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1.
N-Chlorotaurine (NCT), a well-tolerated endogenous long-lived oxidant that can be applied topically as an antiseptic, was tested on its fungicidal activity against Scedosporium and Lomentospora, opportunistic fungi that cause severe infections with limited treatment options, mainly in immunocompromised patients. In quantitative killing assays, both hyphae and conidia of Scedosporium apiospermum, Scedosporium boydii, and Lomentospora prolificans (formerly Scedosporium prolificans) were killed by 55 mM (1.0%) NCT at pH 7.1 and 37°C, with a 1- to 4-log10 reduction in CFU after 4 h and a 4- to >6-log10 reduction after 24 h. The addition of ammonium chloride to NCT markedly increased this activity. LIVE/DEAD staining of conidia treated with 1.0% NCT for 0.5 to 3 h increased the permeability of the cell wall and membrane. Preincubation of the test fungi in 1.0% NCT for 10 to 60 min delayed the time to germination of conidia by 2 h to >12 h and reduced their germination rate by 10.0 to 100.0%. Larvae of Galleria mellonella infected with 1.0 × 107 conidia of S. apiospermum and S. boydii died at a rate of 90.0 to 100% after 8 to 12 days. The mortality rate was reduced to 20 to 50.0% if conidia were preincubated in 1.0% NCT for 0.5 h or if heat-inactivated conidia were used. Our study demonstrates the fungicidal activity of NCT against different Scedosporium and Lomentospora species. A postantifungal effect connected with a loss of virulence occurs after sublethal incubation times. The augmenting effect of ammonium chloride can be explained by the formation of monochloramine.  相似文献   

2.
Scedosporium prolificans is an opportunistic saprophytic fungus that rapidly disseminates and is intrinsically resistant to currently available antifungal drugs. We report a fatal case of disseminated S. prolificans infection that started with orbital and ocular involvement in a patient with secondary acute myeloblastic leukemia.  相似文献   

3.
ObjectiveTo describe the prevalence of and risk factors for renal infarction (RI) in patients with cardiac amyloidosis.Patients and MethodsWe evaluated 87 patients with cardiac amyloidosis who underwent renal technetium-99m-labeled dimercaptosuccinic acid scintigraphy in the Amyloidosis Referral Center of Henri-Mondor Hospital from October 1, 2015, through February 28, 2018.ResultsThree groups of patients were identified according to the underlying amyloidosis disorder: AL amyloidosis in 24 patients, mutated-transthyretin amyloidosis in 24 patients, and wild-type transthyretin amyloidosis in 39 patients. Patients with wild-type transthyretin amyloidosis were older (P<.001), more likely to be men (P=.02), to have arrhythmic heart diseases (P<.001), and to be receiving anticoagulation treatment (P<.001). Patients with AL amyloidosis had significantly higher N-terminal pro-B-type natriuretic peptide levels (P=.02) and were more likely to have nephrotic syndrome (P<.001). Renal infarction was detected in 18 patients (20.7%), at similar frequencies in the various groups. Baseline urinary protein to creatinine ratio was the only parameter for which a significant difference (P=.03) was found between patients with and without RI diagnoses. The likelihood of RI diagnosis was 47.1% (8 of 17) in the presence of AKI and 14.5% (10 of 69) in its absence (P=.003). Overall, heart transplant–censored patient survival did not differ significantly between patients with and without RI (P=.64), but death- and heart transplant–censored renal survival was significantly lower in patients with RI (P<.001).ConclusionOur study suggests that prevalence of RI in patients with cardiac amyloidosis is higher than previously thought, regardless of the underlying amyloidosis disorder. Acute kidney injury in a patient with cardiac amyloidosis should alert clinicians to the possibility of RI.  相似文献   

4.
Outbreaks of Pneumocystis pneumonia have been described in renal transplant recipients. Aerosolized pentamidine is frequently used for prophylaxis in this setting. We report our experience with aerosolized pentamidine use in 56 renal transplant recipients. We found high rates of adverse reactions in patients with chronic respiratory disease.  相似文献   

5.
Aim: Post-transplant diabetes mellitus (PTDM) is one of the main complications after kidney transplantation. It is known that leptin plays an important role in glucose metabolism and mutations in the leptin receptor gene (LEPR) are responsible for different complications in renal transplant recipients. We aimed to analyse the association of polymorphisms in LEPR with the development of PTDM in these patients.Methods: A total of 315 renal transplant recipients were genotyped for the Lys109Arg, Gln223Arg and Lys656Asn polymorphisms. The impact of these genetic variables together with other clinical and demographic parameters on PTDM risk was evaluated in a multivariate regression analysis.Results: The 223Arg variant showed a significant association with PTDM risk [OR = 3.26 (1.35–7.85), p = 0.009] after correcting for multiple testing. Carriers of this variant also showed higher BMI values (26.95 ± 4.23) than non-carriers (25.67 ± 4.43, p = 0.025). In addition, it was BMI at transplant and not the BMI increment in the first year after grafting that was associated with PTDM (p > 0.00001). Haplotype analyses did not reveal significant associations.Conclusions: Our result show, for the first time to our knowledge, that genetic variability in the LEPR may contribute significantly to the risk for PTDM in renal transplant recipients.

KEY MESSAGES

  • The LEPR Gln223Arg polymorphism significantly contributes to the development of PTDM in renal transplant recipients.
  • The effect of the 223Arg variant on PTDM is strongly modulated by the age of the recipient.
  • The 223Arg variant in the leptin receptor is related to higher BMI in renal transplant recipients.
  相似文献   

6.
An automated method for the assay of N-acetyl-β-glucosaminidase in human urine is described and a normal range of urinary N-acetyl-β-glucosaminidase activity is reported. The automated method has been used routinely over a twelve month period in two London hospitals for monitoring the excretion of N-acetyl-β-glucosaminidase in renal transplant patients. The abnormal elevation of urinary N-acetyl-β-glucosaminidase provides an early warning of rejection by indicating the presence of renal parenchymal damage. The automated assay of urinary N-acetyl-β-glucosaminidase may also be used in screening for the presence of renal disease.  相似文献   

7.
Urinary β-galactosidase, β-glucuronidase and N-acetyl-β-glucosaminidase were measured in patients with renal allotransplants and compared with normal controls. Increased excretion of all three enzymes was noted in the transplant patients resulting possibly from mild chronic rejection.A second part of the investigation correlated renal function with daily N-acetyl-β-glucosaminidase excretion by the patients. In acute rejection, enzyme levels rose sharply from a baseline then decreased following successful treatment. With cadaveric grafts and initially good urinary flow, N-acetyl-β-glucosaminidase levels were high and decreased as creatinine clearance improved; however, with initial oliguria, levels were low and rose as diuresis began then decreased to a baseline. This was attributed to a washing out of enzyme released during the unavoidable ischemic period involved in handling cadaver kidneys.Because it reflects physiological changes in the kidney, daily monitoring of urinary N-acetyl-β-glucosaminidase should be helpful in the diagnosis of renal damage caused by rejection and ischemia.  相似文献   

8.
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10.

Introduction

Data on pulmonary complications in renal transplant recipients are scarce. The aim of this study was to evaluate acute respiratory failure (ARF) in renal transplant recipients.

Methods

We conducted a retrospective observational study in nine transplant centers of consecutive kidney transplant recipients admitted to the intensive care unit (ICU) for ARF from 2000 to 2008.

Results

Of 6,819 kidney transplant recipients, 452 (6.6%) required ICU admission, including 200 admitted for ARF. Fifteen (7.5%) of these patients had combined kidney-pancreas transplantations. The most common causes of ARF were bacterial pneumonia (35.5%), cardiogenic pulmonary edema (24.5%) and extrapulmonary acute respiratory distress syndrome (ARDS) (15.5%). Pneumocystis pneumonia occurred in 11.5% of patients. Mechanical ventilation was used in 93 patients (46.5%), vasopressors were used in 82 patients (41%) and dialysis was administered in 104 patients (52%). Both the in-hospital and 90-day mortality rates were 22.5%. Among the 155 day 90 survivors, 115 patients (74.2%) were dialysis-free, including 75 patients (65.2%) who recovered prior renal function. Factors independently associated with in-hospital mortality were shock at admission (odds ratio (OR) 8.70, 95% confidence interval (95% CI) 3.25 to 23.29), opportunistic fungal infection (OR 7.08, 95% CI 2.32 to 21.60) and bacterial infection (OR 2.53, 95% CI 1.07 to 5.96). Five factors were independently associated with day 90 dialysis-free survival: renal Sequential Organ Failure Assessment (SOFA) score on day 1 (OR 0.68/SOFA point, 95% CI 0.52 to 0.88), bacterial infection (OR 0.43, 95% CI 0.21 to 0.90), three or four quadrants involved on chest X-ray (OR 0.44, 95% CI 0.21 to 0.91), time from hospital to ICU admission (OR 0.98/day, 95% CI 0.95 to 0.99) and oxygen flow at admission (OR 0.93/liter, 95% CI 0.86 to 0.99).

Conclusions

In kidney transplant recipients, ARF is associated with high mortality and graft loss rates. Increased Pneumocystis and bacterial prophylaxis might improve these outcomes. Early ICU admission might prevent graft loss.  相似文献   

11.

Introduction

Continuous erythropoietin receptor activator (C.E.R.A.) effectively enables anemia control in patients with chronic kidney disease, but little information is available in renal transplant recipients. The authors aimed to evaluate the effect of C.E.R.A. under clinical practice conditions on anemia control in renal transplant recipients.

Methods

This was a multicenter, retrospective, observational study carried out in adult renal transplant patients in the immediate posttransplant period and at late posttransplant period receiving C.E.R.A. in clinical practice. Patients?? data were retrieved from their medical charts at baseline and months 1, 3, and 6.

Results

A total of 318 evaluable patients were enrolled into the study: 32 in the immediate posttransplant period and 286 at late posttransplant period (erythropoiesisstimulating agent [ESA]-na?ve, n = 44; converting from other ESAs, n = 242). Patients in the immediate posttransplant period experienced a significant increase in hemoglobin (Hb) levels from baseline to month 1 (9.9±1.5 g/dL vs. 11.5±1.4 g/dL; P< 0.001). ESA-na?ve patients showed increasing mean Hb levels from baseline to month 6 (10.1±0.7 g/dL vs. 11.7±1.0 g/dL; P < 0.001) and 94.7% achieved Hb ??11 g/dL during the study. In patients converted from other ESAs, the percentage of patients with Hb between 11?C13 g/dL was maintained from baseline to month 6 with no significant differences (61.0% vs. 62.4%). Mean monthly doses of C.E.R.A. at baseline were 134.4±56.4 ??g, 81.3±28.1 ??g, and 93.0±44.2 ??g in immediate posttransplant, ESA-na?ve, and converted patients, respectively. C.E.R.A. was well tolerated.

Conclusion

C.E.R.A. enables anemia control in renal transplant recipients, allowing target Hb levels to be achieved and maintained with doses even below those described in the Summary of Product Characteristics.  相似文献   

12.
After transplantation, over a widely variable time course, the cortex of the transplanted kidney becomes stiffer as interstitial fibrosis develops and renal function declines. Elasticity ultrasound imaging (EUI) has been used to assess biomechanical properties of tissue that change in hardness as a result of pathologic damage. We prospectively assessed the hardness of the renal cortex in renal transplant allograft patients using a normalized ultrasound strain procedure measuring quasi-static deformation, which was correlated with the grade of renal cortical fibrosis. To determine cortical strain, we used 2-D speckle-tracking software (EchoInsight, Epsilon Imaging, Ann Arbor, MI, USA) to perform offline analysis of stored ultrasound loops capturing deformation of renal cortex and its adjacent soft tissue produced by pressure applied using the scanning transducer. Normalized strain is defined as the mean developed strain in the renal cortex divided by the overall mean strain measured in the soft tissues from the abdominal wall to pelvic muscles. Using the Banff scoring criteria for renal cortical fibrosis as the gold standard, we classified 20 renal transplant allograft biopsy tissue samples into two groups: group 1 (n = 10) with mild (<25%) renal cortical fibrosis and group 2 (n = 10) with moderate (26%–50%) renal cortical fibrosis. An unpaired two-tailed t-test was used to determine the statistical difference in strains between patients with mild and those with moderate renal cortical fibrosis. Receiver operating characteristic curve analysis was performed to assess the accuracy of developed strain and normalized strain in predicting moderate renal cortical fibrosis. The reference strain did not significantly differ between the two groups (p = 0.10). However, the developed renal cortical strain in group 1 with mild fibrosis was higher than that in group 2 with moderate fibrosis (p = 0.025). The normalized strain in group 1 was also higher than that in group 2 (p = 0.0014). The areas under receiver operating characteristic curves for developed strain and normalized strain were 0.78 and 0.95, respectively. The optimal cutoff for distinguishing moderate renal cortical fibrosis was −0.08 for developed strain (sensitivity = 0.50, specificity = 1.0) and 2.5 for normalized strain (sensitivity = 0.80, specificity = 1.0). In summary, renal cortex strain is strongly correlated with grade of renal cortical fibrosis. Normalized strain is superior to developed strain in distinguishing moderate from mild renal cortical fibrosis. We conclude that free-hand real-time strain EUI may be useful in assessing the progression of cortical fibrosis in renal transplant allografts. Further prospective study using this method is warranted.  相似文献   

13.
Tumor cells with donor genotype have been identified in human skin cancer after allogeneic transplantation; however, the donor contribution to the malignant epithelium has not been established. Kidney transplant recipients have an increased risk of invasive skin squamous cell carcinoma (SCC), which is associated with accumulation of the tumor suppressor p53 and TP53 mutations. In 21 skin SCCs from kidney transplant recipients, we systematically assessed p53 expression and donor/recipient origin in laser-microdissected p53+ tumor cells. In one patient, molecular analyses demonstrated that skin tumor cells had the donor genotype and harbored a TP53 mutation in codon 175. In a kidney graft biopsy performed 7 years before the skin SCC diagnosis, we found p53+ cells in the renal tubules. We identified the same TP53 mutation in these p53+ epithelial cells from the kidney transplant. These findings provide evidence for a donor epithelial cell contribution to the malignant skin epithelium in the recipient in the setting of allogeneic kidney transplantation. This finding has theoretical implications for cancer initiation and progression and clinical implications in the context of prolonged immunosuppression and longer survival of kidney transplant patients.  相似文献   

14.
Objective: Two-hundred thirty-two stable renal transplant outpatients were studied to identify the most useful colour flow Doppler ultrasound indices defining graft function in the long-term follow-up. Method: Renal artery mean velocity (Vm), renal blood flow (RBF), and resistance index (RI) on the renal and interlobar arteries were measured by the same operator. Results: Vm and RBF averaged respectively 42.1 ± 18.4 cm/s and 321 ± 95 ml/min in 85 patients with normal creatinine levels ( < 105 μmol/l). RBF significantly decreased in patients with plasma creatinine > 105 μmol/l (P < 0.0001). An inverse correlation with the degree of renal impairment, measured by plasma creatinine levels, was shown by RBF (r = 0.73) and Vm (r = 0.69). RI increased along with the reduction of renal function (interlobar artery: r = 0.63 and renal artery: r = 0.57). Conclusions: Vm, RBF and interlobar RI appear to be sensitive parameters to describe the hemodynamical status of the graft. The hemodynamical status appears to be influenced by the graft function. RBF appears the most useful index to evaluate the blood supply in the transplanted kidney.  相似文献   

15.
Question I have a 30-year-old patient who had a kidney transplant 2 years ago. She is now planning a pregnancy. She has been treated with tacrolimus since her transplant. Will it be safe for the fetus if she continues to take it during the pregnancy or should she switch to a different antirejection medication?Answer If your patient is stable while taking tacrolimus, there is no reason to switch. The current available information does not suggest that tacrolimus increases the risk of major congenital malformations above the baseline risk in the general population. Premature birth and low birth weight are often reported in this population; however, these effects are frequently reported in pregnant transplant patients treated with other immunosuppressant agents and probably reflect the effects of the maternal condition. As there are some reports of hyperkalemia and renal impairment in infants exposed to tacrolimus in utero, kidney function and electrolytes should be monitored in exposed neonates.  相似文献   

16.
Cupriavidus gilardii is a rare cause of human infection. We report a muscular abscess on the right thigh caused by this organism in a renal transplant recipient, who had suffered a septic shock associated with an extensive cellulitis caused by Streptococcus pyogenes. The patient was successfully treated with surgical drainage and intravenous ciprofloxacin for 13 days. This is the first time that C. gilardii is isolated from a human abscess. C. gilardii should be considered as a cause of human infection, especially in immunocompromised patients. Infection caused by this organism may be underdiagnosed because the identification is very difficult.  相似文献   

17.
Wallace MA 《AORN journal》2003,77(5):945-958
Dialysis and transplantation bring new hope and life to thousands of patients with end-stage renal disease. Renal transplantation restores reasonably normal health to patients whose kidneys no longer function and frees them from the limitations imposed by dialysis. Improved graft survival rates have further enhanced the desirability of transplantation. Currently in the United States, more than 80,000 people are living with a functioning renal transplant. The introduction of laparoscopic and laparoscopy-assisted techniques has proven to be a major improvement to living donation. This less invasive method of donating a kidney has more than doubled the chance that a patient with kidney failure will receive a transplant from a friend or loved one. New immunosuppressant medications, improved success rates, and the proliferation of transplantation centers have made renal transplantation a viable choice for many patients. The future will be dependent upon a marked increase in organ donation, which in turn will bring about earlier transplantation for patients with end-stage organ failure. AORN J 77 (May 2003) 946-966.  相似文献   

18.
Three thermotolerant “Absidia-like” isolates with unique morphologic characteristics, recovered from nasopharyngeal swab of a liver transplant recipient, gastric biopsy of a renal transplant recipient, and skin biopsy of a man with burn, respectively, were characterized. Microscopic examination showed nonseptate hyphae with highly branched sporangiophores. Uniquely, most side branches were circinate, and abundant pleomorphic giant cells with fingerlike projections were observed, characteristics absent from other Absidia/Lichtheimia spp. ITS1-5.8S–ITS2 rRNA gene cluster, partial EF1α gene, and partial β-actin gene sequencing showed that the 3 strains formed a distinct cluster, most closely related to, but distinct from, Lichtheimia corymbifera, Lichtheimia blakesleeana, and Lichtheimia hyalospora. Based on the morphologic and genotypic characteristics, we propose a new species, Lichtheimia hongkongensis sp. nov., to describe this fungus, which caused rhinocerebral, gastrointestinal, and cutaneous mucormycosis, respectively, in 3 patients. A significant proportion of L. corymbifera associated with mucormycosis reported may be L. hongkongensis.  相似文献   

19.
Polymyxins are old antimicrobials, discontinued for many years because of nephrotoxicity and neurotoxicity reports and reintroduced recently due to the increasing frequency of multiresistant Gram-negative bacterial infections. There are very few data related to toxicity and efficacy from transplanted patients, the major subjects of this study. All solid-organ-transplanted patients from our institution during January 2001 to December 2007 who used polymyxins were retrospectively assessed for nephrotoxicity and treatment efficacy. Microbiological and clinical cure rates were 100% and 77.2%, respectively. Only transplant patients subjected to at least 72 h of intravenous polymyxin were entered in the study. Overall, 92 transplant patients were included, and the nephrotoxicity rate was 32.6%. Multivariate analysis showed a statistically significant association between duration of polymyxin treatment (P = 0.037; odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00 to 1.12) and significant renal dysfunction. Polymyxin use is associated with very high rates of significant decrease in renal function; therefore, polymyxin must be used only when no other option is available and for as briefly as possible in the solid organ transplant setting.  相似文献   

20.
OBJECTIVE: To identify single nucleotide polymorphisms (SNPs) associated with risk of developing chronic kidney disease (CKD), a prevalent comorbidity, after liver transplant (LT).PATIENTS AND METHODS: This study consists of a cohort of adult (≥18 years) primary-LT recipients who had normal renal function before LT and who survived 1 year or more after LT at a high-volume US LT program between January 1, 1990, and December 31, 2000. Patients with adequate renal function (estimated glomerular filtration rate, ≥40 mL/min per 1.73 m2 during follow-up; n=308) and patients with incident CKD (estimated glomerular filtration rate, <40 mL/min per 1.73 m2 after LT; n=92) were identified. To investigate the association of 6 candidate genes with post-LT CKD, we selected SNPs that have been associated with renal function in the literature. Hazard ratios were estimated using Cox regression, adjusted for potential confounding variables.RESULTS: The variant allele (298Asp) of the Glu298Asp SNP in the endothelial nitric oxide synthase gene (NOS3) was significantly associated with CKD after LT (P=.05; adjusted for multiple comparisons). The 5-year incidence of CKD was 70% among patients homozygous for the NOS3 variant allele (298Asp) compared with 42% among those not homozygous for the NOS3 variant allele. Specifically, homozygosity for the NOS3 variant allele conferred a 2.5-fold increased risk of developing CKD after LT (P=.005, adjusted for confounding variables).CONCLUSION: Homozygosity for the variant allele of NOS3 (298Asp) is associated with CKD after LT and may be useful for identifying recipients at higher risk of post-LT CKD.BMI = body mass index; CI = confidence interval; CKD = chronic kidney disease; CNI = calcineurin inhibitor; eGFR = estimated glomerular filtration rate; eNOS = endothelial nitric oxide synthase; GFR = glomerular filtration rate; HR = hazard ratio; LT = liver transplant; NO = nitric oxide; PCR = polymerase chain reaction; SNP = single nucleotide polymorphismLiver transplant (LT) is a widely accepted therapy for patients with end-stage liver disease and is an established means of restoring health in these patients by extending survival and improving quality of life. However, there remain opportunities to continue to optimize outcomes of LT. Although effective immunosuppression is critical for graft survival after transplant, prolonged exposure of transplant recipients to these immunosuppressive agents can contribute to the development of long-term medical complications.1-3 Chronic kidney disease (CKD) is a notable example and is increasingly recognized in long-term survivors of LT.4 Up to 18% of LT recipients develop renal failure within 5 years after LT, and those who develop CKD that requires dialysis support have a very poor survival (27% at 6 years).5,6Renal failure is a complex disorder with both genetic and environmental components. A unique environmental risk factor for renal failure in LT recipients is prolonged exposure to calcineurin-based immunotherapies (the calcineurin inhibitors [CNIs] cyclosporine and tacrolimus). These drugs produce intense vasoconstriction of afferent and efferent glomerular arterioles, reducing renal blood flow and glomerular filtration rate (GFR). The exact mechanism of vasoconstriction is unclear, but there appears to be substantial impairment of endothelial cell function, leading to reduced production of vasodilators (such as nitric oxide [NO]) and enhanced release of vasoconstrictors (endothelin and thromboxane).7,8 Additionally, transforming growth factor beta-1, endothelin-1, and reactive oxygen and nitrogen species may contribute.9-11Although some reduction in renal function is common among LT recipients, some maintain intact renal function many years after LT. Thus, there is variability in the degree of individual susceptibility to CKD after LT that may not be fully explained by environmental or treatment-related factors. We hypothesize that genetic predisposition plays a role in an individual''s susceptibility to CNI-induced CKD. Previously published reports in nontransplant populations have suggested a relationship between vasomodulatory factors, CKD, and genetic variation occurring in the form of single nucleotide polymorphisms (SNPs) in the following vasomotor pathways: NO (gene symbol, NOS3), endothelin (gene symbol, EDN1), kinin (gene symbol, BDKRB1), angiotensin (gene symbol, AGTR1), adrenergic system (gene symbol, ADRB2), and transforming growth factor, beta-1 (gene symbol, TGFB1). Thus, we evaluated for associations between 7 common SNPs occurring in the 6 aforementioned genes and the risk of CKD after LT.  相似文献   

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