Different reconstitution of peripheral blood lymphocytes and dendritic cells in liver and kidney transplant patients

T cells and dendritic cells are responsible for immune alloreactivity or tolerance after transplantation. In this study, we compared the levels of circulating T, B, and NK lymphocytes, as well as monocytes, plasmacytoid dendritic cells, and myeloid dendritic cells, in adult patients undergoing a liver transplant or kidney transplant. Our findings show that candidates for liver transplant had significantly lower levels of circulating T, B, and dendritic cells than candidates for kidney transplant. Nevertheless, liver transplant patients showed a greater T-cell recovery, despite the use of thymoglobulin, as compared with kidney transplant patients who were induced with Daclizumab. In four kidney transplant patients with allograft rejection we observed a dramatic drop of circulating T and dendritic cells at the time of rejection, and while myeloid dendritic cells and CD4(+) and CD8(+) cells rapidly recovered after 1 month, plasmacytoid dendritic cells and CD4(+)CD25(+) T-cell numbers remained significantly lower than in patients without rejection. Future studies will evaluate the monitoring of circulating CD4(+)CD25(+) T cells and myeloid dendritic cell:plasmacytoid dendritic cell ratio as potential biomarkers for rejection or, alternatively, for withdrawal of immune suppression.     

Hepatic ischemia/reperfusion injury can be modulated with thymoglobulin induction therapy

BACKGROUND: Thymoglobulin induction therapy has been shown to ameliorate delayed graft function and possibly decrease ischemia reperfusion injury in cadaver renal transplant recipients. This controlled randomized trial was designed to assess whether thymoglobulin also protects liver transplant recipients from ischemia reperfusion injury. PATIENTS AND METHODS: Twenty-two cadaver liver transplant recipients were randomized to receive either thymoglobulin (1.5 mg/kg per dose) during the anhepatic period and two doses every other day or no thymoglobulin. No differences in recipient or donor demographics were present. Maintenance immunosupression consisted of tacrolimus (or cyclosporine) and steroids for both groups. Donor biopsies were obtained during organ procurement, cold storage, and 1 hour after revascularization. Postoperative liver function tests were monitored. Early graft function, length of stay, patient and graft survival rates, incidence of primary nonfunction, and rate of rejection were assessed. RESULTS: Patient and graft survival at 3 months was 100%. There was no incidence of primary graft nonfunction and no need for retransplantation. The incidence of acute rejection was similar between the two groups. Although donor livers randomized to thymoglobulin had less optimal preimplantation biopsies, these recipients had significant decreases in ALT at day 1 compared to the control group (P = .02), near significant decreases of total bilirubin at day 5, and shorter length of hospitalization. CONCLUSION: Thymoglobulin allowed for more compromised liver grafts to be transplanted with less clinical evidence of ischemia reperfusion injury and improved function.     

Ilizarov treatment of tibial nonunions with bone loss

Twenty-five patients aged 19-62 years were treated for tibial nonunions (22 atrophic, three hypertrophic) with bone loss (1-23 cm, mean 6.2 cm) by the Ilizarov technique and fixator. Thirteen had chronic osteomyelitis, 19 had a limb-length discrepancy (2-11 cm), 12 had a bony defect (1-16 cm), and 13 had a deformity. Six had a bone defect with no shortening, 13 had shortening with no defect, and six had both a bone defect and shortening. Nonunion, bone defects, limb shortening, and deformity can all be addressed simultaneously with the Ilizarov apparatus. Bone defects were closed from within without bone grafts by the Ilizarov bone transport technique of sliding a bone fragment internally, producing distraction osteogenesis behind it until the defect is bridged (internal lengthening). Length was reestablished by distraction of a percutaneous corticotomy or through compression and subsequent distraction of the pseudarthrosis site (external lengthening). Distraction osteogenesis resulting from both processes obviated the need for a bone graft in every case. Deformity was corrected by means of hinges on the apparatus. Infection was treated by radical resection of the necrotic bone and internal lengthening to regenerate the excised bone. Union was achieved in all cases. The mean time to union was 13.6 months, but it was only 10.6 months if the time taken for unsuccessful compression-distraction of the nonunion is eliminated from the calculation. The bone results were excellent in 18 cases, good in five, and fair in two based on union in all cases, persistent infection in three, deformity in four, and limb shortening in one. The functional results were excellent in 16 cases, good in seven, fair in one, and poor in one based on return to work and daily activities in all cases, limp in four cases, equinus deformity in five cases, dystrophy in four cases, pain in four cases, and voluntary amputation for neurogenic pain in one case.     

Is CA72-4 a Useful Biomarker in Differential Diagnosis between Ovarian Endometrioma and Epithelial Ovarian Cancer?

Background. Surgical excision of ovarian endometriomas in patients desiring pregnancy has recently been criticized because of the risk of damage to healthy ovarian tissue and consequent reduction of ovarian reserve. A correct diagnosis in cases not scheduled for surgery is therefore mandatory in order to avoid unexpected ovarian cancer misdiagnosis. Endometriosis is often associated with high levels of CA125. This marker is therefore not useful for discriminating ovarian endometrioma from ovarian malignancy. The aim of this study was to establish if the serum marker CA72-4 could be helpful in the differential diagnosis between ovarian endometriosis and epithelial ovarian cancer. Methods. Serums CA125 and CA72-4 were measured in 72 patients with ovarian endometriomas and 55 patients with ovarian cancer. Results. High CA125 concentrations were observed in patients with ovarian endometriosis and in those with ovarian cancer. A marked difference in CA72-4 values was observed between women with ovarian cancer (71.0%) and patients with endometriosis (13.8%) (P < 0.0001). Conclusions. This study suggests that CA72-4 determination can be useful to confirm the benign nature of ovarian endometriomas in women with high CA125 levels.     

Role of chemotherapy in the management of vulvar carcinoma

The aim of this review is to evaluate the use of chemotherapy (CT) in the treatment of squamous vulvar cancer. Since the 90s there was a continuous evolution in the therapeutic approach to this tumour. Although primary surgery is now considered the most effective approach, there are advanced diseases in which surgery may compromise anatomical structures causing severe mutilation. These are the reasons why CHT, with or without concomitant radiotherapy RT, started to be strongly recommended as neoadjuvant strategy. Chemotherapeutic agents have also been used alone as adjuvant treatment or in association with RT, by exploiting the radiosensitizing effect of these drugs. There are few data about the use of CHT as palliative treatment but recent studies point to the use of target therapy. In conclusion, clinical data and the evidence of chemo-sensitivity in vulvar squamous cell carcinoma open new possibilities to future research in this field.     

When words are painful: unraveling the mechanisms of the nocebo effect

The nocebo effect is a phenomenon that is opposite to the placebo effect, whereby expectation of a negative outcome may lead to the worsening of a symptom. Thus far, its study has been limited by ethical constraints, particularly in patients, as a nocebo procedure is per se stressful and anxiogenic. It basically consists in delivering verbal suggestions of negative outcomes so that the subject expects clinical worsening. Although some natural nocebo situations do exist, such as the impact of negative diagnoses upon the patient and the patient's distrust in a therapy, the neurobiological mechanisms have been understood in the experimental setting under strictly controlled conditions. As for the placebo counterpart, the study of pain has been fruitful in recent years to understand both the neuroanatomical and the neurochemical bases of the nocebo effect. Recent experimental evidence indicates that negative verbal suggestions induce anticipatory anxiety about the impending pain increase, and this verbally-induced anxiety triggers the activation of cholecystokinin (CCK) which, in turn, facilitates pain transmission. CCK-antagonists have been found to block this anxiety-induced hyperalgesia, thus opening up the possibility of new therapeutic strategies whenever pain has an important anxiety component. Other conditions, such as Parkinson's disease, although less studied, have been found to be affected by nocebo suggestions as well. All these findings underscore the important role of cognition in the therapeutic outcome, and suggest that nocebo and nocebo-related effects might represent a point of vulnerability both in the course of a disease and in the response to a therapy.