Toll-like receptor 7 gene single nucleotide polymorphisms and the risk for systemic lupus erythematosus: a case-control study.

BACKGROUND: Toll-like receptors (TLRs) are a family of pattern-recognition receptors which play a role in eliciting innate/adaptive immune responses and developing chronic inflammation. So, the aim of this study was to analyze the effect of TLR7 gene single nucleotide polymorphisms (SNPs) rs3853839 and rs179019 on systemic lupus erythematosus (SLE) susceptibility and to assess their relations with various clinical and laboratory data of the patients. METHODS: This is a case-control study including 50 SLE female patients and 50 healthy controls. TLR7 rs3853839 and rs179019 genotyping was performed using real-time polymerase chain reaction (PCR) TaqMan-based allelic discrimination assay. RESULTS: Regarding rs3853839, there was a statistically significant difference in the distribution of the genotypes between SLE patients and the control group in our study (P = 0.009). A significant association was detected between TLR7 genotypes (rs385389) and lupus nephritis (p = 0.021). Regarding rs179019, there was no statistically significant difference in the distribution of the genotypes between SLE patients and the control group in our study (P = 0.271) CONCLUSION: This study revealed the plausible role of TLR7 rs3853839 SNP in SLE in Egyptian women.

Delayed sternal closure is a life saving decision.

Nineteen hundred and fifty open heart operations were performed between January 1995 and December 2000 at the cardiac surgery department of Chest Disease Hospital in Kuwait. Sternal closure was delayed in 40 patients (2%), because of hemodynamic instability limiting primary closure in 23 patients and uncontrollable bleeding in 17 patients. Four patients died in the immediate postoperative period while the chest was open, due to persistent low cardiac output secondary to myocardial failure. The sternum was closed in 36 patients on an average of 22 +/- 0.3 hours (range, 8 to 48 hours) postoperatively. Two patients died in the late postoperative period prior to hospital discharge after sternal closure. Wound infections occurred in 8 patients. The 34 survivors (85%) were discharged and followed up for a mean of 13.2 months. This study demonstrates that delayed sternal closure is an effective and life saving decision with unstable hemodynamics and uncontrollable hemorrhage.

Off-pump on-pump coronary artery bypass decision-making.

BACKGROUND: Coronary revascularization on the beating heart is an attractive to option conventional coronary artery bypass graft (CABG) but remains controversial. Our study encourages sufficient proper time for decision-making when changing CABG from off-pump to on-pump CABG. We report herein patients who changed from off-pump CABG to on-pump CABG. METHODS: A retrospective analysis of 240 patients operated upon at Cardiology Hospital of Lyon University between July 1998 and July 2000, and at one unit of Cardiac Surgery, yielded 88 patients with off-pump coronary surgery (off CAB), 21 patients changed from off-pump CABG to on-pump CABG. The other 131 patients were operated on as on-pump CABG. RESULTS: There was no operative mortality. One month postoperative mortality was only one patient out of 21 due to cardiac failure and arrhythmias. There was no significant difference in the postoperative intensive care unit (ICU) time and length of hospital stay compared with off-pump CABG. CONCLUSION: Our data suggest that a fair number of patients are potential candidates for off CAB. The only contraindication is the technical limitation or the surgeon comfort level. Changing from off CAB to on CAB can be decided for the patient's safety within the appropriate time intraoperatively without fear of more postoperative complications than with off CAB surgery.

15 Years in surgical management of pulmonary hydatidosis.

OBJECTIVES: Echinococcosis remains an endemic surgical problem in countries where sheep and cattle raising is carried out, particularly in many Mediterranean countries. This study aims to evaluate the management of different presentations of pulmonary hydatidosis and their outcome over 15 years. DESIGN: Retrospective study. SETTING: Thoracic surgical department, Chest Diseases Hospital, Kuwait. PATIENTS: Sixty patients operated upon for hydatid disease were evaluated pre- and post- operatively; 35 males, 25 females with a mean age of 28.4 years. Most patients were investigated by laboratory, serological and radiological studies. Different surgical techniques were used to remove the hydatid cyst from the lung. RESULTS: The most common presenting symptoms were cough (41 patients), and 12 patients were asymptomatic. Chest X-ray showed a rounded shadow in 42 patients; 19 cases were of vigorous size >10 cm. Thoracotomy was done in 57 patients; two chest wall cases were managed by minimal skin incision and enucleation, one hydatid cyst of the heart was approached through a median sternotomy. The mean hospital stay was 9 days. Postoperative complications occurred in 9 patients; prolonged air leak in 4 patients, pleural effusion in 3, pneumothorax, and wound infection in one patient each. One patient (65 years old) died on the 6th post-operative day most probably from pulmonary embolism. In a follow-up period of 2-15 years, 4 recurrences have been noted. CONCLUSION: Surgical excision of pulmonary hydatidosis with maximum preservation of the lung parenchyma is the main stay of treatment.

The effect of TNF*B gene polymorphism on TNF-alpha and -beta secretion levels in patients with insulin-dependent diabetes mellitus and healthy controls.

TNF-alpha and -beta have been implicated in the development of HLA-associated autoimmune diseases. It has been suggested that inter-individual differences in the secretion levels of these cytokines may contribute to the predisposition of certain individuals to the development of diseases such as insulin-dependent diabetes mellitus (IDDM). We have investigated whether a diallelic TNF*B polymorphism detected using the enzyme Ncol influences the TNF-alpha and/or -beta secretory capacity of peripheral blood mononuclear cells (PBMC) from PHA stimulated healthy individuals and IDDM patients. We have shown that the level of TNF-beta secreted correlates with the TNF*B genotype in healthy individuals: those with the TNF B*2 allele secreted significantly higher levels of TNF-beta (P = 0.025) than those with the TNF*B1 allele. In IDDM patients, the reverse situation was observed, with those patients with the TNF*B1 allele secreting higher levels of TNF-beta than those with the TNF*B2 allele. No correlation was found between TNF-alpha levels and TNF*B genotype. Furthermore, when IDDM patients and controls were matched for TNF*B genotype, the IDDM patients with the TNF*B2 allele secreted significantly lower levels of TNF-beta than controls with this allele. On analysis of IDDM-susceptible extended HLA haplotypes in the homozygous groups, 4/7 IDDM patients with the TNF*B2 allele were Bw62-DR4 compared with 0/16 matched controls. Thus, the extended haplotype Bw62-DR4-TNF*B2/2 rather than IDDM per se is almost certainly responsible for the depressed TNF-beta secretion found in the IDDM-TNF*B2 homozygous cohort.

A new concept for the pathogenesis and treatment strategies for oral lichen planus.

Mounting evidence points out to the immunologic basis of lichen planus (LP). Tumour necrosis factor (TNF-alpha) is a cytokine with multiple biologic activities, some of which may be relevant to the pathogenesis of LP. The present study was thus conducted to assess its production by peripheral blood leucocytes in patients with active lesions of oral lichen planus (OLP) compared to age matched healthy control volunteers. For the assessment, the quantitative immunometric sandwich technique was employed. Significantly greater amounts of TNF-alpha were found in serum samples of OLP patients compared to healthy individuals, suggesting a possible association between this cytokine and the pathogenesis of OLP and pointing out to the primary initiative role played by altered keratinocytes. This pointed out the beneficial effect of anti-TNF drugs in the management of OLP.

Autoimmune renal disease and tumour necrosis factor beta gene polymorphism.

The genes encoding tumour necrosis factors (TNF) are located within the major histocompatibility complex. Since TNF may be involved in the pathogenesis of autoimmune disease the purpose of the present study was to investigate TNF beta gene polymorphism in two types of immune complex mediated glomerulonephritis, IgA nephropathy (IgAN) and idiopathic membranous glomerulonephritis (IMN) and to compare them with IDDM and healthy controls. DNA was studied by Southern-blot hybridisation methods using Nco I digestion and a TNF beta probe; two alleles were detected size 5.5 kb and 10.5 kb. In healthy controls (n = 107), 9% were 5.5 homozygotes, 47% heterozygotes and 44% 10.5 homozygotes. The corresponding figures in IMN (n = 51) were 21.5%, 61% and 17.5% (p = 0.002), in IDDM (n = 42) 24%, 50% and 26% (p = 0.027) and in IgAN (n = 77) 2.5%, 65% and 32.5% (p = 0.025). The increase in 5.5 homozygotes in both IMN and IDDM was found to be due to an increased frequency of the haplotype A1-B8-TNF beta 5.5-DR3 seen in both these diseases; whereas in IgAN the increased frequency of the 10.5 kb allele can be explained by an association of a Taq 1DQB1-T2 allele with the TNF beta 10.5 allele. These results demonstrate an association of TNF beta gene polymorphism with IMN and IgAN and confirm the associations found in IDDM. Although these disease associations can be explained by linkage disequilibrium with extended MHC haplotypes, a direct role of genetically determined TNF production in the etiology of these diseases remains to be excluded.