with head and neck burns. METHODS: An observational descriptive cross-sectional study was conducted with patients who suffered burns to the head and neck and who were referred to the Division of Orofacial Myology of a public hospital for assessment and rehabilitation. Only patients presenting deep partial-thickness and full-thickness burns to areas of the face and neck were included in the study. Patients underwent clinical assessment that involved an oral-motor evaluation, mandibular range of movement assessment, and facial mimic assessment. Patients were divided into two groups: G1 - patients with deep partial-thickness burns; G2 - patients with full-thickness burns. RESULTS: Our final study sample comprised 40 patients: G1 with 19 individuals and G2 with 21 individuals. The overall scores obtained in the clinical assessment of oral-motor organs indicated that patients with both second- and third-degree burns presented deficits related to posture, position and mobility of the oral-motor organs. Considering facial mimic, groups significantly differed when performing voluntary facial movements. Patients also presented limited maximal incisor opening. Deficits were greater for individuals in G2 in all assessments. CONCLUSION: Patients with head and neck burns present significant deficits related to posture, position and mobility of the oral myofunctional structures, including facial movements. .

Values of transforming growth factor beta-1, thrombopoietin and interleukin-6 in regulation of megakaryopoiesis in various platelets disorders

Megakaryopoiesis requires a highly complex series of cellular events in which a hematopoietic stem cell generates a cascade of committed progenitors and culminates with the production of circulating blood platelets. Megakaryopoiesis is regulated by several factors and cytokines that affect the proliferation and differentiation of megakaryopoietic cells. The aim of this study was to evaluate the role of some cytokines namely Thrombopoietin [TPO], Transforming growth factor [TGF-beta1] and lnterleukin 6 [IL-6] in regulation of megakaryopoiesis in various platelet disorders. This study was conducted on 72 patients with various platelet disorders; they were either thrombocytopenic [ITP "group I" or liver cirrhosis [LC] "group II" patients] or they presented with reactive thrombocytosis "group III". [According to modified Child classification group II patients was divided into three subgroups; Child A, Child B and Child C]. Twelve apparently healthy volunteers were included in the study for comparison. Estimations of serum TPO level, TGF-beta1 level and IL-6 level by ELISA technique were done for all studied groups. A highly significant increase in TPO and significant increase in IL-6 levels was noted in ITP group compared with the control group while TGF-beta1 was non significantly increased. In LC group and subgroups [Child A] a significant increase in TPO was noted on comparing with the control group but non significant increase in Child B and C; with progressive decrease of TPO level from Child A to Child B and Child C respectively. In LC group and Child C and B the TGF-beta1 was highly significantly increased on comparing with control group. Also it was significant increased in Child A when compared with control group i.e. there was progressive increase in TGF-beta1 with the progression of liver damage. A significant reduction in IL-6 was noted in LC group on comparing with the control group. A non significant reduction in IL-6 was noted in Child A, B and C group on comparing to the control group. In thrombocytosis group a significant increase in TPO, TGF-beta1 and IL-6 levels were noted compared to the control group. Estimation of serum TPO in ITP, liver cirrhosis and reactive thrombocytosis seems to be of benefit in diagnosis and evaluation of megakaryopoiesis state in these platelet disorders. Also estimation of TGF- beta1 can be used as good indicator of liver disease progress. TGF-beta1 was increased in thrombocytosis and this makes highlight to its role in feed back inhibition of megakaryopoiesis. Serum IL-6 was significantly increased in reactive thrombocytosis and this may confirm its role in stimulation of megakaryopoiesis

The Analysis of Thrombopoietin and Clinical Parameters as a Marker for Disease Progression in Patients with Multiple Myeloma / 대한진단검사의학회지

BACKGROUND: Multiple myeloma (MM) causes the suppression of hematopoiesis because of malignant cells in the bone marrow. Thrombopoietin (TPO) is regulated by a feedback mechanism with platelets. Recently, it was suggested that an elevated TPO without thrombocytopenia was associated with impaired hematopoiesis. We evaluated whether TPO levels could be a marker for disease progression in MM. METHODS: The TPO levels were measured in 70 blood samples from 27 patients (newly/previously-diagnosed patients=13/14). We analyzed the TPO and clinical parameters, WBC, hemoglobin, creatinine, calcium, M-protein, protein, albumin, and beta2-microglobulin. The TPO in 20 healthy controls ranged from 6 to 69 pg/mL. RESULTS: The TPO levels were significantly higher in MM patients with thrombocytopenia than in patients without thrombocytopenia and the healthy controls (median TPO: 293.0 pg/mL vs 59.6 pg/mL and 35.6 pg/mL, P<0.0001). There was a negative correlation between the TPO levels and the blood cells, i.e., leukocytes (r=-0.293), hemoglobin (r=-0.378) and platelets (r=-0.508) (P<0.05). Elevated TPO were found in association with normal platelet counts (N=20). Among the samples without thrombocytopenia, especially one year after the diagnosis, the hemoglobin (10.3 vs 12.9 g/dL, P=0.025) and albumin (3.3 vs 4.0 g/dL, P=0.085) were lower and the M-protein and protein tended to be higher in patients with elevated TPO compared to those with normal TPO. CONCLUSIONS: Serum TPO was elevated with thrombocytopenia and related to impaired hematopoiesis. The elevated TPO without thrombocytopenia might be considered as impaired hematopoiesis and a marker for disease progression in patients with MM.

Niveles de citoquinas megacariocitopoyéticas en pacientes con trombocitemia esencial y su relación con características clínicas y bioquímicas / Megakaryopoietic cytokine levels in patients with essential thrombocythemia and their relationship with clinical and biochemical features

La megacariocitopoyesis y la producción de plaquetas están regidas por factores de transcripción y citoquinas presentes en el microambiente medular. La trombocitemia esencial (TE) es una enfermedad mieloproliferativa crónica caracterizada por aumento del recuento de plaquetas e hiperplasia megacariocítica. En el presente trabajo se evaluaron los niveles de las citoquinas que participan en el desarrollo megacariocítico en plasma de pacientes con TE que se encontraban sin tratamiento y los de trombopoyetina (TPO) antes y durante el tratamiento con anagrelide. Las determinaciones se realizaron por técnica de ELISA. Dentro de las citoquinas involucradas en la etapa de proliferación, los niveles de interleuquina 3 (IL-3) se encontraron aumentados en los pacientes (p=0.0383) respecto al grupo control. Los niveles de factor estimulante de colonias granulocito-macrofágico y stem cell factor fueron normales. Dentro de las citoquinas con acción sobre la maduración megacariocítica, tanto la interleuquina 6 como la interleuquina 11 y la eritropoyetina estuvieron normales. Los niveles de TPO antes del tratamiento no difirieron del grupo control y durante el tratamiento aumentaron de manera no significativa. Los pacientes que presentaron agregación espontánea tuvieron niveles más altos de TPO que los que no lo hicieron (p=0.049). Los niveles de las citoquinas no tuvieron relación con ninguno de los parámetros clínicos ni de laboratorio evaluados. El aumento de los niveles de IL-3 podría contribuir al incremento en la proliferación megacariocítica en este grupo. La presencia simultánea de niveles más altos de TPO y trombocitosis sería un factor predisponente para la ocurrencia de agregación espontánea en los pacientes con TE

Megakaryopoiesis and platelet production are driven by transcription factors and cytokines present in bone marrow environment. Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by high platelet count and megakaryocytic hyperplasia. In the present work we evaluated plasmatic levels of cytokines involved in megakaryocytic development in a group of patients with ET that were not on treatment, as well as thrombopoietin (TPO) levels before and during anagrelide treatment. The assays were carried out using ELISA techniques. Among the cytokines mainly involved in proliferation of megakaryocytic progenitors, interleukin 3 (IL-3) levels were found increased in patients compared to normal controls (p=0.0383). Granulocyte-macrophage colony stimulating factor and stem cell factor levels were normal. Interleukin 6, as well as interleukin 11 and erythropoietin (EPO), cytokines mainly related to megakaryocytic maturation, were normal. Plasma TPO levels before treatment were within the normal range and increased during treatment but the difference was not statistically significant. Patients who displayed spontaneous platelet aggregation had higher plasma TPO levels compared to those who did not (p=0.049). We did not find any relationship between cytokine levels and clinical or laboratory parameters. The high IL-3 levels seen in some patients with ET could contribute to megakaryocytic proliferation. The simultaneous occurrence of higher TPO levels and elevated platelet count could be a predisposing factor for the development of spontaneous platelet aggregation in ET patients

Role of thrombopoietin and plasma erythropoietin in neonatal sepsis

The objectives is to evaluate the role of thrombopoietin [Tpo] and esythropoietin [Epo], as reliable indicators of neonatal sepsis and the value of rhuEpo in improving the outcome of septic neonates. A prospective study was conducted on 120 sick neonates with sepsis. Sixty two [51.7%] were fullterms and 58 [48.3%] were preterms with a mean gestational age of 32.8. +/- 2.9 weeks. The mean birth weight was 2.7 +/- 0.98 Kg and the mean age of sampling was 5.5 +/- 1.9 days. Sixty neonates received treatment with rhuEpo in addition to the classic therapy of sepsis for 10-14 days. Another group of 60 septic neonates received the classic therapy of sepsis only for 10-14 days. Thirty healthy neonates, age and sex matched with the study groups, were served as a control group. Serum Tpo and Epo levels were measured by ELISA [enzyme-linked immunosorbent assay]. Significant higher differences of serum Tpo and Epo levels were found between septicemic neonates and control group [P<0.001]. The higher the septic score, the higher the serum levels. Septicemic neonates with DIC had significantly higher serum Tpo levels than septicemic neonates without DIC [216.42 +/- 66.5 pg/ml, 172.69 +/- 62.4 pg/ml P=0.042]. Also, septicemic neonates with pallor had significantly higher serum Epo levels than those without pallor [24.1 +/- 7.4 IU/ml, 20.3 +/- 5.2 IU/ml, P=0.022]. On admission, the serum Tpo levels ranged between 39-344 pg/ml with a mean +/- SD of 173.76 +/- 62.67 pg/ml and was statistically significant when compared with control group [32-114 pg/ml, 69.63 +/- 21.4 pg/ml, P=0.001]. After improvement, the serum Tpo levels ranged between 29-133 pg/ml with a mean of 74.5 +/- 25.3 pg/ml and insignificant difference when compared with control group [P=0.37]. Serum Epo levels at the onset [21.14 +/- 6.28 IU/ml] and after improvement [8.81 +/- 3.71 IU/ml] were significantly higher [0.001 and 0.009 respectively] when compared to controls [6.73 +/- 2.9 IU/ml]. Septicemic neonates who received treatment with rhuEpo in addition to the classic therapy showed significantly lower mortality rate [18 patients died, 30%] than those who received the classic therapy only [34 patients died. 56.7%], P=0.003. Serum Tpo and Epo levels are increased in neonates with sepsis, the higher the septic score, the higher the serum levels of both markers. Increase in serum Epo levels during neonatal septicemia is a multifactorial process rather than affecting the haemostatic mechanisms only. The use of rhuEpo in management of septicemic cases could improve the outcome of septicemic patients and decrease the mortality rate

Circulating Thrombopoietin and Interleukin-11 in Thrombocytopenic Neonates with Sepsis

Thrombocytopenia is a commonly encountered hematological complication in neonates with sepsis. Thrombopoietin [TPO] is the major regulator of the platelet production in neonates. It is unique among the haematopoietic cytokines for maintenance of the most primitive haematopoietic stem cells. Interleukin-11[lL-11] stimulates megakaryorytopoiesis and platelet production. The aim of this study was to determine the variation in the TPQ and IL-11 levels and/or if they would correlate with platelet count or not in infected neonates with sepsis. Thirty five neonates with sepsis admitted to the Intensive Care Unit, Pediatric Department, Tanta University Hospital, were enrolled in this study. Twenty healthy neonates sewed as a control group. All these neonates were subjected to the following: Complete blood count [CBC], blood culture, C-reactive protein [CRP], chest X-ray, coagulation studies including prothrombin time, partial thromboplastin time, fibrinogen and D-dimer. Plasma TPO and IL-11 levels were performed using Enzyme-Linked lmmunosorbent Assay[ELISA], The results showed that sick neonates with sepsis had significantly higher plasma levels of both TPO and IL-11 [P<0. 05]. Also, there was significant inverse correlations between the platelet count and TPO and IL-11 levels [r=-0.917 and-0.908 respectively, P value<0.01]. TPO and IL-11 are significantly increased in neonatal sepsis with thrombocytopenia and they are being explored as potential therapeutic agents in these patients

Role of thrombopoietin in thrombocytopenic patients with chronic viral hepatitis with and without liver cirrhosis

Thrombocytopenia is a common hematological defect among patients with chronic liver diseases. Thrombocytopenia secondary to liver cirrhosis and portal hypertension is a well known complication of advanced stage liver disease, but theories about the underlying pathogenetic mechanisms, mostly concentrating on splenic sequestration i.e. hypersplenism and destruction of platelets, have failed to solve the problem so far. Thrombopoietin [TPO] was recently cloned and identified as the primary cytokine involved in the megakaryocyte maturation and formation of platelets. The predominant site of TPO-production is the liver, where parenchymal cells are the TPO-producing cells. Therefore, thrombocytopenia in chronic liver disease may be related to deficient production of thrombopoietin. Thus, altered TPO production in patients with chronic liver disease may in part explain the thrombocytopenia found in these patients. To evaluate the relationship between serum TPO concentrations, circulating platelet count, and the state of liver pathology in patients with chronic viral hepatitis with and without liver cirrhosis, this study included ninety subjects divided into two main groups. Group A included sixty chronic hepatitis patients and group B included thirty apparently normal age- and sex-matched subjects taken as a control group. Etiology of the chronic hepatitis patients was either HBV or HCV. Group A was further subdivided into subgroup AI including thirty chronic hepatitis patients with liver fibrosis, while subgroup AII included thirty chronic hepatitis patients with liver cirrhosis, who were all of Child A group according to Child score. Ultrasonography as well as liver biopsy were used to differentiate the two subgroups. Thorough history taking, full physical examination, as well as biochemical blood tests in the form of serum albumin and total bilirubin were done. Prothrombin time, platelet counts, as well as serum TPO concentrations were all determined in addition to abdominal ultrasonography to evaluate the splenic size. Our data showed that serum albumin level was decreased and serum bilirubin level was increased in both subgroups AI fibrosis and AII cirrhosis compared to group B controls. Prothrombin time was prolonged in subgroup AII cirrhosis patients compared to both subgroup Al fibrosis and to group B controls. Splenic size was highly significantly increased in subgroup AII cirrhosis patients compared to subgroup AI fibrosis patients who showed larger spleen compared to group B controls as well. Serum TPO levels were significantly increased in subgroup Al fibrosis patients and significantly decreased in subgroup All cirrhosis patients compared to group B controls, moreover, TPO levels were highly significantly decreased in subgroup All patients compared to subgroup Al patients. Thus, our study clarified that decreased serum TPO levels parallel the increased serum biliruhin levels, the deterioration of the protein producing liver ability, as well as the prolonged prothrombin time. Thus, TPO concentrations decreased with the progression of liver disease and the reduction in the functional hepatic mass indicating that thrombocytopenia in chronic liver disease might highly be correlated with the hepatocellular damage. Our study also detected a negative correlation between the spleen size and the platelet counts, meanwhile we also demonstrated that the spleen size does not correlate with the TPO levels. In addition we demonstrated a significant positive correlation between TPO concentrations and platelet counts and a negative correlation between TPO concentrations and prothrombin time. Thus, we denoted that TPO concentration is an independent factor affecting positively the platelet counts in chronic viral hepatitis patients regardless of the splenic size, which is also partially implicated, also it is negatively related to the prothrombin time, which is an indicator of the functioning liver mass. This study concluded that serum TPO concentrations are increased above control levels in chronic viral hepatitis patients with liver fibrosis, but as the condition progresses to cirrhosis, the functioning liver mass decreases and so the TPO concentrations fall. Thus, the impaired TPO synthesis by the diseased liver may contribute to the development of thrombocytopenia in liver cirrhosis. Therefore, TPO deficiency due to reduced production, seems to be a major factor for thrombocytopenia in chronic liver disease although increased splenic sequestration of platelets in the enlarged spleen may also have an additional role. Our findings may suggest that recombinant TPO could possibly be an effective drug to treat patients with liver cirrhosis and severe thrombocytopenia during bleeding episodes or when undergoing surgical procedures. Moreover, it may decrease the incidence of splenectomy, with all its intraand postoperative hazards, done in such conditions

The correlation between thrombopoietin and platelet count in adult dengue viral infection patients.

AIM: To investigate alteration in humoral regulation during the course of dengue viral infection. METHODS: A prospective analytic study had been conducted involving 40 subjects with dengue viral infection. Subjects were recruited according to consecutive non-probability sampling. Subjects were categorized according to days of illness, platelet counts and serum thrombopoietin (TPO) levels. The plasma TPO levels examinations were done once daily until the platelet counts reached more than 100,000/mm(3). RESULTS: Statistical analysis showed the mean serum TPO levels were increased during thrombocytopenia phase of the disease, and differ significantly from the convalescent phase (mean value 428 pg/ml vs 220.1 pg/ml, p= 0.00). There was also a statistically significant inverse correlation between serum TPO levels and platelet counts (p= 0.00). CONCLUSION: TPO levels were significantly increased in adult patients with dengue infection in which platelets in circulation were markedly reduced, and the TPO levels were inversely related to the platelet counts.

Significance of circulating intercellular adhesion molecules [sICAM-1] and thrombopoietin [TPO] in hepatitis C vinis related liver cirrhosis

Chronic hepatitis C is a major health problem that causes mortality in the worldwide distribution. The systemic levels of many soluble adhesion molecules and cytokines are altered in autoimmune diseases and liver infection. Among mediators that show altered serum levels are sICAM-1 expressed by immunocompetent cells and thrombopoitin [TPO]. The aim of this study was to evaluate the serum sICAM and TPO and their correlations with clinical and laboratory data in patients with hepatitis C-related cirrhosis. 40 patients with HCV-related cirrhosis and 20 healthy subjects were enrolled in this study. They were subjected to the following investigations: complete blood picture, liver and kidney functions, prothrombin time[PT], abdominal sonography and estimation of serum TPO and sICAM-1. Compared to controls, the patients group showed significant increase in spleen size [P<0.025], portal vein diameter [P<0.0025], ALT, AST, bilirubin, sICAM-1 [P<0.0005], and PT [P<0.05]. However there was significant decrease in serum albumin levels [P<0.01], platelets count [P<0.0005], RBCs count, haemoglobin concentrations [P<0.025] and serum TPO levels [P<0.0025]. The serum creatinine levels and WBCS count showed insignificant changes with control. The serum TPO levels were negatively correlated to ALT [r=-0.97, P<0.0001], PT [r=-0.96, P<0.0001], spleen size [r=-0.95, P<0.0001], and portal vein diameter [r=-0.96, P<0.0001] and positively correlated to platelets [r=0.84, P<0.0005]. While serum sICAM-l were positively correlated to ALT [r=0.99, P<0.0001], PT [r=0.94, P<0.0005], spleen size [r=0.95, P<0.0001], and portal vein diameter [r=0.85, P<0.005] and negatively correlated to platelets count [r=-0.7l, P<0.005]. Our results suggested that impaired synthesis of TPO by cirrhotic liver may contribute to the development of thrombocytopenia and related to liver cirrhosis together with increased splenic sequestration of platelets by the enlarged spleen. So recombinant human TPO should be evaluated in the treatment of thrombocytopenia in HCV-related cirrhosis. In addition, sICAM-1 elevation in plasma of patients suffering from HCV-related cirrhosis was related to the degree of cirrhosis and portal hypertension. So, sICAM-1 may be used as a marker of the disease activity and may provide diagnostic and prognostic information. However this needs to be further studied to detect the cut off level of sICAM-1 in Egyptian HCV-related liver cirrhosis