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Cytomegalovirus (CMV) disease typically occurs 1 to 4 months (median 35 days) after solid organ transplantation. Recent reports documented that the natural history of CMV disease associated with solid organ transplantation has been modified as a result of the widespread use of potent immunosuppressents and antiviral prophylaxis. We herein report three pretransplant CMV seropositive recipients (with unknown donor status) who were diagnosed recently to display late and atypical CMV disease. Two men and one woman included two patients who presented with allograft dysfunction at 12 years and at 3 years after transplantation. Both patients showed increased serum creatinine approximately from baseline 200 to >400 micromol/L over 3 months in the absence of features of rejection or cyclosporine toxicity. A renal biopsy was refused by both patients. Two of the three patients presented with symptoms of enterocolitis (diarrhea, nausea, weight loss), which had persisted for more than 6 months. Other symptoms and signs of overt CMV disease (fever, leukopenia) were absent. None had pulmonary, hepatic, or other major organ involvement. In all patients IgG antibodies and CMV DNA by polymerase chain reaction were positive with negative IgM antibodies. The immunosuppressive regimen consisted of mycophenolate mofetil (MMF), steroids, and calcineurin inhibitors. The kidney function significantly improved in both patients with renal dysfunction. Gastrointestinal symptoms resolved completely with gradual weight gain. The recognition and early diagnosis of late atypical CMV disease in kidney transplant patients presenting with allograft dysfunction and/or other organ systems is important. The MMF has a red herring effect in our cases due to its GI side effects.
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PMID:Late cytomegalovirus disease with atypical presentation in renal transplant patients: case reports. 1535 Apr 93

Gastrointestinal complications are frequent in renal transplant recipients and can include oral lesions, esophagitis, peptic ulcer, diarrhea, colon disorders and malignancy. Oral lesions may be caused by drugs such as cyclosporine and sirolimus, by virus or fungal infections. Leukoplakia may develop in patients with Epstein-Barr virus (EBV) infection. The commonest esophageal disorder is represented by fungal esophagitis usually caused by candida. A number of patients may suffer from nausea, vomiting and gastric discomfort. These disorders are more frequent in patients treated with mycophenolate mofetil (MMF). Peptic ulcer is more rare than in the past. Patients with a history of peptic ulcer are particularly prone to this complication. Other gastroduodenal disorders are caused by cytomegalovirus (CMV) and herpes simplex infection. Diarrhea is a frequent disorder which may be caused by pathogen microorganisms or by immunosuppressive agents. The differential diagnosis may be difficult. Colon disorders mainly consist of hemorrhage, usually sustained by CMV infection, or perforation which may be caused by diverticulitis or intestinal ischemia. Colon cancer, anal carcinoma, and EBV-associated lymphoproliferative disorders are particularly frequent in transplant recipients. A particular gastric lymphoma called mucosa-associated lymphoid tissue (MALT) lymphoma may develop in renal transplant patients. It usually responds to the eradication of Helicobacter pylori.
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PMID:Gastrointestinal complications in renal transplant recipients. 1591 Feb 87

Vestibular neuritis is characterized by the sudden onset of nausea, vomiting, and spontaneous horizontal or horizonto-rotatory nystagmus. The etiology of the disease is multifactorial. Mumps, rubella, herpes simplex virus type 1, cytomegalovirus, and Epstein-Barr virus may have a role in the disease. Enteroviruses are among the other rare causes. This report presents a 7-year-old male admitted with nausea, vomiting, rotatory vertigo, horizonto-rotatory nystagmus with positive Romberg's sign and positive head-thrust test. Cranial magnetic resonance imaging and audiometry of the patient were normal. He was diagnosed with vestibular neuritis, and steroid therapy was initiated. At the second month of follow-up, all symptoms had regressed. To the best of our knowledge, this case report describes the first pediatric patient in whom enteroviral ribonucleic acid is documented both in cerebrospinal fluid and in nasopharyngeal material in active disease. This finding supports the possible role of enteroviruses in the etiology of vestibular neuritis.
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PMID:Vestibular neuritis caused by enteroviral infection. 1637 78

The management of nephrotic syndrome (NS) in children remains a clinical challenge for pediatricians and pediatric nephrologists. Especially, the treatment of patients with steroid-resistant (SR) and steroid-dependent (SD) nephrotic syndrome, because they are at risk for developing complications from prolonged exposure to steroids, CsA and alkylating agents. Mycophenolate mofetil (MMF) is a selective and reversible inhibitor of inosine monophosphate dehydrogenase used above all in transplantology and recently also in patients with nephrotic syndrome. The aim of this study was to tentatively assess the usefulness and the safety of MMF as an immunosuppressive agent in children with steroid-resistant NS, in whom remission was not obtained with previous treatment regimens, and those with steroid-dependent NS, in whom severe adverse reactions were observed in steroid and cyclosporine therapy. The study included 19 children with NS (11 girls, 8 boys) aged 7 to 19.5 years (a mean of 13.5), treated at the Deptartment of Pediatric Nephrology. The duration of disease was from 1 to 16 years (a mean of 9.3). The patients were divided into 3 groups: I--9 children with steroid-dependent NS; II--6 children with steroid-dependent NS and episodes of steroid-resistance; III--4 children with steroid-resistant NS. All patients in groups II and III required multi-drug therapy (prednisone, cyclosporine A, methylprednisolone, chlorambucil, cyclophosphamide) before MMF was introduced. MMF was administered orally: 180-600 mg/m2 body surface/dose, twice daily. The follow-up period lasted for 4 to 16 months (a mean of 7.7). The clinical outcome analysis included decrease or disappearance of proteinuria, clinical improvement and/or possibility of tapering therapy intensity, especially the dosage of steroids and/or CsA. Also, renal function was monitored with serum cystatine C concentration. Particular attention was paid to adverse effects of MMF upon the gastro- intestinal tract and/or opportunistic infections. All medication (apart from MMF) could be discontinued in 4 patients; in 15 cases, prednizone dose was reduced and in 9 cases CsA dose was reduced or discontinued. In group I (SD) steroid treatment could be reduced from a mean prednisone dose of 22.8 to 3.6 mg/m2/48 hours (p=0.018), in groups II and III, in spite of 50 % reduction of a mean prednisone dose, the difference did not reach statistical significance. During MMF therapy Csa treatment could be reduced from a mean CsA dose 4.3 to 2.9 mg/kg/24 hours (p=0.008). Improvement or preservation of stable renal function was observed in all patients--cystatin C levels decreased significantly from a mean 1.35 to 0.96 mg/l (p=0.007). Adverse reaction to MMF (abdominal pain) was observed in 2 patients (nausea, vomiting, diarrhoea in 1, CMV infection in 1). The initial clinical observation of MMF treatment in nephrotic patients shows its best effect in the group of patients with steroid-dependent NS. MMF can safely be used in children with NS. The introduction of MMF allows for reduction of other chronically used medications, especially CsA and steroids.
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PMID:[Mycophenolate mofetil in treatment of childhood nephrotic syndrome--preliminary report]. 1689 86

Alemtuzumab is a humanized monoclonal antibody directed against lymphocytes through the CD-52 receptor, an antigen being found on > 95% of peripheral blood lymphocytes and monocytes, and to a smaller extent on granulocytes. It is an effective immunotherapeutic agent in patients with malignancies such as non-Hodgkin lymphoma, B cell chronic lymphocytic leukemia and T cell pro- lymphocytic leukemia. Adverse side effects are increasingly recognized in patients receiving alemtuzumab, mainly including fever, rigors, nausea/vomiting, skin rash; other severe alemtuzumab-related reactions have also been described, such as lymphopenia and neutropenia leading to both opportunistic (e.g. cytomegalovirus) and non-opportunistic infections. Digestive complications have more rarely been described, i.e.: gastroenteritis and peritonitis. We recently observed a case of particular interest as the patient with T cell prolymphocytic leukaemia treated with alemtuzumab, exhibited symptomatic reactivation of CMV infection and developed subsequently typhlitis.
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PMID:Typhlitis as a complication of alemtuzumab therapy. 1756 96

Cytomegalovirus (CMV) is a cause of significant morbidity and mortality in solid organ transplant recipients. Gastrointestinal (GI) tract infection by CMV in this population can cause symptomatic disease, which typically manifests as fever, abdominal pain, nausea, and bloody diarrhea. Erosive lesions of the GI mucosa are often evident on endoscopic exam. We report an unusual presentation of CMV enteritis in a kidney and liver transplant recipient with the development of acute onset voluminous watery diarrhea in the absence of other typical symptoms and subsequent progression to hypovolemic shock and acute renal failure. This case emphasizes the atypical presentations of common opportunistic infections that may occur in immunosuppressed hosts.
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PMID:Unusual presentation of cytomegalovirus enteritis after liver and kidney transplantation. 1785 Feb 46

The anti-cytomegalovirus (CMV) activity and safety of oral maribavir in CMV-seropositive allogeneic stem-cell transplant recipients were evaluated in a randomized, double-blind, placebo-controlled, dose-ranging study. After engraftment, 111 patients were randomized to receive CMV prophylaxis with maribavir (100 mg twice daily, 400 mg once daily, or 400 mg twice daily) or placebo. Within the first 100 days after transplantation, the incidence of CMV infection based on CMV pp65 antigenemia was lower in each of the respective maribavir groups (15%, P = .046; 19%, P = .116; 15%, P = .053) compared with placebo (39%). Similarly, the incidence of CMV infection based on plasma CMV DNA was lower in each of the respective maribavir groups (7%, P = .001; 11%, P = .007; 19%, P = .038) compared with placebo (46%). Anti-CMV therapy was also used less often in patients receiving each respective dose of maribavir (15%, P = .001; 30%, P = .051; 15%, P = .002) compared with placebo (57%). There were 3 cases of CMV disease in placebo patients but none in the maribavir patients. Adverse events, mostly taste disturbance, nausea, and vomiting, were more frequent with maribavir. Maribavir had no adverse effect on neutrophil or platelet counts. These results show that maribavir can reduce the incidence of CMV infection and, unlike ganciclovir, does not cause myelosuppression.
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PMID:Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem cell transplant recipients: a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study. 1850 38

A 67-year-old woman with systemic lupus erythematosus (SLE) was admitted to our hospital because of lupus nephritis. Methylprednisolone minipulse therapy dramatically reduced her proteinuria; however; she then complained of general fatigue with low-grade fever. Radiological and culture studies revealed no infectious focus, but she was treated with meropenem and micafungin, considering her immunosuppressive state. Cytomegalovirus antigenemia was later determined and ganciclovir was added. She became afebrile, but complained of nausea and headache, and disorientation, without meningeal signs. Because a brain computed tomography (CT) scan showed no abnormality, we initially suspected some kind of drug interaction. Despite the discontinuation of all drugs, however, she still suffered from disturbance of consciousness. A lumbar puncture revealed yeast cells stained by India ink. A diagnosis of cryptococcal meningitis was confirmed. Though fluconazole and meropenem were administered, the patient died. Autopsy findings revealed disseminated cryptococcosis concomitant with pulmonary aspergillosis. Micafungin is a recently approved echinocandin-class antifungal agent that is now widely used in Japan because of its minimal toxicity and broadspectrum activity. However, such echinocandins have limited activity against a number of fungi. Indeed, breakthrough trichosporonosis is becoming a significant problem in patients with hematological malignancies who are receiving echinocandins. To the best of our knowledge, breakthrough cryptococcosis, as seen in our patient, has not been reported previously in patients who were receiving micafungin as an empiric antifungal therapy. This case highlights that cryptococcosis should be kept in mind as a possible breakthrough infection during the administration of echinocandins, especially in patients with cellular immunodeficiency.
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PMID:Breakthrough cryptococcosis in a patient with systemic lupus erythematosus (SLE) receiving micafungin. 1870 36

Sevoflurane, a halogenated anesthetic, is associated with mild aminotransferase elevations but does not tend to cause clinically significant hepatotoxicity. We report a rare case of severe hepatic necrosis following exposure to sevoflurane during surgery. A 37-year-old man presented with nausea,vomiting, abdominal pain, and jaundice on the third postoperative day after an abdominal wall mass resection. Laboratory tests showed markedly elevated aminotransferase levels, hyperbilirubinemia, and coagulopathy. His viral hepatitis and human immunodeficiency virus (HIV) serologies were negative for acute infection, and his Epstein-Barr virus (EBV) and cytomegalovirus (CMV) serologies were suggestive of recent EBV infection and remote CMV infection. Antinuclear antibody and anti-smooth muscle antibody screens were negative. Ceruloplasmin and serum copper values were in the normal range. The histopathological findings included an acute centrilobular cholestatic hepatocellular injury compatible with the clinical history of acute drug-induced hepatotoxicity. The patient improved with conservative management. Unlike other halogenated anesthetics, proposed mechanisms of sevoflurane hepatotoxicity include production of compound A, increased cytosolic free Ca(2+), and activation of free radical metabolizing enzymes. The patient was likely susceptible to toxicity due to an underlying EBV infection and a probable history of exposure to halogenated anesthetics. Sevoflurane is generally considered to be relatively safe for subjects with mild liver dysfunction, in comparison with other halogenated anesthetics. However, this case suggests that sevoflurane can lead to severe life-threatening hepatic necrosis in at-risk individuals.
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PMID:Sevoflurane hepatotoxicity: a case report of sevoflurane hepatic necrosis and review of the literature. 1945 19

Cytomegalovirus (CMV) is an important pathogen in organ-transplant recipients. There have been frequent reports of CMV-induced adrenal insufficiency in patients with human immunodeficiency virus infection. Herein, we report CMV-induced renal insufficiency in a renal transplant recipient. A 24-year-old woman had gradual onset of weakness, anorexia, nausea, hypotension, and skin hyperpigmentation at 5 months after renal transplantation. The immunosuppression regimen included cyclosporine, mycophenolate mofetil, and corticosteroid (prednisolone, 5 mg/d). Recent history included acute CMV infection, which was treated with ganciclovir. Basal serum cortisol concentration was 4 microg/dL, and stimulated serum cortisol concentration was less than 10 microg/dL. All clinical signs and symptoms and hypotension gradually improved after the oral prednisolone dose was increased to 10 mg/d. Clinicians must be aware of the possibility of CMV-induced adrenal insufficiency in renal transplant recipients. The condition may be symptomatic despite low-dose prednisolone therapy.
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PMID:Cytomegalovirus-induced adrenal insufficiency in a renal transplant recipient. 1976 72


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