The impact of the prevention strategies on the indirect effects of CMV infection in solid organ transplant recipients

Transplant recipients receiving immunosuppressive therapy are at increased risk of active cytomegalovirus (CMV) infection and disease. Without appropriate prophylaxis, as many as 80% of solid organ transplant recipients may experience CMV infection. In addition to the direct effects of CMV, infection may be associated with a range of indirect effects, including an increase in risk of other infections, as well as a higher incidence of rejection, graft loss and death. The indirect effects of CMV infection can vary depending on the transplanted organ. For example, CMV-infected kidney transplant recipients may be at increased risk of cardiovascular disease and diabetes, while CMV infection in liver transplant recipients may potentiate hepatitis C infection and increase the risk of post-transplant lymphoproliferative disease. Indirect effects result from a number of pathological processes, including immune modulation and immunosuppression, generation of cytotoxic, pro-inflammatory responses, and smooth muscle proliferation. Prophylactic treatment with antiviral medication can reduce the risk of CMV disease, thereby improving graft survival and overall outcomes, particularly in kidney and heart transplant recipients. Antiviral prophylaxis should be considered for all patients at risk of CMV infection after solid organ transplantation. In this paper we review the main indirect effects of CMV infection in solid organ transplant recipients, and the impact of CMV prophylaxis on these effects.     

Treatment of 125 sinonasal tumors: Prognostic factors, outcome, and follow-up

We reviewed our experience with sinonasal cancer patients to assess the prognostic factors. Between 1974 and 1995, we enrolled 125 patients (58 + 16 years [mean age + SD]; 94 males and 31 females). Tumor stage distribution was: T1, 64 patients; T2, 36 patients; and T3, 25 patients. Surgery as a primary treatment was selected for 106 patients (55 cases of surgery alone, 40 cases of surgery plus radiotherapy, and 11 cases of surgery plus chemotherapy with/without radiotherapy). The 1-, 5-, and 10-year overall survival was 75.0%, 37.2%, and 24.7%, respectively. The parameters with statistical prognostic significance were nodal stage, locoregional failure, and tumor stage. Histological type and primary site had no prognostic value. There were no significant survival differences between surgery alone and surgery plus radiotherapy. Sinonasal tumors have a poor survival, despite early diagnosis, radical surgical resection, and strict follow-up. Radiotherapy seems not to be clearly necessary in stage T1.     

Induced adiposity and adipocyte hypertrophy in mice lacking the AMP-activated protein kinase-alpha2 subunit

AMP-activated protein kinase (AMPK) is considered as a cellular energy sensor that regulates glucose and lipid metabolism by phosphorylating key regulatory enzymes. Despite the major role of adipose tissue in regulating energy partitioning in the organism, the role of AMPK in this tissue has not been addressed. In the present study, we subjected AMPKalpha2 knockout (KO) mice to a high-fat diet to examine the effect of AMPK on adipose tissue formation. Compared with the wild type, AMPKalpha2 KO mice exhibited increased body weight and fat mass. The increase in adipose tissue mass was due to the enlargement of the preexisting adipocytes with increased lipid accumulation. However, we did not observe any changes in adipocyte marker expression, such as peroxisome proliferator-activated receptor-gamma, CCAAT/enhancer-binding protein alpha (C/EBPalpha) and adipocyte fatty acid-binding protein (aFABP/aP2), or total cell number. Unlike impaired glucose homeostasis observed on normal diet feeding, when fed a high-fat diet AMPKalpha2 KO mice did not show differences in glucose tolerance and insulin sensitivity compared with wild-type mice. Our results suggest that the increase in lipid storage in adipose tissue in AMPKalpha2 KO mice may have protected these mice from further impairment of glucose homeostasis that normally accompanies high-fat feeding. Our study also demonstrates that lack of AMPKalpha2 subunit may be a factor contributing to the development of obesity.     

Predictors of Success in Conversion from Calcineurin Inhibitor to Sirolimus in Chronic Allograft Dysfunction

Chronic allograft dysfunction (CAD) is a major cause of graft loss in long-term kidney transplant recipients. To identify predictors of successful conversion from calcineurin inhibitor (CNI) to sirolimus (SRL) we investigated 59 renal transplant patients with CAD without histological signs of acute rejection. They received 12-15 mg SRL once, then 4-5 mg/day, target trough level 8-12 ng/mL. CNI dose was reduced by 50% simultaneously, and withdrawn at 1-2 months. Concomitant immunosuppression remained unchanged. After 1 year patient survival was 100% and graft survival 92%. In responders (54%) creatinine improved (2.75 +/- 0.75 to 2.22 +/- 0.64 mg/dL; p < 0.01). In nonresponders (46%) creatinine deteriorated (3.15 +/- 1.02 to 4.44 +/- 1.60 mg/dL; p < 0.01). Baseline renal function did not differ, however, baseline proteinuria (519 +/- 516 vs. 1532 +/- 867 mg/day, p < 0.01), histological grade of chronic allograft nephropathy (CAN) (1.2 +/- 0.5 vs. 1.9 +/- 0.6; p < 0.01), grade of vascular fibrous intimal thickening (1.2 +/- 0.7 vs. 1.7 +/- 0.7; p = 0.048) and number of acute rejections before conversion (0.73 +/- 0.69 vs. 1.27 +/- 0.96; p < 0.05) differed significantly between responders and nonresponders. In a multivariate analysis low proteinuria was the only independent variable. Proteinuria below 800 mg/day has a positive predictive value of 90%. Proteinuria at conversion below 800 mg/day is the only independent predictor for positive outcome in conversion from CNI to SRL in CAD.     

Predictive factors of excess body weight loss 1?year after laparoscopic bariatric surgery

Background

Bariatric surgery (BS) is widely accepted for the treatment of patients with morbid obesity (MO). We aimed to determine presurgical predictors of and surgical technique-related differences in excess weight loss (EWL) 1?year after BS.

Methods

This retrospective study included 407 subjects (F/M 3:1, median age?=?44?years) who underwent laparoscopic Roux-en-Y gastric bypass (RYGB, n?=?307) or sleeve gastrectomy (SG, n?=?100) at our University Hospital and were evaluated 1?year after surgery.

Results

Baseline median (min–max) body mass index (BMI) was 47?kg/m² (range?=?36–71). BMI was higher in the SG than in the RYGB group (53 vs. 46?kg/m², p?p?p?=?0.2), was lower in diabetic than in nondiabetic subjects (71?±?17% vs. 79?±?17%, p?p?p?=?0.4) after taking into account baseline BMI. Multiple regression and logistic analysis showed that younger individuals with lower BMI but higher WC, and lower HbA1c and TG, had higher EWL and a higher rate of successful (EWL?≥?60%) weight loss.

Conclusions

Our data indicate that some of the characteristics that would have subjects referred early for BS were associated with higher weight loss. Therefore, the timing of laparoscopic BS might be an important factor for MO individuals in which medical weight loss intervention has failed.     

Alloplastic bladder substitution: are we making progress?

Radical cystectomy with lymphadenectomy and urinary diversion is the gold standard treatment for bladder cancer in organ-confined muscle-invasive disease and selected patients who have high-grade non-muscle-invasive disease or are non-responders to BCG. The main and most morbid complications of this challenging surgery are related to the use of bowel for urinary tract reconstruction. For this reason, many past projects were devoted to finding an alternative to the use of bowel. The aim of this review is to provide a summary of the evolution of alloplastic bladder substitution. A comprehensive review of the literature was performed using the Medline National Library of Medicine database and Google Scholar. Keywords used were cystectomy and intestine/bowel, replacement, bladder substitution, organ replacement, artificial bladder, alloplastic material, biomaterial, and tissue engineering. Various prostheses have been proposed for replacement of the urinary bladder, silicone being the most frequently used material. The first published model of an alloplastic bladder was described by Bogash et al. in late 1959, while the last, in 1996, was suggested by Rohrmann. Interprofessional collaboration, recent advances in technology, and tissue engineering may help in developing suitable bladder prostheses. Urologists as well as engineers and the industry need to give this matter serious attention.     

Osmotic tolerance limits and properties of rhesus monkey (Macaca mulatta) spermatozoa

Fundamental cryobiological characteristics of rhesus spermatozoa must be determined for successful cryopreservation techniques to be established. The main objectives of the present study were to determine the osmotic behavior and osmotic tolerance limits of rhesus macaque spermatozoa. Cell volume changes over anisotonic conditions were assessed using an electronic particle counter and sperm motility was evaluated with a computer-assisted sperm analysis system. Analysis of membrane integrity and mitochondrial membrane potential was performed using flow cytometry. Rhesus monkey spermatozoa behave as linear osmometers in the osmotic range tested (75-900 mOsmol kg(-1)), as shown by the Boyle van't Hoff plot (r(2) =.99). Rhesus spermatozoa have a mean cell volume of 36.8 +/- 0.5 micro m(3) at 22 degrees C, with 77.2% of the intracellular volume being osmotically inactive. Results regarding sperm tolerance to osmotic stress showed that sperm motility was more sensitive than membrane integrity to deviations from isotonicity and, in addition, that rhesus sperm motility and membrane integrity were more sensitive to hypertonic than hypotonic conditions. Mitochondrial membrane potential did not explain the lack of sperm motility observed under anisosmolal conditions in our study. Although most spermatozoa were able to recover initial volume after osmotic stress, they were not able to recover initial motility.     

Biomechanical evaluation of fixation of clavicular fractures

Reproducible fractures of the midshaft of the clavicle were created in 14 fresh frozen human cadaveric clavicles. Under the three-point bending loading by a materials testing machine, the load to failure of fixation of the clavicular fractures treated with steel reconstruction plates (five specimens) and Herbert cannulated bone screw (nine specimens), was compared with a group control formed by five specimens of clavicles without osteosynthesis material. No statistically significant differences were observed between the three groups. In consequence and in terms of biomechanics, in clavicular acute fractures, both plating and intramedullary Herbert cannulated bone screw may be utilized in the treatment of these lesions.     

Main traumatic events in Europe: PTSD in the European study of the epidemiology of mental disorders survey

A potentially traumatic event (PTE) contributes to trauma through its frequency, conditional probability of posttraumatic stress disorder (PTSD), and experience of other PTEs. A cross-sectional survey was conducted, enrolling 21,425 adults nationally representative of six European countries. Using the WHO-Composite International Diagnostic Interview, 8,797 were interviewed on 28 PTEs and PTSD. Prevalence of 12-month PTSD was 1.1%. When PTSD was present, the mean number of PTEs experienced was 3.2. In a multivariate analysis on PTEs and gender, six PTEs were found to be more traumatic, and to explain a large percentage of PTSD, as estimated by their attributable risk of PTSD: rape, undisclosed private event, having a child with serious illness, beaten by partner, stalked, beaten by caregiver.     

Improved renal function, with similar proteinuria, after two years of early tacrolimus withdrawal from a regimen of sirolimus plus tacrolimus

Results at 1 year of a pilot randomized trial with 87 kidney graft recipients, comparing the maintenance treatment with sirolimus, tacrolimus and steroids (group I) versus tacrolimus withdrawal since the third month onward, followed by maintenance with SRL and steroids (group II) have shown that early elimination of tacrolimus may result in improved renal function and blood pressure control. At 2 years, 26 and 25 patients in groups I and II, respectively, were analyzed in an on-therapy and an ITT analysis. In the on-therapy analysis, group II showed lower serum creatinine (1.3+/-0.2 vs. 1.6+/-0.6 mg/dL) and lower diastolic blood pressure (74+/-9 vs. 80+/-11 mm Hg). No acute rejections occurred during the second year of follow-up. In more than 90% of patients, proteinuria was less than 1 g/d, and in 50% it was negative. In the ITT analysis, differences were found only in diastolic blood pressure (80+/-10 vs. 74+/-8 mm Hg in groups I and II respectively, P=0.009). Tacrolimus withdrawal from a combination of sirolimus and tacrolimus, in selected patients, may be observed at 2 years by an improvement in renal function and blood pressure without a higher incidence of proteinuria.