Proteomic Analysis of Kidney Preservation Solutions Prior to Renal Transplantation.

One of the main issues in kidney transplantation is the optimal functional preservation of the organ until its transplantation into the appropriate recipient. Despite intensive efforts, the functional preservation period remains limited to hours. During this time, as a result of cellular injury, various proteins, peptides, and other molecules are released by the organ into the preservation medium. In this study, we used proteomic techniques to analyze the protein profiles of preservation solutions in which organs had been preserved prior to their transplantation. Samples were obtained from the preservation solutions of 25 deceased donor kidneys scheduled for transplantation. The protein profiles of the solutions were analyzed using 2D gel electrophoresis/MALDI-TOF and LC-MS/MS. We identified and quantified 206 proteins and peptides belonging to 139 different groups. Of these, 111 proteins groups were belonging to kidney tissues. This study used proteomic techniques to analyze the protein profiles of organ preservation solutions. These findings will contribute to the development of improved preservation solutions to effectively protect organs for transplantation.

Prophylactic Eculizumab Use in Kidney Transplantation: A Review of the Literature and Report of a Case with Atypical Hemolytic Uremic Syndrome.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a very rare disease, which presents with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Progression to end-stage renal disease (ESRD) from acute kidney injury is observed in 60% of aHUS cases. The prognosis of aHUS patients who undergo kidney transplantation (Ktx) is generally poor, but these patients should be treated prophylactically with eculizumab to prevent recurrence after transplantation. CASE REPORT: An 18-year-old man was referred to our center with a history of rapid progression to ESRD with unknown etiology. He had anemia, thrombocytopenia, high levels of LDH, and indirect bilirubin and creatinine on initial laboratory results. Our diagnosis was aHUS due to initial results, normal level of ADAMTS activity, and lack of predisposing factors seen in typical HUS. We planned to perform genetic analysis for the patient and the donor candidate (mother). The variations found on exon 7 of the CFH gene had not been reported previously. According to PolyPhen analysis, this mutation was reported as a potential cause for aHUS. We decided to perform Ktx under eculizumab prophylaxis. Weekly administration of prophylaxis was extended to 1 month. The graft functioned immediately after Ktx. The patient has completed his first year uneventfully in our follow-up, with a creatinine 0.79 mg/dl at his last control visit. CONCLUSIONS: We found favorable results of an aHUS case successfully treated with kidney transplantation combined with short-term prophylactic eculizumab therapy.

Proteinuria associated with mTOR inhibitors after kidney transplant.

OBJECTIVES: The mammalian target of rapamycin inhibitors sirolimus and everolimus are immunosuppressive drugs for kidney transplant patients, but adverse events may include proteinuria. The purpose of this study was to compare the effects of sirolimus and everolimus on creatinine clearance and proteinuria after kidney transplant. MATERIALS AND METHODS: This study was a prospective evaluation period of 50 patients (age, 16-65 y) who had kidney transplant. There were 25 patients who used sirolimus and 25 patients who used everolimus. Evaluation at the beginning mTOR and end of the evaluation period included complete blood count, blood pressure, serum creatinine level, creatinine clearance, and proteinuria level in a 24-hour urine collection. RESULTS: Mean creatinine clearance at the beginning and end of the evaluation period was significantly less in the everolimus than sirolimus group. There was no significant change in creatinine clearance from the beginning to end of the evaluation period in either the sirolimus or everolimus group. Mean proteinuria at the beginning and end of the evaluation period was similar between the sirolimus and everolimus groups. Both groups had a significant increase in mean proteinuria from beginning to end of the evaluation period, but the increase in proteinuria was similar for the sirolimus and everolimus groups (difference not significant). CONCLUSIONS: In kidney transplant recipients, sirolimus and everolimus are associated with a similar level of increased mean proteinuria.

Paraoxonase and arylesterase activities, lipid profile, and oxidative damage in experimental ischemic colitis model.

Objective. In the present study, since PON1 is known as an HDL-associated antioxidant enzyme that inhibits the oxidative modification of LDL and oxidative stress plays a role in the pathogenesis of mesenteric ischemia, we investigated the changes in PON1 activity and lipid profile in an experimental ischemic colitis model. Methods. Forty male Wistar albino rats were divided into two groups: the control group (N = 15) and the experimental group (N = 25). All animals were anesthetized with ether and ketamine anesthesia to undergo a midline laparotomy. Ischemic colitis was induced by marginal vessel ligation in the splenic flexura (devascularization process). A sham laparotomy was performed in the control group. All animals were sacrificed on the seventh postoperative day. Oxidative stress marker (malonyldialdehyde, MDA), lipid profile, and paraoxonase (PON-1) and arylesterase activities were determined. Histopathological evaluation was done under light microscopy, after sectioning and staining with hematoxyline and eosin. Statistical analysis was conducted using Student's t-test and Mann-Whitney U test, and P < 0.05 was considered as statistically significant. Results. There was a significant decrease in both serum and tissue PON1 activity in ischemic colitis group (P < 0.01, for each). Similarly, arylesterase levels showed a parallel decrease in both tissue and serum of the experimental group (P < 0.01 and P < 0.001, retrospectively). MDA, an oxidative stress marker, was seen to increase in the experimental group (P < 0.01, tissue; P < 0.05, serum). In experimental group, there was a significant rise in serum total cholesterol and LDL levels (P < 0.001, for each). However, HDL level decreased significantly (P < 0.001). Triglycerides did not show any change between the groups (P > 0.05). Conclusions. PON1 and arylesterase play an important role in the pathophysiology of ischemic colitis.

The utility of amylase and lipase as reliable predictive markers for functioning renal graft.

BACKGROUND: The aim of this study was to evaluate the utility of amylase and lipase as reliable predictive markers for functioning renal grafts, either short- or long-term. MATERIAL/METHODS: Serum amylase (Amyl), lipase, creatinine (Cr), creatinine clearance (Cr Cl) and 24-hr proteinuria (Prot) were studied in 190 kidney recipients. The correlation of these outcomes for each parameter was tested. Sensitivity and specificity of the variables were obtained in patients with graft failure (GF) and acute cellular rejection (ACR). RESULTS: Mean follow-up was 66.7 month. Amyl and lipase were elevated 67% vs. 45% in GF (N=23); 60% vs. 44% in ACR (N=42) patients and were inversely correlated with Cr Cl (p>.05). Lipase was notably superior to amylase and creatinine; the specificity of lipase (Amyl, Cr) was 87% (59%, 28%). Increases in amylase were more predictive in the presence of mild or moderate kidney failure (33% and 52%, respectively). However, the highest intensity of lipase elevation (39%) was in advanced kidney failure (Cr Cl <30 ml/min). CONCLUSIONS: Serum amylase and lipase should be used as markers monitoring graft function. For early detection of graft dysfunction, amylase seems to be superior to lipase.

Delivery in female kidney transplant recipients with hepatitis C virus infection: is it safe for mother and newborn?

The aim of this report is to evaluate whether pregnancy is a risk factor for poor outcome of infection with hepatitis C virus or for allograft deterioration among kidney transplant recipients. The first case was in a 41-year-old pregnant kidney transplant recipient with hypercreatinemia and a history of toxic hepatitis. The second case was treated with interferon before transplant. Tacrolimus-based immunosuppressive regimens were used during the pregnancies. Hypertension complicated both pregnancies, and the pregnancies ended with cesarean delivery at preterm and term with healthy but low-weight newborns. The first patient became positive for hepatitis C virus RNA after pregnancy without a flare in transaminase level. Antibodies to hepatitis C virus were negative in the newborns. In conclusion, pregnancy should be promoted for kidney recipients infected with hepatitis C virus who have stable graft and liver function.

Ramsay Hunt syndrome with atypical progress in a renal transplant recipient: a case report.

Ramsay Hunt syndrome is a rare complication of herpes zoster disease in which reactivation of latent varicella zoster virus infection occurs in the geniculate ganglion causing otalgia, unilateral vesicular eruption in a restricted dermatomal distribution, and peripheral facial paralysis. Dermal infections caused by human pathogenic herpes viruses are common in organ transplant recipients. For a transplant surgeon, it is imperative to remember that viral prophylaxis is essential in the follow-up of the transplant patients. Here, we presented a case of renal transplant and Ramsay Hunt syndrome with multiple cranial nerve involvement, with an atypical course. Management and differential diagnosis of this particular case are discussed with a review of the literature.

Acute abdomen in pregnancy requiring surgical management: a 20-case series.

OBJECTIVES: The obstetrician often has a difficult task in diagnosing and managing the acute abdomen in pregnancy. A reluctance to operate during pregnancy adds unnecessary delay, which may increase morbidity for both mother and fetus. In this study, we present our experience in pregnant patients with acute abdomen. STUDY DESIGN: Pregnant patients with acute abdomen requiring surgical exploration were enrolled from 2007 to 2010. Demographics, gestational age, symptoms, fetal loss, preterm delivery, imaging studies, operative results, postoperative complications and histopathologic evaluations were recorded. Ultrasound (US) and magnetic resonance (MR) imaging studies were evaluated. Data analyses were performed with Microsoft Excel and statistical evaluations were done by using Student's t-test. RESULTS: There were 20 patients with a mean age of 32 years. The rate of emergency surgery was seen to be significantly higher in the second trimester (p<0.05). Most common symptoms were abdominal pain (100%) and nausea (80%). US was done in all patients while MR imaging was used in 30%. However, US findings were consistent with surgical findings in only 55%, while MR was successful in assigning the correct diagnosis in 83.3%. Appendicitis and adhesive small bowel obstruction were the most common etiologies causing acute abdomen (30% and 15%, respectively). All patients tolerated surgery well, and postoperative complications included wound infection, 10%, preterm labor, 5%, and prolonged paralytic ileus, 5%. One patient died from advanced gastric carcinoma and the only fetal death was seen in this case. CONCLUSIONS: Prompt diagnosis and appropriate therapy are crucial in pregnant with acute abdomen. The use of US may be limited and CT is not desirable due to fetal irradiation. MR has thus become increasingly popular in the evaluation of such patients. Adhesive small bowel obstruction should be kept in mind as an important etiology.

Denervation point for neuromuscular blockade on lateral pectoral nerves: a cadaver study.

PURPOSE: The objective of our study was to clarify the topography of the medial and lateral pectoral nerves (LPNs) and the vascularity in the infraclavicular fossa and to propose an ideal injection point for neuromuscular blockade of the pectoralis major (PM) muscle. METHODS: The pectoral muscles and their nerves were examined bilaterally on 10 formalin-fixed cadavers. The PM muscle was dissected from its clavicular origin and sternocostal attachments. It was reflected superolaterally to expose the pectoralis minor muscle and neurovascular bundle at the infraclavicular fossa. We took the measurements to identify a landmark point and reach the neurovascular bundle from an overlying point on the skin. RESULTS: The LPN was closely related to the thoracoacromial artery and veins on the lower surface of the PM muscle and was visible under the muscle fascia as a neurovascular bundle. The point where the pM line (perpendicular to midsternal line beginning from the inferior border of the jugular notch) transects the neurovascular bundle was sufficiently close to the point at which the neurovascular bundle enters the PM muscle. Hence, this point was determined as the denervation point in all cadaveric dissections. This denervation point is 2.81 ± 0.33 cm distant vertically from the 1/3 medial part of the clavicle and 8.12 ± 1.09 cm distant horizontally from the midsternal line. CONCLUSIONS: We have identified an injection point which may be and suitable and safe location to administer neuromuscular motor blockade of the pectoralis muscles with a percutaneous local anesthetic agent in some clinical pathologies requiring elective denervation.

Evaluation of intraoperative parathormone measurement for predicting successful surgery in patients undergoing subtotal/total parathyroidectomy due to secondary hyperparathyroidism.

OBJECTIVES/BACKGROUND: The aim of this study is to investigate the predictive value of intraoperative parathormone measurement addressing successful surgical resection in patients with secondary hyperparathyroidism. METHODS: The study included 42 consecutive patients operated on between May 2006 and July 2008. Patients were grouped according to successful surgery (Group 1, n = 36) and persistent postoperative hyperparathyroidism (Group 2, n = 6). Serum phosphorus (P), total calcium (tCa), ionized calcium (iCa), intact parathormone (iPTH), and alkaline phosphatase (ALP) were drawn preoperatively and intraoperatively upon 15 minutes after completion of resection (iPTH(15)). The rate of decrease of pith detected by iPTH(15) compared to preoperative values was calculated (iPTH(%)). RESULTS: Preoperative P, tCa, iCa, iPTH, and ALP were comparable. Subtotal parathyroidectomy (sPx) (n = 27) and total parathyroidectomy with autotransplantation (tPx) (n = 15) were performed. Mean iPTH(15) value, iPTH(%) rates were 145.9 +/- 12.3 pg/mL, % 91.6 +/- 0.7, and 522.5 +/- 85.4 pg/mL, % 75.1 +/- 2.0 (P = ,001) in Groups 1 and 2, respectively. Mean serum tCa and iCa at POD#1 in Group 1 were 7.6 +/- 0.1 mg/dL, 0.910 +/- 0.4 mmol/L, and Group 2 were 8.3 +/- 0.3 mg/dL, 1.050 +/- 0.4 mmol/L (P < .05), respectively. ALP levels were similar. CONCLUSION: iPTH(15) value and iPTH(%) rate accurately predicts the completeness of resection in secondary hyperparathyroidism. The rate of decrease in serum iPTH detected intraoperatively compared to preoperative baseline levels exceeding 90% in sPx, 95% in tPx, accurately predicts the success of surgery. Postoperative normocalcemia without calcium replacement would raise a suspicion about completeness of surgical resection.

Does thyroid gland examination by palpation alter serum hormone levels?

OBJECTIVES/HYPOTHESIS: The goal of this study was to investigate the effects of routine thyroid gland palpation on serum thyroid hormone levels. STUDY DESIGN: Prospective study at Haydarpasa Numune Research and Education Hospital, Istanbul, Turkey. METHODS: This study was carried out in two groups with a total of 50 consecutive adults. Group I consisted of 20 patients (12 female and 8 male, aged 20-48 years) with a diagnosis of nodular thyroid disease confirmed by ultrasound imaging techniques. The second group consisted of 30 otherwise healthy subjects (17 female and 13 male, aged 18-50 years) referred for neck and thyroid ultrasound and with no thyroid pathology detected. Thyroid gland palpations were performed by the same physician. Blood samples were obtained before and 2 hours after thyroid gland palpation. Serum total T3 (TT3), total T4 (TT4), free T3 (FT3), free T4 (FT4), thyroid stimulating hormone (TSH), and thyroglobulin (TG) measurements were made. RESULTS: We found that routine palpation in the first group caused a significant increase in serum TT3 (P < .05), FT3 (P < .01), FT4 (P < .05), and TG (P < .05) levels. In the second group, TT3 (P < .01), FT3 (P < .05), FT4 (P < .05), and TG (P < .05) levels also increased significantly after palpation. Differences in TSH and TT4 levels were not significant in any of the groups (P > .05). CONCLUSIONS: Preliminary data proposing a possible effect of routine thyroid gland palpation on serum thyroid hormone levels suggest that serum thyroid hormone measurements should be performed before any manipulation of the gland, including palpation, to avoid misdiagnosis.

Acute rejection in low-toxicity regimens: clinical impact and risk factors in the Symphony study.

The Symphony study assessed whether mycophenolate mofetil (MMF)-based regimens containing reduced doses of adjunct immunosuppressants could reduce toxicity while maintaining efficacy. Here, we examined the impact of acute rejection and associated risk factors. The incidence of biopsy-proven acute rejection in the low-dose tacrolimus group was approximately half that of the standard-dose cyclosporine and low-dose cyclosporine groups, and a third of that in the low-dose sirolimus group. The low-dose cyclosporine group had more severe rejection episodes (≥grade II) compared with other groups. Acute rejection was associated with a 10 mL/min glomerular filtration rate (GFR) reduction and a 5.3% absolute increase in graft loss at 12 months. Overall, the highest GFR was found in both rejecters and non-rejecters receiving low-dose tacrolimus, both in an intent-to-treat analysis and in patients successfully treated according to the protocol. In Cox regression models, human leukocyte antigen (HLA) mismatches and expanded criteria donors increased the acute rejection risk, while recipient age, living related donor, and MMF dose were associated with a reduced risk. Acute rejection was associated with worse outcome but did not entirely explain the differences among the treatment groups. The 2 g MMF plus low-dose tacrolimus combination appears to be the most efficient of all regimens examined regardless of acute rejection.

Evaluation of gadolinium pre-treatment with or without splenectomy in the setting of renal ischemia reperfusion injury in rats.

INTRODUCTION: This study aims to investigate gadolinium chloride (Gd) pre-treatment with/without splenectomy (Splx) in the setting of renal ischemia/reperfusion (IR) injury in rats. MATERIALS AND METHODS: Under anesthesia, male Wistar albino rats with or without splenectomized (Splx) were right nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 3 h of reperfusion. Gadolinium chloride (10 mg kg(-1)) or saline was administered 24 hours prior to ischemia via penile vein. Right nephrectomy and intravenous saline administration was performed in the control group. At the end of the reperfusion period, following decapitation, kidney samples were taken for histological examination or determination of renal malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and Na(+)-K(+) ATPase activities. Creatinine, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), TNF-alpha, and IL-1 beta were assayed in the serum samples. RESULTS: Ischemia/reperfusion caused significant increases in the serum TNF-alpha, IL-1 beta, BUN, creatinine, AST, ALT, LDH, and tissue MDA levels and MPO activity, while either Gd pre-treatment or Splx decreased these parameters significantly. On the other hand, IR induced a decrease in the tissue GSH, and Na(+)-K(+) ATPase activity was restored by both gadolinium and Splx. Furthermore, histopathological alterations induced by IR were also reversed. CONCLUSION: The extent of renal IR injury depends on the pro-inflammatory cytokine response. Gd pre-treatment decreases macrophage-derived cytokine secretion and thereby effectively limits the extent of renal IR injury in rats similar to Splx. Further studies needed to define an optimal way of decreasing macrophage-derived cytokine release due to the clinical limitations of Gd.

Biliary peritonitis due to "fallen" hydatid cyst after abdominal trauma.

Hepatic hydatid cysts may cause serious complications. Intraperitoneal rupture of hepatic hydatid cyst is rarely seen and the prognosis can be fatal. By experience, we know that it might be difficult to diagnose an unruptured cyst expulsed into the peritoneal cavity. In this report, we present the case of a 54-year-old man with an intraperitoneal cystic mass of 10 cm of diameter which had extruded out from the liver due to a blunt abdominal trauma.

Analysis of CC chemokine receptor 5 and 2 polymorphisms and renal transplant survival.

Chronic rejection is an immune process leading to graft failure. By regulating the trafficking of leukocytes, chemokines and chemokine receptors are thought to be one of the reasons causing acute renal rejection (ARE), which increases the possibility of chronic rejection and organ destruction. This study was designed to investigate, in the Turkish population, an association of chemokine receptor genetic variants, CCR2V641, CCR5-59029-A/G, CCR5-Delta32 and acute renal rejection after renal transplant surgery. We carried out our study in 85 Turkish renal transplant patients (45 men, 40 women; mean age 39 +/- 2 years) by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. We found no significant difference in the incidence of rejection among patients possessing or lacking CCR5-Delta32. For the groups with and without acute renal rejection, we found a significant difference between the groups in A and G allele distribution in both CCR2V641and CCR559029 gene variants (p = 0.003 and p = 0.003, respectively). According to our findings, the risk of acute rejection in renal transplantation may be associated with genetic variation in the chemokine receptor genes CCR5-59029 and CCR2V641 in Turkey, and studies on these gene polymorphisms could be an ideal target for future interventions intended to prevent renal transplant loss.

Prognostic parameters for the prediction of acute gangrenous cholecystitis.

BACKGROUND/PURPOSE: The aim of this study was to identify preoperative prognostic parameters for gangrenous cholecystitis to differentiate this subgroup of patients with acute cholecystitis in order to provide immediate surgical therapy. METHODS: The medical records of patients who had an emergency cholecystectomy with the diagnosis of acute cholecystitis between January 2002 and June 2005 were reviewed retrospectively. Univariate and multivariate analysis were performed on the data. RESULTS: Out of 203 individuals with the clinical diagnosis of acute cholecystitis, 21 (10.3%) patients had a histological diagnosis of gangrenous cholecystitis. Multivariate analysis demonstrated an independent association of male sex, diabetes mellitus and white blood cell (WBC) count with the development of acute gangrenous cholecystitis. CONCLUSIONS: The risk for gangrenous cholecystitis is increased in male patients who have diabetes and a greater WBC count than 14 900/mm(3). Urgent surgical intervention should be considered for these patients because of the high morbidity and mortality rate of the condition.

Serum free prostate-specific antigen and zinc levels in experimental acute pancreatitis.

Serum free prostate-specific antigen (fPSA) is the most useful tumor marker for prostatic cancer screening. However, recently, fPSA has also been detected in sera from patients with pancreatic diseases. In addition, it has been shown that zinc (Zn) concentration might change in both serum and tissues in pancreatic disease. In the present study, we measured serum concentrations of fPSA and Zn as possible markers and prognostic factors in an experimental acute-pancreatitis model. Twenty-five female Wistar albino rats were divided into two groups: the control group (n=10) and the experimental group (n=15). Acute pancreatitis was induced by injection of ethyl alcohol into the common biliary duct. The animals were sacrificed 24 h later to detect the concentrations of serum fPSA and Zn. fPSA values were detected to be significantly higher in the experimental group (p < 0.001). There was also a significant decrease in the serum Zn level of the acute-pancreatitis group (p < 0.001). In conclusion, these findings suggested that a combination of these parameters might represent a significant improvement on the diagnostic value of each of them separately and provide a powerful tool for differential diagnosis and prognosis in pancreatic diseases.

Serum paraoxonase (a high-density lipoprotein-associated lipophilic antioxidant) activity and lipid profile in experimental acute pancreatitis.

OBJECTIVE: This study was designed to determine the serum lipid profile and the activity of paraoxonase (PON1, the lipophilic antioxidant component of high-density lipoprotein [HDL]-cholesterol) in acute pancreatitis. METHODS: Acute pancreatitis was induced by injection of ethyl alcohol into the common biliary duct. Oxidative stress marker (malonyldialdehyde), lipid profile, and PON1 activity were determined in the serum. RESULTS: In the acute pancreatitis group, whereas the mean levels of total cholesterol, low-density lipoproteins, and malonyldialdehyde were significantly higher (P < 0.001 for each), HDL level and PON1 activity were found to be significantly lower (P < 0.001 for each). CONCLUSIONS: Our results suggest that an abnormal lipid profile and decreased PON1 activity may have a role in the pathogenesis of acute pancreatitis in which HDL-associated antioxidant defense is impaired.

Plasma leptin levels in rats with pancreatitis.

Diagnosis of pancreatitis is based on the determination of serum amylase and lipase levels. However, recent identification of specific leptin receptors in the pancreas suggests that this peptide may also play some roles in the modulation of pancreatic function. The objective of the present study was to investigate the relationship between serum leptin levels and pancreatitis. Thirty male Wistar rats were divided into 3 groups: the control group, acute pancreatitis group and chronic pancreatitis group. Pancreatitis was induced by injection of ethyl alcohol into the common biliary duct. A sham laparotomy was performed in the control group. Control and acute pancreatitis groups were sacrificed 24 hours later, and chronic pancreatitis group was sacrificed on postoperative day 7. Blood was taken by cardiac puncture for the determination of plasma leptin levels, and the pancreatic tissue was excised for histopathologic confirmation of pancreatitis. Plasma leptin rose significantly from the median of 0.78 +/- 0.12 ng/ml in the control group to 1.92 +/- 0.10 ng/ml and 1.86 +/- 0.13 ng/ml in acute and chronic pancreatitis groups, respectively (p < 0.001, for both). There was no significant difference in the plasma leptin levels between the acute pancreatitis group and the chronic pancreatitis group (p > 0.05). These findings confirm that leptin has a role in pancreas inflammation, and the inflamed tissue can be the source of local production of leptin.