In vivo CYP2E1 phenotyping as a new potential biomarker of occupational and experimental exposure to benzene.

Assessing CYP2E1 phenotype in vivo may be important to predict individual susceptibility to those chemicals, including benzene, which are metabolically activated by this isoenzyme. Chlorzoxazone (CHZ), a specific CYP2E1 substrate, is readily hydroxylated to 6-OH-chlorzoxazone (6-OH-CHZ) by liver CYP2E1 and the metabolic ratio 6-OH-CHZ/CHZ in serum (MR) is a specific and sensitive biomarker of CYP2E1 activity in vivo in humans. We used this MR as a potential biomarker of effect in benzene-treated rats and, also, in humans occupationally exposed to low levels of benzene. Male Sprague-Dawley rats (375-400g b.w.) were treated i.p. for 3 days with either a 0.5ml solution of benzene (5mmol/kg b.w.) in corn oil, or 0.5ml corn oil alone. Twenty-four hours after the last injection, a polyethylene glycol (PEG) solution of CHZ (20mg/kg b.w.) was injected i.p. in both treated and control animals. After 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, and 240min from injection, 0.2ml blood was taken from the tip tail and stored at -20 degrees C until analysis. A modified reverse phase HPLC method using a 5microm Ultrasphere C18 column equipped with a direct-connection ODS guard column, was used to measure CHZ and its metabolite 6-OH-CHZ in serum. No statistically significant difference in the MR was observed, at any sampling time, between benzene-treated and control rats. The concentration-versus-time area under the curve (AUC), however, was lower (p<0.05, Mann-Whitney test), whereas the systemic clearance was higher (p<0.05) in treated than in control rats. Eleven petrochemical workers occupationally exposed to low levels of airborne benzene (mean+/-SD, 25.0+/-24.4microg/m(3)) and 13 non-exposed controls from the same factory (mean+/-SD, 6.7+/-4.0microg/m(3)) signed an informed consent form and were administered 500mg CHZ p.o. Two hours later a venous blood sample was taken for CHZ and 6-OH-CHZ measurements. Despite exposed subjects showed significantly higher levels of t,t-MA and S-PMA, two biomarkers of exposure to benzene, than non-exposed workers, no difference in the MR mean values+/-SD was found between exposed (0.59+/-0.29) and non-exposed (0.57+/-0.23) subjects. So, benzene was found to modify CHZ disposition, but not CYP2E1 phenotype in benzene-treated rats, nor in workers exposed to benzene, probably due to the levels of exposure being too low.

Kidney transplantation from donors with viral B and C hepatitis.

INTRODUCTION: The success of renal transplantation as a treatment for end-stage renal disease has created a chronic shortage of donor organs. We present our experience in transplanting kidneys from donors with hepatitis B virus (HBV) or hepatitis C virus (HCV) among matched serology-positive recipients. MATERIALS AND METHODS: From January 2002 to November 2005, 44 patients with end-stage renal disease and HCV seropositivity underwent kidney transplantation. In 28 transplants in HCV+ recipients, the donor was HCV+ (DC+/RC+) and in 16 of these cases the donor (one living donor) was HCV- (DC-/RC+). In the same period 14 patients with HBV infection and HbsAg seropositivity underwent kidney transplantation: eight received their graft from a cadaveric HbsAg-positive donor (DB+/RB+), while six patients received their graft from an HbsAg-negative donor. RESULTS: Viral reactivation was higher among DC+/RC+ (21.4%) than DC-/RC+ patients (6%). Graft survivals were 90% and 88% for DC+/RC+ and DC-/RC+, respectively; patient survivals were 100% for DC+/RC+ and 94% for DC-/RC+. Among the group of DB+/RB+, all the patients developed an HBV-DNA positivity in the early postoperative period. Patient and graft survivals were 100% in both groups. CONCLUSIONS: Our results suggest that HBV- and HCV-positive donors can be considered as an alternative donor source, because their kidneys are allocated to the matched serology-positive recipients, shortening their time on the waiting list.

Caspofungin in the treatment of azole-refractory esophageal candidiasis in kidney transplant recipients.

BACKGROUND: Infection is a common cause of morbidity and mortality in kidney transplant recipients. The incidence of esophageal and urogenital candidiasis in kidney and kidney-pancreas transplant recipients has not been well documented. Azoles are safe, effective agents to treat esophageal candidiasis. However, resistance to azoles is now becoming common. This study reports the use of caspofungin for the treatment of azole-resistant esophageal and urogenital candidiasis in kidney transplant recipients. PATIENTS AND METHODS: The incidence of esophageal and urogenital candidiasis was evaluated among 140 kidney transplantations and four combined kidney-pancreas transplants performed over a 2-year period. RESULTS: Twenty-two patients (15.7%) presented with esophageal candidiasis, while seven patients (5%) showed urogenital candidiasis. Thirteen patients with esophageal candidiasis (59%) and four patients (57%) with urogenital candidiasis did not improve after a week of azole treatment. A regimen of caspofungin was started in these patients, who tolerated the treatment. Urogenital candidiasis recurred in two patients 2 and 3 months after the treatment. One patient with esophageal candidiasis did not improve with caspofungin and was switched to amphotericin B therapy. There were no other recurrences of candidiasis among patients treated with caspofungin for a median follow-up of 8 months. CONCLUSIONS: Renal transplant patients remain at high risk for fungal infections. Although the number of patients was limited, the results of this study indicated that caspofungin is an effective, well-tolerated alternative for difficult-to-treat, azole-resistant candida infections in kidney and pancreas transplant recipients. The high costs of the drug limit the use of caspofungin as first-line antifungal therapy, reserving its use to recipients who had undergone unsuccessful azole therapy.

[Burnout: rising interest phenomenon in stressful workplace]. / Burnout: fenomeno di crescente interesse in ambienti di lavoro stressante.

Many stressful situations, particularly strong and long time lasting, can induce the burnout syndrome. The definition "burnout" refers to emotional and exhausting conditions related to working environment. Since 70'ties, many studies, have focused on this topic, have assessed that this condition is much more frequent in some particular professional categories: teachers, physicians, nurses, social workers, policemen, judges (the so-called helping professions). The main syndrome characteristics are: physical and emotional fatigue, depersonalization, frustration for unsuccessful professional realization and reduced personal accomplishment in competence and productivity with decreasing critical sense towards working field. The Maslach Burnout Inventory (MBI) has been the most popular instrument for measuring burnout in medical research. The coherence of many studies results on helping professions in different countries, leads to the conclusion that basically burnout is a psycho-social phenomenon of international relevance. These studies have also identified personal, relational and environmental risk factors susceptible to prevention.

Kidney transplantation from cadaveric donors unsuitable for other centers and older than 60 years of age.

INTRODUCTION: The demand for kidney transplants and the improvement in recipient outcomes over the last years have stimulated surgeons to expand the criteria for usable donor organs, by accepting older patients to expand their donor pool. We herein report our experience with kidney transplants from donors aged older than 60 years, who have been declined by other transplantation centers. PATIENTS AND METHODS: Sixty kidney transplantations were performed with grafts procured from donors aged older than 60 years. Forty-five patients received a single kidney graft (SKG) and 15 received a dual kidney graft (DKG). Mean donor age was 62 years for SKG and 64 years for DKG. Double kidney transplantations were performed with the ipsilateral allocation of both grafts. RESULTS: No primary graft nonfunction occurred. Delayed graft function was observed in 22 SKG (48.8%) and in 7 DKG (46.6%). Acute rejection rates were 9% for SKG and 0% for DKG. One-year patient survival rates were 95% and 100% for SKG and DKG, respectively. Mean serum creatinine levels at 1-year posttransplantation were 1.9 mg/dL for SKG and 1.3 mg/dL for DKG. There were no surgical postoperative complications and mortality. Death censored 1-year graft survival rate was 88% for SKG and 94% for DKG. CONCLUSIONS: Our experience with marginal donors who have been declined by other transplantation centers has demonstrated that such organs, with accurate selection criteria, could be safely allocated to elderly recipients with no increase in postoperative complications, guaranteeing satisfactory results in the short and medium term, allowing a significant improvement in the number of transplants.

Kidney transplantation from hepatitis B surface antigen-positive donors into hepatitis B surface antigen-positive recipients: preliminary findings.

INTRODUCTION: The success of renal transplantation as a treatment for end-stage renal disease has created a chronic shortage of donor organs. We present our initial experience in transplanting kidneys from hepatitis B surface antigen (HbsAg)-positive donors into HbsAg-positive recipients. MATERIAL AND METHODS: From January 2002 to March 2004, 5 patients with end-stage renal disease, hepatitis B virus (HBV) infection, and HbsAg seropositivity underwent a kidney transplantation from a cadaveric HbsAg-positive donor. The median time on the waiting list was 8 months, compared with the median of 3 years on the national waiting list. RESULTS: One patient experienced an acute rejection; 1 patient had an increase in serum level of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) with no signs of recurrence of hepatitis. Graft and patient survival at a median follow-up of 12 months was 100%. CONCLUSIONS: Although the number of patients is small and the follow-up is short, our results suggest that HbsAg-positive donors can be considered as an alternative donor source because their kidneys are allocated to the matched serology-positive recipients, shortening their time on the waiting list.

Kidney transplantation from hepatitis C virus-positive donors into hepatitis C virus-positive recipients: a safe way to expand the donor pool?

INTRODUCTION: Because the disparity between the number of patients waiting for kidney transplants and the number of available cadaveric renal allografts continues to increase, there is a clear need to review the inclusion criteria for cadaveric donors. PATIENTS AND METHODS: From January 2001 to March 2004, 24 patients with end-stage renal disease and hepatitis C virus (HCV) seropositivity underwent a kidney transplantation. In 10 transplants in HCV-positive recipients, the donor was HCV-positive (D+/R+) and in 14 cases the donor (1 living donor) was HCV-negative (D-/R+). RESULTS: Two of 3 HCV-RNA-negative recipients who received a HCV-RNA+ kidney became HCV-RNA+ in the posttransplantation period. There was a low rate of acute rejection (8.3%). One D+/R+ patient experienced an acute vascular rejection, which finally resulted in graft loss, due to the resurgence of severe infectious disease. The serum creatinine levels at 6 months posttransplantation were similar in both groups. Acute liver dysfunction was observed in 1 patient. There was no death in the entire series. Graft survival was 92% and 90% for D+/R+ and D-/R+, respectively.

Use of hepatitis B core antibody-positive donor kidneys in hepatitis B surface antibody-positive and -negative recipients.

INTRODUCTION: The rate of hepatitis B virus transmission via organs from with isolated hepatitis B virus core antibody-positive (HBcAb+) donors in kidney transplant recipients seems very low. PATIENTS AND METHODS: Over 4 years, we performed 36 transplants from Ig HBcAb+, hepatitis B surface antigen (HBsAg)-negative donors into recipients with a history of prior hepatitis B virus (HBV) infection or reported vaccination (28 patients) and in recipients who were not immunized and received a pretransplant prophylaxis with hepatitis B immunoglobulins. We examined the HBV-related outcomes in these 36 patients in comparison with 40 recipients of allografts from HBcAb- donors. RESULTS: No patient receiving an allograft from an HBcAb+ donor developed clinical HBV infection or HBSAg positivity. The rate of seroconversion was 14.2% in immunized patients, 12.5% in nonimmunized patients, and 0% in the control group. The 17.8% of immunized patients developed elevated transaminases after transplant, in comparison with 25% and 10% in the nonimmunized patients and the control group, respectively. Graft and patient survival was 93% and 93% for immunized patients, 100% and 100% for nonimmunized patients, and 98% and 95% for the control group, respectively. CONCLUSION: The use of anti-HBc antibody-positive kidneys was associated with no risk of transmission of HBV infection, without affecting graft and patient survival, and could be considered a safe way to expand the donor pool. Our preliminary results suggest that such kidneys could be safely transplanted even in not immunized patients who underwent a prophylaxis with hepatitis B immunoglobulins.