influence of HLA-DRB1 alleles on polyarticular onset juvenile rheumatoid arthritis susceptibility, severity, and prognosis

The genetic background of juvenile rheumatoid arthritis [JRA] in Egyptian children is understudied. The association between class II human leukocyte antigen [HLA] and RA in adults had been reported in different ethnic populations. To detect the frequency prevalence of HLA-DRB1 genes, and to study the influence of such alleles on JRA susceptibility or protection among a group of Egyptian children having polyarticular onset JRA. Also, to clarify the genetic contribution of the shared epitope [SE] positive alleles in relation to JRA severity and progression. Genotyping of HLA-DRB1 alleles were analyzed by polymerase chain reaction- sequence-specific primer amplification and allele specific probing technique in 60 JRA Egyptian children and 50 healthy children serving as controls. Measurement of bone mineral density [BMD using single energy quantitative computed tomography [SEOCT] was done to all patients and controls. The strength of the association of these alleles with JRA susceptibility, severity [clinical and radiological], and progression was expressed as relative risk estimated by odd ratio [OR]. The most frequent DRB1 specificities among JRA were *04 [allele frequency = 25.2%], *14 [20.7%], and *01[10.8%] compared to *08 [25.6%] and *04 [16.9%] among controls. In a logistic regression model, both DRB1 *04, and *14 alleles were significantly associated with JRA susceptibility while *08 allele was protective. Among JRA, the most common SE-containing DRB1 haplotypes were *1001 [5.4%], *0101 *0401, *0404, and *1402 [4.5% for each]. SE sequences were present in 40% of patients compared to 10% of controls [P=0.0001]. SE was present in homozygous state in 22% of patients. Furthermore, in a logistic regression model, the likelihood of having JRA was 29.6-fold higher among homozygote SE [P=0.002], compared to 1.94-fold higher among heterozygote SE [P=0.06]. The SE sequence [QKRAA, QRRAA and RRRAA] was found in [10%, 41.6%, and 10% respectively in JRA versus 2%, 8%, and 2% respectively in controls]. The carriage of [SE+/+] alleles encoding glutamine [0] at beta 70 [Q70 + or high risk SE] were associated with the greatest risk of JRA, while possession of alleles encoding aspartic [D] at beta 70 [D70 + or low risk SE] were associated with the lowest risk [OR 0.46 and 0.64, respectively] There were significant associations between disease clinical severity, radiological progression, and reduced BMD and the presence of [*04] and [*01] alleles. Our findings confirm the association of DRB1 *04 and *14 alleles with JRA susceptibility, and DRB1*08 with protection. A double allelic dose of SE particularly *04 and *01 alleles may contribute to the risk of developing severe forms of JRA, and are strong determinant of disease progression and aggressiveness. We recommended that DRB1 genotyping is one of the parameters to be taken into account to predict the course and prognosis of JRA and to aid in selecting children who deserve early aggressive therapy, thereby helping to prevent some of the associated morbidity and mortality. Further wide scale prospective hospital-based controlled studies are warranted to verify this conclusion and extend preliminary results

Hepatocyte growth factor and interleukin - 6 as markers for evaluation of tissue trauma and stress response after laparoscopic and open cholecystectomy

The present prospective r and omized study was planned to compare the clinical outcome and tissue trauma after two cholecystectomy techniques; namely, open and laparoscopic surgical procedures. Forty patients were r and omized to either laparoscopic or open approaches. Blood samples were drawn preoperatively as well as at 12 and 36 hours following the operation. Hepatocyte growth factor [HGF] and interleukin-6 [IL-6] levels were used to evaluate cytokine release, while C-reactive protein [CRP] and morning cortisol were used to clarify the inflammatory response. It was found that hepatocyte growth factor and interleukin-6 elevation in response to stress and tissue trauma is an inevitable metabolic response in both laparoscopic and open approaches, this is associated with increased acute phase reactants [CRP and stress hormones as morning cortisol]. However, laparoscopic surgery exhibited significant lower levels of both hepatocyte growth factor and interleukin-6 at 36 hours postoperatively, which can be attributed to the amelioration of tissue trauma on using the laparoscopic approach. Thus, it can provide less perception of pain as well as shorter convalescence time and postoperative hospital stay

Efficacy of cystatin C as a screening test for reduced glomerular filtration rate

The objective of this study was to evaluate the efficacy of cystatin C as a screening test for reduced glomerular filtration rate [GFR] in comparison to S. creatinine and to assess whether cystatin C is performed differentially in either glomerular or tubular renal diseases or not. This study involved 105 patients with different renal diseases they were admitted as inpatients in Internal Medicine Department at Ain Shams University Hospital, and were classified according to GFR ml/min/1.73 m[2] into : group I patients, n = 35, GFR >/= 70 ml/min/1.73 m[2] group II patients, n = 33, GFR [< 70 - >/= 50] ml/mins/1.73m[2] and group III patients, n= 37, GFR < 50ml/min/1.73m[2], and a control group of 30 volunteers with matched age and sex to evaluate the reference value of cystatin C. All groups were subjected to the following : complete history taking and thorough clinical examination. Kidney function tests including : Bun, S. creatinine, creatinine clearance, 24 hours urinary proteins quantitation, [99m]Tc DTPA renal isotope scanning for accurate evaluation of glomerular filtration rate [GFR]. Abdominal U/S with full comment on the kidneys. Qualitative assessment of urinary proteins. Assessment of serum cystatin C by DAKO cystatin C pet kit which is particle enhanced turbidimetric immunassay. Our results revealed that the mean S. cystatin C was 7.9 +/- 3.8, 14.3 +/- 8.2 and 16.2 +/- 3.6 mg/l in groups I, II and III respectively when compared with that of the control group with a mean of 0.9 +/- 1 mg/l it was statically highly significant [F = 61.8, P < 0.01]. S. cystatin C was more sensitive than S. creatinine in reflecting the true GFR, this was specially observed in group I patients [mild renal impairment] as their mean serum creatinine was still within its normal range 0.97 +/- 0.4 mg/dl, while their mean GFR measured by both creatinine clearance and isotope clearance was 68.3 +/- 4.7, 67.5 +/- 45 ml/min/1.73 m[2] respectively. Meanwhile, their mean S. cystatin C was 7.9 +/- 3.8 mg/l statistically highly significant than that of the control group with a mean of 0.9 +/- 1 mg/l, [P < 0.05]. Also there was statistically non significant correlation between S. cystatin C and S. creatinine in group I patients [r = 0.1, P > 0.05] while there was significant correlation between them in group II and III patients [r = 0.38, 0.59, P < 0.05]. Moreover, S. cystatin C has a significant negative correlation with GFR measured by both creatinine clearance [r = -0.37, -0.54 and -0.48] and radioisotope clearance [r = -0.34, -0.35 and -0.37], [P < 0.05] in groups I, II and III respectively, i.e., throughout the whole range of renal impairment. Cystatin C had non significant correlation with either age or sex of the patients. While, S. creatinine had a significant correlation with creatinine clearance and isotope clearance in group II and III patients, i.e., with advanced renal diseases, but not with group I patients [mild renal impairment]. Also S. cystatin C had higher sensitivity [90% [vs] 83%] and negative predictive value [NPV] [89 [vs] 80] than S. creatinine in assessing GFR measured by both creatinine clearance or by radioisotope clearance. There was non significant difference regarding the mean S. cystatin C between subgroup [A] [glomerular diseases] and subgroup [B] [tubular diseases] within the same GFR category [P > 0.05]. S. cystatin C was more sensitive and superior to S. creatinine in detecting reduced GFR measured by both creatinine and radioisotope clearance. S. cystatin C is more efficacious than S. creatinine as a screening test as it had a higher sensitivity and higher negative predictive values than S. creatinine. In detecting reduced GFR. The efficacy of cystatin C is independent on either glomerular or tubular renal diseases and showed a high degree of reproducibility