Molecular Identification of Cutaneous Alternariosis in a Renal Transplant Patient

Cutaneous alternariosis is a rare condition, caused by an uncommon opportunistic pathogen. The most frequently affected individuals are immunosuppressed patients, e.g., organ transplant patients on immunosuppressive therapy. Clinical manifestations range from local skin lesions to disseminated disease. We present a case report of cutaneous alternariosis in a renal transplant recipient, confirmed by histological examination and molecular means. In addition, a review of the literature was performed.     

Effectiveness and Long-Term Safety of Thiazolidinediones and Metformin in Renal Transplant Recipients

ObjectiveTo investigate the long-term safety and effectiveness of thiazolidinediones and metformin in renal transplant recipients with posttransplant diabetes mellitus (PTDM) or preexisting diabetes mellitus (DM).MethodsRetrospective chart review was performed for renal transplant recipients with PTDM or preexisting DM followed up during the years 2000-2006. Data collected included baseline characteristics; glomerular filtration rate (GFR); creatinine; hemoglobin A_1c; and development of congestive heart failure, edema, and liver function abnormalities. GFR was calculated using the Modification of Diet in Renal Disease study equation calculator.ResultsThirty-two patients comprised the metformin group (PTDM = 21, preexisting DM = 11), and 46 patients were included in the TZD group (PTDM = 33, preexisting DM = 13). Only 24 patients taking metformin and 31 patients taking TZDs were included for effectiveness analysis since the others required additional medications to control their DM. Mean follow-up was 16.4 months (range, 1-55 months) for patients treated with metformin and 37.1 months (range, 6-72 months) for patients treated with TZDs. GFR was decreased from baseline in all patients, but the only significant change was in patients with preexisting DM. While there was a significant change in creatinine levels in the metformin group, only 5 patients had to discontinue the drug because of this elevation (3 in preexisting DM group, 2 in PTDM group). Change in hemoglobin A_1c from baseline was not significant in either study group. Development of congestive heart failure or liver function abnormalities was not observed.ConclusionsMetformin appears to be safe in the renal transplant population for a mean duration of 16 months, although caution should be exercised using close monitoring in patients with preexisting DM. TZDs appear to be safe for a mean duration of 37 months after renal transplant. (Endocr Pract. 2008;14:979-984)     

Isolated Oral Histoplasmosis Presenting as Fever of Unknown Origin in a Portuguese Hemodialysis Patient

The authors report a clinical case of an isolated oral histoplasmosis in a hemodialysis patient that presented with fever of unknown origin and had an unremarkable physical examination. During the investigation, a Gallium scan showed uptake in the oral cavity and soon after the oral cavity examination revealed a granulomatous lesion on the tooth 26. Histopathologic findings were compatible with histoplasmosis. The treatment regimen included liposomal amphotericin B followed by itraconazole consolidation therapy, and side effects did not occur. Both clinical evolution and outcome were favorable. Oral histoplasmosis in a non-immunosuppressed patient is extremely rare.     

Long-Term,High-Dose Intravenous Immunoglobulin Therapy in a Patient with Banker-Type Juvenile Dermatomyositis

Juvenile dermatomyositis (JDM) is a multisystem disease characterized by non-purulent inflammation in the striated muscle and skin. Banker-type JDM is difficult to treat and control, especially when it is a form that is resistant to steroid treatment. Here, we report a 2-year-old girl with Banker-type JDM resistant to steroid treatment. The patient received intravenous immunoglobulin (IVIg) at 400 mg/kg/5 days a week every 6 weeks. Motor function improved and the patient was able to walk after six cycles. IVIg was administered every four weeks for six cycles thereafter, and the patient was able to walk more quickly with an improvement in quality of life. No apparent adverse effects were observed during IVIg treatment.     

Efficacy and Safety of an Everolimus- vs. a Mycophenolate Mofetil-Based Regimen in Pediatric Renal Transplant Recipients

Introduction

Data on the efficacy and safety of everolimus in pediatric renal transplantation compared to other immunosuppressive regimens are scarce.

Patients/Methods

We therefore performed a multicenter, observational, matched cohort study over 4 years post-transplant in 35 patients on everolimus plus low-dose cyclosporine, who were matched (1:2) with a control group of 70 children receiving a standard-dose calcineurin-inhibitor- and mycophenolate mofetil-based regimen.

Results

Corticosteroids were withdrawn in 83% in the everolimus vs. 39% in the control group (p<0.001). Patient and graft survival were comparable. The rate of biopsy-proven acute rejection episodes Banff score ≥ IA during the first year post-transplant was 6% in the everolimus vs. 13% in the control group (p = 0.23). The rate of de novo donor-specific HLA antibodies (11% in everolimus, 18% in controls) was comparable (p = 0.55). At 4 years post-transplant, mean eGFR in the everolimus group was 56±33 ml/min per 1.73 m² vs. 63±22 ml/min per 1.73 m² in the control group (p = 0.14). Everolimus therapy was associated with less BK polyomavirus replication (3% vs. 17% in controls; p = 0.04), but with a higher percentage of arterial hypertension and more hyperlipidemia (p<0.001).

Conclusion

In pediatric renal transplantation, an everolimus-based regimen with low-dose cyclosporine yields comparable four year results as a standard regimen, but with a different side effect profile.     

Comparison of Long-Term Outcomes between Peritoneal Dialysis Patients with Diabetes as a Primary Renal Disease or as a Comorbid Condition

ObjectiveTo investigate the long-term outcomes of peritoneal dialysis (PD) patients with diabetes as primary renal disease and patients with diabetes as a comorbid condition.MethodsAll diabetic patients who commenced PD between January 1, 1995 and June 30, 2012 at Ren Ji Hospital, China were included. Patients were divided into diabetic nephropathy group (DN group) and non-diabetic nephropathy group (NDN group) according to their diagnosis of primary renal disease at the initiation of PD. They were followed until death, cessation of PD, transferred to other centers or to the end of study (June 30, 2013). Outcomes were analyzed by Kaplan-Meier method and Cox regression models.ResultsA total of 163 diabetic patients were enrolled in the study, including 121 (74.2%) in DN group and 42 (25.8%) in NDN group. The 1-, 2-, 3- and 5-year patient survival rates were 89%, 78%, 66% and 51% for DN group, and 85%, 63%, 53% and 25% for NDN group, respectively. Kaplan-Meier analysis showed that patients in NDN group had a worse patient survival compared with DN group (log rank 4.830, P=0.028). Patients in NDN group had a marginally shorter peritonitis-free period (log rank 3.297, P=0.069), however, there was no significant difference in technique survival (log rank 0.040, P=0.841). Multivariate Cox regression analysis showed that older age (HR 1.047, 95% CI 1.022-1.073, p<0.001), cardiovascular disease comorbidity (HR 2.200, 95% CI 0.1.269-3.814, P=0.005) and diabetes as a comorbidity condition (HR 1.806, 95% CI 1.003-3.158, P=0.038) were the independent predictors of increased mortality.ConclusionsPD patients with diabetes as a comorbidity had an inferior patient survival compared to those with diabetic nephropathy, and closer monitoring and extra attention in the former subgroup of patients are therefore warranted.     

Long-Term Stabilization Effects of Leptin on Brain Functions in a Leptin-Deficient Patient

Context

Congenital leptin deficiency, caused by a very rare mutation in the gene encoding leptin, leads to severe obesity, hyperphagia and impaired satiety. The only systemic treatment is the substitution with metreleptin leading to weight reduction based on hormonal changes. Several studies have also shown alterations in brain function after metreleptin therapy. In a previous study, we were able to show changes in homeostatic (hypothalamus) and reward-related brain areas (striatum, orbitofrontal cortex (OFC), substantia nigra/ventral tegmental area, amygdala) 3 days and 6 months after therapy start in a leptin-deficient adolescent girl. To further access the time course of functional brain activation changes, we followed the patient for 2 years after initiation of the therapy.

Design, Patient

Functional magnetic resonance imaging during visual stimulation with food (high- and low-caloric) and non-food pictures was performed 1 and 2 years after therapy start in the previously described patient.

Results

The comparison of ‘food vs. non-food’ pictures showed a stabilization of the long-term effects in the amygdala and in the OFC. Therefore, no significant differences were observed between 6 months compared to 12 and 24 months in these regions. Additionally, a reduction of the frontopolar cortex activity over the whole time span was observed. For the comparison of high- and low-caloric pictures, long-term effects in the hypothalamus showed an assimilating pattern for the response to the food categories whereas only acute effects after 3 months were observed in hedonic brain regions.

Conclusion

This follow-up study shows that the long lasting benefit of metreleptin therapy is also associated with activation changes in homeostatic, hedonic and frontal control regions in congenital leptin deficiency.     

Metabolic Activity of Macrophages Infected with Hantavirus,an Agent of Hemorrhagic Fever with Renal Syndrome

Monocytes/macrophages are thought to play an important role in pathogenesis of viral infections. These cells are involved in distribution and persistence of viruses in the organism and also influence the regulation of immune reactions. The functional and enzymatic activities of macrophages infected with an agent of hemorrhagic fever with renal syndrome were analyzed for the first time. This disease is caused by a virus of the Hantavirus genus, the Bunyaviridae family. Activities of ectoenzymes 5 -nucleotidase and ATPase of the plasma membrane of the hantavirus-infected macrophages decreased along with the antigen accumulation in the infected cells. The contact of phagocytes with hantavirus resulted in activation in the cells of the oxygen-dependent metabolism and NO-synthase. The NO-synthase-dependent system of the infected macrophages was activated earlier than their oxygen-dependent system. The intracellular contents of acid and alkaline phosphatases increased within the first hours after the infection. The bactericidal activity of the hantavirus-infected macrophages relatively to Staphylococcus aureus increased during the specific antigen accumulation in the phagocytes. Thus, the infection of macrophages with hantavirus was associated with intracellular metabolic changes.     

Forty-Day Fever: An Epidemic of Cytomegalovirus Disease in a Renal Transplant Population

An epidemic of cytomegalovirus disease (CMV) occurred in 38 percent of 34 renal transplant recipients during an 18-month period. A characteristic clinical pattern was noted: 40 days following transplantation, daily fevers recurred for periods of four to six weeks. This fever in conjunction with a diffuse interstitial pneumonitis and impaired hepatic and renal function constituted a diagnostic tetrad. Of all the laboratory techniques, throat and urine cultures were the most consistent in confirming the diagnosis.Analysis of the epidemic implicated the communal hemodialysis unit as the source of exposure to the virus. CMV was not seen in the first 86 patients who received transplants in the program, but with increasing use of hemodialysis, the percentage of patients with positive serologic reaction for CMV increased dramatically.     

Construction and Characterization of a CTLA-4-Targeted scFv–Melittin Fusion Protein as a Potential Immunosuppressive Agent for Organ Transplant

Immunotoxins with selective cytotoxicity are frequently used as therapeutic immunosuppressive agents in solid-organ transplantation because of their efficiency and high specificity. In this study, we present a new recombinant immunotoxin termed anti-CTLA-4-scFv–melittin prepared from Escherichia coli aimed at clearing activated T cells at the same time avoiding all-round decline in systematic immunity. This fusion protein is composed of anti-CTLA-4-scFv unit and melittin analog unit with properties of low immunogenicity and selective cytotoxicity to CTLA-4-positive T cells. In preliminary biological activity assays, our results confirmed the feasibility of activated T cell clearance strategy and there were significant differences in cell survival rates between CTLA-4-positive group and control group at all experimental concentrations of the immunotoxin. The selective cytotoxicity, low immunogenicity, and low production cost make it an attractive alternate to traditional immunosuppressants.     

Tapetoretinal Degeneration in Childhood Presenting as a Disturbance of Behaviour

Four children presented at the age of 6 years with progressive disturbances of behaviour due to increasing visual handicap. In three of them routine ophthalmological examination was carried out in the early stages, but no objective evidence of eye disease was found. The severity and nature of the visual defect and its causal relationship to the behaviour disorder went unrecognized for periods ranging from 18 to 30 months. Eventually the development of retinal changes enabled a diagnosis of tapetoretinal degeneration to be made which was confirmed by the finding of extinction of the electroretinographic response. Transfer of the children to schools for the visually handicapped resulted in improvement in their behaviour disorder.Electroretinography is of great importance in the early diagnosis of juvenile tapetoretinal degeneration.     

Voriconazole Proves Effective in Long-Term Treatment of a Cerebral Cryptococcoma in a Chronic Nephropathic HIV-Negative Patient,after Fluconazole Failure

Although being a rare occurrence, brain cryptococcoma may represent an emerging issue, because of its relationship with a broadening range of risk factors, including malignancies, neutropenia, end-organ failure, bone marrow and solid-organ transplantation, and multiple underlying causes of primary-secondary immunodeficiency. A cerebral cryptococcoma in a chronic nephropathic HIV-negative subject with homocystinuria, completely cured with neurosurgery and voriconazole after fluconazole failure, is described.