Apremilast to treat oral ulcers in Behçet syndrome.

Apremilast, an oral small molecule, is a phosphodiesterase 4 (PDE-4) blocker. It has been shown to be efficacious in managing psoriasis (PS) and psoriatic arthritis (PSA). In two controlled studies, it was also effective in controlling oral ulcers of Behçet syndrome (Bsy). The main side effects associated with apremilast are diarrhea, nausea and headaches. These are usually transient and apremilast requires almost no laboratory monitoring during its use. An important issue is whether apremilast will also be useful in other debilitating and life-threatening manifestations of Bsy, for which there is yet no negative or positive evidence. The experience with apremilast use in PS/PSA will surely be helpful in foreseeing and managing potential adverse events of apremilast use for any other indication in Bsy. On the other hand, the author does not consider the proposed similarities in disease mechanisms between PS/PSA and Bsy strong enough to guide us as to where and when to use apremilast in Bsy.

Serum and urine TNF-like weak inducer of apoptosis, monocyte chemoattractant protein-1 and neutrophil gelatinase-associated lipocalin as biomarkers of disease activity in patients with systemic lupus erythematosus.

OBJECTIVES: TNF-like weak inducer of apoptosis (TWEAK), monocyte chemoattractant protein-1 (MCP-1) and neutrophil gelatinase-associated lipocalin (NGAL) are proinflammatory cytokines/chemokines that are considered as potential biomarkers reflecting disease activity in systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of serum (s) and urine (u) levels of TWEAK, MCP-1 and NGAL with disease activity in both renal and extra-renal SLE. METHODS: Thirty active patients with SLE (15 renal and 15 extra-renal) were recruited. Thirty-one inactive patients with SLE (16 renal and 15 extra-renal), 14 patients with ANCA-associated vasculitis (AAV) all of whom had active renal involvement and 20 healthy volunteers were selected as control groups. Serum and urine levels of TWEAK, MCP-1 and NGAL were tested using ELISA. RESULTS: Serum and urine levels of TWEAK and NGAL were significantly higher in the active SLE group compared to the inactive SLE group (sTWEAK p = 0.005; uTWEAK p = 0.026; sNGAL p < 0.001; uNGAL p = 0.002), whilst no significant differences regarding serum and urine MCP-1 levels were observed (p = 0.189 and p = 0.106, respectively). uTWEAK (p = 0.237), sMCP-1 (p = 0.141), uMCP-1 (p = 0.206), sNGAL (p = 0.419) and uNGAL (p = 0.443) levels did not differ between patients with active renal and extra-renal SLE. Serum TWEAK was higher in patients with active renal SLE (p = 0.006). There were no differences between active renal SLE and active renal AAV. Levels of all biomarkers were correlated with the SLE Disease Activity Index. CONCLUSION: sTWEAK, uTWEAK, sNGAL and uNGAL are biomarkers showing disease activity in SLE. However, our results implicate that these biomarkers may not be specific for SLE, and can be elevated in patients with active renal involvement of AAV.

Predictive Value of Interleukin 2 and Interleukin 8 on Early Rejection in Living Related Kidney Transplant Recipients.

INTRODUCTION: Early diagnosis of rejection in kidney transplant (KTx) recipients is of paramount importance for long-term graft survival. Cytokines play an important role in rejection via activating T cells. Neutrophil accumulation in the graft indicates cell-mediated rejection. Cellular infiltration is mediated through chemoattractant factors. The aim of this study was to investigate the relationship between graft function and serum levels of interleukin 2 (IL-2) and interleukin 8 (IL-8) in KTx. METHOD: Sixty-five patients undergoing KTx were enrolled in the study. Serum samples of IL-2 and IL-8 were collected the day before the operation, on postoperative days 1 and 7 day, and during the first and third month after the onset of rejection. The enzyme-linked immunosorbent assay method was used to determine the IL-2 and IL-8 values. RESULTS: A total of 9 (13.8%) patients had rejection documented on biopsy samples. Fifty-six patients had stable graft function (SGF). IL-2 and IL-8 values before KTx of both the rejected and SGF patients were not statistically different. Univariate analysis revealed that IL-2 and IL-8 were correlated with rejection (P = .046, P = .015). IL-8 levels were higher in the rejection group compared to the SGF group on the seventh day and first month postoperatively (P = .023, P = .038). The rejection group maintained higher levels of IL-8 for 11 days (range: 7-30) compared to the SGF group (P = .002) and the IL-8 levels correlated with serum creatinine levels (r = 0.621, P = .001). IL-2 levels were higher in the rejection group on days 1 and 7 compared to the SGF group (P = .042, P = .031). IL-2 and IL-8 levels were correlated with low eGFR in the third month in the rejection group (r = 0.421, P = .037; r = 0.518, P = .008). CONCLUSION: Determining the cytokine levels in the early post-KTx period may be helpful in tailoring immunosuppressive regimens in patients with a risk of rejection.

Effects of Rituximab on Atherosclerotic Biomarkers in Kidney Transplant Recipients.

INTRODUCTION: Cardiovascular disease is the leading cause of mortality in kidney transplant recipients. Rituximab is widely used in kidney transplantation for a variety of situations, and rituximab may inhibit some cytokines and antibodies that may play an active role in the atherosclerotic process. The aim of the study was to evaluate the efficacy of rituximab on atherosclerosis biomarkers in kidney transplant recipients. METHODS: All patients, 18 years of age and older, who underwent kidney transplantation and received at least 1 dose of 375 mg/m2 rituximab were considered for participation in this study. The primary study endpoint was the development of cardiovascular diseases after rituximab therapy. The secondary endpoint was the onset of cytomegalovirus (CMV) disease or biopsy-confirmed BK virus nephropathy. In addition, comparison of atherosclerosis biomarkers was performed between study and control groups. RESULTS: There were no cardiovascular events observed during follow up. Only 8 patients in the study group suffered from CMV disease during follow up. Serum interleukin 10 levels were significantly higher in the rituximab group compared with the control group, although anti-oxidized low-density lipoprotein levels were lower in the rituximab group compared with the control group, though this did not achieve statistical significance. DISCUSSION: Rituximab treatment may increase the risk of CMV reactivation and decrease lymphocyte counts and interleukin 10 levels; however, significant decreases in all atherosclerotic-related biomarkers have not been shown in our study.

Panel Reactive Antibody Responses Against Influenza Vaccination in Kidney Transplant Recipients.

INTRODUCTION: Seasonal influenza is an important cause of morbidity and mortality in the post-transplant period; therefore, the influenza vaccination has been recommended for all kidney transplant recipients before the influenza season. However, at least theoretically, the introduction of antigens via vaccines may trigger rejection attacks by causing an antibody response. In this study, we examined the development of de novo panel reactive antibody (PRA) development against the influenza vaccine in kidney transplant recipients. MATERIALS AND METHODS: Overall, 41 kidney transplant recipients who received the influenza vaccination and 50 kidney transplant recipients (study group) who refused to receive the influenza vaccination (control group) were enrolled in the study. Following basal biochemistry examination, the inactivated trivalent influenza vaccine was administered intramuscularly. Panel reactive antibodies were screened in all patients before and after vaccination on days 30 and 180. The primary outcome variable was development of de novo panel reactive antibodies. RESULTS: One patient in the study group developed de novo class I and II PRA at 6 months after vaccination (P > .05), while no antibody development was noted in the control group. Graft dysfunction or biopsy-confirmed rejection was not observed during the follow-up period in both groups. CONCLUSION: The influenza vaccination is generally effective and safe in solid organ transplant recipients. The vaccination procedure has the potential to trigger antibody development and occurrence of rejection. Therefore, vaccinated kidney transplant recipients should be monitored more carefully with regard to PRA; if the graft deteriorates, a rapid transplant biopsy should be performed.

Association Between HLA Antibodies and Different Sensitization Events in Renal Transplant Candidates.

BACKGROUND: Human leukocyte antigen (HLA) allo-immunization is caused by various events such as blood transfusions, pregnancies, or organ transplantations, which can lead to sensitization. In this retrospective study, we evaluated different sensitization models and their effects on panel-reactive antibody (PRA) profiles of renal transplantation candidates. METHODS: Anti-HLA class I/II antibody screening tests were performed in 906 renal transplantation candidates with the use of a microbead-based assay (Luminex). RESULTS: Two hundred ninety-seven (32.8%) of the patients were determined as positive in terms of PRA, and 609 (67.2%) were negative. Sensitized and non-sensitized patients were compared separately in terms of each sensitization type. The anti-HLA class I, II, and I+II positivity rates in patients sensitized only by blood transfusion were 13.1%, 6.3%, and 14.1%, the rates with pregnancy sensitization were 35.5%, 29%, and 45.2%, and rates with previous transplantation sensitization were 15.6%, 34.4%, and 38.9%, respectively. Prevalence of PRA positivity was significantly higher in patients with previous pregnancy than with transplantation and transfusion (odds ratio, 1.003; 95% confidence interval, 0.441-2.281; P = .031). The risk of developing HLA class I antibodies was higher in pregnancies (P < .001), and the risk of developing anti-HLA class II antibodies was higher in patients who had undergone a previous transplantation (P < .001). The rate of developing HLA-B antibodies in patients sensitized by pregnancy were significantly higher compared with sensitization after transfusion (P = .015), as was the rate of developing HLA-DQ antibodies in patients sensitized by previous transplantation compared with sensitization through pregnancy (P = .042). CONCLUSIONS: In patients who are waiting for kidney transplantation, sensitization by pregnancy and transplantation have a significant impact on development of HLA class I and class II antibodies.

Comparison of Two Different Inhalation Anesthetics on Grafted Kidney Function in Patients Undergoing Renal Transplantation Surgery: Desflurane or Sevoflurane?

BACKGROUND: Anesthetic management of patients during renal transplantation is vitally important for ensuring proper functioning of kidneys that have undergone ischemia-reperfusion damage. The goal of this prospective study was to compare the effects of 2 different inhalation agents (sevoflurane and desflurane) on grafted kidney function in renal transplantation surgery. METHODS: Sixty-five patients who were scheduled for living donor renal transplantation were enrolled in the study. General anesthesia was performed on all patients. Thirty-five pairs of recipients and donors were anesthetized with sevoflurane (group S) and 30 pairs of recipients and donors were anesthetized with desflurane (group D). Each patient's demographic characteristics, immunologic and clinical data, and hemodynamic parameters were recorded. The estimated glomerular filtration rate was calculated in the preoperative period and on postoperative days 1 and 7. The blood samples were collected before the operation and on postoperative days 1 and 7 for measurement of serum creatinine, neutrophil gelatinase-associated lipocalin, and interleukin 18. RESULTS: There were no significant differences in demographic characteristics or immunologic data between group D and group S. Intraoperative heart rate and mean arterial blood pressure were the same between groups. Creatinine, estimated glomerular filtration rate, neutrophil gelatinase-associated lipocalin, and interleukin 18 values did not differ between groups (P > .05) in the preoperative period and postoperative days 1 and 7. CONCLUSIONS: Sevoflurane and desflurane had no adverse effects on grafted kidney functions according to short-term graft outcomes in patients undergoing living donor renal transplantation.

Tac-MMF Versus CsA-MMF/CsA-AZA-Based Regimens in Development of De Novo Complement-Binding Anti-HLA Antibodies After Kidney Transplantation.

BACKGROUND: Immunosuppressive regimens with tacrolimus or cyclosporine A (CsA) were compared for graft-related outcomes in conjunction with complement-binding de novo donor-specific antibodies (DSAs). METHODS: Non-sensitized adult patients without rejection episodes within 3 months after transplantation were screened for the presence of de novo DSAs and C1q binding. Clinical and biopsy data were retrospectively obtained. RESULTS: The analysis included 118 patients (68 tacrolimus, 50 CsA), with mean age and follow-up of 36.1 ± 11.4 and 7.2 ± 4.8 years, respectively. As compared with tacrolimus, the CsA group had higher rates of both class II DSAs and C1q-binding DSAs (20% vs 4.4%, P = .008, and 18% vs 0%, P = .003, respectively). Rates of chronic antibody-mediated rejection (cAMR), proteinuria >500 mg/g, and levels of creatinine both at last visits were also higher in the CsA group (20% vs 0%, P = .002, 30% vs 5.9%, P = .005, 1.67 ± 1.31 vs 1.18 ± 0.45 mg/dL, P = .019, respectively).Class II DSAs and C1q-binding class II DSAs were significantly correlated with the clinical outcomes (creatinine levels, proteinuria, and cAMR). CONCLUSIONS: Compared with tacrolimus, CsA appears to pose a higher risk for the development of de novo anti-HLA antibodies with C1q-binding properties and, consequently, adverse graft-related outcomes.

Influence of Proton Pump Inhibitors on Mycophenolic Acid Pharmacokinetics in Patients With Renal Transplantation and the Relationship With Cytochrome 2C19 Gene Polymorphism.

BACKGROUND: Most patients have serious digestive complications after renal transplantation. Therefore, it is important to protect gastrointestinal function to improve the survival rate of transplant patients. Proton pump inhibitors (PPIs) such as lansoprazole and rabeprazole are widely administered to renal transplant patients with mycophenolic acid (MPA) in the perioperative period. PPIs are metabolized by cytochrome (CYP) 2C19 enzymes. Mycophenolate sodium (MYF) and mycophenolate mofetil (MMF) have been used in immunosuppression. Clinically relevant drug-drug interactions have been described between immunosuppressive drugs. In the present study, we investigated the drug interaction between MPA and lansoparazole or rabeprazole and the impact of CYP2C19 polymorphisms on these drug interactions after renal transplantation. MATERIALS AND METHODS: A total of 125 renal transplant patients taking MPA derivatives between 2012 and 2016 were included in this study. The 125 patients were divided into 6 groups: MMF/tacrolimus/steroid together with lansoprazole or rabeprazole; MYF/tacrolimus/steroid together with lansoprazole or rabeprazole and without PPI. The single nucleotide polymorphisms of CYP2C19 were determined by the polymerase chain reaction-restriction fragment length polymorphism. Plasma concentrations of MPA were measured by cloned enzyme donor immunoassay. Clinical parameters such as incidence of delayed graft function and acute rejection, the rate of change of serum creatinine, toxicity, and gastrointestinal adverse effects were analyzed retrospectively. RESULTS: The mean concentrations of MPA in the MYF group were higher than those in the MMF group. The mean dose-adjusted blood concentration of MPA coadministered with lansoprazole was lower than that of MPA with rabeprazole or without PPI in MMF and MYF groups (P < .05). In patients with the CYP2C19*2/*2 genotype, the mean concentrations of MMF with lansoprazole were significantly lower than those with rabeprazole with MMF or without PPI (P < .05). Gastrointestinal side effects were significantly higher in MMF with lansoprazole group than in MYF with lansoprazole group (P < .05). However, no differences were found according to genotype distribution in all groups (P > .05). CONCLUSION: Polymorphisms in CYP2C19 are related to the metabolic oxidation of drugs to varying degrees. Both genetic and clinical factors in pharmacokinetics may help to make further progress toward individualized therapy to yield maximum efficacy with minimal side effects.

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.

Association of paraoxonase 1 (PON1) gene polymorphisms and concentration with essential hypertension.

Human serum paraoxonase 1 (PON1) is carried by high-density lipoprotein in blood circulation and is shown to be effective in preventing oxidized phospholipids carried by low-density lipoprotein particles, thus it acts as an antioxidant. Polymorphism in this gene has been investigated for many metabolic diseases, but it is not thought to be a genetic risk factor for essential hypertension. The aim of this study was to determine whether there was an association between PON1 gene polymorphisms and concentration with essential hypertension. The study population was comprised of 100 patients with essential hypertension and 100 healthy controls. One promoter region [C(-108)T] and two coding region (Q192R and L55M) polymorphisms in the PON1 gene were genotyped in individuals by using the TaqMan assay. Plasma PON1 concentration in all volunteers was also measured spectrophotometrically by the enzyme-linked immunosorbent assay method. The genotype and allele frequencies of the PON1 C(-108)T polymorphism showed significant differences between the essential hypertensive and control groups (CT vs. CC: p<0.001; T allele vs. C allele: p<0.001). There was no significant difference for the PON1 L55M polymorphism between the groups, while the heterozygote genotype of the PON1 Q192R polymorphism showed significant difference (p = 0.03). The PON1 concentration was also found to be significantly lower in hypertensive patients (p < 0.001). Decline in the level of PON1 gene may be one of the main factors in the development of essential hypertension, and the PON1 C(-108)T polymorphism may have a prognostic value in the patients with essential hypertension.

Comparative Analysis of Outcomes of Kidney Transplantation in Patients With AA Amyloidosis and Chronic Glomerulonephritis.

BACKGROUND: Amyloid A (AA) amyloidosis is a multisystemic, progressive, and severe disease. Renal involvement is a prominent feature of the disease, and the outcome of patients on dialysis is poor. We aimed to analyze the outcomes of kidney transplantation in patients with AA amyloidosis in comparison with chronic glomerulonephritis (CGN). METHODS: Charts of patients who underwent kidney transplantation between 1988 and 2012 were reviewed; 41 patients with AA amyloidosis were identified, and 41 age- and sex-matched control patients with chronic CGN were included. Baseline characteristics, immunosuppressive regimens, and transplantation-related outcomes were retrieved using a standardized form. RESULTS: The mean follow-up period was 70.9 ± 44.9 months. The 10-year patient survival was found to be significantly worse in the AA amyloidosis group (62.5%) compared to CGN group (100%) (P = .008). During the follow-up period, three of the 41 patients (9.7%) died of sepsis and one patient died of cardiac complications in the amyloidosis group, whereas there was no patients were lost in the CGN group. The first-year, fifth-year, and tenth-year mean graft survival rates, acute and chronic rejections, and mean creatinine levels at last visits were not significantly different between the groups. Proteinuria >1 g/d, cytomegalovirus and tuberculosis infections, and rhabdomyolysis were recorded at a significantly higher rate in patients with amyloidosis. CONCLUSION: As compared to patients with CGN, patients with AA amyloidosis had a lower patient survival; equal graft survival and rejection rates; and higher risks of developing proteinuria, cytomegalovirus and tuberculosis infections, and rhabdomyolysis.

A Deletion Mutation of the Connexin 26 (Gjb2) Gene in a Turkish Patient with Vohwinkel Syndrome .

Vohwinkel syndrome (VS), also known as keratoderma hereditaria mutilans, is a rare keratinization genetic disorder characterized by palmoplantar keratoderma, skeletal dysmorphisms and varying degrees of sensorineural deafness. Its mode of inheritance is autosomal-dominant, with mutations in loricrin and connexin 26 (GJB2) genes that manifest during infancy and boceme more evident during adulthood. We herein report a case of VS in a 23-year-old female exhibiting sensorineural hearing loss, palmar keratoderma and homozygous deletion mutation delE120 (c.358-360delGAG) in the GJB2 gene. VS, is a rare genetic disorder, should be considered in patients with palmoplantar keratoderma and hearing loss and should be investigated connexin 26 (GJB2) gene mutation.

The impact of intravascular ultrasound guidance during drug eluting stent implantation on angiographic outcomes.

OBJECTIVE: Major limitation for the use of stent in the treatment of coronary artery disease is development of stent restenosis. The impact of intravascular ultrasound (IVUS) guidance during drug eluting stent (DES) implantation is presently not yet well established. PATIENTS AND METHODS: For the present study, we included 30 patients who received DES with IVUS-guided stenting (Group A) and 30 patients receiving the DES without IVUS-guided stenting (Group B). The patients were evaluated for their ninth month control angiographies and were followed during two years for the development of relevant clinical events after the DES implantations. The angiographic and clinical results were compared between the groups. RESULTS: After the percutaneous intervention, the minimal luminal diameter and net acute gain were significantly increased in Group A in respect to Group B (3.3 ± 0.34 vs. 2.8 ± 0.33, p < 0.01). Moreover, the rate for performing post-dilatation following stent implantation was higher in Group A than in Group B (p = 0.01). By contrast, stent restenosis rates were similar between the groups (p > 0.3). CONCLUSIONS: The present results indicate that the use of IVUS for the implantation of DES can increase the success rate of the intervention. The IVUS guidance during DES implantation can be complementary percutaneous intervention, in particularly by detecting the situations that need for post-dilatation.

A new approach for cerumenolytic treatment in children: In vivo and in vitro study.

OBJECTIVES: To demonstrate the effects of various cerumenolytic solutions in vivo and in vitro and to measure the change in pain following treatment. METHODS: The study was done as a single-centre, prospective and double-blind study. Among 1243 paediatric patients with total or nearly total occlusive plug in 4 years period, those who accepted endoscopic ear examination and cleaning via aspiration after a follow-up period of at least 10 days following treatment were included in the study. Day of total TM visualisation was noted and removal co-efficient was calculated. The pre and post-treatment pain levels of the patients were assessed using analogue chromatic continuous scale (ACCS). In the in vitro part, cerumen samples collected at equal amounts from 20 patients were treated at 36-400°C in 6 different tubes with the same solutions and their dissolution degrees were assessed over a period of 5 days (Hour 6, Hour 12, Hour 48, Hour 72, Hour 92, Hour 120). Additionally, the degree of resolution in the tube treated with distilled water was considered to be the control reference. RESULTS: In the in vivo part of the study, total TM visualisation was observed in Group 1 at 50.2% (Day 3), in Group at 57.1%, in Group at 62.3%, in Group at 44.3% and in Group 5 at 73.5%. The group with the lowest removal co-efficient was Group 5 (removal co-efficient=1.623). In reference to the ACCS pain scores of the patients, the intra-group change pre-post treatment was found statistically significant for all groups (p=0.008; p=0.0222; p=0.005; p=0.026; p=0.018). After statistical analysis between the groups the difference between Group 5 and other groups was found statistically significant (p=0.002; p=0.026; p=0.044; p=0.034). In the in vitro part of the study, the best dissolution was observed in Group 2. CONCLUSIONS: In our study, the best cerumenolytic solutions were identified to be glycerine 10cc+3% hydrogen peroxide 10cc+10% sodium bicarbonate 10cc+distilled water 10cc. Especially the use of this mixture ease in terms of pain for the patient and in terms of time and comfort for the physician during the removal procedure.

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.

Relationship between hypoplastic right coronary artery and coronary artery anomalies.

OBJECTIVES: The frequency of hypoplastic right coronary artery (HRCA) and its contribution to coronary artery anomalies (CAAs) has not been thoroughly studied. Here we aimed to investigate whether a casual relationship exists between the presence of HRCA and CAAs. MATERIALS AND METHODS: We retrospectively reviewed coronary angiography records of 7500 patients. The images were carefully assessed for coronary artery (CA) anatomy and CAAs. Overall, we compared CAAs at the presence and absence of HRCA and evaluated potential association between HRCA and CAAs. Besides, we grouped HRCA patients according to the presence of CA disease (CAD) into two groups and compared their CAAs. RESULTS: While the percentage of HRCA was 6.2%, it was 3.34% for CAAs. The percentage of CA with anomalous origin (CAAO) at the presence of HRCA was significantly higher than the presence of normal right coronary artery (NRCA) (p < 0.01). Similarly, the percentage of absent left main coronary artery (ALMCA) was also considerable increased in HRCA patients with respect to the patients with NRCA (p < 0.01). The percentage of CAAO was notably higher in the CAD (-) than CAD (+) patients with HRCA (p < 0.01). Likewise, the prevalence of ALMCA was also noticeably higher in the CAD (-) than CAD (+) patients with HRCA (p < 0.01). CONCLUSIONS: HRCA is a clinically significant and frequently encountered congenital variation. The present observations indicate that the presence of HRCA is closely associated with a high prevalence of CAAO, particularly with increased rate of ALMCA.

Biological response on a titanium implant-grade surface functionalized with modular peptides.

Titanium (Ti) and its alloys are among the most successful implantable materials for dental and orthopedic applications. The combination of excellent mechanical and corrosion resistance properties makes them highly desirable as endosseous implants that can withstand a demanding biomechanical environment. Yet, the success of the implant depends on its osteointegration, which is modulated by the biological reactions occurring at the interface of the implant. A recent development for improving biological responses on the Ti-implant surface has been the realization that bifunctional peptides can impart material binding specificity not only because of their molecular recognition of the inorganic material surface, but also through their self-assembly and ease of biological conjugation properties. To assess peptide-based functionalization on bioactivity, the present authors generated a set of peptides for implant-grade Ti, using cell surface display methods. Out of 60 unique peptides selected by this method, two of the strongest titanium binding peptides, TiBP1 and TiBP2, were further characterized for molecular structure and adsorption properties. These two peptides demonstrated unique, but similar molecular conformations different from that of a weak binder peptide, TiBP60. Adsorption measurements on a Ti surface revealed that their disassociation constants were 15-fold less than TiBP60. Their flexible and modular use in biological surface functionalization were demonstrated by conjugating them with an integrin recognizing peptide motif, RGDS. The functionalization of the Ti surface by the selected peptides significantly enhanced the bioactivity of osteoblast and fibroblast cells on implant-grade materials.

Frequent oral ulceration during early disease may predict a severe disease course in males with Behçet's syndrome.

OBJECTIVES: The numbers and recurrence rates of mucocutaneous manifestations can be highly variable among patients with Behçet's syndrome (BS) but it is not known whether these differences influence the disease course at the long-term. METHODS: We evaluated the outcome of 30 patients that made up the placebo arm of a 6 months controlled trial of thalidomide and looked at the relation between the frequencies of mucocutaneous manifestations during the trial and the development of major organ involvement necessitating immunosuppressives during the post-trial period. RESULTS: Fifteen (50%) patients had received immunosuppresives for major organ involvement during the post-trial period. Patients receiving immunosuppressive treatment were significantly younger at the onset of BS compared to those who did not (24.5±5 vs. 29.7±3.8 SD years; p=0.003). The mean number of oral ulcers recorded throughout the trial was significantly higher among patients using immunosuppressives compared to those who did not (2.09±0.96 vs. 1.43±0.8; p=0.029). This significance disappeared when adjusted for age of onset of BS (p=0.16). ROC curve analysis showed that having 10 or more ulcers during 6 months has a sensitivity of 86.7% and a specificity of 53% for the subsequent necessity of immunosuppressive use. The same association was not true for genital ulcers, follicular lesions and erythema nodosum. CONCLUSIONS: These findings on a limited number of patients suggest that frequent occurrence of oral ulceration during the initial years of the disease may predict the development of major organ involvement in men with BS.