Safety Profile of the Concomitant Use of Atorvastatin and Cyclosporine in Renal Transplant Recipients.

Cyclosporine (CyA) and atorvastatin (AT) are often administered concomitantly to treat dyslipidemia in renal transplant recipients. However, CyA greatly increases the plasma concentration of AT; therefore, concomitant use might increase the frequency of statin-induced adverse effects. The aim of this study was to investigate whether concomitant use of CyA and AT increases intolerance of the latter agent in Japanese renal transplantation recipients. We performed a retrospective cohort analysis of renal transplant recipients aged 18 years and older who had concomitantly received AT and CyA, or tacrolimus (Tac) therapy. We defined statin intolerance as a decrease in dose or discontinuation of AT due to adverse effects. We evaluated the incidence of statin intolerance in concomitant therapy with CyA for 100 days after the initial administration of AT in comparison with Tac. A total of 144 renal transplant recipients who received AT and CyA, or Tac between January 2013 and December 2019 were included. There was no statistical difference in the incidence of statin intolerance in both the CyA (1.8%; 1/57 patients) and Tac (3.4%; 3/87 patients) groups. Concomitant use of CyA and AT might not increase the incidence of statin intolerance in Japanese renal transplant recipients.

Effects of postoperative dietary intake on functional recovery of patients undergoing cardiac surgery.

BACKGROUND AND AIM: Among elderly patients undergoing cardiac surgery, malnutrition is very common and related to muscle wasting known as sarcopenia. Cardiac surgery causes a further decline of nutritional status due to reduced dietary intake (DI); however, the impact of postoperative DI on functional recovery is unclear. METHODS AND RESULTS: We enrolled 250 consecutive patients undergoing cardiac surgery. Daily DI was measured between postoperative days 3 and 7. Patients were categorized as having sufficient or insufficient DI based on whether their DI met or was less than estimated total energy requirements. Functional capacity was measured using the 6-minute walking distance (6MWD) preoperatively and at discharge. Mean postoperative DI was 22.4 ± 3.0 kcal/kg/day, and postoperative DI was insufficient in 92 patients (36.8%). The prevalence of sarcopenia was not different by postoperative DI. Although there was no significant difference in preoperative 6MWD results (P = 0.65), the sufficient DI group had longer 6MWD at discharge than the insufficient DI group (P = 0.04). In multivariate regression analysis, preoperative poor nutritional status (ß = -0.29), duration of surgery (ß = -0.18), and postoperative DI (ß = 0.40) remained statistically significant predictors for improvement of 6MWD (P < 0.0001, adjusted R2 = 0.41). CONCLUSIONS: Postoperative DI was independently associated with functional recovery, but preoperative sarcopenia was not. Regardless of preoperative nutritional status or the presence of sarcopenia, aggressive nutritional intervention in the early stage after surgery helps support functional recovery.

Experience of Lymphangiography as a Therapeutic Tool for Lymphatic Leakage After Kidney Transplantation.

INTRODUCTION: Lymphatic leakage after kidney transplantation is a relatively frequent complication but sometimes resistant to treatment, and there is no fixed treatment algorithm. The effectiveness of therapeutic lymphangiography for postoperative lymphatic or chyle leakage has been reported, but few reports are available regarding patients who have undergone kidney transplantation. In this study, we report our experience with lymphangiography as a therapeutic tool for lymphatic leakage after kidney transplantation. PATIENTS AND METHODS: Intranodal lymphangiography for lymphatic leakage was performed in 4 patients (3 male, 1 female; age range, 38 to 70 years old) after living kidney transplantation at the Osaka City University Hospital in Japan. The amount of drainage before lymphangiography was 169 to 361 mL/day. The procedure for intranodal lymphangiography was as follows: the inguinal lymph node was punctured under ultrasound guidance, and the tip of the needle was instilled at the junction between the cortex and the hilum, after which Lipiodol was slowly and manually injected. RESULTS: Lymphangiography was technically successful in 3 out of the 4 patients. In all successful cases, the amount of drainage decreased and leakage finally stopped without additional therapy such as sclerotherapy or fenestration. In 2 cases, we were able to directly detect the leakage site using lymphangiography. The time between lymphangiography and leakage resolution ranged from 8 to 13 days. There were neither complications of lymphangiography nor recurrence of lymphatic leakage in the successful cases. CONCLUSIONS: Intranodal lymphangiography may be not only a diagnostic tool but also an effective, minimally-invasive, and safe method for treatment of lymphatic leakage resistant to drainage after kidney transplantation.

Insulin degludec overdose may lead to long-lasting hypoglycaemia through its markedly prolonged half-life.

BACKGROUND: Overdose of insulin often causes long-lasting severe hypoglycaemia. Insulin degludec has the longest duration of action among the available insulin products; thus, an overdose of insulin degludec can lead to long-lasting hypoglycaemia. In the present paper, we report the case of a woman with long-lasting hypoglycaemia attributable to insulin degludec overdose and markedly prolonged insulin degludec half-life. CASE REPORT: A 64-year-old woman with Type 2 diabetes receiving insulin therapy was taken to an emergency department because of disturbed consciousness 21 h after self-injection of 300 units of insulin degludec (4.34 units/kg). Her plasma glucose level was 2.3 mmol/l. She received repeated intravenous boluses of dextrose for 43 h with continuous intravenous dextrose infusion, but no improvement in long-lasting hypoglycaemia or consciousness was observed. Considering the possibility of adrenal insufficiency, intravenous dexamethasone was administered, and her plasma glucose levels subsequently remained above 5.5 mmol/l without intravenous dextrose boluses. She gradually regained consciousness. A total of 34 h after the overdose, her plasma immunoreactive insulin levels were markedly increased and then gradually declined over ~400 h. The insulin degludec half-life was 40.76 h. CONCLUSION: Although the reported half-life of insulin degludec in the body is ~25 h when administered in standard doses (0.4-0.8 units/kg), no study has investigated its half-life after overdose. In the present case, the half-life of insulin degludec was ~1.6 times longer than that observed with standard doses, probably leading to long-lasting hypoglycaemia. Physicians should be aware of the possibility of unexpected long-lasting severe hypoglycaemia resulting from insulin degludec overdose.

Clinical Experience of Late Conversion From Antimetabolites With Standard Exposure Calcineurin Inhibitors to Everolimus With Calcineurin Inhibitor Minimization in Stable Kidney Transplant Recipients With Good Renal Function.

INTRODUCTION: This study describes our clinical experience of late conversion from antimetabolites with standard exposure calcineurin inhibitors (CNIs) to everolimus with CNI minimization in stable kidney transplant recipients with good graft function. PATIENTS AND METHODS: A 1-year retrospective pilot study of 26 kidney recipients converted from antimetabolites with standard exposure CNIs to everolimus with CNI minimization was performed. The recipients enrolled in this study had normal or slightly impaired renal function defined as a serum creatinine value <2.0 mg/dL, and normal or slightly increased albuminuria defined as a urinary albumin excretion rate <100 mg/g creatinine. RESULTS: The median time from transplant to conversion was 39.5 months posttransplant (range, 3-275). Treatment with everolimus was stopped owing to adverse events in 11 patients (42.3%). In the analysis of the patients in whom everolimus was maintained, the mean estimated glomerular filtration rate (eGFR) significantly increased from 50.7 ± 11.9 mL/min/1.73 m(2) at baseline to 53.6 ± 13.9 mL/min/1.73 m(2) at 1 year after conversion. In the patients in whom everolimus was stopped during the observation period, there was no difference in eGFR between baseline and 1 year after conversion. CONCLUSIONS: This study demonstrated that, among the patients converted to everolimus at a late stage, there was no deterioration in renal function whether everolimus was maintained or stopped within 1 year after conversion.

Effects of Granulocyte and Monocyte Adsorptive Apheresis in Renal Transplantation Recipients With Concomitant Cytomegalovirus Infection.

BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMAA) is widely used as a treatment for active ulcerative colitis (UC) in Japan. Much attention has been paid to the possibility of GMAA for the treatment and control of cytomegalovirus (CMV) reactivation in patients with refractory UC and concomitant CMV infection. In this study, the effects of the combination of GMAA and antiviral therapy were examined in renal transplant recipients with concomitant CMV infection. METHODS: Combination therapy of GMAA and antiviral drugs was performed 9 times in 7 renal transplant recipients with concomitant CMV infection. Four of the cases were positive for CMV-IgG, and 3 were negative. The clinical presentation of CMV infection was viremia in 6 cases and disease (CMV retinitis) in 1 case. CMV infection was diagnosed by using an antigenemia assay (C7-HRP). GMAA session was performed once, and the duration of the session was 120 min. Immediately after the GMAA session, ganciclovir was administered at 5 mg/kg/body weight. CMV infection was monitored based on C7-HRP and CMV-DNA in the peripheral blood samples. RESULTS: All cases became negative for C7-HRP and CMV-DNA within 21 days (median, 14 days; range, 3-21 days) and 17 days (median, 6 days; range, 3-17 days), respectively, after starting the combination therapy. No side effects of GMAA were observed. CONCLUSIONS: This case series found that GMAA in combination with antiviral drugs may shorten the duration of treatment against CMV infection in renal transplant recipients. Further studies in a larger number of patients are required to confirm these results.

Investigation of urinary angiotensinogen in renal transplant recipients.

BACKGROUND: Recent studies have indicated that angiotensinogen (AGT) is also locally produced in the kidney and that urinary AGT is a marker of local renal renin-angiotensin system activation. Because urinary AGT levels are significantly higher in patients with chronic kidney disease (CKD) than in patients without CKD and correlate with urinary albumin and other levels, urinary AGT is increasingly recognized as a marker for CKD monitoring, prognosis, and treatment. In this study, we investigated urinary AGT levels in renal transplant recipients. METHODS: Among the patients who were treated as outpatients at the Department of Urology of Osaka City University Hospital from March 2012 to April 2013, 146 stable renal transplant recipients and 50 donors who gave informed consent were studied. Urinary AGT and creatinine (Cr) levels were measured. The urinary AGT-to-Cr ratio was calculated, and its correlation with clinical parameters was examined. RESULTS: The urinary AGT-to-Cr ratio of the renal transplant recipients was significantly higher than that of the renal transplant donors (P = .0143). Furthermore, the urinary AGT-to-Cr ratio had a significantly positive correlation with the urinary albumin-to-Cr ratio (ACR; r = 0.39, P < .0001), while on the other hand, it had a significantly negative correlation with estimated glomerular filtration rate (eGFR; r = -0.31, P = .0002). Multiple linear regression analysis of factors associated with eGFR showed that urinary AGT was a significant and independent factor after adjusting for age, sex, and ACR. CONCLUSIONS: Our results indicated that urinary AGT levels were elevated in renal transplant recipients. In addition, urinary AGT significantly correlated with renal function and degree of albuminuria.

Effects of conversion from a twice-daily tacrolimus to a once-daily tacrolimus on glucose metabolism in stable kidney transplant recipients.

INTRODUCTION: The adverse effects of tacrolimus are known to play major roles in new-onset diabetes after transplantation. The purpose of this study was to investigate the effects of conversion from a twice-daily tacrolimus (Tac-BID) to a once-daily tacrolimus (Tac-OD) on glucose metabolism in stable kidney transplant recipients. PATIENTS AND METHODS: Twenty-six patients were converted from Tac-BID to Tac-OD on a 1:1 mg basis and examined for its effects on glucose metabolism. Unless rejection or tacrolimus toxicity was suspected, we did not perform dose adjustments of Tac-OD or reconversion to Tac-BID until 4 weeks after conversion. Subsequent dose adjustments were allowed to maintain tacrolimus target trough concentration within the. Changes in clinical parameters were compared between baseline and 24 weeks after conversion. RESULTS: Conversion from Tac-BID to Tac-OD on a 1:1 mg basis resulted in a significant decrease in tacrolimus trough level at 4 weeks after conversion. Because dose adjustments were performed, the trough level did not differ significantly between baseline and 24 weeks after conversion. At 4 and 24 weeks after conversion, the homeostasis model assessment of pancreas ß-cell function (HOMA-ß) increased significantly. CONCLUSIONS: Although there was no change in tacrolimus trough level between baseline and 24 weeks after transplantation, HOMA-ß at 24 weeks after conversion was significantly higher than that at baseline. These results indicated that conversion from Tac-BID to Tac-OD may improve pancreas ß-cell function in kidney transplant recipients.

A retrospective analysis of 335 Japanese lung cancer patients who responded to initial gefitinib treatment.

BACKGROUND: Gefitinib treatment results in considerably better progression-free survival compared with that of platinum doublets in the first line treatment of nonsmall-cell lung cancer (NSCLC) carrying an activating epidermal growth factor receptor (EGFR) mutation. Some patients who respond to gefitinib have an overall survival (OS) of more than 5 years, whereas other initial responders do less well. Although there has been considerable effort made to elucidate the mechanisms of acquired resistance, there have only been a few studies that addressed the effect of clinical backgrounds and treatment histories on the survival of the patients who had responded to an EGFR-tyrosine kinase inhibitor (TKI). In this study, we especially focused on the clinical benefit of EGFR-TKI administration after progression. PATIENTS AND METHODS: We retrospectively analyzed consecutive patients with advanced NSCLC who were diagnosed before October 2010, treated with gefitinib after July 2002, and responded to it. The primary objective of this study was to evaluate how clinical backgrounds and treatment histories influence survival of the patients who respond to gefitinib. The secondary objectives were to evaluate the safety of long-term gefitinib use and to establish the optimal treatment sequence using a dynamic treatment regimen analysis (DTRA). RESULTS: A total of 335 patients were recruited. Twenty-eight (8.4%) patients survived more than 5 years. Sixty-five and 93 patients received gefitinib as rechallenge and beyond progressive disease (BPD), respectively. A statistically significant difference in OS was observed between the patients who underwent gefitinib rechallenge and those who did not rechallenge (median: 1272 days vs. 774 days; p < 0.001), a result supported by a DTRA. Patients treated with gefitinib BPD also showed a tendency of longer survival. CONCLUSIONS: Gefitinib rechallenge and BPD played a central role in long term survival of the patients who initially responded to gefitinib.

Glucose intolerance is associated with increased intimal-medial thickness of the carotid artery and increased pulse-wave velocity in renal transplant recipients.

BACKGROUND: Although new-onset diabetes after transplantation has been demonstrated to have a significant negative impact on allograft and patient survival, the role of glucose intolerance (impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT], as asymptomatic hyperglycemia and borderline diabetes, has not been identified in renal transplant recipients. METHODS: We enrolled 32 renal transplant recipients (at least 1 year after transplantation) without prior evidence of diabetes at our institution in this study. Transplant recipients were divided into 2 groups (normal glucose tolerance group and glucose intolerance group) according to the results of their oral glucose tolerance test with 75 g of glucose. Glucose intolerance included IFG, IGT, and IFG/IGT. Normal glucose tolerance was detected in 19 patients, and glucose intolerance in 13: had 6 IGT, 2 IFG, and 5 IGT/IFG. Bilateral brachial-ankle pulse-wave velocity (baPWV) and intimal-media thickness (IMT) measured as markers of atherosclerosis were compared between the 2 groups. Insulin resistance was estimated with the homeostasis model assessment of insulin resistance (HOMA-R), and pancreatic ß-cell function evaluated by the homeostasis model assessment of ß-cell function and insulinogenic index. RESULTS: The patients in the glucose intolerance group showed significantly greater baPWV and IMT than those in the normal glucose tolerance group. HOMA-R in the glucose intolerance patients was significantly higher than in the normal glucose tolerance patients. Linear regression analysis showed the increased IMT in the renal transplant recipients to be significantly correlated with HOMA-R. CONCLUSIONS: Renal transplant recipients with glucose intolerance had increased IMT and baPWV, suggesting that glucose intolerance in renal transplant recipients may induce atherosclerosis and that the rise in insulin resistance may contribute to the increased IMT in renal transplant recipients.

Insulin resistance and insulin secretion in renal transplant recipients with hepatitis C.

BACKGROUND: Several reports have suggested an association between hepatitis C virus (HCV) infection and new-onset diabetes after transplantation (NODAT). NODAT is a common complication after renal transplantation, and it has been associated with increased long-term morbidity and mortality. HCV-positive recipients may have abnormal glucose metabolism, even though NODAT has never been previously diagnosed. The aim of this study was to analyze the pathogenic factors responsible for glucose metabolism in a series of HCV-positive renal transplant recipients. METHODS: The study population comprised 16 renal transplant patients who received their grafts from deceased or living donors with anti-HCV antibodies. HCV-negative transplant recipients were individually matched with these HCV-positive recipients by year of transplantation, sex, age, serum creatinine levels, and type of calcineurin inhibitors. None of the patients had been diagnosed with diabetes. Insulin secretion and insulin resistance were determined by a 75-g oral glucose tolerance test (OGTT) and compared between the 2 groups. Categories of glucose tolerance were defined according to World Health Organization criteria. RESULTS: Glucose intolerance (impaired fasting glucose, impaired glucose tolerance, diabetes mellitus) as assessed by OGTT was detected in 7 of the HCV-positive recipients (43.8%) and 3 of the HCV-negative recipients. The homeostasis model assessment of insulin resistance was greater in the HCV-positive recipients than in the HCV-negative recipients. The homeostasis model assessment of ß-cell function was higher in the HCV-positive recipients than in the HCV-negative recipients. CONCLUSIONS: The frequency of glucose intolerance tended to be higher in HCV-positive recipients. Furthermore, insulin resistance was greater and insulin secretion higher in HCV-positive recipients, which indicated that the increase in insulin secretion compensated for insulin resistance observed in these patients. However, HCV-positive renal transplant recipients may ultimately develop NODAT as this compensation diminishes with time.

Conversion of stable kidney transplant recipients from a twice-daily prograf to a once-daily tacrolimus formulation: a short-term study on its effects on glucose metabolism.

BACKGROUND: The adverse effects of tacrolimus are known to play major roles in posttransplantation diabetes mellitus (PTDM). In the present study, we investigated the effects of conversion from a twice-daily (Tac BID) to a once-daily prolonged release of tacrolimus formulation (Tac OD) on glucose metabolism in stable kidney transplant recipients. PATIENTS AND METHODS: In this prospective study, 26 patients converted from Tac BID to the same milligram-milligram daily dose of Tac OD were examined for the effects on renal function, drug trough levels, and glucose metabolism over a 4-week period. RESULTS: Conversion from Tac BID to Tac OD on a 1:1 mg basis resulted in a significant decrease in tacrolimus trough levels, but no significant changes in renal function. At 4 weeks after conversion, a homeostasis model assessment of ß-cell function, and hemoglobin A1c (HbA1c) decreased significantly. CONCLUSIONS: This study demonstrated a significant reduction in tacrolimus trough levels after switching from Tac BID to Tac OD, which increased insulin secretion and decreased HbA1c, suggesting that it may decrease the frequency of PTDM among stable renal transplant recipients.

Excellent outcomes of ABO-incompatible kidney transplantation: a single-center experience.

INTRODUCTION: Due to the severe shortage of deceased donors in Japan, ABO-incompatible living donor kidney transplantation has been performed since the late 1980s. Excellent long-term outcomes have been achieved; the rates of graft survival among these patients are currently similar to those of recipients of ABO-compatible grafts. Our single-center experience describing the immunosuppressive protocols, complications, and grafts survivals is documented in this study. PATIENTS AND METHODS: Among 123 patients with end-stage renal disease who underwent living donor kidney transplantation between January 1999 and December 2010, 25 cases were ABO-incompatible grafts. All of these patients were followed until August 2011. Analyzing these patients, we focused on their immunosuppressive protocols, complications, and graft survivals. RESULTS: Patient and graft survival rates were 100%. One patient experienced antibody-mediated rejection and an intractable acute cellular rejection episode, 1 patient an antibody-mediated rejection, and 6 patients had acute cellular rejection episodes. However, there were no severe complications. CONCLUSION: Although ABO-incompatible kidney transplantation is a high-risk procedure, a short-term graft survival rate of 100% may be expected due to recent significant improvements in desensitization and recipient management.

Desensitization protocol in highly HLA-sensitized and ABO-incompatible high titer kidney transplantation.

BACKGROUND: A positive crossmatch indicates the presence of donor-specific alloantibodies and is associated with a graft loss rate of >80%; anti-ABO blood group antibodies develop in response to exposure to foreign blood groups, resulting in immediate graft loss. However, a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation has not yet been established. METHODS: We treated 6 patients with high (≥1:512) anti-A/B antibody titers and 2 highly HLA-sensitized patients. Our immunosuppression protocol was initiated 1 month before surgery and included mycophenolate mofetil (1 g/d) and/or low-dose steroid (methylprednisolone 8 mg/d). Two doses of the anti-CD20 antibody rituximab (150 mg/m(2)) were administered 2 weeks before and on the day of transplantation. We performed antibody removal with 6-12 sessions of plasmapheresis (plasma exchange or double-filtration plasmapheresis) before transplantation. Splenectomy was also performed on the day of transplantation. Postoperative immunosuppression followed the same regimen as ABO-compatible cases, in which calcineurin inhibitors were initiated 3 days before transplantation, combined with 2 doses of basiliximab. RESULTS: Of the 8 patients, 7 subsequently underwent successful living-donor kidney transplantation. Follow-up of our recipients showed that the patient and graft survival rates were 100%. Acute cellular rejection and antibody-mediated rejection episodes occurred in 1 of the 7 recipients. CONCLUSIONS: These findings suggest that our immunosuppression regimen consisting of rituximab infusions, splenectomy, plasmapheresis, and pharmacologic immunosuppression may prove to be effective as a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation.

Identification of thymidylate synthase as a potential therapeutic target for lung cancer.

BACKGROUND: Thymidylate synthase (TS), a key enzyme in the de novo synthesis of thymidine, is an important chemotherapeutic target for malignant tumours including lung cancer. Although inhibition of TS has an antiproliferative effect in cancer cells, the precise mechanism of this effect has remained unclear. METHODS: We examined the effects of TS inhibition with an RNA interference-based approach. The effect of TS depletion on the growth of lung cancer cells was examined using colorimetric assay and flow cytometry. RESULTS: Measurement of the enzymatic activity of TS in 30 human lung cancer cell lines revealed that such activity differs among tumour histotypes. Almost complete elimination of TS activity by RNA interference resulted in inhibition of cell proliferation in all tested cell lines, suggestive of a pivotal role for TS in cell proliferation independent of the original level of enzyme activity. The antiproliferative effect of TS depletion was accompanied by arrest of cells in S phase of the cell cycle and the induction of caspase-dependent apoptosis as well as by changes in the expression levels of cyclin E and c-Myc. Moreover, TS depletion induced downregulation of the antiapoptotic protein X-linked inhibitor of apoptosis (XIAP), and it seemed to activate the mitochondrial pathway of apoptosis. CONCLUSION: Our data provide insight into the biological relevance of TS as well as a basis for clinical development of TS-targeted therapy for lung cancer.

A Recurrent Epiphytotic of Guava Rust on Rose Apple, Syzygium jambos, in Hawaii.

A Neotropical rust of the Myrtaceae, Puccinia psidii Winter, was described from Psidium guajava L., or guava, in Brazil in 1884 (1). It was first discovered in Hawaii on potted Metrosideros polymorpha Gaud. on Oahu in April 2005 (2) with pathogenicity and identity established (3). It spread quickly, and by January 2006, severe outbreaks of this rust occurred statewide on new leaves of Syzygium jambos (L.) Alston, or rose apple. Rose apple, a native to South and Southeast Asia, was introduced to Hawaii in 1825 and is locally abundant to invasive from just above sea level to as high as 1,000 m in elevation in wet sites. Healthy, reddish green immature leaves on new twigs become deformed, yellow-red, and covered with masses of yellow urediniospores following infection. As the disease progresses, infected leaves are blackened and defoliate, with no functional leaves formed. Stem tips and branches are killed and the canopy becomes progressively smaller. Repeated mortality of juvenile leaves was observed to kill 8 to12 m tall trees in the Haiku area of Maui. Wind dispersal of urediniospores resulted in heavy infection of even small groups of S. jambos isolated by 1 km or more and billions of urediniospores covered the ground under diseased trees. On Hawaii, Maui, and Oahu, trees with many dead branches are becoming common with concerns about the fire hazard of these dead trees surrounded by dry grasses. At low humidity levels, or on more mature leaves characterized by soft expanded yellow-green tissue, fewer, mostly circular spots are formed that do not expand. S. jambos is an example of a highly vulnerable host in Hawaii and represents one of approximately 3,500 species of Myrtaceae outside the Neotropics growing in Australasia, Southeast Asia, the Pacific, and tropical Africa, which have evolved unexposed to P. psidii. Severely infected S. jambos plants have been the major source of spores in the environment, exposing many Myrtaceae hosts to P. psidii. The pathogenicity of P. psidii has been consistent among and within islands with S. jambos severely infected and M. polymorpha, Melaleuca quinquenervia, Rhodomyrtus tomentosa, Myrtus communis, and Eugenia species commonly infected. Other hosts such as S. cumini, S. malaccense, and Myriciaria cauliflora are also infected, although guava and Eucalyptus spp. are rarely infected. Strain differences within P. psidii are suspected (4). In the tropics, it is rare for mature trees to be killed by a foliar pathogen, but given the devastation of new growth, death of more S. jambos trees is likely. References: (1) T. A. Coutinho et al. Plant Dis. 82:819, 1998. (2) E. M. Killgore and R. A. Heu. New Pest Advisory No. 05-04. Hawaii Department of Agriculture, 2007. (3) J. Y. Uchida et al. Plant Dis. 90:524, 2006. (4) S. Zhong et al. Mol. Ecol. Res. 8:348. 2008.

Dose-ranging study of fluticasone furoate nasal spray for Japanese patients with perennial allergic rhinitis*.

BACKGROUND: This study was designed to evaluate the efficacy and safety of fluticasone furoate nasal spray (FFNS), a novel enhanced-affinity intranasal corticosteroid, in Japanese patients with perennial allergic rhinitis (PAR), and to determine the optimal dose. METHODS: In this phase II, multicenter, double-blind, randomized, placebo-controlled, parallel-group, dose-ranging study, 240 patients (aged >or= 16 years) received once-daily (od) treatment for 2 weeks with either FFNS 110 microg (n = 80), 220 microg (n = 81) or placebo (n = 79). Patients evaluated 3 nasal symptoms using a 4-point scale. Efficacy was assessed as the mean change from baseline in total nasal symptom score (TNSS). RESULTS: Treatment with FFNS resulted in a significantly greater decrease over the treatment period in the mean 3TNSS (sneezing, rhinorrhea, and nasal congestion; p < 0.001 each dose vs. placebo), compared with placebo. More patients receiving FFNS had a markedly or moderately improved impression of treatment than placebo recipients (48% and 49% for FFNS 110 micro and 220 microg, respectively, vs. 18% for placebo; p < 0.001). Nasal rhinoscopy findings revealed significant improvements in mucosal swelling of the inferior turbinate (110 microg: p = 0.004; 220 micro: p = 0.011) and amount of watery rhinorrhea (110 microg: p = 0.003; 220 microg: p < 0.001), compared with placebo. Both doses of FFNS were well tolerated. CONCLUSIONS: Both FFNS 110 microg and 220 microg od were effective in alleviating nasal symptoms in Japanese patients with PAR over the 2-week duration of this study. FFNS 110 microg od was selected as the optimal dose for further evaluation in phase III clinical trials.

A novel approach to successful ABO-incompatible high-titer renal transplantation.

BACKGROUND: Currently the long-term outcome among recipients of ABO-incompatible renal transplantations is excellent in Japan. However, previous reports have documented poor outcomes in patients with high (> 1:256) anti-A/B antibody titers pretreatment. The immunosuppressive protocol for ABO-incompatible high-titer renal transplantation has remained a medical challenge. METHODS: We treated 3 patients with high (> 1:512) anti-A/B antibody titers prior to ABO-incompatible renal transplantation. Our immunosuppressive protocol was initiated 1 month prior to surgery and included mycophenolate mofetil (1 g/d) and low-dose steroid (methylprednisolone [8 mg/d]). Two doses of the anti-CD20 antibody rituximab, (150 mg/m2) were administered 2 weeks before and on the day of transplantation. We performed antibody removal with 6 to 8 sessions of plasmapheresis (plasma exchange or double-filtration plasmapheresis) before transplantation. Splenectomy was also performed on the day of transplantation. Postoperative immunosuppression followed the same regimen as ABO-compatible cases, in which calcineurin inhibitors were initiated 3 days before transplantation combined with 2 doses of basiliximab. RESULT: With this protocol, the anti-A/B antibody was reduced to below 1:16 in all cases. All 3 patients underwent successful transplantation with a mean current serum creatinine of 1.32 mg/dL (range, 1.22-1.50 mg/dL). There were no episodes of antibody-mediated rejection. No serious complications or side effects were encountered. CONCLUSIONS: A preconditioning protocol consisting of rituximab infusions, splenectomy, plasmapheresis, and pharmacologic immunosuppression enabled ABO-incompatible renal transplantation in patients with high (> 1:512) anti-A/B antibody titer.

Anesthetic management for cesarean section in moyamoya disease: a report of five consecutive cases and a mini-review.

We report five consecutive cases of neuraxial anesthesia for cesarean section in women with moyamoya disease. Either epidural or combined spinal-epidural anesthesia was provided, with adequate sedation using intravenous diazepam and/or opioid(s). Hemodynamic stability and normocapnia were well maintained, except in one patient who exhibited transient hypertension and hypocapnia due to anxiety. None of the parturients suffered from neurological deficit in the intra- or postoperative period, although one patient complained of numbness in her fingers at the end of surgery, but she was not hypotensive or hypocapneic. The neonates were all in good health. The literature is reviewed on the anesthetic management for cesarean section in patients with moyamoya disease.

First Report of a Rust Disease on Ohia Caused by Puccinia psidii in Hawaii.

Several species of Metrosideros (Myrtaceae), referred to as ohia in Hawaii, are endemic trees that comprise as much as 80% of the native Hawaiian forests. For centuries, these trees have provided niches for many indigenous and endangered plants and animals and are treasured by Hawaiians for their beauty and role in folklore and legends. During April 2005, a cultivated ohia plant was diagnosed by the Agricultural Diagnostic Service Center at the University of Hawaii at Manoa as infected by a rust fungus. Rust pustules containing abundant urediniospores were observed on leaves, stems, and sepals, causing discolored spots and severe deformity of young leaves and growing tips. By July 2005, a similar rust disease was observed on other plants in the family Myrtaceae; namely Syzygium jambos (L.) Alston, Eugenia koolauensis Degener, E. reinwardtiana (Blume) DC, and Psidium guajava L. Microscopic examination of the uredinia and urediniospores showed that the rust was morphologically similar to Puccinia psidii, which is reported as the guava or eucalyptus rust in Florida and Central and South America (1,2). To confirm the identity of this fungus, DNA was extracted from urediniospores of two isolates collected from ohia plants, and their nuclear ribosomal internal transcribed spacer (ITS) was amplified with two universal primers, ITS4 and ITS5 (3). Sequences of the ITS region of these isolates from ohia were identical to the P. psidii isolates provided by A. Alfenas in Brazil and M. Rayachhetry in Florida. Koch's postulate of the isolates, obtained from ohia, was performed using 1 × 108 spores/ml of urediniospores suspension in distilled water. The suspension was sprayed onto 6-month-old ohia seedlings. These inoculated seedlings were placed in clear plastic chambers maintained at 100% relative humidity and 22°C with a combination of 10-h fluorescent light period and a 14-h dark period. After 48 h of incubation, the seedlings were removed from the chambers and transferred to a greenhouse where the ambient temperature ranged from 20 to 24°C. Rust pustules appeared after 1 to 2 weeks of incubation. Symptoms first appeared as tiny, bright yellow, powdery eruptions that developed into circular, uredinial pustules on the stem and foliage. These pustules later expanded, coalesced, and became necrotic, spreading over the entire leaf and stem surfaces, and then leaves and stems were deformed and tip dieback ensued. These symptoms were the same as those observed on the naturally infected cultivated ohia plant mentioned above. P. psidii is reported to be native to South and Central America that later spread to some Myrtaceous plants in the Caribbean countries (1). It has a very wide host range within the family Myrtaceae (2). To our knowledge, this is the first report of P. psidii in Hawaii. This rust disease may pose a formidable threat to Myrtaceous species that make up the native Hawaiian forests and are grown as ornamental plants or for the production of wood chips. References: (1) T. A. Coutinho et al. Plant Dis. 82:819. 1998. (2) M. B. Rayachhetry et al. Biol. Control 22:38. 2001. (3) T. J. White et al. Page 315 in: PCR Protocols. M. A. Innis et al., eds. 1990.