Relevance of Flow Cytometric Auto-Crossmatch to the Post-transplant Course of Kidney Transplant Recipients.

INTRODUCTION: The crossmatch test is essential prior to kidney transplantation (tx) to confirm compatibility between the donor and the recipient. However, its results can be misleading due to "undetectable antibodies" in the recipient's serum. To establish if undetectable autoantibodies are responsible for a positive result, an auto-crossmatch test can be performed. In this study, we aim to determine the long-term prognostic value of auto-flow cytometric auto-crossmatch (FCXM) test on kidney survival in kidney tx recipients. MATERIALS AND METHODS: The primary outcome variable was reduced renal function. Secondary endpoints were incidence of biopsy-confirmed chronic antibody-mediated rejection (CAMR) and recurrent glomerulonephritis (GN). RESULTS: There were no differences regarding initial serum creatinine levels between the study and control groups (P = .441). Patients who had positive auto-B FCXM had a significantly reduced renal function compared with the control group (P = .016). Four patients developed biopsy-confirmed CAMR in the study group and 1 patient in the control group (P = .047). Five patients had biopsy-confirmed recurrent GN in the GN study group, and only 1 patient had recurrent GN in the GN control group (P = .026). DISCUSSION: Kidney transplant recipients with positive auto-FCXM test had significantly reduced renal function and a higher incidence of recurrent GN and CAMR compared with the control group. The findings of this study suggest a potential role of auto-antibody causing positive auto-FCXM test result, meanwhile increasing the risk of CAMR, recurrent GN, and new-onset diabetes after tx.

A Novel Biomarker for Post-Transplant Recurrent IgA Nephropathy.

BACKGROUND: The serum levels of galactose-deficient immunoglobulin (Ig)A1 (Gd-IgA1) represent the most promising candidate biomarker for IgA nephropathy (IgAN). The aim of this study was to evaluate the serum levels of Gd-IgA1 as a novel noninvasive biomarker for post-transplant IgAN recurrence. METHODS: Serum Gd-IgA1 levels of 18 patients with recurrent IgAN were compared with control renal transplant recipients (n = 23) with non-recurrent IgAN and control non-transplant IgAN patients (n = 44) and healthy relatives (n = 11). Serum Gd-IgA1 levels of patients were measured with the use of KM55 enzyme-linked immunosorbent assay (ELISA). The effects of serum Gd-IgA1 concentrations on IgAN recurrence, post-transplant events, and graft survival were evaluated. RESULTS: All recurrent IgAN patients presented with renal dysfunction (mean serum creatinine, 1.62 ± 0.39 mg/dL) and detectable proteinuria at the time of diagnosis. Serum Gd-IgA1 levels of recurrent IgAN patients (8735 ± 10854 ng/mL [log10: 3.71 ± 0.45]) were significantly higher than those of non-recurrent IgAN patients (4790 ± 6089 ng/µL [log10: 3.31 ± 0.64]) (P = .027). Serum Gd-IgA1 levels of non-transplant IgAN patients were significantly higher (8791 ± 8700 ng/µL [log10: 3.79 ± 0.36]) than those of non-recurrent IgAN patients (4790 ± 6089 ng/µL [log10: 3.31 ± 0.64]) and healthy relatives (2615 ± 1611 ng/µL [log10: 3.34 ± 0.27]) (P < .001 and P = .021, respectively). Receiver-operating characteristic curve analysis revealed that the area under the curve for recurrence of IgAN was 0.69 (0.53-0.85) for serum Gd-IgA1 (P = .038). Biopsy-confirmed allograft rejection rates were similar in the recurrent IgAN group [3 (17%)] compared with the non-recurrent IgAN [6 (26%)] group (P = .47). Graft failure rate was not also significantly different in the recurrent IgAN group [4 (22.2%)] compared with the non-recurrent IgAN group [2 (8.7%)] (P = .224). CONCLUSIONS: This novel lectin-independent Gd-IgA1 ELISA that can detect serum Gd-IgA1 in patients with recurrent IgAN can be used as a biomarker for diagnosis and activity assessment of post-transplant recurrent IgAN.

Contribution of fragmented QRS on myocardial perfusion imaging in the assessment of functionally significant coronary artery stenoses.

OBJECTIVE: The evaluation of the functional significance of coronary artery stenosis is of great clinical importance in patient management or for decisions concerning coronary intervention. Recently, fragmented QRS (fQRS) on electrocardiography (ECG) has been introduced as a predictor of myocardial scarring as well as myocardial ischaemia in coronary artery disease. We aimed to investigate any additive value of fQRS to myocardial perfusion SPECT in evaluating the functional significance of the intermediate degree of coronary stenosis. PATIENTS AND METHODS: Patients who were referred for myocardial perfusion imaging (MPI) to evaluate the functional significance of intermediate (40-70%) coronary artery stenosis were analyzed retrospectively; 102 patients were included in the study. ECG records were evaluated to detect fQRS. MPI was interpreted visually and semiquantitatively by two nuclear medicine physicians blinded to the electrocardiographic findings. Summed stress scores (SSS), summed rest scores and summed difference scores (SDS) were calculated according to the 17-segment model. RESULTS: The mean age of the patients was 62.56±9.5 years, and 64 were males (62.7%). Ischaemia was detected in 30 patients, and the frequency of fQRS was significantly higher in patients with ischaemia than in patients with normal perfusion (54.8% vs. 23.8%, respectively; p<0.001). Myocardial scarring was detected in 15 patients, 7 of whom had coexistent myocardial ischaemia. fQRS was positively correlated with the SSS (r=374, p=0.001), SDS (r=0.460, p=0.001) and summed motion score (r=0.228, p=0.024). fQRS was an independent predictor of myocardial ischemia in multivariate analyses (OR=11.181; CI=3.900-32.057; p<0.001). CONCLUSIONS: The presence of fQRS on ECG is associated with myocardial ischaemia in patients who had an intermediate degree of coronary stenosis.

The Effect of the iNOS Inhibitor S-Methylisothiourea and Hyperbaric Oxygen Treatment on Radiation Colitis in Rats.

INTRODUCTION: External radiotherapy is one of the main treatment modalities for a variety of malignancies. However, the lower gastrointestinal tract is sensitive to the ionizing radiation. Hyperbaric oxygen treatment (HOT) has been suggested as a viable treatment for refractory radiation colitis, but the effect of S-Methylisothiourea (SMT) in the radiation colitis have not reported. To investigate the effect of SMT, HOT and the combination of both in an acute radiation-induced enterocolitis model. METHODS: Sixty Sprague-Dawley rats were divided randomly into five equal groups. A single dose of gamma irradiation (25 Gy) was administered through the colorectal region to anesthetized rats. In the control group, we applied 2 ml of saline solution intraperitoneally for five days. In the HOT group, 100-per-cent oxygen at 2.5 atm pressure was applied for five days. In the SMT group, 10 mg/kg/day of SMT was applied intraperitoneally for five days. In the HOT+SMT group, HOT and SMT were both applied in the same dosages as in the preceding two groups. At the end of five days, the rats were sacrificed and colon samples were collected for histological grading. Blood samples were collected to test for : tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), IL-1ß, transforming growth factor-ß (TGF-ß) and intercellular adhesion molecule-1 (ICAM-1) mRNA. RESULTS: The TNF-α, IL-1ß, IL-10 and TGF-ß levels were reduced by SMT, HOT and HOT+SMT applications (p < 0.05). However ICAM-1 mRNA levels were not significantly lower (p:0.19). The microscopic scores differed significantly between the SMT, HOT and HOT+SMT groups and the control group. There was significant improvement histologically, especially in the HOT+SMT group. When we compared the weight of the rats before and after the study, weight loss was significantly lower in the SMT, HOT and HOT+SMT groups compared with the control group (p < 0.05). CONCLUSION: HOT and SMT together were significantly more effective in preventing weight loss and in reducing inflammation and the severity of colitis histology when compared with HOT and SMT separately.

Renal transplantation in a patient with chronic granulomatous disease: case report.

Chronic granulomatous disease (CGD) is a genetic disease caused by structural mutations in the enzyme NADPH oxidase that results in severe immunodeficiency. End-stage renal disease occurs in this patient population and is attributed to various factors, including infections, amyloidosis, and nephrotoxic anti-infective agents. In this report, we present our experience in transplantation for a patient with CGD complicated by isolated hepatic tuberculosis abscess. The course of the case demonstrates the absolute requirements for a multidisciplinary and compulsive approach before, during, and after transplantation. This case report also highlights the unexpectedly benign effects of immunosuppressive therapy in this patient population.

The novel benzimidazole derivative BRP-7 inhibits leukotriene biosynthesis in vitro and in vivo by targeting 5-lipoxygenase-activating protein (FLAP).

BACKGROUND AND PURPOSE: Leukotrienes (LTs) are inflammatory mediators produced via the 5-lipoxygenase (5-LOX) pathway and are linked to diverse disorders, including asthma, allergic rhinitis and cardiovascular diseases. We recently identified the benzimidazole derivative BRP-7 as chemotype for anti-LT agents by virtual screening targeting 5-LOX-activating protein (FLAP). Here, we aimed to reveal the in vitro and in vivo pharmacology of BRP-7 as an inhibitor of LT biosynthesis. EXPERIMENTAL APPROACH: We analysed LT formation and performed mechanistic studies in human neutrophils and monocytes, in human whole blood (HWB) and in cell-free assays. The effectiveness of BRP-7 in vivo was evaluated in rat carrageenan-induced pleurisy and mouse zymosan-induced peritonitis. KEY RESULTS: BRP-7 potently suppressed LT formation in neutrophils and monocytes and this was accompanied by impaired 5-LOX co-localization with FLAP. Neither the cellular viability nor the activity of 5-LOX in cell-free assays was affected by BRP-7, indicating that a functional FLAP is needed for BRP-7 to inhibit LTs, and FLAP bound to BRP-7 linked to a solid matrix. Compared with the FLAP inhibitor MK-886, BRP-7 did not significantly inhibit COX-1 or microsomal prostaglandin E2 synthase-1, implying the selectivity of BRP-7 for FLAP. Finally, BRP-7 was effective in HWB and impaired inflammation in vivo, in rat pleurisy and mouse peritonitis, along with reducing LT levels. CONCLUSIONS AND IMPLICATIONS: BRP-7 potently suppresses LT biosynthesis by interacting with FLAP and exhibits anti-inflammatory effectiveness in vivo, with promising potential for further development.

Clinico-electrophysiological findings and prognosis of Guillain-Barré syndrome--10 years' experience.

OBJECTIVE: To assess correlation between the prognosis and epidemiological, clinical, laboratory, electrophysiological findings in patients with Guillain-Barré syndrome (GBS). METHODS: We reviewed the medical records of 104 GBS patients who were hospitalized and followed up at our outpatient clinic during October 1997-November 2007. RESULTS: Guillain-Barré syndrome patients were followed up with a median period of 232 days. Full recovery or minor deficits were observed in 41% of patients in the first month, 71% in the third month, 86% in the sixth month and 92% in the first year. We found that there was a correlation between Medical Research Council (MRC) sum scores at admission, clinical subtypes, respiratory distress, interference pattern and prognosis. CONCLUSIONS: Demographic, clinical and electrophysiological findings of our GBS cases were highly similar to those of the previous reports. Two of our cases were presented with preceding tuberculosis infection, which was not reported before in the literature.

Is anterior oblique view alone in surgical position sufficient for preoperative sentinel lymph node mapping in breast cancer? A quantitative comparative analysis with conventional views.

PURPOSE: Since the anterior projection alone has several limitations in the conventional preoperative sentinel lymph node (SLN) mapping, multiple projections including anterior oblique (AO) view are preferred. There are many AO acquisition techniques described in the literature but none of them creates an image which fully reflects the surgical perspective. We aimed to compare the AO view in the surgical position with the conventional projections according to quantitative parameters. PATIENTS AND METHODS: Sixty female breast cancer patients entered the study. Two hours after the radiotracer injection, preoperative SLN mapping at anterior, lateral and 35 degrees AO projections in surgical position was performed. For each projection, mapping success rate (MSR), the mean number of SLNs, lymphatic channel visualization rate, image contrast and distance measurements between each SLN and between the SLNs and the injection site were recorded. RESULTS: The best MSR and image contrast for the first and the consecutive axillary SLNs were found at the AO projection. The longest distance between the injection site and the SLNs and between the two SLNs were observed at the AO views. Although the AO view gave the best results for intramammary SLNs the difference was not statistically significant from the anterior view. CONCLUSION: The 35 degrees AO view in the surgical position was superior to the anterior and lateral projections. Therefore, the simple 4-min AO view in the surgical position may entirely reflect the surgeon's perspective and could be used safely alone in the preoperative lymphatic mapping for breast cancer patients.

Bladder dysfunction in infants with primary vesicoureteric reflux.

There is growing evidence that bladder dysfunction is a negative prognostic factor for spontaneous resolution of vesicoureteric reflux (VUR). This study evaluated the prevalence of urodynamic abnormalities in infants with primary VUR who were referred over a 4-year period. The urodynamic evaluations and medical records of 54 infants with primary VUR (79 ureters with reflux) were reviewed prospectively. Urodynamic dysfunction was observed in 46.3% (n = 25) of infants with primary VUR; 35.2% (n = 19) had a low bladder capacity and 11.1% (n = 6) had a large bladder capacity. All infants with large bladder capacities also had high grade (IV - V) VUR. In conclusion, there was a close relationship between bladder dysfunction and primary VUR. For that reason, urodynamic testing of infants with primary VUR should be performed as part of routine clinical evaluations.

Reversible MRI findings of porphyric encephalopathy. A report of two cases.

We describe the magnetic resonance imaging (MRI) findings in two patients admitted to our institution with neuropsychiatric symptoms and severe abdominal pain diagnosed as acute intermittent porphyria (AIP). MRI revealed multiple lesions which regressed following treatment. We suggest reversible cerebral vasospasm underlies the MRI abnormalities and the cerebral symptoms in porphyria.