B-cell activation and allosensitization after left ventricular assist device implantation is due to T-cell activation and CD40 ligand expression

Left ventricular assist device (LVAD) implantation is frequently complicated by B-cell activation and allosensitization, posing a significant risk to successful transplant outcome. This study investigated whether B-cell hyperreactivity and alloantibody production in LVAD recipients involves T-cell dependent pathways. T-cell calcium flux and nuclear translocation of NFATc were used to determine states of T-cell activation. Flow cytometry was used to assess human T- and B-cell activation after culture with LVAD-derived biomaterial particles. Sera from LVAD recipients and controls were tested for the presence of anti-HLA antibodies, and for soluble CD40 ligand. LVAD-derived biomaterial induced rapid and sustained calcium flux into normal T cells, resulting in calcineurin-dependent nuclear translocation of NFATc. This resulted in increased T-cell expression of CD40 ligand and subsequent B-cell activation, which was reduced by inhibitors of T-cell activation (CsA or anti-CD25 mAb) or by anti-CD40 ligand mAb. LVAD recipients demonstrated higher frequencies of anti-HLA antibodies and serum levels of soluble CD40 ligand compared with heart failure controls. The results indicate that exposure of human mononuclear cells to LVAD-derived biomaterial leads to T-cell dependent B-cell activation via CD40--CD40 ligand interaction, and suggest that treatment with calcineurin inhibitors or monoclonal antibodies against either CD25 or CD40 ligand could be effective at preventing B-cell hyperreactivity and allosensitization after LVAD implantation.     

Immunohistochemical study on histogenesis of congenital epulis and review of the literature

Congenital epulis is a very rare lesion found only in newborn infants. This tumor is multiple in about 10% of reported cases, rarely with the simultaneous involvement of the maxilla and mandibula, as in this article. In the presented case, light microscopy demonstrated large eosinophilic granular cells arranged in solid nests that are separated by thin fibrovascular areas. The tumors In the maxilla and mandibula were investigated with a panel of polyclonal and monoclonal antibodies, and using immunoperoxidase methods on formalin-fixed, paraffin-embedded sections. Immunohistochemical studies revealed strong and diffuse cytoplasmic staining for neuron specific enolase and vimentin. However, all other reactions were negative. These results suggest that the congenital epulis may be derived from uncommitted nerve-related mesenchymal cells.     

PS2 and HSP70 expression in rectal adenocarcinomas: an immunohistochemical investigation of 45 cases.

OBJECTIVE: To evaluate the expression of HSP70 and pS2 and to determine whether it may be an additional prognostic variable in the prediction of recurrence and survival in rectal adenocarcinomas. METHODS: The paraffin sections of 45 patients with rectal carcinoma who were treated with surgical resection were stained with HSP70 and pS2 antibodies by using the standard biotin immunoperoxidase method. Cytoplasmic staining for both antibodies was scored semiquantitatively. RESULTS: Only 16 (35.6%) tumors showed a positive cytoplasmic reaction with HSP70 antibody, while pS2 expression was observed in 26 (57.8%) tumors. There was an association between HSP70 and pS2 expression (P=0.002). No correlations were found between HSP70 and pS2 expression and tumor recurrence or overall survival and other prognostic factors. However, the type of surgical resection was significantly associated with pS2 expression status (P=0.013). Significant correlations were detected between tumor recurrence and other clinicopathologic parameters, such as clinical stage, lymph node involvement, and resection type (P=0.015, P=0.015, and P=0.03, respectively). Resection type was significantly associated with clinical outcome, recurrence, and metastasis (P=0.009, P=0.03, P<0.01, respectively). In addition, there was a statistically significant relationship between clinical stage and final outcome (P=0.005). CONCLUSIONS: The strong correlation between pS2 expression and incomplete surgical resection suggests that pS2 may be related to invasive tumor behavior and may also play a role in tumor recurrence, although this latter association did not reach statistical significance in this study. HSP70 expression does not appear to be related to tumor invasiveness or tumor recurrence.     

Early impact of hormone replacement therapy on vascular hemodynamics detected via ocular colour Doppler analysis

Objective: To determine the effects of hormone replacement therapy (HRT) on ocular blood flow.

Study design: In a prospective controlled study, 40 healthy women who presented to the menopause clinic between December 2000 and December 2001 were randomly assigned into the study. The HRT-receiving group was administered estradiol 17-valerate 2 mg the first 11 days, and estradiol 17-valerate 2 mg plus ciproterone acetate 1 mg the next 10 days of the monthly cycle for 6 months. The control group did not receive any HRT for 6 months. The ocular colour Doppler analysis were performed at baseline and after 3 and 6 months. The ocular Doppler analysis was performed in the first half of the cycle in the HRT-receiving group.

Results: Central retinal artery and ophthalmic artery basal Doppler index (peak systolic velocity, end-diastolic velocity, resistive index and pulsatility index) values of the two groups at the beginning of the study did not show any statistically significant difference. Both the right and the left central retinal artery pulsatility index (PI) values of the study group, who received HRT at the end of the third and sixth months, showed a statistically significant decline (paired-samples test, P < 0.05), while the decrease in the resistive indexes was not significant.

Conclusion: These results suggest that 6 months of combined hormone replacement therapy with estradiol 17-valerate 2 mg plus ciproterone acetate 1 mg improves ocular vascular Doppler indices which may be a reflection of cerebral vascular status.     

Role of insulin like growth factor-I in repair response in immature cartilage

OBJECTIVE: The purpose of this study was to investigate the effects of exogenous local Insulin like growth factor-I (IGF-I) on the repair of full-thickness articular cartilage defects in immature rabbits. DESIGN: Thirty-six skeletally immature New Zealand rabbits between 6 and 8 weeks old were used. A single defect, 3.5-mm-wide by 4-mm-deep full-thickness articular cartilage defect in the medial femoral condyle, was created. The defect was either filled with a collagen sponge or with a collagen sponge impregnated with 5 mug of recombinant IGF-I. The animals were sacrificed at 4, 8 or 12 weeks, and the repair tissue was examined macroscopically and histologically. Repair tissue was also examined immunohistochemically for the presence of type-I collagen, type-II collagen and PCNA at all weeks. RESULTS: Newly formed tissue in all of the defects in the IGF-I group had the gross, histological and histochemical appearance of a smooth, intact hyaline articular cartilage. The average total scores on the histological grading scale were significantly better (p<0.05) for the defects treated with recombinant IGF-I at all time points. Immunostaining with an antibody against type-II collagen showed the diffuse presence of the repair cartilage in the IGF-I treated defects. The control groups demonstrated minimum staining with type-II collagen antibody. CONCLUSIONS: These findings suggest that repair of full-thickness immature cartilage defects can be enhanced by recombinant IGF-I.     

Device related infections while on left ventricular assist device support do not adversely impact bridging to transplant or posttransplant survival

We conducted a retrospective review of our bridge to transplant experience over the last 7 years using the Heartmate device (Thoratec, Pleasanton, CA) by studying patients who developed device related infections. Of the 174 patients who underwent device implantation, 32 (18.4%) developed a device related infection while on support (12 patients with drive line infections, 14 patients with pocket infections, 4 patients with pump infections, and 2 patients with device endocarditis). There was no significant difference in rate of successful bridging to transplant between patients with and without a device related infection occurring in 23 (71.9%) patients with infection and 103 (72.5%) patients without infection (p = 0.406). In addition, posttransplant survival at 1, 3, and 5 years was similar for both groups--95.6%, 86.2%, and 79.3%, respectively, for patients with infection, versus 90.9%, 88.1%, and 82.2%, respectively, for patients without infection (p = 0.911).     

Oxidative stress and enzymatic antioxidant status in patients with nonalcoholic steatohepatitis

Oxidative stress is an important pathophysiological mechanism in nonalcoholic steatohepatitis (NASH). To assess whether there are relationships between oxidative stress and antioxidant enzymes in the development of NASH, we investigated oxidative stress by measuring serum malondialdehyde (MDA) and nitric oxide (NO) and antioxidant status by measuring serum glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and superoxide dismutase (SOD). The study included 18 patients (13 men, 5 women; mean age 42 yr) with biopsy proven NASH and 16 healthy volunteers (10 men, 6 women; mean age 38 yr). Serum levels of MDA, NO, GSH, GSH-Px, GR and SOD were determined by spectrophotometric methods. Serum levels (mean +/- SD) of MDA (6.7 +/- 1.6 vs 2.8 +/- 1.7 nmol/ml, p 0.0001), NO (135 +/- 28 vs 113 +/- 35 mmol/L, p 0.04), GSH (919 +/- 137 vs 770 +/- 128 mmol/L, p 0.003) were increased in patients with NASH vs controls. Serum levels of GSH-Px (1063 +/- 152 vs 1000 +/- 94 U/L) and GR (47 +/- 22 vs 40 +/- 21 U/L) were not singnificantly different in the patients vs controls. However, the serum level of SOD (1.24 +/- 0.32 vs 1.51 +/- 0.37 U/ml, p: 0.04) was significantly decreased. Impaired antioxidant defense mechanisms may be an important factor in the pathogenesis of NASH. Treatment approaches that affect the antioxidant enzymes may be beneficial in patients with NASH.     

Laparoscopic presacral neurolysis for endometriosis-related pelvic pain

BACKGROUND: Some patients with endometriosis are candidates for sympathectomy of the superior hypogastric plexus. The objective of this paper is to describe our technique of laparoscopic presacral neurolysis for sympathectomy and to report 1 year results of the first 15 cases. METHODS: To achieve this objective in a prospective observational study of 1 year follow-up; we performed laparoscopic presacral chemical neurolysis with phenol in 15 patients with pelvic pain and minimal-moderate endometriosis. The main outcome measures were: the impact of treatment on pelvic symptom resolution, non-opioid analgesic consumption during menses, sexual performance and observed complications and side effects during 1 year follow-up. RESULTS: We noted a significant reduction in total pelvic symptom score as compared with baseline mean (SD) of 9.04 (1.2). The mean difference [95% confidence interval (CI)] of reduction was 5.7 (4.9-6.5), 5.8 (5.0-6.6) and 5.8 (4.9-6.6) from the baseline at the 3rd, 6th and 12th postoperative month (P < 0.001). We observed a significant improvement in Sabbatberg Sexual Rating Scale as compared with baseline mean (SD) of 30.9 (4.3). The mean difference (95% CI) of increase was 33.4 (30.3-36.4), 33.2 (30.1-36.2) and 33.2 (30.1-36.3) from the baseline at the 3rd, 6th and 12th postoperative month. We observed a significant reduction in analgesic consumption during menses in terms of total naproxen sodium tablets as compared with baseline mean (SD) of 8.9 (1.1). The mean difference (95% CI) of reduction in the total number of naproxen sodium 250 mg tablets was 6.5 (5.5-7.5), 6.7 (5.7-7.7) and 6.6 (5.6-7.6) from the baseline at the 3rd, 6th and 12th postoperative month. The most common side effect was constipation. CONCLUSION: Laparoscopic presacral neurolysis is feasible and simple. More data is needed to support its efficacy and safety.     

Diabetes education: a chance to improve well-being of Turkish people with type 2 diabetes

To examine the influence of diabetes education on well-being, 255 patients with type 2 diabetes were recruited according to whether they attended a diabetes education program (n=126) or not (n=129). In patients who had participated in the program, the mean anxiety score was significantly lower, whereas positive well-being and general well-being scores were significantly higher than for patients who had not participated. Factors related to lower well-being included: being female, taking insulin, not attending a diabetes education program and having HbA(1c) level greater than 8%. The odds of having better well-being were two-fold higher in patients participating the diabetes education program compared with those who had not. Diabetes education has a crucial role in improving the well-being of patients with type 2 diabetes. All patients with diabetes should be encouraged to attend a diabetes education program.     

Antioxidant capacity and nitric oxide in patients with hepatic cirrhosis

This study investigated the relationship between the antioxidant capacity of blood and the serum level of nitric oxide (NO) in patients with hepatic cirrhosis. The study included 20 patients with compensated cirrhosis (group I), 30 with decompensated cirrhosis (group II), and 30 healthy controls (group III). The serum levels of NO, albumin, bilirubin, and uric acid, and the erythrocyte activity of superoxide dismutase (SOD) were measured in all groups. The mean erythrocyte SOD activity (5.94 +/- 3.21 U/mg protein) and serum NO level (25.19 +/- 8.15 micromol/L) in group I were similar to those of controls (6.86 +/- 2.47 U/mg protein and 21.67 +/- 6.51 micromol/L, respectively). However, erythrocyte SOD activity in group II was significantly lower than in groups I and III and mean serum NO level was significantly higher in group II than in groups I and III. In regard to non-enzymatic antioxidants, the mean serum albumin level was lower and the mean serum total bilirubin level was higher in group II than in groups I and III. As expected, group I had higher mean serum total bilirubin level than the control group. Correlation analysis showed that erythrocyte SOD activity in cirrhotic patients was negatively correlated with their serum levels of NO. These results suggest that disturbances of antioxidative mechanisms may diminish hepatic resistance to oxidative stress, thereby contributing to the development of fibrogenesis.