Splenic Status Research Articles

Discordant Post-natal Patterns in Fetuses With Heterotaxy Syndrome: A Retrospective Single-Centre Series on Outcome After Fetal Diagnosis.

ObjectiveCardiac and extra-cardiac anomalies in 46 pre-natally diagnosed cases of heterotaxy were compared to post-natal anatomical patterns in order to reveal discordant findings. Second, the outcome of these fetuses was evaluated.MethodsFetuses with heterotaxy, diagnosed in a tertiary referral centre, were analysed retrospectively. Based on the foetal abdominal situs view, right atrial isomerism (RAI) and left atrial isomerism (LAI) were defined as foetal sub-types. Post-natally, discordant anatomical patterns for broncho-pulmonary branching, atrial appendage morphology, and splenic status were further clarified with CT scans. In summary, the spectrum of pre-natally and post-natally detected cardiac and extra-cardiac anomalies is systematically reviewed. Necessary surgical interventions and mid-long-term outcomes were compared between the two sub-types in surviving infants.ResultsA total of 46 fetuses with heterotaxy were included; LAI was diagnosed in 29 (63%) fetuses and RAI was diagnosed in 17 (37%) fetuses. Extra-cardiac anomalies were noted in 35% of fetuses. Seven out of the 29 fetuses (24%) with LAI had atrio-ventricular block (AVB) and four of these cases presented with hydrops. Twenty nine out of the 46 participating fetuses (63%) were live births, with 62% in the LAI group and 65% in the RAI group. Five fetuses were lost to follow-up. At the age of 1 year, the overall survival of live births [estimate (95% CI)] was 67% (48; 92%) in patients with LAI and 55% (32; 94%) in patients with RAI. At the age of 5 years, the estimates were 67% (48; 92%) in the LAI group and 46% (24–87%) in the RAI group. The median survival (first quartile; third quartile) was 11.1 (0.1; 14) years for patients with LAI and 1.3 (0.09; NA) years for patients with RAI. Of 17 children who had undergone cardiac surgery, five (29%) children achieved a bi-ventricular repair and 12 (70%) children achieved a uni-ventricular palliation. Three were primarily palliated, but converted to bi-ventricular thereafter. Foetal subtype definition of heterotaxy based on the abdominal situs and post-natal thoracic imaging studies showed a discordant pattern of broncho-pulmonary branching and atrial appendage anatomy in 40% of our live-born children.ConclusionHeterotaxy is a rare and complex condition with significant morbidity and mortality related to severe cardiac and extra-cardiac associations. Accurate pre-natal diagnosis can help identify the fetuses at risk and allow for timely intervention in a multi-disciplinary setting. Further studies are warranted to shed light on the exact sub-type definition in fetuses with heterotaxy and the presence of discordant post-natal patterns.

ASSESSMENT OF SERUM SCLEROSTIN LEVEL AS A BIOMARKER ASSOCIATED WITH BONE DISORDERS IN Β-THALASSEMIA PATIENTS IN AL- NAJAF CITY, IRAQ

Background: β-thalassemia is a blood disorder in which the body does not make hemoglobin normally. Aim: To assess serum sclerostin in female patients with beta-thalassemia and compare with the healthy controls and to predict its complication associated with the bone pathophysiology, for designed improvement the lifestyle goodliness for these patients. Material and methods: Sixty-nine female beta-thalassemia (βT) patients (54 βT major and 15 βT Intermedia), aged 8-40 years who dependent on transfused blood, and 20 healthy controls were evaluated serum sclerostin, and was examined the relationship with hematological parameters RBC, Hb, PCV, WBC, PLT, BMI, splenic status, iron, and ferritin levels. The information of beta-thalassemia patients was collected and records by the questioner. Results: A significantly increased serum sclerostin level (mean 26.80±0.91) pg/ml was showed in βT patients compared with the healthy controls (10.03±0.68, p smaller than 0.001) pg/ml. Furthermore, a significant decrease (p smaller than 0.05) of the sclerostin level was observed in β-thalassemia major compared to intermedia β-thalassemia patients. Serum sclerostin level revealed a significant increase in progress age; it is highest in the age group (30-40) year as compared with age group (8-18) and (19-29) year respectively. Sclerostin showed no associations with the RBC, Hb, PCV, and significantly positively correlated (p smaller than 0.05) with serum iron, ferritin levels, WBC, and PLT count. Significantly higher sclerostin levels in splenectomized and underweight groups were observed compared to unsplenectomized and normal-weight groups (p smaller than 0.05) of βT patients. Conclusions: Sclerostin plays an important role in beta-thalassemia patients and can serve as a biomarker associated with the bone pathophysiology and indicator to prevent the continuation of such serious diseases caused by iron overload in these patients.

E-SELECTIN AS A BIOMARKER IN FEMALE PATIENTS WITH Β-THALASSEMIA IN AL-NAJAF PROVENCE, IRAQ

E-selectin, as identified (CD62E), is expressed on endothelial cells after stimulation with inflammation cytokines. β-Thalassemia diseases (βT) and early diagnosis are of utmost significance in the entire world population. This study was performed in the Thalassemia Center of the Al-Zahraa Educational Hospital in Al-Najaf Province, Iraq, on sixty-nine with β-thalassemia (54 βT major and 15 βT Intermedia) aged 8-40 years who transfused blood. Compared to 20 healthy volunteers as a control group. In both βT patients and healthy groups were assessed serum E-selectin levels. It was investigated the relationship with RBC, Hb, PCV, WBC, PLT, BMI, splenic status, iron, and ferritin levels. The results revealed a significant (P<0.05) decreased values of HB, RBC, P.C.V, and BMI. In contrast, values of WBC, PLT, Iron, and Ferritin were significantly increased in βT patients as compared to the healthy control groups. A significant (P<0.05) increase in serum E- Selectin level in βT patients (20.55±0.47) ng/ml to compare with the healthy group (9.16±0.50) ng/ml. Furthermore, it was a significant decrease in groups of βT major (19.87±0.42) ng/ml more than in βT intermedia (23±1.42) ng/ml. E-Selectin revealed a significant increase (P<0.05) in progress age and associated with splenectomies and underweight groups compared to splenectomies and the normal weight groups, respectively. Also, E-Selectin levels significantly positively correlated with WBC, PLT value, iron, and Ferritin levels. However, it was no significant with RBC, PCV, Hb. As a conclusion from this study, E- Selectin is an important biomarker in β-thalassemia patients can be identified as the complications associated with iron overload, inflammatory process, and endothelial dysfunction in βT disease.

Abnormal red blood cell morphological changes in thalassaemia associated with iron overload and oxidative stress

AimsIron overload is a major factor contributing to the overall pathology of thalassaemia, which is primarily mediated by ineffective erythropoiesis and shorter mature red blood cell (RBC) survival. Iron accumulation...

Estimation of Procollagen Type III Peptide (PIIIP) Level in β Thalassemia Patients

Procollagen type III peptide (PIIIP) is established as biochemical markers of liver fibrosis. So that, type III (Pro-C3) can be used as diagnostic tools for liver fibrosis. Collagen type III amino-terminal pro-peptide (PIIINP) is a degradation product of collagen type III, the increase of which may reflect an ongoing fibrotic process. Procollagen type III is found abundantly in skeletal muscle and other soft tissues such as skin, and in negligible amounts in bone. During the late phases of collagen synthesis, the N-terminal end of procollagen type III is cleaved releasing P3NP into the circulation. According to case-control study. This study was conducted with eighty-eight of males that age ranges from 2–29 years, which divided in 60 of males with β-thalassemia whom have visited the Thalassemia Center at Al-Zahraa Teaching Hospital in Al-Najaf province, Iraq, for managed of the disease, and 28 voluntary healthy as a control groups of. The study was carried out from January 2018 to July 2018., Procollagen type III in β-thalassemic patients and healthy groups of males. It also investigates the relationship between these biomarkers levels was measurement by using a solid phase enzyme-linked immunosorbent assay (ELISA) and also, determined Hb, Body Mass Index, splenic status liver function test (ALT, ASTand ALP).

Long-term survival and phenotypic spectrum in heterotaxy syndrome: A 25-year follow-up experience

BackgroundHeterotaxy syndrome (HS) is a group of congenital disorders characterized by abnormal arrangement of thoraco-abdominal organs across the left-right axis of the body, classified as right (RAI) and left atrial isomerism (LAI)·We investigated the long-term survival and phenotypic spectrum in our HS cohort. Results are compared to literature data. MethodsThis is a single centre, observational, both retro and prospective study. Cardiac features, surgical management and abdominal ultrasound (US) of all HS patients were reviewed or investigated if missing. We evaluated all anatomical data and their clinical impact on survival, arrhythmias, infections, and heart transplant (HT). Results136 patients were classified as RAI (81) and LAI (55). Long-term survival and freedom from HT reached 69.8% and 87.8% at 40 years in RAI and LAI, respectively. Multivariate analysis showed that LAI is an independent predictor for pacemaker implantation (p = 0.019). Splenic status varied in both groups: in RAI, abdominal US showed asplenia, polysplenia and normal spleen in 48%, 4% and 32% of patients, respectively, whereas in LAI polysplenia, asplenia and normal spleen occurred in 64%, 4% and 16% of cases, respectively. ConclusionsMortality was significantly lower (9%) compared to literature (50%). Although patients with RAI experienced a higher mortality, no independent predictors were found. We demonstrated that the obsolete cardiac definition of “asplenia” and “polysplenia” instead of RAI and LAI is misleading, because of the high variability of the splenic phenotype among patients of both groups.

Microstructural changes and immunohistological analysis of pro-inflammatory cytokines in spleens of lipopolysaccharide-induced rats

This study investigated splenic status changes in weaned Sprague-Dawley rats induced by lipopolysaccharide. There were forty 26-day-old rats selected randomly and equally divided into two groups. The treatment group received daily single doses of lipopolysaccharide, and the control group was treated with normal saline. We conducted haematoxylin-eosin staining, immunohistochemical staining and semi-quantitative optical density analysis for both groups on the 29th, 32nd, 35th and 38th days after treatment. The results indicated that splenic marginal zone in the lipopolysaccharide group was thinner or disappeared compared to that of the saline group. However, the periarterial lymphoid sheath and the diameters of splenic lymphoid follicles appeared thicker and wider than those in the saline group (P less than 0.05). The expression of interleukin-1 beta, interleukin-6 and tumour necrosis factor alpha was mainly localized within the periarterial lymphoid sheath and splenic lymphoid follicles in the lipopolysaccharide treated rats. The integrated optical density and the average optical density in the lipopolysaccharide group were greater than those in the normal saline treated group (P less than 0.05). In conclusion, splenic immune function is probably strengthened by altering microstructures and releasing pro-inflammatory cytokines following lipopolysaccharide treatment.

Highlights From the Circulation Family of Journals

Highlights From the <i>Circulation</i> Family of Journals

Disharmonious Patterns of Heterotaxy and Isomerism: How Often Are the Classic Patterns Breached?

It is advocated that heterotaxy should be segregated into right or left isomerism according to atrial appendage morphology. However, atrial situs determination is often based on the pattern of associated findings rather than on atrial morphology itself, which can be difficult to define. The objective was to assess how often concordant patterns of isomerism classified by atrial appendage morphology, bronchopulmonary pattern, and splenic status are breached using cardiac magnetic resonance or computed tomography. The secondary objective was to determine the feasibility of defining atrial appendage morphology using cardiac magnetic resonance or computed tomography. Retrospective review of 114 pediatric patients (median, 2.4 years; range, 1 day-17.9 years) with heterotaxy who underwent cardiac magnetic resonance or computed tomography was performed to evaluate atrial appendage, bronchopulmonary, and visceral organ arrangements. Atrial appendage and splenic anatomy were not definable in 17 of 114 (15%) and 4 of 114 (3.5%) patients, respectively. In the remaining 93 patients, 39% had classic right isomerism (bilateral right atrial appendages, right bronchopulmonary pattern, and asplenia) and 40% had classic left isomerism (bilateral left atrial appendages, left bronchopulmonary pattern, and polysplenia). Classic pattern of isomerism was breached in 20 of 93 (21.5%) patients: 13 (65%) displayed incongruent abdominal situs, 5 (25%) incongruent bronchial situs, 1 (5%) had discrepant appendage morphology, and 1 (5%) incongruent situs at all levels. Atrial appendage morphology is difficult to assess and not always indicative of bronchopulmonary or abdominal situs. Discordance between bronchopulmonary branching, atrial appendage arrangement, and splenic status was identified in >20% patients with heterotaxy. Independent description of each organ system is required when arrangements are disharmonious among different organ systems.

Classifying Heterotaxy Syndrome

Heterotaxy syndrome is a complex set of abnormalities related to abnormal left–right axis patterning. Although rare (occurring in just over 1 in 10 000 live births1), congenital heart defects associated with heterotaxy syndrome carry a disproportionate burden of morbidity and mortality.2,3 Despite numerous investigations on the genetic underpinning, epidemiology, anatomic pathology, diagnostic imaging, and management, agreement regarding the best method to classify patients with heterotaxy continues to elude our field.4 Specifically, a growing body of experience has noted that the 2 most common methods of classifying patients with heterotaxy—based on the status of the spleen or on the morphology of the atrial appendages—is frequently incongruent with the expected pattern of cardiac and noncardiac anomalies,5 is difficult to ascertain clinically, and may not be helpful in guiding clinical management.2–4 See Article by Yim et al In this issue of Circulation: Cardiovascular Imaging , Yim et al6 provide further evidence that the prevailing classification schemes used in heterotaxy syndrome are flawed. In a retrospective analysis of noninvasive imaging data from 114 patients with heterotaxy, they noted that the classic pattern of isomerism was breached in 1 of every 5 patients. Furthermore, they documented the limited clinical utility of relying on atrial appendage morphology or the status of the spleen and …

Factors influencing bacteraemia in patients with isomerism and CHD: the effects of functional splenic status and antibiotic prophylaxis.

"Heterotaxy syndrome", best segregated as isomerism, is characterised by laterality defects of the thoraco-abdominal organs, causing functional impairment. In particular, the spleen is frequently affected, increasing susceptibility to bacteraemia. This study explored factors that may increase the risk of bacteraemia in patients with isomerism. We identified patients with CHD and isomerism. Review of outpatient, inpatient, and surgical records was conducted to collect data and determine trends in the cohort. A Cox regression analysis was conducted to determine factors influencing freedom from bacteraemia (Fig 1). We identified 83 patients with CHD and isomerism - 17 (20%) who had documented episodes of bacteraemia with a total of 21 episodes. A majority (86%) were nosocomial. The median age at the time of bacteraemia was 4 months. Although splenic anatomy did appear to influence the risk of bacteraemia in univariate analysis, this significance was lost with multivariate analysis. None of the other factors was significantly associated in either univariate or multivariate analysis. Specific factors such as splenic anatomy, atrial appendage isomerism, and antibiotic prophylaxis status are not significantly associated with the risk of bacteraemia in patients with CHD and isomerism. Nosocomial infections represent a majority of bacteraemia in these patients.

Involvement of splenic iron accumulation in the development of nonalcoholic steatohepatitis in Tsumura Suzuki Obese Diabetes mice.

Nonalcoholic steatohepatitis (NASH) is a common hepatic manifestation of metabolic syndrome and can lead to hepatic cirrhosis and cancer. It is considered that NASH is caused by multiple parallel events, including abnormal lipid metabolism, gut-derived-endotoxin-induced inflammation, and adipocytokines derived from adipose tissue, suggesting that other tissues are involved in NASH development. Previous studies demonstrated that spleen enlargement is observed during the course of NASH pathogenesis. However, the involvement of splenic status in the progression of NASH remains unclear. In this study, we examined hepatic and splenic histopathological findings in the early stage of NASH using the Tsumura Suzuki Obese Diabetes (TSOD) mouse model established for assessing NASH. We found that 12-week-old TSOD mice clearly exhibited the histopathological features of NASH in the early stage. At this age, the spleen of TSOD mice showed markedly higher iron level than that of control Tsumura Suzuki Non Obesity (TSNO) mice. The level of accumulated iron was significantly decreased by feeding a diet with glucosyl hesperidin, a bioactive flavonoid, accompanied with alleviation of hepatic lesions. Furthermore, we found that splenic iron level was positively correlated with the severity of NASH manifestations, suggesting that abnormalities in the spleen are involved in the development of NASH.

Postpartum Catastrophic Anti-Phospholipid Syndrome

Multi-organ dysfunction during peripartum period in the background of anti-phospholipid syndrome (APS) poses a tremendous diagnostic dilemma leading to extremely high morbidity and mortality. We present a diagnosed APS case of 29 year old multigravida, who was admitted to intensive care unit with post-partum pulmonary edema, severe thrombocytopenia, paralytic ileus, hepatic and splenic infarcts, status epilepticus and lower limb venous thrombosis despite being on prophylactic anticoagulation. She recovered after treatment with escalating doses of prednisolone, antiepileptics, mechanical ventilator support with muscle paralysis and therapeutic plasma exchange (TPE).This case highlights the utmost importance of awareness, high degree of suspicion and prompt adoption of appropriate supportive treatment to achieve a favourable outcome in catastrophic anti phospholipid syndrome (CAPS).

Response to hydroxycarbamide in pediatric β-thalassemia intermedia: 8 years' follow-up in Egypt.

Hydroxycarbamide (hydroxyurea or HU) has been shown to increase fetal hemoglobin (HbF) in patients with β-thalassemia intermedia (TI). The reported effects of HU in increasing the total hemoglobin (Hb) have been inconsistent. Studies of long-term therapy with HU in pediatric TI are rather uncommon. A retrospective observational study was carried out to evaluate the clinical responses to HU in Egyptian patients with β-TI. One hundred patients; children (n = 82, mean age 9.9 ± 4.1 years) and adults (n = 18) were studied for the mean Hb, HbF%, median serum ferritin, transfusion history, and splenic size before and after HU therapy (mean dose 20.0 ± 4.2 mg/kg/day, range 10-29 mg/kg/day) over a follow-up period 4 to 96 months (mean 35.4 ± 19.2 months). Molecular studies were also done for group of patients (n = 42). The overall response rate to HU was 79 %; 46 % were minor responders (with a reduction in transfusion rate by 50 % or more and/or an increase in their total hemoglobin level by 1-2 g/dl) and 33 % major responders (becoming transfusion-free and/or having an increase in total hemoglobin level by >2 g/dl). Mean hemoglobin increased among responders from 6.9 ± 0.9 g/dl to 8.3 ± 1.4 g/dl (p < 0.001). A significant rise in mean HbF (27.0 vs. 42.5 %; p < 0.011) and a decrease in median serum ferritin (800 vs. 644 ng/ml; p < 0.001) were also observed among responders (n = 45). Transfusions stopped in 44 % of pretreatment frequently transfused responders (n = 11/25). Splenic size decreased in 37 % of patients (n = 30/81). The predominant β-thalassemia mutation was 1-6 (T > C) in 32/42 (76 %) of studied patients; 28/32 were responders. Bivariate analysis showed no predictors of response as regards sex, pediatric and adult age, splenic status, or genotype. Hydroxycarbamide is a good therapeutic modality in the management of pediatric as in adult TI patients. It can minimize the need for blood transfusion, concomitant iron overload, and blood-born viral transmission especially in developing countries like Egypt.

Pulmonary Function Abnormalities in Non-Splenectomized and Splenectomized Adult Hemoglobin E/β-Thalassemia Patients and Their Correlation With Pulmonary Hypertension

The effect of splenectomy on pulmonary function test (PFT) and pulmonary hypertension (PH) in thalassemia remains unclear. We aimed to investigate PFT and their association with PH in patients with hemoglobin E/β-thalassemia stratified by their splenic status. Thirteen splenectomized patients (SP) and 12 non-splenectomized patients (NSP) were compared regarding to the PFT abnormalities and PH (mean pulmonary artery pressure from right-heart catheterization ≥25 mmHg or estimated systolic pulmonary artery pressure from echocardiography ≥40 mmHg). Eleven (84%) SP and 9 (75%) NSP had restrictive impairment (RI). Of these, more patients having severe RI in SP than in NSP (8 vs. 2, P = 0.035). FVC and PaO2 were lower in SP than in NSP (66 ± 15% vs. 77 ± 12%, P = 0.043, and 79.38 ± 1.6 mmHg vs. 98.83 ± 6.2 mmHg, P &lt; 0.001, respectively). Residual volume was higher in SP than in NSP (78 ± 17% vs. 64 ± 15%, P = 0.036). Seven (54%) SP who developed PH had a longer time interval between splenectomy and the onset of PH than those who did not (17 ± 4.9 years vs. 9.8 ± 6.1 years, P = 0.04). In conclusion, greater severity of extrapulmonary restrictive impairment and hypoxemia were more common in SP. These patients developed PH as a late complication unrelated to hypoxemia and PFT parameters.

Characterization of the Hepatic and Splenic Immune Status and Immunoglobulin Synthesis in Aged Male Mice Lacking the Peroxisome Proliferator-Activated Receptor-Alpha (PPARα)

It is now well established that the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPARα) is expressed in different types of immune cells and plays a pivotal role in the regulation of age-related production of inflammatory cytokines. However, the role(s) of this receptor in the regulation of immune cell homoeostasis in ageing non-lymphoid and lymphoid organs has not yet been resolved. We examine this issue here by evaluating the hepatic and splenic immune status and immunoglobulin (Ig) production in male PPARα-null mice and their wild-type littermates at one and 2 years of age. In comparison with the age-matched control animals, PPARα-null mice exhibited age-related elevations in the numbers of total, as well as of phenotypically distinct subpopulations of intrahepatic immune cells (IHIC) and splenocytes. Moreover, at 2 years of age, these alterations in hepatic immune cells were accompanied by significant increases in hepatic levels of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interferon-gamma (IFN-γ), in combination with the development of hepatic inflammatory loci containing mixtures of leucocytes. Alterations in splenocytes of old PPARα-null mice were also accompanied by increases in cellularity of both white and red pulps of the spleen. Furthermore, these same animals exhibited pronounced increases in the numbers of splenic plasma cells and enhanced production of Ig of different isotypes, including IgG1, IgG2a and IgE. Thus, our findings indicate that upon ageing, PPARα plays a crucial role in regulating the total numbers, compositions and functions of immune cells in both lymphoid and non-lymphoid immune organs of mice.

Activation of mononuclear phagocytes and its relationship to asplenia and phosphatidylserine exposing red blood cells in hemoglobin E/β-thalassemia patients

Aged or abnormal red blood cells with exposed phosphatidylserine (PSRBCs) are cleared from the circulation by splenic macrophages. In asplenic patients, other mononuclear phagocytic cells in tissues and in circulation may function in this capacity. To better understand these changes and the relationship among splenic status, PS-RBCs, blood monocytes, and serum tumor necrosis factor (TNF-α), a product of mononuclear phagocyte activation, patients with hemoglobin E/β-thalassemia (E/β-Thal) were studied. Whole blood of 20 nonsplenectomized, 20 splenectomized E/β-Thal patients, and 20 healthy subjects was assayed for PS-RBCs; for monocytes, activated monocytes, and monocyte response to lipopolysaccharide stimulation; and serum was assayed for TNF-α. Asplenic E/β-Thal patients had significantly increased (P < 0.05) amounts of PS-RBCs, monocytes, activated monocytes, and levels of serum TNF-α. The amount of PS-RBCs correlated with levels of serum TNF-α, but the amount of activated monocytes did not correlate with either the amount of PS-RBCs or levels of serum TNF-α. Monocyte response to lipopolysaccharide stimulation in asplenic patients was not as efficient as in the other patients or in normals (77 vs. 404, and 304 folds increment, respectively). The results suggest that splenectomy in E/β-Thal patients led to an increased amount of PSRBCs and activation in the mononuclear phagocytic system.

Study of the immunomodulatory and anti-inflammatory effects of evening primrose oil in adjuvant arthritis

The present study was carried out to evaluate the anti-arthritic nature of evening primrose oil (EPO) rich in γ-linolenic acid (GLA), on adjuvant-induced arthritic rats. Results were compared to those of diclofenac sodium, a reference standard non-steroidal anti-inflammatory drug. Arthritis was induced by subcutaneous injection of complete Freund’s adjuvant (CFA) in the right hind paw of male Wistar rats. EPO (5 g/kg b.w.) was orally administered from day 0 till day 28, while diclofenac sodium (5 mg/kg b.w.) was orally given from day 10 to day 28 after adjuvant injection. In the arthritic group, the results revealed significant decrease in body weight together with increased spleen weight, increase in serum immunoglobulin G (IgG), immunoglobulin M (IgM) and tumor necrosis factor-α (TNF-α) levels whereas serum interleukin-4 (IL-4) level was decreased. Serum N-acetyl-β-D-glucosaminidase (NAG) and β-glucuronidase enzyme activities were also elevated. Splenic antioxidant status was suppressed as manifested by increased malondialdehyde (MDA) level, decreased glutathione (GSH) content along with decreased enzymatic activity of glutathione peroxidase (GSHPx), glutathione reductase (GR) and glutathione-S-transferase (GST). Moreover, the splenic activity of the pathophysiological enzymes, γ-glutamyltransferase (γ-GT) and lactate dehydrogenase (LDH) was enhanced. Oral administration of EPO exerted a significant elevation in serum IgG and IgM levels. In addition, normalization of body weight, serum IL-4 and TNF-α levels together with serum NAG, β-glucuronidase and splenic LDH enzyme activities were observed. It could be suggested that administration of plant oils rich in GLA may provide a way to modulate the inflammatory response through alteration of certain inflammatory indices. Key words: Adjuvant-induced arthritis, evening primrose oil, immunoglobulins, IL- 4, TNF-α, rat.

PULMONARY HYPERTENSION IN β-THALASSEMIA MAJOR AND THE ROLE OF L-CARNITINE THERAPY

Cardiac complications, such as pulmonary hypertension (PHT), are the leading cause of death in β-thalassemia patients. L-Carnitine, due to its role in fatty acid oxidation, might help control the elevation in pulmonary artery systolic pressure (PASP). The objectives of this study were to assess the prevalence of PHT in β-thalassemia major patients, identify clinical predictors for its development, and determine the potential effects of L-carnitine. In total, 32 patients with β-thalassemia major were recruited; 16 age- and sex-matched children constituted the control group. Cardiac evaluation was performed by using echocardiography. The patients with PHT received 50 mg/kg/day L-carnitine orally for 3 months and were then reevaluated. Based on PASP, the patients were divided into group A without PHT and group B with PHT. The prevalence of PHT was 37.5%. The other echocardiographic measurements were not significantly different between groups A and B. PASP did not have any significant correlation with the following variables: age, total number of blood units received, splenic status, serum ferritin level, and ejection fraction. Following the administration of L-carnitine, there was a significant decrease in the mean PASP from 33.96 ± 7.85 to 24.11 ± 7.61. All cardiac dimensions decreased following L-carnitine, but the changes were not statistically significant. Even though β-thalassemia major resulted in an elevation in the PASP in only a fraction of the patients, it seems to have an impact on the heart dimensions and function of all patients. No clinical predictors were identified. Oral administration of L-carnitine appears to significantly improve PASP.

Reduced levels of T-cell subsets CD4+ and CD8+ in homozygous sickle cell anaemia patients with splenic defects.

T-lymphocyte subsets were studied in two patient groups: (1) 50 patients with homozygous sickle cell anaemia (SCA) (mean age 12 (range 3-32) years old) in good health at the time of the study who showed no infectious complication. (2) 50 patients (mean age 13 (range 4-29) years old) with normal haemoglobin rate. The global response revealed a significant increase in levels of CD3+ (P=0.04) and CD8+ (P=0.04) cells when compared with the control group, there was no significant difference in levels of CD4+ cells (P=0.05) between the two groups. However, there was a relationship between T-cell subpopulation levels and spleen status. The average values of T-cell subsets (CD4+ and CD8+) in patients with SCA-induced splenic defects (asplenic, splenomegaly or splenectomized patients) were significantly reduced when compared to SCA patients with normal spleens and the control groups. These data show that T-cell activity was reduced in patients with splenic defects. A correlation between splenic status and a perturbed host defence system in patients with SCA suggests that monitoring T-cell subsets might have prognostic value in the course of sickle cell disease.