Thyroid dysfunction and thyroid autoantibodies in Egyptian patients with systemic lupus erythematosus [SLE]

Background: Systemic lupus erythematosus [SLE] is a systemic autoimmune disease with many clinical manifestations and immunological abnormalities. SLE and autoimmune thyroid disease are at the two endpoints of a shared immunogenetic mechanism

Aim of the study: To evaluate the link between SLE and thyroid disorders

Patients and Methods: Thirty patients known to have SLE were recruited in this study, with age ranged from 17 to 35 years. All patients were submitted to history taking, clinical examination, and relevant laboratory investigation

Results: Thyroid disorders were common [33.3%] in lupus patients. Hypothyroidism was the commonest [16.6%] abnormality in SLE patients then euthyroid [10.0%], and lastly hyperthyroidism [6.6%]. The mean age of SLE patients was 26.1 +/- 1.5 year. Eighty percent of the patients were females. The most common SLEcharacteristics were malar flush [90.0%], photosenstivity [80.0%], fever [70.0%], and arthritis [50.0%]. Mean Hb level was 9.2 +/- 0.59 g/dL. While, mean values of acute phase reactants were erythrocyte sedmentaion rate [ESR] at 1[st] and 2[nd] hour [74.3 +/- 6.6 and 121.4 +/- 5.26 mm/h, respectively] and C-reactive protein [20 +/- 6.7 mg/L]. The means of FT[3], FT[4], TSH, TG Ab, and anti thyroperoxidase [TPO] Abin SLE patients were 136.6 +/- 14.1 ng/dL, 8.83 +/- 1.2 ng/dL, 4.15 +/- 1.27ng/dL, 15.12 +/- 11.15ng/dL, and 121 +/- 65.4 IU/mL, respectively. Meanwhile, 30.0% and 76.7% of SLE patients were +ve for rheumatoid factor [RF] and antineuclearAb, respectively. There were 6.7% and 16.7% of the patients +ve for thyroglobulin Ab and anti TPO Ab, respectively. The statistically significant differences parameters in SLE patients with normal and abnormal thyroid function were ESR at 1 and 2 hours, RF, and antiTPO Ab [P=0.00, 0.00, 0.03, and 0.03, respectively]. The statistically significant differences parameters of demographic, clinical, and laboratory data in SLE patients with normal and subgroups of abnormal thyroid function were age, SLE duration, Hb level, RBC, WBC, PLT, and ESR at 1 and 2 hours [P=0.00, 0.00, 0.00, 0.001, 0.0001, 0.00, 0.00, and 0.00, respectively]

Conclusion and Recommendation: Thyroid disorders are common in SLE patients. The most common form is hypothyrodism. Patients with SLE should be evaluated for thyroid disorders by testing FT[3], FT[4], TSH, TG Ab, and anti PO Ab for early detection of thyroid abnormalities. Further studies are needed to support and clarify the association between SLE and thyroid disorders

Frequent dose of peginterferon alfa 2a evaluation in treatment-naive chronic HCV, genotype 4 Egyptian patients

More frequent dosing with decreasing time intervals between injections of pegylated interferon in the treatment of HCV genotype 4, to our knowledge, was not tested before. The purpose of reducing the intervals between doses particularly in the first 12 weeks is to decrease the peak/trough ratio of the blood concentration of interferon in order to give no chance for the virus to recover. Therefore, the aim of this study is to explore the effect of such frequent dosing in the first 12 weeks as a trial to increase the response rates of our Egyptian patients with HCV genotype 4. This study includes 28 Egyptian patients, discovered to have chronic hepatitis C genotype 4 infection within 1-11 years before enrolling to study. They include 17 males and 11 females with mean age 41.57. Patients with active HCV infection without any vascular or parenchymatous decompensation were given pegasys 180 micro g every 5 days and ribavirin according the weight [800-1400 mg/day] for the first 4 injections. PCR is then done. Those with RVR [negative PCR after 4[th] injection] were treated in usual way with pegasys given every week. Those with detectable HCV RNA continued in the same way as first month for 12 injections. PCR was then repeated. Those showing EVR continued treatment in the usual way. Those with partial or slow EVR [detected HCV but viral load decreased at least 2 logs] continued as first month for 24 injections. Those with non EVR stopped treatment. All other patients continued treatment till 48 injections. Re-evaluation was done at end of treatment and after 6 and 12 months of end of treatment. Rapid virological response with disappearance of HCV RNA after 4 injections of treatment was detected in 14 cases [50%] in whom treatment in usual way continued till the end of 48 weeks. Additional 8 patients [28.6%] showed disappearance of HCV after 12 weeks of treatment to reach total of 22 cases [78.6%] in whom treatment in usual way continued till the end of 48 weeks. Three patients showed 2 log reduction of viral load continue treatment per protocol while 3 patients showed less viral load reduction were withdrawn from treatment. Additional 2 patients showed disappearance of HCV RNA at 24 weeks of treatment to reach a total of 24 patients [85.7%] the patient showing positive RNA stopped treatment. All those patients continuing treatment to 48 weeks remain negative for HCV RNA at end of treatment. Therefore, the ETR is 85.7% using this frequent dose administration of pegylated interferon. Only one patient relapse at week 72 [after 6 months of end of treatment]. Thus, the SVR occurred in 23/28 patient [82.14%]. Dose reduction was done for Ribavirin in 3 cases during treatment due to clinically significant decrease in the hemoglobin levels, all showed SVR. No reduction of interferon dose was commenced. General side effects were as usual and controlled with paracetamol. It is concluded that the use of more frequent peginterferon is associated with the best SVR in genotype 4, and whenever possible this strategy can be used particularly in patients with early disease as indicated by absence of sever hepatic or hematological abnormalities

Pegylated interferon alfa 2a and small dose ribavirin in the treatment of HCV genotype 4 in end-stage renal disease

As hepatitis C virus [HCV] infection is a major health problem in patients with end-stage renal disease [ESRD]. Explore the response rate and adverse effects of pegylated interferon and ribavirin in treating HCV genotype 4 in patients withend stage renal disease [ESRD] waiting renal transplantation. This study included 24 patients with ESRD and active HCV infection as detected by clinical, sonographic, biochemical, serological, virological and histological examination with liver biopsy. All patients were under hemodialysis with HCV antibodies positive > 6 months. Viral genotyping and both qualitative and quantitative PCR were carried out before starting therapy. Treatment was continued for 48 weeks using pegasys 135 micro g weekly and ribavirin 200 mg daily. The biochemical and virological responses were evaluated regularly during and after treatment. The sustained virological response [SVR] being evaluated 24 weeks later. The side effects were monitored throughout the treatment period. Rapid virological response [RVR] after week 4 was achieved in 11/24 [46%] patients. The sustained virological response [SVR] was achieved in 16/24 [66.7%] patients. No break through or relapses were detected during and after treatment respectively. Correlation was found between the viral load before treatment and that at week 4 with p < 0.001and at 12 weekand between the reduction of hemoglobin and the reduction of viral load at week 12 with p < 0.045. Genotype 4 HCV patients with ESRD can be considered for therapy pre-operatively to overcome all the morbidities associated with persistence of HCV after renal transplantation provided that the general condition, the hematological parameters and all other factors of treatment allowed such therapy

Detection of thrombogenicity induced by radiofrequency catheter ablation

The aim of this study is to determine the independent and incremental procoagidant effect of RF ablation by assessing biochemical marker of thrombogenicity. The biochemical markers used in this study is direct measures of fibrinolysis [d-dimer, DD]. This study is a comparative clinical trial that was conducted in EP laboratory of National Heart Institute. This study included forty patients are divided into twenty patients referred for radio-frequency transcatheter ablation in right side of the heart [patients with AVNRT] and twenty patients with accessory pathway in the left side of heart with supraventricular tachycardia. Patients with history of recent electrophysiological study [EPS], malignant disease, history of embolic events, recent surgery or trauma, history of atrial fibrillation, active thrombotic process, renal failure, cerebrovascular stroke or previously identified coagulopathy or thrombocytopenia were excluded from the study. No medications affecting the function of the platelets and coagulation system was administered in any of the study subjects. Any antiarrhythmic drugs were withdrawn prior to study. All patients included in the study were subjected to full history taking, thorough clinical examination, resting 12-lead electrocardiogram, transthoracic echocardiography, CBC, FT, PTT, routine laboratory investigations. D-dimer measurement was measured immediately after insertion of the venous sheaths, before introduction of the electrode catheters, on completion of EPS and mapping, before production of the first RF ablation [post-EPS measurements], after completion of the RF procedure [post-RF measurements], before sheath removal and at 36 to 40 hours later and before discharge from the hospital. The D-dimer level in all the studied patients increased significantly after EPS and in spite of that it decrease before discharge it is still significantly higher than that of the baseline level [P < 0.001]. In patients with AVNRT [right sided] and in patients with AP [left sided] the D-dimer level increased significantly after EPS and it decrease before discharge but it was still significantly higher than that of the baseline level [P < 0.001]. Comparison between left and right sided ablation showed no significant difference in the D-dimer level [P > 0.05]. Both right and left sided EPS ablation was associated with an increase in the D-dimer level and this increase continued until discharge

Pro and antiinflammatory cytokines in unstable angina

Recent studies suggest that inflammation may play an important role in the pathogenesis of acute coronary syndromes. Several inflammav tory markers are increased in acute coronary syndromes as the nonspecific hepatically synthesized CRP, instead, several cytokines are direct inflammatory mediators as lL-6 and TNF-alpha which increase in many disease states, including the acute coronary syndromes. lL-10 is an anti-inflammatory cytokine, is produced by Th2 lymphocytes, B cells, and monocytes. It inhibits macrophagedependent cytokine synthesis by Th1 cells thus regulate balance between ceII-and humeral-mediated immune response. The proinflammatory cytokines play a role in acute coronary syndrome. however. the potential role of anti-inflammatory cytokines in the modulation of atherosclerotic process remains unknown. The objective of this study is to assess the value of pro and entiinilammatory cytokines in patients with unstable angina. The present work assessed the serum level of proinflammatory cytokines lL-6 and TNF-alpha and anti-inflammatory cytokine lL-10 in 36 patients, 20 patients had chronic stable angina, their ages ranged between 48-62 years with mean age 53 years and 16 patients with unstable angina class IIIB according to Braunwald classification, their ages ranged between 4861 years and their mean age is 54 years. All patients were diagnosed by coronary angiography. A control group comprise 10 subjects oi matched age and sex also included in this study. Serum lL-6 end TNF-alpha show a highly significant elevation in unstable angina versus the other two groups [P<0.001], these proinflammatory cytokines are positively correlated with serum cholesterol, LDL-c. TG and negatively correlated with mm in whole groups. Serum anti-inflammatory cytokine IL-10 shows a highly significant decrease in patients with unstable angina when compared to the control group [P=0.002] and also shows significant decrease when compared to patients with stable angina group [P=0.02]. Also serum lL-10 shows a negative correlation with lL-6, TNF-alpha, serum cholesterol, LDL-c, TG and PPBS in whole groups. These results indicate that the level at antiinlammatory cytokine lL-10 decrease in patients with unstable angina and this decrease may be the cause of plaque instability and rupture

Usefulness of carotid intima-media thickness and brachial artery flow mediated dilatation in diabetic patients with suspected coronary artery disease

Objective: flow associated dilatation [FXD%] and intima media thickness are established markers of early atherosclerosis. This study aimed to compare the ability of the non-invasive measurements FAD% and intima media thickness to predict coronary artery disease in asymptomatic diabetic males

Methods: B-mode ultrasonography was used to assess both intima media thickness in the common carotid artery and endothelial function in the brachial artery in 64 non-insulin dependent diabetic male patients asymptomatic for coronary artery disease. They were divided into two groups, Group A comprise patients with positive stress test, and group B patients with negative stress test. Brachial artery diameter was measured at rest, during reactive hyperemia, and after sublingual administration of nitroglycerin

Results: patients with positive exercise stress test had reduced FAD% compared with those with negative exercise stress test [4.4 +/- 0.67 v 5.8 +/- 1.1 5%. p<0.001], whereas intima media thick-ness tended to be increased in patients with positive exercise stress test but not statistically significant [1.1 +/- 0.16 v 0.96 +/- 0.0lmm, p > 0.05]. There was a negative correlation between FAD% and intima media thickness [r =-0.498, p <0.001]. Receiver operating character-istic analysis showed that FAD% > 4.6% predicted coronary artery disease with a sensitivity of 0.70 and a specificity of 0.87

Conclusions: brachial artery FMD may become a useful tool for screening diabetic male patients with suspected CALI while determination of increased intima media thickness is not useful in discrimina between presence or absence of coronary artery disease

Clinical value of total HCV core antigen detection and quantification

Recently, the availability of total HCV core antigen assay in peripheral blood gains more interest in clinical evaluation of HCV patients. The aims of the present study were to assess the value of total HCV core antigen as a marker of viral replication, to determine the sensitivity of core antigen assay relative to molecular biology technique and to study the clinical value of HCV core antigen in relation to interferon-based treatment. This study included 150 patients sero-positive for antibodies to HCV. Viral load was assessed by both HCV RNA quantitative assay [bDNA] and HCV core antigen quantitative immunoassay [Ortho trak-C assay]. Spearman rank correlation coefficient was used to determine significant correlations among parameters. Of the 150 studied patients, 128 [85%] were positive to HCV RNA assay [bDNA] and 22 [15%] were negative. Have the 128 patients tested positive for HCV RNA, 125 patients tested positive by HCV core antigen assay with a sensitivity of 98%. All patients tested negative for HCV RNA assay [bDNA] gave negative results by HCV core antigen assay with a specificity of 100%. In the 125 patients that were positive in both assays, HCV RNA and total HCV core antigen were significantly related [r = 0.984; p< 0.001]. The relationship between HCV RNA in IU/ml and total HCV core antigen in pg/ml was given by the following equation: Log HCV core antigen = 0.649 x Log HCV RNA - 2.018. It was found that 1 core pg/ml is equivalent to approximately 8000 HCV RNA IU/ml in clinical samples of the studied patients. The correlation between HCV RNA IU/ml and HCV core antigen pg/ml varied around this average ratio when individual samples were considered, with the majority of the ratios lying between 5000 and 13000 HCV RNA IU/ml per core pg/ml. To evaluate the clinical use of total HCV core antigen quantification in the pretreatment assessment and in monitoring the response; to interferon therapy, sera from ten patients who were treated with a combination therapy of interferon alpha-2a and ribavirin had been studied. Serum samples were collected at baseline, 12 weeks after initiating therapy and at the end of treatment to be tested by both assays. There were significant correlations between log HCV RNA titer [IU/ml] and log HCV core antigen [pg/ml] [r = 0.693. 1.0 and 1.0 for the three comparisons respectively; p< 0.031. 0.003. and 0.017 respectively]. A weak relation had been found between necro-inflammatory changes in liver biopsy and viral load assessed by both assays. No relation could be found with the stage of liver fibrosis. In conclusion, the HCV core antigen assay can be used in confirming HCV infection when antibodies have been detected, in screening of patients, and in monitoring therapeutic interventions