Urothelial Cancer in Patients with Endemic Balkan Nephropathy (EN) after Renal Transplantation

Goal. Analysis of the incidence of urothelial cancer and outcome of treatment in patients with Endemic Balkan Nephropathy (EN) after renal transplantation. Methods. From January 1985 until October 2006, 550 kidney transplantations (389 cadaveric) and 5 combined kidney and pancreas transplantations were performed in University Hospital Center Rijeka. In only 6 (1.1%) of 555 transplant recipients, EN was diagnosed as the original kidney disease, based on medical history, clinical findings, and laboratory results, but without pathohistologic verification. All patients with EN received the first renal transplant from a cadaver. Patients' mean age at transplantation was 50.3 ±15.9 yrs, five patients (83.3%) were male. The incidence of malignant tumors in all 555 transplant recipients was analyzed, with an emphasis on the incidence of urothelial cancer and outcome of treatment in the group of patients with EN. Results. During posttransplant follow-up period, malignancy was diagnosed in 27 (4.9%) out of 555 transplant recipients. Skin cancer was diagnosed in 7 patients (1.3%), followed by cancer of the urinary tract in 6 patients (1.1%) and breast cancer in 3 patients (0.5%). In 3 of 6 patients with EN, urothelial cancer was diagnosed, resulting in the death in two patients. In the third patient, urothelial cancer showed a high affinity for recurrence, and besides the strong reduction of immunosuppressive therapy, repeated surgical treatment was needed. Conclusions. Patients with EN show a high incidence of urothelial cancer after renal transplantation. A thorough nephro-urological evaluation is needed before transplantation, and a careful follow-up is required afterward to ensure an early diagnosis of malignancy. Preventive nephroureterectomy is recommended.     

Receptor activator of NF-κB ligand-dependent expression of caveolin-1 in osteoclast precursors, and high dependency of osteoclastogenesis on exogenous lipoprotein

Although extensive studies have done much to clarify the molecular mechanisms of osteoclastogenesis during the last ten years, there may still be unknown molecules associated with osteoclast differentiation. Thus, we used fluorescent differential display to screen for genes whose expression is induced by receptor activator of NF-κB ligand (RANKL), a crucial molecule for osteoclast formation. We identified caveolin-1 (Cav-1) as a RANKL-induced gene. Cav-1 is a major structural protein of caveolae and lipid rafts, cholesterol-enriched microdomains in the plasma membrane (PM). The RANKL-induced Cav-1 was immediately conveyed to lipid rafts. Conversely, expression of flotillin-1 (Flot-1), another scaffolding protein of lipid rafts, was reduced during osteoclastogenesis, indicating conversion of Flot-1-predominant rafts into Cav-1-enriched rafts. However, in vitro osteoclastogenesis of precursor cells from Cav-1-null mice was comparable to that of wild-type mice, while Cav-2 expression in the knockout osteoclasts was maintained. Conversely, Cav-2 gene silencing in Cav-1-null osteoclast precursors using siRNA for Cav-2 increased osteoclast formation, suggesting that the Cav-1/Cav-2 complex may act as a negative regulator for osteoclastogenesis. On the other hand, destruction of lipid rafts by removal of cholesterol from the PM by methyl-ß-cyclodextrin (MCD) treatment caused disordered signal transductions for osteoclastogenesis, such as hyperactivation of Erk1/2 and insensitivity of Akt to RANKL stimulus. The abnormal signaling was reproduced by deleting exogenous lipoproteins from the culture medium, which also resulted in reduced osteoclast formation. In addition, the deletion caused delayed expression of nuclear factor of activated T cells c1 (NFATc1), and depressed its activation in the cytosol and inhibited its translocation into nuclei. Simultaneously, the deletion reduced the level of FcRγ, a trigger protein for initiating the calcium signaling needed to activate NFATc1, and decreased Cav-1 in lipid rafts. These findings indicate that the molecular mechanisms of osteoclastogenesis are highly dependent on extracellular lipoprotein and the integrity of lipid rafts, and suggest possible involvement of cholesterol.     

Changes in core temperature associated with lower extremity tourniquet--the influence of ambient temperature and warming equipments

BACKGROUND: We investigated changes in core temperature associated with lower extremity tourniquet (TQ) under two different ambient temperatures (1) and two different warming equipments (2) under general anesthesia combined with lumbar epidural anesthesia. METHODS: (1) The values of core temperature at ambient temperature of either 22 degrees C (n = 15) or 20 degrees C (n=15) were recorded after induction of anesthesia, at start of TQ application, at the termination of TQ application, and 14 minute after TQ release. (2) The values of core temperature using either air-forced warming or active heated i.v. at ambient temperature 20 degrees C were recorded at four points as mentioned above. RESULTS: (1) Changes in core temperature were not observed during TQ application at ambient temperature both 20 degrees C and 22 degrees C. Core temperatures in both groups decreased significantly after TQ release, and core temperatures at termination of TQ application and after TQ release at ambient temperature 20 degrees C were significantly lower than those at ambient temperature 22 degrees C. (2) Significant increases in core temperatures using two different warming equipments were observed at termination of TQ application and after TQ release at ambient temperature 20 degrees C. Core temperatures using air-forced warming were maintained during the investigation, though significant decrease in core temperature using active heated i.v. was recorded after TQ release. CONCLUSIONS: Air-forced warming maintains core temperature efficiently associated with lower extremity tourniquet.     

Can we influence the neurological development and hair cortisol concentration of offspring by reducing the stress of the mother during pregnancy? A randomized controlled trial

The objective was to evaluate the effects of a stress management cognitive behavioural therapy followed during pregnancy on subsequent childhood on hair cortisol at birth and on neurodevelopment and Hair Cortisol Concentrations (HCC) at 6 months of age. The study sample included 48 pregnant women, divided into two groups: 24 women in the Therapy Group (TG) and 24 women who received standard pregnancy care (control group (CG); CG). To test the therapy efficacy, an evaluation of the HCC and psychological stress, psychopathological symptomatology and resilience was conducted before and after the treatment. The level of cortisol in their hair was obtained during pregnancy and that of their babies at birth. Six months after birth, a cortisol sample was taken from the hair and the babies' neurodevelopment was evaluated based on a Bayley-III test. The TG presented reductions in psychological stress and psychopathological symptomatology after treatment. On the other hand, the CG increased their cortisol concentrations between the pre and post intervention, remaining stable in the TG. Moreover, results showed that TG babies had lower cortisol concentrations at birth and obtained significantly higher cognitive and motor development scores at 6 months. These findings support that providing psychological care to pregnant women may not only have a benefit on these women's mental state, but may also benefit the neurodevelopment of their offspring.     

Axillary Recurrence after Negative Sentinel Lymph Node Biopsy: Frequency and Factors Influencing Recurrence on the Long Term

Abstract:  Sentinel lymph node (SLN) biopsy is a less invasive method for determining tumor stage. Purpose of this study was to determine the frequency of axillary recurrence after negative SLN biopsy for women with breast cancer. A total of 121 patients with a negative SLN biopsy, from January 1, 2000 to December 31, 2004, were identified from a maintained pathology database. Retrospective chart review and data analysis were performed until September 1, 2006, to determine frequency of axillary recurrence and identify variables predictive of recurrence. Two hundred and sixty eight patients had undergone SLN biopsy in the researched period, of which 121 were SLN negative and had no further axillary treatment. The median follow-up was 44 months (range, 15–76 months). Three patients (2.5%) developed isolated axillary recurrence. Five patients (4.1%) developed distant disease recurrence. Grade 3 tumor differentiation was significantly associated with tumor recurrence. Tumor size, hormone receptor state, and mitotic activity/2 mm² were not significantly associated with disease recurrence. Patients with a negative SLN biopsy with no further axillary treatment, show a low rate of axillary recurrence. SLN biopsy is a less invasive and accurate method for determining tumor stage and a negative SLN biopsy provides good regional control of the axilla on the long term.     

Relationship between serum pre-B cell colony-enhancing factor/visfatin and atherosclerotic parameters in chronic hemodialysis patients

Pre-B cell colony-enhancing factor (PBEF)/visfatin is produced by adipose tissue, skeletal muscle, bone marrow, the liver and lymphocytes. Although serum PBEF/visfatin is related to the pathogenesis of atherosclerosis, and its level is elevated in patients with chronic kidney disease, it remains unclear whether increased PBEF/visfatin is associated with atherosclerotic parameters in hemodialysis (HD) patients. In this study, we measured serum PBEF/visfatin in 68 chronic HD patients (age 66 +/- 14 years, time on HD 76 +/- 76 months, 41 males, 27 females) and examined the association of serum PBEF/visfatin with serum asymmetric dimethylarginine, arteriosclerotic parameters such as pulse wave velocity, ankle brachial pressure index and the percent of abdominal aortic wall calcification in a cross-sectional fashion. Serum PBEF/visfatin was significantly correlated with time on HD (r = 0.29, p = 0.02), but not with age, gender and diabetes. There was no association between PBEF/visfatin and body mass index, abdominal visceral and subcutaneous fat mass area, and total adiponectin. Serum PBEF/visfatin was significantly positively correlated with log-transformed highly sensitive C-reactive protein (r = 0.26, p < 0.05) but negatively with serum albumin (r = -0.33, p < 0.01). In contrast, there was no association between serum PBEF/visfatin and asymmetric dimethylarginine, aortic pulse wave velocity, brachial ankle pressure index and percent of abdominal aortic wall calcification. It follows from these findings that serum PBEF/visfatin may reflect the inflammatory status rather than atherosclerotic changes in chronic HD patients.     

Heparin-coated circuits (Duraflo II) with reduced versus full anticoagulation during coronary artery bypass surgery

BACKGROUND: Introduction of completely heparin-coated cardiopulmonary bypass (CPB) circuits combined with reduced systemic anticoagulation has been shown to reduce postoperative bleeding and requirements for allogeneic transfusions after cardiac surgery. However, some uncertainty exists whether this effect is due to the reduced amount of heparin or to the heparinized surface itself. Therefore, a retrospective study was undertaken, comparing two different anticoagulation protocols applied to coronary artery bypass patients treated with identical heparin-coated CPB equipment. METHOD: Over a 12 month period all coronary artery bypass patients operated with extracorporeal circulation were subjected to a Duraflo II heparin-coated circuit (Baxter Healthcare Corp, Bentley Laboratories Division, Irvine, Calif) and full heparin dose (activated clotting time [ACT] > 480 seconds; Group F, n = 651). Over the next 24 months, all coronary patients who were treated with an identical circuit combined with reduced systemic heparinization (ACT > 250 seconds) were included in Group R (n = 675). Except for the different anticoagulation protocols, all treatment regimens before, during, and after the operation remained unchanged throughout the study period. RESULTS: There were no statistically significant differences in any major demographic or operative parameters. In Group R, the postoperative bleeding was mean 665 +/- 257 ml versus 757 +/- 367 ml in Group F (p < 0.0001), and the perioperative decrease in hemoglobin concentration was significantly lower in Group R (22 +/- 1.2 gm/L versus 25 +/- 1.3 gm/L, p < 0.0001). The time for postoperative ventilatory support was shorter in Group R (1.7 +/- 1.3 hours versus 1.9 +/- 1.1 hours in Group F, p = 0.0006), and the incidence of new episodes of atrial fibrillation after the operation was lower (26.4% in Group R versus 32.8% in Group F, p = 0.01). There were no significant differences in the incidences of perioperative myocardial infarction, stroke, transient neurological disturbances, physical rehabilitation, or mortality. No technical or coagulation problems were recorded in either group. CONCLUSION: The use of Duraflo II coated circuits for CPB combined with reduced anticoagulation decrease postoperative bleeding and hemoglobin loss compared with full heparin dose treatment. In addition, the intubation time was shorter and the incidence of postoperative atrial fibrillation was lower in the patients treated with low heparin doses.     

Reverse pharmacological effect of loop diuretics and altered rBSC1 expression in rats with lithium nephropathy

BACKGROUND: Renal urinary concentration is associated with enhanced expression of rBSC1, a rat sodium cotransporter, in the thick ascending limb of Henle. Increased expression of rBSC1 was reported recently in nephrogenic diabetes insipidus induced by lithium chloride (Li nephropathy). However, the pathophysiological implication of altered rBSC1 expression has not yet been investigated. METHODS: Li nephropathy was induced in rats by an oral administration of 40 mmol lithium/kg dry food. In rats with reduced urinary osmolality to less than 300 mOsm/kg H2O, we examined the expression of rBSC1 mRNA and protein, plasma arginine vasopressin (AVP) and RNA expression of kidney-specific water channel, aquaporin-2 (AQP2), of collecting ducts. Rats with Li nephropathy were treated with furosemide (3 mg/kg body weight), which blocks the activity of rBSC1, and changes in urine concentration, plasma AVP, medullary accumulation of Li ions, and apical AQP2 expression were determined. RESULTS: Rats with Li nephropathy showed increased rBSC1 RNA and protein expression and reduced AQP2 RNA. In these rats, furosemide, which induces dilution of urine and polyuria in normal rats, resulted in a progressive and significant rise in urine osmolality from 167 +/- 11 (mean +/- SD) at baseline to 450 +/- 45 mOsm/kg H2O at three hours after administration, and significant oliguria. In the same rats, plasma AVP decreased significantly from 5.7 to 3.0 pg/mL. In addition, recovery of apical AQP2 expression was noted in a proportion of epithelial cells of the collecting ducts. Although Li+ in the renal medulla was slightly lower in rats with Li nephropathy treated with furosemide, statistical significance was not achieved. CONCLUSIONS: Our results suggest that dehydration or high plasma AVP results in an enhanced rBSC1 expression in Li nephropathy, and that rBSC1 expression is closely associated with the adverse effects of Li ions on collecting duct function.     

Technological development and advances in single-photon emission computed tomography/computed tomography

Single-photon emission computed tomography/computed tomography (SPECT/CT) has emerged during the past decade as a means of correlating anatomical information from CT with functional information from SPECT. The integration of SPECT and CT in a single imaging device facilitates anatomical localization of the radiopharmaceutical to differentiate physiological uptake from that associated with disease and patient-specific attenuation correction to improve the visual quality and quantitative accuracy of the SPECT image. The first clinically available SPECT/CT systems performed emission-transmission imaging using a dual-headed SPECT camera and a low-power x-ray CT subsystem. Newer SPECT/CT systems are available with high-power CT subsystems suitable for detailed anatomical diagnosis, including CT coronary angiography and coronary calcification that can be correlated with myocardial perfusion measurements. The high-performance CT capabilities also offer the potential to improve compensation of partial volume errors for more accurate quantitation of radionuclide measurement of myocardial blood flow and other physiological processes and for radiation dosimetry for radionuclide therapy. In addition, new SPECT technologies are being developed that significantly improve the detection efficiency and spatial resolution for radionuclide imaging of small organs including the heart, brain, and breast, and therefore may provide new capabilities for SPECT/CT imaging in these important clinical applications.